Plaque formation inhibitor
A plaque formation inhibitor using cocoyl arginine ethyl DL-pyrrolidone carboxylate targets Fusobacterium to inhibit plaque formation, effectively addressing dental caries and periodontal disease risks.
Patent Information
- Application Number
- JP2023210523
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-12-13
- Publication Date
- 2025-06-25
AI Technical Summary
Existing technologies have not effectively addressed the formation of dental plaque, which is a cause of dental caries and periodontal disease.
A plaque formation inhibitor containing cocoyl arginine ethyl DL-pyrrolidone carboxylate, specifically cocoyl arginine ethyl PCA salt, is developed to target and inhibit plaque formation by exhibiting a bactericidal effect against Fusobacterium, a key bacterium involved in the initial stage of plaque development.
The inhibitor effectively suppresses plaque formation by demonstrating a strong bactericidal action against Fusobacterium, thereby reducing the risk of dental caries and periodontal disease.
Smart Images
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Abstract
Description
Technical Field
[0001] The present disclosure relates to a plaque formation inhibitor and the like. Specifically, it relates to a plaque formation inhibitor containing cocoyl arginine ethyl · DL-pyrrolidone carboxylate and the like.
Background Art
[0002] Plaque (dental plaque) is considered to be a cause of dental caries and periodontal disease.
[0003] Generally speaking, plaque is formed as follows. That is, first, a thin film of protein derived from saliva and physiological gingival sulcus exudate called "pellicle" is formed on the surface of teeth, and facultative anaerobic bacteria such as Streptococcus attach to the tooth surface through the pellicle. Mediating bacteria such as Fusobacterium that co-aggregate with various oral bacteria attach to these initially attached bacteria, and further, late-attaching bacteria such as Porphyromonas gingivalis and Treponema denticola, which are anaerobic bacteria, attach and aggregate, and the plaque matures.
Prior Art Documents
Non-Patent Documents
[0004]
Non-Patent Document 1
Summary of the Invention
Problems to be Solved by the Invention
[0005] An object is to provide a means for suppressing the formation of plaque.
Means for Solving the Problems
[0006] The inventors have found that cocoyl arginine ethyl DL-pyrrolidone carboxylate (cocoyl arginine ethyl PCA salt) has a bactericidal effect against Fusobacterium, which is responsible for the initial stage of plaque formation, and have further improved it.
[0007] This disclosure includes, for example, the subject matter described in the following items. Item 1. A plaque formation inhibitor containing cocoyl arginine ethyl DL-pyrrolidone carboxylate (cocoyl arginine ethyl PCA salt) represented by the following general formula (1).
Chemical formula
Effect of the Invention
[0008] A plaque formation inhibitor is provided.
Brief Description of the Drawings
[0009]
Figure 1
Figure 2
Figure 3
Modes for Carrying Out the Invention
[0010] Hereinafter, each embodiment included in the present disclosure will be described in more detail. The plaque formation inhibitor included in the present disclosure contains cocoyl arginine ethyl · DL - pyrrolidone carboxylate. In this specification, the agent may be referred to as "the plaque formation inhibitor of the present disclosure" or the like.
[0011] Cocoyl arginine ethyl · DL - pyrrolidone carboxylate (in this specification, may be referred to as cocoyl arginine ethyl PCA salt, or CAE, etc.) is represented by the following general formula (1).
Chemical formula
[0012] Cocoyl arginine ethyl · DL - pyrrolidone carboxylate is such that when R is C7H 15 (n = 7) CAE, C9H 19 (n = 9) CAE, C 11 H 23 (n = 11) CAE, C 13 H 27 (n = 13) CAE, and C 15 H 31It can be at least one selected from the group consisting of CAEs where (n = 15). Coconut oil arginine ethyl DL-pyrrolidone carboxylate may be a single species or a combination of two or more species.
[0013] Among them, R is C9H 19 (n = 9), and C 11 H 23 (n = 11) is preferable, and C 11 H 23 (n = 11) is more preferable.
[0014] Coconut oil arginine ethyl DL-pyrrolidone carboxylate is not particularly limited, such as a synthetic product or a commercially available product. For example, as the commercially available coconut oil arginine ethyl DL-pyrrolidone carboxylate, "CAE" manufactured by Ajinomoto Co., Inc. etc. can be used. Also, as the coconut oil arginine ethyl DL-pyrrolidone carboxylate, a commercially available coconut oil arginine ethyl DL-pyrrolidone carboxylate further purified etc. may be used.
[0015] In the plaque formation inhibitor of the present disclosure, the total content of the above-mentioned coconut oil arginine ethyl DL-pyrrolidone carboxylate is not particularly limited, but can be appropriately set, for example, with a limit of 100% by mass.
[0016] Per the total content of the above-mentioned coconut oil arginine ethyl DL-pyrrolidone carboxylate contained in the plaque formation inhibitor of the present disclosure, in the general formula (1), the content of CAE where R is C9H 19 (n = 9) may be, for example, about 0 to 30% by mass. The upper or lower limit of this range may be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25% by mass. For example, this range may be about 1 to 25% by mass. In other words, in the plaque formation inhibitor of the present disclosure, in the general formula (1), R is C9H 19The content of CAE (n = 9) may be, for example, about 0 to 30% by mass. The upper or lower limit of this range may be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25% by mass. For example, this range may be about 1 to 25% by mass.
[0017] Per the total content of the above-mentioned cocoyl arginine ethyl DL-pyrrolidone carboxylate contained in the plaque formation inhibitor of the present disclosure, in general formula (1), R is C 11 H 23 The content of CAE (n = 11) may be, for example, about 40 to 100% by mass. The upper or lower limit of this range may be, for example, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95% by mass. For example, this range may be about 50 to 95% by mass. In other words, in the general formula (1) contained in the plaque formation inhibitor of the present disclosure, R is C 11 H 23 The content of CAE (n = 11) may be, for example, about 40 to 100% by mass. The upper or lower limit of this range may be, for example, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95% by mass. For example, this range may be about 50 to 95% by mass.
[0018] Per the total content of the above-mentioned cocoyl arginine ethyl DL-pyrrolidone carboxylate contained in the plaque formation inhibitor of the present disclosure, in general formula (1), R is C7H 15 The content of CAE (n = 7) may be, for example, about 0 to 30% by mass. The upper or lower limit of this range may be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29% by mass. For example, this range may be about 1 to 15% by mass. In other words, in the general formula (1) contained in the plaque formation inhibitor of the present disclosure, R is C7H 15The content of CAE with (n = 7) may be, for example, about 0 to 30% by mass. The upper or lower limit of this range may be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29% by mass. For example, this range may be about 1 to 15% by mass.
[0019] Per the total content of the above-mentioned cocoyl arginine ethyl DL-pyrrolidone carboxylate contained in the plaque formation inhibitor of the present disclosure, in general formula (1), R is C 13 H 27 (n = 13) The content of CAE may be, for example, about 0 to 30% by mass. The upper or lower limit of this range may be about 1, 5, 10, 15, 20, or 25% by mass. For example, this range may be about 1 to 25% by mass. In other words, in the general formula (1) contained in the plaque formation inhibitor of the present disclosure, R is C 13 H 27 (n = 13) The content of CAE may be, for example, about 0 to 30% by mass. The upper or lower limit of this range may be about 1, 5, 10, 15, 20, or 25% by mass. For example, this range may be about 1 to 25% by mass.
[0020] Per the total content of the above-mentioned cocoyl arginine ethyl DL-pyrrolidone carboxylate contained in the plaque formation inhibitor of the present disclosure, in general formula (1), R is C 15 H 31 (n = 15) The content of CAE may be, for example, about 0 to 15% by mass. The upper or lower limit of this range may be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14% by mass. For example, this range may be about 1 to 14% by mass. In other words, in the general formula (1) contained in the plaque formation inhibitor of the present disclosure, R is C 15 H 31The content of CAE with (n = 15) may be, for example, about 0 to 15% by mass. The upper or lower limit of this range may be about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14% by mass. For example, this range may be about 1 to 14% by mass.
[0021] Per the total content of the above-described cocoyl arginine ethyl DL-pyrrolidone carboxylate contained in the plaque formation inhibitor of the present disclosure, in general formula (1), when R is C7H 15 (n = 7) of CAE, C 13 H 27 (n = 13) of CAE and C 15 H 31 The total content of CAE with (n = 15), (n = 13) of CAE and C, (n = 7) of CAE, C, and H may be, for example, about 0 to 30% by mass. The upper or lower limit of this range may be about 1, 5, 10, 15, 20, or 25% by mass. For example, this range may be about 1 to 25% by mass. In other words, per the total content of the plaque formation inhibitor of the present disclosure, in general formula (1), when R is C7H 15 (n = 7) of CAE, C 13 H 27 (n = 13) of CAE and C 15 H 31 (n = 15) of CAE, C, (n = 13) of CAE and C, (n = 7) of CAE, C, and H may be, for example, about 0 to 30% by mass. The upper or lower limit of this range may be about 1, 5, 10, 15, 20, or 25% by mass. For example, this range may be about 1 to 25% by mass.
[0022] Per the total content of the above-described cocoyl arginine ethyl DL-pyrrolidone carboxylate contained in the plaque formation inhibitor of the present disclosure, in general formula (1), when R is C9H 19 (n = 9) of CAE and C 11 H 23 (n = 11) of CAE, C, and H, the total content may be, for example, about 40 to 100% by mass. The upper or lower limit of this range may be, for example, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95% by mass. For example, this range may be about 50 to 95% by mass. In other words, in the general formula (1) included in the plaque formation inhibitor of the present disclosure, R is C9H 19 (n = 9) of CAE and C 11 H 23 (n = 11) of the total content of CAE may be, for example, about 40 to 100% by mass. The upper or lower limit of the range may be, for example, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95% by mass. For example, the range may be about 50 to 95% by mass. Further, in the plaque formation inhibitor of the present disclosure, in the general formula (1), R is C9H 19 (n = 9) of CAE and C 11 H 23 (n = 11) When including CAE, for 1 part by mass of CAE where R is C9H 19 (n = 9), the content of C 11 H 23 (n = 11) CAE can be, for example, about 1 to 100 parts by mass. The upper or lower limit of the range may be, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, or 90 parts by mass. For example, the range may be about 1 to 5 parts by mass.
[0023] In the general formula (1) included in the plaque formation inhibitor of the present disclosure, R is C7H 15 (n = 7) of CAE, C 13 H 27 (n = 13) of CAE and C 15 H 31 (n = 15) of the total content of CAE, for 1 part by mass of CAE where R is C 11 H 23 (n = 11) of the content of CAE may be, for example, 1.0 part by mass or more. The upper or lower limit of the range may be, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 25, or 30 parts by mass. For example, the range may be about 1.0 to 30 parts by mass.
[0024] In the general formula (1) included in the plaque formation inhibitor of the present disclosure, R is C7H 15 (n = 7) of CAE, C 13 H27 (n = 13) CAE and C 15 H 31 For the total content of CAE of (n = 15), R is C9H with respect to 1 part by mass 19 (n = 9) CAE and C 11 H 23 (n = 11) The total content of CAE may be, for example, 1.5 parts by mass or more. The upper or lower limit of the range may be, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30 parts by mass. For example, the range may be about 1.5 to 30 parts by mass.
[0025] The plaque formation inhibitor of the present disclosure contains the above-mentioned cocoyl arginine ethyl·DL - pyrrolidone carboxylate and may further contain other components. Examples of such other components include pharmacologically or food hygienically acceptable bases, carriers, solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants, thickeners, surfactants, antioxidants, preservatives, coating agents, coloring agents, fragrances, pH adjusters, etc., and further components and materials that can be used as other foods or feeds are exemplified. These components can be used alone or in combination of two or more.
