WO2007012960A1 - Compositions pharmaceutiques à base d’éplérénone - Google Patents
Compositions pharmaceutiques à base d’éplérénone Download PDFInfo
- Publication number
- WO2007012960A1 WO2007012960A1 PCT/IB2006/002072 IB2006002072W WO2007012960A1 WO 2007012960 A1 WO2007012960 A1 WO 2007012960A1 IB 2006002072 W IB2006002072 W IB 2006002072W WO 2007012960 A1 WO2007012960 A1 WO 2007012960A1
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- Prior art keywords
- eplerenone
- microns
- particles
- pharmaceutical composition
- eplerenone particles
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Definitions
- the present invention generally relates to a pharmaceutical composition containing at least micronized particles of one or more aldosterone antagonists and a process for its preparation.
- Aldosterone antagonists are known to be useful in treatment of hypertension and associated cardiac disease or insufficiency.
- the compound methyl hydrogen 9,1 la-epoxy-17a-hydroxy-3-oxopregn-4-ene-7a,21-dicarboxylate,y- lactone (referred to herein as eplerenone) was first reported in U.S. Patent No. 4,559,332 ("the '332 patent") which discloses a class of 9,11-epoxy steroid compounds and their salts together with processes for the preparation of such compounds.
- Eplerenone is an aldosterone receptor antagonist that can be administered in a therapeutically effective amount where use of an aldosterone receptor antagonist is indicated for treatment of, for example, pathological conditions associated with hyperaldosteronism such as hypertension, heart failure including cardiac insufficiency and cirrhosis of the liver.
- the '332 patent further discloses formulations such as tablets and capsules for oral administration of the 9,11-epoxy steroid compounds including eplerenone.
- Eplerenone can be represented by the structure of Formula I
- Eplerenone is marketed under the tradename Inspra ® .
- Inspra ® is indicated to improve survival of stable patients with left ventricular systolic dysfunction (ejection fraction less than or equal to 40%) and clinical evidence of congestive heart failure after an acute myocardial infarction.
- Inspra ® is also indicated for the treatment of hypertension. See, e.g., Physician's Desk Reference, "Inspra", 60th Edition, pp. 2520-2524 (2005).
- Spironolactone also known as (7 ⁇ ,17 ⁇ )-7-(acetylthio)-17-hydroxy-3 ⁇ oxopregn-4-ene-21-carboxylic acid ⁇ -lactone, a 20-spiroxane steroid compound having activity as an aldosterone receptor antagonist and can be represented by the structure of
- Spironolactone is marketed under the tradename Aldactone ® .
- Spironolactone exhibits antiandrogenic activity that can result in gynecomastia and impotenance in men, and weak progestational activity that produces menstrual irregularities in women.
- Commercial formulations sold under the name Aldactone ® provide 25, 50 and 100 mg unit doses of spironolactone. See, e.g., The Merck Index, Thirteenth Edition, 2001, p. 1562, monograph 8839.
- WO 00/33847 discloses pharmaceutical compositions useful as aldosterone receptor blockers containing micronized eplerenone as the active ingredient in a daily dosage amount of about 10 mg to about 1000 mg.
- WO 00/33847 further discloses the micronized eplerenone having a D 90 particle size of 25 to 400 microns. Problems associated with the use of such micronized particles of eplerenone include poor dissolution and erratic bioavailability.
- WO 01/41770 discloses pharmaceutical composition using eplerenone particles wherein 90% of the particles are smaller than about 15 microns. It would be desirable to provide alternative pharmaceutical compositions containing micronized particles of one or more aldosterone antagonists such as micronized eplerenone that eliminate and reduce the drawbacks of the prior art in a convenient and cost efficient manner for efficient, commercial scale production.
- aldosterone antagonist particles having a D90 particle size of less than 25 microns and greater than 15 microns is provided.
- aldosterone antagonist particles having a D 90 particle size of less than about 20 microns and greater than 15 microns is provided.
- eplerenone particles having a D90 particle size of less than 25 microns and greater than 15 microns is provided.
- eplerenone particles having a D90 particle size of less than about 20 microns and greater than 15 microns is provided.
