HRP20221232T1 - L-ornitin fenil acetat i postupci njegove pripreme - Google Patents

L-ornitin fenil acetat i postupci njegove pripreme Download PDF

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Publication number
HRP20221232T1
HRP20221232T1 HRP20221232TT HRP20221232T HRP20221232T1 HR P20221232 T1 HRP20221232 T1 HR P20221232T1 HR P20221232T T HRP20221232T T HR P20221232TT HR P20221232 T HRP20221232 T HR P20221232T HR P20221232 T1 HRP20221232 T1 HR P20221232T1
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Croatia
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preparation
crystalline form
weight
composition
ppm silver
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HRP20221232TT
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English (en)
Inventor
Keith Anderson
Jim Behling
Christine Henderson Dougan
Stephen William Watt
Peter Manini
Attilia Figini
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Ocera Therapeutics, Inc.
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Publication of HRP20221232T1 publication Critical patent/HRP20221232T1/hr
Publication of HRP20221232T8 publication Critical patent/HRP20221232T8/hr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/26—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one amino group bound to the carbon skeleton, e.g. lysine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
    • C07C57/32—Phenylacetic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/38—Separation; Purification; Stabilisation; Use of additives
    • C07C227/40—Separation; Purification
    • 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
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • 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
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/38—Separation; Purification; Stabilisation; Use of additives
    • C07C227/40—Separation; Purification
    • C07C227/42—Crystallisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/41—Preparation of salts of carboxylic acids
    • C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Claims (14)

1. Pripravak koji sadrži kristalni oblik L-ornitin fenilacetata, naznačen time što kristalni oblik pokazuje uzorak difrakcije X-zraka praha koji sadrži najmanje tri karakteristična vrha, pri čemu su karakteristični vrhovi odabrani iz skupine koja se sastoji od 5.8°±0.2° 2θ, 14.1°±0.2° 2θ, 18.6°±0.2° 2θ, 19.4°±0.2° 2θ, 22.3°±0,2° 2θ i 24.8°±0,2° 2θ.
2. Pripravak prema zahtjevu 1, naznačen time što navedeni kristalni oblik pokazuje uzorak difrakcije X-zraka praha koji sadrži karakteristične vrhove na 5.8°±0.2° 2θ, 14.1°±0.2° 2θ, 18.6°±0.2° 2θ, 19.4°±0.2° 2θ, 22.3°±0.2° 2θ, i 24.8°±0.2° 2θ.
3. Pripravak prema zahtjevu 1 ili 2, naznačen time što je kristalni oblik karakteriziran diferencijalnom skenirajućom kalorimetrijom kao endoterma na oko 40° C.
4. Pripravak prema bilo kojem od zahtjeva 1 do 3, naznačen time što kristalni oblik ima talište od oko 203° C.
5. Pripravak prema bilo kojem od zahtjeva 1 do 4, naznačen time što sadrži najmanje oko 50% težine kristalnog oblika L-ornitin fenilacetata.
6. Pripravak prema zahtjevu 5, naznačen time što sastav sadrži: najmanje oko 0.01% težinski benzojeve kiseline ili njene soli, ili najmanje oko 0.10% težinski benzojeve kiseline ili njene soli.
7. Pripravak prema zahtjevu 5 ili 6, naznačen time što pripravak sadrži: ne više od oko 5% težinski benzojeve kiseline ili njene soli, ili ne više od oko 1% težinski benzojeve kiseline ili njene soli.
8. Pripravak prema bilo kojem od zahtjeva 5 do 7, naznačen time što pripravak nadalje sadrži najmanje oko 10 ppm srebra, najmanje oko 20 ppm srebra, ili najmanje oko 25 ppm srebra.
9. Pripravak prema bilo kojem od zahtjeva 5 do 8, naznačen time što pripravak nadalje ne sadrži više od oko 600 ppm srebra, ne više od oko 100 ppm srebra, ili ne više od oko 65 ppm srebra.
10. Pripravak prema bilo kojem od zahtjeva 1 do 9, naznačen time što je 50 mg/mL navedenog pripravka u vodi izotonično s tjelesnim tekućinama.
11. Pripravak prema zahtjevu 10, naznačen time što izotonična otopina ima osmolalnost u rasponu od oko 280 do oko 330 mOsm/kg.
12. Pripravak prema bilo kojem od zahtjeva 1 do 11 za uporabu u liječenju ili ublažavanju hiperamonijemije kod subjekta.
13. Pripravak za uporabu prema zahtjevu 12, naznačen time što subjekt ima hepatičku encefalopatiju.
14. Pripravak za uporabu prema zahtjevu 12 ili 13, naznačen time što je količina L-ornitin fenilacetata koja se daje od oko 500 mg do oko 50 g.
HRP20221232TT 2009-04-03 2010-04-01 L-ornitin fenil acetat i postupci njegove pripreme HRP20221232T8 (hr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16667609P 2009-04-03 2009-04-03
EP20161306.4A EP3686183B1 (en) 2009-04-03 2010-04-01 L-ornithine phenyl acetate and methods of making thereof

Publications (2)

Publication Number Publication Date
HRP20221232T1 true HRP20221232T1 (hr) 2022-12-23
HRP20221232T8 HRP20221232T8 (hr) 2023-02-03

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HRP20221232TT HRP20221232T8 (hr) 2009-04-03 2010-04-01 L-ornitin fenil acetat i postupci njegove pripreme
HRP20171962TT HRP20171962T1 (hr) 2009-04-03 2017-12-19 L-ornitin fenilacetat i metode za njegovu pripremu

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US (9) US8173706B2 (hr)
EP (4) EP2413924B1 (hr)
JP (6) JP6144488B2 (hr)
KR (6) KR20220067001A (hr)
CN (3) CN106810464B (hr)
AU (1) AU2010232521B2 (hr)
BR (1) BRPI1013657A2 (hr)
CA (5) CA3077846C (hr)
CY (1) CY1119843T1 (hr)
DK (3) DK3686183T3 (hr)
EA (2) EA034409B1 (hr)
ES (3) ES2928586T3 (hr)
HK (1) HK1248558A1 (hr)
HR (2) HRP20221232T8 (hr)
HU (2) HUE035921T2 (hr)
IL (2) IL215449B (hr)
LT (2) LT3686183T (hr)
MX (3) MX2011010262A (hr)
NO (1) NO2413924T3 (hr)
NZ (3) NZ595706A (hr)
PL (2) PL3686183T3 (hr)
PT (2) PT2413924T (hr)
SG (3) SG174982A1 (hr)
SI (1) SI2413924T1 (hr)
WO (1) WO2010115055A1 (hr)
ZA (1) ZA201107189B (hr)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE602005019319D1 (de) 2004-11-26 2010-03-25 Ucl Business Plc Zusammensetzungen mit ornithin und phenylacetat oder phenylbutyrat zur behandlung von hepatischer enzephalopathie
MX2011010262A (es) * 2009-04-03 2012-01-25 Ocera Therapeutics Inc Fenil acetato de l-ornitina y metodos para elaborar el mismo.
DK2799067T3 (da) 2009-06-08 2019-06-03 Ucl Business Plc Behandling af hjerneinflammation ved anvendelse af L-Ornithin-phenylacetat
US8068011B1 (en) 2010-08-27 2011-11-29 Q Street, LLC System and method for interactive user-directed interfacing between handheld devices and RFID media
EA028395B1 (ru) 2010-10-06 2017-11-30 Осера Терапьютикс, Инк. Способы получения фенилацетата l-орнитина
CN102993037B (zh) * 2012-11-20 2015-03-04 南京工业大学 一种l-鸟氨酸苯乙酸盐的制备方法
CN105481725B (zh) * 2014-09-18 2019-01-22 博瑞生物医药（苏州）股份有限公司 L-精氨酸苯乙酸盐的晶型及其制备方法
CA2968544A1 (en) 2014-11-24 2016-06-02 Ucl Business Plc Treatment of diseases associated with hepatic stellate cell activation using ammonia-lowering therapies
JP2018513171A (ja) * 2015-04-20 2018-05-24 オセラ セラピューティクス， インコーポレイテッド Ｌ−オルニチンフェニルアセテート製剤
CA2995823A1 (en) 2015-08-18 2017-02-23 Ocera Therapeutics, Inc. Treatment and prevention of muscle loss using l-ornithine in combination with at least one of phenylacetate and phenylbutyrate
EP3352748A4 (en) * 2015-09-25 2019-06-05 Ocera Therapeutics, Inc. TREATMENT AND PREVENTION OF NEURONAL CELL LOSS BY L-ORNITHIN IN COMBINATION WITH AT LEAST ONE PHENYL ACETATE AND PHENYL BUTYRATE
US11219611B2 (en) * 2015-11-13 2022-01-11 Ocera Therapeutics, Inc. Formulations of L-ornithine phenylacetate
BR112018009349A8 (pt) * 2015-11-13 2019-02-26 Ocera Therapeutics Inc formulações de fenilacetato de l-ornitina
JOP20190146A1 (ar) 2016-12-19 2019-06-18 Axcella Health Inc تركيبات حمض أميني وطرق لمعالجة أمراض الكبد
EP3621947A4 (en) * 2017-05-11 2021-03-10 Ocera Therapeutics, Inc. L-ORNITHINE PHENYLACETATE MANUFACTURING PROCESSES
CN111295187A (zh) 2017-08-14 2020-06-16 胺细拉健康公司 用于治疗肝脏疾病的氨基酸组合物
AR115585A1 (es) 2018-06-20 2021-02-03 Axcella Health Inc Composiciones y métodos para el tratamiento de la infiltración de grasa en músculo
CN110707221B (zh) * 2019-09-25 2023-09-01 北京大学深圳研究生院 氨基酸离子液体在制备钙钛矿光电器件中钙钛矿层的应用
EP4045028A4 (en) * 2019-10-16 2023-11-08 Ocera Therapeutics, Inc. DOSAGE AND USES OF ORNITHINE PHENYLACETATE FOR THE TREATMENT OF HYPERAMMONEMIA
WO2023240081A1 (en) * 2022-06-06 2023-12-14 Yale University Treatment, amelioration, and/or prevention of inflammatory and autoimmune diseases

