WO1998037895A1 - Medicaments permettant d'ameliorer la circulation pulmonaire - Google Patents
Medicaments permettant d'ameliorer la circulation pulmonaire Download PDFInfo
- Publication number
- WO1998037895A1 WO1998037895A1 PCT/JP1998/000801 JP9800801W WO9837895A1 WO 1998037895 A1 WO1998037895 A1 WO 1998037895A1 JP 9800801 W JP9800801 W JP 9800801W WO 9837895 A1 WO9837895 A1 WO 9837895A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- carbon atoms
- alkyl
- phenyl
- carbons
- hydrogen
- Prior art date
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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
-
- 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/558—Eicosanoids, e.g. leukotrienes or prostaglandins having heterocyclic rings containing oxygen as the only ring hetero atom, e.g. thromboxanes
- A61K31/5585—Eicosanoids, e.g. leukotrienes or prostaglandins having heterocyclic rings containing oxygen as the only ring hetero atom, e.g. thromboxanes having five-membered rings containing oxygen as the only ring hetero atom, e.g. prostacyclin
Definitions
- the present invention relates to a pulmonary circulation improving agent comprising a prostaglandin I derivative or a salt thereof as an active ingredient and a method for improving pulmonary circulation using the same.
- Vasodilators have different vascular selectivities depending on their types. For example, it is known that Ca antagonists such as difendipine and nitrates such as nitroglycerin have high selectivity for coronary vessels. However, it has been reported that conventional vasodilators have low selectivity for pulmonary blood vessels, and when used for treatment of pulmonary hypertension, for example, cause side effects due to a decrease in systemic blood pressure.
- PGI Prossue Cyclin
- aprost As other compounds having increased stability of prostaglandin I, aprost, iloprost, clinprost, cyprosten, naxaprosten, yuprosten, cicaprost, pimilprost, CH-169 and CS570 are known. [Hyundai Medical Company
- vasodilators have low selectivity for pulmonary vessels, Attempts to treat increased patients have been reported to cause side effects such as headache, vomiting, reflex tachycardia, and worsening right heart failure due to lower systemic blood pressure.
- An object of the present invention is to provide a pulmonary circulation improving agent and a method for improving pulmonary circulation having reduced side effects and excellent efficacy and practicality. Disclosure of the invention
- the present invention relates to a pulmonary circulation improving agent comprising a prostaglandin I derivative, particularly a prostaglandin I 2 derivative as an active ingredient, and a pulmonary circulation improving method using the same.
- FIG. 1 shows the results of changes in the pulmonary artery pressure / systemic blood pressure ratio in Example 1.
- FIG. 2 shows the results of changes in the pulmonary vascular resistance Z-body vascular resistance ratio in Example 1.
- the prostaglandin I derivative of the present invention includes a prostaglandin I derivative
- prostaglandin I 2 derivative any of a prostaglandin I 2 derivative, a prostaglandin I 3 derivative or a salt thereof may be used, but a prostaglandin I 2 derivative or a salt thereof is preferably used. More preferably, the following general formula (I)
- Z is a valence bond or C ( a linear or branched alkylene represented by H 2 T)
- t is an integer of 1 to 6
- R 3 is a cycloalkyl having 3 to 12 carbon atoms. or a has been 3-1 2 substituted cycloalkyl carbon atoms substituted 1 with 1-3 R 4
- R 4 is hydrogen or alkyl having a carbon number of 1 to 5
- n is an integer from 1 to 5
- R 5 is hydrogen or benzoyl
- R 6 is phenyl, p-promophenyl, p-chlorophenyl, p-biphenyl, p-nitrophenyl, P-benzamidophenyl, 2-naphthyl,
- R 8 is alkyl or acyl having 1 to 30 carbon atoms
- R 9 is hydrogen, linear alkyl having 1 to 12 carbons, branched alkyl having 3 to 12 carbons, cycloalkyl having 3 to 12 carbons, alkylalkylene having 4 to 13 carbons, phenyl, substitution Phenyl (where the substituent is the same as in (A) 5) above), represents aralkyl having 7 to 12 carbon atoms or 1 S0 2 R '°, and R 1Q is alkyl having 1 to 10 carbon atoms and 3 carbon atoms.
