CN102512379B - A kind of novel Echinocandin antifungal pharmaceutical composition and preparation method thereof - Google Patents
A kind of novel Echinocandin antifungal pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN102512379B CN102512379B CN201110427784.2A CN201110427784A CN102512379B CN 102512379 B CN102512379 B CN 102512379B CN 201110427784 A CN201110427784 A CN 201110427784A CN 102512379 B CN102512379 B CN 102512379B
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Abstract
The invention belongs to pharmaceutical formulation technical field, provide the ejection preparation compositionss that a kind of MFG is effective ingredient.This ejection preparation compositionss, including MFG or its pharmaceutically available salt 5 200mg/ml, excipient 5 250mg/ml, buffer 10 250mM and appropriate sodium hydroxide or salt acid for adjusting pH value are 4.0 7.0.
Description
Technical field：
The present invention relates to antifungal preparation, more particularly, to a kind of novel Echinocandin antifungal pharmaceutical composition.
Background technology：
It has been found that spine ball diphtheria chlorins compound has good antibacterial activity, therefore, people have studied within 1974
The pharmacologically active of many semisynthetic spine ball diphtheria chlorins compounds.Wherein, MFG (Micafungin) is one of which,
Already function as preparation treatment or prevention antifungal preparation.United States Patent (USP) US5376634, US5569646, WO9611210 and
WO9940108 discloses this compound and preparation method thereof.
Content of the invention：
The invention provides a kind of stable pharmaceutical composition, it comprises：
(1) MFG or its pharmaceutically available salt；
(2) buffer and appropriate sodium hydroxide or hydrochloric acid adjust pH adjusting agent；
(3) it is effectively formed the pharmaceutically acceptable excipient of lyophilized cake.
Wherein, the described preferred FK463 of MFG pharmaceutically acceptable salt, described excipient be Sorbitol,
Mannitol, Lactose, sucrose, glucose, maltose or its mixture, preferably Mannitol and the mixture of Lactose.Described buffering
Agent is Sodium Acetate Trihydrate, sodium bisulfate, sodium citrate, sodium phosphate, sodium lactate or its mixture, preferably Sodium Acetate Trihydrate.
In addition, a kind of the invention provides lyophilizing being obtained by lyophilizing pharmaceutical composition of the present invention as above
Powder.This lyophilized powder is suitable for re-dissolved and becomes intravenous fluid composition.
Present invention also offers the method for the pharmaceutical composition of pharmaceutically acceptable salt containing MFG for the preparation, the party
Method comprises the following steps：
(1) will be soluble in water for the compositionss of excipient or excipient；
(2) MFG or its pharmaceutically acceptable salt are added in the aqueous solution obtaining in step (1), and it is molten
Solution；
(3) add PH regulator in the aqueous solution obtaining in step (2), reach required pH value；
(4) filter the solution that simultaneously prepared by lyophilization step (3).
The pharmaceutical composition prepared according to the method described above is than existing preparation stabilization, and preparation method is easier.
Specific embodiment：
Below in conjunction with embodiment, embodiment of the present invention is described in detail, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and should not be taken as limiting the scope of the invention.
Embodiment 1
Table 1-1 embodiment 1 composite formula
| Component | Consumption |
| MFG | 50mg/ml |
| Mannitol | 30mg/ml |
| Sorbitol | 20mg/ml |
| Sodium dihydrogen phosphate | 20mM |
| Hydrochloric acid | In right amount, it is adjusted to pH to 5.2 |
Its preparation process is as follows：Add 75g Mannitol, 50g Sorbitol, 1750ml water in 2500ml beaker, add rice
Card is fragrant net, is 50mg/ml to its final constant volume concentration, adds sodium dihydrogen phosphate to be 20mM to its concentration, and uses 1N hydrochloric acid
By pH regulator to 5.2.Plus water for injection constant volume.Before filtration, 12.5g activated carbon, heat of adsorption under agitation are added in injection
Former 30 minutes, decarburization was filtered.Filtrate is filtered through 0.22 μm of titanium rod filter, then through 0.22 μm of microporous filter membrane aseptic filtration.Every bottle
10ml vial, lyophilization, tamponade, Zha Gai are packed into the amount of 1.25ml, obtain injection MFG preparation.
