WO2013043033A2 - Method for extracting and checking a dialysed extract of leukocytes from shark spleen, in order to obtain a transfer factor with increased potential, specifically designed to be used as an adjuvant for increasing the potential of viral vaccines - Google Patents

Method for extracting and checking a dialysed extract of leukocytes from shark spleen, in order to obtain a transfer factor with increased potential, specifically designed to be used as an adjuvant for increasing the potential of viral vaccines Download PDF

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Publication number
WO2013043033A2
WO2013043033A2 PCT/MX2012/000090 MX2012000090W WO2013043033A2 WO 2013043033 A2 WO2013043033 A2 WO 2013043033A2 MX 2012000090 W MX2012000090 W MX 2012000090W WO 2013043033 A2 WO2013043033 A2 WO 2013043033A2
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leukocyte
transfer factor
adjuvant
extract
spleen
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PCT/MX2012/000090
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Spanish (es)
French (fr)
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WO2013043033A3 (en
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Héctor Manuel ZEPEDA LOPEZ
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Zepeda Lopez Hector Manuel
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Publication of WO2013043033A2 publication Critical patent/WO2013043033A2/en
Publication of WO2013043033A3 publication Critical patent/WO2013043033A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/60—Fish, e.g. seahorses; Fish eggs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators

Definitions

  • the present invention relates to a leukocyte extract containing polypeptides equal to or less than 10,000 daltons of shark spleen origin and its use as an adjuvant in viral preparations used as vaccines eg. Influenza AH1N1.
  • the present invention relates to compositions comprising transfer factor and its combinations with viral antigens. It is also the object of the present invention to provide the methods for making the compositions and formulations of the transfer factor as an adjuvant.
  • Adjuvants are chemical substances or preparations that, incorporated into the antigen or injected with it simultaneously, make the immune response more effective. With its use, an economy of time and antigen is achieved, as well as a higher level of specific antibodies.
  • the free antigen normally diffuses very rapidly from the local tissues surrounding the inoculation site, and one of its important functions is to create a reservoir or deposit of the long-lived antigen.
  • adjuvants activate or stimulate the immune system, mainly macrophages; these when activated stimulate the immune response by an increase in the amount of antigen expressed in the cell membrane and the efficiency of its presentation to lymphocytes.
  • the macrophage also releases soluble stimulatory factors, which amplify lymphocyte proliferation.
  • some adjuvants have the ability to act specifically on lymphocytes; but, in general, these work best if they facilitate the simultaneous release of the antigen and immunomodulatory substances to lymphoid tissue.
  • US patent 4816563 PROCESS FOR OBTAINING TRANSFER FACTOR FROM COLOSTRUM, TRANSFER FACTOR SO OBTAINED AND USE THERE OF, uses as an extraction source the transfer factor to colostrum of animals, specifically mammals.
  • the amount of transfer factor units obtained from colostrum is minimal compared to the present invention, since the transfer factor found in from the shark is 10 12 leukocytes x mm 3 , against 10 6 leukocytes x mm 3 of colostrum.
  • COMPOSITIONS CONTAINING DIFFERENT TYPES OF TRANSFER FACTOR, METHODS TO PREPARE COMPOSITIONS AND TREATMENT METHODS USING COMPOSITIONS It combines a composition to produce an immune response mediated by T cells in an individual, which contains the transfer factor of at least two different types of animals.
  • the composition may contain the mammalian transfer factor and a non-mammalian transfer factor.
  • An example of the composition may be a combination of a product derived from colostrum, which includes the mammalian transfer factor, and an egg derived product, which includes the non-mammalian transfer factor.
  • this patent presents two problems, eliminating the lipids contained in the egg yolk and the low amount of leukocytes x mm 3 , which reduces the power of said invention.
  • oligopeptides from 1,000 to 10,000 daltons
  • a set of oligopeptides from 1,000 to 10,000 daltons
  • the cells are broken, suspensions are made by adjusting volumes, and by ultracentrifugation, the suspension of the cell debris (cell detritus) is clarified, the oligopeptides are recovered by diafiltration medium and concentrate by tangential ultrafiltration.
  • the product is formulated based on its formula of finished product in pharmaceutical presentation.
  • WO 97/12915 PURIFICATION PROCEDURE OF THE TRANSFER FACTOR FROM LEUCOCITOS. Denotes a Purification process of the Transfer Factor (oligopeptides of 1,000 to 10,000 daltons, which possess biological activity), from leukocytes, comprising the following steps: the cells are lysed under sterile conditions, the suspension is clarified by ultrafiltration, recover the Transfer Factor by diafiltration and concentrate by tangential ultrafiltration. Transfer Factor is used pharmaceutically as a regulator of the immune response.
  • this patent is related to MX 9504215 and consists of the same problem of using human blood as a means of leukocyte extraction.
  • IMMUNE MODULATORS PREPARATIONS AND COMPOSITIONS INCLUDING IMMUNE MODULATORS, TESTS FOR EVALUATING THE ACTIVITY OF IMMUNE MODULATORS AND PREPARATIONS AND COMPOSITIONS INCLUDING THE SAME, AND METHODS.
  • compositions that include extracts from sources of immune modulators that include the immune molecules of the nanofraction modulator (i.e., molecules that have molecular weights of about 3,000 DA and less). These compositions may also include other immune modulators, such as transfer factor.
  • US 4468379 LEUKOCYTE EXTRACTS FOR AFFECTING THE IMMUNE SYSTEM.
  • the invention relates to the substantially pure transfer factor with a specific activity of at least 5000 units per unit of absorption at 214 nm.
  • the present invention also relates to a process for preparing the cell lysate transfer factor.
  • the present invention includes the use of the substantially pure transfer factor with a specific activity of at least 5000 units per unit of absorption at 214 nanometers to treat infectious diseases.
  • the present invention refers to a leukocyte extract containing polypeptides equal to or less than 10,000 daltons of shark spleen origin and its use as an immunomodulatory adjuvant in viral preparations used as vaccines eg. Influenza AH1N1.
  • the present invention relates to compositions comprising transfer factor and its combinations with antigens. It is also the object of the present invention to provide the methods for making the compositions and formulations of the transfer factor as an adjuvant.
  • the present invention relates generally to compositions comprising the transfer factor, particularly transfer factor whose source or origin is from shark cells, tissues or organs, more specifically shark spleen; and to compositions comprising transfer factor in conjunction with antigens. Such compositions are useful in the prevention and / or treatment of diseases.
  • Transfer factors which are leukocyte extracts produced by leukocytes, that is, are amino acids that stimulate and transfer cell-borne immunity from one individual to another and across species to another, without creating contraindicated effects or known harmful responses. .
  • the prevention of infections and / or diseases from vaccines combined with potentialized transfer factor of the present invention increases the effectiveness thereof as it promotes cell excitation to obtain acquired immunity.
  • the transfer factor can be obtained from a dialysable extract of the cells contained in the shark spleen and containing extracellular fluid. This one facilitates the recognition antigen-antibody and strengthens the chemical bond avoiding breaks of the same.
  • the chemical antigen-antibody bond may not be made or not.
  • the adjuvant of the leukocyte extract from shark of the present invention the chemical binding antigen-lymphocyte B, in addition to being strengthened, is performed in less time.
  • leukocyte extract of the present invention gives greater durability to the chemical antigen-lymphocyte B bond formed.
  • the transfer factor obtained from a dialysable extract of the cells contained in the shark spleen and that contains extracellular fluid serves as an immunomodulatory adjuvant transfer factor, since in the state of the art it is known for a skilled in the art, that the function of a transfer factor is to increase cell arousal, as well as improve chemical signals for the production of white blood cells.
  • common sources of transfer factors are colostrum, egg yolk, human blood, etc.
  • the transfer factor units obtained from the above sources are much smaller than those obtained in the present invention, that is to say about 10 6 leukocytes x mm 3.
  • immunomodulating adjuvant transfer factor of spleen origin of shark of the present invention consists of a potency of 10 12 leukocytes x mm 3 (understood by potency to the quantity of leukocytes and quality of the smooth, round and innocuous cells)), amount necessary for leukocyte excitation and optimization of the chemical signals for the production of white blood cells.
  • NK cells provide protection against viruses as part of the natural immune defense system.
  • compositions and formulations that may comprise powdered, encapsulated components, including, but not limited to, encapsulated transfer factor or powder and / or antibody or encapsulated antibody fraction. Additional aspects of the present invention are directed to the methods of compositions and manufacturing formulations according to the vaccine. It is an aspect of the present invention, the methods of treating and / or preventing certain conditions comprising the administration of an effective amount of a composition and / or a formulation comprising transfer factor.
  • the process of the present invention for obtaining dialysable leukocyte extract containing polypeptides less than or equal to 10,000 Daltons whose source or origin is from shark cells, tissues or organs, more specifically shark spleen, focused or specifically designed as Immunomodulator is as follows:
  • Spleen Extraction This step consists in extracting the leukocyte extract, from the surgical extraction of a specific area of the shark spleen, rich in B lymphocytes, which when administered to the individual, produces chemical signals that when interacting with Cooperative T lymphocytes have a positive collaboration for the synthesis of antibodies, that when the chemical signals are linked with the viral antigen of the vaccine, a greater amount of antibodies directed against the viral antigen of the vaccine is generated, in addition to the response immune is faster expressed by the production of IgM and durable expressed by the production of IgG.
  • Counting and quantification The number of leukocytes per field in the Neubauer grid is counted through the Neubauer Chamber and microscope, to know the power of the transfer factor that will be obtained, that is, the number of leukocytes per cubic millimeter. Likewise, it is necessary to assess the quality of said cells, that there is no anisocytosis, that is, by microscopy it is observed that the cells are round and smooth.
  • Dialysis is the process of separating the molecules in a solution by the difference in their diffusion rates through a semipermeable membrane. Then, the leukocyte extract, after the separation and rupture of components has been carried out, is placed in a semipermeable dialysis bag, as for example, in a cellulose membrane with pores, and the bag is sealed. The sealed dialysis bag is placed in a container with a different solution, or pure water. Leukocyte extracts, being small enough to pass through the pores, tend to move in or out of the dialysis bag in the direction of the lowest concentration. The largest molecules (often proteins, DNA, or polysaccharides) that have dimensions significantly larger than the pore diameter are retained inside the dialysis bag. In this way, leukocyte extracts less than or equal to 10,000 Daltons are separated.
  • the leukocyte extract is filtered through a pore size membrane between 2 and 4 micrometers. Also, the solution is sterilized again.
  • Formulation.- A lyophilization process is carried out to remove the water from the leukocyte extract through the generation of a vacuum, likewise in this step the aggregation of a vehicle is carried out, such as milk, water, gel or artificial flavoring, to give a presentation and pleasant taste to the product.
  • a vehicle such as milk, water, gel or artificial flavoring
  • the cytosine (s) required for its function as an adjuvant is induced, this from the dilution of the leukocyte extract until reaching the title of the required cytosines according to the type of vaccine to which the leukocyte extract will function as an adjuvant.
  • the cytosine or cytosines suitable for functioning as an adjuvant of the present invention will be chosen according to the type of vaccine that will be administered to the patient, such that the cytosine required by the vaccine will be isolated, such is the case. of the AH1 N1 viruses, among others.
  • the present figure illustrates the type of cytosine induced when from the inoculation of the leukocyte extract in Balb-c mice.
  • Groups of 8 mice are used, which will be inoculated with the amount equivalent to the weight-unit ratio of transfer factor (0.005 unit of transfer factor).
  • Whey is extracted from each mouse, 50 microliters of serum are used, exposed against the microarray membranes that contain the cytosine receptor antibodies and the wells that develop color will be induced cytosines.
  • the serum is diluted with a regulatory solution in multiples of 2 initially and then diluted in multiples of 100.
  • the baseline dilution of time 0 and the dilution that preserves the color development in the microarrays prior to dilution where it is no longer present is eliminated.
  • the development of color is the title of the leukocyte extract. In this way, suitable cytosines can be isolated to support the required viral vaccine.

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Abstract

The invention relates to a leukocyte extract containing 10,000 daltons or less of polypeptides from shark spleen, and to the use thereof as an adjuvant in viral preparations used as vaccines. The invention also relates to a method for extracting and processing a dialysable leukocyte extract from selachimorpha in order to obtain a transfer factor with increased potential. The invention further relates to compositions comprising a transfer factor and to the combinations thereof with viral antigens, and provides methods for producing the compositions and formulations of the transfer factor as an adjuvant.

Description

MÉTODO DE EXTRACCIÓN, COMPROBACIÓN Y CONTEO DE EXTRACTO DIALIZADO DE LEUCOCITOS DE ORIGEN BAZO DE TIBURÓN, PARA LA OBTENCIÓN DE FACTOR DE TRANSFERENCIA POTENCIALIZADO, ESPECÍFICAMENTE DISEÑADO PARA SU USO COMO ADYUVANTE POTENCIALIZADOR DE VACUNAS VIRALES  METHOD OF EXTRACTION, CHECKING AND COUNTING OF DIALIZED EXTRACT OF LEUCOCITS OF ORIGIN BATTERY OF SHARK, FOR THE OBTAINING OF POTENTIALIZED TRANSFER FACTOR, SPECIFICALLY DESIGNED FOR USE AS A POTENTIALIZING VOTENTIALIZING ASSISTANT
Campo de la invención Field of the Invention
La presente invención se refiere a un extracto leucocitario que contiene polipéptidos iguales o menores a 10,000 daltones de origen bazo de tiburón y su utilización como adyuvante en preparaciones virales utilizadas como vacunas ej. Influenza AH1 N1.  The present invention relates to a leukocyte extract containing polypeptides equal to or less than 10,000 daltons of shark spleen origin and its use as an adjuvant in viral preparations used as vaccines eg. Influenza AH1N1.
Así mismo, la presente invención se relaciona con composiciones que comprenden factor de transferencia y sus combinaciones con antígenos virales. Es también objeto de la presente invención proporcionar los métodos para realizar las composiciones y formulaciones del factor de transferencia como adyuvante. Likewise, the present invention relates to compositions comprising transfer factor and its combinations with viral antigens. It is also the object of the present invention to provide the methods for making the compositions and formulations of the transfer factor as an adjuvant.
Es también otro objeto de la presente invención, proveer de un método de extracción y procesamiento de extracto leucocitario dializable a partir de selacimorfos para la obtención de factor de transferencia potencializado específicamente diseñado para ser utilizado como adyuvante. Antecedentes It is also another object of the present invention to provide a method of extracting and processing dialysable leukocyte extract from selacimorphs to obtain a potentialized transfer factor specifically designed to be used as an adjuvant. Background
La búsqueda de nuevas sustancias con actividad adyuvante, constituye una de las tendencias más importantes en la investigación inmunológica actual. Esto con el objetivo de incrementar la efectividad de la respuesta inmune, ya que se investigan sustancias con propiedades inmunoestimulantes para la potencialización de vacunas debido a que los virus cada día se vuelven más resistentes contra las vacunas ya desarrolladas, lo que se traduce en baja efectividad de las mismas. The search for new substances with adjuvant activity is one of the most important trends in current immunological research. This with the objective of increasing the effectiveness of the immune response, since substances with immunostimulatory properties are investigated for the potentialization of vaccines because the viruses become increasingly resistant against the already developed vaccines, which translates into low effectiveness from the same.
Los avances experimentados en la última década en la síntesis de péptidos, la secuenciación de nucleótidos y la ingeniería genética han posibilitado el desarrollo de las denominadas "vacunas de nueva generación". Sin embargo, la utilización exitosa de estas nuevas tecnologías requiere de un esfuerzo investigativo sostenido para hallar sustancias con actividad adyuvante, eficaces en la estimulación de la respuesta inmune y desprovistas de propiedades biológicas adversas. The advances experienced in the last decade in peptide synthesis, nucleotide sequencing and genetic engineering have enabled the development of so-called "new generation vaccines". However, the successful use of these new technologies requires a sustained research effort to find substances with adjuvant activity, effective in stimulating the immune response and devoid of adverse biological properties.
Los adyuvantes son sustancias o preparados químicos que, incorporados al antígeno o inyectados simultáneamente con él, hacen más efectiva la respuesta inmune. Con su empleo se logra una economía de antígeno y de tiempo, así como un mayor nivel de anticuerpos específicos. Adjuvants are chemical substances or preparations that, incorporated into the antigen or injected with it simultaneously, make the immune response more effective. With its use, an economy of time and antigen is achieved, as well as a higher level of specific antibodies.
El antígeno libre normalmente difunde con mucha rapidez desde los tejidos locales que rodean el sitio de inoculación, y una de sus funciones importantes es crear un reservorio o depósito del antígeno de larga vida. En el estado de la técnica, se ha demostrado que virtualmente todos los adyuvantes activan o estimulan al sistema inmunológico, principalmente a los macrófagos; éstos cuando son activados estimulan la respuesta inmune por un incremento de la cantidad de antígeno expresado en la membrana celular y de la eficiencia de su presentación a los linfocitos. El macrófago también libera factores solubles estimulantes, que amplifican la proliferación de los linfocitos. Por otro lado, algunos adyuvantes poseen la capacidad de actuar específicamente sobre los linfocitos; pero, en general, éstas funcionan mejor si facilitan la liberación simultánea del antígeno y de sustancias inmunomoduladoras al tejido linfoide. The free antigen normally diffuses very rapidly from the local tissues surrounding the inoculation site, and one of its important functions is to create a reservoir or deposit of the long-lived antigen. In the state of the art, it has been shown that virtually all adjuvants activate or stimulate the immune system, mainly macrophages; these when activated stimulate the immune response by an increase in the amount of antigen expressed in the cell membrane and the efficiency of its presentation to lymphocytes. The macrophage also releases soluble stimulatory factors, which amplify lymphocyte proliferation. On the other hand, some adjuvants have the ability to act specifically on lymphocytes; but, in general, these work best if they facilitate the simultaneous release of the antigen and immunomodulatory substances to lymphoid tissue.
En el nivel internacional, la lista de productos naturales y derivados de la síntesis química, con propiedades adyuvantes/inmunopotenciadoras, es cada vez mayor; sin embargo, sólo un reducido número se utiliza en la formulación de vacunas humanas, existiendo una tendencia relacionada con la evaluación de nuevas sustancias con esta finalidad. At the international level, the list of natural products and derivatives of chemical synthesis, with adjuvant / immunopotentiating properties, is increasing; however, only a small number is used in the formulation of human vaccines, there being a trend related to the evaluation of new substances for this purpose.