- n is an integer from 1 to 3
- Y is hydrogen, alkyl having 1 to 4 carbon atoms, chlorine, bromine, fluorine, formyl, methoxy or nitro,
- R 1 ′ is hydrogen or alkyl having 1 to 4 carbons
- R 13 is hydrogen —, acyl having 1 to 14 carbons, aroyl having 6 to 15 carbons, tetrahydropyranyl, tetrahydrofuranyl, 1-etoxyshetyl or t-butyl, and X is
- R 12 is
- Ar 2 is phenyl, ⁇ -naphthyl, ⁇ -naphthyl, or at least one of chlorine, bromine, fluorine, iodine, trifluoromethyl, alkyl having 1 to 4 carbon atoms, nitro, cyano, Represents methoxy, phenyl or phenyl substituted phenyl, or
- C t H 2t is the same as defined above, and R 14 is straight-chain alkyl having 1 to 6 carbons, branched alkyl having 3 to 6 carbons, phenyl, at least one chlorine, bromine, fluorine, iodine, and trifur. Substituted with 1 to 4 carbon atoms, alkyl having 1 to 4 carbon atoms, nitro, cyano, methoxy, phenyl or phenoxy-substituted phenyl, cyclopentyl, cyclohexyl, or linear alkyl having 1 to 4 carbon atoms Represents pentyl or cyclohexyl, or
- C t H 2 t is the same as defined above, R 15 , R ' s represents hydrogen, methyl, ethyl, propyl, or butyl; or 6) — C u H 2u — C3 C— R ' 7
- C u H 2U represents a straight or branched alkylene emissions
- R 17 represents a straight chain alkyl of 1 to 6 carbon atoms
- E is hydrogen or -OR 13
- R 18 represents an acyl having 1 to 12 carbons, an aroyl having 7 to 15 carbons or R 2 (where R 2 is the same as defined above);
- a 4,8-inter-m-phenylene prostaglandin I 2 derivative represented by or a pharmacologically acceptable salt thereof is used.
- prostaglandin I derivatives of the present invention include beraprost represented by the following (I) or a salt thereof,
- the prostaglandin I derivative of the present invention can be produced by a known method.
- the compound represented by the general formula (I) or a salt thereof is described in Japanese Patent Publication No. 1-53672. It can be manufactured by a method.
- the pulmonary circulation improving agent of the present invention has a pulmonary vascular selective dilating action and is effective as a therapeutic agent for diseases that cause an increase in pulmonary vascular resistance. It is also effective in increasing pulmonary vascular resistance that occurs after surgery. Furthermore, it selectively reduces pulmonary vascular resistance, which is an afterload in the right heart, and is therefore effective as a therapeutic agent for right heart failure.
- diseases that cause an increase in pulmonary vascular resistance include congenital heart diseases such as Eisenmenger syndrome, diseases that cause hypoxemia such as adult respiratory distress syndrome (ARDS), and pulmonary fibrosis.
- ARDS adult respiratory distress syndrome
- pulmonary fibrosis Associated diseases, thrombotic diseases in pulmonary vessels such as pulmonary embolism, primary pulmonary hypertension, and diseases causing pulmonary hypertension such as pulmonary hypertension associated with collagen disease.
- the present invention also provides a method for improving pulmonary circulation, which comprises administering a drug containing the above-mentioned prostaglandin I derivative as an active ingredient to a patient with increased pulmonary vascular resistance.
- the prostaglandin I derivative is administered to adults from 0.01 to: L0O mg / person 1 to 3 times a day.
- one or several prostaglandin I derivatives may be used as they are, or they may be orally administered in the form of a solid containing the following additives.
- additives include excipients such as starches, lactose, sucrose, glucose, mannitol, calcium carbonate, calcium sulfate, and the like: binders, such as starches, dextrin, gum arabic, tragacanth, methylcellulose, gelatin, Polyvinylpyrrolidone, polyvinyl alcohol, etc .: disintegrators, for example, powders, polyvinylpyrrolidone, crystalline cellulose, etc., lubricants, for example, magnesium stearate, talc, etc .: coloring agents, fragrances and the like.
