CH651048A5 - SALTS OF CEFADROXIL WITH AMINO ACIDS. - Google Patents
SALTS OF CEFADROXIL WITH AMINO ACIDS. Download PDFInfo
- Publication number
- CH651048A5 CH651048A5 CH1733/81A CH173381A CH651048A5 CH 651048 A5 CH651048 A5 CH 651048A5 CH 1733/81 A CH1733/81 A CH 1733/81A CH 173381 A CH173381 A CH 173381A CH 651048 A5 CH651048 A5 CH 651048A5
- Authority
- CH
- Switzerland
- Prior art keywords
- cefadroxil
- salt
- salts
- cooh
- arginine
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/22—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with radicals containing only hydrogen and carbon atoms, attached in position 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
La presente invenzione ha per oggetto nuovi sali del cefradroxil con aminoacidi, aventi attività antibiotica. The present invention relates to new salts of cefradroxil with amino acids, having antibiotic activity.
Il Cefadroxil è un composto antibiotico ben noto, descritto nel brevetto USA 3 985 741. Cefadroxil is a well-known antibiotic compound, described in U.S. Patent 3 985 741.
Il Cefadroxil è normalmente somministrato-per via orale. Cefadroxil is normally administered-orally.
Uno scopo della presente invenzione è quello di ottenere dei nuovi sali del Cefadroxil i quali siano iniettabili e non provochino reazioni dolorose all'atto della loro somministrazione. An object of the present invention is to obtain new Cefadroxil salts which are injectable and do not cause painful reactions upon their administration.
Altro scopo è quello di realizzare dei sali del Cefadroxil che favoriscano l'assorbimento dell'antibiotico e che, una volta assorbiti nell'organismo, sviluppino ed associno alla attività antibiotica propria del Cefadroxil, la loro specifica attività che può essere interessante dal punto di vista farmacologico. Another purpose is to make Cefadroxil salts which promote the absorption of the antibiotic and which, once absorbed in the body, develop and associate their specific activity with Cefadroxil's antibiotic activity, which may be interesting from the point of view. pharmacological.
Questi ed altri scopi vengono conseguiti mediante salificazione del Cefadroxil con un aminoacido scelto dal gruppo costituito da L-lisina, L-arginina e acetilcisteina. These and other purposes are achieved by salification of Cefadroxil with an amino acid chosen from the group consisting of L-lysine, L-arginine and acetylcysteine.
Per ottenere questa salificazione il Cefadroxil viene fatto reagire in soluzione acquosa ed a temperatura ambiente, con una soluzione acquosa di una aminoacido o suo derivato scelto dal gruppo costituito da L-lisina, L-arginina e acetilcisteina, dalla soluzione acquosa venendo isolato il sale del Cefadroxil per liofilizzazione. To obtain this salification, Cefadroxil is reacted in an aqueous solution and at room temperature, with an aqueous solution of an amino acid or its derivative chosen from the group consisting of L-lysine, L-arginine and acetylcysteine, from the aqueous solution the salt of the Cefadroxil for freeze drying.
Al fine di rendere più chiara la comprensione della pre-5 sente invenzione, verrà descritta, a titolo puramente esemplificativo una preparazione di ciascuno dei tre sali formanti oggetto della presente invenzione. In order to clarify the understanding of the present invention, a preparation of each of the three salts forming the subject of the present invention will be described purely by way of example.
Esempio 1 Cefadroxil sale di arginina avente formula cooh. h„n Example 1 Cefadroxil arginine salt having the formula cooh. h "n
HO. I HAVE.
W W
NH„ NH "
■ e. ■ e.
^c-nh- (ch2) 3-cr-c00h nh ^ c-nh- (ch2) 3-cr-c00h nh
43,6 g (0,1 mole) di Cefadroxil dimetilformamidesolvato 20 si sospendono in 300 mi di HzO distillata, alla sospensione così ottenuta si aggiungono 21 g (0.1 mole) di L-arginina il pH sale a 8 e si ha dissoluzione completa. 43.6 g (0.1 mole) of Cefadroxil dimethylformamidesolvate 20 are suspended in 300 ml of distilled HzO, 21 g (0.1 mole) of L-arginine are added to the suspension thus obtained, the pH rises to 8 and complete dissolution is obtained.
Alla soluzione così ottenuta si aggiungono 3 g di carbone decolorante e si filtra su dicalite. La soluzione così otte-25 nuta si pone in bacinella facendo uno strato di 1 cm, si pone in precongelatore e dopo aver congelato a —40°C si inizia la liofilizzazione che si termina in 36 h. To the solution thus obtained, 3 g of bleaching carbon are added and filtered on dicalite. The solution thus obtained is placed in a basin making a layer of 1 cm, it is placed in a pre-freezer and after freezing at -40 ° C the freeze-drying is started which ends in 36 h.
Finita la liofilzzazione si setaccia e si ottengono 50,1 g di Cefadroxil sale di arginina. Once the freeze-drying is finished, it is sieved and 50.1 g of Cefadroxil arginine salt are obtained.
30 K.F. 1% 30 K.F. 1%
TLG macchia singola TLG single spot
Eluente: acetonitrile: H20 : Acido Formico = 20:5:2 [a]„(C= 1, H20) + 118° Eluent: acetonitrile: H20: Formic Acid = 20: 5: 2 [a] "(C = 1, H20) + 118 °
Titolo microbiologico: 665 mcg/mg come Cefadroxil base 35 anidra. Microbiological titre: 665 mcg / mg as anhydrous Cefadroxil base 35.
Lo stesso risultato viene ottenuto utilizzando 38.1 g di Cefadroxil monoidrato al posto del Cefadroxil dimetilform-amide solvato. The same result is obtained by using 38.1 g of Cefadroxil monohydrate instead of Cefadroxil dimethylform-amide solvate.
40 Esempio 2 40 Example 2
Cefadroxil acetilcisteinato avente formula ho ch-conh Cefadroxil acetylcysteinate having formula ho ch-conh
ch, ch,
nh2.h00c cooh nh2.h00c cooh
50 dlh-ch0-sh i 2 50 dlh-ch0-sh i 2
nh-c0ch3 nh-c0ch3
4.36 g (0.1 mole) di Cefadroxil dimetilformamide sol-55 vato si sospendono in 350 mi di H20 distillata; a 15° - 20°C si aggiungono 16.32 g (0.1 mole) di N-acetilcisteina sciolta in 200 mi di H20 distillata. Si ha dissoluzione completa; dopo 30' a 0°C alla soluzione così ottenuta si aggiungono 2.5 di carbone, si mantiene in agitazione per 30' e si filtra 60 su decalite. La soluzione limpida così ottenuta si pone in bacinella facendo uno strato di 1 cm, si congela a —40°C quindi si liofilizza. 4.36 g (0.1 mole) of Cefadroxil dimethylformamide sol-55 vate are suspended in 350 ml of distilled H2O; at 15 ° - 20 ° C 16.32 g (0.1 mole) of N-acetylcysteine dissolved in 200 ml of distilled H2O are added. Complete dissolution occurs; after 30 'at 0 ° C, 2.5 of carbon are added to the solution thus obtained, stirring for 30' and filtered on decalite. The clear solution thus obtained is placed in a basin making a 1 cm layer, freezing at -40 ° C and then freeze-drying.
Il prodotto cristallino bianco ottenuto si setacci e >i ottengono 49 g di cefadroxilacetilcisteinato. The white crystalline product obtained is sieved and> 49 g of cefadroxylacetylcysteinate are obtained.
65 K.F. 0.7% 65 K.F. 0.7%
TLC: macchia singola TLC: single spot
Eluente : acetonitrile: H20 : acido formico = 20 : 5 :2 [a]„(c= 1,H20) = +115° Eluent: acetonitrile: H20: formic acid = 20: 5: 2 [a] "(c = 1, H20) = + 115 °
3 3
651 048 651 048
E'^m a 262 nm = 163 It is ^ m at 262 nm = 163
Titolo microbiologico : 688 mcg/mg come Cefadroxil base secca. Microbiological title: 688 mcg / mg as dry Cefadroxil base.
Lo stesso risultato si ottiene utilizzando 38.1 g di Cefadroxil monoidrato invece del Cefadroxil formamide solvato. The same result is obtained by using 38.1 g of Cefadroxil monohydrate instead of Cefadroxil formamide solvate.