De particular interés resulta la valoración de nuevos inmunoadyuvantes para incrementar la efectividad de las vacunas. Es por ello que la presente invención propone utilizar como adyuvante a un extracto dializable leucocitario cuya fuente son los tiburones. ¡ Of particular interest is the assessment of new immunoadjuvants to increase the effectiveness of vaccines. That is why the present invention proposes to use as an adjuvant a leukocyte dialysable extract whose source is sharks. ¡¡
En el estado de la técnica se encuentra la patente: US 2009/0053197 TRANSFER FACTOR COMPOSITIONS AND METHODS, la cual menciona la posibilidad de utilizar factor de transferencia como adyuvante, cuya característica principal radica en que la composición que comprende factor de transferencia y un anticuerpo, cada una es derivada independientemente de una fuente seleccionada del grupo que consiste en huevos, calostro, sangre, y combinaciones de los mismos. Esto quiere decir que el extracto leucocitario tiene como fuente huevos, calostro, sangre o sus combinaciones. Sin embargo, para un experto en el estado de la técnica, es bien sabido que esta patente presenta los siguientes problemas, si se utiliza yema de huevo, resulta muy difícil eliminar los lípidos que contiene, así mismo, tanto la yema de huevo, como las demás fuentes constan de una baja cantidad de leucocitos x mm3, lo que resta potencia a dicha invención. Así mismo, la síntesis de las anteriores fuentes de extracto leucocitario resulta muy complicada para separar las células leucocitarias de las proteínas, lípidos, carbohidratos y toxinas. Por ejemplo, la patente WO/2002/024746. FACTOR DE TRANSFERENCIA A PARTIR DE HUEVOS DE AVE. Utiliza un método para obtener un factor a de transferencia a partir de la yema de huevos de animales, sin embargo, un experto en la materia, sabe que el método para extraer factor de transferencia a partir de huevos es muy complicado, sobre todo en la separación de los lípidos. Al igual que las unidades de factor de transferencia obtenidas por huevo es miles de veces menor que la presente invención. In the state of the art is the patent: US 2009/0053197 TRANSFER FACTOR COMPOSITIONS AND METHODS, which mentions the possibility of using transfer factor as an adjuvant, whose main characteristic is that the composition comprising transfer factor and an antibody, each is derived independently from a source selected from the group consisting of eggs, colostrum, blood, and combinations of the same. This means that the leukocyte extract has as its source eggs, colostrum, blood or their combinations. However, for an expert in the state of the art, it is well known that this patent presents the following problems, if egg yolk is used, it is very difficult to eliminate the lipids contained in the egg yolk, as well as the other sources consist of a low amount of leukocytes x mm 3 , which reduces the power of said invention. Likewise, the synthesis of the previous sources of leukocyte extract is very complicated to separate the leukocyte cells from proteins, lipids, carbohydrates and toxins. For example, WO / 2002/024746. TRANSFER FACTOR FROM AVE EGGS. It uses a method to obtain a transfer factor a from the egg yolk of animals, however, one skilled in the art knows that the method to extract transfer factor from eggs is very complicated, especially in the lipid separation. Like the transfer factor units obtained per egg, it is thousands of times smaller than the present invention.
Así mismo, la patente US 4816563. PROCESS FOR OBTAINING TRANSFER FACTOR FROM COLOSTRUM, TRANSFER FACTOR SO OBTAINED AND USE THERE OF, utiliza como fuente de extracción del factor de transferencia al calostro de animales, en específico de mamíferos. Sin embargo, al igual que la patente anterior, la cantidad de unidades de factor de transferencia obtenidas a partir de calostro es mínima a comparación con la presente invención, ya que el factor de transferencia encontrado en a partir de los tiburón es de 1012 leucocitos x mm3, contra 106 leucocitos x mm3 del calostro. Likewise, US patent 4816563. PROCESS FOR OBTAINING TRANSFER FACTOR FROM COLOSTRUM, TRANSFER FACTOR SO OBTAINED AND USE THERE OF, uses as an extraction source the transfer factor to colostrum of animals, specifically mammals. However, like the previous patent, the amount of transfer factor units obtained from colostrum is minimal compared to the present invention, since the transfer factor found in from the shark is 10 12 leukocytes x mm 3 , against 10 6 leukocytes x mm 3 of colostrum.
De la misma manera, la patente WO 2005/028622. COMPOSICIONES QUE CONTIENEN DIFERENTES TIPOS DE FACTOR DE TRANSFERENCIA, METODOS PARA PREPARAR LAS COMPOSICIONES Y METODOS DE TRATAMIENTO UTILIZANDO LAS COMPOSICIONES. Combina una composición para producir una respuesta inmunitaria mediada por células T en un individuo, que contiene el factor de transferencia de por lo menos dos diferentes tipos de animales. Por ejemplo, la composición puede contener el factor de transferencia de mamífero y un factor de transferencia no mamífero. Un ejemplo de la composición puede ser una combinación de un producto derivado de calostro, que incluya el factor de transferencia mamífero, y un producto derivado de huevo, que incluye el factor de transferencia no mamífero. Al igual que las anteriores, esta patente presenta dos problemas, eliminar los lípidos que contiene la yema de huevo y la baja cantidad de leucocitos x mm3, lo que resta potencia a dicha invención. In the same way, WO 2005/028622. COMPOSITIONS CONTAINING DIFFERENT TYPES OF TRANSFER FACTOR, METHODS TO PREPARE COMPOSITIONS AND TREATMENT METHODS USING COMPOSITIONS. It combines a composition to produce an immune response mediated by T cells in an individual, which contains the transfer factor of at least two different types of animals. For example, the composition may contain the mammalian transfer factor and a non-mammalian transfer factor. An example of the composition may be a combination of a product derived from colostrum, which includes the mammalian transfer factor, and an egg derived product, which includes the non-mammalian transfer factor. Like the previous ones, this patent presents two problems, eliminating the lipids contained in the egg yolk and the low amount of leukocytes x mm 3 , which reduces the power of said invention.
De la misma manera, se encontró que la patente MX 9504215 PROCEDIMIENTO MEJORADO PARA LA PURIFICACION DE OLIGOPEPTIDOS CON PESOS MOLECULARES DE 1000 A 10,000 DALTONES, A PARTIR DE ESTRACTOS LEUCOCITOS Y SU PRESENTACION FARMACEUTICA. Se refiere a un procedimiento mejorado para el fraccionamiento con alto rendimiento, de un conjunto de oligopéptidos (de 1 ,000 a 10,000 daltones), recuperados a partir del rompimiento de leucocitos y que poseen actividad biológica para la regulación de la respuesta inmune que comprende los siguientes pasos: a partir de paquetes leucocitarios de donadores sanos, TODO BAJO CONDICIONES ASEPTICAS, se rompen las células, se hacen suspensiones ajustando volúmenes, y mediante ultracentrifugación, se clarifica la suspensión de los restos celulares (detritus celulares), se recuperan los oligopéptidos por medio de diafiltración y se concentran por ultrafiltración tangencial. Se formula el producto con base en su fórmula de producto terminado en presentación farmacéutica. Sin embargo, un experto en la materia sabe que el uso o utilización de sangre humana y sus derivados destilados o componentes separados a partir de procedimientos químicos, no pueden ser comercializados, ya que diferentes legislaciones en el mundo lo prohiben y se cataloga como delito la comercialización de sangre humana y sus derivados. Así mismo, las unidades de factor de transferencia obtenidas por cada 450 mi de sangre de donadores sanos de la presente invención, aunque superior a las unidades de factor de transferencia obtenidas a partir de yema de huevo y de calostro, es tan solo de 108 leucocitos x mm3. In the same way, it was found that patent MX 9504215 IMPROVED PROCEDURE FOR PURIFICATION OF OLIGOPEPTIDES WITH MOLECULAR WEIGHTS FROM 1000 TO 10,000 DALTONS, FROM LEUCOCIT STRATUS AND ITS PHARMACEUTICAL PRESENTATION. It refers to an improved procedure for high performance fractionation of a set of oligopeptides (from 1,000 to 10,000 daltons), recovered from the breakdown of leukocytes and that have biological activity for the regulation of the immune response comprising the following steps: from leukocyte packages from healthy donors, ALL UNDER ASEPTIC CONDITIONS, the cells are broken, suspensions are made by adjusting volumes, and by ultracentrifugation, the suspension of the cell debris (cell detritus) is clarified, the oligopeptides are recovered by diafiltration medium and concentrate by tangential ultrafiltration. The product is formulated based on its formula of finished product in pharmaceutical presentation. However, one skilled in the art knows that the use or use of human blood and its distilled derivatives or separate components from chemical procedures cannot be commercialized, since different laws in the world prohibit it and are classified as a crime. commercialization of human blood and its derivatives. Likewise, the transfer factor units obtained for every 450 ml of blood from healthy donors of the present invention, although higher than the transfer factor units obtained from egg yolk and colostrum, is only 10 8 leukocytes x mm 3 .
