HRP20171962T1 - L-ornitin fenilacetat i metode za njegovu pripremu - Google Patents

L-ornitin fenilacetat i metode za njegovu pripremu Download PDF

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Publication number
HRP20171962T1
HRP20171962T1 HRP20171962TT HRP20171962T HRP20171962T1 HR P20171962 T1 HRP20171962 T1 HR P20171962T1 HR P20171962T T HRP20171962T T HR P20171962TT HR P20171962 T HRP20171962 T HR P20171962T HR P20171962 T1 HRP20171962 T1 HR P20171962T1
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Prior art keywords
preparation according
crystalline form
preparation
weight
ppm silver
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HRP20171962TT
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English (en)
Inventor
Keith Anderson
Jim Behling
Christine Henderson Dougen
Stephen William Watt
Peter Manini
Attilia Figini
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Ocera Therapeutics, Inc.
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Publication of HRP20171962T1 publication Critical patent/HRP20171962T1/hr

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    • 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
    • A61K31/195—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 or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [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
    • C07C227/18—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
    • 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
    • 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
    • C07C57/30—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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (10)

1. Pripravak koji sadrži kristalni oblik L-ornitin fenilacetata, naznačen time, što spomenuti kristalni oblik izražava model rendgenske difrakcije praha koji se sastoji od najmanje tri karakteristične vršne točke, naznačen time, što su spomenute karakteristične vršne točke odabrane iz grupe koja se sastoji od 6,0°±0,2° 2θ, 13,9°±0,2° 2θ, 14,8°±0,2° 2θ, 17,1°±0,2° 2θ, 17,8°±0,2° 2θ i 24,1° ±0,2° 2θ, opcionalno naznačen time, što: (i) spomenuti kristalni oblik izražava monokristalnu rendgensku kristalografsku analizu s parametrima kristala otprilike jednakim sljedećim vrijednostima: dimenzije elementarne ćelije: a=6,594(2) Å, b=6,5448(18) Å, c=31,632(8) Å, α=90°, β=91,12(3)°, γ=90°; kristalni sustav: monoklinski; i prostorna grupa: P21; i/ili (ii) spomenuti kristalni oblik je predstavljen formulom [C5H13N2O2][C8H7O2].
2. Pripravak prema zahtjevu 1, naznačen time, što spomenuti kristalni oblik izražava model rendgenske difrakcije praha koji se sastoji od vršnih točaka na 6,0°±0,2° 2θ, 13,9°±0,2° 2θ, 14,8°±0,2° 2θ, 17,1°±0,2° 2θ, 17,8°±0,2° 2θ i 24,1° ±0,2° 2θ.
3. Pripravak prema zahtjevu 1, naznačen time, što spomenuti kristalni oblik ima točku topljenja od 202 °C.
4. Pripravak prema bilo kojem zahtjevu od 1 do 3 koji sadrži: najmanje oko 50 % po težini kristalnog oblika L-ornitin fenilacetata; i najmanje oko 0,01 % po težini benzojeve kiseline ili njene soli.
5. Pripravak prema zahtjevu 4, naznačen time, što pripravak sadrži: (i) najmanje oko 0,10 % po težini benzojeve kiseline ili njene soli; i/ili (ii) najviše 5 % po težini benzojeve kiseline ili njene soli ili najviše 1 % po težini benzojeve kiseline ili njene soli.
6. Pripravak prema zahtjevu 4 ili 5, naznačen time, što pripravak dodatno sadrži: (i) najmanje 10 ppm srebra ili najmanje 20 ppm srebra ili najmanje 25 ppm srebra; i/ili (ii) najviše 600 ppm srebra ili najviše 100 ppm srebra ili najviše 65 ppm srebra.
7. Pripravak prema bilo kojem zahtjevu od 1 do 6, naznačen time, što je 50 mg/ml spomenutog pripravka u vodi izotonično s tjelesnim tekućinama.
8. Pripravak prema zahtjevu 7, naznačen time, što izotonična otopina ima oslmolalnost u rasponu od oko 280 do oko 330 mOsm/kg.
9. Pripravak prema bilo kojem zahtjevu od 1 do 8 za primjenu u liječenju ili ublažavanju hiperamonijemije kod ispitanika.
10. Pripravak prema zahtjevu 9, naznačen time, što ispitanik ima hepatičnu encefalopatiju ili hiperamonijemiju.
HRP20171962TT 2009-04-03 2010-04-01 L-ornitin fenilacetat i metode za njegovu pripremu HRP20171962T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US16667609P 2009-04-03 2009-04-03
EP10759442.6A EP2413924B1 (en) 2009-04-03 2010-04-01 L-ornithine phenyl acetate and methods of making thereof
PCT/US2010/029708 WO2010115055A1 (en) 2009-04-03 2010-04-01 L-ornithine phenyl acetate and methods of making thereof

Publications (1)

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HRP20171962T1 true HRP20171962T1 (hr) 2018-02-09

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

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HRP20221232TT HRP20221232T8 (hr) 2009-04-03 2010-04-01 L-ornitin fenil acetat i postupci njegove pripreme

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US (9) US8173706B2 (hr)
EP (4) EP3686183B1 (hr)
JP (6) JP6144488B2 (hr)
KR (6) KR102399540B1 (hr)
CN (3) CN104230730B (hr)
AU (1) AU2010232521B2 (hr)
BR (1) BRPI1013657A2 (hr)
CA (5) CA2757373C (hr)
CY (1) CY1119843T1 (hr)
DK (3) DK2413924T3 (hr)
EA (2) EA023051B1 (hr)
ES (3) ES2652187T3 (hr)
HR (2) HRP20171962T1 (hr)
HU (2) HUE060371T2 (hr)
IL (2) IL215449B (hr)
LT (2) LT2413924T (hr)
MX (4) MX356608B (hr)
NO (1) NO2413924T3 (hr)
NZ (3) NZ708458A (hr)
PL (2) PL3686183T3 (hr)
PT (2) PT3686183T (hr)
SG (3) SG10201406300YA (hr)
SI (1) SI2413924T1 (hr)
SM (2) SMT201700601T1 (hr)
WO (1) WO2010115055A1 (hr)
ZA (1) ZA201107189B (hr)

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