JP6953811B2 - Oral composition and growth promoter for indigenous bacteria in the oral cavity - Google Patents

Description

The present invention relates to an agent for promoting the growth of indigenous bacteria in the oral cavity and an oral composition containing the same.

Current oral care is aimed at preventing oral diseases such as dental caries and periodontal disease. Therefore, technologies such as sterilization of pathogenic bacteria and pathogenic bacteria biofilms that cause dental caries and periodontal disease, strengthening of dentin and gingiva, and anti-inflammatory have been developed and commercialized.
On the other hand, indigenous bacteria that coexist in humans are greatly involved in maintaining and promoting human health. It has been reported that indigenous bacteria in the intestine are important for human intestinal regulation, and that they are involved in improving immunity and obesity. In addition, some lactic acid bacteria have been used as probiotics as products represented by yogurt.

As for oral bacteria, it is known that indigenous bacteria such as Streptococcus and Rothia have an antibacterial action against pathogenic bacteria. Oral diseases are not infections of pathogenic bacteria alone, but multiple bacterial infections involving indigenous bacteria represented by these, and it is considered that indigenous bacteria other than pathogenic bacteria are involved in the onset and progression of oral diseases. Be done. Furthermore, the relationship between oral bacteria and enteritis and Alzheimer's disease has been reported, and it is beginning to be shown that oral bacteria may be involved not only in the oral cavity but also in human general health. Therefore, it is important for oral care not only to eliminate pathogenic bacteria in the oral cavity, but also to maintain indigenous bacteria and keep them in a particularly healthy state. However, sterilization, which is the current mainstream of bacterial control, has a problem of sterilizing and removing not only pathogenic bacteria but also other indigenous bacteria. Therefore, antibodies have been studied as a technique for selectively suppressing only pathogens, but sufficient effects have not been obtained.

On the other hand, phospholipid lecithins and lysolecithins contained in soybeans, egg yolks, etc., such as phosphatidylcholine and lysophosphatidylcholine, may be added to oral compositions as surfactants or have antibacterial activity. It is also known.
Patent Document 1 (Patent No. 2794072) proposes that phosphatidylglycerol and / or lysophosphatidylglycerol has a good antibacterial action and is effective as an antibacterial agent for cosmetics and the like. Patent Document 2 (Japanese Unexamined Patent Publication No. 7-149619) states that the surfactant lysophosphatidylcholine is effective in preventing a decrease in the bactericidal activity of a phenolic bactericidal agent in an oral composition, and Patent Document 3 (Japanese Unexamined Patent Publication No. 2014-). 88333) proposes that lysophosphatidic acid and other lysophospholipids have an alveolar bone absorption inhibitory effect and an inflammatory cytokine secretion inhibitory effect, and are effective in preventing or ameliorating oropharyngeal diseases and periodontal diseases. doing. Patent Document 4 (Japanese Unexamined Patent Publication No. 7-67552) discloses that acidic phospholipids or their lysates are excellent in reducing the bitterness of bitterness substances such as cosmetics as the active ingredient of the bitterness reducing agent.

Japanese Patent No. 2794072 Japanese Unexamined Patent Publication No. 7-149619 Japanese Unexamined Patent Publication No. 2014-88333 Japanese Unexamined Patent Publication No. 7-67552

Therefore, it has been desired to develop a new technique for promoting the growth of indigenous bacteria in the oral cavity, which is also effective for maintaining the health of indigenous bacteria.

The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a growth-promoting agent for indigenous bacteria in the oral cavity and an oral composition containing the same, which has an excellent effect of promoting the growth of indigenous bacteria in the oral cavity. do.

As a result of diligent studies to achieve the above object, the present inventors have found a compound represented by the structural formula (1) or a salt thereof, which will be described later, and a compound represented by the structural formula (2) or a salt thereof. When used in combination at a specific ratio, it exerts an excellent effect of promoting the growth of indigenous bacteria in the oral cavity, and it was found that the oral composition containing this combination system is excellent in promoting the growth of indigenous bacteria in the oral cavity. This has led to the present invention.

In the present invention, a compound represented by (A) structural formula (1), particularly a specific lysophosphatidic acid or a derivative thereof or a salt thereof, and a compound represented by (B) structural formula (2), particularly specific When combined with phosphatidic acid or a derivative thereof or a salt thereof, the effect of promoting the growth of indigenous bacteria in the oral cavity is excellent within a specific range of the mass ratio of (A) / (B), and in particular, indigenous bacteria other than pathogenic bacteria are present. It has a previously unknown effect on bacteria, especially the bacteria of the genus Streptococcus of the Mitis group, which promotes their growth rather than antibacterial action. As a result, the combination of the components (A) and (B) according to the present invention can be used for a new application as a growth promoter for indigenous bacteria in the oral cavity, and is suitably used as an active ingredient for an oral composition. Can be done.
More specifically, it is known that some lecithins and lysolecithins have antibacterial activity, but with respect to microorganisms such as bacteria, the action of antibacterial agents and the like is complicated, and they act on certain microorganisms. However, it cannot be said that it acts on other microorganisms in the same way. On the other hand, in the present invention, as shown in the comparative example described later, the component (A) alone exhibits an antibacterial effect against pathogenic bacteria (porphyromonas gingivalis, a periodontopathogenic bacterium), but other than that. The effect of promoting the growth of the indigenous bacteria (Bacteria of the genus Streptococcus of the Mitis group) was not observed (Comparative Example 1), and the effect of promoting the growth of the above-mentioned indigenous bacteria was not observed even with the component (B) alone. (Comparative example 2). However, as shown in Examples described later, when the components (A) and (B) are combined in a specific ratio, surprisingly, they have an excellent effect of promoting the growth of the above-mentioned indigenous bacteria, and also. It can also have an antibacterial effect against pathogenic bacteria. Such an action and effect of the present invention is inferior when the amount ratio of both components is inappropriate even if the components (A) and (B) are combined (Comparative Examples 3 and 4), and (A) / ( B) The ratio is specific and exceptionally remarkable, which can be obtained only within a specific range.

