WO2004014340A1 - Injectable composition comprising florfenicol as an active ingredient - Google Patents

Injectable composition comprising florfenicol as an active ingredient Download PDF

Info

Publication number
WO2004014340A1
WO2004014340A1 PCT/KR2003/001265 KR0301265W WO2004014340A1 WO 2004014340 A1 WO2004014340 A1 WO 2004014340A1 KR 0301265 W KR0301265 W KR 0301265W WO 2004014340 A1 WO2004014340 A1 WO 2004014340A1
Authority
WO
WIPO (PCT)
Prior art keywords
florfenicol
active ingredient
liquid composition
solvent
injectable liquid
Prior art date
Application number
PCT/KR2003/001265
Other languages
French (fr)
Inventor
Si-Young Chang
Jae-Seung Choi
Sung-Bae Park
Jong-Myung Park
Byeung-Gie Kim
Ji-Hoon Park
Original Assignee
Dae Han New Pharm Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dae Han New Pharm Co., Ltd. filed Critical Dae Han New Pharm Co., Ltd.
Priority to AU2003244257A priority Critical patent/AU2003244257A1/en
Publication of WO2004014340A1 publication Critical patent/WO2004014340A1/en

Links

Classifications

    • 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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to an injectable composition comprising florfenicol as an active ingredient, and more particularly to an injectable liquid composition comprising a solubilized active ingredient therein with excellent bioavailability and rapid absorption when administered intramuscularly.
  • Florfenicol [D-(threo)- 1 -p-methylsulfonylphenyl-2-dichloroacetoamido-3- fluoro-1-propanol] is a derivative wherein the hydroxyl group at C-3 position of thiamphenicol [D-d-threo-2-dichloroacetoamido- 1 -(4-methylsulfonyl)phenyl- 1,3- propandiol] is substituted with a fluorine atom. Florfenicol exhibits a broad antibacterial activity against pathogenic bacterial strains including enteric bacteria such as Enterobacter, Shigella, Salmonella and E. coli.
  • enteric bacteria exhibit a resistance to chloramphenicol and thiamphenicol due to enzymatic inactivation by chloramphenicol transacetylase.
  • Florfenicol is widely used for veterinary purposes (Atep, M., Disposition Kinetics of Florfenicol in Goats by Using Two Analytical Methods. J. Vet. Med. A 48, 129-146, 2001; Varma, K., Pharmacokinetics of Florfenicol in veal calves. J. Vet. Pharmacol. Therap. 9, 412- 425, 1986).
  • florfenicol has an antibacterial mechanism similar to chloramphenicol, it exhibits excellent antibacterial effects compared to chloramphenicol.
  • florfenicol has an advantage of not causing irreversible aplastic anemia (AA). Since florfenicol, however, has a low water- solubility (about 1.3 mg/ml), it is difficult to formulate a concentrated aqueous solution of florfenicol in organic solvents such as 1,2-propandiol, glycerin, polyethylene glycol, propylene glycol and benzyl alcohol, which is required for oral therapeutic dosing.
  • organic solvents such as 1,2-propandiol, glycerin, polyethylene glycol, propylene glycol and benzyl alcohol, which is required for oral therapeutic dosing.
  • PCT publication WO 92/04016 and U. S. Pat. No. 5,082,863 disclose a method for solubilizing water-insoluble florfenicol in aprotic polar solvents, e.g., N-methyl-2-pyrrolidone or 2-pyrrolidone.
  • aprotic polar solvents e.g., N-methyl-2-pyrrolidone or 2-pyrrolidone.
  • these solvents were proven to cause irritation at injected sites and tissue damage when administered intramuscularly.
  • the present inventor has conducted intensive research to solve the above- mentioned problems of prior arts. As a result, the present inventor has found that when florfenicol as an active ingredient is dissolved in a mixture of a hydrophilic solvent and a lipophilic solvent to prepare an injectable solution, the injectable solution exhibits excellent bioavailability and rapid absorption in the body when administered intramuscularly, thus accomplishing the present invention.
  • an object of the present invention to provide an injectable liquid composition with excellent bioavailability and rapid absorption when administered intramuscularly, comprising florfenicol as a solubilized active ingredient.
  • an injectable liquid composition comprising florfenicol as an active ingredient, a hydrophilic solvent and a lipophilic solvent in which the active ingredient is dissolved in a mixture of the hydrophilic solvent and the lipophilic solvent.
  • hydrophilic solvent examples include, but not particularly limited to, diethyleneglycol monoethylether, 1,2-propyleneglycol, tetrahydrofurfuryl alcohol polyethyleneglycolether, polyethyleneglycol and mixtures thereof.
