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WO2021180250A1 - Préparation pour inhiber le candida albicans - Google Patents

Préparation pour inhiber le candida albicans Download PDF

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Publication number
WO2021180250A1
WO2021180250A1 PCT/CN2021/088996 CN2021088996W WO2021180250A1 WO 2021180250 A1 WO2021180250 A1 WO 2021180250A1 CN 2021088996 W CN2021088996 W CN 2021088996W WO 2021180250 A1 WO2021180250 A1 WO 2021180250A1
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candida albicans
saα2
sugar chain
chain structure
preparation
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Chinese (zh)
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李铮
王艳
王喜龙
马恬然
于汉杰
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Northwest University
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Northwest University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/20—Milk; Whey; Colostrum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A61K38/1741—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals alpha-Glycoproteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • A61P31/10—Antimycotics
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • This application relates to a preparation for inhibiting Candida albicans.
  • Candida albicans also known as Candida albicans, is the most common conditional pathogenic fungus. It mainly exists in the human respiratory tract, oral cavity and epidermis. It will not cause disease under normal conditions, but when the body’s immune function is low, it will cause disease, which will threaten the body’s mucous membranes, tissues, skin and other organs, causing different Candida albicans disease can cause infections of organs such as the oral cavity in mild cases, and systemic candida disease in humans in severe cases.
  • Candida albicans mainly grows as a single cell, and Gram staining is positive, but the staining is not very uniform.
  • Candida albicans causes disease due to its ability to adapt to the environment and many virulence factors that cause different degrees of infection to the host. Its ability to adapt to the environment includes the ability to take in nutrients from the surrounding environment, flexible anti-stress response, and rapid adaptation to changes in the environment.
  • Its virulence factors mainly include extracellular hydrolase, morphological transformation and surface adhesin. After Candida albicans adhere to host cells, hyphae grow and secrete a variety of enzymes, such as hydrolases, proteases, and lipases. The hydrolases secreted can help Candida albicans extract nutrients from the external environment.
  • SAP extracellular aspartase
  • Candida albicans is a single-celled fungus that grows in an elliptical and oval shape and can form bud tubes. Under normal circumstances, Candida albicans exists in three forms: spores, pseudohyphae and fungal filaments. The fungal filaments are parallel and straight hyphae, and pseudohyphae are a long string of yeast cells, and the cells are not separated from each other. , Pseudohyphae easily form a branched state, so it is easy to absorb nutrients from the outside world. The hyphae of Candida albicans can cause tissue infections. Its phenotypic transformation means that its pathogenicity is gradually increasing.
  • the phenotype transformation speed is closely related to the pathogenic ability, and the formed hyphae can help It escapes the attack of immune cells and is therefore more pathogenic.
  • Studies have shown that when Candida albicans turns from white to gray (Opaque), it can avoid host cell invasion and cause infection. Experiments have shown that the hyphae of Candida albicans are more pathogenic than normal spores. . Some researchers have also proved that the morphological transformation of Candida albicans can avoid the phagocytosis of host cells, which in turn causes host cell infection. It can be seen that Candida albicans flexibly changes between multiple forms, which not only helps it quickly adapt to changes in the surrounding environment, but also lays the foundation for infecting host cells and coexisting with the host.
  • the surface of eukaryotic yeast cells has the characteristics of adhesion, mainly because the surface of yeast cells carries different kinds of adhesin, which can adhere to different substrates, and produce different adhesin according to the substrate, which provides survival for fungi to adapt to the environment.
  • the adhesion of Candida albicans to the host means the occurrence of infection. After the host cell is adhered, the bacteria will form hyphae, thereby exerting a pathogenic effect. If Candida albicans cannot form hyphae, its pathogenicity will be Significantly weakened.
  • T2DM type 2 diabetes
  • sugar chains are constantly being recognized, such as glycoprotein sugar chains, proteoglycans, glycolipid sugar chains and sugar binding proteins, which participate in many important life activities, and are also related to Many diseases, such as cancer, bacterial and viral infections, are closely related.
