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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

• the present invention relates to a combination of Thiamphenicol and Diclofenac for use in veterinary medicine in the treatment of infections associated with inflammatory conditions.
• an antibiotic and an antiinflammatory are often administered simultaneously, but in different formulations, to counteract the noxious effects of the infection associated with inflammatory conditions.
• This kind of treatment involves the unnegligible drawback of repeated administrations, with consequent possible errors in times and dosages of the different products, in addition to the inconvenience for the patient.
• compositions of antibiotic and steroidal antiinflammatories for the topical use are known .
• THIAMPHENICOL is an antibiotic belonging to the class of phemcolates having a wide spectrum antibacterial activity. At the pharmacokinetic/pharmaco- dinamic level, Thiamphenicol has a low plasma protein binding, a rapid and complete absorption, a high tissue distribution; moreover it is not metabolized, therefore it circulates in the free form in the body.
• DICLOFENAC is a molecule having higher antiinflammatory , antipyretic and analgesic activities than the other NSADs .
• DICLOFENAC is a molecule having higher antiinflammatory , antipyretic and analgesic activities than the other NSADs .
• Diclofenac is quickly and completely absorbed and largely distributed in tissues.
• the combination of the two compounds in a single formulation provides the following advantages m the veterinary field:
• compositions containing Thiamphenicol (TAF) and Diclofenac ( DCF ) suitable to the oral, parenteral and topical administrations preferably a precise time to slaughter the animal or to milk, and therefore a better control of the operations, mainly in large stock farms. Disclosure of the invention The present invention relates to compositions containing Thiamphenicol (TAF) and Diclofenac ( DCF ) suitable to the oral, parenteral and topical administrations .
• TAF Thiamphenicol
• DCF Diclofenac
• compositions which can be in the solid, liquid, semisolid or spray form, contain the active principles dispersed or solubilised and make use of pharmaceutically acceptable excipients and carriers, selected to assure a prompt or extended release.
• the dosage intervals will range depending on a number of factors, such as the weight of the animal and the seriousness of the infection to treat. Examples of preferred dosages for the various compositions are reported in the following.
• Oral unitary dosage compositions DCF 20 mg - Ig + TAF 100 mg -5 g and preferably DCF 100 mg + TAF 500 mg .
• Oral multidose compositions DCF 0.5 - 5% + TAF 5 - 60% and preferably DCF 5 % + TAF 20%.
• Injectable compositions DCF 2 - 10% + TAF 10 - 50% and preferably DCF 5% + TAF 25%.
• Intramammary compositions - ointments/spray DCF 2 - 10% + TAF 10 - 50% and preferably DCF 5% + TAF 25%.
• Topical compositions DCF 0.5 - 5% + TAF 2 - 10% and preferably DCF 1% + TAF 5%.
• the solid compositions (mainly for the oral use) comprise powders, tablets, granulates, capsules (both soft-gelatin and hard-gelatin capsules) pills, lozenges, boluses and pessaries (for the endouterine use).
• the antibiotic and the antiinflammatory can be mixed with solid diluents, such as sugars, for example lactose, mannitol, saccharose, sorbitol and/or calcium phosphates; binders, such as starch, gelatin, gums, polyvinylpyrrolidone , cellulose compounds; disinte- grants, such as amides and carboxymethylamide , cross- linked polyvinylpyrrolidone, agar, alginic acid and the salts thereof, such as sodium alginate.
• solid diluents such as sugars, for example lactose, mannitol, saccharose, sorbitol and/or calcium phosphates
• binders such as starch, gelatin, gums, polyvinylpyrrolidone , cellulose compounds
• disinte- grants such as amides and carboxymethylamide , cross- linked polyvinylpyrrolidone, agar, alginic acid and the salts
• compositions can also contain glidants, lubricants and tableting aids such as talc, stearic acid, magnesium stearate, silicic acid, polyethylene glycols, hydrogenated castor oil; pigments, such as titanium dioxide and dyes, release-controlling agents such as cellulose polymers and others.
• glidants such as talc, stearic acid, magnesium stearate, silicic acid, polyethylene glycols, hydrogenated castor oil
• pigments such as titanium dioxide and dyes
• release-controlling agents such as cellulose polymers and others.
• the active principles can be included in the conventional gelatin capsules in the form of granules, and preferably in the form of suspensions in vegetable or mineral oils, or in low molecular weight polyethylene glycols.
• Capsules consist of gelatin and a plasticizer, generally glycerol and sorbitol.
• Syrups, oral suspensions and oral pastes contain the active principles dispersed in a suitable carrier consisting of water, oily solvents, alcohols or polyalcohols and inorganic suspending agents, for example colloidal silicates having a high content in aluminium and magnesium, such as bentonite, veegum, kaolin and colloidal silica, such as Aero ⁇ il, Carbosil; organic stabilizers; swelling agents such as alginate ⁇ , gum arabic, tragacanth, carrageenins , guar gum, agar , and lipophilic thickening agents in case of, for example, oily pastes, synthetic or semi-synthetic agents such as ethylene oxide homopolymers , for example Polyoxil, preferably cellulose ethers, for example methyl- or ethylcellulose , hydroxyethyl cellulose, hydroxypropyl ethylcellulose, carboxymethylcellulose , microcrystalline cellulose; soluble polyvinyl compounds such as poly
• the parenteral compositions comprise liquid pharmaceutical forms prepared formulating the antibiotic and the antiinflammatory in a sterile carrier.
• Active principles can be either suspended or solubilised in the carrier, depending on the nature and concentration thereof.
• the active principles are dissolved in mixtures of water and organic solvents, for example N,N-dimethylacetamide , N- methylpyrrolidone , 2-pyrrol ⁇ done , propylene glycol, low molecular weight alcohols, low molecular weight polyethylene glycols, and filtered m sterile before being distributed in suitable containers.
• Specific adjuvants, such as preservatives, local anaesthetics, buffering agents can be dissolved in the carrier.
• composition can be freeze-dried to increase its stability, and commercialized together with a solvent container for reconstitution prior to use.
• Parenteral suspensions are prepared substantially the same way, with the exception that the already sterilized active principles are suspended and not solubilised in the carrier.
• a wetting agent, or a surface-active agent, can be used to facilitate the homogeneous distribution of the active components.
• Parenteral suspensions are usually oily suspensions with a lipophilic carrier, such as fatty oils, for example sesame oil, fatty acids synthetic esters, such as ethyl oleate, or triglycerids or diglycerids such as fractioned coconut oil and propylene glycol dicapryl dicaprate .
• thickeners such as sodium carboxymethylcellulose, polyvinylpyrrolidone, dextrans, sorbitol and stabilizing agents can be included.
• the preparations for the topical use in the veterinary field are administered through the intramammary , endouterine, ophthalmic and auricular routes and are mainly ointments, creams, gels, salves, and liquid spray products or foams, tinctures and drops.
• Ointments contain the active principles suitably micronized, dispersed m an emulsified base (cream) or in a single-phase, generally anhydrous excipient.
• the oil in water emulsions have a water content > 50%, the water m oil emulsions contain up to 70%, but preferably
• hydrophilic e ulsifiers are present, for example non- ionic surfactants, such as fatty acids esters with polyalcohols or ethylene oxide, such as sorbitan polyethoxylates esters (tween), polyoxyethylene alkylethers (cetheareth-20), and ionic derivatives such as alkylsulfonate or aryl ⁇ ulfonate derivatives, such as sodium laurylsulfate , sodium cetyl ⁇ ulfate , and lipohilic e ulsifier ⁇ such as sorbitan esters, for example sorbitan monooleate and sorbitan iso ⁇ tearate.
• non- ionic surfactants such as fatty acids esters with polyalcohols or ethylene oxide, such as sorbitan polyethoxylates esters (tween), polyoxyethylene alkylethers (cetheareth-20), and ionic derivatives such as alkylsulfonate or aryl ⁇ ul
• the oily components of these formulations comprise hydrocarbons, for example white soft paraffin and/or liquid paraffin and/or hard paraffin, natural or synthetic fat ⁇ , for example coconut oil triglycerid, hydrogenated oils, such as hydrogenated castor oil, glycerol partial esters with fatty acids, such as glyceryl mono- and distearate, fatty acids, for example palmitic and stearic acids, solid waxes, such as beeswax, wool fat, fatty alcohols or ester ⁇ such as cetyl or stearyl alcohols, or wool wax alcohols derivatives.
