FR3126869A1 - Pharmaceutical composition comprising metabolites derived from the bacterium Bacillus subtilis Gozen GZN-08 isolated from Camellia sinensis and modulating the immune response. - Google Patents
Pharmaceutical composition comprising metabolites derived from the bacterium Bacillus subtilis Gozen GZN-08 isolated from Camellia sinensis and modulating the immune response. Download PDFInfo
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- FR3126869A1 FR3126869A1 FR2109752A FR2109752A FR3126869A1 FR 3126869 A1 FR3126869 A1 FR 3126869A1 FR 2109752 A FR2109752 A FR 2109752A FR 2109752 A FR2109752 A FR 2109752A FR 3126869 A1 FR3126869 A1 FR 3126869A1
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 20
- 244000063299 Bacillus subtilis Species 0.000 title claims abstract description 10
- 235000006468 Thea sinensis Nutrition 0.000 title claims abstract description 10
- 239000002207 metabolite Substances 0.000 title claims abstract description 6
- 244000052707 Camellia sinensis Species 0.000 title claims abstract 5
- 230000028993 immune response Effects 0.000 title description 5
- 241000736262 Microbiota Species 0.000 claims abstract description 25
- 238000004519 manufacturing process Methods 0.000 claims abstract description 11
- DATAGRPVKZEWHA-YFKPBYRVSA-N N(5)-ethyl-L-glutamine Chemical compound CCNC(=O)CC[C@H]([NH3+])C([O-])=O DATAGRPVKZEWHA-YFKPBYRVSA-N 0.000 claims abstract description 10
- 230000002685 pulmonary effect Effects 0.000 claims abstract description 10
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- 239000005017 polysaccharide Substances 0.000 claims abstract description 8
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 8
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 5
- 229940026510 theanine Drugs 0.000 claims abstract description 5
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- DANYIYRPLHHOCZ-UHFFFAOYSA-N 5,7-dihydroxy-4'-methoxyflavone Chemical compound C1=CC(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 DANYIYRPLHHOCZ-UHFFFAOYSA-N 0.000 claims description 8
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- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 8
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- JMSVCTWVEWCHDZ-UHFFFAOYSA-N syringic acid Chemical compound COC1=CC(C(O)=O)=CC(OC)=C1O JMSVCTWVEWCHDZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000011701 zinc Substances 0.000 claims description 6
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- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 claims description 4
- MXYUKLILVYORSK-UHFFFAOYSA-N (+/-)-allo-lobeline Natural products C1CCC(CC(=O)C=2C=CC=CC=2)N(C)C1CC(O)C1=CC=CC=C1 MXYUKLILVYORSK-UHFFFAOYSA-N 0.000 claims description 4
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- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 claims description 4
- HGUVPEBGCAVWID-KETMJRJWSA-N 7-O-(beta-D-glucosyl)isovitexin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C(=C1O)[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC2=C1C(=O)C=C(C=1C=CC(O)=CC=1)O2 HGUVPEBGCAVWID-KETMJRJWSA-N 0.000 claims description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims description 4
- 102000001554 Hemoglobins Human genes 0.000 claims description 4
- 108010054147 Hemoglobins Proteins 0.000 claims description 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 4
- KYWSCMDFVARMPN-LCSVLAELSA-N Saikosaponin D Chemical compound O([C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@]([C@H]3[C@]([C@@H]4[C@@]([C@@]5(C[C@@H](O)[C@]67CO[C@]5([C@@H]6CC(C)(C)CC7)C=C4)C)(C)CC3)(C)CC2)(C)CO)O[C@@H]([C@@H]1O)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O KYWSCMDFVARMPN-LCSVLAELSA-N 0.000 claims description 4
- 235000009962 acacetin Nutrition 0.000 claims description 4
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- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 claims description 4
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- YIBXWXOYFGZLRU-UHFFFAOYSA-N syringic aldehyde Natural products CC12CCC(C3(CCC(=O)C(C)(C)C3CC=3)C)C=3C1(C)CCC2C1COC(C)(C)C(O)C(O)C1 YIBXWXOYFGZLRU-UHFFFAOYSA-N 0.000 claims description 3
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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
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
-
- 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
-
- 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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/82—Theaceae (Tea family), e.g. camellia
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- 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
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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
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Abstract
L’invention concerne une composition pharmaceutique comprenant une association de bioactifs comprenant de la théanine et des polysaccharides extraits de Camellia sinensis, et au moins 2 métabolites, typiquement produits par la bactérie Bacillus subtilis, de préférence Bacillus subtilis Gozen GZN-08 isolée de Camellia sinensis. L’invention concerne également la composition pharmaceutique pour son utilisation pour moduler le microbiote pulmonaire tout en modulant l’intensité de la réponse du système immunitaire en rétablissant un taux normal de globules blancs, et pour augmenter la production d’anticorps tout en réduisant la production de cytokines pro inflammatoires.The invention relates to a pharmaceutical composition comprising a combination of bioactives comprising theanine and polysaccharides extracted from Camellia sinensis, and at least 2 metabolites, typically produced by the bacterium Bacillus subtilis, preferably Bacillus subtilis Gozen GZN-08 isolated from Camellia sinensis . The invention also relates to the pharmaceutical composition for its use to modulate the pulmonary microbiota while modulating the intensity of the response of the immune system by restoring a normal level of white blood cells, and to increase the production of antibodies while reducing the production pro-inflammatory cytokines.
