WO2008001499A1 - Agent prophylactique et/ou thérapeutique pour le traitement de la polyarthrite rhumatoïde - Google Patents
Agent prophylactique et/ou thérapeutique pour le traitement de la polyarthrite rhumatoïde Download PDFInfo
- Publication number
- WO2008001499A1 WO2008001499A1 PCT/JP2007/000700 JP2007000700W WO2008001499A1 WO 2008001499 A1 WO2008001499 A1 WO 2008001499A1 JP 2007000700 W JP2007000700 W JP 2007000700W WO 2008001499 A1 WO2008001499 A1 WO 2008001499A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- solvate
- rheumatoid arthritis
- phenyl
- hmg
- salt
- Prior art date
Links
Classifications
-
- 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
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- the present invention relates to a preventive and / or therapeutic agent for rheumatoid arthritis.
- Rheumatoid arthritis causes swelling and painful inflammation in many joints, and it progresses over a long period of time, resulting in a significant quality of life due to irreversible joint deformation and dysfunction (Q ua I ityof L ife : A disease that leads to a decrease in QOL).
- Q ua I ityof L ife A disease that leads to a decrease in QOL.
- Japan there are 0.6% of the population and 1% of the population over 30 years of age. In particular, with the progress of an aging society, the number of elderly rheumatic patients is increasing. is there.
- the stage of rheumatoid arthritis is the stage when there is still evidence of arthralgia and arthritis, but a definitive diagnosis of rheumatoid arthritis cannot be made yet.
- the treatment method differs depending on the stage.
- the current treatment goal is to diagnose rheumatoid arthritis early and suppress the inflammation of rheumatoid arthritis as quickly and maximally as possible to prevent or prevent the development of irreversible changes.
- the goal is to improve the patient's physical, mental and social quality of life. Therefore, in the treatment, after fully explaining the disease and treatment method to the patient, various means such as physical therapy, exercise therapy, drug therapy, and surgical treatment are used. Yes.
- Non-Patent Document 1 As pharmacotherapy for rheumatoid arthritis, non-steroidal anti-inflammatory drugs (NSA ID s), disease-modifying anti-rheumatic drugs (DMARD s), steroid drugs, etc. are used in clinical practice. Biologics such as piles targeting inflammatory cytokines are also used (see Non-Patent Document 1).
- DMARDs are classified into immunomodulators and immunosuppressants based on their mechanism of action, and among them, methotrexate and leflunomide have a high anti-rheumatic effect.
- methotrexate and leflunomide induce serious side effects such as infection and interstitial pneumonia, so it is not only necessary to strictly control the administration method and dose,
- Interleukin-1 an inflammatory site-in, is found in many diseases such as rheumatoid arthritis, osteoarthritis, osteoporosis, inflammatory bowel disease, immunodeficiency syndrome, sepsis, hepatitis , Nephritis, ischemic disease, insulin-dependent diabetes mellitus, arteriosclerosis, Parkinson's disease, Alzheimer's disease, leukemia, etc., increased production is considered to be involved in inflammation such as collagenase, CO X and PLA 2 It is known to induce the synthesis of the enzymes described and to cause joint destruction very similar to rheumatoid arthritis when injected into an joint in animals.
- diseases such as rheumatoid arthritis, osteoarthritis, osteoporosis, inflammatory bowel disease, immunodeficiency syndrome, sepsis, hepatitis , Nephritis, ischemic disease, insulin-dependent diabetes mellitus, arteriosclerosis, Parkinson's disease, Alzheimer's disease,
- IL-1; 5 inhibitors have been researched and developed as therapeutic agents for inflammatory diseases.
- Substances derived from biological components such as IL-1 receptor antagonists (see Non-Patent Document 2), T_61 4 ( Non-patent document 3), S_247 4 (refer to non-patent document 4), 2_Benzyl_5_ (4_Black mouth phenyl) _6-[4- (Methylthio) phenyl] _2 H-pyridazine _3_one (Patent text)
- Low molecular weight compounds such as FR 1 33605 (see Non-Patent Document 5) are known.
- Arteriosclerotic diseases are typical lesions that occur in the vascular system.
