CN108042532A - A kind of antimycotic pharmaceutical composition - Google Patents
A kind of antimycotic pharmaceutical composition Download PDFInfo
- Publication number
- CN108042532A CN108042532A CN201711116808.6A CN201711116808A CN108042532A CN 108042532 A CN108042532 A CN 108042532A CN 201711116808 A CN201711116808 A CN 201711116808A CN 108042532 A CN108042532 A CN 108042532A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- drugs
- econazole
- mic
- antimycotic
- 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.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses a kind of antimycotic pharmaceutical composition, which includes the A drugs of antifungal activity and the B drugs of concertedness；Wherein, fungi inhibition concentration coefficient FICI=(MIC when MIC/A drugs of A drugs are used alone in pharmaceutical composition)+(MIC when MIC/B drugs of B drugs are used alone in pharmaceutical composition)≤0.5 of the pharmaceutical composition, wherein, A drugs include econazole, and B drugs include qinghaosu.The present invention can effectively reduce the minimal inhibitory concentration (MIC) of antifungal drug econazole, can significantly improve the anti-mycotic efficiency of econazole, so as to reduce the dosage of econazole in therapeutic process, and then reduce its toxic side effect.
Description
Technical field
The invention belongs to antifungal therapy technical field more particularly to a kind of antimycotic pharmaceutical compositions.
Background technology
Fungal infection includes the mycotic infection of superficial part that incidence is high but harm is lighter and incidence is relatively low but harm is serious
Deep fungal infection.Due to the morbidity of the abuse, especially immunocompromised patients' opportunistic fungal infection of antibiotic in recent years
Rate constantly rises, and the treatment of fungal infection is made to be faced with formidable challenges.It is true to resist although constantly there is new antifungal drug to come out
Bacterium treatment provides new opportunity, but the drug resistance report in relation to drug therapy also gradually increases simultaneously.Therefore need to develop newly
Antifungal therapy method.
Pyroles antifungal drug, also known as triazole antifungal agent object are clinical most widely used antifungal drug at present,
And there is one kind of preferable prospect in antifungal drug, mainly by inhibiting the biosynthesis of steroid in fungal cell membrane,
It is divided into imidazoles and triazole type.Econazole is the representative drug of pyroles antibiotic.Pyroles antifungal drug have curative effect compared with
Well, the advantages that antimicrobial spectrum is extensively, toxicity is small compared with amphotericin B.But in recent years due to the abuse phenomenon of antibiotic and antifungal drug,
Cause the decline of pyroles antifungal drug curative effect or even drug resistance phenomenon occur, while have pyroles antifungal drug certain more
Liver renal toxicity, has many cases to cause the even dead report of hepatotoxicity wind agitation in recent years, and some pyroles antifungal drugs separately have gastrointestinal tract
Toxicity, system genitale toxicity, teratogenesis mutagenesis, paropsia, fash, fever, headache, illusion, Nausea and vomiting, abdominal pain etc.
Adverse reaction.Therefore it will be antifungal in a period of time from now on to research and develop efficient, hypotoxicity pyroles antifungal drug combination
The emphasis of object development.
The content of the invention
It is an object of the invention to provide a kind of antimycotic pharmaceutical compositions, it is intended to solve in the prior art anti-
The problem of fungi-medicine combination is deficient, antifungal drug toxic side effect is big.
The present invention is achieved in that a kind of antimycotic pharmaceutical composition, which includes the A of antifungal activity
The B drugs of drug and concertedness；Wherein, the fungi inhibition concentration coefficient FICI=(A in pharmaceutical composition of the pharmaceutical composition
MIC when the MIC/A drugs of drug are used alone)+(MIC when MIC/B drugs of B drugs are used alone in pharmaceutical composition)
≤0.5。
Preferably, the A drugs include the analog of pyroles antibiotic or pyroles antibiotic, derivative, prodrug,
Metabolin and pharmaceutically active salt.
Preferably, the B drugs include the analog of Sesquiterpene lactones drug or Sesquiterpene lactones drug, spread out
Biology, prodrug, metabolin and pharmaceutically active salt.
