CN102512379A - Novel Echinocandin antifungal pharmaceutical composition and preparation method thereof - Google Patents
Novel Echinocandin antifungal pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN102512379A CN102512379A CN2011104277842A CN201110427784A CN102512379A CN 102512379 A CN102512379 A CN 102512379A CN 2011104277842 A CN2011104277842 A CN 2011104277842A CN 201110427784 A CN201110427784 A CN 201110427784A CN 102512379 A CN102512379 A CN 102512379A
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Abstract
The invention, belonging to the technical field of pharmaceutical preparations, provides an injection preparation composition containing Micafungin as an effective component. The injection preparation composition comprises 5-200 mg/ml Micafungin or its pharmaceutically acceptable salts, 5-250 mg/ml of excipient, 10-250 mM of buffer and a proper amount of sodium hydroxide or hydrochloric acid for regulating pH to 4.0-7.0.
Description
Technical field:
The present invention relates to antifungal preparation, relate in particular to a kind of novel echinocandin class antifungal medicine composition.
Background technology:
1974, it is found that sour jujube ball diphtheria chlorins compound has good antibacterial activity, therefore, people have studied the pharmacologically active of many semisynthetic sour jujube ball diphtheria chlorins compounds.Wherein, Mi Kafen clean (Micafungin) is wherein a kind of, as preparation treatment or prevention antifungal preparation.U.S. Pat 5376634, US5569646, WO9611210 and WO9940108 disclose this chemical compound and preparation method thereof.
Summary of the invention:
The invention provides a kind of stable pharmaceutical composition, it comprises:
(1) clean or its pharmaceutically available salt of Mi Kafen;
(2) buffer and an amount of sodium hydroxide or hydrochloric acid are regulated the pH regulator agent;
(3) effectively form the pharmaceutically acceptable excipient of lyophilized cake.
Wherein, the clean sodium of the preferred Mi Kafen of the clean pharmaceutically acceptable salt of described Mi Kafen, said excipient are sorbitol, mannitol, lactose, sucrose, glucose, maltose or its mixture, the mixture of preferred mannitol and lactose.Said buffer agent is sodium acetate, sodium bisulfate, sodium citrate, sodium phosphate, sodium lactate or its mixture, preferred sodium acetate.
In addition, the invention provides a kind of lyophilized powder that obtains through the aforesaid pharmaceutical composition of the present invention of lyophilizing.This lyophilized powder is suitable for being dissolved into intravenous fluid composition again.
The present invention also provides preparation to contain the method for the pharmaceutical composition of the clean pharmaceutically acceptable salt of Mi Kafen, and this method may further comprise the steps:
(1) compositions of excipient or excipient is soluble in water;
(2) add clean or its pharmaceutically acceptable salt of Mi Kafen in the aqueous solution that in step (1), obtains, and with its dissolving;
(3) add the PH regulator in the aqueous solution that in step (2), obtains, reach required pH value;
(4) filter the also solution of lyophilization step (3) preparation.
The pharmaceutical composition for preparing according to the method described above is than existing preparation stabilization, and method for preparing is easier.
The specific embodiment:
To combine embodiment that embodiment of the present invention are described in detail below, but it will be understood to those of skill in the art that the following example only is used to explain the present invention, and should not be regarded as limiting scope of the present invention.
Embodiment 1
Table 1-1 embodiment 1 composite formula
| Component | Consumption |
| Mi Kafen is clean | 50mg/ml |
| Mannitol | 30mg/ml |
| Sorbitol | 20mg/ml |
| Sodium dihydrogen phosphate | 20mM |
| Hydrochloric acid | In right amount, transfer to pH to 5.2 |
Its preparation process is following: in the 2500ml beaker, add 75g mannitol, 50g sorbitol, 1750ml water; It is clean to add Mi Kafen; To its final standardize solution concentration be 50mg/ml, adding sodium dihydrogen phosphate to its concentration is 20mM, and with 1N hydrochloric acid with pH regulator to 5.2.Add injection water standardize solution.Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered.Filtrating is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration.Every bottle of amount with 1.25ml is packed into the 10ml vial, lyophilization, and tamponade, Zha Gai obtains the clean preparation of injection Mi Kafen.
Make 1000 in the clean preparation of injection Mi Kafen by embodiment 1, logical accelerated test is investigated its stability.Through animal blood vessels zest, muscle irritation, haemolysis and anaphylaxis experiment, local irritation is investigated.Through with the common infusion fluid compatibility, observe its outward appearance, related substance and changes of contents and investigated its stability in common infusion fluid.
Accelerated test:
Listing reference substance and the contrast of embodiment 1 sample:
Respectively a collection of sample of clean preparation reference substance of commercially available injection Mi Kafen and embodiment 1 being put into temperature is that 40 ± 2 ℃, relative humidity are that 75% ± 5% climatic chamber is investigated; 0,1,2,3 and sampling and measuring 6 months the time, the result sees table 1-2 and table 1-3 respectively.
The commercially available reference substance accelerated test of table 1-2 result
Table 1-3 embodiment 1 sample accelerated test result
Can find out through table 1-2 and table 1-3; Investigate 6 months through accelerated test; The clean preparation of injection Mi Kafen of embodiment 1 preparation compares with the clean preparation of the injection Mi Kafen that has gone on the market; Appearance luster, pH, clarity of solution index are suitable, but the sample of embodiment 1 preparation than the impurity of the test sample that has gone on the market increase, content descends obviously, shows that the sample of embodiment 1 preparation is stablized not as the test sample that has gone on the market.
Blood vessel irritation, muscle irritation, anaphylaxis and hemolytic experiment:
Blood vessel irritation:
Choose 6 of the undamaged healthy rabbits of ears, left side auricular vein injection embodiment 1 injection 1ml, capacity 5% glucose injections such as auris dextra injection, were injected 7 days continuously at every day 1 time.
During the injection, regularly observe the irritative response of auricular vein every day.Put to death rabbit on the 8th day, and got bilateral auricular vein and surrounding tissue, use formaldehyde fixed, proximal part is done the conventional organization section in the injection site, and light microscopic is observed down and had or not pathological change.Observation index and criterion are seen table 1-4.
Table 1-4 blood vessel irritation scoring and criterion
The result shows that the zest of rabbit auricular vein injection embodiment 1 injection compares no significant difference with 5% glucose injection.Inflammatory reactions such as the congestion of blood vessel, surrounding tissue edema are not seen in perusal.Tissue slice inspection does not see that blood vessel structure is unusual, endothelial injury, thrombosis and other pathological change.The blood vessel of its naked eyes and om observation, the cumulative score of surrounding tissue show nonirritant all less than 0.5.
Muscle irritation:
Get 6 of healthy rabbits, injection embodiment 1 injection 1ml in every rabbit left side quadriceps femoris, inject with the volume normal saline on the right side.The injection back is observed injection site muscle and is had or not reactions such as hyperemia, edema, and (the 3rd day) sacrificed by exsanguination behind the Half animals 48h is vertically cut skin, and injection site, perusal both sides has or not reactions such as hyperemia, edema, and gets its tissue and do pathologic finding.Then by the IR of showing this medicine of standard evaluation among the 1-5.Remaining animal continues to observe 14d, repeats aforesaid operations in the 18th day after the sacrificed by exsanguination, and evaluation criterion is seen table 1-5.
Table 1-5 muscular irritation reaction evaluating standard
The result shows; After injecting embodiment 1 injection in the quadriceps femoris of rabbit left side; Perusal injection site muscle does not have reactions such as hyperemia, edema, and explicitly IRs such as tissue degeneratiaon or necrosis are not also seen in the pathological tissue inspection, compare no significant difference with the normal saline side.
Sensitization to Cavia porcellus:
Choose 6 of healthy guinea pigs, every lumbar injection embodiment 1 injection 0.5ml, the next day, inject 1 time, injects altogether 3 times.Be divided into 2 groups then at random, after the 1st administration 14 or 21 days respectively, intravenous injection embodiment 1 injection 1ml.Observe Cavia porcellus and have or not allergic symptoms such as excited uneasiness, dyspnea.
Two groups of Cavia porcelluss of result are all movable normal, do not see adnormal respiration etc.
External hemolytic test:
Prepare 2% rabbit red cell suspension.Get 7 in test tube, 1-6 adds various liquid by table.Each test tube is shaken up gently, put in 37 ℃ of waters bath with thermostatic control and hatch, observe 0.5,1,2,3,6 hour result.Erythrocyte agglutination in vitro and hemolytic criterion are seen table 1-7.
The external hemolytic test application of sample of table 1-6 sample table
Outer haemolysis of table 1-7 red cell body and agglutination test criterion
As a result, the distilled water control tube was complete hemolysis in 0.5 hour.Normal saline and each concentration of embodiment 1 sample did not all have haemolysis in 6 hours.Jolting gently, the erythrocyte of normal saline and each concentration embodiment 1 sample cell bottom sediments all can disperse fully, shows that the clean injection of Mi Kafen does not have red cell agglutination.
Blood vessel irritation, muscle irritation, external hemolytic and anaphylaxis experiment show that embodiment 1 injection does not have tangible zest, anaphylaxis, can not cause hemolytic reaction yet.
Stability experiment in the transfusion:
Injection Mi Kafen with 10.5ml purified water dilution embodiment 1 preparation is clean; Draw 10ml respectively; Use common infusion fluid respectively: 0.9% sodium chloride injection (0.9%NS), 5% glucose injection (5%GS), be diluted to 200ml, making the Mi Kafen net concentration is 0.25mg/ml.Respectively at 25 ℃, minute is observed its outward appearance, impurity, changes of contents, and the result sees table 1-8.
Table 1-8 injection stability experiment
The result shows; The clean preparation of Mi Kafen and the common infusion fluid of embodiment 1 preparation, 0.9% sodium chloride injection (0.9%NS), 5% glucose injection (5%GS) compatibility use, and stability is all not so good; Therefore, this embodiment makes sample and cannot use with these compatibilities of infusing.
Embodiment 2
Table 2-1 embodiment 2 composite formulas
| Component | Consumption |
| Mi Kafen is clean | 50mg/ml |
| Mannitol | 50mg/ml |
| Sodium acetate | 50mM |
| Hydrochloric acid | In right amount, transfer to pH to 6.0 |
Its preparation process is following: in the 2500ml beaker, add 125g mannitol, and 1750ml water, Mi Kafen is clean in adding; To its final standardize solution concentration be 50mg/ml; Adding sodium acetate to its concentration is 50mM, and with 1N hydrochloric acid with pH regulator to 6.0, add and inject the water standardize solution.Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered.Filtrating is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration.Every bottle of amount with 1.25ml is packed into the 10ml vial, lyophilization, and tamponade, Zha Gai obtains the clean preparation of injection Mi Kafen.
Make 1000 in the clean preparation of injection Mi Kafen by embodiment 2, its stability is investigated through accelerated test.Through animal blood vessels zest, muscle irritation, haemolysis and anaphylaxis experiment, local irritation is investigated.Through with the common infusion fluid compatibility, observe its outward appearance, related substance and changes of contents and investigated its stability in common infusion fluid.
Accelerated test:
Listing reference substance and the contrast of embodiment 2 samples
Respectively a collection of sample of clean preparation reference substance of commercially available injection Mi Kafen and embodiment 2 being put into temperature is that 40 ± 2 ℃, relative humidity are that 75% ± 5% climatic chamber is investigated; 0,1,2,3 and sampling and measuring 6 months the time, the result sees table 2-2 and table 2-3 respectively.
The commercially available reference substance accelerated test of table 2-2 result
Table 2-3 embodiment 2 sample accelerated test results
Can find out through table 2-2 and table 2-3; Investigate 6 months through accelerated test; The clean preparation of injection Mi Kafen of embodiment 2 preparation and the clean preparation of the injection Mi Kafen that has gone on the market relatively, appearance luster, pH, clarity of solution index are suitable, the impurity of the test sample of listing increases, content descends obviously; Show that the clean injection of Mi Kafen that the present invention prepares can preserve under room temperature, stability increases.
Blood vessel irritation, muscle irritation, anaphylaxis and hemolytic experiment:
Blood vessel irritation:
Choose 6 of the undamaged healthy rabbits of ears, left side auricular vein injection embodiment 2 injection 1ml, capacity 5% glucose injections such as auris dextra injection, were injected 7 days continuously at every day 1 time.
During the injection, regularly observe the irritative response of auricular vein every day.Put to death rabbit on the 8th day, and got bilateral auricular vein and surrounding tissue, use formaldehyde fixed, proximal part is done the conventional organization section in the injection site, and light microscopic is observed down and had or not pathological change.Observation index and criterion are seen table 2-4.
Table 2-4 blood vessel irritation scoring and criterion
The result shows that the zest of rabbit auricular vein injection embodiment 2 injection compares no significant difference with 5% glucose injection.Inflammatory reactions such as the congestion of blood vessel, surrounding tissue edema are not seen in perusal.Tissue slice inspection does not see that blood vessel structure is unusual, endothelial injury, thrombosis and other pathological change.The blood vessel of its naked eyes and om observation, the cumulative score of surrounding tissue show nonirritant all less than 0.5.
Muscle irritation:
Get 6 of healthy rabbits, injection embodiment 2 injection 1ml in every rabbit left side quadriceps femoris, inject with the volume normal saline on the right side.The injection back is observed injection site muscle and is had or not reactions such as hyperemia, edema, and (the 3rd day) sacrificed by exsanguination behind the Half animals 48h is vertically cut skin, and injection site, perusal both sides has or not reactions such as hyperemia, edema, and gets its tissue and do pathologic finding.Then by the IR of showing this medicine of standard evaluation among the 2-5.Remaining animal continues to observe 14d, repeats aforesaid operations in the 18th day after the sacrificed by exsanguination, and evaluation criterion is seen table 2-5.
Table 2-5 muscular irritation reaction evaluating standard
The result shows; After injecting embodiment 2 injection in the quadriceps femoris of rabbit left side; Perusal injection site muscle does not have reactions such as hyperemia, edema, and explicitly IRs such as tissue degeneratiaon or necrosis are not also seen in the pathological tissue inspection, compare no significant difference with the normal saline side.
Sensitization to Cavia porcellus:
Choose 6 of healthy guinea pigs, every lumbar injection embodiment 2 injection 0.5ml, the next day, inject 1 time, injects altogether 3 times.Be divided into 2 groups then at random, after the 1st administration 14 or 21 days respectively, intravenous injection embodiment 2 injection 1ml.Observe Cavia porcellus and have or not allergic symptoms such as excited uneasiness, dyspnea.
Two groups of Cavia porcelluss of result are all movable normal, do not see adnormal respiration etc.
External hemolytic test:
Prepare 2% rabbit red cell suspension.Get 7 in test tube, 2-6 adds various liquid by table.Each test tube is shaken up gently, put in 37 ℃ of waters bath with thermostatic control and hatch, observe 0.5,1,2,3,6 hour result.Erythrocyte agglutination in vitro and hemolytic criterion are seen table 2-7.
The external hemolytic test application of sample of table 2-6 sample table
Outer haemolysis of table 2-7 red cell body and agglutination test criterion
As a result, the distilled water control tube was complete hemolysis in 0.5 hour.Normal saline and each concentration of embodiment 2 samples did not all have haemolysis in 6 hours.Jolting gently, the erythrocyte of normal saline and each concentration embodiment 2 sample cell bottom sediments all can disperse fully, shows that the clean injection of Mi Kafen does not have red cell agglutination.
Blood vessel irritation, muscle irritation, external hemolytic and anaphylaxis experiment show that embodiment 2 injection do not have tangible zest, anaphylaxis, can not cause hemolytic reaction yet.
Stability experiment in the transfusion:
Injection Mi Kafen with 10.5ml purified water dilution embodiment 2 preparations is clean; Draw 10ml respectively; Use common infusion fluid respectively: 0.9% sodium chloride injection (0.9%NS), 5% glucose injection (5%GS), be diluted to 200ml, making the Mi Kafen net concentration is 0.25mg/ml.Respectively at 25 ℃, minute is observed its outward appearance, impurity, changes of contents, and the result sees table 2-8.
Table 2-8 injection stability experiment
The result shows; The clean preparation of Mi Kafen and the common infusion fluid of embodiment 2 preparations, 0.9% sodium chloride injection (0.9%NS), 5% glucose injection (5%GS) compatibility use, and stability is all better; Therefore, this embodiment makes sample and can use with these compatibilities of infusing.
Embodiment 3
Table 3-1 embodiment 3 composite formulas
| Component | Consumption |
| Mi Kafen is clean | 50mg/ml |
| Mannitol | 30mg/ml |
| Lactose | 30mg/ml |
| Sodium acetate | 50mM |
| Hydrochloric acid | In right amount, transfer to pH to 6.0 |
Its preparation process is following: in the 2500ml beaker, add 75g mannitol, 75g lactose, 1750ml water; It is clean to add Mi Kafen, to its final standardize solution concentration be 50mg/ml, adding sodium acetate to its concentration is 50mM; And with pH regulator to 6.0, add injection water standardize solution with 1N hydrochloric acid.Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered.Filtrating is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration.Every bottle of amount with 1.25ml is packed into the 10ml vial, lyophilization, and tamponade, Zha Gai obtains the clean preparation of injection Mi Kafen.
Make 1000 in the clean preparation of injection Mi Kafen by embodiment 3, its stability is investigated through accelerated test.Through animal blood vessels zest, muscle irritation, haemolysis and anaphylaxis experiment, local irritation is investigated.Through with the common infusion fluid compatibility, observe its outward appearance, related substance and changes of contents and investigated its stability in common infusion fluid.
Accelerated test:
Listing reference substance and the contrast of embodiment 3 samples
Respectively a collection of sample of clean preparation reference substance of commercially available injection Mi Kafen and embodiment 3 being put into temperature is that 40 ± 2 ℃, relative humidity are that 75% ± 5% climatic chamber is investigated; 0,1,2,3 and sampling and measuring 6 months the time, the result sees table 3-2 and table 3-3 respectively.
The commercially available reference substance accelerated test of table 3-2 result
Table 3-3 embodiment 3 sample accelerated test results
Can find out through table 3-2 and table 3-3; Investigate 6 months through accelerated test, the clean preparation of injection Mi Kafen of embodiment 3 preparations and the clean preparation of the injection Mi Kafen that has gone on the market relatively, appearance luster, pH, clarity of solution index are suitable; The impurity of the test sample of listing increases, content descends obviously; The sample of embodiment 3 preparations does not have significant change, so the clean injection of Mi Kafen of embodiment 3 preparations can be preserved the stability increase under room temperature.Blood vessel irritation, muscle irritation, anaphylaxis and hemolytic experiment:
Blood vessel irritation:
Choose 6 of the undamaged healthy rabbits of ears, left side auricular vein injection embodiment 3 injection 1ml, capacity 5% glucose injections such as auris dextra injection, were injected 7 days continuously at every day 1 time.
During the injection, regularly observe the irritative response of auricular vein every day.Put to death rabbit on the 8th day, and got bilateral auricular vein and surrounding tissue, use formaldehyde fixed, proximal part is done the conventional organization section in the injection site, and light microscopic is observed down and had or not pathological change.Observation index and criterion are seen table 3-4.
Table 3-4 blood vessel irritation scoring and criterion
The result shows that the zest of rabbit auricular vein injection embodiment 3 injection compares no significant difference with 5% glucose injection.Inflammatory reactions such as the congestion of blood vessel, surrounding tissue edema are not seen in perusal.Tissue slice inspection does not see that blood vessel structure is unusual, endothelial injury, thrombosis and other pathological change.The blood vessel of its naked eyes and om observation, the cumulative score of surrounding tissue show nonirritant all less than 0.5.
Muscle irritation:
Get 6 of healthy rabbits, injection embodiment 3 injection 1ml in every rabbit left side quadriceps femoris, inject with the volume normal saline on the right side.The injection back is observed injection site muscle and is had or not reactions such as hyperemia, edema, and (the 3rd day) sacrificed by exsanguination behind the Half animals 48h is vertically cut skin, and injection site, perusal both sides has or not reactions such as hyperemia, edema, and gets its tissue and do pathologic finding.Then by the IR of showing this medicine of standard evaluation among the 3-5.Remaining animal continues to observe 14d, repeats aforesaid operations in the 18th day after the sacrificed by exsanguination, and evaluation criterion is seen table 3-5.
Table 3-5 muscular irritation reaction evaluating standard
The result shows; After injecting embodiment 3 injection in the quadriceps femoris of rabbit left side; Perusal injection site muscle does not have reactions such as hyperemia, edema, and explicitly IRs such as tissue degeneratiaon or necrosis are not also seen in the pathological tissue inspection, compare no significant difference with the normal saline side.
Sensitization to Cavia porcellus:
Choose 6 of healthy guinea pigs, every lumbar injection embodiment 3 injection 0.5ml, the next day, inject 1 time, injects altogether 3 times.Be divided into 2 groups then at random, after the 1st administration 14 or 21 days respectively, intravenous injection embodiment 2 injection 1ml.Observe Cavia porcellus and have or not allergic symptoms such as excited uneasiness, dyspnea.
Two groups of Cavia porcelluss of result are all movable normal, do not see adnormal respiration etc.
External hemolytic test:
Prepare 2% rabbit red cell suspension.Get 7 in test tube, 3-6 adds various liquid by table.Each test tube is shaken up gently, put in 37 ℃ of waters bath with thermostatic control and hatch, observe 0.5,1,2,3,6 hour result.Erythrocyte agglutination in vitro and hemolytic criterion are seen table 3-7.
The external hemolytic test application of sample of table 3-6 sample table
Outer haemolysis of table 3-7 red cell body and agglutination test criterion
As a result, the distilled water control tube was complete hemolysis in 0.5 hour.Normal saline and each concentration of embodiment 3 samples did not all have haemolysis in 6 hours.Jolting gently, the erythrocyte of normal saline and each concentration embodiment 3 sample cell bottom sediments all can disperse fully, shows that the clean injection of Mi Kafen does not have red cell agglutination.
Blood vessel irritation, muscle irritation, external hemolytic and anaphylaxis experiment show that embodiment 3 injection do not have tangible zest, anaphylaxis, can not cause hemolytic reaction yet.
Stability experiment in the transfusion:
Injection Mi Kafen with 10.5ml purified water dilution embodiment 3 preparations is clean; Draw 10ml respectively; Use common infusion fluid respectively: 0.9% sodium chloride injection (0.9%NS), 5% glucose injection (5%GS), be diluted to 200ml, making the Mi Kafen net concentration is 0.25mg/ml.Respectively at 25 ℃, minute is observed its outward appearance, impurity, changes of contents, and the result sees table 3-8.
Table 3-8 injection stability experiment
The result shows; The clean preparation of Mi Kafen and the common infusion fluid of embodiment 3 preparations, 0.9% sodium chloride injection (0.9%NS), 5% glucose injection (5%GS) compatibility use, and stability is all better; Therefore, this embodiment makes sample and can use with these compatibilities of infusing.
Claims (10)
1. the clean ejection preparation compositions of Yi Zhong Mi Kafen; It is characterized in that: comprise that it is 4.0-7.0 that Mi Kafen clean or its pharmaceutically available salt 5-200mg/ml, excipient 5-250mg/ml, buffer 10-250mM and an amount of sodium hydroxide or hydrochloric acid are regulated pH value, wherein buffer agent is acetate, sulfate, citrate, phosphate, lactate or its mixture.
2. the clean ejection preparation compositions of Mi Kafen according to claim 1, the clean pharmaceutically acceptable salt of wherein said Mi Kafen are and the alkali metal addition salts that described alkali metal is selected from sodium, potassium, calcium, magnesium etc.
3. according to the pharmaceutical composition of claim 1 or 2, the clean pharmaceutically acceptable salt of wherein said Mi Kafen is the clean sodium of Mi Kafen.
4. according to the described pharmaceutical composition of claim 1-3, clean or its pharmaceutically acceptable salt content of wherein said Mi Kafen is preferably 40-100mg/ml.
5. the clean ejection preparation compositions of Mi Kafen according to claim 1 is characterized in that: said excipient is sorbitol, mannitol, lactose, sucrose, glucose, maltose or its mixture.
6. the clean ejection preparation compositions of Mi Kafen according to claim 5 is characterized in that: the mixture of preferred mannitol of said excipient and lactose, the preferred 50-70mg/ml of content.
7. the clean ejection preparation compositions of Mi Kafen according to claim 1 is characterized in that: said buffer agent is sodium acetate, sodium bisulfate, sodium citrate, sodium phosphate, sodium lactate or its mixture.
8. the clean ejection preparation compositions of Mi Kafen according to claim 1 is characterized in that: the preferred sodium acetate of said buffer agent, the preferred 10-50mM of content.
9. the clean ejection preparation compositions of Mi Kafen according to claim 1 is characterized in that: the preferred 5.0-7.0 of pH value.
10. prepare the clean ejection preparation method for compositions of the described Mi Kafen of claim 1, this method comprises the following steps:
(1) compositions of excipient or excipient is soluble in water;
(2) add clean or its pharmaceutically acceptable salt of Mi Kafen in the aqueous solution that in step (1), obtains, and with its dissolving;
(3) add the PH regulator in the aqueous solution that in step (2), obtains, reach required pH value;
(4) filter the also solution of lyophilization step (3) preparation.
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| CN201110427784.2A CN102512379B (en) | 2011-12-16 | 2011-12-16 | A kind of novel Echinocandin antifungal pharmaceutical composition and preparation method thereof |
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| CN201110427784.2A CN102512379B (en) | 2011-12-16 | 2011-12-16 | A kind of novel Echinocandin antifungal pharmaceutical composition and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104888222A (en) * | 2015-06-09 | 2015-09-09 | 深圳市健元医药科技有限公司 | Medicinal composition for treating complex infection and preparation method of medicinal composition |
| CN105106933A (en) * | 2015-09-06 | 2015-12-02 | 江苏奥赛康药业股份有限公司 | Freeze-dried composition containing micafungin and preparation method of freeze-dried composition |
| CN105748414A (en) * | 2016-03-02 | 2016-07-13 | 张光泉 | Anti-infection micafungin freeze-drying composition and preparation method thereof |
| US20180169180A1 (en) * | 2016-12-16 | 2018-06-21 | Baxter International Inc. | Micafungin compositions |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1100104A (en) * | 1993-05-17 | 1995-03-15 | 藤泽药品工业株式会社 | New polypeptide compound and a process for preparation thereof |
| CN101444492A (en) * | 2008-12-04 | 2009-06-03 | 山西普德药业有限公司 | Lomefloxacin hydrochloride lyophilized powder for injection and preparation method therefor |
-
2011
- 2011-12-16 CN CN201110427784.2A patent/CN102512379B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1100104A (en) * | 1993-05-17 | 1995-03-15 | 藤泽药品工业株式会社 | New polypeptide compound and a process for preparation thereof |
| CN101444492A (en) * | 2008-12-04 | 2009-06-03 | 山西普德药业有限公司 | Lomefloxacin hydrochloride lyophilized powder for injection and preparation method therefor |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104888222A (en) * | 2015-06-09 | 2015-09-09 | 深圳市健元医药科技有限公司 | Medicinal composition for treating complex infection and preparation method of medicinal composition |
| CN105106933A (en) * | 2015-09-06 | 2015-12-02 | 江苏奥赛康药业股份有限公司 | Freeze-dried composition containing micafungin and preparation method of freeze-dried composition |
| CN105748414A (en) * | 2016-03-02 | 2016-07-13 | 张光泉 | Anti-infection micafungin freeze-drying composition and preparation method thereof |
| US20180169180A1 (en) * | 2016-12-16 | 2018-06-21 | Baxter International Inc. | Micafungin compositions |
| JP2020510619A (en) * | 2016-12-16 | 2020-04-09 | バクスター・インターナショナル・インコーポレイテッドＢａｘｔｅｒ Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｉｎｃｏｒｐ０Ｒａｔｅｄ | Micafungin composition |
| AU2017376960B2 (en) * | 2016-12-16 | 2023-12-14 | Baxter Healthcare Sa | Micafungin compositions |
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|---|---|
| CN102512379B (en) | 2017-03-08 |
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