WO2013095166A1 - Antibiotic formulations - Google Patents
Antibiotic formulations Download PDFInfo
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- WO2013095166A1 WO2013095166A1 PCT/NZ2012/000245 NZ2012000245W WO2013095166A1 WO 2013095166 A1 WO2013095166 A1 WO 2013095166A1 NZ 2012000245 W NZ2012000245 W NZ 2012000245W WO 2013095166 A1 WO2013095166 A1 WO 2013095166A1
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- Prior art keywords
- oil
- suspension formulation
- formulation
- suspension
- container
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- 238000007918 intramuscular administration Methods 0.000 description 1
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- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
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- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- KTAVBOYXMBQFGR-MAODNAKNSA-J tetrasodium;(6r,7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyimino-1-oxidoethylidene]amino]-3-[(2-methyl-5,6-dioxo-1h-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate;heptahydrate Chemical compound O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C([O-])=NN1C.S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C([O-])=NN1C KTAVBOYXMBQFGR-MAODNAKNSA-J 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 1
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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
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61K47/14—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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0068—Rumen, e.g. rumen bolus
-
- 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 antibiotic formulations.
- the present invention relates to cephalosporin antibiotic suspension formulations, their methods of manufacture and use.
- Cephalosporin antibiotics are a subset of the ⁇ -lactam family of antibiotics and are used to treat bacterial infections, typically in the veterinary industry.
- the core structure of cephalosporin antibiotic is shown below:
- cephalosporin antibiotics are classified into "generations” as outlined in Martindale: The Complete Drug Reference, 35th Edition, the content of which is incorporated by reference. It is generally understood cephalosporins act by blocking the production of the peptidoglycan layer of bacterial cell walls. Although first-generation cephalosporins are predominantly active against Gram-positive bacteria, successive generations have heightened activity against Gram-negative bacteria (albeit often with reduced activity against Gram-positive organisms). New types of cephalosporin antibiotics have been identified, which have yet to be assigned to a particular generation.
- Cephalosporin antibiotics are characterised as being difficult to provide in a formulation due to their low solubility and poor stability. While cephalosporin antibiotics, such as Ceftiofur (a third generation antibiotic), can be administered orally or topically, it has been found that they are poorly absorbed upon oral administration, and are more rapidly absorbed after intramuscular administration. However, ceftiofur in aqueous solution degrades rapidly and must be stored as a sterile powder for reconstitution when required, such as the commercial product ExcenelTM. Following dissolution of ceftiofur in sterile water, storage stability is limited to 12 hours at room temperature, or up to 7 days in a refrigerator.
- a ready-to-use (TU) Ceftiofur and other cephalosporin antibiotics are preferentially administered in an oily (typically vegetable oil) suspension for parenteral injection.
- oily typically vegetable oil
- oily suspensions containing cephalosporin antibiotics can be problematic due to formulations being physically and/or chemically unstable. This is due to suspensions being present in more than one state, such as a liquid and a solid, and also the difficult insoluble nature of the active itself.
- Four major issues may arise in relation to such suspensions: a) dispersion of particles in a vehicle; b) settling of the dispersed particles; c) caking of such particles in the sediment so as to prevent dispersion when required (typically just prior to administration); and d) degradation of the cephalosporin antibiotic.
- flocculation There has been much investigation into how these problems can be avoided in suspensions, the aim being to achieve controlled aggregation (termed flocculation). Many different types of vehicles are used to help with flocculation, including a preserved sodium chloride solution or a parenterally acceptable vegetable oil.
- cephalosporin antibiotic suspensions flocculate as set out below.
- Ceftiofur is a particularly effective antibiotic.
- Ceftiofur hydrochloride is a broad spectrum cephalosporin antibiotic active against Fusobacterium necrophorum and Bacteroides melaninogenicus the two main pathogens associated with bovine foot rot. Ceftiofur hydrochloride also has excellent in vitro and in vivo activity against Pasteurella hemolytica and P.
- BTD bovine respiratory disease
- Ceftiofur has excellent in vitro activity against other Gram-negative pathogens, such as E. coli, Salmonella choleraesuis, Salmonella typhimurium and
- Ceftiofur has excellent in vitro and in vivo activity against Gram-negative pathogens such as Actinobacillus (Haemophilus) pleuropneumoniae, Salmonella choleraesuis, Pasteurella multocida and the Gram-positive pathogen
- Streptococcus suis all of which singly or in combination can be associated with swine bacterial respiratory disease (swine-bacterial pneumonia).
