CN116785304A - Application of kriborow combined azole antifungal medicine in preparation of drug-resistant candida albicans medicine - Google Patents
Application of kriborow combined azole antifungal medicine in preparation of drug-resistant candida albicans medicine Download PDFInfo
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- 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
- A61K31/69—Boron compounds
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- 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
- A61K31/4196—1,2,4-Triazoles
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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Abstract
The invention discloses an application of a kriborow combined azole antifungal drug in preparing drug-resistant candida albicans drugs. The azole antifungal drug is one of fluconazole, voriconazole and itraconazole; the drug-resistant candida albicans is as follows: drug resistant candida albicans CA10, drug resistant candida albicans CA103, drug resistant candida albicans CA137, and drug resistant candida albicans CA632. Experimental data shows that the clenbuterol has a certain inhibition effect on fluconazole, voriconazole and itraconazole, and that the fluconazole and the clenbuterol Luo Lian have obvious synergistic effect on drug-resistant candida albicans, the voriconazole and the clenbuterol Luo Lian and the itraconazole and the clenbuterol Luo Lian.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of a kriborow combined azole antifungal medicine in preparation of an anti-drug-resistant candida albicans medicine.
Background
The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art.
Candida albicans (Candida albicans) is the most widely distributed opportunistic fungal pathogen in humans and can cause mucosal and systemic infections. In immunosuppressed and hospitalized patients, the mortality rate of blood stream infections caused by candida is as high as 40-60%. In addition to direct infection, candida colonization and infection are also believed to be associated with pathophysiological diseases such as inflammatory bowel disease, cancer, diabetes, metabolic diseases, and the like. Despite the rise in invasive candida infection caused by various non-candida albicans, candida albicans is still currently the most prominent pathogen causing invasive candida infection.
Given that fungi, like their human hosts, are eukaryotes, the number of unique molecular targets available for antifungal is very limited. At present, azole drugs are still one of the most commonly used antifungal drugs in clinic. However, long-term widespread use has led to increased resistance to azoles, making clinical control of infections more difficult. Considering the characteristics of low toxicity, wide clinical application and the like of azole drugs, and the time and labor consumption for developing new drugs, the combined use of taking common azole drug resistance paths as targets has become a hotspot of the current antifungal drug resistance research.
Crisabelole (Crisabelole) is a novel non-steroidal phosphodiesterase 4 (PDE 4) inhibitor with molecular formula C 14 H 12 BNO 3 . The product is developed by pharmaceutical company of medicine of American Anacol (currently purchased by the same pharmaceutical company as Buddha), approved by the FDA in the United states in 2016 and used for treating mild to moderate allergic dermatitis of 2 years old and above, and is a topical ointment with the trade name of sultamMing (Staquis). Clenbuterol is the first new molecular entity approved by the U.S. FDA for the treatment of atopic dermatitis in the past 15 years.
Disclosure of Invention
In order to overcome the problems, the invention provides application of the kriborow combined azole antifungal medicament in preparing an anti-drug-resistant candida albicans medicament.
In a first aspect, the invention provides application of the combined kribuprole antifungal medicament in preparing an anti-drug resistant candida albicans medicament.
In one or more embodiments, the azole antifungal drug is one of fluconazole, voriconazole, and itraconazole.
In one or more embodiments, the drug-resistant candida albicans is: drug resistant candida albicans CA10, drug resistant candida albicans CA103, drug resistant candida albicans CA137, and drug resistant candida albicans CA632.
Preferably, when the clenbuterol is combined with fluconazole to resist candida albicans CA10, the minimum inhibitory concentration of the clenbuterol is 8 mug/mL, and the minimum inhibitory concentration of the fluconazole is 2 mug/mL;
when the clenbuterol is combined with fluconazole anti-drug resistant candida albicans CA103, the minimum inhibitory concentration of the clenbuterol is 4 mug/mL, and the minimum inhibitory concentration of the fluconazole is 2 mug/mL;
when the clenbuterol is combined with fluconazole anti-drug resistant candida albicans CA137, the minimum inhibitory concentration of the clenbuterol is 8 mug/mL, and the minimum inhibitory concentration of the fluconazole is 8 mug/mL;
when the clenbuterol is combined with fluconazole anti-drug resistant candida albicans CA632, the minimum inhibitory concentration of the clenbuterol is 16 mug/mL, and the minimum inhibitory concentration of the fluconazole is 8 mug/mL.
