IT202000002641A1 - ANTIVIRAL COMPOSITIONS - Google Patents
ANTIVIRAL COMPOSITIONS Download PDFInfo
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- IT202000002641A1 IT202000002641A1 IT102020000002641A IT202000002641A IT202000002641A1 IT 202000002641 A1 IT202000002641 A1 IT 202000002641A1 IT 102020000002641 A IT102020000002641 A IT 102020000002641A IT 202000002641 A IT202000002641 A IT 202000002641A IT 202000002641 A1 IT202000002641 A1 IT 202000002641A1
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Classifications
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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
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- 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
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- 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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- A61K31/728—Hyaluronic acid
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
Description
Descrizione del brevetto per invenzione industriale avente per titolo: Description of the patent for industrial invention entitled:
"COMPOSIZIONI ANTIVIRALI" "ANTIVIRAL COMPOSITIONS"
La presente invenzione riguarda composizioni aventi aspecifiche propriet? immunostimolanti, utili per la prevenzione e il trattamento delle infezioni virali, in particolare delle infezioni del tratto respiratorio causate dal coronavirus e/o dal virus dell'influenza. The present invention relates to compositions having non-specific properties. immunostimulants, useful for the prevention and treatment of viral infections, in particular respiratory tract infections caused by the coronavirus and / or the influenza virus.
Background dell'invenzione Background of the invention
La somministrazione di cellule batteriche vive o attenuate ? stata ampiamente studiata come strumento di immunoterapia per la prevenzione e il trattamento di patologie virali o tumorali. Administering live or attenuated bacterial cells? It has been extensively studied as an immunotherapy tool for the prevention and treatment of viral or cancer pathologies.
In particolare, i micobatteri e i corinebatteri sono stati utilizzati in numerosi studi preclinici e clinici. In particular, mycobacteria and corynebacteria have been used in numerous preclinical and clinical studies.
L'approccio immunoterapico rimane il metodo preferito e talvolta l'unico disponibile per le infezioni causate da virus contro i quali non ? stato sviluppato alcun farmaco specifico. The immunotherapy approach remains the preferred and sometimes the only method available for infections caused by viruses against which it does not? no specific drug was developed.
Ad esempio, mentre sono stati recentemente sviluppati efficaci farmaci antivirali per il trattamento delle infezioni da virus dell'immunodeficienza umana (HIV), virus dell'epatite C e virus dell'herpes, nessun farmaco si ? ancora dimostrato efficace contro i virus pi? comuni responsabili delle infezioni respiratorie (e-. g. rinovirus, virus respiratorio sinciziale e virus influenzale) e contro virus come i coronavirus responsabili della recente diffusione di infezioni in Cina o contro i virus responsabili di alcuni dei recenti casi di zoonosi. For example, while effective antiviral drugs have recently been developed to treat infections with human immunodeficiency virus (HIV), hepatitis C virus, and herpes virus, no drugs are. still proven effective against viruses pi? common responsible for respiratory infections (eg rhinovirus, respiratory syncytial virus and influenza virus) and against viruses such as coronaviruses responsible for the recent spread of infections in China or against the viruses responsible for some of the recent cases of zoonosis.
EP 681479 descrive una composizione immunoterapica comprendente una frazione insolubile in acqua della parete cellulare di batteri, in particolare di Mycobacterium phlei, facoltativamente in combinazione con un glicosamminoglicano come l'acido ialuronico. Non ? stata tuttavia fatta alcuna descrizione specifica dell'acido ialuronico e non sono state fornite informazioni sul suo possibile ruolo. EP 681479 describes an immunotherapeutic composition comprising a water-insoluble fraction of the cell wall of bacteria, in particular of Mycobacterium phlei, optionally in combination with a glycosaminoglycan such as hyaluronic acid. Do not ? however, no specific description has been made of hyaluronic acid and no information has been provided on its possible role.
