WO2011007552A1

WO2011007552A1 - Bad breath-removing agent

Info

Publication number: WO2011007552A1
Application number: PCT/JP2010/004531
Authority: WO
Inventors: 児玉悠史; 樋口裕明; 成瀬敦; 桜井孝治
Original assignee: 株式会社ロッテ
Priority date: 2009-07-14
Filing date: 2010-07-13
Publication date: 2011-01-20
Also published as: KR20120042969A; JP2011020936A; CN102470114A; CN103690385A; TW201116272A

Abstract

Disclosed is a bad breath-removing agent which contains a sugar alcohol as an active ingredient. Specifically disclosed is a breath-removing agent which is characterized by the inhibitory activity of a sugar alcohol on the production of a volatile sulfur compound. The breath-removing agent contains a sugar alcohol, in particular lactitol, as an active ingredient.

Description

Bad breath remover

The present invention relates to a bad breath removing agent characterized by suppressing production of volatile sulfur compounds by sugar alcohol.

According to the Ministry of Health, Welfare and Health Trend Survey of approximately 30,000 people in Japan, 70% of people with dental problems in the oral cavity are recognized, and 14.5% of those who are worried about bad breath (Multiple answers allowed), the fourth highest after complaints related to periodontal disease and caries, and interest in bad breath is increasing year by year. As an unpleasant odor component emitted from the oral cavity, volatile sulfur compounds (VSC), volatile nitrogen compounds, lower fatty acids and the like have been reported. Of these, VSC is reported to show a strong correlation between the odor intensity of the sensory test and the concentration detected in the oral cavity. VSCs detected in oral gas include hydrogen sulfide, methyl mercaptan, and dimethyl sulfide, either alone or in combination. Other substances are detected in exhaled breath, but it is rare to detect concentrations above the human odor threshold.

VSC, the main cause of bad breath, is produced by the metabolism of anaerobic bacteria in the oral cavity using debris from oral cells and sulfur-containing amino acids in food as a substrate. In particular, hydrogen sulfide is produced from cysteine due to the involvement of bacterial cystathionine-β-syntase and cystathionine-γ-lyase, and methyl mercaptan is produced from methionine due to the involvement of L-methionine-γ-lyase.

VSC is not only a malodorous substance but also has a strong biotoxicity. It has been reported that VSC enhances permeability of mucous membranes having a barrier function, promotes collagen synthesis inhibition of fibroblasts and damage of epithelial basement membrane, and inhibits synthesis. In particular, in experiments using human leukocytes, hydrogen sulfide increases the production of active oxygen, while strongly inhibiting superoxide dismutase (SOD), suggesting the possibility that VSC has carcinogenicity. Therefore, suppressing bad breath becomes important in maintaining oral health.

In recent years, the demand for sugar alcohol has increased from the viewpoint of oral care, particularly anti-caries, but the influence of sugar alcohol on bad breath remains unclear.

Therefore, the influence of bad breath on the xylitol, maltitol, erythritol, and lactitol sugar sugars currently used in sugarless gum was evaluated by a saliva incubation test and a bacterial metabolism inhibition test.

There are the following patent documents as prior art related to sugar alcohols, bad breath, and deodorant reducing action.

Patent Document 1 relates to the invention of chewing gum. A composition containing calcium dihydrogen phosphate and calcium glycerophosphate is kneaded with a gum base to produce a chewing gum, which is chewed, and has an immediate effect and sustainability of a bad breath effect. Panelists made a sensory evaluation. As a result, in the case of 60% xylitol blended gum, 10/10 people recognized immediate effect and 7/10 people recognized durability. On the other hand, when xylitol was replaced with 60% sucrose, 5/10 people recognized immediate effect and 3/10 people recognized sustainability. In addition, there is no description about the mastication time or the specific time in which immediate effect / sustainability is recognized. In the detailed description 0017 of the invention of Patent Document 1, the effect of removing bad breath is improved by containing one or more sugar alcohols from the group consisting of xylitol, sorbitol, and erythritol in the chewing gum. It is described that 20 to 85% by weight, more preferably 30 to 80% by weight of the whole chewing gum is desirable.

Patent Document 2 relates to a composition for oral cavity. Disclosed is an oral composition that prevents and suppresses bad breath, particularly bad breath caused by methioninase. Claim 1 describes that it contains one or more selected from the group consisting of mannitol, maltitol, sorbitol and a mixture thereof, and is usually 0.1% by mass or more in products and preparations. Preferably, it is blended at a ratio of 1 to 70% by mass. As a result of measuring the methyl mercaptan after adding Porphyromonas.gingivalis cell suspension and methionine to the sample solution, the sample solution containing 1% by mass of maltitol inhibits methionase activity by 20.0%. A report has been made.