Preferably, when the clenbuterol is combined with the voriconazole-resistant candida albicans CA10, the minimum inhibitory concentration of the clenbuterol is 8 mug/mL, and the minimum inhibitory concentration of the voriconazole is 0.0625 mug/mL;
when the clenbuterol is combined with the voriconazole and the drug-resistant candida albicans CA103, the minimum inhibitory concentration of the clenbuterol is 4 mug/mL, and the minimum inhibitory concentration of the voriconazole is 0.0625 mug/mL;
when the clenbuterol is combined with voriconazole and drug-resistant candida albicans CA137, the minimum inhibitory concentration of the clenbuterol is 16 mug/mL, and the minimum inhibitory concentration of the voriconazole is 0.0625 mug/mL;
when the clenbuterol is combined with the voriconazole-resistant candida albicans CA632, the minimum inhibitory concentration of the clenbuterol is 16 mug/mL, and the minimum inhibitory concentration of the voriconazole is 0.125 mug/mL.
Preferably, when the clenbuterol is combined with the itraconazole drug-resistant candida albicans CA10, the minimum inhibitory concentration of the clenbuterol is 8 mug/mL, and the minimum inhibitory concentration of the itraconazole is 0.125 mug/mL;
when the clenbuterol is combined with the itraconazole anti-drug resistant candida albicans CA103, the minimum inhibitory concentration of the clenbuterol is 8 mug/mL, and the minimum inhibitory concentration of the itraconazole is 0.25 mug/mL;
when the clenbuterol is combined with the itraconazole anti-drug resistant candida albicans CA137, the minimum inhibitory concentration of the clenbuterol is 16 mug/mL, and the minimum inhibitory concentration of the itraconazole is 0.25 mug/mL;
when the clenbuterol is combined with the itraconazole drug-resistant candida albicans CA632, the minimum inhibitory concentration of the clenbuterol is 16 mug/mL, and the minimum inhibitory concentration of the itraconazole is 0.5 mug/mL.
In a second aspect of the invention, there is provided a medicament against drug-resistant candida albicans, the medicament comprising clenbuterol and an azole antifungal.
In one or more embodiments, the azole antifungal drug is one of fluconazole, voriconazole, and itraconazole.
In one or more embodiments, the drug-resistant candida albicans is: drug resistant candida albicans CA10, drug resistant candida albicans CA103, drug resistant candida albicans CA137, and drug resistant candida albicans CA632.
In a third aspect of the invention, a pharmaceutical formulation is provided, comprising the above drug-resistant candida albicans medicament and a medical carrier or adjuvant.
The pharmaceutical carrier or adjuvant comprises one or more pharmaceutically or food acceptable diluents, wetting agents, binders, disintegrants, lubricants, conditioning agents and other adjuvants.
The dosage forms of the pharmaceutical preparation are tablets, pills, sprays, capsules, granules, oral liquid, powder, syrup, injection, spray, suppositories and the like.
(1) For drug-resistant candida albicans CA10, CA103, CA137 and CA632, if the minimum inhibitory concentration of fluconazole is more than 512 mug/mL, the minimum inhibitory concentration of the clenbuterol is 32-64 mug/mL, which indicates that the clenbuterol alone has a certain inhibition effect on the strains. When the clenbuterol and the fluconazole are combined, the FICI values are less than or equal to 0.5, which proves that the fluconazole and the clenbuterol Luo Lian have obvious synergistic effect when being used by drug-resistant candida albicans.
(2) For drug-resistant candida albicans CA10, CA103, CA137 and CA632, if the minimum inhibitory concentration of voriconazole is 256-512 mug/mL and the minimum inhibitory concentration of the clenbuterol is 32-64 mug/mL, the single use of the clenbuterol has a certain inhibition effect on the strains. When the voriconazole and the voriconazole are combined, the FICI values are all less than or equal to 0.5, which proves that the voriconazole and the voriconazole Luo Lian have obvious synergistic effect with the drug-resistant candida albicans.
