WO2021160559A1 - Compositions antivirales - Google Patents

Compositions antivirales Download PDF

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Publication number
WO2021160559A1
WO2021160559A1 PCT/EP2021/052956 EP2021052956W WO2021160559A1 WO 2021160559 A1 WO2021160559 A1 WO 2021160559A1 EP 2021052956 W EP2021052956 W EP 2021052956W WO 2021160559 A1 WO2021160559 A1 WO 2021160559A1
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WO
WIPO (PCT)
Prior art keywords
composition according
compositions
cells
hyaluronic acid
salts
Prior art date
Application number
PCT/EP2021/052956
Other languages
English (en)
Inventor
Beniamino Palmieri
Original Assignee
Altergon S.A.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from IT102020000002641A external-priority patent/IT202000002641A1/it
Priority claimed from IT102020000002866A external-priority patent/IT202000002866A1/it
Application filed by Altergon S.A. filed Critical Altergon S.A.
Publication of WO2021160559A1 publication Critical patent/WO2021160559A1/fr

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Classifications

    • 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
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/05—Actinobacteria, e.g. Actinomyces, Streptomyces, Nocardia, Bifidobacterium, Gardnerella, Corynebacterium; Propionibacterium
    • 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
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
    • A61K2039/521—Bacterial cells; Fungal cells; Protozoal cells inactivated (killed)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541—Mucosal route
    • A61K2039/543—Mucosal route intranasal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles

Definitions

  • the present invention concerns compositions having aspecific immunostimulant properties useful for the prevention and treatment of viral infections, particularly of infections of the respiratory tract caused by corona virus and/or influenza virus.
  • Mycobacteria and Corynebacteria have been used in a number of preclinical and clinical studies.
  • the immunotherapeutic approach remains the preferred and sometimes the only approach available for infections caused by viruses against which no specific drug has been developed.
  • HIV human immunodeficiency virus
  • hepatitis C virus hepatitis C virus
  • Herpes virus no drug has yet proven effective against the most common viruses responsible of respiratory infections (e-.g. rhinovirus, respiratory syncytial virus and influenza virus) and against viruses such as Coronaviruses responsible of the recent outspread of infections in China or against viruses responsible of some of the recent cases of zoonosis.
  • viruses responsible of respiratory infections e-.g. rhinovirus, respiratory syncytial virus and influenza virus
  • Coronaviruses responsible of the recent outspread of infections in China or against viruses responsible of some of the recent cases of zoonosis.
  • EP 681479 discloses an immunotherapeutic composition
  • an immunotherapeutic composition comprising a water insoluble fraction of the cell wall of bacteria, particularly of Mycobacterium phlei , optionally in combination with a glycosaminoglycan such as hyaluronic acid. No specific disclosure has however been made of hyaluronic acid and no information has been provided as to its possible role.
  • HA hyaluronic acid
  • compositions which may prevent and protect from the viral infections, accelerating and attenuating the clinical course, reducing the death rate and the damages to parenchymal tissues of organs such as lungs, liver, spleen, kidneys, lymph nodes, etc.).
  • hyaluronic acid or salts thereof which may be of natural or biosynthetic origin, linear or cross-linked or in form of complexes of fractions having different molecular weight (low molecular weight, typically from 10 to 300 kDa) and high molecular weight, typically from 1000 to 6000 kDa).
  • Sodium hyaluronans are the most commonly used hyaluronic acid salts.
  • the invention accordingly provides antiviral compositions comprising inactivated cells of Corynebacterium parvum included in a matrix comprising hyaluronic acid or salts thereof.
  • hyaluronic acid exerts a mechanism of positive chemiotaxis attracting theCD44 + cells (usually leucocytes, immunocompetent cells and fibroblasts) of a subject treated with the compositions of the invention.
  • hyaluronic acid in view of its hydrophilic characteristics, attracts in its structure water molecules with a consequent swelling promoting the immune cells viability and the contact with the viral particles entrapped within the matrix. The virucidal effect is thereby enhanced by the close contact of the virus, the immune cells and the immunogenic Corynebacterium cells.
  • hyaluronic acid or of salts thereof allows the control of the residence time within the organism, for instance from a few days to several weeks, enhancing the clinical efficacy and promoting the continuous afflux of new immunocompetent cells destroying the viral units.
  • Hyaluronic acid in the compositions of the invention, differs from the conventional adjuvants used in the preparation of vaccines since it also exerts by its own an antiviral activity, acting as a booster co-operating synergistically with Corynebacterium cells determining optimal protective/preventive results in short times, even allowing the cure of the full-blown infection.
  • the preferred strain of Corynebacterium parvum has the deposit number NCTC 10390, available from the obtained from the National Collection of Type Cultures, Colindale, London. Bacteria Collection: NTC Number:0387.
  • fractions of the bacterial cell wall may also be used, for instance the fraction named p40 disclosed in EP 2900274, or bacterial extracts comprising DNA or RNA fractions.
  • the immunostimulant activity of C. parvum may further be enhanced by adjuvants such microcrystalline 1-tyrosine or polymers thereof, mucopolysaccharides, selenium and other oligoelements.
  • the cells are preferably inactivated by conventional methods as treatment with phenol or formaldehyde or by thermal or osmotic shock.
  • the cell counts in each dose of the composition will typically contain from 2 x 10 6 to 5 x 10 9 cells, generally corresponding to 2-7 mg of bacterial mass. Lower counts will preferably be used for the inhalatory route.
  • the low molecular weight hyaluronic acid or hyaluronan has an average molecular weight Mw ranging from 10 to 300 kDa, preferably from 20 to 150 kDa, more preferably from 50 to 100 kDa.
  • the high molecular weight hyaluronic acid or hyaluronan has an average molecular weight Mw ranging from 1000 to 6000 kDa, preferably from 1000 to 45000 kDa, more preferably from 1000 to 3500 kDa.
  • cross-linked forms may also be used.
  • Cross- linked hyaluronic acid derivatives are commercially available or may prepared by known methods, such as those disclosed in Carbohydrate polymers, 85, (2011), 469-489.
  • hyaluronic acid or of salts thereof may vary within wide limits and will be ultimately determined by the desired physical form of the composition (liquid, gel, powder, spray).
  • the amount will generally range from 20 to 40 mg for the inhalatory route and from 40 to 100 mg/ml for liquid/gel form. Higher doses are possible in view of the high tolerability of hyaluronic acid.
  • compositions may be in form of gel, suitable for intradermal administration, or in form of micronized powder, suitable for inhalation, prepared by dispersing the inactivated bacterial cells (freeze-dried or lyophilized) in a powder of micronized (20-40 micron) hyaluronic acid or hyaluronan.
  • compositions in powder form may be inhaled by means of known devices such as those known as capsule based powder inhalers (Pill-haler®, Breezhaler®) and similar devices.
  • the particulate mixture is inhaled in the medium and low respiratory airways sensitizing the cellular structures along the respiratory tree, from the tonsillar Waldeier ring, a structure comprising a chain of lymphocyte aggregates and lymphoid structures located in the oral cavity, to the trachea and lung alveoli.
  • the powder hydrated by the interstitial liquid forms on the mucosae an hydrophilic biofilm attracting the immunocompetent cells, immobilizing the free viral particles or the virus-infected cells, exposing them to the inactivation induced by Corynebacterium parvum through immuno-potentiation of dendritic cells as well as to their removal by phagocytosis and to the suppression of the viral particles by means of interferon secreted by the cell themselves.
  • the powder inhalation allows, in prevention protocols, the formation of a coating over the respiratory mucosa, alerting the defense mechanisms and preventing the entry of the viruses into the cells of the respiratory epithelium, preventing thereby also the expansion of viral granulomatous pneumonia or the onset of inflammatory damages of other parenchymal tissues.
  • compositions of the invention may also be absorbed on a sponge material suitable for insertion into the nasal cavity.
  • a sponge material suitable for insertion into the nasal cavity.
  • suitable material is lyophilized heterologous collagen.
  • the sponges may be inserted in the nostrils in each choana, where are shaped by means of an external massage of the outer nose skin.
  • the sponge remains in situ until it is lysed and dissolved after having scavenged the living inflammatory cells transudated from the nasal sub-mucosa, neutralizing the viruses and preventing their diffusion towards other tissues/organs.
  • compositions in form of gel, liquid or spray are administered by the intradermal or subcutaneous route so as to induce a wheal acting as a systemic stimulant of immune defenses.
  • compositions of the invention may also be administered topically, in form of lotions, ointments, creams, gels, suppositories or ovules for the treatment of dermatitis or skin, vaginal, anal or ear diseases caused by viruses.
  • Said topical compositions may also comprise keratolytic agents such as salicylic acid, vitamins, surfactants, glycols or other useful agents.
  • keratolytic agents such as salicylic acid, vitamins, surfactants, glycols or other useful agents.
  • other suitable forms included cream, gel, fluid (milk) or spray or powder for exudating lesions or wet sweating skin areas (such as groin, axillae etc.).
  • the compositions may be administered both by the inhalatory and by the parenteral route, either simultaneously or separately, the intradermal route being preferred when the maximal and persistent protection is desired.
  • the inhalatory route is especially indicated in case of localized inflammatory virus infections such as tracheitis, bronchitis, interstitial pneumonia, alveolitis, laryngitis, tonsillitis, pharyngitis, in order to quick recovery the physiological functions of the respiratory functions.
  • the compositions of the invention are characterized by outstanding efficacy in contrasting infections by different types of pathogenic viruses for human and animal species, as a consequence of a very marked incretion of interferon from the leukocytes after 24-72 hours from the administration. Likewise, the number and the activity of the killer T-cells and of macrophages is also increased.
  • the compositions of the invention are also useful for the treatment of cutaneous or skin infections by bacteria, protozoa and mycetes.

Abstract

L'invention concerne une composition antivirale et anti-infectieuse comprenant des cellules inactivées de Corynebacterium parvum incluses dans une matrice comprenant de l'acide hyaluronique ou des sels de celui-ci. Les compositions de l'invention sont pourvues de propriétés antivirales et immunostimulantes et peuvent être administrées avantageusement pour la prévention et le traitement d'une infection par des virus et d'autres agents infectieux. Les compositions, sous forme de gels, de liquides ou de poudres, peuvent être administrées par voie inhalatoire, topique ou systémique.
PCT/EP2021/052956 2020-02-11 2021-02-08 Compositions antivirales WO2021160559A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IT102020000002641A IT202000002641A1 (it) 2020-02-11 2020-02-11 Composizioni antivirali
IT102020000002641 2020-02-11
IT102020000002866A IT202000002866A1 (it) 2020-02-13 2020-02-13 Composizioni antivirali
IT102020000002866 2020-02-13

Publications (1)

Publication Number Publication Date
WO2021160559A1 true WO2021160559A1 (fr) 2021-08-19

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Country Status (2)

Country Link
CN (1) CN113244384A (fr)
WO (1) WO2021160559A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024079492A1 (fr) * 2022-10-12 2024-04-18 Semmelweis Egyetem Souches de corynebacterium, associations et formulations lyophilisées associées destinées à être utilisées dans la prévention d'une infection virale

Citations (3)

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Publication number Priority date Publication date Assignee Title
WO1994016727A1 (fr) * 1993-01-29 1994-08-04 Vetrepharm, Inc. Composition immunotherapeutique
WO2012032151A2 (fr) 2010-09-09 2012-03-15 Altergon S.A. Complexes hybrides coopératifs d'acide hyaluronique
EP2900274A2 (fr) 2012-09-25 2015-08-05 Claride Pharma S.A. Conjugué d'un fragment d'une paroi cellulaire d'une bactérie et d'un vecteur mucopolysaccharidique, et utilisations médicales associées

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994016727A1 (fr) * 1993-01-29 1994-08-04 Vetrepharm, Inc. Composition immunotherapeutique
EP0681479A1 (fr) 1993-01-29 1995-11-15 Vetrepharm, Inc. Composition immunotherapeutique
WO2012032151A2 (fr) 2010-09-09 2012-03-15 Altergon S.A. Complexes hybrides coopératifs d'acide hyaluronique
EP2900274A2 (fr) 2012-09-25 2015-08-05 Claride Pharma S.A. Conjugué d'un fragment d'une paroi cellulaire d'une bactérie et d'un vecteur mucopolysaccharidique, et utilisations médicales associées

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ANONYMOUS: "Immunovag Tubo gel vaginale utile per prurito e irritazione 35ml", 19 October 2020 (2020-10-19), XP055741495, Retrieved from the Internet <URL:https://www.amicafarmacia.com/immunovag-tubo-gel-vaginale-utile-per-prurito-e-irritazione-35ml.html> [retrieved on 20201019] *
B. PALMIERI ET AL: "Propionibacterium Acnes: A Putative Immunemodulating Weapon Against the Coronavirus Impending Epidemy", INTERNATIONAL JOURNAL OF INNOVATIVE SCIENCE AND RESEARCH TECHNOLOGY, vol. 5, no. 2, 29 February 2020 (2020-02-29), pages 431 - 440, XP055738749 *
BENIAMINO PALMIERI ET AL: "The long-standing history of Corynebacterium parvum , immunity, and viruses", JOURNAL OF MEDICAL VIROLOGY, vol. 92, no. 11, 30 May 2020 (2020-05-30), US, pages 2429 - 2439, XP055738669, ISSN: 0146-6615, DOI: 10.1002/jmv.26100 *
C. S. CUMMINS ET AL: "Corynebacterium parvum: a synonym for Propionibacterium acnes?", J GEN MICROBIOL ., vol. 80, no. 2, 1 January 1974 (1974-01-01), pages 433 - 442, XP055738684 *
CARBOHYDRATE POLYMERS, vol. 85, 2011, pages 469 - 489
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LUCA RONCATI ET AL: "COVID-19 vaccine and boosted immunity: nothing ad interim to do?", VACCINE, 1 October 2020 (2020-10-01), AMSTERDAM, NL, XP055739665, ISSN: 0264-410X, DOI: 10.1016/j.vaccine.2020.10.013 *
MAK N K ET AL: "Protection of mice against influenza virus infection: Enhancement of nonspecific cellular responses by Corynebacterium parvum", CELLULAR IMMUNOLOGY, ACADEMIC PRESS, SAN DIEGO, CA, US, vol. 78, no. 2, 1 June 1983 (1983-06-01), pages 314 - 325, XP024006642, ISSN: 0008-8749, [retrieved on 19830601], DOI: 10.1016/0008-8749(83)90286-1 *
MELIS GIAN BENEDETTO ET AL: "The stimulation of the vaginal immune system with short-term administration of a vaginal gel containing fraction of Propionibacterium acnes, hyaluronic acid and polycarbophil is efficacious in vaginal infections dependent on disorders in the vaginal ecosystem.", GYNECOLOGICAL ENDOCRINOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF GYNECOLOGICAL ENDOCRINOLOGY OCT 2018, vol. 34, no. 10, October 2018 (2018-10-01), pages 880 - 883, XP009523443, ISSN: 1473-0766 *
NILTON NASSER: "Treatment of common warts with the immune stimulant Propionium bacterium parvum", ANAIS BRASILEIROS DE DERMATOLOGIA, vol. 87, no. 4, 1 August 2012 (2012-08-01), BR, pages 585 - 589, XP055742151, ISSN: 0365-0596, DOI: 10.1590/S0365-05962012000400011 *
PALMIERI BENIAMINO ET AL: "Letter to the Editor: Corynebacterium Parvum ( Propionibacterium Acnes ): Cytokines Cells, Innate Immunity, and Putative Antiviral Adoption", JOURNAL OF INTERFERON AND CYTOKINE RESEARCH., vol. 41, no. 3, 1 March 2021 (2021-03-01), US, pages 132 - 136, XP055801715, ISSN: 1079-9907, DOI: 10.1089/jir.2020.0216 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024079492A1 (fr) * 2022-10-12 2024-04-18 Semmelweis Egyetem Souches de corynebacterium, associations et formulations lyophilisées associées destinées à être utilisées dans la prévention d'une infection virale

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