JP6150271B2 - Bacteriostatic agent for oral aerobic bacteria - Google Patents

Description

  The present invention relates to a bacteriostatic agent for oral aerobic bacteria.

There are hundreds of bacteria in the oral cavity. It is known to participate in formation and cause caries. In addition, it is known that Staphylococcus aureus, an aerobic bacterium, causes pyogenic diseases in the oral cavity.
Therefore, in order to prevent the occurrence of caries and purulent diseases in the oral cavity, it is an effective method to suppress the growth of the aerobic bacteria.

  Conventional techniques aimed at bacteriostasis of oral aerobic bacteria include an anti-cariogenic composition characterized by containing a smoke component and a sucrose fatty acid ester (see Patent Document 1), α- Antibacterial agent for oral cavity containing linolenic acid monoglyceride or linoleic acid monoglyceride as an active ingredient (see Patent Document 2), antibacterial agent containing ricinoleic acid monoglyceride or diglycerin ricinoleic acid monoester as an active ingredient (see Patent Document 3), vascular plant Antibacterial agent (see Patent Document 4) characterized by comprising lignin extracted from xylem, ascomycetous fungi and / or basidiomycetes, and a normal oral flora regulator having a predetermined viscosity and moisturizing action (patent Reference 5) is disclosed. However, none of these techniques has been completely satisfactory.

Japanese Patent No. 3178888 JP 2009-155257 A JP 2009-126845 A JP 2000-247900 A JP 2010-064961 A

  An object of the present invention is to provide a bacteriostatic agent having a bacteriostatic effect against oral aerobic bacteria involved in caries and oral purulent diseases.

The present inventors have solved the above problems with a bacteriostatic agent for oral aerobic bacteria, which is a monoglycerin fatty acid ester, diglycerin fatty acid ester or triglycerin fatty acid ester having a monoester content of 50% or more. I found out to solve it. The present inventors have further studied based on these findings and have completed the present invention.
That is, the present invention
(1) a bacteriostatic agent for oral aerobic bacteria, which is a monoglycerin fatty acid ester, diglycerin fatty acid ester or triglycerin fatty acid ester having a monoester content of 50% or more,
(2) An oral composition comprising the bacteriostatic agent of (1),
(3) A food comprising the bacteriostatic agent of (1),
It is made up of.

  ADVANTAGE OF THE INVENTION According to this invention, the bacteriostatic agent which shows a bacteriostatic effect with respect to the aerobic bacteria in an oral cavity which is concerned with a caries and an oral purulent disease can be provided.

  Examples of the monoglycerin fatty acid ester used in the present invention include esterified products of glycerin and fatty acids, or products obtained by transesterification of glycerin and fats and oils.

  As a fatty acid used as a raw material of monoglycerin fatty acid ester, a C8-C16 saturated or unsaturated linear fatty acid is preferable. More preferred are saturated fatty acids having 8 to 16 carbon atoms, such as caprylic acid, lauric acid, myristic acid, palmitic acid, and more preferred is caprylic acid. These fatty acids may be used alone or in any combination of two or more. In addition, when the carbon number of the saturated fatty acid is less than 8, the flavor of the food may be affected by its unique pungent taste, and when the carbon number exceeds 16, the bacteriostatic effect may not be exhibited.

  The monoester content constituting the monoglycerin fatty acid ester used in the present invention is about 50% or more, preferably about 70% or more. As the monoglycerol fatty acid ester, a commercially available product can be used, and examples thereof include Poem M-100 (trade name; manufactured by Riken Vitamin Co., Ltd.).

  The monoglycerin fatty acid ester is usually added to a mixture of fat and glycerin with an alkali (for example, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, etc.) as a catalyst, and any inert gas such as nitrogen or carbon dioxide. Under an atmosphere, for example, in the range of about 180 to 260 ° C., preferably at about 200 to 250 ° C., for about 0.5 to 5 hours, preferably about 1 to 3 hours for transesterification, or fatty acid and glycerin Acid or alkali is added to the mixture as a catalyst and under any inert gas atmosphere, such as nitrogen or carbon dioxide, for example in the range of about 180-260 ° C, preferably about 200-250 ° C and about 0.5-5. The esterification reaction is carried out by heating for about 1 to 3 hours, preferably after completion of the reaction, the catalyst is neutralized, and the reaction mixture obtained is unreacted. Glycerin, can be obtained by as much as possible remove diglyceride and triglyceride. Examples of the method for removing the unreacted glycerin, diglyceride, and triglyceride include known methods such as vacuum distillation, molecular distillation, column chromatography, or liquid-liquid extraction. After removing glycerin, diglyceride, and triglyceride, treatment such as decolorization and deodorization may be performed as desired.

  The diglycerin fatty acid ester used in the present invention is an esterification reaction product of diglycerin and a fatty acid, and is produced by a method known per se such as an esterification reaction.

  The diglycerin used as a raw material for the diglycerin fatty acid ester is usually a small amount of acid (for example, concentrated sulfuric acid, p-toluenesulfonic acid) or alkali (for example, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate). Etc.) as a catalyst and heated at a temperature of, for example, about 180 ° C. or higher in an inert gas atmosphere such as nitrogen or carbon dioxide, and the average degree of polymerization of glycerin obtained by polycondensation reaction is about 1. A diglycerin mixture of 5 to 2.4, preferably an average degree of polymerization of about 2.0 is mentioned. Further, diglycerin may be obtained using glycidol or epichlorohydrin as a raw material. After completion of the reaction, treatments such as neutralization, desalting, and decolorization may be performed as desired. In the present invention, the diglycerin mixture is purified using a method known per se, such as distillation or column chromatography, and the diglycerin composed of two molecules of glycerin has a high concentration of about 50% or more, preferably about 80% or more. Highly purified diglycerin is preferably used.

  As a fatty acid used as a raw material of diglycerin fatty acid ester, a C8-C16 saturated or unsaturated linear fatty acid is preferable. More preferred are saturated fatty acids having 12 to 16 carbon atoms such as lauric acid, myristic acid, palmitic acid, and more preferred is palmitic acid. These fatty acids may be used alone or in any combination of two or more. In addition, when the carbon number of the saturated fatty acid is less than 8, the flavor of the food may be affected by its unique pungent taste, and when the carbon number exceeds 16, the bacteriostatic effect may not be exhibited.

  The monoester content constituting the diglycerin fatty acid ester used in the present invention is about 50% or more, preferably about 70% or more. Commercially available diglycerin fatty acid esters can be used, such as Poem DL-100 (trade name; manufactured by Riken Vitamin), Poem DM-100V (trade name; manufactured by Riken Vitamin), and Poem DP-. 95RF (trade name; manufactured by Riken Vitamin Co., Ltd.).

The outline of the production method of the diglycerin fatty acid ester having such a composition is as follows.
For example, a normal reaction vessel equipped with a stirrer, a heating jacket or a baffle plate is charged with diglycerin and a fatty acid (for example, palmitic acid) at a molar ratio of about 1: 1, and sodium hydroxide is usually added as a catalyst. The mixture is stirred and mixed, and heated at a predetermined temperature in a nitrogen gas atmosphere while removing water produced by the esterification reaction out of the system. The predetermined temperature is usually in the range of about 180 to 260 ° C, preferably in the range of about 200 to 250 ° C. Moreover, the pressure conditions in the reaction are under reduced pressure or normal pressure, and the reaction time is about 0.5 to 15 hours, preferably about 1 to 3 hours. As the end point of the reaction, it is preferable that the acid value of the reaction mixture is usually measured and the acid value is about 12 or less. The obtained reaction liquid is a mixture containing unreacted fatty acid, unreacted diglycerin, diglycerin monofatty acid ester, diglycerin difatty acid ester, diglycerin trifatty acid ester, diglycerin tetrafatty acid ester and the like.

  After completion of the esterification reaction, the catalyst remaining in the reaction mixture is neutralized. At that time, when the temperature of the esterification reaction is about 200 ° C. or higher, it is preferable to perform the neutralization after cooling the liquid temperature to about 180 to 200 ° C. Moreover, when reaction temperature is about 200 degrees C or less, you may neutralize at the same temperature. After neutralization, the reaction mixture is optionally cooled and maintained at about 100-180 ° C., preferably about 130-150 ° C., preferably about 0.5 hours or longer, more preferably about 1-10 hours. Is preferred. When unreacted diglycerin is separated into the lower layer, it is preferably removed.

  The diglycerin fatty acid ester obtained by the above treatment is preferably further distilled under reduced pressure to distill off the remaining unreacted diglycerin. Subsequently, for example, a falling film molecular distillation apparatus or a centrifugal molecular distillation apparatus The diglycerin fatty acid ester containing about 70% or more of the monoester can be obtained by molecular distillation using the above or by purification using a method known per se such as column chromatography or liquid-liquid extraction.

  The triglycerin fatty acid ester used in the present invention is an esterification reaction product of triglycerin and a fatty acid, and is produced by a method known per se such as an esterification reaction.

