WO2006108519A1 - Combinaison pour traiter une hyperplasie benigne de la prostate - Google Patents

Combinaison pour traiter une hyperplasie benigne de la prostate Download PDF

Info

Publication number
WO2006108519A1
WO2006108519A1 PCT/EP2006/002941 EP2006002941W WO2006108519A1 WO 2006108519 A1 WO2006108519 A1 WO 2006108519A1 EP 2006002941 W EP2006002941 W EP 2006002941W WO 2006108519 A1 WO2006108519 A1 WO 2006108519A1
Authority
WO
WIPO (PCT)
Prior art keywords
inhibitor
pde
tablet
controlled
layer
Prior art date
Application number
PCT/EP2006/002941
Other languages
German (de)
English (en)
Inventor
Helmut Haning
Peter Serno
Erwin Bischoff
Original Assignee
Bayer Healthcare Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer Healthcare Ag filed Critical Bayer Healthcare Ag
Priority to EP06723901A priority Critical patent/EP1888075A1/fr
Priority to BRPI0610634-0A priority patent/BRPI0610634A2/pt
Priority to JP2008505765A priority patent/JP2008535877A/ja
Priority to AU2006233567A priority patent/AU2006233567A1/en
Priority to CA002605224A priority patent/CA2605224A1/fr
Priority to MX2007012567A priority patent/MX2007012567A/es
Publication of WO2006108519A1 publication Critical patent/WO2006108519A1/fr
Priority to IL186604A priority patent/IL186604A0/en
Priority to TNP2007000385A priority patent/TNSN07385A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • This invention relates to a novel method of treating the symptoms of benign prostatic hyperplasia.
  • BPH benign prostatic hyperplasia
  • Outflow obstruction in the urethra is symptomatically improved by an enlarged prostate.
  • Examples of such compounds are tamsulosin, alfuzosin, doxazosin and
  • 5- ⁇ reductase inhibitors such as finasteride or dutasteride. This inhibits the reduction of testosterone to dihydrotestosterone. As a result, after prolonged therapy, the prostate volume is reduced and the symptoms of BPH improved. Even with this therapy, the extent of the improvements is limited and it is desirable to increase the effect. Furthermore, occur under the therapy with 5- ⁇ reductase inhibitors side effects, such as an impairment of male sexual function.
  • PDE 5 inhibitors to treat symptoms of benign prostatic hyperplasia has also been proposed (Forssmann et al., US Application 2003/0199517 Al). However, as described in section 0027 on page 3 of the application, their oral administration is carried out in "conventional pharmaceutical preparations such as tablets, coated tablets, capsules ." This form of therapy has in addition to insufficient efficacy and too short duration of action the problem of moderate Compatibility.
  • a triple combination of selective ⁇ -1 adrenoceptor antagonist in controlled-release formulation, 5- ⁇ reductase inhibitors and PDE 5 inhibitor is also possible,
  • tamsulosin in controlled release formulation, finasteride and vardenafil in controlled release formulation is also possible.
  • the combination of said compounds can be carried out freely, for example by a combination pack containing drug forms of the respective substances and on the package, the package insert or a label contains an instruction to take the drug forms on the same day.
  • the individual dosage forms can be taken approximately at the same time or at different times in the course of a day.
  • fixed combinations ie dosage forms containing all the drugs to be combined.
  • These may be, for example, tablets, hard gelatin or soft gelatine capsules.
  • ⁇ -1 adrenoceptor antagonist for example vardenafil or sildenafil
  • two-sidedly retarded drug forms are used. These are a combination of controlled release ⁇ -1 adrenoceptor antagonist portion with a controlled release PDE 5 - inhibitor - proportion.
  • This is for example capsules containing two types of pellets, minitablets or tablets, namely those that the ⁇ - Adrenoceptor antagonists and those that release the PDE 5 inhibitor in a controlled manner.
  • slow-release tablets which consist of at least two different active ingredient layers. One of them releases the ⁇ -1 adrenoceptor antagonist controlled, another the PDE 5 inhibitor.
  • osmotic-releasing tablets are also possible. These contain both combination partners in the active substance layer.
  • an osmotically active, drug-free swelling layer is also possible.
  • the resulting one- or two-layer tablet is coated with a water-insoluble, but permeable lacquer, for example of cellulose acetate, and provided on the active substance-containing side with at least one hole for drug release.
  • ⁇ -1 adrenoceptor antagonists for example tadalafil
  • a 5- ⁇ reductase inhibitor for example vardenafil or sildenafil
  • unilaterally sustained dosage forms are used.
  • the dosage form releases the ⁇ -1 adrenoceptor antagonist in controlled form and contains the tadalafil in a rapidly releasing form.
  • the dosage form releases the PDE 5 inhibitor in a controlled manner and contains the 5- ⁇ reductase inhibitor in a rapidly releasing form.
  • Single-sidedly retarded dosage forms are, for example, capsules which contain the controlled release partner in the form of pellets, minitablets or tablets and which can be rapidly released. _
  • slow-release tablets which consist of at least two different active ingredient layers.
  • Another active ingredient layer of the tablet contains the uncontrollably released combination partner in the usual fast-release form.
