JP5196997B2 - Oral composition - Google Patents

Description

  The present invention relates to an agent for promoting secretion of immunoglobulin A into saliva and a composition for oral cavity, which has excellent usability and has preventive effects such as caries, periodontal disease and bad breath.

  Biofilms such as plaque and tongue coating exist in the oral cavity, plaque causes caries and periodontal disease, and tongue coating causes bad breath. Immunoglobulin A (hereinafter referred to as IgA) contained in saliva is known to exist in many dimeric secreted forms, unlike IgA present in serum. It is known that this secretory immunoglobulin A (hereinafter secretory IgA) attaches to invading bacteria as an infection defense and functions to prevent its adhesion and establishment.

  For example, when the amount of IgA secretion in saliva decreases due to various stresses including mental stress, bacteria on the oral tissues are likely to adhere and settle. Established bacteria grow and biofilms such as plaque and tongue coating are formed, and as a result, it is thought to lead to oral diseases such as touch and periodontal disease.

On the other hand, there is an attempt to enhance the ability to secrete IgA in saliva by smelling a scent (see, for example, Patent Document 1). However, even if these flavor components are directly applied to the oral cavity as a composition for the oral cavity, no effect is observed due to the clearance action by saliva. In addition, oral administration vaccines containing antigens to produce antibodies in saliva (see, for example, Patent Document 2) and oral compositions imparted with passive immunity by incorporating IgA specific to oral bacteria have been attempted. (For example, refer to Patent Document 3). However, since there are more than several hundred types of oral bacteria in the oral cavity, the biofilm suppression effect using specific antigens and antibodies is limited.
JP 7-20115 A JP-A-4-5243 JP 58-164518 A

  In view of such a background, the present invention provides an agent for promoting the secretion of IgA into saliva, an agent for suppressing the formation of oral biofilm, which suppresses the biofilm in the oral cavity by increasing the amount of secreted IgA in the saliva that decreases due to stress or the like. It is an object of the present invention to provide an oral composition for preventing caries, periodontal disease, and bad breath containing them.

Therefore, the present inventors examined a component that increases the production amount of secretory IgA and suppresses biofilm formation such as plaque when applied to the oral cavity. As a result, the fragrance selected from synthetic alcohol and perilaldehyde is used. and compounds, sucrose fatty acid esters, when used in combination with sorbitan fatty acid esters and a nonionic surfactant selected from polyoxyethylene sorbitan fatty acid esters, significant IgA secretion promoting effect on the saliva, as well as the mouth of a It has been found that an oral composition having an effect of suppressing plaque adhesion by suppressing biofilm production can be obtained.

The present invention comprises (A) cinnamic alcohol and fragrant compound selected from perillaldehyde, and (B) a sucrose fatty acid ester, sorbitan fatty acid esters and a nonionic surfactant selected from polyoxyethylene sorbitan fatty acid esters The present invention provides an agent for promoting secretion of IgA into saliva and a composition for oral cavity containing these.

  If the composition for oral cavity of the present invention is used, the secretion amount of IgA in saliva is remarkably increased, the production of oral biofilm such as plaque and tongue coating is suppressed, and it is possible to prevent touching, periodontal disease, bad breath, etc. it can.

  The fragrant compound selected from the component (A) cinnamic alcohol and perilaldehyde used in the present invention has an action of promoting the secretion of IgA in saliva. It is not known at all that these compounds have a salivary IgA secretion promoting action, and this is the first finding of the present inventors. These compounds may be used alone or in combination of two kinds. These compounds may be refined products from natural essential oils or synthetic products. Further, perilla aldehyde may be used as perilla aldehyde containing perilla aldehyde or perilla oleoresin, or may be used as per seinal alcohol containing lilac essential oil or lily of the valley leaf essential oil. .

  The content of the component (A) in the composition of the present invention is preferably 0.005 to 2% by mass, more preferably 0.01 to 2% by mass, from the viewpoint of IgA secretion promoting effect, palatability and stability. 0.02 to 1.5% by mass is most preferable. The content of perilaldehyde is preferably 0.005 to 1% by mass because of a characteristic fragrance, and the content of the synthetic alcohol is preferably 0.1% by mass or more from the viewpoints of palatability and IgA secretion promoting effect.

