CH434285A - Process for the production of the L-aspartic acid salt of L-ornithine or its monohydrate - Google Patents
Process for the production of the L-aspartic acid salt of L-ornithine or its monohydrateInfo
- Publication number
- CH434285A CH434285A CH502063A CH502063A CH434285A CH 434285 A CH434285 A CH 434285A CH 502063 A CH502063 A CH 502063A CH 502063 A CH502063 A CH 502063A CH 434285 A CH434285 A CH 434285A
- Authority
- CH
- Switzerland
- Prior art keywords
- ornithine
- aspartic acid
- monohydrate
- production
- acid salt
- Prior art date
Links
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 title claims description 32
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 title claims description 24
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical class OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 title claims description 19
- 229960003104 ornithine Drugs 0.000 title claims description 18
- 238000000034 method Methods 0.000 title claims description 9
- 150000004682 monohydrates Chemical class 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 229960005261 aspartic acid Drugs 0.000 claims description 16
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 11
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 11
- AHLPHDHHMVZTML-SCSAIBSYSA-N D-Ornithine Chemical compound NCCC[C@@H](N)C(O)=O AHLPHDHHMVZTML-SCSAIBSYSA-N 0.000 claims description 2
- 238000001640 fractional crystallisation Methods 0.000 claims description 2
- VZLDSDZYNAJGLX-ZBRNBAAYSA-N (2s)-2,4-diamino-4-oxobutanoic acid;(2s)-2,5-diaminopentanoic acid Chemical compound NCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CC(N)=O VZLDSDZYNAJGLX-ZBRNBAAYSA-N 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 6
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 4
- 235000003704 aspartic acid Nutrition 0.000 description 4
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- GGTYBZJRPHEQDG-WCCKRBBISA-N (2s)-2,5-diaminopentanoic acid hydrochloride Chemical compound Cl.NCCC[C@H](N)C(O)=O GGTYBZJRPHEQDG-WCCKRBBISA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 206010020575 Hyperammonaemia Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 150000001510 aspartic acids Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
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
- A61K31/185—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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/20—Synthetic spices, flavouring agents or condiments
- A23L27/21—Synthetic spices, flavouring agents or condiments containing amino acids
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Polymers & Plastics (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung des L"Asparaginsäuresalzes des L-Ornithins bzw. dessen Monohydrats
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von L-Ornithin-L-asparaginat bzw. dessen Monohydrat.
Es ist bereits bekannt, dass L-Ornithin eine als für die Beibehaltung des Wachstums von Ratten nicht unentbehrlich klassifizierte Aminosäure ist, aber es spielt eine wichtige Rolle im Stoffwechsel im lebenden Körper als Glied des Ornithinzyklus bei der Erzeugung von Harnstoff.
Es ist ebenfalls bekannt, dass Asparaginsäure im Stoffwechsel eine wichtige Rolle spielt als Vorläufer des Oxaloacetats oder Fumarates des TCA-Zyklus und ammoniämie wirksamer als L-Ornithin oder L-Asparaginsäure ist auch wichtig als Ausgangsmaterial bei der Biosynthese von Orthosäure.
Es wurde gefunden, dass freies L- oder DL-Ornithin mit L-Asparaginsäure unter Bildung eines äquimolaren Salzes bzw. dessen Monohydrats reagieren kann, und das dadurch erhaltene Produkt ist eine therapeutisch wertvolle, neue Verbindung.
Die Verbindung hat im wasserfreien Zustand die folgende Formel:
EMI1.1
Es ist bereits bekannt, dass, wenn L-Ornithin oder L-Asparaginsäure intravenös an Tieren mit hohen Ammoniakspiegeln im Blut verabreicht wird, eine beträchtliche Abnahme des Ammoniakstickstoffspiegels und eine Zunahme des Harnstoffs im Blut beobachtet werden.
Es ist angenommen worden, dass diese Phänomene teilweise der Beschleunigung des hepatischen Ornithinzyklus zuzuschreiben sind, die zu einer erhöhten Geschwindigkeit des Verschwindens von Ammoniak im Blut führt. Das erfindungsgemäss hergestellte L-Ornithin-L-asparaginat ist für die Behandlung von Hyperammoniämie wirksamer als L-Ornithin oder L-Asparaginsäure allein in äquimolaren Mengen.
Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass eine L-Ornithin und gegebenenfalls auch D-Ornithin enthaltende Lösung mit L-Asparaginsäure umgesetzt und das Produkt gewonnen wird.