  • Another possibility is single-layered sustained-release tablets. These contain the ⁇ -1 adrenoceptor antagonist in the form of diffusion pellets and the PDE 5 inhibitor - long half-life or 5- ⁇ reductase inhibitor to be combined. Alternatively, they contain the PDE 5 inhibitor short half-life in the form of diffusion pellets and the 5- ⁇ reductase inhibitor to be combined.
  • osmotically releasing tablets are possible. These are, for example, constructed in three layers and contain a first layer with the uncontrollably release combination partner, a second layer with the combination partner to be released in a controlled manner and an osmotically active, active substance-free swelling layer.
  • the resulting three-layer tablet is coated with a water-insoluble, but permeable lacquer, for example of cellulose acetate, and provided on the active substance-containing side with at least one hole for drug release.
  • tablets or capsules which contain both combination partners in rapidly releasing form are particularly preferred.
  • the tablets can be made from a granulate or a powder mixture which already contains both combination partners.
  • granules or powders can be mixed and then pressed together, each containing only one of the combination partners.
  • the production of a two-layer tablet in which the active ingredients contained separately in the two layers.
  • separate powders, granules, pellets or tablets can be used or such powders, granules, pellets or tablets that already contain both combination partners.
  • Soft gelatin capsule formulations with both combination partners are also possible. These contain a suspension or solution of both combination partners in an oil or water-miscible vehicle such as polyethylene glycol.
  • ⁇ -1 and ⁇ -IA adrenoceptor antagonists are known and are summarized in the context of this invention by the term ⁇ -1 adrenoceptor antagonist.
  • Particularly preferred are tamsulosin, alfuzosin, doxazosin and terazosin.
  • the compounds can be used as base or salt and these in each case in different Hydratease and modification.
  • the preferred doses and forms are 0.2-0.8 mg tamsulosin HCl, 5-20 mg alfuzosin HCl, 1-16 mg doxazosin mesilate, and 2-20 mg terazosin HCl.
  • 5- ⁇ reductase inhibitors are known. Particularly preferred is finasteride and dutasteride. The preferred doses are 1-10 mg finasteride and 0.2-1 mg dutasteride.
  • cGMP PDE 5 inhibitors are known. Particularly preferred are vardenafil, sildenafil and tadalafil. The compounds can be used as base or salt and these in each case in different Hydratease and modification.
  • CGMP PDE 5 inhibitors with a long half-life are to be understood as those whose half-life is more than 8 hours.
  • CGMP PDE 5 inhibitors with a short half-life should be understood as those whose half-life is equal to or less than 8 hours.
  • a preferred cGMP PDE 5 inhibitor with long half-life is tadalafil.
  • vardenafil hydrochloride trihydrate 5 - 30 mg (calculated as vardenafil)
  • sildenafil citrate 25 - 150 mg (calculated as sildenafil)
  • tadalafil 5 - 30 mg The most preferred doses and forms are: vardenafil hydrochloride trihydrate 5 - 30 mg (calculated as vardenafil), sildenafil citrate 25 - 150 mg (calculated as sildenafil) and tadalafil 5 - 30 mg.
  • the invention relates to a pharmaceutical formulation which controls an ⁇ -1 adrenoceptor antagonist with an average release rate of 80% in more than 45 minutes and a PDE 5 inhibitor controlled with an average release rate of 80% in longer than
  • compositions containing an ⁇ -1 are particularly preferred.
  • Adrenoceptor antagonists controlled with a mean release rate between 80% in
  • the invention further relates to a pharmaceutical formulation containing an ⁇ -1 adrenoceptor antagonist controlled with an average release rate of 80% in more than 45 minutes and a long half-life PDE 5 inhibitor.
  • Particularly preferred are drug formulations containing an ⁇ -1 adrenoceptor antagonist controlled with an average release rate between 80% in 2 hours and 80% in 16 hours and a long half-life PDE 5 inhibitor.
  • the invention further provides a pharmaceutical formulation containing a 5- ⁇ reductase inhibitor and delivering a PDE 5 inhibitor controlled at a mean release rate of 80% in more than 45 minutes.
  • Particularly preferred are drug formulations containing a 5- ⁇ reductase inhibitor and deliver a PDE 5 inhibitor controlled with an average release rate between 80% in 2 hours and 80% in 16 hours.
  • the invention also provides a pharmaceutical formulation containing a 5- ⁇ reductase inhibitor and a long half-life PDE 5 inhibitor.
  • the invention further relates to a pharmaceutical formulation containing an ⁇ -1 adrenoceptor
  • Antagonist controls at a mean release rate of 80% in more than 45 minutes and delivers a PDE 5 inhibitor controlled at a mean release rate of 80% in more than 45 minutes and contains a 5- ⁇ reductase inhibitor.
  • PDE 5 inhibitor controlled at a mean release rate of 80% in more than 45 minutes and contains a 5- ⁇ reductase inhibitor.
  • Drug formulations that control an ⁇ -1 adrenoceptor antagonist with an average release rate between 80% in 2 hours and 80% in 16 hours and a PDE 5
  • the invention further relates to a pharmaceutical formulation which controls an ⁇ -1 adrenoceptor antagonist with an average release rate of 80% in more than 45 minutes and a PDE 5 - long half-life inhibitor and a 5- ⁇ reductase inhibitor.