The nonionic surfactant selected from the component (B) sucrose fatty acid ester, sorbitan fatty acid ester and polyoxyethylene sorbitan fatty acid ester used in the present invention synergistically enhances the IgA secretion promoting effect of the component (A). Have When these nonionic surfactants are used, an effect of synergistically enhancing the IgA secretion promoting action of the component (A) is observed without reducing the saliva secretion amount. The average carbon number of each fatty acid moiety of these nonionic surfactants is preferably 10 to 18 from the viewpoint of enhancing the IgA secretion promoting effect. As long as the IgA secretion promoting action of the present invention is not greatly changed, other fatty acids may be contained. That is, the sorbitan fatty acid ester and polyoxyethylene sorbitan fatty acid ester used in the present invention include those containing a part of other types of fatty acids having 10 or more and 18 or less carbon atoms. Those having an average of 10 to 18 carbon atoms are preferred.
Moreover, the polyoxyethylene addition mole number of polyoxyethylene sorbitan fatty acid ester is 1-300, Furthermore, 1-100, Especially 1-50 are preferable. More specifically, as sucrose fatty acid ester, sucrose capric acid ester, sucrose undecyl acid ester, sucrose lauric acid ester, sucrose tridecyl acid ester, sucrose myristic acid ester, sucrose pentadecyl acid ester, sucrose palmitic acid Examples include acid esters, sucrose oleate esters, and sucrose stearate esters. Sorbitan monocapric acid ester, sorbitan monoundecylate, sorbitan monolaurate, sorbitan monotridecylate, sorbitan monomyristate, sorbitan monopalmitate, sorbitan monooleate, sorbitan triolein Examples include acid esters, sorbitan tetraoleate, sorbitan sesquioleate, sorbitan monostearate, sorbitan tristearate, and the like.

  The mass ratio [(A) :( B)] of the component (A) and the component (B) in the IgA secretion promoter of the present invention is the point of enhancing the IgA secretion promoting effect and the retention in the oral cavity of the component (A). From this point, 1: 0.2 to 1:50 is preferable, 1: 0.5 to 1:50 is more preferable, 1: 0.5 to 1:25 is more preferable, and 1: 1 to 1:15 is preferable. Particularly preferred. Moreover, it is preferable that content of the component (A) and (B) in this invention composition is 6 mass% or less from points, such as a usability | use feeling other than an IgA secretion promotion effect enhancement effect.

  Moreover, content of the component (B) in this invention composition is 0.01-5.0 mass% from points, such as a feeling of use other than IgA secretion promotion effect enhancement effect, Furthermore, 0.02-4. 0 mass%, 0.05-3.0 mass% is especially preferable.

