JP5033605B2 - Oral care composition - Google Patents

Description

  The present invention relates to a composition for oral care. More specifically, the present invention relates to a composition for oral care having a salivary function assisting action capable of moisturizing and smoothing the oral cavity against a decrease in salivary secretion function and suppressing the growth of oral microorganisms, particularly Candida.

  Normally, saliva is constantly secreted into the oral cavity. Saliva is essential for maintaining health such as antibacterial, mucosal protection, pH buffering, tooth remineralization, digestion, and self-cleaning, including the action of moisturizing and smoothing the mouth (lubricating) It has various functions that cannot be performed. However, salivary secretion is known to decrease due to salivary gland disorders, side effects of various drugs, mouth breathing, aging, daily life stress, and the like. If saliva secretion decreases and the dry state persists for a long time, dry mouth (dry mouth) is caused. Xerostomia is a disease that is commonly seen in the elderly, and is thought to be caused by degenerative changes in the salivary glands with age. In addition, for those who use dentures, wearing dentures is a great psychosomatic stress, and many people suffer from xerostomia as a result of a marked decrease in saliva secretion due to this stress.

  If you suffer from xerostomia, you will not only feel dryness in the mouth, but also develop pain, tongue pain, abnormal taste, inflammation of the oral mucosa, erosion, ulceration, cracks in the tongue and mouth corners, mastication and conversation, May cause serious problems in daily life, such as difficulty in breathing. In addition, the antibacterial action of saliva is reduced and the oral environment deteriorates due to dryness, facilitating the growth of oral microorganisms, causing caries, periodontal disease, bad breath, etc. Increase the risk of developing.

It is said that there are usually 400 or more resident bacteria in the oral cavity. Among these, the causative bacteria of various oral diseases include Streptococcus mutans which is a causative agent of caries, Porphyromonas gingivalis which is a causative agent of periodontal disease, and oral malodor cause is a bacterium Fusobacterium nucleatum (Fusobacterium nucletum), Candida albicans responsible fungus candidiasis (Candida albicans), or the like is typical. These are resident bacteria that are also detected in the oral cavity of healthy people, but it is said that the detection rate and the number of detected bacteria increase with a decrease in the amount of saliva secretion, especially for elderly people, especially bedridden elderly people who need care. Of Candida albicans in the elderly is a problem.

  When suffering from candidiasis, it causes dysphagia and anorexia, not only lowering the patient's QOL (Quality of Life), but also lowering the nutritional status further reduces immune function and worsens symptoms Often brings a vicious circle. In addition, aged people with reduced swallowing function often aspirate and may shift from candidiasis to pneumonia, leading to serious consequences.

  As described above, in the elderly, appropriate oral care for the reduction of the salivary secretion function is necessary more than the younger.

  In response to such a demand, for example, Patent Document 1 discloses a composition for reducing dry mouth symptoms using an organic acid as a salivary secretion promoter, and Patent Document 2 includes a cricket seed powder or an extract thereof. Oral compositions and denture stabilizers used as salivary secretion promoters have been proposed. It aims to moisturize and smooth the mouth by promoting the secretion of saliva. However, these stimulate the salivary glands with an acidity such as an organic acid, and are strongly stimulated, so that their use may be limited in terms of palatability. Moreover, in elderly people, there are many cases where the salivary gland has a disorder or a drug that suppresses salivary secretion is used for disease treatment. In such a case, stimulation of the salivary gland is not effective.

Patent Document 3 proposes artificial saliva that uses hyaluronic acid as a moisturizing component, and Patent Document 4 proposes a denture surface treatment agent and denture stabilizing material that uses sericin as a moisturizing component. However, these did not have sufficient effect of moisturizing and smoothing the oral cavity.
Above all, the techniques proposed in Patent Documents 1 to 4 do not have an effect of positively suppressing the growth of oral microorganisms.

