CH428735A - Process for the preparation of water-soluble salts of ampicillin - Google Patents
Process for the preparation of water-soluble salts of ampicillinInfo
- Publication number
- CH428735A CH428735A CH1040863A CH1040863A CH428735A CH 428735 A CH428735 A CH 428735A CH 1040863 A CH1040863 A CH 1040863A CH 1040863 A CH1040863 A CH 1040863A CH 428735 A CH428735 A CH 428735A
- Authority
- CH
- Switzerland
- Prior art keywords
- ampicillin
- salt
- trialkylamine
- filtrate
- preparation
- Prior art date
Links
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical class C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 title claims description 30
- 229960000723 ampicillin Drugs 0.000 title claims description 30
- 150000003839 salts Chemical class 0.000 title claims description 13
- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- 125000005270 trialkylamine group Chemical group 0.000 claims description 13
- 239000000706 filtrate Substances 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 239000012535 impurity Substances 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 4
- -1 alkali metal salt Chemical class 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 239000003208 petroleum Substances 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- MCLMZMISZCYBBG-UHFFFAOYSA-N 3-ethylheptanoic acid Chemical compound CCCCC(CC)CC(O)=O MCLMZMISZCYBBG-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- GJJAKJNPJXXMCY-UHFFFAOYSA-N [K].CC(C)=O Chemical compound [K].CC(C)=O GJJAKJNPJXXMCY-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000003460 beta-lactamyl group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- GNVRJGIVDSQCOP-UHFFFAOYSA-N n-ethyl-n-methylethanamine Chemical compound CCN(C)CC GNVRJGIVDSQCOP-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/21—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a nitrogen atom directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/44—Compounds with an amino radical acylated by carboxylic acids, attached in position 6
- C07D499/48—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical
- C07D499/58—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical
- C07D499/64—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical by nitrogen atoms
- C07D499/68—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical by nitrogen atoms with aromatic rings as additional substituents on the carbon chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
Verfahren zur Herstellung von wasserlöslichen Salzen des Ampicillins
Verfahren zur Herstellung von wasserlöslichen Salzen des Ampicillins, die sich zur Herstellung von Injektionslösungen eignen, wurden bisher nicht beschrieben. Es mag dieses daran liegen, dass wässrige Lösungen solcher Salze des Ampicillins, die man sich beispielsweise durch Lösen des Ampicillins in der berechneten Menge einer wässrigen Natriumbicarbonatlösung herstellen kann, nicht sehr beständig sind. Dampft man zur Gewinnung des Salzes solche Lösungen unter den schonendsten Bedingungen ein (Rotationsverdampfer; Gefriertrocknung), so wird dabei ein Salz gewonnen, in welchem das Penicillin bereits etwa zur Hälfte zerstört ist. Es scheint nicht möglich zu sein, Salze des Ampicillins aus wässrigen Lösungen zu isolieren, ohne dass dabei beträchtliche Zersetzung des Ampicillins stattfindet.
Es wurde nun gefunden, dass man auch ohne Verwendung von Wasser als Lösungsmittel zu Salzen des Ampicillins gelangen kann, wenn man Ampicillin in einem organischen Lösungsmittel suspendiert, es durch Zugeben eines Trialkylaminsalzes, z. B. Triäthylamin, in Lösung bringt, gegebenenfalls Verunreinigungen abfiltriert und nun das Trialkylaminsalz des Ampicillins durch Eindampfen des Filtrates in Substanz gewinnt.
Man kann aber auch so verfahren, dass man das Salz durch Zugeben eines Lösungsmittels, in dem es schwer löslich ist, abscheidet. Ferner ist es möglich, dass man zu dem Filtrat, in dem sich das Trialkylaminsalz des Ampicillins befindet, eine Lösung eines anderen Salzes hinzugibt und durch doppelte Umsetzung (Austausch der Kationen) ein in dem betreffenden Lösungsmittel oder Lösungsmittelgemisch schwer lösliches Salz des Ampicillins ausfällt.