  The oral composition of the present invention may contain various known components in addition to the essential components according to the form. For example, dicalcium phosphate, tricalcium phosphate, calcium pyrophosphate, magnesium phosphate, insoluble sodium metaphosphate, anhydrous silicic acid, aluminum hydroxide, alumina, hydroxyapatite, calcium carbonate, magnesium carbonate, calcium sulfate, zeolite, synthetic aluminosilicate, Abrasives such as Bengala; Granular abrasives granulated from the above abrasives using a binder; Glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol, polypropylene glycol, erythritol, xylitol, sorbitol Humectants such as maltitol; carboxymethylcellulose and its salts, methylcellulose, hydroxyethylcellulose, carrageenan, sodium polyacrylate, Binders such as droxypropylcellulose, sodium carboxymethylhydroxyethylcellulose, sodium alginate, propylene glycol alginate, xanthan gum, tragacanth gum, karaya gum, arabic gum, polyvinyl alcohol, polyvinylpyrrolidone, vegam, laponite; sodium monofluorophosphate, fluorine Dental strengthening agents such as tin fluoride and sodium fluoride; bactericides such as chlorhexidine and its salts, triclosan, cetylpyridinium chloride, thymols, benzalkonium chloride; pH adjusters such as sodium phosphate; dextranase and amylase Enzymes such as protease, lysozyme, mutanase; sodium chloride, hinokitiol, ε-aminocaproic acid, tranexamic acid, allantoins, Tokov Rolls, Octylphthalide, Nicotinates, Dihydrocholesterol, Glycyrrhetinic acid, Glycyrrhizic acid and its salts, Glycerophosphate, Chlorophyll, Water-soluble inorganic phosphate compounds, Azulene, Chamomile, Assembly, Toki, Senkyu, Crude drugs Anti-inflammatory agents / blood circulation promoters such as saccharin sodium, stevioside, thaumatin, aspartylphenylalanine methyl ester, etc .; p-hydroxybenzoic acid, p-hydroxybenzoic acid ethyl, p-hydroxybenzoic acid propyl, p-hydroxybenzoic acid Preservatives such as butyl acid and sodium benzoate; colorants and pigments such as titanium dioxide; peppermint oil, spearmint oil, menthol, carvone, anethole, eugenol, methyl salicylate, limonene, osimene, -Decyl alcohol, citronellol, α-terpineol, methyl acetate, citronellyl acetate, methyl eugenol, cineol, linalool, ethyl linalool, vanillin, thymol, anise oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, Fragrances such as pimento oil, cinnamon oil, winter green oil, clove oil, and eucalyptus oil can be used as appropriate.

  As an embodiment of the composition of the present invention, in the case of toothpaste, among the above components, the abrasive is contained in the composition of the present invention in an amount of 5.0 to 50% by mass, and further 15 to 40% by mass. Is preferred. The binder is preferably contained in an amount of 0.2 to 4.0% by mass, more preferably 0.5 to 2.0% by mass. Moreover, it is preferable to contain a wetting agent 10-50 mass%, and also 20-40 mass%. In the case of a mouthwash, the wetting agent is preferably contained in an amount of 2.0 to 30% by mass, more preferably 4.0 to 20% by mass. In the case of a troche or gum, it is preferable to contain 50-99 mass%, and also 60-95 mass% of wetting agents.

  Furthermore, surfactants other than the specific nonionic surfactants described above can be used within a range that does not inhibit the IgA secretion promoting effect (content, production method, dosage form, etc.). For example, lauryl sulfate, myristyl sulfate, α-olefin sulfonate, N-acyl amino acid salt, acyl monoglyceride sulfate, soap, fatty acid monoglyceride, fatty acid monoalkanolamide, polyglycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, alkyl Glycosides, imidazolinium betaines, alkylbetaines, alkylamidobetaines, sulfobetaines, amine oxides and the like can also be used in combination. These surfactants are preferably contained in the composition of the present invention in an amount of 0.05 to 5.0 mass%, more preferably 0.1 to 2.0 mass%.

  The oral composition of the present invention can be produced by conventional methods, such as toothpaste, powder toothpaste, liquid toothpaste, oral pasta, mouthwash (mouth wash), mouthwash, mouthwash, gum massage cream, chewing gum, It can be in the form of a troche or candy.

Examples 1 to 4 (Effect on salivary secretory immunoglobulin A concentration)
Two subjects with a low saliva secretion rate having a saliva secretion amount of 1.2 mL / min or less when chewing 1 g of Fusen gum base were chewed with various chewing gums, and the amount of secretory IgA secretion in saliva was measured. Chewing gum (Examples 1 to 4) in which a nonionic surfactant is blended with cinnamic alcohol or perilaldehyde, those in which only cinnamic alcohol or perilaldehyde is blended (Comparative Examples 1 and 2), and only nonionic surfactants are blended. Samples (Comparative Examples 3 to 4), gum bases containing no ingredients (Comparative Example 5), and other aromatic components blended with nonionic surfactants (Comparative Examples 6 to 9) were used as test samples ( Tables 1-3).
Examples 2 and 4 are reference examples and are not included in the scope of the present invention. The same applies to Examples 6, 7 and 10 below.