  • Particularly preferred are drug formulations which deliver an ⁇ -1 adrenoceptor antagonist controlled with an average release rate between 80% in 2 hours and 80% in 16 hours and a PDE 5 - long half-life inhibitor and a 5 ⁇ reductase inhibitor included.
  • the pharmaceutical formulations of the present invention are tested in USP "Apparatus 2" (The United States Pharmacopeia) 900 ml of pH 6.8 phosphate buffer with 0.1% sodium lauryl sulfate are used as the test medium The speed of rotation of the stirrer is 75 revolutions per minute Samples are passed through an 8 ⁇ m filter and their active ingredient content is determined, the amount of active substance determined in this way being converted into percent by weight of the active substance used.
  • compositions described above are present, for example, in a capsule.
  • This consists for example of glycerol, gelatin and dyes, hypromellose, pullulan or other known materials and may contain:
  • the ⁇ -1 adrenoceptor antagonist and the PDE 5 - inhibitor in controlled release form for subsequent filling in a capsule are particularly suitable diffusion-controlled pellets.
  • the binders used are preferably hydroxypropylmethylcellulose or polyvinylpyrrolidone.
  • methylcellulose hydroxypropylcellulose, sodium carboxymethylcellulose, polyacrylic acids, polyvinyl alcohols or gelatin
  • Particularly suitable as a diffusion coating is ethylcellulose, as it is commercially available, for example, as an aqueous dispersion under the name Aquacoat® or Surelease®.
  • ethylcellulose as it is commercially available, for example, as an aqueous dispersion under the name Aquacoat® or Surelease®.
  • other materials such as poly [(methacrylic acid) (ethyl acrylate)] (1: 1) or other acrylates (Eudragit®), cellulose acetate or cellulose acetate butyrate may also be used.
  • Suitable plasticizers are, for example, phthalic acid derivatives (for example dimethyl phthalate, diethyl phthalate, dibutyl phthalate), citric acid derivatives (eg triethyl citrate, tributyl citrate, acetyl triethyl citrate), other esters (eg diethyl sebacate, triacetin), fatty acids and derivatives (glycerol monostearate, acetylated fatty acid glycerides, castor oil and other native oils , Miglyol), polyols (glycerol, 1,2-propanediol, polyethylene glycol of different chain length).
  • phthalic acid derivatives for example dimethyl phthalate, diethyl phthalate, dibutyl phthalate
  • citric acid derivatives eg triethyl citrate, tributyl citrate, acetyl triethyl citrate
  • other esters eg diethyl se
  • the type and amount of the plasticizer are adjusted so that the above-defined inventive release and the required stability of the pellets are achieved.
  • the adjustment of the above-defined release is further effected by controlling the pore size of the diffusion coating and / or its thickness.
  • Soluble polymers such as polyethylene glycols, polyvinylpyrolidones, hydroxypropylmethylcelluloses, carboxymethylcelluloses or their salts, methylcelluloses, dextrins, maltodextrins, cyclodextrins, dextranes or other soluble compounds, such as, for example, salts (sodium chloride, potassium chloride, Ammonium chloride, etc.), urea, sugars (glucose, sucrose, fructose, lactose, etc.), sugar alcohols (mannitol, sorbitol, lactitol, etc.).
  • G mass
  • Parts of the plasticizer used can evaporate during painting and tempering.
  • a change in the coating amount of diffusion coating is required. Such is for example a higher coating amount is required if the desired rate of release is reduced, the amount of pore former is increased, or in certain plasticizers the level of plasticizer is reduced.
  • the diffusion pellets can be prepared, for example, by suspending or dissolving the active ingredient in water and thickening with a concentrated hydroxypropylmethylcellulose solution. The suspension or solution thus obtained is applied to neutral pellets in a fluidized-bed plant in a spraying process. This is followed by the coating of the pellets with a diffusion membrane, preferably in a fluidized-bed plant, by spraying, for example, an aqueous dispersion of ethylcellulose or organic ethylcellulose, which contains a suitable, physiologically compatible plasticizer.
  • the pellets are then tempered at temperatures of 50 to 125 ° C, preferably 60 to 110 0 C. In this case, higher tempering temperatures lead to lower coating application quantities being sufficient to achieve the release according to the invention and the resulting pellets being physically more stable during storage.
  • the thickness of the diffusion membrane, type of plasticizer, amount of plasticizer and pellet size are chosen such that a rate of release of the ⁇ -1 adrenoceptor antagonist and PDE 5 inhibitor of 80% results in more than 45 minutes, preferably between 80% in 2 hours to 16 hours.
  • the amount of pellets corresponding to a daily dose of, for example, 0.4 mg tamsulosin HCL and 10 mg Vardenaf ⁇ l HCl trihydrate is filled into a hard gelatine capsule.
  • pellet production In addition to the described coating of neutral pellets, other methods of pellet production are feasible, such as moisture extrusion and rounding, rotor granulation, fluidized-bed agglomeration or thermal extrusion. Alternatively, minitablets with a diameter of 1 - 4 mm can be produced. Subsequently, the active ingredient-containing pellets or minitablets are coated with a diffusion membrane as described.
