CN103212059A - Composition containing antifungal drug and lactate buffering liquid - Google Patents
Composition containing antifungal drug and lactate buffering liquid Download PDFInfo
- Publication number
- CN103212059A CN103212059A CN2012104475763A CN201210447576A CN103212059A CN 103212059 A CN103212059 A CN 103212059A CN 2012104475763 A CN2012104475763 A CN 2012104475763A CN 201210447576 A CN201210447576 A CN 201210447576A CN 103212059 A CN103212059 A CN 103212059A
- Authority
- CN
- China
- Prior art keywords
- caspofungin
- pharmaceutical composition
- compositions
- pharmaceutically acceptable
- preferred
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- OLXIURNGEYFIGA-UPNFTXAFSA-N CCC(C)CC(C)CCCCCCCCC(NC(C[C@H]([C@@H](NCCN)NC([C@H]([C@H](CC1)O)N1C([C@H]([C@@H](CCN)O)NC(C([C@H]([C@H](C)c(cc1)ccc1O)O)NC([C@H](C[C@H](C1)O)N1C([C@H]([C@@H](C)O)N1)=O)=O)=O)=O)=O)O)C1=O)=O Chemical compound CCC(C)CC(C)CCCCCCCCC(NC(C[C@H]([C@@H](NCCN)NC([C@H]([C@H](CC1)O)N1C([C@H]([C@@H](CCN)O)NC(C([C@H]([C@H](C)c(cc1)ccc1O)O)NC([C@H](C[C@H](C1)O)N1C([C@H]([C@@H](C)O)N1)=O)=O)=O)=O)=O)O)C1=O)=O OLXIURNGEYFIGA-UPNFTXAFSA-N 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a drug composition, containing caspofungin or pharmaceutically acceptable salts thereof, and a lactate buffering liquid in a pharmaceutically acceptable amount. By addition of the lactate buffering liquid, the composition greatly decreases generation of caspofungin degradation product, greatly raises stability of caspofungin, and is convenient for preservation and clinic usage, thereby raising usage security of caspofungin.
Description
Technical field
The present invention relates to treat and/or prevent the pharmaceutical composition of fungal infection, it comprises Caspofungin or its officinal salt and lactate buffer.
Background technology
Caspofungin has following structural formula,
It belongs to the antifungal agent of azacyclo-six peptides of echinocandin class, and its preparation method is at US5378804 (ZL94191487.9), US5552521, and US595230, US6136783, CN101305018A, CN101792486A is described and discloses.Caspofungin can suppress the synthetic of β-(1,3)-D-glucosan, and this is then not have β-(1,3)-D-glucosan in the cell of a kind of fundamental component mammal of many filamentous fungis and yeast cell wall.Caspofungin has antibacterial activity to pathogenic Eurotium of many kinds and Candida fungus, and effective to the fungus of anti-amphotericin B and fluconazol.
Caspofungin chemical compound itself is highly unstable, can degrade in every way, and described mode includes, but is not limited to hydrolysis, dimerization and oxidation.Because the unstability of Caspofungin for long-time stability and the medication stability that guarantees Caspofungin, needs a kind of technical scheme and preparation thereof that can guarantee that Caspofungin is stable of exploitation, with the generation of the unwanted degradation product of minimizing of trying one's best.
Disclosed the Pharmaceutical composition that contains acetate buffer of Caspofungin among patent ZL97195514.X or the US6136783, think and prolonged the storage life of compositions because of having used acetate buffer to make, and the lyophilized products ratio uses the buffer of other salt more stable, contains unwanted degradation product still less,, it does not provide the data of clear and definite catabolite but disclosing some embodiment schemes, through inventor's test, this contains the Pharmaceutical composition of acetate buffer and stable inadequately.