Le propriet? antibatteriche e antivirali dell'acido ialuronico (HA) sono state riportate da in Virol J. 2011; 8: 141. Gli autori hanno concluso che ?lo spettro dell'attivit? antivirale esibito da HA contro virus RNA e DNA, noti per avere diverse strutture (con o senza envelope) e strategie di replicazione, suggerisce un meccanismo d'azione non specifico, probabilmente coinvolgendo i passaggi dell'interazione tra membrana cellulare e virus. I risultati degli esperimenti cinetici supportano questa ipotesi." La tecnica nota nel suo insieme non fornisce tuttavia una conclusione positiva sulla possibilit? di trattare con successo le infezioni virali combinando batteri e glicosamminoglicano. The properties antibacterials and antivirals of hyaluronic acid (HA) were reported by in Virol J. 2011; 8: 141. The authors concluded that it is the spectrum of activity. antiviral exhibited by HA against RNA and DNA viruses, known to have different structures (with or without envelopes) and replication strategies, suggests a non-specific mechanism of action, possibly involving the steps of the interaction between cell membrane and virus. The results of the kinetic experiments support this hypothesis. "However, the known technique as a whole does not provide a positive conclusion on the possibility of successfully treating viral infections by combining bacteria and glycosaminoglycan.
? pertanto necessario migliorare le composizioni che possono prevenire e proteggere dalle infezioni virali, accelerando e attenuando il decorso clinico, riducendo il tasso di mortalit? e i danni ai tessuti parenchimatici di organi (come polmoni, fegato, milza, reni, linfonodi, eccetera.). ? therefore it is necessary to improve the compositions that can prevent and protect from viral infections, accelerating and attenuating the clinical course, reducing the mortality rate? and damage to parenchymal tissues of organs (such as lungs, liver, spleen, kidneys, lymph nodes, etc.).
Descrizione dell'invenzione Description of the invention
? stato ora trovato che l'attivit? immunostimolante delle cellule di Corynebacterium migliora notevolmente includendole in un sistema di rilascio comprendente acido ialuronico, che pu? essere di origine naturale o biosintetica, lineare o reticolato o in forma di complessi di frazioni aventi diverso peso molecolare (basso peso molecolare, in genere da 10 a 300 kDa) e alto peso molecolare, in genere da 1000 a 6000 kDa). Di conseguenza, l'invenzione fornisce composizioni antivirali comprendenti cellule inattivate di Corynebacterium parvum incluse in una matrice comprendente acido ialuronico o suoi sali. In particolare, ? stato trovato che l'acido ialuronico esercita un meccanismo di chemiotassi positiva che attira le cellule CD44 (solitamente leucociti, cellule immunocompetenti e fibroblasti) di un soggetto trattato con le composizioni dell'invenzione. Inoltre, l'acido ialuronico, in considerazione delle sue caratteristiche idrofile, attira nella sua struttura molecole d'acqua con un conseguente rigonfiamento che promuove la vitalit? delle cellule immunitarie e il contatto con le particelle virali intrappolate nella matrice. L'effetto virucida ? quindi potenziato dallo stretto contatto del virus, delle cellule immunitarie e delle cellule immunogeniche del Corynebacterium. ? has now been found that the activity? Corynebacterium cell immunostimulant improves considerably by including them in a delivery system comprising hyaluronic acid, which can be of natural or biosynthetic origin, linear or cross-linked or in the form of complexes of fractions having different molecular weight (low molecular weight, generally from 10 to 300 kDa) and high molecular weight, generally from 1000 to 6000 kDa). Accordingly, the invention provides antiviral compositions comprising inactivated cells of Corynebacterium parvum included in a matrix comprising hyaluronic acid or its salts. In particular, ? it has been found that hyaluronic acid exerts a positive chemotaxis mechanism which attracts CD44 cells (usually leukocytes, immunocompetent cells and fibroblasts) of a subject treated with the compositions of the invention. Furthermore, hyaluronic acid, in consideration of its hydrophilic characteristics, attracts water molecules into its structure with a consequent swelling that promotes vitality. of immune cells and contact with viral particles trapped in the matrix. The virucidal effect? then enhanced by the close contact of the virus, immune cells and Corynebacterium immunogenic cells.
