WO2000012088A1 - Formulation pharmaceutique d'amoxycilline de sodium et de clavulanate de potassium - Google Patents
Formulation pharmaceutique d'amoxycilline de sodium et de clavulanate de potassium Download PDFInfo
- Publication number
- WO2000012088A1 WO2000012088A1 PCT/EP1999/006192 EP9906192W WO0012088A1 WO 2000012088 A1 WO2000012088 A1 WO 2000012088A1 EP 9906192 W EP9906192 W EP 9906192W WO 0012088 A1 WO0012088 A1 WO 0012088A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- desiccant
- vial
- formulation
- amoxycillin
- potassium clavulanate
- Prior art date
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Classifications
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
Definitions
- This invention relates to a pharmaceutical formulation comprising a combination of the antibiotic amoxycillin and the beta-lactamase inhibitor potassium clavulanate adapted for administration by intravenous injection (iv), to vials containing such formulations, to the use of such formulations in therapy and to methods for the manufacture of such formulations.
- antibiotic amoxycillin as amoxycillin trihydrate, and potassium clavulanate
- amoxycillin trihydrate as amoxycillin trihydrate
- potassium clavulanate is a well known and widely used medicament for bacterial infections, marketed by SmithKline Beecham in many countries under the trade mark Augmentin.
- Formulations already available for oral administration include various tablet types, paediatric suspensions, chewables and granules in sachets. These comprise amoxycillin and clavulanate in a variety of ratios, 2: 1, 4: 1, 7: 1 and 8: 1, 5 depending on the particular formulation, for either a three times a day (tid) or, more recently, a twice a day (bid) dosage regimen.
- Such formulations are marketed by SmithKline Beecham under the trade name Augmentin, for reconstitution as an intravenous injection or infusion, for treatment of inter alia upper respiratory tract , lower respiratory tract, genito-urinary tract, skin and soft tissue and bone and joint 0 infections.
- European patent application EP 0 131 147-A1 (Beecham Group pic) describes a further form of sodium amoxycillin, crystalline sodium amoxycillin. This is anhydrous, non-hygroscopic, with a high degree of stability. Furthermore, it is essentially pure, in contrast to the lesser degree of purity achievable with the spray- dried form. Crystalline sodium amoxycillin is said to be suitable for incorporation into a formulation further comprising potassium clavulanate, adapted for parenteral administration. No details are however provided of specific formulations, either by weight of drug substance or ratio, or of a dosage regimen.
- WO 96/04189 describes inter alia containers with closures formed from an elastomeric material compounded with a desiccant material such as calcium oxide or molecular sieve (so-called desiccant stoppers). Such containers are said to be particularly suitable for use with mixtures of potassium clavulanate and crystalline sodium amoxycillin.
- the present invention provides for a pharmaceutical formulation adapted for intravenous administration and consisting essentially of crystalline sodium amoxycillin and potassium clavulanate in the weight ratio 10:1.
- the weights of sodium amoxycillin and potassium clavulanate are expressed, for convenience, as the equivalent weights of the corresponding free acids, amoxycillin and clavulanic acid, respectively. It will also be appreciated that, in determining the actual quantity to be included in a formulation, due allowance will be made for the potency (activity) of the sodium amoxycillin and potassium clavulanate, according to procedures well known in the art.
- the crystalline sodium amoxycillin is anhydrous.
- the sodium amoxycillin is sterile.
- a preferred formulation is provided as a unit dosage which comprises 2000mg crystalline sodium amoxycillin and 200mg potassium clavulanate, within a tolerance of ⁇ 10%.
- the formulation has no added excipients or carriers.
- a further preferred formulation is provided as a unit dosage which comprises lOOOmg crystalline sodium amoxycillin and lOOmg potassium clavulanate, within a tolerance of ⁇ 10%.
- the formulation is provided as a unit dosage which consists essentially of lOOOmg crystalline sodium amoxycillin and lOOmg potassium clavulanate, within a tolerance of ⁇ 10%.
