WO2023095075A1 - Combination of one or more antibiotics of the ansamycin class with one or more other antibiotics for the prevention and treatment of coronavirus-caused infections, related diseases and clinical effects caused by toxins product after viral infection - Google Patents
Combination of one or more antibiotics of the ansamycin class with one or more other antibiotics for the prevention and treatment of coronavirus-caused infections, related diseases and clinical effects caused by toxins product after viral infection Download PDFInfo
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- WO2023095075A1 WO2023095075A1 PCT/IB2022/061434 IB2022061434W WO2023095075A1 WO 2023095075 A1 WO2023095075 A1 WO 2023095075A1 IB 2022061434 W IB2022061434 W IB 2022061434W WO 2023095075 A1 WO2023095075 A1 WO 2023095075A1
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- antibiotics
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- coronavirus
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- 239000003242 anti bacterial agent Substances 0.000 title claims abstract description 106
- 229940088710 antibiotic agent Drugs 0.000 title claims abstract description 100
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- 208000015181 infectious disease Diseases 0.000 title claims abstract description 18
- 230000002265 prevention Effects 0.000 title claims abstract description 14
- 239000003053 toxin Substances 0.000 title description 21
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- 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 abstract description 36
- 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 abstract description 36
- 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 abstract description 35
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- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 claims abstract description 30
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims abstract description 30
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- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 claims description 9
- JDECNKBYILMOLE-CJQFIEQYSA-N chembl1255887 Chemical compound O1COC(=C(C)C2=O)C3=C1\C(C)=C\[C@@](C)(O)[C@H](O)[C@@H](C)[C@@H](O)[C@H](C(=O)OC)[C@H](O)[C@H](C)[C@H](O)[C@H](C)\C=C/C=C(C)/C(=O)NC1=C(C)C(OC(C)=O)=C3C2=C1O JDECNKBYILMOLE-CJQFIEQYSA-N 0.000 claims description 9
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- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/54—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
Definitions
- the invention relates to the combination of one or more antibiotics of the class of ansamycins, such as rifaximin or rifampin, or other of the same family, with one or more compounds of the class of antibiotics selected within the group comprising azithromycin, clindamycin, amoxicillin, ampicillin, penicillin, metronidazole and ceftriaxone, for the prevention and treatment of infections caused by viral and phage forms of coronavirus, such as SARS-CoV-2 and BCoV, of related diseases, such as COVID-19, and for the control of the harmful effects induced by toxins produced in the body in the event of coronavirus infection.
- one or more antibiotics of the class of ansamycins such as rifaximin or rifampin, or other of the same family
- one or more compounds of the class of antibiotics selected within the group comprising azithromycin, clindamycin, amoxicillin, ampicillin, penicillin, metronidazole and ceftriaxone
- said rifaximin when said one or more antibiotics of the class of ansamycins is rifaximin, said rifaximin may be present in the pharmaceutical composition, for the above-mentioned use, in an amount from 0.0001 mg to 2000 mg, for example from 0.0001 mg to 1600 mg or from 0.0001 mg to 800 mg or from 400 mg to 1600 mg.
- said rifampicin when said one or more antibiotics of the class of ansamycins is rifampicin, said rifampicin may be present in the pharmaceutical composition, for the above-mentioned use, in an amount of 0.0001 mg to 1200 mg, for example 0.0001 mg to 900 mg or 0.0001 mg to 600 mg.
- the present invention also relates to a pharmaceutical composition
- a pharmaceutical composition comprising one or more antibiotics of the class of ansamycins and one or more additional antibiotics chosen from azithromycin, clindamycin, amoxicillin, ampicillin, penicillin, metronidazole and ceftriaxone, as active ingredients, together with one or more pharmaceutically acceptable excipients and/or adjuvants.
- - clindamycin may be present in an amount of 0 mg to 2000 mg, e.g. 0 mg to 1500 mg or 0 mg to 1000 mg or 500 mg to 1500 mg;
- the pharmaceutical composition according to the invention may comprise rifaximin and ampicillin; rifaximin and clindamycin; rifaximin and penicillin; rifaximin and metronidazole; herbimycin and amoxicillin; herbimycin and azithromycin; herbimycin and ampicillin; herbimycin and clindamycin; herbimycin and penicillin; herbimycin and ceftriaxone; herbimycin and metronidazole; ansatrienin and amoxicillin; ansatrienin and azithromycin; ansatrienin and ampicillin; ansatrienin and clindamycin; ansatrienin and ceftriaxone; ansatrienin and metronidazole rifampicin and amoxicillin; rifampicin and azithromycin; rifampicin and ampicillin; rifampicin and clindamycin; rifampicin and penicillin; rifampicin and ceftriaxone; or r
- EXAMPLE 1 Study of the efficacy of combinations of antibiotics according to the invention (in particular rifaximin in combination with other antibiotics) against SARS- CoV-2.
- Table 2 shows Luminex data on the efficacy of formulations tested on bacteria cultured with B-Cov virus.
- the graph shown in Figure 8 represents the difference between the control group (10 cases), the study group (49 cases) and the double control group (10 subjects with other pathology, NOT LONG CO VID and who never had COVID-19).
- the 10 cases in the control group took a placebo supplement.
- 28 received the high dosage formulation (1.5 times the intermediate dosage) and 21 cases received the intermediate dosage (normal allowable dose for the individual compounds making up the formulation).
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- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT102021000029909A IT202100029909A1 (it) | 2021-11-26 | 2021-11-26 | Combinazione di uno o più antibiotici della classe delle ansamicine con uno o più altri antibiotici per la prevenzione e il trattamento di infezioni causate da coronavirus, delle relative malattie e degli effetti clinici indotti dalle tossine prodotte a seguito dell’infezione da coronavirus. |
| IT102021000029909 | 2021-11-26 |
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| WO2023095075A1 true WO2023095075A1 (en) | 2023-06-01 |
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| PCT/IB2022/061434 WO2023095075A1 (en) | 2021-11-26 | 2022-11-25 | Combination of one or more antibiotics of the ansamycin class with one or more other antibiotics for the prevention and treatment of coronavirus-caused infections, related diseases and clinical effects caused by toxins product after viral infection |
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