US4418058A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Protection of lyophilized betalactams from color formation
Assignee: Shionogi and Co Ltd
•
Filing: 1981-06-12
•
Granted: 1983-11-29
•
Expires: 2001-06-12
Abstract
Abstract A stable preparation of a lyophilized β-lactam antibacterial containing a 7β-(α-carboxy-α-arylacetamido)-7α-methoxy-3-heterocyclic thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid (I) alkali metal salt as the antibacterial component and a sugar or sugar alcohol compound as the stabilizing agent. ##STR1## (wherein Ar is a p-hydroxyaryl group and Het is a heterocyclic group optionally substituted by an alkyl group)
Inventors
- 👤 Eizo Hirai
- 👤 Kazuhiro Shima
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 20:25
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/54; A61K31/542; A61K31/545; A61K9/00; A61K9/0012; A61K9/0019; A61K31/535; A61K47/00; A61K47/06; A61K47/26; A61P; A61P31/00; A61P31/04
Claims Analysis
Total Claims: 28
Claim 1
Independent Claim
144 words
A stable lyophilized antibacterial preparation containing an alkali metal salt of 7β-(α-carboxy-α-arylacetamido)-7α-methoxy-3-heterocyclic thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid of the formula ##STR3## wherein Ar is a p-hydroxyphenyl group which is unsubstituted or substituted by halogen, hydroxy, 1 to 3 C alkoxy or 1 to 3 C alkyl, and Het is a 5 to 6 membered monocyclic heterocyclic group having 3 or 4 heteroatoms selected from nitrogen, oxygen or sulfur which is unsubstituted or is substituted by 1 to 5 C alkyl as antibacterial component and 0.1 to 1.0 part per part by weight antibacterial component of a sugar or sugar alcohol compound selected from arabitol, dambonitrol, dulcitol, inositol, mannitol, ononitol, pinitol, quercitol, sequoytol, sorbitol, viburnitol, xylitol, allose, altrose, arabinose, fructose, galactose, glucose, gulose, idose, lactose, lyxose, maltose, mannose, ribose, ribulose, sedoheptulose, sorbose, sucrose, tagatose, talose and xylose as stabilizing agent for the purpose of preventing blue color formation.
Claim 2
Dependent Claim
144 words
A stable lyophilized antibacterial preparation containing an alkali metal salt of 7β-(α-carboxy-α-arylacetamido)-7α-methoxy-3-heterocyclic thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid of the formula ##STR3## wherein Ar is a p-hydroxyphenyl group which is unsubstituted or substituted by halogen, hydroxy, 1 to 3 C alkoxy or 1 to 3 C alkyl, and Het is a 5 to 6 membered monocyclic heterocyclic group having 3 or 4 heteroatoms selected from nitrogen, oxygen or sulfur which is unsubstituted or is substituted by 1 to 5 C alkyl as antibacterial component and 0.1 to 1.0 part per part by weight antibacterial component of a sugar or sugar alcohol compound selected from arabitol, dambonitrol, dulcitol, inositol, mannitol, ononitol, pinitol, quercitol, sequoytol, sorbitol, viburnitol, xylitol, allose, altrose, arabinose, fructose, galactose, glucose, gulose, idose, lactose, lyxose, maltose, mannose, ribose, ribulose, sedoheptulose, sorbose, sucrose, tagatose, talose and xylose as stabilizing agent for the purpose of preventing blue color formation.
Claim 3
Dependent Claim
19 words
A preparation claimed in claim 1 in which the Ar group of the antibacterial component is p-hydroxyphenyl or 4-hydroxy-2-fluorophenyl.
Claim 4
Dependent Claim
26 words
A preparation claimed in claim 1 in which the Het group of the antibacterial component is unsubstituted or has methyl, ethyl or isobutyl as the substituent.
Claim 5
Dependent Claim
23 words
A preparation claimed in claim 1 in which the Het group of the antibacterial component is selected from 1,2,3-triazol-4-yl, 1-methyl-5-tetrazolyl, 1,3,4-thiadiazol-2-yl and 2-methyl-1,3,4-thiadiazol-5-yl.
Claim 6
Dependent Claim
19 words
A preparation claimed in claim 1 in which the alkali metal salt is a lithium, sodium or potassium salt.
Claim 7
Dependent Claim
24 words
A preparation claimed in claim 1 in which the antibacterial component is a mixture of one or more kinds of the alkali metal salts.
Claim 8
Dependent Claim
15 words
A preparation claimed in claim 1 in which the sugar alcohol has 6 carbon atoms.
Claim 9
Dependent Claim
24 words
A preparation claimed in claim 1 in which the sugar alcohol or sugar is selected from mannitol, sorbitol, xylitol, arabinose, fructose, sorbose and xylose.
Claim 10
Dependent Claim
21 words
A preparation claimed in claim 1 in which the sugar alcohol or sugar is selected from dulcitol, inositol, glucose, and mannose.
Claim 11
Dependent Claim
13 words
A preparation claimed in claim 1 that contains mannitol as the sugar alcohol.
Claim 12
Dependent Claim
25 words
A preparation claimed in claim 1 which is prepared by freeze drying of a mixed aqueous solution containing the antibacterial component and the stabilizing agent.
Claim 13
Dependent Claim
21 words
A preparation claimed in claim 1 that contains a sodium salt of 7β-(α-carboxy-α-p-hydroxyphenylacetamido)-7α-methoxy-3-(1-methyl-5-tetrazolyl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid, 7β-(α-carboxy-α-p-hydroxyphenylacetamido)-7α-methoxy-b 3-(1,3,4-thiadiazol-2-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid, 7β-(α-carboxy-α-p-hydroxyphenylacetamido)-7α-methoxy-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylicacid or 7β-(α-(4-hydroxy-2-fluorophenyl)-α-carboxyacetamido)-7.alpha.-methoxy-3-(2-methyl-1,3,4-thiadiazol-5-yl)thiomethyl-1-dethia-1-oxa-3-cephem-4-carboxylic acid.
Claim 14
Dependent Claim
16 words
A preparation claimed in claim 1 in which the salt is a sodium or potassium salt.
Claim 15
Dependent Claim
15 words
A preparation claimed in claim 1 in which the salt is a mono-salt or di-salt.
Claim 16
Dependent Claim
19 words
A preparation claimed in claim 1 in which the antibacterial component is a mixture of the alkali metal salts.
Claim 17
Dependent Claim
11 words
A preparation claimed in claim 1 stored in an inert gas.
Claim 18
Dependent Claim
73 words
A method for the production of a lyophilized antibacterial preparation as defined in claim 1 which comprises (1) dissolving the antibacterial component and the stabilizing agent, said component and agent being as defined in claim 1, in an injectable aqueous carrier to obtain a mixed aqueous solution; (2) cooling the solution to freezing at subzero temperature and (3) subliming the water contained in the frozen mass to obtain a non-coloring table lyophilized preparation.
Claim 19
Dependent Claim
19 words
A method claimed in claim 17 wherein the freezing and subliming are carried out in a tray or vial.
Claim 20
Dependent Claim
19 words
A method claimed in claim 17 in which the Ar group of the antibacterial component is p-hydroxyphenyl or 4-hydroxy-2-fluorophenyl.
Claim 21
Dependent Claim
26 words
A method claimed in claim 17 in which the Het group of the antibacterial component is unsubstituted or has methyl, ethyl or isobutyl as the substituent.
Claim 22
Dependent Claim
23 words
A method claimed in claim 17 in which the Het group of the antibacterial component is selected from 1,2,3-triazol-4-yl, 1-methyl-5-tetrazolyl, 1,3,4-thiadiazol-2-yl and 2-methyl-1,3,4-thiadiazol-5-yl.
Claim 23
Dependent Claim
19 words
A method claimed in claim 17 in which the alkali metal salt is a lithium, sodium or potassium salt.
Claim 24
Dependent Claim
22 words
A method claimed in claim 17 in which the antibacterial component is a mixture of one or more kinds of the salts.
Claim 25
Dependent Claim
15 words
A method claimed in claim 17 in which the sugar alcohol has 6 carbon atoms.
Claim 26
Dependent Claim
24 words
A method claimed in claim 17 in which the sugar alcohol or sugar is selected from mannitol, sorbitol, xylitol, arabinose, fructose, sorbose and xylose.
Claim 27
Dependent Claim
21 words
A method claimed in claim 17 in which the sugar alcohol or sugar is selected from dulcitol, inositol, glucose and mannose.
Claim 28
Dependent Claim
13 words
A method claimed in claim 17 in which the sugar alcohol is mannitol.
References Cited (Backward Citations)
US3993753A
Cited
US4180571A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-11-28 | 1987-05-30 | 1987-11-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-11-28 | 1991-05-30 | 1991-11-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-11-28 | 1995-05-30 | 1995-11-29 | $7700.00 | Window Closed / Lapsed |