GB2073192A - Cefadroxil Salts - Google Patents
Cefadroxil Salts Download PDFInfo
- Publication number
- GB2073192A GB2073192A GB8109981A GB8109981A GB2073192A GB 2073192 A GB2073192 A GB 2073192A GB 8109981 A GB8109981 A GB 8109981A GB 8109981 A GB8109981 A GB 8109981A GB 2073192 A GB2073192 A GB 2073192A
- Authority
- GB
- United Kingdom
- Prior art keywords
- cefadroxil
- aminoacid
- salts
- solution
- 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
- NBFNMSULHIODTC-CYJZLJNKSA-N cefadroxil monohydrate Chemical class O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=C(O)C=C1 NBFNMSULHIODTC-CYJZLJNKSA-N 0.000 title claims abstract description 18
- 229960004841 cefadroxil Drugs 0.000 claims abstract description 15
- 235000001014 amino acid Nutrition 0.000 claims abstract description 10
- -1 Aminoacid salts Chemical class 0.000 claims abstract description 6
- 150000001413 amino acids Chemical class 0.000 claims abstract description 6
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims abstract description 4
- 229930064664 L-arginine Natural products 0.000 claims abstract description 4
- 235000014852 L-arginine Nutrition 0.000 claims abstract description 4
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 claims abstract description 4
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims abstract description 3
- 229960004308 acetylcysteine Drugs 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 abstract description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 8
- 238000004108 freeze drying Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 230000003226 decolorizating effect Effects 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-M lysinate Chemical compound NCCCCC(N)C([O-])=O KDXKERNSBIXSRK-UHFFFAOYSA-M 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- FSILHPZFNRDTOR-RZVRUWJTSA-N (2R)-2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)N[C@@H](CS)C(O)=O.CC(=O)N[C@@H](CS)C(O)=O FSILHPZFNRDTOR-RZVRUWJTSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- PEWXENMTDDNSMK-BYPYZUCNSA-N acetyl (2r)-2-amino-3-sulfanylpropanoate Chemical compound CC(=O)OC(=O)[C@@H](N)CS PEWXENMTDDNSMK-BYPYZUCNSA-N 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 229960001065 cefadroxil monohydrate Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
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)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (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)
Abstract
Aminoacid salts of cefadroxil can be administered parenterally to release the antibiotic cefadroxil and the aminoacid. The aminoacid may be L-lysine, L-arginine or acetylcysteine.
Description
SPECIFICATION
Cefadroxil Salts
The antibiotic cefadroxil, i.e. p-hydroxycephalexin, is described in US Patent Specification No.
3,489,752. It is a broad-spectrum antibiotic which is usually adminsitered orally. It would be desirable to provide a form of cefadroxil which could be injected without causing painful reaction.
The novel compounds of this invention are amino-acid salts of cefadroxil. The aminoacid is preferably L-lysine, L-arginine or acetylcysteine.
A salt of the invention may be perpared by reacting an aqueous solution of cefadroxil with an aqueous solution of the aminoacid, or a derivative thereof. the reaction may be conducted at ambient temperature. The cefadroxil salt may be isolated from the aqueous solution by lyophilisation.
For administration to a subject, a salt of this invention may be provided in association with a physiologically acceptable excipient, in the form of a pharmaceutical composition. When administered, a salt of this invention may break down to the antibiotic principle cefadroxil and an aminoacid which may itself have a desirable action.
The following Examples illustrate how the compounds of this invention may be prepared.
Example 1
Cefadroxil Arginine Salt
L-arginine (21 g, 0.1 mole) was added to a suspension of cefadroxil dimethylformamide solvate (43.6 g, 0.1 mole) in distilled water (300 ml); the pH rose to 8 and complete dissolution was obtained.
3 g of decolourising carbon were added to the resultant solution, which was then filtered through
Decalite. The filtered solution was poured into a tray to give a 1 cm deep layer; after pre-freezing, the solution was frozen at -400C and lyophilisation was started. Lyophilisation was complete in 36 hours.
After lyophilisation, the product was screened and 50.1 g of the arginine salt of cefadroxil were obtained.
Example 2
Cephadroxyl Acetylcysteinate
N-acetylcysteine (16.32 g, 0.1 mole), dissolved in distilled water (200 ml) at 1 5-200C, was added to a suspension of cefadroxil dimethylformamide solvate (43.6 g, 0.1 mole) in distilled water (350 ml). Complete dissolution was obtained. After 30 minutes, carbon (2.5 g) was added to the resultant solution at OOC. After 30 minutes stirring, the solution was filtered through Decalite. The resultant clear solution was poured into a tray to give a 1 cm deep layer which was frozen at -400C and lyophilised. Lyophilisation lasted 36 hours. The white crystalline product which was obtained was screened and 49 g of cephadroxyl acetylcysteinate were obtained.
Example 3
Cephadroxyl Lysinate
Twice distilled water (600 mi) and cephadroxyl dimethylformamide solvate (43.6 g, 0.1 mole) were charged into a reaction vessel at OOC. A 50% L-lysine base aqueous solution, containing 14.6 g (0.1 mole) L-lysine, was added to the resultant suspension; the mixture was stirred for 1 hour at OOC.
Complete dissolution was obtained and the pH rose to 8.5. Decolourising carbon (1.5 g) was added to the resultant solution which was filtered through filter plates and poured into a tray to give a 1 cm deep layer was obtained. The solution was then frozen at -350C and lyophilised. The resulting material was discharged and screened; cephadroxyl lysinate (48 g) was obtained.
The results obtained in each of the above Examples could be repeated by using cefadroxil monohydrate (38.1 g) instead of the cefadroxil dimethylformamide solvate.
The properties of the products of Examples are tabulated below. Thin layer chromatography (TLC) was conducted using a 20:5:2 v/v/v mixture of acetonitrile, water and formic acid as eluent. The optical rotation values were obtained using sodium D light (c=1, H20). The microbiological (Mb) titres were obtained with respect to cefadroxil in dry base form.
Example 1 2 3 K. F. (%) 1 0.7 1.3
TLC (spots) 1 1 1 []D ( ) +118 +115 +110
Mb titre (mcg/mg) 665 668 709
The formulae of the products of the Examples may be respectively represented as follows
Claims (6)
1. An aminoacid salt of cefadroxil.
2. An aminoacid salt of cefadroxil, in which the aminoacid is L-lysine, L-arginine cr acetylcysteine
3. A compound of formula I as herein defined.
4. A compound of formula Il as herein defined.
5. A compound of formula Ill as herein defined.
6. A pharmaceutical composition comprising a compound as claimed in any preceding claim in
association with a physiologically acceptable excipient.
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 (2)
| Publication Number | Publication Date |
|---|---|
| GB2073192A true GB2073192A (en) | 1981-10-14 |
| GB2073192B GB2073192B (en) | 1983-12-07 |
Family
ID=11176702
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8109981A Expired GB2073192B (en) | 1980-04-01 | 1981-03-31 | Cefadroxil salts |
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) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102351885A (en) * | 2011-08-19 | 2012-02-15 | 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 YU YU00846/81A patent/YU84681A/en unknown
- 1981-03-31 GB GB8109981A patent/GB2073192B/en not_active Expired
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102351885A (en) * | 2011-08-19 | 2012-02-15 | 深圳立健药业有限公司 | Method for preparing cefuroxime-L-arginine hydrate |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| IT1148778B (en) | 1986-12-03 |
| CH651048A5 (en) | 1985-08-30 |
| CA1146543A (en) | 1983-05-17 |
| JPH0161115B2 (en) | 1989-12-27 |
| JPS56140996A (en) | 1981-11-04 |
| IL62377A (en) | 1984-10-31 |
| IT8021098A0 (en) | 1980-04-01 |
| IL62377A0 (en) | 1981-05-20 |
| FR2479226B1 (en) | 1984-11-02 |
| FR2479226A1 (en) | 1981-10-02 |
| GB2073192B (en) | 1983-12-07 |
| NL8101272A (en) | 1981-11-02 |
| YU84681A (en) | 1983-10-31 |
| DE3112168A1 (en) | 1982-01-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19950331 |