IT202000022414A1 - PHARMACEUTICAL COMPOUNDS OF THE CLASS OF ANTIBIOTICS AND CHEMOTHERAPICS FOR USE IN THE PREVENTION AND TREATMENT OF CORONAVIRUS DISEASES, SUCH AS COVID-19, IN BOTH HUMAN AND VETERINARY MEDICINE FIELDS. - Google Patents
PHARMACEUTICAL COMPOUNDS OF THE CLASS OF ANTIBIOTICS AND CHEMOTHERAPICS FOR USE IN THE PREVENTION AND TREATMENT OF CORONAVIRUS DISEASES, SUCH AS COVID-19, IN BOTH HUMAN AND VETERINARY MEDICINE FIELDS. Download PDFInfo
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- IT202000022414A1 IT202000022414A1 IT102020000022414A IT202000022414A IT202000022414A1 IT 202000022414 A1 IT202000022414 A1 IT 202000022414A1 IT 102020000022414 A IT102020000022414 A IT 102020000022414A IT 202000022414 A IT202000022414 A IT 202000022414A IT 202000022414 A1 IT202000022414 A1 IT 202000022414A1
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- pharmaceutical compounds
- amoxicillin
- covid
- human
- antibiotics
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- 150000001875 compounds Chemical class 0.000 title claims description 23
- 241000711573 Coronaviridae Species 0.000 title claims description 14
- 201000010099 disease Diseases 0.000 title claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 9
- 208000025721 COVID-19 Diseases 0.000 title claims description 8
- 230000002265 prevention Effects 0.000 title claims description 6
- 239000003242 anti bacterial agent Substances 0.000 title description 8
- 229940088710 antibiotic agent Drugs 0.000 title description 8
- 229960003022 amoxicillin Drugs 0.000 claims description 16
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims description 16
- 229960000282 metronidazole Drugs 0.000 claims description 16
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims description 16
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims description 16
- 229960004099 azithromycin Drugs 0.000 claims description 13
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 claims description 13
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- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims description 6
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- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 claims description 6
- IPWKIXLWTCNBKN-UHFFFAOYSA-N Madelen Chemical compound CC1=NC=C([N+]([O-])=O)N1CC(O)CCl IPWKIXLWTCNBKN-UHFFFAOYSA-N 0.000 claims description 4
- 108010053950 Teicoplanin Proteins 0.000 claims description 4
- 229960002129 cefixime Drugs 0.000 claims description 4
- OKBVVJOGVLARMR-QSWIMTSFSA-N cefixime Chemical compound S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QSWIMTSFSA-N 0.000 claims description 4
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- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 claims description 4
- DDTDNCYHLGRFBM-YZEKDTGTSA-N chembl2367892 Chemical compound CC(=O)N[C@H]1[C@@H](O)[C@H](O)[C@H](CO)O[C@H]1O[C@@H]([C@H]1C(N[C@@H](C2=CC(O)=CC(O[C@@H]3[C@H]([C@H](O)[C@H](O)[C@@H](CO)O3)O)=C2C=2C(O)=CC=C(C=2)[C@@H](NC(=O)[C@@H]2NC(=O)[C@@H]3C=4C=C(O)C=C(C=4)OC=4C(O)=CC=C(C=4)[C@@H](N)C(=O)N[C@H](CC=4C=C(Cl)C(O5)=CC=4)C(=O)N3)C(=O)N1)C(O)=O)=O)C(C=C1Cl)=CC=C1OC1=C(O[C@H]3[C@H]([C@@H](O)[C@H](O)[C@H](CO)O3)NC(C)=O)C5=CC2=C1 DDTDNCYHLGRFBM-YZEKDTGTSA-N 0.000 claims description 4
- 229960002313 ornidazole Drugs 0.000 claims description 4
- 229960001608 teicoplanin Drugs 0.000 claims description 4
- HJLSLZFTEKNLFI-UHFFFAOYSA-N Tinidazole Chemical compound CCS(=O)(=O)CCN1C(C)=NC=C1[N+]([O-])=O HJLSLZFTEKNLFI-UHFFFAOYSA-N 0.000 claims description 3
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- 208000025370 Middle East respiratory syndrome Diseases 0.000 claims description 2
- ZVGNESXIJDCBKN-WUIGKKEISA-N R-Tiacumicin B Natural products O([C@@H]1[C@@H](C)O[C@H]([C@H]([C@H]1O)OC)OCC1=CC=CC[C@H](O)C(C)=C[C@@H]([C@H](C(C)=CC(C)=CC[C@H](OC1=O)[C@@H](C)O)O[C@H]1[C@H]([C@@H](O)[C@H](OC(=O)C(C)C)C(C)(C)O1)O)CC)C(=O)C1=C(O)C(Cl)=C(O)C(Cl)=C1CC ZVGNESXIJDCBKN-WUIGKKEISA-N 0.000 claims 1