Esempio 3 Cefadroxil Ihinato avente formula Example 3 Cefadroxil Ihinate having formula
^-C0NH ^ -C0NH
CH, CH,
C00H.H2N-(CH2)4-CH-C00H NH„ C00H.H2N- (CH2) 4-CH-C00H NH "
In reattore si caricano 600 mi di H,0 bidistillata e a 600 ml of H, 0 bidistilled and a are added to the reactor
0°C 43.6 g (0.1 mole) di Cefadroxil dimetilformamide solvato. A questa sospensione si aggiunge poi una soluzione acquosa al 50% contenente 14.6 g (0.1 mole) di L-lisina base e si lascia in agitazione a 0°C per 1 h. Si ha una solu-5 zione completa ed il pH sale a 8.5. Alla soluzione così ottenuta si aggiungono 1.5 g di carbone decolorante si filtra su filtro a piastre, si pone quindi in bacinella facendo uno strato di soluzione alto 1 cm, si congela a —35°C e si liofilizza. Dopo 24 h si scarica, si setaccia e si raccolgono 48 g 10 di Cefadroxil lisinato. 0 ° C 43.6 g (0.1 mole) of Cefadroxil dimethylformamide solvate. To this suspension is then added a 50% aqueous solution containing 14.6 g (0.1 mole) of L-lysine base and is left under stirring at 0 ° C for 1 h. A complete solution is obtained and the pH rises to 8.5. 1.5 g of bleaching carbon are added to the solution thus obtained, filtered on a plate filter, then placed in a basin making a 1 cm high layer of solution, freezing at -35 ° C and freeze-drying. After 24 h it is discharged, sieved and 48 g 10 of Cefadroxil lysinate are collected.
K.F. 1.3% K.F. 1.3%
TLC macchia singola [a]D = +110° (C = 1, H20) Single spot TLC [a] D = + 110 ° (C = 1, H20)
Titolo microbiologico : 709 mcg/mg come. Cefadroxil base 15 anidra. Microbiological title: 709 mcg / mg as. Cefadroxil base 15 anhydrous.
Lo stesso risultato si ottiene utilizzando 38.1 di cefradroxil monoidrato invece del Cefadroxil formamide solvato. The same result is obtained by using 38.1 of cefradroxil monohydrate instead of Cefadroxil formamide solvate.
v v
Claims (5)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT21098/80A IT1148778B (en) | 1980-04-01 | 1980-04-01 | SALTS CEFADROVIXIL WITH AMINO ACIDS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH651048A5 true CH651048A5 (en) | 1985-08-30 |
Family
ID=11176702
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1733/81A CH651048A5 (en) | 1980-04-01 | 1981-03-13 | SALTS OF CEFADROXIL WITH AMINO ACIDS. |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS56140996A (en) |
| CA (1) | CA1146543A (en) |
| CH (1) | CH651048A5 (en) |
| DE (1) | DE3112168A1 (en) |
| FR (1) | FR2479226A1 (en) |
| GB (1) | GB2073192B (en) |
| IL (1) | IL62377A (en) |
| IT (1) | IT1148778B (en) |
| NL (1) | NL8101272A (en) |
| YU (1) | YU84681A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102351885B (en) * | 2011-08-19 | 2012-08-22 | 深圳立健药业有限公司 | Method for preparing cefuroxime-L-arginine hydrate |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3985741A (en) * | 1972-09-15 | 1976-10-12 | Bristol-Myers Company | Production of p-hydroxycephalexin |
| ES412429A1 (en) * | 1973-03-08 | 1976-01-01 | Gallardo Antonio Sa | Soluble salt of a cephalosporin |
| JPS5089517A (en) * | 1973-12-18 | 1975-07-18 | ||
| JPS557434A (en) * | 1978-06-30 | 1980-01-19 | Matsushita Electric Works Ltd | Preparation of woody cement board |
| ES472186A1 (en) * | 1978-07-28 | 1979-02-16 | Liofilizaciones Esterilizacion | Procedure for the obtaining of salts from the acid 7- (d - (-) a-amino a- (4-hydroxypenyl) acetamido) -3-methyl-3-cefem-4-carboxylic with amino acids. (Machine-translation by Google Translate, not legally binding) |
-
1980
- 1980-04-01 IT IT21098/80A patent/IT1148778B/en active
-
1981
- 1981-03-11 CA CA000372782A patent/CA1146543A/en not_active Expired
- 1981-03-13 CH CH1733/81A patent/CH651048A5/en not_active IP Right Cessation
- 1981-03-16 NL NL8101272A patent/NL8101272A/en not_active Application Discontinuation
- 1981-03-16 IL IL62377A patent/IL62377A/en unknown
- 1981-03-16 JP JP3666881A patent/JPS56140996A/en active Granted
- 1981-03-25 FR FR8106000A patent/FR2479226A1/en active Granted
- 1981-03-27 DE DE19813112168 patent/DE3112168A1/en not_active Withdrawn
- 1981-03-31 GB GB8109981A patent/GB2073192B/en not_active Expired
- 1981-03-31 YU YU00846/81A patent/YU84681A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NL8101272A (en) | 1981-11-02 |
| CA1146543A (en) | 1983-05-17 |
| GB2073192A (en) | 1981-10-14 |
| IL62377A0 (en) | 1981-05-20 |
| IL62377A (en) | 1984-10-31 |
| FR2479226A1 (en) | 1981-10-02 |
| YU84681A (en) | 1983-10-31 |
| JPH0161115B2 (en) | 1989-12-27 |
| JPS56140996A (en) | 1981-11-04 |
| FR2479226B1 (en) | 1984-11-02 |
| GB2073192B (en) | 1983-12-07 |
| IT1148778B (en) | 1986-12-03 |
| IT8021098A0 (en) | 1980-04-01 |
| DE3112168A1 (en) | 1982-01-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4950687A (en) | Diacetylrhein salts and their therapeutical use in the treatment of arthrosis | |
| US4942166A (en) | Crystalline purine compounds | |
| CZ286621B6 (en) | Tromethamine salt of (+)-(S)-2-(3-benzoylphenyl)propionic acid, process of its preparation and pharmaceutical preparation containing thereof | |
| DE1670625C3 (en) | y-alpha-aminobenzyl-S-methylcephalosporin analogs and their preparation | |
| KR950003612B1 (en) | Cephalosporin salts | |
| CH651048A5 (en) | SALTS OF CEFADROXIL WITH AMINO ACIDS. | |
| DE69222570D1 (en) | Phosphonic acid derivatives, process for their preparation and their use | |
| HU200186B (en) | Process for producing crystalline cefem acid addition salts and pharmaceutical compositions comprising same as active ingredient | |
| US4354023A (en) | Cefadroxil acetylcysteinate salt | |
| US4235900A (en) | Cephradine compositions | |
| DK157858B (en) | NIFLUMIC ACID COMPOUND AND PAIN AND ANTI-INFLAMMATIVE AGENT CONTAINING THIS | |
| CH651050A5 (en) | SALTS OF CEPHAPIRINE WITH AMINO ACIDS. | |
| US2890979A (en) | Procaine-2-pyrrolidone-5-carboxylate | |
| US3953497A (en) | 2,4,6-Triiodo-5-methoxyacetamido-N-methylisophthalamic acid and salts, acyl halides and esters thereof | |
| KR840000036B1 (en) | Process for preparing d-sesquisodium salt of the oxa- -lactam diacid | |
| DE2527291A1 (en) | ACYLDER DERIVATIVES | |
| CA1286285C (en) | Stable hydrate of penicillin derivative and process for preparing same | |
| US4189499A (en) | Lysine 4-allyloxy-3-chlorophenylacetate and method of its preparation | |
| US4734408A (en) | Crystalline cephalosporin antibiotic salts and solvates | |
| US4252953A (en) | Antibiotic crystalline epimer | |
| Haskel et al. | Semisynthetic penicillins. A structure-activity study of a new series of acyl amino acid-pyridone and pyrimidone amoxicillin analogs | |
| EP0160513B1 (en) | Fenoldopam 4', 8-bis-hydrogen sulfates | |
| JPS60169457A (en) | Novel lysine salt crystal and its preparation | |
| DE213711C (en) | ||
| DE2137386C3 (en) | 3-pyridylthiomethylcephalosporin compounds, processes for producing the same and pharmaceutical agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |