DE1768655A1 - New salts of N-carbamylglutamic acid and N-carbamylaspartic acid - Google Patents
New salts of N-carbamylglutamic acid and N-carbamylaspartic acidInfo
- Publication number
- DE1768655A1 DE1768655A1 DE19681768655 DE1768655A DE1768655A1 DE 1768655 A1 DE1768655 A1 DE 1768655A1 DE 19681768655 DE19681768655 DE 19681768655 DE 1768655 A DE1768655 A DE 1768655A DE 1768655 A1 DE1768655 A1 DE 1768655A1
- Authority
- DE
- Germany
- Prior art keywords
- acid
- carbamylaspartic
- manganese
- salts
- metal salt
- 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.)
- Granted
Links
- 150000003839 salts Chemical class 0.000 title claims description 15
- HLKXYZVTANABHZ-REOHCLBHSA-N N-carbamoyl-L-aspartic acid Chemical class NC(=O)N[C@H](C(O)=O)CC(O)=O HLKXYZVTANABHZ-REOHCLBHSA-N 0.000 title claims description 7
- LCQLHJZYVOQKHU-VKHMYHEASA-N carglumic acid Chemical class NC(=O)N[C@H](C(O)=O)CCC(O)=O LCQLHJZYVOQKHU-VKHMYHEASA-N 0.000 title description 3
- 229910052751 metal Inorganic materials 0.000 claims description 13
- 239000002184 metal Substances 0.000 claims description 13
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 239000010941 cobalt Substances 0.000 claims description 3
- 229910017052 cobalt Inorganic materials 0.000 claims description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 3
- 229910052742 iron Inorganic materials 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 239000011572 manganese Substances 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 229910052748 manganese Inorganic materials 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- 238000001784 detoxification Methods 0.000 description 3
- 239000003701 inert diluent Substances 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 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 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- -1 manganese N-carbamylaspartate Chemical compound 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 241001181114 Neta Species 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 150000001510 aspartic acids Chemical class 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000002307 glutamic acids Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229940093474 manganese carbonate Drugs 0.000 description 1
- 235000006748 manganese carbonate Nutrition 0.000 description 1
- 239000011656 manganese carbonate Substances 0.000 description 1
- 229910000016 manganese(II) carbonate Inorganic materials 0.000 description 1
- XMWCXZJXESXBBY-UHFFFAOYSA-L manganese(ii) carbonate Chemical compound [Mn+2].[O-]C([O-])=O XMWCXZJXESXBBY-UHFFFAOYSA-L 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000003867 tiredness Effects 0.000 description 1
- 208000016255 tiredness Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
- C07C275/06—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton
- C07C275/16—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton being further substituted by carboxyl groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
SPA SOCISTA PEODOiDOiI ÄNTIBIOTICI S.p.A., Mailand / ItalienSPA SOCISTA PEODOiDOiI ÄNTIBIOTICI S.p.A., Milan / Italy
Hcuc Salae der N-Carbamylglutami.nsäure und der N-Carbamyl-Hcuc Salae of the N-carbamylglutamic acid and the N-carbamyl-
asparaginaäureaspartic acid
Die Erfindimg betrifft neue Metallsalze der N-Carbamylasparaginsäure und der N-Carbaraylglutaminsäure, ihre Herstellung sov/ie dieue neuen Salze enthaltende pharmazeutische Zusammen--Setzungen. The invention relates to new metal salts of N-carbamylaspartic acid and N-carbaraylglutamic acid, their production pharmaceutical compositions containing the new salts.
Die neuen Salze der Erfindung sind aus der N-Carbamylglutanineluire und der N-Carbamylasparaginsäure mit Eisen, Mangan, Zink, und Kobalt, also Metallen, welche therapeutische Brauchbarkeit aufweisen und/oder an e^zymatischen biologischen Systemen teilhaben, gebildet.The new salts of the invention are from the N-Carbamylglutanineluire and N-carbamylaspartic acid with iron, manganese, zinc, and cobalt, i.e. metals which have therapeutic utility and / or participate in e ^ zymatic biological systems, educated.
Es wurde gefunden, daß die erfindungsgemäßen neuen Metallsalze besonders wertvoll sind bsi der Behandlung von Vergiftungsauetänden und Müdigkeit bzw. Erschöpfung.It has been found that the new metal salts according to the invention are particularly valuable for the treatment of poisoning conditions and tiredness or exhaustion.
Mo Natriumsalse von Glutamin- und Asparaginsäuren wurden in großem Umfang in der Humantherapie als Entgiftungsmittel bei der syiiiptomatischen Behandlung von Encephalopathien verwendet, welche mit einer Labersehädigung in Verbindung stehen, da diese Krankheiten auf ein Ansteigen deo Ammoniakspiegel3 im Blut zurücksu.fuhrer. sind. Me Brauchbarkeit dieser beiden Xiatriuwcalze für diesen Zweck laßt sich wahrscheinlich darauf zurück-Mo sodium salts of glutamic and aspartic acids were used in has been widely used in human therapy as a detoxification agent used in the syiiiptomatic treatment of encephalopathies, which are associated with a Labersehädigung, as this Illnesses due to an increase in the ammonia level3 in the blood. are. Me usefulness of these two Xiatriuwcalze for this purpose it can probably be traced back to
109847/1909109847/1909
. 4.3. 4.3
BAD ORIGINALBATH ORIGINAL
fuhren, daß sowohl Glutaminsäure als auch Asparaginsäure an einem komplizierten Stoffwechselzyklus teilnehmen, mittels dessen Ammoniak in Harnstoff umgewandelt wird, einen nichttoxischen Metaboliten, der hauptsächlich über die Nieren eliminiert wird.lead to both glutamic acid and aspartic acid participate in a complicated metabolic cycle that converts ammonia into urea, a non-toxic one Metabolites, mainly through the kidneys is eliminated.
Es wurde jedoch gefunden, daß nach Verabreichung dieser beiden Säuren diese in die entsprechenden Carbamylverbindungen umgewandelt werden, ehe sie an dem oben erwähnten Entgiftungsmechanisious teilhaben können. Weiter ist es möglich, daß sie ihre biologische Wirkung in Verbindung mit bestimmten Aminosäuren wie Ornithin, Arginin und Citrullin ausüben, welche ebenfalls eine wichtige Rolle im Entgiftungsmechanismus spielen.It has been found, however, that upon administration of these two acids, they are converted to the corresponding carbamyl compounds before joining the above mentioned detoxification mechanism can participate. It is also possible that they have their biological effect in connection with certain amino acids like ornithine, arginine and citrulline, which also play an important role in the detoxification mechanism.
Die neuen Metallsalze gemäß der Erfindung lassen sich durch Umsetzung von N-Carbamylglutaminsäure oder N-Carbamylasparaginsaure portionsweise unter Rühren in wässriger Lösung mit einer basischen Verbindung einer der in Präge kommenden Metalle herstellen« Die hierbei gebildeten gewünschten Salze lassen sich in bekannter Weise isolieren, beispielsweise durch Verdampfen der erhaltenen Lösung in einem Vakuum oder Ausfällung durch Zusatz eines mit Wasser mischbaren organischen Lösungsmittels wie einem Alkohol, Keton oder Glykolhalbester, Beispiele für derartige organische Lösungsmittel sind Methanol, Äthanol, Isopropanol, Aceton, Methyläthylketon und Äthylenglykolmonomethyläther. The new metal salts according to the invention can be converted into of N-carbamylglutamic acid or N-carbamylaspartic acid Prepare one of the metals to be embossed in portions while stirring in an aqueous solution with a basic compound « The desired salts formed in this way can be isolated in a known manner, for example by evaporation the resulting solution in a vacuum or precipitation by adding a water-miscible organic solvent such as an alcohol, ketone or glycol half-ester, examples of such organic solvents are methanol, ethanol, Isopropanol, acetone, methyl ethyl ketone and ethylene glycol monomethyl ether.
Es wurde festgestellt, daß einige dieser neuen Metallsalze eine ausgeprägte Wirkung gegen Erschöpfungszustände besitzen, was wahrscheinlich auf die Tatsache zurückzuführen ist, daß N-Carbamylasparaginsäure und N-Carbamy!glutaminsäure physiologische Metaboliten der Nervenzellen darstellen, während bestimmte Metalle bekanntlich an endocellulären respiratorischen Enzymprozessen der Heuronen teilnehmen. Erschöpfungszustände scheinen in enger Verbindung mit einer funktioneilen Erschöpfung dieser respiratorischen Prozesse zu stehen.It has been found that some of these new metal salts have a pronounced effect against states of exhaustion, which is probably due to the fact that N-carbamylaspartic acid and N-carbamylaspartic acid are physiological Metabolites represent nerve cells, while certain metals are known to be involved in endocellular respiratory Enzyme processes of the heurons take part. States of exhaustion seem to be closely related to functional exhaustion to face these respiratory processes.
