CN105287403A - Freeze-drying composition of posaconazole prodrug and preparation method and application of freeze-drying composition of posaconazole prodrug - Google Patents
Freeze-drying composition of posaconazole prodrug and preparation method and application of freeze-drying composition of posaconazole prodrug Download PDFInfo
- Publication number
- CN105287403A CN105287403A CN201410376086.8A CN201410376086A CN105287403A CN 105287403 A CN105287403 A CN 105287403A CN 201410376086 A CN201410376086 A CN 201410376086A CN 105287403 A CN105287403 A CN 105287403A
- Authority
- CN
- China
- Prior art keywords
- posaconazole
- freeze
- prodrug
- drying composition
- dried composition
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a freeze-drying composition of a posaconazole prodrug and a preparation method and application of the freeze-drying composition of the posaconazole prodrug. The freeze-drying composition has the advantages that the freeze-drying composition is high in water solubility, and safety of the freeze-drying composition is guaranteed due to the fact that cyclodextrins auxiliary materials need not to be added during the preparation of the freeze-drying composition; the freeze-drying composition is suitable for being used for treating various amphotericin-intolerant or refractory adult invasive fungal infections; the freeze-drying composition is used as a preventive drug for high-risk patients, the freeze-drying composition is applicable to patients above 13 years old and with impaired immunity and especially applicable to patients who have graft versus host disease (GVHD) after hematopoietic stem cell transplant, patients with leukemia and patients with long-term leukopenia due to chemotherapy; compared with control drugs such as fluconazole and itraconazole, the freeze-drying composition can effectively prevent invasive aspergillosis and can lower the mortality related to the invasive fungal infections.
Description
Technical field
The present invention relates to a kind of compositions, particularly relate to a kind of posaconazole prodrug freeze-dried composition and its production and use.
Background technology
Posaconazole (Posaconazolc), molecular formula: C
37h
42f
2n
8o
4.Posaconazole is the derivant of itraconazole, in the second filial generation antifungal drug in triazole class of listing in 2006.Has a broad antifungal spectrum, for Candida, Histoplasma capsulatum, the many pityrosporion ovales of plug, bipolar bacterium zygomycete, Fusarium spp., yeast.Comprise the non-white beads bacterial strain of resistance to fluconazol, Cryptococcus histolyticus and aspergillosis and have powerful inhibit activities; Especially also effective to rarer but life-threatening fungal disease (zygomycosis, fusaridiosis and coccidioidomycosis etc.).This product is applicable to multiple can not tolerance amphotericin or the treatment of intractable adult's invasive infections with fungi; To high-risk patient prophylactic, for more than 13 years old, the patient of immunologic hypofunction, particularly suffer from graft versus host disease (
graftversushostdisease, GVHD) hematopoietic stem cell transplantation person, leukaemic and long-term leukopenic patient due to chemotherapy.This product, than control drug fluconazol and itraconazole, more effectively can be prevented aggressive aspergillin infection and can reduce the relevant case fatality rate of invasive infections with fungi.
The dosage form of external listing has oral administration mixed suspension, injection, slow releasing tablet at present, and wherein injection have employed Sulfobutyl ether β _ cyclodextrin to improve the water solublity of posaconazole, too increases the incidence rate of side reaction simultaneously.Cyclodextrin is the novel adjuvant of one occurred in recent years, and because this adjuvant has good solubilization to multiple insoluble drug, thus the domestic use to this adjuvant has the trend increased fast.But up to the present we understand not deeply its safety.This adjuvant of bibliographical information has certain hemolytic, nephrotoxicity and carcinogenecity, but also may there is more serious toxic and side effects still not known to us, and thus its use is more cautiously suitable.
Posaconazole prodrug is the di by posaconazole, obtains posaconazole phosphate compounds, and the water solublity of this compounds is better.After posaconazole phosphate compounds enters human body, posaconazole can be hydrolyzed to by the phosphatase effect in body, thus be played clinical effect.The object done like this is exactly just do not need cyclodextrin adjuvant making intravenous administration formulation, adds the safety coefficient of this medicine.