  • the weight ratio of the florfenicol to the hydrophilic solvent is preferably within the range of 1: 0.5 ⁇ 5, and more preferably 1: 0.5 ⁇ 3. When the ratio is less than 1: 0.5, florfenicol is likely to be precipitated. When the ratio exceeds 1: 5, there is a risk of phase separation.
  • this range is given only for the purpose of illustration, and is not to be construed as limiting the scope of the invention.
  • the lipophilic solvent is added to promote the absorption of the active ingredient in the body, and preferably is laurocapram, but is not particularly limited thereto.
  • the weight ratio of the florfenicol to the lipophilic solvent is preferably within the range of 1: 0.3-2, and more preferably 1: 0.5-1. When the ratio is out of this range, there is a danger of low absorption of the florfenicol.
  • the florfenicol and the solvent are out of this range, it will be appreciated that the present invention can be sufficiently realized. Accordingly, this range is given only for the purpose of illustration, and is not to be construed as limiting the scope of the invention.
  • the injectable liquid composition of the present invention may further comprise polyethyleneglycol as a solution adjuvant.
  • the weight ratio of the florfenicol to the polyethyleneglycol is within the range of 1: 1 ⁇ 4, and preferably 1: 2-3.
  • the inj ectable liquid composition of the present invention may further comprise medically acceptable additives.
  • additives examples include surfactants (sorbitan monooleate, polyoxyethylene 20 oleate, polyoxy 20 cetyl ether, etc), antioxidants (butylparahydroxy benzoic acid, butylhydroquinone, tocopherol, etc.), viscosity enhancing agents (sodium alginate, carboxymethylcellulose, methylcellulose, tragacanth, agar, polyvinylpyrrolidone, etc.), preservative agents (methyl paraoxybenzoate, propyl paraoxybenzoate, sodium benzoylbenzoate, benzalkonium chloride), and the like.
  • surfactants sorbitan monooleate, polyoxyethylene 20 oleate, polyoxy 20 cetyl ether, etc
  • antioxidants butylparahydroxy benzoic acid, butylhydroquinone, tocopherol, etc.
  • viscosity enhancing agents sodium alginate, carboxymethylcellulose, methylcellulose, tragacanth, agar, polyviny
  • Fig. 1 is a graph showing the concentration of an active ingredient in blood, measured at predetermined time intervals after an injectable solution of the present invention (Example 1) and a commercially available preparation as a control group are intramuscularly injected to male rats.
  • Examples 1 ⁇ 4> Preparation of injectable liquid solutions Florfenicol was added to a mixture of Glycofurol and laurocapram, in accordance with the compositions shown in Table 1 below. The resulting mixture was heated to 80°C to completely dissolve the florfenicol, and then cooled to room temperature. Polyethyleneglycol as a solution adjuvant was added thereto until the total volume reached 100ml.
  • the injectable solution prepared (florfenicol lOOmg/kg) in Example 1 and a commercially available preparation (Florocol 200, Handong Co., Ltd.), as a control group were intramuscularly injected for an adsorption experiment, respectively.
  • As experimental animals Sprague-Dawley rats (male, body weight 300 ⁇ 20g) were used. The three rats were divided into one group, respectively, and starved before the experiment. Relative bioavailability was measured on the experimental animal groups. Blank blood samples were obtained prior to the administration. Blood samples (0.2ml) were obtained from the jugular veins at predetermined time intervals after administration for analysis of florfenicol in blood. High performance liquid chromatography (HPLC) was used to analyze the concentrations of florfenicol in the blood samples.
  • HPLC high performance liquid chromatography
  • the concentrations of florfenicol in the blood samples are shown in Fig. 1.
  • the bioavailability of florfenicol in the experimental animal groups was identified to be excellent.
  • the injectable liquid composition according to the present invention comprising solubilized florfenicol as an active ingredient, shows excellent bioavailability and rapid abso ⁇ tion when administered intramuscularly.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

Disclosed herein is an injectable liquid composition comprising florfenicol as an active ingredient, a hydrophilic solvent and a lipophilic solvent wherein the active ingredient is dissolved in a mixture of the hydrophilic solvent and the lipophilic solvent. The injectable liquid composition comprising solubilized florfenicol as an active ingredient, exhibits excellent bioavailability and rapid absorption when administered intramuscularly.

Description

INJECTABLE COMPOSITION COMPRISING FLORFENICOL AS AN ACTIVE INGREDIENT
Technical Field
The present invention relates to an injectable composition comprising florfenicol as an active ingredient, and more particularly to an injectable liquid composition comprising a solubilized active ingredient therein with excellent bioavailability and rapid absorption when administered intramuscularly.
Background Art
Florfenicol [D-(threo)- 1 -p-methylsulfonylphenyl-2-dichloroacetoamido-3- fluoro-1-propanol] is a derivative wherein the hydroxyl group at C-3 position of thiamphenicol [D-d-threo-2-dichloroacetoamido- 1 -(4-methylsulfonyl)phenyl- 1,3- propandiol] is substituted with a fluorine atom. Florfenicol exhibits a broad antibacterial activity against pathogenic bacterial strains including enteric bacteria such as Enterobacter, Shigella, Salmonella and E. coli. These enteric bacteria exhibit a resistance to chloramphenicol and thiamphenicol due to enzymatic inactivation by chloramphenicol transacetylase. Florfenicol is widely used for veterinary purposes (Atep, M., Disposition Kinetics of Florfenicol in Goats by Using Two Analytical Methods. J. Vet. Med. A 48, 129-146, 2001; Varma, K., Pharmacokinetics of Florfenicol in veal calves. J. Vet. Pharmacol. Therap. 9, 412- 425, 1986). Although florfenicol has an antibacterial mechanism similar to chloramphenicol, it exhibits excellent antibacterial effects compared to chloramphenicol. In addition, florfenicol has an advantage of not causing irreversible aplastic anemia (AA). Since florfenicol, however, has a low water- solubility (about 1.3 mg/ml), it is difficult to formulate a concentrated aqueous solution of florfenicol in organic solvents such as 1,2-propandiol, glycerin, polyethylene glycol, propylene glycol and benzyl alcohol, which is required for oral therapeutic dosing.
PCT publication WO 92/04016 and U. S. Pat. No. 5,082,863 disclose a method for solubilizing water-insoluble florfenicol in aprotic polar solvents, e.g., N-methyl-2-pyrrolidone or 2-pyrrolidone. However, these solvents were proven to cause irritation at injected sites and tissue damage when administered intramuscularly.
Disclosure of the Invention
The present inventor has conducted intensive research to solve the above- mentioned problems of prior arts. As a result, the present inventor has found that when florfenicol as an active ingredient is dissolved in a mixture of a hydrophilic solvent and a lipophilic solvent to prepare an injectable solution, the injectable solution exhibits excellent bioavailability and rapid absorption in the body when administered intramuscularly, thus accomplishing the present invention.
Therefore, it is an object of the present invention to provide an injectable liquid composition with excellent bioavailability and rapid absorption when administered intramuscularly, comprising florfenicol as a solubilized active ingredient. In order to accomplish the above object of the present invention, there is provided an injectable liquid composition comprising florfenicol as an active ingredient, a hydrophilic solvent and a lipophilic solvent in which the active ingredient is dissolved in a mixture of the hydrophilic solvent and the lipophilic solvent. When florfenicol is dissolved in a mixture of a hydrophilic solvent and a lipophilic solvent, it is rapidly absorbed in the body and exhibits increased bioavailability upon intramuscular injection.
Examples of the hydrophilic solvent include, but not particularly limited to, diethyleneglycol monoethylether, 1,2-propyleneglycol, tetrahydrofurfuryl alcohol polyethyleneglycolether, polyethyleneglycol and mixtures thereof. The weight ratio of the florfenicol to the hydrophilic solvent is preferably within the range of 1: 0.5~5, and more preferably 1: 0.5~3. When the ratio is less than 1: 0.5, florfenicol is likely to be precipitated. When the ratio exceeds 1: 5, there is a risk of phase separation. However, although the florfenicol and the solvent are out of this range, it will be appreciated that the present invention can be sufficiently realized. Accordingly, this range is given only for the purpose of illustration, and is not to be construed as limiting the scope of the invention.
The lipophilic solvent is added to promote the absorption of the active ingredient in the body, and preferably is laurocapram, but is not particularly limited thereto. The weight ratio of the florfenicol to the lipophilic solvent is preferably within the range of 1: 0.3-2, and more preferably 1: 0.5-1. When the ratio is out of this range, there is a danger of low absorption of the florfenicol. However, although the florfenicol and the solvent are out of this range, it will be appreciated that the present invention can be sufficiently realized. Accordingly, this range is given only for the purpose of illustration, and is not to be construed as limiting the scope of the invention.
The injectable liquid composition of the present invention may further comprise polyethyleneglycol as a solution adjuvant. The weight ratio of the florfenicol to the polyethyleneglycol is within the range of 1: 1~4, and preferably 1: 2-3. If necessary, the inj ectable liquid composition of the present invention may further comprise medically acceptable additives. Examples of these additives include surfactants (sorbitan monooleate, polyoxyethylene 20 oleate, polyoxy 20 cetyl ether, etc), antioxidants (butylparahydroxy benzoic acid, butylhydroquinone, tocopherol, etc.), viscosity enhancing agents (sodium alginate, carboxymethylcellulose, methylcellulose, tragacanth, agar, polyvinylpyrrolidone, etc.), preservative agents (methyl paraoxybenzoate, propyl paraoxybenzoate, sodium benzoylbenzoate, benzalkonium chloride), and the like.
BRIEF DESCRIPTION OF THE DRAWINGS
The above and other objects, features and other advantages of the present invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawing, in which:
Fig. 1 is a graph showing the concentration of an active ingredient in blood, measured at predetermined time intervals after an injectable solution of the present invention (Example 1) and a commercially available preparation as a control group are intramuscularly injected to male rats.
Best Mode for Carrying Out the Invention
Hereinafter, the present invention will be described in more detail with reference to the following Examples. However, these Examples are given for the purpose of illustration and are not to be construed as limiting the scope of the invention.
<Examples 1~4> Preparation of injectable liquid solutions Florfenicol was added to a mixture of Glycofurol and laurocapram, in accordance with the compositions shown in Table 1 below. The resulting mixture was heated to 80°C to completely dissolve the florfenicol, and then cooled to room temperature. Polyethyleneglycol as a solution adjuvant was added thereto until the total volume reached 100ml.
<Table 1> Compositions of injectable solutions
Figure imgf000006_0001
<Test Example>
Measurement of pharmacological effects
The injectable solution prepared (florfenicol lOOmg/kg) in Example 1 and a commercially available preparation (Florocol 200, Handong Co., Ltd.), as a control group were intramuscularly injected for an adsorption experiment, respectively. As experimental animals, Sprague-Dawley rats (male, body weight 300±20g) were used. The three rats were divided into one group, respectively, and starved before the experiment. Relative bioavailability was measured on the experimental animal groups. Blank blood samples were obtained prior to the administration. Blood samples (0.2ml) were obtained from the jugular veins at predetermined time intervals after administration for analysis of florfenicol in blood. High performance liquid chromatography (HPLC) was used to analyze the concentrations of florfenicol in the blood samples.
The concentrations of florfenicol in the blood samples are shown in Fig. 1. The bioavailability of florfenicol in the experimental animal groups was identified to be excellent.
Industrial Applicability
As apparent from the above description, the injectable liquid composition according to the present invention comprising solubilized florfenicol as an active ingredient, shows excellent bioavailability and rapid absoφtion when administered intramuscularly.
Although the preferred embodiments of the present invention have been disclosed for illustrative puφoses, those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.