Family Cites Families (59)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB965637A (en) 1962-04-23 1964-08-06 Tanabe Seiyaku Co L-ornithine l-aspartate
NL302572A (hr) 1962-12-27
GB1067742A (en) 1963-09-16 1967-05-03 Kyowa Hakko Kogyo Kk Process for the preparation of l-ornithine l-aspartate
ZA716628B (en) 1970-10-15 1972-06-28 Richardson Merrell Spa Composition and method for treatment of hepatic disease and mental fatigue
FR2113774A1 (en) 1970-11-13 1972-06-30 Roques Ets Prepn of l-ornithine salts with org acids - using silver oxides
US4100293A (en) * 1974-04-15 1978-07-11 The Johns Hopkins University Treatment of hepatic disorders with therapeutic compositions comprising keto analogs of essential amino acids
US3950529A (en) * 1975-02-03 1976-04-13 Massachusetts General Hospital Amino acid formulations for patients with liver disease and method of using same
US4228099A (en) 1978-03-17 1980-10-14 The Johns Hopkins University Ornithine and arginine salts of branched chain keto acids and uses in treatment of hepatic and renal disorders
US4320146A (en) * 1978-03-17 1982-03-16 The Johns Hopkins University Treatment of hepatic and renal disorders with ornithine and arginine salts of branched chain keto acids
US4352814A (en) * 1979-04-18 1982-10-05 The Johns Hopkins University Treatment of hepatic and renal disorders with mixed salts of essential or semi-essential amino acids and nitrogen-free analogs
US4284647A (en) * 1980-03-31 1981-08-18 The Johns Hopkins University Process for waste nitrogen removal
US4457942A (en) 1982-08-20 1984-07-03 Brusilow Saul W Process for waste nitrogen removal
US4783443A (en) 1986-03-03 1988-11-08 The University Of Chicago Amino acyl cephalosporin derivatives
US5139981A (en) 1987-06-24 1992-08-18 Union Carbide Chemicals & Plastics Technology Corporation Process for preparing silver(I)-exchanged resins
JP2522034B2 (ja) * 1988-12-27 1996-08-07 味の素株式会社 α−ケト酸・アミノ酸塩化合物及びその製造方法
JPH03273578A (ja) 1990-03-23 1991-12-04 Ricoh Co Ltd 対物レンズクリーニング装置
US5591613A (en) 1990-07-02 1997-01-07 Degussa Aktiengesellschaft Method for the preparation of D-arginine and L-ornithine
DE4020980C1 (hr) 1990-07-02 1991-09-26 Degussa Ag, 6000 Frankfurt, De
JP3127484B2 (ja) 1991-02-28 2001-01-22 味の素株式会社 肝炎治療薬
US5767086A (en) 1992-04-03 1998-06-16 Terrapin Technologies, Inc. Bone marrow stimulation by certain glutathione analogs
JP3166123B2 (ja) 1992-09-09 2001-05-14 フアイソンズ・ピーエルシー 薬剤パッケージング