Así mismo, la patente WO 97/12915. PROCEDIMIENTO DE PURIFICACION DEL FACTOR DE TRANSFERENCIA A PARTIR DE LEUCOCITOS. Denota un procedimiento de purificación del Factor de Transferencia (oligopéptidos de 1 ,000 a 10,000 daltones, que poseen actividad biológica), a partir de leucocitos, que comprende los siguientes pasos: se lisan las células en condiciones estériles, se clarifica la suspensión mediante ultrafiltración, se recupera el Factor de Transferencia por diafiltración y se concentra por ultrafiltración tangencial. El Factor de Transferencia se utiliza farmacéuticamente como regulador de la respuesta inmune. Sin embargo, esta patente se encuentra relacionada con la MX 9504215 y consta del mismo problema de utilizar sangre humana como medio de extracción de leucocitos. Likewise, WO 97/12915. PURIFICATION PROCEDURE OF THE TRANSFER FACTOR FROM LEUCOCITOS. Denotes a Purification process of the Transfer Factor (oligopeptides of 1,000 to 10,000 daltons, which possess biological activity), from leukocytes, comprising the following steps: the cells are lysed under sterile conditions, the suspension is clarified by ultrafiltration, recover the Transfer Factor by diafiltration and concentrate by tangential ultrafiltration. Transfer Factor is used pharmaceutically as a regulator of the immune response. However, this patent is related to MX 9504215 and consists of the same problem of using human blood as a means of leukocyte extraction.
La patente MX20089296A, OPTIMISED PROCESS FOR THE OBTENTION OF DIALYZABLE LEUKOCYTE EXTRACT, CONTAINING PEPTIDES WITH MOLECULAR WEIGHT EQUAL TO OR LOWER THAN 10, 000 DALTONS, FROM CROCODILE LYMPHOID TISSUE AND THE PREPARATION THEREOF IN AN ORAL AND/OR INJECTABLE PHARMACEUTIC, se refiere a un procedimiento optimizado para la obtención del extracto leucocitario que contiene péptidos con peso molecular igual o inferior a 10,000 Daltones, a partir de células de tejido linfoide provenientes de cocodrilo y que posee la propiedad de regular la respuesta inmune en humanos y animales. Sin embargo, la potencia del factor de transferencia obtenido es de 108 leucocitos x mm3 The patent MX20089296A, OPTIMISED PROCESS FOR THE OBTENTION OF DIALYZABLE LEUKOCYTE EXTRACT, CONTAINING PEPTIDES WITH MOLECULAR WEIGHT EQUAL TO OR LOWER THAN 10, 000 DALTONS, FROM CROCODILE LYMPHOID TISSUE AND THE PREPAREC THEREOAR PHARM IN AN ORACE PHARM IN AN ORACE PHARM IN AN ORTA IN PHARMACE Optimized procedure for obtaining the leukocyte extract containing peptides with molecular weight equal to or less than 10,000 Daltons, from lymphoid tissue cells from crocodile and which has the property of regulating the immune response in humans and animals. However, the power of the transfer factor obtained is 10 8 leukocytes x mm 3
Por último, se mencionan las patentes: WO/2008/042604. IMMUNE MODULATORS, PREPARATIONS AND COMPOSITIONS INCLUDING IMMUNE MODULATORS, TESTS FOR EVALUATING THE ACTIVITY OF IMMUNE MODULATORS AND PREPARATIONS AND COMPOSITIONS INCLUDING THE SAME, AND METHODS. Que divulga las composiciones que incluyen los extractos de fuentes de moduladores inmunes que incluyan las moléculas inmunes del modulador de nanofracción (es decir, moléculas que tienen pesos moleculares de cerca de 3,000 DA y menos). Estas composiciones pueden también incluir otros moduladores inmunes, tales como factor de transferencia. US 4468379, LEUKOCYTE EXTRACTS FOR AFFECTING THE IMMUNE SYSTEM. Que describe a un grupo de sustancias derivadas de los léucocitos humanos (glóbulos blancos) que amplifican, suprime, o modula de otra manera la respuesta del sistema inmune a la reintroducción de antígenos. Y US 5840700, METHODS OF PRODUCING TRANSFER FACTOR. Que ilustra que la invención se relaciona con el factor de transferencia substancialmente puro con una actividad específica por lo menos de 5000 unidades por unidad de la absorción en 214 nanómetro. La actual invención también se relaciona con un proceso para preparar el factor de transferencia de lisados de la célula. La actual invención incluye el uso del factor de transferencia substancialmente puro con una actividad específica por lo menos de 5000 unidades por unidad de la absorción en 214 nanómetros para tratar enfermedades infecciosas. PROBLEMA A RESOLVER: Finally, the patents are mentioned: WO / 2008/042604. IMMUNE MODULATORS, PREPARATIONS AND COMPOSITIONS INCLUDING IMMUNE MODULATORS, TESTS FOR EVALUATING THE ACTIVITY OF IMMUNE MODULATORS AND PREPARATIONS AND COMPOSITIONS INCLUDING THE SAME, AND METHODS. It discloses compositions that include extracts from sources of immune modulators that include the immune molecules of the nanofraction modulator (i.e., molecules that have molecular weights of about 3,000 DA and less). These compositions may also include other immune modulators, such as transfer factor. US 4468379, LEUKOCYTE EXTRACTS FOR AFFECTING THE IMMUNE SYSTEM. It describes a group of substances derived from human leukocytes (white blood cells) that amplify, suppress, or otherwise modulate the immune system's response to the reintroduction of antigens. AND US 5840700, METHODS OF PRODUCING TRANSFER FACTOR. Illustrating that the invention relates to the substantially pure transfer factor with a specific activity of at least 5000 units per unit of absorption at 214 nm. The present invention also relates to a process for preparing the cell lysate transfer factor. The present invention includes the use of the substantially pure transfer factor with a specific activity of at least 5000 units per unit of absorption at 214 nanometers to treat infectious diseases. PROBLEM TO SOLVE:
En la actualidad no se dispone de un adyuvante eficaz para la potencialización de vacunas, sin efectos adversos o tóxicos. Se ha intentado utilizar factor de transferencia a partir de yema de huevo, leche y sangre, que aunque funge como inmunomodulador, existe una baja concentración de leucocitos en dichas fuentes, lo que se traduce en una baja potencialización de la vacuna, es decir, una baja adyuvancia del factor de transferencia y a su vez una ineficacia o bajo rendimiento de la vacuna. Así mismo, algunas de estas fuentes para extracción de extracto leucocitario, al administrarlas, pueden provocar a los pacientes reacciones alérgicas. At present there is no effective adjuvant for the potentialization of vaccines, without adverse or toxic effects. Attempts have been made to use transfer factor from egg yolk, milk and blood, which although it works As an immunomodulator, there is a low concentration of leukocytes in these sources, which translates into a low potentialization of the vaccine, that is, a low adjuvant of the transfer factor and in turn an inefficiency or low yield of the vaccine. Also, some of these sources for leukocyte extract extraction, when administered, can cause patients allergic reactions.
SOLUCIÓN: SOLUTION:
Es objeto de la presente invención proveer un adyuvante inmunomodulador en preparaciones virales utilizadas como vacunas, que potencialice eficazmente dicha vacuna, sin provocar a los pacientes reacciones alérgicas.  It is an object of the present invention to provide an immunomodulatory adjuvant in viral preparations used as vaccines, which effectively potentiate said vaccine, without causing patients allergic reactions.
Es otro objeto de la presente invención proporcionar una fuente de extracto leucocitario cuyo origen no sea a partir de mamíferos, huevos, ni calostro, y que brinde una potencia de 1012 leucocitos x mm3 (entendiéndose por potencia a la cantidad de leucocitos y calidad de las células lisas, redondas e inocuas)), cantidad necesaria para la excitación celular y optimización de las señales químicas. It is another object of the present invention to provide a source of leukocyte extract whose origin is not from mammals, eggs, or colostrum, and that provides a potency of 10 12 leukocytes x mm 3 (understood as potency to the quantity of leukocytes and quality of the smooth, round and innocuous cells)), necessary quantity for the cellular excitation and optimization of the chemical signals.
Por lo que la presente invención, se refiere a un extracto leucocitario que contiene polipéptidos iguales o menores a 10,000 daltones de origen bazo de tiburón y su utilización como adyuvante inmunomodulador en preparaciones virales utilizadas como vacunas ej. Influenza AH1 N1. Así mismo, la presente invención se relaciona con composiciones que comprenden factor de transferencia y sus combinaciones con antígenos. Es también objeto de la presente invención proporcionar los métodos para realizar las composiciones y formulaciones del factor de transferencia como adyuvante. As regards the present invention, it refers to a leukocyte extract containing polypeptides equal to or less than 10,000 daltons of shark spleen origin and its use as an immunomodulatory adjuvant in viral preparations used as vaccines eg. Influenza AH1N1. Likewise, the present invention relates to compositions comprising transfer factor and its combinations with antigens. It is also the object of the present invention to provide the methods for making the compositions and formulations of the transfer factor as an adjuvant.
Es también otro objeto de la presente invención, proveer de un método de extracción y procesamiento de extracto leucocitario dializable a partir de selacimorfos para la obtención de factor de transferencia potencializado específicamente diseñado para ser utilizado como adyuvante inmunomodulador. It is also another object of the present invention, to provide a method of extracting and processing dialysable leukocyte extract from selacimorphs to obtain a potentialized transfer factor specifically designed to be used as an immunomodulatory adjuvant.
Descripción de la invención Description of the invention
La presente invención se relaciona en general con las composiciones que comprenden el factor de transferencia, particularmente factor de transferencia cuya fuente u origen es a partir de células, tejidos u órganos de tiburón, más específicamente bazo de tiburón; y a las composiciones que comprenden factor de transferencia conjuntamente con antígenos. Tales composiciones son útiles en la prevención y/o el tratamiento de enfermedades. The present invention relates generally to compositions comprising the transfer factor, particularly transfer factor whose source or origin is from shark cells, tissues or organs, more specifically shark spleen; and to compositions comprising transfer factor in conjunction with antigens. Such compositions are useful in the prevention and / or treatment of diseases.