  • the main purpose of this application is to study a preparation that can effectively inhibit Candida albicans.
  • the active ingredient with sialic acid (SA) ⁇ 2-3Gal sugar chain structure has an inhibitory effect on Candida albicans. As the concentration of sialic acid glycoprotein increases, it has The inhibitory effect of Candida growth was significantly enhanced.
  • a preparation for inhibiting Candida albicans the active ingredient of which contains SA ⁇ 2-3Gal sugar chain structure (especially a glycoprotein rich in SA ⁇ 2-3Gal sugar chain structure).
  • the preparation can directly act on the skin surface, oral cavity and other parts with potential for the growth of Candida albicans.
  • the type of formulation is spray or film coating.
  • the SA ⁇ 2-3Gal sugar chain structure is derived from milk.
  • the active ingredient to which the SA ⁇ 2-3Gal sugar chain structure belongs is a glycoprotein enriched in the SA ⁇ 2-3Gal sugar chain structure separated and purified from milk.
  • the glycoprotein rich in SA ⁇ 2-3Gal sugar chain structure is obtained by separating and purifying from milk based on the lectin MAL-II-magnetic particle complex or serotonin-magnetic particle complex.
  • the use of the active ingredient having the sugar chain structure of SA ⁇ 2-3Gal in the preparation of a preparation for inhibiting Candida albicans is not limited.
  • the active ingredient with SA ⁇ 2-3Gal sugar chain structure is a glycoprotein enriched in SA ⁇ 2-3Gal sugar chain structure separated and purified from milk.
  • the active ingredient with the SA ⁇ 2-3Gal sugar chain structure is a sugar chain structure rich in SA ⁇ 2-3Gal based on the lectin MAL-II-magnetic particle complex or serotonin-magnetic particle complex separated and purified from milk. Glycoprotein.
  • the milk extract is used in the preparation of a preparation for inhibiting Candida albicans.
  • the milk extract is a glycoprotein rich in SA ⁇ 2-3Gal sugar chain structure obtained by separation and purification.
  • Figure 1 shows the results of Candida albicans culture. Among them, (a) culture until a milky white round colony grows, (b) transfer to an agar plate, and after the streaked bacteria liquid has dried out, continue to cultivate until a milky white colony grows.
  • Figure 2 shows the results of CAL-27 cell culture (40 ⁇ ).
  • Figure 3 shows the effects of different substances on the growth curve of Candida albicans. Among them, (a) the influence of different concentrations of sialoglycoprotein A on the growth curve of Candida albicans; (b) the influence of different control proteins on the growth curve of Candida albicans: the control group and the same concentration (400 ⁇ g/mL) saliva Acid monomer, BSA, asialoprotein B1 (NaIO 4 oxidation), asialoprotein (sialidase) C1, sialoglycoprotein A.
  • saliva Acid monomer BSA, asialoprotein B1 (NaIO 4 oxidation), asialoprotein (sialidase) C1, sialoglycoprotein A.
  • Figure 4 shows the experimental results of the effect of sialylated glycoprotein on the adhesion of Candida albicans.
  • Merge stands for superimposed field
  • DAPI stands for fluorescence field
  • Bright stands for bright field. The blue ones are DAPI channels.
  • Figure 5 shows the statistical results of the effect of sialylated glycoprotein on the adhesion of Candida albicans.
  • Extraction method 1 Based on serotonin-magnetic particle complex, separate and purify the glycoprotein rich in sialylation from the material rich in sialic acid sugar chain structure.
  • This sialylated glycoprotein contains SA ⁇ 2-3Gal and SA ⁇ 2-6Gal sugar chain structures.
  • Chinese patent document Serotonin-magnetic particle complex and method for enriching sialylated glycoprotein, application number: 201711206127.9.