Preferably, the A drugs are econazole, and the B drugs are qinghaosu.
Preferably, the quality of the econazole, qinghaosu is (0.125~0.5) than scope：(1.5625~100).
Preferably, the mass ratio 0.125 of the econazole, qinghaosu：100.
Preferably, the fungi includes endangering body lighter superficial mycosis and endangers serious deep fungal.
Preferably, the fungi includes Candida albicans.
Compared with the prior art the shortcomings that and deficiency, the invention has the advantages that：The present invention can be reduced effectively
The minimal inhibitory concentration (MIC) of antifungal drug econazole, can significantly improve the anti-mycotic efficiency of econazole, be controlled so as to reduce
The dosage of econazole during treatment, and then reduce its toxic side effect.
Specific embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
It will be clear that the experimental method used in following embodiments is unless otherwise specified, it is conventional method, under
Material, reagent used in embodiment etc. is stated, is commercially available unless otherwise specified.
Candida albicans Candida albicans SC5314 are purchased from Unite States Standard biology product collecting center (American
Type Culture Collection), preserving number is ATCC MYA-2876.
Qinghaosu is purchased from lark prestige company (catalog number 949289-1g).
Econazole is purchased from MCE companies (catalog number HY-B0885).
First, the interactive antifungal activity of qinghaosu and econazole is tested
Using chessboard method (Candida albicans, Candida antimycotic to the interaction of qinghaosu and econazole
AlbicansSC5314) activity is tested.
1st, by Candida albicans Candida albicans SC5314 in RPMI1640 culture mediums, 35 DEG C, humidity is
80%, 5%CO2Under conditions of be incubated.
2nd, qinghaosu and econazole are dissolved in DMSO respectively, until concentration is respectively 20mg/ml and 8mg/ml, in refrigerator
Stored for future use.
3rd, minimal inhibitory concentration (MIC) is measured
(1) with reference to clinical and Laboratory Standard association (CLSI) M27-A3 schemes, i.e., " saccharomycete fluid nutrient medium dilutes
Method antifungal susceptibility test scheme ".With fluid nutrient medium (1640 culture mediums of RPMI) by the sweet wormwood of the 20mg/ml of storage
The econazole solution of element and 8mg/ml are configured to a series of qinghaosu of diluted concentrations and econazole liquid.
(2) albicans cell is inoculated into 96 orifice plates, per hole 96ul (about 1 × 104A cell), it is separately added into
2ul qinghaosus and econazole liquid, the combined method of liquid are as follows：
First drug econazole presses diluted concentration longitudinal arrangement (each horizontally-arranged econazole from top to bottom on 96 orifice plates
Concentration is identical), per hole 2ul, second drug artemisinin is from left to right laterally arranged the (qinghaosu of each tandem by diluted concentration
Concentration is identical), per hole 2ul, the concentration of each empty qinghaosu and econazole is recorded, while sets and is individually added into gradient dilution
Group per hole 2ul of qinghaosu or econazole liquid and the blank control group for being not added with any drug, do three 96 parallel holes
Plate, results are averaged.
(3) by 96 orifice plates in 35 DEG C be incubated 16~20 it is small when after 600nm test OD values.
(4) pyroles antifungal drug MIC value is defined as substantially inhibiting the lowest concentration of drug of fungi growth.Each drug
The hole of combination is compared to determine MIC value by the OD values with blank control.
It sets and is defined as below herein：Judge it is collaboration between two drugs A and B by inhibition concentration coefficient FICI, be added
Or antagonism.
Wherein, FICI=(A/MICA in MIC pharmaceutical compositions is independent)+(B/MICB in MIC pharmaceutical compositions is independent), such as
Fruit FICI value≤0.5 then shows there is synergistic effect between drug A and B, if FICI values show medicine between 0.5~4.0
Object A is added with the activity of B, if FICI values ＞ 4.0, shows that there are antagonisms between drug A and B.
