CN102382125B - Cefditoren water-soluble composite, preparation method and corresponding pharmaceutical preparation thereof - Google Patents
Cefditoren water-soluble composite, preparation method and corresponding pharmaceutical preparation thereof Download PDFInfo
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- CN102382125B CN102382125B CN201110215906.1A CN201110215906A CN102382125B CN 102382125 B CN102382125 B CN 102382125B CN 201110215906 A CN201110215906 A CN 201110215906A CN 102382125 B CN102382125 B CN 102382125B
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- Prior art keywords
- cefditoren
- water
- salt
- phosphoric acid
- basic metal
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Abstract
The invention discloses a cefditoren water-soluble composite, which is the composite prepared from cefditoren and alkali metal phosphates, and is presented in the structural formula (I), wherein in the formula, Y equals to 0 or 1, and X equals to 3-Y. The composite has good solubility, and can be produced into lyophilized pharmaceutical preparation (I) for practicable application.
Description
Technical field
What the present invention relates to is a kind of water-soluble compound of cefditoren, with and preparation method thereof and application in pharmaceutical preparation.
Background technology
Cefditoren (Cefditoren) (II)
be the active part of cefditoren (Cefditoren Pivoxil) (III), thereby cefditoren (III) is a kind of prodrug of cefditoren (II), US Patent No. 4839350 has been reported this.
（Ⅱ） （Ⅲ）
-COOH acid owing to having in the structure of cefditoren (II) simultaneously and alkalescence-NH
2eP0695548A1 reports the acid in this compound structure or alkali being formed to the compound of salt, the particularly preparation to the mixture aqueous solution of cefditoren and arginine, Methionin, and make freeze-dried preparation and make to be used as report as injection, and proposed cefditoren (II) can with the basic metal salify such as sodium salt, sylvite, with the alkaline-earth metal salify such as calcium salt, and with the organic bases such as triethylamine and with the mineral acid salify such as the organic acid such as formic acid and hydrochloric acid.In addition the report that also has, the preparation content of pair cefditoren sodium and cefditoren potassium in the document such as WO2005016936A2, WO2005100369, WO2007054777.
Summary of the invention
For above-mentioned situation, first the present invention provides a kind of water-soluble cefditoren mixture of new form, and its preparation method is further provided.
The water-soluble compound of cefditoren of the present invention, is the mixture that cefditoren becomes with the salt of basic metal phosphoric acid class, and structure is as shown in formula I, and the Y in formula is 0 or 1, X=3-Y,
（Ⅰ） 。
In the composite structure of above-mentioned formula I, the salt of said basic metal phosphoric acid class, is preferably sodium phosphate or potassiumphosphate, and particularly lower-cost sodium phosphate is more preferred, and the mol ratio of itself and cefditoren is preferably 0.5 ~ 0.8
:1.Wherein, the salt of said basic metal phosphoric acid class, can be without the alkali metal phosphate of crystal water form.Therefore but because it is by being prepared by the aqueous solution, more preferably as sodium phosphate dodecahydrate etc., directly contain the sodium phosphate of crystal water.
Salt for the basic metal phosphoric acid class in the above-mentioned formula I structural composites of the present invention, except the alkali metal phosphates such as above-mentioned said sodium phosphate or potassiumphosphate, can also adopt the hydrophosphates such as Sodium phosphate dibasic or dipotassium hydrogen phosphate.While adopting hydrophosphate, the mol ratio of itself and cefditoren is 1 ~ 6.3
:1.Equally, hydrophosphate used can be for containing or do not contain the salt of crystal water form, but the hydrophosphate that more preferably contains crystal water as disodium hydrogen phosphate dodecahydrate etc.
The preparation method of the above-mentioned mixture of the present invention is simple and easy to do, after the salt water of cefditoren and said basic metal phosphoric acid class is dissolved completely, in lyophilize mode, removes moisture content, can obtain pulverous said mixture lyophilize product.Experiment demonstration, this mixture can dissolve completely in being less than the water of its quintuple.
In above-mentioned preparation method, more preferred a kind of mode, is the consoluet aqueous solution of salt to said cefditoren and said basic metal phosphoric acid class, first in modes such as gacs, decolours after removal of impurities processing, carry out again lyophilize processing, can obtain the more composite product of purifying.
