WO1996011682A1 - Composition preventive et remede pour les maladies allergiques de type i - Google Patents
Composition preventive et remede pour les maladies allergiques de type i Download PDFInfo
- Publication number
- WO1996011682A1 WO1996011682A1 PCT/JP1995/002027 JP9502027W WO9611682A1 WO 1996011682 A1 WO1996011682 A1 WO 1996011682A1 JP 9502027 W JP9502027 W JP 9502027W WO 9611682 A1 WO9611682 A1 WO 9611682A1
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- WIPO (PCT)
- Prior art keywords
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- branched
- linear
- cyano
- oxo
- Prior art date
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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
- A61K31/655—Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
-
- 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
- A61K31/275—Nitriles; Isonitriles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
Definitions
- the present invention relates to a composition for preventing and treating type I allergic diseases. More specifically, the present invention relates to a composition for preventing and treating type I allergic diseases comprising an anilide compound as an active ingredient. Furthermore, the present invention relates to the use of an anilide compound for producing a preventive and therapeutic agent for a type I allergic disease. The present invention further relates to a method for preventing and treating type I allergic disease, which comprises administering an anilide compound to human or mammal.
- m-type includes bacterial endocarditis, systemic lupus erythematosus
- IV-type includes tuberculosis, leishmaniasis, and listerosis.
- the causes of type I allergic monogenic disease are generally considered as follows.
- allergens such as pollen and ticks enter the body percutaneously or through mucous membranes of the respiratory and digestive organs, the body produces immunoglobulin E (hereinafter referred to as IgE) for those allergens.
- IgE immunoglobulin E
- IgE binds to basophils and mast cells via receptors.
- allergens are taken again while IgE is bound to basophils / fertilizer cells via the receptor, that is, in the sensitized state, allergens are transferred to the sensitized basophil / fertilizer cells.
- Conventional therapeutic agents for allergic diseases include chemical mediator release inhibitors such as Intal ® (Fujisawa Pharmaceutical) (common name sodium cromoglycate), Celtect (Kyowa Hakko) (common name Oxatomid) and Rizaben ® Chemical mediators such as (Xisey) (generic name: tranilast) are used to inhibit the release and antagonists of chemical mediators, and synthetic corticosteroids such as prednisolone are often used.
- the mechanism of action of these drugs is to suppress the binding of chemical mediators to their receptors by inhibiting or antagonizing the release of chemical mediators that cause allergic symptoms. It also makes use of the anti-inflammatory and immunosuppressive effects of corticosteroids.
- the problem with these drugs is that they are symptomatic treatments, and that they must be taken every time an allergen enters the body and symptoms develop, and that the allergic constitution itself is characterized by high blood IgE levels It does not improve. Disclosure of the invention
- An object of the present invention is to provide a composition capable of fundamentally preventing or treating type I allergic disease by suppressing the production of IgE, which is a direct cause of type I allergic disease.
- the present invention provides a compound represented by the general formula (I):
- R 4 is a straight-chain or branched C! -C 4 alkyl group, straight chain even properly is branched c 2 to c e alkenyl group, a linear or branched means Jo of c 2 to c e Al Kiniru group or c 3 to c 7 cycloalkyl group) that means the group having the. And a stereoisomer thereof or a physiologically acceptable salt thereof as an active ingredient.
- the present invention further relates to a type I allergic substance, comprising administering to a human or mammal a anilide compound having the above formula (I), a stereoisomer thereof or a physiologically acceptable salt thereof. It relates to methods for preventing or treating sexually transmitted diseases.
- the present invention relates to the use of an anilide compound having the above formula (I), a stereoisomer thereof or a physiologically acceptable salt thereof for producing a preventive or therapeutic agent for type I allergic disease.
- halogen atom examples include fluorine, chlorine, bromine and iodine, in particular chlorine, bromine being preferred.
- straight-chain or branched C, -alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isoptyl, t-butyl, etc. chain ⁇ C 2 alkyl group is preferable.