- Ischemic heart diseases such as myocardial infarction and angina pectoris, cerebral infarction and obstructive arteriosclerosis are increasing worldwide. It is a disease with a high fatality rate. Atherosclerosis is thought to be mainly composed of cellular components typified by smooth muscle cells, proliferation of extracellular matrix, and thickening of the intima due to accumulation of lipids such as cholesterol. It has come to be regarded as inflammation involving lymphocytes (see Non-Patent Document 6).
- statins a series of drugs collectively called statins whose mechanism is HMG_CoA reductase inhibitory action is known as the therapeutic drug for hyperlipidemia having the strongest effect.
- statins pravastatin sodium, sympastatin, fluvastatin sodium, atorvastatin calcium hydrate, pitavastatin calcium, and the like are known as statins used clinically.
- statins which are HMG_CoA reductase inhibitors
- statins have anti-inflammatory effects
- inflammatory arthritis models see non-patent document 7
- rheumatoid arthritis patients see non-patent document 8
- administration of statins to patients is effective.
- the therapeutic target of antihyperlipidemic drugs is to lower blood cholesterol, a factor that causes arteriosclerosis.
- macrophages that play a central role in the formation of plaque which is a cause of arteriosclerotic diseases, produce inflammatory cytokines such as IL-1; 5 that cause inflammation.
- An alloy that triggers curing is formed (see Non-Patent Document 9).
- suppression of IL-1; 8 production is considered to be effective in arteriosclerotic diseases, which are the target diseases of antihyperlipidemic drugs.
- Non-Patent Document 10 It has been reported that having inflammatory cytokines such as IL-1 ⁇ , which is strongly involved in the onset, has a high risk of developing atherosclerotic disease (non- (See Patent Document 10) It has been reported that arteriosclerosis is suppressed in rheumatic patients (see Non-Patent Document 11) and that statin suppresses the production of inflammatory cytokines from macrophages (see Non-Patent Document 12).
- HMG-CoA reductase inhibitors and IL-1 / 8 inhibitors have been suggested to be useful in the treatment of rheumatoid arthritis alone, but when both drugs are used in combination. It is not yet known what kind of effect will occur.
- Patent Document 1 International Publication No. 99 25697 Pamphlet
- Non-Patent Document 1 A r t h r i t i s & R h u u m a t i s m 4 6, p P 32
- Non-Patent Document 2 A r t h r i t i s & R h u m at i s m 4 2, p P 49
- Non-Patent Document 3 J. P h a m a c o b i o— D y n 1 1, P p 64 9-6
- Non-Patent Document 4 YAKUGAKU Z A S S H I 1 2 3, p P 323 ⁇ 33
- Non-Patent Document 5 J. Rheumato I 23, p P 1 778 ⁇ 1 78 3, 1
- Non-Patent Document 6 N. E n l. J. Me d. 340, P P 5-1 2 6, 1
- Non-Patent Document 7 J. I mm u no I. 1 7 0, p p 1 5 24- 1 530 '20
- Non-Patent Document 8 A r t h r i t i s & R h e u m a t i s m 4 8 (s u P P
- Non-Patent Document 9 Natre 4 20, P p 868 ⁇ 8F 4, 2 002
- Non-Patent Document 10 A r t h r i t i s & R h u uma t i sm 46, p p 8 62-873, 2002.
- Non-Patent Document 11 A nn. R he um. D i s. 63, pp 1 57 1-1 57 5, 2004.
- Non-Patent Document 12 J. C I i n. I nv e s t. 1 00, pp 267 1-26 7 9, 1 9 9 7.
- An object of the present invention is to provide a drug excellent in the treatment and prevention effect of rheumatoid arthritis.
- the present invention relates to 2_benzyl-l 5_ (4-chlorophenyl) _6_
- the present invention provides a prophylactic and / or therapeutic drug for rheumatoid arthritis comprising a combination of [4- (methylthio) phenyl] _ 2 H-pyridazin _ 3 _one and an HMG—CoA reductase inhibitor.
- the present invention is characterized in that it is administered in combination with an HMG_CoA reductase inhibitor for the purpose of preventing and / or treating rheumatoid arthritis. It is intended to provide a prophylactic and / or therapeutic drug for rheumatoid arthritis comprising phenyl) _ 6 _ [4- (methylthio) phenyl] _ 2 H_pyridazin _ 3 _one as an active ingredient.