By the interaction of detection qinghaosu defined above and econazole, since qinghaosu anti-candida albicans itself are lived
Property it is poor, (qinghaosu/MIC qinghaosus in MIC pharmaceutical compositions) is negligible, and the results are shown in Table 1.
FICI after 1 qinghaosu of table and econazole combination
Table 1 shows the final concentration of 0.500ug/ml of econazole, the final concentration of 1.5625ug/ml of qinghaosu；Econazole is dense eventually
It spends for 0.500ug/ml, the final concentration of 3.125ug/ml of qinghaosu；The final concentration of 0.500ug/ml of econazole, qinghaosu final concentration
For 6.25ug/ml；The final concentration of 0.250ug/ml of econazole, the final concentration of 12.5ug/ml of qinghaosu；Econazole is final concentration of
The final concentration of 25ug/ml of 0.250ug/ml, qinghaosu；The final concentration of 0.125ug/ml of econazole, the final concentration of 50ug/ of qinghaosu
ml；In this seven groups of pharmaceutical compositions of the final concentration of 0.125ug/ml of econazole, the final concentration of 100ug/ml of qinghaosu, econazole and green grass or young crops
There is collaboration antifungic action in artemisin.Wherein as qinghaosu final concentration raises, the antimycotic work of collaboration of econazole and qinghaosu
Property constantly enhances.
2nd, pyroles antibiotic and the interaction of sesquiterpene lactone class drug are antimycotic
Pyroles antibiotic or its analog, derivative, prodrug, metabolin and pharmaceutically active salt can be used to replace for econazole
Generation.Sesquiterpene lactones drug and the like, derivative, prodrug, metabolin and pharmaceutically active salt can be used to substitute for qinghaosu.
The selection of more specific component is according to the fungi of required inhibition between pyroles antibiotic and sesquiterpene lactone class drug
Type makes choice and determines that the originated from fungus that pharmaceutical composition of the present invention can inhibit is extensive, is not limited to including working as to body
The lighter superficial mycosis of harm and the serious deep fungal of harm, can also lead to the optimal inhibition effect of fungi pharmaceutical composition
It crosses above-mentioned implementation and determines optimum mixture ratio example between the two to obtain.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
All any modification, equivalent and improvement made within refreshing and principle etc., should all be included in the protection scope of the present invention.
Claims (8)
1. a kind of antimycotic pharmaceutical composition, which is characterized in that the pharmaceutical composition includes A drugs and the association of antifungal activity
The B drugs of the same sex；Wherein, the fungi inhibition concentration coefficient FICI=(MIC/ of A drugs in pharmaceutical composition of the pharmaceutical composition
MIC when A drugs are used alone)+(MIC when MIC/B drugs of B drugs are used alone in pharmaceutical composition)≤0.5.
2. antimycotic pharmaceutical composition as described in claim 1, which is characterized in that the A drugs include pyroles antibiosis
The analog of element or pyroles antibiotic, derivative, prodrug, metabolin and pharmaceutically active salt.
3. antimycotic pharmaceutical composition as claimed in claim 2, which is characterized in that the B drugs include sesquiterpene lactone
The analog of class drug or Sesquiterpene lactones drug, derivative, prodrug, metabolin and pharmaceutically active salt.
4. antimycotic pharmaceutical composition as described in claim 1, which is characterized in that the A drugs are econazole, the B
Drug is qinghaosu.
5. antimycotic pharmaceutical composition as claimed in claim 4, which is characterized in that the econazole, the quality of qinghaosu
It is (0.125~0.5) than scope：(1.5625~100).
6. antimycotic pharmaceutical composition as claimed in claim 5, which is characterized in that the econazole, the quality of qinghaosu
Than 0.125：100.
7. antimycotic pharmaceutical composition as described in claim 1, which is characterized in that the fungi include to body harm compared with
Light superficial mycosis and the serious deep fungal of harm.