US5571783A (en) * 1993-03-09 1996-11-05 Clintec Nutrition Company Composition and method for treating patients with hepatic disease
JP3273578B2 (ja) 1993-09-21 2002-04-08 第一化学薬品株式会社 オルニチンと酸性アミノ酸類又はケト酸類との塩の製造法
US5856481A (en) * 1994-07-28 1999-01-05 Syntex (U.S.A.) Inc. 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol derivative
IL139728A (en) 1995-01-09 2003-06-24 Penwest Pharmaceuticals Compan Aqueous slurry composition containing microcrystalline cellulose for preparing a pharmaceutical excipient
AU2251897A (en) 1996-02-13 1997-09-02 Trustees Of The University Of Pennsylvania, The Method of treating liver disorders
ZA986614B (en) * 1997-07-25 1999-01-27 Gilead Sciences Nucleotide analog composition
GB9815567D0 (en) * 1998-07-18 1998-09-16 Glaxo Group Ltd Antiviral compound
US6258849B1 (en) * 1998-07-23 2001-07-10 Stanislaw R. Burzynski Treatment regimen for administration of phenylacetylglutamine, phenylacetylisoglutamine, and/or phenylacetate
EP1179347A4 (en) 1999-05-21 2002-06-26 Takeda Chemical Industries Ltd HEPATIC FUNCTION REGULATORS
US6768024B1 (en) * 2000-08-04 2004-07-27 Lion Bioscience Ag Triamine derivative melanocortin receptor ligands and methods of using same
JP3211824B1 (ja) 2000-10-26 2001-09-25 味の素株式会社 分岐鎖アミノ酸含有医薬用顆粒製剤とその製造方法
DE60233558D1 (de) 2001-03-15 2009-10-15 Takashi Abe Aminosäurezusammensetzungen zur linderung einer fehlfunktion der leber
US6503530B1 (en) * 2001-11-01 2003-01-07 Chunghee Kimberly Kang Method of preventing development of severe metabolic derangement in inborn errors of metabolism
US20030105104A1 (en) * 2001-11-27 2003-06-05 Burzynski Stanislaw R. Formulation of amino acids and riboflavin useful to reduce toxic effects of cytotoxic chemotherapy
US20040229948A1 (en) 2002-04-12 2004-11-18 Summar Marshall L. Method for preventing hepatic encephalopathic episodes
US20030195255A1 (en) 2002-04-12 2003-10-16 Summar Marshall L. Method for treating hepatic encephalopathies
CN1383815A (zh) 2002-05-08 2002-12-11 刘万忠 防治肝病、肝性脑病的鸟氨酸和门冬氨酸的复方制剂及其制备方法
US20040152784A1 (en) * 2002-07-23 2004-08-05 Special Products Limited Pharmaceutical composition and method for treatment of a urea cycle deficiency or sickle-cell anaemia
AU2003261825A1 (en) 2002-08-30 2004-03-19 Ajinomoto Co., Inc. Therapeutic agent for hepatic disease
US20050059150A1 (en) * 2003-09-17 2005-03-17 Becton, Dickinson And Company Environments that maintain function of primary liver cells