  • Extraction method 2 Lectin MAL-II and SNA-magnetic particle complexes were separated and purified to separate and purify glycoproteins rich in SA ⁇ 2-3Gal sugar chain structures and glycoproteins rich in SA ⁇ 2-6Gal sugar chain structures.
  • Chinese patent document Lizenges for the prevention of influenza virus, application number: 201610654636.7.
  • one extract is obtained from the milk, divided into 3 parts, and denoted as A, B, and C respectively.
  • the terminal SA of the 3Gal sugar chain structure retains its SA ⁇ 2-6Gal sugar chain structure, and is then denoted as C1.
  • Candida albicans (Candida albicans ATCC 10231), purchased from China Medical Culture Collection.
  • the CAL-27 (human tongue squamous cell carcinoma) cell line was cultured in DMEM containing 10% fetal bovine serum, 1% penicillin-streptomycin double antibody solution, and placed in a 5% CO 2 , 37°C constant temperature incubator. Cultivate until the cells grow to the logarithmic phase.
  • YMA medium and liquid Sabouraud medium were prepared according to standard formulas and sterilized at 115°C for 20 minutes, and stored at 4°C for later use.
  • 10 ⁇ PBS buffer 0.1mol/L Na 2 HPO 4 , 1.37mol/L NaCl, 0.027mol/L KCl, 0.0176mol/L KH 2 PO 4 dissolved in ultrapure water, adjust the pH to 7.4, Store at room temperature, dilute to 1 ⁇ PBS when used.
  • BSA (0.8mg/mL): Weigh 0.8mg of BSA and dissolve it in 1mL of ultrapure water. After it is completely dissolved, store it at -20°C for use.
  • DAPI Dissolve 2 ⁇ l DAPI in 10mL sterile 1 ⁇ PBS buffer (1:5000) and store at 4°C in the dark.
  • CAL-27 cells are human oral squamous cell carcinoma cells. Under the microscope, the cells are flat and polygonal, arranged relatively tightly, and are paving stones ( Figure 2). It was cultured in high-sugar DMEM medium containing 10% fetal bovine serum and 1% penicillin-streptomycin double antibody solution, and placed in a constant temperature cell incubator with 5% CO 2 and 37°C.
  • Change the medium firstly pour out the old culture medium in the culture flask gently, rinse 2-3 times with sterile 1 ⁇ PBS to wash off the excess medium, then add fresh culture medium, gently shake the culture flask, and put it in Incubator, take log phase cells for follow-up experiments.
  • the cells Before the adhesion experiment, the cells must be hungry culture. Serum-free culture can make the cells hungry. After adding the sialic acid protein, it can be better absorbed, which will help the protein to play its role.
  • the cells used in this experiment need to be cultured in a 3.5cm cell culture dish.
  • the cells in the culture flask grow to the logarithmic phase, use the same method as above to digest the cells, add fresh medium and blow evenly to ensure When the cells are in suspension, add 200 ⁇ l to the cell culture dish, make up the volume to 990 ⁇ l with high-sugar DMEM medium, and culture for 24h under the same conditions as above.
  • After the cells adhere to the wall slowly aspirate the old medium and replace it with Serum-free DMEM medium, shake gently, continue to culture at 37°C in a 5% CO 2 incubator, and take log phase cells for subsequent experiments.
  • the concentration of sialylated glycoprotein was determined by Nano-drop to be 0.8 mg/mL, and the sterile glycoprotein solution was obtained after filtration with a 0.22 ⁇ m filter membrane, which was stored at -20°C for later use. Adjust the concentration of the BSA and asialoprotein solution to 0.8 mg/mL, and set aside at -20°C.
  • the CO 2 produced by Candida albicans is discharged through the space around the plate during the culture process.
  • the water vapor in the plate will also be taken out of the plate. This will cause the volume in the edge of the 96-well plate to decrease. Therefore, we should pay attention to several points during the above experiment: first add 200 ⁇ l of sterile water or PBS to the wells near the edge of the 96-well plate to avoid the rapid evaporation of the liquid in the experimental wells resulting in protein concentration during the shaking of the 96-well plate. Or the high concentration of the culture medium will affect the measurement results.
  • Sialyl glycoprotein inhibits the adhesion of Candida albicans to CAL-27 cells
  • Candida albicans For the growth curve of Candida albicans, various characteristics are generally selected at the end of the logarithmic growth phase and the beginning of the stable phase, because the bacteria at this stage are the most typical in terms of biological characteristics and metabolic activity. Therefore, in this experiment, Candida albicans was cultured to the end of the logarithmic stage, and subsequent adhesion experiments were carried out.
  • Fixation Use a pipette to slowly suck up the excess culture solution from the petri dish along the wall, add 1mL sterile PBS to rinse the excess culture solution and pour it away, then quickly add 1mL 4% paraformaldehyde solution, room temperature Reaction for 30min. In order to prevent the culture dish from drying out during this process, it must be washed quickly to prevent the cells from leaving the culture solution and deforming.
  • DAPI staining After washing is finished, aspirate the excess 1 ⁇ PBS buffer, add 200 ⁇ l of DAPI staining solution, and react for 20min in the dark at 4°C.
  • the average value and SD value of OD 595 measured in the experiment were calculated and graphed by Graphpad Prism8 software.
  • the image taken by the fluorescence microscope was adjusted with PhotoShop software to adjust the brightness and gray level, and then the Image J software was used to count the cells and bacteria.
  • the SPSS software was used for statistical analysis.
  • This experiment uses mixed culture of Candida albicans and different concentrations of sialoglycoprotein A in a 96-well plate. The absorption peak at 595nm is measured with a microplate reader every 12h. The experiment is repeated three times, and Graphpad is used according to the OD 595 value of each group. Prism8 software draws a line graph of the effect of sialic acid protein on the growth of Candida albicans ( Figure 3a).
  • the OD 595 values of the 200 ⁇ g/mL and 400 ⁇ g/mL experimental groups are almost unchanged; when the incubation time is longer than 24h, only the number of bacteria in the 400 ⁇ g/mL experimental group remains unchanged. All grow to a stable period. During the whole process, the OD 595 value of Candida albicans treated with 400 ⁇ g/mL sialic acid protein was almost unchanged. It may be that the protein concentration is too high, which has a bactericidal effect on the bacteria.
  • the OD 595 value of each group after the stable period was analyzed by variance analysis.
  • the experimental group and the control group were compared, and it was found that 50 ⁇ g/mL, 100 ⁇ g/mL, 200 ⁇ g/mL, 400 ⁇ g/mL sialoglycoprotein A was effective against Candida albicans.
  • the growth of the plant has a significant inhibitory effect (p ⁇ 0.001). From the above results, within the same time frame, as the concentration of sialylated glycoprotein increased, the OD 595 value decreased significantly, and the number of Candida albicans growth decreased, indicating that sialylated glycoprotein A has a significant effect on the growth of Candida albicans The inhibitory effect, and was concentration-dose-dependent.
  • sialoglycoprotein A within the concentration range (400 ⁇ g/mL) has a significant inhibitory effect on the growth of Candida albicans, and when the sialoglycoprotein concentration reaches 400 ⁇ g/mL, the bacterial cells hardly grow.
  • the same concentration of BSA, asialoprotein B1, glycoprotein C1 and sialic acid monomer at the end SA of the sugar chain structure of SA ⁇ 2-3Gal have weaker inhibitory effects on Candida albicans than that of sialic acid glycoprotein A, indicating that sugar The SA ⁇ 2-3 sugar chain structure of the protein plays a major role in the inhibition of Candida albicans.
  • the cells that have grown to the logarithmic phase were first co-cultured with sialylated protein and Candida albicans for 4.5 hours, and after a series of steps such as washing, fixing, and staining, Take pictures under a fluorescence microscope to get the experimental results shown in Figure 4.
  • Cells treated with different concentrations of sialic acid protein and bacterial cells were used as the experimental group, and the remaining groups were used as the control group.
  • the adhesion rates of the experimental group and the control group were statistically analyzed with the blank control group, and it was found that the adhesion effects of 50 ⁇ g/mL sialoglycoprotein A and 200 ⁇ g/mL asialoprotein (B1 and C1) on Candida albicans There was no significant effect, but 200 ⁇ g/mL, 400 ⁇ g/mL sialoglycoprotein A had a significant inhibitory effect on the adhesion of Candida albicans compared with the control group, and the difference was statistically significant (p ⁇ 0.001). At the same time, the sialoprotein A inhibition group was significantly larger than the blank control group and other protein groups.
  • glycoprotein D rich in SA ⁇ 2-3Gal sugar chain structure and glycoprotein E rich in SA ⁇ 2-6Gal sugar chain structure are separately purified from milk.
  • the Candida albicans and glycoprotein D rich in SA ⁇ 2-3Gal sugar chain structure were mixed cultured in 96-well plates, and the absorption peak at 595nm was measured with a microplate reader every 12h, and the experiment was repeated. three times.
  • the OD 595 value of Candida albicans treated with different concentrations of sialoprotein did not change significantly; when it grew to 16h, except for the increase in the OD 595 value of the blank control group, there was no significant change in the OD 595 value of each experimental group; In the range of 18h-24h, the OD 595 value of the blank control group continued to rise, and gradually reached the end of the logarithm of bacterial growth.
  • the OD 595 value of the 25 ⁇ g/mL and 50 ⁇ g/mL experimental groups also continued to increase, but both were lower than the control.
  • the OD 595 values of the 100 ⁇ g/mL and 200 ⁇ g/mL experimental groups were almost unchanged; when the culture time was longer than 24h, only the number of bacteria in the 200 ⁇ g/mL experimental group remained unchanged, and the rest of the groups grew to a stable phase.
  • the OD 595 value of Candida albicans treated with 200 ⁇ g/mL sialoprotein D was almost unchanged. It may be that the protein concentration is too high, which has a bactericidal effect on the bacteria.
  • the OD 595 values of each group were analyzed by variance analysis. Comparing the experimental group with the control group, it can be seen that 25 ⁇ g/mL, 100 ⁇ g/mL, 200 ⁇ g/mL sialoglycoprotein D has an effect on the growth of Candida albicans. Significant inhibition (p ⁇ 0.001). From the above results, in the same time frame, as the concentration of sialylated glycoprotein increased, the OD 595 value decreased significantly, and the number of Candida albicans growth decreased, indicating that the glycoprotein D pair rich in SA ⁇ 2-3Gal sugar chain structure The growth of Candida albicans has a significant inhibitory effect, and it is concentration-dose-dependent.
  • glycoprotein D which is rich in SA ⁇ 2-3Gal sugar chain structure, has a significant inhibitory effect on the growth of Candida albicans within the concentration range (200 ⁇ g/mL), and when its concentration reaches 200 ⁇ g/mL, the bacteria The body hardly grows.
  • the same concentration of glycoprotein E rich in SA ⁇ 2-6Gal sugar chain structure has an effect on the normal growth curve of Candida albicans, but there is no significant difference, indicating that the SA ⁇ 2-3 sugar chain structure of glycoprotein inhibits Candida albicans in is a main factor.
  • the cells that have grown to the logarithmic phase are co-cultured with sialylated protein and Candida albicans for 4.5h. After a series of steps such as washing, fixing, and staining, the cells treated with different concentrations of D and bacterial cells were used as the experimental group, and the remaining groups were used as the control group. With the increase of the concentration of D, the number of Candida albicans decreased, and the aggregation phenomenon between the bacteria gradually weakened. Correspondingly, the number of bacteria attached to the cell surface also decreased, while the aggregation of the other control groups did not occur.
  • glycoprotein D rich in SA ⁇ 2-3Gal sugar chain structure when glycoprotein D rich in SA ⁇ 2-3Gal sugar chain structure is in the range of 50 ⁇ g/mL ⁇ 100 ⁇ g/mL, it has a significant inhibitory effect on the adhesion of Candida albicans to CAL-27 cells, and with sialic acid
  • the increase in protein concentration the more obvious its inhibitory effect on the adhesion of Candida albicans, which is concentration-dose dependent.
  • the aggregation phenomenon of Candida albicans is also continuously weakened.
  • Candida albicans mainly infects host cells through processes such as adhesion, hyphae growth, and biofilm formation. When Candida albicans forms a biofilm on the outermost side, it can not only reduce its sensitivity to antibacterial drugs, but also avoid the host. Attacks by the immune system pose a serious threat to human health.
  • the first step for Candida albicans to infect the host is adhesion.
  • the adhesion is mainly through the combination of glycoproteins on the surface of the bacteria and glycoprotein receptors on the surface of the host cell.
  • the adherent substances mainly include mannan, adhesin and chitin. Wait.
  • Candida albicans become resistant to antifungal drugs, which can also affect human health. Therefore, the development of new non-toxic and harmless drugs to inhibit the growth and adhesion of Candida albicans has become a hot research topic at this stage.
  • Sialylglycoprotein A which is rich in SA ⁇ 2-3Gal sugar chain structure, has a significant inhibitory effect on the growth and adhesion of Candida albicans.
  • sialoglycoprotein A 400 ⁇ g/mL
  • it has a certain inhibitory effect on the growth of Candida albicans, and when the sialoglycoprotein concentration reaches 400 ⁇ g/mL, white Candida hardly grows, which can also indicate that 400 ⁇ g/mL is the bactericidal concentration of sialoglycoprotein.
  • proteins (BSA, asialoprotein, sialic acid monomer) in other control groups have no obvious inhibitory effect on the growth of Candida albicans, which further shows that the inhibitory effect of sialoglycoprotein on the growth of Candida albicans is mainly SA ⁇ 2-3 is at work.
  • Sialylglycoprotein D which is rich in SA ⁇ 2-3Gal sugar chain structure, has a significant inhibitory effect on the growth and adhesion of Candida albicans.
  • concentration of glycoprotein D rich in SA ⁇ 2-3Gal sugar chain structure is in the range of 50 ⁇ g/mL ⁇ 100 ⁇ g/mL, it has a good inhibitory effect on the growth and adhesion of Candida albicans.
  • concentration of sialoglycoprotein reached 200 ⁇ g/mL, Candida albicans hardly grew, which can also indicate that 200 ⁇ g/mL is the bactericidal concentration of glycoprotein D rich in SA ⁇ 2-3Gal sugar chain structure.
  • milk products such as pure milk
  • sprayed on the skin surface, oral cavity and other parts with potential for the growth of Candida albicans can also inhibit Candida albicans to a certain extent.

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Abstract

Une préparation pour inhiber le candida albicans est divulguée. Le principe actif de la préparation contient une structure de chaîne de sucre SA α 2-3 Gal, en particulier, une glycoprotéine riche en une structure de chaîne de sucre SA α 2-3 Gal. Le principe actif de la formulation est de préférence une glycoprotéine riche en une structure de chaîne de sucre SA α 2-3 Gal séparée du lait de vache et purifiée.
PCT/CN2021/088996 2020-03-10 2021-04-22 Préparation pour inhiber le candida albicans Ceased WO2021180250A1 (fr)

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CN111249444B (zh) * 2020-03-10 2023-04-07 西北大学 一种用于抑制白色念珠菌的制剂

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003094970A1 (fr) * 2002-04-26 2003-11-20 Dennis Reisch Compose biologique fongicide
WO2011073685A1 (fr) * 2009-12-17 2011-06-23 The Queen's University Of Belfast Modulateur
CN102192941A (zh) * 2010-03-05 2011-09-21 西北大学 一种快速评估甲型流感病毒宿主特异性的方法
WO2011158388A1 (fr) * 2010-06-16 2011-12-22 東光薬品工業株式会社 Complexe de chaîne de sucre contenant de l'acide sialique et son procédé de production, agent antigrippal et filtre
CN104144613A (zh) * 2011-12-07 2014-11-12 菲仕兰品牌有限公司 用于提供唾液酸化寡糖的方法
CN105473728A (zh) * 2013-05-31 2016-04-06 基因化学株式会社 用于制备唾液酸衍生物的方法
WO2019086613A1 (fr) * 2017-11-03 2019-05-09 Agriculture And Food Development Authority (Teagasc) Composition et utilisations associées
CN111249444A (zh) * 2020-03-10 2020-06-09 西北大学 一种用于抑制白色念珠菌的制剂

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7863020B2 (en) * 2000-06-28 2011-01-04 Glycofi, Inc. Production of sialylated N-glycans in lower eukaryotes
US7238677B2 (en) * 2003-03-28 2007-07-03 Kimberly-Clark Worldwide, Inc. Prevention of urogenital infections
CA2588871A1 (fr) * 2004-12-02 2006-07-13 Csir Proteine de recombinaison gram-positives pour la production de bacteries
AU2013204249B2 (en) * 2007-05-30 2016-10-20 Xencor, Inc. Methods and compositions for inhibiting CD32b expressing cells
WO2013113326A1 (fr) * 2012-01-31 2013-08-08 Curevac Gmbh Composition pharmaceutique comprenant un complexe support polymère - charge et au moins un antigène de protéine ou de peptide
US10766951B2 (en) * 2015-04-01 2020-09-08 Taipei Medical University Antibodies against infectious diseases
CN106581638B (zh) * 2017-01-05 2019-08-13 马晟利 血链球菌蛋白在制备抑制白色念珠菌的药物上的应用
CN108085273B (zh) * 2017-12-11 2022-01-21 暨南大学 一株抗真菌链霉菌及其代谢物、代谢物制备方法与应用
CN108785291A (zh) * 2018-08-13 2018-11-13 华南农业大学 竹红菌素在制备抗白色念珠菌的产品中的应用
CN109750058A (zh) * 2018-11-07 2019-05-14 安徽大学 一种白色念珠菌的研究方法

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003094970A1 (fr) * 2002-04-26 2003-11-20 Dennis Reisch Compose biologique fongicide
WO2011073685A1 (fr) * 2009-12-17 2011-06-23 The Queen's University Of Belfast Modulateur
CN102192941A (zh) * 2010-03-05 2011-09-21 西北大学 一种快速评估甲型流感病毒宿主特异性的方法
WO2011158388A1 (fr) * 2010-06-16 2011-12-22 東光薬品工業株式会社 Complexe de chaîne de sucre contenant de l'acide sialique et son procédé de production, agent antigrippal et filtre
CN104144613A (zh) * 2011-12-07 2014-11-12 菲仕兰品牌有限公司 用于提供唾液酸化寡糖的方法
CN105473728A (zh) * 2013-05-31 2016-04-06 基因化学株式会社 用于制备唾液酸衍生物的方法
WO2019086613A1 (fr) * 2017-11-03 2019-05-09 Agriculture And Food Development Authority (Teagasc) Composition et utilisations associées
CN111249444A (zh) * 2020-03-10 2020-06-09 西北大学 一种用于抑制白色念珠菌的制剂

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
WANG, YAN: "Inhibition of Oral Candida Albicans by SAα2-3Gal Structure of Glycoprotein in Patients with Type 2 Diabetes Mellitus", DOCTORAL DISSERTATION, no. 02, 1 June 2020 (2020-06-01), CN, pages 1 - 68, XP009530316 *

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