- Examples of straight-chain or branched C 2 -C e alkenyl group vinyl, Ariru, 2 - Moshiku 3 - butenyl, 1-methyl - 3-butenyl, 3 -, 4 - or 5 - Examples include pentenyl, 1-methyl-5-pentenyl, 3-, 4- or 6-hexenyl, and a C 2 -C 4 alkenyl group is particularly preferred.
- Examples of the C 3- (: 7- cycloalkyl group include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexyl, and the like, and a C 3 -C 5 cycloalkyl group is preferred.
- R 2 is hydrogen, methyl or ethyl
- R 3 is isoxazole, a group having the above formula ( ⁇ ) or ( ⁇ )
- R 4 is methyl, ethyl, propyl , Aryl, 2-butenyl, propargyl, 2-butynyl, cyclopropyl or cyclobutyl.
- Preferred examples of the compound having the above formula (I) include:
- Leflunomide is metabolized immediately after administration and is converted to the compound A having drug activity.
- Oral LD 50 for Refuruno Mi de is 445ragZkg in mice, in 235ragZkg in rats Bok [Investigator's Brochure, Version 3; LEFLUNOMIDE (HWA486) October 1989, revised August 1991].
- leflunomide and Compound A are effective for autoimmune diseases such as rheumatoid arthritis and systemic erythematosus [Publication of Japanese Patent Application Sho 62-72614. Bartlett, R. et al. Springer Semin Immunopathol (1993) 14: 381-394].
- leflunomide was known to have an effect of suppressing histamine release from mast cells (Bartlett, R. et al. Springer Semin Immunopathol (1993) 14: 381-394). This suggests that leflunomide has a chemical inhibitory effect on release of chemical media, similar to conventional drugs for treating allergic diseases.
- the compounds BD are described in Japanese Patent Publication No. 288048Z1993, and the compound E is described in EP 551230, and these compounds are known to have anti-inflammatory effects.
- anilide compound having the formula (I) markedly suppresses the production of IgE itself, which is a direct cause of type I allergic disease. Elucidated and completed the present invention.
- anilide compound (I) varies depending on the administration method, patient age, body weight, symptoms, etc., but is usually in the range of 5 to 20 mg.
- Leflunomide has been used in more than 500 patients outside Japan as a treatment for rheumatoid arthritis. That is, there is no side effect, toxicity, etc. K at the above-mentioned amount of use.
- Administration methods include intravenous, intramuscular, oral, and rectal administration.
- intravenous administration normal intravenous injection and intravenous drip infusion are possible.
- Formulations containing leflunomide are manufactured by ordinary methods using ordinary excipients and additives.
- the preparation for injection can be, for example, a powder preparation for injection.
- a suitable water-soluble excipients such as mannitol, sucrose, nipple, maltose, glucose, fructose, etc.
- mannitol sucrose, nipple, maltose, glucose, fructose, etc.
- dissolve in water and dispense into vials or ampoules.
- a systemic administration it can be administered nasally or pulmonary as an aerosol preparation of fine particles.
- Oral preparations include ordinary tablets, capsules, granules, fine granules, powders, and enteric preparations.
- excipients such as mannitol, sucrose, nipples, maltose, starch, maleic anhydride, calcium phosphate, lubricants such as talc, magnesium stearate, carboxymethylcellulose, methylcellulose, gelatin
- Additives such as a binder such as gum arabic and a disintegrant such as carboxymethyl cellulose calcium are added as needed to make tablets, granules, fine granules, etc., and then cellulose acetate phthalate.
- enteric bases such as chill-methacrylic acid copolymer, etc. and a coloring agent such as titanium oxide, if necessary, are coated to form a formulation, and the enteric granules produced here
- a capsule or a fine granule can be filled into a capsule to prepare a capsule.
- the capsule prepared by the usual method can be made enteric by coating it with the above-mentioned enteric base, or a capsule made of the above-mentioned enteric base alone or by mixing gelatin with it. It can be used as an enteric capsule.
