Composition for inhibiting the growth of oral flora

Abstract

The present invention aims to provide a novel and highly safe composition or agent for inhibiting the growth of normal oral bacteria, specifically a composition or agent for inhibiting the growth of cariogenic bacteria, periodontal disease bacteria, or Candida bacteria, as well as a composition or agent for preventing caries, preventing periodontal disease, and inhibiting biofilm formation, and a composition or agent for preventing aspiration pneumonia. [Solution] The inventors have discovered that heated ginger extract can effectively inhibit the growth of cariogenic bacteria, periodontal disease bacteria, or Candida bacteria, and therefore the above problem can be solved by preparing a composition or agent containing heated ginger extract as an active ingredient and using this as a composition or agent for oral use.

Description

[Technical Field]

[0001] The present invention relates to a novel composition for inhibiting the growth of oral resident bacteria, which contains heated ginger extract as an active ingredient. More specifically, the present invention relates to a composition and agent for inhibiting the growth of oral resident bacteria such as cariogenic bacteria, periodontal disease bacteria, and Candida bacteria, preventing oral diseases such as dental caries and periodontal disease caused by the oral resident flora, inhibiting the formation of biofilms composed of the oral resident flora and extracellular substances, and preventing aspiration pneumonia caused by the oral resident flora and biofilms. [Background technology]

[0002] In recent years, the relationship between oral disease and overall health has become widely recognized, and the concept of oral care, rather than dental care, has become increasingly widespread. For example, aspiration pneumonia has become a problem as the number of people requiring care due to difficulties with oral care increases. Aspiration pneumonia can occur not only through the inhalation of food and drink, but also through the infiltration of resident oral flora into the lungs via the trachea. The main bacteria that make up this resident oral flora are cariogenic bacteria, periodontal disease bacteria, and Candida. Candida is known to form biofilms. Streptococcus mutans, a well-known cariogenic bacteria, produces glucan using sucrose as a substrate. This adhesive glucan, along with the resident oral flora, adheres to teeth and the oral mucosa, forming a biofilm. This biofilm is known to maintain the homeostasis of the resident oral flora.

[0003] The aforementioned periodontal disease is prevalent among people in their 30s to 60s, but because there are few noticeable symptoms in the early stages, many people lose their teeth without realizing they have periodontal disease. Furthermore, it has been reported that periodontal disease can cause or worsen various diseases such as diabetes, premature birth / low birth weight, obesity, and arteriosclerosis of blood vessels, so prevention of periodontal disease is attracting attention.

[0004] Non-Patent Document 1 investigated the antibacterial activity of Hengel Root (HST) against oral microorganisms and that of purified HST components such as 6-shogaol and 6-gingerol, and found that while 6-shogaol had antibacterial activity against Porphyromonas gingivalis, it had no activity against Fusobacterium nucleatum, and that 6-gingerol showed no antibacterial activity against either bacteria. Patent Document 1 also shows that an organic solvent extract of ginger has an inhibitory effect on the plaque-forming ability of Streptococcus mutans.

[0005] Ginger rhizomes contain a lot of 6-gingerol, and it is known that regular ginger extracts and Zingiber officinale, a traditional Chinese medicine, contain more 6-gingerol than 6-shogaol, and that 6-gingerol is converted to 6-shogaol by heating (Patent Document 2). However, it was not known that ginger extract itself, which contains more 6-shogaol than 6-gingerol, effectively inhibits the growth of normal oral bacteria such as cariogenic bacteria, periodontal disease bacteria, or Candida. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Special Publication No. 62-034005 [Patent Document 2] Patent No. 5885153 [Non-patent literature]

[0007] [Non-Patent Document 1] Haruka Fukamachi et al., "Effects of Hangeshashinto on Growth of Oral Microorganisms," Evidence-Based Complementary and Alternative Medicine, 2015, Vol. 2015, ID512947, pp. 1-6 Summary of the Invention [Problem to be solved by the invention]

[0008] The object of the present invention is to provide a novel and useful composition for inhibiting the growth of oral resident bacteria, and more specifically, to provide a composition and agent for inhibiting the growth of oral resident bacteria such as cariogenic bacteria, periodontal disease bacteria, and Candida, preventing dental caries or periodontal disease caused by these oral resident flora, inhibiting biofilm formation, and preventing aspiration pneumonia. [Means for solving the problem]

[0009] The inventors conducted various studies to solve this problem and discovered that heated ginger extract effectively inhibits the growth of cariogenic bacteria, periodontal disease bacteria, and Candida bacteria, which are normal inhabitants of the oral cavity, and thus completed the present invention.