  Immunoglobulin was measured according to the sandwich antibody method of Nishida et al. ("Ayumi of Medicine" 129 (11) 767-779, 1984). This will be specifically described below.

  1 g of the test sample of Examples 1 to 4 or Comparative Examples 1 to 9 was chewed for 2 minutes at 60 strokes per minute, and all the saliva accumulated in the mouth and the test sample were once discharged. Thereafter, 1 g of a new test sample was again chewed at 60 strokes per minute, and all the secreted saliva was collected by the discharge method. The collected whole saliva was diluted 40 times with a reaction buffer. 0.4 mL of the reaction buffer was added to the test tube, and 10 μL of the diluted saliva was added and mixed. A polystyrene ball to which an anti-human secretary component (hereinafter abbreviated as SC) was uniformly bonded was added, and the mixture was heated at 37 ° C. for 1 hour. After completion of the reaction, the reaction solution was removed by suction, 1 mL of PBS (pH 7.4) was added, and after shaking well, suction was removed again and washed. This washing operation was repeated twice. 0.3 mL of peroxidase-labeled anti-human IgA was added to the test tube after washing, and allowed to stand at room temperature for 1 hour. After completion of the reaction, the reaction solution was removed by suction, 1 mL of PBS (pH 7.4) was added, and after shaking well, suction was removed again and washed. This washing operation was repeated three times. 0.5 mL of a substrate solution containing o-phenylenediamine and hydrogen peroxide was placed in a new test tube, and the cleaned SC-bonded polystyrene balls were transferred. After reacting for 30 minutes at room temperature, 2 mL of 4.1 N sulfuric acid was added to stop the reaction. After thoroughly mixing the test tubes, the absorbance at 492 nm, which is the color of 2,2-diaminoazobenzol, was measured using the reagent blank as a control for the spectrophotometer. In addition, a standard curve was prepared in the range of 0.06 to 64 μg / mL for standard human s-IgA for quantitative calculation. All reagents were manufactured by Medical and Biological Laboratories.

  The results are shown in Tables 1 to 3 and FIG.

From Tables 1 to 3 and FIG.
The composition for oral cavity which mix | blended synthetic alcohol or perilaldehyde, and sucrose fatty acid ester or polyoxyethylene sorbitan fatty acid ester remarkably increases the IgA density | concentration in saliva (Examples 1-4). The effect is that when synthesizing alcohol or perilaldehyde alone without using a specific nonionic surfactant such as sucrose fatty acid ester or polyoxyethylene sorbitan fatty acid ester (Comparative Examples 1 and 2), etc. This is more remarkable than the combination of the fragrance of sucrose and sucrose fatty acid ester or polyethylene sorbitan fatty acid ester (Comparative Examples 6 and 7).

  As is apparent from Tables 1 to 3, the composition containing cinnamic alcohol or perilaldehyde and sucrose fatty acid ester or polyoxyethylene sorbitan fatty acid ester increased IgA concentration without reducing salivary secretion. .

Examples 5-6 (clinical effect on oral biofilm)
Using the same two subjects as in Examples 1 to 4 and Comparative Examples 1 to 9 described above, a mouthwash further containing sucrose laurate in synthetic alcohol (Example 5) or perilaldehyde (Example 6) The clinical evaluation of the agent on plaque formation was performed. As a control mouthwash, a substance (Comparative Example 10) in which synthetic alcohol or perilaldehyde was substituted with ethyl alcohol was prepared and used in this clinical study. To two subjects in their 30s, thorough dental plaque removal by dental hygienists, and after stopping all oral hygiene habits such as toothpaste, toothpick, and gum use, any mouthwash After each meal and before going to bed, it was moistened four times a day, and the amount of plaque formation and tongue coating formation after 48 hours was measured. The amount of plaque formation was calculated using Quigley &Hein's plaque index (QHI), with the side incisors, first premolars, and first molars as observation teeth, and a total of 24 tooth surfaces on the buccal and lingual sides to be examined. The value was an average QHI value. The examination was performed by a single dental hygienist and was double-blind.

