AU2015349969B2 - Methods of manufacturing treprostinil and treprostinil derivative prodrugs - Google Patents

Methods of manufacturing treprostinil and treprostinil derivative prodrugs Download PDF

Info

Publication number
AU2015349969B2
AU2015349969B2 AU2015349969A AU2015349969A AU2015349969B2 AU 2015349969 B2 AU2015349969 B2 AU 2015349969B2 AU 2015349969 A AU2015349969 A AU 2015349969A AU 2015349969 A AU2015349969 A AU 2015349969A AU 2015349969 B2 AU2015349969 B2 AU 2015349969B2
Authority
AU
Australia
Prior art keywords
alkyl
linear
treprostinil
formula
branched
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.)
Active
Application number
AU2015349969A
Other languages
English (en)
Other versions
AU2015349969A1 (en
Inventor
Donna M. Konicek
Franziska LEIFER
Zhili Li
Vladimir Malinin
Walter Perkins
Adam PLAUNT
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Insmed Inc
Original Assignee
Insmed Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Insmed Inc filed Critical Insmed Inc
Publication of AU2015349969A1 publication Critical patent/AU2015349969A1/en
Application granted granted Critical
Publication of AU2015349969B2 publication Critical patent/AU2015349969B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/14—All rings being cycloaliphatic
    • C07C2602/24—All rings being cycloaliphatic the ring system containing nine carbon atoms, e.g. perhydroindane

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
AU2015349969A 2014-11-18 2015-11-18 Methods of manufacturing treprostinil and treprostinil derivative prodrugs Active AU2015349969B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462081515P 2014-11-18 2014-11-18
US62/081,515 2014-11-18
PCT/US2015/061427 WO2016081658A1 (en) 2014-11-18 2015-11-18 Methods of manufacturing treprostinil and treprostinil derivative prodrugs

Publications (2)

Publication Number Publication Date
AU2015349969A1 AU2015349969A1 (en) 2017-05-25
AU2015349969B2 true AU2015349969B2 (en) 2020-02-06

Family

ID=56014536

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2015349969A Active AU2015349969B2 (en) 2014-11-18 2015-11-18 Methods of manufacturing treprostinil and treprostinil derivative prodrugs

Country Status (7)

Country Link
US (5) US10343979B2 (https=)
EP (2) EP3221291B1 (https=)
JP (1) JP6866043B2 (https=)
AU (1) AU2015349969B2 (https=)
CA (1) CA2967385C (https=)
ES (1) ES2873873T3 (https=)
WO (1) WO2016081658A1 (https=)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3712142B1 (en) 2013-01-11 2022-07-06 Corsair Pharma, Inc. Prodrugs of treprostinil
US9505737B2 (en) 2013-01-11 2016-11-29 Corsair Pharma, Inc. Treprostinil derivative compounds and methods of using same
LT3060041T (lt) 2013-10-25 2021-03-25 Insmed Incorporated Prostaciklino junginiai
JP6866043B2 (ja) 2014-11-18 2021-04-28 インスメッド インコーポレイテッド トレプロスチニルプロドラッグおよびトレプロスチニル誘導体プロドラッグの製造方法
US9643911B2 (en) 2015-06-17 2017-05-09 Corsair Pharma, Inc. Treprostinil derivatives and compositions and uses thereof
US9394227B1 (en) 2015-06-17 2016-07-19 Corsair Pharma, Inc. Treprostinil derivatives and compositions and uses thereof
WO2017223400A1 (en) * 2016-06-24 2017-12-28 Insmed Incorporated Prostacyclin compounds and compositions for treating sarcoidosis
JP7220650B2 (ja) * 2016-09-26 2023-02-10 ユナイテッド セラピューティクス コーポレイション トレプロスチニルプロドラッグ
JP7455144B2 (ja) 2019-04-29 2024-03-25 インスメッド インコーポレイテッド トレプロスチニルプロドラッグの乾燥粉末組成物およびその使用方法
JP2022546314A (ja) 2019-08-23 2022-11-04 ユナイテッド セラピューティクス コーポレイション トレプロスチニルプロドラッグ
US10781160B1 (en) 2019-10-04 2020-09-22 Chirogate International Inc. Hexadecyl Treprostinil crystals and methods for preparation thereof
AU2021255621A1 (en) 2020-04-17 2022-10-20 United Therapeutics Corporation Treprostinil for use in the treatment of intersitial lung disease
JP7608480B2 (ja) 2020-06-09 2025-01-06 ユナイテッド セラピューティクス コーポレイション トレプロスチニルのフマリルジケトピペリジンプロドラッグ
WO2022132655A1 (en) 2020-12-14 2022-06-23 United Therapeutics Corporation Methods of treating disease with treprostinil prodrugs
AU2022229367A1 (en) 2021-03-03 2023-09-14 United Therapeutics Corporation A dry powder composition of trestinil and its prodrug thereof and further comprising comprising (e)-3,6-bis[4-(n-carbonyl-2-propenyl)amidobutyl]-2,5-diketopiperazine (fdkp)
US20230263807A1 (en) 2022-02-08 2023-08-24 United Therapeutics Corporation Treprostinil iloprost combination therapy
AU2024208919A1 (en) 2023-01-19 2025-07-17 United Therapeutics Corporation Treprostinil analogs
US20250197338A1 (en) 2023-11-09 2025-06-19 United Therapeutics Corporation Syntheses of compounds useful for producing treprostinil