1000, injection MFG preparation is obtained by embodiment 1, logical accelerated test is investigated to its stability.
Tested by animal blood vessels zest, muscle irritation, haemolysis and anaphylaxis, local irritation is investigated.By with
Some infusion fluids, observe its outward appearance, have investigated its stability in common infusion fluid about material and changes of contents.
Accelerated test：
Listing reference substance and embodiment 1 sample contrast：
Respectively by a batch sample of commercially available injection MFG preparations. Control product and embodiment 1 put into temperature be 40 ±
2 DEG C, relative humidity be 75% ± 5% climatic chamber in investigated, respectively when 0,1,2,3 and 6 months be measured by sampling,
The results are shown in Table 1-2 and table 1-3.
Table 1-2 commercially available reference substance accelerated test result
Table 1-3 embodiment 1 sample accelerated test result
Accelerated experiment investigation be can be seen that 6 months by table 1-2 and table 1-3, the injection rice card of embodiment 1 preparation
Fragrant net system agent is compared with the injection MFG preparation of listing, and appearance luster, pH, clarity of solution index are suitable, but real
The impurity applying the test sample than listing for the sample of example 1 preparation increases, content declines substantially, shows the sample of embodiment 1 preparation
Be not as stable as the test sample of listing.
Blood vessel irritation, muscle irritation, anaphylaxis and hemolytic experiment：
Blood vessel irritation：
Choose the undamaged healthy rabbits of ears 6, left side auricular vein injects embodiment 1 injection 1ml, auris dextra is injected
Deng capacity 5% Glucose Injection, once a day, continuous injection 7 days.
During injection, the irritative response of auricular vein is observed in daily timing.Put to death rabbit within 8th day, take bilateral ear edge quiet
Arteries and veins and surrounding tissue, are fixed with formaldehyde, make conventional organization section in injection site proximal part, and light Microscopic observation has or not pathology and becomes
Change.Observation index and criterion are shown in Table 1-4.
The scoring of table 1-4 blood vessel irritation and criterion
Result shows, rabbit auricular vein injects the zest of embodiment 1 injection, compares with 5% Glucose Injection
No significant difference.Perusal, has no the inflammatory reactions such as the congestion of blood vessel, peripheral tissue edema.Tissue slice checks, has no blood vessel
Textural anomaly, endothelial injury, thrombosiss and other pathological change.Its visually with the blood vessel of om observation, surrounding tissue tired
Meter score is respectively less than 0.5, shows nonirritant.
Muscle irritation：
Take healthy rabbits 6, injection embodiment 1 injection 1ml in quadriceps femoris on the left of every rabbit, consubstantiality is injected on right side
Long-pending normal saline.Observe injection site muscle after injection and have or not the reaction such as hyperemia, edema, (the 3rd day) blood-letting after half animal 48h
Put to death, longitudinally slit skin, perusal both sides injection site has or not the reaction such as hyperemia, edema, and take its tissue to do pathology inspection
Look into.Then the irritant reaction of this medicine is evaluated by the standard in table 1-5.Remaining animal continues to observe 14d, in the 18th day sacrificed by exsanguination
Repeat aforesaid operations afterwards, evaluation criterion is shown in Table 1-5.
Table 1-5 muscular irritation reaction evaluating standard
Result shows, after injection embodiment 1 injection in quadriceps femoris on the left of rabbit, perusal injection site muscle is no
Hyperemia, edema etc. are reacted, and pathologic diagnosis also have no the explicitly irritant reaction such as tissue degeneratiaon or necrosis, with normal saline side
Compare no significant difference.
Sensitization to Cavia porcelluss：
Choose healthy guinea pig 6, every lumbar injection embodiment 1 injection 0.5ml, the next day inject 1 time, co-injection 3 times.
Then it is randomly divided into 2 groups, respectively 14 or 21 days after the 1st administration, intravenous injection embodiment 1 injection 1ml.Observing Cavia porcelluss has
The allergic symptoms such as no excited uneasiness, dyspnea.
The all activities of two groups of Cavia porcelluss of result are normal, have no adnormal respiration etc..
Hemolysis in vitro is tested：
Prepare 2% rabbit red cell suspension.Take 7, test tube, add various liquid by table 1-6.Each test tube is gently shaken up,
Put incubation in 37 DEG C of waters bath with thermostatic control, observe the result of 0.5,1,2,3,6 hours.Erythrocyte agglutination in vitro and the criterion of haemolysis
It is shown in Table 1-7.
Table 1-6 sample hemolysis in vitro test sample-adding table
Table 1-7 erythrocyte hemolysis in vitro and agglutination test criterion
As a result, distilled water control tube was in complete hemolysis in 0.5 hour.Normal saline and each concentration of embodiment 1 sample were at 6 hours
Inside equal no haemolysises.Gently shake, the erythrocyte of normal saline and each concentration embodiment 1 sample cell bottom sediments all can divide completely
Dissipate, show MFG injection no red cell agglutination.
Blood vessel irritation, muscle irritation, hemolysis in vitro and anaphylaxis experiment show, embodiment 1 injection is no obvious
Zest, anaphylaxis, also will not cause hemolytic reaction.
Stability experiment in transfusion：
Dilute the injection MFG of embodiment 1 preparation with 10.5ml purified water, draw 10ml respectively, respectively with commonly using
Transfusion：0.9% sodium chloride injection (0.9%NS), 5% Glucose Injection (5%GS), it is diluted to 200ml, make MFG
Concentration is 0.25mg/ml.Respectively at 25 DEG C, minute observes its outward appearance, impurity, changes of contents, the results are shown in Table 1-8.
Table 1-8 injection stability experiment
Result shows, MFG preparation and common infusion fluid prepared by embodiment 1,0.9% sodium chloride injection (0.9%
NS), 5% Glucose Injection (5%GS) compatibility uses, and stability is all not so good, and therefore, this embodiment is obtained sample cannot
Use with these infusions.
Embodiment 2
Table 2-1 embodiment 2 composite formula
| Component | Consumption |
| MFG | 50mg/ml |
| Mannitol | 50mg/ml |
| Sodium Acetate Trihydrate | 50mM |
| Hydrochloric acid | In right amount, it is adjusted to pH to 6.0 |
Its preparation process is as follows：Add 125g Mannitol, 1750ml water in 2500ml beaker, add MFG, extremely
Its final constant volume concentration is 50mg/ml, adds Sodium Acetate Trihydrate to be 50mM to its concentration, and with 1N hydrochloric acid by pH regulator to 6.0,
Plus water for injection constant volume.Before filtration, add 12.5g activated carbon in injection, under agitation absorption pyrogen 30 minutes, decarburization
Filter.Filtrate is filtered through 0.22 μm of titanium rod filter, then through 0.22 μm of microporous filter membrane aseptic filtration.Every bottle of amount filling with 1.25ml
Enter 10ml vial, lyophilization, tamponade, Zha Gai, obtain injection MFG preparation.
1000, injection MFG preparation is obtained by embodiment 2, by accelerated test, its stability is examined
Examine.Tested by animal blood vessels zest, muscle irritation, haemolysis and anaphylaxis, local irritation is investigated.Pass through
With some infusion fluids, observe its outward appearance, investigated its stability in common infusion fluid about material and changes of contents.
Accelerated test：
Listing reference substance and embodiment 2 sample contrast
Respectively by a batch sample of commercially available injection MFG preparations. Control product and embodiment 2 put into temperature be 40 ±
2 DEG C, relative humidity be 75% ± 5% climatic chamber in investigated, respectively when 0,1,2,3 and 6 months be measured by sampling,
The results are shown in Table 2-2 and table 2-3.
Table 2-2 commercially available reference substance accelerated test result
Table 2-3 embodiment 2 sample accelerated test result
Accelerated experiment investigation be can be seen that 6 months by table 2-2 and table 2-3, the injection rice card of embodiment 2 preparation
Fragrant net system agent is compared with the injection MFG preparation of listing, and appearance luster, pH, clarity of solution index are suitable,
The impurity of the test sample of listing increases, content declines substantially, shows that the MFG injection of present invention preparation can be at room temperature
Preserve, stability increases.
Blood vessel irritation, muscle irritation, anaphylaxis and hemolytic experiment：
Blood vessel irritation：
Choose the undamaged healthy rabbits of ears 6, left side auricular vein injects embodiment 2 injection 1ml, auris dextra is injected
Deng capacity 5% Glucose Injection, once a day, continuous injection 7 days.
During injection, the irritative response of auricular vein is observed in daily timing.Put to death rabbit within 8th day, take bilateral ear edge quiet
Arteries and veins and surrounding tissue, are fixed with formaldehyde, make conventional organization section in injection site proximal part, and light Microscopic observation has or not pathology and becomes
Change.Observation index and criterion are shown in Table 2-4.
The scoring of table 2-4 blood vessel irritation and criterion
Result shows, rabbit auricular vein injects the zest of embodiment 2 injection, compares with 5% Glucose Injection
No significant difference.Perusal, has no the inflammatory reactions such as the congestion of blood vessel, peripheral tissue edema.Tissue slice checks, has no blood vessel
Textural anomaly, endothelial injury, thrombosiss and other pathological change.Its visually with the blood vessel of om observation, surrounding tissue tired
Meter score is respectively less than 0.5, shows nonirritant.
Muscle irritation：
Take healthy rabbits 6, injection embodiment 2 injection 1ml in quadriceps femoris on the left of every rabbit, consubstantiality is injected on right side
Long-pending normal saline.Observe injection site muscle after injection and have or not the reaction such as hyperemia, edema, (the 3rd day) blood-letting after half animal 48h
Put to death, longitudinally slit skin, perusal both sides injection site has or not the reaction such as hyperemia, edema, and take its tissue to do pathology inspection
Look into.Then the irritant reaction of this medicine is evaluated by the standard in table 2-5.Remaining animal continues to observe 14d, in the 18th day sacrificed by exsanguination
Repeat aforesaid operations afterwards, evaluation criterion is shown in Table 2-5.
Table 2-5 muscular irritation reaction evaluating standard
Result shows, after injection embodiment 2 injection in quadriceps femoris on the left of rabbit, perusal injection site muscle is no
Hyperemia, edema etc. are reacted, and pathologic diagnosis also have no the explicitly irritant reaction such as tissue degeneratiaon or necrosis, with normal saline side
Compare no significant difference.
Sensitization to Cavia porcelluss：
Choose healthy guinea pig 6, every lumbar injection embodiment 2 injection 0.5ml, the next day inject 1 time, co-injection 3 times.
Then it is randomly divided into 2 groups, respectively 14 or 21 days after the 1st administration, intravenous injection embodiment 2 injection 1ml.Observing Cavia porcelluss has
The allergic symptoms such as no excited uneasiness, dyspnea.
The all activities of two groups of Cavia porcelluss of result are normal, have no adnormal respiration etc..
Hemolysis in vitro is tested：
Prepare 2% rabbit red cell suspension.Take 7, test tube, add various liquid by table 2-6.Each test tube is gently shaken up,
Put incubation in 37 DEG C of waters bath with thermostatic control, observe the result of 0.5,1,2,3,6 hours.Erythrocyte agglutination in vitro and the criterion of haemolysis
It is shown in Table 2-7.
Table 2-6 sample hemolysis in vitro test sample-adding table
Table 2-7 erythrocyte hemolysis in vitro and agglutination test criterion
As a result, distilled water control tube was in complete hemolysis in 0.5 hour.Normal saline and each concentration of embodiment 2 sample were at 6 hours
Inside equal no haemolysises.Gently shake, the erythrocyte of normal saline and each concentration embodiment 2 sample cell bottom sediments all can divide completely
Dissipate, show MFG injection no red cell agglutination.
Blood vessel irritation, muscle irritation, hemolysis in vitro and anaphylaxis experiment show, embodiment 2 injection is no obvious
Zest, anaphylaxis, also will not cause hemolytic reaction.
Stability experiment in transfusion：
Dilute the injection MFG of embodiment 2 preparation with 10.5ml purified water, draw 10ml respectively, respectively with commonly using
Transfusion：0.9% sodium chloride injection (0.9%NS), 5% Glucose Injection (5%GS), it is diluted to 200ml, make MFG
Concentration is 0.25mg/ml.Respectively at 25 DEG C, minute observes its outward appearance, impurity, changes of contents, the results are shown in Table 2-8.
Table 2-8 injection stability experiment
Result shows, MFG preparation and common infusion fluid prepared by embodiment 2,0.9% sodium chloride injection (0.9%
NS), 5% Glucose Injection (5%GS) compatibility uses, and stability is all preferable, and therefore, this embodiment is obtained sample can be with this
A little infusions use.
Embodiment 3
Table 3-1 embodiment 3 composite formula
| Component | Consumption |
| MFG | 50mg/ml |
| Mannitol | 30mg/ml |
| Lactose | 30mg/ml |
| Sodium Acetate Trihydrate | 50mM |
| Hydrochloric acid | In right amount, it is adjusted to pH to 6.0 |
Its preparation process is as follows：Add 75g Mannitol, 75g Lactose, 1750ml water in 2500ml beaker, add rice card
Fragrant net, it is 50mg/ml to its final constant volume concentration, add Sodium Acetate Trihydrate to be 50mM to its concentration, and with 1N hydrochloric acid, pH is adjusted
Save to 6.0, plus water for injection constant volume.Before filtration, add 12.5g activated carbon in injection, adsorb 30 points of pyrogen under agitation
Clock, decarburization is filtered.Filtrate is filtered through 0.22 μm of titanium rod filter, then through 0.22 μm of microporous filter membrane aseptic filtration.Every bottle with
The amount of 1.25ml is packed into 10ml vial, lyophilization, tamponade, Zha Gai, obtains injection MFG preparation.
1000, injection MFG preparation is obtained by embodiment 3, by accelerated test, its stability is examined
Examine.Tested by animal blood vessels zest, muscle irritation, haemolysis and anaphylaxis, local irritation is investigated.Pass through
With some infusion fluids, observe its outward appearance, investigated its stability in common infusion fluid about material and changes of contents.
Accelerated test：
Listing reference substance and embodiment 3 sample contrast
Respectively by a batch sample of commercially available injection MFG preparations. Control product and embodiment 3 put into temperature be 40 ±
2 DEG C, relative humidity be 75% ± 5% climatic chamber in investigated, respectively when 0,1,2,3 and 6 months be measured by sampling,
The results are shown in Table 3-2 and table 3-3.
Table 3-2 commercially available reference substance accelerated test result
Table 3-3 embodiment 3 sample accelerated test result
Accelerated experiment investigation be can be seen that 6 months by table 3-2 and table 3-3, the injection rice card of embodiment 3 preparation
Fragrant net system agent is compared with the injection MFG preparation of listing, and appearance luster, pH, clarity of solution index are suitable,
The impurity of the test sample of listing increases, content declines substantially, the sample no significant change of embodiment 3 preparation, and therefore embodiment 3 is made
Standby MFG injection can preserve at room temperature, and stability increases.Blood vessel irritation, muscle irritation, anaphylaxis and molten
Blood is tested：
Blood vessel irritation：
Choose the undamaged healthy rabbits of ears 6, left side auricular vein injects embodiment 3 injection 1ml, auris dextra is injected
Deng capacity 5% Glucose Injection, once a day, continuous injection 7 days.
During injection, the irritative response of auricular vein is observed in daily timing.Put to death rabbit within 8th day, take bilateral ear edge quiet
Arteries and veins and surrounding tissue, are fixed with formaldehyde, make conventional organization section in injection site proximal part, and light Microscopic observation has or not pathology and becomes
Change.Observation index and criterion are shown in Table 3-4.
The scoring of table 3-4 blood vessel irritation and criterion
Result shows, rabbit auricular vein injects the zest of embodiment 3 injection, compares with 5% Glucose Injection
No significant difference.Perusal, has no the inflammatory reactions such as the congestion of blood vessel, peripheral tissue edema.Tissue slice checks, has no blood vessel
Textural anomaly, endothelial injury, thrombosiss and other pathological change.Its visually with the blood vessel of om observation, surrounding tissue tired
Meter score is respectively less than 0.5, shows nonirritant.
Muscle irritation：
Take healthy rabbits 6, injection embodiment 3 injection 1ml in quadriceps femoris on the left of every rabbit, consubstantiality is injected on right side
Long-pending normal saline.Observe injection site muscle after injection and have or not the reaction such as hyperemia, edema, (the 3rd day) blood-letting after half animal 48h
Put to death, longitudinally slit skin, perusal both sides injection site has or not the reaction such as hyperemia, edema, and take its tissue to do pathology inspection
Look into.Then the irritant reaction of this medicine is evaluated by the standard in table 3-5.Remaining animal continues to observe 14d, in the 18th day sacrificed by exsanguination
Repeat aforesaid operations afterwards, evaluation criterion is shown in Table 3-5.
Table 3-5 muscular irritation reaction evaluating standard
Result shows, after injection embodiment 3 injection in quadriceps femoris on the left of rabbit, perusal injection site muscle is no
Hyperemia, edema etc. are reacted, and pathologic diagnosis also have no the explicitly irritant reaction such as tissue degeneratiaon or necrosis, with normal saline side
Compare no significant difference.
Sensitization to Cavia porcelluss：
Choose healthy guinea pig 6, every lumbar injection embodiment 3 injection 0.5ml, the next day inject 1 time, co-injection 3 times.
Then it is randomly divided into 2 groups, respectively 14 or 21 days after the 1st administration, intravenous injection embodiment 2 injection 1ml.Observing Cavia porcelluss has
The allergic symptoms such as no excited uneasiness, dyspnea.
The all activities of two groups of Cavia porcelluss of result are normal, have no adnormal respiration etc..
Hemolysis in vitro is tested：
Prepare 2% rabbit red cell suspension.Take 7, test tube, add various liquid by table 3-6.Each test tube is gently shaken up,
Put incubation in 37 DEG C of waters bath with thermostatic control, observe the result of 0.5,1,2,3,6 hours.Erythrocyte agglutination in vitro and the criterion of haemolysis
It is shown in Table 3-7.
Table 3-6 sample hemolysis in vitro test sample-adding table
Table 3-7 erythrocyte hemolysis in vitro and agglutination test criterion
As a result, distilled water control tube was in complete hemolysis in 0.5 hour.Normal saline and each concentration of embodiment 3 sample were at 6 hours
Inside equal no haemolysises.Gently shake, the erythrocyte of normal saline and each concentration embodiment 3 sample cell bottom sediments all can divide completely
Dissipate, show MFG injection no red cell agglutination.
Blood vessel irritation, muscle irritation, hemolysis in vitro and anaphylaxis experiment show, embodiment 3 injection is no obvious
Zest, anaphylaxis, also will not cause hemolytic reaction.
Stability experiment in transfusion：
Dilute the injection MFG of embodiment 3 preparation with 10.5ml purified water, draw 10ml respectively, respectively with commonly using
Transfusion：0.9% sodium chloride injection (0.9%NS), 5% Glucose Injection (5%GS), it is diluted to 200ml, make MFG
Concentration is 0.25mg/ml.Respectively at 25 DEG C, minute observes its outward appearance, impurity, changes of contents, the results are shown in Table 3-8.
Table 3-8 injection stability experiment
Result shows, MFG preparation and common infusion fluid prepared by embodiment 3,0.9% sodium chloride injection (0.9%
NS), 5% Glucose Injection (5%GS) compatibility uses, and stability is all preferable, and therefore, this embodiment is obtained sample can be with this
A little infusions use.
Claims (3)
1. a kind of novel Echinocandin antifungal pharmaceutical composition, is characterized in that said preparation is a kind of MFG ejection preparation
Compositionss, its preparation technology is as follows：Add 75g Mannitol, 50g Sorbitol, 1750mL water in 2500mL beaker, add rice card
Fragrant net, it is 50mg/mL to its final constant volume concentration, add sodium dihydrogen phosphate to its concentration to be 20mM, and will with 1N hydrochloric acid
PH regulator is to 5.2, plus water for injection constant volume；Before filtration, add 12.5g activated carbon in injection, adsorb pyrogen under agitation
30min, decarburization is filtered, and filtrate is filtered through 0.22 μm of titanium rod filter, then through 0.22 μm of microporous filter membrane aseptic filtration；Every bottle with
The amount of 1.25mL is packed into 10mL vial, lyophilization, tamponade, Zha Gai, 1000, prepared injection MFG preparation.
2. a kind of novel Echinocandin antifungal pharmaceutical composition, is characterized in that said preparation is a kind of MFG ejection preparation
Compositionss, its preparation technology is as follows：Add 125g Mannitol, 1750mL water in 2500mL beaker, add MFG, to it
Final constant volume concentration is 50mg/mL, adds Sodium Acetate Trihydrate to be 50mM to its concentration, and with 1N hydrochloric acid by pH regulator to 6.0, plus
Water for injection constant volume；Before filtration, add 12.5g activated carbon in injection, adsorb pyrogen 30min under agitation, decarburization is filtered,
Filtrate is filtered through 0.22 μm of titanium rod filter, then through 0.22 μm of microporous filter membrane aseptic filtration；Every bottle of amount with 1.25mL is packed into
10mL vial, lyophilization, tamponade, Zha Gai, 1000, prepared injection MFG preparation.
3. a kind of novel Echinocandin antifungal pharmaceutical composition, is characterized in that said preparation is a kind of MFG ejection preparation
Compositionss, its preparation technology is as follows：Add 75g Mannitol, 75g Lactose, 1750mL water in 2500mL beaker, add meter Ka Fen
Only, it is 50mg/mL to its final constant volume concentration, add Sodium Acetate Trihydrate to its concentration to be 50mM, and with 1N hydrochloric acid by pH regulator
To 6.0, plus water for injection constant volume；Before filtration, add 12.5g activated carbon in injection, adsorb pyrogen 30min under agitation,
Decarburization is filtered, and filtrate is filtered through 0.22 μm of titanium rod filter, then through 0.22 μm of microporous filter membrane aseptic filtration；Every bottle with 1.25mL's
Amount is packed into 10mL vial, lyophilization, tamponade, Zha Gai, 1000, prepared injection MFG preparation.
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| 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 |
| PT3554474T (en) * | 2016-12-16 | 2024-02-12 | Baxter Healthcare Sa | 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 |
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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 |
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