EP1682086A2 - Arzneimittelformulierung, enthaltend einen ltb4-antagonisten, sowie verfahren zu deren herstellung und deren verwendung - Google Patents
Arzneimittelformulierung, enthaltend einen ltb4-antagonisten, sowie verfahren zu deren herstellung und deren verwendungInfo
- Publication number
- EP1682086A2 EP1682086A2 EP04790806A EP04790806A EP1682086A2 EP 1682086 A2 EP1682086 A2 EP 1682086A2 EP 04790806 A EP04790806 A EP 04790806A EP 04790806 A EP04790806 A EP 04790806A EP 1682086 A2 EP1682086 A2 EP 1682086A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- alkyl
- pharmaceutical formulation
- active ingredient
- cellulose
- formula
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
Classifications
-
- 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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- Drug formulation containing an LTB 4 antagonist. and processes for their manufacture and their use
- A is a group of the formula -OC m H 2m -O- (PHE) n - (II), where m is an integer from 2 to 6, preferably 2 to 5, n is 0 or 1, PHE for an optionally 1,4-phenylene group substituted by one or two Ci-C 6 alkyl groups, preferably one by ortho Position to the oxygen-linked C 2 -C alkyl substituted 1,4-phenylene group; or A is a group of the formula
- R 5 is CC 4 alkyl, CF 3 , CH 2 OH, COOH or COO (C 1 -C alkyl), preferably d-C 4 alkyl, in particular methyl;
- R 6 is H, Ci-Gi-alkyl or CF 3 , preferably -CC 4 alkyl, in particular methyl;
- R 7 is CH 2 OH, COOH, COO (C 1 -C 4 alkyl), CONR 8 R 9 or CH 2 NR 8 R9;
- the compounds corresponding to formula I have an extremely low solubility in water and solubility in the physiological pH range (approx. ⁇ 0.5 ⁇ g / rni) combined with poor wettability. Because of the importance of the above-mentioned LTB 4 antagonists, there is therefore a constant need to find ways to improve the bioavailability and thus effectiveness of these compounds.
- WO 03/007922 describes that the bioavailability of the active ingredient can be increased if the active ingredient is formulated together with a wetting agent.
- Another object of the present invention is to provide a dosage form with improved bioavailability for LTB 4 antagonists, ie to develop a dosage form which releases an active ingredient of the formula I relatively quickly and completely and thus to an increased bioavailability of this active ingredient leads. Furthermore, an orally administrable pharmaceutical formulation should be able to be provided. Another object of the present invention is to provide a formulation which is easy to handle during the manufacturing process and thereby allows the technical manufacture in a reproducible manner with a consistently high quality.
- physiologically acceptable acid addition salts are understood to be pharmacologically acceptable salts which are selected from the salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid and maleic acid. If appropriate, mixtures of the abovementioned acids can also be used to prepare the salts.
- the salts of the formula I are preferably selected from the group consisting of hydrochloride, hydrobromide, sulfate, phosphate, fumarate and methanesulfonate.
- the salts are particularly preferably selected from hydrochloride, hydrobromide and fumarate.
- the active ingredient may optionally be in the form of a hydrate. According to the invention, however, the compound of the formula I is preferably in the form of the free base.
- a particularly preferred compound of formula I is the compound amelubant, i.e. [4- ((3 - ((4- (1- (4-Hydroxyphenyl) -l-methylethyl) phenoxy) methyl) benzyl) oxy) benzenecarboximide-amide-N-ethylcarboxylate], shown below in Formula IA:
- the compounds of the formula I in which R ⁇ is different from hydrogen are generally prodrugs which are converted in vivo to the corresponding compounds of the formula I in which Ri is hydrogen.
- the compound of the formula IA1 is formed from the compound IA in vivo: (Formula IA1) wherein X is OH, HSO 3 -O-, a carbohydrate radical of the formula C 6 H ⁇ 0 5 -O- or a glycosyl radical and represent Metabo lite of the above compound.
- Polyethylene glycols, polypropylene glycols, cellulose ethers, polyvinylpyrrolidones, polyvinyl acetates, copolymers and mixtures thereof can be used as polymers, for example.
