A series of naringin ester derivatives, its enzyme catalytic preparation method and application

Abstract

This invention discloses a series of naringin ester derivatives, their enzyme-catalyzed preparation methods, and applications. Using naringin as a substrate, an immobilized lipase... IM Under TL catalysis, esterification with corresponding vinyl ester acyl donors is carried out in an organic solvent, followed by separation and purification after the reaction. This invention is the first to prepare a series of naringin ester derivatives with different chain lengths via enzymatic catalysis. This preparation method is mild, highly regioselective, has a high conversion rate (>99%), and is easy to scale up for production. Compared to naringin, the naringin ester derivatives exhibit better activity against *Porphyromonas gingivalis* (…). Porphyromonas gingivalis Bacterial gingival protein K (KGP) and its virulence factor exhibit significantly enhanced inhibitory activity, effectively disrupting bacterial cell membranes, inhibiting biofilm formation, and inducing bacterial apoptosis. They have broad application prospects in the preparation of oral care compositions or drugs for the prevention or treatment of periodontitis.

Description

Technical Field

[0001] This invention relates to the fields of natural product modification and biomedicine, specifically to a series of naringin derivatives, their enzyme-catalyzed preparation methods, and the inhibitory effects of these derivatives on Porphyromonas gingivalis (Porphyromonas gingivalis). Porphyromonas gingivalis Applications in the activity of ) and gingipain. Background Technology

[0002] Periodontitis is a chronic inflammatory disease caused by dental plaque biofilm. It has a high global prevalence and is closely associated with various systemic diseases, such as cardiovascular disease, Alzheimer's disease, and rheumatoid arthritis. *Porphyromonas gingivalis* (… P. gingivalis *Gingivitis* is a key pathogenic bacterium in periodontitis, and its secreted virulence factor—gingival protease (especially KGP)—plays a central role in bacterial colonization, nutrient acquisition, immune evasion, and tissue destruction. Therefore, developing effective inhibitors is crucial. P. gingivalis Preparations containing KGP-active compounds are an important strategy for treating periodontitis.

[0003] Currently, clinical treatment often involves mechanical debridement combined with antibiotics (such as metronidazole and doxycycline) or chemical drugs (such as chlorhexidine). However, the widespread use of antibiotics has led to increasingly serious drug resistance problems, and chemical drugs often have side effects (such as tooth discoloration and altered taste). Finding safe and effective antibacterial components from natural products has become a research hotspot.

[0004] Naringin is a flavonoid compound widely found in citrus fruits, possessing various biological activities such as anti-inflammatory, antioxidant, and antibacterial properties, and exhibiting high safety. However, naringin is highly water-soluble but poorly lipid-soluble, resulting in low bioavailability and limited antibacterial activity, which severely restricts its practical application.

[0005] Improving the lipophilicity of flavonoids through structural modification is an effective way to enhance their antibacterial properties. Esterification reactions, especially enzyme-catalyzed esterification, are widely used due to their mild conditions and high regioselectivity. However, currently, there is no method to enhance the antibacterial properties of naringin through esterification modification. P. gingivalis Related research and reports on the inhibition of KGP activity. Summary of the Invention

[0006] The primary objective of this invention is to overcome the shortcomings of the prior art and provide a series of novel naringin derivatives.

[0007] Another objective of this invention is to provide a green, efficient, and highly regioselective enzymatic method for the preparation of the naringin derivative.

[0008] Another object of the present invention is to clarify the inhibitory effect of the said naringin derivative on... P. gingivalis The excellent effects of KGP activity and its application in the preparation of oral antibacterial drugs or care products.

[0009] To achieve the above objectives, the technical solution of the present invention is as follows:

[0010] In a first aspect, the present invention provides a series of naringin ester derivatives, the structural formulas of which are shown below:

[0011] In the naringin molecule, the hydroxyl group at the C6'' position of the glucose unit is replaced by different acyl groups -OCOR, where R is acetyl-COCH3 or hexanoyl-COC5H. 11 Or octanoyl-COC7H 15 .

[0012] Secondly, the present invention provides a method for preparing a series of naringin ester derivatives, comprising the following steps: In an organic solvent, using naringin as a substrate and vinyl ester R′COOCH=CH2 (R′ being a C1-C7 straight-chain or branched alkyl group) as an acyl donor, the reaction was carried out at 45-55°C and 150-200 rpm for 6-10 hours under the catalysis of lipase. After the reaction, the enzyme was removed by centrifugation, and the reaction solution was subjected to post-processing steps such as concentration, hexane precipitation, methanol dissolution-concentration purification, and freeze-drying to obtain the high-purity target product.