Zur Aufnahme des Trialkylaminsalzes des Ampicillins eignen sich zum Beispiel folgende Lösungsmittel: Methylenchlorid, Chloroform, Methanol, Dimethylformamid, Formamid, Aceton, Acetonitril, Äthanol, Dimethylsulfoxyd und Glykolmonomethyläther. Besonders bewährt haben sich Methylenchlorid und Chloroform.
Unter den Trialkvlaminen hat sich besonders das Tri äthylamin bewährt, aber auch Trimethylamin, Methyldiäthylamin, Tripropylamin usw. sind geeignet. Um das Ampicillin in diesen Lösungsmitteln in Lösung zu bringen, benötigt man 1 Mol Trialkylamin pro Mol Ampicillin. Man verfährt dabei beispielsweise wie folgt: Das Ampicillin wird in dem betreffenden Lösungsmittel suspendiert, die Suspension auf etwa 0 C abgekühlt, das Trialkylamin zugegeben, dann etwa 45 Minuten bei 0 C gerührt, von ungelöst gebliebenen Verunreinigungen abfiltriert und das Filtrat in einem Rotationsverdampfer eingedampft. Als Eindampfrückstand erhält man das Trialkylaminsalz des Ampicillins als schönes, lockeres, weisses Pulver. Es löst sich sehr gut in Wasser.
Die wässrige Lösung hat je nach Konzentration einen pH von etwa 7,8 bis 8,3. Es ist daher zur Bereitung von Injektionslösungen geeignet. Wenn das verwendete Ampillin eine Reinheit von 77,35 % hat, erhält man daraus auf dem geschilderten Wege ein 99,09 % reines Triäthyl aminsalz in einer Ausbeute von 92 % der Theorie.
Man kann das Trialkylaminsalz des Ampicillins aus dem Filtrat aber auch so isolieren, dass man es durch Zugabe von Äther, Petroläther, Ligroin, Essigester, Benzol, Tetrachlorkohlenstoff, Butanol ausfällt und abfiltriert.
Will man nicht ein Trialkylaminsalz, sondern beispielsweise ein Alkalisalz des Ampicillins herstellen, so gibt man zu dem Filtrat eine Lösung eines Alkalisalzes einer Carbonsäure in einem organischen Lösungsmittel, beispielsweise eine ätherische oder acetonische Lösung des Kaliumsalzes der 2-Athylhexancar- bonsäure. Dann fällt sofort das Kaliumsalz des Ampicillins aus und kann abgesaugt werden. Auch das Kaliumsalz des Ampicillins ist in Wasser sehr gut löslich und kann daher zur Herstellung von Injektionslösungen verwendet werden.
Beispiel 1
40 g gepulvertes Ampicillin (Reinheit 77,35 %) werden in 500 cm8 trockenem Methylenchlorid suspendiert, auf etwa 0 C abgekühlt, dann 9,14 g Triäthylamin zugegeben, anschliessend 45 Minuten bei 0 C gerührt, dann ungelöste Verunreinigungen abgesaugt (4,6 g), das Filtrat im Rotationsverdampfer in einem Bad von 250 C eingedampft, der Rückstand über P2Os getrocknet, gepulvert, nochmals mit etwas abs. Äther gewaschen und getrocknet.
Ausbeute: 36,2 g Triäthylaminsalz des Ampleillins (92 % der Theorie)
Reinheit: 99,09 %
Beispiel 2
400 g Ampicillin (Reinheit 77, 35 %) werden in 5 Liter Methylenchlorid unter Zusatz von 91,4 g Tri äthylamin - wie im Beispiel 1 beschrieben - gelöst, Verunreinigungen abfiltriert und aus dem Filtrat durch Zugeben reichlicher Mengen Petroläther - (man kann das Filtrat auch erst im Vakuum etwas einengen) - das Triäthylaminsalz des Ampicillins ausgefällt.
Ausbeute: 285 g (72 % der Theorie).