- Particularly preferred polymers are poloxamers, ie known copolymers of polyethylene glycols and polypropylene glycols, methyl cellulose, ethyl cellulose, propyl cellulose, carboxymethyl cellulose, ethylhydroxyethyl cellulose, hydroxypropyl cellulose, Kollidone ®, mixed polymers of polyvinylpyrrolidone and polyvinyl acetate or polyethylene glycols with various chain lengths. Poloxamers, such as poloxamer 188, are very particularly preferred.
- the pharmaceutical formulation according to the invention optionally contains one or more auxiliaries and / or carriers, such as fillers, binders, disintegrants, disintegrants, flow or flow regulators, lubricants, mold release agents, pH corrections, in particular buffer substances, antioxidants and dyes.
- auxiliaries and / or carriers such as fillers, binders, disintegrants, disintegrants, flow or flow regulators, lubricants, mold release agents, pH corrections, in particular buffer substances, antioxidants and dyes.
- Carbohydrates such as lactose or mannose, in particular finely divided lactose, or sugar alcohols such as mannitol, sorbitol or xylitol, in particular mannitol, have proven to be particularly advantageous as fillers which can be used in the context of the present invention.
- the pharmaceutical formulation according to the invention can also contain disintegrants, which are sometimes also referred to as disintegrants.
- disintegrants are preferably selected from the group consisting of sodium starch glycolate, cross-linked polyvinylpyrrolidones (crospovidone), croscarmellose sodium salt (cellulose-carboxymethyl ether sodium salt, cross-linked), sodium carboxymethyl cellulose, dried corn starch and mixtures thereof.
- sodium starch glycolate, crospovidone and, preferably crospovidone or croscarmellose sodium salt are particularly preferably used.
- the pharmaceutical formulation according to the invention can contain one or more synthetic or natural, pharmaceutically acceptable dyes, preferably indigo carmine.
- the compound of the formula I for example of the formula IA, according to the invention is preferably about 0.5 to about 50% by weight, particularly preferably about 0.5 to about 25% by weight, in particular about 1 to about 10% by weight. % contain.
- the proportion of the free base, based on the total mass of the formulation is preferably between about 0.5 and about 25% by weight, particularly preferably between about 1 and about 10% by weight.
- the invention also relates to a method for producing the pharmaceutical formulation described above, comprising the steps:
- melt is poured into suitable molds and allowed to solidify while cooling (step 3a), or the solid solution or solid dispersion obtained is allowed to cool and then comminuted into the appropriate mold (Step 3b).
- the crushing is preferably achieved by grinding, but can be carried out using any known technique. An additional sieving can then be carried out.
- step (3a) or (3b) can expediently be processed further into tablets, film-coated tablets, dragées, powders or powder sachets, or, for example, filled directly into capsules, such as hard gelatin capsules.
- the invention also relates to a solid solution or solid dispersion containing an LTB 4 antagonist of the formula I, as previously defined, in a polymer matrix.
- the invention also relates to a solid solution or solid dispersion containing an LTB antagonist of the formula IA, as previously defined, in a polymer matrix.
- Another object of the invention is the use of the pharmaceutical formulation according to the invention for the manufacture of a pharmaceutical with increased bioavailability for the treatment or prevention of diseases in which LTB 4 antagonists can be used therapeutically or preventively.
- the invention also relates to the use of the pharmaceutical formulation according to the invention for the manufacture of a pharmaceutical for the treatment or prevention of arthritis, asthma, chronic obstructive pulmonary diseases, psoriasis, ulcerative colitis, Alzheimer's disease, shock, reperfusion damage / ischemia, cystic fibrosis, arteriosclerosis and multiple sclerosis ,
- a new pharmaceutical dosage form is made available which represents a solid solution or solid dispersion of an LTB 4 antagonist as an active ingredient in a polymer matrix. This achieves an extraordinary improvement in the dissolution behavior and thus the bioavailability of the active ingredient, which provides an inherently thermodynamically unstable and therefore supersaturated active ingredient concentration.