Composition of mouthwash used in Example 5 Ethyl alcohol 12
Erythritol 5
Concentrated glycerin 4
Sucrose laurate 1.5
Synthetic alcohol 0.3
Saccharin sodium 0.01
Purified water balance
Total 100 (parts by mass)

Composition of mouthwash used in Example 6 Ethyl alcohol 12
Erythritol 5
Concentrated glycerin 4
Sucrose laurate 1.5
Perilaldehyde 0.3
Saccharin sodium 0.01
Purified water balance
Total 100 (parts by mass)

Composition of mouthwash used in Comparative Example 10 Ethyl alcohol 12.3
Erythritol 5
Concentrated glycerin 4
Sucrose laurate 1.5
Saccharin sodium 0.01
Purified water balance
Total 100 (parts by mass)

  As a result, as shown in Table 4, the mouthwash containing the synthetic alcohol, perilaldehyde, and monolauric acid sucrose ester showed significant plaque formation compared to the control mouthwash containing the monolauric acid sucrose ester. Reduced the amount.

Example 7
A typical formulation of the toothpaste of the present invention is as follows.
Toothpaste sorbit solution 50
Silicic anhydride 20
Concentrated glycerin 5
Alkyl glucoside 1.3
Sodium carboxymethylcellulose 1
Toothpaste fragrance 1
Polyoxyethylene (20) sorbitan monostearate 0.25
Sodium fluoride 0.2
Perilaldehyde 0.05
Purified water balance
Total 100 (parts by mass)

Example 8
A typical formulation of the mouthwash of the present invention is as follows.
Mouthwash ethyl alcohol 12
Xylitol 5
Concentrated glycerin 4
Sucrose oleate 1.5
Synthetic alcohol 0.1
l-Menthol 0.1
Ethylparaben 0.01
Saccharin sodium 0.01
Purified water balance
Total 100 (parts by mass)

Example 9
A typical formulation for the lozenges of the present invention is as follows.
Lozenge Paratynit 60
Xylitol 20
Guam gum 5
Sucrose stearate 3
Polydextrose 3
Calcium carbonate 1.2
Fragrance 0.5
Synthetic alcohol 0.2
Aspartame 0.1
Total 100 (parts by mass)

Example 10
A typical formulation for the chewing gum of the present invention is as follows: Gum Base 25
Xylitol 60
Minamata 9.4
Fragrance 0.5
Sucrose stearate 0.05
Perilaldehyde 0.05
Total 100 (parts by mass)

It is a figure which shows the relationship between the secretion amount in a saliva IgA secretion amount (bar graph) and the saliva amount (line graph) of the composition of Examples 1-4 and Comparative Examples 1-9. In the figure, None (Comparative Example 5), None + S (Comparative Example 3), None + R (Comparative Example 4), Synthetic alcohol (Comparative Example 1), Perilaldehyde (Comparative Example 2), Synthetic alcohol + S (Example) 1), Perilaldehyde + S (Example 3), Synthetic alcohol + R (Example 3), Perilaldehyde + R (Example 4), Eucalyptol + S (Comparative Example 6), Lavandin + S (Comparative Example 7), Anethole + S (Comparative Example 8), Peppermint oil + S (Comparative Example 9).

Claims (4)

(A) cinnamic alcohol 0.1-1.5% by weight, and (B) an immunoglobulin A in saliva in containing sucrose fatty acid esters 及 beauty polyoxyethylene sorbitan nonionic surfactant selected from sorbitan fatty acid esters Secretagogue. The agent for promoting secretion of immunoglobulin A into saliva according to claim 1, wherein the mass ratio [(A) :( B)] of component (A) to component (B) is 1: 1 to 1:15 .   The agent for promoting secretion of immunoglobulin A into saliva according to claim 1 or 2, wherein each fatty acid moiety of the nonionic surfactant of component (B) has an average carbon number of 10 to 18. (A) cinnamic alcohol 0.1-1.5% by weight, and (B) a sucrose fatty acid ester 及 beauty polyoxyethylene sorbitan oral compositions containing a nonionic surfactant selected from sorbitan fatty acid esters.

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