CN105168139B - Application of the silver-colored bag palladium nanometer formulation in anti-Cryptococcus infections medicine is prepared - Google Patents
Application of the silver-colored bag palladium nanometer formulation in anti-Cryptococcus infections medicine is prepared Download PDFInfo
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- CN105168139B CN105168139B CN201510587107.5A CN201510587107A CN105168139B CN 105168139 B CN105168139 B CN 105168139B CN 201510587107 A CN201510587107 A CN 201510587107A CN 105168139 B CN105168139 B CN 105168139B
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Abstract
The present invention relates to pharmaceutical technology field, and in particular to application of the silver-colored bag palladium nanometer formulation (Pd@Ag) in anti-Cryptococcus infections medicine is prepared.The present invention shows through cell experiment, among a variety of common invasive fungi pathogen, and different-diameter silver bag palladium nanometer formulation only has good inhibitory activity to cryptococcus, and its antifungal activity is significantly higher than Fluconazole (FCZ).The present invention still further provides silver-colored bag palladium nanometer formulation and combine the application in anti-Cryptococcus infections medicine is prepared with amphotericin B.The present invention the experiment proved that Pd@Ag nanometer formulations have with AmB and cooperate with anti-cryptococcus effect.The present invention opens new purposes for silver-colored bag palladium nanometer formulation, use it for the synergist of antifungal drug or antifungal drug, the antifungic action of medicine can not only be improved, and it is increasingly universal in clinic Antifungal resistance of curing the disease, the situation that drug-resistant intensity is on the rise, antifungal drug is set to recover the effect to drug resistance fungal, with good potential applicability in clinical practice.
Description
Technical field
The present invention relates to pharmaceutical technology field, and in particular to silver-colored bag palladium nanometer formulation is in anti-Cryptococcus infections medicine is prepared
Application.
Background technology
Cryptococcus (Cryptococcosus) is a kind of important saccharomycete for spreading all over nature, and Cryptococcus includes more than 70
Kind, wherein clinical pathogenic infection is most commonly seen with neogenesis cryptococcus and Ge Te cryptococcus.Cryptococcus mainly inhales through host respiratory
Enter and invade lung, it is clinical to show as asymptomatic pneumonia more, often remove or be converted into latent sense by host's normal immunological function
Dye state；When body's immunity seriously suppresses or weakened, the cryptococcus in lung that hides activates into blood circulation, sends out initiation
Systemic infection, outstanding thermophilic infection central nervous system.The Clinical Outcome of Cryptococcus infections depends primarily on the expression of its virulence factor
With the interaction between host immune response ability, when immunity of organisms declines, pathogen can directly invade and cause blood
Row is propagated, therefore the patient such as immunodepressant or patient, AIDS, the leukaemia of glucocorticoid is used for a long time and is susceptible to suffer from this disease.It is hidden
Coccus infection can be divided into pulmonary cryptococosis, cryptococcal meningitis, skin and mucosa cryptococcosis, bone according to clinical manifestation
Cryptococcosis and the type of internal organ cryptococcosis five.
The clinical treatment of cryptococcosis depends on antifungal drug, and it is mould that usual available medicine mainly includes both sexes
Plain B and its liposome, Fluconazole, Flucytosine etc..However, these antifungal drugs have significant toxic side effect and increasingly on
The drug resistance risen, is the significant challenge of puzzle studies of invasive fungal infections clinical treatment.Amphotericin B determined curative effect, but dosage
The patient test not good to base case of related poisonous side effect of medicine (such as liver renal toxicity, hemolytic anemia) is great, and order is very
Many clinicians inspire awe even from distance；Fluconazole can enter central nervous system through blood-brain barrier, be clinical few in number available
The optional medicine treated in Cryptococcus infections, but the strain of its clinical drug-resistant already occurs, and unsatisfactory curative effect during independent medication；Fluorine born of the same parents
Pyrimidine single therapy can induce clinical drug-resistant rapidly.Therefore, the efficient antifungal drug of new type of safe or joint are developed as early as possible
Therapeutic regimen is already extremely urgent.