- a 2.2g formulation (consisting of 2000mg amoxycillin and 200mg clavulanate) is used in a twice a day (bid, ql2hr) or a three times a day (tid, q8hr) dosage regimen and a l.lg formulation (consisting of lOOOmg amoxycillin and lOOmg clavulanate) is used in a twice a day (bid, ql2hr) or a three times a day (tid, q8hr) dosage regimen.
- Such formulations may also be more frequently, at the discretion of the physician.
- the bid administration is at 12 hour intervals, although a greater or lesser interval between administrations may be used.
- the tid administration is at 8 hour intervals, although a greater or lesser interval between administrations may be used.
- the formulation will be reconstituted as an aqueous solution and may be administered either by slow intravenous injection over a period of 3-4 minutes directly into a vein or via a drip tube or, preferably, by infusion, preferably over a period of 60 min.
- the 2.2g formulation is administered only by infusion.
- the preferred diluent is Water for Injections BP.
- For the l.lg formulation preferably 20ml diluent is used.
- the 1.1 and 2.2g formulations are preferably reconstituted by the addition of infusion fluid (an initial volume of 20ml which is then immediately diluted to 100ml).
- Preferred infusion fluids include Sodium Chloride intravenous infusion BP (0.9%w/v), Water for Injections BP, Sodium Lactate Infusion BP (M/6), Compound Sodium Chloride Injection BPC 1959 (Ringer's), and Compound Sodium Lactate Intravenous Infusion BP (Ringer-Lactate:Hartmann's), of which Sodium Chloride intravenous infusion BP (0.9%w/v) is more preferred.
- reconstituted formulations have limited stability (up to 90min for the 2.2g formulation and up to 120min for l.lg formulation) and accordingly should be administered without undue delay, for instance no more than 30 and 60 minutes after reconstitution for the 2.2g and l.lg formulations, respectively, allowing for a 60min period for infusion.
- compositions include unit dosages which comprises 250mg crystalline sodium amoxycillin and 25mg potassium clavulanate, or 500mg crystalline sodium amoxycillin and 50mg potassium clavulanate, within a tolerance of ⁇ 10%.
- the formulation has no added excipients or carriers.
- a the vial provided with desiccating means, to remove water which is picked up on the surface of the crystals of potassium clavulanate during the packaging process, from the interior of the vial, at a rate sufficient to reduce degradation of the clavulanate to an acceptable level.
- desiccating capacity may be provided by using a so-called "desiccant" stopper.
- desiccant stoppers are described in WO 96/04189 (SmithKline Beecham) and WO 97/29151 (The West Company (UK) Ltd).
- the present invention provides a vial having a desiccant stopper made at least in part from a desiccant elastomeric material and containing crystalline sodium amoxycillin and potassium clavulanate, as hereinbefore defined.
- the vial contains essentially 2000mg crystalline sodium amoxycillin and 200mg potassium clavulanate or lOOOmg sodium amoxycillin and lOOmg potassium clavulanate, within a tolerance of ⁇ 10%, preferably with no added excipients or carriers.
- the term "desiccant elastomeric material” refers to an elastomeric material which comprises essentially an elastomeric base material compounded with a desiccant material, and optionally further comprising additional ingredients selected from a filler, an acid acceptor, a curative pigment and a processing aid.
- the compounding of the elastomeric base material with a desiccant material causes the resultant desiccant elastomeric material to exercise a desiccant effect upon the interior of the container.
- the quantity of elastomeric base material compounded with a desiccant material should be sufficient to ensure abso ⁇ tion of sufficient of the water vapour in the container, or water in or on the material contents of the vial and its surfaces, to prevent or reduce to an acceptable degree any degradation of the material by the said water or water vapour.
- the elastomeric material may further comprise additional reinforcing fillers, preservatives, antioxidants, additives etc. to modify its stiffness, chemical resistance and other properties.
- the elastomeric base material may be a rubber.
- a rubber may be a natural rubber, or a synthetic rubber such as a butadiene-based rubber, e.g. based on styrene- butadiene or CZJ- 1,4-polybutadiene, butyl rubber, halogenated butyl rubber, ethylene- propylene rubber, neoprene, nitrile rubber, polyisoprene, silicone rubber, chlorosulphonated polyethylene or epichlorhydrin elastomer, or a mixture, blend or copolymer thereof.
- Halobutyl e.g.
- bromobutyl, chlorobutyl, rubbers and silicone rubbers are pharmaceutically acceptable rubbers known for use as materials for stoppers etc. to be maintained in contact with pharmaceutical products.
- Such elastomeric materials are sufficiently permeable to atmospheric water vapour that the desiccant material compounded with the rubber can exert its desiccant effect through a thin layer of the material.
- the elastomeric base material is a halogenated butyl rubber, more preferably a chlorinated or a brominated butyl rubber, which may be a copolymer and/or blend with other suitable co-polymers, particularly other elastomers and rubbers.
- Preferred copolymers/blend for use in making stoppers for pharmaceutical vials are well known.
- ingredients e.g. filler, desiccant etc. and others identified below are normally used as powders and are preferably in a particle size of less than 20 micron, more preferably 10 micron or less, for instance from 1 to 10 micron.
- filler is present in the range 0 to lOOphr, more preferably 0 to 50phr, yet more preferably, 20 to 50phr, most preferably 35 to 45 phr, particularly around 40 ⁇ 2phr.
- Preferred fillers include talc and clay, for instance a calcined clay, or a mixture of such filler materials, for instance a mixture of a talc and a clay.
- the filler and the elastomeric base material should be mutually inert to each other.
- Representative examples of talcs and clays for use as fillers in stoppers for pharmaceutical vials are well known and include talcs such as Luzenac Mistrobond.
- Other talc-like materials which may also be used include finely powdered alumino silicates and other metal silicates.
- Conventional reinforcing fillers include inorganic reinforcing fillers such as china clay and other clays.
- the desiccant material should be one which is inert relative to the elastomeric material, and vice versa. Furthermore, the desiccant material should be one which can chemically or physicochemically absorb or fix absorbed water, e.g. by formation of a hydration product, so that there is a reduced possibility of subsequent reversible release of the absorbed water, which might for example occur if the temperature of the desiccant material should rise, e.g. to around 40°C subsequent after earlier desiccation at a lower temperature.
- the desiccant material is an inorganic desiccant material which is wholly or substantially insoluble in water so that none or only a pharmaceutically insignificant amount of the desiccant material or its hydration product, or undesirable ions, is likely to enter solution during the period when the stopper is in contact with water or aqueous medium, following reconstitution.
- desiccant materials include dried molecular sieve, especially a sieve of the zeolite type, calcium oxide, desiccating magnesium oxide or mixtures thereof. Calcium oxide chemically fixes water by formation of calcium hydroxide, from which water can only be released at extreme temperatures.
- Absorbed water can generally only be released from molecular sieves at several hundred °C, that is, well above the temperatures containers of pharmaceutical substances would be expected to experience under normal storage.
- Representative examples include the products sold in the UK under the names Molecular Sieve 4A, Grace A3TM, SiliporiteTM and Ferben 200TM.
- inorganic desiccant is present in the range 20 to lOOphr, more preferably 30 to 80phr, most preferably 30 to 50phr. The appropriate quantity for a particular application may be readily determined experimentally.
- a desiccant stopper for use in the present invention is compounded from a halobutyl, e.g. chlorobutyl, rubber and an inorganic desiccant such as a molecular sieve or calcium oxide, more preferably, a chlorobutyl rubber compounded with a molecular sieve.
- a halobutyl e.g. chlorobutyl
- an inorganic desiccant such as a molecular sieve or calcium oxide, more preferably, a chlorobutyl rubber compounded with a molecular sieve.
- Acid acceptors may be usefully inco ⁇ orated, to bind halogens such as bromine that may be liberated from the rubber.
- Preferred acid acceptors include magnesium oxide and zinc oxide, inco ⁇ orated in the range 0.5 to lOphr, preferably from 3 to 7phr.
- Magnesium oxide is preferably present in the range 5 to 7phr.
- .Zinc oxide is preferably present in the range 3 to 6phr.
- Curative agents may be usefully included to form cross links in the rubber. Preferred such agents include elemental sulphur, inco ⁇ orated in conventional amounts. Other curative agents include halogenated phenolic resin, peroxides and alkylated resins.
- Pigments which may be inco ⁇ orated include titanium oxide and carbon black.
- Processing aids may be inco ⁇ orated to prevent sticking of the elastomeric material in the blending process and to moulds, etc.
- Examples of such aids conventionally used for stoppers for pharmaceutical vials include stearic acid and /or other fatty acids, such as blends of fatty acids, waxes such as polyethylene, silicones etc..
- the desiccant elastomeric material comprises: 100 phr of an elastomeric base material; from 0 to 110 phr of a filler; and from 20 to 100 phr of an inorganic desiccant.
- the desiccant elastomeric material comprises as its essential ingredients (within ⁇ 10% tolerance):
- Talc clay or talc/clay mixture (filler) 40;
- Molecular sieve desiccant 40 and curative, acid acceptor, processing aids and pigment, present in from 0.5 to 15phr (combined total).
- Such rubbers may be compounded in the manner with which they are conventionally compounded for manufacture of a stopper as known in the art of manufacture of rubber stoppers.
- the compounding process typically comprises the following process steps:
- a stopper for use in the present invention is may be made wholly of the said desiccant elastomeric material. Stoppers may also be made only partly of the said desiccant elastomeric material.
- parts of the stopper which engage the mouth opening are at least partly, more preferably wholly made of an elastomeric material comprising a natural or synthetic rubber (which may be the above-described desiccant elastomeric material), thereby allowing a tight compression fit with the mouth of the vessel.
- the sealing engagement of the closure with the mouth opening may be by a generally conventional construction e.g. similar to a conventional stopper.
- the stopper may be engaged with the rim of the neck of a vial by a screw thread, a friction/compression fitting, and/or a circlip-type clamp around the neck of the vial.
- the stopper may seal the mouth in a generally conventional manner, e.g. by a compression fitting of the closure wall against the rim of the mouth, or by a sealing ring compressed between the closure face and the rim of the mouth etc.
- the stopper comprises a puncturable region in direct communication with the interior of the vial, through which a hypodermic needle may be inserted
- the puncturable region may suitably comprise a thinned region, and is preferably provided in a region of elastomeric material (which may comprise the desiccant material) which can resiliently seal around a hypodermic needle which is inserted therethrough, so as to facilitate sterile insertion and withdrawal.
- Water may be introduced into the vessel by means of a hypodermic needle puncturing the closure face through the puncturable region, so as to dissolve the contents, and the so-formed solution then withdrawn via the needle, for administration.
- the closure including the puncturable region, may all be made of the desiccant elastomeric material.
- a vial closure may correspond in shape and size to conventional vial closures made of elastomeric material, and may be retained on the mouth of the vial by a conventional metal circlip.
- Such conventional vial closures also include closures for use in the ADD-vantage (Trade mark) system, from Abbott.
- Desiccant elastomeric materials may be moulded into such shapes and sizes by a moulding process entirely analogous to that used to mould closures out of conventional elastomeric materials such as rubbers.
- the closure may be of multi-part construction having only parts, including those parts which are exposed to the interior of the vial body, made of the said desiccant elastomeric material.
- Other parts of the stopper which are not made of desiccant elastomeric material and which come into contact with the atmosphere within the vial may be made of generally conventional materials, preferably pharmaceutically acceptable materials, such as plastics materials, elastomeric materials etc., or composite materials such as metal and plastics or elastomeric materials.
- such parts are made of plastics or elastomeric materials which are of low moisture content, of low moisture permeability and low moisture affinity.
- the distribution of the desiccant elastomeric material may be such that the desiccant elastomeric material is located on only part of the closure wall of the stopper, so that for example the puncturable region may be situated between areas of the closure wall on which is the desiccant polymer, or to one side of such an area, thereby facilitating the construction of the puncturable region as a thinned region of the closure face.
- Such a multi-part construction includes the possibility that the closure may be integrally made of a co-moulded, or fused together, desiccant elastomeric material and an elastomeric or plastics material making up parts of the structure of the stopper.
- the desiccant elastomeric material may be provided as a separate part, retained by the closure on a suitable inward surface, e.g. in an inwardly facing holder or cavity.
- stoppers having multi-part construction are described in WO 96/04189 (SmithKline Beecham).
- Preferred stoppers for use with formulations of the present invention are able to take up atmospheric moisture at 30% RH or less, preferably at 10%RH or less. Preferred stoppers exercise such a desiccant function for a long period, ideally throughout the shelf life of the formulation, typically two years.
- Preferred stoppers should also be capable of being washed and sterilised, without loss of their desiccant ability at these low RH values.
- desiccant polymer vial closures are ideally sterilised by gamma irradiation prior to use, without loss of their desiccant ability.
- desiccant rubbers such as halogenatedbutyl, e.g. chlorobutyl, rubber compounded with calcium oxide or molecular sieves are capable of being washed without a significant deleterious effect on their desiccant ability.
- stoppers may be re-activated by microwave radiation as described in WO 98/17711 (SmithKline Beecham).
- the nature and quantity of desiccant material to be used in a stopper can be readily determined by straightforward experimentation or calculation, e.g. from the moisture content of the contents of the vial.
- the stopper should scavenge up to 25 milligrams of water with a residual RH of less than 10% throughout a two year storage period.
- a desiccating stopper is available from West Pharmaceutical Services (Pheonixville, Pennsylvania, USA), as a LyoDryTM stopper. This has a moisture capacity which approximately 5% of the mass of the stopper . with an initial uptake rate of 0.04mg/cm2/day which then decreases over a period of time.
- Preferred vials for use in the present invention are of generally conventional construction, the mouth opening being defined by the rim of the neck of the vial.
- the vial is made of a moisture-impermeable material, such as glass.
- Preferred vials will have a nominal capacity in the range 5 to 150 ml, more preferably about 20 ml for the l.lg formulation and 100ml for the 2.2g formulation.
- the present invention also provides a method of desiccating a formulation of the present invention, which comprises enclosing the said formulation in a vial and maintaining a stopper formed from an elastomeric material compounded with a desiccant material in contact with the atmosphere inside the vial.
- This method may be a method of long-term storage and/or protection against hydrolysis during storage.
- desiccant stopper for use with a formulation of the present invention is described in WO 95/25045 (SmithKline Beecham). This is formed from an elastomer which has an annular groove on the inwardly facing region which accommodates a pre-formed ring of desiccant material such as molecular sieve, separated from the interior of the vessel by a semi-permeable membrane.
- a so-called “leaky vial” is described in WO 95/34488 (SmithKline Beecham). This comprises a vial formed from a material which is permeable to water vapour but impermeable to liquid water and provided with a puncturable seal. The vial is enclosed within an outer container which is less permeable to water vapour, the intermediate space between the outer container and the inner vial containing a desiccant.
- a conventional vial and stopper may be used, with desiccating means provided by a pharmaceutically acceptable water soluble inorganic desiccant such as desiccating metal salt, for instance sodium chloride, calcium chloride or magnesium chloride, which is co-formulated with the crystalline sodium amoxycillin and potassium clavulanate (see WO 95/33487, SmithKline Beecham).
- desiccating metal salt for instance sodium chloride, calcium chloride or magnesium chloride
- a formulation of the invention may be manufactured using techniques which are generally conventional in the field of manufacture of injectable formulations. For instance, crystalline sodium amoxycillin and potassium clavulanate may be mixed in a nominal 10: 1 ratio and the bulk formulation then filled into vials, under sterile conditions. Formulations of the present invention may be used in treating bacterial infections, by bolus or infusion administration of a reconstituted solution thereof. Accordingly, in a further aspect, the present invention provides for a pharmaceutical formulation as hereinbefore defined, for use in therapy.
- the formulations are used for short term treatment of bacterial infections, for instance:
- Upper Respiratory Tract Infections e.g. recurrent tonsillitis, sinusitis, otitis media, typically caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes;
- Genito-urinary Tract Infections e.g. cystitis, urethritis, pyelonephritis, female genital infections, typically caused by Enterobacteriaceae (mainly Escherichia col ⁇ ), staphylococcus saprophyticus and Enterococcus species, and gonorrohoea caused by Enterobacteriaceae (mainly Escherichia col ⁇ ), staphylococcus saprophyticus and Enterococcus species, and gonorrohoea caused by Enterobacteriaceae (mainly Escherichia col ⁇ ), staphylococcus saprophyticus and Enterococcus species, and gonorrohoea caused by Enterobacteriaceae (mainly Escherichia col ⁇ ), staphylococcus saprophyticus and Enterococcus species, and gonorrohoea caused by Enterobacteriaceae (mainly Escherichia col ⁇ ), staphylococcus sap
- Neisseria gonorrhoeae Neisseria gonorrhoeae
- Streptococcus pyogenes and Bacteroides species Streptococcus pyogenes and Bacteroides species; Bone and Joint Infections e.g. osteomyelitis, typically caused by Staphylococcus aureus, where more prolonged therapy may be appropriate; and
- Infections e.g. septic abortion, pue ⁇ eral sepsis, intra-abdominal sepsis, septicaemia, peritonitis, post surgical infections.
- the 1000/200mg formulation may also be used prophylaxis against infection which may be associated with major surgical procedures such as gastro-intestinal, pelvic, head and neck, cardiac, renal, joint replacement and biliary tract surgery.
- the 2000/200mg formulation may also be used for prophylaxis against infection caused by susceptible organisms in gastro-intestinal surgery.
- the dosage is l.lg every eight hours or 2.2g every 12 hours.
- a desiccant elastomeric material was made having the following composition:
- This composition was compounded via a conventional process, as broadly outlined above, and was made into stoppers for pharmaceutical vials of a shape and size identical to conventional stoppers made of conventional non-desiccating elastomers, and having a puncturable region as described above.
- Example 1 may be modified, for example varying within + 10% of that listed above.
- Crystalline anhydrous sodium amoxycillin (EP 0 131 147-A1) and potassium clavulanate in the weight ratio 10:1 were blended together in bulk (scale approximately 100kg total), at a relative humidity of less than 30%
- a vial (50ml) containing 1.1 gram or 2.2 gram is reconstituted by adding approximately 20 mL of 0.9% Sodium Chloride Injection, USP, and shaking well, and immediately diluting to a total volume of 100 mL. The solution of reconstituted drug is then be administered over a period of 60 minutes by direct infusion.
- the l.lg formulation is stable for 120 minutes after final dilution and should be administered no more than 60 minutes after reconstitution.
- the 2.2g formulation is stable for 90 minutes after final dilution and should be administered no more than 30 minutes after reconstitution.
- Example 4 Clinical Pharmacology of an intravenous (IV) formulation of Amoxycillin/Clavulanate (A C).
- the pu ⁇ ose of this study was to determine and compare A & C pharmacokinetics after IV and oral administration, integrating these data with defined pharmacodynamic (PD) correlates.
- 15 healthy volunteers received at each session an infusion of 1000/lOOmg (l.lg) or 2000/200 (2.2g) A/C over a period of 60 minutes or a single oral dose of 875/125mg A/C.
- the wash-out period was at least three days and each subject received each of the three doses once. Twelve timed blood samples were obtained after each dose and analyzed by HPLC. IV and oral A C were well tolerated. A & C disposition was linear over the 3.5 fold dose range.
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Abstract
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU57394/99A AU5739499A (en) | 1998-08-28 | 1999-08-24 | Pharmaceutical formulation of sodium amoxycillin and potassium clavulanate |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9818927.7A GB9818927D0 (en) | 1998-08-28 | 1998-08-28 | Pharmaceutical formulation |
GB9818927.7 | 1998-08-28 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000012088A1 true WO2000012088A1 (fr) | 2000-03-09 |
Family
ID=10838082
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1999/006192 WO2000012088A1 (fr) | 1998-08-28 | 1999-08-24 | Formulation pharmaceutique d'amoxycilline de sodium et de clavulanate de potassium |
Country Status (3)
Country | Link |
---|---|
AU (1) | AU5739499A (fr) |
GB (1) | GB9818927D0 (fr) |
WO (1) | WO2000012088A1 (fr) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1044680A1 (fr) * | 1999-04-13 | 2000-10-18 | Beecham Pharmaceuticals (Pte) Limited | Nouvelle méthode de traitement à l'aide d'un fort régime de dosage d'Amoxycillin et de Clavulanate de Potassium |
WO2000061115A2 (fr) * | 1999-04-13 | 2000-10-19 | Beecham Pharmaceuticals (Pte) Limited | Nouvelle methode de traitement |
US6726908B2 (en) | 1995-09-07 | 2004-04-27 | Smithkline Beecham P.L.C. | Pharmaceutical formulation |
US6746692B2 (en) | 1999-04-13 | 2004-06-08 | Beecham Pharmaceuticals (Pte) Limited | Modified release pharmaceutical formulation comprising amoxycillin |
US6756057B2 (en) | 2000-10-12 | 2004-06-29 | Beecham Pharmaceuticals (Pte) Limited | Amoxicillin and potassium clavulanate dosage form |
US7217430B2 (en) | 1999-04-13 | 2007-05-15 | Beecham Pharmaceuticals (Pte) Limited | Compositions and methods of treatment comprising amoxicillin and potassium clavulanate with xanthan |
WO2007093425A2 (fr) * | 2006-02-17 | 2007-08-23 | Grünenthal GmbH | Forme d'administration par voie orale stable au stockage d'amoxicilline et d'acide clavulanique |
EP1296672B2 (fr) † | 2000-06-09 | 2018-10-24 | LEK Pharmaceuticals d.d. | Produit et preparation pharmaceutiques stables |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4282202A (en) * | 1978-10-27 | 1981-08-04 | Beecham Group Limited | Intramammary compositions |
WO1995033487A1 (fr) * | 1994-06-06 | 1995-12-14 | Smithkline Beecham Farmaceutici S.P.A. | Formulations injectables contenant un dessiccatif |
WO1996004189A1 (fr) * | 1994-08-05 | 1996-02-15 | Smithkline Beecham P.L.C | Reservoir pour materiau sensible a l'humidite |
WO1997029151A1 (fr) * | 1996-02-05 | 1997-08-14 | The West Company(Uk) Limited | Composition |
-
1998
- 1998-08-28 GB GBGB9818927.7A patent/GB9818927D0/en not_active Ceased
-
1999
- 1999-08-24 AU AU57394/99A patent/AU5739499A/en not_active Abandoned
- 1999-08-24 WO PCT/EP1999/006192 patent/WO2000012088A1/fr active Application Filing
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4282202A (en) * | 1978-10-27 | 1981-08-04 | Beecham Group Limited | Intramammary compositions |
WO1995033487A1 (fr) * | 1994-06-06 | 1995-12-14 | Smithkline Beecham Farmaceutici S.P.A. | Formulations injectables contenant un dessiccatif |
WO1996004189A1 (fr) * | 1994-08-05 | 1996-02-15 | Smithkline Beecham P.L.C | Reservoir pour materiau sensible a l'humidite |
WO1997029151A1 (fr) * | 1996-02-05 | 1997-08-14 | The West Company(Uk) Limited | Composition |
Cited By (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6726908B2 (en) | 1995-09-07 | 2004-04-27 | Smithkline Beecham P.L.C. | Pharmaceutical formulation |
JP2002541187A (ja) * | 1999-04-13 | 2002-12-03 | ビーチャム・ファーマシューティカルズ・(プライベイト)・リミテッド | 新規治療法 |
WO2000061116A3 (fr) * | 1999-04-13 | 2001-02-01 | Beecham Pharm Pte Ltd | Nouveau procede de traitement |
EP1269997A1 (fr) * | 1999-04-13 | 2003-01-02 | Beecham Pharmaceuticals (Pte) Limited | Dose unitaire comprenant de l'amoxicilline et du clavulanate |
GB2351661A (en) * | 1999-04-13 | 2001-01-10 | Beecham Pharma | High dose of amoxycillin and potassium clavulanate for treatment of bacterial infections using a BID dosage regime |
EP1269996A1 (fr) * | 1999-04-13 | 2003-01-02 | Beecham Pharmaceuticals (Pte) Limited | Dose unitaire comprenant de l'amoxycilline et du clavulanate |
NL1014915C2 (nl) * | 1999-04-13 | 2001-02-12 | Beecham Pharm Pte Ltd | Nieuwe behandelingsmethode. |
WO2000061115A3 (fr) * | 1999-04-13 | 2001-03-01 | Beecham Pharm Pte Ltd | Nouvelle methode de traitement |
US6660299B2 (en) | 1999-04-13 | 2003-12-09 | Beecham Pharmaceuticals Limited | Modified release pharmaceutical formulation comprising amoxycillin |
US6294199B1 (en) | 1999-04-13 | 2001-09-25 | Beecham Pharmaceuticals (Pte) Limited | Method of treating a bacterial infection comprising administering amoxycillin |
GB2351661B (en) * | 1999-04-13 | 2001-10-10 | Beecham Pharma | Novel method of treatment |
BE1013309A5 (fr) * | 1999-04-13 | 2001-11-06 | Beecham Pharm Pte Ltd | Formulations pharmaceutiques nouvelles comprenant l'amoxycilline et du clavulanate de potassium. |
EP1044680A1 (fr) * | 1999-04-13 | 2000-10-18 | Beecham Pharmaceuticals (Pte) Limited | Nouvelle méthode de traitement à l'aide d'un fort régime de dosage d'Amoxycillin et de Clavulanate de Potassium |
FR2792198A1 (fr) * | 1999-04-13 | 2000-10-20 | Beecham Pharm Pte Ltd | Formulations pharmaceutiques nouvelles comprenant de l'amoxycilline et du clavulanate de potassium |
WO2000061116A2 (fr) * | 1999-04-13 | 2000-10-19 | Beecham Pharmaceuticals (Pte) Limited | Nouveau procede de traitement |
GR1003560B (el) * | 1999-04-13 | 2001-03-16 | Beecham Pharmaceuticals (Pte) Limited | Σκευασματα τροποποιημενης απελευθερωσης αμοξυκιλλινης και κλαβουλανικου καλιου |
WO2000061115A2 (fr) * | 1999-04-13 | 2000-10-19 | Beecham Pharmaceuticals (Pte) Limited | Nouvelle methode de traitement |
US6746692B2 (en) | 1999-04-13 | 2004-06-08 | Beecham Pharmaceuticals (Pte) Limited | Modified release pharmaceutical formulation comprising amoxycillin |
JP4880125B2 (ja) * | 1999-04-13 | 2012-02-22 | ビーチャム・ファーマシューティカルズ・(プライベイト)・リミテッド | 新規治療法 |
US6878386B1 (en) | 1999-04-13 | 2005-04-12 | Beecham Pharmaceuticals (Pte) Limited | Method of treating a bacterial infection comprising amoxycillin and potassium clavulanate |
US7217430B2 (en) | 1999-04-13 | 2007-05-15 | Beecham Pharmaceuticals (Pte) Limited | Compositions and methods of treatment comprising amoxicillin and potassium clavulanate with xanthan |
EP1296672B2 (fr) † | 2000-06-09 | 2018-10-24 | LEK Pharmaceuticals d.d. | Produit et preparation pharmaceutiques stables |
US6756057B2 (en) | 2000-10-12 | 2004-06-29 | Beecham Pharmaceuticals (Pte) Limited | Amoxicillin and potassium clavulanate dosage form |
WO2007093425A2 (fr) * | 2006-02-17 | 2007-08-23 | Grünenthal GmbH | Forme d'administration par voie orale stable au stockage d'amoxicilline et d'acide clavulanique |
DE102006007830A1 (de) * | 2006-02-17 | 2007-08-30 | Grünenthal GmbH | Lagerstabile orale Darreichungsform von Amoxicillin und Clavulansäure |
WO2007093425A3 (fr) * | 2006-02-17 | 2007-10-18 | Gruenenthal Gmbh | Forme d'administration par voie orale stable au stockage d'amoxicilline et d'acide clavulanique |
Also Published As
Publication number | Publication date |
---|---|
AU5739499A (en) | 2000-03-21 |
GB9818927D0 (en) | 1998-10-21 |
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