WO2009150264A1 - Procedure for improving the general state of ruminants - Google Patents

Procedure for improving the general state of ruminants Download PDF

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Publication number
WO2009150264A1
WO2009150264A1 PCT/ES2009/000213 ES2009000213W WO2009150264A1 WO 2009150264 A1 WO2009150264 A1 WO 2009150264A1 ES 2009000213 W ES2009000213 W ES 2009000213W WO 2009150264 A1 WO2009150264 A1 WO 2009150264A1
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mixture
process according
extract
synthesis
active ingredients
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PCT/ES2009/000213
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Spanish (es)
French (fr)
Inventor
Joan Carles Ferrater Martorell
Luca Christopher Kamel
Juan Antonio Fernandez Martin
Nuria Sanroma Virgili
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Carotenoid Technologies, S.A.
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Publication of WO2009150264A1 publication Critical patent/WO2009150264A1/en

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/111Aromatic compounds
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/10Feeding-stuffs specially adapted for particular animals for ruminants

Definitions

  • This report describes a procedure to improve the general state of ruminants, which consists in increasing the energy efficiency of the metabolic process of food in the rumen of animals by inhibiting one of the processes of energy loss, perhaps the most important, which constitutes the generation of methane or methanogenesis. In this way it is possible to maintain the necessary balance in said metabolic process between the energy generated and the synthesis of proteins, which leads to an improvement in the general state of the animals and an optimal situation of the productive indicators.
  • the first one consists of an extract or garlic oil, a natural product extracted from the Allium genus plants, their fractions or components, isolated or reproduced by synthesis.
  • the other principle consists of an extract or cinnamon oil, a natural product extracted from the Cinnamomum plants, their fractions or components, isolated or reproduced by synthesis. The mixture of both is conveniently formulated for progressive release and in the right place.
  • the production line (meat, milk, labor force), the nutritional principles to obtain the maximum results (energy and proteins) and the productive indicators (growth curves, production indices, etc.) must be considered. among others).
  • Energy is used, among other things, to generate heat, maintain blood pressure, transmit nerve impulses, transport ions through the membranes, promote reabsorption in the kidneys, synthesize proteins and fats, and depending of the animals considered, to secrete milk, produce eggs and wool and develop work.
  • B It helps to maintain the reaction of various media such as plasma, and in others they are biological catalysts.
  • C They act as transport of gases such as oxygen and carbon dioxide in the blood (hemoglobin).
  • Resistance Collagen is the main integral protein of supportive tissues.
  • the objective, therefore, of the present invention is to achieve said balance in ruminants by modulating ruminal fermentation.
  • the increase in energy efficiency in the rumen of animals is proposed, inhibiting one of the processes, perhaps the most important, of energy loss, the generation of methane or methanogenesis.
  • This inhibition is achieved by the action of a formulated product that is incorporated into animal feed and that is constituted by a mixture of two active ingredients.
  • the first one consists of an extract or garlic oil, a natural product extracted from the Allium genus plants, their fractions or components, isolated or reproduced by synthesis.
  • the other principle consists of an extract or cinnamon oil, a natural product extracted from the Cinnamomum plants, their fractions or components, isolated or reproduced by synthesis.
  • the mixture of both is formulated according to the procedure described below and the resulting product is incorporated as is or as a premix into the animal's feed.
  • European Patent EP0835120 of June 1996 stands out, in which antimicrobial pharmaceutical compositions constituted based on essential oils obtained from Origanum vulgare are claimed, together with a pharmaceutically acceptable carrier.
  • compositions in which the active ingredient, oregano essential oil is formulated by the action of an excipient that is selected from a wide variety of products, paraffin, starch and its derivatives, calcium carbonate, and many others.
  • an excipient that is selected from a wide variety of products, paraffin, starch and its derivatives, calcium carbonate, and many others.
  • the product thus obtained was very useful in the prevention and treatment of gastrointestinal disorders of microbial origin.
  • the generation of methane in the rumen of animals represents a mechanism of energy loss and, therefore, an alteration of the necessary balance between energy and synthesis of proteins
  • the objective of the present invention is the minimization of this mechanism of energy loss through the inhibition of methanogenesis, which translates into a greater use of food by the ruminant and therefore, in a better general state of animals .
  • the inhibition of the methanogenesis that constitutes the object of the present invention, as advanced, is achieved by the combined action of two active principles conveniently formulated to cause the desired optimum effect.
  • the first active ingredient consists of an extract or essential oil of garlic, a natural product extracted from the Allium plants, obtained by the usual methods. Any individual fraction or component of the garlic oil or extract or any mixture of the individual components obtained by extraction from natural sources, or prepared by synthesis, is also included within the scope of the present invention.
  • the second active ingredient that forms the basis of the present invention is the extract or essential oil of cinnamon, a natural product extracted from the Cinnamomum plants, obtained by the usual methods.
  • any individual fraction or component of the extract or essential oil or any mixture obtained by extraction from natural seeds, or prepared by synthesis, is also included within the scope of the invention. In this case, it deserves special Mention the main component of cinnamon extract, cinnamaldehyde, whose activity has proved particularly important.
  • the formulation object of the present invention consists, as described in detail below, in a microencapsulation of the active ingredients by the action of suitable excipients by a novel manufacturing process.
  • the process consists of fixing the mixture of the plant extracts or their components in a porous inorganic support, consisting mainly of precipitated silica, and the subsequent coating with a protective layer, constituted by an emulsifier, of the type mono and / or diglyceride of saturated fatty acids, or their derivatives esterified with acetic acid, lactic acid or the like.
  • the first one consists of an extract or garlic oil, a natural product extracted from the Allium genus plants, their fractions or components, isolated or reproduced by synthesis.
  • the other principle was in an extract or cinnamon oil, a natural product extracted from the Cinnamomum plants, their fractions or components, isolated or reproduced by synthesis. The mixture of both is conveniently formulated for progressive release and in the right place.
  • the individual components can be obtained by fractionation of the extract or essential oil or they can be prepared by synthesis according to any of the methods described in the literature. In all cases they should be considered within the scope of the present invention.
  • cinnamon oil cinnamaldehyde
  • cinnamaldehyde cinnamaldehyde
  • the relative proportion in which the two active ingredients are formulated can be very variable. It should be noted that in all the cases tested, even maintaining very unequal relative proportions, a very marked synergy of its effects is detected. The best results have been obtained maintaining a weight ratio between the first active ingredient, garlic oil or extract, and the second, cinnamon oil or extract, from 0.01 to 0.50, preferably from 0.05 to 0.2. These proportions are similar when the product is formulated using instead of natural oils or extracts, their fractions and / or components.
  • the formulation object of the present invention represents, as justified above, an aspect of great importance for obtaining the desired results.
  • it can be described as a microencapsulation of the active ingredients by the action of suitable excipients by a novel manufacturing process.
  • the mixture of the plant extracts, or of their main components is fixed, by adsorption and / or absorption on a porous inorganic support constituted, mainly, by precipitated silica, and coated with a protective layer constituted by an emulsifier.
  • a porous inorganic support constituted, mainly, by precipitated silica, and coated with a protective layer constituted by an emulsifier.
  • the inorganic support consisting basically of precipitated silica is completely inert, in the sense that it does not react with any of the active ingredients and, therefore, does not cause or induce any type of degradation process.
  • the physicochemical characteristics of this support are perfectly suitable for the intended purpose. They are spherical particles with an approximate size of between 80 to 500 microns. Precipitated silica has an optimal characteristic for liquid formulation. It is about its microporosity. The particles contain a multitude of pores that, logically, increase the specific surface area with respect to similar particle sizes of other types of supports. But, in addition, the active principle penetrates these pores and is occluded in them. The result is evident, increases the load capacity and also guarantees its fixation in the support.
  • the support is kept in continuous motion and the mixture of plant extracts is sprayed or fogged on it.
  • the mixing is kept under stirring at the appropriate temperature until reaching the level of fixation of the oil in the support.
  • acceptable results are achieved with mixing times of 3 minutes to 2 hours at temperatures between 15 0 C and 4O 0 C.
  • the mixture of the plant extracts or their components previously dissolved in a suitable solvent can be added.
  • these solvents are hexane, methanol, ethanol and the like.
  • the product will It undergoes a complete solvent removal process using the usual methods, such as vacuum evaporation, drying in the fluid bed, or some other.
  • the concentration values of the mixture of active ingredients that are considered suitable for this type of products are reached, that is, between 20% and 50% of the total weight of the formulated product, preferably between 30 % and 45%.
  • the second phase in the preparation of the product object of the present invention consists in coating the plant extract deposited on the precipitated silica with a protective layer.
  • an emulsifying agent commonly used as a feed additive has been selected. It is mono- and di-glycerides of saturated fatty acids, additive to which the code E-471 corresponds.
  • This emulsifying agent is added directly to the fluid bed or to the mixer, where the plant extract is fixed on the support, producing a homogeneous dispersion on the surface of the support and, therefore, giving rise to a very effective protective layer.
  • concentrations of the order of 10-25% of mono- and di-glycerides are sufficient to carry out an effective coating.
  • Values of the order of 15% to 20% emulsifier are common.
  • fatty acid esters are used in order to be solid at room temperature and, with melting points greater than 7O 0 C. This parameter is very important since a solid coating of the Active ingredient in the support is less permeable to degrading agents than a liquid one.
  • E-471 being a non-ionic surfactant, exhibits excellent performance in terms of hydrophilic fixation and lipophilic resistance.
  • the coating based on mono and di-glycerides of fatty acids can be replaced by their corresponding esterified derivative.
  • Short-chain organic acids such as acetic, lactic and the like, are used to make this last product. These are additives authorized in food and included in the code E-472.
  • the correct dosage of the protective agent is achieved by spraying in the fluid bed or in the mixer used in the previous phase.
  • the emulsifying agent is usually dosed molten, that is, at temperatures between 7O 0 C and 8O 0 C or higher.
  • the product thus obtained is usually incorporated into the food of the animals after preparing a premix with different usual ingredients in the formulation of rations for animals such as soybean meal, hazelnut husks or calcium carbonate, among many others.
  • Example 1 In a 5 liter capacity reactor equipped with mechanical agitation, the following are introduced:
  • each particle contains a portion of plant extract and maintains a remaining ability to absorb more liquid.
  • Example 2 On the granular product obtained while maintaining a strong stirring, 420 g of a mixture of mono and diglycerides of stearic acid (E-471) previously heated until melting are added, around 7O 0 C. In this way it is deposited on the surface of the particles of plant-sipernat extract. Subsequent cooling to room temperature allows the final product to be isolated in the form of granular powder, suitable for use as an additive for animal feed.
  • E-471 a mixture of mono and diglycerides of stearic acid
  • 370 kg of sipernat 2200 are arranged in an industrial fluid-type dryer unit operated by air flow under conditions such that a high fluidization of the pulverulent solid is ensured.
  • Example 3 In a Forberg type shovel mixer, enter:

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  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Animal Husbandry (AREA)
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Abstract

Procedure for improving the general state of ruminants consisting in increasing the energy yield of metabolic processing of foods, inhibiting the generation of methane in the rumen through the joint and simultaneous action of two active principles with different relative proportions and conveniently formulated to ensure progressive release thereof, incorporated into the food of the animals and which consist, the first thereof, of an extract or oil of garlic, a natural product extracted from plants of the genus Allium, its fractions or components, isolated or reproduced by synthesis and, the second thereof, of an extract or oil of cinnamon, a natural product extracted from plants of the genus Cinnamomum, its fractions or components, isolated or reproduced by synthesis.

Description

PROCEDIMIENTO PARA MEJORAR EL ESTADO GENERAL DE LOS PROCEDURE TO IMPROVE THE GENERAL STATUS OF
RUMIANTESRuminants
DESCRIPCIÓNDESCRIPTION
Ámbito de aplicación.-Area of application.-
La presente memoria describe un procedimiento para mejorar el estado general de los rumiantes que consiste en incrementar el rendimiento energético del proceso metabólico de los alimentos en el rumen de los animales inhibiendo uno de los procesos de pérdida de energía, quizás el más importante, que constituye la generación de metano ó metanogénesis. De esta manera se consigue mantener el necesario equilibrio en dicho proceso metabólico entre la energía generada y la síntesis de proteínas, lo que conduce a una mejora del estado general de los animales y a una situación óptima de los indicadores productivos.This report describes a procedure to improve the general state of ruminants, which consists in increasing the energy efficiency of the metabolic process of food in the rumen of animals by inhibiting one of the processes of energy loss, perhaps the most important, which constitutes the generation of methane or methanogenesis. In this way it is possible to maintain the necessary balance in said metabolic process between the energy generated and the synthesis of proteins, which leads to an improvement in the general state of the animals and an optimal situation of the productive indicators.
Esta inhibición se consigue por la acción conjunta y simultánea de dos principios activos que se incorporan al alimento de los animales. El primero de ellos consiste en un extracto ó aceite de ajo, producto natural extraído de las plantas de género Allium, sus fracciones o componentes, aislados o reproducidos por síntesis. El otro principio consiste en un extracto o aceite de canela, producto natural extraído de las plantas de género Cinnamomum, sus fracciones o componentes, aislados o reproducidos por síntesis. La mezcla de ambos se formula convenientemente para su liberación progresiva y en el lugar adecuado.This inhibition is achieved by the joint and simultaneous action of two active ingredients that are incorporated into animal feed. The first one consists of an extract or garlic oil, a natural product extracted from the Allium genus plants, their fractions or components, isolated or reproduced by synthesis. The other principle consists of an extract or cinnamon oil, a natural product extracted from the Cinnamomum plants, their fractions or components, isolated or reproduced by synthesis. The mixture of both is conveniently formulated for progressive release and in the right place.
En un sistema de explotación de animales se debe considerar la línea de producción (carne, leche, fuerza de trabajo), los principios nutritivos para obtener los máximos resultados (energía y proteínas) y los indicadores productivos (curvas de crecimiento, índices de producción, entre otros).In an animal exploitation system, the production line (meat, milk, labor force), the nutritional principles to obtain the maximum results (energy and proteins) and the productive indicators (growth curves, production indices, etc.) must be considered. among others).
La energía se utiliza, entre otras cosas, para generar calor, mantener la presión sanguínea, trasmitir impulsos nerviosos, transportar iones a través de las membranas, favorecer la reabsorción en los ríñones, sintetizar proteínas y grasas, y dependiendo de los animales considerados, para secretar leche, producir huevos y lana y desarrollar trabajo.Energy is used, among other things, to generate heat, maintain blood pressure, transmit nerve impulses, transport ions through the membranes, promote reabsorption in the kidneys, synthesize proteins and fats, and depending of the animals considered, to secrete milk, produce eggs and wool and develop work.
Un ejemplo de especial interés es el caso de los rumiantes. En ellos se puede describir el metabolismo energético de una forma simplificada. Así, los hidratos de carbono ingeridos fermentan en el rumen transformándose en glucosa, que evoluciona posteriormente a piruvato. Estos procesos implican transferencias y capturas de hidrógenos metabólicos, cuyo equilibrio garantiza un funcionamiento correcto de la glicólisis y, por tanto, del aporte de la energía necesaria.An example of special interest is the case of ruminants. They can describe the energy metabolism in a simplified way. Thus, ingested carbohydrates ferment in the rumen transforming into glucose, which subsequently evolves into pyruvate. These processes involve transfers and captures of metabolic hydrogens, whose equilibrium guarantees the proper functioning of glycolysis and, therefore, the contribution of the necessary energy.
La deficiencia en la generación de la energía necesaria por parte de los animales, en general, y del ganado bovino, en particular, tiene importantes efectos negativos y, frecuentemente, se traduce en:The deficiency in the generation of the necessary energy on the part of the animals, in general, and of the cattle, in particular, has important negative effects and, frequently, it is translated in:
1. Crecimiento lento o incluso, nulo.1. Slow or even zero growth.
2. Pérdida de tejido corporal.2. Loss of body tissue.
3. Disminución en la producción (leche, carne, fibra o trabajo).3. Decrease in production (milk, meat, fiber or work).
En el caso de los rumiantes, la liberación de hidrógenos al medio o su transferencia para la generación de metano son procesos energéticamente poco eficientes, puesto que estos gases se expulsan. Se han publicado estudios donde se estima que las pérdidas por generación de metano oscilan entre el 3% y el 15% de la energía total (Van Nevel y Demeyer en The Rumen Mycrobial Ecosystem, ed. Elsevier, 1988). Un incremento de la retención de hidrógenos metabólicos es, por tanto, en este caso un mecanismo que permitiría la optimización de la utilización de energía en el rumen.In the case of ruminants, the release of hydrogens into the environment or their transfer to the generation of methane are energy efficient processes, since these gases are expelled. Studies have been published where it is estimated that methane generation losses range between 3% and 15% of total energy (Van Nevel and Demeyer in The Rumen Mycrobial Ecosystem, ed. Elsevier, 1988). An increase in the retention of metabolic hydrogens is, therefore, in this case a mechanism that would allow the optimization of energy use in the rumen.
El otro principio nutritivo mencionado anteriormente, y necesario para el correcto desarrollo de los animales, es la síntesis de proteínas. De forma resumida se pueden listar algunas de las funciones principales que desarrollan las proteínas en los animales: A. Forman parte de los jugos digestivos, hormonas y vitaminas.The other nutritional principle mentioned above, and necessary for the proper development of animals, is protein synthesis. In summary, some of the main functions that proteins develop in animals can be listed: A. They are part of digestive juices, hormones and vitamins.
B. Ayuda a mantener la reacción de diversos medios como el plasma, y en otros son catalizadores biológicos. C. Actúan como transporte de gases como oxígeno y dióxido de carbono en sangre (hemoglobina).B. It helps to maintain the reaction of various media such as plasma, and in others they are biological catalysts. C. They act as transport of gases such as oxygen and carbon dioxide in the blood (hemoglobin).
D. Forman parte de los anticuerpos y participan en la defensa contra infecciones o agentes extraños.D. They are part of the antibodies and participate in the defense against infections or foreign agents.
E. Permiten el movimiento celular a través de la miosina y actina (proteínas contráctiles musculares).E. They allow cell movement through myosin and actin (muscle contractile proteins).
F. Resistencia. El colágeno es la principal proteína integrante de los tejidos de sostén.F. Resistance Collagen is the main integral protein of supportive tissues.
De hecho la situación óptima para el desarrollo de los animales se alcanza cuando se logra un equilibrio entre la generación de energía y la producción de proteínas.In fact, the optimal situation for the development of animals is reached when a balance between energy generation and protein production is achieved.
Cuando existe un desequilibrio entre ambas, en un sentido u otro, los animales no alcanzan a cubrir sus requerimientos para lograr las producciones deseadas (ganancia de peso, estado. corporal para lograr preñez adecuada, etc).When there is an imbalance between the two, in one way or another, the animals fail to meet their requirements to achieve the desired productions (weight gain, body condition to achieve adequate pregnancy, etc).