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7417070B2 (en) * 2003-05-22 2008-08-26 United Therapeutics Corporation Compounds and methods for delivery of prostacyclin analogs
US20140256730A1 (en) * 2013-01-11 2014-09-11 Corsair Pharma, Inc. Treprostinil derivative compounds and methods of using same
WO2015061720A2 (en) * 2013-10-25 2015-04-30 Insmed Incorporated Prostacyclin compounds, compositions and methods of use thereof

Family Cites Families (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2947526A1 (de) 1978-11-29 1980-06-12 Ono Pharmaceutical Co Prostacyclin-analoge
US4668814A (en) 1984-03-08 1987-05-26 The Upjohn Company Interphenylene carbacyclin derivatives
JPS61289034A (ja) 1985-06-17 1986-12-19 Teijin Ltd イソカルバサイクリン類脂肪乳剤
US4837342A (en) 1986-02-28 1989-06-06 Sagami Chemical Research Center Prostacyclin analogue, and blood circulation improving agent and anti-ulcer composition containing it as active ingredient
GB8814438D0 (en) 1988-06-17 1988-07-20 Wellcome Found Compounds for use in medicine
GB9011588D0 (en) 1990-05-24 1990-07-11 Wellcome Found Prostaglandin analogues for use in medicine
US6165500A (en) 1990-08-24 2000-12-26 Idea Ag Preparation for the application of agents in mini-droplets
CA2056039A1 (en) 1991-01-22 1992-07-23 Philip L. Fuchs Carbacyclin analogs
US5190972A (en) 1992-01-27 1993-03-02 The University Of Melbourne Method of combatting cyclosporine organ toxicity with prostaglandin analogs
CA2091152C (en) 1993-03-05 2005-05-03 Kirsten Westesen Solid lipid particles, particles of bioactive agents and methods for the manfuacture and use thereof
US5576016A (en) 1993-05-18 1996-11-19 Pharmos Corporation Solid fat nanoemulsions as drug delivery vehicles
US6638621B2 (en) 2000-08-16 2003-10-28 Lyotropic Therapeutics, Inc. Coated particles, methods of making and using
US6441245B1 (en) 1997-10-24 2002-08-27 United Therapeutics Corporation Process for stereoselective synthesis of prostacyclin derivatives
EP1045695B1 (en) 1997-11-14 2004-03-24 United Therapeutics Corporation Use of 9-deoxy-2', 9-alpha-methano-3- oxa-4,5,6- trinor-3, 7-(1',3'-interphenylene) -13,14-dihydro- prostaglandin f 1? to treat peripheral vascular disease
EP1043031A4 (en) 1997-12-26 2007-05-02 Astellas Pharma Inc MEDICINAL COMPOSITIONS WITH PROLONGED RELEASE
JP2002521423A (ja) 1998-07-31 2002-07-16 コリア インスティチュート オブ サイエンス アンド テクノロージ 遺伝子又は薬物運搬体としての脂質エマルジョン及び固形脂質微粒子
US6265495B1 (en) 1998-09-22 2001-07-24 Nippon Shokubai Co., Ltd. Method for production of esterified product
US6521212B1 (en) 1999-03-18 2003-02-18 United Therapeutics Corporation Method for treating peripheral vascular disease by administering benzindene prostaglandins by inhalation
CN1354622A (zh) 1999-03-31 2002-06-19 联合治疗公司 前列腺素类化合物、组合物和治疗外周血管疾病和肺动脉高压的方法
US6242482B1 (en) 2000-06-05 2001-06-05 United Therapeutics Corporation Prostaglandin compounds and derivatives thereof, compositions containing the same and method of using the same for the treatment of congestive heart failure