  On the other hand, as an agent for suppressing the growth of oral microorganisms, particularly Candida, for example, Patent Document 5 discloses an oral composition for dentures using sorbic acid or a salt thereof and benzoic acid or a salt thereof as an antifungal component in combination. Has been proposed. However, in order to obtain sufficient antifungal properties with the above components, it is necessary to make the liquid property acidic, which causes a problem of mucous membrane irritation.

Patent Document 6 proposes a denture stabilizer that uses a sugar alcohol selected from erythritol, trehalose, and trehalulose, and Patent Document 7 uses xylitol as an antifungal component. However, these require blending of the above components at a high concentration, and have problems of mucous membrane irritation and high taste of sweetness. In addition, Candida bacteria proliferate even when sleeping without wearing a denture, but the denture stabilizer has a problem that the effect is limited only when the denture is worn.
Above all, the techniques proposed in Patent Documents 5 to 7 do not have the effect of moistening and smoothing the oral cavity.

  Further, for example, Patent Document 8 discloses an oral care using a combination of poly-γ-glutamic acid as a moisturizing component and polyphenol as an antibacterial component in order to moisturize and smooth the oral cavity and suppress the growth of oral microorganisms. Compositions have been proposed. However, this has a problem that the effect of suppressing the growth of Candida is not sufficient.

Japanese Patent Laid-Open No. 7-101856 Japanese Patent Laid-Open No. 10-182392 International Publication No. 2000/56344 Pamphlet International Publication No. 2006/101268 Pamphlet JP-A-5-262631 JP 2001-149388 A Japanese Patent Laid-Open No. 2000-333973 JP 2006-83100 A

  The present invention moisturizes and smoothes the oral cavity against a decrease in salivary secretion function, suppresses the growth of oral microorganisms, particularly Candida, and prevents or symptoms of xerostomia and various diseases associated therewith. An object of the present invention is to provide an oral care composition with salivary function assisting action that can be improved, and that is free from problems such as taste and irritation and has excellent safety. .

As a result of repeated studies to achieve the above object, the present inventors have found that a composition containing both a sericin hydrolyzate and a triterpenoid saponin moisturizes and smoothes the oral cavity, as well as oral microorganisms, particularly Candida spp. It has been found that proliferation can be suppressed, and the present invention has been completed.
That is, the present invention is an oral care composition characterized by containing a sericin hydrolyzate and a triterpenoid saponin.

  ADVANTAGE OF THE INVENTION According to this invention, the composition for oral care which can assist a saliva function with respect to the fall of a saliva secretion function can be provided. By using the composition of the present invention for oral care, the oral cavity can be moisturized and smoothed, and the growth of oral microorganisms, particularly Candida can be suppressed. In particular, by using a sericin hydrolyzate and a triterpenoid saponin in combination, the above effects can be synergistically enhanced. The composition of the present invention has no problems such as taste and irritation and is excellent in safety, and is useful for the prevention or improvement of symptoms of xerostomia and various diseases associated therewith.

  The composition for oral care of the present invention contains a sericin hydrolyzate and a triterpenoid saponin as essential components. By using sericin hydrolyzate, which is a moisturizing component, and triterpenoid saponins, which are antibacterial and antifungal components, it has the effect of moisturizing and smoothing the oral cavity and the effect of suppressing the growth of oral microorganisms, especially Candida. Beyond the predictions from each single use, can be enhanced synergistically.

  Sericin is one of the main proteins constituting the kite thread, and is considered to have a role as a lubricant when the kite spits out and as an adhesive that binds the thread. Sericin has been reported to have various effects such as a moisturizing effect, an antioxidant effect, a colon cancer preventing effect, and a constipation relieving effect. The present invention focuses on the moisturizing action of sericin, and is blended into the oral care composition as a hydrolyzate.