- excipients such as starches, lactose, sucrose, glucose, mannitol, calcium carbonate, calcium sulfate, and the like
- binders such as starches, dextrin, gum arabic, tragacanth, methylcellulose, gelatin, Polyvinylpyrrolidone, polyvinyl alcohol, etc .
- disintegrators for example, powder
- the prostaglandin I derivative used in the present invention can be used in various dosage forms.Specifically, conventionally used dosage forms such as tablets, dragees, powders, granules, troches, capsules, pills, and syrups are used. No.
- pulmonary circulation improving agent of the present invention can be applied to a wide range of parenteral administration methods such as various injections and suppositories, in addition to the oral preparations described above.
- the pulmonary arterial pressure was increased by continuous infusion of the thromboxane agonist U-46619 at a dose of 0.3 g / kg / min into anesthetized dogs.
- Beraprost sodium 100, 300 ng / kg / min
- prostaglandin E [(0.3, 1 g / kg / min), nitroglycerin (3, 10 g / kg / min), which give almost the same blood pressure reduction )
- And difendipine (0.3, 1 g / kg / min) was continuously administered intravenously to investigate reductions in pulmonary artery pressure and systemic blood pressure, as well as pulmonary vascular resistance and body vascular resistance.
- FIG. 1 shows the change in the pulmonary artery pressure / systemic blood pressure ratio
- FIG. 2 shows the change in the pulmonary vascular resistance / body resistance ratio
- BPS represents beraprost sodium
- PGE prostaglandin
- GTN represents nitroglycerin
- NIF represents difuedipine.
- the ratio of each vertical axis is 1 before drug administration.
- *, ** are p ⁇ 0.05, 0.01 vs. comparison before drug administration (paired t-test).
- the pulmonary circulation improving agent of the present invention has a pulmonary vascular selective dilating action, and provides a pulmonary circulation improving agent having excellent efficacy and practicality.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98905676A EP0925787A4 (en) | 1997-02-27 | 1998-02-26 | DRUGS TO IMPROVE PULMONARY CIRCULATION |
KR1019980708584A KR20000065039A (ko) | 1997-02-27 | 1998-02-26 | 폐순환 개선제 |
AU61173/98A AU6117398A (en) | 1997-02-27 | 1998-02-26 | Drugs for ameliorating pulmonary circulation |
CA002253717A CA2253717A1 (en) | 1997-02-27 | 1998-02-26 | Drugs for ameliorating pulmonary circulation |
CN199898800548A CN1224354A (zh) | 1997-02-27 | 1998-02-26 | 肺循环改善剂 |
NO984974A NO984974L (no) | 1997-02-27 | 1998-10-26 | Middel som forbedrer pulmonar sirkulasjon |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP9/44363 | 1997-02-27 | ||
JP4436397 | 1997-02-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998037895A1 true WO1998037895A1 (fr) | 1998-09-03 |
Family
ID=12689438
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1998/000801 WO1998037895A1 (fr) | 1997-02-27 | 1998-02-26 | Medicaments permettant d'ameliorer la circulation pulmonaire |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP0925787A4 (ja) |
KR (1) | KR20000065039A (ja) |
CN (1) | CN1224354A (ja) |
AU (1) | AU6117398A (ja) |
CA (1) | CA2253717A1 (ja) |
NO (1) | NO984974L (ja) |
