WO2004014339A1 - Composition injectable contenant du ceftiofur sodique comme ingredient actif - Google Patents

Composition injectable contenant du ceftiofur sodique comme ingredient actif Download PDF

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Publication number
WO2004014339A1
WO2004014339A1 PCT/KR2003/001264 KR0301264W WO2004014339A1 WO 2004014339 A1 WO2004014339 A1 WO 2004014339A1 KR 0301264 W KR0301264 W KR 0301264W WO 2004014339 A1 WO2004014339 A1 WO 2004014339A1
Authority
WO
WIPO (PCT)
Prior art keywords
injectable suspension
suspension composition
ceftiofur
fatty acid
composition according
Prior art date
Application number
PCT/KR2003/001264
Other languages
English (en)
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 AU2003244255A priority Critical patent/AU2003244255A1/en
Publication of WO2004014339A1 publication Critical patent/WO2004014339A1/fr

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
    • A61K31/33—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
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin

Definitions

  • the present invention relates to an injectable composition comprising ceftiofur sodium as an active ingredient and an excipient, and more particularly to an injectable suspension composition comprising ceftiofur sodium as an active ingredient which has a low viscosity and excellent redispersibility and bioavailability.
  • Ceftiofur ([6R-[6 ⁇ , 7 ⁇ (Z)]]7-[[(2-amino-4- thiazolyl)(methoxyimino)acetyl]amino]-3-[[(2-furanylcarbonyl)thio]methyl]-8- oxo-5-thia-l-azacyclo[4.2.0]oct -2-ene-2-carboxylic acid) is a third- generation cephalosporin-based antiobiotic, and exhibits an extended beta-lactamase resistance and a broad antibacterial activity against pathogenic bacterial strains including gram-positive and gram-negative bacteria. Ceftiofur is widely used for veterinary purposes (Brown, S.
  • Korean Patent No. 96- 0008236 discloses an aqueous composition containing nicotine amide as a solution adjuvant for improving the stability of ceftiofur in water. Hovfeever, the aqueous composition still has a problem in terms of instable formulation.
  • a technique for preparing a sustained-release composition in which active ingredients are dispersed in a vegetable oil as a non-aqueous injectable suspension is disclosed in PCT Publication WO 94/20505.
  • PCT Publication WO 98/25621 discloses an oil suspension of ceftiofur hydrochloride salt with improved dispersibility. The oil suspension is prepared by adding water to a ceftiofur hydrochloride salt containing lecithin and a surfactant and having a particle size of lO ⁇ m or less.
  • ceftiofur sodium formulations are those prepared by lyophilizing in a sterilized state for stabilizing active ingredients, followed by powdering. Thus, these formulations must be dissolved in water before use, and have a problem of complex preparation processes.
  • 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 a vegetable fatty acid ester is used as a dispersion medium of ceftiofur sodium, redispersibility and bioavailability of an active ingredient are improved, thus accomplishing the present invention.
  • an object of the present invention to provide an injectable suspension composition with increased viscosity and excellent redispersibility and bioavailability, comprising ceftiofur sodium as an active ingredient.
  • an injectable suspension composition comprising ceftiofur sodium as an active ingredient, an excipient, and a vegetable fatty acid ester as a dispersion medium.
  • the term 'vegetable fatty acid ester' used herein refers to an esterified compound obtained through a condensation reaction between a known fatty acid present in a vegetable oil and a known primary, secondary or tertiary alcohol.
  • the vegetable fatty acid ester may be a single component or a mixture of at least two components.
  • fatty acid ester preferably include monoglyceride, diglyceride, triglyceride, benzyl alcohol, benzyl benzoate, ethyl oleate, ethyl linolate, isopropylpalmitate and isopropylmyristate.
  • the content of the fatty acid ester in the injectable composition of the present invention varies according to the kind of the fatty acid ester used, but is not particularly limited.
  • the weight ratio of the ceftiofur sodium to the fatty acid ester is preferably within the range of 1: 0.1-40, and more preferably 1: 0.5 ⁇ 3. When the ratio is less than 1: 0.1, the dispersibility of the active ingredient is poor. When the ratio exceeds 1: 10, there is a problem of inconvenient use due to too diluted concentration.
  • 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 suspension composition of the present invention may further comprise an appropriate amount of ethanol (or anhydrous ethanol), etc., as a viscosity enhancing agent for improving redispersibility and controlling viscosity of the composition.
  • ethanol or anhydrous ethanol
  • the amount of ethanol added can be appropriately varied by those skilled in the art according to a desired viscosity and dispersibility, but is not particularly limited.
  • the injectable suspension composition of the present invention may further comprise medically acceptable additives.
  • 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.) and the like.
  • the injectable suspension composition of the present invention comprising ceftiofur sodium as an active ingredient can be intramuscularly injected at different doses in accordance with needs of animals to be treated.
  • ceftiofur sodium is dissolved in 20ml of an injectable solution containing the dispersion medium.
  • the solution is intramuscularly injected in the volume of l ⁇ 2ml/50kg of body weight once daily (the solution can be injected for three consecutive days, and in the case of no improvements for five consecutive days).
  • the solution is intramuscularly injected in the volume of 0.6 ⁇ lml/10kg of body weight once daily (the solution can be injected for three consecutive days).
  • Fig. 1 is a graph showing the concentration of an active ingredient in blood, measured at predetermined time intervals after an injectable suspension of the present invention (Example 1) and a commercially available preparation (Excenel) as a control group are intramuscularly injected to male rats.
  • the concentrations of ceftiofur in the blood samples are shown in Fig. 1.
  • the bioavailability of ceftiofur in the experimental animal groups was identified to be excellent.
  • the injectable suspension composition according to the present invention comprising ceftiofur sodium as an active ingredient, shows improved viscosity and excellent redispersibility and bioavailability.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Dermatology (AREA)
  • Dispersion Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention concerne une composition sous forme de suspension injectable contenant du ceftiofur sodique comme ingrédient actif, un excipient et un ester d'acide gras végétal comme milieu de dispersion. Cette composition sous forme de suspension injectable comprenant du ceftiofur sodique comme ingrédient actif présente une viscosité accrue ainsi que d'excellentes propriétés de redispersibilité et de biodisponibilité.
PCT/KR2003/001264 2002-08-13 2003-06-27 Composition injectable contenant du ceftiofur sodique comme ingredient actif WO2004014339A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003244255A AU2003244255A1 (en) 2002-08-13 2003-06-27 Injectable composition comprising ceftiofur sodium as an active ingredient