(3) For drug-resistant candida albicans CA10, CA103, CA137 and CA632, if the minimum inhibitory concentration of itraconazole is more than 512 mug/mL, the minimum inhibitory concentration of the clenbuterol is 32-64 mug/mL, which indicates that the clenbuterol alone has a certain inhibition effect on the strains. When the clenbuterol and the fluconazole are combined, the FICI values are less than or equal to 0.5, which proves that the fluconazole and the clenbuterol Luo Lian have obvious synergistic effect when being used by drug-resistant candida albicans.
Detailed Description
It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the invention. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the present invention. As used herein, the singular is also intended to include the plural unless the context clearly indicates otherwise, and furthermore, it is to be understood that the terms "comprises" and/or "comprising" when used in this specification are taken to specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof.
In order to enable those skilled in the art to more clearly understand the technical scheme of the present invention, the technical scheme of the present invention will be described in detail with reference to specific embodiments.
Example 1
1. The following examples used test materials and characterization patterns as follows:
drug resistant candida albicans (CA 10, CA103, CA137, CA 632) were offered (identified) by the university of eastern shan;
the quality control strain is candida albicans ATCC10231;
yeast extract peptone glucose medium (Qingdao sea Bo Biol.Co., ltd., batch number: 20220927);
RPMI1640 medium (Semer Feier technologies Co., ltd., lot number: 2465381);
keliborow (Shanghai Yuan leaf Biotechnology Co., ltd., lot number: S02GS 159582);
voriconazole (Shanghai Ala Biochemical technologies Co., ltd.; lot number: V129745);
itraconazole (Shanghai Ala Biochemical technologies Co., ltd., lot number: I129771);
fluconazole (Dalian Mei Lun Biotechnology Co., ltd.; batch number: MB 1288);
an electrothermal incubator (eastern European Lebo instruments Co., ltd.);
pipettes (Ai Bende, germany);
microplate reader (berteng, usa).
Preparing a bacterial suspension: resuscitates fungus strain frozen at-80deg.C for 24 hr. After 3 consecutive resuscitations, single colonies on the plates were picked and inoculated to yeast extract peptoneGlucose culture medium, shake-incubated at 35deg.C for 16h, diluted with sterile physiological saline, and adjusted to 1×10 with standard Maillard turbidimeter tube 5 CFU/mL, followed by adjusting the concentration of the bacterial suspension to 2X 10 with RPMI1640 medium 3 CFU/mL。
Preparing a medicine stock solution:
fluconazole stock solution: 20.48mg of fluconazole powder and 1mL of dimethyl sulfoxide are placed in a sterile EP tube, and a fluconazole mother solution with the concentration of 20480 mu g/mL is obtained as A drug.
Voriconazole stock solution: 20.48mg of voriconazole and 1mL of dimethyl sulfoxide are placed in a sterile EP tube to obtain a fluconazole mother solution with the concentration of 20480 mu g/mL, which is A medicine B.
Itraconazole stock solution: itraconazole 20.48mg and dimethyl sulfoxide 1mL were placed in a sterile EP tube to obtain a fluconazole mother liquor with a concentration of 20480. Mu.g/mL as A-drug C.
gram-Libo Luo Zhubei liquid: gram-B Luo Fenmo 25.6.6 mg and 2.5mL of dimethyl sulfoxide are placed in a sterile EP tube to obtain gram-B Luo Muye with the concentration of 10240 mug/mL as a drug B.
2. Determination of drug action
The following experimental procedure was performed according to the guidelines of the American society for clinical and laboratory standards (Clinical and Laboratory Standards Institute M27-Ed 4). All experiments were performed in triplicate.
MIC for fluconazole, voriconazole and itraconazole alone: 200. Mu.L of the bacterial liquid (2X 10) was added to each well of the first column of the 96-well plate 3 CFU/mL), 100 μl of the same bacterial liquid was added to each of the remaining seven columns. A maximum drug concentration of 512 μg/mL was then added to each well of the first column, respectively. The sampling method adopts a double dilution method, namely 100 mu L of the medicine is taken out from a first hole of each row, added into a second hole for blowing and mixing, 100 mu L of the medicine is taken out and added into a third hole for fully mixing, and the medicine is taken out and discarded after the last and last holes are mixed uniformly, so that a series of medicine concentration gradients (512, 256, 128, 64, 32, 16,8 mu g/mL) are obtained and negative control is included. Standing the sealed 96-well plate in a 35 ℃ incubator for 24 hours, taking the lowest concentration without fungi growth as the lowest antibacterial concentration, and recording fluconazole,MIC values for voriconazole and itraconazole alone.
MIC for clenbuterol: 200. Mu.L of the bacterial liquid (2X 10) was added to each well of the first column of the 96-well plate 3 CFU/mL), 100 μl of the same bacterial liquid was added to each of the remaining seven columns. A maximum drug concentration of 512 μg/mL was then added to each well of the first column, respectively. The sampling was done by double dilution, i.e., 100 μl was removed from the first well of each row and added to the second well for blow mixing, 100 μl was removed and added to the third well for thorough mixing, and so on until 100 μl was removed after the last but one well was mixed, to obtain a series of drug concentration gradients (512, 256, 128, 64, 32, 16,8 μg/mL) and contained negative controls. The sealed 96-well plate is kept stand in a 35 ℃ incubator for 24 hours, and the minimum concentration without fungi growth is taken as the minimum inhibitory concentration, and MIC value for the clenbuterol is recorded.
MIC of fluconazole in combination with clenbuterol: 50 mu L of fluconazole solution with different working concentrations are respectively sucked by a pipette from low concentration to high concentration (64, 32, 16,8,4,2,1,0.5,0.25,0.125 mu g/mL), and are respectively added to the 2 nd column to the 11 th column of the 96-well plate from left to right; 50 mu L of the different concentrations of the clibrole solution are respectively sucked from low concentration to high concentration (64, 32, 16,8,4,2,1 mu G/mL) by a pipette, and are respectively added to the G line to the A line of the 96-well plate from bottom to top; after column 1 and row H were filled to 100. Mu.L with medium, the medium was pipetted to a concentration of 2 Xl 0 3 100. Mu.L of CFU/mL of the bacterial liquid was added to each well of columns 1 to 11, and column 12 was supplemented with 200. Mu.L of the medium. After the 96-well plate is placed in a 35 ℃ incubator for culturing for 24 hours, the minimum concentration without fungi growth is taken as the minimum inhibitory concentration, and MIC values of the two drugs used in combination at the time of the optimal combined effect are selected and recorded.
MIC of voriconazole in combination with clenbuterol: 50 mu L of voriconazole solution with different working concentrations are respectively sucked from low concentration to high concentration (64, 32, 16,8,4,2,1,0.5,0.25,0.125 mu g/mL) by a pipette, and are respectively added to the 2 nd column to the 11 th column of a 96-well plate from left to right; 50. Mu.L of the solution of the different concentrations of the cliorole is respectively sucked from low concentration to high concentration (64, 32, 16,8,4,2, 1. Mu.g/mL) by a pipette, and added from bottom to topG to A lines into 96-well plates; after column 1 and row H were filled to 100. Mu.L with medium, the medium was pipetted to a concentration of 2 Xl 0 3 100. Mu.L of CFU/mL of the bacterial liquid was added to each well of columns 1 to 11, and column 12 was supplemented with 200. Mu.L of the medium. After the 96-well plate is placed in a 35 ℃ incubator for culturing for 24 hours, the minimum concentration without fungi growth is taken as the minimum inhibitory concentration, and the MIC of the two drugs used in combination at the optimal combined effect is selected and recorded.