Among the hundreds of types of bacteria that grow in the oral cavity, the pathogenic bacteria are Porphyromonas gingivalis, which is the causative agent of periodontal disease, and Streptococcus mutans, which is the causative agent of caries. There are only a few types of bacteria represented by (Streptococcus mutans). Most of the rest are represented by Streptococcus gordonii, Streptococcus mitis, Streptococcus tyris, Streptococcus spheres such as Streptococcus spheres (Streptococcus spheres), which are usually not pathogenic to humans. ) Bacteria, Streptococcus genus such as Veillonella parvula, Streptococcus genus such as Neisseria subflava, which are usually non-pathogenic indigenous bacteria in the oral cavity. In particular, the Streptococcus genus bacteria of the Mitis Group are known to be involved in the elimination of pathogenic bacteria that cause periodontal disease and the like. In the present invention, such indigenous bacteria in the oral cavity, particularly Streptococcus spp. In the Mitis group, have an excellent growth promoting effect and also have an antibacterial effect against pathogenic bacteria, so that the balance of the indigenous bacteria in the oral cavity is balanced. It is also possible to prevent it from collapsing and becoming pathogenic and to maintain a healthy condition.
In Patent Document 1, lysophosphatidylglycerol and / or phosphatidylglycerol has been found to have antibacterial properties against pathogenic bacteria such as food poisoning bacteria, acne bacteria, and dental caries bacteria, and its efficacy against other bacteria is not described and is unknown. Patent Document 1 has a different purpose and a target bacterium from at least the growth-promoting action of the bacterium according to the present invention, which is the opposite action to the antibacterial action, particularly the growth-promoting action on the indigenous bacteria in the oral cavity.

（式（１）中、Ｒ¹及びＲ²は、いずれか一方が−ＯＨ、他方が−ＯＣＯＲ（Ｒは、炭素数１１〜２３の飽和又は不飽和の直鎖状又は分岐鎖状の炭化水素基）であり、Ｘ¹は−Ｈ、−Ｃ₂Ｈ₄Ｎ⁺（ＣＨ₃）₃、−Ｃ₂Ｈ₃（Ｎ⁺Ｈ₃）ＣＯＯＨ、−Ｃ₂Ｈ₄Ｎ⁺Ｈ₃、−Ｃ₆Ｈ₆（ＯＨ）₅、又は−Ｃ₂Ｈ₃（ＯＨ）ＣＨ₂（ＯＨ）である。）
で表される化合物又はその塩と、
（Ｂ）下記構造式（２）

（式（２）中、Ｒ³及びＲ⁴は、それぞれ互いに同一でも異なってもよく、−ＯＣＯＲ⁵（Ｒ⁵は、炭素数１１〜２３の飽和又は不飽和の直鎖状又は分岐鎖状の炭化水素基）であり、Ｘ²は−Ｈ、−Ｃ₂Ｈ₄Ｎ⁺（ＣＨ₃）₃、−Ｃ₂Ｈ₃（Ｎ⁺Ｈ₃）ＣＯＯＨ、−Ｃ₂Ｈ₄Ｎ⁺Ｈ₃、又は−Ｃ₆Ｈ₆（ＯＨ）₅である。）
で表される化合物又はその塩と
を含有し、（Ｂ）成分に対する（Ａ）成分の比率を示す（Ａ）／（Ｂ）が、質量比で０．１〜１０であることを特徴とする口腔用組成物。
〔２〕
（Ａ）／（Ｂ）が、質量比で０．２〜５である〔１〕に記載の口腔用組成物。
〔３〕
上記式（１）で示される化合物が、リゾホスファチジン酸、リゾホスファチジルコリン、リゾホスファチジルセリン、リゾホスファチジルエタノールアミン、リゾホスファチジルイノシトール及びリゾホスファチジルグリセリンから選ばれる１種以上のリゾホスファチジン酸又はその誘導体である〔１〕又は〔２〕に記載の口腔用組成物。
〔４〕
上記式（２）で示される化合物が、ホスファチジン酸、ホスファチジルコリン、ホスファチジルセリン、ホスファチジルエタノールアミン及びホスファチジルイノシトールから選ばれる１種以上のホスファチジン酸又はその誘導体である〔１〕〜〔３〕のいずれかに記載の口腔用組成物。
〔５〕
（Ａ）成分を０．００１〜１０質量％、（Ｂ）成分を０．００１〜１０質量％含有する〔１〕〜〔４〕のいずれかに記載の口腔用組成物。
〔６〕
口腔内常在菌を増加させるための口腔用製剤である〔１〕〜〔５〕のいずれかに記載の口腔用組成物。
〔７〕
（Ａ）上記式（１）で表される化合物又はその塩と、（Ｂ）上記式（２）で表される化合物又はその塩とからなる口腔内常在菌の生育促進剤。
〔８〕
（Ｂ）成分に対する（Ａ）成分の比率を示す（Ａ）／（Ｂ）が、質量比で０．１〜１０である〔７〕に記載の口腔内常在菌の生育促進剤。
〔９〕
口腔内常在菌が、ストレプトコッカス ミティス、ストレプトコッカス オラリス及びストレプトコッカス ゴルドニアイから選ばれる１種以上のミティスグループのストレプトコッカス属細菌である〔７〕又は〔８〕に記載の口腔内常在菌の生育促進剤。 Therefore, the present invention provides the following oral compositions and growth promoters for indigenous bacteria in the oral cavity.
[1]
(A) The following structural formula (1)

(In the formula (1), ^one of R 1 and R ² is -OH and the other is -OCOR (R is a saturated or unsaturated linear or branched hydrocarbon having 11 to 23 carbon atoms. Group), where X ¹ is -H, -C ₂ H ₄ N ⁺ (CH ₃ ) ₃ , -C ₂ H ₃ (N ⁺ H ₃ ) COOH, -C ₂ H ₄ N ⁺ H ₃ , -C ₆ H ₆ (OH) ₅ or -C ₂ H ₃ (OH) CH ₂ (OH).)
The compound represented by or a salt thereof and
(B) The following structural formula (2)

(In formula (2), R ³ and R ⁴ may be the same or different from each other, and -OCOR ⁵ (R ⁵ is a saturated or unsaturated linear or branched chain having 11 to 23 carbon atoms. Hydrocarbon group), where X ² is -H, -C ₂ H ₄ N ⁺ (CH ₃ ) ₃ , -C ₂ H ₃ (N ⁺ H ₃ ) COOH, -C ₂ H ₄ N ⁺ H ₃ , or -C ₆ H ₆ (OH) ₅ )
(A) / (B), which contains the compound represented by (1) or a salt thereof and indicates the ratio of the component (A) to the component (B), is 0.1 to 10 by mass ratio. Oral composition.
[2]
The oral composition according to [1], wherein (A) / (B) is 0.2 to 5 in mass ratio.
[3]
The compound represented by the above formula (1) is one or more lysophosphatidic acids selected from lysophosphatidic acid, lysophosphatidylcholine, lysophosphatidylserine, lysophosphatidylethanolamine, lysophosphatidylinositol and lysophosphatidylglycerin or a derivative thereof [ The oral composition according to 1] or [2].
[4]
The compound represented by the above formula (2) is any one or more of phosphatidic acid selected from phosphatidic acid, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and phosphatidylinositol or a derivative thereof [1] to [3]. The above-mentioned oral composition.
[5]
The oral composition according to any one of [1] to [4], which contains 0.001 to 10% by mass of the component (A) and 0.001 to 10% by mass of the component (B).
[6]
The oral composition according to any one of [1] to [5], which is an oral preparation for increasing indigenous bacteria in the oral cavity.
[7]
An agent for promoting the growth of indigenous bacteria in the oral cavity, which comprises (A) a compound represented by the above formula (1) or a salt thereof, and (B) a compound represented by the above formula (2) or a salt thereof.
[8]
The growth promoter for indigenous bacteria in the oral cavity according to [7], wherein (A) / (B) indicating the ratio of the component (A) to the component (B) is 0.1 to 10 by mass.
[9]
The growth promoter of the indigenous bacteria in the oral cavity according to [7] or [8], wherein the indigenous bacteria in the oral cavity are Streptococcus spp. ..

According to the present invention, it is possible to provide a growth-promoting agent for indigenous bacteria in the oral cavity and an oral composition containing the same, which is excellent in promoting the growth of indigenous bacteria in the oral cavity. These are also effective in maintaining indigenous bacteria in the oral cavity.

Hereinafter, the present invention will be described in more detail. The growth-promoting agent for indigenous bacteria in the oral cavity of the present invention comprises (A) a compound represented by the structural formula (1) or a salt thereof, and (B) a compound represented by the structural formula (2) or a salt thereof. Use as an active ingredient.

In the present invention, the component (A) is a compound represented by the following structural formula (1) or a salt thereof. These act as growth promoters for indigenous bacteria in the oral cavity when used in combination with the component (B). It also acts as an antibacterial agent for pathogenic bacteria.

（式（１）中、Ｒ¹及びＲ²は、いずれか一方が−ＯＨ、他方が−ＯＣＯＲ（Ｒは、炭素数１１〜２３の飽和又は不飽和の直鎖状又は分岐鎖状の炭化水素基）であり、Ｘ¹は−Ｈ、−Ｃ₂Ｈ₄Ｎ⁺（ＣＨ₃）₃、−Ｃ₂Ｈ₃（Ｎ⁺Ｈ₃）ＣＯＯＨ、−Ｃ₂Ｈ₄Ｎ⁺Ｈ₃、−Ｃ₆Ｈ₆（ＯＨ）₅、又は−Ｃ₂Ｈ₃（ＯＨ）ＣＨ₂（ＯＨ）である。）

(In the formula (1), ^one of R 1 and R ² is -OH and the other is -OCOR (R is a saturated or unsaturated linear or branched hydrocarbon having 11 to 23 carbon atoms. Group), where X ¹ is -H, -C ₂ H ₄ N ⁺ (CH ₃ ) ₃ , -C ₂ H ₃ (N ⁺ H ₃ ) COOH, -C ₂ H ₄ N ⁺ H ₃ , -C ₆ H ₆ (OH) ₅ or -C ₂ H ₃ (OH) CH ₂ (OH).)

In -OCOR in the above formula (1), R is a saturated or unsaturated linear or branched hydrocarbon group having 11 to 23 carbon atoms, preferably 15 to 21 carbon atoms. Specific examples of −OCOR include lauric acid residue (CH ₃ (CH ₂ ) ₁₀ COO −), myristic acid residue (CH ₃ (CH ₂ ) ₁₂ COO −), and palmitic acid residue (CH ₃ (CH _2)). ) ₁₄ COO-), stearic acid residue (CH ₃ (CH ₂ ) ₁₆ COO-), arachidic acid residue (CH ₃ (CH ₂ ) ₁₈ COO-), bechenic acid residue (CH ₃ (CH ₂ ) ₂₀₎ COO-), lignoceric acid residue (CH ₃ (CH ₂ ) ₂₂ COO-), palmitoleic acid residue (CH ₃ (CH ₂ ) ₅ CH = CH (CH ₂ ) ₇ COO-), oleic acid residue (CH) ₃ (CH ₂ ) ₇ CH = CH (CH ₂ ) ₇ COO-), linoleic acid residue (CH ₃ (CH ₂ ) ₄ (CH = CH CH ₂ ) ₂ (CH ₂ ) ₆ COO-), γ-linolenic acid residue Group (CH ₃ (CH ₂ ) ₄ (CH = CH CH ₂ ) ₃ (CH ₂ ) ₃ COO −), α-linoleic acid residue (CH ₃ (CH ₂ ) (CH = CH CH ₂ ) ₃ (CH ₂ ) ₆ COO -), Erucic acid residue (CH ₃ (CH ₂ ) ₇ CH = CH (CH ₂ ) ₁₁ COO-), Eicopentaenoic acid residue (CH ₃ CH ₂ (CH = CH CH ₂ ) ₅ (CH ₂ ) ₂ COO-), docosahexaenoic acid residue (CH ₃ CH ₂ (CH = CH CH ₂ ) ₆ CH ₂ COO-), etc., especially palmitate residue (CH ₃ (CH ₂ ) ₁₄ COO-), stearic acid residue Group (CH ₃ (CH ₂ ) ₁₆ COO-), oleic acid residue (CH ₃ (CH ₂ ) ₇ CH = CH (CH ₂ ) ₇ COO-), linoleic acid residue (CH ₃ (CH ₂ ) ₄ ( CH = CHCH ₂ ) ₂ (CH ₂ ) ₆ COO−) is preferred.

As the compound represented by the above formula (1), lysophosphatidic acid or a derivative thereof is specifically preferable, and for example, lysophosphatidic acid (LPA, X ¹ ; -H), lysophosphatidylcholine (LPC, X ¹ ; -C _2). H ₄ N ⁺ (CH ₃ ) ₃ ), lysophosphatidylserine (LPS, X ¹ ; -C ₂ H ₃ (N ⁺ H ₃ ) COOH), lysophosphatidylethanolamine (LPE, X ¹ ; -C ₂ H ₄ N) ⁺ H ₃ ), lysophosphatidyl inositol (LPI, X ¹ ; -C ₆ H ₆ (OH) ₅ ), lysophosphatidyl glycerin (LPG, X ¹ ; -C ₂ H ₃ (OH) CH ₂ (OH)), etc. Can be mentioned. These may be used alone or in combination of two or more. Among them, lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), lysophosphatidylinositol (LPI), especially lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC). , Lysophosphatidylethanolamine (LPE), particularly lysophosphatidylcholine (LPC), is preferable in terms of the effect of promoting the growth of indigenous bacteria in the oral cavity. The compound may be a salt, and examples of the salt include an alkali metal salt such as a sodium salt and an ammonium salt.

As the component (A), egg yolk lysolecithin LPL-1, egg yolk lecithin LPL-20W, egg yolk lecithin LPL-20S (manufactured by Kewpie Co., Ltd.), SLP-white lyso, SLP-LPC70, SLP-white lyso H, SLP- Commercially available products such as LPC70H (manufactured by Tsuji Oil Co., Ltd.) and LIPOID RLPC20 (manufactured by H. Holstein) can be used.

The component (B) is a compound represented by the following structural formula (2) or a salt thereof. These act as growth promoters for indigenous bacteria in the oral cavity when used in combination with the component (A). It also contributes to an appropriate suppression of the antibacterial action of the component (A).

（式（２）中、Ｒ³及びＲ⁴は、それぞれ互いに同一でも異なってもよく、−ＯＣＯＲ⁵（Ｒ⁵は、炭素数１１〜２３の飽和又は不飽和の直鎖状又は分岐鎖状の炭化水素基）であり、Ｘ²は−Ｈ、−Ｃ₂Ｈ₄Ｎ⁺（ＣＨ₃）₃、−Ｃ₂Ｈ₃（Ｎ⁺Ｈ₃）ＣＯＯＨ、−Ｃ₂Ｈ₄Ｎ⁺Ｈ₃、又は−Ｃ₆Ｈ₆（ＯＨ）₅である。）

(In formula (2), R ³ and R ⁴ may be the same or different from each other, and -OCOR ⁵ (R ⁵ is a saturated or unsaturated linear or branched chain having 11 to 23 carbon atoms. Hydrocarbon group), where X ² is -H, -C ₂ H ₄ N ⁺ (CH ₃ ) ₃ , -C ₂ H ₃ (N ⁺ H ₃ ) COOH, -C ₂ H ₄ N ⁺ H ₃ , or -C ₆ H ₆ (OH) ₅ )