[0013] Furthermore, the organic solvent is one of tert-amyl alcohol and tert-butanol.

[0014] Furthermore, the acyl donor is one of vinyl acetate, vinyl hexanoate, and vinyl octanoate.

[0015] Furthermore, the sources of the lipase include Thermomyces lanuginosus , Rhizomucor miehei or Candida antarctica .

[0016] Furthermore, in the system, the concentration of the enzyme catalyst is 10-25 mg / mL, the concentration of the naringin is 20-40 mmol / L, and the concentration of the acyl donor is 500-700 mmol / L.

[0017] Thirdly, the present invention provides a pharmaceutical composition or oral care composition comprising an effective amount (1% by weight) of the above-mentioned naringin derivative and a pharmaceutically or cosmetically acceptable carrier.

[0018] Fourthly, the present invention provides the composition for the preparation of a product for inhibiting Porphyromonas gingivalis (…). Porphyromonas gingivalis Application in products containing biofilms of the organism and / or its biofilms.

[0019] Fifthly, the present invention provides the use of the naringin derivative or the pharmaceutical composition or oral care composition described herein in the preparation of products for inhibiting the protease activity and / or hemolytic activity of gingival proteinase K (KGP), particularly in the prevention or treatment of periodontitis.

[0020] Through in-depth structure-activity relationship (SAR) studies, the naringin derivative yielded the following findings: Introducing an acyl chain of a specific length (R being a C2-C10 straight-chain or branched alkyl group) onto the C6'' hydroxyl group of the naringin core significantly overcomes the poor lipophilicity and low bioavailability of the original naringin, and significantly enhances its inhibitory activity against *Porphyromonas gingivalis* and its virulence factor, gingival protease. This performance enhancement is a first-time discovery. Crucially, the antibacterial activity and ability to disrupt bacterial cell membranes of the derivative show a positive correlation with the length of the introduced acyl chain; that is, within a certain range, the longer the acyl chain, the superior its antibacterial performance.

[0021] Compared with the prior art, the advantages and beneficial effects of the present invention are as follows: 1. Innovation: This invention is the first to design and synthesize three naringin ester derivatives with specific structures, and for the first time uses them to inhibit... P. gingivalis Together with KGP, they have opened up new application areas for naringin.

[0022] 2. The method is green and efficient: It adopts an enzyme catalysis method with mild reaction conditions, high regioselectivity (88.39%-97.06%), extremely high conversion rate (>99%), simple post-processing, and the process can be scaled up, making it suitable for industrial production.

[0023] 3. Significantly enhanced activity: Experiments have shown that the naringin derivatives (especially caprylates) described in this invention, compared to the original naringin, exhibit significantly enhanced activity. P. gingivalis The MIC value decreased from 400 μg / mL to 100 μg / mL, the inhibition rate of KGP protease activity increased from 9.68% to 38.99%, and the anti-hemolytic activity was retained.

[0024] 4. Synergistic effect of multiple mechanisms: The derivatives can not only directly kill bacteria, but also effectively destroy bacterial cell membranes, inhibit biofilm formation, and induce bacterial apoptosis, exhibiting a multi-target antibacterial mechanism and are less likely to develop drug resistance.

[0025] 5. High safety: The derivatives prepared from natural and safe naringin are expected to have good safety and are suitable for long-term oral care. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of the enzyme-catalyzed synthesis route of the naringin derivative of the present invention.

[0027] Figure 2 , Figure 3 , Figure 4 The structural formulas are, in order, naringin acetate, naringin hexanoate, and naringin octanoate.

[0028] Figure 5 This diagram illustrates the inhibitory effects of the naringin derivative of this invention on KGP protease activity and hemolytic activity.

[0029] Figure 6 For naringin and its ester derivatives P. gingivalis The MIC / MBC value (A) and its effect on cell membrane permeability (LDH leakage) (B).

[0030] Figure 7 After treatment with naringin (A1, A2), naringin acetate (B1, B2), naringin hexanoate (C1, C2), naringin octanoate (D1, D2), and a blank control (E1, E2), P. gingivalis Scanning electron microscope (SEM) images (A1-E1) and confocal laser scanning microscope (CLSM) fluorescent staining images (A2-E2).

[0031] Figure 8 Molecular docking scores (A1-D1), relative conformational energy distributions (A2-D2), and CDOCKER interactions (E1-E4) of naringin and its ester derivatives with each functional domain (4RBM, 4ITC, 3KM5, 3M1H) of KGP are shown.

[0032] Figure 9 , Figure 10 , Figure 11 , Figure 12 The following are detailed diagrams of the molecular docking binding modes of naringin (A), naringin acetate (B), naringin hexanoate (C), and naringin octanoate (D) in the KGP catalytic domain (4RBM) and the KGP hemagglutinin auxiliary domains K1: 4ITC, K2: 3KM5, and K3: 3M1H, respectively.

[0033] Figure 13 For naringin and its ester derivatives P. gingivalisThe effects of biofilm content (A), biofilm activity (B), biofilm protein content (C), cell surface hydrophobicity (D), and AI-2 quorum sensing signal (E). Detailed Implementation

[0034] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanatory of the present invention, and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention. Unless otherwise stated, the raw materials and reagents used in the following embodiments are commercially available products, or can be prepared by known methods.

[0035] Figure 1 This is a schematic diagram of the enzymatic synthesis route of the naringin ester derivative of this invention. Using naringin as a substrate, an immobilized lipase... IM Under TL catalysis, the esterification reaction is carried out with the corresponding vinyl ester acyl donor in an organic solvent, and the product is obtained by separation and purification after the reaction is completed.

[0036] Example 1: Preparation of naringin acetate (NA) To 50 mL of tert-amyl alcohol, add naringin (30 mmol / L), vinyl acetate (600 mmol / L), and immobilized lipase. IM TL (625 mg). The mixture was placed in a constant temperature air shaker at 50°C and 180 rpm for 8 hours. Samples were taken periodically during the reaction, and the reaction progress was monitored by HPLC after centrifugation. After the reaction, the immobilized enzyme was removed by centrifugation at 12,000 rpm for 2 minutes. The supernatant was concentrated under vacuum, and the residue was redissolved in methanol. This process was repeated 2-3 times to obtain the crude product. Hexane was added to the crude product to precipitate it, and the precipitate was separated to remove residual acyl donors. The precipitate was dissolved again in methanol and concentrated, repeated 2-3 times to completely remove hexane. The final product was freeze-dried for 48 hours to obtain a white powder of naringin acetate, with the structural formula shown below. Figure 2 HPLC analysis showed a substrate conversion rate of 99.45% and a regioselectivity of 88.39%. The product structure was confirmed by HRMS and ¹H NMR.

[0037]

[0038] Example 2: Preparation of naringin hexanoate (NH) The procedure was the same as in Example 1, except that the acyl donor was replaced with an equimolar amount of vinylhexanoate. After reacting for 8 hours, post-treatment yielded naringin hexanoate, with the structural formula shown below. Figure 3HPLC analysis showed that the substrate conversion rate was 99.56% and the regioselectivity was 97.06%.

[0039]

[0040] Example 3: Preparation of naringin octanoate (NO) The procedure was the same as in Example 1, except that the acyl donor was replaced with an equimolar amount of vinyl octanoate. After reacting for 9 hours, post-treatment yielded naringin octanoate, with the structural formula shown below. Figure 4 HPLC analysis showed that the substrate conversion rate was 99.75% and the regioselectivity was 94.02%.

[0041]

[0042] Example 4: Inhibition test of naringin derivatives on KGP protease activity and hemolytic activity Protease activity inhibition: Reaction systems containing KGP enzyme solution and different concentrations of candidate compounds were established in 96-well plates using either the azocasein method or the Lys-PND method. Absorbance changes were monitored at 405 nm to calculate the inhibition rate of the compounds on KGP protease activity.

[0043] Inhibition of hemolytic activity: A 0.5% sheep erythrocyte suspension was prepared and co-incubated with KGP enzyme solution and candidate compounds. After centrifugation, the absorbance of the supernatant at 540 nm was measured, and the hemolysis rate and the inhibition rate of the compounds were calculated.

[0044] Result: As Figure 5 As shown, at a concentration of 100 μg / mL, the inhibition rates of NAR, NA, NH, and NO on KGP protease activity were 9.68%, 21.83%, 31.51%, and 38.99%, respectively. The inhibition rates on KGP hemolytic activity were 32.36%, 27.23%, 29.26%, and 31.06%, respectively. This indicates that acylation modification significantly enhanced its inhibition of KGP protease activity while maintaining its anti-hemolytic activity.

[0045] Example 5: Inhibition of naringin derivatives P. gingivalis Activity assay (MIC / MBC determination) A micro-broth dilution method was used. P. gingivalis The W83 strain was anaerobically cultured for 96 hours in BHI medium supplemented with 5% sheep serum and 100 mg / L bovine hemoglobin. The bacterial concentration was then adjusted to 1×10⁻⁶. 6CFU / mL, add 100 μL of bacterial suspension to each well of a 96-well plate. Then, serially dilute the naringin derivatives and naringin prototype (NAR) prepared in Examples 1-3 with culture medium (concentration range 3.125-400 μg / mL), adding 100 μL of the drug solution to each well. A drug-free culture medium is set up as a negative control. After anaerobic incubation at 37°C for 72 hours, observe visually and incubate with 20 μL of 1% resazurin solution for 2 hours. The lowest drug concentration at which the solution remains blue is recorded as MIC. Bacterial suspensions from wells with MIC and higher concentrations are spread onto BHI agar plates. The lowest concentration at which no bacterial growth occurs after 48 hours of incubation is recorded as MBC.

[0046] Result: As Figure 6 As shown in Figure A, the MIC values ​​of NAR, NA, NH, and NO were 400, 200, 200, and 100 μg / mL, respectively, and the MBC values ​​were all twice the MIC values. This indicates that acylation modification significantly enhanced the antibacterial and bactericidal activities of naringin, and the activity increased with the length of the acyl chain.

[0047] Example 6: Naringin derivatives on P. gingivalis The effect of cell membrane permeability (LDH leakage assay) Will P. gingivalis Adjust the bacterial concentration to OD 550 = 1.0. The experimental group was treated with candidate compounds (NAR, NA, NH, NO) at a final concentration of 100 μg / mL, while the control group was treated with an equal volume of distilled water. After anaerobic incubation at 37°C for 4 hours, the mixture was centrifuged at 4°C and 5000 rpm for 10 minutes. The supernatant was collected, and the LDH enzyme activity was measured according to the instructions of the lactate dehydrogenase (LDH) assay kit.

[0048] Result: As Figure 6 As shown in Figure B, compared with the blank group (7.12 U / L), the LDH activity in the supernatant of the NAR, NA, NH, and NO treatment groups significantly increased to 55.52, 88.97, 226.33, and 385.77 U / L, respectively. This indicates that all compounds can disrupt the integrity of bacterial cell membranes, leading to leakage of intracellular contents, and the degree of disruption increases with the length of the acyl chain.

[0049] Example 7: Molecular docking analysis The three-dimensional structures of the catalytic domain (4RBM) and hemagglutinin auxiliary domains (K1:4ITC, K2:3KM5, K3:3M1H) of KGP were obtained from the RCSB PDB database. Using Discovery Studio 2021 software, the NAR, NA, NH, and NO molecules were coupled to the active site regions of each protein using the LibDock and CDOCKER methods, respectively. Their binding scores, conformational energies, and interaction modes (hydrogen bonds, hydrophobic interactions, etc.) were analyzed.

[0050] Result: As Figure 8 As shown in Figure 12, acylation modification enhances the binding ability of the derivative to key regions such as 4RBM and 4ITC, resulting in higher binding scores. With increasing acyl chain length, the hydrophobic interactions between the derivative and the protein increase, leading to more stable binding, consistent with its enhanced enzyme inhibitory activity.

[0051] Example 8: Application of naringin derivatives in toothpaste The naringin caprylate (NO) prepared according to this invention is mixed at a weight ratio of 0.1% with an abrasive (hydrated silica), a humectant (glycerin), a foaming agent (sodium lauroyl sarcosinate), a binder (sodium carboxymethyl cellulose), a fragrance, and deionized water to form a toothpaste. This toothpaste can inhibit the growth of bacteria in the oral cavity. P. gingivalis And dental plaque biofilm, effectively prevents and assists in the treatment of periodontitis.

[0052] Figure 7 After treatment with naringin (A1, A2), naringin acetate (B1, B2), naringin hexanoate (C1, C2), naringin octanoate (D1, D2), and a blank control (E1, E2), P. gingivalis Scanning electron microscopy (SEM) images (A1-E1) and confocal laser scanning microscopy (CLSM) images with fluorescence staining (A2-E2) are shown. It can be seen that in the control group, bacterial cells are plump, uniform in morphology, and without rupture or abnormal shrinkage. After treatment with NAR, NA, NH, and NO, the cells show shrinkage, deformation, and leakage of contents, indicating potential damage to the cell membrane. After acridine orange (AO) and propidium iodide (PI) staining, the control group shows obvious green fluorescence, indicating the presence of a large number of viable cells. After naringin treatment, green fluorescence decreases and yellow fluorescence appears, indicating that some cells undergo apoptosis. NA treatment leads to almost the disappearance of green fluorescence, a significant increase in yellow fluorescence, and the appearance of some red fluorescence, indicating that a large number of cells undergo apoptosis and some cells have died. The results after treatment with NH and NO are similar, with most of the red fluorescence remaining, indicating that most cells have died. Therefore, it can be inferred that naringin derivatives can induce apoptosis in *Porphyromonas gingivalis* cells, and this ability increases with the increase of the introduced acyl chain length.

[0053] Figure 8 The diagram shows the molecular docking scores (A1-D1), relative conformational energy distributions (A2-D2), and CDOCKER interactions (E1-E4) of naringin and its ester derivatives with various functional domains of KGP (4RBM, 4ITC, 3KM5, 3M1H). It can be seen that naringin and its ester derivatives exhibit a large number of data points in the docking results with the 4RBM, 4ITC, and 3KM5 regions, indicating a high binding probability with the target regions and good docking scores. Furthermore, naringin ester derivatives achieve a higher score range with increasing acyl chain length. In the 4RBM, 4ITC, and 3KM5 regions, the ligand-acceptor binding energy required for the ester derivatives is increased compared to naringin. In the docking results with the 3M1H region, NA shows a decrease in the number of docking sites, while NH and NO both show an increase, with NO showing a more significant increase. This indicates that the increased acyl chain length of the ester derivatives enhances their binding potential within the 3M1H region. Therefore, this acylation modification may have a positive impact on the ability of naringin to inhibit KGP activity. The CDOCKER method provides another perspective on the docking results. CDOCKER results show that the binding ability of naringin ester derivatives to the 4RBM, 3KM5, and 3M1H domains is poor, exhibiting high binding energy requirements and low binding potential. However, for the 4ITC region, CDOCKER provides a better evaluation. With increasing acyl chain length, the number of binding sites of naringin ester derivatives to the 4ITC domain increases, the binding energy requirement decreases, and the binding ability to the 4ITC region improves, making binding more likely. This suggests that extending the acyl chain length of naringin may enhance its anti-hemolytic potential.

[0054] Figure 9 This diagram shows the detailed molecular docking binding modes of naringin (A), naringin acetate (B), naringin hexanoate (C), and naringin octanoate (D) within the KGP catalytic domain (4RBM). It can be seen that acylation modification of naringin does not significantly negatively affect its binding to active residues in the 4RBM domain. For NA, NH, and NO, the key active residues ASP388-HIS444-CYS477 in the 4RBM domain still tend to bind to the glycosidic backbone; the added acyl chain does not participate in the binding of these key active residues. However, with increasing chain length, NO exhibits some binding ability with other residues, suggesting that further elongation of the acyl chain may encourage its participation in the binding process.

[0055] Figure 10This diagram shows the detailed molecular docking binding modes of naringin (A), naringin acetate (B), naringin hexanoate (C), and naringin caprylate (D) within the KGP hemagglutinin auxiliary domain K1: 4ITC. It can be seen that the acyl chains in NA, NH, or NO do not participate in binding to the key active residues Thr1098-Ser1104 in the 4ITC domain. This implies that, based on the mechanism of action of this domain, acylated naringin may not show significant changes in its antihemolytic activity. However, with increasing acyl chain length, the acyl chain begins to form alkyl bonds with other residues, which may lead to a change in this stable binding state, potentially altering its antihemolytic activity.

[0056] Figure 11 This diagram shows the detailed molecular docking binding modes of naringin (A), naringin acetate (B), naringin hexanoate (C), and naringin octanoate (D) within the KGP hemagglutinin auxiliary domain K2: 3KM5. As can be seen, similar to naringin, NA and NH bind to the key active residues Lys1276-Arg1280-Lys1291 of the 3KM5 domain via van der Waals forces or hydrogen bonds. No significant changes in the binding to these key residues were observed. This indicates that chain length elongation from acetyl to octanoyl does not significantly affect the binding to the 3KM5 domain.

[0057] Figure 12 This diagram shows the detailed molecular docking binding modes of naringin (A), naringin acetate (B), naringin hexanoate (C), and naringin caprylate (D) within the KGP hemagglutinin auxiliary domain K3: 3M1H. It can be seen that among the key residues in the 3M1H domain, naringin and NA both interact with Pro1553, NH interacts with Leu1544, and NO does not interact with Leu1544 or Pro1553. This indicates that further increasing the acyl chain length may alter the binding ability of naringin ester derivatives within the 3M1H domain, thereby affecting their antihemolytic activity.

[0058] Figure 13 For naringin and its ester derivatives P. gingivalisThe effects of naringin on biofilm content (A), biofilm activity (B), biofilm protein content (C), cell surface hydrophobicity (D), and AI-2 quorum sensing signal (E) were investigated. It can be seen that treatment with naringin and its ester derivatives led to a decrease in overall biofilm content. Acylation modification of naringin enhanced its ability to reduce biofilm content, but the length of the acyl chain had no significant effect on this effect. Furthermore, neither naringin nor its ester derivatives showed the ability to inhibit the metabolic activity of *Porphyromonas gingivalis* biofilm, indicating that acylation modification did not enhance the effectiveness of naringin in this regard. In addition, the protein content within the biofilm did not change significantly after treatment, indicating that none of the compounds, including the ester derivatives, affected the protein composition of the biofilm. Figure 13 As shown in D, treatment with naringin and its ester derivatives significantly reduced the hydrophobicity of the cell surface of *Porphyromonas gingivalis*, but with increasing acyl chain length, the hydrophobicity slightly increased. This may be due to the increased lipophilicity of the ester derivatives, which enhanced hydrophobic-hydrophobic interactions on the bacterial cell surface. Figure 13 As shown in E, naringin and its ester derivatives can significantly reduce the activity of the interbacterial signaling molecule AI-2, indicating that naringin and its ester derivatives can interfere with intercellular communication of Porphyromonas gingivalis. However, this inhibitory ability does not change significantly with acylation and the extension of acyl chain length.

Claims

1. A series of naringin derivatives, characterized in that, The structural formula is as follows: In the naringin molecule, the hydroxyl group at the C6'' position of the glucose unit is replaced by different acyl groups -OCOR, where R is acetyl-COCH3 or hexanoyl-COC5H. 11 Or octanoyl-COC7H 15 .

2. The method for preparing the naringin ester derivative according to claim 1, characterized in that, Includes the following steps: In an organic solvent, using naringin as a substrate and vinyl ester R′COOCH=CH2 as an acyl donor, wherein R′ is a C1-C7 straight-chain or branched alkyl group, an esterification reaction is carried out under the catalysis of lipase. After the reaction is completed, the naringin ester derivative is obtained by post-treatment.

3. The preparation method according to claim 2, characterized in that, The organic solvent is one of tert-amyl alcohol and tert-butanol; the acyl donor is one of vinyl acetate, vinyl hexanoate, and vinyl octanoate.

4. The preparation method according to claim 2, characterized in that, The lipase source includes Thermomyces lanuginosus , Rhizomucor miehei or Candida antarctica .

5. The preparation method according to claim 2, characterized in that, The reaction temperature is 45-55°C, and the reaction time is 6-10 hours.

6. The preparation method according to claim 2, characterized in that, In the system, the concentration of the enzyme catalyst is 10-25 mg / mL, the concentration of the naringin is 20-40 mmol / L, and the concentration of the acyl donor is 500-700 mmol / L.

7. The preparation method according to claim 2, characterized in that, The post-processing includes: after terminating the reaction, removing the enzyme, concentrating the reaction solution, removing excess acyl donors, and finally drying to obtain the purified product.

8. A pharmaceutical composition or oral care composition, characterized in that, It comprises an effective amount of the naringin derivative of claim 1 and a pharmaceutically or cosmetically acceptable carrier.

9. The naringin derivative of claim 1 or the composition of claim 8 in the preparation of a product for inhibiting Porphyromonas gingivalis. Porphyromonas gingivalis Application in products containing biofilms or other biofilms.

10. The use of the naringin derivative of claim 1 or the composition of claim 8 in the preparation of a product for inhibiting the protease activity and / or hemolytic activity of gingival proteinase K.

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