  The sericin hydrolyzate used in the present invention can be obtained by extraction by a known method from silkworms and raw silk produced by rabbits and wild silkworms, and silk fabrics produced using them. Specifically, for example, sericin can be partially hydrolyzed by boiling it with hot water using cocoon, raw silk or silk fabric as a raw material, and eluted into water. At this time, if necessary, an acid, an alkali, an enzyme, or the like may be used in combination.

  Next, the extract is separated and purified by a known method such as filtration, dialysis, or ultrafiltration, whereby a high-purity sericin hydrolyzate aqueous solution can be obtained. Furthermore, it may be subjected to a treatment such as hot air drying, reduced pressure drying, freeze drying, etc., and dried to form a solid form such as powder. In the present invention, these aqueous solutions or solids of sericin hydrolyzate can be directly blended into the oral care composition, but if necessary diluted or dissolved in water, buffer solution, physiological saline, alcohol or the like. Or after suspending, you may mix | blend with the composition for oral care.

  In the present invention, the weight average molecular weight of the sericin hydrolyzate is not particularly limited, but is preferably 1,000 to 100,000, and more preferably 5,000 to 40,000. If the weight average molecular weight is less than 1,000, the effect of moistening and smoothing the oral cavity may not be sufficiently obtained. When the weight average molecular weight exceeds 100,000, the aqueous solution may gel at a concentration of about 0.5% by weight and the handling property may be lowered, and the use form may be limited.

  The content of sericin hydrolyzate in the oral care composition is an effective amount that exhibits a moisturizing action. The specific content varies depending on the form of the oral care composition and the type of other components, but in the case of the oral care composition of a general form, it may be 0.01 to 10% by weight. Preferably, it is 0.05 to 5 weight%, More preferably, it is 0.1 to 3 weight%. If the content is less than 0.01% by weight, the effect of moisturizing and smoothing the oral cavity may not be obtained. When the content exceeds 10% by weight, a sticky feeling is produced in the oral cavity, which may reduce the feeling of use.

  The sericin hydrolyzate used in the present invention is easily water-soluble and can maintain stable properties as an aqueous solution. For this reason, it is excellent in miscibility with the component which can be normally added to the composition for oral care. The sericin hydrolyzate is non-toxic, tasteless and odorless and has excellent safety. For this reason, there is no concern about sensory characteristics such as smell and taste and side effects.

Saponin is a general term for glycosides having polycyclic compounds as aglycones, and is widely distributed in plants, and is also found in some animals such as starfish and sea cucumbers.
In general, saponin has been used as a foaming agent, an emulsifier, and a cleaning agent because it produces a colloidal aqueous solution that foams like a soap and emulsifies oils. In addition, it has the property of destroying cell membranes by surface-active action, destroying red blood cells (hemolysis), stimulating mucous membranes, and addicting to fish. Generally known to be harmless. As other physiological actions, antibacterial action, antifungal action, insecticidal action, expectorant action, cardiotonic action, tonic action, etc. have been reported, and application of these physiological actions is being promoted. Many herbal medicines such as herbal medicines contain this saponin. The present invention focuses on the antibacterial and antifungal effects of saponins.

  Saponins are roughly classified into triterpenoid saponins and steroidal saponins depending on the structure of aglycone. Triterpenoid saponins are widely distributed in plants and many have weak hemolytic action, and most saponins belong to this system. On the other hand, many steroidal saponins have strong physiological effects such as hemolysis and cardiotonic effects. In the present invention, a triterpenoid saponin is selected as a saponin that is an antibacterial component or an antifungal component, and is usually blended into the oral care composition in the form of a plant extract.