The cefditoren water-soluble compound preparing with aforesaid method, directly conduct can be for the medicine of actual freeze-dried formulation.
The water-soluble cefditoren mixture of the above-mentioned formula I form of the present invention, it is the cefditoren water-soluble structure compound of a class new form, can have can meet injection preparation institute essential and be satisfied with water-soluble, and preparation method is easy, product yield is high, and after preparation, directly obtaining can be for actual freeze-dried pharmaceutical formulation.
On the other hand, in the water-soluble cefditoren mixture of the above-mentioned formula I form of the present invention, although with regard to water-soluble, the mixture that cefditoren becomes with sodium salt with said sylvite does not have difference substantially, but because physiologically active and the effect of sylvite and sodium salt are totally different, therefore when preparing intravenous injection medicine, generally should adopt the corresponding sodium salt such as sodium phosphate, Sodium phosphate dibasic, should not use sylvite.
Embodiment is by the following examples described in further detail foregoing of the present invention again.But this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following example.Without departing from the idea case in the present invention described above, various replacements or the change according to ordinary skill knowledge and customary means, made, all should comprise within the scope of the invention.
Embodiment
Embodiment 1
By the cefditoren of formula II form (as follows) 30g, Na
3pO
412H
2o 11.2g(mol ratio 1
:0.5) and water 400ml add in reaction flask, stirring and dissolving, pH value of solution 6.0, adds after activated carbon filtration, gained clear filtrate frost drying, must talk yellow loose powder with quantitative yield.
Embodiment 2
By cefditoren 30g, Na
3pO
412H
2o 12.7g(mol ratio 1
:0.56) and water 400ml add in reaction flask, stirring and dissolving, pH value of solution 6.5, adds after activated carbon filtration, gained clear filtrate frost drying, must talk yellow loose powder with quantitative yield.
Embodiment 3
By cefditoren acid 30g, Na
3pO
412H
2o 15.1g(mol ratio 1
:0.67) and water 400ml add in reaction flask, stirring and dissolving, pH value of solution 7.0, adds after activated carbon filtration, gained clear filtrate frost drying, must talk yellow loose powder with quantitative yield.
Embodiment 4
By cefditoren acid 30g, Na
3pO
412H
2o 18.0g(mol ratio 1
:0.8) and water 400ml add in reaction flask, stirring and dissolving, pH value of solution 7.5, adds after activated carbon filtration, gained clear filtrate frost drying, must talk yellow loose powder with quantitative yield.
Embodiment 5
By cefditoren acid 30g, Na
2hPO
412H
2o 21.3g(mol ratio 1
:1) and water 400ml add in reaction flask, stirring and dissolving, pH value of solution 6.0, adds after activated carbon filtration, gained clear filtrate frost drying, must talk yellow loose powder with quantitative yield.
Embodiment 6
By cefditoren acid 30g, Na
2hPO
412H
2o 29.6g(mol ratio 1
:1.4) and water 400ml add in reaction flask, stirring and dissolving, pH value of solution 6.5, adds after activated carbon filtration, gained clear filtrate frost drying, must talk yellow loose powder with quantitative yield.
Embodiment 7
By cefditoren acid 30g, Na
2hPO
412H
2o 54.3g(mol ratio 1
:2.5) and water 400ml add in reaction flask, stirring and dissolving, pH value of solution 7.0, adds after activated carbon filtration, gained clear filtrate frost drying, must talk yellow loose powder with quantitative yield.
Embodiment 8
By cefditoren acid 30g, Na
2hPO
412H
2o 135.1g(mol ratio 1
:6.3) and water 400ml add in reaction flask, stirring and dissolving, pH value of solution 7.5, adds after activated carbon filtration, gained clear filtrate frost drying, must talk yellow loose powder with quantitative yield.
Claims (10)
1. the water-soluble compound of cefditoren, is the mixture that cefditoren becomes with the salt of basic metal phosphoric acid class, and structure is as shown in formula I, and the Y in formula is 0 or 1, X=3-Y,
（Ⅰ） 。
2. the water-soluble compound of cefditoren as claimed in claim 1, the salt that it is characterized in that said basic metal phosphoric acid class is sodium phosphate, the mol ratio of itself and cefditoren is 0.5 ~ 0.8
:1.
3. the water-soluble compound of cefditoren as claimed in claim 2, the salt that it is characterized in that said basic metal phosphoric acid class is the sodium phosphate that contains crystal water.
4. the water-soluble compound of cefditoren as claimed in claim 3, the salt that it is characterized in that said basic metal phosphoric acid class is sodium phosphate dodecahydrate.
5. the water-soluble compound of cefditoren as claimed in claim 1, the salt that it is characterized in that said basic metal phosphoric acid class is Sodium phosphate dibasic, the mol ratio of itself and cefditoren is 1 ~ 6.3
:1.
6. the water-soluble compound of cefditoren as claimed in claim 5, the salt that it is characterized in that said basic metal phosphoric acid class is the Sodium phosphate dibasic that contains crystal water.
7. the water-soluble compound of cefditoren as claimed in claim 6, the salt that it is characterized in that said basic metal phosphoric acid class is disodium hydrogen phosphate dodecahydrate.
8. the pharmaceutical preparation that the described cefditoren water-soluble compound of one of claim 1 to 7 of take is effective constituent, is characterized in that for freeze-dried preparation.
9. the preparation method of the described cefditoren water-soluble compound of one of claim 1 to 7, after it is characterized in that the salt water of cefditoren and said basic metal phosphoric acid class to dissolve completely, in lyophilize mode, remove moisture content, obtain pulverous said mixture lyophilize product.
10. preparation method as claimed in claim 9, is characterized in that the consoluet aqueous solution of salt to said cefditoren and said basic metal phosphoric acid class, after the removal of impurities of first decolouring is processed, then carries out lyophilize processing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110215906.1A CN102382125B (en) | 2011-07-29 | 2011-07-29 | Cefditoren water-soluble composite, preparation method and corresponding pharmaceutical preparation thereof |
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|---|---|---|---|
| CN201110215906.1A CN102382125B (en) | 2011-07-29 | 2011-07-29 | Cefditoren water-soluble composite, preparation method and corresponding pharmaceutical preparation thereof |
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|---|---|
| CN102382125A CN102382125A (en) | 2012-03-21 |
| CN102382125B true CN102382125B (en) | 2014-04-09 |
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ID=45822013
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|---|---|---|---|
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0695548A1 (en) * | 1994-08-03 | 1996-02-07 | Meiji Seika Kaisha Ltd. | A stably storable and readily water soluble composition of cephalosporin for injections |
| CN101001613A (en) * | 2004-06-28 | 2007-07-18 | 生命周期药物公司 | Porous article for delivering chemical substances |
| CN101591347A (en) * | 2009-05-25 | 2009-12-02 | 漆又毛 | Cefixime acid type double salt compound and preparation method thereof |
| CN101633665A (en) * | 2009-07-27 | 2010-01-27 | 杭州奥默医药技术有限公司 | Cephalosporin antibiotic acidic complex salt and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6219593A (en) * | 1985-07-18 | 1987-01-28 | Meiji Seika Kaisha Ltd | Novel cephem compound |
| WO2006106529A1 (en) * | 2005-04-05 | 2006-10-12 | Lupin Limited | A co-spray dried composition of cefepime with base and process for preparation thereof |
-
2011
- 2011-07-29 CN CN201110215906.1A patent/CN102382125B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0695548A1 (en) * | 1994-08-03 | 1996-02-07 | Meiji Seika Kaisha Ltd. | A stably storable and readily water soluble composition of cephalosporin for injections |
| CN101001613A (en) * | 2004-06-28 | 2007-07-18 | 生命周期药物公司 | Porous article for delivering chemical substances |
| CN101591347A (en) * | 2009-05-25 | 2009-12-02 | 漆又毛 | Cefixime acid type double salt compound and preparation method thereof |
| CN101633665A (en) * | 2009-07-27 | 2010-01-27 | 杭州奥默医药技术有限公司 | Cephalosporin antibiotic acidic complex salt and preparation method thereof |
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| CN102382125A (en) | 2012-03-21 |
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