CN1557314A - Prulifloxacin water-soluble salt and its injection formulation - Google Patents
Prulifloxacin water-soluble salt and its injection formulation Download PDFInfo
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- CN1557314A CN1557314A CNA2004100049885A CN200410004988A CN1557314A CN 1557314 A CN1557314 A CN 1557314A CN A2004100049885 A CNA2004100049885 A CN A2004100049885A CN 200410004988 A CN200410004988 A CN 200410004988A CN 1557314 A CN1557314 A CN 1557314A
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- acid
- prulifloxacin
- soluble salt
- water soluble
- injection
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Abstract
The present invention aims at providing one kind of water soluble Prulifloxacin salt for muscular injection or intravenous injection and its proper injection form. The water solution of these soluble salts is easy to release Prulifloxacin salt, and the injection of Prulifloxacin salt has the same antiseptic effect as orally taken Prulifloxacin preparation. In addition, the injected medicine enters blood directly to produce treating effect and thus has faster effect and less medicine consumption compared with available orally taken form.
Description
Technical field
The present invention relates to the water soluble salt of prulifloxacin and the injection type of making by its water soluble salt.
Background technology
Prulifloxacin is developed by Japanese Mingzhi drugmaker, gets permission to go on the market in Japan in July, 2002.This product is the precursor medicine of NM394, to the antibacterial ability of gram negative bacteria and gram positive bacteria, particularly to the antimicrbial power of the gram negative bacteria headed by the bacillus pyocyaneus considerably beyond other xacin-series, also surpass other antibiotic medicine of listing at present; And oral absorption is good, and repetitively administered does not have the property of accumulating in vivo, and the incidence rate of side effect is 3.4%, is mainly symptom of digestive tract (accounting for 2.1%).This medicine is mainly used in treatment infective enteritis, suppurative illness, biliary tract infection and gynecological infection disease.At present, Shang Weijian comprises other countries' list marketing of China.
Summary of the invention
The purpose of this invention is to provide a kind of muscle or intravenous prulifloxacin water soluble salt of being directly used in.
Another object of the present invention provides a kind of dosage form that muscle or intravenous prulifloxacin water soluble salt are suitable for injecting that is directly used in.
This salt and injection type thereof are to can not also using with the patient of oral medicine.
The inventor considers because prulifloxacin is an acidulous material, to have a carboxyl in its molecular structure, therefore might make one mole the prulifloxacin and the various acid or the alkali reaction of equivalent, can make it become soluble-salt.Here said equivalent is for residue base in the organic acid.For example, some have the aminoacid of the amino and carboxyl of similar number owing to there is remaining carboxyl can not with prulifloxacin reaction generation soluble-salt.But glutamic acid and aspartic acid belong to acidic amino acid, they all have an amino and two carboxyls, just have one the 8th carboxyl to combine with the amino of prulifloxacin, therefore one mole of prulifloxacin can generate soluble-salt with two moles glutamic acid or aspartic acid reaction.Other situations are analogized.The inventor finds that also the aqueous solution that is formed by these soluble-salts and water very is easy to disengage the former medicine of prulifloxacin again, when for example carrying out thin layer chromatography, can obtain the speckle with the identical RT of free prulifloxacin.As seen the salt of this class prulifloxacin can play the antibacterial action same with oral prulifloxacin after being made into the injection administration.And medicine directly enters blood during owing to injection, therefore can bring into play therapeutical effect rapidly, can fully be absorbed by living organism again, all is being much better than existing prulifloxacin peroral dosage form aspect instant effect and low-consuming two.
Thereby, the invention provides a kind of prulifloxacin water soluble salt, it is characterized in that it is formed by any or the two reaction in prulifloxacin and the mineral acid that pharmaceutically allows, organic acid, alkali metal, the alkaline-earth metal.
Said acid will be done suitable selection among the present invention, it must be mineral acid, the organic acid that pharmaceutically allows, and it is wanted and can generate the salt with enough aqueous solutions with prulifloxacin, the PH of the aqueous solution of its formation simultaneously is moderate, for example pH value is in 4.5～6.5 scopes, so just can guarantee that contained prulifloxacin is not damaged.In addition, formed salt also will be easy to disengage prulifloxacin in aqueous solution, can bring into play drug effect rapidly and fully to guarantee it.
Show that behind overtesting preferable organic acid comprises acidic amino acid, hydroxy acid and C
1-12(be preferably C
1-16) directly and/or branched chain fatty acid etc.
The preferred example of said acidic amino acid has: glutamic acid and aspartic acid.It also can be the mixture of the two.
The preferred example of said hydroxy acid has: lactic acid, hydroxybutyric acid, malic acid, tartaric acid, citric acid and lactobionic acid.It also can be any mixture more than 2 kinds in them.
The preferred example of said fatty acid has: acetic acid, propanoic acid and butanoic acid.It also can be any mixture more than 2 kinds in them.
In addition, the present invention also provides a kind of prulifloxacin water needle injection, it is characterized in that, the aqueous injection that the aqueous solution that it is formed by above-mentioned prulifloxacin water soluble salt and water makes, with and through lyophilization and the injectable powder type made.
Above-mentioned aqueous solution can be that prulifloxacin and organic acid react in water and the aqueous solution of the prulifloxacin water soluble salt that directly forms, also can be again that it is the soluble in water and aqueous solution that forms after obtaining the water-soluble fluidity salt of prulifloxacin.
In the aqueous solution that forms by prulifloxacin water soluble salt of the present invention, store at normal temperatures and do not separate out solid, and composition is still stable.But when drug level is too high, direct injection will cause pain.Therefore must be made into the injection type of debita spissitudo and proper volume usually with normal saline.Yet according to the present invention, the preferably aqueous solution lyophilizing of the prulifloxacin water soluble salt that will generate through reaction and make injectable powder, from several respects such as storage, transportation and uses bigger benefit is arranged all like this, the water of injection ormal weight faces with preceding as long as promptly can be used for injection or add in the venous transfusion using after the thixotropy.As for its consumption, can calculate according to the absorbance of oral dose.But preferably determine as the case may be by the doctor.
Compare with the prulifloxacin oral agents of prior art, the invention has the beneficial effects as follows: the good water solubility of medicine, and, therefore can bring into play therapeutical effect rapidly because medicine directly enters blood, can fully be absorbed by the body again, all play more significant effect aspect instant effect and low-consuming two.
The specific embodiment
Embodiment 1
With the 0.01mol prulifloxacin, 0.01mol lactic acid and 30ml water add in the 100ml vial, at room temperature stir 10 minutes raw materials and dissolve rapidly, and gained solution is water white transparency, and the pH value that records solution with pH meter is 4.3.The gained saline solution is under reduced pressure concentrated, move in the plate then and in exsiccator, place, allow it fling to moisture, become clear glass shape solid behind the branch that anhydrates, continue placement again and allow moisture volatilize fully, gradually become white solid, the heavy 5.85g of institute's product that obtains.This product is the water soluble salt of prulifloxacin of the present invention.Add 30ml water in this solid and stir with Glass rod, within one minute, solid i.e. all dissolvings.
Solution is by predetermined solubility dilute with water, and through aseptic filtration, the ampoule fusion sealing of packing under aseptic condition had both got aqueous injection; Be sub-packed in the flat middle lyophilizing of glass by predetermined close in addition, promptly obtain powder needle injection of the present invention.Face water, can use after the thixotropy with preceding adding scheduled volume.
Embodiment 2
With the 0.01mol prulifloxacin, 0.01mol methanesulfonic acid and 30ml water add in the 100ml vial, at room temperature stir 10 minutes raw materials and dissolve rapidly, and gained solution is water white transparency, and the pH value that records solution with pH meter is 5.1.The gained saline solution is under reduced pressure concentrated, move in the plate then and in exsiccator, place, allow it fling to moisture, become clear glass shape solid behind the branch that anhydrates, continue placement again and allow moisture volatilize fully, gradually become white solid, the heavily about 6.15g of institute's product that obtains.This product is the property salt of prulifloxacin of the present invention.Add 30ml water in this solid and stir with Glass rod, within one minute, solid i.e. all dissolvings.
Solution is by predetermined solubility dilute with water, and through aseptic filtration, the ampoule fusion sealing of packing under aseptic condition had both got aqueous injection; Be sub-packed in the flat middle lyophilizing of glass by predetermined close in addition, promptly obtain powder needle injection of the present invention.Face water, can use after the thixotropy with preceding adding scheduled volume.
Embodiment 3
With the 0.01mol prulifloxacin, 0.01mol hydrochloric acid and 30ml water add in the 100ml vial, at room temperature stir 10 minutes raw materials and dissolve rapidly, and gained solution is water white transparency, and the pH value that records solution with pH meter is 4.6.The gained saline solution is under reduced pressure concentrated, move in the plate then and in exsiccator, place, allow it fling to moisture, become clear glass shape solid behind the branch that anhydrates, continue placement again and allow moisture volatilize fully, gradually become white solid, the heavy 4.1g of institute's product that obtains.This product is the water soluble salt of prulifloxacin of the present invention.Add 30ml water in this solid and stir with Glass rod, within one minute, solid i.e. all dissolvings.Solution is by predetermined solubility dilute with water, and through aseptic filtration, the ampoule fusion sealing of packing under aseptic condition had both got aqueous injection; Be sub-packed in the flat middle lyophilizing of glass by predetermined close in addition, promptly obtain powder needle injection of the present invention.Face water, can use after the thixotropy with preceding adding scheduled volume.
Claims (12)
1, a kind of prulifloxacin water soluble salt is characterized in that: it by in prulifloxacin and the mineral acid that pharmaceutically allows, organic acid, alkali metal, the alkaline-earth metal any or more than the two reaction form.
2, prulifloxacin water soluble salt according to claim 1, it is characterized in that: described mineral acid can be hydrochloric acid, sulphuric acid, phosphoric acid or hydrobromic acid.
3, prulifloxacin water soluble salt according to claim 1, it is characterized in that: described organic acid can be acidic amino acid, hydroxy acid, the formic acid in the fatty acid, acetic acid, propanoic acid, butanoic acid, lactic acid, hydroxybutyric acid, malic acid, tartaric acid, citric acid, lactic acid, maleic acid, fumaric acid, succinic acid, methanesulfonic acid, ethyl sulfonic acid, benzenesulfonic acid, how any in sulfonic acid, triolefin sulfonic acid, camphorsulfonic acid, glutamic acid, the aspartic acid or any mixture more than 2 kinds.
4, prulifloxacin water soluble salt according to claim 1 is characterized in that: described alkali metal, alkaline-earth metal can be any or any mixture more than 2 kinds in sodium, potassium or the calcium.
5, a kind of injection type of prulifloxacin water soluble salt as claimed in claim 1 is characterized in that, the sterile preparation of the injection that it is formed by prulifloxacin water soluble salt and water comprises liquid drugs injection, transfusion, powder pin.
6, the injection of prulifloxacin water soluble salt according to claim 5 is characterized in that: injectable sterile powder is made through solvent crystallization or lyophilization by water solublity prulifloxacin salt.
7, the injection of prulifloxacin water soluble salt according to claim 5 is characterized in that: contain cosolvent, PH regulator in the injectable sterile powder of described solution-type injection or lyophilization preparation.
8, the injection of prulifloxacin water soluble salt according to claim 5, it is characterized in that: cosolvent wherein is selected from Macrogol 200, Liquid Macrogol, PEG400, tween 80,1,2-propylene glycol, glycerol or polyvinylpyrrolidone.
9, the injection of prulifloxacin water soluble salt according to claim 5 is characterized in that: PH wherein regulates from phosphate buffer, acetate buffer, maleic acid, citric acid, hydrochloric acid or sodium hydroxide.
10, the injection of prulifloxacin water soluble salt according to claim 5 is characterized in that: contain the prulifloxacin water soluble salt that is equivalent to prulifloxacin 50-500mg, with 1, the 2-propylene glycol is a cosolvent, water is solvent, and sodium hydroxide is the PH regulator, and adjusting PH is 4.5-7.5.
11, the injection of prulifloxacin water soluble salt according to claim 5 is characterized in that: contain the prulifloxacin water soluble salt that is equivalent to prulifloxacin 250mg, with 1, the 2-propylene glycol is a cosolvent, water is solution, and sodium hydroxide is the PH regulator, and PH is 5.0-7.0.
12, the injection of prulifloxacin water soluble salt according to claim 5 is characterized in that: contain the prulifloxacin aqueous solvent of suitable prulifloxacin 250mg, water is solvent, and sodium hydroxide is the PH regulator, is adjusted to 5.0-7.0.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2004100049885A CN1557314A (en) | 2004-02-13 | 2004-02-13 | Prulifloxacin water-soluble salt and its injection formulation |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2004100049885A CN1557314A (en) | 2004-02-13 | 2004-02-13 | Prulifloxacin water-soluble salt and its injection formulation |
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| Publication Number | Publication Date |
|---|---|
| CN1557314A true CN1557314A (en) | 2004-12-29 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2004100049885A Pending CN1557314A (en) | 2004-02-13 | 2004-02-13 | Prulifloxacin water-soluble salt and its injection formulation |
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| CN (1) | CN1557314A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102198135A (en) * | 2010-03-22 | 2011-09-28 | 北京联木医药技术发展有限公司 | Use of new stable Prulifloxacin hydrochloride in preparation of anti-infection medicines |
| CN102475704A (en) * | 2010-11-24 | 2012-05-30 | 胡定国 | Application of novel stable prulifloxacin mesylate in preparing anti-infectives |
-
2004
- 2004-02-13 CN CNA2004100049885A patent/CN1557314A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102198135A (en) * | 2010-03-22 | 2011-09-28 | 北京联木医药技术发展有限公司 | Use of new stable Prulifloxacin hydrochloride in preparation of anti-infection medicines |
| CN102198135B (en) * | 2010-03-22 | 2013-05-08 | 北京联木医药技术发展有限公司 | Use of new stable Prulifloxacin hydrochloride in preparation of anti-infection medicines |
| CN102475704A (en) * | 2010-11-24 | 2012-05-30 | 胡定国 | Application of novel stable prulifloxacin mesylate in preparing anti-infectives |
| CN102475704B (en) * | 2010-11-24 | 2013-07-10 | 胡定国 | Preparation method of stable prulifloxacin mesylate |
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