Reinheit: 98,26 %
Beispiel 3
30 g Ampicillin (Reinheit 86,5R) werden mittels 11,25 g Triäthylamin - wie im Beispiel 1 beschrieben in 385 cm3 Methylenchlorid gelöst, Verunreinigungen abfiltriert, mit 30 cm3 Methylenchlorid nachgewaschen, zu den vereinigten Filtraten bei 0 C soviel einer acetonischen Kaliumsalzlösung der 2-Athylcapronsäure (50 g Kalium im Liter enthaltend) gegeben, bis nichts mehr ausfällt. Man lässt noch 30 Minuten bei 0 C stehen, saugt dann das ausgeschiedene K-Salz des Ampicillins ab, wäscht mit insgesamt 150 cm3. Äther und trocknet über P205 im Exseccator.
Ausbeute: 20,5 g (72 % der Theorie)
Reinheit: 98 %
Die Reinheitsangaben beziehen sich auf eine jodometrische Bestimmung des ss-Lactamringes.
Process for the preparation of water-soluble salts of ampicillin
Processes for the production of water-soluble salts of ampicillin, which are suitable for the production of injection solutions, have not yet been described. This may be due to the fact that aqueous solutions of such salts of ampicillin, which can be prepared, for example, by dissolving the ampicillin in the calculated amount of an aqueous sodium bicarbonate solution, are not very stable. If such solutions are evaporated under the most gentle conditions to obtain the salt (rotary evaporator; freeze-drying), a salt is obtained in which the penicillin is already about half destroyed. It does not seem to be possible to isolate salts of ampicillin from aqueous solutions without considerable decomposition of the ampicillin taking place.
It has now been found that you can get to salts of ampicillin without using water as a solvent, if ampicillin is suspended in an organic solvent, it by adding a trialkylamine salt, for. B. triethylamine, dissolves, any impurities are filtered off and the trialkylamine salt of ampicillin wins by evaporating the filtrate in substance.
However, one can also proceed in such a way that the salt is separated off by adding a solvent in which it is sparingly soluble. It is also possible that a solution of another salt is added to the filtrate in which the trialkylamine salt of ampicillin is located and a salt of ampicillin which is sparingly soluble in the solvent or solvent mixture in question is precipitated by double conversion (exchange of cations).
The following solvents, for example, are suitable for taking up the trialkylamine salt of ampicillin: methylene chloride, chloroform, methanol, dimethylformamide, formamide, acetone, acetonitrile, ethanol, dimethyl sulfoxide and glycol monomethyl ether. Methylene chloride and chloroform have proven particularly useful.
Among the trialkvlamines, triethylamine has proven particularly useful, but trimethylamine, methyldiethylamine, tripropylamine, etc. are also suitable. In order to bring the ampicillin into solution in these solvents, 1 mole of trialkylamine per mole of ampicillin is required. The procedure is as follows, for example: the ampicillin is suspended in the solvent in question, the suspension is cooled to about 0 ° C., the trialkylamine is added, then stirred for about 45 minutes at 0 ° C., undissolved impurities are filtered off and the filtrate is evaporated in a rotary evaporator. The trialkylamine salt of ampicillin is obtained as an evaporation residue as a nice, loose, white powder. It dissolves very well in water.
The aqueous solution has a pH of about 7.8 to 8.3, depending on the concentration. It is therefore suitable for the preparation of injection solutions. If the ampillin used has a purity of 77.35%, a 99.09% pure triethylamine salt is obtained therefrom in a yield of 92% of theory in the route described.
The trialkylamine salt of ampicillin can also be isolated from the filtrate in such a way that it is precipitated and filtered off by adding ether, petroleum ether, ligroin, ethyl acetate, benzene, carbon tetrachloride and butanol.
If one does not want to prepare a trialkylamine salt but, for example, an alkali salt of ampicillin, a solution of an alkali salt of a carboxylic acid in an organic solvent, for example an ethereal or acetone solution of the potassium salt of 2-ethylhexanecarboxylic acid, is added to the filtrate. Then the potassium salt of the ampicillin precipitates immediately and can be suctioned off. The potassium salt of ampicillin is also very soluble in water and can therefore be used to make injection solutions.
example 1
40 g of powdered ampicillin (purity 77.35%) are suspended in 500 cm8 of dry methylene chloride, cooled to about 0 C, then 9.14 g of triethylamine are added, then stirred for 45 minutes at 0 C, then undissolved impurities are suctioned off (4.6 g ), the filtrate evaporated in a rotary evaporator in a bath at 250 ° C., the residue dried over P2Os, powdered, again with a little abs. Ether washed and dried.