Disclosed the use nonreducing sugar among the WO2009002481A1, as trehalose, prepare freeze-dried composition, think that the use nonreducing sugar can improve the glass transition temperature (Tg) of lyophilized powder and improve the stability of freeze-dried composition to heat, what it still used is acetate buffer, play the still acetate buffer of Stabilization, whole invention does not break away from the invention scope of patent ZL97195514.X or US6136783, and this pharmaceutical composition is also stable inadequately.
Disclosed among patent application CN101516397A or the WO2008012310A1 and used the acetic acid of minute quantity can prepare the Caspofungin pharmaceutical composition that has good stability as the pH regulator agent, still be to have adopted the acetate buffer system, invention is still at the invention scope of patent ZL97195514.X or US6136783, and this pharmaceutical composition is more more unstable than disclosed pharmaceutical composition among patent ZL97195514.X or the US6136783, can't adopt in the practice.
CN102166186A claims and has made a kind of sulfate that contains, citrate, phosphate, or Lactated Caspofungin compositions, and think that the combination that adds sorbitol or sorbitol and other excipient is for improving stability of formulation greatly, but through investigating, experimental data and practical situation differ greatly in the document, Caspofungin is extremely unstable, lyophilized powder needs to preserve down at 2-8 ℃, and meeting produces a large amount of impurity rapidly behind the redissolution contact water, and according to this application, place down for 40 ℃, commercially available Caspofungin also has good stability after redissolution, with practical situation contradiction, the inventor tests the back and finds that sorbitol not only can not improve stability of formulation, makes stability of formulation descend on the contrary.
As seen, the utmost point need be developed a kind of pharmaceutical composition of stable Caspofungin, makes it easily to preserve, and convenient clinical use improves its safety.
Summary of the invention
The inventor has found a kind of pharmaceutical composition better more stable than the Caspofungin pharmaceutical composition that contains acetate buffer that have unexpectedly, and this is fully for the beyong contemplation to existing open source literature and known technology.
Compositions of the present invention can improve the chemical stability of Caspofungin or its pharmaceutically acceptable salt, and the raising of stability can guarantee that it is as the business-like probability of medicinal product and its storage life as medicinal product of prolongation.
Pharmaceutical composition of the present invention, it contains Caspofungin or its pharmaceutically acceptable salt, also contains the lactate buffer of pharmaceutically acceptable amount.The inventor finds pleasantly surprisedly, behind the interpolation lactate buffer, can reduce the degraded of Caspofungin or its pharmaceutically acceptable salt greatly.
Described pharmaceutical composition can be injectable gastrointestinal external medicine preparation, and preferred described compositions is the lyophilized powder form.
For making the suitable injection of described pharmaceutical composition, the consumption of lactate buffer makes described pharmaceutical composition effectively obtain pH value between the 4-8, preferred 5-7, the more preferably pH value of 5.5-6.5 in the preferred pharmaceutical composition of the present invention.
In preferred embodiments, pharmaceutical composition of the present invention also contains the excipient of pharmaceutically acceptable amount, and described excipient does not contain sorbitol.In a preferred embodiment, described excipient is selected from one or more in sodium chloride, mannitol, sucrose, fructose, xylitol, dextrose, trehalose, albumin, aminoacid, the hetastarch, preferred mannitol, sucrose or their mixture.
In a preferred embodiment, compositions of the present invention comprises a) Caspofungin or its pharmaceutically acceptable salt in the 0.1-500mg/mL of Caspofungin alkali, preferred 5-200mg/mL, more preferably 10-70mg/mL; B) lactate buffer of pharmaceutically acceptable amount effectively obtains the pH value between the 4-8, preferred 5-7, the more preferably pH value of 5.5-6.5; C) excipient of 10-200mg/mL, the excipient of preferred 30-70mg/mL.
The inventor is surprised to find, the consumption of described lactate buffer has produced comparatively significantly influence to the stability of compositions, the consumption of lactate buffer is excessive or too small, stability is all produced negative effect, and select suitable amount ranges, then can greatly improve stability, reduce the generation of related substance.In the preferred embodiment of the invention, the consumption of described lactate buffer is 10-60mM, preferred 20-60mM, more preferably 25-50mM.Usually, the material consumption that plays Stabilization is high more, and compositions should be stable more, but the inventor finds that when also continuing to increase consumption, not only the stability of compositions does not continue raising, step-down on the contrary more than 60mM.
In embodiment preferred more, compositions of the present invention comprises a) Caspofungin or its pharmaceutically acceptable salt in the 30-50mg/mL of Caspofungin alkali; B) lactic acid of 10-60mM or lactate buffer; C) excipient of 30-70mg/mL, and water.
In another preferred embodiment, compositions of the present invention comprises a) Caspofungin or its pharmaceutically acceptable salt in the 42mg/mL of Caspofungin alkali; B) lactic acid of 25-50mM or lactate buffer; C) sucrose of 30mg/mL, the mannitol of 20mg/mL, and water.
In preferred embodiments, the pharmaceutically acceptable salt of Caspofungin is oxalic acid Caspofungin (or claiming caspofungin acetate) in the pharmaceutical composition of the present invention.
The present invention provides above-mentioned pharmaceutical composition to be used for the treatment of or to prevent purposes on the medicine of fungal infections in mannals in preparation on the other hand.
The present invention also provides above-mentioned preparation of drug combination method method, and this method comprises the following steps, and is a) that excipient and lactic acid is soluble in water; B) add and dissolving Caspofungin or its pharmaceutically acceptable salt, and be adjusted to required pH value with alkali; In a preferred embodiment, also comprise the cryodesiccated step of described pharmaceutical composition.
The specific embodiment
Following examples are in order to set forth invention, and limit the scope of the invention never in any form.
Embodiment 1(contrast)
The compositions 1 for preparing caspofungin acetate according to the embodiment 1 of ZL97195514.X.
The mannitol of 2g and the sucrose of 3g are joined in the volumetric flask of 100ml, add about 70ml water, the dissolving back adds the acetic acid solution 2mL mix homogeneously of 75mg/mL, adds the caspofungin acetate (being equivalent to the 4.2g Caspofungin) of 4.66g afterwards, jolting makes it dissolving gently, avoids producing foam.Use the pH of the sodium hydrate regulator solution of 1mol/mL to add water to final volume then then and be 100mL to 6.0..After using the 0.22um filtering with microporous membrane, divide the 10mL cillin bottle of packing into, carry out lyophilization, prepare the lyophilized cake of caspofungin acetate according to 1.3mL/vial.
Embodiment 2(contrast)
The compositions 2 that does not add the caspofungin acetate of buffer salt.
The mannitol of 2g and the sucrose of 3g are joined in the volumetric flask of 100ml, add about 70ml water, stirring and dissolving adds the caspofungin acetate (being equivalent to the 4.2g Caspofungin) of 4.66g afterwards, and jolting makes it dissolving gently, avoids producing foam.Adding water to final volume then is 100mL.After using the 0.22um filtering with microporous membrane, divide the 10mL cillin bottle of packing into, carry out lyophilization, prepare the lyophilized cake of caspofungin acetate according to 1.3mL/vial.
Embodiment 3
The Caspofungin compositions 3 that contains lactate buffer.
The mannitol of 2g and the sucrose of 3g are joined in the volumetric flask of 100ml, add about 60ml water, the dissolving back adds the lactic acid solution 10mL mix homogeneously of 22.50mg/mL, the caspofungin acetate (being equivalent to the 4.2g Caspofungin) that adds 4.66g afterwards, jolting makes it dissolving gently, avoids producing foam.Use the pH of the sodium hydrate regulator solution of 1mol/mL to add water to final volume then then and be 100mL to 6.0..After using the 0.22um filtering with microporous membrane, divide the 10mL cillin bottle of packing into, carry out lyophilization, prepare the lyophilized cake of caspofungin acetate according to 1.3mL/vial.
Embodiment 4
The sucrose of 5g is joined in the volumetric flask of 100ml, add about 60ml water, the dissolving back adds the lactic acid solution 10mL mix homogeneously of 22.50mg/mL, adds the caspofungin acetate (being equivalent to the 4.2g Caspofungin) of 4.66g afterwards, jolting makes it dissolving gently, avoids producing foam.Use the pH to 5.0 of the sodium hydrate regulator solution of 1mol/mL then, adding water to final volume then is 100mL.After using the 0.22um filtering with microporous membrane, divide the 10mL cillin bottle of packing into, carry out lyophilization, prepare the lyophilized cake of caspofungin acetate according to 1.3mL/vial.Through observing, the stability of caspofungin acetate is suitable with compositions 3 in the said composition.
Embodiment 5
The mannitol of 5g is joined in the volumetric flask of 100ml, add about 60ml water, the dissolving back adds the lactic acid solution 10mL mix homogeneously of 22.50mg/mL, adds the caspofungin acetate (being equivalent to the 4.2g Caspofungin) of 4.66g afterwards, jolting makes it dissolving gently, avoids producing foam.Use the pH to 6.0 of the sodium hydrate regulator solution of 1mol/mL then, adding water to final volume then is 100mL.After using the 0.22um filtering with microporous membrane, divide the 10mL cillin bottle of packing into, carry out lyophilization, prepare the lyophilized cake of caspofungin acetate according to 1.3mL/vial.Through observing, the stability of caspofungin acetate is suitable with compositions 3 in the said composition.
Embodiment 6
The trehalose of 5g is joined in the volumetric flask of 100ml, add about 60ml water, the dissolving back adds the lactic acid solution 10mL mix homogeneously of 22.50mg/mL, adds the caspofungin acetate (being equivalent to the 4.2g Caspofungin) of 4.66g afterwards, jolting makes it dissolving gently, avoids producing foam.Use the pH to 7.0 of the sodium hydrate regulator solution of 1mol/mL then, adding water to final volume then is 100mL.After using the 0.22um filtering with microporous membrane, divide the 10mL cillin bottle of packing into, carry out lyophilization, prepare the lyophilized cake of caspofungin acetate according to 1.3mL/vial.Through observing, the stability of caspofungin acetate is suitable with compositions 3 in the said composition.
Embodiment 7
Method by embodiment 3 prepares compositions 7,8,9,10,11, these compositionss are except that the consumption difference of lactate buffer, all the other compositions and content are all identical, wherein the pH value of compositions uses NaOH to regulate, each composition consumption unit is mg/ml, through converting, the consumption of lactate buffer is respectively 5mM, 20mM, 50mM, 60mM, 70mM in each compositions.
| Component | Compositions 7 | Compositions 8 | Compositions 9 | Compositions 10 | Compositions 11 |
| Caspofungin acetate | 46.6 | 46.6 | 46.6 | 46.6 | 46.6 |
| Mannitol | 20.0 | 20.0 | 20.0 | 20.0 | 20.0 |
| Sucrose | 30.0 | 30.0 | 30.0 | 30.0 | 30.0 |
| Lactic acid | 0.45 | 1.8 | 4.5 | 5.4 | 6.3 |
| pH | 6.0 | 6.0 | 6.0 | 6.0 | 6.0 |
Embodiment 8
Prepare compositions 12,13,14 by embodiment 3 similar methods, wherein the pH value of compositions uses NaOH to regulate, and each composition consumption unit is mg/ml.
| Component | Compositions 12 | Compositions 13 | Compositions 14 |
| Caspofungin acetate | 46.6 | 46.6 | 46.6 |
| Mannitol | 20.0 | 20.0 | - |
| Sucrose | 30.0 | - | - |
| Sorbitol | - | 30.0 | 50 |
| Lactic acid | 1.8 | 1.8 | 1.8 |
| pH | 6.6 | 6.6 | 6.6 |
Embodiment 9
Stability of solution is investigated contrast
Respectively according to compositions 3 prescriptions among 1 prescription of the compositions among the embodiment 1 and the embodiment 3, the solution of preparation caspofungin acetate, and the stability of solution under 4 ℃ and 25 ℃ of conditions is investigated in contrast, main contrast impurity L-747969, L-404339, L-404340 and total assorted variation, wherein impurity L-747969 is the main hydrolysis and the thermal degradation impurity of caspofungin acetate.
The stability of solution of compositions 1 under 4 ℃ and 25 ℃ of conditions
The stability of solution of compositions 3 under 4 ℃ and 25 ℃ of conditions
By the stability of solution comparing result of compositions 1 and compositions 3 as can be known, compositions 3 is compared than compositions 1 has better stability of solution.
Embodiment 10
With compositions 1 and compositions 3 freeze-dried powders that obtain,, store under 25 ℃ of conditions respectively at 30 ℃, and sampling regularly, sample is carried out assay determination, contrast impurity L-747969 and total assorted variation, wherein impurity L-747969 is the main hydrolysis and the thermal degradation impurity of caspofungin acetate.The results are shown in following table:
Compositions 1 and compositions 3 stability under 30 ℃ and 25 ℃ of conditions
By the stable comparing result of compositions 1 and compositions 3 as can be known, compositions 3 is compared than compositions 1 has better stability, significantly reduces the generation of impurity.
Embodiment 11
Will be according to embodiment 2(contrast) and embodiment 3 prepare the compositions 2 and compositions 3 freeze-dried powders that obtain, under 40 ℃ of conditions, store respectively, and sampling regularly, sample is carried out assay determination, contrast impurity L-747969 and total assorted variation, wherein impurity L-747969 is the main hydrolysis and the thermal degradation impurity of caspofungin acetate.The results are shown in following table:
Compositions 2 and compositions 3 stability under 40 ℃ of conditions
By the stable comparing result of compositions 2 and compositions 3 as can be known, compositions 3 is compared than compositions 2 has better stability, and the existence of lactate buffer salt can significantly reduce the generation of impurity.
Embodiment 12
Investigate contrast under the caspofungin acetate lyophilized powder preparation of different pH value and 30 ℃ of conditions
The mannitol of 2g and the sucrose of 3g are joined in the volumetric flask of 100ml, add about 60ml water, the dissolving back adds the lactic acid solution 10mL mix homogeneously of 22.50mg/mL, the caspofungin acetate (being equivalent to the 4.2g Caspofungin) that adds 4.66g afterwards, jolting makes it dissolving gently, avoids producing foam.Use the pH to 5.0 of the sodium hydrate regulator solution of 1mol/mL then.Adding water to final volume then is 100mL.After using the 0.22um filtering with microporous membrane, divide the 10mL cillin bottle of packing into, carry out lyophilization, prepare the lyophilized cake of caspofungin acetate according to 1.3mL/vial.
PH6.0,7.0,8.0 sample preparation and top identical preparation process preparation.
With the lyophilized powder that makes, under 30 ℃ of conditions, keep sample and investigate, respectively at 5 days, sampling in 10 days, sample is carried out assay determination, contrast impurity L-747969 and total assorted variation, wherein impurity L-747969 is the main hydrolysis and the thermal degradation impurity of caspofungin acetate.The results are shown in following table:
By the stable comparing result of the caspofungin acetate lyophilized powder of different pH value as can be known, in the scope of pH5.0-8.0, the existence of lactic acid or lactate buffer can guarantee the stable of caspofungin acetate and the significantly generation of minimizing impurity.
Embodiment 13
The compositions 7,8,9,10,11 that embodiment 7 is made, under 30 ℃ of conditions, store respectively, and sampling regularly, sample is carried out assay determination, contrast impurity L-747969 and total assorted variation, wherein impurity L-747969 is the main hydrolysis and the thermal degradation impurity of caspofungin acetate.
Embodiment 13
The compositions 12,13,14 that embodiment 8 is made, under 30 ℃ of conditions, store respectively, and sampling regularly, sample is carried out assay determination, contrast impurity L-747969 and total assorted variation, wherein impurity L-747969 is the main hydrolysis and the thermal degradation impurity of caspofungin acetate, in form, represent with single mixing, find that through observing the compositions 13,14 that contains sorbitol metachromatism just occurs, white lyophilized powder yellowing after placing 1 day under 30 ℃ of conditions.
Claims (14)
1. a pharmaceutical composition contains Caspofungin or its pharmaceutically acceptable salt, it is characterized in that also containing the lactate buffer of pharmaceutically acceptable amount.
2. pharmaceutical composition according to claim 1, the consumption of wherein said lactate buffer make described pharmaceutical composition effectively obtain pH value between the 4-8, the pH value of preferred 5-7, the more preferably pH value of 5.5-6.5.
3. pharmaceutical composition according to claim 1 and 2, wherein said pharmaceutical composition are injectable gastrointestinal external medicine preparations, and preferred described compositions is the lyophilized powder form.
4. pharmaceutical composition according to claim 3, the excipient that wherein also contains pharmaceutically acceptable amount, described excipient is selected from one or more in sodium chloride, mannitol, sucrose, fructose, xylitol dextrose, trehalose, albumin, aminoacid, the hetastarch, preferred mannitol, sucrose or their mixture.
5. pharmaceutical composition according to claim 3, wherein said compositions does not contain sorbitol.
6. according to claim 4 or 5 described pharmaceutical compositions, wherein Caspofungin or its pharmaceutically acceptable salt consumption are 0.1-500mg/mL in Caspofungin alkali consumption, preferred 5-200mg/mL, more preferably 10-70mg/mL.
7. pharmaceutical composition according to claim 6, wherein the consumption of lactate buffer agent is 10-60mM, preferred 20-60mM, most preferably 25-50mM.
8. pharmaceutical composition according to claim 6, wherein the consumption of excipient is 10-200mg/mL, preferred 30-70mg/mL.
9. pharmaceutical composition according to claim 8 contains Caspofungin or its pharmaceutically acceptable salt in the 30-50mg/mL of Caspofungin alkali, the lactate buffer agent of 10-60mM, the excipient of 30-70mg/mL and water.
10. pharmaceutical composition according to claim 9 contains Caspofungin or its pharmaceutically acceptable salt in the 42mg/mL of Caspofungin alkali, the lactate buffer agent of 25mM-50mM, the sucrose of 30mg/mL, the manna alcohol and water of 20mg/mL.
11. according to any described pharmaceutical composition of claim 1 to 10, wherein said Caspofungin pharmaceutically acceptable salt is the oxalic acid Caspofungin.
12. any described pharmaceutical composition of claim 1 to 11 is used for the treatment of or prevents purposes on the medicine of fungal infections in mannals in preparation.
13. prepare the method for any described pharmaceutical composition of claim 4 to 11, this method comprises the following steps:
A) excipient and lactic acid is soluble in water;
B) add and dissolving Caspofungin or its pharmaceutically acceptable salt, and be adjusted to required pH value with alkali.