- the present invention is also directed to the prevention and / or treatment of rheumatoid arthritis.
- the present invention provides a prophylactic and / or therapeutic drug for rheumatoid arthritis comprising an HMG_Co A reductase inhibitor as an active ingredient, characterized by being administered in combination with pyridazine_3_one.
- the present invention provides 2_benzyl mono 5_ (4-cyclophenyl) _6_ [4- (methylthio) phenyl] _ 2 H-pyridazine for the manufacture of a preventive and / or therapeutic agent for rheumatoid arthritis. It provides the use of a combination of 1-one and an HMG—CoA reductase inhibitor.
- the present invention provides a method for producing a preventive and / or therapeutic agent for rheumatoid arthritis administered in combination with an HMG_CoA reductase inhibitor for the purpose of preventing and / or treating rheumatoid arthritis.
- Nylyl_5_ (4-cyclophenyl) -6- [4- (methylthio) phenyl] _2 H-pyridazin_3_one is provided for use.
- the present invention is also directed to the prevention and / or treatment of rheumatoid arthritis with 2_benzyl_5_ (4-cyclophenyl) _6_ [4- (methylthio) phenyl] _2H-pyridazine_3_one.
- the present invention provides the use of an HMG_CoA reductase inhibitor for the manufacture of a prophylactic and / or therapeutic agent for rheumatoid arthritis administered in combination.
- the present invention provides an effective amount of 2_benzyl-1 5_ (4-cyclophenyl) _6_ [4- (methylthio) phenyl] _2H-pyridazin_3_one and HMG-CoA reductase inhibitors It is intended to provide a method for treating rheumatoid arthritis, which comprises administering
- the prophylactic and / or therapeutic agent for rheumatoid arthritis of the present invention can be administered orally, has an excellent anti-arthritis inhibitory effect with few side effects, and is useful not only for the prevention and treatment of rheumatoid arthritis, but also for arteries. It is also useful for patients with sclerotic disease. Brief Description of Drawings
- FIG. 3 is a graph showing E d ema Index of a rat collagen-induced arthritis model in the case of combined use of single administration and atorvastatin calcium hydrate (drug B 1) 3 Omg / kg once daily.
- FIG. 3 is a graph showing Edema Index of a rat collagen-induced arthritis model when combined with calcium hydrate (drug B 1) 10 Omg / kg once daily.
- 2_benzyl _ 5-(4-clothiophenyl) _6_ [4- (methylthio) phenyl] _2 H_ pyridazine _ 3 —one (hereinafter referred to as drug A) used in the preventive and / or therapeutic agent for rheumatoid arthritis of the present invention Can be produced by, for example, the method described in International Publication No. WO 99 25697 or a similar method. That is, p-chlorophenylacetic acid and thioamine are reacted with a condensing agent such as polyphosphoric acid to obtain 2_ (4-chlorophenyl) 1 '-(methylthio) acetophenone.
- the HMG_CoA reductase inhibitor (hereinafter also referred to as drug B) used in the preventive and / or therapeutic drug for rheumatoid arthritis of the present invention is It includes all of the so-called statins that have an inhibitory activity on serum synthesis and are known as therapeutic agents for hyperlipidemia.
- statins that have an inhibitory activity on serum synthesis and are known as therapeutic agents for hyperlipidemia.
- examples of the HMG_CoA reductase inhibitor used in the preventive and / or therapeutic agent for rheumatoid arthritis of the present invention include 3,5-dihydroxyheptanoic acid or a compound having 3,5-dihydroxy-6_heptenoic acid structure.
- Examples thereof include compounds described in JP-A-1-279866, JP-A-5_178841, and the like, and both lactones and lactone ring-opened products or salts thereof are included.
- Suitable HMG_CoA reductase inhibitors in the present invention include pravastatin ((+) _ (3R, 5R) -3,5-dihydroxy-7 _ [(1S, 2S, 6S, 8 S, 8 a R)-6-Hydroxy mono 2_methyl _ 8 _ [(S) _ 2 _methyl propylyloxy] _ 1, 2, 6, 7, 8, 8 a— 1-naphthyl] heptanoic acid, JP-A-57-2240) or a salt thereof or a solvate thereof, simbastin ((+)-(1S, 3R, 7S, 8S, 8a R)-1, 2, 3, 7, 8, 8 a—Hexahydro _3, 7—Dimethyl 1 8_ [2— [(2 R, 4 R) —Sultrahydro 1 4-Hydroxy 1 6 _Oxo _ 2 H —Pyran _ 2 _ethyl]
- a solvate thereof such as sodium flupastatin ((sat One (3 R *, 5 S *, 6 E)-7-[3-(4-Fluorophenyl) _ 1 _ (1-Methylethyl) _ 1 H-indole _2_yl] ⁇ 3, 5-Dihydroxy 1 6 _Heptenoic acid, JP-T-60-50001-5) or a salt thereof or a solvate thereof, atorvastatin calcium hydrate Atorvastatin ((3 R, 5 R) -7-[2- (4-Fluorophenyl) _5_ (1 -methylethyl) _3_phenyl mono 4_phenylaminocarbonyl _ 1 H-pyrrole _ 1 _yl _3,5-dihydroxyheptanoic acid, JP-A-3-58967) or a salt thereof or a solvate thereof, pitapastatin calcium, pitapastatin (
- the HMG-CoA reductase inhibitor can be produced by a known method in addition to the method described in the above-mentioned published patent publication.
- atorvastatin calcium hydrate which is a hydrate of salt of atorvastatin
- commercially available products such as those manufactured by Nftz Alchem International Corporation can also be used.
- the combination ratio of the doses or doses of drug A and drug B used in the preventive and / or therapeutic drug for rheumatoid arthritis of the present invention is, as a mass ratio, 100: 1 to 1:30, and further 80: 1.
- ⁇ 3: 100, in particular, 50: 1 to 3: 100 is preferable, since a particularly excellent synergistic effect can be obtained.
- the dosage form of the drug used in the preventive and / or therapeutic drug for rheumatoid arthritis of the present invention is not particularly limited and can be appropriately selected according to the therapeutic purpose.
- tablets, capsules, granules, film coating agents, powders, Oral administration by syrup or the like, or parenteral administration by injection, suppository, inhalation, transdermal absorption agent, eye drop, nasal drop and the like can be mentioned, and oral administration is particularly preferable.
- the prevention of rheumatoid arthritis comprising the combination of the drug A and the drug B, and Alternatively, the therapeutic agents may be administered as separate active agents, Drug A and Drug B, which may be administered simultaneously or at intervals, or as a pharmaceutical preparation containing both active ingredients. Also good. Further, the preventive and / or therapeutic agent for rheumatoid arthritis containing the drug A as an active ingredient administered in combination with the drug B for the purpose of preventing and / or treating rheumatoid arthritis of the present invention contains the drug A. The formulation should be administered at the same time or at intervals with the formulation containing Drug B.
- the preventive and / or therapeutic drug for rheumatoid arthritis containing Drug B as an active ingredient administered in combination with Drug A for the purpose of preventing and / or treating rheumatoid arthritis according to the present invention,
- the containing formulation should be administered at the same time or at intervals from the formulation containing Drug A.
- compositions suitable for these dosage forms include pharmaceutically acceptable carriers such as starches, lactose, sucrose, mannitol, silicic acid excipients and fillers; agar, calcium carbonate, potato or Disintegrants such as tapio force starch, alginic acid, specific complex silicates; binders such as hydroxypropylmethylcellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose, gum arabic; talc, calcium stearate, magnesium stearate, Lubricants such as solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof; diluents such as lactose and corn starch; organic acids such as citrate, tartaric acid and lactic acid; inorganic acids such as phosphoric acid and hydrochloric acid; hydroxylation Sodium, hydroxide power Buffering agents such as ethanolamines, diethanolamines, diisopropanolamines, etc .; paraoxybenzoates, pre
- the dose of 2_benzyl-5_ (4-cyclophenyl) _6_ [4- (methylthio) phenyl] _2H-pyridazine_3_one is determined by the patient's weight, age, The dose is appropriately selected according to sex, symptoms, etc. In general, for adults, 2 to 32 Omg per day, preferably 4 to 16 Omg, should be administered. The dose of HMG-CoA reductase inhibitor varies depending on the type. For adults, 1 to 6 Omg per day is recommended. Furthermore, administration may be performed once a day or divided into two or more times.