109847/1909109847/1909
BAD ORIGINALBATH ORIGINAL
Das folgende Beispiel erläutert die Erfindung weiter: BeispielThe following example further explains the invention: Example
Etwa 176 g N-Carbamyl-djl-asparaginsäure werden in 1 1 Wasser unter Rühren suspendiert und dann werden etwa 115 g Mangancarbonat portionsweise zugesetzt, Zur Vervollständigung der Auflösung wird unter fortsetzen des Rührens schwach erwärmt. Hach dem Filtrieren wird das Salz aus der wässrigen Lösung durch Zugabe von Äthanol oder Aceton ausgefällt. Der Niederschlag wird abfiltriert, mit Äthanol oder Aceton gewaschen und ^ im Vakmim getrocknet. Dan Mangan-N-carbamylasparaginat wird als kristallines weißes Pulver erhalten, welches in Wasser löslich und in den üblichen organischen Lösungsmitteln unlöslich ist. Der pH-Wert einer 1#igen wässrigen Lösung ist 7,5.About 176 g of N-carbamyl-djl-aspartic acid are dissolved in 1 l of water suspended with stirring and then about 115 g of manganese carbonate added in portions. To complete the dissolution, the mixture is warmed gently while continuing to stir. After filtering, the salt is precipitated from the aqueous solution by adding ethanol or acetone. The precipitation is filtered off, washed with ethanol or acetone and ^ dried in a vacuum. Dan will manganese N-carbamylaspartate obtained as a crystalline white powder which is soluble in water and insoluble in common organic solvents is. The pH of a 1 # aqueous solution is 7.5.
Analyse für C5H6N2O5Mn (MO 229,06) Analysis for C 5 H 6 N 2 O 5 Mn (MO 229.06)
Ber.: C 26,23; H 2,64ϊ N 12,24; 0 34,93; Hn 24,00 + Oef.: 26,2 2,64 12,2 34,9 24,0 #Calc .: C 26.23; H 2.64ϊ N 12.24; 0 34.93; Hn 24.00 + Oef .: 26.2 2.64 12.2 34.9 24.0 #
Vie oben angegeben, umfaßt die Erfindung auch pharmazeutische Zusammensetzungen, welch« eines oder mehrere der neuen Metall- «alse enthalten. Diese pharmazeutischen Zusammensetzungen " können oral oder parenteral gemischt mit einem festen oder flüssigen pharaazeutisehen Träger verabreicht werden.As stated above, the invention also includes pharmaceutical compositions which "one or more of the new metal «As included. These pharmaceutical compositions " can be administered orally or parenterally in admixture with a solid or liquid pharmaceutical carrier.
feste Zusammensetzungen für die orale Verabreichung können in Fora von gepreßten Tabletten, Pillen, dispergierbaren Pulvern und Granulaten vorliegen. Xn diesen festen Zusammensetzungen findet sich mindesten« eines der neue* Hetallsala· gemischt mit aiodestens «im·* inerten Verdünnungsmittel wie Calciueearboaat, Stärke, Alginsäure oder Lactose. Die Zusaiaaen-Setzungen köaaten auch, wie die« üblich ist, weitere Substanzen außer den imertea Verdüanungeaitteln enthaltext, beispielsweise Gleitmittel wie Hagnesiimstearat.solid compositions for oral administration come in the form of compressed tablets, pills, dispersible powders and granules. Xn these solid compositions there is at least "one of the new * Hetallsala · mixed with aiodesten" in the · * inert diluent such as Calciueearboaat, starch, alginic acid or lactose. The Composition-Settlements As is customary, they can also contain other substances in addition to the imertea diluents contained, for example Lubricants such as hagnesium stearate.
109847/1909 -/109847/1909 - /
Flüssige Zusammensetzungen zur oralen Verabreichung umfassen pharmazeutisch verträgliche Emulsionen, Lösungen, Suspensionen Sirup.? und KLixiere, welche die üblicherweise verwendeten inerten Verdünnungsmittel wie Wasser und flüssiges Paraffin enthalten. Außer den inerten Verdünnungsmitteln können derartige Zusammensetzungen auch Zusatzstoffe enthalten wie Neta- und Suspendiermittel sowie Süß- und Gesclimacksstoffe.Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, syrup suspensions.? and KLixirs which are commonly used contain inert diluents such as water and liquid paraffin. In addition to the inert diluents, such Compositions also contain additives such as neta and suspending agents, as well as sweeteners and flavorings.
Die erfindungcgemäßen Zusammensetzungen für die orale Verabreichung umfassen Kapseln aus absorbierbarem Material wie Gelatine, welche mindestens eines der neuen Metallsalze mit P oder ohne Zusatz von Verdünnungsmittel oder Exzipienten enthalten. The compositions of the invention for oral administration include capsules made of absorbable material such as gelatin, which contain at least one of the new metal salts P or without the addition of diluents or excipients.
