Use of tannic acid in the preparation of a medicament for inhibiting candida glabrata and treating associated diseases

Abstract

The application provides application of tannic acid in preparation of medicines for inhibiting Candida glabrata and treating related diseases. The application verifies that the tannic acid has certain bacteriostatic effect on the Candida glabrata, inhibits adhesion of the Candida glabrata, and provides a strategy for treating the Candida glabrata related diseases.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, specifically to the application of tannic acid in the preparation of drugs for inhibiting Candida glabrata and treating related diseases. Background Technology

[0002] Tannic acid (TA), also known as tannic acid, has the CAS number 1401-55-4 and the molecular formula C. 76 H 52 O 46 Tannic acid, also known as tannin, is mainly isolated from gallnut. Modern pharmacological studies have shown that gallnut has broad-spectrum antibacterial, anti-inflammatory, detoxifying, hemostatic, and astringent effects. Traditional Chinese medicine records that the main active ingredient in gallnut is tannin, reaching up to 70% or more. It has astringent, antibacterial, and detoxifying effects and is easily hydrolyzed under the catalysis of acids, alkalis, and enzymes to produce gallic acid and polyols. Studies have shown that tannic acid has an inhibitory effect on four common bacteria associated with dental caries, and its antibacterial effect is stronger than that of gallic acid. Other studies have shown that tannic acid has a certain antibacterial effect on both Gram-positive and Gram-negative bacteria, with better effects on Gram-positive bacteria than on Gram-negative bacteria.

[0003] The infection rate of Candida glabrata (Cg) is rapidly increasing, and it has become the second leading cause of invasive fungal infections worldwide, accounting for 35%-65% of all infections, with a mortality rate as high as 30%. It readily invades cell surfaces, causing invasive lung infections, oral and vaginal diseases, and life-threatening bloodstream infections. It is characterized by a long course of illness, low immune response, and natural resistance to azole drugs.

[0004] Currently, there are no reports on the role of tannic acid in inhibiting Candida glabrata. Summary of the Invention

[0005] In order to overcome the shortcomings of the prior art, the present invention provides the application of tannic acid in the preparation of drugs for inhibiting Candida glabrata and treating related diseases.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] A first aspect of the present invention is to provide the use of tannic acid in the preparation of a reagent for inhibiting Candida glabrata, the reagent comprising tannic acid and one or more of its derivatives, hydrolysates, solvates, and hydrates as active ingredients.

[0008] A second aspect of the present invention is to provide the use of tannic acid in the preparation of a medicament for treating diseases related to Candida glabrata, the medicament comprising tannic acid and one or more of its derivatives, hydrolysates, solvates, and hydrates as active ingredients.

[0009] Furthermore, the aforementioned Candida glabrata-related diseases are selected from one or more of pneumonia, angular cheilitis, vaginitis, oral thrush, and skin diseases.

[0010] Furthermore, the aforementioned drugs also include pharmaceutically acceptable carriers or excipients.

[0011] Furthermore, the dosage forms of the above-mentioned drugs are tablets, orally disintegrating tablets, sustained-release tablets, granules, capsules, lyophilized powder for injection, pills, suspensions, syrups, emulsions, or injections.

[0012] A third aspect of the present invention is to provide a medicament for inhibiting Candida glabrata and / or treating Candida glabrata-related diseases, comprising tannic acid and one or more of its derivatives, hydrolysates, solvates, and hydrates.

[0013] Furthermore, the aforementioned Candida glabrata-related diseases are selected from one or more of pneumonia, angular cheilitis, vaginitis, oral thrush, and skin diseases.

[0014] Furthermore, the aforementioned drugs also include pharmaceutically acceptable carriers or excipients.

[0015] Furthermore, the dosage forms of the above-mentioned drugs are tablets, orally disintegrating tablets, sustained-release tablets, granules, capsules, lyophilized powder for injection, pills, suspensions, syrups, emulsions, or injections.

[0016] The present invention adopts the above technical solution and has the following technical effects compared with the prior art:

[0017] This invention verifies that tannic acid has a certain antibacterial effect on Candida glabrata and inhibits the adhesion of Candida glabrata, providing a strategy for treating Candida glabrata-related diseases. Attached Figure Description

[0018] Figure 1 The adhesion rate of tannic acid to Candida glabrata after 4 hours of incubation is shown (* indicates statistical significance).

[0019] Figure 2 The effect of tannic acid on the expression of adhesion-related genes in Candida glabrata was shown (** indicates statistical difference). Detailed Implementation

[0020] The present invention will now be described in detail with reference to specific embodiments and accompanying drawings to enable a better understanding of the invention. However, the following embodiments do not limit the scope of the invention.

[0021] Unless otherwise specified, the methods used in the embodiments are conventional methods, and the reagents used are commercially available reagents or reagents prepared according to conventional methods, unless otherwise specified.

[0022] Example 1

[0023] This embodiment studies the inhibitory effect of tannic acid on Candida glabrata. The specific experimental steps and results are as follows:

[0024] 1. The antibacterial effect was observed by the checkerboard dilution method. The concentration of Candida glabrata bacterial suspension was 0.5 McFarland (MCF), and the final concentration was obtained by diluting it with RPMI broth culture medium at a ratio of 1:1000. Preparation of tannic acid drug concentration: Weigh 100mg of tannic acid powder, add 1ml of ddH2O, and dilute with RPMI broth to a concentration of 32μg / mL. Serial dilutions yielded concentrations of 16μg / mL, 8μg / mL, 4μg / mL, 2μg / mL, 1μg / mL, 0.5μg / mL, 0.25μg / mL, 0.125μg / mL, and 0.0625μg / mL. Preparation of fluconazole (FLC) concentration: Add 20mL of sterile distilled water to 100mg of fluconazole powder, and dilute with RPMI broth to a concentration of 1024μg / mL. Serial dilutions yielded concentrations of 512μg / mL, 256μg / mL, 128μg / mL, 64μg / mL, 32μg / mL, 16μg / mL, 8μg / mL, 4μg / mL, and 2μg / mL. Using a power pipette, the solution was spread across 96-well plates. 100 μl of diluted bacterial suspension was added to each well. Tannic acid solution was added in ascending order of concentration to columns 2-11 of the 96-well plate. An equal volume of RPMI culture medium was added to column 1. Fluconazole was added to the 96-well plate in the same manner as a positive control. The plates were incubated at 37°C for 24 hours. The inhibitory concentration of the drug was determined by the wells showing 80% inhibition. Fluconazole was used as a positive control. The results showed that tannic acid has a certain inhibitory effect on Candida glabrata, especially against drug-resistant strains. The minimum inhibitory concentration (MIC) was 2 μg / ml, while the MIC for FLC was 256 μg / ml.

[0025] 2. Adhesion of *Candida glabrata* is the first step in the colonization and development of virulence, and is an important virulence factor. Therefore, the XTT method was used to study whether tannic acid affects the adhesion of *Candida glabrata*. The drug (fluconazole 64 μg / mL or tannic acid 2 μg / mL) was applied at 37℃, and 1×10... 6 The bacterial culture was co-cultured for 4 hours, the supernatant was discarded, and the culture was washed with PBS. XTT was then added and incubated at 37°C in the dark for 2 hours. The absorbance value (A) was measured at OD 490 nm. It was found that the adhesion rate of tannic acid decreased by 22% compared to the control group, while the adhesion rate of FLC was 100%, and the difference was statistically significant (P<0.05). Figure 1 Furthermore, the molecular mechanism of adhesion was investigated using RT-PCR, revealing that tannic acid can reduce the expression of adhesin genes EPA1, EPA6, and PDR1, with statistically significant differences (P<0.05). Figure 2 ).

[0026] The specific embodiments of the present invention have been described in detail above, but they are only examples, and the present invention is not limited to the specific embodiments described above. For those skilled in the art, any equivalent modifications and substitutions to the present invention are also within the scope of the present invention. Therefore, all equivalent changes and modifications made without departing from the spirit and scope of the present invention should be covered within the scope of the present invention.

Claims

1. The application of tannic acid as the sole active ingredient in the preparation of drugs for treating Candida glabrata-related diseases, characterized in that, The diseases mentioned are angular cheilitis, vaginitis, and oral thrush caused by Candida glabrata; the drugs also include pharmaceutically acceptable carriers; the dosage forms of the drugs are tablets, granules, capsules, pills, syrups, and injections.

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