US6306435B1 (en) 2000-06-26 2001-10-23 Yung Shin Pharmaceutical Industrial Co. Ltd. Oral pharmaceutical preparation embedded in an oily matrix and methods of making the same
US6991809B2 (en) 2001-06-23 2006-01-31 Lyotropic Therapeutics, Inc. Particles with improved solubilization capacity
US20030108512A1 (en) 2001-12-10 2003-06-12 Robert Shorr Modified prostaglandin compounds and analogs thereof, compositions containing the same useful for the treatment of cancer
US6803386B2 (en) 2002-01-16 2004-10-12 United Therapeutics Corporation Prostacyclin derivative containing compositions and methods of using the same for the treatment of cancer
US20040156816A1 (en) 2002-08-06 2004-08-12 David Anderson Lipid-drug complexes in reversed liquid and liquid crystalline phases
MXPA05012467A (es) 2003-05-19 2006-02-22 Baxter Int Particulas solidas que comprenden un anticonvulsivo o un inmunosupresor revestido con uno o mas modificadores de superficie.
ES2272914T3 (es) 2003-05-20 2007-05-01 Ethypharm Composicion farmaceutica oral de liberacion sostenida.
CN1917866B (zh) 2003-12-16 2010-12-15 联合治疗公司 曲前列环素或它的衍生物，或其药学上可接受的盐在制备治疗和预防缺血性损害的药物中的用途
CA2549801C (en) 2003-12-16 2012-10-16 United Therapeutics Corporation Use of treprostinil to improve kidney functions
ATE462427T1 (de) 2004-04-12 2010-04-15 United Therapeutics Corp Verwendung von treprostinil zur behandlung von neuropathischen diabetischen fussgeschwüren
GB0416328D0 (en) 2004-07-21 2004-08-25 Univ Cardiff Use of dry powder compositions for pulmonary delivery
MX2007000979A (es) 2004-07-26 2007-07-11 Cotherix Inc Tratamiento de la hipertension pulmonar por iloprost inhalado con una formulacion microparticulada.
JP4893999B2 (ja) 2004-10-22 2012-03-07 小野薬品工業株式会社 吸入用医薬組成物
WO2007070851A2 (en) 2005-12-15 2007-06-21 Acusphere, Inc. Processes for making particle-based pharmaceutical formulations for pulmonary or nasal administration
CN101495122B (zh) 2006-05-15 2011-10-05 联合治疗公司 使用定量吸入器给予曲前列尼
US20090036465A1 (en) 2006-10-18 2009-02-05 United Therapeutics Corporation Combination therapy for pulmonary arterial hypertension
CA2678258A1 (en) 2007-02-09 2008-08-14 United Therapeutics Corporation Treprostinil treatment for interstitial lung disease and asthma
WO2008124632A1 (en) 2007-04-04 2008-10-16 Massachusetts Institute Of Technology Amphiphilic compound assisted nanoparticles for targeted delivery
CA2698721A1 (en) 2007-09-07 2009-03-12 United Therapeutics Corporation Buffer solutions having selective bactericidal activity against gram negative bacteria and methods of using same
KR20160048222A (ko) 2007-12-17 2016-05-03 유나이티드 세러퓨틱스 코오포레이션 레모둘린?의 활성 성분인 트레프로스티닐의 개선된 제조 방법
US8350079B2 (en) 2008-05-08 2013-01-08 United Therapeutics Corporation Treprostinil formulation
WO2009152160A1 (en) 2008-06-10 2009-12-17 Gilead Sciences, Inc. Inhaled carbaprostacyclin and prostacyclin prodrugs for the treatment of pulmonary arterial hypertension
US20110294815A1 (en) 2008-06-27 2011-12-01 Harbeson Scott L Prostacyclin analogs
WO2010039531A1 (en) 2008-09-23 2010-04-08 Resolvyx Pharmaceuticals, Inc. Therapeutic compounds
KR20110081204A (ko) 2008-09-25 2011-07-13 아라다임 코포레이션 트레프로스티닐의 폐 심부 전달
CA2749352A1 (en) 2009-02-20 2010-09-10 Micro Labs Limited Storage stable prostaglandin product
JP5649645B2 (ja) 2009-05-07 2015-01-07 ユナイテッド セラピューティクス コーポレイション プロスタサイクリンアナログの固形製剤
JP6087147B2 (ja) 2009-06-22 2017-03-01 ジョンソン、マッセイ、パブリック、リミテッド、カンパニーＪｏｈｎｓｏｎ Ｍａｔｔｈｅｙ Ｐｕｂｌｉｃ Ｌｉｍｉｔｅｄ Ｃｏｍｐａｎｙ プロスタグランジンの精製方法
US20120270934A1 (en) 2009-07-03 2012-10-25 Concert Pharmaceuticals, Inc. Prostacyclin derivatives
RS53234B (sr) 2009-08-07 2014-08-29 Scipharm Sàrl Kompozicija za lečenje cistične fibroze
BR112012003834A2 (pt) 2009-08-21 2017-08-08 Targeted Delivery Tech Limited métodos para tratamento de distúrbios e para tratamentos de deficiências em ácidos graxos, hipertrigliceridemia ou hipercolesterolemia e pacote
CN101669904B (zh) 2009-09-29 2011-06-22 北京中海康医药科技发展有限公司 一种依前列醇脂质纳米粒及制备方法
WO2011089215A1 (en) 2010-01-22 2011-07-28 Ascendis Pharma As Dipeptide-based prodrug linkers for aromatic amine-containing drugs
EP2525830B1 (en) 2010-01-22 2016-05-11 Ascendis Pharma A/S Dipeptide-based prodrug linkers for aliphatic amine-containing drugs
EP3108888B1 (en) 2010-03-15 2020-02-12 United Therapeutics Corporation Treatment for pulmonary hypertension
WO2011153363A1 (en) 2010-06-03 2011-12-08 United Therapeutics Corporation Treprostinil production
WO2011159693A2 (en) 2010-06-15 2011-12-22 United Therapeutics Corporation Oral treatment of digital ischemic lesions
WO2012006273A1 (en) 2010-07-09 2012-01-12 United Therapeutics Corporation Combination therapies with cox-2 inhibitors and treprostinil
CA2710726C (en) 2010-07-22 2016-02-23 Alphora Research Inc. Synthesis of treprostinil and intermediates useful therein
WO2012107364A1 (en) 2011-02-07 2012-08-16 Scipharm Sàrl Novel composition for the treatment of cystic fibrosis
JP5780775B2 (ja) 2011-02-18 2015-09-16 株式会社Ｌｔｔバイオファーマ プロスタグランジンｉ２誘導体を含有するナノ粒子
EP2681204B1 (en) 2011-03-02 2016-04-27 United Therapeutics Corporation Synthesis of intermediate for treprostinil production
CN103561725B (zh) 2011-03-14 2018-08-31 国立大学法人北海道大学 用于肺递送的载体、导入剂及用途
WO2013024047A1 (en) 2011-08-12 2013-02-21 Ascendis Pharma A/S High-loading water-soluble carrier-linked prodrugs
HK1198913A1 (en) 2011-08-12 2015-06-19 Ascendis Pharma A/S Carrier-linked prodrugs having reversible carboxylic ester linkages
HK1198358A1 (en) 2011-08-12 2015-04-10 Ascendis Pharma A/S Sustained release composition of prostacyclin
AU2012296951B2 (en) 2011-08-12 2016-09-15 Ascendis Pharma A/S Protein carrier-linked prodrugs
AU2012296950B2 (en) 2011-08-12 2016-09-22 Ascendis Pharma A/S Polymeric hyperbranched carrier-linked prodrugs
MX349950B (es) 2011-08-12 2017-08-22 Ascendis Pharma As Profarmacos de treprostinil enlazados a un portador.
US8524939B2 (en) 2011-08-24 2013-09-03 Chirogate International Inc. Intermediates for the synthesis of benzindene prostaglandins and preparations thereof
US9387214B2 (en) 2012-01-13 2016-07-12 United Therapeutics Corporation Method of identifying therapies for pulmonary hypertension
PL2674413T3 (pl) 2012-06-15 2018-05-30 Scipharm Sàrl Sposób wytwarzania treprostynilu i jego pochodnych
ES2869701T3 (es) 2012-08-01 2021-10-25 United Therapeutics Corp Tratamiento de hipertensión arterial pulmonar con células progenitoras endoteliales tratadas con prostaciclina
CA2880808C (en) 2012-08-01 2023-01-24 United Therapeutics Corporation Treatment of pulmonary arterial hypertension with mesenchymal stem cells
AU2013351934B2 (en) 2012-11-30 2018-03-29 Insmed Incorporated Prostacylin compositions and methods for using the same
JP6431850B2 (ja) 2013-01-09 2018-11-28 ユナイテッド セラピューティクス コーポレイション プロスタサイクリンおよび間葉系幹細胞による脈管障害の処置
US9505737B2 (en) 2013-01-11 2016-11-29 Corsair Pharma, Inc. Treprostinil derivative compounds and methods of using same
EP2970091A4 (en) 2013-03-14 2017-02-08 United Therapeutics Corporation Solid forms of treprostinil
US20140275616A1 (en) 2013-03-15 2014-09-18 United Therapeutics Corporation Salts of treprostinil
EP2978313B1 (en) 2013-03-25 2018-02-21 United Therapeutics Corporation Process of making prostacyclin compounds with linker thiol and pegylated forms
CN105407883A (zh) 2013-04-30 2016-03-16 联合治疗学有限公司 控释药物制剂
WO2014203278A2 (en) 2013-06-19 2014-12-24 Msn Laboratories Private Limited NOVEL PROCESS FOR THE PREPARATION OF (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-HEXAHYDRO-2-HYDROXY-1-[(3S)-3-HYDROXYOCTYL]-1H-BENZ[f]INDEN-5-YL]OXY]ACETIC ACID
US9925184B2 (en) 2013-10-11 2018-03-27 Pulmokine, Inc. Spray-dry formulations
WO2015138423A1 (en) 2014-03-11 2015-09-17 Insmed Incorporated Prostacylin compositions and methods for using the same
CN106573066A (zh) 2014-06-13 2017-04-19 联合治疗学有限公司 曲前列环素制剂
ES2778274T3 (es) 2014-10-20 2020-08-10 United Therapeutics Corp Síntesis de productos intermedios para producir derivados de prostaciclina
JP6866043B2 (ja) 2014-11-18 2021-04-28 インスメッド インコーポレイテッド トレプロスチニルプロドラッグおよびトレプロスチニル誘導体プロドラッグの製造方法
WO2016176555A1 (en) 2015-04-29 2016-11-03 Insmed Incorporated Prostacyclin compounds, compositions and methods of use thereof
US10898494B2 (en) 2016-05-05 2021-01-26 Liquidia Technologies, Inc. Dry powder treprostinil for the treatment of pulmonary hypertension
WO2017223400A1 (en) 2016-06-24 2017-12-28 Insmed Incorporated Prostacyclin compounds and compositions for treating sarcoidosis
JP7220650B2 (ja) 2016-09-26 2023-02-10 ユナイテッド セラピューティクス コーポレイション トレプロスチニルプロドラッグ
EP3673895A1 (en) 2018-12-28 2020-07-01 Université Libre de Bruxelles Dry powder inhalation formulation and its use for the therapeutic treatment of lungs
JP7455144B2 (ja) 2019-04-29 2024-03-25 インスメッド インコーポレイテッド トレプロスチニルプロドラッグの乾燥粉末組成物およびその使用方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7417070B2 (en) * 2003-05-22 2008-08-26 United Therapeutics Corporation Compounds and methods for delivery of prostacyclin analogs
US20140256730A1 (en) * 2013-01-11 2014-09-11 Corsair Pharma, Inc. Treprostinil derivative compounds and methods of using same
WO2015061720A2 (en) * 2013-10-25 2015-04-30 Insmed Incorporated Prostacyclin compounds, compositions and methods of use thereof