[0026] The form of the plaque formation inhibitor of the present disclosure can be, for example, solid or liquid.
[0027] The plaque formation inhibitor of the present disclosure can be prepared by a known method or a method easily conceivable from a known method. For example, it can be prepared by appropriately mixing the above-mentioned cocoyl arginine ethyl·DL - pyrrolidone carboxylate and other components as necessary.
[0028] In addition, examples of the microorganisms that form plaques targeted by the plaque formation inhibitor of the present disclosure include, for example, Fusobacterium, Aggregatibacter, and the like. Here, Fusobacterium is not particularly limited as long as it is a bacterium of the genus Fusobacterium that is a mediating bacterium between early adherent bacteria and late adherent bacteria in plaque formation, but Fusobacterium nucleatum is preferably exemplified.
[0029] In addition, since the plaque formation inhibitor of the present disclosure has a bactericidal effect on Fusobacterium, it can also be preferably used for killing Fusobacterium.
[0030] The plaque formation inhibitor of the present disclosure can be used for the preparation of an oral composition.
[0031] In this specification, “comprising” includes “consisting essentially of” and “consisting of.” The present disclosure also includes any combination of the constituent elements described in this specification.
[0032] In addition, the various characteristics (properties, structures, functions, etc.) described for each of the above-described embodiments of the present disclosure may be combined in any way when specifying the subject matter encompassed by the present disclosure. That is, the present disclosure includes all subject matters consisting of any combination of the combinable characteristics described in this specification.
Examples
[0033] The content of the present disclosure will be specifically described using the following experimental examples. However, the present disclosure is not limited thereto in any way. In the following, unless otherwise specified, the experiments are carried out under atmospheric pressure and normal temperature conditions. Also, unless otherwise specified, “%” means “mass%”.
[0034] Experimental Example 1: Examination of the Influence of Differences in Side Chain R in CAE on the Bactericidal Activity Against Fusobacterium Cetylpyridinium chloride (CPC), cocoyl arginine ethyl · DL-pyrrolidone carboxylate (cocoyl arginine ethyl PCA salt; CAE), and agents with different R (n = 7, 9, 11, 13, 15) in CAE were each dissolved in water and used as bactericidal solutions. For CPC, it was prepared to be 0.05% by mass, and for CAE and CAE with different side chain n, they were each prepared to be 0.04% by mass. In the figure, n represents the number of carbon atoms of the alkyl group represented by R in CAE represented by the general formula (1). Also, "CAE" manufactured by Ajinomoto Co., Inc. was used.
[0035] Fusobacterium nucleatum ssp. nucleatum ATCC23726 was used as the test bacterium.
[0036] The test bacterium was inoculated into 10 ml of GAM broth medium (Nissui Pharmaceutical Co., Ltd.) and anaerobically cultured at 37°C for 2 days. The culture solution was used as the test bacterium solution (adjusted to approximately 1×10 9 CFU / ml).
[0037] 200 μl of the test bacterium solution was mixed with 200 μl of the bactericidal solution. 100 μl of the mixed solution was collected 60 seconds after mixing, and 900 μl of drug-inactivated PBS to which soybean lecithin and Tween 80 were added to final concentrations of 0.07% and 0.5% respectively was added (the mixed solution was diluted 10-fold) to inactivate the bactericidal action of the bactericide. Also, the mixed solution was serially diluted with drug-inactivated PBS, and the mixed solution was diluted from 10 1 ~10 7 times (serial mixed solution dilutions).
[0038] 100 μl of each of the prepared serial mixed solution dilutions was spread on CDC anaerobic bacterium sheep blood agar medium (Nippon Becton Dickinson Co., Ltd.), anaerobically cultured at 37°C for 3 days, and the viable cell count was counted.
[0039] The results are shown in Fig. 1. Fig. 1 is a graph with the number of sterilization digits on the vertical axis. The number of sterilization digits was calculated by subtracting Log[number of viable bacteria (CFU / ml)] when using the bactericide solution from Log[number of viable bacteria (CFU / ml)] when using water as a control. A higher number of sterilization digits indicates a higher sterilization effect. As shown in Fig. 1, CAE had a higher sterilization effect than CPC. In particular, it was found that CAE with R being C9H 19 (n = 9) or C 11 H 23 (n = 11) had a high sterilization effect and showed a stronger sterilization effect than CPC.
[0040] Experimental Example 2: Examination of the influence of the composition ratio of n = 11 in CAE on the bactericidal effect against Fusobacterium In the same manner as in Experimental Example 1, the bactericidal effects of various bactericide solutions were evaluated. The bactericide solutions were prepared by mixing CAE (the same as that used in Experimental Example 1) and CAE with n = 11, and dissolving them in water so that the CAE with n = 11 had each concentration. The specific preparation method is described at the bottom of Table 1.
[0041] Table 1 shows the composition ratios of each chain length in each bactericide solution. All the aqueous solutions had a concentration where the solute was approximated to 0.04% (w / w). Analysis of the ratio of the chain lengths contained in CAE revealed that it was a mixture containing 55.0% of CAE with n = 11, 24.0% of CAE with n = 13, 8.0% of CAE with n = 7, 9.0% of CAE with n = 9, and 4.0% of CAE with n = 15.
[0042]
Table 1
[0043] As shown in Fig. 2, it was found that as the composition ratio of CAE with C 11 H 23 (n = 11) increased, the bactericidal effect increased.
[0044] Experimental Example 3: Examination of the influence of the composition ratio of n = 11 in CAE on the bactericidal effect against Fusobacterium The bactericidal effects of various bactericidal agent solutions were evaluated in the same manner as in Experimental Example 1, except that the test bacterium was changed to Fusobacterium nucleatum ssp. nucleatum ATCC25586. The bactericidal agent solutions were prepared by dissolving in water bactericidal agent solutions with different composition ratios of CAE (the same as those used in Experimental Example 1) and CAE with n = 11, which were mixed (A, B, D). For E, bactericidal agent solutions were prepared by mixing CAE with n = 9 and CAE with n = 11, respectively.
[0045] Table 2 shows the composition ratios of each chain length in each bactericidal agent solution. The concentration of each aqueous solution approximated 0.04% (w / w) of the solute.
[0046]
Table 2
[0047] As shown in Figure 3, it was found that the bactericidal effect increased as the concentration of CAE with C 11 H 23 (n = 11) increased. It was also found that E composed only of n = 9 and n = 11 showed a high bactericidal effect.
Claims
1. A plaque formation inhibitor containing cocoyl arginine ethyl DL-pyrrolidone carboxylate (cocoyl arginine ethyl PCA salt) represented by the following general formula (1). 【Chemical Formula 1】 [wherein, R represents C ｎ H ２ｎ＋１ and n represents 7, 9, 11, 13, or 15.]
2. In general formula (1), R is C ９ H １９ The plaque formation inhibitor according to claim 1, comprising at least coixoyl arginine ethyl PCA salt in which is, and / or C １１ H ２３ coixoyl arginine ethyl PCA salt in which is.
3. Based on the total content of the cocoyl arginine ethyl PCA salt represented by the general formula (1) contained R is C ９ H １９ The content of the coiled arginine ethyl PCA salt which is is 0 to 30% by mass, and / or R is C １１ H ２３ The content of the coiled arginine ethyl PCA salt which is is 40% by mass or more; and R is C ７ H １５ Cocoyl arginine ethyl PCA salt which is, C １３ H ２７ Cocoyl arginine ethyl PCA salt which is, and C １５ H ３１ The total content of cocoyl arginine ethyl PCA salt which is is 0 to 30% by mass, The plaque formation inhibitor according to claim 1 or 2.