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WO2019058268A1 - Formulation anti-infectieuse topique - Google Patents

Formulation anti-infectieuse topique Download PDF

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Publication number
WO2019058268A1
WO2019058268A1 PCT/IB2018/057203 IB2018057203W WO2019058268A1 WO 2019058268 A1 WO2019058268 A1 WO 2019058268A1 IB 2018057203 W IB2018057203 W IB 2018057203W WO 2019058268 A1 WO2019058268 A1 WO 2019058268A1
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Prior art keywords
topical formulation
veterinary topical
veterinary
antibiotic
formulation
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Ceased
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PCT/IB2018/057203
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English (en)
Inventor
Martin Donnelly
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Omnipharm Developments Ltd
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Omnipharm Developments Ltd
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Publication date
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Publication of WO2019058268A1 publication Critical patent/WO2019058268A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • 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
    • A61K31/435—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
    • 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
    • A61K31/436—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 six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • 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
    • 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
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/609—Amides, e.g. salicylamide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A61K9/0017—Non-human animal skin, e.g. pour-on, spot-on
    • 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

Definitions

  • the present invention relates to a topical veterinary anti-infective formulation.
  • Anti-infective agents are used in the treatment of infections in both animals and humans. Infections arising in animals and humans from the same bacterial strain may be treated using the same anti- infective agent.
  • the use of anti-infective agents in animals can result in the development of bacterial strains that are resistant to the anti- infective agent, and zoonotic transfer of the resistant bacterial strains from animals to humans can render existing human therapies ineffective. There is genuine potential for such zoonotic transfer to occur through the intimate contact between humans (pet owners, farmers, etc.) and animals (cats, dogs, pigs, chickens, cows etc.) meaning that the transfer of resistant bacterial strains from animals to humans is likely.
  • EMA European Medicines Agency
  • a further concern regarding the spread of bacterial resistance is the transfer of resistance genes between different bacteria and across species. Bacteria that have developed genes resulting in antibiotic resistance can transfer such genes encoded data via plasmids, etc. to other bacterial species. This DNA transfer can result in antibiotic resistance being passed from one bacterial species to another, even though the second bacterial species had no prior exposure to antibiotics.
  • bacteria have developed resistance to ⁇ -lactam antibiotics (such as cephalosporins, penicillins and monolactams) by producing ⁇ -lactamase enzymes that break the structure of the antibiotic. Codes on how to manufacture such enzymes are DNA swapped between bacteria resulting in transfer of resistance.
  • ⁇ -lactam antibiotics such as cephalosporins, penicillins and monolactams
  • Staphylococci bacteria also carry genes that code for resistance (such as vga, Isa, erm and cfr) which can easily be transferred to other staphylococci bacteria via DNA swapping.
  • genes that code for resistance such as vga, Isa, erm and cfr
  • Particular genes causing bacterial resistance in staphylococci bacteria have been identified (Wendlandt et al. "Multidrug resistance genes in staphylococci from animals that confer resistance to critically and highly important antimicrobial agents in human medicine", Trends in Microbiology, 2015, 23(1), 44- 54).
  • Some genes which code for resistance are present in both human and animal staphylococci bacteria, but others are only present in animal staphylococci bacteria, and pose a risk to humans if they transfer to other bacterial species.
  • technology to reduce the transfer of resistance between bacteria is also desired to reduce the spread of antibiotic resistance, as well as technology to reduce the zoonotic transfer of resistant bacterial strains from animals to humans.
  • Fusidic acid is used in human medicine in an oral form (sodium fusidate) to treat systemically active Gm+ life-threatening infections.
  • fusidic acid is now almost exclusively used as a combination therapy when dosed systemically.
  • sodium fusidate is co-prescribed with oral rifampicin to reduce or prevent the occurrence of resistance (Dobie et al., "Fusidic acid resistance in Staphylococcus aureus" Arch Dis Child 2004, 89, 74-77).
  • fusidic acid is prescribed in veterinary and human medicine as a topical cream, gel or ointment for skin/eye infections with fusidic acid as a single active ingredient, or in combination with a steroid to provide anti-inflammatory control where needed.
  • fusidic acid e.g. fusidic acid
  • rifampicin a topical treatment which can prevent the development of resistance (like, for example, the oral combination of fusidic acid and rifampicin).
  • a reduced MIC would offer improved potency of the antibiotic leading to lower transmission/transferrence of gene resistance between bacteria and lower resistance development.