^{In −OCOR 5} in the above formula (2) ^{, R 5} is a saturated or unsaturated linear or branched hydrocarbon group having 11 to 23 carbon atoms, preferably 15 to 21 carbon atoms. Examples of -OCOR ^5, lauric acid residue _{(CH 3 (CH 2) 10} COO-), myristic acid residue _{(CH 3 (CH 2) 12} COO-), palmitic acid residues (CH ₃ (CH ₂ ) ₁₄ COO-), stearic acid residue (CH ₃ (CH ₂ ) ₁₆ COO-), arachidic acid residue (CH ₃ (CH ₂ ) ₁₈ COO-), bechenic acid residue (CH ₃ (CH ₂ )) ₂₀ COO-), lignoceric acid residue (CH ₃ (CH ₂ ) ₂₂ COO-), palmitoleic acid residue (CH ₃ (CH ₂ ) ₅ CH = CH (CH ₂ ) ₇ COO-), oleic acid residue (CH 3 (CH 2) 7 COO-), oleic acid residue (CH 3 (CH 2) 5 CH = CH (CH 2) 7 COO-) CH ₃ (CH ₂ ) ₇ CH = CH (CH ₂ ) ₇ COO-), linoleic acid residue (CH ₃ (CH ₂ ) ₄ (CH = CH CH ₂ ) ₂ (CH ₂ ) ₆ COO-), γ-linolenic acid Residues (CH ₃ (CH ₂ ) ₄ (CH = CH CH ₂ ) ₃ (CH ₂ ) ₃ COO−), α-linolenic acid residues (CH ₃ (CH ₂ ) (CH = CH CH ₂ ) ₃ (CH ₂ ) ₆ COO-), oleic acid residue (CH ₃ (CH ₂ ) ₇ CH = CH (CH ₂ ) ₁₁ COO-), eicopentaenoic acid residue (CH ₃ CH ₂ (CH = CH CH ₂ ) ₅ (CH ₂ )) ₂ COO-), docosahexaenoic acid residue (CH ₃ CH ₂ (CH = CH CH ₂ ) ₆ CH ₂ COO-), etc., especially palmitic acid residue (CH ₃ (CH ₂ ) ₁₄ COO-), stearic acid Residues (CH ₃ (CH ₂ ) ₁₆ COO-), oleic acid residues (CH ₃ (CH ₂ ) ₇ CH = CH (CH ₂ ) ₇ COO-), linoleic acid residues (CH ₃ (CH ₂ ) ₄₎ (CH = CHCH ₂ ) ₂ (CH ₂ ) ₆ COO−) is preferable.

Specifically, the compound represented by the above formula (2) is preferably phosphatidylic acid or a derivative thereof, for example, phosphatidylic acid (PA, X ² ; -H), phosphatidylcholine (PC, X ² ; -C ₂ H _4). N ⁺ (CH ₃ ) ₃ ), phosphatidylserine (PS, X ² ; -C ₂ H ₃ (N ⁺ H ₃ ) COOH), phosphatidylethanolamine (PE, X ² ; -C ₂ H ₄ N ⁺ H ₃ ) , Phosphatidylinositol (PI, X ² ; -C ₆ H ₆ (OH) ₅ ) and the like. These may be used individually by 1 type or in combination of 2 or more type. Of these, phosphatidylic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and particularly phosphatidylcholine (PC) are preferable in terms of the effect of promoting the growth of indigenous bacteria in the oral cavity. The compound may be a salt, and examples of the salt include an alkali metal salt such as a sodium salt and an ammonium salt.

As the component (B), egg yolk lecithin PL-100P, egg yolk lecithin PL-30S (manufactured by Kewpie Co., Ltd.), SLP-white, SLP-PC70, SLP-white H, SLP-PC70H (manufactured by Tsuji Oil Co., Ltd.) , COATSOME NC-21 (manufactured by NOF CORPORATION) and other commercially available products can be used.

In the present invention, (A) / (B) indicating the amount ratio of the component (A) to the component (B) is 0.1 to 10 as a mass ratio, preferably 0.2 to 5, and more preferably 0. .25-5. If it is less than 0.1, the effect of promoting the growth of indigenous bacteria in the oral cavity is inferior. If it exceeds 10, the antibacterial effect of the component (A) is not suppressed and even indigenous bacteria other than pathogenic bacteria are antibacterial, and the growth promoting effect of the indigenous bacteria in the oral cavity is inferior.

Since the oral composition of the present invention has an excellent growth promoting action of indigenous bacteria in the oral cavity and also has an antibacterial action of indigenous bacteria in the oral cavity, it increases the indigenous bacteria in the oral cavity and / or its ratio (resident in the oral cavity). It has the effect of increasing the number of bacteria and / or the effect of increasing the ratio of the number of indigenous bacteria in the oral cavity to the number of pathogenic bacteria in the oral cavity. Therefore, it can be prepared as various oral preparations for increasing the ratio of indigenous bacteria in the oral cavity and / or the ratio thereof, and further as various oral preparations for making the oral cavity predominantly indigenous bacteria.
Specific oral preparations include solids, liquids (including those in which some or all of the ingredients are dispersed or suspended without solubilization; the same applies hereinafter), pastes, gels, etc. However, for example, orally disintegrating tablets, chewable tablets, troches, candy and other tablets, granules and other granules, chewing gum, gummy, beverages, etc. It can be used in various dosage forms such as mouthwash, mouth spray, mouth refreshing agent, and gel for application. The oral preparation may be a concentrated type, and may be prepared as a concentrated powdered beverage that can be appropriately diluted with water and used, for example.

In this case, the blending amount of the component (A) is preferably 0.001 to 10% (mass%, the same applies hereinafter) of the entire composition, more preferably 0.01 to 5%, still more preferably 0.01 to 1. %. When it is 0.001% or more, the growth promoting effect of indigenous bacteria in the oral cavity is sufficiently excellent, and when it is 10% or less, the growth promoting effect is sufficiently maintained. If too much is added, the antibacterial action of the component (A) cannot be suppressed, and the effect of promoting the growth of indigenous bacteria in the oral cavity may be inferior.

The blending amount of the component (B) is not particularly limited, but is preferably 0.001 to 10%, more preferably 0.01 to 5%, still more preferably 0.01 to 1% of the entire composition. .. When it is 0.001% or more, the growth promoting effect of indigenous bacteria in the oral cavity is sufficiently excellent, and when it is 10% or less, the growth promoting effect is sufficiently maintained. If too much is added, the antibacterial action of the composition against pathogenic bacteria is reduced, the bacterial flora balance in the oral cavity is inclined to the predominance of pathogenic bacteria, and the effect of maintaining a healthy state may be weakened.

Further, in the oral composition of the present invention, known components other than the above-mentioned components (A) and (B) can be blended as necessary according to the purpose of use, dosage form and the like. For example, a dentifrice such as dentifrice can be prepared by a usual method by blending an abrasive, a thickener, a binder, a surfactant, a sweetener, a preservative, a coloring agent, a fragrance, an active ingredient, and the like. ..

Examples of the abrasive include silica-based abrasives such as precipitated silica, aluminosilicate and zirconosilicate, calcium phosphate-based abrasives, calcium carbonate and the like (the blending amount is usually 2 to 50%, particularly 10 to 40%). ).

Examples of the viscous agent include sugar alcohols such as sorbitol and xylit, and polyhydric alcohols such as glycerin, propylene glycol, and polyethylene glycol having an average molecular weight of 160 to 4000 (average molecular weight described in the Pharmaceutical Non-Pharmaceutical Raw Material Standard 2006). The blending amount is usually 5 to 50%).

Examples of the binder include cellulose derivatives such as sodium carboxymethyl cellulose, hydroxyethyl cellulose and hydroxypropyl cellulose, alginic acid or its derivatives such as sodium alginate, gums such as xanthan gum, and organic binders such as carrageenan, polyvinyl alcohol and sodium polyacrylate. Examples thereof include inorganic binders such as agents, gelling silica, gelling aluminum silica, bee gum, and laponite (the blending amount is usually 0.1 to 10%).

Examples of the surfactant include anionic surfactants and nonionic surfactants.
Examples of the anionic surfactant include alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, and acyl sarcosate salts.
Nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters, sugar alcohol fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil and the like. Examples thereof include polyoxyethylene higher alcohol ethers such as polyoxyethylene fatty acid ester and polyoxyethylene lauryl ether.
The blending amount of the surfactant is usually 0.01 to 10%, particularly 0.01 to 5%.

Examples of the sweetener include sodium saccharin, and examples of the preservative include paraoxybenzoic acid ester such as methyl paraoxybenzoate, benzoic acid such as sodium benzoate, or a salt thereof.
Examples of the colorant include Blue No. 1, Yellow No. 4, Titanium Dioxide and the like.

As fragrances, peppermint oil, sparemint oil, anis oil, eucalyptus oil, winter green oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamon oil, coriander oil, mandarin oil, Lime oil, lavender oil, rosemary oil, laurel oil, camomill oil, caraway oil, majorum oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweetie Natural fragrances such as oil, yuzu oil, iris concrete, absolute peppermint, absolute rose, orange flower, and processing of these natural fragrances (front reservoir cut, rear reservoir cut, distilling, liquid extraction, essence, powder Perfume (scented, etc.) and menthol, carboxylic, anator, cineole, methyl salicylate, synamic aldehyde, eugenol, 3-l-mentoxypropane-1,2-diol, timol, linalol, linalyl acetate, limonene, Menton, Menthylacetate, N-Substituted-Peppermint-3-Carboxamide, Pinen, Octylaldehyde, Citral, Pregon, Calvia Acetate, Anisaldehyde, Ethylacetate, Ethylbutyrate, Allylcyclohexanepropionate, Methylanthranilate, Ethyl Single fragrances such as methylphenylglycidate, vanillin, undecalactone, hexanal, butanol, isoamyl alcohol, hexenol, dimethylsulfide, cycloten, furfural, trimethylpyrazine, ethyllactate, ethylthioacetate, strawberry flavor, apple flavor, banana Known fragrance materials used in oral compositions, such as flavors, pineapple flavors, grape flavors, mango flavors, butter flavors, milk flavors, fruit mix flavors, tropical fruit flavors and the like, can be used in combination. The blending amount is not particularly limited, but usually 0.000001 to 1% is preferable for the above-mentioned fragrance material, and 0.1 to 2% is preferable for the fragrance for fragrance using the above fragrance material.

Active ingredients include fluorine-containing compounds such as sodium fluoride and sodium monofluorophosphate, anti-inflammatory agents, enzymes such as dextranase, water-soluble phosphate compounds and copper compounds, vitamins, plant extracts, and plaque prevention. Examples include agents and anti-plaque agents. The active ingredient can be blended in an effective amount within a range that does not interfere with the effects of the present invention.

Hereinafter, the present invention will be specifically described with reference to Examples, Comparative Examples, and Formulation Examples, but the present invention is not limited to the following Examples. In the following examples,% indicates mass% unless otherwise specified. In addition, the blending amount is a net conversion value (hereinafter, the same applies).

[Examples, comparative examples]
The compounds shown in Table 1 are used as the components (A) and (B), and oral compositions (mouthwashes) having the compositions shown in Tables 2 to 4 are prepared by a conventional method and evaluated by the experimental method shown below. bottom. The results are also shown in Tables 2-4.

<Experimental method>
Using the indigenous bacteria in the oral cavity and periodontal pathogens described below, each bacterium was prepared in 200 μL of tryptic soy medium (TS medium, manufactured by Becton and Dickinson) to which an evaluation sample or distilled water (control) was added, and a 96-well plate. Was aerobically cultured at 37 ° C. for 12 hours. The amount of bacterial growth was measured at a turbidity with a wavelength of 550 nm, and the degree of bacterial growth was evaluated. Before measuring the turbidity, the plate was shaken to stir the culture solution.
The growth degree of the bacterium was taken as a relative value Tr (Ts / Tc) of the turbidity (Ts) of the turbidity (Ts) of the bacterium culture solution to which the evaluation sample was added with respect to the turbidity (Tc) of the bacterium culture solution to which the control (distilled water) was added. That is, when Tr is larger than 1.0, growth is promoted, and when Tr is smaller than 1.0, growth is suppressed (with antibacterial effect).

Evaluation Criteria Growth-promoting effect of indigenous bacteria in the oral cavity Tr (Ts / Tc)
⊚: 1.5 or more ○: 1.1 or more and less than 1.5 Δ: more than 1.0 and less than 1.1 ×: 1.0 or less Antibacterial effect of periodontal disease bacteria Tr (Ts / Tc)
⊚: less than 0.05 ○: 0.05 or more and less than 0.2 Δ: 0.2 or more and less than 0.5 ×: 0.5 or more

The bacteria used for the evaluation were the following bacterial species purchased from the American Type Culture Collection (hereinafter abbreviated as ATCC).
Indigenous bacteria in the oral cavity:
Streptococcus mitis ATCC 47456 (hereinafter abbreviated as S. mitis)
Streptococcus olalis ATCC 9811 (hereinafter abbreviated as S. oralis)
Streptococcus gordonii ATCC 10558 (hereinafter abbreviated as S. gordonii)
Periodontal pathogens:
Porphyromonas gingivalis ATCC 33277 (hereinafter abbreviated as P. gingivalis)

Further, a prescription example is shown below. These were excellent in the effect of promoting the growth of indigenous bacteria in the oral cavity. In addition, it has an excellent antibacterial effect on pathogens and is useful as an oral composition. As described above, the blending amount is a net conversion value.

The following components were used as the component (A) and the component (B).
(A) Ingredient (A) -i: Egg yolk lysolecithin LPC-1 (manufactured by Kewpie Co., Ltd.)
((A) component: LPC 94.5%)
(A) -ii: SLP-White Reso (manufactured by Tsuji Oil Co., Ltd.)
((A) component: 27.5% (LPC), (B) component: 24.2% (PC 5.1%,)
PE 3.3%, PI 13.5%, PA 2.3%))
(A) -iii: SLP-LPC70H (manufactured by Tsuji Oil Co., Ltd.)
((A) component: 69.5% (LPC), (B) component: 7% (PC 2.3%, PE)
1.8%, PI 1.8%, PA 1.1%))
(B) Ingredient (B) -i: Egg yolk lecithin PL-100P (manufactured by Kewpie Co., Ltd.)
((B) component: 97.4% (PC83.2%, PE14.2%), (A) component:
0.7% (LPC))
(B) -ii: SLP-white (manufactured by Tsuji Oil Co., Ltd.)
((B) component: 82.4% (PC29.3%, PE24.5%, PI18.8%,
PA 9.8), (A) component: 3.3% (LPC))
(B) -iii: SLP-PC70 (manufactured by Tsuji Oil Co., Ltd.)
((B) component: 85.2% (PC69.4%, PE13.3%, PI0.3%, PA)
2.2), (A) component: 3.1% (LPC))

[Prescription Example 1] Toothpaste Silicic Anhydride 15.0
Sodium lauryl sulfate 1.0
Xanthan gum 0.5
Sodium alginate 0.5
Saccharin sodium 0.1
Sorbitol 10.0
Xylitol 5.0
(A) -i 0.05
(B) -i 0.05
Fragrance 1.0
Water balance
Total 100.0%
(A) / (B) = 0.98

[Prescription Example 2] Toothpaste Silicic Anhydride 15.0
Sodium lauryl sulfate 1.0
Sodium Carboxymethyl Cellulose 1.0
Carrageenan 0.5
Saccharin sodium 0.1
Glycerin 15.0
(A) -iii 0.1
(B) -i 0.02
Fragrance 1.0
Water balance
Total 100.0%
(A) / (B) = 3.4

[Prescription Example 3] Mouthwash propylene glycol 3.0
Glycenrin 15.0
Xylitol 5.0
(A) -i 0.1
(B) -i 0.05
Saccharin sodium 0.2
Sodium citrate 0.3
Citric acid 0.1
Fragrance 0.5
Water balance
Total 100.0%
(A) / (B) = 2

[Prescription Example 4] Oral refreshing agent Ethanol 10.0
Glycenrin 5.0
Xylitol 20.0
(A) -iii 0.1
(B) -i 0.05
Sodium citrate 0.3
Citric acid 0.05
Fragrance 1.0
Water balance
Total 100.0%
(A) / (B) = 1.4

[Prescription Example 5] Gel for application Hydroxyethyl cellulose 2.0
Glycerin 20.0
Sucrose stearic acid ester 0.5
POE monostearate (20) sorbitan 0.2
(A) -i 0.1
(B) -i 0.1
Ethyl paraoxybenzoate 0.03
Water balance
Total 100.0%
(A) / (B) = 0.98

[Prescription Example 6] Chewing Gum Xylitol 49.8
Maltitol 20.0
Gum base 20.0
(A) -ii 0.1
(B) -ii 0.1
Gum arabic 9.0
Fragrance 1.0
Total 100.0%
(A) / (B) = 0.29

[Prescription Example 7] Tablets Sorbitol 70.0
Maltitol 25.0
(A) -ii 0.5
(B) -iii 0.5
Fragrance 3.5
Fine silicon dioxide 0.5
Total 100.0%
(A) / (B) = 0.28

[Prescription example 8] Gummy sugar 30.0
Syrup 30.0
Gelatin 10.0
(A) -ii 0.1
(B) -ii 0.05
Fragrance 0.2
Water balance
Total 100.0%
(A) / (B) = 0.58

[Prescription example 9] Candy sugar 40.0
Syrup 40.0
Citric acid 2.0
(A) -ii 0.05
(B) -iii 0.05
l-menthol 0.5
Fragrance 0.2
Water balance
Total 100.0%
(A) / (B) = 0.28

[Prescription Example 10] Beverage (A) -ii 0.05
(B) -ii 0.05
Citric acid 0.1
Vitamin C 0.04
Fragrance 0.1
Water balance
Total 100.0%
(A) / (B) = 0.29

[Prescription Example 11] Powdered beverage (prepared by adding 100 mL of hot water or water)
(A) -ii 0.5
(B) -ii 0.1
Powdered green tea 1.0
1.6g in total
(A) / (B) = 1.4

Claims (8)

(A) The following structural formula (1)

(In the formula (1), ^one of R 1 and R ² is -OH and the other is -OCOR (R is a saturated or unsaturated linear or branched hydrocarbon having 11 to 23 carbon atoms. Group), where X ¹ is -H, -C ₂ H ₄ N ⁺ (CH ₃ ) ₃ , -C ₂ H ₃ (N ⁺ H ₃ ) COOH, -C ₂ H ₄ N ⁺ H ₃ , -C ₆ H ₆ (OH) ₅ or -C ₂ H ₃ (OH) CH ₂ (OH).)
The compound represented by or a salt thereof and
(B) The following structural formula (2)

(In formula (2), R ³ and R ⁴ may be the same or different from each other, and -OCOR ⁵ (R ⁵ is a saturated or unsaturated linear or branched chain having 11 to 23 carbon atoms. Hydrocarbon group), where X ² is -H, -C ₂ H ₄ N ⁺ (CH ₃ ) ₃ , -C ₂ H ₃ (N ⁺ H ₃ ) COOH, -C ₂ H ₄ N ⁺ H ₃ , or -C ₆ H ₆ (OH) ₅ )
Containing a compound or a salt thereof in, (B) shows the proportion of the component (A) to component (A) / (B) is, Ri 0.1-10 der in mass ratio, buccal normal oral composition, wherein the oral formulation der Rukoto for increasing flora. The oral composition according to claim 1, wherein (A) / (B) is 0.2 to 5 in mass ratio. Claims that the compound represented by the above formula (1) is one or more lysophosphatidic acids selected from lysophosphatidic acid, lysophosphatidylcholine, lysophosphatidylserine, lysophosphatidylethanolamine, lysophosphatidylinositol and lysophosphatidylglycerin or a derivative thereof. Item 2. The oral composition according to Item 1 or 2. 13. Oral composition. The oral composition according to any one of claims 1 to 4, which contains 0.001 to 10% by mass of the component (A) and 0.001 to 10% by mass of the component (B). (A) The following structural formula (1)

(In the formula (1), ^one of R 1 and R ² is -OH and the other is -OCOR (R is a saturated or unsaturated linear or branched hydrocarbon having 11 to 23 carbon atoms. Group), where X ¹ is -H, -C ₂ H ₄ N ⁺ (CH ₃ ) ₃ , -C ₂ H ₃ (N ⁺ H ₃ ) COOH, -C ₂ H ₄ N ⁺ H ₃ , -C ₆ H ₆ (OH) ₅ or -C ₂ H ₃ (OH) CH ₂ (OH).)
The compound represented by or a salt thereof and
(B) The following structural formula (2)

(In formula (2), R ³ and R ⁴ may be the same or different from each other, and -OCOR ⁵ (R ⁵ is a saturated or unsaturated linear or branched chain having 11 to 23 carbon atoms. Hydrocarbon group), where X ² is -H, -C ₂ H ₄ N ⁺ (CH ₃ ) ₃ , -C ₂ H ₃ (N ⁺ H ₃ ) COOH, -C ₂ H ₄ N ⁺ H ₃ , or -C ₆ H ₆ (OH) ₅ )
An agent for promoting the growth of indigenous bacteria in the oral cavity, which comprises a compound represented by (1) or a salt thereof. The growth promoter for indigenous bacteria in the oral cavity according to claim 6 , wherein (A) / (B) indicating the ratio of the component (A) to the component (B) is 0.1 to 10 by mass. The growth-promoting agent for an orally indigenous bacterium according to claim 6 or 7, wherein the indigenous bacterium in the oral cavity is a bacterium belonging to the genus Streptococcus of one or more Mitis groups selected from Streptococcus mitis, Streptococcus olaris and Streptococcus gordonii.