- Sensitive collagen emulsion used to induce arthritis in rats is a type II collagen 0.3% solution (collagen technical workshop), A djuvantpeptide (peptide laboratory) and A djuvant I nc omp lete F reund (DI FCO) was prepared by homogenization under ice-cooling using H andy Micro Homo genizer (Microtech ⁇ Nithion Co., Ltd.). The prepared collagen emulsion was administered intradermally to the back of the rat with 0.1 mL Zsite in 10 places for the first sensitization. Furthermore, 7 days after the first sensitization, additional sensitization was carried out by intradermal administration of 0.12 ml of the same iliajon into the ridge.
- Table 1 and Fig. 1 show the Edema Index of the drug A 3 mg Zkg single administration group, the drug B 1 30 mg / kg single administration group, and both drug combination administration groups.
- Table 2 and Figure 2 show that Drug A 3 mg Zkg alone administration group, Drug B 1 1 0 shows the edema index of the Omg / kg single administration group and the combination administration group of both drugs.
- E d ema Index is expressed as the average soil standard error of 8 rats in each group. The rate of decrease is represented by ((X—Y) X) X100 (X: control group Edema Index average value, Y: each group Edema Index average value).
- Drug B 1 was administered in combination with Drug A and Drug B 1 even though the doses of 30 and 10 OmgZkg were not effective against this model of edema (E de ma Index) As a result, E d ema I ndex was strongly reduced.
- the relative index of EdemaIndex in the group administered with drug A and drug B1 was smaller than the product of the relative indices of the group administered with each drug alone, and a clear synergistic effect was observed.
- the preventive and therapeutic effects of rheumatoid arthritis by the combined use of drug A and drug B far exceeded the expected therapeutic effects from each single effect.
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Rheumatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2008522303A JPWO2008001499A1 (ja) | 2006-06-29 | 2007-06-27 | 関節リウマチの予防及び/又は治療薬 |
EP07790222A EP2033646A4 (en) | 2006-06-29 | 2007-06-27 | PROPHYLACTIC AND / OR THERAPEUTIC AGENT FOR THE TREATMENT OF RHEUMATOID ARTHRITIS |
US12/305,302 US20090203701A1 (en) | 2006-06-29 | 2007-06-27 | Prophylactic and/or therapeutic agent for rheumatoid arthritis |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US81709106P | 2006-06-29 | 2006-06-29 | |
US60/817,091 | 2006-06-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2008001499A1 true WO2008001499A1 (fr) | 2008-01-03 |
Family
ID=38845274
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2007/000700 WO2008001499A1 (fr) | 2006-06-29 | 2007-06-27 | Agent prophylactique et/ou thérapeutique pour le traitement de la polyarthrite rhumatoïde |
Country Status (4)
Country | Link |
---|---|
US (1) | US20090203701A1 (ja) |
EP (1) | EP2033646A4 (ja) |
JP (1) | JPWO2008001499A1 (ja) |
WO (1) | WO2008001499A1 (ja) |
Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS56122375A (en) | 1980-02-04 | 1981-09-25 | Merck & Co Inc | Novel antihypercholesteremic compound* its intermediate and its manufacture |
JPS572240A (en) | 1980-06-06 | 1982-01-07 | Sankyo Co Ltd | Ml-236b derivative |
JPS57163374A (en) | 1979-06-15 | 1982-10-07 | Merck & Co Inc | Hypocholesterolemic fermentation product and manufacture |
JPS60500015A (ja) | 1982-11-22 | 1985-01-10 | サンド・アクチエンゲゼルシヤフト | メバロラクトン同族体とその誘導体、これらの製造法およびこれらを含有する製薬学的組成物 |
JPH01216974A (ja) | 1988-01-20 | 1989-08-30 | Bayer Ag | 置換ピリジン類 |
JPH01279866A (ja) | 1987-08-20 | 1989-11-10 | Nissan Chem Ind Ltd | キノリン系メバロノラクトン類 |
JPH0358967A (ja) | 1989-07-21 | 1991-03-14 | Warner Lambert Co | 〔R―(R‖,R‖)〕―2―(4―フルオロフエニル)―β,δ―ジヒドロキシ―5―(1―メチルエチル)―3―フエニル―4―〔(フエニルアミノ)カルボニル〕―1H―ピロール―1―ヘプタン酸、そのラクトン体およびその塩 |
JPH05178841A (ja) | 1991-07-01 | 1993-07-20 | Shionogi & Co Ltd | ピリミジン誘導体 |
WO1999025697A1 (fr) | 1997-11-19 | 1999-05-27 | Kowa Co., Ltd. | Nouveaux derives de pyridazine et medicaments contenant ces composes comme principe actif |
JP2000198776A (ja) * | 1997-11-19 | 2000-07-18 | Kowa Co | 新規ピリダジン誘導体及びこれを有効成分とする医薬 |
JP2002509529A (ja) * | 1996-12-06 | 2002-03-26 | アムジェン インコーポレイテッド | Il−1媒介疾患を処置するためにil−1インヒビターを使用する組合せ療法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003042190A1 (en) * | 2001-11-12 | 2003-05-22 | Pfizer Products Inc. | N-alkyl-adamantyl derivatives as p2x7-receptor antagonists |
US20030195167A1 (en) * | 2002-04-15 | 2003-10-16 | Kowa Co., Ltd. | PTX3-gene expression inhibitor |
EP1797882A4 (en) * | 2004-09-29 | 2009-11-18 | Kowa Co | PROPHYLACTIC AND / OR THERAPEUTIC DRUGS FOR RHEUMATOID ARTHRITIS |
EP1864663A1 (en) * | 2005-03-29 | 2007-12-12 | Kowa Co., Ltd. | Preventive and/or therapeutic agent for rheumatoid arthritis |
-
2007
- 2007-06-27 WO PCT/JP2007/000700 patent/WO2008001499A1/ja active Application Filing
- 2007-06-27 JP JP2008522303A patent/JPWO2008001499A1/ja active Pending
- 2007-06-27 EP EP07790222A patent/EP2033646A4/en not_active Withdrawn
- 2007-06-27 US US12/305,302 patent/US20090203701A1/en not_active Abandoned
Patent Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS57163374A (en) | 1979-06-15 | 1982-10-07 | Merck & Co Inc | Hypocholesterolemic fermentation product and manufacture |
JPS56122375A (en) | 1980-02-04 | 1981-09-25 | Merck & Co Inc | Novel antihypercholesteremic compound* its intermediate and its manufacture |
JPS572240A (en) | 1980-06-06 | 1982-01-07 | Sankyo Co Ltd | Ml-236b derivative |
JPS60500015A (ja) | 1982-11-22 | 1985-01-10 | サンド・アクチエンゲゼルシヤフト | メバロラクトン同族体とその誘導体、これらの製造法およびこれらを含有する製薬学的組成物 |
JPH01279866A (ja) | 1987-08-20 | 1989-11-10 | Nissan Chem Ind Ltd | キノリン系メバロノラクトン類 |
JPH01216974A (ja) | 1988-01-20 | 1989-08-30 | Bayer Ag | 置換ピリジン類 |
JPH0358967A (ja) | 1989-07-21 | 1991-03-14 | Warner Lambert Co | 〔R―(R‖,R‖)〕―2―(4―フルオロフエニル)―β,δ―ジヒドロキシ―5―(1―メチルエチル)―3―フエニル―4―〔(フエニルアミノ)カルボニル〕―1H―ピロール―1―ヘプタン酸、そのラクトン体およびその塩 |
JPH05178841A (ja) | 1991-07-01 | 1993-07-20 | Shionogi & Co Ltd | ピリミジン誘導体 |
JP2002509529A (ja) * | 1996-12-06 | 2002-03-26 | アムジェン インコーポレイテッド | Il−1媒介疾患を処置するためにil−1インヒビターを使用する組合せ療法 |
WO1999025697A1 (fr) | 1997-11-19 | 1999-05-27 | Kowa Co., Ltd. | Nouveaux derives de pyridazine et medicaments contenant ces composes comme principe actif |
JP2000198776A (ja) * | 1997-11-19 | 2000-07-18 | Kowa Co | 新規ピリダジン誘導体及びこれを有効成分とする医薬 |
Non-Patent Citations (14)
Title |
---|
ANN. RHEUM. DIS., vol. 63, 2004, pages 1571 - 1575 |
ARTHRITIS & RHEUMATISM, vol. 42, 1999, pages 498 - 506 |
ARTHRITIS & RHEUMATISM, vol. 46, 2002, pages 328 - 346 |
ARTHRITIS & RHEUMATISM, vol. 46, 2002, pages 862 - 873 |
ARTHRITIS & RHEUMATISM, vol. 48, 2003, pages S666 |
J. CLIN. INVEST., vol. 100, 1997, pages 2671 - 2679 |
J. IMMUNOL., vol. 170, 2003, pages 1524 - 1530 |
J. PHARMACOBIO-DYN., vol. 11, 1992, pages 649 - 655 |
J. RHEUMATOL., vol. 23, 1996, pages 1778 - 1783 |
MCCAREY D.W. ET AL.: "Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial", LANCET, vol. 363, no. 9426, 2004, pages 2015 - 2021, XP004773745 * |
N. ENGL. J. MED., vol. 340, 1999, pages 115 - 126 |
NATURE, vol. 420, 2002, pages 868 - 874 |
See also references of EP2033646A4 * |
YAKUGAKUZASSHI, vol. 123, 2003, pages 323 - 330 |
Also Published As
Publication number | Publication date |
---|---|
JPWO2008001499A1 (ja) | 2009-11-26 |
US20090203701A1 (en) | 2009-08-13 |
EP2033646A1 (en) | 2009-03-11 |
EP2033646A4 (en) | 2009-11-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2006035876A1 (ja) | 関節リウマチの予防及び/又は治療薬 | |
TW200401768A (en) | Methods of treatment with CETP inhibitors and antihypertensive agents | |
EP2359826B1 (en) | Combination of HMG-COA reductase inhibitor rosuvastatin with a phosphodiesterase 4 inhibitor, such as roflumilast, roflumilast-N-oxide for the treatment of inflammatory pulmonary diseases | |
EA032028B1 (ru) | СТИМУЛЯТОРЫ рГЦ | |
US7163945B2 (en) | Compositions and treatments for inhibiting kinase and/or HMG-CoA reductase | |
JP2022507533A (ja) | 肺動脈性高血圧症および他疾患に関連する肺動脈性肺高血圧症の治療法 | |
US9498464B2 (en) | Treatment of arterial wall by combination of RAAS inhibitor and HMG-CoA reductase inhibitor | |
WO2008001499A1 (fr) | Agent prophylactique et/ou thérapeutique pour le traitement de la polyarthrite rhumatoïde | |
JP4409295B2 (ja) | Ptx3遺伝子発現抑制方法 | |
US20020151734A1 (en) | 12-HETrE analogs and methods of use thereof | |
WO2012116985A1 (en) | TREATMENT OF ARTERIAL AGEING BY COMBINATION OF RAAS INHIBITOR AND HMG-CoA REDUCTASE INHIBITOR | |
JP2002518448A (ja) | 高血中コレステロールを治療する組成物および方法 | |
EP1920772A1 (en) | Prophylactic and/or therapeutic method for rheumatoid arthritis | |
WO2011153247A1 (en) | Combination therapies | |
JP4719572B2 (ja) | Lklf/klf2遺伝子発現促進剤 | |
WO2007049732A1 (ja) | 関節リウマチの予防及び/又は治療法 | |
WO2004096276A1 (ja) | 糖取り込み能増強剤 | |
WO2004096278A1 (ja) | アディポネクチン産生増強剤 | |
JPWO2006104172A1 (ja) | 関節リウマチの予防及び/又は治療薬 | |
US20140005412A1 (en) | TREATMENT OF ARTERIAL AGEING BY HMG CoA REDUCTASE INHIBITOR | |
EP2680831A1 (en) | Treatment of arterial ageing by raas inhibitor | |
WO2007123126A1 (ja) | 慢性心不全における運動耐容能低下の改善剤 | |
JP2005126343A (ja) | 免疫抑制用薬剤組成物 | |
JP2005232151A (ja) | 糖取り込み能増強剤 | |
WO2005117853A1 (ja) | 高脂血症治療剤及び糖尿病治療剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 07790222 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2008522303 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007790222 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12305302 Country of ref document: US |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
NENP | Non-entry into the national phase |
Ref country code: RU |