Los factores de transferencia, que son extractos leucocitarios producidos por los leucocitos, es decir, son aminoácidos que estimulan y transfieren la inmunidad transmitida por células a partir de un individuo a otro y a través de especie a otra, sin crear efectos contraindicados o respuestas dañinas conocidas. La prevención de infecciones y/o enfermedades a partir de vacunas combinadas con factor de transferencia potencializado de la presente invención, aumenta la efectividad de la misma ya que promueve la excitación celular para obtener una inmunidad adquirida. El factor de transferencia se puede obtener de un extracto dializable de las células contenidas en el bazo de tiburón y que contiene fluido extracelular. Éste facilita el reconocimiento antígeno-anticuerpo y fortalece el enlace químico evitando rupturas del mismo. Transfer factors, which are leukocyte extracts produced by leukocytes, that is, are amino acids that stimulate and transfer cell-borne immunity from one individual to another and across species to another, without creating contraindicated effects or known harmful responses. . The prevention of infections and / or diseases from vaccines combined with potentialized transfer factor of the present invention, increases the effectiveness thereof as it promotes cell excitation to obtain acquired immunity. The transfer factor can be obtained from a dialysable extract of the cells contained in the shark spleen and containing extracellular fluid. This one facilitates the recognition antigen-antibody and strengthens the chemical bond avoiding breaks of the same.
En el estado de la técnica, el enlace químico antígeno-anticuerpo puede no realizarse o no haberlo. Con la adyuvancia del extracto leucocitario a partir de tiburón de la presente invención, el enlace químico antígeno-linfocito B, además de ser fortalecido, se realiza en menor tiempo. In the state of the art, the chemical antigen-antibody bond may not be made or not. With the adjuvant of the leukocyte extract from shark of the present invention, the chemical binding antigen-lymphocyte B, in addition to being strengthened, is performed in less time.
Así mismo, otra ventaja del extracto leucocitario de la presente invención sobre el estado de la técnica es también que da mayor durabilidad al enlace químico antígeno-linfocito B formado. Also, another advantage of the leukocyte extract of the present invention over the state of the art is also that it gives greater durability to the chemical antigen-lymphocyte B bond formed.
Por lo tanto, el factor de transferencia obtenido a partir de un extracto dializable de las células contenidas en el bazo de tiburón y que contiene fluido extracelular, funge como factor de transferencia adyuvante inmunomodulador, ya que en el estado de la técnica es conocido para un experto en la materia, que la función de un factor de transferencia es aumentar la excitación celular, al igual que mejorar las señales químicas para la producción de glóbulos blancos. Como se mencionó anteriormente, las fuentes comunes de factores de transferencia son calostro, yema de huevo, sangre humana, etc. Sin embargo las unidades de factor de transferencia obtenidas a partir de las fuentes anteriores son mucho menores que las obtenidas en la presente invención es decir de alrededor de 106 leucocitos x mm3 Por lo que cabe destacar que factor de transferencia adyuvante inmunomodulador de origen bazo de tiburón de la presente invención, consta de una potencia de 1012 leucocitos x mm3 (entendiéndose por potencia a la cantidad de leucocitos y calidad de las células lisas, redondas e inocuas)), cantidad necesaria para la excitación de los leucocitos y optimización de las señales químicas para la producción de glóbulos blancos. Therefore, the transfer factor obtained from a dialysable extract of the cells contained in the shark spleen and that contains extracellular fluid, serves as an immunomodulatory adjuvant transfer factor, since in the state of the art it is known for a skilled in the art, that the function of a transfer factor is to increase cell arousal, as well as improve chemical signals for the production of white blood cells. As mentioned earlier, common sources of transfer factors are colostrum, egg yolk, human blood, etc. However, the transfer factor units obtained from the above sources are much smaller than those obtained in the present invention, that is to say about 10 6 leukocytes x mm 3. It should be noted that immunomodulating adjuvant transfer factor of spleen origin of shark of the present invention, it consists of a potency of 10 12 leukocytes x mm 3 (understood by potency to the quantity of leukocytes and quality of the smooth, round and innocuous cells)), amount necessary for leukocyte excitation and optimization of the chemical signals for the production of white blood cells.
Uno de los efectos específicos del factor de transferencia es una actividad perceptiblemente creciente de las células NK (asesino natural por sus siglas en inglés). Las células NK proporcionan la protección contra virus como parte del sistema de defensa inmune natural. One of the specific effects of the transfer factor is a significantly increased activity of NK (natural killer) cells. NK cells provide protection against viruses as part of the natural immune defense system.
Los aspectos adicionales de la invención se relacionan con las composiciones y las formulaciones que pueden comprender componentes en presentación en polvo, encapsulados, incluyendo, pero no limitado a, factor de transferencia encapsulado o polvo y/o anticuerpo o fracción encapsulado del anticuerpo. Los aspectos adicionales de la actual invención se dirigen a los métodos de composiciones y de formulaciones de la fabricación según la vacuna. Es aspecto de la presente invención, los métodos de tratar y/o de prevenir ciertas condiciones que comprenden la administración de una cantidad eficaz de una composición y/o de una formulación que comprenden factor de transferencia. Método de extracción y procesamiento de extracto leucocitario Additional aspects of the invention relate to compositions and formulations that may comprise powdered, encapsulated components, including, but not limited to, encapsulated transfer factor or powder and / or antibody or encapsulated antibody fraction. Additional aspects of the present invention are directed to the methods of compositions and manufacturing formulations according to the vaccine. It is an aspect of the present invention, the methods of treating and / or preventing certain conditions comprising the administration of an effective amount of a composition and / or a formulation comprising transfer factor. Method of extraction and processing of leukocyte extract
específicamente diseñado como adyuvante specifically designed as an adjuvant
El procedimiento de la presente invención para la obtención de extracto dializable de leucocitos que contiene polipéptidos menores o iguales a 10,000 Daltones cuya fuente u origen es a partir de células, tejidos u órganos de tiburón, más específicamente bazo de tiburón, enfocado o específicamente diseñado como inmunomodulador, es el siguiente: The process of the present invention for obtaining dialysable leukocyte extract containing polypeptides less than or equal to 10,000 Daltons whose source or origin is from shark cells, tissues or organs, more specifically shark spleen, focused or specifically designed as Immunomodulator is as follows:
1. Esterilización - Involucra que todo instrumento utilizado para la extracción del extracto leucocitario se encuentre estéril. 1. Sterilization - Involves that any instrument used for the extraction of leukocyte extract is sterile.
2. Extracción de Bazo.- Este paso consiste en extraer el extracto leucocitario, a partir de la extracción quirúrgica de una zona específica del bazo del tiburón, rica en linfocitos B, que al ser administrada al individuo, produce señales químicas que al interaccionar con los linfocitos T cooperadores, tienen una colaboración positiva para la síntesis de anticuerpos, que al estar ligadas las señales químicas con el antígeno viral de la vacuna se genera una cantidad mayor de anticuerpos dirigidos contra el antígeno viral de la vacuna, adicionalmente de que la respuesta inmunológica es más rápida expresada por la producción de IgM y duradera expresada por la producción de IgG. 2. Spleen Extraction.- This step consists in extracting the leukocyte extract, from the surgical extraction of a specific area of the shark spleen, rich in B lymphocytes, which when administered to the individual, produces chemical signals that when interacting with Cooperative T lymphocytes have a positive collaboration for the synthesis of antibodies, that when the chemical signals are linked with the viral antigen of the vaccine, a greater amount of antibodies directed against the viral antigen of the vaccine is generated, in addition to the response immune is faster expressed by the production of IgM and durable expressed by the production of IgG.
Conteo y cuantificación.- Mediante la Cámara de Neubauer y microscopio se cuenta el número de leucocitos por campo en la cuadrícula de Neubauer, para saber la potencia del factor de transferencia que se obtendrá, es decir, el número de leucocitos por milímetro cúbico. Así mismo se requiere valorar la calidad de dichas células, que no exista anisocitosis, es decir, mediante el microscopio se observa que las células sean redondas y lisas. Counting and quantification.- The number of leukocytes per field in the Neubauer grid is counted through the Neubauer Chamber and microscope, to know the power of the transfer factor that will be obtained, that is, the number of leukocytes per cubic millimeter. Likewise, it is necessary to assess the quality of said cells, that there is no anisocytosis, that is, by microscopy it is observed that the cells are round and smooth.
Rompimiento o separación de componentes.- Se deben separar las células leucocitarias de las proteínas, lípidos, carbohidratos y toxinas. Diálisis.- La diálisis es el proceso de separar las moléculas en una solución por la diferencia en sus índices de difusión a través de una membrana semipermeable. Entonces, el extracto leucocitario, después de haber sido realizada la separación y rompimiento de componentes, es puesto en un bolso semipermeable de diálisis, como por ejemplo, en una membrana de la celulosa con poros, y el bolso es sellado. El bolso de diálisis sellado se coloca en un envase con una solución diferente, o agua pura. Los extractos leucocitarios, al ser lo suficientemente pequeños como para pasar a través de los poros tienden a moverse hacia adentro o hacia afuera del bolso de diálisis en la dirección de la concentración más baja. Las moléculas más grandes (a menudo proteínas, ADN, o polisacáridos) que tiene dimensiones significativamente mayores que el diámetro del poro son retenidas dentro del bolso de diálisis. De ésta manera, se separan los extractos leucocitarios menores o iguales a 10,000 Daltones. Breaking or separation of components.- Leukocyte cells must be separated from proteins, lipids, carbohydrates and toxins. Dialysis.- Dialysis is the process of separating the molecules in a solution by the difference in their diffusion rates through a semipermeable membrane. Then, the leukocyte extract, after the separation and rupture of components has been carried out, is placed in a semipermeable dialysis bag, as for example, in a cellulose membrane with pores, and the bag is sealed. The sealed dialysis bag is placed in a container with a different solution, or pure water. Leukocyte extracts, being small enough to pass through the pores, tend to move in or out of the dialysis bag in the direction of the lowest concentration. The largest molecules (often proteins, DNA, or polysaccharides) that have dimensions significantly larger than the pore diameter are retained inside the dialysis bag. In this way, leukocyte extracts less than or equal to 10,000 Daltons are separated.
Filtración y esterilización.- Después de la diálisis se filtra el extracto leucocitario por medio de una membrana de tamaño de poro entre 2 y 4 micrómetros. Así mismo, se esteriliza la solución nuevamente. Filtration and sterilization.- After dialysis, the leukocyte extract is filtered through a pore size membrane between 2 and 4 micrometers. Also, the solution is sterilized again.
Formulación.- Se realiza un proceso de liofilización para quitar el agua del extracto leucocitario por medio de la generación de un vacío, así mismo en este paso se realiza la agregación de un vehículo, como puede ser leche, agua, gel o saborizante artificial, para darle una presentación y sabor agradable al producto. Formulation.- A lyophilization process is carried out to remove the water from the leukocyte extract through the generation of a vacuum, likewise in this step the aggregation of a vehicle is carried out, such as milk, water, gel or artificial flavoring, to give a presentation and pleasant taste to the product.
Evaluación Fisicoquímica. En este punto se evalúan los procesos físico-químicos como son densidad, PH, color, olor y sabor. Cabe mencionar que si al producto no se le agregó ningún vehículo, el factor de transferencia obtenido será inoloro, incoloro e insaboro. Evaluación de actividad biológica. Se inducen la o las citosinas requeridas para su función como adyuvante, esto a partir de la dilución del extracto leucocitario hasta llegar al título de las citosinas requeridas según sea el tipo de vacuna al cual el extracto leucocitario fungirá como adyuvante. Esto quiere decir que se elegirá la o las citosinas adecuadas para el funcionamiento como adyuvante de la presente invención según el tipo de vacuna que se administrará al paciente, de tal forma que se aislará la o las citosinas requeridas según la vacuna, tal es el caso de los virus AH1 N1 , entre otros. Asimismo se analiza el extracto leucocitario con membranas de microarreglos para determinar el tipo de citosina que se encuentra en el extracto leucocitario. Physicochemical Evaluation At this point the physical-chemical processes such as density, PH, color, smell and taste are evaluated. It should be mentioned that if no vehicle was added to the product, the transfer factor obtained will be colorless, colorless and insaboro. Evaluation of biological activity. The cytosine (s) required for its function as an adjuvant is induced, this from the dilution of the leukocyte extract until reaching the title of the required cytosines according to the type of vaccine to which the leukocyte extract will function as an adjuvant. This means that the cytosine or cytosines suitable for functioning as an adjuvant of the present invention will be chosen according to the type of vaccine that will be administered to the patient, such that the cytosine required by the vaccine will be isolated, such is the case. of the AH1 N1 viruses, among others. The leukocyte extract with membranes of microarrays to determine the type of cytosine found in the leukocyte extract.
El resultado del proceso anterior es un factor de transferencia potencializado en presentación en polvo, lo que le da la virtud de ser fácilmente transportado y almacenado, no requiere refrigeración y se obtiene una potencia de factor de transferencia de 1012 leucocitos x mm3, lo cual es altamente superior a cualquier factor de transferencia conocido, entendiéndose por potencia a la concentración de leucocitos por mm3 y la calidad de las células (lisas, redondas e inocuas). The result of the above process is a potentialized transfer factor in powder presentation, which gives it the virtue of being easily transported and stored, does not require refrigeration and a transfer factor power of 10 12 leukocytes x mm 3 is obtained , which is highly superior to any known transfer factor, understood as potency at the concentration of leukocytes per mm 3 and the quality of the cells (smooth, round and harmless).
Descripción de la figura Description of the figure
La presente figura ilustra el tipo de citosinas inducida cuando a partir de la inoculación del extracto leucocitario en ratones Balb-c. Se utilizan grupos de 8 ratones, los cuales se inocularán con la cantidad equivalente a la relación peso- unidad de factor de transferencia (0.005 unidad de factor de transferencia). Se extrae suero de cada ratón, se utilizan 50 microlitros de suero, se exponen frente a las membranas de microarreglos que contienen los anticuerpos receptores de las citosinas y los pozos que desarrollen color serán las citosinas inducidas. El suero se diluye con solución reguladora en múltiplos de 2 inicialmente para después realizar diluciones en múltiplos de 100. Se elimina la dilución basal del tiempo 0 y la dilución que conserve el desarrollo de color en los microarreglos previo a la dilución donde ya no se presente el desarrollo de color, es el título del extracto leucocitario. De esta manera, se pueden aislar las citosinas adecuadas para adyuvar la vacuna viral requerida. The present figure illustrates the type of cytosine induced when from the inoculation of the leukocyte extract in Balb-c mice. Groups of 8 mice are used, which will be inoculated with the amount equivalent to the weight-unit ratio of transfer factor (0.005 unit of transfer factor). Whey is extracted from each mouse, 50 microliters of serum are used, exposed against the microarray membranes that contain the cytosine receptor antibodies and the wells that develop color will be induced cytosines. The serum is diluted with a regulatory solution in multiples of 2 initially and then diluted in multiples of 100. The baseline dilution of time 0 and the dilution that preserves the color development in the microarrays prior to dilution where it is no longer present is eliminated. the development of color, is the title of the leukocyte extract. In this way, suitable cytosines can be isolated to support the required viral vaccine.

Claims

REIVINDICACIONES
1. Extracto dializable de leucocitos a partir de células leucocitarias que contiene polipéptidos iguales o menores a 10,000 daltones, para la obtención de factor de transferencia potencializado específicamente diseñado como adyuvante, cuya fuente es una zona específica del bazo que forma parte del sistema linfático y es el centro de actividad del sistema inmune de los selacimorfos, conocidos comúnmente como tiburones; la cual es rica en linfocitos B que producen señales químicas que al interaccionar con los linfocitos T cooperadores, tienen una colaboración positiva para la síntesis de anticuerpos, que al estar ligadas las señales químicas con el antígeno viral de la vacuna se genera una cantidad mayor de anticuerpos dirigidos contra el antígeno viral de la vacuna, adicionalmente de que la respuesta inmunológica es más rápida expresada por la producción de IgM y duradera expresada por la producción de IgG. 1. Dialyzable leukocyte extract from leukocyte cells containing polypeptides equal to or less than 10,000 daltons, to obtain a potentialized transfer factor specifically designed as an adjuvant, whose source is a specific area of the spleen that is part of the lymphatic system and is the center of activity of the immune system of selacimorphs, commonly known as sharks; which is rich in B lymphocytes that produce chemical signals that, when interacting with the cooperating T lymphocytes, have a positive collaboration for the synthesis of antibodies, which, when chemical signals are linked with the viral antigen of the vaccine, generates a greater amount of antibodies directed against the viral antigen of the vaccine, additionally that the immune response is faster expressed by the production of IgM and durable expressed by the production of IgG.
2. Extracto dializable de leucocitos a partir de células leucocitarias que contiene polipéptidos iguales o menores a 10,000 daltones, cuya fuente específica es una zona del bazo, rica en linfocitos B, que forma parte del sistema linfático y es el centro de actividad del sistema inmune de los selacimorfos, conocidos comúnmente como tiburones, para la obtención de factor de transferencia potencializado específicamente diseñado como adyuvante, que de acuerdo a la reivindicación 1 , se caracteriza porque su método de extracción, comprobación y conteo consistente en los siguientes pasos: 2. Dialyzable leukocyte extract from leukocyte cells containing polypeptides equal to or less than 10,000 daltons, whose specific source is an area of the spleen, rich in B lymphocytes, which is part of the lymphatic system and is the center of activity of the immune system of the selacimorphs, commonly known as sharks, for obtaining a potentialized transfer factor specifically designed as an adjuvant, which according to claim 1, is characterized in that its method of extraction, checking and counting consisting of the following steps:
a) Esterilización.- Involucra que todo instrumento utilizado para la extracción del extracto leucocitario se encuentre estéril.  a) Sterilization.- Involves that any instrument used for the extraction of the leukocyte extract is sterile.
b) Extracción de Bazo.- Este paso consiste en extraer el extracto leucocitario, a partir de la extracción quirúrgica de una zona específica del bazo del tiburón, rica en linfocitos B, que al ser administrada al individuo, produce señales químicas que al interaccionar con los linfocitos T cooperadores, tienen una colaboración positiva para la síntesis de anticuerpos, que al estar ligadas las señales químicas con el antígeno viral de la vacuna se genera una cantidad mayor de anticuerpos dirigidos contra el antígeno viral de la vacuna, adicionalmente de que la respuesta inmunológica es más rápida expresada por la producción de IgM y duradera expresada por la producción de IgG.  b) Spleen Extraction.- This step consists in extracting the leukocyte extract, from the surgical extraction of a specific area of the shark spleen, rich in B lymphocytes, which when administered to the individual, produces chemical signals that when interacting with Cooperative T lymphocytes have a positive collaboration for the synthesis of antibodies, that when the chemical signals are linked with the viral antigen of the vaccine, a greater amount of antibodies directed against the viral antigen of the vaccine is generated, in addition to the response Immunological is faster expressed by the production of IgM and durable expressed by the production of IgG.