Claims

Claims:
1. An injectable liquid composition comprising florfenicol as an active ingredient, a hydrophilic solvent and a lipophilic solvent, wherein the active ingredient is dissolved in a mixture of the hydrophilic solvent and the lipophilic solvent.
2. The injectable liquid composition according to claim 1, wherein the the hydrophilic solvent is tetrahydrofurfuryl alcohol polyethyleneglycolether or polyethyleneglycol.
3. The injectable liquid composition according to claim 1 or 2, wherein the weight ratio of the florfenicol to the hydrophilic solvent is within the range of 1: 0.5-5.
4. The injectable liquid composition according to claim 1, wherein the lipophilic solvent is laurocapram.
5. The injectable liquid composition according to claim 1 or 4, wherein the weight ratio of the florfenicol to the lipophilic solvent is within the range of 1:
0.3-2.
6. The injectable liquid composition according to claim 1, further comprising polyethyleneglycol as a solution adjuvant.
PCT/KR2003/001265 2002-08-13 2003-06-27 Injectable composition comprising florfenicol as an active ingredient WO2004014340A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003244257A AU2003244257A1 (en) 2002-08-13 2003-06-27 Injectable composition comprising florfenicol as an active ingredient

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020020047909A KR20040015623A (en) 2002-08-13 2002-08-13 Injectable Composition Comprising Florfenicol as Active Ingredient
KR10-2002-0047909 2002-08-13

Publications (1)

Publication Number Publication Date
WO2004014340A1 true WO2004014340A1 (en) 2004-02-19

Family

ID=31713127

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2003/001265 WO2004014340A1 (en) 2002-08-13 2003-06-27 Injectable composition comprising florfenicol as an active ingredient

Country Status (3)

Country Link
KR (1) KR20040015623A (en)
AU (1) AU2003244257A1 (en)
WO (1) WO2004014340A1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008524311A (en) * 2004-12-21 2008-07-10 インターベツト・インターナシヨナル・ベー・ベー Injectable veterinary composition
FR2925335A1 (en) * 2007-12-21 2009-06-26 Ceva Sante Animale Sa FLORFENICOL LIQUID ORAL COMPOSITIONS DILUABLE IN DRINKING WATER
EP2995297A1 (en) 2014-09-09 2016-03-16 Ceva Sante Animale Parenteral compositions and uses thereof
CN106176605A (en) * 2016-08-30 2016-12-07 河南牧翔动物药业有限公司 A kind of method using non-polar support to prepare florfenicol submicron emulsion

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992004016A1 (en) * 1990-08-29 1992-03-19 Schering Corporation Pharmaceutical composition of florfenicol
US5177110A (en) * 1989-10-27 1993-01-05 Ciba-Geigy Corporation Injectable parasiticidal composition

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5177110A (en) * 1989-10-27 1993-01-05 Ciba-Geigy Corporation Injectable parasiticidal composition
WO1992004016A1 (en) * 1990-08-29 1992-03-19 Schering Corporation Pharmaceutical composition of florfenicol

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008524311A (en) * 2004-12-21 2008-07-10 インターベツト・インターナシヨナル・ベー・ベー Injectable veterinary composition
US8680154B2 (en) 2004-12-21 2014-03-25 Intervet International B.V. Injectable veterinary composition
FR2925335A1 (en) * 2007-12-21 2009-06-26 Ceva Sante Animale Sa FLORFENICOL LIQUID ORAL COMPOSITIONS DILUABLE IN DRINKING WATER
WO2009083520A2 (en) * 2007-12-21 2009-07-09 Ceva Sante Animale Liquid oral florfenicol compositions which can be diluted in drinking water
WO2009083520A3 (en) * 2007-12-21 2009-12-03 Ceva Sante Animale Liquid oral florfenicol compositions which can be diluted in drinking water
EP2995297A1 (en) 2014-09-09 2016-03-16 Ceva Sante Animale Parenteral compositions and uses thereof
WO2016038059A1 (en) 2014-09-09 2016-03-17 Ceva Sante Animale Parenteral compositions and uses thereof
EP3513781A1 (en) 2014-09-09 2019-07-24 Ceva Sante Animale Parenteral compositions and uses thereof
CN106176605A (en) * 2016-08-30 2016-12-07 河南牧翔动物药业有限公司 A kind of method using non-polar support to prepare florfenicol submicron emulsion

Also Published As

Publication number Publication date
KR20040015623A (en) 2004-02-19
AU2003244257A1 (en) 2004-02-25

Similar Documents

Publication Publication Date Title
CA2166388C (en) Antifungal composition for external use retentive in stratum corneum
DK1610613T3 (en) TOPICAL ANTHELMINTIC VETERINARY FORMULATIONS
EP3870227B1 (en) Deep eutectic solvent platform for oral pharmaceutical formulations
EP0315648B1 (en) Sebum-dissolving nonaqueous minoxidil formulation
US20190175491A1 (en) Topical compositions of apremilast
JP5017122B2 (en) Injectable veterinary composition
MX2011002936A (en) Liquid formulations of bendamustine.
JP6482570B2 (en) Transdermal absorption enhancer and transdermal absorption enhancer
WO2004014340A1 (en) Injectable composition comprising florfenicol as an active ingredient
BG64664B1 (en) Nimesulide gel systems for local administration
WO2004014341A1 (en) Oral injectable pharmaceutical composition comprising florfenicol as an active ingredient
KR100893469B1 (en) Compositions containing minoxidil for the hair generation which have an improved skin permeation
JP2002356426A (en) Skin care preparation comprising pyridone carboxylic acid-based compound
WO2004014339A1 (en) Injectable composition comprising ceftiofur sodium as an active ingredient
RU2699022C1 (en) Galenic composition containing a drug for topical application
EP0021847B1 (en) Long acting sulfonamide injectable compositions
FI72651B (en) FOERFARANDE FOER FRAMSTAELLNING AV EN LAONGTIDSVERKANDE INJEKTIONSLOESNING AV SULFAMETAZIN.
FI57883C (en) FOER FARING FOR FRAMSTAELLNING AV EN STABLE KLORTETRACYKLINLOESNING
JPH07304690A (en) Keratin solubilizer, percutaneous absorption accelerator and external skin preparation
HRP960519A2 (en) Novel therapeutic anti-inflammatory and analgesic pharmaceutical composition for the transdermal use

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP