JP2010064961A - Agent for adjusting normal oral bacterial flora and method for adjusting normal oral bacterial flora using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To show a high antibacterial activity against periodontal disease bacteria, caries-causing bacteria, and opportunistic infection-causing bacteria, and does not show antibacterial activity against oral resident flora, and thus does not disrupt the flora balance. Disclosed is a composition having an excellent ability to adjust the normal oral flora. Moreover, the method which can perform oral care by a simple and effective method is provided.
SOLUTION: An oral resident flora adjusting agent having a predetermined viscosity, which exhibits antibacterial activity against at least one of periodontal disease bacteria, caries-causing bacteria, and opportunistic infection-causing bacteria. Is an oral resident flora regulator that does not exhibit antibacterial activity and has a moisturizing action. It preferably contains an effective amount of catechin and xanthan gum. A gel agent is particularly preferable. Further, the present invention is a method for adjusting the normal microbial flora characterized by applying the oral microbial flora adjusting agent to the oral cavity by at least one of application, brushing, oral intake, and eating.
[Selection] Figure 1

Description

  The present invention relates to an oral microbial flora adjusting agent, and in particular, by using xanthan gum as a gelling agent for oral care having a moisturizing effect, catechin having an antibacterial action is kept in a good state of the oral resident flora. It is related with the oral cavity normal flora regulator which made it possible to adjust. The present invention also relates to a method for adjusting the normal oral flora using the same.

  In the human oral cavity, extremely many types of bacteria exceeding 700 species have been found, and the number of the bacteria is large, and an aggregate, that is, a flora is constantly formed on the mucosal surface. This intraoral flora is maintained in a balanced state by complex interactions, and has a function of preventing invasion, that is, imparting resistance by antagonizing foreign bacteria. However, there are many bacteria called opportunistic bacteria in this flora. Although this bacterium usually does not exert pathogenicity on healthy bodies, it may cause infections due to decreased immunity of the host. In particular, the increase and transition of resident bacteria in the oral cavity not only cause oral infections such as caries and periodontal disease, but also infective endocarditis, myocardial infarction, pneumonia, premature birth and low weight The possibility of causing systemic diseases such as childbirth has also been reported.

  Furthermore, with the recent increase in the number of elderly people, prevention of oral infections and improvement of oral hygiene among the elderly people are extremely important issues. In particular, it is known that elderly people requiring nursing care and the like are more likely to detect opportunistic bacteria such as Candida albicans in the oral cavity than independent elderly people (Non-patent Document 1). When dysphagia occurs in such elderly people, there is a concern that oral bacteria including opportunistic bacteria may increase the respiratory system and develop pneumonia. Therefore, it is important to make the oral cavity a healthy oral bacterial flora with less opportunistic bacteria.

  Numerous studies have been conducted so far on the prevention of dental caries and periodontal disease in the oral cavity. In addition, various studies have been conducted so far as countermeasures against individual bacteria and the entire oral bacterial flora.

  For example, Patent Document 1 discloses (−)-epigallocatechin gallate, (−)-epi for the purpose of inhibiting adhesion of polyphyromonas gingivalis, which is a causative agent of periodontal disease, to the buccal mucosa epithelial cell surface layer. A composition for inhibiting periodontal disease-causing bacterial adhesion comprising at least one of catechin gallate and (−)-gallocatechin gallate is disclosed. The composition disclosed in Patent Document 1 prevents infection by not attaching specific bacteria, and takes a slightly different approach from the so-called antibacterial action.

  Patent Document 2 discloses that a catechin chloroplast compound is contained as an effective composition for the prevention of caries and periodontal disease. Excellent results are shown. In this patent document 2, as a general problem, it is described as a conventional problem that antibiotics and fungicides kill oral bacteria non-selectively, disrupt the balance of the resident flora, and cause fungal complications. However, as an actual technique, a composition exhibiting antibacterial properties against specific bacteria has been proposed, and neither the effects on the oral bacterial flora nor the ability to adjust them have been examined or suggested.