Summary of the invention
The object of the present invention is to provide freeze-dried composition of a kind of posaconazole prodrug and preparation method thereof.
The compositions of posaconazole prodrug of the present invention does not need to add cyclodextrin adjuvant.
The freeze-dried composition purposes that another object of the present invention is to a kind of posaconazole prodrug is has a broad antifungal spectrum, for Candida, Histoplasma capsulatum, the many pityrosporion ovales of plug, bipolar bacterium zygomycete, Fusarium spp., yeast.Comprise the non-white beads bacterial strain of resistance to fluconazol, Cryptococcus histolyticus and aspergillosis and have powerful inhibit activities; Especially also effective to rarer but life-threatening fungal disease (zygomycosis, fusaridiosis and coccidioidomycosis etc.).
The structural formula of posaconazole prodrug is as follows
:
X represents H, Na, K, aminoacid, meglumine, gallbladder alkali; N represents 0 ~ 12.
For achieving the above object, the technical solution used in the present invention is:
A freeze-dried composition for posaconazole prodrug, described compositions is by posaconazole prodrug and be not prepared from containing the pharmaceutically useful adjuvant of cyclodextrin, and described pharmaceutic adjuvant is selected from excipient, pH adjusting agent.
The freeze-dried composition of above-mentioned posaconazole prodrug, can not add or add excipient, as added excipient, described excipient is mannitol, dextran, glucose, lactose, sucrose, maltose, any one or a few in fructose, described pH adjusts as there being hydrochloric acid, sulphuric acid, lactic acid, citric acid, aminoacid, acetic acid, malic acid, maleic acid, citric acid: sodium citrate buffer solution, acetic acid: sodium acetate buffer system, sodium hydroxide, sodium bicarbonate, sodium carbonate, potassium hydroxide, potassium bicarbonate, potassium carbonate, any one or a few in basic amino acid.
The freeze-dried composition of above-mentioned posaconazole prodrug is as added excipient, the consumption of described excipient is 0.01-10 times of posaconazole prodrug mass ratio, and described pH adjusting agent consumption is adjust pH to be 6.5-11.0 the posaconazole prodrug solution before lyophilizing.
A kind of freeze-dried composition preparation method of posaconazole prodrug, its preparation process is: active component posaconazole prodrug is dissolved in water for injection and adds or do not add excipient, pH is adjusted to be 6.5-11.0 by pH adjusting agent, be stirred to dissolve clearly, again through medicinal charcoal absorption thermal source, filter, be sub-packed in lyophilizing cillin bottle and be prepared from through lyophilization.
Preparation method of the present invention comprises the following steps: the water for injection adding 10%-95% in liquid dispensing container, add the posaconazole prodrug of accurate recipe quantity 90%-110%, under stirring, add or do not add excipient, slowly dripping pH adjusting agent, tune pH is 6.5-11.0, benefit adds water to full dose, then adds the medicinal charcoal of 0.01%-1.0% (W/V), stirs 15-60 minute, sand stick coarse filtration takes off charcoal, and qualified to clarity with the microporous filter membrane fine straining of 0.22um; After mensuration intermediates content is qualified, determines loading amount and be sub-packed in cillin bottle, adding half plug, sample is through lyophilization, and control moisture 0.1%-8%, tamponade, rolls lid.
Freeze-dried composition of posaconazole prodrug provided by the present invention and preparation method thereof has following advantages:
(1) compositions of posaconazole prodrug provided by the present invention is to stable performances such as light, heat, oxygen, water, pollution-free, applied range, and convenient operation, transport and storage.
(2) freeze-dried composition of posaconazole prodrug provided by the present invention, product appearance is full, do not subside, cavity etc. bad phenomenon.
(3) freeze-dried composition of posaconazole prodrug provided by the present invention is simple, is easy to large-scale industrial production, obtains quality high, the freeze-drying prods that outward appearance is good.