ße Präparate zur parenteralen Verabreichung umfassen Dtorile wässrige oder nicht-wässrige Lösungen, Suspensionen oder Emulsionen. Beispiele für nicht-wässrige Lösungsmittel oder Suspensioncmedien sind Propylenglykol, Polyäthylenglykol, pflanzliche Öle wie Olivenöl und injizierbare organische Ester wie Äthyloleat. Diese Zusammensetzungen können auch Zusatzstoffe, enthalten wie Netz-, Emulgier- und Dispergiermittel. Sie können sterilisiert sein, beispielsweise durch Filtration über bakteriendichte Filter, Einverleibung von Sterilisierungsmitteln in die Zusammensetzungen, Bestrahlung oder Erhitzung. Sie können auch in Form von sterilen feeten Zusammensetzungen hergestellt werden, welche unmittelbar vor der Verwendung in sterilem Wasser oder einen anderen sterilen injizierbaren Medium aufgelöst werden.These include preparations for parenteral administration Torile aqueous or non-aqueous solutions, suspensions or emulsions. Examples of non-aqueous solvents or suspension media are propylene glycol, polyethylene glycol, vegetable oils such as olive oil and injectable organic esters such as ethyl oleate. These compositions can also contain additives such as wetting, emulsifying and dispersing agents. They can be sterilized, for example by filtration through bacteria-proof filters, incorporation of Sterilizing agents in the compositions, irradiation or heating. They can also be in the form of sterile feasts Compositions are prepared which immediately prior to use in sterile water or another sterile injectable medium to be dissolved.
Der Virkstoffgehalt in den erfindungsgemäßen Zusammensetzungen kann variiert werden, es ist jedoch notwendig, daß er einen solchen Anteil darstellt, daß eine geeignete Dosierung für den gewünschten therapeutischen Effekt erhalten wird. Im allgemeinen r.elltcn die erfindungsgemäßen Präparate bei oraler VerabrcichnLft so suceführt werden, daß man G,ν bis 5 g Wirkstoff pro Taß erhält und irc Fall der parenteralen Verabreichung 0,1 bic 4 g Wirküvoif pro Tag«The active ingredient content in the compositions according to the invention can be varied, but it is necessary that it represent such a proportion that a suitable dosage for the desired therapeutic effect is obtained. In general, the preparations according to the invention, when administered orally, are carried out in such a way that G, ν to 5 g of active ingredient per cup are obtained and, in the case of parenteral administration, 0.1 to 4 g of active ingredient per day.
1 09847/ 1 9091 09847/1 909
Claims (5)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB27168/67A GB1182815A (en) | 1967-06-13 | 1967-06-13 | New Salts of N-Carbamyl-Glutamic Acid and of N-Carbamyl-Aspartic Acid. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE1768655A1 true DE1768655A1 (en) | 1971-11-18 |
| DE1768655B2 DE1768655B2 (en) | 1974-03-07 |
| DE1768655C3 DE1768655C3 (en) | 1974-10-24 |
Family
ID=10255306
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19681768655 Granted DE1768655A1 (en) | 1967-06-13 | 1968-06-12 | New salts of N-carbamylglutamic acid and N-carbamylaspartic acid |
Country Status (3)
| Country | Link |
|---|---|
| DE (1) | DE1768655A1 (en) |
| FR (1) | FR7642M (en) |
| GB (1) | GB1182815A (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1297080A (en) * | 1970-04-17 | 1972-11-22 | ||
| FR2230094A1 (en) * | 1973-05-14 | 1974-12-13 | Mascart Francis | Safety plug has circular insulating housing with contact pins - and is held to wall socket front by strip of adhesive tape |
| EP0029000A1 (en) * | 1979-08-03 | 1981-05-20 | Interco S.A. | Mixed salts of an alkaline earth metal and of dimethylamino ethanol of N-acyl-glutamic acids and N-acyl-aspartic acids |
| CN102599347A (en) * | 2010-03-12 | 2012-07-25 | 广州英赛特生物技术有限公司 | Application of cupric glutamate or derivate thereof being taken as animal growth promotion feed additive |
| CN102718685A (en) * | 2012-06-01 | 2012-10-10 | 广州九益生物技术有限公司 | Preparation method and application of N-carbamyl-L-glutamic acid manganese complex |
| CN108017561B (en) * | 2016-11-04 | 2021-03-30 | 武汉武药科技有限公司 | Method for refining carglutamic acid |
| CN107445868A (en) * | 2017-08-04 | 2017-12-08 | 仲恺农业工程学院 | Manganese N-carbamylglutamate chelate and preparation method thereof |
| CN111100039A (en) * | 2019-12-24 | 2020-05-05 | 长沙兴嘉生物工程股份有限公司 | Preparation method and application of argininyl zinc |
-
1967
- 1967-06-13 GB GB27168/67A patent/GB1182815A/en not_active Expired
-
1968
- 1968-06-12 DE DE19681768655 patent/DE1768655A1/en active Granted
- 1968-06-13 FR FR154834A patent/FR7642M/fr not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR7642M (en) | 1970-02-02 |
| GB1182815A (en) | 1970-03-04 |
| DE1768655B2 (en) | 1974-03-07 |
| DE1768655C3 (en) | 1974-10-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) | ||
| E77 | Valid patent as to the heymanns-index 1977 | ||
| 8339 | Ceased/non-payment of the annual fee |