JP4318921B2 - 移植片の機能発現遅延の処置のための医薬の製造のためのリンパ球ホーミング促進剤の使用 - Google Patents
移植片の機能発現遅延の処置のための医薬の製造のためのリンパ球ホーミング促進剤の使用 Download PDFInfo
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- JP4318921B2 JP4318921B2 JP2002567283A JP2002567283A JP4318921B2 JP 4318921 B2 JP4318921 B2 JP 4318921B2 JP 2002567283 A JP2002567283 A JP 2002567283A JP 2002567283 A JP2002567283 A JP 2002567283A JP 4318921 B2 JP4318921 B2 JP 4318921B2
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- pharmaceutically acceptable
- amino
- rapamycin
- agent
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- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
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- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
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Classifications
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- 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
- A61K31/133—Amines having hydroxy groups, e.g. sphingosine
-
- 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
- A61K31/131—Amines acyclic
-
- 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
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Description
R1は、所望により置換されていてもよいフェニレンにより所望により割り込まれていてもよい12〜22個の炭素原子を有する所望により置換されていてもよい直鎖−または分枝鎖の炭素鎖であり、そして
各R2、R3、R4およびR5は、独立して、Hまたは低級アルキルである。〕
で示される2−アミノプロパン−1,3−ジオール化合物である。
式Iの化合物が分子内に1またはそれ以上の不斉中心を有する場合、本発明は、種々の光学異性体、ならびにラセミ体、立体異性体およびその混合物を包含すると理解されるべきである。
1.1. 器官または組織移植のレシピエントにおいて、該レシピエントに治療上有効量のALH剤、例えば遊離の形態または薬学的に許容される塩の形態の「化合物A」を投与することを含む、DGFを低下させる方法;
1.2. 器官または組織移植のレシピエントにおいて、該レシピエントに治療上有効量のALH剤、例えば遊離の形態または薬学的に許容される塩の形態の「化合物A」を投与することを含む、移植器官または組織の機能の回復を改善する方法、
が提供される。
1.3 腎移植のレシピエントにおいて移植された腎臓の糸球体濾過率を改善する方法であって、該レシピエントに治療上有効量のALH剤、例えば、遊離の形態または薬学的に許容される塩の形態の「化合物A」を投与することを含む方法。
1.4 上で定義した方法であって、治療上有効量のALH剤、例えば、遊離の形態または薬学的に許容される塩の形態の「化合物A」、および免疫抑制剤または免疫調節剤である第二の医薬物質を共投与することを含む方法。
1.5 上で定義した方法であって、治療上有効量のALH剤、例えば、遊離の形態または薬学的に許容される塩の形態の「化合物A」、およびカルシニューリンインヒビター以外の免疫抑制剤または免疫調節剤である第二の医薬物質を共投与することを含む方法。
3. 前記1.1から1.5で定義された任意の方法において使用するための医薬組成物の製造における使用のための、ALH剤、例えば遊離の形態または薬学的に許容される塩の形態の「化合物A」;あるいは
5. 例えば前記1.1から1.5で定義された任意の方法における使用のための、下記:
a) ALH剤、例えば、遊離の形態または薬学的に許容される塩の形態の「化合物A」である第一の剤、および
b) 例えば上で開示したような、免疫抑制剤または免疫調節剤である、コエージェント(co-agent)、
を含む医薬組成物。好ましくは該コエージェント b)は、カルシニューリンインヒビター以外の、例えば上で開示したような、免疫抑制剤または免疫調節剤である。
DAラットからの腎臓を移植前に4℃にて40時間保存し、次いで、Lewisラットに生命維持同種移植片として移植する。糸球体濾過率(GFR)をモニターすることにより、移植後1週間にわたって、DGFを評価する。レシピエントは、単独または、例えば40−O−(2−ヒドロキシエチル)−ラパマイシン、またはカルシニューリンインヒビター、例えばミクロエマルジョン中のシクロスポリンAとの組合せのどちらかで、試験されるALH剤で処置される。対照群において、シクロスポリンAを5mg/kg/日(該投与量は少なくとも80日間の移植片生着を上昇させる。)にて投与する。本アッセイにおいて、単独で、またはカルシニューリンインヒビターもしくは大環状ラクトンと組み合わせて投与されるALH剤は、対照よりもDGFを改善する。
DGFのリスクが増加した30〜60の新規(de novo)生体腎移植レシピエントを、1年間の非盲検研究に包含させる。移植前の24時間以内にベースライン評価を行う。中心腎同種移植片生検を、0日(Day 0)における移植および血行再建の前に行い、必要とされるその後の生検の評価のためのベースライン比較として提供する。(移植前の)ベースラインおよび本試験への参加のための登録の直前時に、個々の患者は包含基準を満たし、かつ、排除基準を満たしてはならない。
Claims (5)
- 式Iで示される化合物が2−アミノ−2−[2−(4−オクチルフェニル)エチル]プロパン−1,3−ジオールである、請求項1記載の薬物。
- 請求項1または2記載の薬物と1種以上の薬学的に許容される希釈剤または担体を含む、器官または組織移植のレシピエントにおける移植片の機能発現遅延の低下または移植された器官もしくは組織の機能回復に、あるいは腎移植のレシピエントにおける移植された腎臓の糸球体濾過率の改善に使用するための医薬組成物。
- 免疫抑制剤または免疫調節剤である共作用剤(coagent)と同時的に又は個別的に組み合わせて使用するための請求項3記載の医薬組成物。
- 共作用剤が40−O−(2−ヒドロキシエチル)−ラパマイシンである、請求項4記載の組成物。
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GB0104438A GB0104438D0 (en) | 2001-02-22 | 2001-02-22 | Organic compounds |
GB0105000A GB0105000D0 (en) | 2001-02-28 | 2001-02-28 | Organic compounds |
