CN1795864A - Stable medication composition of cefathiamidine - Google Patents
Stable medication composition of cefathiamidine Download PDFInfo
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- CN1795864A CN1795864A CN 200410102451 CN200410102451A CN1795864A CN 1795864 A CN1795864 A CN 1795864A CN 200410102451 CN200410102451 CN 200410102451 CN 200410102451 A CN200410102451 A CN 200410102451A CN 1795864 A CN1795864 A CN 1795864A
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- cefathiamidine
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Abstract
A stable cefathiamidine composition contains the cefathiamidine and the antioxidizing agent chosen from L-cysteine, sodium hydrogen sulfite, VC and sodium thiosulfate in weight ratio of 1: (0.0001-1). It has high stability.
Description
Technical field
The present invention relates to a kind of stable medication composition of cefathiamidine, specifically, the present invention relates to the medication composition of cefathiamidine that a kind of quality is good, color and luster is stable, and improve the method for cefathiamidine stability.
Background technology
Cefathiamidine (cephathiamidin) is the first generation cephalosporin class antibacterials of succeeding in developing and carrying out clinical research and application in the world at present, and its antibiotic characteristics are to G
+The coccus effect is stronger, especially staphylococcus and enterococcus had very strong antibacterial activity, in addition, it all has good antibacterial action to Streptococcus viridans, Hemolytic streptococcus, anhemolytic streptococcus, staphylococcus epidermidis, encephalitis coccus, diphtheria corynebacterium, aerogenesis folder film bacillus, clostridium tetani and anthrax bacillus, hemophilus influenza, mucositis branhamella, and adverse reaction rate is lower.
In recent years, people have carried out various clinical researches to it, proved that cephathiamidin is used for the treatment of various gram-positive coccis (comprising the drug resistance coccus) infection clinically and has good and clinical curative effect, clinical total effective rate is up to 93.61%, compare with other antimicrobial drug commonly used clinically, more excellent and the less adverse effect of curative effect, this makes cephathiamidin establish its status firmly in clinical practice, has become to treat at present the choice drug that various gram-positive coccis infect clinically.
Cefathiamidine structure uniqueness; for having zwitterionic inner salt structure; chemical name is (6R; 7R)-and the 3[(acetyl group) methyl]-7-[a-(N; N '-diisopropylamidinateand sulfenyl)-acetylamino]-8-oxo-5-thia-1-azabicyclo [4; 2,0]-and oct-2-ene-2-formic acid betaine, molecular formula is: C
19H
18N
40
6S, structural formula is as follows:
Because the characteristics of structure, cefathiamidine is subject to the influence of external environmental condition and the variation of quality takes place, particularly to be subjected to temperature, humidity, illumination and conditions of air to influence variation bigger for color and luster, easily causes color and luster to deepen in packing, transportation and the storage process because of carelessness, influences the quality of product.This phenomenon has become the 'bottleneck' restrictions problem of this outstanding kind development.Because cefathiamidine is responsive to temperature, moisture and light application ratio, during, strong illumination higher in temperature and moisture, along with the prolongation of time, the easy variation of product quality, even lose medical value.
Not good to the problem of cefathiamidine color and luster, stability in the market solution, and more need the cefathiamidine preparation that matter is measured, color and luster is stable clinically.
Summary of the invention
The purpose of this invention is to provide the medication composition of cefathiamidine that a kind of quality is good, color and luster is stable.
Another object of the present invention provides a kind of method that improves medication composition of cefathiamidine stability.
The inventor finds to have improved the quality of cefathiamidine greatly by add specific antioxidizing agent in cefathiamidine, has obtained the stable cefathiamidine preparation of color and luster, thereby has solved the problem of prior art cefathiamidine color and luster mutability.
Technical scheme of the present invention is as follows:
A kind of stable medication composition of cefathiamidine, the antioxidant that it comprises cefathiamidine and is selected from a kind of or its mixture in L-cysteine, sodium sulfite, vitamin C and the sodium thiosulfate, wherein the weight ratio of cefathiamidine and antioxidant is 1: 0.0001-1.
The preparation method of medication composition of cefathiamidine of the present invention is to adopt conventional aseptic method for producing medicines, makes cefathiamidine and antioxidant uniform mixing or mixed forming in the aforementioned proportion scope.Wherein conventional powder pin production technology program is with behind the pure or pure water mixed dissolution of target compound water, aseptic filtration, in the organic solvents such as adding alcohols, ketone, esters, ethers, hydro carbons one or both or two or more mixed solvent are separated out solid, washing, the dry dry product that gets; Or with behind the pure or pure water mixed dissolution of target compound water, aseptic filtration, solvent flashing and separate out solid; Or sieve the target compound solid mixed through grinding.
The present invention also provides a kind of method that improves cefathiamidine stability, comprise adding the antioxidant that is selected from a kind of or its mixture in L-cysteine, sodium sulfite, vitamin C and the sodium thiosulfate in the cefathiamidine medicine, wherein the weight ratio of cefathiamidine and antioxidant is 1: 0.0001-1.
Analyzing cefathiamidine color and luster variation of the present invention and unsettled main cause may be that the cefathiamidine structure is easily oxidized, and the oxygen in the atmosphere is the major reason that causes oxidation of drug, and the general source of the oxygen in the preparation is water and air.Temperature raises, and generally accelerates oxidation reaction speed; Light also can excite oxidation reaction as a kind of radiant energy, quickens the decomposition of medicine, and reaction has remarkable catalytic action to trace metal ion to autoxidation; Humidity and moisture also quicken the oxidation and the decomposition of medicine.But the cefathiamidine color and luster changes and unsettled exact mechanism is also unclear at present.The way that the inventor selects to add antioxidant solves variation of cefathiamidine color and luster and instability problem, but the inventor finds not to be that any antioxidant can both address this problem.Suitable antioxidant of the present invention comprises L-cysteine, sodium sulfite, vitamin C or sodium thiosulfate or their mixture, preferred L-cysteine, vitamin C or sodium sulfite or their mixture, more preferably L-cysteine or vitamin C or their mixture.Said antioxidant blends can be any two or more mixture with any weight ratio in L-cysteine, sodium sulfite, vitamin C or the sodium thiosulfate.The weight ratio of this antioxidant and cefathiamidine is suitably 0.0001-1: 1, be preferably 0.001-0.5: and 1, more preferably 0.01-0.5: 1.
The inventor finds obviously to have improved by the antioxidant described in adding the present invention the stability of cefathiamidine, and particularly under the condition of illumination and high humidity, color and luster is stable, and hot conditions also has improvement.And not adding the sample of antioxidant, color and luster changes highly significant under its similarity condition.
Further specify medication composition of cefathiamidine of the present invention and stability thereof by the following examples, but these embodiment do not limit protection scope of the present invention.
The specific embodiment mode
Embodiment 1
10 gram cefathiamidines, 0.1 gram L-cysteine are ground respectively, cross behind 60 mesh sieves evenly mixedly, promptly get pharmaceutical composition of the present invention.
Embodiment 2
10 gram cefathiamidines, 0.01 gram sodium sulfite grind respectively, cross behind 60 mesh sieves evenly mixedly, promptly get pharmaceutical composition of the present invention.
Embodiment 3
10 gram cefathiamidines, 0.1 gram vitamin C grind respectively, cross behind 60 mesh sieves evenly mixedly, promptly get pharmaceutical composition of the present invention.
Embodiment 4
10 gram cefathiamidines, 0.05 gram sodium thiosulfate grinds respectively, crosses behind 60 mesh sieves evenly mixedly, promptly gets pharmaceutical composition of the present invention.
Embodiment 5
10 gram cefathiamidines, 0.05 gram vitamin C and 0.05 gram L-cysteine grind respectively, cross behind 60 mesh sieves evenly mixedly, promptly get pharmaceutical composition of the present invention.
Embodiment 6
10 gram cefathiamidines, 0.05 gram sodium sulfite and 0.05 gram L-cysteine grind respectively, cross behind 60 mesh sieves evenly mixedly, promptly get pharmaceutical composition of the present invention.
Embodiment 7
10 gram cefathiamidines, 0.005 gram L-cysteine grinds respectively, crosses behind 60 mesh sieves evenly mixedly, promptly gets pharmaceutical composition of the present invention.
Embodiment 8
10 gram cefathiamidines, 0.5 gram vitamin C grinds respectively, crosses behind 60 mesh sieves evenly mixedly, promptly gets pharmaceutical composition of the present invention.
The stability of the pharmaceutical composition of pure cefathiamidine and the foregoing description 1-8 is measured in the requirement of two appendix medicine stability tests of employing Pharmacopoeia of the People's Republic of China version in 2000 guideline, wherein hot test was to place 10 days under 60 ℃ of temperature, in the 5th day and sampling detection in the 10th day; The high humility test was placed 10 days under 25 ℃ of relative humidity 90% ± 5% conditions, in the 5th day and sampling detection in the 10th day; Strong illumination test was to place 10 days under the condition of 45001x ± 5001x in illumination, in the 5th day and sampling detection in the 10th day.Result of the test is as shown in the table:
| Material | High temperature | High humidity | Illumination | ||||
| 0 day | 5 days | 10 days | 5 days | 10 days | 5 days | 10 days | |
| Pure cefathiamidine | ?＜YG3 | ?＞Y10 | ?＞Y10 | ?＜YG5 | ?＜YG6 | ?＜YG7 | ?＜YG9 |
| Embodiment 1 | ?＜YG3 | ?＜Y7 | ?＞Y8 | ?＜YG3 | ?＜YG4 | ?＜YG3 | ?＜YG5 |
| Embodiment 2 | ?＜YG3 | ?＜Y9 | ?＞Y9 | ?＜YG3 | ?＜YG4 | ?＜YG4 | ?＜YG6 |
| Embodiment 3 | ?＜YG3 | ?＜Y9 | ?＞Y9 | ?＜YG3 | ?＜YG4 | ?＜YG4 | ?＜YG5 |
| Embodiment 4 | ?＜YG3 | ?＜Y9 | ?＞Y9 | ?＜YG4 | ?＜YG5 | ?＜YG4 | ?＜YG6 |
| Embodiment 5 | ?＜YG3 | ?＜Y8 | ?＞Y8 | ?＜YG3 | ?＜YG4 | ?＜YG3 | ?＜YG5 |
| Embodiment 6 | ?＜YG3 | ?＜Y9 | ?＞Y9 | ?＜YG3 | ?＜YG4 | ?＜YG4 | ?＜YG5 |
| Embodiment 7 | ?＜YG3 | ?＜Y9 | ?＞Y9 | ?＜YG4 | ?＜YG5 | ?＜YG4 | ?＜YG7 |
| Embodiment 8 | ?＜YG3 | ?＜Y8 | ?＞Y9 | ?＜YG3 | ?＜YG4 | ?＜YG3 | ?＜YG5 |
Alphabetical Y represents that color and luster is yellow in the table, and YG represents that color and luster is a yellow green, and numerical value is high more, and color and luster is dark more, and product is unstable more.This result of the test shows that antioxidant mixture by a certain percentage stability under high humidity, illumination condition that cefathiamidine and the present invention select obviously is better than pure cefathiamidine, is better than pure cefathiamidine under hot conditions.
Claims (5)
1. stable medication composition of cefathiamidine, the antioxidant that it comprises cefathiamidine and is selected from a kind of or its mixture in L-cysteine, sodium sulfite, vitamin C and the sodium thiosulfate, wherein the part by weight of cefathiamidine and antioxidant is 1: 0.0001-1.
2. stable medication composition of cefathiamidine according to claim 1, wherein said antioxidant are L-cysteine, sodium sulfite or vitamin C or their mixture.
3. stable medication composition of cefathiamidine according to claim 2, wherein said antioxidant are L-cysteine or vitamin C or their mixture.
4. according to claim 1,3 described stable medication composition of cefathiamidine, wherein the part by weight of cefathiamidine and antioxidant is 1: 0.001-0.5.
5. stable medication composition of cefathiamidine according to claim 4, wherein the part by weight of cefathiamidine and antioxidant is 1: 0.01-0.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410102451 CN1795864A (en) | 2004-12-27 | 2004-12-27 | Stable medication composition of cefathiamidine |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410102451 CN1795864A (en) | 2004-12-27 | 2004-12-27 | Stable medication composition of cefathiamidine |
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| CN1795864A true CN1795864A (en) | 2006-07-05 |
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| CN 200410102451 Pending CN1795864A (en) | 2004-12-27 | 2004-12-27 | Stable medication composition of cefathiamidine |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101744824B (en) * | 2009-12-25 | 2011-11-30 | 吴秋萍 | composition preparation of cefathiamidine compound and preparation method thereof |
-
2004
- 2004-12-27 CN CN 200410102451 patent/CN1795864A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101744824B (en) * | 2009-12-25 | 2011-11-30 | 吴秋萍 | composition preparation of cefathiamidine compound and preparation method thereof |
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