  On the other hand, many compositions that are effective against caries and periodontal disease-causing bacteria have been studied without affecting the growth of non-pathogenic oral resident bacteria. For example, the composition for oral cavity containing the extract of the Chinese medicine disclosed in Patent Document 3, the anti-periodontal fungus composition containing the cocoa content disclosed in Patent Document 4, and the ganglioside disclosed in Patent Document 5 as the active ingredient Oral bacterial flora improving agents have been proposed. In these, the influence test with respect to the non-pathogenic oral resident bacteria which are useful bacteria is shown and examined to some extent, but it is unclear whether or not the same effect can be actually obtained in the oral cavity.

  Furthermore, Patent Document 6 contains substances useful for oral hygiene, such as substances having antibacterial action such as plant polyphenols and bacteriocin, and substances that develop viscosity, such as xanthan gum, and the viscosity can be adjusted by the amount of water added. An invention relating to an oral care composition is disclosed. And the green tea catechin is disclosed as a substance which has an antibacterial action. The object of the present invention is to allow a substance useful for oral hygiene to stay in the oral cavity for a predetermined time and to release components gradually. Therefore, the evaluation is limited only to the dissolution property, that is, the retention property, and the actual antibacterial activity and the effect on the oral resident flora of the active ingredient and the composition, that is, the adjusting ability has not been studied.

Masanori Takada, Tsutomu Sato, Hidenobu Izumi, Nobuhiro Hanada, “Comparison of oral microbiota of elderly living alone and elderly people requiring care”, Journal of Oral Hygiene, 2004, Vol. 3, No. 3, 178-188 JP-A-5-944 JP-A-9-110687 JP-A-6-157259 International Publication WO03 / 099304 Pamphlet Japanese Patent Laid-Open No. 2005-320275 JP 2007-16021 A

  As described above, there has been a demand for the development of a composition effective against caries-causing bacteria and periodontal disease-causing bacteria without affecting the non-pathogenic oral resident flora. Moreover, in elderly people, the amount of saliva secretion often decreases, which has been a serious problem in oral hygiene. Generally, a toothbrush is used to clean the oral cavity. However, in the case of elderly people requiring care who need help from a caregiver, complete oral cleaning is very difficult and oral cleaning is insufficient. Will increase. Therefore, there has been a demand for the development of an effective oral care method in a short time to assist oral cleaning with a general toothbrush.

  Therefore, the object of the present invention is to provide high antibacterial activity against caries-causing bacteria, periodontal disease-causing bacteria and opportunistic infection-causing bacteria, while against oral resident flora, especially against useful bacteria. Does not show antibacterial activity, and therefore does not significantly affect the flora balance, that is, has an extremely excellent ability to adjust the normal oral flora, and can be used in a simple and effective manner. It is in providing a composition capable of imparting a moisturizing effect.

  In view of the above-mentioned conventional problems, the present inventors have conducted extensive research, and by gelling catechin having antibacterial action with xanthan gum which is a moisturizing agent, caries-causing bacteria, periodontal disease-causing bacteria. It exhibits high antibacterial activity against bacteria that cause opportunistic infections, but does not affect the normal resident flora in the oral cavity, does not disrupt the flora balance, and exhibits high moisturizing action. The headline and the present invention were completed.

  That is, one embodiment of the present invention shows antibacterial activity against caries-causing bacteria, periodontal disease-causing bacteria and opportunistic infection-causing bacteria, but does not exhibit antibacterial activity in oral resident bacteria, Oral resident flora regulator with viscosity and moisturizing action.

  The oral resident flora regulator according to the present invention preferably contains an effective amount of catechin, and the content thereof is preferably 0.05% by weight to 0.5% by weight.

  And it is preferable that the oral cavity normal flora regulator by this invention contains the effective amount of a moisturizing substance. At this time, the moisturizing substance is preferably at least one substance selected from the group consisting of xanthan gum, carrageenan and hyaluronic acid, and most preferably xanthan gum. In this case, the content of xanthan gum is preferably 1.0% by weight to 5.0% by weight.