- ZVGNESXIJDCBKN-UUEYKCAUSA-N fidaxomicin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@H]([C@H]1O)OC)OCC\1=C/C=C/C[C@H](O)/C(C)=C/[C@@H]([C@H](/C(C)=C/C(/C)=C/C[C@H](OC/1=O)[C@@H](C)O)O[C@H]1[C@H]([C@@H](O)[C@H](OC(=O)C(C)C)C(C)(C)O1)O)CC)C(=O)C1=C(O)C(Cl)=C(O)C(Cl)=C1CC ZVGNESXIJDCBKN-UUEYKCAUSA-N 0.000 claims 1
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Classifications
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/424—Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
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- A—HUMAN NECESSITIES
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
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- A—HUMAN NECESSITIES
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- 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
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- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Composti farmaceutici della classe degli antibiotici e chemioterapici per l?uso nella prevenzione e nel trattamento delle malattie da coronavirus, come Covid-19, in ambito sia di medicina umana sia di medicina veterinaria. Pharmaceutical compounds of the class of antibiotics and chemotherapeutics for use in the prevention and treatment of coronavirus diseases, such as Covid-19, in both human medicine and veterinary medicine.
La presente invenzione concerne composti farmaceutici della classe degli antibiotici e chemioterapici per l?uso nella prevenzione e nel trattamento delle malattie da coronavirus, come Covid-19, in ambito sia di medicina umana sia di medicina veterinaria. In particolare, i suddetti composti sono capaci di produrre la diminuzione della replicazione dei patogeni virali che utilizzano, attraverso altri meccanismi biologici di tipo fagico o modello analogo, le cellule batteriche per la loro replicazione e moltiplicazione. E? noto che il virus SARS-CoV-2 ha manifestato il suo potere negli ultimi 10 mesi. Attualmente circa 20 milioni di persone risultano contagiate e pi? di ottocentomila sono morte in tutto il mondo. The present invention relates to pharmaceutical compounds of the class of antibiotics and chemotherapeutics for use in the prevention and treatment of coronavirus diseases, such as Covid-19, in both human medicine and veterinary medicine. In particular, the aforesaid compounds are capable of reducing the replication of viral pathogens which use, through other biological mechanisms of the phage type or analogous model, bacterial cells for their replication and multiplication. AND? known that the SARS-CoV-2 virus has manifested its power in the last 10 months. Currently about 20 million people are infected and more? of eight hundred thousand died worldwide.
I virus appartenenti alla categoria coronavirus si dividono in cinque classi e molti di essi causano malattie gastrointestinali nei seguenti animali, oltre che nell?uomo: suino, bovino e volatili (Bovine-like Coronaviruses in domestic and wild ruminants,2015). The viruses belonging to the coronavirus category are divided into five classes and many of them cause gastrointestinal diseases in the following animals, as well as in humans: pigs, cattle and birds (Bovine-like Coronaviruses in domestic and wild ruminants, 2015).
Ad oggi non sono disponibili cure efficaci contro le malattie causate dall?infezione da coronavirus, in particolare contro la malattia causata dall?infezione da SARS-CoV-2 (Covid-19). To date, there is no effective treatment available against the diseases caused by the coronavirus infection, especially against the disease caused by the SARS-CoV-2 (Covid-19) infection.
Alla luce di quanto sopra esposto, appare evidente la necessit? di poter disporre di terapie efficaci contro le malattie causate da coronavirus, in particolare contro Covid-19. In the light of the foregoing, the need is evident to be able to have effective therapies against diseases caused by coronavirus, in particular against Covid-19.
In questo contesto viene ad inserirsi la soluzione secondo la presente invenzione, che si propone di fornire una cura efficace contro le malattie causate da coronavirus e, in particolare, contro Covid-19. The solution according to the present invention fits into this context, which aims to provide an effective cure against the diseases caused by coronavirus and, in particular, against Covid-19.
A questo scopo i Richiedenti hanno approfondito lo studio dei meccanismi di replicazione del coronavirus, in particolare di SARS-CoV-2. To this end, the Applicants have deepened the study of the replication mechanisms of the coronavirus, in particular of SARS-CoV-2.
E? noto che dagli anni 1952 in poi, attraverso il modello di esperimento proposto da di Alfred D. Hershey e Martha Chase, ? stato possibile individuare molti Batteriofagi (virus che infettano le cellule procariotiche) (Callanan et al., 2018). Tale metodologia richiedeva l?utilizzo dei radioisotopi fosforo (P32) e zolfo (S34). Oggi questa tecnica risulta desueta e poco praticabile soprattutto per i rischi di gestione e smaltimento dei radioisotopi all?interno degli ambienti ed istituti di ricerca. L?assenza di una metodologia analoga e rapida ha limitato nel corso degli ultimi decenni la scoperta di nuovi fagi e di virus patogeni nel regno animale, specie umana inclusa, che potessero avere anche dei meccanismi di replicazione e diffusione simile a quella dei fagi, all?interno delle cellule procariotiche (batteriche) oltre alle classiche vie molecolari conosciute nelle cellule eucariotiche (quelle umane incluse). L?avvento dell?utilizzo della linea cellulare ?vero cell?, ovvero linee di cellule multi potenti, derivate da rene di scimmia africana, capace di replicarsi continuamente, ha indirizzato molti ricercatori a studiare i virus e i vaccini in questo nuovo vettore, trascurando una valutazione iniziale: le nuove specie virali aventi un comportamento da Fago (Ammerman, Beier-Sexton and Azad, 2008). Infatti, nei protocolli di utilizzo delle ?vero Cell? vengono usati gli antibiotici al fine di evitare le contaminazioni di laboratorio, ma ci? ha condotto alla perdita di un possibile attore, quale la cellula procariotica, capace di giocare un ruolo nei meccanismi di replicazione e trascrizione dei virus in generale. Inoltre, per quanto validata, la linea Vero cell non ? una linea cellulare eucariotica, umana, pura. AND? known that from the years 1952 onwards, through the model of experiment proposed by Alfred D. Hershey and Martha Chase,? It was possible to identify many bacteriophages (viruses that infect prokaryotic cells) (Callanan et al., 2018). This methodology required the use of the radioisotopes phosphorus (P32) and sulfur (S34). Today this technique is obsolete and impractical especially due to the risks of management and disposal of radioisotopes inside research environments and institutes. The absence of an analogous and rapid methodology has limited, over the last few decades, the discovery of new phages and pathogenic viruses in the animal kingdom, including the human species, which could also have mechanisms of replication and diffusion similar to that of phages, ?inside prokaryotic (bacterial) cells as well as the classical molecular pathways known in eukaryotic cells (humans included). The advent of the use of the ?vero cell? cell line, i.e. multipotent cell lines, derived from African monkey kidneys, capable of continuously replicating itself, has led many researchers to study viruses and vaccines in this new vector, neglecting a initial evaluation: the new viral species having a phage-like behavior (Ammerman, Beier-Sexton and Azad, 2008). In fact, in the protocols for using the ?vero Cell? antibiotics are used in order to avoid laboratory contamination, but there? has led to the loss of a possible actor, such as the prokaryotic cell, capable of playing a role in the replication and transcription mechanisms of viruses in general. Furthermore, although validated, the Vero cell line is not? a pure, human, eukaryotic cell line.
I Richiedenti hanno ora sorprendentemente trovato che i coronavirus, in particolare SARS-CoV-2, hanno un comportamento fagico. L?individuazione di un nuovo meccanismo di replicazione, non solo presente o tipico nella cellula eucariotica (quella umana inclusa), ma anche nella cellula procariotica (batterica), ovvero l?osservazione diretta o indiretta di tale possibile evento, cambia e rivoluziona l?approccio terapeutico contro il patogeno virale coronavirus e apre nuovi scenari e nuovi meccanismi molecolari. Tutto ci? pu? portare anche a significativi avanzamenti nella scelta del trattamento e nel monitoraggio delle patologie sopra menzionate, ossia tutte le patologie dei tipi conosciuti di coronavirus. La presente invenzione riguarda quindi l?applicazione di composti farmaceutici della classe degli antibiotici e chemioterapici ai fini della prevenzione, della cura e della diminuzione delle virosi, infezioni virali, zoonosi e malattie infettive in genere causate dal virus SARS-CoV-2 e dai suoi congeneri che utilizzano, nel e sul corpo degli esseri del regno animale, specie umana inclusa, oltre alle cellule eucariotiche anche le cellule procariotiche per la loro replicazione e diffusione. The Applicants have now surprisingly found that coronaviruses, especially SARS-CoV-2, have phage behaviour. The identification of a new replication mechanism, not only present or typical in the eukaryotic cell (human included), but also in the prokaryotic (bacterial) cell, or the direct or indirect observation of this possible event, changes and revolutionizes the? therapeutic approach against the viral pathogen coronavirus and opens up new scenarios and new molecular mechanisms. All of that? can? also lead to significant advances in the choice of treatment and monitoring of the pathologies mentioned above, i.e. all pathologies of the known types of coronaviruses. The present invention therefore relates to the application of pharmaceutical compounds of the antibiotic and chemotherapeutic class for the purposes of prevention, treatment and reduction of viroses, viral infections, zoonoses and infectious diseases in general caused by the SARS-CoV-2 virus and its congeners that use, in and on the body of beings of the animal kingdom, the human species included, in addition to eukaryotic cells also prokaryotic cells for their replication and diffusion.
I Richiedenti hanno individuato, attraverso un approccio innovativo, un metodo non convenzionale, e altrimenti non pensabile, una serie di composti farmaceutici (antibiotici e chemioterapici), capaci di produrre una diminuzione della replicazione virale da Sars-Cov2 e congeneri e capaci di abbassare in maniera significativa la diffusione del virus e dei suoi congeneri e di permettere una prevenzione su larga scala. Tali composti sono specifici in quanto privano il virus del suo substrato rinvenuto per la prima volta nel presente studio, ovvero le cellule batteriche, utile alla propria replicazione e diffusione. The Applicants have identified, through an innovative approach, an unconventional and otherwise unthinkable method, a series of pharmaceutical compounds (antibiotics and chemotherapeutics), capable of producing a decrease in viral replication from Sars-Cov2 and congeners and capable of lowering the significantly the spread of the virus and its congeners and to allow for large-scale prevention. These compounds are specific as they deprive the virus of its substrate found for the first time in the present study, i.e. bacterial cells, useful for its replication and diffusion.
Forma pertanto oggetto specifico della presente invenzione una serie di Antibiotici e chemioterapici capaci di produrre una diminuzione della diffusione e della replicazione del coronavirus in utilizzo singolo o associato. I composti sopra menzionati quando associati possono essere somministrati singolarmente (in modo separato), congiuntamente (in modo simultaneo) o in via differita (in modo sequenziale). Therefore, the specific object of the present invention is a series of antibiotics and chemotherapeutics capable of producing a decrease in the diffusion and replication of the coronavirus in single or associated use. The above mentioned compounds when combined can be administered singly (separately), jointly (simultaneously) or deferred (sequentially).
In particolare, la presente invenzione concerne l?uso singolo o in combinazione dei seguenti antibiotici che sono in grado di abbassare la replicazione del virus SARS-CoV-2 e congeneri. Tali principi attivi sperimentati nell?invenzione sono: il metronidazolo, l? amoxicillina, la Vancomicina, la Fidaxomicina, la Teicoplanina, l? Ornidazolo, il Tenidazolo , l?Amoxicillina con l? acido, clavulanico , l? azitromicina, Metronidazolo associato alla azitromicina e Metronidazolo associato alla azitromicina, ceftriaxone, cefixima. Secondo la presente invenzione, i principi attivi sopra menzionati possono essere impiegati a dosaggi clinici consueti e non. In particular, the present invention relates to the single or combination use of the following antibiotics which are capable of lowering the replication of the SARS-CoV-2 virus and congeners. These active ingredients tested in the invention are: metronidazole, l? amoxicillin, vancomycin, fidaxomycin, teicoplanin, l? Ornidazole, Tenidazole, Amoxicillin with l? acid, clavulanic acid, l? azithromycin, Metronidazole combined with azithromycin and Metronidazole combined with azithromycin, ceftriaxone, cefixime. According to the present invention, the above mentioned active ingredients can be used at usual and non-usual clinical dosages.