Also Published As

Publication number Publication date
JP2017535555A (ja) 2017-11-30
ES2873873T3 (es) 2021-11-04
JP6866043B2 (ja) 2021-04-28
US20230250051A1 (en) 2023-08-10
US20220135513A1 (en) 2022-05-05
CA2967385C (en) 2023-05-16
HK1244783A1 (en) 2018-08-17
EP3221291A4 (en) 2018-06-27
US11148997B2 (en) 2021-10-19
AU2015349969A1 (en) 2017-05-25
US20170320813A1 (en) 2017-11-09
EP3221291A1 (en) 2017-09-27
US10343979B2 (en) 2019-07-09
EP3221291B1 (en) 2021-03-31
CA2967385A1 (en) 2016-05-26
US20250162982A1 (en) 2025-05-22
US20190337888A1 (en) 2019-11-07
EP3904326A1 (en) 2021-11-03
WO2016081658A1 (en) 2016-05-26

Similar Documents

Publication Publication Date Title
AU2015349969B2 (en) Methods of manufacturing treprostinil and treprostinil derivative prodrugs
RU2604193C2 (ru) Новое соединение с эффектами тромболизиса, акцептирования свободных радикалов и направленного действия на тромб, а также способ его получения и применение
AU2021408119B2 (en) Fibroblast activation protein inhibitor
JPH06501950A (ja) 環状ペプチド、その調製法およびその薬理組成物としての使用
EA016804B1 (ru) Циклические конструкты натрийуретических пептидов
JPH05500061A (ja) 甲状腺刺激ホルモン放出ホルモンのプロドラッグ誘導体
AU2014310619B2 (en) Peptide-oligourea chimeric compounds and methods of their use
CA3216095A1 (en) Preparation and application of polypeptide
EP2036918A1 (en) Peptide derivative
HK1244783B (en) Methods of manufacturing treprostinil and treprostinil derivative prodrugs
JP6140187B2 (ja) 心筋灌流イマジニング用造影剤
WO2024155552A1 (en) Formulations of lipidated peptide inhibitors of interleukin-23 receptor
JP6894498B2 (ja) 軟組織硬化用組成物
JPH03236397A (ja) 新規ペプチド誘導体
JPH05105627A (ja) 腸機能性疾患の治療に用いられる新規な医薬組成物と、その調整方法と、治療用医薬の調製方法
JP7458984B2 (ja) テトラヒドロイソキノリン系誘導体、その製造方法及び用途
JPH07509441A (ja) Ｎ−（メルカプトアシル）アミノ酸と、その製造方法と、その治療での使用と、それを含む医薬組成物
TWI389899B (zh) 具口服活性之凝血酶抑制劑
JP2021066690A (ja) オピオイドペプチド誘導体及びこれを含む医薬組成物
HK40031655A (en) Tetrahydroisoquinoline derivative, preparation method therefor and uses thereof
HK40031655B (zh) 四氢异喹啉类衍生物及其制备方法和用途

Legal Events

Date Code Title Description
FGA Letters patent sealed or granted (standard patent)