ES2600281T3 - Composiciones inmunoestimuladoras que comprenden una nucleobase y un polisacárido obtenible a partir de hongos, levaduras o bacterias - Google Patents
Composiciones inmunoestimuladoras que comprenden una nucleobase y un polisacárido obtenible a partir de hongos, levaduras o bacterias Download PDFInfo
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- ES2600281T3 ES2600281T3 ES09782755.4T ES09782755T ES2600281T3 ES 2600281 T3 ES2600281 T3 ES 2600281T3 ES 09782755 T ES09782755 T ES 09782755T ES 2600281 T3 ES2600281 T3 ES 2600281T3
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- 239000000203 mixture Substances 0.000 title abstract description 9
- 241000894006 Bacteria Species 0.000 title abstract 2
- 241000233866 Fungi Species 0.000 title abstract 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 title abstract 2
- 150000004676 glycans Chemical class 0.000 title 1
- 230000003308 immunostimulating effect Effects 0.000 title 1
- 229920001282 polysaccharide Polymers 0.000 title 1
- 239000005017 polysaccharide Substances 0.000 title 1
- 229920000310 Alpha glucan Polymers 0.000 abstract 1
- 239000002777 nucleoside Substances 0.000 abstract 1
- 125000003835 nucleoside group Chemical group 0.000 abstract 1
- 239000002773 nucleotide Substances 0.000 abstract 1
- 125000003729 nucleotide group Chemical group 0.000 abstract 1
- 241000282472 Canis lupus familiaris Species 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 7
- 230000037396 body weight Effects 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 230000036737 immune function Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 2
- 108010082126 Alanine transaminase Proteins 0.000 description 2
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 229950004398 broxuridine Drugs 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010047620 Phytohemagglutinins Proteins 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
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- 239000000463 material Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000001885 phytohemagglutinin Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
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- 230000000405 serological effect Effects 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
- A61P37/04—Immunostimulants
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
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- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
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- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
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- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
Una composición que comprende: - un componente a) que comprende una nucleobase, una fuente de nucleobases seleccionada del grupo que consiste en nucleósidos, nucleótidos, ARN y ADN o una mezcla de los mismos; y - un componente b) que comprende un α-glucano obtenible a partir de un extracto de hongos, levaduras o bacterias.
Description
El incremento en la recuperación de las poblaciones linfocitarias tipo B se observó claramente en la producción de anticuerpos inespecíficos. La figura 1 muestra como en el grupo control C la concentración de IgA cayó bruscamente siete días después del tratamiento quimioterápico mientras que en el grupo A (Nucleoforce® Dogs) y en el grupo B (AHCC®) se mantuvo, y en el grupo A+B (combinación de Nucleoforce® Dogs y AHCC®) se incrementó ligeramente
El mismo patrón de respuesta se observa en la figura 2 para la IgM (P<0,05). En el caso de la IgG (figura 3), se detectó un incremento significativo (P<0,001) de la concentración plasmática de inmunoglobulinas en el grupo que recibió la composición de la invención (combinación de Nucleoforce® Dogs y AHCC®) con respecto a los grupos A (Nucleoforce® Dogs), B (AHCC®) y C (control), observándose un efecto sinérgico.
Aparte del efecto sobre la función inmunitaria, el complemento de la dieta con la composición de la invención (Nucleoforce® Dogs y AHCC®) ejerció un efecto protector sobre la hepatotoxicidad asociada al tratamiento quimioterápico. Tal y como puede observarse en la figura 4, en el día 28 se observó un incremento en los niveles
15 serológicos de alanina aminotransferasa (ALT) que fue significativamente más elevado (P<0,05) en el grupo control (563,8 Ul/l) que en los grupos A (Nucleoforce® Dogs) (266,3 Ul/l), B (AHCC®) (221 UI/l) y A+B (Nucleoforce® Dogs y AHCC®) (141,9 Ul/l).
En su conjunto los resultados del ensayo muestran que la administración de una composición de la invención que comprende la combinación de Nucleoforce® Dogs con AHCC® permite mejorar la función inmunitaria y reducir las lesiones hepáticas en animales sometidos a tratamiento quimioterápico. También muestran que existe un efecto sinérgico entre Nucleoforce® Dogs y AHCC®, ya que el efecto de la combinación sobrepasa la suma de los efectos individuales de cada componente por separado.
25 Ejemplo 4: Refuerzo de la respuesta inmunitaria en animales sanos
El fin del experimento fue estudiar el impacto de la administración de una composición de la invención que comprende Nucleoforce® Dogs y AHCC® sobre la función inmunitaria de perros sanos.
Materiales y métodos
El diseño del estudio clínico fue aleatorizado y con ocultación doble. El protocolo fue aprobado por el Comité Ético de Investigación Animal de la Universidad de Murcia. Se dividió aleatoriamente un total de 24 perros Beagle adultos de 15 kg de peso corporal medio (machos y hembras sanos entre 1 y 2 años de edad) en cuatro grupos (C, A, B y
35 A+B) (n=6) y se alimentaron durante un periodo de 30 días con una dieta comercial convencional complementada con:
Grupo control C: producto placebo (microcelulosa cristalina). Grupo A: Nucleoforce® Dogs (60 mg/kg de peso corporal). Grupo B: AHCC® (60 mg/kg de peso corporal) Grupo A+B: una composición de la invención formada por Nucleoforce® Dogs (30 mg/kg de peso corporal) y AHCC® (30 mg/kg de peso corporal).
Los animales se vigilaron diariamente y se vigiló cualquier signo clínico de enfermedad. Al principio (día 0) y al final
45 del periodo experimental (día 30) se tomaron muestras de sangre para determinar el índice de proliferación linfocitaria in vitro. Se utilizó este índice porque se considera que es una determinación que determina de forma fiable la capacidad del sistema inmunitario para responder a una infección.
Para la determinación de la proliferación de linfocitos se aislaron los linfocitos de muestras de sangre heparinizada de los animales y se cultivaron en ausencia o presencia de fitohemaglutinina con presencia en el medio de 10 μmol de 5-bromodeoxyuridina (BrdU). El índice de proliferación celular se determinó utilizando una técnica de ELISA no radioactiva (Cell proliferation ELISA; Boehringer Mannheim, Alemania). Los resultados se expresaron como unidades de densidad óptica (DO).
55 Todos los datos se analizaron mediante un análisis de la varianza (ANOVA) utilizando el procedimiento GLM (modelo general lineal) del programa estadístico SAS (1996). Los valores medios se compararon usando el procedimiento LS-MEANS de SAS. Se consideró significativo un valor de P bilateral <0,05.
Resultados
Tal como se muestra en la figura 5, tras 30 días de administrar los productos a ensayar, los animales que recibieron la composición de la invención (combinación de Nucleoforce® Dogs y AHCC®) presentaron un índice de proliferación linfocitaria significativamente superior (13,42±0,72 DO) (P<0,05) al de los animales que recibieron Nucleoforce® Dogs (7,04±1,72 DO), AHCC® (7,18+1,79 DO) o el producto placebo (8,01±1,81 DO).
65 No se detectó ningún signo de toxicidad asociado a la administración del producto.
9
Claims (1)
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imagen1 imagen2
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES200802731A ES2341163B1 (es) | 2008-09-26 | 2008-09-26 | Composiciones inmunoestimulantes. |
ES200802731 | 2008-09-26 | ||
PCT/EP2009/061620 WO2010034615A1 (en) | 2008-09-26 | 2009-09-08 | Immunostimulant compositions comprising a nucleobase and a polysaccharide obtainable from fungi, yeast or bacteria |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2600281T3 true ES2600281T3 (es) | 2017-02-08 |
Family
ID=41606685
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES200802731A Active ES2341163B1 (es) | 2008-09-26 | 2008-09-26 | Composiciones inmunoestimulantes. |
ES09782755.4T Active ES2600281T3 (es) | 2008-09-26 | 2009-09-08 | Composiciones inmunoestimuladoras que comprenden una nucleobase y un polisacárido obtenible a partir de hongos, levaduras o bacterias |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES200802731A Active ES2341163B1 (es) | 2008-09-26 | 2008-09-26 | Composiciones inmunoestimulantes. |
Country Status (6)
Country | Link |
---|---|
US (1) | US9161979B2 (es) |
EP (1) | EP2346530B1 (es) |
JP (1) | JP2012503615A (es) |
CA (1) | CA2738599A1 (es) |
ES (2) | ES2341163B1 (es) |
WO (1) | WO2010034615A1 (es) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10335412B2 (en) * | 2013-04-10 | 2019-07-02 | Energenesis Biomedical Co., Ltd | Method for activating AMPK and the use of adenine |
US10500206B2 (en) | 2017-03-13 | 2019-12-10 | Energenesis Biomedical Co., Ltd. | Method for enhancing wound healing by administrating adenine |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5231085A (en) | 1988-10-31 | 1993-07-27 | Sandoz Ltd. | Compositions and methods for the enhancement of host defense mechanisms |
EP0367724B1 (en) | 1988-10-31 | 1993-02-10 | Sandoz Nutrition Ltd. | Improvements in or relating to organic compounds |
JP3651697B2 (ja) | 1995-03-24 | 2005-05-25 | 株式会社アミノアップ化学 | 新規多糖体物質 |
ATE502042T1 (de) | 2001-02-08 | 2011-04-15 | Amino Up Chemical Co Ltd | Neue substanzen mit physiologischer aktivität, verfahren zu deren herstellung und deren verwendung |
US20050058671A1 (en) * | 2003-05-09 | 2005-03-17 | Bedding Peter M.J. | Dietary supplement and method for treating digestive system-related disorders |
US20100166831A1 (en) * | 2006-02-10 | 2010-07-01 | The Roan Group, Inc | Microencapsulated Nucleotide Formulations for Aquaculture and Land Animal Feeds |
-
2008
- 2008-09-26 ES ES200802731A patent/ES2341163B1/es active Active
-
2009
- 2009-09-08 US US13/121,147 patent/US9161979B2/en active Active
- 2009-09-08 EP EP09782755.4A patent/EP2346530B1/en active Active
- 2009-09-08 CA CA2738599A patent/CA2738599A1/en not_active Abandoned
- 2009-09-08 JP JP2011528283A patent/JP2012503615A/ja active Pending
- 2009-09-08 WO PCT/EP2009/061620 patent/WO2010034615A1/en active Application Filing
- 2009-09-08 ES ES09782755.4T patent/ES2600281T3/es active Active
Also Published As
Publication number | Publication date |
---|---|
JP2012503615A (ja) | 2012-02-09 |
EP2346530A1 (en) | 2011-07-27 |
ES2341163A1 (es) | 2010-06-15 |
WO2010034615A1 (en) | 2010-04-01 |
EP2346530B1 (en) | 2016-07-27 |
ES2341163B1 (es) | 2011-05-11 |
CA2738599A1 (en) | 2010-04-01 |
US9161979B2 (en) | 2015-10-20 |
US20110213020A1 (en) | 2011-09-01 |
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