  • the topical veterinary composition of the present invention which comprises a halogenated salicylanilide and a further antibiotic, provides an unexpected reduction in the MIC of the antibiotic.
  • the topical veterinary composition of the present invention provides a surprising synergy between the halogenated salicylanilide and the antibiotic in Gram-positive (Gm+) bacteria.
  • halogenated salicylanilides particularly oxyclosanide and closantel
  • the MIC of the antibiotic in the topical veterinary formulation of the present invention particularly fusidic acid
  • Halogenated salicylanilides are known to have antibacterial action and act by interfering with bacterial cell membranes, but they do not cause cell wall lysis (unlike ⁇ -lactam antibiotics, for example) (Rajamuthiah et al, "Repurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus", PLoS ONE, 2015, 10(4)).
  • the antibiotic in the topical veterinary formulation of the present invention targets protein synthesis at ribosomes within the bacterial RNA/DNA, a process which only occurs within the cell and not at the outer membrane.
  • the synergy provided is surprising because the halogenated salicylanilide and the antibiotic in the topical veterinary formulation of the present invention work on differing targets separately inside and outside the bacteria with no obvious common mechanism to interact with.
  • the halogenated salicylanilide particularly oxyclosanide and closantel, creates small holes in the outer membrane of the bacterium which allows increased diffusion of the antibiotic in the topical veterinary formulation of the present invention, particularly fusidic acid, into the bacterium thus allowing greater RNA protein blockade and cell death/stasis.
  • the “potentiation" of the antibiotic in the topical veterinary formulation of the present invention, particularly fusidic acid, by halogenated salicylanilides, particularly oxyclosanide and closantel, provides an improved topical treatment for Gm+ skin bacteria for the following reasons:
  • the lower MIC of the antibiotic in the topical veterinary formulation of the present invention leads to greater treatment success and improved pharmacodynamic parameters such as the AUC (area under curve)/MIC ratio when compared to dosing the antibiotic as a single active component.
  • the present invention provides a veterinary topical formulation which can prevent transference of resistance-causing genes, and minimises the chances of these mutants developing and additionally transferring between humans/animals.
  • the present invention relates to a veterinary topical formulation comprising a halogenated salicylanilide, and an antibiotic selected from the group consisting of: fusidic acid, mupirocin, a pleuromutilin antibiotic, florfenicol, clindamycin, gentamicin, teicoplanin, vancomycin, tigecycline, fosfomycin, daptomycin, rifampicin, linezolid, quinupristin, dalfopristin, pristinamycin, cloxacillin, dicloxacillin, flucloxacillin, oxacillin and nafcillin.
  • an antibiotic selected from the group consisting of: fusidic acid, mupirocin, a pleuromutilin antibiotic, florfenicol, clindamycin, gentamicin, teicoplanin, vancomycin, tigecycline, fosfomycin,
  • the present invention further relates to the veterinary topical formulation as described herein for use in the treatment of a non-human animal.
  • the present invention further relates to the veterinary topical formulation as described herein for use in treating a bacterial infection a non-human animal.
  • the present invention also relates to a method of treating a bacterial infection in a non-human animal comprising administering a therapeutically-effective amount of the veterinary topical formulation of the present invention to the non-human animal.
  • the present invention also relates to a veterinary topical formulation comprising a halogenated salicylanilide, for use in a method of treating a bacterial infection in a non-human animal, wherein the method comprises administering the veterinary topical formulation comprising a halogenated salicylanilide together with or sequentially with a veterinary topical formulation comprising an antibiotic selected from the group consisting of: fusidic acid, mupirocin, a pleuromutilin antibiotic, florfenicol, clindamycin, gentamicin, teicoplanin, vancomycin, tigecycline, fosfomycin, daptomycin, rifampicin, linezolid, quinupristin, dalfopristin, pristinamycin, cloxacillin, dicloxacillin, flucloxacillin, oxacillin and nafcillin.
  • an antibiotic selected from the group consisting of: fusi
  • the present invention also relates to a veterinary topical formulation comprising an antibiotic selected from the group consisting of: fusidic acid, mupirocin, a pleuromutilin antibiotic, florfenicol, clindamycin, gentamicin, teicoplanin, vancomycin, tigecycline, fosfomycin, daptomycin, rifampicin, linezolid, quinupristin, dalfopristin, pristinamycin, cloxacillin, dicloxacillin, flucloxacillin, oxacillin and nafcillin, for use in a method of treating a bacterial infection a non-human animal, wherein the method comprises administering the veterinary topical formulation comprising an antibiotic selected from the group consisting of: fusidic acid, mupirocin, a pleuromutilin antibiotic, florfenicol, clindamycin, gentamicin,
  • the veterinary topical formulation of the present invention comprises a halogenated salicylanilide.