Die Reaktion zwischen dem Ornithin und der Asparaginsäure lässt sich durch blosses Mischen der beiden in Lösung leicht ausführen. Als Reaktionslösungsmittel wird vorzugsweise Wasser verwendet. Vorzugsweise werden wässrige Lösungen von L-Ornithin und L-Asparaginsäure gemischt, Methanol zu dem Gemisch gege ben und die Kristallisation vor sich gehen gelassen. Erforderlichenfalls kann das Gemisch teilweise eingedampft werden, bis Kristallisation stattfindet. Das L Asparaginsäuresali des bOrnithins kristallisiert. Das so erhaltene Salz kristallisiert gewöhnlich aus wässerigem Methanol mit einem Mol Wasser (d. h. als Monohydrat).
Das Hydratwasser kann durch längeres Erhitzen in einer trockenen Atmosphäre oder im Vakuum entfernt werden, wird aber wieder aufgenommen, wenn das Salz der feuchten Luft ausgesetzt wird. Das hydratisierte Salz schmilzt bei 215 C bis 2170 C unter Zer setzung. Seine spezifische Drehung [a] D bei 200 C und einer Konzentration von 38 O/u beträgt + 7,10.
Gemäss einer anderen Ausführungsform des erfindungsgemässen Verfahrens kann L-Ornithin-L-asparaginat durch Umsetzung von L-Asparaginsäure mit einem Gemisch von D-Oloithin und L-Ornithin und fraktionierte Kristallisation des Produktes aus wässrigem Methanol hergestellt werden. In diesem Falle kristallisiert zu Anfang das L-Asparaginsäuresalz des D Ornithins aus, wobei das L-Ornithin-L-asparaginat in der Mutterlauge zurückbleibt. Das L-Ornithin-Lasparaginat kann durch Zusatz von Methanol oder durch Eindampfen aus der Mutterlauge gewonnen werden. Wenn man wünscht, ein Produkt von höherer Reinheit zu erhalten, kann dies durch Umkristallisieren des anfänglichen Produktes aus wässrigem Methanol erreicht werden. Für die Kristallisation kann auch ein Gemisch von Athanol und Wasser verwendet werden.
Beispiel 1
16,8 g L-Ornithin-Hydrochlorid wurden in 400 cm3 Wasser gelöst. Die Lösung wurde durch ein 150 cm3 Bett von Amberlite IR- 120 > -Kationenaustauscherharz in der Ammoniumform geleitet, das dann mit 100 cm3 Wasser gewaschen wurde. Das Harzbett wurde mit einem Liter 50/oigem wässrigem Ammoniak extrahiert und die ausfliessende Flüssigkeit durch Eindampfen von Ammoniak befreit. Die resultierende L-Ornithinlösung wurde mit 11,8 g bAsparaginsäure gemischt und mit 30 cm3 Wasser verdünnt. Das Gemisch wurde erwärmt, um die Asparaginsäure zu lösen, und im Vakuum bis zu einem Gesamtgewicht von 28 g eingedampft. Zu dem Gemisch wurden 4 cm3 Methanol zugegeben und über Nacht stehengelassen. Die ausgefällten Kristalle wurden abfiltriert, mit Methanol gewaschen und getrocknet.
Es wurden 24 g L-Ornithin-L-asparaginat-Monohydrat erhalten, das bei 2150 C unter Zersetzung schmilzt.
Berechnet für C9Ht90ssN3 H2O: C 38,00 H 7, 13 N 14, 47 H2O 6,70 Gefunden: C 38,12 H 7, 47 N 14, 83 H2O 6,37 [a]D20 = +7, 1 (C = 38 O/o, Wasser)
Beispiel 2
30 cm3 einer wässrigen, 14 g freies DL-Ornithin enthaltenden Lösung wurden mit 14 g L-Asparaginsäure gemischt. Das Gemisch wurde erwärmt, um die Asparaginsäure zu lösen, dann auf ca. 250 C abgekühlt und mit 20 cm3 Methanol gemischt. Das Gemisch wurde über Nacht bei der gleichen Temperatur stehengelassen. Die Kristalle, die während des Stehens ausfielen, wurden abfiltriert, mit 20 cm3 500/obigem wässrigem Methanol gewaschen und getrocknet.
Es wurden 12,6 g D-Ornithin-L-asparaginat erhalten, das bei 2150 C unter Zersetzung schmilzt. Die spezifische Drehung des Produktes in Wasser bei einer Konzentration von 38 O/o und 20 Cbetrug-70.
Die Mutterlauge, aus der das D-Ornithin-L-aspar- aginat abfiltriert worden war, wurde mit 100 cm3 Methanol gemischt und gerührt. Die resultierenden Niederschläge wurden abfiltriert, mit Methanol gewaschen und getrocknet. Es wurden 11 g L-Ornithin-L-asparaginat- Monohydrat erhalten, das bei 214 bis 2150 C unter Zersetzung schmilzt.