Yield: 36.2 g of triethylamine salt of ampleillin (92% of theory)
Purity: 99.09%
Example 2
400 g of ampicillin (purity 77, 35%) are dissolved in 5 liters of methylene chloride with the addition of 91.4 g of triethylamine - as described in Example 1 -, impurities are filtered off and removed from the filtrate by adding copious amounts of petroleum ether - (the filtrate can also concentrate a little in a vacuum) - the triethylamine salt of ampicillin precipitated.
Yield: 285 g (72% of theory).
Purity: 98.26%
Example 3
30 g of ampicillin (purity 86.5R) are dissolved using 11.25 g of triethylamine - as described in Example 1 in 385 cm3 of methylene chloride, impurities are filtered off, washed with 30 cm3 of methylene chloride, and the combined filtrates at 0 ° C. are as much as an acetone potassium salt solution of the 2nd -Athylcaproic acid (containing 50 g of potassium per liter) added until nothing more precipitates. It is left to stand at 0 C for a further 30 minutes, then the precipitated K salt of the ampicillin is filtered off with suction and washed with a total of 150 cm3. Ether and dry over P205 in the Exseccator.
Yield: 20.5 g (72% of theory)
Purity: 98%
The purity information relates to an iodometric determination of the ß-lactam ring.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF37738A DE1197460B (en) | 1962-09-04 | 1962-09-04 | Process for the production of very pure alkali salts of alpha-aminobenzylpenicilli |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH428735A true CH428735A (en) | 1967-01-31 |
Family
ID=7097030
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1040863A CH428735A (en) | 1962-09-04 | 1963-08-23 | Process for the preparation of water-soluble salts of ampicillin |
Country Status (7)
| Country | Link |
|---|---|
| AT (1) | AT242296B (en) |
| BE (1) | BE636974A (en) |
| CH (1) | CH428735A (en) |
| DE (1) | DE1197460B (en) |
| DK (1) | DK103185C (en) |
| GB (1) | GB980240A (en) |
| NL (2) | NL141198B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3856779A (en) * | 1966-03-03 | 1974-12-24 | D Clark | Process for the preparation of sodium salt of ampicillin |
| US3932386A (en) | 1973-06-18 | 1976-01-13 | American Home Products Corporation | Sodium 6-(L-aminocyclohexane carboxamido)penicillanic acid |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2985648A (en) * | 1958-10-06 | 1961-05-23 | Doyle Frank Peter | Alpha-aminobenzylpenicillins |
-
0
- NL NL297405D patent/NL297405A/xx unknown
- BE BE636974D patent/BE636974A/xx unknown
-
1962
- 1962-09-04 DE DEF37738A patent/DE1197460B/en active Pending
-
1963
- 1963-08-23 CH CH1040863A patent/CH428735A/en unknown
- 1963-08-28 GB GB3403963A patent/GB980240A/en not_active Expired
- 1963-09-02 AT AT704363A patent/AT242296B/en active
- 1963-09-02 NL NL297405A patent/NL141198B/en not_active IP Right Cessation
- 1963-09-03 DK DK417163A patent/DK103185C/en active
Also Published As
| Publication number | Publication date |
|---|---|
| GB980240A (en) | 1965-01-13 |
| NL141198B (en) | 1974-02-15 |
| AT242296B (en) | 1965-09-10 |
| DE1197460B (en) | 1965-07-29 |
| DK103185C (en) | 1965-11-29 |
| NL297405A (en) | |
| BE636974A (en) |
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| CH273250A (en) | Process for the preparation of a new derivative of p-amino-salicylic acid. | |
| CH243026A (en) | Process for the preparation of a soluble salt of 4,4'-di-amidino-diphenyl ether. | |
| CH304877A (en) | Process for the production of a sparingly soluble penicillin compound. |