• hydrocarbons for example white soft paraffin and/or liquid paraffin and/or hard paraffin, natural or synthetic fat ⁇ , for example coconut oil triglycerid
• hydrogenated oils such as hydrogenated castor oil
• glycerol partial esters with fatty acids such as glyceryl mono- and distearate
• fatty acids for example palmitic and stearic acids
• solid waxes such
• Excipients for the aqueous phase can be used in creams to prevent drying out, for example polyalcohols such as glycerol, sorbitol, propylene glycol, and/or polyethylene glycol, and also antimicrobial preservative ⁇ .
• polyalcohols such as glycerol, sorbitol, propylene glycol, and/or polyethylene glycol, and also antimicrobial preservative ⁇ .
• gel ⁇ which can be anhydrous or aqueous
• various gelling agents are generally u ⁇ ed, such as those already cited for oral suspensions, comprising inorganic compounds, natural, synthetic or semi ⁇ ynthetic organic macromolecules .
• Endomammary ointments are prepared in single unit doses, usually tubes- ⁇ yringe ⁇ , to facilitate the intracanalicular administration and preserve the sterility of the product.
• Foams and spray solution ⁇ are dispensed from pressurized containers containing suitable propellers, for example halogenated hydrocarbons, such as dichlorodifluoromethane and dichlorotetraf luoroethane and hydrocarbons such as butane, propane and isobutane.
• suitable propellers for example halogenated hydrocarbons, such as dichlorodifluoromethane and dichlorotetraf luoroethane and hydrocarbons such as butane, propane and isobutane.
• Suitable carriers for topical sprays can be all the organic solvents compatible with the active ingredient and with the characteristics of the container, and in particular, low boiling alcohols, for example ethyl alcohol, low boiling acetals, for example methylal, highly solubili ⁇ ing ⁇ olvents, ⁇ uch as acetone, N- methylpyrrolidone .
• low boiling alcohols for example ethyl alcohol
• low boiling acetals for example methylal
• highly solubili ⁇ ing ⁇ olvents ⁇ uch as acetone, N- methylpyrrolidone .
• Emulsion foams can be similar to the formulations of creams for the topical u ⁇ e , or anhydrous bases in cases of non-aqueous foams mainly containing oil ⁇ , higher alcohol ⁇ ⁇ uch as cetylstearyl alcohol, myristyl alcohol, glycols such as propylene glycol, propylene glycol monostearate and generally ethoxylated surfactants, such as vegetable oils polyglycosylated glyceride ⁇ .
• the invention relates to the combination of Diclofenac and Thiamphenicol for the treatment of infections and related inflammatory conditions, preferably in the form of suitable pharmaceutical formulation ⁇ .
• the following examples further illustrate the invention without limiting it.
• the resulting su ⁇ pension has pH 4.20 and viscosity of 150 cPs.
• the ointment is whitish and its visco ⁇ ity l ⁇ 300.000 cPs.
• N,N-dimethylacetamide 40 g propylene glycol q.s. to 100 ml
• the injectable ⁇ olution is obtained by ⁇ olubilizing in ⁇ ucce ⁇ ion Thiamphenicol and Diclofenac in N,N-di- methylacetamide and ⁇ ub ⁇ equently diluting to final volume with propylene glycol.
• the re ⁇ ulting ⁇ olution i ⁇ filtered in ⁇ terile through a 0.2 ⁇ filter and distributed in asepsis into the previously sterilised vials.

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• Health & Medical Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Chemical & Material Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• Life Sciences & Earth Sciences (AREA)
• General Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Rheumatology (AREA)
• Pain & Pain Management (AREA)
• Epidemiology (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Medicinal Preparation (AREA)
• Physical Deposition Of Substances That Are Components Of Semiconductor Devices (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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Cited By (6)

Citations (1)

• 1997
  • 1997-10-21 IT IT97MI002365A patent/IT1295369B1/it active IP Right Grant
• 1998
  • 1998-10-16 TR TR2000/01075T patent/TR200001075T2/tr unknown
  • 1998-10-16 WO PCT/EP1998/006567 patent/WO1999020259A2/en active IP Right Grant
  • 1998-10-16 AU AU11543/99A patent/AU1154399A/en not_active Abandoned
  • 1998-10-16 PL PL98339950A patent/PL339950A1/xx unknown
  • 1998-10-16 SK SK568-2000A patent/SK5682000A3/sk unknown
  • 1998-10-16 CZ CZ20001441A patent/CZ290411B6/cs not_active IP Right Cessation

Patent Citations (1)

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