- melt embedding or “polymer melt embedding” and abbreviated as “JPSE”.
- the starter stirrer speed is increased to 100 rpm.
- the direction of rotation of the anchor stirrer is set to the left.
- the laboratory reactor is opened from the 15th to the 20th minute and any active ingredient residues on the anchor stirrer, temperature sensor and the glass wall are stripped off and returned to the melt.
- the laboratory reactor is closed again, an absolute pressure of 100 to 200 mbar is applied, the speed is left at 100 rpm and the anchor stirrer is set to the right-hand direction of rotation.
- the water bath temperature setting is reset to 86 ° C. 25 minutes after adding the active ingredient, the direction of rotation of the anchor stirrer is set to the left.
- the direction of rotation of the anchor stirrer is then set to the right again.
- the anchor stirrer speed is set to 20 rpm.
- the laboratory reactor is opened 60 minutes after the active ingredient has been added and the melt bed is poured out thinly on a glass plate or a stainless steel sheet.
- the melt embedding is poured out thinly on a glass plate or a stainless steel sheet (layer thickness approx. 1.5 to 2.5 mm) and allowed to solidify.
- the solidification time is approx. 2 to 3 hours.
- the solidified melt embedding is scraped off the glass pane or the stainless steel sheet with a dough scraper and stored temporarily in a brown wide-necked glass.
- BILL 315 ZW is present as a zwitterion.
- the compound BIIL 284 BS is converted in the human body in the manner described into BUL 315 ZW and represents its active metabolite.
- FIGS. 1 to 4 show the mean plasma concentration of BIIL 315 ZW, plotted against the time after a single dose of 75 mg BILL 284 BS, either as a melt embedding according to the invention (PSE) or in the form of a WIF tablet (wettability improved formulation, a formulation accordingly the prior art according to WO 03/007922, containing a wetting agent) - under fasting conditions (parallel groups), in each case at different times.
- PSE melt embedding according to the invention
- WIF tablet wettability improved formulation, a formulation accordingly the prior art according to WO 03/007922, containing a wetting agent
- Release medium 400 mL 0.1N HCl with 20mg Methocel A 15 LV
- Release medium 500 mL 0.1N HCl with 50mg Methocel A 15 LV
- Active ingredient BILL 284 BS, amount: 75 mg polymer matrix amount: 0.750 g (10% melt embedding)
- the laboratory reactor is preheated for about 30 minutes at a water bath temperature of 90 ° C.
- the laboratory reactor is filled with 600.0000 g of Poloxamer 188 Pharm (02) (liquid).
- the anchor stirrer is set to 20 rpm, the direction of rotation to the right and an absolute pressure of 100 to 200 mbar is applied. After 5 min the reactor is opened and the entire BIIL 284 BS (01) in jet-milled form is placed in the laboratory reactor (66.6667 g) and closed within 5 min.
- the anchor stirrer is left at 20 rpm and the direction of rotation remains on the right. 3 minutes after the addition of the active ingredient, the absolute pressure is set to 100 to 200 mbar.
- the anchor stirrer speed is increased to 100 rpm.
- the direction of rotation of the anchor stirrer is set to the left. From the 15th to the 20th min the laboratory reactor is opened and any Material residues on the anchor stirrer, temperature sensor and the glass wall are stripped off and returned to the melt. The laboratory reactor is closed, an absolute pressure of 100 to 200 mbar is applied, the speed is left at 100 rpm, and the anchor stirrer is turned to the right. 25 minutes after adding the active ingredient, the direction of rotation is set to the left by the anchor stirrer.
- the water bath temperature setting is reset to 86 ° C and the direction of rotation of the anchor stirrer is then set to the right again.
- the anchor stirrer speed is set to 20 rpm.
- the laboratory reactor is opened 60 minutes after the active ingredient has been added and the melt bed is poured out thinly on a glass plate or a stainless steel sheet.
- the melt embedding is poured out thinly on a glass plate or a stainless steel sheet (layer thickness approx. 1.5 to 2.5 mm) and allowed to solidify.