MIC of itraconazole in combination with clenbuterol: 50 mu L of itraconazole solution with different working concentrations are respectively sucked from low concentration to high concentration (64, 32, 16,8,4,2,1,0.5,0.25,0.125 mu g/mL) by a pipette, and are respectively added to the 2 nd column to the 11 th column of a 96-well plate from left to right; 50 mu L of the different concentrations of the clibrole solution are respectively sucked from low concentration to high concentration (64, 32, 16,8,4,2,1 mu G/mL) by a pipette, and are respectively added to the G line to the A line of the 96-well plate from bottom to top; after column 1 and row H were filled to 100. Mu.L with medium, the medium was pipetted to a concentration of 2 Xl 0 3 100. Mu.L of CFU/mL of the bacterial liquid was added to each well of columns 1 to 11, and column 12 was supplemented with 200. Mu.L of the medium. After the 96-well plate is placed in a 35 ℃ incubator for culturing for 24 hours, the minimum concentration without fungi growth is taken as the minimum inhibitory concentration, and the MIC of the two drugs used in combination at the optimal combined effect is selected and recorded.
3. Evaluation of synergy
The antibacterial drug combination can show four effects of irrelevant, additive, synergistic and antagonistic in vitro or in animal body, and for the combination of different drugs, the toxicity is likely to be increased or the antagonistic effect is likely to occur due to the fact that the action mechanism and the action mode of the drugs are different, and the generation of the induced inactivating enzyme or the competition of the same target position is likely to occur; moreover, the same kind of drugs do not necessarily have the same effect, such as cephalosporins, first-generation cephalosporins are mainly resistant to gram-positive bacteria, third-generation cephalosporins and fourth-generation cephalosporins are mainly resistant to gram-negative bacteria, and only part of third-generation cephalosporins and fourth-generation cephalosporins have the effect of resisting pseudomonas aeruginosa, so that the combined use of the drugs has great unpredictability on the combined use of the drugs.
Combined useThe drug sensitivity test results are used for judging the interaction of the two drugs after combination by the following indexes. Fici=mic Medicine combination /MIC Single use of first-aid medicine +MIC Medicine B combination /MIC Medicine B singly used The method comprises the steps of carrying out a first treatment on the surface of the FICI less than or equal to 0.5 is synergistic, FICI less than or equal to 0.5 is additive, FICI less than or equal to 2 is irrelevant, and FICI > 2 is antagonistic.
4. Experimental results:
TABLE 1 synergistic effect of combination of clenbuterol and fluconazole against drug resistant Candida albicans
TABLE 2 synergistic effects of voriconazole-combined drug-resistant Candida albicans
TABLE 3 synergistic effects of Criborow in combination with itraconazole against drug resistant Candida albicans
For the drug-resistant candida albicans CA10, CA103, CA137 and CA632, if the minimum inhibitory concentration of the single use of fluconazole is more than 512 mug/mL, the minimum inhibitory concentration of the single use of the clenbuterol is 32-64 mug/mL, which proves that the single use of the clenbuterol has a certain inhibition effect on the strains. When the clenbuterol and the fluconazole are combined, the FICI values are less than or equal to 0.5, which proves that the fluconazole and the clenbuterol Luo Lian have obvious synergistic effect when being used by drug-resistant candida albicans.
For drug-resistant candida albicans CA10, CA103, CA137 and CA632, if the minimum inhibitory concentration of voriconazole is 256-512 mug/mL and the minimum inhibitory concentration of the clenbuterol is 32-64 mug/mL, the single use of the clenbuterol has a certain inhibition effect on the strains. When the voriconazole and the voriconazole are combined, the FICI values are all less than or equal to 0.5, which proves that the voriconazole and the voriconazole Luo Lian have obvious synergistic effect with the drug-resistant candida albicans.
For drug-resistant candida albicans CA10, CA103, CA137 and CA632, if the minimum inhibitory concentration of itraconazole is more than 512 mug/mL, the minimum inhibitory concentration of the clenbuterol is 32-64 mug/mL, which indicates that the clenbuterol alone has a certain inhibition effect on the strains. When the clenbuterol and the itraconazole are combined, the FICI values are less than or equal to 0.5, which proves that the itraconazole and the clenbuterol Luo Lian have obvious synergistic effect when being used by the drug-resistant candida albicans.
Claims (10)
1. The application of the kriborow combined azole antifungal medicine in preparing drug-resistant candida albicans medicines.