WO (1) | WO1998037895A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013147518A (ja) * | 2006-11-16 | 2013-08-01 | Gemmus Pharma Inc | A型インフルエンザウィルス感染の治療のための薬剤としてのep2およびep4作動薬 |
JP2021054725A (ja) * | 2019-09-27 | 2021-04-08 | 学校法人日本医科大学 | イヌ肺高血圧症治療薬 |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4834224B2 (ja) | 1999-03-05 | 2011-12-14 | デューク ユニバーシティ | C16不飽和fp−選択的プロスタグランジン類縁体 |
US6894175B1 (en) | 1999-08-04 | 2005-05-17 | The Procter & Gamble Company | 2-Decarboxy-2-phosphinico prostaglandin derivatives and methods for their preparation and use |
US20020172693A1 (en) | 2000-03-31 | 2002-11-21 | Delong Michell Anthony | Compositions and methods for treating hair loss using non-naturally occurring prostaglandins |
US20020013294A1 (en) | 2000-03-31 | 2002-01-31 | Delong Mitchell Anthony | Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives |
US20110293549A1 (en) | 2009-02-03 | 2011-12-01 | Athena Cosmetics, Inc. | Composition, method and kit for enhancing hair |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS57206679A (en) * | 1980-10-31 | 1982-12-18 | Schering Ag | Novel prostacycline derivative, manufacture and prostacycline medicine containing same |
JPS58124778A (ja) * | 1982-01-20 | 1983-07-25 | Toray Ind Inc | 5,6,7−トリノル−4,8−インタ−m−フエニレンPGI↓2誘導体 |
JPS6036477A (ja) * | 1983-06-23 | 1985-02-25 | シエ−リング・アクチエンゲゼルシヤフト | 5−シアノプロスタシクリン,その製法及び該化合物を含有する細胞保護作用,気管支拡張作用及び胃酸分秘抑制作用を有する医薬 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5931510B2 (ja) * | 1979-09-03 | 1984-08-02 | 東レ株式会社 | 5,6,7−トリノル−4,8−インタ−m−フエニレンPGI↓2誘導体 |
JPS57144276A (en) * | 1981-03-03 | 1982-09-06 | Toray Ind Inc | 5,6,7-trinor-4,8-inter-m-phenylene pgi2 derivative |
KR0158870B1 (ko) * | 1988-06-17 | 1998-12-01 | 마틴 에이. 로쓰블랫 | 폐순환 승압의 치료, 예방 또는 진단용 조성물 |
DE4104607A1 (de) * | 1991-02-12 | 1992-08-13 | Schering Ag | Prostacyclin- und carbacyclinderivate als mittel zur behandlung von fiebrigen erkrankungen |
JP4062743B2 (ja) * | 1995-02-27 | 2008-03-19 | 東レ株式会社 | 「肺性心治療剤」 |
-
1998
- 1998-02-26 WO PCT/JP1998/000801 patent/WO1998037895A1/ja not_active Application Discontinuation
- 1998-02-26 CA CA002253717A patent/CA2253717A1/en not_active Abandoned
- 1998-02-26 CN CN199898800548A patent/CN1224354A/zh active Pending
- 1998-02-26 EP EP98905676A patent/EP0925787A4/en not_active Withdrawn
- 1998-02-26 AU AU61173/98A patent/AU6117398A/en not_active Abandoned
- 1998-02-26 KR KR1019980708584A patent/KR20000065039A/ko not_active Application Discontinuation
- 1998-10-26 NO NO984974A patent/NO984974L/no unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS57206679A (en) * | 1980-10-31 | 1982-12-18 | Schering Ag | Novel prostacycline derivative, manufacture and prostacycline medicine containing same |
JPS58124778A (ja) * | 1982-01-20 | 1983-07-25 | Toray Ind Inc | 5,6,7−トリノル−4,8−インタ−m−フエニレンPGI↓2誘導体 |
JPS6036477A (ja) * | 1983-06-23 | 1985-02-25 | シエ−リング・アクチエンゲゼルシヤフト | 5−シアノプロスタシクリン,その製法及び該化合物を含有する細胞保護作用,気管支拡張作用及び胃酸分秘抑制作用を有する医薬 |
Non-Patent Citations (2)
Title |
---|
See also references of EP0925787A4 * |
UENO Y., ET AL.: "EFFECT OF BERAPROST SODIUM, A STABLE PROSTACYCLIN ANALOGUE, ON PULMONARY THROMBOEMBOLISM IN MICE.", THROMBOSIS RESEARCH, TARRYTOWN, NY, US, vol. 77., no. 02., 1 January 1995 (1995-01-01), US, pages 193 - 198., XP002910939, ISSN: 0049-3848, DOI: 10.1016/0049-3848(95)91625-U * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013147518A (ja) * | 2006-11-16 | 2013-08-01 | Gemmus Pharma Inc | A型インフルエンザウィルス感染の治療のための薬剤としてのep2およびep4作動薬 |