La selezione del tipo di acido ialuronico o dei suoi sali (peso molecolare, lineare o reticolato) consente il controllo del tempo di permanenza all'interno dell'organismo, ad esempio da pochi giorni a diverse settimane, migliorando l'efficacia clinica e promuovendo l?afflusso continuo di nuove cellule immunocompetenti che distruggono le unit? virali. The selection of the type of hyaluronic acid or its salts (molecular weight, linear or cross-linked) allows the control of the residence time inside the organism, for example from a few days to several weeks, improving clinical efficacy and promoting the ? continuous influx of new immunocompetent cells that destroy the units? viral.
L'acido ialuronico, nelle composizioni dell'invenzione, differisce dai coadiuvanti convenzionali utilizzati nella preparazione dei vaccini poich? esercita di per s? un'attivit? antivirale, fungendo da booster cooperando sinergicamente con le cellule di Corynebacterium determinando risultati protettivi/preventivi ottimali in tempi brevi, anche permettendo la cura dell'infezione conclamata. The hyaluronic acid, in the compositions of the invention, differs from the conventional adjuvants used in the preparation of vaccines since exercises itself? an activity? antiviral, acting as a booster cooperating synergistically with the Corynebacterium cells, determining optimal protective / preventive results in a short time, also allowing the cure of the full-blown infection.
Descrizione dettagliata dell'invenzione Detailed description of the invention
Il ceppo preferito di Corynebacterium parvum ha il numero di deposito NCTC 10390, disponibile presso la National Collection of Type Cultures, Colindale, Londra. Raccolta di batteri: Numero NTC: 0387, National Collection of Type Cultures, Porton Down, Salisbury, Regno Unito, nonch? dall'ATCC. Uno o pi? ceppi possono essere vantaggiosamente utilizzati contemporaneamente. In alternativa alle cellule intere o in combinazione con esse, possono anche essere utilizzate frazioni della parete cellulare batterica, ad esempio la frazione denominata p40 descritta in EP 2900274, o estratti batterici comprendenti frazioni di DNA o RNA. The preferred strain of Corynebacterium parvum has NCTC filing number 10390, available from the National Collection of Type Cultures, Colindale, London. Bacteria Collection: NTC Number: 0387, National Collection of Type Cultures, Porton Down, Salisbury, UK, as well as by the ATCC. One or more? strains can advantageously be used simultaneously. As an alternative to whole cells or in combination with them, fractions of the bacterial cell wall can also be used, for example the fraction named p40 described in EP 2900274, or bacterial extracts comprising DNA or RNA fractions.
L'attivit? immunostimolante di C. parvum pu? essere ulteriormente potenziata da adiuvanti quali l-tirosina microcristallina o suoi polimeri, mucopolisaccaridi, selenio e altri oligoelementi. The activity? immunostimulant of C. parvum pu? be further enhanced by adjuvants such as microcrystalline l-tyrosine or its polymers, mucopolysaccharides, selenium and other trace elements.
Le cellule vengono preferibilmente inattivate con metodi convenzionali, come trattamento con fenolo o formaldeide o mediante shock termico o osmotico. La conta cellulare in ciascuna dose della composizione conterr? tipicamente da 2 x 10<6 >a 5 x 10<9 >cellule, generalmente corrispondenti a 2-7 mg di massa batterica. Conteggi inferiori saranno preferibilmente utilizzati per la via inalatoria. The cells are preferably inactivated by conventional methods, such as treatment with phenol or formaldehyde or by thermal or osmotic shock. Will the cell count in each dose of the composition count? typically 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 inhalation route.
L'acido ialuronico a basso peso molecolare ha un peso molecolare medio Mw compreso tra 10 e 300 kDa, preferibilmente tra 20 e 150 kDa, pi? preferibilmente tra 50 e 100 kDa. The low molecular weight hyaluronic acid has an average molecular weight Mw between 10 and 300 kDa, preferably between 20 and 150 kDa, plus? preferably between 50 and 100 kDa.
L'acido ialuronico ad alto peso molecolare ha un peso molecolare medio Mw compreso tra 1000 e 6000 kDa, preferibilmente tra 1000 e 45000 kDa, pi? preferibilmente da 1000 a 3500 kDa. The high molecular weight hyaluronic acid has an average molecular weight Mw between 1000 and 6000 kDa, preferably between 1000 and 45000 kDa, plus? preferably from 1000 to 3500 kDa.
In alternativa agli acidi ialuronici lineari, possono anche essere utilizzate forme reticolate. I derivati dell'acido ialuronico reticolati sono disponibili in commercio o possono essere preparati con metodi noti, come quelli descritti in Carbohydrate polymers, 85, (2011), 469-489. As an alternative to linear hyaluronic acids, cross-linked forms can also be used. Cross-linked hyaluronic acid derivatives are commercially available or can be prepared by known methods, such as those described in Carbohydrate polymers, 85, (2011), 469-489.
Possono essere convenientemente usati anche i complessi di acido ialuronico ad alto e basso peso molecolare descritti in WO 2012032151. The high and low molecular weight hyaluronic acid complexes described in WO 2012032151 can also be conveniently used.
Le dosi di acido ialuronico possono variare entro ampi limiti e saranno in definitiva determinate dalla forma fisica desiderata della composizione (liquido, gel, polvere, spray). La quantit? generalmente varia da 20 a 40 mg per la via inalatoria e da 40 a 100 mg/ml per forma liquida/gel. Dosi pi? elevate sono possibili in considerazione dell'alta tollerabilit? dell'acido ialuronico. The doses of hyaluronic acid can vary within wide limits and will ultimately be determined by the desired physical form of the composition (liquid, gel, powder, spray). The quantity generally it varies from 20 to 40 mg for the inhalation route and from 40 to 100 mg / ml for the liquid / gel form. Doses more? high are possible in consideration of the high tolerability? of hyaluronic acid.
Le composizioni possono essere in forma di gel, adatte per la somministrazione intradermica, o in forma di polvere micronizzata, adatte per inalazione, preparate disperdendo le cellule batteriche inattivate (liofilizzate o liofilizzate) in una polvere di micronizzata (20-40 micron) acido ialuronico. The compositions can be in gel form, suitable for intradermal administration, or in the form of micronized powder, suitable for inhalation, prepared by dispersing the inactivated bacterial cells (lyophilized or lyophilized) in a micronized powder (20-40 micron) hyaluronic acid. .
Le composizioni in polvere possono essere inalate per mezzo di dispositivi noti come quelli noti come inalatori di polvere a base di capsule (Pill-haler?, Breezhaler?) e dispositivi simili. La miscela di particolato viene inalata nelle vie respiratorie medie e basse, sensibilizzando le strutture cellulari lungo l'albero respiratorio, dall'anello tonsillare di Waldeier, una struttura comprendente una catena di aggregati linfocitari e strutture linfoidi situate nella cavit? orale, alla trachea e agli alveoli polmonari. The powder compositions can 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 into the middle and lower respiratory tract, sensitizing the cellular structures along the respiratory tree, from Waldeier's tonsillar ring, a structure comprising a chain of lymphocyte aggregates and lymphoid structures located in the cavity. oral, trachea and pulmonary alveoli.
La polvere idratata del liquido interstiziale forma sulle mucose un biofilm idrofilo che attira le cellule immunocompetenti, immobilizzando le particelle virali libere o le cellule infette da virus, esponendole all'inattivazione indotta dal Corynebacterium parvum attraverso l'immuno-potenziamento delle cellule dendritiche e alla loro rimozione mediante fagocitosi e alla soppressione delle particelle virali mediante interferone secreto dalle cellule stesse. The hydrated powder of the interstitial fluid forms a hydrophilic biofilm on the mucous membranes that attracts immunocompetent cells, immobilizing free viral particles or virus-infected cells, exposing them to inactivation induced by Corynebacterium parvum through the immuno-enhancement of dendritic cells and their removal by phagocytosis and suppression of viral particles by interferon secreted by the cells themselves.
L'inalazione di polvere consente, nei protocolli di prevenzione, la formazione di un rivestimento sulla mucosa respiratoria, allertando i meccanismi di difesa e impedendo l'ingresso dei virus nelle cellule dell'epitelio respiratorio, prevenendo cos? anche l'espansione della polmonite virale o l'insorgenza di danni infiammatori di altri tessuti parenchimatici. The inhalation of dust allows, in the prevention protocols, the formation of a coating on the respiratory mucosa, alerting the defense mechanisms and preventing the entry of viruses into the cells of the respiratory epithelium, thus preventing? also the expansion of viral pneumonia or the onset of inflammatory damage of other parenchymal tissues.
A scopo preventivo ? raccomandata un'inalazione due volte al giorno, mentre per la terapia sono indicate da tre a sei somministrazioni, che durano fino a sei giorni o pi?. For preventive purposes? inhalation twice a day is recommended, while three to six doses are indicated for therapy, lasting up to six days or more.
Le composizioni dell'invenzione possono anche essere assorbite su un materiale spugnoso adatto per l'inserimento nella cavit? nasale. Un esempio di materiale adatto ? il collagene eterologo liofilizzato. The compositions of the invention can also be absorbed onto a spongy material suitable for insertion into the cavity. nasal. An example of suitable material? lyophilized heterologous collagen.
Le spugne possono essere inserite nelle narici in ciascuna coana, dove sono modellate mediante un massaggio esterno della pelle esterna del naso. La spugna rimane in situ fino a quando non viene lisata e sciolta dopo aver recuperato le cellule infiammatorie viventi trasudate dalla sub-mucosa nasale, neutralizzando i virus e prevenendo la loro diffusione verso altri tessuti/organi. The sponges can be inserted into the nostrils in each choana, where they are shaped by an external massage of the outer skin of the nose. The sponge remains in place until it is lysed and dissolved after recovering the living inflammatory cells exuded from the nasal sub-mucosa, neutralizing the viruses and preventing their spread to other tissues / organs.
Le composizioni in forma di gel, liquido o spray sono somministrate per via intradermica o sottocutanea in modo da indurre un wheal che agisce come stimolante sistemico delle difese immunitarie. The compositions in the form of gel, liquid or spray are administered intradermally or subcutaneously in order to induce a wheal which acts as a systemic stimulant of the immune defenses.
Le composizioni dell'invenzione possono anche essere somministrate per via topica, sotto forma di lozioni, pomate, creme, gel, supposte o ovuli, per il trattamento di dermatiti o malattie della pelle, vaginali, anali o dell'orecchio causate da virus. Dette composizioni topiche possono anche comprendere agenti cheratolitici come l?acido salicilico, vitamine, tensioattivi, glicoli o altri agenti utili. In caso di somministrazione topica, della pelle o delle mucose per contrastare le infezioni virali localizzate, altre forme adatte includono crema, gel, liquido (latte) o spray o polvere per lesioni essudanti o aree della pelle sudate bagnate (come inguine, ascelle, ecc.). The compositions of the invention can also be administered topically, in the 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 can also comprise keratolytic agents such as salicylic acid, vitamins, surfactants, glycols or other useful agents. In case of topical, skin or mucosal administration to counter localized viral infections, other suitable forms include cream, gel, liquid (milk) or spray or powder for exuding lesions or wet sweaty skin areas (such as groin, armpits, etc. .).
Se necessario, le composizioni possono essere somministrate sia per via inalatoria sia per via parenterale, simultaneamente o separatamente, essendo preferita la via intradermica quando si desidera la protezione massima e persistente. If necessary, the compositions can be administered both by inhalation and parenterally, simultaneously or separately, the intradermal route being preferred when maximum and persistent protection is desired.
La via inalatoria ? particolarmente indicata in caso di infezioni da virus infiammatorio localizzate come tracheite, bronchite, polmonite interstiziale, alveolite, laringite, tonsillite, faringite, al fine di ripristinare rapidamente le funzioni fisiologiche delle funzioni respiratorie. The inhalation route? particularly indicated in case of localized inflammatory virus infections such as tracheitis, bronchitis, interstitial pneumonia, alveolitis, laryngitis, tonsillitis, pharyngitis, in order to quickly restore the physiological functions of respiratory functions.
Le composizioni dell'invenzione sono caratterizzate da un'eccezionale efficacia nel contrastare le infezioni di diversi tipi di virus patogeni per le specie umane e animali, come conseguenza di una marcata increzione di interferone dai leucociti dopo 24-72 ore dalla somministrazione. Allo stesso modo, aumenta anche il numero e l'attivit? delle cellule T killer e dei macrofagi. The compositions of the invention are characterized by an exceptional efficacy in contrasting the infections of different types of pathogenic viruses for human and animal species, as a consequence of a marked increase of interferon from leukocytes after 24-72 hours from administration. Likewise, the number and activity also increases. killer T cells and macrophages.
Le composizioni dell'invenzione sono utili anche per il trattamento di infezioni cutanee o cutanee da batteri, protozoi e miceti. The compositions of the invention are also useful for the treatment of skin or skin infections by bacteria, protozoa and fungi.
L'invenzione ? descritta pi? dettagliatamente nel seguente Esempio 1. The invention? described more? in detail in the following Example 1.
Esempio 1 - Prove cliniche preliminari Example 1 - Preliminary clinical trials
17 pazienti affetti da infezioni virali di diversa origine sono stati trattati con una composizione costituita da 5.000.000 di cellule di Corynebacterium parvum inattivate liofilizzate NCTC 10390 in 1 ml di acido ialuronico. Il programma di somministrazione e i risultati sono riportati nella seguente Tabella 1. 17 patients with viral infections of different origins were treated with a composition consisting of 5,000,000 lyophilized NCTC 10390 inactivated Corynebacterium parvum cells in 1 ml of hyaluronic acid. The administration schedule and results are shown in the following Table 1.
Tabella 1 Table 1
Claims (15)
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| IT102020000002641A IT202000002641A1 (en) | 2020-02-11 | 2020-02-11 | ANTIVIRAL COMPOSITIONS |
| CN202010149922.4A CN113244384A (en) | 2020-02-11 | 2020-03-06 | Antiviral composition |
| PCT/EP2021/052956 WO2021160559A1 (en) | 2020-02-11 | 2021-02-08 | Antiviral compositions |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994016727A1 (en) * | 1993-01-29 | 1994-08-04 | Vetrepharm, Inc. | Immunotherapeutic composition |
| WO2012032151A2 (en) | 2010-09-09 | 2012-03-15 | Altergon S.A. | Hybrid cooperative complexes of hyaluronic acid |
| EP2900274A2 (en) | 2012-09-25 | 2015-08-05 | Claride Pharma S.A. | Conjugate of a fragment of a cellular wall of a bacterium and a mucopolysaccharidic carrier, and uses in medicine thereof |
-
2020
- 2020-02-11 IT IT102020000002641A patent/IT202000002641A1/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994016727A1 (en) * | 1993-01-29 | 1994-08-04 | Vetrepharm, Inc. | Immunotherapeutic composition |
| EP0681479A1 (en) | 1993-01-29 | 1995-11-15 | Vetrepharm, Inc. | Immunotherapeutic composition |
| WO2012032151A2 (en) | 2010-09-09 | 2012-03-15 | Altergon S.A. | Hybrid cooperative complexes of hyaluronic acid |
| EP2900274A2 (en) | 2012-09-25 | 2015-08-05 | Claride Pharma S.A. | Conjugate of a fragment of a cellular wall of a bacterium and a mucopolysaccharidic carrier, and uses in medicine thereof |
Non-Patent Citations (11)
| Title |
|---|
| ALESSANDRO DI CERBO ET AL: "Comparison of the effects of hyaluronidase and hyaluronic acid on probiotics growth", BMC MICROBIOLOGY, BIOMED CENTRAL LTD, GB, vol. 13, no. 1, 4 November 2013 (2013-11-04), pages 243, XP021165871, ISSN: 1471-2180, DOI: 10.1186/1471-2180-13-243 * |
| 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 |
| CERMELLI, PALMIERI ET AL., VIROL J., vol. 8, 2011, pages 141 |
| 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 * |
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