  • the halogenated salicylanilides are a series of compounds generally used as anthelmintic agents.
  • niclosamide (5-chloro-N-(2-chloro-4-nitrophenyl)-2- hydroxybenzamide):
  • halogenated salicylanilide is closantel (N-(5-chloro-4-((4-chlorophenyl)(cyano)methyl)-2- methylphenyl)-2-hydroxy-3,5-diiodobenzamide):
  • halogenated salicylanilide is rafoxanide (N-(4-chloro-3-(4-chlorophenoxy)phenyl)-2- hydroxy-3,5-diiodobenzamide):
  • halogenated salicylanilide is oxyclozanide (2,3,5-trichloro-N-(3,5-dichloro-2- hydroxyphenyl)-6-hydroxybenzamide):
  • the halogenated salicylanilides in the veterinary topical formulation of the present invention may be selected from the group consisting of: closantel, rafoxanide, oxyclozanide, niclosamide and resorantel.
  • the halogenated salicylanilide is closantel or oxyclozanide.
  • the halogenated salicylanilide may be closantel.
  • the halogenated salicylanilide may be oxyclozanide.
  • the veterinary topical formulation may comprise from 0.01 to 20% by weight (based on the total mass) of the halogenated salicylanilide, optionally from 1 to 10% by weight (based on the total mass) of the halogenated salicylanilide, or from 1 to 7% by weight (based on the total mass) of the halogenated salicylanilide.
  • the veterinary topical formulation of the present invention also comprises an antibiotic selected from the group consisting of: fusidic acid, mupirocin, a pleuromutilin antibiotic, florfenicol, clindamycin, gentamicin, teicoplanin, vancomycin, tigecycline, fosfomycin, daptomycin, rifampicin, linezolid, quinupristin, dalfopristin, pristinamycin, cloxacillin, dicloxacillin, flucloxacillin, oxacillin and nafcillin.
  • an antibiotic selected from the group consisting of: fusidic acid, mupirocin, a pleuromutilin antibiotic, florfenicol, clindamycin, gentamicin, teicoplanin, vancomycin, tigecycline, fosfomycin, daptomycin, rifampicin, linezolid
  • the antibiotic is selected from the group consisting of: fusidic acid, mupirocin, a pleuromutilin antibiotic, florfenicol, clindamycin and gentamicin.
  • the pleuromutilin antibiotic may be selected from the group consisting of: rumblemulin, tiamulin, valnemulin, azamulin and lefamulin.
  • the antibiotic is selected from the group consisting of: fusidic acid, cloxacillin, dicloxacillin, oxacillin, nafcillin, mupirocin, tiamulin and valnemulin.
  • the antibiotic is fusidic acid or mupirocin.
  • the antibiotic is fusidic acid.
  • the antibiotic is mupirocin.
  • the veterinary topical formulation may comprise from 0.01 to 20% by weight (based on the total mass) of the antibiotic, optionally from 1 to 17% by weight (based on the total mass) of the antibiotic, or from 8 to 17% by weight (based on the total mass) of the antibiotic.
  • the veterinary topical formulation of the present invention may also comprise an antihistamine.
  • the antihistamine is levocetirizine.
  • the veterinary topical formulation may comprise from 0.01 to 5% by weight (based on the total mass) of the antihistamine.
  • the veterinary topical formulation of the present invention may also comprise a steroid.
  • the veterinary topical formulation may comprise from 0.01 to 5% by weight (based on the total mass) of the steroid.
  • the veterinary topical formulation of the present invention may also comprise an
  • the immunosuppressant is tacrolimus or cyclosporin.
  • the immunosuppressant is tacrolimus.
  • the immunosuppressant is cyclosporin.
  • the veterinary topical formulation may comprise from 0.01 to 5% by weight (based on the total mass) of the immunosuppressant.
  • the veterinary topical formulation of the invention does not contain rifampicin.
  • a “topical formulation” is a formulation that is applied to body surfaces of animals or humans, such as the skin or mucous membranes, to treat ailments via a large range of classes.
  • the topical formulation may be a liquid, spot-on formulation, pour-on formulation, cream, spray, foam, gel, droplet, lotion or ointment.
  • the topical formulation is a liquid formulation, optionally a spray formulation, a pour-on formulation or a spot-on formulation.
  • the topical formulation is a spot-on formulation.
  • Spot-on formulations are known in the art and may be applied to an animal by deposition onto the skin. After the spot-on formulation has been applied, the composition diffuses over the animal's skin, preferably over the animal's entire body.
  • the topical formulation of the present invention is typically administered in an amount of approximately about 0.075 to about 0.25 ml_ per kg body weight of the animal to a single locus, typically at the location of the skin infection or as a general application between the shoulder blades down to the tail of the animal.
  • the characteristics of the formulation mean that the formulation spreads from the single locus across the skin of the animal. Wthout wishing to be bound by theory, this is believed to be as a consequence of a combination of penetration to the lower dermal layers and spreading through the animal's sebum.
  • Spot-on solvents known in the art which may be used to prepare the formulation are, for example, aliphatic and aromatic alcohols, such as isopropanol, ethanol, methanol, octanol and benzyl alcohol; organic carbonates, such as propylene carbonate or ethylene carbonate, pyrrolidones, such as N-methylpyrrolidone, 2-pyrrolidone or octylpyrrolidone, aliphatic ethers, in particular glycol ethers, such as diethylene glycol monomethyl ether and dipropylene glycol monomethyl ether, esters, for example isopropyl myristate, and ketals, such as solketal.
  • the said solvents can be provided with the customary stabilizers, UV absorbers, acidifying agents and oligomeric as well as polymeric spreading agents.
  • the invention furthermore relates, in particular, to a veterinary spot-on formulation comprising:
  • a solvent selected from: cyclic carbonates, benzyl alcohol, isopropyl alcohol, N-methylpyrrolidone (NMP), and dimethyl sulphoxide (DMSO) or mixtures thereof.
  • the veterinary spot-on formulation comprises from 1 to 10% by weight (based on the total mass) of the halogenated salicylanilide, optionally from 1 to 7% by weight (based on the total mass) of the halogenated salicylanilide. In another embodiment, the veterinary spot-on formulation comprises from 1 to 17% by weight (based on the total mass) of the antibiotic, optionally from 8 to 17% by weight (based on the total mass) of the antibiotic.
  • the veterinary spot-on formulation comprises from 40 to 99.98% by weight (based on the total mass) of a solvent selected from: cyclic carbonates, benzyl alcohol, isopropyl alcohol, N-methylpyrrolidone (NMP), and dimethyl sulphoxide (DMSO) or mixtures thereof.
  • the veterinary spot-on formulation comprises from 50 to 90% by weight (based on the total mass) of a solvent selected from: cyclic carbonates, benzyl alcohol, isopropyl alcohol, N-methylpyrrolidone (NMP), and dimethyl sulphoxide (DMSO) or mixtures thereof.
  • the solvent is selected from: propylene carbonate, benzyl alcohol, isopropyl alcohol, N- methylpyrrolidone (NMP), and dimethyl sulphoxide (DMSO) or mixtures thereof.
  • the veterinary spot-on formulation may further comprise an antioxidant, optionally a phenolic antioxidant.
  • the veterinary spot-on formulation may comprise from 0.01 to 0.75% by weight (based on the total mass) of a phenolic antioxidant, for example butylated hydroxytoluene (BHT) and/or butylated hydroxyanisole (BHA).
  • BHT butylated hydroxytoluene
  • BHA butylated hydroxyanisole
  • the veterinary spot-on formulation may further comprise from 0.05 to 0.4% by weight (based on the total mass) of a phenolic antioxidant.
  • the veterinary spot-on formulation may further comprise from 0 to 10% by weight (based on the total mass) of triglycerides or esters of dihydric alcohols, for example, Miglyol ® 812 and/or Myritol® PC PH.
  • the veterinary spot-on formulation may further comprise from 4 to 10% by weight (based on the total mass) of triglycerides or esters of dihydric alcohols.
  • the veterinary spot-on formulation may further comprise from 0 to 50% by weight (based on the total mass) of glycol ethers, for example diethylene glycol monomethyl ether.
  • the veterinary spot-on formulation may further comprise from 10 to 30% by weight (based on the total mass) of glycol ethers, for example diethylene glycol monomethyl ether.
  • the veterinary spot-on formulation may further comprise from 0 to 10% by weight (based on the total mass) of water, optionally from 0 to 5% by weight (based on the total mass) of water.
  • the veterinary spot-on formulation may further comprise, typically in an amount of up to about 40% by weight (e.g., 0%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% by weight), one or more veterinary acceptable excipients.
  • excipients include but are not limited to surfactants and spreading agents.
  • Suitable surfactants include non-ionic surfactants, such as polyethoxylated castor oil, polysorbates (ethoxylated esters or partial esters of sorbitol), polyethoxylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate,
  • polyoxyethylene alkylphenols and poloxamers polyoxyethylene-polyoxypropylene block copolymers
  • ampholytic surfactants such as di-sodium N-lauryl ⁇ -imino-dipropionate or lecithin, phosphatidylcholine, alkyl betaines (e.g. cocamidopropyl betaine); anionic surfactants, such as sodium lauryl sulphate, fatty alcohol ether sulphates, mono/dialkyl polyglycol ether orthophosphoric acid ester monoethanolamine salt, sodium stearate; and cationic surfactants such as
  • cetyltrimethylammonium chloride cetyltrimethylammounium bromide, octadecylamine
  • Suitable spreading agents include spreading oils such as di-2-ethylhexyl adipate, isopropyl myristate, dipropylene glycol pelargonate, cyclic and acylic silicone oils, such as dimethicone and further co- and terpolymers thereof with ethylene oxide, propylene oxide and formaldehyde, fatty acid esters, triglycerides, fatty alcohols.
  • spreading oils such as di-2-ethylhexyl adipate, isopropyl myristate, dipropylene glycol pelargonate, cyclic and acylic silicone oils, such as dimethicone and further co- and terpolymers thereof with ethylene oxide, propylene oxide and formaldehyde, fatty acid esters, triglycerides, fatty alcohols.
  • the present invention further relates to the veterinary topical formulation of the invention for use in the treatment of a non-human animal.
  • the present invention further relates to the veterinary topical formulation of the invention for use in treating a bacterial infection in a non-human animal.
  • the present invention also relates to a method of treating a bacterial infection in a non-human animal comprising administering a therapeutically-effective amount of the veterinary topical formulation of the present invention to the non-human animal.
  • the bacterial infection is caused by Gram-positive bacteria.
  • the bacterial infection may be caused by multiple Staphylococcus spp. or Streptococcus spp.
  • the bacterial infection is a skin infection.
  • the non-human animal is a farm animal or companion animal.
  • the non- human animal may be selected from the group consisting of: dogs, cats, rabbits, hamsters, guinea pigs, mice, horses, ponies, donkeys, pigs, sheep, cattle, goats, and poultry.
  • the veterinary topical formulation is administered to the skin of the non- human animal.
  • the present invention also relates to a veterinary topical formulation comprising a halogenated salicylanilide, for use in a method of treating a bacterial infection in a non-human animal, wherein the method comprises administering the veterinary topical formulation comprising a halogenated salicylanilide together with or sequentially with a veterinary topical formulation comprising an antibiotic selected from the group consisting of: fusidic acid, mupirocin, a pleuromutilin antibiotic, florfenicol, clindamycin, gentamicin, teicoplanin, vancomycin, tigecycline, fosfomycin, daptomycin, rifampicin, linezolid, quinupristin, dalfopristin, pristinamycin, cloxacillin, dicloxacillin, flucloxacillin, oxacillin and nafcillin.
  • an antibiotic selected from the group consisting of: fusi
  • the halogenated salicylanilide and the antibiotic are administered together.
  • the halogenated salicylanilide and the antibiotic are administered sequentially, for example the halogenated salicylanilide is administered first and the antibiotic administered second, or the antibiotic is administered first and the halogenated salicylanilide second.
  • the present invention also relates to a veterinary topical formulation comprising an antibiotic selected from the group consisting of: fusidic acid, mupirocin, a pleuromutilin antibiotic, florfenicol, clindamycin, gentamicin, teicoplanin, vancomycin, tigecycline, fosfomycin, daptomycin, rifampicin, linezolid, quinupristin, dalfopristin, pristinamycin, cloxacillin, dicloxacillin, flucloxacillin, oxacillin and nafcillin, for use in a method of treating a bacterial infection a non-human animal, wherein the method comprises administering the veterinary topical formulation comprising an antibiotic selected from the group consisting of: fusidic acid, mupirocin, a pleuromutilin antibiotic, florfenicol, clindamycin, gentamicin,
  • the halogenated salicylanilide and the antibiotic are administered together.
  • the halogenated salicylanilide and the antibiotic are administered sequentially, for example the halogenated salicylanilide is administered first and the antibiotic administered second, or the antibiotic is administered first and the halogenated salicylanilide second.
  • formulations according to the invention can be prepared by stirring the halogenated salicylanilide and antibiotic with the given ingredients at room temperature.
  • Miglyol® 812 is a mixture of 50.0% - 65.0% caprylic triglyceride and 30.0% - 45.0% capric triglyceride and is available from Peter Cremer North America, Cincinnati, OH 45204.
  • Myritol® PC PH is Ph. Eur.: "propylene glycol dicaprylocaprate"

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Zoology (AREA)
  • Dermatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des formulations topiques vétérinaires comprenant un salicylanilide halogéné, et un antibiotique choisi dans le groupe constitué des suivants : acide fusidique, mupirocine, antibiotique pleuromutiline, florfénicol, clindamycine, gentamicine, téicoplanine, vancomycine, tigécycline, fosfomycine, daptomycine, rifampicine, linézolide, quinupristine, dalfopristine, pristinamycine, cloxacilline, dicloxacilline, flucloxacilline, oxacilline et nafcilline. Les formulations topiques vétérinaires de l'invention sont utiles dans le traitement d'une infection bactérienne chez un animal non humain.
PCT/IB2018/057203 2017-09-19 2018-09-19 Formulation anti-infectieuse topique Ceased WO2019058268A1 (fr)

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CN111214449A (zh) * 2020-03-02 2020-06-02 广东彼迪药业有限公司 一种盐酸西替利嗪片剂及其制备方法
US11318149B2 (en) * 2018-09-27 2022-05-03 Board Of Trustees Of Michigan State University Compositions and methods for inhibiting biofilm-forming bacteria
WO2023111296A1 (fr) * 2021-12-17 2023-06-22 Basf Se Composition comprenant un agent antimicrobien et un carboxamide

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WO2001037828A1 (fr) * 1999-11-22 2001-05-31 Novartis Ag Utilisation de derives de pleuromutiline pour le traitement transdermique de maladies bacteriennes
GB2403905A (en) * 2003-07-12 2005-01-19 Norbrook Lab Ltd Parasiticidal composition
WO2007044745A1 (fr) * 2005-10-11 2007-04-19 Biosynexus Incorporated Compositions de lantibiotiques et de mupirocine pour le traitement des infections bacteriennes
WO2012023082A1 (fr) * 2010-08-17 2012-02-23 Sulur Subramaniam Vanangamudi Crème médicamenteuse à base d'acide fusidique préparée avec du fusidate de sodium et comprenant un biopolymère, un corticostéroïde - acétate d'hydrocortisone, et un agent antifongique - chlorhydrate de terbinafine, et procédé de préparation correspondant
WO2013182990A1 (fr) * 2012-06-04 2013-12-12 Virbac Composition vétérinaire à administration cutanée à base d'oxyclozanide

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WO2001037828A1 (fr) * 1999-11-22 2001-05-31 Novartis Ag Utilisation de derives de pleuromutiline pour le traitement transdermique de maladies bacteriennes
GB2403905A (en) * 2003-07-12 2005-01-19 Norbrook Lab Ltd Parasiticidal composition
WO2007044745A1 (fr) * 2005-10-11 2007-04-19 Biosynexus Incorporated Compositions de lantibiotiques et de mupirocine pour le traitement des infections bacteriennes
WO2012023082A1 (fr) * 2010-08-17 2012-02-23 Sulur Subramaniam Vanangamudi Crème médicamenteuse à base d'acide fusidique préparée avec du fusidate de sodium et comprenant un biopolymère, un corticostéroïde - acétate d'hydrocortisone, et un agent antifongique - chlorhydrate de terbinafine, et procédé de préparation correspondant
WO2013182990A1 (fr) * 2012-06-04 2013-12-12 Virbac Composition vétérinaire à administration cutanée à base d'oxyclozanide

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11318149B2 (en) * 2018-09-27 2022-05-03 Board Of Trustees Of Michigan State University Compositions and methods for inhibiting biofilm-forming bacteria
CN111214449A (zh) * 2020-03-02 2020-06-02 广东彼迪药业有限公司 一种盐酸西替利嗪片剂及其制备方法
CN111214449B (zh) * 2020-03-02 2021-09-07 广东彼迪药业有限公司 一种盐酸西替利嗪片剂及其制备方法
WO2023111296A1 (fr) * 2021-12-17 2023-06-22 Basf Se Composition comprenant un agent antimicrobien et un carboxamide

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