Preparation vascular irritation prepared by preparation method of the present invention, without hemolytic.
Detailed description of the invention:
Embodiment 1: the preparation of injection posaconazole phosphate ester
Prescription: posaconazole phosphate ester 200g
Water for injection 2000ml
Make 1000 bottles
The water for injection of 1500ml is added in liquid dispensing container, add the posaconazole phosphate ester of accurate recipe quantity, be stirred to dissolve, slowly add sodium hydroxide, adjust pH to be 8.0, mend and add water to full dose, then the medicinal charcoal of 0.05% (W/V) is added, stir 20 minutes, sand stick coarse filtration takes off charcoal, and qualified to clarity with the microporous filter membrane fine straining of 0.22 μm; Measure intermediates content qualified after, determine loading amount and be sub-packed in cillin bottle, adding half plug, sample-40 DEG C of pre-freezes 4 hours, evacuation, maintenance vacuum 10-30Pa is slowly warming up to-20 DEG C, keeps 12 hours; Slowly be warming up to 20 DEG C again, keep 4 hours, control moisture 2%, tamponade, rolls lid.
Embodiment 2: the preparation of injection posaconazole disodium phosphate
Prescription: posaconazole disodium phosphate 200g
Water for injection 2000ml
Make 1000 bottles
The water for injection of 1500ml is added in liquid dispensing container, add the posaconazole disodium phosphate of accurate recipe quantity, be stirred to dissolve, slowly add acetic acid, adjust pH to be 8.5, mend and add water to full dose, then the medicinal charcoal of 0.05% (W/V) is added, stir 60 minutes, sand stick coarse filtration takes off charcoal, and qualified to clarity with the microporous filter membrane fine straining of 0.22 μm; Measure intermediates content qualified after, determine loading amount and be sub-packed in cillin bottle, adding half plug, sample-45 DEG C of pre-freezes 4 hours, evacuation, maintenance vacuum 10-30Pa is slowly warming up to-20 DEG C, keeps 12 hours; Slowly be warming up to 0 DEG C again, keep 6 hours, be more slowly warming up to 25 DEG C, keep controlling moisture 1% in 4 hours, tamponade, rolls lid.
Embodiment 3: the preparation of injection posaconazole disodium phosphate pentahydrate
Prescription: posaconazole disodium phosphate pentahydrate 200g
Mannitol 2g
Water for injection 2500ml
Make 1000 bottles
The water for injection of 2000ml is added in liquid dispensing container, add the posaconazole disodium phosphate pentahydrate of accurate recipe quantity, under mannitol 2g stirs, slowly add sodium carbonate, adjust pH to be 9.0, mend and add water to full dose, then the medicinal charcoal of 0.1% (W/V) is added, stir 10 minutes, sand stick coarse filtration takes off charcoal, and qualified to clarity with the microporous filter membrane fine straining of 0.22 μm; Measure intermediates content qualified after, determine loading amount and be sub-packed in cillin bottle, adding half plug, sample-40 DEG C of pre-freezes 4 hours, evacuation, maintenance vacuum 10-30Pa is slowly warming up to-20 DEG C, keeps 12 hours; Slowly be warming up to 5 DEG C again, keep 10 hours, be more slowly warming up to 20 DEG C, keep controlling moisture 5% in 2 hours, tamponade, rolls lid.
Embodiment 4: the preparation of injection posaconazole phosphate ester
Prescription: posaconazole phosphate ester 150g
Mannitol 200g
Water for injection 2500ml
Make 1000 bottles
The water for injection of 2000ml is added in liquid dispensing container, add the posaconazole phosphate ester of accurate recipe quantity, mannitol 200g, under stirring, slowly adds sodium bicarbonate, pH is adjusted to be 6.5, benefit adds water to full dose, then adds the medicinal charcoal of 1.0% (W/V), stirs 10 minutes, sand stick coarse filtration takes off charcoal, and qualified to clarity with the microporous filter membrane fine straining of 0.22 μm; Measure intermediates content qualified after, determine loading amount and be sub-packed in cillin bottle, adding half plug, sample-50 DEG C of pre-freezes 5 hours, evacuation, maintenance vacuum 10-30Pa is slowly warming up to-10 DEG C, keeps 12 hours; Slowly be warming up to 0 DEG C again, keep 8 hours, be more slowly warming up to 20 DEG C, keep 4 hours, control moisture 3%, tamponade, rolls lid.
Embodiment 5: the preparation of injection posaconazole phosphate ester dipotassium
Prescription: posaconazole phosphate ester dipotassium 200g
Glucose 10g
Water for injection 2000ml
Make 1000 bottles
The water for injection of 1500ml is added in liquid dispensing container, add the posaconazole phosphate ester dipotassium of accurate recipe quantity, be stirred to dissolve, slowly add hydrochloric acid, adjust pH to be 8.5, mend and add water to full dose, then the medicinal charcoal of 0.05% (W/V) is added, stir 45 minutes, sand stick coarse filtration takes off charcoal, and qualified to clarity with the microporous filter membrane fine straining of 0.22 μm; Measure intermediates content qualified after, determine loading amount and be sub-packed in cillin bottle, adding half plug, sample-45 DEG C of pre-freezes 4 hours, evacuation, maintenance vacuum 10-30Pa is slowly warming up to-20 DEG C, keeps 12 hours; Slowly be warming up to 20 DEG C again, keep 4 hours, control moisture 3%, tamponade, rolls lid.
Embodiment 6: the preparation of injection posaconazole phosphate ester arginine salt
Prescription: posaconazole phosphate ester arginine salt 300g
Sucrose 20g
Water for injection 2000ml
Make 1000 bottles
The water for injection of 1500ml is added in liquid dispensing container, add posaconazole phosphate ester arginine salt, the sucrose of accurate recipe quantity, be stirred to dissolve, slowly add acetic acid, adjust pH to be 7.0, mend and add water to full dose, then the medicinal charcoal of 0.05% (W/V) is added, stir 25 minutes, sand stick coarse filtration takes off charcoal, and qualified to clarity with the microporous filter membrane fine straining of 0.22 μm; Measure intermediates content qualified after, determine loading amount and be sub-packed in cillin bottle, adding half plug, sample-55 DEG C of pre-freezes 4 hours, evacuation, maintenance vacuum 10-30Pa is slowly warming up to-15 DEG C, keeps 10 hours; Slowly be warming up to 0 DEG C again, keep 8 hours, be more slowly warming up to 20 DEG C, keep 4 hours, control moisture 4%, tamponade, rolls lid.
Embodiment 7: the preparation of injection posaconazole phosphate ester meglumine salt
Prescription: posaconazole phosphate ester meglumine salt 200g
Dextran 100 g
Water for injection 2000ml
Make 1000 bottles
The water for injection of 1500ml is added in liquid dispensing container, add the posaconazole phosphate ester meglumine salt of accurate recipe quantity, dextran, is stirred to dissolve, and slowly adds hydrochloric acid, pH is adjusted to be 8.5, benefit adds water to full dose, then adds the medicinal charcoal of 0.05% (W/V), stirs 20 minutes, sand stick coarse filtration takes off charcoal, and qualified to clarity with the microporous filter membrane fine straining of 0.22 μm; Measure intermediates content qualified after, determine loading amount and be sub-packed in cillin bottle, adding half plug, sample-55 DEG C of pre-freezes 4 hours, evacuation, maintenance vacuum 10-30Pa is slowly warming up to-20 DEG C, keeps 12 hours; Slowly be warming up to 20 DEG C again, keep 4 hours, control moisture 5%, tamponade, rolls lid.
Embodiment 8: injection posaconazole disodium phosphate hemolytic is tested
Method and result
Get blood from rabbit heart and be about 15ml, put into clean beaker, stir with Glass rod and remove Fibrinogen and make into defibrinated blood, then moved in 10ml centrifuge tube by blood, it is appropriate to add normal saline, gently after mixing, centrifugal 5 minutes with 2500 revs/min, removing supernatant liquid, so repeatedly, until supernatant liquid water white transparency, finally gained erythrocyte is diluted to 2% suspension by its volume with sterile saline and is for experiment.
Get cleaned glass pipe 7,2% red cell suspension and normal saline is added successively by table 1 proportional quantity, in 37 DEG C of thermostatted waters, half an hour is placed after mixing, then (the 6th pipe does not add test sample as blank pipe to add not commensurability tested medicinal liquid by table 1,7th effective distilled water replaces normal saline as positive control pipe), after shaking up, put in 37 DEG C of water-baths.Start to observe once every 15 minutes, after 1 hour, observed once every one hour, Continuous Observation 4 hours.The results are shown in Table 1, the criterion of blood coagulation, coagulation is in table 2.
The hemolysis in vitro test of table 1 injection posaconazole phosphate ester
Note: "-" represents in 4 hours without haemolysis; "+" represents 15 minutes is complete hemolysis.
The criterion of table 2 erythrocyte hemolysis, coagulation
Conclusion injection posaconazole disodium phosphate external to family's rabbit erythrocyte without haemolysis and cause coagulation.
Embodiment 9: injection posaconazole disodium phosphate sensitivity test
Method and result
Get Cavia porcellus 18, be divided into saline control group, 4% fresh albumen normal saline positive controls and injection posaconazole disodium phosphate group at random, often organize 6.Solution 0.5ml tested by lumbar injection next day of each group of Cavia porcellus, continuous 3 times.Then often organize and get 3 Cavia porcelluss and be placed in respectively the 14th day after first administration and solution attacks tested by 21 days hind paw lateral vein or forelimb cephalic vein injection 1ml.Observe the reaction of Cavia porcellus in 30 minutes after administration, and press that table 3 is listed reacts classification.Result of the test is in table 4.
Result of the test shows: after Cavia porcellus was attacked in the 14th day with injection posaconazole disodium phosphate, and slight reaction of trembling appears in 2 Cavia porcelluss, and wherein vomiting reaction appears in 1 Cavia porcellus, and other 1 Cavia porcellus is without significant reaction; After within 14th day, attacking with sterile saline, Cavia porcellus is all without significant reaction.After within 21st day, attacking with injection posaconazole disodium phosphate and sterile saline all there is slight reaction of trembling in Cavia porcellus.14th, after within 21 days, attacking with Ovum Gallus domesticus album normal saline, all there is dyspnea, spasm, tic in Cavia porcellus, finally dead.
Table 3 Cavia porcellus anaphylaxis progression
Note: during the order of reaction >=2, hypersensitive test is failed, during order of reaction <2, anaphylaxis is qualified.
The sensitivity test result of table 4 injection posaconazole phosphate ester
Conclusion injection posaconazole disodium phosphate is to the systemic anaphylaxis pass the test of Cavia porcellus.
Embodiment 10 injection posaconazole disodium phosphate vascular stimulation tests
Method and result
Get healthy without hindering rabbit 3, by sterile working's method every rabbit side auricular vein injection injection posaconazole disodium phosphate sterilized water for injection solution, opposite side auricular vein inject isopyknic sterile saline in contrast administration volume be 1ml/kg (being equivalent to clinical administration dosage), intravenous injection speed is 1ml/ minute, for three days on end, every day 1 time.Auricular vein and surrounding tissue is observed before each administration with or without phenomenons such as venous congestion, hemorrhage, edema and necrosis during administration, then carotid artery sacrificed by exsanguination rabbit, from the basal part of the ear, portion cuts the rabbit ear, fix with 10% formalin, carry out check pathological section, to observe in whether degeneration and the necrosis of auricular vein endotheliocyte, tube chamber with or without congested or thrombosis, tube wall and surrounding tissue with or without changes such as cell infiltration.
Result shows: rabbit auricular vein is for three days on end after posaconazole disodium phosphate sterilized water for injection solution used for intravenous injection and sterile saline, during administration and last administration after 24 hours, perusal rabbit ear edge and surrounding tissue are except there is hyporrhea injection site, and other position has no obvious pathological change.
Conclusion injection posaconazole disodium phosphate for three days on end intravenous injection to rabbit auricular vein without obvious stimulation.
Claims (7)
1. a freeze-dried composition for posaconazole prodrug, described compositions is by posaconazole prodrug and be not prepared from containing the pharmaceutically useful adjuvant of cyclodextrin, and described pharmaceutic adjuvant is selected from excipient, pH adjusting agent.
2. the preparation method of the freeze-dried composition of posaconazole prodrug according to claim 1, it is characterized in that concrete steps are as follows: the water for injection adding 10%-95% in liquid dispensing container, add the posaconazole prodrug of accurate recipe quantity 90%-110%, under stirring, add or do not add excipient, slowly drip pH adjusting agent, tune pH is 6.0-11, benefit adds water to full dose, then the medicinal charcoal of 0.01%-1.0% (W/V) is added, stir 15-60 minute, sand stick coarse filtration takes off charcoal, and qualified to clarity with the microporous filter membrane fine straining of 0.22um; After mensuration intermediates content is qualified, determines loading amount and be sub-packed in cillin bottle, adding half plug, sample is through lyophilization, and control moisture 0.1%-8%, tamponade, rolls lid.
3. the freeze-dried composition of posaconazole prodrug according to claim 1, described excipient is any one or a few in mannitol, dextran, glucose, lactose, sucrose, maltose, fructose.
4. the freeze-dried composition of posaconazole prodrug according to claim 1, described pH adjusts as having hydrochloric acid, sulphuric acid, lactic acid, citric acid, aminoacid, acetic acid, malic acid, maleic acid, citric acid: sodium citrate buffer solution, acetic acid: any one or a few in sodium acetate buffer system, sodium hydroxide, sodium bicarbonate, sodium carbonate, potassium hydroxide, potassium bicarbonate, potassium carbonate, basic amino acid.
5. the freeze-dried composition of posaconazole prodrug according to claim 1, the consumption of described excipient is 0.01 ~ 10 times of posaconazole prodrug mass ratio, preferably 0.1 ~ 5 times, most preferably 0.5 ~ 2 times.
6. the freeze-dried composition of posaconazole prodrug according to claim 1, described pH adjusting agent consumption is adjust pH to be 6.5 ~ 11.0 the posaconazole prodrug solution before lyophilizing, preferably 8.0 ~ 10.0, most preferably 8.5 ~ 9.5.
7. the freeze-dried composition of posaconazole prodrug according to claim 1, the purposes of described compositions is applicable to multiple can not tolerance amphotericin or the treatment of intractable adult's invasive infections with fungi; To high-risk patient prophylactic; for more than 13 years old, the patient of immunologic hypofunction; particularly suffers from graft versus host disease (graftversushostdisease; GVHD) hematopoietic stem cell transplantation person, leukaemic and long-term leukopenic patient due to chemotherapy; this product, than control drug fluconazol and itraconazole, more effectively can be prevented aggressive aspergillin infection and can reduce the relevant case fatality rate of invasive infections with fungi.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410376086.8A CN105287403A (en) | 2014-08-02 | 2014-08-02 | Freeze-drying composition of posaconazole prodrug and preparation method and application of freeze-drying composition of posaconazole prodrug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410376086.8A CN105287403A (en) | 2014-08-02 | 2014-08-02 | Freeze-drying composition of posaconazole prodrug and preparation method and application of freeze-drying composition of posaconazole prodrug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105287403A true CN105287403A (en) | 2016-02-03 |
Family
ID=55185702
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410376086.8A Pending CN105287403A (en) | 2014-08-02 | 2014-08-02 | Freeze-drying composition of posaconazole prodrug and preparation method and application of freeze-drying composition of posaconazole prodrug |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105287403A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017133632A1 (en) * | 2016-02-04 | 2017-08-10 | 武汉朗来科技发展有限公司 | Posaconazole derivative, pharmaceutical composition and use thereof |
| WO2020056974A1 (en) * | 2018-09-21 | 2020-03-26 | 陕西合成药业股份有限公司 | Posaconazole phosphate ester mono choline salt, preparation method therefor and use thereof |
| CN112778369A (en) * | 2019-11-05 | 2021-05-11 | 华创合成制药股份有限公司 | Triazole derivative and preparation method and application thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1142828A (en) * | 1993-12-21 | 1997-02-12 | 先灵公司 | Tetrahydrofuran antifungals |
| US20060160823A1 (en) * | 2004-05-28 | 2006-07-20 | Leonore Witchey-Lakshmanan | Particulate-stabilized injectable pharmaceutical compositions of Posaconazole |
| CN101213193A (en) * | 2005-05-03 | 2008-07-02 | 卫材R&D管理有限公司 | Mono-lysine salts of azole compounds |
| CN101744778A (en) * | 2010-02-01 | 2010-06-23 | 陕西合成药业有限公司 | Voriconazole phosphate ester for injection and preparation method thereof |
| CN101780096A (en) * | 2010-03-05 | 2010-07-21 | 陕西合成药业有限公司 | Propofol phosphate for injection and preparation method and application thereof |
| CN102516298A (en) * | 2011-12-09 | 2012-06-27 | 陕西合成药业有限公司 | Stable pharmaceutical salt of L-aonitrate phosphate ester, its preparation method and application |
| CN103284959A (en) * | 2012-02-22 | 2013-09-11 | 重庆圣华曦药业股份有限公司 | Posaconazole freeze-dried powder injection and preparation method thereof |
-
2014
- 2014-08-02 CN CN201410376086.8A patent/CN105287403A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1142828A (en) * | 1993-12-21 | 1997-02-12 | 先灵公司 | Tetrahydrofuran antifungals |
| US20060160823A1 (en) * | 2004-05-28 | 2006-07-20 | Leonore Witchey-Lakshmanan | Particulate-stabilized injectable pharmaceutical compositions of Posaconazole |
| CN101213193A (en) * | 2005-05-03 | 2008-07-02 | 卫材R&D管理有限公司 | Mono-lysine salts of azole compounds |
| CN101744778A (en) * | 2010-02-01 | 2010-06-23 | 陕西合成药业有限公司 | Voriconazole phosphate ester for injection and preparation method thereof |
| CN101780096A (en) * | 2010-03-05 | 2010-07-21 | 陕西合成药业有限公司 | Propofol phosphate for injection and preparation method and application thereof |
| CN102516298A (en) * | 2011-12-09 | 2012-06-27 | 陕西合成药业有限公司 | Stable pharmaceutical salt of L-aonitrate phosphate ester, its preparation method and application |
| CN103284959A (en) * | 2012-02-22 | 2013-09-11 | 重庆圣华曦药业股份有限公司 | Posaconazole freeze-dried powder injection and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 孙禾，等: "泊沙康唑临床应用研究进展", 《中国感染与化疗杂志》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017133632A1 (en) * | 2016-02-04 | 2017-08-10 | 武汉朗来科技发展有限公司 | Posaconazole derivative, pharmaceutical composition and use thereof |
| CN107033186A (en) * | 2016-02-04 | 2017-08-11 | 武汉朗来科技发展有限公司 | Posaconazole derivative, its pharmaceutical composition and purposes |
| US10517867B2 (en) | 2016-02-04 | 2019-12-31 | Wuhan Ll Science And Technology Development Co., Ltd. | Posaconazole derivative, pharmaceutical composition and use thereof |
| CN107033186B (en) * | 2016-02-04 | 2020-06-09 | 武汉朗来科技发展有限公司 | Posaconazole derivatives, pharmaceutical compositions and uses thereof |
| WO2020056974A1 (en) * | 2018-09-21 | 2020-03-26 | 陕西合成药业股份有限公司 | Posaconazole phosphate ester mono choline salt, preparation method therefor and use thereof |
| CN110938093A (en) * | 2018-09-21 | 2020-03-31 | 陕西合成药业股份有限公司 | Posaconazole phosphate monocholine salt and preparation method and application thereof |
| JP2021515049A (en) * | 2018-09-21 | 2021-06-17 | 華創合成制薬股▲ふん▼有限公司 | Posaconazole phosphate monocholine salt, its preparation method and use |
| JP7026264B2 (en) | 2018-09-21 | 2022-02-25 | 華創合成制薬股▲ふん▼有限公司 | Posaconazole phosphate monocholine salt, its preparation method and use |
| CN110938093B (en) * | 2018-09-21 | 2022-08-19 | 华创合成制药股份有限公司 | Posaconazole phosphate monocholine salt and preparation method and application thereof |
| CN112778369A (en) * | 2019-11-05 | 2021-05-11 | 华创合成制药股份有限公司 | Triazole derivative and preparation method and application thereof |
| CN112778369B (en) * | 2019-11-05 | 2024-01-26 | 华创合成制药股份有限公司 | Triazole derivative and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101744778B (en) | Voriconazole phosphate ester for injection and preparation method thereof | |
| JP2009502930A (en) | Removal of peroxide from drug delivery vehicles | |
| RU2007119724A (en) | COMPOSITIONS CONTAINING EKTINESAYDIN AND DISACCHARID | |
| CN105287403A (en) | Freeze-drying composition of posaconazole prodrug and preparation method and application of freeze-drying composition of posaconazole prodrug | |
| CN106806937A (en) | A kind of preparation method of styptic powder | |
| Wu et al. | Nano-metal–organic-frameworks for treating H2O2-secreting bacteria alleviate pulmonary injury and prevent systemic sepsis | |
| CN104771370A (en) | Parecoxib sodium freeze-dried powder injection and preparation method thereof | |
| Xu et al. | In situ formation of ferrous sulfide in glycyrrhizic acid hydrogels to promote healing of multi-drug resistant Staphylococcus aureus-infected diabetic wounds | |
| KR20160093636A (en) | Solutions for increasing the stability and shelf life of an organ and tissue preservation solution | |
| KR102350526B1 (en) | Method of preparing wound dressing composition for treating skin wounds having improved aggregation | |
| KR20090095668A (en) | A forsythoside injection and preparation thereof | |
| CN104666247A (en) | Heparin-modified cleavable adriamycin liposome preparation and preparation method thereof | |
| US10111844B2 (en) | Lyophilized mesna compositions | |
| CN104324007B (en) | Preparation technology and application of natural recombinant nanostructured lipid carrier | |
| CN105213330A (en) | A kind of Parecoxib sodium freeze-dried preparation and preparation method thereof | |
| EP3058958A1 (en) | Anidulafungin composition | |
| CN104666255A (en) | Omeprazole sodium freeze drying powder injection pharmaceutical composition for injection | |
| RU2563818C2 (en) | Method of obtaining substance, possessing antimicrobial, antiviral and immunostimulating activity, in particular, with respect to dendrite cells, substance, thereof obtained, and based on it pharmaceutical composition | |
| Thomas Jr et al. | Candida albicans infection of sternum and costal cartilages: combined operative treatment and drug therapy with 5-fluorocytosine | |
| CN108186617B (en) | New application of geraniol and derivatives thereof in preparation of MRSA infectious disease drugs | |
| CN103239447B (en) | Storage-stable lansoprazole composition for injection | |
| AU2013377404B2 (en) | Composition of cabazitaxel and sulfobutylether beta-cyclodextrin | |
| CN105596302A (en) | Ulinastatin freeze-dried powder preparation and preparation method thereof | |
| RU2497521C1 (en) | Pharmaceutical composition possessing antifungal activity, and method for preparing it | |
| EA024344B1 (en) | Formulations for infusion of type b lantibiotics |
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: 20160203 |