c) Conteo y cuantificación.- Mediante la Cámara de Neubauer y microscopio se cuenta el número de leucocitos por campo en la cuadrícula de Neubauer, para saber la potencia del factor de transferencia que se obtendrá, es decir, el número de leucocitos' por milímetro cúbico. Así mismo se requiere valorar la calidad de dichas células, que no exista anisocitosis, es decir, mediante el microscopio se observa que las células sean redondas y lisas. c) Counting and quantification.- The number of leukocytes per field in the Neubauer grid is counted through the Neubauer Chamber and microscope, to know the power of the transfer factor to be obtained, that is, the number of leukocytes ' per millimeter cubic. Likewise, it is necessary to assess the quality of said cells, that there is no anisocytosis, that is, by microscopy it is observed that the cells are round and smooth.
d) Rompimiento o separación de componentes.- Se deben separar las células leucocitarias de las proteínas, lípidos, carbohidratos y toxinas. e) Diálisis.- La diálisis es el proceso de separar las moléculas en una solución por la diferencia en sus índices de difusión a través de una membrana semipermeable. Entonces, el extracto leucocitario, después de haber sido realizada la separación y rompimiento de componentes, es puesto en un bolso semipermeable de diálisis, como por ejemplo, en una membrana de la celulosa con poros, y el bolso es sellado. El bolso de diálisis sellado se coloca en un envase con una solución diferente, o agua pura. Los extractos leucocitarios, al ser lo suficientemente pequeños como para pasar a través de los poros tienden a moverse hacia adentro o hacia afuera del bolso de diálisis en la dirección de la concentración más baja. Las moléculas más grandes (a menudo proteínas, ADN, o polisacáridos) que tiene dimensiones significativamente mayores que el diámetro del poro son retenidas dentro del bolso de diálisis. De ésta manera, se separan los extractos leucocitarios menores o iguales a 10,000 Daltones. d) Breaking or separation of components.- Leukocyte cells must be separated from proteins, lipids, carbohydrates and toxins. e) Dialysis.- Dialysis is the process of separating the molecules in a solution by the difference in their diffusion rates through a semipermeable membrane. Then, the leukocyte extract, after the separation and rupture of components has been carried out, is placed in a semipermeable dialysis bag, as for example, in a cellulose membrane with pores, and the bag is sealed. The sealed dialysis bag is placed in a container with a different solution, or pure water. Leukocyte extracts, being small enough to pass through the pores, tend to move in or out of the dialysis bag in the direction of the lowest concentration. Larger molecules (often proteins, DNA, or polysaccharides) that have dimensions significantly larger than the pore diameter are retained within the dialysis bag. In this way, leukocyte extracts less than or equal to 10,000 Daltons are separated.
f) Filtración y esterilización.- Después de la diálisis se filtra el extracto leucocitario por medio de una membrana de tamaño de poro entre 2 y 4 micrómetros. Así mismo, se esteriliza la solución nuevamente. f) Filtration and sterilization.- After dialysis the leukocyte extract is filtered through a pore size membrane between 2 and 4 micrometers. Also, the solution is sterilized again.
g) Formulación.- Se realiza un proceso de liofilización para quitar el agua del extracto leucocitario por medio de la generación de un vacío, así mismo en este paso se realiza la agregación de un vehículo, como puede ser leche, agua, gel o saborizante artificial, para darle una presentación y sabor agradable al producto. h) Evaluación Fisicoquímica. En este punto se evalúan los procesos físico-químicos como son densidad, PH, color, olor y sabor. Cabe mencionar que si al producto no se le agregó ningún vehículo, el factor de transferencia obtenido será inoloro, incoloro e insaboro. g) Formulation.- A lyophilization process is carried out to remove the water from the leukocyte extract through the generation of a vacuum, likewise in this step the aggregation of a vehicle is carried out, such as milk, water, gel or flavoring artificial, to give a presentation and pleasant taste to the product. h) Physicochemical Evaluation. At this point the physical-chemical processes such as density, PH, color, smell and taste are evaluated. It should be mentioned that if no vehicle was added to the product, the transfer factor obtained will be colorless, colorless and insaboro.
i) Evaluación de actividad biológica. Se inducen la o las citosinas requeridas para su función como adyuvante, esto a partir de la dilución del extracto leucocitario hasta llegar al título de las citosinas requeridas según sea el tipo de vacuna al cual el extracto leucocitario fungirá como adyuvante. Esto quiere decir que se elegirá la o las citosinas adecuadas para el funcionamiento como adyuvante de la presente invención según el tipo de vacuna que se administrará al paciente, de tal forma que se aislará la o las citosinas requeridas según la vacuna, tal es el caso de los virus AH1 N1 , entre otros. Asimismo se analiza el extracto leucocitario con membranas de microarreglos para determinar el tipo de citosina que se encuentra en el extracto leucocitario.  i) Evaluation of biological activity. The cytosine (s) required for its function as an adjuvant is induced, this from the dilution of the leukocyte extract until reaching the title of the required cytosines according to the type of vaccine to which the leukocyte extract will function as an adjuvant. This means that the cytosine or cytosines suitable for functioning as an adjuvant of the present invention will be chosen according to the type of vaccine that will be administered to the patient, such that the cytosine required by the vaccine will be isolated, such is the case. of the AH1 N1 viruses, among others. The leukocyte extract is also analyzed with microarray membranes to determine the type of cytosine found in the leukocyte extract.
3. Extracto dializable de leucocitos a partir de células leucocitarias que contiene polipéptidos iguales o menores a 10,000 daltones, cuya fuente específica es una zona del bazo, rica en linfocitos B, que forma parte del sistema linfático y es el centro de actividad del sistema inmune de los selacimorfos, conocidos comúnmente como tiburones, para la obtención de factor de transferencia, que de acuerdo a la reivindicación 1 , se caracteriza porque el producto obtenido es un factor de transferencia potencializado, específicamente diseñado como adyuvante de vacunas virales, de tal forma que se aislan la o las citosinas adecuadas para su funcionamiento como adyuvante para cada tipo de vacuna que se administrará al paciente, según el tipo de virus. 3. Dialyzable leukocyte extract from leukocyte cells containing polypeptides equal to or less than 10,000 daltons, whose specific source is an area of the spleen, rich in B lymphocytes, which is part of the lymphatic system and is the center of activity of the immune system of the selacimorphs, commonly known as sharks, for obtaining transfer factor, which according to claim 1, is characterized in that the product obtained is a potentialized transfer factor, specifically designed as an adjuvant for viral vaccines, in such a way that the appropriate cytosine (s) are isolated for its functioning as an adjuvant for each type of vaccine that will be administered to the patient, depending on the type of virus.
4. Extracto dializable de leucocitos a partir de células leucocitarias que contiene polipéptidos iguales o menores a 10,000 daltones, cuya fuente específica es una zona del bazo, rica en linfocitos B, que forma parte del sistema linfático y es el centro de actividad del sistema inmune de los selacimorfos, conocidos comúnmente como tiburones, para la obtención de factor de transferencia potencializado específicamente diseñado como adyuvante, que de acuerdo a la reivindicación 1 , se caracteriza porque el producto obtenido se encuentra en presentación en polvo, el cual puede ser fácilmente transportado y almacenado, así mismo no requiere refrigeración. 4. Dialyzable leukocyte extract from leukocyte cells containing polypeptides equal to or less than 10,000 daltons, whose specific source is an area of the spleen, rich in B lymphocytes, which is part of the lymphatic system and is the center of activity of the immune system of the selacimorphs, commonly known as sharks, to obtain the potentialized transfer factor specifically designed as an adjuvant, which according to claim 1, is characterized in that the product obtained is in powder form, which can be easily transported and stored, also does not require refrigeration.
5. Extracto dializable de leucocitos a partir de células leucocitarias que contiene polipéptidos iguales o menores a 10,000 daltones, cuya fuente específica es una zona del bazo, rica en linfocitos B, que forma parte del sistema linfático y es el centro de actividad del sistema inmune de los selacimorfos, conocidos comúnmente como tiburones, para la obtención de factor de transferencia potencializado específicamente diseñado como adyuvante, que de acuerdo a la reivindicación 4, se caracteriza porque el producto obtenido también comprende composiciones y formulaciones en presentación en polvo, encapsulados, incluyendo, pero no limitado a, factor de transferencia encapsulado o polvo y/o anticuerpo o fracción encapsulado del anticuerpo. 5. Dialyzable leukocyte extract from leukocyte cells containing polypeptides equal to or less than 10,000 daltons, whose specific source is an area of the spleen, rich in B lymphocytes, which is part of the lymphatic system and is the center of activity of the immune system of the selacimorphs, commonly known as sharks, for obtaining a potentialized transfer factor specifically designed as an adjuvant, which according to claim 4, is characterized in that the product obtained also comprises compositions and formulations in powder form, encapsulated, including, but not limited to, factor of encapsulated transfer or powder and / or antibody or encapsulated antibody fraction.