8. antimycotic pharmaceutical composition as claimed in claim 7, which is characterized in that the fungi includes Candida albicans.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711116808.6A CN108042532B (en) | 2017-11-13 | 2017-11-13 | Antifungal pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711116808.6A CN108042532B (en) | 2017-11-13 | 2017-11-13 | Antifungal pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108042532A true CN108042532A (en) | 2018-05-18 |
| CN108042532B CN108042532B (en) | 2021-05-18 |
Family
ID=62119151
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711116808.6A Active CN108042532B (en) | 2017-11-13 | 2017-11-13 | Antifungal pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108042532B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111419841A (en) * | 2020-03-25 | 2020-07-17 | 山东省肿瘤防治研究院（山东省肿瘤医院） | Anti-candida albicans combined medicine |
-
2017
- 2017-11-13 CN CN201711116808.6A patent/CN108042532B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| KAAT DE CREMER等: "Artemisinins, New Miconazole Potentiators Resulting in Increased Activity against Candida albicans Biofilms", 《ANTIMICROBIAL AGENTS AND CHEMOTHERAPY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111419841A (en) * | 2020-03-25 | 2020-07-17 | 山东省肿瘤防治研究院（山东省肿瘤医院） | Anti-candida albicans combined medicine |
| CN111419841B (en) * | 2020-03-25 | 2021-05-14 | 山东省肿瘤防治研究院（山东省肿瘤医院） | Anti-candida albicans combined medicine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108042532B (en) | 2021-05-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Pound et al. | Overview of treatment options for invasive fungal infections | |
| CN103536613B (en) | A kind of antifungal pharmaceutical composition | |
| CN103289901B (en) | Echinocandin B producing strain and application thereof | |
| CN108042532A (en) | A kind of antimycotic pharmaceutical composition | |
| CN107812011A (en) | A kind of antimycotic pharmaceutical composition | |
| CN101209952B (en) | Sesquiterpenoids, composition thereof, method for extracting the same from plants and application | |
| CN102274215A (en) | Synergist with synergetic antifungal effect with fluconazole | |
| CN102783496A (en) | Composite bactericide comprising prochloraz and use thereof | |
| CN102579435A (en) | Oil-in-water compound fluconazole nano-emulsion and preparation method thereof | |
| Thirach et al. | Antifungal activity of some medicinal plant extracts against Candida albicans and Cryptococcus neoformans | |
| CN109769837A (en) | A kind of pesticide synergistic combination preventing and treating fruits and vegetables gray mold | |
| CN108354926B (en) | Application of scutellarin and derivatives thereof in antifungal medicines | |
| CN102755628B (en) | Antifungal pharmaceutical composition | |
| CN111991390B (en) | Amphotericin B synergist and application thereof | |
| CN102349530A (en) | Fungicide composition for controlling gummosis of peach tree | |
| CN103585143A (en) | Application of formononetin in preparation of aspergillus fumigatus resistant medicament | |
| Negi et al. | P013 Green synthesis of silver nanoparticles using Trillium govanianum and its antifungal potential against Candida auris | |
| Sharma et al. | P017 Echinocandin resistance mechanism in Candida tropicalis and Candida glabrata | |
| Riyaz et al. | P016 Selected trans-Himalayan medicinal plants and their nano-particles express potent antifungal and antibiofilm activity against Candida auris and Candida glabarata | |
| Kumari et al. | P012 Antibiofilm activity of staphylococcal peptide derivative (s) against Candida auris biofilms in vitro and in an animal model of catheter-associated infection | |
| Pandey et al. | P014 Prevalence and antifungal susceptibility of Wickerhamomyces anomalus in a tertiary care center | |
| Habibi et al. | Evaluating the effect of a novel ionic liquid ([prolinium chloride][1-methylimidazolium 3-sulfonate]) on a candida albicans standard strain and its cytotoxicity to mammalian cells | |
| Reddy et al. | P015 A study to demonstrate heteroresistance and tolerance to azoles in Candida tropicalis | |
| CN103621513B (en) | The Triadimenol of control rice green smut and alkene oxime amine Mixed Pharmacy | |
| GÜMRÜKÇÜOĞLU | ANTIFUNGAL COMPOUNDS |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |