CN102755628B - Antifungal pharmaceutical composition - Google Patents
Antifungal pharmaceutical composition Download PDFInfo
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- CN102755628B CN102755628B CN 201210245954 CN201210245954A CN102755628B CN 102755628 B CN102755628 B CN 102755628B CN 201210245954 CN201210245954 CN 201210245954 CN 201210245954 A CN201210245954 A CN 201210245954A CN 102755628 B CN102755628 B CN 102755628B
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- posaconazole
- antifungal
- medicine
- pharmaceutical composition
- echinomycin
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Abstract
The invention discloses an antifungal pharmaceutical composition which is composed of A and B, wherein A is selected from at least one of quinoxaline antibiotics, and analogs, derivatives, prodrugs, metabolites and pharmaceutical active salts thereof; and B is selected from at least one of triazole compounds, and analogs, derivatives, prodrugs, metabolites and pharmaceutical active salts thereof.The in-vitro antimicrobial test proves that the combination of posaconazole and echinomycin has strong synergic activity. When the amounts of the posaconazole and echinomycin are respectively reducedby 32-64 times, the posaconazole and echinomycin can still ensure that the test fungi can be 100% cleared in an in-vitro test. The antifungal pharmaceutical composition can provide combined treatment, and is effective for refractory and invasive fungal infections, thereby lowering the amounts of posaconazole, relieving the economic burden of the patient, reducing the toxic reaction of posaconazole and effectively reducing the development of drug tolerance of fungi.
Description
Technical field
The present invention relates to a kind of antifungal pharmaceutical composition.
Background technology
Fungal infection, the especially sickness rate of hypoimmunity patient opportunistic fungal infection constantly rise the treatment of fungal infection are faced with formidable challenges.Although there are some fungi-medicines to come out one after another, treatment has brought new favourable turn to fungal infection, and the report of simultaneously relevant Drug therapy drug resistance also increases gradually.Therefore need the new antifungal therapy method of development.
Posaconazole generally is used for intractable and invasive infections with fungi or other medicines drug resistance cause fungal infection.This kind infection generally occurs in the patient of immunity infringement, for example organ transplantation or carry out the patient of chemotherapy.Compare with itraconazole with the control drug fluconazol of anti-fungal infection, posaconazole more can effectively prevent the aggressive aspergillin infection and can reduce the relevant mortality rate of invasive infections with fungi.But posaconazole is expensive, and often follows some serious adverse reactions such as hyperbilirubinemia in the therapeutic process, and liver enzyme raises, the symptoms such as hepatocellular damage and nausea and vomiting.
Summary of the invention
The purpose of this invention is to provide a kind of antifungal medicine composition with synergistic function.
Antifungal medicine composition provided by the present invention is comprised of A and B; Wherein, described A is selected from following at least a: quinoxaline antibiotic and analog thereof, derivant, prodrug, metabolite and pharmaceutically active salt, described B is selected from following at least a: triazole class compounds and analog thereof, derivant, prodrug, metabolite and pharmaceutically active salt.
In some embodiments, described A is selected from following any one material: Quinomycin A. and analog thereof, derivant, prodrug, metabolite and pharmaceutically active salt.
In some embodiments, described B is selected from following any one material: posaconazole and analog thereof, derivant, prodrug, metabolite and pharmaceutically active salt.
In the preferred embodiment, described A is Quinomycin A., and described B is posaconazole, and both mass ratioes are (12.5-1600): 1, and preferred mass is than being (200-1600): 1.
The antibiotic of quinoxaline described in the present invention and analog thereof, derivant, prodrug, metabolite and pharmaceutically active salt can obtain by microbial fermentation, chemical improvement, chemosynthesis or commercial sources.
Triazole class compounds described in the present invention and analog thereof, derivant, prodrug, metabolite and pharmaceutically active salt can obtain by chemosynthesis or commercial sources.
Another object of the present invention provides the application of above-mentioned antifungal medicine composition.
Application provided by the present invention is it for the preparation of the application in the medicine for the treatment of fungal infection.
In some embodiments, the fungus that infects can be selected from but be not limited to by aspergillosis, Fusarium spp., Candida albicans (being saccharomyces albicans).
The present invention also protects a kind of medicine that is used for the treatment of fungal infection.
The medicine that the present invention protects, its active component are antifungal medicine composition of the present invention.
Said medicine can import by the method for oral, external, injection, infiltration, absorption, physics or chemistry mediation body such as muscle, Intradermal, subcutaneous, vein or mucosal tissue; Or mixed by other material or wrap up after import body.
When needing, in said medicine, can also add one or more pharmaceutically acceptable carriers.Described carrier comprises diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier and the lubricant etc. of pharmaceutical field routine.
The described medicine that is used for the treatment of fungal infection can be made the various ways such as injection, tablet, powder, granule, capsule, unguentum, cream.The medicine of above-mentioned various dosage forms all can be according to the conventional method preparation of pharmaceutical field.
In vitro Bactericidal Experiments proves, with posaconazole and Quinomycin A. use in conjunction, shows very strong synergistic activity.Make both sides' dosage all reduce 32-64 doubly, can guarantee still in the experiment in vitro that tested fungus is by 100% removing.Such compositions will provide therapeutic alliance, and will be intractable for having, and invasive fungal infection is effective.And can therefore reduce the dosage of posaconazole, alleviate patient's financial burden, alleviate the toxic reaction of posaconazole, effectively reduce the development of Antifungal resistance.
Description of drawings
Fig. 1 is the collaborative antifungal activity result (composition of medicine MIC value during the growth of 100% Antifungi) of posaconazole and Quinomycin A.
The specific embodiment
The present invention will be described below by specific embodiment, but the present invention is not limited thereto.
Experimental technique described in the following embodiment if no special instructions, is conventional method; Described reagent and biomaterial if no special instructions, all can obtain from commercial channels.
Used Candida albicans (Candida albicans SC5314/ATCC MYA-2876) is available from the biological product collecting center (American Type Culture Collection) of Unite States Standard among the following embodiment.
The interactive antifungal activity test of embodiment 1, Quinomycin A. and posaconazole
Using chessboard method tests interactive antifungal (the Candida albicans SC5314) activity of Quinomycin A. and posaconazole.Concrete grammar is:
Candida albicans SC5314 in the RPMI1640 culture medium, 35 ℃, humidity 80%, 5%CO
2Condition under hatch.Quinomycin A. and posaconazole are dissolved in respectively among the DMSO, to concentration be 1mg/mL, stored for future use in refrigerator.In order to measure minimal inhibitory concentration (MIC), adopt doubling dilution during sample test.Specifically with reference to the M-27A of standardization committee of American National clinical laboratory (NCCLS) scheme, i.e. " yeast liquid media dilution method antifungal susceptibility test scheme ".Adopt 2 times of dilution methods to prepare the medicinal liquid of a series of diluted concentrations with fluid medium (RPMI1640), then with Candida albicans SC5314 cell (78 μ l ,～1 * 10
4Individual) be inoculated in 96 orifice plates rear adding 2 μ l drug solutions.First medicine posaconazole is vertically arranged by diluted concentration on 96 orifice plates, and second medicine Quinomycin A. laterally arranged by diluted concentration.Hatch test OD value after 18 hours for 35 ℃.Compare to determine the MIC value by the OD value with blank.The MIC value is defined as the lowest concentration of drug of energy 100% Antifungi growth herein.
For determine to work in coordination with between two medicine A and the B, addition or antagonism, we judge by inhibition concentration coefficient FICI.FICI=(A/MICA in the MIC drug regimen is independent)+(B/MICB in the MIC drug regimen is independent), if FICI value＜0.50, then show and have interactive activity, if the FICI value is between 0.5-4.0, then for showing active addition, if FICI value＞4.0 then show to have antagonism between the two.
Table 1. is worked in coordination with the antifungal activity test result
The result shows, posaconazole concentration is 0.002ug/ml, and Quinomycin A. concentration is 0.025ug/ml; Posaconazole concentration is 0.001ug/ml, and Quinomycin A. concentration is 0.05ug/ml; Posaconazole concentration is 0.0005ug/ml, and Quinomycin A. concentration is 0.1ug/ml; Posaconazole concentration is 0.00025ug/ml, and Quinomycin A. concentration is 0.1ug/ml; Posaconazole concentration is 0.000125ug/ml, and all there was collaborative antifungic action in two chemical compounds when Quinomycin A. concentration was 0.2ug/ml.Wherein posaconazole concentration is 0.00025ug/ml, and when Quinomycin A. concentration was 0.1ug/ml, collaborative antifungal activity was the strongest.
Claims (5)
1. an antifungal medicine composition is comprised of Quinomycin A. and posaconazole, and the mass ratio of described Quinomycin A. and posaconazole is (12.5-1600): 1.
Antifungal medicine composition claimed in claim 1 for the preparation of the treatment fungal infection medicine in application.
3. application according to claim 2 is characterized in that, described fungal infection is caused by following at least a fungus: aspergillosis, Fusarium spp. and Candida albicans.
4. medicine that is used for the treatment of fungal infection, its active component is antifungal medicine composition claimed in claim 1.
5. medicine according to claim 4 is characterized in that, described fungal infection is caused by following at least a fungus: aspergillosis, Fusarium spp. and Candida albicans.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210245954 CN102755628B (en) | 2012-07-16 | 2012-07-16 | Antifungal pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210245954 CN102755628B (en) | 2012-07-16 | 2012-07-16 | Antifungal pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102755628A CN102755628A (en) | 2012-10-31 |
| CN102755628B true CN102755628B (en) | 2013-10-23 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 201210245954 Expired - Fee Related CN102755628B (en) | 2012-07-16 | 2012-07-16 | Antifungal pharmaceutical composition |
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Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006503839A (en) * | 2002-09-23 | 2006-02-02 | シェーリング コーポレイション | Use of posaconazole for the treatment of fungal infections |
| PE20060291A1 (en) * | 2004-05-28 | 2006-04-14 | Schering Corp | POSACONAZOLE INJECTABLE PHARMACEUTICAL COMPOSITIONS WITH STABILIZED PARTICLES |
| CN102391968B (en) * | 2011-11-17 | 2012-12-19 | 中国科学院微生物研究所 | Streptomyces and its application in echinomycin production |
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