Description
La présente invention a pour objet une composition pharmaceutique comprenant une association de théanine et de polysaccharides extraits deCamellia sinensis, et d’au moins 2 métabolites produits par la bactérieBacillus subtilis Gozen GZN-08parmi le groupe : acide gallique, lobéline, biotine, catéchine, pyridoxine, acide syringique, butyrate, propionate, zinc, acide linoléique, saikosaponine, acacétine, saponarine, acide butyrique, caractérisée en ce que ladite composition module le microbiote pulmonaire et augmente l’intensité de la réponse du système immunitaire.The subject of the present invention is a pharmaceutical composition comprising a combination of theanine and polysaccharides extracted from Camellia sinensis , and at least 2 metabolites produced by the bacterium Bacillus subtilis Gozen GZN-08 from the group: gallic acid, lobeline, biotin, catechin, pyridoxine, syringic acid, butyrate, propionate, zinc, linoleic acid, saikosaponin, acacetin, saponarin, butyric acid, characterized in that said composition modulates the pulmonary microbiota and increases the intensity of the immune system response.
On sait que le microbiote est l'ensemble des microorganismes notamment bactéries, levures, champignons ou virus vivant dans un environnement spécifique appelé le microbiome chez un hôte. L’être humain possède plusieurs microbiotes : intestinal, pulmonaire, vaginal, au niveau de la peau ou encore de la zone nez/bouche/pharynx. Le microbiote d’un individu se constitue à partir du microbiote vaginal de la mère lors de la naissance, qui va dès la naissance coloniser la peau tandis ce que le microbiote issu du lait maternel va coloniser les intestins. L’exposition aux bactéries de l’environnement aux antibiotiques, à l’alimentation ou encore aux facteurs génétiques vont ensuite faire évoluer le microbiote durant les premières années. La présence du microbiote permet de limiter le risque de colonisation par une bactérie pathogène. Avant la découverte du microbiote, les bactéries étaient considérées majoritairement comme néfastes ou pathogènes mais aujourd’hui le rôle du microbiote est mieux connu. On sait qu’il est essentiel dans le bon fonctionnement de la digestion, du métabolisme, du système immunitaire et même du système neurologique. Cependant l’équilibre du microbiote est fragile. On appelle dysbiose un déséquilibre de ce microbiote. Ce déséquilibre peut être causé par un événement perturbateur comme un changement d’environnement, d’alimentation ou de traitement médical. Une dysbiose peut favoriser de nombreuses maladies comme l’obésité, le diabète, les allergies ou encore la dépression.We know that the microbiota is the set of microorganisms including bacteria, yeasts, fungi or viruses living in a specific environment called the microbiome in a host. Human beings have several microbiota: intestinal, pulmonary, vaginal, in the skin or even in the nose/mouth/pharynx area. An individual's microbiota is formed from the mother's vaginal microbiota at birth, which will colonize the skin from birth, while the microbiota from breast milk will colonize the intestines. Exposure to environmental bacteria, antibiotics, food or even genetic factors will then cause the microbiota to evolve during the first years. The presence of the microbiota makes it possible to limit the risk of colonization by a pathogenic bacterium. Before the discovery of the microbiota, bacteria were mainly considered harmful or pathogenic, but today the role of the microbiota is better known. It is known to be essential in the proper functioning of digestion, metabolism, the immune system and even the neurological system. However, the balance of the microbiota is fragile. An imbalance of this microbiota is called dysbiosis. This imbalance can be caused by a disruptive event such as a change in environment, diet, or medical treatment. Dysbiosis can promote many diseases such as obesity, diabetes, allergies or depression.
L’inventeur s’est intéressé plus particulièrement au microbiote pulmonaire. Il a longtemps été pensé que les poumons étaient stériles, cependant les récentes études ont démontré que les poumons abritent un large éventail d'espèces microbiennes différentes. Il a été observé que le microbiote des voies aériennes est altéré dans le cadre de nombreux troubles respiratoires. La modulation du microbiote pulmonaire est donc un outil intéressant pour maintenir les poumons en bonne santé.The inventor was particularly interested in the pulmonary microbiota. The lungs have long been thought to be sterile, however recent studies have shown that the lungs harbor a wide range of different microbial species. The airway microbiota has been observed to be altered in many respiratory disorders. Modulating the lung microbiota is therefore an interesting tool to keep the lungs healthy.
Le microbiote intestinal, avec celui de la peau, est le plus important microbiote du corps. Il peut fermenter les résidus alimentaires indigestes, favoriser l'absorption de certains nutriments, assurer l'hydrolyse de plusieurs substances, participer à la synthèse de multiples vitamines et réguler diverses voies métaboliques. La flore intestinale est également impliquée dans le fonctionnement du système immunitaire intestinal, essentiel à la fonction de barrière de la paroi intestinale. En effet des bactéries commeEscherichia colicombattent directement la colonisation du tube digestif par des bactéries pathogènes grâce à des phénomènes de compétition et par la production de substances bactéricides. La flore intestinale est aussi très importante dès le plus jeune âge puisqu’elle permet au système immunitaire intestinal d’apprendre à faire la distinction entre les bactéries bonnes pour les corps et les bactéries pathogènes.The intestinal microbiota, along with that of the skin, is the most important microbiota in the body. It can ferment indigestible food residues, promote the absorption of certain nutrients, ensure the hydrolysis of several substances, participate in the synthesis of multiple vitamins and regulate various metabolic pathways. The intestinal flora is also involved in the functioning of the intestinal immune system, which is essential for the barrier function of the intestinal wall. In fact, bacteria such as Escherichia coli directly combat the colonization of the digestive tract by pathogenic bacteria thanks to competition phenomena and the production of bactericidal substances. The intestinal flora is also very important from an early age since it allows the intestinal immune system to learn to distinguish between bacteria that are good for the body and pathogenic bacteria.
On sait que l'influence du microbiote sur la formation de la réponse immunitaire est un sujet de plus en plus étudié aujourd'hui. Ces études indiquent l’importance de l’influence du microbiote sur son hôte et démontrent le rôle clef de certaines bactéries du microbiote dans l’activation du système immunitaire, notamment au niveau de l’intestin. Une dysbiose peut donc conduire à un dysfonctionnement dans l’activation de ce système, à une réponse immunitaire insuffisante, ou encore à la colonisation de bactéries pathogènes inflammatoires dans l’intestin.We know that the influence of the microbiota on the formation of the immune response is a subject that is increasingly studied today. These studies indicate the importance of the influence of the microbiota on its host and demonstrate the key role of certain microbiota bacteria in the activation of the immune system, particularly in the intestine. Dysbiosis can therefore lead to a dysfunction in the activation of this system, to an insufficient immune response, or to the colonization of inflammatory pathogenic bacteria in the intestine.