- a pharmaceutical composition comprising aldosterone antagonist particles having a D90 particle size of less than 25 microns and greater than 15 microns.
- a pharmaceutical composition comprising aldosterone antagonist particles having a D 90 particle size of less than about 20 microns and greater than 15 microns.
- a pharmaceutical composition having improved solubility comprising eplerenone particles having a D 90 particle size of less than 25 microns and greater than 15 microns.
- a pharmaceutical composition having improved solubility comprising eplerenone particles having a D 90 particle size of less than about 20 microns and greater than 15 microns.
- a tablet dosage form comprising aldosterone antagonist particles having a D 9 0 particle size of less than 25 microns and greater than 15 microns.
- a tablet dosage form comprising aldosterone antagonist particles having a D 90 particle size of less than about 20 microns and greater than 15 microns.
- a tablet dosage form comprising eplerenone particles having a Dgo particle size of less than 25 microns and greater than 15 microns.
- a tablet dosage form comprising eplerenone particles having a D 9 0 particle size of less than about 20 microns and greater than 15 microns.
- a pharmaceutical composition comprising eplerenone particles having a D 9 0 particle size of less than 25 microns and greater than 15 microns, wherein the dissolution profile includes releasing about 25 to about 40% of the eplerenone in 5 minutes, about 60 to about 85% of the eplerenone in 10 minutes and about 90% of the eplerenone in 30 minutes as determined using USP Apparatus II at 50 rpm in 1000 ml of 0.1N HCl medium at 37°C.
- a therapeutic method comprising administering aldosterone antagonist particles having a D 90 particle size of less than 25 microns and greater than 15 microns to a subject having an aldosterone-mediated condition or disorder.
- a therapeutic method comprising administering eplerenone particles having a Dg 0 particle size of less than 25 microns and greater than 15 microns to a subject having an aldosterone-mediated condition or disorder.
- aldosterone antagonist such as eplerenone
- eplerenone may result in an increase in the effective exposed surface to the dissolving media, aid in solubility and increase the bioavailability of the pharmaceutical dosage form.
- the aldosterone antagonist particles having a smaller aspect ratio can facilitate processing during the production of pharmaceutical dosage forms of an aldosterone antagonist such as eplerenone.
- compositions of the present invention can be a bioequivalent to Inspra ® .
- the term "therapeutically effective amount” as used herein means the amount of a compound that, when administered to a mammal for treating a state, disorder or condition, is sufficient to effect such treatment.
- the “therapeutically effective amount” will vary depending on the compound, the disease and its severity and the age, weight, physical condition and responsiveness of the mammal to be treated.
- the term "subject” or “a patient” or “a host” as used herein refers to mammalian animals, preferably human.
- the term “buffering agent” as used herein is intended to mean a compound used to resist a change in pH upon dilution or addition of acid of alkali. Such compounds include, by way of example and without limitation, potassium metaphosphate, potassium phosphate, monobasic sodium acetate and sodium citrate anhydrous and dehydrate and other such material known to those of ordinary skill in the art.
- sweetening agent as used herein is intended to mean a compound used to impart sweetness to a preparation.
- Such compounds include, by way of example and without limitation, aspartame, dextrose, glycerin, mannitol, saccharin sodium, sorbitol, sucrose, fructose and other such materials known to those of ordinary skill in the art.
- binder as used herein is intended to mean substances used to cause adhesion of powder particles in tablet granulations.
- Such compounds include, by way of example and without limitation, acacia alginic acid, tragacanth, carboxymethylcellulose sodium, poly (vinylpyrrolidone), compressible sugar (e.g., NuTab), ethylcellulose, gelatin, liquid glucose, methylcellulose, povidone and pregelatinized starch, combinations thereof and other material known to those of ordinary skill in the art.
- binders include starch, poly(ethylene glycol), guar gum, polysaccharide, bentonites, sugars, invert sugars, poloxamers (PLURONICTM F68, PLURONICTM F127), collagen, albumin, celluloses in nonaqueous solvents, combinations thereof and the like.
- Other binders include, for example, poly(propylene glycol), polyoxyethylene- polypropylene copolymer, polyethylene ester, polyethylene sorbitan ester, poly(ethylene oxide), macrocrystalline cellulose, poly(vinylpyrrolidone), combinations thereof and other such materials known to those of ordinary skill in the art.
- filler is intended to mean inert substances used as fillers to create the desired bulk, flow properties, and compression characteristics in the preparation of tablets and capsules.
- Such compounds include, by way of example and without limitation, dibasic calcium phosphate, kaolin, sucrose, mannitol, microcrystalline cellulose, powdered cellulose, precipitated calcium carbonate, sorbitol, starch, combinations thereof and other such materials known to those of ordinary skill in the art.
- glidant as used herein is intended to mean agents used in tablet and capsule formulations to improve flow-properties during tablet compression and to produce an anti-caking effect.
- Such compounds include, by way of example and without limitation, colloidal silica, calcium silicate, magnesium silicate, silicon hydrogel, cornstarch, talc, combinations thereof and other such materials known to those of ordinary skill in the art.
- lubricant as used herein is intended to mean substances used in tablet formulations to reduce friction during tablet compression. Such compounds include, by way of example and without limitation, calcium stearate, magnesium stearate, mineral oil, stearic acid, zinc stearate, combinations thereof and other such materials known to those of ordinary skill in the art.
- disintegrant as used herein is intended to mean a compound used in solid dosage forms to promote the disruption of the solid mass into smaller particles which are more readily dispersed or dissolved.
- exemplary disintegrants include, by way of example and without limitation, starches such as corn starch, potato starch, pre- gelatinized and modified starched thereof, sweeteners, clays, such as bentonite, microcrystalline cellulose (e.g. AvicelTM), carsium (e.g. AmberliteTM), alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin, tragacanth, combinations thereof and other such materials known to those of ordinary skill in the art.
- starches such as corn starch, potato starch, pre- gelatinized and modified starched thereof, sweeteners, clays, such as bentonite, microcrystalline cellulose (e.g. AvicelTM), carsium (e.g. AmberliteTM), alginates, sodium starch glycolate, gums such
- wetting agent as used herein is intended to mean a compound used to aid in attaining intimate contact between solid particles and liquids.
- exemplary wetting agents include, by way of example and without limitation, gelatin, casein, lecithin (phosphatides), gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glycerol monostearate, cetostearyl alcohol, cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers (e.g., macrogol ethers such as cetomacrogol 1000), polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, (e.g., TWEENTMs), polyethylene glycols, polyoxyethylene stearates colloidal silicon dioxide, phosphates, sodium dodecylsulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, methylcellulose, hydroxye
- Tyloxapol (a nonionic liquid polymer of the alkyl aryl polyether alcohol type, also known as superinone or triton) is another useful wetting agent, combinations thereof and other such materials known to those of ordinary skill in the art.
- Tyloxapol a nonionic liquid polymer of the alkyl aryl polyether alcohol type, also known as superinone or triton
- Most of these excipients are described in detail in, e.g., Howard C. Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery Systems, (7th Ed. 1999); Alfonso R. Gennaro et al., Remington: The Science and Practice of Pharmacy, (20th Ed. 2000); and A. Kibbe, Handbook of Pharmaceutical Excipients, (3rd Ed. 2000), which are incorporated by reference herein.
- the present invention is directed to aldosterone antagonist particles having a D 9 0 particle size of less than 25 microns and greater than 15 microns (see Figure 1) and their use in pharmaceutical compositions.
- the present invention is directed to pharmaceutical compositions containing at least aldosterone antagonist particles having a Dg 0 particle size of less than about 20 microns and greater than 15 microns.
- the term 'particle size as used herein is an average diameter upon conversion of the volume of the particles into a sphere.
- the particle size of the aldosterone antagonist such as eplerenone was measured using a Malvern I Mastersizer.
- the aldosterone antagonists for use herein can be any aldosterone antagonists include, but are not limited to, spironolactone, eplerenone and the like with eplerenone being preferred.
- the aldosterone antagonists such as spironolactone and eplerenone can be prepared by processes well known in the art. See, e.g., U.S. Patent Nos. 4,559,332 and 7,038,040.
- Micronization of the aldosterone antagonist particles may be carried out using, for example, a ball mill, colloid mill, grinding mill, air jet mill, roller mill, impact mill, etc.
- An air jet mill is particularly suited as the majority of the milling in an air jet mill occurs through particle-particle collision rather than collision of the particles with the metal surfaces of the equipment.
- the process of micronization in an air jet mill involves at least exposing the particles to streams of compressed air or gas creating a fluidized bed of the particles; and accelerating the particles towards the center of the mill such that collision of the particles with each other can be achieved.
- the impact of the particles colliding with each other will break the particles into smaller micron size particles by balancing airflow force and centrifugal force.
- compositions and dosage forms include, for example, compacted tablets, powder suspensions, capsules, and the like.
- compositions of the present invention can be administered to humans and animals either orally, rectally, parenterally (intravenous, intramuscular, or subcutaneous), intracistemally, intravaginally, intraperitoneally, locally (powders, ointments or drops), or as a buccal or nasal spray.
- the active ingredient of the invention can be administered orally, buccally or sublingually in the form of tablets, capsules (including soft gel capsules), ovules, elixirs, solutions or suspensions, which may contain flavoring or coloring agents, for immediate-, delayed-, modified-, or controlled-release such as sustained-, dual-, or pulsatile delivery applications.
- the active ingredient of the invention may also be administered via fast dispersing or fast dissolving dosage forms or in the form of a high energy dispersion or as coated particles.
- Suitable pharmaceutical composition of the invention may be in coated or uncoated form as desired.
- Capsule dosages will contain the micronized aldosterone antagonist particles of the present invention within a capsule which may be coated with gelatin. Tablets and powders may also be coated with an enteric coating.
- the enteric-coated powder forms may have coatings comprising phthalic acid cellulose acetate, hydroxypropylmethyl cellulose phthalate, polyvinyl alcohol phthalate, carboxy methyl ethyl cellulose, a copolymer of styrene and maleic acid, a copolymer of methacrylic acid and methyl methacrylate, and like materials, and if desired, they may be employed with suitable plasticizers and/or extending agents.
- a coated capsule or tablet may have a coating on the surface thereof or may be a capsule or tablet comprising a powder or granules with an enteric-coating.
- Tableting compositions may have few or many components depending upon the tableting method used, the release rate desired and other factors.
- compositions of the present invention may contain diluents such as cellulose-derived materials like powdered cellulose, microcrystalline cellulose, microFine cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose salts and other substituted and unsubstituted celluloses; starch; pregelatinized starch; inorganic diluents such calcium carbonate and calcium diphosphate and other diluents known to one of ordinary skill in the art.
- suitable diluents include waxes, sugars (e.g. lactose) and sugar alcohols such as mannitol and sorbitol, acrylate polymers and copolymers, as well as pectin, dextrin and gelatin.
- compositions of the present invention may be varied to obtain an amount of micronized aldosterone antagonist that is effective to obtain a desired therapeutic response for a particular composition and method of administration.
- the compositions of the present invention in the form of individual dosage units contain the micronized aldosterone antagonist particles in an amount of about 10 mg to about 1000 mg, preferably from about 20 mg to about 400 mg, more preferably from about 25 mg to about 200 mg and still more preferably from about 25 mg to about 150 mg.
- the selected dosage level therefore depends upon such factors as, for example, the desired therapeutic effect, the route of administration, the desired duration of treatment, and other factors.
- the total daily dose of the compounds of this invention administered to a host in single or divided dose can vary widely depending upon a variety of factors including, for example, the body weight, general health, sex, diet, time and route of administration, rates of absorption and excretion, combination with other drugs, the severity of the particular condition being treated, etc.
- the daily dose can be administered in one to four doses per day.
- the present compositions may provide a therapeutic effect as aldosterone receptor blockers over a period of about 12 hours to about 24 hours after oral administration.
- the pharmaceutical compositions of the present invention can also contain one or more pharmaceutically inert carriers.
- pharmaceutically inert carrier refers to a substance that is physiologically acceptable, and compatible with the micronized aldosterone antagonist particles and other excipients in the formulation, while having a capacity to absorb the micronized aldosterone antagonist on its surface.
- the use of a carrier may also prevent the reagglomeration of the micronized aldosterone antagonist particles and assist in wetting the micronized aldosterone antagonist particles by the uptake of water via capillary action thereby enhancing dissolution.
- the pharmaceutical compositions of the present invention can also contain one or more pharmaceutically acceptable inert excipients.
- Such pharmaceutically acceptable inert excipients include, but are not limited to, one or more binders, diluents, surfactants, disintegrants, lubricants/glidants, coloring agents, and the like and mixtures thereof.
- the pharmaceutically acceptable inert excipients may be used intragranularly and/or extragranularly.
- Suitable binders include, but are not limited to, one or more methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, gelatin, gum arable, ethyl cellulose, polyvinyl alcohol, pullulan, pregelatinized starch, agar, kagacanth, sodium alginate, propylene glycol, and the like and mixtures thereof.
- Suitable diluents include, but are not limited to, one or more of calcium carbonate, calcium phosphate dibasic, calcium phosphate tribasic, calcium sulfate, microcrystalline cellulose, cellulose powdered, dextrates, dextrins, dextrose excipients, fructose, kaolin, lactitol, lactose, mannitol, sorbitol, starch, starch pregelatinized, sucrose, sugar compressible, sugar confectioners, and the like and mixtures thereof.
- Suitable lubricants/glidants include, but are not limited to, one or more colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated castor oil, sucrose esters of a fatty acid, microcrystalline wax, yellow beeswax, white beeswax, and the like and mixtures thereof.
- the pharmaceutical compositions of the present invention can be obtained by at least sifting the micronized particles with a diluent/filler followed by granulation in, for example, a high shear mixer using a binder solution, e.g., hydroxypropyl methyl cellulose in water.
- the granulation can be carried out in a Rapid Mixer Granulator (RMG) and the granules are wet milled, and the wet granules are dried and then lubricated.
- RMG Rapid Mixer Granulator
- the lubricated blend can then be compressed into minitablets and the tablets are optionally coated with a film coating composition.
- Eplerenone was micronized by being passed through a spiral jet mill
- micronized eplerenone obtained was measured for its particle size through a Malvern particle size analyzer.
- the D 90 of the eplerenone particles was 15.17 microns.
- Eplerenone of Example 1 having a particle size D 9 0 less than 25 microns and greater than 15 microns, lactose monohydrate, microcrystalline cellulose, and croscarmellose sodium were sifted through an ASTM 60# sieve and mixed for 10 minutes.
- a binder solution was prepared with hydroxypropyl methylcellulose (3 cps) and purified water.
- step II The binder solution of step II was added to the dry mixture of step I and mixed for 15 minutes in a rapid mixer granulator.
- the rapid mixer granulator was run at a slow speed for 3-5 minutes and then at a fast speed for 10 minutes to get the desired wet granule consistency.
- step III The wet material of step III was sifted through an ASTM 10 # sieve.
- step IV The sifted wet material of step IV was dried in a Rapid Dryer at a temperature of 6O 0 C for 30 minutes.
- step V The dried material of step V was sifted through an ASTM 18# sieve and the fines were collected through an ASTM 40# sieve.
- step VI The fines collected in step VI were lubricated with Avicel PH 101, sodium lauryl sulphate , croscarmellose sodium, talc and magnesium stearate.
- the dissolution of the eplerenone tablets was determined as directed in the U.S. Pharmacopoeia (USP) in 1000 ml of 0.1N HCl at 37°C ( ⁇ 0.5 0 C) using an USP Dissolution Apparatus Type II at an agitation of 50 rotations per minute (rpm).
- USP U.S. Pharmacopoeia
- the dissolution profile of the eplerenone tablets is in the range of about 25 to about 40% in 5 minutes, about 60 to about 85% in 10 minutes and not less than about 70% in 30 minutes.
- the dissolution profile of the eplerenone tablets are set forth below in Table 2.
- the dissolved eplerenone is expressed in cumulative percent of drug dissolved over an elapsed time period in minutes.
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Abstract
La présente invention concerne des particules antagonistes de l’aldostérone telles que des particules d’éplérénone ayant une taille particulaire D90 inférieure à 25 microns et supérieure à 15 microns. La présente invention concerne également des compositions pharmaceutiques contenant des particules antagonistes de l’aldostérone.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
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IN891MU2005 | 2005-07-29 | ||
IN891/MUM/2005 | 2005-07-29 | ||
US72095705P | 2005-09-27 | 2005-09-27 | |
US60/720,957 | 2005-09-27 |
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WO2007012960A1 true WO2007012960A1 (fr) | 2007-02-01 |
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PCT/IB2006/002072 WO2007012960A1 (fr) | 2005-07-29 | 2006-07-28 | Compositions pharmaceutiques à base d’éplérénone |
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008074098A1 (fr) * | 2006-12-21 | 2008-06-26 | Alphapharm Pty Ltd | Composition pharmaceutique |
WO2012050539A1 (fr) * | 2010-09-20 | 2012-04-19 | Mahmut Bilgic | Composition pharmaceutique comprenant l'eplérenone |
USD744087S1 (en) | 2013-10-01 | 2015-11-24 | Mahmut Bilgic | Dry powder inhaler |
US9345848B2 (en) | 2009-10-20 | 2016-05-24 | Sima Patent Ve Lisanslama Hizmetleri Ltd. Sti. | Dry powder inhaler |
US9849255B2 (en) | 2011-11-25 | 2017-12-26 | Mahmut Bilgic | Inhalation device |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000033847A1 (fr) * | 1998-12-09 | 2000-06-15 | G.D. Searle & Co. | Compositions d'eplerenone microfine |
WO2001041770A2 (fr) * | 1999-12-08 | 2001-06-14 | Pharmacia Corporation | Compositions d'eplerenone nanoparticulaire |
WO2001087284A2 (fr) * | 2000-05-11 | 2001-11-22 | Pharmacia Corporation | Composition antagoniste de l'aldosterone destinee a etre liberee durant l'acrophase de l'aldosterone |
-
2006
- 2006-07-28 WO PCT/IB2006/002072 patent/WO2007012960A1/fr active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000033847A1 (fr) * | 1998-12-09 | 2000-06-15 | G.D. Searle & Co. | Compositions d'eplerenone microfine |
WO2001041770A2 (fr) * | 1999-12-08 | 2001-06-14 | Pharmacia Corporation | Compositions d'eplerenone nanoparticulaire |
WO2001087284A2 (fr) * | 2000-05-11 | 2001-11-22 | Pharmacia Corporation | Composition antagoniste de l'aldosterone destinee a etre liberee durant l'acrophase de l'aldosterone |
Non-Patent Citations (1)
Title |
---|
GASPARO DE M ET AL: "ANTIALDOSTERONES: INCIDENCE AND PREVENTION OF SEXUAL SIDE EFFECTS", JOURNAL OF STEROID BIOCHEMISTRY, PERGAMON PRESS PLC, GB, vol. 32, no. 1B, 1989, pages 223 - 227, XP002406674, ISSN: 0022-4731 * |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008074098A1 (fr) * | 2006-12-21 | 2008-06-26 | Alphapharm Pty Ltd | Composition pharmaceutique |
US9345848B2 (en) | 2009-10-20 | 2016-05-24 | Sima Patent Ve Lisanslama Hizmetleri Ltd. Sti. | Dry powder inhaler |
US9795750B2 (en) | 2009-10-20 | 2017-10-24 | Sima Patent Ve Lisanslama Hizmetleri Ltd. Sti. | Dry powder inhaler |
US9795751B2 (en) | 2009-10-20 | 2017-10-24 | Sima Patent Ve Lisanslama Hizmetleri Ltd. Sti. | Dry powder inhaler |
US10842952B2 (en) | 2009-10-20 | 2020-11-24 | Sima Patent Ve Lisanslama Hizmetleri Ltd. Sti. | Dry powder inhaler |
WO2012050539A1 (fr) * | 2010-09-20 | 2012-04-19 | Mahmut Bilgic | Composition pharmaceutique comprenant l'eplérenone |
US9849255B2 (en) | 2011-11-25 | 2017-12-26 | Mahmut Bilgic | Inhalation device |
USD744087S1 (en) | 2013-10-01 | 2015-11-24 | Mahmut Bilgic | Dry powder inhaler |
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