Patent Document 3 relates to a bad breath component cleaning composition and a composition for oral cavity containing the same, chewing gum and refreshing confectionery in the mouth. In particular, the present invention relates to a cleaning composition for cleaning odor components such as indole, skatole, phenol, p-cresol, and the composition for oral cavity. According to claim 4, it is described that one or more kinds selected from sugar alcohols having 4 to 24 carbon atoms are included. Among the above sugar alcohols, sorbitol, xylitol, lactitol, maltitol, and palatinit are reported to be desirable. In the examples using dentifrices, those containing erythritol and maltitol showed the most significant reduction in bad breath after 30 minutes of use for subjects with bad breath (sensory evaluation by three specialist panels).

Patent Document 4 discloses a bad breath removal agent for phase transition, and in particular, a bad breath removal agent comprising a monoglyceride as a main base and comprising a polymer, a polyol, a bad breath removal active ingredient, and a solvent. From claim 14, it describes that non-fermentable sugar alcohol is included as a bad breath removing active ingredient, and from claim 16, as non-fermentable sugar alcohol, xylitol, sorbitol, erythritol, mannitol, maltitol, lactitol, paratinitol, palatinose. Describes oligosaccharides. Although patent document 4 is evaluating the bad breath removal effect by sensory evaluation using the comparative example and example which contain xylitol, the correlation between the xylitol content and the result of sensory evaluation is not confirmed.

As described above, in the prior art, disclosure showing a bad breath reducing effect was recognized for xylitol, erythritol, and maltitol, including the examples. However, with regard to lactitol, although there is a description as a composition and an active ingredient in the claims, no examples showing a specific deodorizing effect were found.

JP 2006-325455 A JP 2003-160458 A JP 2004-203872 A Special table 2009-500399

An object of the present invention is to provide a bad breath removing agent characterized by suppressing production of volatile sulfur compounds by sugar alcohol.

VSC, volatile nitrogen compounds, lower fatty acids, etc. have been reported as unpleasant odor components emitted from the oral cavity. Among these, VSC has been reported to show a strong correlation between the odor intensity of the sensory test and the concentration detected from the oral cavity. In order to confirm the effects of sugar alcohols on bad breath, the effects of each sugar alcohol on VSC generation were examined, and it was confirmed that erythritol, lactitol, and maltitol suppressed the generation of hydrogen sulfide and methyl mercaptan in a pH-independent manner. . It was also confirmed that lactitol and maltitol reduce hydrogen sulfide production to about 40-60% at a concentration of 10% against P. gingivalis, the main causative agent of periodontal disease.

Since the present invention exhibits a remarkable volatile sulfur compound production inhibitory action, it can be used as a preparation such as a mouthwash, a toothpaste, an inhalant, a troche, and chewing gum, candy, tablet confectionery, gummy jelly, It can be used and ingested daily as a food such as biscuits and chocolates, sorbets and beverages, and is effective in improving and preventing bad breath.

It is a graph which shows the influence with respect to VSC generation | occurrence | production of sucrose. It is a graph which shows the influence with respect to VSC generation | occurrence | production of a xylitol. It is a graph which shows the influence with respect to VSC generation | occurrence | production of an erythritol. It is a graph which shows the influence with respect to VSC generation | occurrence | production of lactitol. It is a graph which shows the influence with respect to VSC generation | occurrence | production of the lactitol under neutral conditions. It is a graph which shows the influence with respect to VSC generation | occurrence | production of maltitol. It is a graph which shows the influence with respect to VSC generation | occurrence | production of maltitol under neutral conditions. It is a graph which shows the microbial metabolism inhibitory effect of sugar alcohol. It is a graph which shows the microbial metabolism inhibitory effect of sugar alcohol.

One embodiment of the present invention is a bad breath remover containing sugar alcohol as an active ingredient.

A further embodiment of the present invention is the bad breath remover as described above, wherein the sugar alcohol is lactitol.

Another embodiment of the present invention is a mouthwash, a toothpaste, an inhalant, and a troche comprising a bad breath remover containing sugar alcohol as an active ingredient.

Still another embodiment of the present invention is a food comprising a bad breath remover containing sugar alcohol as an active ingredient.