  • ⁇ -1 adrenoceptor antagonist and the PDE 5 - inhibitor in controlled release form for subsequent filling in a capsule are in another embodiment of the drug formulation according to the invention tablets containing the active ingredient in a matrix of a water-swellable polymer.
  • the size of these tablets is such that one or more tablets fit inside the capsule.
  • the tablets may be filled in uncoated form into the capsule or previously coated with a varnish, for example a gastric juice-insoluble varnish.
  • Tablets for subsequent filling in a capsule containing the ⁇ -1 adrenoceptor antagonist or PDE 5 inhibitor in a matrix of a water-swellable polymer are prepared as follows. These so-called matrix formulations suitably contain from 0.1 to ,
  • compositions according to the invention in the form of erosion tablets are particularly preferred. These tablets are characterized in that they contain, in addition to customary auxiliaries and excipients and tabletting excipients, a certain amount of water-swellable hydrogel-forming polymers, these polymers having a viscosity of at least 15, preferably at least 50 cps (measured as 2% aqueous solution at 20 0 C).
  • Typical excipients and carriers are, for example, lactose, microcrystalline cellulose, mannitol or calcium phosphates.
  • Typical Tablettierzsmittel are for example magnesium stearate, talc or fumed silica (Aerosil ® ).
  • magnesium stearate these are expediently present in an amount of from 0.5 to 3% by weight, in the case of highly dispersed silicon dioxide, advantageously in an amount of from 0.1 to 1% by weight.
  • Preferred water-soluble, hydrogel-forming polymers are hydroxypropylcelluloses, hydroxypropylmethylcelluloses (HPMC), methylcelluloses, carboxymethylcellulose, alginates, galactomannans, polyacrylic acids, polymethacrylic acids or copolymers of methacrylic acid and methyl methacrylate, guar, agar, pectin, tragacanth, gum arabic, xanthan or mixtures of these substances used. Particularly preferred is the use of HPMC.
  • the erosion tablets according to the invention should preferably contain at least 10 wt .-% of a hydroxypropylmethylcellulosetypses based on the mass of a tablet whose viscosity (measured as 2% aqueous solution at 20 0 C) is at least 15, preferably at least 50 cps.
  • the drug formulation comprising the active ingredient in a matrix of a water-swellable polymer is prepared by mixing the active ingredient, the polymer and suitable excipients and excipients (as described above) and conventional tabletting aids (as described above) and tableting directly. It is also possible to granulate the active substance, the water-swellable polymer and suitable carriers in the fluidized bed.
  • the amount and viscosity of the water-swellable polymer is chosen so that tablets with the above-described average release rates of the ⁇ -1 adrenoceptor antagonist or PDE 5 - inhibitor result.
  • the dry granules are sieved, mixed with a lubricant, such as magnesium stearate, and tableted. If necessary, the tablet is still painted.
  • Erosionstabletten are preferred with a diameter of 3 mm to 7 mm.
  • the PDE 5 long half-life inhibitor or the 5- ⁇ reductase inhibitor may be incorporated into the capsule as a powder, granule, pellet or tablet.
  • customary fast-release formulations are suitable.
  • the combination partners are present in a bilayer tablet. It consists of two controlled release layers, one controlled and one rapidly releasing layer or two rapidly releasing layers. These can be:
  • each controlled release layer is based on the principles set forth above for the matrix formulation for subsequent filling into a capsule.
  • the active compound is mixed with suitable auxiliaries and excipients (as described above) and customary tabletting aids (as described above) and directly tabletted.
  • suitable auxiliaries and excipients as described above
  • customary tabletting aids as described above
  • the dry granules are sieved, mixed with a lubricant, such as magnesium stearate, and tableted.
  • a lubricant such as magnesium stearate
  • the combination partners are present in a single-layer tablet. This contains:
  • a PDE 5 inhibitor with a long half-life for combination with an ⁇ -1 A adrenoceptor antagonist
  • a 5- ⁇ reductase inhibitor for combination PDE 5 - short half-life inhibitor
  • Suitable controlled-release formulations for subsequent incorporation into a single-layer tablet are, in particular, the above-described diffusion-controlled pellets. These are mixed with the active ingredient to be combined in a rapidly releasing form and further hips, excipients and tabletting aids and pressed into a single-layer tablet. Granulation of the fast-release adjuvant and subsequent coating of the tablet are also possible.
  • the pharmaceutical formulation of the present invention is an osmotic drug delivery system.
  • osmotic drug delivery systems are generally known in the art and are e.g. reviewed in detail in Richard W. Baker, "Osmotic Drug Delivery: A Review of the Patent Literature,” Journal of Controlled Release 35 (1995) 1-21.
  • the drug formulation as an osmotic drug delivery system is preferably composed
  • a core which contains the active substances, optionally a hydrophilic polymeric swelling agent and optionally a water-soluble substance for inducing osmosis, and
  • hydrophilic polymeric swelling agents reference may be made, for example, to the polymeric swelling agents mentioned in EP-A-0 277 092 and WO 96/40080.
  • ethylene oxide homopolymers polyethylene glycol
  • Polyox having various degrees of polymerization, known for example by the name Polyox, having molecular weights of between 100,000 and 8,000,000
  • vinylpyrrolidone-vinyl acetate copolymers and others in US Pat. No. 3,865,108, US Pat 002 173 and US-A-4207 893 mentioned water-swellable polymers can be used.
  • Water-soluble substances for the induction of osmosis are, in principle, all water-soluble substances whose use is unobjectionable in pharmacy, as mentioned in the Pharmacopoen or in "Hager's Handbook of Pharmaceutical Practice, 1990-1995, Springer Verlag” and Remington's Pharmaceutical Sciences as water-soluble excipients are.
  • Special water-soluble substances are salts of inorganic or organic acids or nonionic organic substances with high water solubility such as carbohydrates such as sugar etc.
  • the preparation of an opening in the shell of the tablet is known per se in the prior art and described, for example, in US Pat. Nos. 3,485,770 and 3,916,899.
  • the release rate is adjusted by the nature and amount of the semipermeable material forming the shell, by the nature and amount of the optional hydrophilic polymeric swelling agent and any water-soluble substance which is present to induce osmosis.
  • the combination partners of the present invention may be incorporated into an osmotic drug delivery system in a variety of ways. For controlled release of both active ingredients, these are mixed with the excipients and compressed to a common drug layer. If only one combination partner is to be released in a controlled manner, it can either be introduced separately into the coating shell of the tablet or the active substance not to be released in a controlled manner is pressed into a separate active substance layer which is first pumped free of the drug release system before the combination partner to be released in a controlled manner.
  • 12.5 g of tamsulosin HCl is dissolved together with 12.5 g of hypromellose in a mixture of 47.5% water and 427.5 g of methanol.
  • This solution is sprayed onto 2 500 g of neutral pellets of microcrystalline cellulose having a mean particle diameter of 125 ⁇ m in a fluidized bed system.
  • 2 500 g of the thus coated pellets are sprayed in a fluidized bed system with a dispersion consisting of the following constituents: 1167 g of poly (ethyl acrylate-methyl methacrylate) - dispersion 30%, 350 g of talc and 1260 g of water.
  • the coated with this diffusion membrane pellets are post-dried at 40 0 C.
  • a three-layer tablet is prepared as follows: For layer 1, 75.4 kg of hypromellose, 5 kg of ethylcellulose and 15 kg of hydrogenated castor oil are mixed and granulated with a solution consisting of 3.2 kg of povidone K 30 and 28.8 kg of ethanol. The dried granules are mixed with 0.5 kg highly dispersed Sicliciumdioxid and 1 kg magnesium stearate. For layer 2, 5 kg of alfuzosin hydrochloride, 15 kg of hypromellose and 75 kg of microcrystalline cellulose in the fluidized bed are granulated with a solution of 3 kg of povidone K 30 and 97 kg of water.
  • the granules are dried and mixed with 0.5 kg of highly dispersed Sicliciumdioxid and 1.5 kg of magnesium stearate.
  • layer 3 23.7 kg of vardenafil hydrochloride trihydrate, 130 kg of hypromellose and 3.1 kg of microcrystalline cellulose are mixed and granulated dry on a roller.
  • the granules are mixed with 0.8 kg of highly dispersed Sicliciumdioxid and 2.4 kg of magnesium stearate.
  • the three granules are placed in the hopper of a three-layer tablet press such that layer 2 represents the middle tablet layer. It For example, round three - layer tablets of 8 mm diameter are pressed, layer 1 having a mass of 100 mg, layer 2 of 100 mg and layer 3 of 160 mg.
  • the dried granules are mixed with magnesium stearate and pressed on a rotary press into round tablets of 7 mm diameter and 125 mg mass.
  • the tablets are coated with a lacquer consisting of: 2.391 mg hypromellose, 0.797 mg Macrogol 3350, 0.653 mg titanium dioxide and 0.144 mg iron oxide yellow.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne un nouveau procédé pour traiter les symptômes en cas d'hyperplasie bénigne de la prostate. A cette fin on utilise (1) un antagoniste de récepteur adrénergique a-1 dans une préparation à libération contrôlée ou un inhibiteur de la 5-a réductase et (2) un inhibiteur de cGMP PDE 5 dans une préparation à libération contrôlée ou un inhibiteur de cGMP PDE 5 présentant une demi-vie plus longue.
PCT/EP2006/002941 2005-04-13 2006-03-31 Combinaison pour traiter une hyperplasie benigne de la prostate WO2006108519A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
EP06723901A EP1888075A1 (fr) 2005-04-13 2006-03-31 Combinaison pour traiter une hyperplasie benigne de la prostate
BRPI0610634-0A BRPI0610634A2 (pt) 2005-04-13 2006-03-31 combinação para a terapia de hiperplasia benigna da próstata
JP2008505765A JP2008535877A (ja) 2005-04-13 2006-03-31 良性前立腺肥大症の治療用の組合せ
AU2006233567A AU2006233567A1 (en) 2005-04-13 2006-03-31 Therapeutic combination in case of benign prostate hyperplasia
CA002605224A CA2605224A1 (fr) 2005-04-13 2006-03-31 Combinaison pour traiter une hyperplasie benigne de la prostate
MX2007012567A MX2007012567A (es) 2005-04-13 2006-03-31 Combinacion para terapia en hiperplasia benigna de prostata.
IL186604A IL186604A0 (en) 2005-04-13 2007-10-11 Therapeutic combination in case of benign prostate hyperplasia
TNP2007000385A TNSN07385A1 (en) 2005-04-13 2007-10-11 Therapeutic combination in case of benign prostate hyperplasia

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102005016981.3 2005-04-13
DE102005016981A DE102005016981A1 (de) 2005-04-13 2005-04-13 Kombination zur Therapie bei benigner Prostatahyperplasie

Publications (1)

Publication Number Publication Date
WO2006108519A1 true WO2006108519A1 (fr) 2006-10-19

Family

ID=36608700

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2006/002941 WO2006108519A1 (fr) 2005-04-13 2006-03-31 Combinaison pour traiter une hyperplasie benigne de la prostate

Country Status (22)

Country Link
EP (1) EP1888075A1 (fr)
JP (1) JP2008535877A (fr)
KR (1) KR20080007252A (fr)
CN (1) CN101193638A (fr)
AR (1) AR053575A1 (fr)
AU (1) AU2006233567A1 (fr)
BR (1) BRPI0610634A2 (fr)
CA (1) CA2605224A1 (fr)
CR (1) CR9427A (fr)
DE (1) DE102005016981A1 (fr)
DO (1) DOP2006000074A (fr)
GT (1) GT200600145A (fr)
IL (1) IL186604A0 (fr)
MA (1) MA29683B1 (fr)
MX (1) MX2007012567A (fr)
PE (1) PE20061338A1 (fr)
RU (1) RU2007141518A (fr)
SV (1) SV2008002477A (fr)
TN (1) TNSN07385A1 (fr)
TW (1) TW200716122A (fr)
UY (1) UY29473A1 (fr)
WO (1) WO2006108519A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007047282A1 (fr) * 2005-10-12 2007-04-26 Lilly Icos Llc Traitement d'une hypertrophie benigne de la prostate et de symptomes dans les voies urinaires inferieures
WO2007072156A1 (fr) * 2005-12-21 2007-06-28 Pfizer Products Inc. Combinaison pharmaceutique d'un inhibiteur de pde-5 et d'un inhibiteur de 5-alpha reductase
EP1875914A1 (fr) * 2006-07-07 2008-01-09 Teva Pharmaceutical Industries Ltd. Les compositions solides comprenant tadalafil et au moins d'un agent de support
EP2036560A1 (fr) * 1998-09-16 2009-03-18 ICOS Corporation (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-pyrazino[2',1':6,1]pyrido[3,4-b]indole-1,4-dione pour le traitement de l'hypertrophie prostatique bénigne
WO2009076663A1 (fr) 2007-12-13 2009-06-18 Vanda Pharmaceuticals Inc. Procédé et composition pour traiter une affection véhiculée par alpha-adrénocepteur
WO2013123965A1 (fr) * 2012-02-20 2013-08-29 Synthon Bv Formulation pharmaceutique à dose fixe
US8654746B2 (en) 2010-04-26 2014-02-18 Intel Corporation Method, apparatus and system for fast session transfer for multiple frequency band wireless communication
US9238007B2 (en) 2007-06-22 2016-01-19 Ratiopharm Gmbh Method for the production of a medicament containing tadalafil
US9446038B2 (en) 2007-12-13 2016-09-20 Vanda Pharmaceuticals, Inc. Method and composition for treating a serotonin receptor-mediated condition
EP3013327A4 (fr) * 2013-06-28 2016-11-16 Hanmi Pharm Ind Co Ltd Préparation composite pour gélule pharmaceutique comprenant du tadalafil et de la tamsulosine
EP3162363A4 (fr) * 2014-06-30 2018-01-03 Hanmi Pharm. Co., Ltd. Préparation composite comprenant une couche de revêtement par film contenant un principe actif

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102727456B (zh) * 2012-07-03 2016-06-22 北京科信必成医药科技发展有限公司 药物口腔崩解片及其制备方法
MX2016001030A (es) 2013-07-23 2016-10-07 Allergan Inc Métodos y composiciones que comprenden desmopresina en combinación con un agonista del receptor beta 3-adrenérgico.
KR20150056443A (ko) * 2013-11-15 2015-05-26 한미약품 주식회사 타다라필 및 암로디핀을 포함하는 복합제제
WO2016003180A1 (fr) * 2014-06-30 2016-01-07 한미약품 주식회사 Preparation composite comprenant une couche de revêtement pelliculaire contenant un inhibiteur de la 5-alpha-réductase, et procédé pour produire la préparation composite
BR112016030731A2 (pt) * 2014-06-30 2017-08-22 Hanmi Pharm Ind Co Ltd Preparação de compósito, e, método de preparação de uma preparação de compósito
KR20170097045A (ko) * 2014-11-20 2017-08-25 알레간 인코포레이티드 알파-아드레날린성 수용체 길항제와 조합된 데스모프레신을 포함하는 방법 및 조성물
KR102391495B1 (ko) * 2016-03-31 2022-04-28 한미약품 주식회사 안정성 및 용출율이 개선된 타다라필 및 탐수로신 함유 캡슐 복합제제
KR101835506B1 (ko) * 2016-10-25 2018-03-07 주식회사 에스텍파마 두타스테리드와 타다라필을 함유하는 속효성 복합정제
CN108066347B (zh) * 2016-11-16 2021-02-02 深圳万和制药有限公司 包含坦索罗辛和度他雄胺的口腔崩解片药物组合物
KR101879133B1 (ko) * 2017-07-11 2018-07-17 (주)동구바이오제약 비뇨기 질환 예방 또는 치료용 제제 및 이의 제조방법
TR201715231A2 (tr) * 2017-10-09 2019-04-22 Montero Gida Sanayi Ve Ticaret Anonim Sirketi Dapokseti̇n ve fosfodi̇esteraz ti̇p-5 i̇nhi̇bi̇törü i̇çeren farmasöti̇k kombi̇nasyon

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005013937A2 (fr) * 2003-07-23 2005-02-17 Elan Pharma International Ltd. Nouvelles compositions de base libre de sildenafil

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005013937A2 (fr) * 2003-07-23 2005-02-17 Elan Pharma International Ltd. Nouvelles compositions de base libre de sildenafil

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
AUERBACH S M ET AL: "Simultaneous administration of vardenafil and tamsulosin does not induce clinically significant hypotension in patients with benign prostatic hyperplasia", UROLOGY, BELLE MEAD, NJ, US, vol. 64, no. 5, November 2004 (2004-11-01), pages 998 - 1003, XP004632598, ISSN: 0090-4295 *
COSTA FRANK ET AL: "The dual 5alpha-reductase inhibitor dutasteride is safe and effective in men with benign prostatic hyperplasia receiving a PDE-5 inhibitor.", JOURNAL OF UROLOGY, vol. 171, no. 4 Supplement, April 2004 (2004-04-01), & ANNUAL MEETING OF THE AMERICAN UROLOGICAL ASSOCIATION; SAN FRANCISCO, CA, USA; MAY 08-13, 2004, pages 360, XP009069022, ISSN: 0022-5347 *
GIULIANO ET AL: "537Tadalafil shows no clinically significant haemodynamic interaction with alfuzosin", EUROPEAN UROLOGY SUPPLEMENTS, XX, XX, vol. 4, no. 3, March 2005 (2005-03-01), pages 137, XP005006998, ISSN: 1569-9056 *
KLONER ET AL: "INTERACTION BETWEEN THE PHOSPHODIESTERASE 5 INHIBITOR, TADALAFIL AND 2 alpha-BLOCKERS, DOXAZOSIN AND TAMSULOSIN IN HEALTHY NORMOTENSIVE MEN", JOURNAL OF UROLOGY, BALTIMORE, MD, US, vol. 172, no. 5, November 2004 (2004-11-01), pages 1935 - 1940, XP005376728, ISSN: 0022-5347 *
MCKEAGE K ET AL: "A REVIEW OF THE THERAPEUTIC USE OF THE PROLONGED-RELEASE FORMULATION GIVEN ONCE DAILY IN THE MANAGEMENT OF BENIGN PROSTATIC HYPERPLASIA", DRUGS, ADIS INTERNATIONAL LTD, AT, vol. 62, no. 4, 2002, pages 633 - 653, XP009004987, ISSN: 0012-6667 *
NARAYAN PERINCHERY ET AL: "Concomitant use of sildenafil with tamsulosin or terazosin: A retrospective safety evaluation.", JOURNAL OF UROLOGY, vol. 171, no. 4 Supplement, April 2004 (2004-04-01), & ANNUAL MEETING OF THE AMERICAN UROLOGICAL ASSOCIATION; SAN FRANCISCO, CA, USA; MAY 08-13, 2004, pages 357, XP009069023, ISSN: 0022-5347 *

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2036560A1 (fr) * 1998-09-16 2009-03-18 ICOS Corporation (6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-pyrazino[2',1':6,1]pyrido[3,4-b]indole-1,4-dione pour le traitement de l'hypertrophie prostatique bénigne
WO2007047282A1 (fr) * 2005-10-12 2007-04-26 Lilly Icos Llc Traitement d'une hypertrophie benigne de la prostate et de symptomes dans les voies urinaires inferieures
WO2007072156A1 (fr) * 2005-12-21 2007-06-28 Pfizer Products Inc. Combinaison pharmaceutique d'un inhibiteur de pde-5 et d'un inhibiteur de 5-alpha reductase
EP1875914A1 (fr) * 2006-07-07 2008-01-09 Teva Pharmaceutical Industries Ltd. Les compositions solides comprenant tadalafil et au moins d'un agent de support
WO2008005039A1 (fr) * 2006-07-07 2008-01-10 Teva Pharmaceutical Industries Ltd. Compositions solides comprenant du tadalafil et au moins un véhicule
US9238007B2 (en) 2007-06-22 2016-01-19 Ratiopharm Gmbh Method for the production of a medicament containing tadalafil
US9987264B2 (en) 2007-12-13 2018-06-05 Vanda Pharmaceuticals Inc. Method and composition for treating a serotonin receptor-mediated condition
WO2009076663A1 (fr) 2007-12-13 2009-06-18 Vanda Pharmaceuticals Inc. Procédé et composition pour traiter une affection véhiculée par alpha-adrénocepteur
JP2011506481A (ja) * 2007-12-13 2011-03-03 ヴァンダ ファーマシューティカルズ インコーポレイテッド αアドレナリン受容体介在状態を治療する方法及び組成物
US10272075B2 (en) 2007-12-13 2019-04-30 Vanda Pharmaceuticals Inc. Method and composition for treating an alpha adrenoceptor-mediated condition
US8729100B2 (en) 2007-12-13 2014-05-20 Vanda Pharmaceuticals, Inc. Method and composition for treating an alpha adrenoceptor-mediated condition
US9446038B2 (en) 2007-12-13 2016-09-20 Vanda Pharmaceuticals, Inc. Method and composition for treating a serotonin receptor-mediated condition
US8654746B2 (en) 2010-04-26 2014-02-18 Intel Corporation Method, apparatus and system for fast session transfer for multiple frequency band wireless communication
WO2013123965A1 (fr) * 2012-02-20 2013-08-29 Synthon Bv Formulation pharmaceutique à dose fixe
EP3013327A4 (fr) * 2013-06-28 2016-11-16 Hanmi Pharm Ind Co Ltd Préparation composite pour gélule pharmaceutique comprenant du tadalafil et de la tamsulosine
RU2672573C2 (ru) * 2013-06-28 2018-11-16 Ханми Фарм. Ко., Лтд. Фармацевтический комбинированный состав капсулы, содержащий тадалафил и тамсулозин
AU2014299447B2 (en) * 2013-06-28 2019-01-17 Hanmi Pharm. Co., Ltd. Pharmaceutical capsule composite formulation comprising tadalafil and tamsulosin
EP3162363A4 (fr) * 2014-06-30 2018-01-03 Hanmi Pharm. Co., Ltd. Préparation composite comprenant une couche de revêtement par film contenant un principe actif

Also Published As

Publication number Publication date
AR053575A1 (es) 2007-05-09
EP1888075A1 (fr) 2008-02-20
GT200600145A (es) 2007-04-10
CR9427A (es) 2007-12-17
UY29473A1 (es) 2006-11-30
BRPI0610634A2 (pt) 2010-07-13
MX2007012567A (es) 2007-12-10
AU2006233567A1 (en) 2006-10-19
MA29683B1 (fr) 2008-08-01
DOP2006000074A (es) 2006-10-15
DE102005016981A1 (de) 2006-10-19
IL186604A0 (en) 2008-01-20
RU2007141518A (ru) 2009-05-20
SV2008002477A (es) 2008-02-08
CA2605224A1 (fr) 2006-10-19
JP2008535877A (ja) 2008-09-04
CN101193638A (zh) 2008-06-04
TNSN07385A1 (en) 2009-03-17
TW200716122A (en) 2007-05-01
PE20061338A1 (es) 2007-01-28
KR20080007252A (ko) 2008-01-17

Similar Documents

Publication Publication Date Title
WO2006108519A1 (fr) Combinaison pour traiter une hyperplasie benigne de la prostate
EP1435915B1 (fr) Formes d'administration orale de propiverine ou de ses sels pharmaceutiquement acceptables, a liberation prolongee de l'agent actif
DE60021749T2 (de) Pharmazeutische formulierung enthaltend tolterodin sowie ihre verwendung
DE60016920T2 (de) Arzneistoffverabreichungsystem zur verzögerten, völlstandigen wirkstoffabgabe im verdauungstrakt
DE60034565T2 (de) Verfahren zur herstellung eines umhüllten geschmackmaskierten granulats mit sofortiger wirkstofffreisetzung
EP2057984B1 (fr) Comprimé à effet différé contenant de l'hydromorphone
EP1113787B1 (fr) Preparations pharmaceutiques a liberation controlee en fonction de l'agitation et leur procede de production
EP1439829A1 (fr) Medicament contenant du 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, caracterise par une liberation differee du principe actif
EP1830855A1 (fr) Produits pharmaceutiques solides, administres par voie orale et contenant du rivaroxaban, a liberation modifiee
EP1017392B1 (fr) Formulation medicamenteuse a liberation controlee du principe actif
DE112011101605T5 (de) Pharmazeutische Zusammensetzung umfassend Hydromorphon und Naloxon
DE3856555T2 (de) Diltiazem-Zusammensetzungen mit kontrollierter Wirkstoffabsorption
DE69817848T2 (de) Monolithsysteme enthaltend mindestens einer wirkstoff, bestehend aus drei schichten mit unterschiedlichen freisetzungmechanismus
US20120003307A1 (en) Levetiracetam controlled release composition
DE60307819T2 (de) Venlafaxine Hydrochloridformulierungen mit verzögerter Freisetzung
DE602004006443T2 (de) Beschichtete minitabletten von venlafaxinhydrochlorid mit verlängerter freisetzung
DE10209979A1 (de) Arzneimittel mit Cholesterolspiegel-senkenden Wirkstoffen mit zeitverzögerter Wirkstofffreisetzung
DE60319983T2 (de) Universelle Zusammensetzung zur kontrollierten Wirkstoffabgabe enthaltend Chitosan
EP2704698B1 (fr) Forme galénique pour libération ciblée de principes actifs
DE60312642T2 (de) Pharmazeutische zusammensetzung mit modifizierter freisetzung
EP2116232B1 (fr) Médicament à libération contrôlée comprenant de la galanthamine
EP2089006B1 (fr) Médicament à libération contrôlée contenant de la galanthamine
US20080206338A1 (en) Controlled release formulations of an alpha-adrenergic receptor antagonist
AU2022392482A1 (en) Controlled release formulations of flavoxate and process for preparation thereof
DE10248309A1 (de) 3-(3- Dimethylamino-1-ethyl-2-methyl-propyl) phenol enthaltendes Arzeimittel mit verzögerter Wirkstofffreisetzung

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2006723901

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 7655/DELNP/2007

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: CR2007-009427

Country of ref document: CR

WWE Wipo information: entry into national phase

Ref document number: 2605224

Country of ref document: CA

Ref document number: 562352

Country of ref document: NZ

Ref document number: MX/a/2007/012567

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 12007502263

Country of ref document: PH

Ref document number: 186604

Country of ref document: IL

Ref document number: 07107195

Country of ref document: CO

WWE Wipo information: entry into national phase

Ref document number: 2008505765

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

WWW Wipo information: withdrawn in national office

Ref document number: DE

WWE Wipo information: entry into national phase

Ref document number: 2006233567

Country of ref document: AU

ENP Entry into the national phase

Ref document number: 2007000653

Country of ref document: KE

WWE Wipo information: entry into national phase

Ref document number: 1020077026260

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 2007141518

Country of ref document: RU

Ref document number: A20071311

Country of ref document: BY

WWP Wipo information: published in national office

Ref document number: 2006233567

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 200680020781.4

Country of ref document: CN

WWP Wipo information: published in national office

Ref document number: 2006723901

Country of ref document: EP

ENP Entry into the national phase

Ref document number: PI0610634

Country of ref document: BR

Kind code of ref document: A2