Essi sono in grado di abbassare la replicazione virale che avviene nei batteri cos? come ? stato osservato nelle cinque repliche di esperimento prodotte, ossia impediscono la replicazione negli organismi procarioti (batteri, ecc) all?interno dell?organismo umano e in diverse aree del medesimo (es: tratto-oro-fecale). I composti sopra menzionati prevengono, e/o curano, e/o rallentano, e/ o bloccano la replicazione del virus SARS-CoV-2 e dei suoi congeneri (inclusi SARS e MERS) all?interno dei batteri presenti sia nell?essere umano e sia negli animali in generale. Ci? consente di prevenire l?accumulo del virus all?interno dell?organismo ospite prevenendone la diffusione ed il contagio. They are able to lower the viral replication that occurs in bacteria as well as how ? been observed in the five experimental replicas produced, i.e. they prevent replication in prokaryotic organisms (bacteria, etc.) within the human organism and in different areas of the same (eg: fecal-oral-tract). The above compounds prevent, and/or cure, and/or slow down, and/or block the replication of the SARS-CoV-2 virus and its congeners (including SARS and MERS) within bacteria present both in humans and both in animals in general. There? allows you to prevent the accumulation of the virus inside the host organism, preventing its spread and contagion.
La presente invenzione verr? ora descritta, a titolo illustrativo, ma non limitativo, secondo forme di realizzazione, con particolare riferimento alla figura 1 che mostra il diagramma di replicazione virale nei batteri. This invention will come now described, for illustrative but not limiting purposes, according to embodiments, with particular reference to figure 1 which shows the diagram of viral replication in bacteria.
ESEMPIO 1 EXAMPLE 1
Attraverso un approccio di nuovo concetto ? stato documentato un aumento della replicazione virale (Sars-Cov2) nelle cellule procariotiche, attraverso terreni di coltura multipotenti. Le colture sono state divise in pozzetti e la carica di concentrazione virale ? stata determinata al tempo zero e al tempo massimo 30 gg. Sono state eseguite cinque repliche. La carica virale ? stata monitorata con test specifici Luminex tecnology (Dunbar, 2006). Through a new concept approach ? An increase in viral replication (Sars-Cov2) has been documented in prokaryotic cells, through multipotent culture media. Were the cultures divided into wells and the viral concentration load ? was determined at time zero and at the maximum time of 30 days. Five replicas were performed. The viral load? been monitored with specific Luminex technology tests (Dunbar, 2006).
Sono stati testati i composti descritti di seguito riproducendo un antibiogramma a 3 giorni e a 6 giorni. I composti che hanno determinato una significativa diminuzione della replicazione virale, che avveniva sulle cellule procariotiche sono stati i seguenti: The compounds described below were tested by reproducing an antibiogram at 3 days and at 6 days. The compounds that resulted in a significant decrease in viral replication, which occurred on prokaryotic cells were the following:
? Metronidazolo ? Metronidazole
? Amoxicillina ? Amoxicillin
? Vancomicina Ornidazolo ? Vancomycin Ornidazole
? Tinidazolo ? Tinidazole
? Amoxicillina con acido clavulanico ? Amoxicillin with clavulanic acid
? Teicoplanina ? Teicoplanin
? Fidaxomicina ? Fidaxomycin
? Azitromicina ? Azithromycin
? Metronidazolo associato alla azitromicina ? Metronidazole combined with azithromycin
? Metronidazolo associato alla amoxicillina ? Metronidazole combined with amoxicillin
? Ceftriaxone ? Ceftriaxone
? cefixima ? cefixime
Il Richiedente ha individuato attraverso un approccio contrapposto alla comune pratica di sperimentazione, un dato innovativo e altrimenti non pensabile ed ? emerso che il Covid-19 ? ?anche? un virus di tipo ?fago?, e la sua crescita e la sua replicazione avviene anche nei batteri (Fig.1). La Metodica ? meglio descritta di seguito: La flora multicellulare di un tampone del tratto oro-naso-congiuntivo-fecale o del tratto cutaneo di essere affetto dal virus viene fatta crescere in coltura e fatta crescere per diversi giorni. Has the Applicant identified, through an approach opposed to the common practice of experimentation, an innovative and otherwise unthinkable datum and ? emerged that the Covid-19? ?also? a ?phage? type virus, and its growth and replication also occurs in bacteria (Fig.1). The Method? better described below: The multicellular flora of a swab of the oro-nose-conjunctive-fecal tract or cutaneous tract to be affected by the virus is grown in culture and grown for several days.
I campioni biologici umani utilizzati in questa sperimentazione sono stati raccolti con l'espresso consenso, libero e informato, al prelievo e utilizzazione, della persona da cui ? stato prelevato il materiale, in base alla normativa vigente. Were the human biological samples used in this experimentation collected with the express, free and informed consent of the person from whom they were collected and used? the material has been collected, in accordance with current legislation.
Il controllo della concentrazione virale ? stato eseguito giornalmente con metodica luminex tecnology (Dunbar, 2006). Nella finestra temporale tra il quattordicesimo e il ventunesimo giorno sono stati preparati dei pozzetti singoli nei quali sono stati introdotte delle colture antibiotiche. I dati ottenuti sono stati nuovamente elaborati con la metodica luminex tecnology. I valori pi? bassi indicano la cessazione della replicazione virale, mentre i valori pi? alti sono direttamente proporzionali alla replicazione del Virus. I seguenti composti bloccano la replicazione virale, determinando nulla la sua replicazione nei batteri a 3 giorni: Viral concentration control? performed daily with the luminex technology method (Dunbar, 2006). In the time window between the fourteenth and twenty-first day, individual wells were prepared in which antibiotic cultures were introduced. The data obtained were processed again with the luminex technology method. The highest values? low indicate the cessation of viral replication, while the pi? high are directly proportional to the replication of the virus. The following compounds block viral replication, resulting in no replication in bacteria at 3 days:
? Metronidazolo ? Metronidazole
? Amoxicillina con acido clavulanico Amoxicillina ? Vancomicina ? Amoxicillin with clavulanic acid Amoxicillin ? Vancomycin
? Azitromicina ? Azithromycin
? Metronidazolo associato alla amoxicillina ? Metronidazole combined with amoxicillin
? Metronidazolo associato alla azitromicina ? Metronidazole combined with azithromycin
I seguenti composti bloccano la replicazione virale, determinando nulla la sua replicazione nei batteri a 6 giorni: The following compounds block viral replication, resulting in zero replication in bacteria at 6 days:
? Ornidazolo ? Ornidazole
? Tinidazolo ? Tinidazole
? Teicoplanina ? Teicoplanin
? Fidaxomicina ? Fidaxomycin
? Cefixima ? Cefixime
? ceftriaxone ? ceftriaxone
? Metronidazolo associato alla azitromicina ? Metronidazole combined with azithromycin
La tabella 1 mostra i dati luminex su replicazione virale pre- e post- antibiotici. Table 1 shows luminex data on pre- and post-antibiotic viral replication.
Tabella 1 Table 1
Le colture sono state portate fino al 30 giorno e nessuna replicazione ? stata osservata dopo la cessazione dell?introduzione degli antibiotici giorni prima avevano diminuito la stessa. Were cultures carried through to day 30 and no replications? been observed after the cessation of the introduction of antibiotics days before had decreased the same.
I composti che hanno dato una pronta ed immediata diminuzione della replicazione virale, e quindi sono preferiti, sono i seguenti: The compounds which gave a prompt and immediate decrease in viral replication, and therefore are preferred, are the following:
? Metronidazolo ? Metronidazole
? Amoxicillina con acido clavulanico ? Amoxicillin with clavulanic acid
? Amoxicillina ? Amoxicillin
? Vancomicina ? Vancomycin
? Azitromicina ? Azithromycin
? Metronidazolo associato alla amoxicillina ? Metronidazole combined with amoxicillin
? Metronidazolo associato alla azitromicina ? Metronidazole combined with azithromycin
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