2. The use according to claim 1, wherein the azole antifungal is one of fluconazole, voriconazole and itraconazole.
3. The use according to claim 2, wherein the drug-resistant candida albicans is: drug resistant candida albicans CA10, drug resistant candida albicans CA103, drug resistant candida albicans CA137, and drug resistant candida albicans CA632.
4. The use according to claim 3, wherein the minimum inhibitory concentration of clenbuterol is 8 μg/mL and the minimum inhibitory concentration of fluconazole is 2 μg/mL when clenbuterol is combined with fluconazole resistant candida albicans CA 10;
when the clenbuterol is combined with fluconazole anti-drug resistant candida albicans CA103, the minimum inhibitory concentration of the clenbuterol is 4 mug/mL, and the minimum inhibitory concentration of the fluconazole is 2 mug/mL;
when the clenbuterol is combined with fluconazole anti-drug resistant candida albicans CA137, the minimum inhibitory concentration of the clenbuterol is 8 mug/mL, and the minimum inhibitory concentration of the fluconazole is 8 mug/mL;
when the clenbuterol is combined with fluconazole anti-drug resistant candida albicans CA632, the minimum inhibitory concentration of the clenbuterol is 16 mug/mL, and the minimum inhibitory concentration of the fluconazole is 8 mug/mL.
5. The use according to claim 3, wherein the minimum inhibitory concentration of clenbuterol is 8 μg/mL and the minimum inhibitory concentration of voriconazole is 0.0625 μg/mL when clenbuterol is combined with voriconazole-resistant candida albicans CA 10;
when the clenbuterol is combined with the voriconazole and the drug-resistant candida albicans CA103, the minimum inhibitory concentration of the clenbuterol is 4 mug/mL, and the minimum inhibitory concentration of the voriconazole is 0.0625 mug/mL;
when the clenbuterol is combined with voriconazole and drug-resistant candida albicans CA137, the minimum inhibitory concentration of the clenbuterol is 16 mug/mL, and the minimum inhibitory concentration of the voriconazole is 0.0625 mug/mL;
when the clenbuterol is combined with the voriconazole-resistant candida albicans CA632, the minimum inhibitory concentration of the clenbuterol is 16 mug/mL, and the minimum inhibitory concentration of the voriconazole is 0.125 mug/mL.
6. The use according to claim 3, wherein the minimum inhibitory concentration of clenbuterol is 8 μg/mL and the minimum inhibitory concentration of itraconazole is 0.125 μg/mL when clenbuterol is combined with itraconazole resistant candida albicans CA 10;
when the clenbuterol is combined with the itraconazole anti-drug resistant candida albicans CA103, the minimum inhibitory concentration of the clenbuterol is 8 mug/mL, and the minimum inhibitory concentration of the itraconazole is 0.25 mug/mL;
when the clenbuterol is combined with the itraconazole anti-drug resistant candida albicans CA137, the minimum inhibitory concentration of the clenbuterol is 16 mug/mL, and the minimum inhibitory concentration of the itraconazole is 0.25 mug/mL;
when the clenbuterol is combined with the itraconazole drug-resistant candida albicans CA632, the minimum inhibitory concentration of the clenbuterol is 16 mug/mL, and the minimum inhibitory concentration of the itraconazole is 0.5 mug/mL.
7. An anti-drug-resistant candida albicans medicament, which is characterized by comprising clenbuterol and azole antifungal medicaments.
8. The medicament of claim 7, wherein the azole antifungal agent is one of fluconazole, voriconazole, and itraconazole;
or, the drug-resistant candida albicans is: drug resistant candida albicans CA10, drug resistant candida albicans CA103, drug resistant candida albicans CA137, and drug resistant candida albicans CA632.
9. A pharmaceutical formulation comprising the drug-resistant candida albicans resistant formulation of claim 8 and a medical carrier or adjuvant.
10. The pharmaceutical formulation of claim 9, wherein the pharmaceutically acceptable carrier or adjuvant comprises one or more pharmaceutically or food acceptable diluents, wetting agents, binders, disintegrants, lubricants, conditioning agents and other adjuvants;
or the dosage forms of the pharmaceutical preparation are tablets, pills, sprays, capsules, granules, oral liquid, powder, syrup, injection, spray and suppositories.
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