6. Extracto dializable de leucocitos a partir de células leucocitarias que contiene polipéptidos iguales o menores a 10,000 daltones, cuya fuente específica es una zona del bazo, rica en linfocitos B, que forma parte del sistema linfático y es el centro de actividad del sistema inmune de los selacimorfos, conocidos comúnmente como tiburones, para la obtención de factor de transferencia potencializado específicamente diseñado como adyuvante, que de acuerdo a cualquiera de las reivindicaciones anteriores, se caracteriza porque aumenta la efectividad de la vacuna al promover la excitación celular para obtener una inmunidad adquirida, ya que facilita el reconocimiento antígeno-anticuerpo y fortalece el enlace químico evitando rupturas del mismo, de tal manera que el enlace químico antígeno-linfocito B, además de ser fortalecido, se realiza en menor tiempo. 6. Dialyzable leukocyte extract from leukocyte cells containing polypeptides equal to or less than 10,000 daltons, whose specific source is an area of the spleen, rich in B lymphocytes, which is part of the lymphatic system and is the center of activity of the immune system of the selacimorphs, commonly known as sharks, for obtaining a potentialized transfer factor specifically designed as an adjuvant, which according to any of the preceding claims, is characterized in that it increases the effectiveness of the vaccine by promoting cell excitation to obtain immunity. acquired, since it facilitates the recognition of antigen-antibody and strengthens the chemical bond avoiding ruptures thereof, so that the chemical bond antigen-lymphocyte B, in addition to being strengthened, is carried out in less time.
7. Extracto dializable de leucocitos a partir de células leucocitarias que contiene polipéptidos iguales o menores a 10,000 daltones, cuya fuente específica es una zona del bazo, rica en linfocitos B, que forma parte del sistema linfático y es el centro de actividad del sistema inmune de los selacimorfos, conocidos comúnmente como tiburones, para la obtención de factor de transferencia potencializado específicamente diseñado como adyuvante, que de acuerdo a cualquiera de las reivindicaciones anteriores, se caracteriza porque da mayor durabilidad al enlace químico antígeno-linfocito B formado. 7. Dialyzable leukocyte extract from leukocyte cells containing polypeptides equal to or less than 10,000 daltons, whose specific source is an area of the spleen, rich in B lymphocytes, which is part of the lymphatic system and is the center of activity of the immune system of the selacimorphs, commonly known as sharks, for obtaining a potentialized transfer factor specifically designed as an adjuvant, which according to any of the preceding claims, is characterized in that it gives greater durability to the formed antigen-lymphocyte B chemical bond.
8. Extracto dializable de leucocitos a partir de células leucocitarias que contiene polipéptidos iguales o menores a 10,000 daltones, cuya fuente específica es una zona del bazo, rica en Iinfocitos B, que forma parte del sistema linfático y es el centro de actividad del sistema inmune de los selacimorfos, conocidos comúnmente como tiburones, para la obtención de factor de transferencia potencializado específicamente diseñado como adyuvante, que de acuerdo a cualquiera de las reivindicaciones anteriores, se caracteriza porque se obtiene una potencia de factor de transferencia de 1012 leucocitos x mm3, entendiéndose por potencia a la concentración de leucocitos por mm3 y la calidad de las células (lisas, redondas e inoquas). 8. Dialyzable leukocyte extract from leukocyte cells containing polypeptides equal to or less than 10,000 daltons, whose specific source is an area of the spleen, rich in Iinfocitos B, which is part of the lymphatic system and is the center of activity of the immune system of the selacimorphs, commonly known as sharks, for obtaining a potentialized transfer factor specifically designed as an adjuvant, which according to any of the preceding claims, is characterized in that a transfer factor power of 10 12 leukocytes x mm 3 is obtained , understood as power to the concentration of leukocytes per mm 3 and the quality of the cells (smooth, round and innocuous).
9. Extracto dializable de leucocitos a partir de células leucocitarias que contiene polipéptidos iguales o menores a 10,000 daltones, cuya fuente específica es una zona del bazo, rica en Iinfocitos B, que forma parte del sistema linfático y es el centro de actividad del sistema inmune de los selacimorfos, conocidos comúnmente como tiburones, para la obtención de factor de transferencia potencializado específicamente diseñado como adyuvante, que de acuerdo a cualquiera de las reivindicaciones anteriores, se caracteriza porque el método de comprobación de la potencia del extracto leucocitario a partir de la inoculación del extracto leucocitario en ratones Balb-c, realizado en el paso de la comprobación de la actividad biológica, consiste en: Se utilizan grupos de 8 ratones, los cuales se utilizarán en cada tiempo de la cinética, se inocularán con la cantidad equivalente a la relación peso-unidad de factor de transferencia (0.005 unidad de factor de transferencia), se mantienen los ratones en los tiempos determinados, siendo el tiempo 0 el nivel basal de citosinas inducidas de los ratones, la cual se eliminará con la intención de conocer el tipo, título y permanencia de las citosinas inducidas. Se extrae suero de cada ratón en su tiempo de acuerdo a la cinética y se utilizan 50 microlitros de suero, se exponen frente a las membranas de microarreglos que contienen los anticuerpos receptores de las citosinas y los pozos que desarrollen color serán las citosinas inducidas. El suero se diluye con solución reguladora en múltiplos de 2 inicialmente para después realizar diluciones en múltiplos de 100. Se elimina la dilución basal del tiempo 0 y la dilución que conserve el desarrollo de color en los microarreglos previo a la dilución donde ya no se presente el desarrollo de color, es el título del extracto leucocitario. El grupo de ratones que conserve el título máximo con mayor tiempo de inducción será el tiempo de permanencia de la inducción de citosinas. 9. Dialyzable leukocyte extract from leukocyte cells containing polypeptides equal to or less than 10,000 daltons, whose specific source is an area of the spleen, rich in lymphocytes B, which is part of the lymphatic system and is the center of activity of the immune system of the selacimorphs, commonly known as sharks, for obtaining a potentialized transfer factor specifically designed as an adjuvant, which according to any of the preceding claims, is characterized in that the method of checking the potency of the leukocyte extract from inoculation of the leukocyte extract in Balb-c mice, performed in the step of checking the biological activity, consists of: Groups of 8 mice are used, which will be used at each time of the kinetics, they will be inoculated with the amount equivalent to weight-unit ratio of transfer factor (0.005 unit of transfer factor), is maintained they have the mice in the determined times, being the time 0 the basal level of induced cytosines of the mice, which will be eliminated with the intention of knowing the type, title and permanence of the induced cytosines. Whey is extracted from each mouse in its time according to the kinetics and 50 microliters of serum are used, exposed against the microarray membranes that contain the cytosine receptor antibodies and the wells that develop color will be induced cytosines. The serum is diluted with a regulatory solution in multiples of 2 initially and then diluted in multiples of 100. The baseline dilution of time 0 and the dilution that preserves the color development in the microarrays prior to dilution where it is no longer present is eliminated. Color development is the title of the leukocyte extract. The group of mice that retain the maximum titer with the longest induction time will be the residence time of the cytosine induction.
10. Extracto dializable de leucocitos a partir de células leucocitarias que contiene polipéptidos iguales o menores a 10,000 daltones, cuya fuente específica es una zona del bazo, rica en linfocitos B, que forma parte del sistema linfático y es el centro de actividad del sistema inmune de los selacimorfos, conocidos comúnmente como tiburones, para la obtención de factor de transferencia potencializado específicamente diseñado como adyuvante, que de acuerdo a cualquiera de las reivindicaciones anteriores, se caracteriza porque a mayor título y tiempo de inducción encontrado, mayor potencia del factor de transferencia. 10. Dialyzable leukocyte extract from leukocyte cells containing polypeptides equal to or less than 10,000 daltons, whose specific source is an area of the spleen, rich in B lymphocytes, which is part of the lymphatic system and is the center of activity of the immune system of the selacimorphs, commonly known as sharks, to obtain the potentialized transfer factor specifically designed as an adjuvant, which according to any of the preceding claims, is characterized in that the greater the title and induction time found, the greater the power of the transfer factor .
11. Extracto dializable de leucocitos a partir de células leucocitarias que contiene polipéptidos iguales o menores a 10,000 daltones, cuya fuente específica es una zona del bazo, rica en linfocitos B, que forma parte del sistema linfático y es el centro de actividad del sistema inmune de los selacimorfos, conocidos comúnmente como tiburones, para la obtención de factor de transferencia potencializado específicamente diseñado como adyuvante, que de acuerdo a cualquiera de las reivindicaciones anteriores, se caracteriza porque promueve una actividad perceptiblemente creciente de las células NK (asesino natural por sus siglas en inglés), las cuales proporcionan la protección contra virus como parte del sistema de defensa inmune natural. 11. Dialyzable leukocyte extract from leukocyte cells containing polypeptides equal to or less than 10,000 daltons, whose specific source is an area of the spleen, rich in B lymphocytes, which is part of the lymphatic system and is the center of activity of the immune system of the selacimorphs, commonly known as sharks, for obtaining a potentialized transfer factor specifically designed as an adjuvant, which according to any of the preceding claims, is characterized in that it promotes a significantly increased activity of NK cells (natural killer by its acronym in English), which provide protection against viruses as part of the natural immune defense system.
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US20160317615A1 (en) * 2015-05-01 2016-11-03 Jose Javier Lopez GONZALEZ T cell modulator
WO2016195469A1 (en) * 2015-06-04 2016-12-08 Zepeda López Hector Manuel Potentiated t-cell modulator able to modulate immune response, specifically designed for therapeutic use as a potentiating adjuvant in virus vaccines

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