An oral care composition having a gingival protective effect and use thereof

Abstract

This invention belongs to the field of oral care technology, specifically relating to an oral care composition with gingival protection effects and its application. The oral care composition comprises: 1) palmitoyl hexapeptide-12; 2) dipotassium glycyrrhizate; and 3) an orally acceptable carrier. The amino acid sequence of palmitoyl hexapeptide-12 is palmitoyl-valine-glycine-valine-alanine-proline-glycine. This invention has found that palmitoyl hexapeptide-12 and dipotassium glycyrrhizate have a significant synergistic effect within the specified mass ratio range, significantly enhancing the effect of dipotassium glycyrrhizate on the lysine-specific cysteine ​​protease gene of *Porphyromonas gingivalis*. kgp and arginine-specific cysteine ​​protease gene rgpA The composition inhibits the expression of certain substances, thereby effectively preventing and improving periodontal disease. It can be formulated as toothpaste, gel, mouthwash, or tooth powder, and shows promising potential for gingival protection.

Description

Technical Field

[0001] This invention belongs to the field of oral care technology, specifically relating to an oral care composition with gingival protection function, particularly to an oral care composition containing palmitoyl hexapeptide-12 and dipotassium glycyrrhizate and its application in inhibiting the expression of Porphyromonas gingivalis protease gene. Background Technology

[0002] Periodontal disease is one of the most common oral diseases in humans, mainly including gingivitis and periodontitis. Studies have shown that *Porphyromonas gingivalis* (… Porphyromonas gingivalis Gingipains are one of the main pathogens causing periodontal disease. These bacteria produce gingipains, including lysine-specific cysteine ​​proteases. kgp and arginine-specific cysteine ​​protease rgpA Porphyromonas gingivalis and its virulence genes (such as...) possess strong virulence, capable of directly damaging oral soft tissues and degrading host immune proteins, thereby causing severe periodontal tissue damage such as gingival bleeding, swelling, and even alveolar bone resorption. Therefore, effectively inhibiting Porphyromonas gingivalis and its virulence genes (such as...) is crucial. kgp and rgpA The expression of ) is of vital importance for oral care, improvement and prevention of gum disease.

[0003] Currently, glycyrrhizic acid and its salts (such as dipotassium glycyrrhizate DPG) are commonly added to oral care products as gingival protective ingredients due to their anti-inflammatory and antibacterial activities. However, with the increasing demands for effective oral care, the question remains: how can we significantly enhance the virulence of glycyrrhizic acid or its salts against Porphyromonas gingivalis-related virulence genes (such as...) while using conventional doses or lower amounts? kgp and rgpA Inhibiting the expression of ) to achieve a more efficient and faster repair of the gingival protective barrier is one of the current research directions in this field.

[0004] Palmitoyl hexapeptide-12, as an active lipopeptide compound, is widely used in the skincare field for its significant anti-wrinkle, firming, and barrier repair effects. However, in the field of oral care, there are no reports of it inhibiting the expression of Porphyromonas gingivalis protease genes.

[0005] Therefore, how to formulate a highly efficient and safe oral care composition that can significantly enhance the inhibitory effect on the expression of virulence genes of Porphyromonas gingivalis while maintaining a low amount of added ingredients, thereby achieving better gingival protection, is a technical problem that urgently needs to be solved in the field of oral care technology. Summary of the Invention

[0006] The first technical problem to be solved by the present invention is to provide an oral care composition with a gingival protective effect, the composition comprising palmitoyl hexapeptide-12 and dipotassium glycyrrhizate, wherein the palmitoyl hexapeptide-12 has the effect of enhancing the inhibitory effect of dipotassium glycyrrhizate on the expression of Porphyromonas gingivalis protease gene, that is, enhancing the gingival protective effect.

[0007] The second problem to be solved by this invention is to provide an application of palmitoyl hexapeptide-12 in enhancing the inhibitory effect of dipotassium glycyrrhizate on the expression of Porphyromonas gingivalis protease gene.

[0008] This invention is achieved through the following technical solution: To solve the first technical problem mentioned above, the present invention adopts the following technical solution: An oral care composition with gingival protection properties, the composition comprising: 1) Palmitoyl hexapeptide-12; 2) Dipotassium glycyrrhizate; 3) Oral-acceptable carriers.