MXPA03009902A (es) * 2003-10-29 2005-05-03 Manuel Francisco Lara Och Jose Compuestos para reducir la hiperamonemia en pacientes con cirrosis u otras incapacidad para la eliminacion de amonio.
EP1718667B1 (en) * 2004-02-23 2013-01-09 Genentech, Inc. Heterocyclic self-immolative linkers and conjugates
CA2565840A1 (en) * 2004-05-06 2005-11-17 Osteologix A/S High yield and rapid syntheses methods for producing metallo-organic salts
EP1799759A1 (en) * 2004-08-30 2007-06-27 Lunamed Inc. 4-phenylbutyric acid controlled-release formulations for therapeutic use
DE602005019319D1 (de) * 2004-11-26 2010-03-25 Ucl Business Plc Zusammensetzungen mit ornithin und phenylacetat oder phenylbutyrat zur behandlung von hepatischer enzephalopathie
GB0426141D0 (en) * 2004-11-26 2004-12-29 Ucl Biomedica Plc Treatment
SI1948224T1 (sl) 2005-11-17 2014-07-31 Silverstone Pharma Est. Stabilna formulacija amorfnih perindoprilnih soli, postopek za njihovo pripravo, posebno industrijsko pripravo, in njihova uporaba pri zdravljenju hipertenzije
AU2015221466B2 (en) 2009-04-03 2017-02-02 Ocera Therapeutics, Inc. L-ornithine phenyl acetate and methods of making thereof
MX2011010262A (es) 2009-04-03 2012-01-25 Ocera Therapeutics Inc Fenil acetato de l-ornitina y metodos para elaborar el mismo.
CA2763894A1 (en) 2009-06-02 2011-01-13 Salix Pharmaceuticals, Ltd. Use of rifaximin to maintain remission of hepatic encephalopathy
DK2799067T3 (da) 2009-06-08 2019-06-03 Ucl Business Plc Behandling af hjerneinflammation ved anvendelse af L-Ornithin-phenylacetat
AU2014250643B2 (en) 2009-06-08 2016-07-14 Ocera Therapeutics, Inc. Treatment of portal hypertension and restoration of liver function using L-ornithine phenylacetate
JP2011236160A (ja) 2010-05-11 2011-11-24 Shinshu Univ 非アルコール性肝疾患治療薬
EA028395B1 (ru) 2010-10-06 2017-11-30 Осера Терапьютикс, Инк. Способы получения фенилацетата l-орнитина
US9289406B2 (en) 2012-11-21 2016-03-22 Horizon Therapeutics, Inc. Methods of administering and evaluating nitrogen scavenging drugs for the treatment of hepatic encephalopathy
CA2968544A1 (en) 2014-11-24 2016-06-02 Ucl Business Plc Treatment of diseases associated with hepatic stellate cell activation using ammonia-lowering therapies
JP2018513171A (ja) 2015-04-20 2018-05-24 オセラ セラピューティクス， インコーポレイテッド Ｌ−オルニチンフェニルアセテート製剤
CA2995823A1 (en) 2015-08-18 2017-02-23 Ocera Therapeutics, Inc. Treatment and prevention of muscle loss using l-ornithine in combination with at least one of phenylacetate and phenylbutyrate

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