- lipophilic bases such as cocoa butter, semi-synthetic bases in which fatty acid monoglyceride and fatty acid diglyceride are mixed with fatty acid triglyceride in various ratios, and hydrophilic properties such as polyethylene glycol / glycerose gelatin
- a suppository can be made by adding a solution prepared by heating and dissolving the base, uniformly mixing the mixture, placing the mixture in a mold and molding.
- a 7-week-old female BNZCrj rat was sensitized with OVA as follows.
- LOmgZkg of c OVA and 300 mgZkg of aluminum hydroxide (Alura) were administered intraperitoneally (lOral kg) on day 0.
- Blood was collected on days 3, 7, and 9 after sensitization, serum was separated, and IgE was measured.
- sensitization 10 stated that OVA was dissolved in physiological saline and 60 mg kg was administered via the tail vein of rats to induce anaphylactic shock.
- Blood was collected from the venous vein before and after the onset of anaphylactic shock by OVA, plasma was separated, and histamine was measured.
- the drug was suspended using 1% carboxymethylcellulose (CMC), and repeated oral administration was performed from 0 to 1 once and 9 to 9 times.
- the dose of leflunomide was Z nigZkg, and each of Compounds A to E was 10 ragZkg, and prednisolone (generic name) as a control was 2 ngZkg.
- Body weight was measured once a week in the morning for all cases in each group, and drug administration was performed based on this body weight.
- 1% CMC for solvent control group The solution was administered. Furthermore, a drug non-administration group and an untreated control group were set. No treatment was performed for this untreated group. The experiment was performed using 6 rats in each group.
- the effect of the anilide compound (I) on BN rat was examined based on the survival rate of BN rat, IgE level in serum, and plasma histamine level before and after the induction of anaphylactic shock by OVA. Table 1 shows the results.
- OVA blednisolone 26 Based on these results, all patients in the OVA and l% CMC administration groups and the OVA and prednisolone (2 mg / kg) administration groups died from anaphylactic shock between 20 minutes and 2 hours after induction. On the other hand, in the untreated control group, the group to which OVA and leflunomide (2 1 ⁇ ), the group to which OVA and compounds BE (10 mg / kg) were administered, no anaphylactic shock was observed, and all cases survived.
- Serum IgE levels were measured using a homemade sandwich-type ELISA system. Table 2 shows the results. Two
- Sensitization Additive compound dose (mg / kg) Number of subjects Soil before challenge SD after challenge SD
- OVA 1% CMC-5 0.3 ⁇ 0.1 29.1 ⁇ 9.2
- OVA Leflunomide 2 6 0.2 ⁇ 0.1 0.1 ⁇ 0.1
- OVA Compound A 10 3 0.2 ⁇ 0.1 0.1 ⁇ 0.0
- Compound B 10 6 0.4 ⁇ 0.1 1.3 ⁇ 1.8
- OVA Compound C 10 6 0.3 ⁇ 0.2 0.1 ⁇ 0.0
- Compound D 10 6 0.4 ⁇ 0.2 0.6 ⁇ 0.5
- Compound E 10 5 0.3 ⁇ 0.1 0.1 ⁇ 0.0
- Prednisolone 2 6 0.6 ⁇ 0.4 23.6 ⁇ 9.8
- the drug was suspended using 1% carboxymethylcellulose (CMC), and repeated oral administration was performed once, and once to 9 times.
- the doses for leflunomide were 0.5, 1 and SragZkg.
- Body weight was measured once a week in the morning for all cases in each group, and drug administration was performed based on this body weight.
- a 1% CMC solution was administered to the solvent control group.
- An untreated control group was set up, and no treatment was performed for this group.
- the experiment was performed using 6 rats in each group. Table 4 shows the results.
- the serum IgE levels were 491.5 // g / ml for OVA and 1% CMC, and 491.5 // g / ml for OVA and refflunomide (O mgZkg), respectively. 7 / igZml and the untreated control group reached extremely high levels compared to 6 / igZml. In those groups, the serum IgE levels of the OVA and leflunomide (IragZkg) and the OVA and leflunomide (2 mgZkg) administration groups were conversely reduced to 0.8 ml and 0, respectively. These results indicated that leflunomide completely suppressed the increase in serum IgE levels after antigen sensitization at a dose of 1 mgZkg.
- Formulation Leflunomide powder passed through a 60-mesh screen, lactose passed through a 50-mesh screen, and corn starch passed through a 120-mesh screen. Mix with a mold mixer to make a powder.
- Manufacturing method Compound B powder passed through a 60-mesh screen, lactose passed through a 50-mesh screen, and corn starch passed through a 120-mesh screen were mixed in a V-type mixer, and then an aqueous solution of hydroxypropyl cellulose was used. After mixing with a twin-screw kneader and granulating with an extrusion granulator, drying at 60 ° C, sizing with an oscillator, and passing through 12 mesh and not passing through 60 mesh are made into granules.
- the anilide compound (I) of the present invention is useful as an agent for preventing and treating type I allergic diseases.
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Description
Claims
Priority Applications (12)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU36186/95A AU695907B2 (en) | 1994-10-17 | 1995-10-04 | Pharmaceutical composition for prophylaxis and treatment of type I allergic diseases |
AT95933609T ATE194912T1 (de) | 1994-10-17 | 1995-10-04 | Mittel zur vorsorge und heilung von typ i allergischen krankheiten |
US08/817,241 US5814649A (en) | 1994-10-17 | 1995-10-04 | Preventive and remedy for type 1 allergic diseases |
NZ293691A NZ293691A (en) | 1994-10-17 | 1995-10-04 | Use of a medicament containing an anilide compound for treatment of type i allergic diseases |
HU9701910A HU222888B1 (hu) | 1994-10-17 | 1995-10-04 | Anilid vegyületek alkalmazása I típusú allergiás betegségek megelőzésére és kezelésére alkalmas gyógyszerkészítmények előállítására |
CA002202904A CA2202904C (en) | 1994-10-17 | 1995-10-04 | Pharmaceutical composition for prophylaxis and treatment of type i allergic diseases |
DK95933609T DK0787491T3 (da) | 1994-10-17 | 1995-10-04 | Middel til forebyggelse og behandling af allergiske sygdomme af type I |
EP95933609A EP0787491B1 (en) | 1994-10-17 | 1995-10-04 | Preventive and remedy for type i allergic diseases |
DE69518159T DE69518159T2 (de) | 1994-10-17 | 1995-10-04 | Mittel zur vorsorge und heilung von typ i allergischen krankheiten |
FI971584A FI971584A0 (fi) | 1994-10-17 | 1997-04-15 | Estävä ja hoitava aine tyypin I allergiatauteja varten |
NO19971743A NO315928B1 (no) | 1994-10-17 | 1997-04-16 | Anvendelse av en anilidforbindelse for fremstilling av et profylaktisk eller terapeutisk middel for behandling av type I allergiske sykdommer |
GR20000402101T GR3034413T3 (en) | 1994-10-17 | 2000-09-15 | Preventive and remedy for type i allergic diseases |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP25029394 | 1994-10-17 | ||
JP6/250293 | 1994-10-17 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996011682A1 true WO1996011682A1 (fr) | 1996-04-25 |
Family
ID=17205757
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1995/002027 WO1996011682A1 (fr) | 1994-10-17 | 1995-10-04 | Composition preventive et remede pour les maladies allergiques de type i |
Country Status (19)
Country | Link |
---|---|
US (1) | US5814649A (ja) |
EP (1) | EP0787491B1 (ja) |
KR (1) | KR100365064B1 (ja) |
AT (1) | ATE194912T1 (ja) |
AU (1) | AU695907B2 (ja) |
CA (1) | CA2202904C (ja) |
DE (1) | DE69518159T2 (ja) |
DK (1) | DK0787491T3 (ja) |
ES (1) | ES2148561T3 (ja) |
FI (1) | FI971584A0 (ja) |
GR (1) | GR3034413T3 (ja) |
HU (1) | HU222888B1 (ja) |
IL (1) | IL115617A (ja) |
NO (1) | NO315928B1 (ja) |
NZ (1) | NZ293691A (ja) |
PT (1) | PT787491E (ja) |
TW (1) | TW429146B (ja) |
WO (1) | WO1996011682A1 (ja) |
ZA (1) | ZA958708B (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6706703B2 (en) | 2001-06-29 | 2004-03-16 | Kowa Co., Ltd. | Bis(5-aryl-2-pyridyl) derivatives |
US6890940B2 (en) | 2001-06-29 | 2005-05-10 | Kowa Co., Ltd. | Bis(2-aryl-5-pyridyl) derivatives |
JP2009280604A (ja) * | 1997-08-08 | 2009-12-03 | Sanofi-Aventis Deutschland Gmbh | N−(4−トリフルオロメチルフェニル)−5−メチルイソオキサゾール−4−カルボキサミドの結晶形態の製造方法 |
US8283515B2 (en) | 2002-05-03 | 2012-10-09 | Sca Hygiene Products Ab | Absorbent article containing a skin conditioning agent |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2320971A1 (en) | 1998-02-19 | 1999-08-26 | Seiichi Sato | Cyclic amide compounds |
US6303652B1 (en) * | 1998-08-21 | 2001-10-16 | Hughes Institute | BTK inhibitors and methods for their identification and use |
JP2004504264A (ja) * | 2000-01-07 | 2004-02-12 | ユニバーシティ オブ シンシナティ | Th1又はth2リンパ球に制御される免疫応答の選択的活性化 |
US6849260B2 (en) | 2000-08-18 | 2005-02-01 | Amgen Inc. | Methods and compositions for treating IgE-related disease using NNT-1 inhibitors |
AU2001236361A1 (en) * | 2000-10-20 | 2002-05-06 | Parker Hughes Institute | Treatment of asthma with lfm analogues |
UA107582C2 (uk) | 2009-09-18 | 2015-01-26 | Таблетований препарат (4'-трифторметилфеніл)аміду (z)-2-ціано-гідроксибут-2-еноєвої кислоти з поліпшеною стійкістю |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH05208909A (ja) * | 1991-08-22 | 1993-08-20 | Hoechst Ag | 臓器移植における拒絶反応治療用医薬 |
EP0617959A1 (en) * | 1993-03-31 | 1994-10-05 | Hoechst Aktiengesellschaft | Pharmaceutical for the treatment of skin disorders |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2854439A1 (de) * | 1978-12-16 | 1980-07-03 | Hoechst Ag | Ein isoxazolderivat, verfahren zu seiner herstellung, diese verbindung enthaltende mittel und verwendung |
DE3534440A1 (de) * | 1985-09-27 | 1987-04-02 | Hoechst Ag | Arzneimittel gegen chronische graft-versus-host-krankheiten sowie gegen autoimmunerkrankungen, insbesondere systemischen lupus erythematodes |
GB8619432D0 (en) * | 1986-08-08 | 1986-09-17 | Lilly Industries Ltd | Pharmaceutical compounds |
DD297328A5 (de) * | 1989-08-18 | 1992-01-09 | �������@���������k���Kk�� | 5-methyl-isoxalol-4-carbonsaeureanilide und 2 hydroxyethyliden-cyanoessigsaeureanilide zur behandlung von augenerkrankungen |
US5001124A (en) * | 1990-02-02 | 1991-03-19 | Syntex (U.S.A.) Inc. | 4-isoxazolecarboxamide derivatives |
-
1995
- 1995-10-04 DK DK95933609T patent/DK0787491T3/da active
- 1995-10-04 KR KR1019970702477A patent/KR100365064B1/ko not_active IP Right Cessation
- 1995-10-04 US US08/817,241 patent/US5814649A/en not_active Expired - Fee Related
- 1995-10-04 AT AT95933609T patent/ATE194912T1/de not_active IP Right Cessation
- 1995-10-04 ES ES95933609T patent/ES2148561T3/es not_active Expired - Lifetime
- 1995-10-04 EP EP95933609A patent/EP0787491B1/en not_active Expired - Lifetime
- 1995-10-04 PT PT95933609T patent/PT787491E/pt unknown
- 1995-10-04 DE DE69518159T patent/DE69518159T2/de not_active Expired - Fee Related
- 1995-10-04 CA CA002202904A patent/CA2202904C/en not_active Expired - Fee Related
- 1995-10-04 HU HU9701910A patent/HU222888B1/hu not_active IP Right Cessation
- 1995-10-04 NZ NZ293691A patent/NZ293691A/xx unknown
- 1995-10-04 WO PCT/JP1995/002027 patent/WO1996011682A1/ja active IP Right Grant
- 1995-10-04 AU AU36186/95A patent/AU695907B2/en not_active Ceased
- 1995-10-13 IL IL11561795A patent/IL115617A/xx not_active IP Right Cessation
- 1995-10-16 ZA ZA958708A patent/ZA958708B/xx unknown
-
1996
- 1996-06-06 TW TW085106747A patent/TW429146B/zh not_active IP Right Cessation
-
1997
- 1997-04-15 FI FI971584A patent/FI971584A0/fi not_active Application Discontinuation
- 1997-04-16 NO NO19971743A patent/NO315928B1/no unknown
-
2000
- 2000-09-15 GR GR20000402101T patent/GR3034413T3/el not_active IP Right Cessation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH05208909A (ja) * | 1991-08-22 | 1993-08-20 | Hoechst Ag | 臓器移植における拒絶反応治療用医薬 |
EP0617959A1 (en) * | 1993-03-31 | 1994-10-05 | Hoechst Aktiengesellschaft | Pharmaceutical for the treatment of skin disorders |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009280604A (ja) * | 1997-08-08 | 2009-12-03 | Sanofi-Aventis Deutschland Gmbh | N−(4−トリフルオロメチルフェニル)−5−メチルイソオキサゾール−4−カルボキサミドの結晶形態の製造方法 |
US6706703B2 (en) | 2001-06-29 | 2004-03-16 | Kowa Co., Ltd. | Bis(5-aryl-2-pyridyl) derivatives |
US6890940B2 (en) | 2001-06-29 | 2005-05-10 | Kowa Co., Ltd. | Bis(2-aryl-5-pyridyl) derivatives |
US7196101B2 (en) | 2001-06-29 | 2007-03-27 | Kowa Co., Ltd | Bis(5-aryl-2-pyridyl) derivatives |
US8283515B2 (en) | 2002-05-03 | 2012-10-09 | Sca Hygiene Products Ab | Absorbent article containing a skin conditioning agent |
Also Published As
Publication number | Publication date |
---|---|
EP0787491B1 (en) | 2000-07-26 |
IL115617A0 (en) | 1996-01-19 |
CA2202904C (en) | 2006-12-19 |
FI971584A (fi) | 1997-04-15 |
AU695907B2 (en) | 1998-08-27 |
EP0787491A4 (en) | 1998-09-30 |
HUT77135A (hu) | 1998-03-02 |
PT787491E (pt) | 2000-11-30 |
NZ293691A (en) | 1999-07-29 |
KR970706811A (ko) | 1997-12-01 |
DE69518159T2 (de) | 2002-01-03 |
ES2148561T3 (es) | 2000-10-16 |
ZA958708B (en) | 1996-05-14 |
IL115617A (en) | 1999-11-30 |
EP0787491A1 (en) | 1997-08-06 |
KR100365064B1 (ko) | 2003-04-11 |
GR3034413T3 (en) | 2000-12-29 |
NO971743D0 (no) | 1997-04-16 |
FI971584A0 (fi) | 1997-04-15 |
DK0787491T3 (da) | 2000-10-16 |
TW429146B (en) | 2001-04-11 |
NO315928B1 (no) | 2003-11-17 |
US5814649A (en) | 1998-09-29 |
CA2202904A1 (en) | 1996-04-25 |
HU222888B1 (hu) | 2003-12-29 |
AU3618695A (en) | 1996-05-06 |
ATE194912T1 (de) | 2000-08-15 |
DE69518159D1 (de) | 2000-08-31 |
NO971743L (no) | 1997-04-16 |
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