Process for the production of the L "aspartic acid salt of L-ornithine or its monohydrate
The present invention relates to a process for the production of L-ornithine-L-asparaginate or its monohydrate.
It is already known that L-ornithine is an amino acid classified as not indispensable for maintaining the growth of rats, but it plays an important role in metabolism in the living body as a member of the ornithine cycle in the production of urea.
It is also known that aspartic acid plays an important role in metabolism as a precursor of the oxaloacetate or fumarate of the TCA cycle and that ammonemia is more effective than L-ornithine or L-aspartic acid is also important as a starting material in the biosynthesis of ortho acid.
It has been found that free L- or DL-ornithine can react with L-aspartic acid to form an equimolar salt or its monohydrate, and the product thus obtained is a therapeutically valuable, new compound.
In the anhydrous state, the compound has the following formula:
EMI1.1
It is already known that when L-ornithine or L-aspartic acid is administered intravenously to animals with high levels of ammonia in the blood, a considerable decrease in ammonia nitrogen level and an increase in urea in the blood are observed.
It has been believed that these phenomena are partly attributable to the acceleration of the hepatic ornithine cycle, which leads to an increased rate of disappearance of ammonia in the blood. The L-ornithine-L-asparaginate prepared according to the invention is more effective for the treatment of hyperammonemia than L-ornithine or L-aspartic acid alone in equimolar amounts.
The method according to the invention is characterized in that a solution containing L-ornithine and optionally also D-ornithine is reacted with L-aspartic acid and the product is obtained.
The reaction between ornithine and aspartic acid can be easily carried out by simply mixing the two in solution. Water is preferably used as the reaction solvent. Preferably, aqueous solutions of L-ornithine and L-aspartic acid are mixed, methanol is added to the mixture, and crystallization is allowed to proceed. If necessary, the mixture can be partially evaporated until crystallization occurs. The L aspartic acid salt of bornithine crystallizes. The salt so obtained usually crystallizes from aqueous methanol with one mole of water (i.e. as the monohydrate).
The water of hydration can be removed by prolonged heating in a dry atmosphere or in a vacuum, but is reabsorbed when the salt is exposed to the moist air. The hydrated salt melts at 215 C to 2170 C with decomposition. Its specific rotation [a] D at 200 C and a concentration of 38 O / u is + 7.10.
According to another embodiment of the process according to the invention, L-ornithine-L-asparaginate can be produced by reacting L-aspartic acid with a mixture of D-olithine and L-ornithine and fractional crystallization of the product from aqueous methanol. In this case, the L-aspartic acid salt of D ornithine crystallizes out at the beginning, the L-ornithine-L-asparaginate remaining in the mother liquor. The L-ornithine lasparaginate can be obtained from the mother liquor by adding methanol or by evaporation. If one desires to obtain a product of higher purity, this can be achieved by recrystallizing the initial product from aqueous methanol. A mixture of ethanol and water can also be used for the crystallization.
example 1
16.8 g of L-ornithine hydrochloride were dissolved in 400 cm3 of water. The solution was passed through a 150 cc bed of Amberlite IR-120> cation exchange resin in the ammonium form, which was then washed with 100 cc of water. The resin bed was extracted with one liter of 50% aqueous ammonia and the liquid flowing out was freed from ammonia by evaporation. The resulting L-ornithine solution was mixed with 11.8 g of b-aspartic acid and diluted with 30 cm3 of water. The mixture was heated to dissolve the aspartic acid and evaporated in vacuo to a total weight of 28 g. 4 cc of methanol was added to the mixture and left to stand overnight. The precipitated crystals were filtered off, washed with methanol and dried.
24 g of L-ornithine-L-asparaginate monohydrate were obtained, which melts at 2150 ° C. with decomposition.
Calculated for C9Ht90ssN3 H2O: C 38.00 H 7, 13 N 14, 47 H2O 6.70 Found: C 38.12 H 7, 47 N 14, 83 H2O 6.37 [a] D20 = +7.1 (C = 38 O / o, water)
Example 2
30 cm3 of an aqueous solution containing 14 g of free DL-ornithine were mixed with 14 g of L-aspartic acid. The mixture was heated to dissolve the aspartic acid, then cooled to about 250 ° C. and mixed with 20 cm3 of methanol. The mixture was left to stand at the same temperature overnight. The crystals which precipitated out while standing were filtered off, washed with 20 cm3 of 500 / above aqueous methanol and dried.
12.6 g of D-ornithine-L-asparaginate were obtained, which melts at 2150 ° C. with decomposition. The specific rotation of the product in water at a concentration of 38 O / o and 20 C was -70.
The mother liquor, from which the D-ornithine-L-asparaginate had been filtered off, was mixed with 100 cm3 of methanol and stirred. The resulting precipitates were filtered off, washed with methanol and dried. 11 g of L-ornithine-L-asparaginate monohydrate, which melts at 214 to 2150 ° C. with decomposition, were obtained.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1654062 | 1962-04-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH434285A true CH434285A (en) | 1967-04-30 |
Family
ID=11919082
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH502063A CH434285A (en) | 1962-04-23 | 1963-04-22 | Process for the production of the L-aspartic acid salt of L-ornithine or its monohydrate |
Country Status (7)
| Country | Link |
|---|---|
| AT (1) | AT246344B (en) |
| BR (1) | BR6348588D0 (en) |
| CH (1) | CH434285A (en) |
| DE (1) | DE1518361B1 (en) |
| DK (1) | DK109694C (en) |
| FR (1) | FR4048M (en) |
| GB (1) | GB965637A (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE789856A (en) * | 1971-10-13 | 1973-02-01 | Tixier Georges | MEDICINAL PRODUCT BASED ON LYSINE DERIVATIVES, WHICH MAY STIMULATE DIFFERENT METABOLISMS, IN PARTICULAR LEUKOCYTE GENESIS |
| US3832465A (en) * | 1971-12-09 | 1974-08-27 | H Ghadimi | Injectable amino acid composition commensurate to the anabolic need of the body and method of using same |
| FR2495608A1 (en) * | 1980-12-04 | 1982-06-11 | Morelle Jean | NEW ASPARTIC ACID DERIVATIVES AND THEIR USES |
| US4972634A (en) * | 1989-01-19 | 1990-11-27 | Dresden Gregory M | Portable walling |
| ATE116285T1 (en) * | 1990-09-28 | 1995-01-15 | Kyowa Hakko Kogyo Kk | METHOD FOR PRODUCING CRYSTALS OF A SALT OF ACID AMINO ACID AND BASIC AMINO ACID. |
| PL2319581T3 (en) | 2004-11-26 | 2015-10-30 | Ucl Business Plc | Compositions comprising ornithine and phenylacetate or phenylbutyrate for treating hepatic encephalopathy |
| MX388894B (en) | 2009-04-03 | 2025-03-20 | Ocera Therapeutics Inc | L-ornithine phenyl acetate and methods of making thereof |
| MX375116B (en) | 2009-06-08 | 2025-03-06 | Ucl Business Plc | TREATMENT OF PORTAL HYPERTENSION AND RESTORATION OF LIVER FUNCTION USING L-ORNITHINE PHENYLACETATE. |
| WO2012048043A1 (en) | 2010-10-06 | 2012-04-12 | Ocera Therapeutics, Inc. | Methods of making l-ornithine phenyl acetate |
| CN102993037B (en) * | 2012-11-20 | 2015-03-04 | 南京工业大学 | Preparation method of L-ornithine phenylacetate |
| JP6797117B2 (en) | 2014-11-24 | 2020-12-09 | ユーシーエル ビジネス リミテッド | Treatment of hepatic stellate cell activation-related diseases with ammonia-lowering therapy |
| MX382121B (en) * | 2015-07-24 | 2025-03-13 | Evonik Technochemie Gmbh | EFFERVESCENT FORMULATIONS OF ORNITHINE ASPARTATE. |
| 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 |
| WO2018208677A1 (en) | 2017-05-11 | 2018-11-15 | Ocera Therapeutics, Inc. | Processes of making l-ornithine phenylacetate |
-
1963
- 1963-04-10 GB GB14309/63A patent/GB965637A/en not_active Expired
- 1963-04-19 DK DK184763AA patent/DK109694C/en active
- 1963-04-22 BR BR148588/63A patent/BR6348588D0/en unknown
- 1963-04-22 CH CH502063A patent/CH434285A/en unknown
- 1963-04-22 DE DE19631518361 patent/DE1518361B1/en active Pending
- 1963-04-23 AT AT327763A patent/AT246344B/en active
- 1963-07-19 FR FR931676A patent/FR4048M/fr not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DK109694C (en) | 1968-06-10 |
| AT246344B (en) | 1966-04-12 |
| BR6348588D0 (en) | 1973-07-03 |
| GB965637A (en) | 1964-08-06 |
| FR4048M (en) | 1966-04-04 |
| DE1518361B1 (en) | 1969-11-13 |
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