  Triglycerin used as a raw material for triglycerin fatty acid ester is usually a small amount of acid (for example, concentrated sulfuric acid, p-toluenesulfonic acid) or alkali (for example, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate). Etc.) as a catalyst and heated at a temperature of, for example, about 180 ° C. or higher under any inert gas atmosphere such as nitrogen or carbon dioxide, and the average degree of polymerization of glycerin obtained by polycondensation reaction is about 2. A triglycerin mixture of 5 to 3.4, preferably an average degree of polymerization of about 3.0 is mentioned. Triglycerin may be obtained using glycidol or epichlorohydrin as a raw material. After completion of the reaction, treatments such as neutralization, desalting, and decolorization may be performed as desired. In the present invention, the above-described triglycerin mixture is purified using a method known per se, such as distillation or column chromatography, and the triglycerin composed of three molecules of glycerin has a high concentration of about 50% or more, preferably about 80% or more. Highly purified triglycerin is preferably used.

  As the fatty acid used as a raw material for the triglycerin fatty acid ester, a saturated or unsaturated linear fatty acid having 8 to 16 carbon atoms is preferable. More preferred are saturated fatty acids having 12 to 16 carbon atoms such as lauric acid, myristic acid, palmitic acid, and more preferred is palmitic acid. These fatty acids may be used alone or in any combination of two or more. In addition, when the carbon number of the saturated fatty acid is less than 8, the flavor of the food may be affected by its unique pungent taste, and when the carbon number exceeds 16, the bacteriostatic effect may not be exhibited.

  The monoester content constituting the triglycerin fatty acid ester used in the present invention is about 50% or more, preferably about 70% or more. A commercially available triglycerin fatty acid ester can be used, and examples thereof include Poem TRP-97RF (trade name; manufactured by Riken Vitamin Co., Ltd.).

The outline of the method for producing the triglycerin fatty acid ester having such a composition is as follows.
For example, an ordinary reaction vessel equipped with a stirrer, a heating jacket, a baffle plate, etc. is charged with triglycerin and a fatty acid (eg, palmitic acid) at a molar ratio of about 1: 1, and sodium hydroxide is added as a normal catalyst. The mixture is stirred and mixed, and heated at a predetermined temperature in a nitrogen gas atmosphere while removing water produced by the esterification reaction out of the system. The reaction temperature is usually in the range of about 180 to 260 ° C, preferably in the range of about 200 to 250 ° C. Moreover, the pressure conditions in the reaction are under reduced pressure or normal pressure, and the reaction time is about 0.5 to 15 hours, preferably about 1 to 3 hours. The end point of the reaction is preferably measured by measuring the acid value of the reaction mixture and using an oxidation of about 12 or less as a guide. The obtained reaction liquid is a mixture containing unreacted fatty acid, unreacted triglycerin, triglycerin monofatty acid ester, triglycerin difatty acid ester, triglycerin trifatty acid ester, triglycerin tetrafatty acid ester, triglycerin pentafatty acid and the like. It is.

  After completion of the esterification reaction, the catalyst remaining in the reaction mixture is neutralized. At that time, when the temperature of the esterification reaction is about 200 ° C. or higher, it is preferable to perform the neutralization after cooling the liquid temperature to about 180 to 200 ° C. Moreover, when reaction temperature is about 200 degrees C or less, you may neutralize at the same temperature. After neutralization, the reaction mixture is optionally cooled and maintained at about 100-180 ° C., preferably about 130-150 ° C., preferably about 0.5 hours or longer, more preferably about 1-10 hours. Is preferred. When unreacted triglycerin is separated into the lower layer, it is preferably removed.

  The triglycerin fatty acid ester obtained by the above treatment is preferably further distilled under reduced pressure to distill off the remaining unreacted triglycerin. Subsequently, for example, a falling film molecular distillation apparatus or a centrifugal molecular distillation apparatus A triglycerin fatty acid ester containing about 70% or more of a monoester can be obtained by molecular distillation using the above or by purification using a method known per se such as column chromatography or liquid-liquid extraction.

  There is no restriction | limiting in particular as an oral aerobic bacterium in which the bacteriostatic agent of this invention shows a bacteriostatic effect, For example, Streptococcus mutans (Streptococcus mutans), Streptococcus mitis (Streptococcus mitis), Streptococcus sanguinis (Streptococcus sanguinis) It exhibits bacteriostatic effects against a wide range of oral aerobic bacteria such as Actinomyces naeslundii and Staphylococcus aureus.

  The bacteriostatic agent of the present invention exhibits a high bacteriostatic effect on oral aerobic bacteria. For this reason, prevention of a caries and an oral purulent disease can be easily performed by mix | blending the bacteriostatic agent which concerns on this invention with an oral composition or foodstuff. The content of the bacteriostatic agent of the present invention in the oral composition (or food) is usually about 0.01 to 2.0% by mass, preferably about 0.01 to 0.5% by mass. . If it is less than 0.01% by mass, the bacteriostatic effect is insufficient, and if it exceeds 2.0% by mass, there is a dislike of adversely affecting the flavor.

  Examples of oral compositions include dentifrices such as toothpastes, liquid toothpastes and foamed toothpastes, gum massage creams, topical application agents, mouthwashes, mouthwashes, mouth fresheners, tablets and the like. Examples of foods include lozenges, chewing gums, and film-like foods.

  The present invention will now be described by way of examples, which are merely illustrative of the invention and do not limit the invention.

<Invention product>
As the present invention products, the present invention products 1 to 5 shown in Table 1 below were used.

[Method for measuring monoester content]
The ester composition analysis was performed using HPLC, and the quantitative analysis was performed by the absolute calibration curve method. That is, the peak area corresponding to the monoester body of the test sample recorded on the chromatogram by the data processor is measured, and the monoglycerin monostearate and diglycerin monostearic acid purified by normal phase column chromatography The monoester content of the test sample was determined from a calibration curve prepared using ester or triglycerol monostearate as a standard sample. The HPLC analysis conditions are shown below.

<HPLC analysis conditions>
Equipment Shimadzu high performance liquid chromatograph pump (model: LC-10A; manufactured by Shimadzu Corporation)
Column oven (model: CTO-10A; manufactured by Shimadzu Corporation)
Data processing device (model: C-R7A; manufactured by Shimadzu Corporation)
Column GPC column (Model: SHODEX KF-802; Showa Denko)
Two-linked mobile phase THF
Flow rate 1.0mL / min
Detector RI detector (model: RID-6A; manufactured by Shimadzu Corporation)
Column temperature 40 ° C
Test solution injection volume 15μL (in THF)

<Bacteriostatic test>
A bacteriostatic test was carried out on oral aerobic bacteria (test bacteria 1-5) listed in Table 2 using the inventive products 1-5.

[Preparation of agar medium]
A Brain Haert Infusin (BHI) agar medium is prepared so that final concentrations of the present invention products 1 to 5 are 10, 100 and 1,000 ppm, respectively, and after autoclaving, 15 mL is injected into a sterilized petri dish to form an agar plate. Produced.

[Test method]
After enrichment of test bacteria 1-5 in the pre-culture, smear the test bacteria with platinum ears on a BHI plate medium, culture under aerobic conditions at 37 ° C for 24 hours, and then visually check for growth. According to the evaluation criteria listed in Table 3, the degree of bacterial growth (degree of bacteriostatic against bacteria) was evaluated. The test was performed four times, and the average value obtained based on Table 3 was symbolized according to the following criteria. The results are shown in Table 4.
Symbolic evaluation score is 0% ◎◎
The evaluation score exceeds 0% and is 32% or less.
Evaluation point exceeds 32% and 65% or less ○
Evaluation score exceeds 65% and less than 100%
Evaluation point is 100% ×

  From Table 4, it turned out that this invention goods 1-5 show the bacteriostatic effect with respect to any microbe of test bacteria 1-5. It turned out that especially this invention product 5 shows a high bacteriostatic effect.

<Production Example 1: Production of tablet>
According to the formulation shown in Table 5 below, each component was uniformly mixed, water was added and kneaded, and then the tablet was dried and a tablet containing the product 5 of the present invention was produced using a single tableting machine.

<Production Example 2: Production of film-like food>
According to the formulation shown in Table 6 below, each component was uniformly mixed, kneaded with water, and then spread on a plastic film and dried to produce a film-like food containing the product 5 of the present invention.

  As described above, the bacteriostatic agent for oral aerobic bacteria of the present invention exhibits an excellent bacteriostatic effect on oral aerobic bacteria. Therefore, the bacteriostatic agent according to the present invention is a composition for oral cavity such as toothpaste, toothpaste such as toothpaste, liquid toothpaste, foam toothpaste, gingival massage cream, topical application agent, mouthwash, mouthwash, mouth freshener, tablet, etc. It can be diverted to foods such as lozenges, chewing gums and film-like foods.

Claims (3)

The following bacteriostatic bacteriostat for oral aerobic bacteria, wherein the monoester content is 50% or more, and the constituent fatty acid contains a diglycerin fatty acid ester or triglycerin fatty acid ester of a saturated fatty acid having 12 to 16 carbon atoms Agent.
Oral aerobic bacteria: Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, Actinomyces nicelandy Characterized in that it contains a bacteriostatic agent according to claim 1, oral composition for bacteriostatic buccal aerobic bacteria below.
Oral aerobic bacteria: Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, Actinomyces nicelandy A food for bacteriostasis of the following oral aerobic bacteria, comprising the bacteriostatic agent according to claim 1.
Oral aerobic bacteria: Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, Actinomyces nicelandy