[0010] That is, the present invention has been completed based on the above findings, and comprises the following [1] to [9]. [1] A composition for inhibiting the proliferation of one or more of cariogenic bacteria, periodontal disease bacteria, and Candida bacteria, which contains heated ginger extract as an active ingredient. [2] The composition described in [1], wherein the heated ginger extract contains more 6-shogaol than 6-gingerol. [3] An oral composition containing heated ginger extract as an active ingredient, which is for one or more of preventing dental caries, preventing periodontal disease, inhibiting biofilm formation, and preventing aspiration pneumonia. [4] The oral composition described in [3], wherein the heated ginger extract contains more 6-shogaol than 6-gingerol. [5] An inhibitor of the growth of one or more of cariogenic bacteria, periodontal disease bacteria, and Candida bacteria, containing heated ginger extract as an active ingredient. [6] The growth inhibitor described in [5], wherein the heated ginger extract contains more 6-shogaol than 6-gingerol. [7] An oral preparation containing heated ginger extract as an active ingredient, for use in preventing dental caries, preventing periodontal disease, inhibiting biofilm formation, or preventing aspiration pneumonia. [8] The oral preparation described in [7], wherein the heated ginger extract contains more 6-shogaol than 6-gingerol. [9] An oral preparation according to [7] or [8], the mechanism of action of which is to inhibit the proliferation of one or more of cariogenic bacteria, periodontal disease bacteria, and Candida bacteria. [Effects of the Invention]

[0011] According to the present invention, the growth of oral flora such as cariogenic bacteria, periodontal disease bacteria, or Candida can be efficiently inhibited. Furthermore, since the active ingredient is a heated ginger extract and is highly safe, the present invention can be provided not only for inhibiting the growth of oral flora itself, but also as an oral composition or agent for preventing dental caries and periodontal disease, inhibiting biofilm formation, and preventing aspiration pneumonia. [Brief explanation of the drawings]

[0012] [Figure 1] This graph shows the growth inhibitory effect of low-polyphenol ginger extract (PL), high-gingerol heated ginger extract (SH), or high-gingerol ginger extract (GH) adjusted to 0.1 mg / mL, 1 mg / mL, or 10 mg / mL with phosphate-buffered saline (PBS) as the negative control and 1% povidone-iodine as the positive control, on the cariogenic bacteria Streptococcus mutans, evaluated in terms of ATP content (RLU). [Figure 2] This graph shows the growth inhibitory effect of PL, SH, or GH adjusted to 0.1 mg / mL, 1 mg / mL, or 10 mg / mL in PBS on the periodontal disease bacterium Aggregatibacter actinomycetemcomitans, evaluated in terms of ATP content (RLU), with PBS as the negative control and 1% povidone-iodine as the positive control. [Figure 3]This graph shows the growth inhibitory effect of PL, SH, or GH adjusted to 0.1 mg / mL, 1 mg / mL, or 10 mg / mL in PBS on the periodontal disease bacterium Porphyromonas gingivalis, evaluated in terms of ATP content (RLU), with PBS as the negative control and 1% povidone-iodine as the positive control. [Figure 4] This graph shows the growth inhibitory effect of PL, SH, or GH adjusted to 0.1 mg / mL, 1 mg / mL, or 10 mg / mL in PBS on the periodontal disease bacteria Fusobacterium nucleatum, evaluated in terms of ATP content (RLU), with PBS as the negative control and 1% povidone-iodine as the positive control. [Figure 5] This graph shows the growth inhibitory effect of PL, SH, or GH adjusted to 0.1 mg / mL, 1 mg / mL, or 10 mg / mL in PBS on the Candida fungus Candida albicans, evaluated in terms of ATP content (RLU), with PBS as the negative control and 1% povidone-iodine as the positive control. DETAILED DESCRIPTION OF THE INVENTION

[0013] One aspect of the present invention is a composition or agent for inhibiting the growth of oral flora, containing a heated ginger extract as an active ingredient. Because the composition or agent can inhibit the growth of oral flora, such as cariogenic bacteria, periodontal disease bacteria, and Candida albicans, it can be used as a composition or agent for preventing dental caries and periodontal disease, as well as for inhibiting the formation of oral biofilms that maintain a homeostatic growth environment for these bacterial flora. Furthermore, it can also be used as a composition or agent for preventing aspiration pneumonia caused by these bacterial flora and biofilms.

[0014] The heated ginger extract used in the present invention refers to an extract of a plant of the Zingiberaceae family that has undergone a heating step before or after the extraction procedure. While the gingerol content is much lower in raw Zingiberaceae plants or in unheated ginger extracts, heated ginger extracts are known to have a relatively higher 6-shogaol content than 6-gingerol because gingerol is converted to shogaol by treatment such as heating before or after extraction. Since the heated ginger extract used in the present invention preferably has a higher 6-shogaol content than 6-gingerol, it is preferable to subject it to a heating process as described above. While the ratio of these components is not specifically limited, as a guideline, the 6-shogaol content is preferably at least 1.5 times that of 6-gingerol, more preferably at least 2 times, and even more preferably at least 3 times. Furthermore, the upper limit is not particularly limited, but is preferably 15 times or less, more preferably 10 times or less, even more preferably 8 times or less, and particularly preferably 6 times or less. To increase the 6-shogaol content in the heated ginger extract, the temperature and time of the heating step may be, for example, 100 to 300°C, preferably 120 to 250°C, and the time may be 3 minutes to 30 hours, preferably 5 minutes to 24 hours.

[0015] Examples of ginger extraction methods include juicing, supercritical extraction, steam distillation, and solvent extraction. Supercritical extraction is preferred, with CO2 supercritical extraction being more preferred. The timing of the heating step is also not particularly limited. For example, in the case of juicing, crushed and squeezed ginger is subjected to solid-liquid separation by filtration or centrifugation using a nonwoven fabric or mesh to obtain an extract. However, crushed and squeezed ginger may be heat-treated before extraction and solid-liquid separation, or the extract may be heat-treated after solid-liquid separation. However, in the present invention, a heated ginger extract obtained by heating an extract is preferred, and it is more preferred that the extract be non-fermented. Furthermore, the heated ginger extract is preferably further concentrated and / or dried to form a concentrated or dried product in terms of convenience, etc. The dried product can be obtained by drying and powdering using drum drying, air drying, spray drying, vacuum drying and / or freeze drying, etc., and in this case, a common excipient such as dextrin can be used.

[0016] The heated ginger extract may be, and preferably is, an emulsion obtained by adding an emulsifier to enhance water dispersibility. The emulsifier is not particularly limited as long as it is a component having emulsifying ability, and examples thereof include polysaccharides such as acacia gum, ghatti gum, xanthan gum, and starch sodium octenyl succinate, proteins or protein hydrolysates such as casein and soy protein, lecithin, enzyme-treated lecithin, polyglycerol fatty acid esters, and sucrose fatty acid esters. The emulsification method may be any common emulsification method, and may be, for example, a method using a combination of one or more emulsifying devices such as a high-pressure homogenizer, a colloid mill, an ultrasonic emulsifier, a homomixer, and a homodisper.

[0017] The heated ginger extract used in the present invention preferably contains 0.1 to 20% by weight of shogaol, more preferably 0.2 to 15% by weight, and even more preferably 0.5 to 10% by weight. Commercially available products include "Ginger Extract NE" (emulsified liquid product, Ikeda Tohka Kogyo Co., Ltd.), "Ginger Extract Powder S," "Ginger Extract Powder H," and "Ginger Extract Powder E" (all emulsified powder products, Ikeda Tohka Kogyo Co., Ltd.), and these can be purchased and used.

[0018] The heated ginger extract of the present invention has an inhibitory effect on the proliferation of oral indigenous bacteria such as cariogenic bacteria, periodontal disease bacteria, and Candida. The genus and species of oral indigenous bacteria are not particularly limited. For example, cariogenic bacteria include Streptococcus mutans ( Streptococcus mutans ) and periodontal disease bacteria include Aggregatibacter actinomycetemcomitans ( Aggregatibacter actinomycetemcomitans ), Porphyromonas gingivalis ( Porphyromonas gingivalis ), Fusobacterium nucleatum ( Fusobacterium nucleatum ) and Candida fungi such as Candida albicans ( Candida albicans ) and others. Note that cariogenic bacteria are gram-positive bacteria, periodontal disease bacteria are gram-negative bacteria, and Candida is a fungus.

[0019] The growth inhibitory effect of the present invention on oral resident bacteria can be evaluated by a common method capable of confirming an increase or decrease in bacterial count, such as agar plate dilution, broth microdilution such as broth dilution, disk diffusion, calculating the minimum inhibitory concentration (MIC) or minimum bactericidal concentration (MBC) using drug susceptibility tests such as E-test, ATP measurement, etc. For example, in the ATP measurement method, a lower ATP level compared to the control product indicates a growth inhibitory effect, and a lower ATP level indicates a lower bacterial count and a stronger growth inhibitory effect.

[0020] The composition or agent containing the heated ginger extract of the present invention as an active ingredient can inhibit the growth of oral flora such as cariogenic bacteria, periodontal disease bacteria, and Candida. Therefore, another embodiment of the present invention is an oral composition or agent for preventing caries and periodontal disease, another embodiment is an oral composition or agent for inhibiting the formation of oral biofilms that stabilize the growth environment of these bacterial flora, and yet another embodiment is an oral composition or agent for preventing aspiration pneumonia caused by these bacterial flora and biofilms.

[0021] The compositions or agents of the present invention may contain heated ginger extract in an amount sufficient to achieve the effects of the present invention. Specifically, the heated ginger extract is preferably contained in an amount such that the concentration of the ginger-derived solids upon use is 0.15 to 15 mg / mL, more preferably 0.3 to 10 mg / mL, and even more preferably 0.5 to 8 mg / mL. For cariogenic bacteria, the heated ginger extract is preferably 1.5 mg / mL or more, more preferably 20 mg / mL or more, and even more preferably 30 mg / mL or more. Furthermore, the heated ginger extract is preferably contained in an amount such that the 6-shogaol concentration upon use is 20 to 2,000 ppm, more preferably 40 to 1,500 ppm, and even more preferably 60 to 1,000 ppm. For cariogenic bacteria, the heated ginger extract is preferably 300 ppm or more, more preferably 400 ppm or more, and even more preferably 500 ppm or more. It is also preferable to include heated ginger extract so that the 6-gingerol concentration during use is 5 to 500 ppm, more preferably 8 to 300 ppm, and even more preferably 10 to 200 ppm. In particular, for cariogenic bacteria, it is preferable that the 6-gingerol concentration is 60 ppm or more, more preferably 80 ppm or more, and even more preferably 100 ppm or more.

[0022] Each composition or agent of the present invention can be provided in any form, and is not particularly limited thereto, and examples thereof include dentifrices such as toothpaste, lubricant dentifrice, and liquid dentifrice, as well as mouthwashes, mouth fresheners, and gargling tablets, and can be prepared and used in various forms ranging from oral care products such as denture cleaners to foods and beverages such as troches, tablets, candies, chewing gums, jellies, and beverages. When the heated ginger extract, which is the active ingredient, is in the form of an emulsion, it has good dispersibility and is less likely to cause problems such as cloudiness, and is therefore particularly useful for use in liquid products such as liquid dentifrices, mouthwashes, and beverages. [Example]

[0023] The present invention will be specifically described below with reference to examples, but the present invention is not limited to the following examples. In the present invention, all % is by weight unless otherwise specified.

[0024] (various ginger extracts) As a low-polyphenol ginger extract (PL), we used a powdered ginger extract (Ginger Extract Powder FX1025, manufactured by Ikeda Tohka Kogyo Co., Ltd., ginger-derived solids content 38.8%, total polyphenol content: 0.70%, shogaol content: 0.029%, gingerol content: 0.47%, S / G = 0.06) obtained by adding dextrin as an excipient to ginger juice and spray-drying the mixture. The heated ginger extract (SH) with a high gingerol content was prepared by heating an extract extracted from ginger using supercritical carbon dioxide extraction, adding an emulsifier to the heated ginger extract, emulsifying it, adding dextrin as an excipient, and spray-drying it to obtain a powder (Ginger Extract Powder E, manufactured by Ikeda Tohka Kogyo Co., Ltd., ginger-derived solid content 15.0%, total polyphenol content: 3.8%, shogaol content: 2.3%, gingerol content: 0.60%, S / G = 3.8). The ginger extract with high gingerol content (GH) was prepared by adding an emulsifier to the ginger extract liquid extracted from ginger using supercritical carbon dioxide, emulsifying it, adding dextrin as an excipient, and spray-drying it to obtain a powder (Ginger Extract Powder G2, manufactured by Ikeda Tohka Kogyo Co., Ltd., ginger-derived solid content 11.0%, total polyphenol content: 3.2%, shogaol content: 0.30%, gingerol content: 2.3%, S / G = 0.13).

[0025] [Example 1] (Growth inhibition test against cariogenic bacteria) 2.8 mL of brain heart infusion broth poured into a 12-well plate was placed in a 1.5 mL tube, and 0.1 mL of either low polyphenol ginger extract (PL), high gingerol heated ginger extract (SH), or high gingerol ginger extract (GH) adjusted to 0.1 mg / mL, 1 mg / mL, or 10 mg / mL with phosphate buffered saline (PBS) was added. 1 × 10 60.005 mL of a suspension of Streptococcus mutans, a cariogenic bacteria, adjusted to CFU / mL was added and the mixture was subjected to static anaerobism culture at 37°C. After 18 hours of culture, the bacterial count in the culture medium was evaluated in terms of ATP content (RLU). ATP content was measured using an ATP measurement kit (Kikkoman Biochemifa), and the results are shown in Figure 1. The lower the ATP content, the lower the bacterial count and the stronger the growth inhibitory effect. Phosphate-buffered saline (PBS) was added instead of each ginger extract as a negative control, and 1% povidone-iodine was added as a positive control.

[0026] As shown in Figure 1, low-polyphenol ginger extract (PL) showed almost no growth inhibitory effect on Streptococcus mutans, whereas high-gingerol ginger extract (GH) showed a slight growth inhibitory effect at 10 mg / mL (ginger-derived solids concentration: 1.1 mg / mL), and high-shogaol heated ginger extract (SH) showed a strong growth inhibitory effect at 10 mg / mL (ginger-derived solids concentration: 1.5 mg / mL).

[0027] [Example 2] (Growth inhibition test against periodontal disease bacteria) The same tests were conducted as in Example 1, except that Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, or Fusobacterium nucleatum, which are periodontal disease bacteria, were used instead of Streptococcus mutans used in Example 1, and tryptic soy broth containing 0.5% yeast extract was used as the culture medium for Aggregatibacter actinomycetemcomitans, and modified GAM broth medium was used for the culture of Porphyromonas gingivalis and Fusobacterium nucleatum. The results are shown in Figures 2 to 4.

[0028] As shown in Figure 2, the polyphenol-low ginger extract (PL), the gingerol-rich heated ginger extract (SH), and the gingerol-rich ginger extract (GH) all exhibited a concentration-dependent growth inhibitory effect on Aggregatibacter actinomycetemcomitans. In particular, the gingerol-rich heated ginger extract (SH) and the gingerol-rich ginger extract (GH) exhibited a very strong growth inhibitory effect at a concentration of 10 mg / mL (ginger-derived solids concentration in SH: 1.5 mg / mL, ginger-derived solids concentration in GH: 1.1 mg / mL), comparable to that of 1% povidone-iodine.

[0029] As shown in Figures 3 and 4, the polyphenol-low ginger extract (PL) did not show any inhibitory effect on the growth of Porphyromonas gingivalis and Fusobacterium nucleatum, whereas the shogaol-rich heated ginger extract (SH) and the gingerol-rich ginger extract (GH) showed a concentration-dependent inhibitory effect on the growth of Porphyromonas gingivalis and Fusobacterium nucleatum. In the case of ginger extract (GH), a very strong growth inhibitory effect equivalent to that of 1% povidone-iodine was observed at 10 mg / mL (ginger-derived solids concentration in SH: 1.5 mg / mL, ginger-derived solids concentration in GH: 1.1 mg / mL).Furthermore, in the case of heated ginger extract with a high gingerol content (SH), a strong growth inhibitory effect was observed against Porphyromonas gingivalis and Fusobacterium nucleatum even at 1 mg / mL (ginger-derived solids concentration: 0.15 mg / mL).

[0030] [Example 3] (Growth inhibition test against Candida fungi) The test was carried out in the same manner as in Example 1, except that Candida albicans was used instead of Streptococcus mutans used in Example 1 and the Candida fungus was cultured aerobically using Sabouraud medium. The results are shown in Figure 5.

[0031] As shown in Figure 5, ginger extract with a low polyphenol content (PL) did not have any inhibitory effect on the growth of Candida albicans, whereas heated ginger extract with a high shogaol content (SH) and gingerol-rich ginger extract (GH) did. In particular, heated ginger extract with a high shogaol content (SH) and gingerol-rich ginger extract (GH) both exhibited a strong inhibitory effect on the growth of Candida albicans at concentrations of 10 mg / mL (ginger-derived solids concentration in SH: 1.5 mg / mL, ginger-derived solids concentration in GH: 1.1 mg / mL).

[0032] From the above, it was found that ginger extracts with high shogaol or gingerol content have a growth inhibitory effect on all bacteria, including cariogenic bacteria, periodontal disease bacteria, and Candida, but that the growth inhibitory effect on periodontal disease bacteria, which are gram-negative bacteria, is stronger than that on cariogenic bacteria, which are gram-positive bacteria, and that they have an even stronger growth inhibitory effect on Candida, which is a fungus.In addition, it was found that heated ginger extract with high shogaol content (SH) showed a stronger growth inhibitory effect on all bacteria, including cariogenic bacteria, periodontal disease bacteria, and Candida, than gingerol-rich ginger extract (GH).

Claims

1. A composition for inhibiting the proliferation of one or more of cariogenic bacteria, periodontal disease bacteria, and Candida fungi, which contains a heated ginger extract as an active ingredient.

2. The composition according to claim 1, wherein the heated ginger extract contains more 6-shogaol than 6-gingerol.

3. An oral composition containing a heated ginger extract as an active ingredient, the oral composition being for one or more of preventing dental caries, preventing periodontal disease, inhibiting biofilm formation, and preventing aspiration pneumonia.

4. The oral composition according to claim 3, wherein the heated ginger extract contains more 6-shogaol than 6-gingerol.

5. An inhibitor of the proliferation of one or more of cariogenic bacteria, periodontal disease bacteria, and Candida bacteria, which contains heated ginger extract as an active ingredient.

6. The growth inhibitor according to claim 5, wherein the heated ginger extract contains more 6-shogaol than 6-gingerol.

7. An oral preparation containing heated ginger extract as an active ingredient, for use in preventing one or more of dental caries, periodontal disease, biofilm formation, and aspiration pneumonia.

8. The oral preparation according to claim 7, wherein the heated ginger extract contains more 6-shogaol than 6-gingerol.

9. The oral preparation according to claim 7 or 8, which has an action mechanism of inhibiting the proliferation of one or more of cariogenic bacteria, periodontal disease bacteria, and Candida fungi.

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