14. method according to claim 13, it also comprises the cryodesiccated step of described pharmaceutical composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012104475763A CN103212059A (en) | 2012-01-18 | 2012-11-09 | Composition containing antifungal drug and lactate buffering liquid |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210015959 | 2012-01-18 | ||
| CN201210015959.3 | 2012-01-18 | ||
| CN2012104475763A CN103212059A (en) | 2012-01-18 | 2012-11-09 | Composition containing antifungal drug and lactate buffering liquid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103212059A true CN103212059A (en) | 2013-07-24 |
Family
ID=48810444
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012104475763A Pending CN103212059A (en) | 2012-01-18 | 2012-11-09 | Composition containing antifungal drug and lactate buffering liquid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103212059A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014071743A1 (en) * | 2012-11-09 | 2014-05-15 | 江苏恒瑞医药股份有限公司 | Composition containing antifungal drug and lactate buffer |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1132624C (en) * | 1996-04-19 | 2003-12-31 | 麦克公司 | Compsns. comprising antifungal agent and acetate buffer |
| CN101516387A (en) * | 2006-07-26 | 2009-08-26 | 桑多斯股份公司 | Caspofungin formulations |
| CN102166186A (en) * | 2011-04-18 | 2011-08-31 | 深圳市健元医药科技有限公司 | More stable nitrogen heterocyclic peptide preparation |
| CN103118663A (en) * | 2010-09-20 | 2013-05-22 | 赛利亚医药公司 | Caspofungin composition |
-
2012
- 2012-11-09 CN CN2012104475763A patent/CN103212059A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1132624C (en) * | 1996-04-19 | 2003-12-31 | 麦克公司 | Compsns. comprising antifungal agent and acetate buffer |
| CN101516387A (en) * | 2006-07-26 | 2009-08-26 | 桑多斯股份公司 | Caspofungin formulations |
| CN103118663A (en) * | 2010-09-20 | 2013-05-22 | 赛利亚医药公司 | Caspofungin composition |
| CN102166186A (en) * | 2011-04-18 | 2011-08-31 | 深圳市健元医药科技有限公司 | More stable nitrogen heterocyclic peptide preparation |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014071743A1 (en) * | 2012-11-09 | 2014-05-15 | 江苏恒瑞医药股份有限公司 | Composition containing antifungal drug and lactate buffer |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102614491B (en) | Pharmaceutical composition containing echinocandin antifungal agent micafungin, its preparation method and application | |
| JP5914486B2 (en) | Caspofungin composition | |
| JP2024045290A (en) | Bendamustine formulation | |
| CN100586422C (en) | Bivalirudin freeze-dried injection and preparation thereof | |
| CN105434373B (en) | A kind of injection Oxiracetam lyophilized preparation and preparation method thereof | |
| US20170348382A1 (en) | Lyophilized injectable compositions of daptomycin | |
| CN102247319B (en) | Thymalfasin-containing medicinal composition and preparation method thereof | |
| CN102614492B (en) | Liquid pharmaceutical composition containing echinocandin antifungal agent micafungin | |
| CN103212058A (en) | Composition containing antifungal drug and lactate buffering agent | |
| CN102302462B (en) | Gemcitabine hydrochloride lyophilized preparation | |
| CN103212059A (en) | Composition containing antifungal drug and lactate buffering liquid | |
| CN103505424B (en) | Preparation method for bortezomib for injection | |
| KR102161866B1 (en) | Composition of cabazitaxel and sulfobutylether beta-cyclodextrin | |
| CN102579372A (en) | Gemcitabine hydrochloride lyophilized composition and preparation method thereof | |
| CN102357081A (en) | Composite fat-soluble vitamin freeze-dried powder injection and preparation method thereof | |
| CN103330933B (en) | Pharmaceutical composition containing MFG or its salt | |
| CN103494779A (en) | Andrographolide powder preparation for injection and preparation method thereof | |
| CN101780084A (en) | Injection composition using levo leucovorin or salt thereof as major ingredients | |
| US11957658B2 (en) | Chlorthalidone compositions and methods | |
| CN102512659B (en) | Medicinal composition containing echinocandin antifungal agent and its preparing method and its use | |
| JP6179939B2 (en) | Method for reducing viscosity of high-concentration gamma globulin preparation | |
| CN102772373A (en) | Tartaric acid vinorelbine powder injection for injection and preparation method thereof | |
| TW201440782A (en) | Pharmaceutical composition of micafungin or the salts thereof | |
| JPH0321252A (en) | Cysplatin high tension liquid | |
| JPWO2013154045A1 (en) | Injectable composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20130724 |