Nearly ten years, nanosecond science and technology have started a new industrial revolution in the world, promoted biological, medicine,
The great development of the field technologies such as information, chemical industry, national defence.Nano silver material, with stable physical and chemical performance (surface etc. from
Daughter resonance effects SPR), most bacteriums, fungi and tumour cell can be effectively killed, health care, doctor is widely used to
Treat the fields such as apparatus, weaving, coating, commodity, ecological environment.However, the photo and thermal stability of nano silver material is poor, through strong light
Physics biological nature can change after irradiation, and the silver-colored bag nanometer Pd material (Pd@Ag) newly synthesized on this basis significantly overcomes
The shortcoming.Silver-colored bag nanometer Pd material adds the reduction of different proportion using the good palladium nanometer formulation of physicochemical property as " seed "
The Pd-Ag Core-shell bimetal nano materials of different-diameter are formed after state silver ion, its size shape is uniform, photothermal conversion
Efficiency high, photo and thermal stability and bio-compatibility are splendid, and anti-malignant tumor and bacterial-infection resisting treatment have been successfully applied at present
Study (Huang X, Tang S, Liu B, Ren B, Zheng N.Enhancing the photothermal stability
of plasmonic metal nanoplates by a core-shell architecture.Adv Mater.2011.23
(30):3420-5.；Mo S, Chen X, Chen M, He C, Lu Y, Zheng N.Two-dimensional
Antibaterial Pd@Ag Nanosheets with a Synergetic Effect of Plasmonic Heating
and Ag+Release.J Mater Chem B.2015(Accepted).)。
But have not yet to see is used for the relevant report that anti-cryptococcus is treated about silver-colored bag palladium nanometer formulation, also has no relevant silver
The relevant report of bag palladium nanometer formulation and other anti-cryptococcus drug combinations.
The content of the invention
It is specifically prepared by silver-colored bag palladium nanometer formulation it is an object of the invention to provide the new application of silver-colored bag palladium nanometer formulation
Application in anti-Cryptococcus infections medicine.
Application of the first aspect of the present invention there is provided silver-colored bag palladium nanometer formulation in anti-Cryptococcus infections medicine is prepared.
Described silver-colored bag palladium Pd@Ag nanometer formulations, particle diameter is 1-120nm.
Described silver-colored bag palladium Pd@Ag nanometer formulations, particle diameter is that 5-120nm has preferably anti-cryptococcus effect；Optimal,
Particle diameter is 80nm.
The present invention shows through cell experiment, among a variety of common invasive fungi pathogen, different-diameter silver bag palladium
Nanometer formulation only has good inhibitory activity to cryptococcus, and its antifungal activity is slightly inferior to amphotericin B (AmB), but significantly
Higher than Fluconazole (FCZ).
Moreover, the Pd@Ag nanometer formulations of low concentration (≤5 μ g/ml) different-diameter are smaller to the toxic side effect of HeLa cells.
In a preferred embodiment of the invention, Pd@Ag nanometer formulations (80nm) are hidden to different genotype new life/lattice spy
The clinical strain or separation strains of coccus have good inhibitory effect.
Anti- Cryptococcus infections medicine of the present invention, be using Pd@Ag nanometer formulations as sole active composition, or bag
The pharmaceutical composition of the Ag nanometer formulations of@containing Pd.
The content of Pd@Ag nanometer formulations is 0.1-99wt% in described anti-Cryptococcus infections medicine.
It is preferred that the content of Pd@Ag nanometer formulations is 0.5-51wt% in described anti-Cryptococcus infections medicine.
Described anti-Cryptococcus infections medicine, is the medicine that Pd@Ag nanometer formulations and conventional pharmaceutical excipients are prepared
Preparation.
The Pd@Ag nanometer formulations of the present invention routinely pharmacy can be prepared into pharmaceutical preparation, such as oral formulations, injection system
Pharmaceutical preparation of agent, infusion preparation or Transdermal absorption etc..
The second aspect of the present invention is combined there is provided silver-colored bag palladium nanometer formulation with amphotericin B is preparing anti-cryptococcus sense
Contaminate the application in medicine.
Further, the invention provides a kind of drug combination method, specially a kind of anti-cryptococcus is combined to be received with metal
Rice medicine, described its active component of combination medicine is silver-colored bag palladium nanometer formulation and amphotericin B.
Scheme of combination drug therapy of the present invention, can simultaneously or sequential administration effective dose silver-colored bag palladium nanometer formulation with effectively
The amphotericin B of amount.Described order can first use silver-colored bag palladium nanometer formulation, then use amphotericin B；Can also be first with two
Property mycin B, then with silver-colored bag palladium nanometer formulation.
The present invention the experiment proved that Pd@Ag nanometer formulations have with AmB cooperates with anti-cryptococcus effect.To common hidden ball
In the drug sensitive test of bacterium type strain, during independent role, the MIC value of Pd@Ag nanometer formulations is 0.25-2 μ g/ml, AmB MIC value
For 0.125-1 μ g/ml, and Pd@Ag nanometer formulations (80nm) and AmB MIC value are reduced to 0.06 and 0.004 respectively after synergy
μ g/ml, Combination Index FICI is respectively less than 0.5, it is seen that Papillary has significant synergetic antibacterial effect to cryptococcus.
Pharmaceutical carrier of the present invention, i.e. pharmaceutically acceptable carrier, refer to that is commonly used in pharmaceutical field removes activity
Additive beyond composition, such as diluent (starch, carbohydrate, cellulose family and inorganic salts), excipient, filler is as formed sediment
Powder sucrose, adhesive such as water, ethanol, cellulose derivative, gelatin and polyvinylpyrrolidone, disintegrant such as dried starch, carboxylic first
Base sodium starch, solubilizer such as poly yamanashi esters and polyoxyethylene fatty acid ester class etc., sorbefacient, surfactant are such as told
Temperature, sapn, absorption carrier, lubricant such as magnesium stearate, superfine silica gel powder etc..Furthermore it is also possible to add in the composition other auxiliary
Expect such as flavouring agent, sweetener.
The present invention opens new purposes for silver-colored bag palladium nanometer formulation, uses it for antifungal drug or antifungal drug
Synergist, can not only improve the antifungic action of medicine, and increasingly universal in clinic Antifungal resistance of curing the disease, drug-resistant intensity day
The situation for becoming serious, makes antifungal drug recover the effect to drug resistance fungal, with good potential applicability in clinical practice.
Brief description of the drawings
Fig. 1 is toxicity detection of the Pd@Ag nanometer formulations to HeLa cells.
Embodiment
The implementation of the present invention is elaborated with reference to embodiments of the invention, following examples are with the present invention
It is lower premised on technical scheme to be implemented, give detailed embodiment, but protection scope of the present invention be not limited to it is following
Embodiment.
Suppression of the silver-colored bag palladium Pd Ag nanometer formulations of the different-diameter of embodiment 1. to a variety of common invasive fungi pathogen
System experiment
Experiment material：
Synthesis material needed for silver-colored bag palladium nanometer formulation：2,4- glutaric acid palladium Pd (acac) 2 (99%) are purchased from Alfa
Aesar companies, PVP (PVP, MW=30000), dimethylformamide (DMF), sodium bromide (NaBr) and nitre
Hydrochlorate (AgNO3) Chemical Reagent Co., Ltd., Sinopharm Group is purchased from, TBAB (TBAB) is purchased from Acros Organics
Company.Fluconazole (FCZ) is purchased from pfizer inc, antifungal drug amphotericin B (AmB), the training of the liquid of RPMI 1640
Nutrient solution and PDA culture medium are purchased from Sigma-Aldrich companies.
The encountered pathogenic fungi type strain of research institute is carried by Shanghai City medical mycology molecular biology key lab
For except H99, R265, SC5314 retain primary standard extra, other type strains are numbered using ATCC.
Instrument and equipment：
Multiskan MK3 type enzyme marks detectors (Finland's Labsystems products)
Water isolation type electro-heating standing-temperature cultivator (Shanghai leap medical apparatus and instruments factory)
THZ-82A Desk type constant-temperatureoscillator oscillators (Shanghai leap medical apparatus and instruments factory)
SW-CT-IF types superpurgative working table (SuZhou Antai Air Tech Co., Ltd.)
Experimental method：
First, nano material is synthesized
The silver-colored bag palladium nanometer formulation of different-diameter (5,11,30,80,120nm) entrusts Xiamen University's surface of solids physics
Chemical National Key Laboratory's synthesis, specific method is with reference to bibliography (Huang X, Tang S, Liu B, Ren B, Zheng
N.Enhancing the photothermal stability of plasmonic metal nanoplates by a
core-shell architecture.Adv Mater.2011.23(30):3420-5.)。
Secondary antibody antifungal susceptibility testing
This experiment is using U.S. clinical Laboratory Standard association (Clinical and Laboratory Standards
Institute, CLSI) CLSI-M27A3 (Safdar A, Hanna HA, Boktour M, et al.Impact of high-
dose granulocyte transfusions in patients with cancer with candidemia:
retrospective case-control analysis of 491 episodes of Candida species
bloodstream infections.Cancer.2004.101(12):2859-65.) with M38A2 (Romani L.Immunity
to fungal infections.Nat Rev Immunol.2011.11(4):275-88.) the micro liquid-based that file is recommended
Dilution method (Broth Microdilution) prepares the storage liquid and doubling dilution liquid (0.125mg/L-64mg/ of said medicine
L)。
All tested bacterium, which are seeded in the upper 28 DEG C of cultures 7d of potato dextrose medium (PDA), before experiment activates it.
The 0.85% salt solution 1mL containing 0.01mL polysorbas20s (1 drop) is added on 7d bacterium colony being incubated, bacteria suspension is prepared；Bacteria suspension is quiet
Put after 3-5min, bulky grain is sunken to bottom, take upper strata homogeneous liquid (containing sporangiospore or conidium and mycelia fragment)；With
Blood cell counting plate adjusts bacteria suspension concentration to 2 × 10 with RPMI 1640 culture mediums6-1×10CFU7/mL.Finally will be above-mentioned
The bacteria suspension being configured dilutes 1000 times with RPMI 1640 culture mediums.Make its concentration between 2 × 103-1×104CFU/mL
Between.Common blastomycosis substance such as cryptococcus, candida albicans use CLSI-M27A3 methods, and common filamentous fungi pathogen is such as
Aspergillus, Mucor are then using CLSI-M38A2 methods (concrete operations see reference document).Sentence read result is observed after quiescent culture 4-7d, most
The criterion of low Mlc (MIC)：Result judgement is carried out under the microscope, is contrasted and is completely inhibited with Positive control wells, nothing
The least concentration of growth.All bacterial strains carry out 2 times repetition experiment, every time experiment comprising reference culture measure with ensure examination
Test accurate.
Experimental result：
As a result as shown in table 1, as a result it is shown among a variety of common invasive fungi pathogen, different-diameter silver bag palladium
Nanometer formulation has good inhibitory activity to cryptococcus, and its MIC value is about 0.25-1mg/L, and its antibacterial activity is slightly inferior to two
Property mycin B (AmB, MIC=0.125-0.5mg/L), but it is significantly higher than Fluconazole (FCZ, MIC=16mg/L).
Table 1：Pd@Ag nanometer formulations are detected to the antifungal activity of common aggressive pathogenic yeast and thread disease fungus and tied
Really
Note：FCZ is Fluconazole；AmB is amphotericin B.
Toxicity test of the silver-colored bag palladium Pd@Ag nanometer formulations of the various concentrations of embodiment 2. to HeLa cells
Experiment material：
Silver-colored bag palladium Pd@Ag nanometer formulations (5,11,30,80,120nm) be the same as Example 1.Human cervical carcinoma cell (HeLa), purchase
From cell institute of the Chinese Academy of Sciences.
The reagent needed：
DMEM culture mediums are purchased from Life Technologies companies of the U.S.
CCK-8 kits are purchased from the eastern Renhua Science and Technology Ltd. in Shanghai
Instrument and equipment：
The multi-testers of Synergy 2 (German BioTek products)
Carbon dioxide cell incubator (Japanese Sanyo Electric companies)
SW-CT-IF types superpurgative working table (SuZhou Antai Air Tech Co., Ltd.)
Experimental method：
By HeLa cells (1 × 10 before experiment4Cells/ml) it is inoculated in 96 orifice plates, DMEM culture mediums, 37 DEG C, 5%CO2
Preculture 24 hours in cell culture incubator.Cell is paved with after bottom hole, by cell in various concentrations (0,1,2,5,10,20mg/L) no
With being incubated 24 hours (37 DEG C, 5%CO again in the silver-colored bag palladium Pd@Ag nanometer formulations of diameter2).After effect 24 hours, to every hole
10ul CCK-8 solution is added, culture plate is incubated 2 hours in incubator, then the suction at 450nm is determined with ELIASA
Luminosity.CCK-8 detections are added in not celliferous culture medium and are used as blank control.Treatment group by with the control for being not added with medicine
Group contrast obtains cytoactive.
Experimental result：
As a result as shown in figure 1, generally with the increase of drug concentration, toxicity of the silver-colored bag palladium nanometer formulation to HeLa cells
Progressively strengthen.In comparable sodium, comparatively toxicity is most strong for the Pd@Ag nanometer formulations of 5nm diameters, and remaining four kinds (11,
30,80,120nm) Pd@Ag nanometer formulations to the inhibitory action of HeLa cells without significant difference (P ＞ 0.05).It is dense in higher drug
When spending, different-diameter nanometer formulation has obvious depression effect to HeLa cells, when being such as incubated altogether with 10 μ g/mL nanometer formulations
The survival rate of HeLa cells is about original 60%-69%.
When silver-colored bag palladium nanometer formulation concentration be less than 5 μ g/mL, then to HeLa cells without obvious inhibiting effect, during 5 μ g/mL
HeLa cells survival rates are about 90%-98%, and HeLa cells survival rates are normal during 1-2 μ g/mL.Therefore, low concentration (≤5 μ g/
ML) Pd@Ag nanometer formulations (11-120nm) are smaller to HeLa cellulotoxic side effects, and substantially nontoxic secondary work during minimum inhibitory concentration
With.
Embodiment 3.Pd@Ag nanometer formulations (80nm) are to the special cryptococcal clinical strain of different genotype new life/lattice or separation
The bacteriostatic experiment of strain
Experiment material：
Silver-colored bag palladium Pd@Ag nanometer formulations (80nm) be the same as Example 1.
All cryptococcus of research institute's different genotype are clinical or environment separation strain is by Shanghai City medical mycology molecule
Biology key lab provides, and its culture presevation number is followed successively by SCZ9001-SCZ9045.
Experimental method：
In conjunction with the embodiments 1 with the result of example 2, it has been found that the Pd@Ag nanometer formulations of 11nm, 30nm, 80nm diameter have
Have when preferably pressing down cryptococcus effect (MIC=0.5 μ g/mL), low concentration to HeLa cells without obvious toxic-side effects, and than
11nm and 30nm nanometer formulations, 80nm nanometer formulations are stronger to other disease fungus bacteriostasis, therefore the present invention is further commented
Pd@Ag nanometer formulations (80nm) have been estimated to different genotype, the cryptococcal intervention effect of separate sources.
This experiment is using U.S. clinical Laboratory Standard association CLSI-M27A3 methods detection Pd@Ag nanometer formulations (80nm)
To different cryptococcal inhibitory effects, its specific method step detailed in Example 1.
Experimental result：
As a result as shown in table 2, as a result show Pd@Ag nanometer formulations (80nm) to the special cryptococcus of different genotype new life/lattice
Clinical strain or separation strains have good inhibitory effect.For neogenesis cryptococcus, the clinic or environment of different genotype
Separation strains, the minimal inhibitory concentration of Pd@Ag nanometer formulations (80nm) is about 0.25-2 μ g/mL (average MIC90=2 μ g/mL)；Silver
The special cryptococcal inhibitory effect of bag palladium plaid matching is close, and MIC is 0.25-2 μ g/mL (average MIC90=1 μ g/mL).
The studies above result is pointed out, and Pd@Ag nanometer formulations (80nm) are to various genotype and the cryptococcosis of separate sources
Opportunistic pathogen is respectively provided with good depression effect, and its bacteriostasis is slightly inferior to amphotericin B, possesses as anti-Cryptococcus infections curative
The potential quality of thing.
The Pd@Ag nanometer formulations (80nm) of table 2 are tied to different genotype and the cryptococcal antifungal activity detection of separate sources
Really.
Remarks：* it is cryptococcal genotype or source, Cn is neogenesis cryptococcus, its genotype (VNI, II, III, IV),
Cg is the special cryptococcus of lattice, its genotype (VGI, II, III, IV)；Source includes clinical patients separation (clinical), animal mark
This separation (animal) and environment sample separation (environmental).
Embodiment 4.Pd@Ag nanometer formulations (80nm) have with amphotericin A mB cooperates with anti-cryptococcus effect experiment
Experiment material：
Silver-colored bag palladium Pd@Ag nanometer formulations (80), amphotericin B be the same as Example 1.The special hidden ball of the new life of different genotype/lattice
Bacterium provides by Shanghai City medical mycology molecular biology key lab.
Experimental method：
The method be the same as Examples 1 such as bacterium solution preparation, result interpretation.
Drug sensitive plate preparation method is as follows：
Each bacterial strain takes sterile one piece of 96 orifice plate respectively, adds the μ l of 1640 fluid nutrient mediums of RPMI 100 to make in every No. 1 hole of row empty
White control；3~No. 12 holes are respectively plus the μ l of bacterium solution 99 for stating Fresh；No. 2 holes add the μ l and Yin Bao palladium Pd Ag of bacterium solution 196 respectively
The μ l of nanometer formulation (80nm) 2；No. 12 holes not drug containing, only plus the μ l of bacterium solution 100 make Growth positive control.Allocate various concentrations
The μ g/mL of AmB 0.128,0.064,0.032,0.016,0.008,0.004, add the AmB2 μ l of respective concentration in No. 2 holes of every row,
3~No. 11 holes respectively add 1 μ l.
10 grades of doubling dilutions are carried out to 2~No. 11 holes, make final silver-colored bag palladium Pd@Ag nanometer formulations (80) concentration point in each hole
Other 2,1,0.5,0.25,0.12,0.06,0.03,0.015,0.008,0.004 μ g/ml.And AmB concentration keeps constant, each hole
Middle DMSO contents are below 1%.By each drug sensitive plate in 30 DEG C of insulating box cultures.
Experimental result：
As a result as shown in table 3, as a result show that Pd@Ag nanometer formulations (80nm) have with AmB and cooperate with anti-cryptococcus effect.
To in the drug sensitive test of common cryptococcus type strain, during independent role, the MIC value of Pd@Ag nanometer formulations (80nm) is 0.25-2 μ
G/ml, AmB MIC value are 0.125-1 μ g/ml, and Pd@Ag nanometer formulations (80nm) and AmB MIC value are distinguished after synergy
0.06 and 0.004 μ g/ml are reduced to, Combination Index FICI is respectively less than 0.5, it is seen that Papillary has significant collaboration anti-to cryptococcus
Bacterium acts on.
The Pd@Ag nanometer formulations (80nm) of table 3 combine antifungal activity detection with AmB's.
The preferred embodiment to the invention is illustrated above, but the invention be not limited to it is described
Embodiment, those skilled in the art can also make a variety of equivalent on the premise of without prejudice to the invention spirit
Modification or replacement, these equivalent modifications or replacement are all contained in the application claim limited range.
Claims (6)
1. application of the silver medal bag palladium nanometer formulation in anti-Cryptococcus infections medicine is prepared, it is characterised in that described anti-cryptococcus
Infection medicine is that silver-colored bag palladium nanometer formulation is combined with amphotericin B.
2. application of the silver-colored bag palladium nanometer formulation according to claim 1 in anti-Cryptococcus infections medicine is prepared, its feature
It is, the particle diameter of described silver-colored bag palladium nanometer formulation is 1-120nm.
3. application of the silver-colored bag palladium nanometer formulation according to claim 1 in anti-Cryptococcus infections medicine is prepared, its feature
It is, the particle diameter of described silver-colored bag palladium nanometer formulation is 80nm.
4. the answering in anti-Cryptococcus infections medicine is prepared of the silver-colored bag palladium nanometer formulation according to any one of claims 1 to 3
With the μ g/ml of, it is characterised in that the concentration of described silver-colored bag palladium nanometer formulation≤5.
5. the answering in anti-Cryptococcus infections medicine is prepared of the silver-colored bag palladium nanometer formulation according to any one of claims 1 to 3
With, it is characterised in that described cryptococcus is different genotype neogenesis cryptococcus, the special cryptococcal clinical strain of lattice or separation strains.
6. a kind of anti-cryptococcus combination medicine, it is characterised in that the active component of described combination medicine is that silver-colored bag palladium is received
Metric system agent and amphotericin B.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2218447A1 (en) * | 2008-11-04 | 2010-08-18 | PharmaSol GmbH | Compositions containing lipid micro- or nanoparticles for the enhancement of the dermal action of solid particles |
| CN104069128A (en) * | 2014-06-25 | 2014-10-01 | 东南大学 | Application of poly vinyl pyrrolidone (PVP) modified nano-silver and imidazole medicines in preparation of drug tolerance resistant fungus active combined medicines |
-
2015
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2218447A1 (en) * | 2008-11-04 | 2010-08-18 | PharmaSol GmbH | Compositions containing lipid micro- or nanoparticles for the enhancement of the dermal action of solid particles |
| CN104069128A (en) * | 2014-06-25 | 2014-10-01 | 东南大学 | Application of poly vinyl pyrrolidone (PVP) modified nano-silver and imidazole medicines in preparation of drug tolerance resistant fungus active combined medicines |
Non-Patent Citations (2)
| Title |
|---|
| Silver nanoparticle production by the fungus Fusarium oxysporum: nanoparticle characterisation and analysis of antifungal activity against pathogenic yeasts;Kelly Ishida et al;《Mem Inst Oswaldo Cruz, Rio de Janeiro》;20140430;第109卷(第2期);第220-228页，第220页摘要，第221页左栏第4段 * |
| Two-dimensional antibacterial Pd@Ag nanosheets with a synergetic effect of plasmonic heating and Ag+ release;Shiguang Mo et al;《Journal of Materials Chemistry B》;20150623;第3卷;第6255-6260页，第6255页摘要，第6256页右栏最后1段，对比文件1第6258页左栏第2段、图3b * |
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