- the solidification time is approx. 2 to 3 hours.
- the solidified melt embedding is scraped off the glass pane or the stainless steel sheet with a dough scraper and stored temporarily in a brown wide-necked glass.
- the individual flakes are ground with a water-cooled IKA universal mill and the regrind is sieved with a 500 ⁇ m Kressner sieve. The grinding and sieving process is repeated until the entire melt embedding ⁇ 500 ⁇ m has been ground.
- the granulate is filled into the low-germ glass bottles and the pilfer proof closure is closed with a PfP flaring machine. Filling quantity: 750 mg tolerance when filling 745 mg to 755 mg IV.
- INPROCESS CONTROLS see example 1
- PSE formulations Two PSE formulations were used, one containing 5% BILL 284 BS and one containing 10% BIIL 284 BS.
- the PSE were stored in glass containers and suspended in 50 ml of tap water immediately before use. After administration of the dose, the bottles were washed once with a further 50 ml of tap water, which was also administered to the animals.
- FIG. 9 shows the plasma concentrations of BIIL 315 ZW, normalized to a dose of 1 mg / kg oral administration of various BILL 284 BS ' formulations to mini-pigs.
- FIG. 10 shows the dose-normalized C m a ⁇ and AUC 0-2 h values of BILL 315 ZW after oral administration of various pharmaceutical formulations of BILL 284 BS to mini-pigs.
- Group formulation AUCo-Mh c , - ⁇ nax 4nax N g medium gCV N g medium gCV medium range [ng-h / ml] [%] [ng / ml] [%] MM / dose / dose
- PSE The dose-normalized AUC 0-24 h and Cmax values of the PSE formulations containing 5% BILL 284 BS were about twice higher than the corresponding values of the PSE formulations containing 10% BILL 284 BS.
- the ratio of BIIL 284 BS to Pluronics influences the release of BILL 315 ZW in the animals.
- a lower loading of the PSE with the active ingredient BIIL 284 BS, i.e. a higher amount of Pluronics (polymer matrix) resulted in higher BILL 315 ZW plasma concentrations.
- Table 4 Individual and average dose normalized AUC 0-2 h of BLTL 315 ZW, after oral administration of various BIIL 284 BS formulations to mini-pigs.
- Table 5 Individual and average dose-normalized C max of BIIL 315 ZW, after oral administration of various formulations of BUL 284 BS to mini-pigs
- Table 6 Individual and average dosisnormalInstitute t ⁇ ma of BITL 315 ZW, after oral administration of formulations of verscMedenen BUL 284 BS to mini-pigs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10350528A DE10350528A1 (de) | 2003-10-29 | 2003-10-29 | Arzneimittelformulierung, enthaltend einen LTB4-Antagonisten, sowie Verfahren zu deren Herstellung und deren Verwendung |
PCT/EP2004/012015 WO2005041855A2 (de) | 2003-10-29 | 2004-10-23 | Arzneimittelformulierung, enthaltend einen ltb4-antagonisten, sowie verfahren zu deren herstellung und deren verwendung |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1682086A2 true EP1682086A2 (de) | 2006-07-26 |
Family
ID=34529886
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP04790806A Withdrawn EP1682086A2 (de) | 2003-10-29 | 2004-10-23 | Arzneimittelformulierung, enthaltend einen ltb4-antagonisten, sowie verfahren zu deren herstellung und deren verwendung |
Country Status (14)
Country | Link |
---|---|
US (1) | US20050129768A1 (de) |
EP (1) | EP1682086A2 (de) |
JP (1) | JP2007513068A (de) |
KR (1) | KR20060108696A (de) |
CN (1) | CN101123950A (de) |
AU (1) | AU2004285271A1 (de) |
BR (1) | BRPI0416121A (de) |
CA (1) | CA2544049A1 (de) |
DE (1) | DE10350528A1 (de) |
IL (1) | IL175293A0 (de) |
MX (1) | MXPA06004435A (de) |
RU (1) | RU2006118273A (de) |
WO (1) | WO2005041855A2 (de) |
ZA (1) | ZA200601360B (de) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1750669A1 (de) * | 2004-05-04 | 2007-02-14 | Boehringer Ingelheim International Gmbh | Solide pharmazeutische form mit einem ltb4-antagonist |
CA3063334A1 (en) | 2017-05-12 | 2019-12-05 | Riken | Modified class a gpcr binding compound |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4424713A1 (de) * | 1994-07-13 | 1996-01-18 | Boehringer Ingelheim Kg | Substituierte Benzamidine, ihre Herstellung und Verwendung als Arnzneistoffe |
EP1120120A4 (de) * | 1998-10-05 | 2009-04-29 | Eisai R&D Man Co Ltd | Tableten die sich unmittelbar in der mundhöhle auflösen |
JP2000178204A (ja) * | 1998-10-05 | 2000-06-27 | Eisai Co Ltd | ホスフォジエステラ―ゼ阻害剤を含有する口腔内速崩壊性錠剤 |
JP2000191518A (ja) * | 1998-10-19 | 2000-07-11 | Eisai Co Ltd | 溶解性の改善された口腔内速崩壊性錠剤 |
DE19856432A1 (de) * | 1998-12-08 | 2000-06-15 | Basf Ag | Nanopartikuläre Kern-Schale Systeme sowie deren Verwendung in pharmazeutischen und kosmetischen Zubereitungen |
KR100381834B1 (ko) * | 2000-05-20 | 2003-04-26 | 이상득 | 용출성이 개선된 프란루카스트 고체분산체 조성물 및 그제조 방법 |
MY140561A (en) * | 2002-02-20 | 2009-12-31 | Nycomed Gmbh | Dosage form containing pde 4 inhibitor as active ingredient |
-
2003
- 2003-10-29 DE DE10350528A patent/DE10350528A1/de not_active Withdrawn
-
2004
- 2004-10-23 BR BRPI0416121-1A patent/BRPI0416121A/pt not_active IP Right Cessation
- 2004-10-23 JP JP2006537151A patent/JP2007513068A/ja active Pending
- 2004-10-23 AU AU2004285271A patent/AU2004285271A1/en not_active Abandoned
- 2004-10-23 RU RU2006118273/15A patent/RU2006118273A/ru not_active Application Discontinuation
- 2004-10-23 MX MXPA06004435A patent/MXPA06004435A/es not_active Application Discontinuation
- 2004-10-23 KR KR1020067010481A patent/KR20060108696A/ko not_active Application Discontinuation
- 2004-10-23 CN CNA2004800322902A patent/CN101123950A/zh active Pending
- 2004-10-23 WO PCT/EP2004/012015 patent/WO2005041855A2/de active Application Filing
- 2004-10-23 EP EP04790806A patent/EP1682086A2/de not_active Withdrawn
- 2004-10-23 CA CA002544049A patent/CA2544049A1/en not_active Abandoned
- 2004-10-29 US US10/977,035 patent/US20050129768A1/en not_active Abandoned
-
2006
- 2006-02-15 ZA ZA200601360A patent/ZA200601360B/xx unknown
- 2006-04-27 IL IL175293A patent/IL175293A0/en unknown
Non-Patent Citations (1)
Title |
---|
See references of WO2005041855A2 * |
Also Published As
Publication number | Publication date |
---|---|
DE10350528A1 (de) | 2005-06-09 |
WO2005041855A2 (de) | 2005-05-12 |
US20050129768A1 (en) | 2005-06-16 |
BRPI0416121A (pt) | 2007-01-02 |
CN101123950A (zh) | 2008-02-13 |
WO2005041855A3 (de) | 2007-05-10 |
RU2006118273A (ru) | 2007-12-20 |
MXPA06004435A (es) | 2006-06-20 |
KR20060108696A (ko) | 2006-10-18 |
AU2004285271A1 (en) | 2005-05-12 |
CA2544049A1 (en) | 2005-05-12 |
ZA200601360B (en) | 2007-03-28 |
JP2007513068A (ja) | 2007-05-24 |
IL175293A0 (en) | 2006-09-05 |
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