Así, en la situación en la que existe un exceso de energía frente a proteína (E/P alta o balance de energía positivo), se suelen observar:Thus, in the situation in which there is an excess of energy against protein (high E / P or positive energy balance), it is usually observed:
1. Debilidad muscular acompañada de una reducción de masa corporal.1. Muscle weakness accompanied by a reduction in body mass.
2. Pérdida de apetito y, cómo consecuencia, reducción del consumo de - alimento.2. Loss of appetite and, as a consequence, reduction of food consumption.
3. Reducción del crecimiento.3. Growth reduction.
4. Retención de energía en forma de grasa corporal.4. Energy retention in the form of body fat.
5. Edema o hinchazón de tejidos subcutáneos por la retención de líquido. En muchos casos se presenta el vientre hinchado. 6. Letargo. En cambio, en la situación inversa, es decir, cuando hay un exceso de proteína frente a energía (E/P baja o balance de energía negativo), lo que se puede observar es:5. Edema or swelling of subcutaneous tissues due to fluid retention. In many cases the swollen belly appears. 6. Lethargy. On the other hand, in the inverse situation, that is, when there is an excess of protein against energy (low E / P or negative energy balance), what can be observed is:
1. Reducción en la formación de ATP 2. Excreción de proteína en heces y orina1. Reduction in ATP formation 2. Excretion of protein in feces and urine
3. Aparición de problemas renales y hepáticos por acumulación de NH3 3. Appearance of kidney and liver problems due to accumulation of NH 3
4. Incremento en la mortalidad embrionaria.4. Increase in embryonic mortality.
5. Disminución de la fertilidad.5. Decrease in fertility.
6. Incremento de los costos de alimentación.6. Increase in food costs.
Por tanto, la consecución del equilibrio entre la energía generada y la síntesis de proteínas, debe conducir a una mejora del estado general de los animales y a una situación óptima de los indicadores productivos.Therefore, the achievement of the balance between the energy generated and the synthesis of proteins, should lead to an improvement of the general state of the animals and an optimal situation of the productive indicators.
El objetivo, por tanto, de la presente invención consiste en la consecución de dicho equilibrio en rumiantes mediante la modulación de la fermentación ruminal. Para ello, se plantea el incremento del rendimiento energético en el rumen de los animales inhibiendo uno de los procesos, quizás el más importante, de pérdida de energía, la generación de metano ó metanogénesis.The objective, therefore, of the present invention is to achieve said balance in ruminants by modulating ruminal fermentation. For this, the increase in energy efficiency in the rumen of animals is proposed, inhibiting one of the processes, perhaps the most important, of energy loss, the generation of methane or methanogenesis.
Esta inhibición se consigue por la acción de un producto formulado que se incorpora al alimento de los animales y que está constituido por una mezcla de dos principios activos. El primero de ellos consiste en un extracto ó aceite de ajo, producto natural extraído de las plantas de género Allium, sus fracciones o componentes, aislados o reproducidos por síntesis. El otro principio consiste en un extracto o aceite de canela, producto natural extraído de las plantas de género Cinnamomum, sus fracciones o componentes, aislados o reproducidos por síntesis. La mezcla de ambos se formula según el procedimiento que se describe más adelante y el producto resultante se incorpora tal cual o en forma de premezcla al pienso del animal. Asociado a la disminución del metano generado por el ganado bovino y, como consecuencia de él, existe un efecto positivo de interés medioambiental. Efectivamente, la generación de metano por parte del ganado vacuno y ovino supone hoy en día una fuente natural muy importante de emisión de gases con efecto invernadero. Por tanto, la inhibición de la metanogénesis se traducirá adicionalmente en una mejora medioambiental de considerable interés.This inhibition is achieved by the action of a formulated product that is incorporated into animal feed and that is constituted by a mixture of two active ingredients. The first one consists of an extract or garlic oil, a natural product extracted from the Allium genus plants, their fractions or components, isolated or reproduced by synthesis. The other principle consists of an extract or cinnamon oil, a natural product extracted from the Cinnamomum plants, their fractions or components, isolated or reproduced by synthesis. The mixture of both is formulated according to the procedure described below and the resulting product is incorporated as is or as a premix into the animal's feed. Associated with the decrease in methane generated by cattle and, as a result, there is a positive effect of environmental interest. Indeed, the generation of methane by cattle and sheep is today a very important natural source of greenhouse gas emissions. Therefore, the inhibition of methanogenesis will further result in an environmental improvement of considerable interest.
Si bien, el efecto por separado de estos extractos vegetales sobre la metanogénesis en rumiantes ha sido estudiado con anterioridad, su utilización de forma conjunta ha mostrado una sinergia extraordinaria y, por tanto, una sorprendente e inesperada eficacia. Además, la formulación de esta mezcla, que consiste en una microencapsulación en unas condiciones determinadas, supone un avance muy importante para su utilización en el pienso de los animales.Although, the separate effect of these plant extracts on methanogenesis in ruminants has been studied previously, their use together has shown extraordinary synergy and, therefore, surprising and unexpected efficacy. In addition, the formulation of this mixture, which consists of a microencapsulation under certain conditions, represents a very important advance for its use in animal feed.
Estado de la técnica:State of the art:
Con la progresiva prohibición de la mayor parte de los antibióticos en la alimentación animal, debido principalmente a posible presencia de residuos o aparición de resistencias cruzadas, se ha potenciado la búsqueda de productos alternativos, fundamentalmente de procedencia natural. En esta línea, se ha encontrado que algunos extractos vegetales muestran una elevada actividad antimicrobiana.With the progressive prohibition of most antibiotics in animal feed, mainly due to the possible presence of residues or the appearance of cross-resistance, the search for alternative products, mainly of natural origin, has been enhanced. In this line, it has been found that some plant extracts show a high antimicrobial activity.
Entre la gran cantidad de antecedentes descritos en la bibliografía destaca la patente europea EP0835120 de junio de 1996, en la que se reivindican composiciones farmacéuticas antimicrobianas constituidas a base de aceites esenciales obtenidos a partir de Origanum vulgare, junto con un vehículo farmacéuticamente aceptable.Among the large amount of background described in the literature, European Patent EP0835120 of June 1996 stands out, in which antimicrobial pharmaceutical compositions constituted based on essential oils obtained from Origanum vulgare are claimed, together with a pharmaceutically acceptable carrier.
Un antecedente más reciente es el constituido por la patente EP 1178736 de mayo de 1999, en la que se describe y reivindica la acción de carvacrol y timol y sus mezclas como productos bactericidas. En esta línea merece especial mención la patente ES200601094 solicitada en 2006 por la firma Carotenoid Technologies, S.A., en la que se reivindica la acción antimicrobiana de extractos vegetales, principalmente, aceite de orégano y su contribución para la mejora del estado general de los animales.A more recent background is that constituted by EP 1178736 of May 1999, in which the action of carvacrol and thymol and its mixtures as bactericidal products is described and claimed. In this line, the patent ES200601094 requested in 2006 by the firm Carotenoid Technologies, SA, in which the antimicrobial action of plant extracts, mainly oregano oil and its contribution to the improvement of the general state of animals is claimed, is worthy of mention.
No sólo se ha podido demostrar un efecto antibiótico de los aceites esenciales. Algunos extractos vegetales y aceites- esenciales han mostrado un importante efecto en los procesos que se desarrollan en el rumen de algunos animales y que resultan especialmente útiles para la mejora del estado general de ellos.Not only has an antibiotic effect of essential oils been demonstrated. Some plant extracts and essential oils have shown an important effect on the processes that develop in the rumen of some animals and are especially useful for improving their general condition.
Unas de las publicaciones pioneras en esta línea en rumiantes son los trabajos llevados a cabo por H.K. Oh y col, en Appl. Microbiol, U, 777-784 (1967) y 16, 39- 44 (1968). Estos autores apuntaron que algunos aceites esenciales podían influir sobre la fermentación microbiana ruminal. Posteriormente se pudo comprobar que el mecanismo de acción afectaba al metabolismo proteico. (Broderick y Balthrop, en J Anim. ScL, 49, 1101-1111 (1979)).Some of the pioneering publications in this line in ruminants are the works carried out by H.K. Oh et al, in Appl. Microbiol, U, 777-784 (1967) and 16, 39-44 (1968). These authors pointed out that some essential oils could influence ruminal microbial fermentation. Subsequently it was found that the mechanism of action affected protein metabolism. (Broderick and Balthrop, in J Anim. ScL, 49, 1101-1111 (1979)).
Estudios más recientes ya pusieron de manifiesto la importante acción de ciertos aceites esenciales sobre la fermentación ruminal, siendo destacables, a título de ejemplo, el Eucalyptus, el Capsicum, la Lavandula y el Origanum, entre otros.More recent studies have already shown the important action of certain essential oils on ruminal fermentation, with Eucalyptus, Capsicum, Lavandula and Origanum, among others, being notable.
Son particularmente interesantes los trabajos publicados por Broudiscou y col., en Anim. FeedSci. TechnoL, 87, 263-277 (2000) y 101, 183-189 (2002). En estos artículos los autores demostraban la acción sobre la metanogénesis de dos extractos vegetales la Equisetum arvense y la Salvia officinalis. Posteriormente, Mohammed y col., en J Anim. ScL, 82, 1839-1846 (2004) publicaron su trabajo en el que se demostraban efectos similares debido a la acción de otro extracto vegetal la Armoracia rusticana. De todos los aceites esenciales y extractos vegetales, parece que son el aceite de ajo y el de canela los que han mostrado una mayor eficacia en el control de la metanogénesis en rumiantes.The works published by Broudiscou et al. In Anim are particularly interesting. FeedSci TechnoL, 87, 263-277 (2000) and 101, 183-189 (2002). In these articles the authors demonstrated the action on the methanogenesis of two plant extracts, Equisetum arvense and Salvia officinalis. Subsequently, Mohammed et al., In J Anim. ScL, 82, 1839-1846 (2004) published their work in which similar effects were demonstrated due to the action of another plant extract the Armoracia rusticana. Of all the essential oils and vegetable extracts, it seems that it is garlic and cinnamon oil that have shown greater efficacy in the control of methanogenesis in ruminants.
Se han llevado a cabo varios estudios para profundizar en el mecanismo de acción del extracto de ajo sobre la metanogénesis. Merece especial mención el trabajo desarrollado por Busquet y col., en J. Dairy Sci, 88 (2005) en el que se estudió el efecto de los cuatro componentes principales del extracto de ajo ( alicina, sulfuro de dialilo, disulfuro de dialilo y alilmercaptano) en condiciones in vitro. Estos autores pudieron concluir que los componentes disulfuro de dialilo y alil mercaptano eran los principales responsables de sus efectos.Several studies have been carried out to deepen the mechanism of action of garlic extract on methanogenesis. The work carried out by Busquet et al., In J. Dairy Sci, 88 (2005), in which the effect of the four main components of garlic extract (allicin, diallyl sulfide, diallyl disulphide and allylcaptan) ) under in vitro conditions. These authors were able to conclude that the disulfide components of diallyl and allyl mercaptan were primarily responsible for their effects.
Un estudio del mecanismo de acción llevó a sugerir a Busquet y col., en J. Dairy Sci, 88, 2508-2516 (2005) que los efectos antimetanogénicos del extracto de ajo se^ debían a un efecto directo sobre las bacterias Archea debido a su efecto específico sobre la estabilidad de su membrana.A study of the mechanism of action led to suggest to Busquet et al., In J. Dairy Sci, 88, 2508-2516 (2005) that the antimetanogenic effects of garlic extract were due to a direct effect on Archea bacteria due to its specific effect on the stability of its membrane.
En un trabajo bastante reciente publicado en International Cόngress Series (Elsevier) 1293, 176-9 (2006), A.K. Patra y col comparan el efecto sobre la metanogénesis en rumiantes de varios extractos vegetales hidroalcohólicos, y concluyen que es el ajo el que presenta un efecto más importante.In a fairly recent work published in the International Series Series (Elsevier) 1293, 176-9 (2006), A.K. Patra et al compare the effect on methanogenesis in ruminants of various hydroalcoholic vegetable extracts, and conclude that it is garlic that has a more important effect.
En el caso del extracto o aceite de canela, los primeros estudios llevados a cabo por Cardozo y col., y publicados en J Anim. Sci. 82, 3230-3236 (2004) sugirieron un efecto sobre el metabolismo proteico del rumen. Estudios posteriores llevados a cabo por Busquets y col., Anim. Feed Sci.Technol. (2005) con este extracto vegetal y, sobre todo, con su componente principal, el cinamaldehído, permitieron concluir su importante efecto de inhibición sobre la metanogénesis.In the case of cinnamon extract or oil, the first studies carried out by Cardozo et al., And published in J Anim. Sci. 82, 3230-3236 (2004) suggested an effect on the protein metabolism of the rumen. Later studies carried out by Busquets et al., Anim. Feed Sci.Technol. (2005) with this plant extract and, above all, with its main component, cinnamaldehyde, allowed to conclude its important inhibition effect on methanogenesis.
En la bibliografía se describen muchos ejemplos de formulaciones de aceites esenciales o extracto vegetales de utilidad en la alimentación animal. Un ejemplo de interés es la patente europea EP0835120, en la que se reivindican composiciones farmacéuticas antimicrobianas constituidas a base de aceites esenciales junto con un vehículo farmacéuticamente aceptable. Se reivindica también su uso en el tratamiento de multitud de enfermedades, tales como, mastitis., afecciones dermatológicas y oftalmológicas, entre otras.Many examples of formulations of essential oils or plant extracts useful in animal feed are described in the literature. An example of interest is European patent EP0835120, in which antimicrobial pharmaceutical compositions constituted based on essential oils are claimed together with a pharmaceutically acceptable carrier. Its use is also claimed in the treatment of a multitude of diseases, such as mastitis, dermatological and ophthalmological conditions, among others.
En esta misma línea, en la patente EP 828502 se reivindican las composiciones farmacéuticas y veterinarias en las que el principio activo, el aceite esencial de orégano se formula mediante la acción de un excipiente que se selecciona entre una gran variedad de productos, parafina, almidón y sus derivados, carbonato calcico, y muchos otros. El producto así obtenido resultó muy útil en la prevención y el tratamiento de desórdenes gastrointestinales de origen microbiano.In this same line, in the patent EP 828502 pharmaceutical and veterinary compositions are claimed in which the active ingredient, oregano essential oil is formulated by the action of an excipient that is selected from a wide variety of products, paraffin, starch and its derivatives, calcium carbonate, and many others. The product thus obtained was very useful in the prevention and treatment of gastrointestinal disorders of microbial origin.
Un antecedente más reciente es el constituido por la patente EP 1178736 de mayo de 1999, en el que se describe y reivindica la acción de carvacrol y timol y sus mezclas, convenientemente formuladas, como productos bactericidas.A more recent antecedent is that constituted by EP 1178736 of May 1999, in which the action of carvacrol and thymol and its mixtures, suitably formulated, as bactericidal products is described and claimed.
Son frecuentes en la bibliografía los trabajos sobre formulaciones de esencias o aromas utilizados en la industria cosmética. Un ejemplo de particular interés es el descrito en Perfurmer and Flavorist, 52-55, vol. 27, (2002). En este artículo se hacen unas consideraciones sobre un procedimiento de encapsulación con el objetivo de proteger el aroma a lo largo de la posterior elaboración del cosmético.The works on formulations of essences or aromas used in the cosmetic industry are frequent in the literature. An example of particular interest is that described in Perfurmer and Flavorist, 52-55, vol. 27, (2002). In this article some considerations are made about an encapsulation procedure with the objective of protecting the aroma throughout the subsequent elaboration of the cosmetic.
Descripción de la invención:Description of the invention:
Como se ha puesto de manifiesto en la descripción del ámbito técnico de la presente memoria, la generación de metano en el rumen de los animales representa un mecanismo de pérdida de la energía y, por tanto, una alteración del necesario equilibrio entre energía y síntesis de proteínas. El objetivo de la presente invención consiste en la minimización de este mecanismo de pérdida de energía mediante la inhibición de la metánogénesis, lo que se traduce en un mayor aprovechamiento de los alimentos por el rumiante y por tanto, en un mejor estado general de los animales.As has been shown in the description of the technical scope of this report, the generation of methane in the rumen of animals represents a mechanism of energy loss and, therefore, an alteration of the necessary balance between energy and synthesis of proteins The objective of the present invention is the minimization of this mechanism of energy loss through the inhibition of methanogenesis, which translates into a greater use of food by the ruminant and therefore, in a better general state of animals .
Una consecuencia adicional, importante desde el punto de vista medioambiental, asociada con la inhibición de la metánogénesis es la consiguiente disminución de la cantidad de metano emitida a la atmósfera. De esta forma se reduce la importante contribución que este gas presenta sobre el efecto invernadero. Se ha de tener en cuenta que las emisiones de gas procedente de los rumiantes están consideradas en la actualidad como una de las fuentes naturales más importantes con efecto invernadero.An additional consequence, important from an environmental point of view, associated with the inhibition of methanogenesis is the consequent decrease in the amount of methane emitted into the atmosphere. In this way the important contribution that this gas presents on the greenhouse effect is reduced. It must be taken into account that gas emissions from ruminants are currently considered one of the most important natural sources with a greenhouse effect.
La inhibición de la metánogénesis que constituye el objeto de la presente invención, tal como se ha avanzado, se consigue por la acción combinada de dos principios activos convenientemente formulados para provocar el efecto óptimo deseado.The inhibition of the methanogenesis that constitutes the object of the present invention, as advanced, is achieved by the combined action of two active principles conveniently formulated to cause the desired optimum effect.
El primer principio activo consiste en un extracto o aceite esencial de ajo, producto natural extraído de las plantas de género Allium, obtenido por los métodos habituales. Se incluye además dentro del ámbito de la presente invención cualquier fracción o componente individual del aceite o extracto de ajo o cualquier mezcla de los componentes individuales obtenido por extracción de fuentes naturales, o preparado por síntesis.The first active ingredient consists of an extract or essential oil of garlic, a natural product extracted from the Allium plants, obtained by the usual methods. Any individual fraction or component of the garlic oil or extract or any mixture of the individual components obtained by extraction from natural sources, or prepared by synthesis, is also included within the scope of the present invention.
El segundo principio activo que constituye la base de la presente invención es el extracto o aceite esencial de canela, producto natural extraído de las plantas de género Cinnamomum, obtenido por los métodos habituales. Igualmente, se incluye además dentro del ámbito de la invención cualquier fracción o componente individual del extracto o aceite esencial o cualquier mezcla obtenida por extracción a partir de ñientes naturales, o preparada por síntesis. En este caso, merece especial mención el principal componente del extracto de canela, el cinamaldehído, cuya actividad ha resultado ser particularmente importante.The second active ingredient that forms the basis of the present invention is the extract or essential oil of cinnamon, a natural product extracted from the Cinnamomum plants, obtained by the usual methods. Likewise, any individual fraction or component of the extract or essential oil or any mixture obtained by extraction from natural seeds, or prepared by synthesis, is also included within the scope of the invention. In this case, it deserves special Mention the main component of cinnamon extract, cinnamaldehyde, whose activity has proved particularly important.
De hecho y tal como se cita en la revisión del estado de la técnica, el efecto por separado de ambos principios activos sobre la metanogénesis en rumiantes ha sido descrito con cierto detalle en algunas referencias bibliográficas.In fact, and as cited in the review of the prior art, the separate effect of both active principles on methanogenesis in ruminants has been described in some detail in some bibliographical references.
De lo que no hay antecedentes y, que resulta extraordinariamente sorprendente, es la sinergia que produce la acción conjunta de ambos principios activos sobre la metanogénesis en rumiantes cuando se aplican simultáneamente. Se ha podido comprobar que el efecto que produce la mezcla de ambos principios activos es muy superior a la que correspondería a la suma de los efectos de cada uno de ellos por separado.Of which there is no background and, which is extraordinarily surprising, is the synergy produced by the joint action of both active principles on methanogenesis in ruminants when applied simultaneously. It has been found that the effect produced by the mixture of both active ingredients is much greater than that corresponding to the sum of the effects of each of them separately.
Un aspecto adicional de particular interés es que la sinergia observada en la combinación de los dos principios activos citados es prácticamente independiente de su proporción relativa. De hecho, tal como se describe más adelante, proporciones .relativas muy diferentes entre ambos principios activos producen un importante incremento de su actividad independiente.An additional aspect of particular interest is that the synergy observed in the combination of the two aforementioned active ingredients is practically independent of their relative proportion. In fact, as described below, very different relative proportions between both active ingredients produce a significant increase in their independent activity.
No se dispone hasta el momento de una justificación de este comportamiento y es probable que no exista una única razón para ello. De hecho, una consideración generalizada entre la mayoría de los trabajos publicados es que los extractos de plantas en general, y los aceites esenciales, en particular, son un grupo de sustancias que no se pueden clasificar en un mecanismo de acción único. Por tanto, el resultado global podría ser la consecuencia de una suma de acciones diferentes.A justification for this behavior is not available so far and there is probably no single reason for it. In fact, a generalized consideration among most published works is that plant extracts in general, and essential oils, in particular, are a group of substances that cannot be classified into a single mechanism of action. Therefore, the overall result could be the consequence of a sum of different actions.
Un apartado de especial importancia en la invención que aquí se describe es el proceso de formulación. De hecho, la mezcla de los principios activos, constituida por los extractos de ajo y de canela, debe una parte muy importante de su actividad al formulado final, que le confiere unas especiales características, lo que adicionalrnente constituye un aspecto totalmente novedoso respecto de lo descrito con anterioridad en la bibliografía.A section of special importance in the invention described herein is the formulation process. In fact, the mixture of the active ingredients, consisting of garlic and cinnamon extracts, owes a very important part of its activity to the final formulation, which confers special characteristics, which additionally It constitutes a totally new aspect with respect to what was previously described in the bibliography.
La utilización de extractos o aceites esenciales en la alimentación animal presenta una serie de problemas que están relacionados más o menos directamente con la naturaleza volátil y aromática de algunos de sus componentes. Los problemas más habituales, entre otros, se refieren a:The use of extracts or essential oils in animal feed presents a series of problems that are more or less directly related to the volatile and aromatic nature of some of its components. The most common problems, among others, refer to:
- Irregular dosificación de cada uno de los componentes que constituyen el extracto. - Importante degradación, generalmente oxidativa, de alguno de los componentes- Irregular dosage of each of the components that constitute the extract. - Important degradation, generally oxidative, of any of the components
- Baja eficacia debida a una liberación insuficiente de los principios activos en el momento y en el lugar adecuado.- Low efficiency due to insufficient release of the active ingredients at the right time and in the right place.
- Rechazo para su ingestión debido al intenso sabor y aroma de estos aceites.- Rejection for ingestion due to the intense flavor and aroma of these oils.
La formulación objeto de la presente invención consiste, tal como se describe en detalle más adelante, en una microencapsulación de los principios activos por acción de los excipientes adecuados mediante un proceso de elaboración novedoso.The formulation object of the present invention consists, as described in detail below, in a microencapsulation of the active ingredients by the action of suitable excipients by a novel manufacturing process.
En esencia, el proceso consiste en la fijación de la mezcla de los extractos vegetales o de sus componentes en un soporte inorgánico poroso, constituido, principalmente, por sílice precipitada, y el posterior recubrimiento con una capa protectora, constituida por un emulgente, del tipo mono y/o diglicérido de ácidos grasos saturados, o bien, sus derivados esterificados con ácido acético., láctico o similar.In essence, the process consists of fixing the mixture of the plant extracts or their components in a porous inorganic support, consisting mainly of precipitated silica, and the subsequent coating with a protective layer, constituted by an emulsifier, of the type mono and / or diglyceride of saturated fatty acids, or their derivatives esterified with acetic acid, lactic acid or the like.
La utilización de este tipo de formulado resuelve todos los problemas planteados anteriormente, lo que permite garantizar la máxima eficacia de la mezcla sinérgica. Así la formulación permite conseguir:The use of this type of formulation solves all the problems raised above, which guarantees the maximum efficiency of the synergistic mixture. Thus the formulation allows to achieve:
- Correcta dosificación de la mezcla de extractos vegetales por fijación de una concentración definida en el soporte inorgánico. Adecuada formulación por estar los principios activos adsorbidos y/o absorbidos de forma adecuada debido a las especiales características del soporte.- Correct dosage of the mixture of plant extracts by fixing a defined concentration in the inorganic support. Adequate formulation because the active ingredients are adsorbed and / or absorbed in an appropriate manner due to the special characteristics of the support.
Estabilidad y persistencia de los principios activos relativamente volátiles por la sólida fijación del agente protector y la acción de la película protectora. - Liberación lenta y progresiva dentro del organismo del animal, debido precisamente a la naturaleza del agente protector.Stability and persistence of the relatively volatile active ingredients due to the solid fixation of the protective agent and the action of the protective film. - Slow and progressive release within the organism of the animal, due precisely to the nature of the protective agent.
Correcto direccionamiento hacia los receptores evitando las pérdidas en procesos metabólicos no deseados.Correct addressing to the receivers avoiding losses in unwanted metabolic processes.
Eliminación de la reacción adversa producida por el intenso aroma y el mal sabor de los principios activos, en particular del extracto de ajo y sus componentes, debido a la presencia de la capa protectora.Elimination of the adverse reaction produced by the intense aroma and bad taste of the active ingredients, in particular garlic extract and its components, due to the presence of the protective layer.
Descripción detallada:Detailed description:
Como se ha mencionado anteriormente la presente memoria describe un procedimiento para mejorar el estado general de los rumiantes que consiste en incrementar el rendimiento energético del proceso metabólico de los alimentos en el rumen de los animales inhibiendo uno de los procesos de pérdida de energía, quizás el más importante, que constituye la generación de metano ó metanogénesis.As mentioned above, it describes a procedure to improve the general condition of ruminants, which consists in increasing the energy efficiency of the metabolic process of food in the rumen of animals by inhibiting one of the processes of energy loss, perhaps the more important, that constitutes the generation of methane or methanogenesis.
Esta inhibición se consigue por la acción conjunta y simultánea de dos principios activos que se incorporan al alimento de los animales. El primero de ellos consiste en un extracto ó aceite de ajo, producto natural extraído de las plantas de género Allium, sus fracciones o componentes, aislados o reproducidos por síntesis. El otro principio corísiste en un extracto o aceite de canela, producto natural extraído de las plantas de género Cinnamomum, sus fracciones o componentes, aislados o reproducidos por síntesis. La mezcla de ambos se formula convenientemente para su liberación progresiva y en el lugar adecuado.This inhibition is achieved by the joint and simultaneous action of two active ingredients that are incorporated into animal feed. The first one consists of an extract or garlic oil, a natural product extracted from the Allium genus plants, their fractions or components, isolated or reproduced by synthesis. The other principle was in an extract or cinnamon oil, a natural product extracted from the Cinnamomum plants, their fractions or components, isolated or reproduced by synthesis. The mixture of both is conveniently formulated for progressive release and in the right place.
Existen muchos métodos más o menos eficaces para la obtención de los extractos o aceites esenciales de ajo y de canela. A título de ejemplo se pueden citar algunos, tales como la disolución mediante la acción de disolventes, filtración y posterior evaporación, o bien, la extracción en condiciones supercríticas, o bien, la obtención del extracto sometiendo la planta o semillas a la acción de la presión, entre otras muchas técnicas. Todas ellas se deben considerar dentro del ámbito de la presente invención.There are many more or less effective methods for obtaining the essential extracts or oils of garlic and cinnamon. As an example you can cite some, such as dissolution through the action of solvents, filtration and subsequent evaporation, or extraction under supercritical conditions, or obtaining the extract by subjecting the plant or seeds to the action of pressure, among many other techniques. All of them should be considered within the scope of the present invention.
Un aspecto importante es que por tratarse de productos naturales su composición puede variar dentro de un intervalo más o menos amplio, dependiendo de su procedencia y de su proceso de aislamiento. Sin embargo, si bien el aceite de ajo presenta concentraciones variables de sus componentes, lo habitual es que contenga una proporción de disulfuro de dialilo superior al 5%. De igual forma, el aceite de canela presenta una composición variable, aunque lo habitual es que contenga proporciones superiores al 50% de su componente principal el cinamaldehido. No obstante, se considera dentro del ámbito de la presente invención cualquier extracto o aceite de ajo y de canela comercial, así como cualquiera de sus fracciones.An important aspect is that since they are natural products, their composition can vary within a more or less wide range, depending on their origin and their isolation process. However, although garlic oil has varying concentrations of its components, it usually contains a proportion of diallyl disulfide greater than 5%. Similarly, cinnamon oil has a variable composition, although it is usual that it contains proportions greater than 50% of its main component cinnamaldehyde. However, any commercial garlic and cinnamon extract or oil, as well as any of its fractions, is considered within the scope of the present invention.
Los componentes individuales se pueden obtener por fraccionamiento del extracto o aceite esencial o bien, se pueden preparar por síntesis siguiendo cualquiera de los métodos descritos en la bibliografía. En todos los casos se deben considerar dentro del ámbito de la presente invención.The individual components can be obtained by fractionation of the extract or essential oil or they can be prepared by synthesis according to any of the methods described in the literature. In all cases they should be considered within the scope of the present invention.
Merece especial mención el componente principal del aceite de canela, el cinamaldehido, con el que se ha observado una sinergia extraordinariamente elevada. Dada la simplicidad estructural de este producto, si bien se puede preparar por fraccionamiento del aceite de canela, también resulta económicamente viable su síntesis, por lo que es habitual acceder a él por vía sintética.Special mention is made of the main component of cinnamon oil, cinnamaldehyde, with which an extraordinarily high synergy has been observed. Given the structural simplicity of this product, although it can be prepared by fractionation of cinnamon oil, its synthesis is also economically viable, so it is usual to access it synthetically.
La proporción relativa en la que se formulan los dos principios activos puede ser muy variable. Hay que destacar que en todos los casos ensayados, incluso manteniendo proporciones relativas muy desiguales, se detecta una sinergia de sus efectos muy acusada. Los mejores resultados se han obtenido manteniendo una proporción en peso entre el primer principio activo, el aceite o extracto de ajo, y el segundo, el aceite o extracto de canela, de 0.01 a 0.50, preferentemente de 0.05 a 0.2. Estas proporciones son similares cuando el producto se formula utilizando en lugar de los aceites o extractos naturales, sus fracciones y/o componentes.The relative proportion in which the two active ingredients are formulated can be very variable. It should be noted that in all the cases tested, even maintaining very unequal relative proportions, a very marked synergy of its effects is detected. The best results have been obtained maintaining a weight ratio between the first active ingredient, garlic oil or extract, and the second, cinnamon oil or extract, from 0.01 to 0.50, preferably from 0.05 to 0.2. These proportions are similar when the product is formulated using instead of natural oils or extracts, their fractions and / or components.
La formulación objeto de la presente invención representa, tal como se ha justificado anteriormente, un aspecto de gran importancia para la obtención de los resultados buscados. De forma resumida, y tal como se describe en detalle a continuación, se puede describir como una microencapsulación de los principios activos por acción de los excipientes adecuados mediante un proceso de elaboración novedoso.The formulation object of the present invention represents, as justified above, an aspect of great importance for obtaining the desired results. In summary, and as described in detail below, it can be described as a microencapsulation of the active ingredients by the action of suitable excipients by a novel manufacturing process.
En esencia, la mezcla de los extractos vegetales, o bien, de sus componentes principales se fija, por adsorción y/o absorción sobre un soporte inorgánico poroso constituido, principalmente, por sílice precipitada, y se recubre con una capa protectora constituida por un emulgente, del tipo mono- y/o diglicéridos de ácidos grasos saturados, o bien, de sus derivados esterificados con ácido acético, láctico o similar.In essence, the mixture of the plant extracts, or of their main components, is fixed, by adsorption and / or absorption on a porous inorganic support constituted, mainly, by precipitated silica, and coated with a protective layer constituted by an emulsifier. , of the mono- and / or diglyceride type of saturated fatty acids, or of its derivatives esterified with acetic, lactic acid or the like.
Tal como se ha avanzado, en la elaboración del producto se consideran dos apartados fundamentales: el soporte inorgánico y la capa protectora.As progress has been made, two fundamental sections are considered in the elaboration of the product: the inorganic support and the protective layer.
El soporte inorgánico constituido básicamente por sílice precipitada es completamente inerte, en el sentido de que no reacciona con ninguno de los principios activos y, por tanto, no provoca ni induce ningún tipo de proceso de degradación.The inorganic support consisting basically of precipitated silica is completely inert, in the sense that it does not react with any of the active ingredients and, therefore, does not cause or induce any type of degradation process.
Por otra parte, las características físico-químicas de este soporte son perfectamente adecuadas para la utilidad que se pretende. Se trata de partículas esféricas con un tamaño aproximado de entre unas 80 a unas 500 mieras. La sílice precipitada presenta una característica óptima para la formulación de líquidos. Se trata de su microporosidad. Las partículas contienen multitud de poros que, lógicamente, aumentan la superficie específica respecto a similares tamaños de partículas de otro tipo de soportes. Pero, además, el principio, activo penetra en dichos poros y queda ocluido en ellos. El resultado es evidente, aumenta la capacidad de carga y además, garantiza su fijación en el soporte.On the other hand, the physicochemical characteristics of this support are perfectly suitable for the intended purpose. They are spherical particles with an approximate size of between 80 to 500 microns. Precipitated silica has an optimal characteristic for liquid formulation. It is about its microporosity. The particles contain a multitude of pores that, logically, increase the specific surface area with respect to similar particle sizes of other types of supports. But, in addition, the active principle penetrates these pores and is occluded in them. The result is evident, increases the load capacity and also guarantees its fixation in the support.
Se pueden utilizar diferentes métodos para fijar el principio activo en el soporte. El procedimiento más adecuado implica la utilización de un lecho fluido. Se trata de mantener la sílice en suspensión en un lecho y esprayar la mezcla de extractos vegetales o de sus componentes en forma de pequeñas gotas que se ponen en un contacto muy íntimo con las partículas del soporte. De esta forma se favorecen los procesos de adsorción y absorción consiguiéndose una correcta fijación.Different methods can be used to fix the active substance in the support. The most appropriate procedure involves the use of a fluid bed. It is about keeping the silica in suspension in a bed and spraying the mixture of plant extracts or their components in the form of small drops that are put in very intimate contact with the particles of the support. In this way the adsorption and absorption processes are favored, achieving a correct fixation.
Una alternativa al procedimiento descrito consiste en la utilización de mezcladoras. Dentro de este tipo, las que fluidifican la carga son las más convenientes, tal es el caso de una mezcladora tipo Forberg. En ellas, los tiempos de mezclado son incluso, inferiores a 5 minutos.An alternative to the procedure described is the use of mixers. Within this type, the ones that fluidize the load are the most convenient, such is the case of a Forberg mixer. In them, mixing times are even less than 5 minutes.
En todos los casos, el soporte se mantiene en movimiento continuado y sobre él se espraya o nebuliza la mezcla de extractos vegetales. El mezclado se mantiene en agitación a la temperatura adecuada hasta alcanzar el nivel de fijación del aceite en el soporte. Dependiendo de la tecnología utilizada en la fluidificación se consiguen resultados aceptables con tiempos de agitación de 3 minutos a 2 horas, a temperaturas entre 150C y 4O0C.In all cases, the support is kept in continuous motion and the mixture of plant extracts is sprayed or fogged on it. The mixing is kept under stirring at the appropriate temperature until reaching the level of fixation of the oil in the support. Depending on the technology used in the fluidization acceptable results are achieved with mixing times of 3 minutes to 2 hours at temperatures between 15 0 C and 4O 0 C.
En ambos procedimientos, opcionalmente, se puede adicionar la mezcla de los extractos vegetales o sus componentes disueltos previamente en un disolvente adecuado. Ejemplos de estos disolventes son hexano, metanol, etanol y similares. En estos casos, cuando se termina el proceso de dosificación y mezclado, el producto se somete a un proceso de eliminación completa del disolvente utilizando los métodos habituales, tales como, evaporación a vacío, secado en el lecho fluido, o algún otro.In both processes, optionally, the mixture of the plant extracts or their components previously dissolved in a suitable solvent can be added. Examples of these solvents are hexane, methanol, ethanol and the like. In these cases, when the dosing and mixing process is finished, the product will It undergoes a complete solvent removal process using the usual methods, such as vacuum evaporation, drying in the fluid bed, or some other.
Con cualquiera de los dos procedimientos se alcanzan los valores de concentración de la mezcla de principios activos que se consideran adecuados para este tipo de productos, es decir, entre un 20% y un 50% del peso total del producto formulado, preferentemente entre un 30% y un 45%.With any of the two procedures, the concentration values of the mixture of active ingredients that are considered suitable for this type of products are reached, that is, between 20% and 50% of the total weight of the formulated product, preferably between 30 % and 45%.
La segunda fase en la elaboración del producto objeto de la presente invención consiste en el recubrimiento del extracto vegetal depositado sobre la sílice precipitada con una capa protectora.The second phase in the preparation of the product object of the present invention consists in coating the plant extract deposited on the precipitated silica with a protective layer.
Para esta fase se ha seleccionado un agente emulgente de uso habitual como un aditivo en la alimentación. Se trata de mono- y di-glicérídos de ácidos grasos saturados, aditivo al que corresponde el código E-471.For this phase, an emulsifying agent commonly used as a feed additive has been selected. It is mono- and di-glycerides of saturated fatty acids, additive to which the code E-471 corresponds.
Este agente emulgente se adiciona directamente al lecho fluido o a la mezcladora, donde se encuentra el extracto vegetal fijado sobre el soporte, produciendo una dispersión homogénea sobre la superficie del soporte y, por tanto, dando lugar a una capa protectora muy eficaz.This emulsifying agent is added directly to the fluid bed or to the mixer, where the plant extract is fixed on the support, producing a homogeneous dispersion on the surface of the support and, therefore, giving rise to a very effective protective layer.
Es importante destacar que, tal como se ha citado anteriormente, el principio activo se dosifica alcanzando concentraciones globales que pueden estar en el ordenIt is important to highlight that, as mentioned above, the active substance is dosed reaching global concentrations that may be in order
40% o superiores. Una de las razones de no incrementar excesivamente esta proporción reside en que se deben dejar centros activos en el soporte inorgánico para, posteriormente fijar la capa protectora.40% or higher. One of the reasons for not increasing this proportion excessively is that active centers must be left in the inorganic support to subsequently fix the protective layer.
Se ha podido evaluar que concentraciones del orden del 10-25 % de mono- y di- glicéridos son suficientes para llevar a cabo un recubrimiento eficaz. Son habituales valores del orden del 15% al 20% de emulgente. En cuanto a sus características físicas, es importante destacar que se utilizan esteres de ácidos grasos con el objeto de que sean sólidos a temperatura ambiente y, con puntos de fusión superiores a 7O0C. Este parámetro es muy importante ya que un recubrimiento sólido del principio activo en el soporte es menos permeable a los agentes degradantes que uno líquido.It has been possible to evaluate that concentrations of the order of 10-25% of mono- and di-glycerides are sufficient to carry out an effective coating. Values of the order of 15% to 20% emulsifier are common. As for its physical characteristics, it is important to highlight that fatty acid esters are used in order to be solid at room temperature and, with melting points greater than 7O 0 C. This parameter is very important since a solid coating of the Active ingredient in the support is less permeable to degrading agents than a liquid one.
Los buenos resultados de estabilidad, dosificación en el lugar y momento adecuados y su correcta liberación, por tanto, su biodisponibilidad, son factores relacionados con la actividad superficial del recubrimiento. Es importante, destacar que el aditivo . E-471, por ser un tensoactivo no iónico presenta un excelente comportamiento en cuanto a su fijación hidrófila y a su resistencia lipófila.The good results of stability, dosage in the right place and time and its correct release, therefore, its bioavailability, are factors related to the surface activity of the coating. It is important to note that the additive . E-471, being a non-ionic surfactant, exhibits excellent performance in terms of hydrophilic fixation and lipophilic resistance.
En algunos casos resulta interesante disminuir el carácter polar del recubrimiento, por ejemplo, cuando se necesite una liberación más lenta en un medio hidrófilo. En estos casos se puede sustituir el recubrimiento a base de mono y di-glicéridos de ácidos grasos, por su correspondiente derivado esterificado. Para la elaboración de este último producto se utilizan ácidos orgánicos de cadena corta, tales como acético, láctico y similares. Se trata de aditivos autorizados en alimentación e incluidos en el código E-472.In some cases it is interesting to decrease the polarity of the coating, for example, when a slower release in a hydrophilic medium is needed. In these cases, the coating based on mono and di-glycerides of fatty acids can be replaced by their corresponding esterified derivative. Short-chain organic acids, such as acetic, lactic and the like, are used to make this last product. These are additives authorized in food and included in the code E-472.
La correcta dosificación del agente protector se consigue por esprayado en el lecho fluido o bien en la mezcladora utilizada en la fase anterior. Dependiendo del tipo de equipo seleccionado y las condiciones utilizadas, el agente emulgente suele dosificarse fundido, es decir, a temperaturas entre 7O0C y 8O0C o superiores.The correct dosage of the protective agent is achieved by spraying in the fluid bed or in the mixer used in the previous phase. Depending on the type of equipment selected and the conditions used, the emulsifying agent is usually dosed molten, that is, at temperatures between 7O 0 C and 8O 0 C or higher.
El producto así obtenido se suele incorporar al alimento de los animales previa elaboración de una premezcla con diferentes ingredientes habituales en la formulación de raciones para animales tales como, harinas de soja, cascaras de avellana o carbonato calcico, entre otros muchos. Con ello se elabora un alimento en el que la cantidad final de la mezcla de principios activos por cada Kilogramo de pienso puede ir desde 0.5 miligramos a 50 gramos, siendo los valores más habituales desde 0.1 gramos a lOgramos. Se describen a continuación algunos ejemplos que ilustran el alcance de la invención que aquí se describe pero que no presentan carácter limitativo alguno.The product thus obtained is usually incorporated into the food of the animals after preparing a premix with different usual ingredients in the formulation of rations for animals such as soybean meal, hazelnut husks or calcium carbonate, among many others. This produces a food in which the final amount of the mixture of active ingredients for each Kilogram of feed can range from 0.5 milligrams to 50 grams, the most common values being from 0.1 grams to 10 grams. Some examples are described below that illustrate the scope of the invention described herein but which do not have any limiting character.
Ejemplo 1. En un reactor de 5 litros de capacidad provisto de agitación mecánica, se introducen:Example 1. In a 5 liter capacity reactor equipped with mechanical agitation, the following are introduced:
90 g de un aceite esencial de ajo 870 g de un aceite esencial de canela, y se mezclan con: 400 g de hexano.90 g of an essential oil of garlic 870 g of an essential oil of cinnamon, and mixed with: 400 g of hexane.
Sobre la mezcla se añade poco a poco:The mixture is added little by little:
750 g de sipernat 2200 y se mantiene una agitación enérgica a temperatura ambiente durante 30 minutos.750 g of sipernat 2200 and vigorous stirring is maintained at room temperature for 30 minutes.
A continuación se aplica vacío y se evapora el hexano sometiendo la mezcla excipientada a una temperatura de 30 0C.Then vacuum is applied and the hexane is evaporated by subjecting the mixture to a temperature excipientada 30 0 C.
Una vez eliminado el disolvente, cada partícula contiene una porción de extracto vegetal y mantiene una capacidad remanente para absorber más líquido.Once the solvent is removed, each particle contains a portion of plant extract and maintains a remaining ability to absorb more liquid.
Sobre el producto granular obtenido manteniendo una fuerte agitación se adicionan 420 g de una mezcla de mono y diglicéridos de ácido esteárico (E-471) previamente calentados hasta su fusión, alrededor de 7O0C. De esta forma se va depositando sobre la superficie de las partículas de extracto vegetal-sipernat. El enfriamiento posterior hasta alcanzar la temperatura ambiente permite aislar el producto final en forma de polvo granular, apto para su utilización como aditivo para la alimentación animal. Ejemplo 2.On the granular product obtained while maintaining a strong stirring, 420 g of a mixture of mono and diglycerides of stearic acid (E-471) previously heated until melting are added, around 7O 0 C. In this way it is deposited on the surface of the particles of plant-sipernat extract. Subsequent cooling to room temperature allows the final product to be isolated in the form of granular powder, suitable for use as an additive for animal feed. Example 2
En un equipo industrial tipo secadero de lecho fluido accionado por corriente de aire se disponen 370 kg de sipernat 2200 en unas condiciones tales que se asegure una elevada fluidificación del sólido pulverulento.370 kg of sipernat 2200 are arranged in an industrial fluid-type dryer unit operated by air flow under conditions such that a high fluidization of the pulverulent solid is ensured.
Sobre este lecho y mediante un sistema de esprayado se agregan 80 kg de extracto vegetal constituido por una mezcla de:On this bed and through a spray system 80 kg of vegetable extract consisting of a mixture of:
40 Kg de aceite de ajo, con un contenido del 12% en Disulfuro de Dialilo, 410 Kg de aceite de canela, con un contenido del 65% en Cinamaldehido.40 Kg of garlic oil, with a content of 12% in Diallyl Disulfide, 410 Kg of cinnamon oil, with a content of 65% in Cinnamaldehyde.
Es importante conseguir que el tamaño de gotícula del extracto vegetal sea sensiblemente inferior al del tamaño de partícula del sipernat 2200, por lo que el sistema de esprayado se ajusta para la generación de gotas con tamaños inferiores a 100 μm.It is important to ensure that the droplet size of the plant extract is significantly smaller than the particle size of the sipernat 2200, so that the spray system is adjusted for the generation of drops with sizes smaller than 100 μm.
Después de mantener el aporte de aire en el sistema durante 1 hora, asegurando una mezcla completa, se adicionan 180 Kg de la mezcla de mono y diglicéridos (E- 471) previamente calentados hasta su fusión.After maintaining the air supply in the system for 1 hour, ensuring a complete mixture, 180 Kg of the mixture of mono and diglycerides (E-471) previously heated until melting is added.
La agitación se mantiene en estas condiciones a medida que se va enfriando el sistema hasta alcanzar de nuevo la temperatura ambiente. El producto así obtenido es apto para su procesado posterior como aditivo para pienso.Stirring is maintained in these conditions as the system cools until it reaches room temperature again. The product thus obtained is suitable for further processing as a feed additive.
Ejemplo 3. En una mezcladora de palas tipo Forberg se introducen:Example 3. In a Forberg type shovel mixer, enter:
500 Kg de sipernat 2200 y manteniendo una agitación enérgica se adiciona mediante un sistema de nebulización una mezcla de: 80 Kg de extracto de ajo 550 Kg de Cinamaldehido La mezcla se mantiene en agitación durante 45 minutos, con lo que se obtiene una mezcla homogénea de las partículas sólidas y la mezcla de extractos.500 Kg of sipernat 2200 and maintaining a vigorous agitation, a mixture of: 80 Kg of garlic extract 550 Kg of Cinnamaldehyde is added by means of a fogging system The mixture is kept under stirring for 45 minutes, whereby a homogeneous mixture of the solid particles and the mixture of extracts is obtained.
Dependiendo de la naturaleza del extracto de ajo y su posible elevada viscosidad en algunos casos es recomendable fluidificar la mezcla por adición de un 10 % de un disolvente orgánico, como etanol, hexano u otros.Depending on the nature of the garlic extract and its possible high viscosity in some cases it is advisable to fluidize the mixture by adding 10% of an organic solvent, such as ethanol, hexane or others.
Se mantiene la agitación durante 30 minutos a la temperatura ambiente, eliminando, en su caso el disolvente utilizado aplicando vacío. En esas condiciones se adicionan 200 Kg de la mezcla de mono y diglicéridos (E-471) previamente fundidos a 70-750C de temperatura.Stirring is maintained for 30 minutes at room temperature, eliminating, where appropriate, the solvent used by applying vacuum. Under these conditions are added 200 kg of the mixture of mono- and diglycerides (E-471) previously melted at 70-75 0 C temperature.
Después de enfriar el sistema hasta alcanzar la temperatura ambiente, se obtiene un producto apto para su procesado posterior como aditivo para pienso.After cooling the system to room temperature, a product suitable for further processing as a feed additive is obtained.
Ejemplo 4.Example 4
Siguiendo el procedimiento descrito en el Ejemplo 3 y utilizando las mismas cantidades de Cinamaldehido, extracto de ajo y sipernat 2200, se obtiene tras la agitación, una mezcla homogénea.Following the procedure described in Example 3 and using the same amounts of Cinnamaldehyde, garlic extract and sipernat 2200, a homogeneous mixture is obtained after stirring.
En esas condiciones se adicionan 190 Kg de la mezcla de mono y diglicéridos parcialmente esterificados con ácido acético (E-472) previamente fundidos.Under these conditions, 190 kg of the mixture of mono-diglycerides partially esterified with acetic acid (E-472) previously melted are added.
La agitación se mantiene a medida que se va enfriando el sistema hasta alcanzar la temperatura ambiente. El producto así obtenido es especialmente útil como aditivo alimentario en los casos en los que se necesita una mayor protección en medio hidrófilo y, por tanto, una liberación más lenta en este medio. Stirring is maintained as the system cools to room temperature. The product thus obtained is especially useful as a food additive in cases where greater protection is needed in hydrophilic medium and, therefore, a slower release in this medium.

Claims

REIVINDICACIONES
L- Un procedimiento para mejorar el estado general de los rumiantes que consiste en incrementar el rendimiento energético del proceso metabólico de los alimentos, inhibiendo la generación de metano en el rumen por la acción conjunta y simultánea de dos principios activos con diferentes proporciones relativas y convenientemente formulados para garantizar su liberación progresiva, que se incorporan al alimento de los animales y que consisten, el primero de ellos, en un extracto ó aceite de ajo, sus fracciones o componentes, aislados o reproducidos por síntesis y, el segundo, en un extracto o aceite de canela, sus fracciones o componentes, aislados o reproducidos por síntesis.L- A procedure to improve the general state of the ruminants that consists in increasing the energy efficiency of the metabolic process of food, inhibiting the generation of methane in the rumen by the joint and simultaneous action of two active principles with different relative proportions and conveniently formulated to ensure their progressive release, which are incorporated into the food of the animals and that consist, the first of them, in an extract or garlic oil, its fractions or components, isolated or reproduced by synthesis and, the second, in an extract or cinnamon oil, its fractions or components, isolated or reproduced by synthesis.
2.- Un procedimiento según la reivindicación 1 en el que el primero de los principios activos es el aceite esencial de ajo, producto natural extraído de las plantas de género Allium, y el segundo, es el aceite esencial de canela, producto natural extraído de las plantas de género Cinnamomum.2. A process according to claim 1 wherein the first of the active ingredients is garlic essential oil, a natural product extracted from the Allium genus plants, and the second is cinnamon essential oil, a natural product extracted from the Cinnamomum genus plants.
3.- Un procedimiento según la reivindicación 1 en el que el primero de los dos principios activos es el aceite esencial de ajo, producto natural extraído de las plantas de género Allium, y el segundo es el Cinamaldehido, tanto obtenido a partir del aceite esencial de canela como preparado por síntesis química.3. A method according to claim 1 wherein the first of the two active ingredients is garlic essential oil, a natural product extracted from the Allium genus plants, and the second is Cinnamaldehyde, both obtained from the essential oil of cinnamon as prepared by chemical synthesis.
4.- Un procedimiento según las reivindicaciones 1 a 3 en el que el aceite esencial de ajo utilizado se caracteriza por contener como mínimo un 5% de Disulfuro de Dialilo, natural y/o reproducido por síntesis.4. A process according to claims 1 to 3 in which the garlic essential oil used is characterized by containing at least 5% of Diallyl Disulfide, natural and / or reproduced by synthesis.
5.- Un procedimiento según las reivindicaciones 1 a 2 en el que el aceite esencial de canela utilizado se caracteriza por contener como mínimo un 50% de Cinamaldehido, natural y/o reproducido por síntesis. 5. A process according to claims 1 to 2 in which the cinnamon essential oil used is characterized by containing at least 50% cinnamaldehyde, natural and / or reproduced by synthesis.
6.- Un procedimiento según la reivindicaciones 1 a 5 en el que las proporciones relativas en peso del primer principio activo frente al segundo están entre 0.01 y 0.50, preferentemente entre 0.05 y 0.2.6. A method according to claims 1 to 5 wherein the relative proportions by weight of the first active principle versus the second are between 0.01 and 0.50, preferably between 0.05 and 0.2.
7.- Un procedimiento según las reivindicaciones 1 a 6 en el que la formulación del producto se lleva a cabo por fijación de la mezcla de los dos principios activos sobre un soporte inorgánico a base de sílice precipitada y posterior recubrimiento con una capa de un agente protector del tipo mono y/o diglicéridos de ácidos grasos o sus esteres.7. A process according to claims 1 to 6 wherein the formulation of the product is carried out by fixing the mixture of the two active ingredients on an inorganic support based on precipitated silica and subsequent coating with a layer of an agent protector of the mono type and / or diglycerides of fatty acids or their esters.
8.- Un procedimiento según la reivindicación 7 en el que la mezcla de los principios activos representa entre un 20% y un 50% del peso total del producto formulado, preferentemente entre un 30% y un 45%.8. A process according to claim 7 wherein the mixture of the active ingredients represents between 20% and 50% of the total weight of the formulated product, preferably between 30% and 45%.
9.- Un procedimiento según las reivindicación 7 en el que el soporte inorgánico es sílice precipitada con un tamaño de partícula entre 80 y 500 mieras, con preferencia entre 90 y 300 mieras.9. A method according to claim 7 wherein the inorganic support is precipitated silica with a particle size between 80 and 500 microns, preferably between 90 and 300 microns.
10.- Un procedimiento según las reivindicaciones 7 a 9 en el que el recubrimiento está constituido por una mezcla de mono y diglicéridos de ácidos grasos saturados, preferentemente, ácido esteárico.10. A process according to claims 7 to 9 wherein the coating is constituted by a mixture of mono and diglycerides of saturated fatty acids, preferably stearic acid.
11.- Un procedimiento según las reivindicaciones 7 a 9 en el que el recubrimiento está constituido por una mezcla de mono y diglicéridos de ácidos grasos saturados en los que el grupo hidroxilo residual está esterificado con ácido acético.11. A process according to claims 7 to 9 wherein the coating is constituted by a mixture of mono and diglycerides of saturated fatty acids in which the residual hydroxyl group is esterified with acetic acid.
12.- Un procedimiento según las reivindicaciones 7 a 11 en el que la fijación de la mezcla de principios activos se lleva a cabo sobre un lecho fluido del soporte inorgánico. 12. A method according to claims 7 to 11 in which the fixation of the mixture of active ingredients is carried out on a fluid bed of the inorganic support.
13.- Un procedimiento según las reivindicaciones 7 a 11 en el que la fijación del extracto vegetal sobre el soporte inorgánico se lleva a cabo dentro de una mezcladora de palas, que garantice una mezcla eficaz.13. A method according to claims 7 to 11 in which the fixation of the plant extract on the inorganic support is carried out within a paddle mixer, which guarantees an effective mixing.
14.- Un procedimiento según las reivindicaciones 7 a 13 en el que el agente protector se deposita fundido a una temperatura superior a 7O0C, preferentemente entre 70° y 8O0C.14. A process according to claims 7 to 13 wherein the protective agent is deposited molten at a temperature greater than 7O 0 C, preferably between 70 ° and 8O 0 C.
15.- Un procedimiento según las reivindicaciones 7 a 14 en el que el agente protector representa entre un 10% y un 25 % del peso total del producto formulado, preferentemente entre un 15% y un 20%.15. A process according to claims 7 to 14 wherein the protective agent represents between 10% and 25% of the total weight of the formulated product, preferably between 15% and 20%.
16.- Un procedimiento para la mejora del estado general de los rumiantes según la reivindicación 1 en el que se incorpora el producto formulado en el alimento previa elaboración de una premezcla con ingredientes habituales en la formulación de raciones para animales, en el que la cantidad final de la mezcla de principios activos por cada Kilogramo de pienso puede ir desde 0.5 miligramos a 50 gramos, siendo los valores más habituales desde 0.1 gramos a lOgramos. 16. A process for the improvement of the general condition of the ruminants according to claim 1, wherein the product formulated in the feed is incorporated prior to the preparation of a premix with usual ingredients in the formulation of animal rations, in which the amount Final mixing of active ingredients per Kilogram of feed can range from 0.5 milligrams to 50 grams, the most common values being from 0.1 grams to 10 grams.
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WO2012084629A1 (en) 2010-12-20 2012-06-28 Dsm Ip Assets B.V. Use of nitrooxy organic molecules in feed for reducing methane emission in ruminants, and/or to improve ruminant performance
WO2015186956A1 (en) * 2014-06-02 2015-12-10 씨제이제일제당 (주) Feed additive composition for reducing methane production of ruminants
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