PCT/EP2002/001860 WO2002067915A1 (en) | 2001-02-22 | 2002-02-21 | Use of accelerated lymphocyte homing agents for the manufacture of a medicament for the treatment of delayed graft function |
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JP2004527490A JP2004527490A (ja) | 2004-09-09 |
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US (2) | US20040087662A1 (ja) |
EP (1) | EP1368015B1 (ja) |
JP (1) | JP4318921B2 (ja) |
CN (1) | CN100479814C (ja) |
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BR (1) | BR0207434A (ja) |
CA (1) | CA2435739A1 (ja) |
DE (1) | DE60213766T2 (ja) |
ES (1) | ES2267993T3 (ja) |
HK (1) | HK1060855A1 (ja) |
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NZ529044A (en) * | 2001-06-08 | 2008-03-28 | Novartis Ag | Treatment or prophylaxis of insulin-producing cell graft rejection |
PT1471054E (pt) | 2002-01-11 | 2009-09-23 | Daiichi Sankyo Co Ltd | Derivado de aminoálcool ou derivado de ácido fosfónico e composição medicinal que os contém |
KR20110136901A (ko) | 2004-02-24 | 2011-12-21 | 상꾜 가부시키가이샤 | 아미노 알코올 화합물 |
JP4917433B2 (ja) * | 2004-07-16 | 2012-04-18 | 杏林製薬株式会社 | 効果的な医薬の使用法及び副作用発現の防御に関する方法 |
PT2511262T (pt) * | 2004-10-12 | 2017-03-30 | Kyorin Seiyaku Kk | Processo para a produção de cloridrato de 2-amino-2-[2-[4-(3- benziloxi-feniltio)-2-clorofenil[etil]-1,3-propanodiol |
EP1932522B1 (en) * | 2005-10-07 | 2012-05-23 | Kyorin Pharmaceutical Co., Ltd. | Therapeutic agent for liver disease containing 2-amino-1,3-propanediol derivative as active ingredient |
TWI389683B (zh) * | 2006-02-06 | 2013-03-21 | Kyorin Seiyaku Kk | A therapeutic agent for an inflammatory bowel disease or an inflammatory bowel disease treatment using a 2-amino-1,3-propanediol derivative as an active ingredient |
RS53080B (en) * | 2006-08-08 | 2014-06-30 | Kyorin Pharmaceutical Co. Ltd. | AMINOPHOSPHORIC ACID ETHAR DERIVATIVE AND S1P RECEPTOR MODULATOR CONTAINING THE SAME AS THE ACTIVE INGREDIENT |
WO2008018447A1 (fr) * | 2006-08-08 | 2008-02-14 | Kyorin Pharmaceutical Co., Ltd. | Dérivé d'aminoalcool et immunodépresseur le contenant en tant que principe actif |
TW200946105A (en) | 2008-02-07 | 2009-11-16 | Kyorin Seiyaku Kk | Therapeutic agent or preventive agent for inflammatory bowel disease containing amino alcohol derivative as active ingredient |
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HU224814B1 (en) * | 1995-12-28 | 2006-02-28 | Mitsubishi Pharma Corp | Use of propane-1,3-diol derivative for the preparation of a medicament useful for the topical treating of inflammatory and immune diseases |
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NZ529044A (en) * | 2001-06-08 | 2008-03-28 | Novartis Ag | Treatment or prophylaxis of insulin-producing cell graft rejection |
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HK1060855A1 (en) | 2004-08-27 |
WO2002067915A1 (en) | 2002-09-06 |
DE60213766T2 (de) | 2007-08-02 |
ES2267993T3 (es) | 2007-03-16 |
BR0207434A (pt) | 2004-07-06 |
EP1368015A1 (en) | 2003-12-10 |
DE60213766D1 (de) | 2006-09-21 |
JP2004527490A (ja) | 2004-09-09 |
ATE335475T1 (de) | 2006-09-15 |
EP1368015B1 (en) | 2006-08-09 |
CN1492757A (zh) | 2004-04-28 |
US20080015261A1 (en) | 2008-01-17 |
CA2435739A1 (en) | 2002-09-06 |
CN100479814C (zh) | 2009-04-22 |
US20040087662A1 (en) | 2004-05-06 |
PT1368015E (pt) | 2006-12-29 |
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