Still another embodiment of the present invention is a food such as chewing gum, candy, tablet confectionery, gummy jelly, biscuits, chocolate and other confectionery, sorbet, beverage and the like containing a bad breath remover containing sugar alcohol as an active ingredient. is there.

Another embodiment of the present invention is a production inhibitor of volatile sulfur compounds by inhibiting methionine and cysteine metabolic pathways containing sugar alcohol as an active ingredient.

Still another embodiment of the present invention is the volatile sulfur compound production inhibitor as described above, wherein the sugar alcohol is lactitol or maltitol.

Hereinafter, the present invention will be described in detail by way of specific examples, but the present invention is not limited thereto.

Example 1
Sugar alcohol saliva incubation test was performed as follows.

1-1. Sample preparation As samples, xylitol, erythritol, lactitol, maltitol, and sucrose were used. Each was dissolved in deionized water to an appropriate concentration to obtain a sample solution.

1-2. Saliva Incubation Test Four healthy adults (A, B, C, D, average age 32.0 years) were subjects, and the test was conducted in duplicate. Between 9:00 am and 9:30 am, 10 ml of unstimulated saliva was collected from each subject (no breakfast or toothpaste on the day of collection). The collected saliva was stored on ice. 0.5 ml of the sample solution was added to 1.0 ml of unstimulated saliva and cultured at 37 ° C. for 23 hours. After incubation for 23 hours, the samples were placed on ice. Before GC analysis, the sample was shaken at 37 ° C. for 15 minutes, an appropriate amount of headspace gas was taken with a syringe, and GC analysis was performed. In the test under neutral conditions, potassium phosphate buffer was added to a final concentration of 20 mM, and the reaction solution was maintained in a neutral region.

1-3. GC analysis For GC analysis, GC6890 manufactured by Agilent was used. HP-PLOTQ (30m × 0.53mm × 40μm) is used as the analytical column, initial temperature: 70 ° C / 2.5min, temperature rise: 30 ° C / min, final temperature: 190 ° C / 3.5min, inlet temperature: 200 ° C, Analysis was performed under the conditions of detector: FPD, detector temperature: 200 ° C., flow rate: 20 ml / min. Regarding RT, hydrogen sulfide is 1.1 min, methyl mercaptan is 4.0 min, dimethyl monosulfide is 5.6 min, and dimethyl disulfide is 8.3 min. All samples were performed in duplicate and calculated as an average value.

1-4. Result 1. Effect of sucrose In the saliva incubation test, sucrose was added to a final concentration of 0.057 and 0.114%. As a result, when the final concentration was 0.057%, there was no change in pH, and there was almost no change in the occurrence of VSC. Generation of methyl mercaptan was also suppressed. These results are shown in FIG.

In addition, when the phosphate buffer was added to the reaction solution and cultured, even when the final sucrose concentration was 0.114%, the pH of the reaction solution was maintained near neutral, and the amount of hydrogen sulfide / methyl mercaptan generated was increased.

It was found that the VSC inhibitory effect of sucrose is pH dependent. The increase in the amount of VSC generated by adding sucrose under neutral conditions is thought to be due to the fact that sucrose becomes a nutrient source for oral bacteria and the number of bacteria that cause bad breath is increased. In the absence of a buffer, bacteria in the oral cavity increase due to sucrose, but as sucrose is assimilated, lactic acid and the like are discharged, pH is lowered, and methioninase activity and cysteine metabolizing enzyme activity are inhibited. Alternatively, it is thought that the occurrence of VSC is suppressed because the growth of bad breath causing bacteria is suppressed.

2. Effect of Xylitol FIG. 2 shows the results of the saliva incubation test described above with xylitol at final concentrations of 1.43% and 5.7%. In this test using xylitol, there was no significant change in the generation amount of hydrogen sulfide / methyl mercaptan and the pH of the reaction solution in all panelists.

3. Effect of Erythritol As shown in FIG. 3, even when erythritol was added, the pH of the reaction solution did not change, but the amount of hydrogen sulfide / methyl mercaptan generated was suppressed depending on the addition concentration.

4). Effect of Lactitol As shown in FIG. 4-1, there was a person (2/4) who did not change the pH of the reaction solution and a person (2/4) whose pH decreased due to the addition of lactitol. In both panelists, the generation of hydrogen sulfide and methyl mercaptan was suppressed.

Further, as shown in FIG. 4-2, when the effect of lactitol was confirmed under neutral conditions, the generation of methyl mercaptan was also suppressed under neutral conditions.

5. The effect of maltitol
Regarding maltitol, there were some people (1/4 people) who did not change the pH of the reaction solution due to the addition of maltitol and others (3/4 people) whose pH decreased. As shown in FIG. 5-1, in all the panelists, even when maltitol was added, the amount of hydrogen sulfide generated hardly changed. On the other hand, the generation of methyl mercaptan was suppressed by the addition of maltitol. Under neutral conditions, as shown in FIG. 5-2, the generation amount of hydrogen sulfide tended to increase, but the generation of methyl mercaptan was suppressed.

From the above results, it was found that xylitol does not adversely affect the occurrence of VSC in the in-vitro test system. In addition, it was found that lactitol, maltitol, and erythritol suppress the generation of VSC in a pH-independent manner. In particular, lactitol had a stronger inhibitory effect than erythritol.

(Example 2)
Bacterial metabolism inhibition test of sugar alcohols was performed as follows.

2-1. Preparation of fungus F. nucleatum and P. gingivalis were used as strains.

F. nucleatum was anaerobically cultured in 3% THB medium containing 0.05% L-cysteine hydrochloride for 1 day. After culturing for 1 day, it was confirmed that the absorbance at 550 nm was 0.8 or more, and the supernatant was discarded after centrifugation at 5000 rpm for 4 minutes. Suspend the bacterial cells in physiological saline and repeat the same procedure. Suspend the bacterial cells in physiological saline twice the amount of the original bacterial solution, and use it for ice cooling. .

P. gingivalis was anaerobically cultured in TSB medium (3% TripticaseticSoy Broth, 0.3% Yeast Extract, 0.0005% hemin, 0.00005% menadione) for 1 day. After culturing for 1 day, it was confirmed that the absorbance at 550 nm was 1.4 or more, and a bacterial solution was prepared in the same manner as described above.

2-2. Methionine metabolic pathway inhibition test 2.47 ml of 0.1 M phosphate buffer (pH 6.5) and 0.03 ml of the test solution were placed in a test tube. The head space was replaced with a mixed gas (nitrogen: hydrogen: carbon dioxide gas = 8: 1: 1), sealed with a silicon stopper, stirred, and kept in a 37 ° C. water bath. After 5 minutes, 0.2 ml of the bacterial solution was injected using a tuberculin syringe, stirred and kept warm. After 5 minutes, 0.3 ml of L-methionine solution (0.5%) was injected using a tuberculin syringe, stirred, and kept at 37 ° C. for 10 minutes. A 500 μl headspace gas was withdrawn and the amount of methyl mercaptan was measured by GC analysis. The GC analysis conditions were the same as in 1-3 above.

2-3. Cysteine metabolic pathway inhibition test A cysteine metabolic pathway inhibition test was conducted in the same manner as the methionine metabolic pathway inhibition test, except that L-cysteine was used as a substrate.

2-4. Result 1. Methionine Metabolic Pathway Inhibition Test The results of confirming the inhibitory activity of sugar alcohol and sucrose on Fusobacterium nucleatum (hereinafter abbreviated as F. nucleatum) and Porphyromonas gingivalis (hereinafter abbreviated as P. gingivalis) methionine metabolic pathway are shown in FIG. Shown in (a) and (b). For the F. nucleatum methionine metabolic pathway, the positive control zinc chloride reduced the amount of methyl mercaptan generated to 40% (100% control) at final 100 ppm. On the other hand, all sugar alcohols suppressed methyl mercaptan generation to about 80% at a final concentration of 10%, and were observed to have a very weak methionine metabolism inhibitory activity. In addition, for the methionine metabolic pathway of P. gingivalis, the positive control zinc chloride suppressed the generation of methyl mercaptan by 23%. Although lactitol and maltitol were weak, the amount of methyl mercaptan produced was suppressed to about 80 to 90%, but no clear inhibitory effect was observed for xylitol and erythritol.

2. Cysteine Metabolic Pathway Inhibition Test The results of confirming the inhibitory activity of sugar alcohol and sucrose on the F.nucleatum and P.gingivalis cysteine metabolic pathways are shown in FIGS. 6-2 (c) and (d). For the F. nucleatum cysteine metabolic pathway, xylitol, erythritol, lactitol, and maltitol reduced hydrogen sulfide production to about 60-80% at a final 10% concentration. Regarding sucrose, the amount of hydrogen sulfide generated was suppressed to about 40%. For P. gingivalis cysteine metabolic pathway, lactitol, maltitol, and sucrose reduced hydrogen sulfide production to about 40-60% at a final concentration of 10%. On the other hand, no clear effect was observed for xylitol and erythritol.

From the above results, for F. nucleatum, xylitol, erythritol, lactitol, and maltitol inhibit both methionine and cysteine metabolic pathways, although they are weak.

On the other hand, for P. gingivalis, only lactitol and maltitol strongly inhibit the cysteine metabolic pathway. Therefore, it was suggested that the cysteine / methionine metabolism inhibitory effect may be caused as a mechanism of the halitosis suppression action of sugar alcohol.

Next, a mouthwash, a toothpaste, a mouth spray, a troche, a chewing gum, a candy, a tablet candy, a gummy jelly, and a beverage containing the halitosis remover of the present invention were produced by conventional methods. Their formulations are shown below. Note that the scope of the present invention is not limited by these.

(Example 3)
A mouthwash was prepared according to the following formulation.
Ethanol 2.0% by weight
Lactitol 10.0
Fragrance 1.0
Water remaining
100.0

Example 4
A toothpaste was produced according to the following formulation.
Calcium carbonate 40.0% by weight
Glycerin 10.0
Maltitol 20.0
Carboxymethylcellulose 2.0
Sodium ralyl sulfate 2.0
Fragrance 1.0
Saccharin 0.1
Chlorhexidine 0.01
Water remaining
100.0

(Example 5)
A mouse spray was produced according to the following formulation.
Ethanol 10.0% by weight
Glycerin 5.0
Lactitol 10.0
Maltitol 10.0
Fragrance 0.05
Coloring 0.001
Water remaining
100.0

(Example 6)
A lozenge was produced according to the following formulation.
Maltitol 72.3 wt%
Xylitol 20.0
Gum arabic 6.0
Fragrance 1.0
Sodium monofluorophosphate 0.7
100.0

(Example 7)
Chewing gum was manufactured according to the following formulation.
Gum base 20.0% by weight
Maltitol 45.0
Lactitol 33.0
Fragrance 2.0
100.0

(Example 8)
Candy was manufactured according to the following prescription.
Maltitol 50.0% by weight
Reduced water candy 34.0
Citric acid 2.0
Fragrance 0.2
Water remaining
100.0

Example 9
Tablet confectionery was produced according to the following prescription.
Maltitol 76.1% by weight
Lactitol 19.0
Sucrose fatty acid ester 0.2
Fragrance 0.2
Water 4.5
100.0

(Example 10)
Gummy jelly was manufactured according to the following prescription.
Gelatin 60.0% by weight
Reduced water candy 21.40
Maltitol 11.5
Vegetable oil 4.5
Malic acid 2.0
Fragrance 0.5
100.0

(Example 11)
A beverage was produced according to the following formulation.
Orange juice 30.0% by weight
Lactitol 15.0
Citric acid 0.1
Vitamin C 0.04
Fragrance 0.1
Water remaining
100.0

The bad breath remover containing the sugar alcohol of the present invention can be applied to gums, candy, tablet confectionery, etc., and can also be applied to bad breath removal specific health foods.

This application claims priority from Japanese Patent Application No. 2009-165556 filed on Jul. 14, 2009, the contents of which are incorporated herein by reference.

Claims

Bad breath remover containing sugar alcohol as an active ingredient
The bad breath removing agent according to claim 1, wherein the sugar alcohol is lactitol.
An oral repellent, toothpaste, inhalant, and lozenge consisting of a bad breath remover containing sugar alcohol as an active ingredient.
The mouthwash, toothpaste, inhalant, and lozenge according to claim 3, wherein the sugar alcohol is lactitol.
Food made of bad breath remover containing sugar alcohol as an active ingredient.
The food according to claim 5, wherein the sugar alcohol is lactitol.
A volatile sulfur compound production inhibitor that inhibits methionine and cysteine metabolic pathways with sugar alcohol as an active ingredient.
The volatile sulfur compound production inhibitor according to claim 7, wherein the sugar alcohol is lactitol or maltitol.
A mouthwash, a toothpaste, an inhalant, and a lozenge comprising a methionine and cysteine metabolic pathway inhibitor that inhibits sugar alcohol as an active ingredient.
10. The mouthwash, toothpaste, inhalant, and lozenge according to claim 9, wherein the sugar alcohol is lactitol or maltitol.
A food comprising an inhibitor of production of volatile sulfur compounds by inhibiting methionine and cysteine metabolic pathways containing sugar alcohol as an active ingredient.