  On the other hand, the oral cavity normal flora adjusting agent according to the present invention is characterized in that the viscosity by a B-type viscometer at 20 to 25 ° C. is 2300 to 8000 mPa · s. And as the dosage form, it is preferable that it is a gel agent.

  The oral resident flora regulator according to the present invention is, in particular, at least one species of Porphyromonas gingivalis, Aggregaactacteractinutiumcedicomitans, Prevotella intermedium, and Fusobacterium nucleatum, which are at least one kind of bacteria that are periodontal disease bacteria. And / or at least one of Candida albicans and methicillin-resistant Staphylococcus aureus (MRSA) that are opportunistic infection-causing bacteria.

  In addition, another aspect of the present invention is characterized in that the oral resident flora adjusting agent according to any one of the above is applied to the oral cavity by at least one method of application, brushing, oral intake, and eating. This is a method for adjusting the oral resident flora.

  In the method for adjusting the oral resident flora according to the present invention, the catechin is contained in the oral microbial flora adjusting agent, and the amount of catechin contained in one application of the oral resident flora adjusting agent is 10 to 100 mg. A range is preferable.

Oral resident flora regulator according to the present invention exhibits antibacterial activity against periodontal disease bacteria, caries-causing bacteria and opportunistic infection-causing bacteria, but does not exhibit antibacterial activity against oral resident bacteria, And has a high moisturizing action. Therefore, by using a gel having a predetermined viscosity, the residence time of the active ingredient in the oral cavity is extended, and it is possible to provide a significantly higher antibacterial activity than in the case of a solution. Furthermore, the preferred combination of catechin and xanthan gum does not exhibit antibacterial activity against oral resident bacteria including useful bacteria and the like, that is, has no effect on oral resident bacterial flora and may disrupt the bacterial flora balance. Absent. Therefore, in combination with antibacterial activity against caries-causing bacteria, periodontal disease-causing bacteria, and opportunistic infection-causing bacteria, it exhibits extremely excellent ability to adjust the normal oral flora. In addition, applying a moisturizing agent such as xanthan gum can provide a very high moisturizing effect.
Moreover, in the method for adjusting the normal microbial flora of the present invention, the oral microbial flora adjusting agent of the present invention is only applied by a simple method such as application, brushing, oral intake, and eating. Therefore, it is possible to use the excellent ability of adjusting the normal microbial flora of the present invention by a very simple method.

  Hereinafter, the present invention will be described in detail, but the present invention is not limited to the individual forms described below.

  The present invention shows antibacterial activity against periodontal disease bacteria, caries-causing bacteria and opportunistic infection-causing bacteria, but does not show antibacterial activity against oral resident bacteria, and has a predetermined viscosity and moisturizing action. It is a resident flora adjusting agent, and preferably contains an effective amount of catechin and also contains an effective amount of xanthan gum.

  In the oral cavity normal flora adjusting agent by this invention, it is preferable to contain the catechin which has an antimicrobial effect. The catechins used in the present invention include epi-forms, hydroxy-forms, gallate esters and the like, and can be used alone or in a mixture. In the present invention, it is preferable to use catechin as a mixture because it is easily available and has a preferable flavor. In addition, synthetic products, extracts from natural products, and the like can be used regardless of this.

  The content of catechin contained in the oral resident flora regulator of the present invention is preferably 0.05% by weight to 0.5% by weight, and more preferably 0.1% by weight to 0.3% by weight. If the catechin content exceeds 0.5% by weight, catechin-derived bitterness is generated, which is not suitable in terms of flavor. If the catechin content is less than 0.05% by weight, the oral resident flora adjusting action required in the present invention is not exhibited.

  It is preferable that the oral resident flora regulator of the present invention contains a moisturizing agent. Examples of moisturizing agents include xanthan gum, carrageenan, hyaluronic acid and the like, which can be used alone or in combination. Moreover, xanthan gum is particularly preferable. These moisturizing substances can be used as they are for normal food addition.

  The content of a moisturizing agent, for example, xanthan gum, contained in the oral resident flora regulator of the present invention is preferably 1.0% by weight to 5.0% by weight, and 2.0% by weight to 4.0% by weight. % Is more preferable. If the content of the substance having a moisturizing action exceeds 5.0% by weight or less than 1.0% by weight, sufficient effects cannot be obtained from the viewpoint of retention in the oral cavity, sustained release, and moisturizing effect. .

  In addition to the above-mentioned compounds, the oral resident flora adjusting agent of the present invention is a general composition for oral care within a range that does not inhibit the effect of the oral resident flora adjusting agent of the present invention and the viscosity state thereof. Additives used in foods and general food additives added to foods can be used.

The oral resident flora adjusting agent of the present invention can be appropriately produced in the process of producing a general oral care composition.
In the oral resident flora adjusting agent of the present invention, it is essential to have a predetermined viscosity. From the viewpoint of retention of active substances and sustained release, a B-type viscometer (temperature: 20 to 25 ° C. ) Is preferably 2300 to 8000 mPa · s, more preferably 2400 to 7000 mPa · s, and still more preferably 2500 to 6000 mPa · s.

  In the oral cavity normal flora adjusting agent of the present invention, it is necessary to have the above-mentioned preferable predetermined viscosity, and as long as it has this viscosity, its dosage form includes liquids, gels, creams, ointments, etc. Can take form. Gels are most preferable from the viewpoints of handling properties such as administration, ingestion, and application, retention in the oral cavity, and sustained release. Moreover, in the case of a gel agent, it can be said that it is a preferable dosage form from satisfy | filling said preferable range.

  The oral resident flora regulator of the present invention is characterized by high antibacterial activity against caries-causing bacteria, periodontal disease-causing bacteria, and opportunistic infection-causing bacteria. Therefore, the oral hygiene condition can be always adjusted to a good condition since the bacterial flora balance is not lost. In particular, the oral flora regulator of the present invention has antibacterial activity against at least one of the activity of Porphyromonas gingivalis, Aggrebacteractinactinometicites, Prevotella intermedia, and Fusobacterium nucleatum as periodontal disease bacteria. Further, it exhibits antibacterial activity against at least one of Actinomyces naeslundii and Streptococcus mutans as caries-causing bacteria. Furthermore, it exhibits antibacterial activity against at least one of Candida albicans and methicillin-resistant Staphylococcus aureus (MRSA) as opportunistic infection-causing bacteria.

The oral microbial flora adjusting agent of the present invention can be applied according to a wide range of usage states and usage scenes such as application to the oral cavity, tooth brushing, drinking (oral intake), and eating. For example, when the oral resident flora regulator of the present invention is orally ingested, the dose at this time is preferably 10 to 100 mg based on catechin. With regard to the component concentration in the regulator of the present invention, catechin preferably has the above-mentioned concentration range, and xanthan gum preferably has the above-mentioned concentration range capable of maintaining a predetermined viscosity state.
The application time is preferably after a normal meal or before going to bed. Particularly preferably, it is applied after dinner and before going to bed, and goes to bed without taking anything.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated, this invention is not limited by this. In the present specification, unless otherwise indicated,% indicates weight%.

  In the examples, the strain described as ATCC in the strain name is a reference strain obtained from the American Type Culture Collection, and the strain described as JCM in the strain name is a microbial material development of RIKEN BioResource Center. Reference strain obtained from the laboratory, FDC is the possession strain of Forsyth Dental Centerno, IFO is the strain of The Institute for Fermentation, Osaka possession strain, MT is the strain of Osaka University Dental School Research possessed strain, NUD is Nihon University School School Held strains of Dentistry, TI is holding strains of Tokai University, WVU is held strains of West Virginia University. In addition, Escherichia coli is a strain possessed by Nihon University School of Dentry.

[Example 1] Antibacterial activity of catechin gel against oral microorganisms Oral care gel according to the present invention (hereinafter sometimes referred to as oral normal flora adjusting gel including other examples) ) Was tested for antibacterial activity. A gel containing no catechin was used as a control.

  Specifically, extracted catechin and purified catechin (trade name: Sanphenon BG3, manufactured by Taiyo Kagaku Co., Ltd.) are each 2.75 mg / ml for gel (trade name: Tromake, manufactured by Meiji Dairies Co., Ltd.). Blended into Further, (−)-epigallocatechin gallate (manufactured by Wako Pure Chemical Industries, Ltd.) was blended in the gel so as to have the same 2.75 mg / ml.

  A total of 25 strains described in Table 1 such as representative oral resident streptococci, periodontal pathogens, Candida, Staphylococcus and Escherichia were used as test bacteria.

The antibacterial action was measured by improving the agar diffusion method using the cup method.
Specifically, first, a plate medium was prepared with 10 ml of BHI agar or GAM agar (1.5%), and 200 μl of the test solution / 15 ml of BHI agar or GAM agar (1%, 55 ° C.) was layered thereon. . On this, a sterilized metal dowel was allowed to stand at 6 to 7 places, and after the medium was cured, the metal dowel was removed. 200 μl of each gel was added to the holes thus prepared and stored in the refrigerator for 1 hour. In the case of an anaerobic culture, it was stored for 30 minutes in the entrance box of the anaerobic culture apparatus. Further, this medium was subjected to aerobic or anaerobic culture at 37 ° C. for 24 hours, and the diameter of the inhibition zone after growth was measured.
The obtained results are shown in FIG.

As can be seen from the graph of FIG. 1, the oral resident flora-adjusting gel of the present invention exhibited an excellent growth inhibitory action, ie, an antibacterial effect, against all pathogenic bacteria. Moreover, a remarkable growth inhibitory action was observed against Actinomyces and Fusobacterium, which have high coaggregation ability with many oral bacteria and are important for plaque accumulation. In addition, a clear growth inhibitory activity was also observed in the caries-causing bacteria Streptococcus mutans, periodontal pathogens, Candida and Staphylococcus, MRSA. Furthermore, the oral resident flora-adjusting gel of the present invention is extremely important for maintaining normal oral environment. sanguinis, S .; oralis, S.M. Gordoni and S. No growth inhibitory activity was observed against mitis.
Therefore, it was found that the oral resident flora adjusting gel of the present invention has an excellent antibacterial effect, but does not affect the normal resident flora. That is, an antibacterial effect was observed only against causative bacteria such as caries, periodontal disease, and Candida disease, and excellent oral resident flora adjusting ability was shown.

[Example 2] Antibacterial activity of catechin gel over time against oral microorganisms When the oral microbial flora adjusting gel according to the present invention remains in the oral cavity, in order to examine whether or not its antibacterial activity is sustained, The antibacterial activity over time was tested. Even if the oral microbial flora adjusting gel of the present invention remains in the oral cavity, it is assumed that catechin is released into saliva without remaining as it is. Therefore, as a model in which catechin is released into saliva, PBS was added onto the gel, and this was used as a test sample. As a negative control, a gel containing no catechin was used.

  Specifically, extracted catechin and purified catechin (trade name: Sanphenon BG3, manufactured by Taiyo Kagaku Co., Ltd.) are each 2.75 mg / ml for gel (trade name: Tromake, manufactured by Meiji Dairies Co., Ltd.). It was blended as follows. Further, (−)-epigallocatechin gallate (manufactured by Wako Pure Chemical Industries, Ltd.) was blended in the gel so as to have the same 2.75 mg / ml.

  3 ml of the obtained gel was placed in a well (diameter: 23 mm) of a 12-well macrotiter plate, and 3 ml of PBS was layered thereon. For the oral resident flora-adjusting gel of the present invention, each of the remaining gels after removing the supernatant (PBS layer) after 30, 60, 180, and 360 minutes was collected and used in the test.

  A total of 25 strains described in Table 1 above, such as representative oral resident streptococci, periodontal pathogens, Candida, Staphylococcus and Escherichia, were used as test bacteria.

  The antibacterial action was measured by the modified agar diffusion method using the cup method in the same manner as in Example 1.

  As for the antibacterial effect of catechin gel against oral microorganisms, the same growth inhibitory action as in Example 1 was observed at any time. In addition, an antibacterial effect was observed in a 360-minute treatment in a PBS supernatant that mimicked that gel remained in the oral cavity and catechin was released with saliva or the like.

[Example 3] Comparative test on antibacterial activity with commercially available product Only oral gel categorizing gel (catechin concentration 2.75 mg / ml) and gel containing no catechin of the present invention, and commercially available product A (main) Antibacterial activity tests were performed using antibacterial components: lactoperoxidase, glucose oxidase, lysozyme, lactoferrin) and commercial product B (main antibacterial components: cetylpyridinium chloride).

  A total of 10 strains described in Table 2 such as representative oral resident streptococci, actinomycetes, periodontal pathogens, Candida, and Staphylococcus were used as test bacteria.

The antibacterial action was measured using a modified agar diffusion method using the same cup method as in Example 1.
The obtained results are shown in FIGS.

  For test bacteria having pathogenicity, the oral resident flora-adjusting gel of the present invention showed a stronger growth inhibitory action than the comparative commercial product. In particular, the commercial product A.C. No effect on albicans was observed. Further, in the normal resident flora, the growth inhibitory action by the oral resident flora-adjusting gel of the present invention was not observed, but the growth inhibitory action was observed in the comparative commercial product. Therefore, the oral resident flora-adjusting gel of the present invention has a strong antibacterial action against causative bacteria such as caries, periodontal disease and Candida disease, compared to commercially available products, while normal resident flora has Since the antibacterial activity was not recognized, it was found that it has an ability to adjust oral resident flora superior to that of a commercially available product.

[Example 4] Residual test in the oral cavity depending on the dosage form In order to analyze the behavior of the oral microbiota-adjusting gel of the present invention in the oral cavity, behavior after gel administration (dilution with saliva, swallowing, disappearance) is assumed. Model system residual test was conducted.

  As samples, the oral resident flora adjusting gel of the present invention (catechin content 2.75 mg / ml) and a comparative catechin aqueous solution (catechin content 2.75 mg / ml) were used.

  A 24-well well was filled with the oral resident flora-adjusting gel or catechin solution of the present invention (3.4 ml / well). Place the 24-well plate in a plastic container, inject artificial saliva from the surrounding area up to 1 cm above the top of the plate (340 ml), leave it for 1 minute, and then discharge the artificial saliva from the bottom of the plastic container. Was recovered. After the artificial saliva was injected and discharged five times, this sample was diluted and the OD 310 nm value was measured (U-1100, Hitachi). The residual ratio was calculated by setting the catechin concentration of the solution and gel before the experiment to 100%. The obtained results are shown in FIG.

  A significant difference in the amount of residual catechin was already observed in the first discharge. At the time when the discharge was completed five times, about 90% of the catechin remained in the oral resident flora-adjusting gel of the present invention, but almost no catechin remained in the comparative catechin solution. Therefore, it became clear that an active ingredient remains over a long period of time by using the oral cavity normal flora adjustment gel of this invention.

[Example 5] Comparative test of antibacterial activity by difference in dosage form A comparative test simulating the case of ingesting the oral resident bacterial flora adjusting gel of the present invention (catechin content 2.75 mg / ml) and a catechin aqueous solution was conducted. . The catechin aqueous solution for comparison was subjected to the same test as in Example 1 using a sample having a 4-fold concentration of the gel (catechin content: 11 mg / ml), and each antibacterial activity was measured. In the case of a catechin aqueous solution, treatment for 1 minute was performed in consideration of swallowing. A total of 6 strains shown in Table 3 such as representative oral resident streptococci, periodontal pathogens, Candida, Staphylococcus and Escherichia were used as test bacteria. The obtained results are shown in FIG.

  When the oral resident flora-adjusting gel of the present invention was used, the growth inhibitory action was observed in all the test strains. In particular, compared to the 1-minute treatment of the catechin quadruple concentration solution as a comparison, the oral resident flora-adjusting gel of the present invention showed a very remarkable growth inhibitory action in all the test bacteria.

[Example 6] Examination of the usefulness of catechin gel in humans The amount of Candida in the oral cavity of 32 elderly people requiring care was examined. A total of 12 persons (8 males in whom Candida was detected and 4 persons in whom Candida was not detected (1 male) 11 women, average age 87.6 ± 8.8 years).

  After daily oral care after dinner, the subject took a portion of 20 ml of the oral microbial flora adjusting gel of the present invention (catechin concentration 2.75 mg / ml) on a sponge brush, and evenly applied to the entire oral cavity. The gel was swallowed. This was done for 2 months. About the saliva sample, per subject, the saliva was soaked into two seed swabs No. 1 (Eiken Chemical). A total of 6 samples were collected. Moreover, the questionnaire by the expert (dental hygienist) was implemented about the oral condition of the test subject 2 weeks after the test. The contents of the questionnaire are shown in FIG.

For the measurement of the collected sample, the cotton part at the tip of the seed swab sample soaked was cut and placed in a tube containing 2 ml of sterile PBS (phosphate buffer solution). After sonication for 10 seconds, 50 μl of a solution diluted with sterile PBS was added to Brain Heart Infusion (BHI) medium, Mitis-Salivarius (MS) medium, Mitis-Salivarius (MSB) medium containing 0.5 M bacitracin and CHROM. The agar medium was inoculated using a spiral device. The number of colonies was calculated after culturing MS and MSB under aerobic conditions containing 5% CO ₂ and CHROM agar medium under aerobic conditions at 37 ° C. for 48 hours. BHI was used for calculating the total number of bacteria, MS was used for calculating the total number of streptococci, MSB was used for calculating the number of Mutans streptococci, and the CHROM agar medium was used for calculating the number of Candida.
The obtained results are shown in FIGS.

  The questionnaire survey showed the average value and standard deviation of scores that increased by one point as the score worsened, with the score of the best survey item as 1 point. The questionnaire results are shown in FIG.

  After the use of the oral resident flora adjusting gel of the present invention, a rapid decrease in the average value of the Candida number was observed early (denoted as “12/26” in the graph on December 26). However, although it recovered in a short time (1/9), the decreasing tendency was maintained from the initial value. The decreasing trend was maintained (up to 2/5), but after the use of the gel of the present invention was stopped (3/4), the number of bacteria recovered rapidly and the level continued to 4/1. S. As with the Candida number, the mutans number decreased in a short time (12/26) after using the oral microbial flora adjusting gel of the present invention, but recovered to 1/9 and then approached the initial value. It was. The total bacterial count and the total streptococcal count were not particularly affected by the oral bacterial flora adjusting gel of the present invention.

From the results of a questionnaire conducted two weeks after the test, the oral microbial flora-adjusting gel of the present invention is not only adjusted for the normal bacterium in the oral cavity, but also by the moisturizing effect of the oral resident flora-adjusting agent of the present invention. The environment was also improved.
From these, it was suggested that the oral resident flora regulator of the present invention is useful for oral care and QOL improvement of the elderly.

  The oral resident flora adjusting agent according to the present invention has a predetermined viscosity and exhibits antibacterial activity against at least one of periodontal disease bacteria, caries-causing bacteria, and opportunistic infection-causing bacteria. Bacteria do not exhibit antibacterial activity and have a high moisturizing action. Therefore, it is possible to utilize the excellent ability to adjust the normal microbial flora of the present invention only by applying the oral microbial flora adjusting agent according to the present invention by a simple method such as application, brushing, oral intake, and eating. . By using this, it is possible to provide an effective oral care gel and oral care method in a short time for assisting oral cleansing of elderly people who particularly require nursing care, and also provides a moisturizing effect. can do.

It is a graph which shows the antibacterial activity with respect to various oral bacteria using the gel for oral care which is an oral resident flora regulator of this invention, and a comparison epigallocatechin gallate gel with the diameter of a growth inhibitory zone (Example 1). ). It is a graph which shows the antibacterial activity with respect to various oral bacteria using the commercial product compared with the normal microbial flora adjustment gel of this invention with the diameter of a growth inhibitory zone (Example 3, Gram positive bacterium). It is a graph which shows the antibacterial activity with respect to various oral bacteria using the commercial product compared with the normal microbial flora adjustment gel of this invention with the diameter of a growth inhibitory zone (Example 3, Gram-negative bacteria). It is a graph which shows the intraoral normal flora adjustment gel of this invention, and the model system residual rate of a catechin solution (Example 4). It is a graph which shows the antibacterial activity with respect to various oral bacteria using the oral resident flora adjustment gel of this invention, and a catechin solution (4 times concentration) with the diameter of a growth element zone (Example 5). It is a graph which shows the effect with respect to Candida after oral care using the oral resident flora adjustment gel of this invention (Example 6). After oral care using the oral resident flora adjusting gel of the present invention, (Example 6) which is a graph which shows the effect with respect to mutans. It is a graph which shows the effect with respect to the total number of bacteria after oral care using the oral resident flora adjustment gel of this invention (Example 6). It is a graph which shows the effect with respect to the total streptococcus after oral care using the oral resident flora adjustment gel of this invention (Example 6). (Example 6) which is a figure which shows the questionnaire content implemented after 2 weeks of oral care using the oral resident flora adjustment gel of this invention. It is a figure which shows the questionnaire result implemented after 2 weeks of oral care using the oral microbial flora adjustment gel of this invention (Example 6). The average value and standard deviation of the score that increased by one point as the score worsened were shown with the score of the best item in each survey item as one point.

Claims (14)

  It exhibits antibacterial activity against at least one of periodontal disease bacteria, caries-causing bacteria, and opportunistic infection-causing bacteria, but does not exhibit antibacterial activity in oral resident bacteria, and has normal viscosity and moisture retention. Bacterial flora regulator.   The oral cavity normal flora regulator of Claim 1 formed by containing an effective amount of catechin.   The oral cavity normal flora adjusting agent according to claim 2, comprising 0.05% to 0.5% by weight of catechin.   The oral cavity normal flora adjusting agent according to any one of claims 1 to 3, comprising an effective amount of a moisturizing agent.   The oral cavity normal flora adjusting agent according to claim 4, wherein the moisturizing agent is at least one substance selected from the group consisting of xanthan gum, carrageenan and hyaluronic acid.   The oral resident flora regulator according to claim 4, wherein the moisturizing agent is xanthan gum.   The oral cavity normal flora adjusting agent of Claim 5 or 6 formed by containing xanthan gum 1.0 to 5.0 weight%.   The oral cavity normal flora adjusting agent according to any one of claims 1 to 7, wherein a viscosity by a B-type viscometer at 20 to 25 ° C is 2300 to 8000 mPa · s.   A dosage form is a gel agent, The oral cavity normal flora adjusting agent in any one of Claims 1-8.   10. The oral preparation of any one of claims 1 to 9, which exhibits antibacterial activity against at least one of Porphyromonas gingivalis, Aggregatacteractinomycetemcomitans, Prevotella intermedia, and Fusobacterium nucleatum, which are periodontal disease bacteria. .   The oral cavity normal flora adjusting agent according to any one of claims 1 to 10, which exhibits antibacterial activity against at least one of Actinomyces naeslundii and Streptococcus mutans which are caries-causing bacteria.   The oral resident bacterial flora adjustment according to any one of claims 1 to 11, which exhibits antibacterial activity against at least one of Candida albicans and methicillin-resistant Staphylococcus aureus (MRSA) which are opportunistic pathogenic bacteria. Agent.   The oral microbial flora characterized by applying the oral microbial flora regulator according to any one of claims 1 to 12 to the oral cavity by at least one of application, brushing, oral intake, and eating. Adjustment method.   The catechin is contained in the oral microbial flora adjusting agent, and the amount of catechin contained in one application of the oral microbial flora adjusting agent is in the range of 10 to 100 mg. The method of adjusting the oral resident flora as described.

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