US8980944B2 (en) | 2006-11-16 | 2015-03-17 | Gemmus Pharma Inc. | EP2 and EP4 agonists as agents for the treatment of influenza a viral infection |
JP2015061885A (ja) * | 2006-11-16 | 2015-04-02 | ジェンムス ファーマ インコーポレイティド | A型インフルエンザウィルス感染の治療のための薬剤としてのep2およびep4作動薬 |
JP2021054725A (ja) * | 2019-09-27 | 2021-04-08 | 学校法人日本医科大学 | イヌ肺高血圧症治療薬 |
Also Published As
Publication number | Publication date |
---|---|
KR20000065039A (ko) | 2000-11-06 |
CN1224354A (zh) | 1999-07-28 |
EP0925787A4 (en) | 1999-12-01 |
AU6117398A (en) | 1998-09-18 |
NO984974L (no) | 1998-12-23 |
CA2253717A1 (en) | 1998-09-03 |
NO984974D0 (no) | 1998-10-26 |
EP0925787A1 (en) | 1999-06-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPH0667900B2 (ja) | プロスタグランジンf類 | |
WO1998037895A1 (fr) | Medicaments permettant d'ameliorer la circulation pulmonaire | |
US5254588A (en) | Treatment of pulmonary dysfunction with 15-ketoprostaglandin compounds | |
KR0153779B1 (ko) | 15-케토-프로스타글란딘 화합물을 이용한 폐 부전증의 치료 | |
US9457032B2 (en) | Therapeutic agent for renal failure | |
JP4062743B2 (ja) | 「肺性心治療剤」 | |
EP0430551A2 (en) | Treatment of cardiac dysfunction with 15-keto-prostaglandin compounds | |
JP3743289B2 (ja) | 腎不全治療薬 | |
US5256696A (en) | Treatment of cardiac dysfunction with 15-ketoprostaglandin compounds | |
JP2608135B2 (ja) | 糖尿病性神経障害治療剤 | |
EP0410652B1 (en) | Use of 15-keto-prostanoic acid derivatives in the manufacture of a medicament for improvement of excretion of potassium ion | |
WO1998040073A1 (fr) | Medicament pour traiter les lesions vasculaires diabetiques | |
JPH11189536A (ja) | 原発性糸球体腎炎治療または予防薬 | |
US5126372A (en) | Excretion of nonprotein nitrogen into the intestine by prostanoic acid derivatives | |
EP0867185B1 (en) | Platelet function potentiator and method of curing platelet dysfunction | |
WO2000009135A1 (fr) | Agents de protection des cellules péridermiques | |
JP3023059B2 (ja) | 脳機能改善処置剤 | |
JPH03218315A (ja) | ガス交換機能不全処置剤 | |
JP2005232003A (ja) | 尿細管間質障害の治療または予防薬 | |
KR100457499B1 (ko) | 폐성심질환치료제 | |
JP2000119183A (ja) | プラスミノ―ゲンアクチベ―タ―インヒビタ―1産生抑制剤。 | |
JP2007238622A (ja) | 肺性心治療剤 | |
JP2000119184A (ja) | 周皮細胞保護剤 | |
JPH0564932B2 (ja) |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 98800548.4 Country of ref document: CN |
|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU CA CN JP KR NO US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 61173/98 Country of ref document: AU |
|
ENP | Entry into the national phase |
Ref document number: 2253717 Country of ref document: CA Ref document number: 2253717 Country of ref document: CA Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1019980708584 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 09171866 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1998905676 Country of ref document: EP |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWP | Wipo information: published in national office |
Ref document number: 1998905676 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1019980708584 Country of ref document: KR |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1998905676 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1019980708584 Country of ref document: KR |