- Ceftiofur also has excellent in vitro activity against other Gram-negative pathogens, such as E. coli and Salmonella typhumurim and against Gram-positive pathogens such as Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis and Streptococcus bovis.
- Ceftiofur was effective when tested in a variety of mouse disease models involving E. coli, Staphylococcus aureus, Streptococcus agalactiae, Pasteurella multocida or Salmonella typhimurium. However, the clinical significance of these findings in swine is not known.
- US 5,736,151 discloses an oily suspension including Ceftiofur and water as a flocculating agent to provide better re-suspendability of the suspension.
- US 4,902,683 discloses a host of excipients which are suggested as being appropriate to help prepare a suspension of Ceftiofur for systemic administration.
- WO 2004/014390 discloses the use of a re-suspendability enhancer for an oily suspension of Ceftiofur, wherein the re-suspendability enhancer is selected from polyoxyl hydrogenated vegetable oil, polyoxyl vegetable oil, glycerol, propylene glycol or polyethylene glycol.
- WO 2010-059747 discloses the use of benzyl alcohol as a re-suspendability enhancer when used for ceftiofur and ketoprofen.
- the additives used to improve physical stability of the cephalosporin antibiotic containing oily suspensions can often lead to chemical instability of the antibiotic itself, obviously resulting in an undesirably short-shelf life of the formulation and/or a shortened effectiveness after administration.
- US 5,736,151 merely uses water as a flocculating agent.
- the present inventors have found such a formulation can have a limited shelf-life and generally undesirable pharmacokinetic properties. Similar results were found for carriers such as glycols as disclosed in WO 2004/014390.
- the use of additives such as glycols can increase the costs associated with the production of such formulations, cause site reaction on delivery, allergies and the like.
- Excenel RTU TM A commercially available ready-to-use Ceftiofur formulation is Excenel RTU TM , marketed by Pfizer.
- Excenel RTU is an oil based suspension that uses a small quantity of water as a flocculating agent. According to the directions that accompanies the Excenel RTU product, shaking for 20-30 seconds is required for re-suspension of the active.
- suspension formulations are kept in glass vials. This has been found to help counter the major problems with suspensions as outlined above. However, there are subsequent concerns with glass storage including the greater likelihood of breakage and higher costs of production/storage. It would be preferable to store suspensions that have an improved flocculation and/or stability in PET
- PET vials have been known to cause caking meaning that currently available formulations do not store particularly well in PET vials.
- water and oxygen can diffuse through the PET packaging and be absorbed into the contents. This can accelerate degradation of the active, and interfere with the physical stability such as by enhancing sedimentation and caking.
- CefaguardTM commercially available Ceftiofur formulation
- Stockguard had 10% less active than the label requirement when the formulation was stored in PET vials. Testing revealed the CefaguardTM formulation had a water content similar to ExcenelTM RTU (ready- to-use).
- suspensions containing water such as that described in US 5,736,151 can have poor storage stability.
- One object of the present invention is therefore to provide a cephalosporin antibiotic containing formulation which is more storage stable in a wider range of conditions and/or for longer durations with lesser or no decrease in the active agent concentration in the suspension, and/or may be effectively stored in PET vials without caking or other problems seen with currently available formulations. It can be appreciated there is a significant commercial advantage if a composition is able to retain an active concentration above the label requirement for a longer duration. This avoids the consumer or retailer having to frequently replenish supplies , making it a more attractive product to supply or purchase.
- An alternative object of the present invention is to address the foregoing problems with cephalosporin antibiotic containing suspensions or at least to provide the public with a useful choice.
- suspension formulation for administration to an animal, the suspension formulation including a) at least one cephalosporin antibiotic or a pharmaceutically similar salt
- a glycerol acetate solvent in present invention provides improved suspension of the cephalosporin antibiotic active agent.
- the glycerol acetate solvent was surprisingly found by the inventors to provide improved mixing and re- suspending of the oil and cephalosporin antibiotic and good anti-caking properties. This is very important not only during the manufacturing stage (to reduce time and resources required) but also for re-suspension prior to delivery by the administrator of the formulation.
- suspensions formulated according to the present invention were particularly stable, and had good anti-caking characteristics, particularly when stored in plastic PET vials. As previously discussed, these results may help to overcome a number of problems associated with current industry practice of storing cephalosporin antibiotic suspensions in glass vials due to poor storage characteristics in other types of containers.