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2002-0047908 2002-08-13
KR1020020047908A KR20040015622A (ko) 2002-08-13 2002-08-13 세프티오푸르나트륨을 활성성분으로 함유하는 현탁주사액조성물

Publications (1)

Publication Number Publication Date
WO2004014339A1 true WO2004014339A1 (fr) 2004-02-19

Family

ID=31713126

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2003/001264 WO2004014339A1 (fr) 2002-08-13 2003-06-27 Composition injectable contenant du ceftiofur sodique comme ingredient actif

Country Status (3)

Country Link
KR (1) KR20040015622A (fr)
AU (1) AU2003244255A1 (fr)
WO (1) WO2004014339A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102341125A (zh) * 2008-11-19 2012-02-01 梅里亚有限公司 包含头孢噻呋和酮洛芬或头孢噻呋和苯甲醇的配制剂
CN104080456A (zh) * 2011-12-23 2014-10-01 拜耳新西兰有限公司 抗生素制剂
CN105232458A (zh) * 2015-10-23 2016-01-13 四川恒通动物制药有限公司 一种头孢噻呋晶体混悬注射液及其制备方法
EP2874624B1 (fr) 2012-07-17 2019-08-21 Bayer New Zealand Limited Formulations antibiotiques injectables et leurs procédés d'utilisation

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113209015A (zh) * 2020-01-21 2021-08-06 江西邦诚动物药业有限公司 长效盐酸头孢噻呋混悬注射液及其制备工艺
CN112645965B (zh) * 2020-12-22 2022-03-25 浙江华尔成生物药业股份有限公司 一种真空冻干注射用头孢噻呋钠的制备工艺
CN112870159A (zh) * 2021-02-03 2021-06-01 西安乐道生物科技有限公司 一种清热解毒退烧的兽用盐酸头孢噻呋注射液及制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998025621A1 (fr) * 1996-12-09 1998-06-18 Pharmacia & Upjohn Company Compositions pharmaceutiques ameliorees
WO2000027369A1 (fr) * 1998-11-10 2000-05-18 Idexx Laboratories, Inc. Microcristaux recouverts de phospholipides pour une libération prolongée de composés pharmacologiquement actifs, élaboration et utilisation de ces microcristaux
WO2002022107A2 (fr) * 2000-09-12 2002-03-21 Pharmacia & Upjohn Company Composition pharmaceutique dotee d'un support modifie
WO2002066006A1 (fr) * 2001-02-19 2002-08-29 Lg Life Sciences Ltd. Suspension d'hydrochlorure de ceftiofur a liberation prolongee

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3887691T2 (de) * 1987-11-10 1994-06-09 Upjohn Co Cephalosporin-antibiotika.
SK283674B6 (sk) * 1993-03-12 2003-11-04 Pharmacia & Upjohn Company Kryštalická voľná kyselina ceftiofuru a spôsob jej prípravy a farmaceutická kompozícia, ktorá ju obsahuje

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998025621A1 (fr) * 1996-12-09 1998-06-18 Pharmacia & Upjohn Company Compositions pharmaceutiques ameliorees
WO2000027369A1 (fr) * 1998-11-10 2000-05-18 Idexx Laboratories, Inc. Microcristaux recouverts de phospholipides pour une libération prolongée de composés pharmacologiquement actifs, élaboration et utilisation de ces microcristaux
WO2002022107A2 (fr) * 2000-09-12 2002-03-21 Pharmacia & Upjohn Company Composition pharmaceutique dotee d'un support modifie
WO2002066006A1 (fr) * 2001-02-19 2002-08-29 Lg Life Sciences Ltd. Suspension d'hydrochlorure de ceftiofur a liberation prolongee

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102341125A (zh) * 2008-11-19 2012-02-01 梅里亚有限公司 包含头孢噻呋和酮洛芬或头孢噻呋和苯甲醇的配制剂
KR101748890B1 (ko) 2008-11-19 2017-06-19 메리얼 인코포레이티드 세프티오퍼 및 케토프로펜 또는 세프티오퍼 및 벤질 알코올을 포함하는 제형
EP2367572B1 (fr) * 2008-11-19 2018-08-29 Merial, Inc. Formulations comprenant du ceftiofur et de l'alcool benzylique
CN104080456A (zh) * 2011-12-23 2014-10-01 拜耳新西兰有限公司 抗生素制剂
EP2874624B1 (fr) 2012-07-17 2019-08-21 Bayer New Zealand Limited Formulations antibiotiques injectables et leurs procédés d'utilisation
CN105232458A (zh) * 2015-10-23 2016-01-13 四川恒通动物制药有限公司 一种头孢噻呋晶体混悬注射液及其制备方法
CN105232458B (zh) * 2015-10-23 2018-05-22 四川恒通动物制药有限公司 一种头孢噻呋晶体混悬注射液及其制备方法

Also Published As

Publication number Publication date
KR20040015622A (ko) 2004-02-19
AU2003244255A1 (en) 2004-02-25

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