Des traitements à base de polysaccharides issus deCamellia sinensis(WO2011069781A1) ont été proposés afin de stimuler la réponse immunitaire, mais cette solution a une action limitée dans le temps puisqu’elle ne permet pas de lutter contre un déséquilibre du microbiote intestinal ou pulmonaire et donc de prévenir une future réaction insuffisante du système immunitaire en cas de dysbiose. D’autres solutions à base de probiotiques ont été proposées comme par exemple une souche deLactobacillus reuteripour prévenir ou traiter une dysbiose du microbiote et ainsi prévenir différents types de maladie liées à cette dysbiose (WO2016066763A1) ou encore une souche deLactobacillus rhamnosuspour favoriser une réponse immunitaire anti-infectieuse et/ou anti-inflammatoire (EP2983685A1). Cependant ces solutions font appel à des souches vivantes qui ne sont donc pas stables dans le temps et qui peuvent alors induire une baisse d’efficacité dans le temps. De plus, les souches vivantes ont un effet limité, dû non seulement à leur faible stabilité dans le temps, mais aussi car elles dépendent de la composition bactérienne du sujet qui peut limiter l’implantation de nouvelles bactéries et par conséquent leur efficacité.Treatments based on polysaccharides from Camellia sinensis (WO2011069781A1) have been proposed in order to stimulate the immune response, but this solution has a limited action over time since it does not make it possible to fight against an imbalance of the intestinal or pulmonary microbiota and therefore to prevent a future insufficient reaction of the immune system in the event of dysbiosis. Other solutions based on probiotics have been proposed, such as for example a strain of Lactobacillus reuteri to prevent or treat dysbiosis of the microbiota and thus prevent different types of disease linked to this dysbiosis (WO2016066763A1) or even a strain of Lactobacillus rhamnosus to promote an anti-infective and/or anti-inflammatory immune response (EP2983685A1). However, these solutions use live strains which are therefore not stable over time and which can then induce a drop in efficiency over time. Moreover, live strains have a limited effect, due not only to their low stability over time, but also because they depend on the bacterial composition of the subject, which can limit the implantation of new bacteria and consequently their effectiveness.
C’est en étudiant l’effet de la fermentation sur l’efficacité des extraits de thé que la Demanderesse a découvert de manière tout à fait inattendue que ces problèmes peuvent être facilement résolus par l’utilisation d’une composition pharmaceutique comprenant une association de théanine et des polysaccharides extraits deCamellia sinensis, et d’au moins 2 métabolites, typiquement produits par une bactérie Bacillus subtilis, typiquementBacillus subtilis Gozen GZN-08, choisis dans le groupe : acide gallique, lobéline, biotine, catéchine, pyridoxine, acide syringique, butyrate, propionate, zinc, acide linoléique, saikosaponine, acacétine, saponarine, acide butyrique, caractérisée en ce que ladite composition module le microbiote pulmonaire et module l’intensité de la réponse du système immunitaire.It was by studying the effect of fermentation on the effectiveness of tea extracts that the Applicant discovered quite unexpectedly that these problems can be easily solved by the use of a pharmaceutical composition comprising a combination of theanine and polysaccharides extracted from Camellia sinensis , and from at least 2 metabolites, typically produced by a Bacillus subtilis bacterium, typically Bacillus subtilis Gozen GZN-08 , chosen from the group: gallic acid, lobeline, biotin, catechin, pyridoxine, acid syringic, butyrate, propionate, zinc, linoleic acid, saikosaponin, acacetin, saponarin, butyric acid, characterized in that said composition modulates the pulmonary microbiota and modulates the intensity of the response of the immune system.
RESUMÉSUMMARY
Dans un premier aspect l’invention concerne une composition pharmaceutique comprenant une association de bioactifs comprenant de la théanine et des polysaccharides extraits des feuilles de matchaCamellia sinensis, et au moins 2 métabolites produits par une bactérieBacillus subtilis, choisis dans le groupe : acide gallique, lobéline, biotine, catéchine, pyridoxine, acide syringique, butyrate, propionate, zinc, acide linoléique, saikosaponine, acacétine, saponarine. Typiquement, la composition pharmaceutique est destinée à moduler le microbiote pulmonaire et à moduler l’intensité de la réponse du système immunitaire.In a first aspect, the invention relates to a pharmaceutical composition comprising a combination of bioactives comprising theanine and polysaccharides extracted from Camellia sinensis matcha leaves, and at least 2 metabolites produced by a Bacillus subtilis bacterium, chosen from the group: gallic acid , lobeline, biotin, catechin, pyridoxine, syringic acid, butyrate, propionate, zinc, linoleic acid, saikosaponin, acacetin, saponarin. Typically, the pharmaceutical composition is intended to modulate the pulmonary microbiota and to modulate the intensity of the response of the immune system.
Dans un mode de réalisation la composition pharmaceutique comprend du zinc à une concentration d’au moins 0,5% et de préférence d’au moins 2% en poids par rapport au poids total de bioactifs dans ladite composition et des polysaccharides à une concentration d’au moins 0,5% et de préférence d’au moins 5%.In one embodiment, the pharmaceutical composition comprises zinc at a concentration of at least 0.5% and preferably at least 2% by weight relative to the total weight of bioactives in said composition and polysaccharides at a concentration of at least 0.5% and preferably at least 5%.
La composition pharmaceutique de l’invention peut être sous la forme de poudre ou d’émulsion lyophilisée. Elle peut être notamment sous forme de crèmes, liquides, pâtes, inhalateurs, lotions, émulsions, gels, sirops, solides, sirop, poudres, masques, stick, comprimés, sprays, aérosol, gélules, huiles, ou boisson prête à l’emploi.The pharmaceutical composition of the invention may be in the form of a powder or a freeze-dried emulsion. It may in particular be in the form of creams, liquids, pastes, inhalers, lotions, emulsions, gels, syrups, solids, syrup, powders, masks, sticks, tablets, sprays, aerosols, capsules, oils, or ready-to-use drinks. .
L’invention concerne également un procédé de préparation d’une composition pharmaceutique selon l’invention. Le procédé comprend au moins une étape de fermentation lente deCamelia sinensisen présence de la bactérieBacillus subtilis Gozen GZN-08.The invention also relates to a process for the preparation of a pharmaceutical composition according to the invention. The method comprises at least one step of slow fermentation of Camelia sinensis in the presence of the bacterium Bacillus subtilis Gozen GZN-08 .
L’invention concerne en outre la composition pharmaceutique telle que décrite ci-dessus, pour son utilisation dans :The invention further relates to the pharmaceutical composition as described above, for its use in:
- le traitement ou la prévention de la dysbiose, de préférence de la dysbiose pulmonaire et/ou intestinale.- the treatment or prevention of dysbiosis, preferably pulmonary and/or intestinal dysbiosis.
- la diminution des signes de l’inflammation et dans la diminution de production des cytokines pro inflammatoires; dans le rétablissement d’un taux normal de globules blancs et l’augmentation de la production d’anticorps par les lymphocytes ;- the decrease in the signs of inflammation and in the decrease in the production of pro-inflammatory cytokines; in the restoration of a normal level of white blood cells and the increase in the production of antibodies by the lymphocytes;
- le rétablissement d’un taux normal de globules blancs et l’augmentation de la production d’anticorps par les lymphocytes ;- the restoration of a normal level of white blood cells and the increase in the production of antibodies by the lymphocytes;
- l’augmentation de la production d’oxide nitrique par les cellules endothéliales et dans la modulation de la vasodilatation des vaisseaux sanguins ; et/ou- the increase in nitric oxide production by endothelial cells and in the modulation of the vasodilation of blood vessels; and or
- l’augmentation de la stabilité de l’hémoglobine et dans l‘augmentation du taux d’hémoglobine circulante.- the increase in the stability of hemoglobin and in the increase in the level of circulating hemoglobin.
Claims (9)
Pharmaceutical composition according to any one of Claims 1 to 3, for its use in increasing the stability of hemoglobin and in increasing the rate of circulating hemoglobin.
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| FR2109752A FR3126869A1 (en) | 2021-09-16 | 2021-09-16 | Pharmaceutical composition comprising metabolites derived from the bacterium Bacillus subtilis Gozen GZN-08 isolated from Camellia sinensis and modulating the immune response. |
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| FR2109752 | 2021-09-16 | ||
| FR2109752A FR3126869A1 (en) | 2021-09-16 | 2021-09-16 | Pharmaceutical composition comprising metabolites derived from the bacterium Bacillus subtilis Gozen GZN-08 isolated from Camellia sinensis and modulating the immune response. |
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