[0009] The amino acid sequence of palmitoyl hexapeptide-12 is palmitoyl-valine-glycine-valine-alanine-proline-glycine.

[0010] More preferably, the palmitoyl hexapeptide-12 is present in the oral care composition at a mass ratio of 0.0001% to 0.0005%.

[0011] More preferably, the dipotassium glycyrrhizate is present in the oral care composition at a mass ratio of 0.1%-0.3%.

[0012] More preferably, the dipotassium glycyrrhizate is present in the oral care composition at a mass ratio of 0.2%-0.3%.

[0013] To solve the second technical problem mentioned above, the present invention adopts the following technical solution: This study provides an application of palmitoyl hexapeptide-12 in enhancing the inhibitory effect of dipotassium glycyrrhizate on the expression of Porphyromonas gingivalis protease genes.

[0014] Any range described in this invention includes the endpoint, any value between the endpoints, and any subrange consisting of the endpoint or any value between the endpoints.

[0015] Unless otherwise specified, all raw materials used in this invention can be obtained commercially, and the equipment used in this invention can be conventional equipment in the relevant field or refer to existing technology in the relevant field.

[0016] The present invention has the following advantages over the prior art: The present invention provides an oral care composition with gingival protection effect, the composition comprising palmitoyl hexapeptide-12 and dipotassium glycyrrhizate, wherein palmitoyl hexapeptide-12 enhances the inhibitory effect of dipotassium glycyrrhizate on the expression of Porphyromonas gingivalis protease gene, that is, enhances the gingival protection effect. Detailed Implementation

[0017] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments, further clarifies the invention. Those skilled in the art should understand that the specific descriptions below are illustrative rather than restrictive, and should not be construed as limiting the scope of protection of the present invention.

[0018] Unless otherwise stated, all percentages and ratios used herein are based on the total weight of the composition. Unless otherwise stated, all percentages, proportions, and contents of ingredients mentioned herein are based on the actual contents of the ingredient and do not include solvents, fillers, or other substances that can be combined with these ingredients in commercially available products.

[0019] The term "includes / contains" in this article refers to other steps and components that may be added without affecting the final result.

[0020] The term "preferred" and its variations herein refer to embodiments of the invention that provide specific beneficial effects under particular conditions. However, other embodiments may also be preferred under the same or other conditions. Furthermore, the detailed description of one or more preferred embodiments does not imply that other embodiments are useless, nor is it intended to exclude other embodiments from the scope of the invention.

[0021] Unless otherwise specified in the embodiments of the present invention, the conditions shall be performed in accordance with conventional conditions or conditions recommended by the manufacturer; if the manufacturers of the reagents or instruments used are not specified, they are all conventional products that can be purchased commercially.

[0022] As one aspect of the present invention, the present invention provides an oral care composition comprising: 1) Palmitoyl hexapeptide-12; 2) Dipotassium glycyrrhizate; 3) Oral-acceptable carriers.

[0023] The present invention unexpectedly discovered that although palmitoyl hexapeptide-12 itself does not inhibit the expression of the gingival protease gene in Porphyromonas gingivalis, when palmitoyl hexapeptide-12 and dipotassium glycyrrhizate are added to the oral care composition, palmitoyl hexapeptide-12 can effectively enhance the inhibitory effect of dipotassium glycyrrhizate on the expression of the gingival protease gene in Porphyromonas gingivalis.

[0024] Palmitoyl hexapeptide-12 The palmitoyl hexapeptide-12 described in this invention refers to an active lipopeptide compound formed by covalently coupling a lipophilic palmitoyl group with an oligopeptide fragment containing six amino acid residues. Due to its extremely high bioactivity and stability, it exhibits significant anti-wrinkle, firming, and barrier repair effects even at low concentrations, and is widely used in skincare products.

[0025] In some embodiments of the present invention, the amino acid sequence of palmitoyl hexapeptide-12 is palmitoyl-valine-glycine-valine-alanine-proline-glycine.

[0026] In some embodiments of the present invention, the palmitoyl hexapeptide-12 may be purchased from Nanjing Leon Biotechnology Co., Ltd.

[0027] glycyrrhizic acid Glycyrrhizic acid, also known as glycyrrhizin or glycyrrhizin, is a natural active ingredient extracted from the dried roots and rhizomes of plants in the genus Glycyrrhiza of the legume family. Its chemical nature is oleanane-type pentacyclic triterpenoid saponin.

[0028]

[0029] Glycyrrhizic acid typically exists in two isomers, namely 18... α - Glycyrrhizic acid and 18 β - Glycyrrhizic acid, of which 18 β - The configuration is the predominant active form. Within the scope of this invention, the term "glycyrrhizic acid" encompasses all its stereoisomers, solvates, crystalline forms, pharmaceutically acceptable salts (e.g., its monoammonium salts, diammonium salts, monopotassium salts, dipotassium salts, tripotassium salts, disodium glycyrrhizate, etc.) and their chemical equivalents.

[0030] The present invention unexpectedly discovered that when palmitoyl hexapeptide-12 and dipotassium glycyrrhizate are added to the oral care composition, the composition significantly enhances the effect of inhibiting the expression of Porphyromonas gingivalis protease gene, but the combination of palmitoyl hexapeptide-12 and glycyrrhetinic acid does not improve the inhibitory effect.

[0031] According to certain embodiments of the present invention, the dipotassium glycyrrhizate can be purchased from Gansu Fanzhi Pharmaceutical Co., Ltd.

[0032] According to certain embodiments of the present invention, the glycyrrhizic acid salt is dipotassium glycyrrhizate (hereinafter referred to as: DPG).

[0033] Oral acceptable carriers The term "orally acceptable carrier" as used in this invention refers to any medium suitable for formulating the gingival composition disclosed herein; an orally acceptable carrier is harmless to mammals when held in the mouth in the amount disclosed herein without being swallowed for a duration sufficient to allow effective contact with the tooth surface as required by this invention; generally, an orally acceptable carrier is not harmful even if unintentionally swallowed; suitable orally acceptable carriers include, for example, a plurality of the following substances: water, thickeners, buffers, humectants, surfactants, abrasives, sweeteners, flavorings, visual aids, anti-caries agents, antibacterial agents, whitening agents, desensitizing agents, vitamins, preservatives, enzymes, and mixtures thereof.

[0034] According to certain embodiments of the present invention, the gum-protecting composition further includes excipients such as humectants, flavoring agents, or thickeners.

[0035] According to certain embodiments of the present invention, the gum-protecting composition is toothpaste, gel, mouthwash, or tooth powder.

[0036] Evaluation method for the efficacy of inhibiting the expression of Porphyromonas gingivalis protease gene. In this invention, the compositions are used to evaluate their effectiveness against Porphyromonas gingivalis (Porphyromonas). Porphyromonas gingivalis The methods for inhibiting protease gene expression are as follows: 1. Experimental Materials Bacterial species: Porphyromonas gingivalis ( Porphyromonas gingivalis ATCC 33277) Culture medium: Brain and heart extract broth (BHI; Difco, Maryland, USA) Primer sequences: see Table 1. Table 1. Main primer sequences

[0037] Test conditions: temperature 37±0.5℃, humidity >90%, anaerobic environment.

[0038] Solution and control: Control group: Deionized water Test substance: Dilute with deionized water to the required test concentration. For compositions containing multiple active ingredients, a mixed solution containing all the corresponding components is used for testing.

[0039] 2. Experimental Procedure: (1) Porphyromonas gingivalis was cultured to the mid-log growth phase, and different concentrations of the test substance were added. After culturing for another 8 hours, the bacterial cells were collected for RNA extraction. (2) RNA was extracted using the Eastep Super Total RNA Extraction Kit (Promega, USA) according to the instructions. (3) The concentration and purity of RNA were detected by ultraviolet spectrophotometer (Implen NanoPhotometer N50, Germany), and the integrity of RNA was assessed by agarose gel electrophoresis; (4) cDNA was synthesized in a 20 μL system using PrimeScript RT Master Mix (Takara, Japan) and RT-qPCR was performed on a MiniOpticon system (Bio-Rad, USA); (5) Data analysis: Changes in the fold expression of virulence genes were analyzed through... Gene expression of *Porphyromonas gingivalis* was calculated using a method with 16S rRNA as a reference (n=3); changes in gene expression in the treatment group compared to the control group were analyzed. Values ​​between 0 and 1 indicate a relative downward adjustment, meaning there is an inhibitory effect; the smaller the value, the more pronounced the inhibition. A value >1 indicates a relative upward adjustment, meaning there is a promoting effect; the larger the value, the more obvious the effect.

[0040] Specific embodiments and comparative examples I. Controlled Experiment with a Single Active Ingredient 1. Effects of palmitoyl hexapeptide-12 alone on gingival protease gene expression (Comparative Examples 1-5) Prepare oral care compositions according to Comparative Examples 1-5 in Table 2 below. All data in the table represent the percentage of each component by weight of the total composition; the remainder is deionized water. Each composition should be prepared by conventional stirring until homogeneous.

[0041] Table 2 Formulations of Comparative Examples 1-5 Comparative Example 1 0.0001 Add to 100% Comparative Example 2 0.0005 Add to 100% Comparative Example 3 0.001 Add to 100% Comparative Example 4 0.01 Add to 100% Comparative Example 5 0.1 Add to 100% The inhibitory effects of Comparative Examples 1-5 on the expression of Porphyromonas gingival protease gene were evaluated according to the above-described method for evaluating the inhibition of gingival protease gene expression. The results are shown in Table 3 below.

[0042] Table 3. Results of gene expression suppression in comparisons 1–5 Comparative Example 1 1.001 1.003 Comparative Example 2 1.01 0.998 Comparative Example 3 1.001 1.005 Comparative Example 4 1.007 0.989 Comparative Example 5 1.01 1.004 Table 3 shows that when palmitoyl hexapeptide-12 is used alone, its treatment effect is different. kgp and rgpA The relative gene expression levels were all close to 1, indicating that different concentrations of palmitoyl hexapeptide-12 did not show any inhibitory or promoting effect on the expression of Porphyromonas gingivalis protease genes.

[0043] 2. Effects of dipotassium glycyrrhizate (DPG) alone on gingival protease gene expression (Comparative studies 6-8) Prepare comparative ratios 6-8 of oral care compositions according to Table 4 below. All data in the table are weight percentages.

[0044] Table 4 Formulations of Comparative Examples 6-8 Comparative Example 6 0.01 Add to 100% Comparative Example 7 0.1 Add to 100% Comparative Example 8 0.3 Add to 100% The inhibitory effects of Comparative Examples 6-8 on the expression of Porphyromonas gingival protease gene were evaluated using the above-described method for evaluating the inhibition of gingival protease gene expression. The results are shown in Table 5 below.

[0045] Table 5. Results of gene expression suppression in comparisons 6–8 Comparative Example 6 0.997 1.001 Comparative Example 7 0.649 0.701 Comparative Example 8 0.588 0.601 Table 5 shows that 0.01% DPG has a significant effect on Porphyromonas gingivalis protease. kgp Relative gene expression and rgpA Neither DPG nor DPG showed a significant promoting or inhibiting effect on the expression of *Porphyromonas gingivalis* protease. kgp Relative gene expression and rgpA The relative gene expression showed a significant inhibitory effect, and the inhibitory effect became more pronounced with increasing DPG concentration.

[0046] II. Synergistic effect of palmitoyl hexapeptide-12 and low-dose DPG (see Examples 1-5) To verify the synergistic effect of palmitoyl hexapeptide-12 and DPG over a wide concentration range, a combination experiment was first conducted using 0.01% low-dose DPG (at which DPG alone has no inhibitory effect) with different concentrations of palmitoyl hexapeptide-12.

[0047] The compositions of Reference Examples 1 to 5 were prepared according to Table 6. All data in the table are weight percentages.

[0048] Table 6 Formulations of Compositions from Examples 1-5 Reference Example 1 0.0001 0.01 Add to 100% See Example 2 0.0005 0.01 Add to 100% See Example 3 0.001 0.01 Add to 100% See Example 4 0.01 0.01 Add to 100% See Example 5 0.1 0.01 Add to 100% The inhibitory effect of Reference Examples 1-5 on the expression of Porphyromonas gingival protease gene was evaluated according to the above-described method for evaluating the inhibition of gingival protease gene expression. The results are shown in Table 7.

[0049] Table 7. Gene expression suppression results of Examples 1-5 Reference Example 1 0.756 0.788 See Example 2 0.721 0.735 See Example 3 0.705 0.711 See Example 4 0.7 0.703 See Example 5 0.698 0.705 The results in Tables 3, 5, and 7 show that although palmitoyl hexapeptide-12 (at various concentrations) and 0.01% DPG, when used alone, have different effects on... kgp and rgpA Neither of the two showed significant inhibitory effects on gene expression, but when added simultaneously, they exhibited a significant synergistic inhibitory effect. This indicates a broad-spectrum synergistic relationship between palmitoyl hexapeptide-12 and DPG.

[0050] III. Preferred embodiments of the present invention: Synergistic effect of palmitoyl hexapeptide-12 and preferred doses of DPG (Examples 1-2) Based on the above findings, in order to further verify the synergistic effect of the preferred ratio range of the present invention (palmitoyl hexapeptide-12 0.0001%~0.0005%, DPG 0.1%~0.3%), compounding experiments were conducted with 0.1% and 0.3% DPG and 0.0001% palmitoyl hexapeptide-12, respectively.

[0051] Example 1 The composition of Example 1 was prepared according to Table 8 below. All data in the table are weight percentages. For ease of comparison, Comparative Example 1 (0.0001% palmitoyl hexapeptide-12) and Comparative Example 7 (0.1% DPG) are included in the table.

[0052] Table 8. Formulations of Comparative Example 1, Comparative Example 7, and Example 1 Comparative Example 1 0.0001 / Add to 100% Comparative Example 7 / 0.1 Add to 100% Example 1 0.0001 0.1 Add to 100% The inhibitory effect of Example 1 on the expression of Porphyromonas gingival protease gene was evaluated according to the above-described method for evaluating the inhibition of gingival protease gene expression. The results are shown in Table 9 below.

[0053] Table 9. Gene expression inhibition results of Comparative Example 1, Comparative Example 7, and Example 1 Comparative Example 1 1.001 1.003 Comparative Example 7 0.649 0.701 Example 1 0.497 0.521 As shown in Table 9, when 0.1% DPG is used alone (Comparative Example 7), kgp and rgpA The expression levels were 0.649 and 0.701, respectively; after adding 0.0001% palmitoyl hexapeptide-12 (Example 1), the levels decreased to 0.497 and 0.521, respectively, indicating a significant enhancement of the inhibitory effect. This demonstrates that within the preferred formulation range of this invention, the two exhibit excellent synergistic inhibitory effects.

[0054] Example 2 The composition of Example 2 was prepared according to Table 10 below. All data in the table are weight percentages. For ease of comparison, Comparative Example 1 (0.0001% palmitoyl hexapeptide-12) and Comparative Example 8 (0.3% DPG) are included in the table.

[0055] Table 10 Formulations of Comparative Example 1, Comparative Example 8 and Example 2 Comparative Example 1 0.0001 / Add to 100% Comparative Example 8 / 0.3 Add to 100% Example 2 0.0001 0.3 Add to 100% The inhibitory effect of Example 2 on the expression of Porphyromonas gingival protease gene was evaluated according to the above-described method for evaluating the inhibition of gingival protease gene expression. The results are shown in Table 11 below.

[0056] Table 11 Gene expression inhibition results of Comparative Example 1, Comparative Example 8 and Example 2 Comparative Example 1 1.001 1.003 Comparative Example 8 0.588 0.601 Example 2 0.454 0.479 As shown in Table 11, when 0.3% DPG is used alone (Comparative Example 8), kgp and rgpA The expression levels were 0.588 and 0.601, respectively; after adding 0.0001% palmitoyl hexapeptide-12 (Example 2), the levels decreased to 0.454 and 0.479, respectively, indicating a further enhancement of the inhibitory effect. This shows that at a concentration of 0.3% DPG, palmitoyl hexapeptide-12 can also significantly enhance the inhibitory effect of DPG.

[0057] Examples 3-4: Verification of Palmitoyl Hexapeptide-12 Concentration Gradient To further verify the effectiveness of the preferred concentration range of palmitoyl hexapeptide-12 (0.0001%~0.0005%) of the present invention, compounding experiments were conducted using 0.0005% palmitoyl hexapeptide-12 with 0.1% and 0.3% DPG, respectively.

[0058] Table 12 Formulations of Examples 3-4 Example 3 0.0005 0.1 Add to 100% Example 4 0.0005 0.3 Add to 100% The inhibitory effect of Examples 3-4 on the expression of gingival protease gene in Porphyromonas gingivalis was evaluated according to the above evaluation method. The results are shown in Table 13 below.

[0059] Table 13 Gene expression inhibition results of Examples 3-4 Example 3 0.479 0.503 Example 4 0.436 0.461 Table 13, combined with Tables 9 and 11, shows that at DPG concentrations of 0.1% or 0.3%, 0.0001% and 0.0005% palmitoyl hexapeptide-12 significantly enhanced the effect of DPG on... kgp and rgpA The gene expression was inhibited, and the inhibitory effect was further enhanced with increasing DPG concentration.

[0060] IV. Comparative Experiments: The Effect of Palmitoyl Hexapeptide-12 Combined with Other Glycyrrhizic Acids / Derivatives (Comparative Examples 9-14, Reference Examples 6-9) To verify the uniqueness of the combination of palmitoyl hexapeptide-12 and dipotassium glycyrrhizate, tripotassium glycyrrhizate, monopotassium glycyrrhizate, disodium glycyrrhizate, glycyrrhizic acid, and glycyrrhetinic acid were used to replace DPG in the compounding experiment.

[0061] Prepare each composition according to Table 14 below. All data in the table are weight percentages.

[0062] Table 14 Formulations of Comparative Examples 9-14 and Reference Examples 6-9 Comparative Example 9 / 0.1 / / / / Add to 100% Comparative Example 10 / / 0.1 / / / Add to 100% Comparative Example 11 / / / 0.1 / / Add to 100% Comparative Example 12 / / / / 0.1 / Add to 100% Comparative Example 13 / / / / / 0.1 Add to 100% Comparative Example 14 0.0001 / / / / 0.1 Add to 100% See Example 6 0.0001 0.1 / / / / Add to 100% See Example 7 0.0001 / 0.1 / / / Add to 100% See Example 8 0.0001 / / 0.1 / / Add to 100% See Example 9 0.0001 / / / 0.1 / Add to 100% The inhibitory effects of each composition on the expression of gingival protease gene in Porphyromonas gingivalis were evaluated according to the above evaluation method. The results are shown in Table 15 below.

[0063] Table 15 Gene expression suppression results of comparative examples 9-14 and reference examples 6-9 Comparative Example 9 0.709 0.734 Comparative Example 10 0.687 0.775 Comparative Example 11 0.677 0.787 Comparative Example 12 0.721 0.769 Comparative Example 13 0.822 0.845 Comparative Example 14 0.835 0.839 See Example 6 0.676 0.697 See Example 7 0.665 0.693 See Example 8 0.642 0.732 See Example 9 0.694 0.729 As shown in Table 15, although tripotassium glycyrrhizate, monopotassium glycyrrhizate, disodium glycyrrhizate, and the combination of glycyrrhizic acid with palmitoyl hexapeptide-12 (see Examples 6-9) have a certain synergistic inhibitory effect, their effects are not as significant as the combination of palmitoyl hexapeptide-12 with DPG (Examples 1-4).

[0064] Glycyrrhetinic acid did not enhance its inhibitory effect when used alone (Comparative Example 13) or in combination with palmitoyl hexapeptide-12 (Comparative Example 14), indicating that the synergistic effect is highly selective.

[0065] V. Comparative Experiments: Effects of Combining Other Palmitoyl Oligopeptides with DPG (Comparative Examples 15-19, Reference Examples 10-14) To verify the structure specificity of palmitoyl hexapeptide-12, palmitoyl pentapeptide-4, palmitoyl tripeptide-1, palmitoyl tripeptide-5, palmitoyl dipeptide-7, and palmitoyl octapeptide-24 were used to replace palmitoyl hexapeptide-12 in DPG formulation experiments.

[0066] Prepare each composition according to Table 16 below. All data in the table are weight percentages.

[0067] Table 16 Formulations of Comparative Examples 15-19 and Reference Examples 10-14 Comparative Example 15 0.0001 / / / / / Add to 100% Comparative Example 16 / 0.0001 / / / / Add to 100% Comparative Example 17 / / 0.0001 / / / Add to 100% Comparative Example 18 / / / 0.0001 / / Add to 100% Comparative Example 19 / / / / 0.0001 / Add to 100% See Example 10 0.0001 / / / / 0.01 Add to 100% See Example 11 / 0.0001 / / / 0.01 Add to 100% See Example 12 / / 0.0001 / / 0.01 Add to 100% See Example 13 / / / 0.0001 / 0.01 Add to 100% See Example 14 / / / / 0.0001 0.01 Add to 100% The inhibitory effects of each composition on the expression of gingival protease gene in Porphyromonas gingivalis were evaluated according to the above evaluation method. The results are shown in Table 17 below.

[0068] Table 17 Gene expression suppression results of comparative examples 15-19 and reference examples 10-14 Comparative Example 15 0.997 1.004 Comparative Example 16 1.002 1.001 Comparative Example 17 1.005 0.998 Comparative Example 18 1.003 0.998 Comparative Example 19 1.002 1.003 See Example 10 0.739 0.765 See Example 11 0.753 0.774 See Example 12 0.748 0.766 See Example 13 0.717 0.728 See Example 14 0.894 0.846 As shown in Table 17, in Comparative Examples 15-19, the other palmitoyl oligopeptides, when used alone, had no inhibitory or promoting effect on gene expression.

[0069] In Examples 10-14, although the combination of the above palmitoyl oligopeptides and DPG had a certain synergistic inhibitory effect, the effect was not as significant as that of the combination of palmitoyl hexapeptide-12 and DPG (Examples 1-4 and Examples 1-5). Among them, the palmitoyl oligopeptides with an amino acid chain length of 2-7 had the second best effect, while the palmitoyl octapeptide-24 with a chain length of 8 had the weakest effect, indicating that palmitoyl hexapeptide-12 has the best synergistic effect.

[0070] In summary, this invention has been proven through numerous experiments to be true that: (1) Palmitoyl hexapeptide-12 and dipotassium glycyrrhizate have a broad-spectrum synergistic inhibitory effect, which can significantly enhance the effect of DPG on key virulence genes of Porphyromonas gingivalis. kgp and rgpA The inhibitory effect on expression.

[0071] (2) When the mass ratio of palmitoyl hexapeptide-12 is 0.0001%~0.0005% and the mass ratio of dipotassium glycyrrhizate is 0.1%~0.3%, the synergistic inhibitory effect is particularly prominent (Examples 1~4), which is significantly better than the use of each component alone and other similar combinations.

[0072] (3) When the mass ratio of dipotassium glycyrrhizate is 0.2%~0.3%, the inhibitory effect is better.

[0073] (4) The synergistic effect is highly specific: the synergistic effect of palmitoyl hexapeptide-12 with other glycyrrhizic acid salts (such as tripotassium, monopotassium, disodium) is not as good as that of DPG; glycyrrhetinic acid has no synergistic effect with palmitoyl hexapeptide-12; the synergistic effect of other palmitoyl oligopeptides (dipeptide, tripeptide, pentapeptide, heptapeptide, octapeptide) with DPG is also not as good as that of palmitoyl hexapeptide-12.

[0074] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. An oral care composition with gingival protection properties, characterized in that, The composition comprises palmitoyl hexapeptide-12, dipotassium glycyrrhizate, and an orally acceptable carrier.

2. The oral care composition with gingival protection effect according to claim 1, characterized in that, The palmitoyl hexapeptide-12 is present in the oral care composition at a mass ratio of 0.0001% to 0.0005%.

3. The oral care composition with gingival protection effect according to claim 1, characterized in that, The mass ratio of dipotassium glycyrrhizate in the oral care composition is 0.1%-0.3%.

4. The oral care composition with gingival protection effect according to claim 1, characterized in that, The mass ratio of dipotassium glycyrrhizate in the oral care composition is 0.2%-0.3%.

5. The oral care composition with gingival protection effect according to claim 1, characterized in that, The oral care composition is in the form of toothpaste, gel, mouthwash, or tooth powder.

6. Application of palmitoyl hexapeptide-12 in the preparation of oral care compositions for enhancing the inhibitory effect of dipotassium glycyrrhizate on the expression of Porphyromonas gingivalis protease gene.

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