- PET vials should be taken as meaning any container or vessel which includes polyethylene terephthalate (also known as poly (ethylene terephthalate). PET consists of polymerised units of ethylene
- cephalosporin antibiotic should be taken as meaning a class of ⁇ -lactam antibiotics derived from Acremonium.
- cephalosporin antibiotics include a number of different members which are commonly classified into “generations”. Currently there are five broad generations as outlined below:
- Generation 1 members include Cefacetrile (cephacetrile), Cefadroxil
- Cefadroxyl Duricef
- Cephalexin cephalexin; Keflex
- Cefaloglycin cephaloglycin
- Cefalonium cephalonium
- Cefaloridine cephaloradine
- Cefalotin cephalothin
- Keflin Cefapirin
- Cefazolin cephazolin
- Cefazolin Cephazolin; Ancef, Kefzol
- Cefradine cephradine; Velosef
- Cefroxadine Ceftezole.
- Generation 2 members include Cefaclor (Ceclor, Distaclor, Keflor,
- Cefonicid Monocid
- Cefprozil cefproxil
- Cefzil Cefuroxime
- Cefu Zinnat, Zinacef, Ceftin, Biofuroksym, Xorimax
- Cefuzonam Second generation cephalosporins with antianaerobe activity: Cefmetazole, Cefotetan, Cefoxitin.
- cephems are also sometimes grouped with second-generation cephalosporins: Carbacephems: loracarbef (Lorabid); Cephamycins: cefbuperazone, cefmetazole (Zefazone), cefminox, cefotetan (Cefotan), cefoxitin (Mefoxin).
- Generation 3 members include Cefcapene, Cefdaloxime, Cefdinir (Zinir, Omnicef, Kefnir), Cefditoren, Cefetamet, Cefixime (Zifi, Suprax),
- Cefmenoxime Cefodizime, Cefotaxime (Claforan), Cefovecin (Convenia), Cefpimizole, Cefpodoxime (Vantin, PECEF), Cefteram, Ceftibuten (Cedax), Ceftiofur, Ceftiolene, Ceftizoxime (Cefizox), Ceftriaxone (Rocephin).
- Third- generation cephalosporins with antipseudomonal activity Cefoperazone (Cefobid), Ceftazidime (Fortum, Fortaz). The following cephems are also sometimes grouped with third-generation cephalosporins: Oxacephems: latamoxef (moxalactam).
- Generation 4 members include Cefclidine, Cefepime (Maxipime),
- Generation 5 members include Ceftobiprole, Ceftaroline. Other cephalosporin antibiotics have been identified, but have yet to be assigned to a particular generation. These include Cefaloram, Cefaparole, Cefcanel,
- Cefedrolor Cefempidone, Cefetrizole, Cefivitril, Cefmatilen, Cefmepidium,
- cephalosporin antibiotics share substantial structural features, similar stability and solubility characteristics, and a similar mode of action. Therefore, it would be reasonably expected by someone skilled in the art that using any one or combination of cephalosporin antibiotics other than Ceftiofur, either as currently known or as developed/identified in future, in combination with a glycerol acetate solvent and an oil in a suspension formulation according to the present invention will provide the same advantageous results as described herein.
- the cephalosporin antibiotic is selected from the group consisting of a third generation cephalosporin antibiotic as listed above.
- the cephalosporin antibiotic is Ceftiofur.
- the suspension formulation includes approximately between 1 - 30% w/v of the cephalosporin antibiotic.
- the suspension formulation includes 5 - 6% w/v of the
- cephalosporin antibiotic The inventors identified that a concentration of 5.35% w/v Ceftiofur HCI was required to give a 5% Ceftiofur base.
- the upper concentration of the cephalosporin is usually governed by the resulting viscosity of the
- oil should be taken as any substance that is liquid at ambient temperatures, is hydrophobic and is soluble in organic solvents.
- the oil is of a vegetable, animal or synthetic origin. More preferably, the oil is selected from the group consisting of canola oil, corn oil, cottonseed oil, olive oil, peanut oil, sesame oil, soybean oil, safflower oil, coconut oil, sunflower oil, palm oil, monoglyceride, diglyceride and triglyceride medium chain succinic acid triglyceride. Most preferably, the oil is cottonseed oil.
- the suspension formulation may include approximately between 70-99% w/v of the oil. However it should be appreciated that the oil may be used at an amount sufficient to increase the suspension to a desired volume (qs), such as 1000 ml.
- glycerol acetate solvent also known as glycerine acetate
- glycerol acetate solvent should be taken as meaning the ester produced from the esterification of glycerol with acetic acid.
- the glycerol acetate solvent is selected from the group consisting of acetin, diacetin and triacetin.
- the glycerol acetate solvent is triacetin.
- Triacetin would work particularly well compared to acetin or diacetin, however any of these solvents from this group can preferably be used.
- Triacetin is also known as triglyceride 1 ,2,3-tricetoxypropane and glycerine triacetate. Triacetin is the triester of glycerol and acidic acid.
- Triacetin compounds (and related acetin and diacetin compounds) have been described as having transdermal and solvent properties and have the general structure: Various patent disclosures describe the use of triacetin as a solvent for veterinary formulations containing different active agents and different modes of delivery (See for example NZ 234802, NZ 520707 and NZ 306249).
- the specific type of formulation e.g. drench, pour-on, parenteral injectable solution, suspension, bolus, and so forth
- drench pour-on, parenteral injectable solution, suspension, bolus, and so forth
- cephalosporin antibiotic active requiring the formulation to be provided as an oily suspension.
- the difficulty in formulating cephalosporin antibiotics such as Ceftiofur is clearly exemplified in US 5,736, 151 , US 4,902,683 and WO
- a glycerol acetate solvent such as triacetin may improve the storage characteristics, shelf-life and persistency of a cephalosporin antibiotic active containing oily suspension. Also, the inventors have determined that the formulations herein described have a site reaction on injection similar or better than currently available references.
- the suspension formulation includes approximately between 0.05 to 5% w/v of a glycerol acetate solvent.
- the suspension formulation includes approximately 0.5 % w/v of a glycerol acetate solvent.
- a glycerol acetate solvent such as triacetin
- the inventors have found that using the same amount of a glycerol acetate solvent (such as triacetin) as a substitute for a glycol (as disclosed in WO 2004/014390) surprisingly leads to substantially improved mixing and resuspendibility characteristics, shelf-life and duration of action of the suspension.
- the suspension formulation includes a surfactant.
- a surfactant Almost any surfactant may be used with the present invention and it should be appreciated that someone skilled in the art would be able to identify an appropriate surfactant to use with the formulation.
- the surfactant is sorbitan monooleate (e.g. Span80).
- the formulation includes a dispersing agent.
- a dispersing agent is phosphatidylcholine, hydrogenated (e.g. Phospolipon H90).
- a suspension formulation as substantially described herein to an animal for the treatment or prevention of a bacterial infection or resulting condition.
- the bacterial infection or condition to be treated or prevented is bovine bacterial respiratory disease or wine bacterial respiratory disease.
- the bacterial infection or condition to be treated or prevented is bovine foot rot.
- the bacterial infection or condition to be treated or prevented is bovine metritis.
- the present invention may be used to treat any infection or condition for which a cephalosporin antibiotic is known to be useful, now or in the future.
- the method of treatment includes administering to the animal in need thereof the formulation substantially as described herein at a rate of between approximately 0.5 - 5 mg of the cephalosporin antibiotic per kilogram body weight of the animal to be treated per day.
- the method of treatment is by injection.
- the formulation may be configured to be administered orally or topically.
- the inventors foresee the present invention may have particular advantage in oral administration, where cephalosporin antibiotics have typically shown poor absorption.
- the use of a glycerol acceptable solvent may have a particular effect in the absorption characteristics of the active.
- the particular dosage used may depend on the animal and condition/infection to be treated. For example, the inventors have found that the following dosages were particularly suitable for the animal and disease/condition outlined in the table below:
- a significant advantage of the present invention is the improved storage stability and re-suspendability characteristics in PET vials. Based on the preferred dosages below, it will become apparent that a single 125 ml PET vial may be sufficient to use in the treatment of an animal for a full dosage regime, or potentially even several animals, depending on the requirements.
- the ability to effectively use PET vials for the present formulation provides a significant advantage over previous formulations which must typically be stored in more fragile and expensive glass vials.
- a method of preparing a formulation substantially as described above wherein the method includes the steps of: (a) adding an amount of an oil to a first container,
- the present manufacturing method is more production friendly as there is no extensive heating required, nor the long incubation times described for example in WO 2004/014390. It is believed by the inventors that the use of triacetin surprisingly leads to better mixing with the oil, making the overall manufacturing process easier and less time consuming.
- the heating step in (b) comprises heating the oil to between 15-90°C.
- the mixture resulting from step (b) is incubated for between 5 minutes and 60 minutes.
- a use in the manufacture of a medicament including a suspension formulation as substantially described above for the treatment or prevention of a bacterial infection or condition in an animal in need thereof.
- the use is for the treatment or prevention of bovine and/or swine bacterial respiratory disease, bovine foot rot or bovine metritis.
- the study reported involves three pilot scale batches (3.5L - batch numbers T1707, T1708, T1709), which were produced using the manufacturing process described above. The batches produced were then packed in 125ml_ clear PET vials and the physical and chemical characteristics recorded at regular intervals as recommended by the ACVM.
- Example 1 has beneficial storage and re-suspendability characteristics in PET vials and is storage stable in a wide variety of conditions. After three months (at 40°C / 75% RH) the composition of Example 1 showed a decrease of 0.9% w/v Ceftiofur (as HCI).
- Example 1 Over a longer test period, this difference in stability between the composition of Example 1 and reference composition would be expected to be even greater.
- Example 1 can be stored for longer periods whilst keeping above the label requirements.
- the time taken to re-suspend the active by shaking the vial, after long-term storage of the formulation of Example 1 was less than 5 seconds. This indicates that there was no deleterious caking even after long periods of storage in PET vials.
- the batches were assessed according to the following test conditions:
- Example 6 Residue studies Animal studies have shown that formulation has remarkably low residues in cattle and pigs in all tissues. The expected withhold period (WHP) for milk when used in cattle is nil.
- WTP The expected withhold period
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Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
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MX2014007735A MX2014007735A (en) | 2011-12-23 | 2012-12-21 | Antibiotic formulations. |
CN201280063872.1A CN104080456A (en) | 2011-12-23 | 2012-12-21 | Antibiotic formulations |
AU2012359296A AU2012359296B2 (en) | 2011-12-23 | 2012-12-21 | Antibiotic formulations |
KR1020147020501A KR20140102319A (en) | 2011-12-23 | 2012-12-21 | Antibiotic formulations |
BR112014014786A BR112014014786A2 (en) | 2011-12-23 | 2012-12-21 | antibiotic formulations |
PH12014501384A PH12014501384A1 (en) | 2011-12-23 | 2014-06-18 | Antibiotic formulations |
IL233299A IL233299A0 (en) | 2011-12-23 | 2014-06-22 | Cephalosporin antibiotic suspension formulations and methods of producing same |
CR20140355A CR20140355A (en) | 2011-12-23 | 2014-07-22 | ANTIBIOTIC FORMULATIONS |
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NZ59738911 | 2011-12-23 | ||
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KR (1) | KR20140102319A (en) |
CN (1) | CN104080456A (en) |
AU (1) | AU2012359296B2 (en) |
BR (1) | BR112014014786A2 (en) |
CL (1) | CL2014001602A1 (en) |
CO (1) | CO7101241A2 (en) |
CR (1) | CR20140355A (en) |
DO (1) | DOP2014000146A (en) |
IL (1) | IL233299A0 (en) |
MX (1) | MX2014007735A (en) |
MY (1) | MY167596A (en) |
NI (1) | NI201400064A (en) |
PE (1) | PE20142373A1 (en) |
PH (1) | PH12014501384A1 (en) |
WO (1) | WO2013095166A1 (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2874623A1 (en) | 2012-07-17 | 2015-05-27 | Bayer New Zealand Limited | Injectable antibiotic formulations and their methods of use |
US10376585B2 (en) | 2012-07-17 | 2019-08-13 | Bayer New Zealand Ltd | Injectable antibiotic formulations and their methods of use |
WO2020181024A1 (en) * | 2019-03-06 | 2020-09-10 | Zoetis Services Llc | Ready-to-use injectable formulations |
RU2777360C1 (en) * | 2019-03-06 | 2022-08-02 | ЗОЕТИС СЕРВИСИЗ ЭлЭлСи | Ready-to-use dosage forms for injection |
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EP0391369A2 (en) * | 1989-04-05 | 1990-10-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Medicinal emulsions |
CN1517090A (en) * | 2003-01-20 | 2004-08-04 | 王玉万 | Animal use suspensoid injection or emulsion containing antibacterial medicine |
WO2009032843A2 (en) * | 2007-09-06 | 2009-03-12 | Auspex Pharmaceuticals, Inc. | Deuterated ethambutols and their use |
CN101401787A (en) * | 2008-11-19 | 2009-04-08 | 肖希龙 | Ceftiofur long-acting injection and preparation method thereof |
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KR20040015622A (en) * | 2002-08-13 | 2004-02-19 | 대한뉴팜(주) | Injectable Composition Comprising Ceftiofur Sodium as Active Ingredient |
CN101953889B (en) * | 2010-09-07 | 2013-04-10 | 西北农林科技大学 | Compound ceftiofur suspension emulsion injection and preparation method thereof |
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2012
- 2012-12-21 BR BR112014014786A patent/BR112014014786A2/en not_active Application Discontinuation
- 2012-12-21 MX MX2014007735A patent/MX2014007735A/en unknown
- 2012-12-21 CN CN201280063872.1A patent/CN104080456A/en active Pending
- 2012-12-21 PE PE2014001010A patent/PE20142373A1/en not_active Application Discontinuation
- 2012-12-21 WO PCT/NZ2012/000245 patent/WO2013095166A1/en active Application Filing
- 2012-12-21 MY MYPI2014701634A patent/MY167596A/en unknown
- 2012-12-21 KR KR1020147020501A patent/KR20140102319A/en not_active Application Discontinuation
- 2012-12-21 AU AU2012359296A patent/AU2012359296B2/en active Active
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2014
- 2014-06-18 DO DO2014000146A patent/DOP2014000146A/en unknown
- 2014-06-18 CL CL2014001602A patent/CL2014001602A1/en unknown
- 2014-06-18 PH PH12014501384A patent/PH12014501384A1/en unknown
- 2014-06-20 NI NI201400064A patent/NI201400064A/en unknown
- 2014-06-22 IL IL233299A patent/IL233299A0/en unknown
- 2014-07-22 CO CO14158889A patent/CO7101241A2/en unknown
- 2014-07-22 CR CR20140355A patent/CR20140355A/en unknown
Patent Citations (4)
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EP0391369A2 (en) * | 1989-04-05 | 1990-10-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Medicinal emulsions |
CN1517090A (en) * | 2003-01-20 | 2004-08-04 | 王玉万 | Animal use suspensoid injection or emulsion containing antibacterial medicine |
WO2009032843A2 (en) * | 2007-09-06 | 2009-03-12 | Auspex Pharmaceuticals, Inc. | Deuterated ethambutols and their use |
CN101401787A (en) * | 2008-11-19 | 2009-04-08 | 肖希龙 | Ceftiofur long-acting injection and preparation method thereof |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2874623A1 (en) | 2012-07-17 | 2015-05-27 | Bayer New Zealand Limited | Injectable antibiotic formulations and their methods of use |
US9452155B2 (en) | 2012-07-17 | 2016-09-27 | Bayer New Zealand Ltd | Injectable antibiotic formulations and their methods of use |
US10376585B2 (en) | 2012-07-17 | 2019-08-13 | Bayer New Zealand Ltd | Injectable antibiotic formulations and their methods of use |
WO2020181024A1 (en) * | 2019-03-06 | 2020-09-10 | Zoetis Services Llc | Ready-to-use injectable formulations |
RU2777360C1 (en) * | 2019-03-06 | 2022-08-02 | ЗОЕТИС СЕРВИСИЗ ЭлЭлСи | Ready-to-use dosage forms for injection |
RU2777360C9 (en) * | 2019-03-06 | 2022-09-14 | ЗОЕТИС СЕРВИСИЗ ЭлЭлСи | Ready-to-use dosage forms for injection |
Also Published As
Publication number | Publication date |
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AU2012359296A1 (en) | 2013-08-01 |
CO7101241A2 (en) | 2014-10-31 |
PE20142373A1 (en) | 2015-02-11 |
CN104080456A (en) | 2014-10-01 |
MX2014007735A (en) | 2014-08-01 |
IL233299A0 (en) | 2014-08-31 |
DOP2014000146A (en) | 2014-07-31 |
MY167596A (en) | 2018-09-20 |
BR112014014786A2 (en) | 2017-06-13 |
CL2014001602A1 (en) | 2014-10-24 |
KR20140102319A (en) | 2014-08-21 |
NI201400064A (en) | 2014-11-28 |
PH12014501384A1 (en) | 2014-09-22 |
CR20140355A (en) | 2014-10-29 |
AU2012359296B2 (en) | 2014-12-11 |
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