  Plants containing triterpenoid saponins include, for example, soybean, azuki bean, green beans, spinach, sugar beet, grapes (fruit skin), kyou (roots), licorice (rhizome), senega (spots; roots), kiraya (bark) , Mugwort (pepper), red snapper (rhizome), ginseng (root), tea seed, enju (bud / flower), and the like. These plant extracts have been used for foods and herbal medicines, and their safety has been confirmed. These can be used alone or in combination of two or more. In particular, the extract of Mukuroji pericarp synergistically suppresses the growth of oral microorganisms, especially Candida fungi, and moisturizes and smoothes the oral cavity caused by sericin hydrolyzate when used in combination with sericin hydrolyzate. It is particularly preferable in view of the effect of enhancing the resistance. Mukuroji is a deciduous tree of the family Mucuroidae that grows in Japan from India to the Asian region of India. The pericarp is called a life-prolonging skin under the name of a crude drug, and is rich in triterpenoid saponins. Hereinafter, a triterpenoid saponin-containing plant extract may be simply referred to as a plant extract.

  The triterpenoid saponin used in the present invention can be obtained by extraction from the above plant by a known method. For the extraction, the plant may be used as it is, or a plant that has been subjected to processing such as shredding or pulverization may be used.

  Examples of the solvent used for extraction include water, methanol, ethanol, propanol, butanol, ethylene glycol, propylene glycol, 1,3-butylene glycol, diethylene glycol, dipropylene glycol, hexylene glycol, glycerin, methyl acetate, and ethyl acetate. And organic solvents such as isopropyl acetate, ethyl ether, and acetone. These can be used alone or in combination of two or more. Considering that it is blended in the composition for oral care, it is preferable to use water, ethanol, or a mixed solvent thereof, which is harmless to the human body, as the extraction solvent from the viewpoint of safety.

  The extract can be blended in the oral care composition of the present invention as it is after removing impurities by filtration, but further purification operation is added within the range that does not impair the physiological action of triterpenoid saponins. May be. For example, the crude saponin fraction may be prepared using liquid chromatography. The extract can be concentrated into a liquid extract by concentration under reduced pressure, or a powdery extract by freeze drying, spray drying, or the like. These extracts can be blended in an oral care composition after being diluted or dissolved in a solvent such as water or alcohol as it is or as necessary. In the present invention, triterpenoid saponins are preferably used in the form of plant extracts from the viewpoint of economy. In this case, a plant extract containing 20 to 50% by weight of a triterpenoid saponin is preferably used.

  In the present invention, a commercially available raw material may be used as the plant extract. For example, “mukuroji extract powder” (Maruzen Pharmaceutical Co., Ltd.) can be used as the plant extract derived from mukuroji peel. These commercial products usually contain 20 to 50% by weight of a triterpenoid saponin.

  The content of the triterpenoid saponin in the composition for oral care is an effective amount for suppressing the growth of oral microorganisms. In the case of a general form oral care composition, the content is preferably 0.001 to 1.0% by weight, more preferably 0.005 to 0.5% by weight, and More preferably, the content is 01 to 0.1% by weight. If the content is less than 0.001% by weight, the effect of suppressing the growth of oral microorganisms, particularly Candida, may not be sufficiently obtained. When the content exceeds 1.0% by weight, the irritation to the oral mucosa may become strong or the taste may deteriorate.

  The oral care composition of the present invention containing a sericin hydrolyzate and a triterpenoid saponin can moisturize and smooth the oral cavity and suppress the growth of oral microorganisms, particularly Candida. It should be noted that the composition of the present invention has an effect of moisturizing and smoothing the oral cavity and the growth of oral microorganisms, particularly Candida, compared to a composition containing one and not containing the other. Both are excellent in suppressing effect. As its mechanism, the coexistence of sericin hydrolyzate, which is a moisturizing component, and triterpenoid saponin, which is also a surface active component, greatly improves the penetration of sericin hydrolyzate into the oral mucosa. As a result, it is considered that the moisturizing effect is synergistically enhanced and the effect of moistening and smoothing the oral cavity can be obtained effectively. The sericin hydrolyzate contains an amino acid having a charge in the side chain and electrically interacts with the cell surface of oral microorganisms such as Candida. As a result, it is considered that the permeability of the cell membrane of oral microorganisms changes, and the antibacterial and antifungal effects of triterpenoid saponins are synergistically increased. Such a synergistic effect in the oral cavity has not been known so far.

  In order to effectively obtain the above synergistic effect, the mixing ratio of the triterpenoid saponin and the sericin hydrolyzate in the composition for oral care is preferably 1: 1 to 1:60, and 1: 1 to 1 in terms of weight ratio. : 50 is more preferable, and 1: 1 to 1:30 is more preferable. By setting the blend ratio of triterpenoid saponin and sericin hydrolyzate within the above range, the effect of moisturizing and smoothing the oral cavity and the effect of suppressing the growth of oral microorganisms, especially Candida, can be further enhanced synergistically. Can do. At this time, the mixing ratio of the triterpenoid saponin-containing plant extract and sericin hydrolyzate varies depending on the saponin content in the plant extract, but is usually 1: 1 to 1:30, more preferably 1: 1 to 1. 1:20, more preferably 1: 1 to 1:10.

The composition for oral care of the present invention is a fungus belonging to the genus Candida , for example, Candida albicans , Candida tropicalis , which is difficult to suppress its growth compared to bacteria. ), Candida glabrata (Candida grabrata), Candida krusei (Candida krusei), it is possible to effectively inhibit the growth of such Candida Parashiroshisu (Candida parapsilosis). In particular, there is a strong demand for inhibiting the growth of Candida albicans, which is a causative fungus of candidiasis and is associated with aspiration pneumonia. Therefore, according to the present invention, a Candida growth inhibitor is also provided.

Further, the oral care compositions of the present invention, microorganisms of the variety present in the oral cavity, e.g., Streptococcus (Streptococcus) genus Actinomyces (Actinomyces) genus Nocardia (Nocardia) genus Corynebacterium (Corynebacterium) genus, Russia (Rothia) genus, bacteriophage nematic (Bacterionema) genus Propionibacterium (Propionibacterium) genus, Porphyromonas (Porphyromonas) genus, against Fusobacterium (Fusobacterium) bacteria belonging to such a growth inhibitory effect Demonstrate.

  The oral care composition of the present invention is effective for the appropriate pharmaceutically acceptable carrier component for oral care as well as a commonly used oral care agent, that is, oral care composition. It contains sericin hydrolyzate and triterpenoid saponin, which are the components, as essential components. Specific examples of the carrier component include water, thickeners, adhesives, fats / waxes, and excipients. The main components of the carrier can be broadly classified into edible components and non-edible components (such as chewing gum gum base), and any of them can be used in the present invention.

  In addition, as in the case of commonly used oral care agents, emulsifiers / dispersing agents, moisturizers, pharmacologically active ingredients, preservatives / preservatives, coloring agents, sweeteners, fragrances, pH adjusters, inorganics as necessary A known pharmaceutically acceptable ingredient for oral care, such as a salt, can be appropriately contained in a normal dose. These can be used alone or in combination of two or more.

  The form of the composition for oral care of this invention and the application method to an oral cavity are not specifically limited. For example, it may be prepared as an aqueous solution and applied in the form of a mist or foam to the oral cavity with a sprayer or the like, or may be used as a mouthwash. Moreover, it may be prepared as a gel or paste and applied to the oral cavity, or it may be molded into tablets (sublingual tablets, troches, solids for jasper, etc.) or chewing gum and contained in the oral cavity. Good. Further, it may be prepared as a patch and affixed to the oral mucosa.

  The composition for oral care of the present invention is preferably adjusted to a pH that does not adversely affect the oral mucosa, for example, 2.0 to 7.5. Examples of the pH adjuster used for this purpose include citric acid, lactic acid, malic acid, phosphoric acid, tartaric acid, and salts thereof.

〔Example〕
EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to these examples.

  In this example, sericin hydrolyzate was used as an aqueous solution. That is, the cocoon was washed with water and then immersed in 10 times the weight of the cocoon, and sodium carbonate was added so that the pH was 9.5. Subsequently, the koji was boiled for 2 hours, and sericin was extracted and hydrolyzed. The obtained extract was filtered to remove impurities and neutralized with citric acid.

Subsequently, the extract was put into a cellulose tube for dialysis having a molecular weight cut-off of 5,000 (Cellotube, Nacalai Tesque Co., Ltd.) and dialyzed overnight against water to obtain an aqueous solution of sericin hydrolyzate. The content of the sericin hydrolyzate in this aqueous solution was 5% by weight. Moreover, it was about 20,000 when the weight average molecular weight of the sericin hydrolyzate was measured by the gel filtration chromatography.
In addition, “mukuroji extract powder” (Maruzen Pharmaceutical Co., Ltd.), which is an extract of mukuroji peel, was used as a triterpenoid saponin.

Example 1 and Comparative Examples 1-3
According to the composition shown in Table 1, the gel compositions of Example 1 and Comparative Examples 1 to 3 were prepared. The appropriate amount of citric acid in Table 1 indicates the amount necessary to adjust the pH of the composition to 5.5, and the remaining amount of water refers to the amount required to make the total 100% by weight. Show.

Evaluation test 1: moisture maintenance function About the composition of Example 1 and Comparative Examples 1-3, the moisture maintenance function by a stratum corneum moisture content measurement was evaluated. After washing the test site (arm) with a detergent, the stratum corneum moisture content (blank value) was measured 15 minutes later. Then, the test substance was applied, and after 3 hours, the stratum corneum moisture content was measured, and the value obtained by subtracting the blank value is shown in Table 2. The stratum corneum moisture content was measured using a high frequency impedance meter: Skicon-200 (manufactured by IBS).
The composition of Example 1 showed a remarkably high value compared with the compositions of Comparative Examples 1 to 3, and had an excellent moisture maintenance function necessary for moistening and smoothing the oral cavity. .

Evaluation test 2: Growth inhibitory effect of Candida albicans The growth inhibitory effect of Candida albicans was evaluated for the compositions of Example 1 and Comparative Examples 1 to 3.
Candida albicans (NBRC No. 1393) was inoculated on a YM agar medium (Kanto Chemical Co., Inc.) and cultured at 25 ° C. for 2 days. The turbidity of the main culture was adjusted (OD610nm = 1.0) to obtain a test bacterial solution.

Each component of the compositions of Example 1 and Comparative Examples 1 to 3 was added to the YM agar medium so as to have the concentrations shown in Table 1, thereby preparing a test medium. A normal YM agar medium was used for the blank. The test bacterial solution of Candida albicans was appropriately diluted and inoculated therein, and the number of colonies after culturing at 25 ° C. for 3 days was counted. Table 3 shows the growth rate of colonies on the test medium containing the compositions of Example 1 and Comparative Examples 1 to 3 with the number of blank colonies as 100%.
The composition of Example 1 showed a significantly superior effect as compared with the compositions of Comparative Examples 1 to 3.

Evaluation test 3: Effect of smoothing the oral cavity, effect of improving pain, improving effect of bad breath The use test was conducted on the compositions of Example 1 and Comparative Examples 1 to 3, and the effect of smoothing the oral cavity and improvement of pain The effect and the improvement effect of bad breath were evaluated by four evaluators. The evaluator used it for one week by spreading about 0.5 g in the mouth twice a day, and then performed self-assessment in the following three stages. The results are shown in Table 4.
+: Greatly improved ±: Improved −: No change or worsening

  The composition of Example 1 showed a significantly superior effect as compared with the compositions of Comparative Examples 1 to 3. In particular, the effect of smoothing the oral cavity and the effect of improving bad breath are remarkable, and it has been shown that the composition of the present invention can assist saliva function. Moreover, no irritation | stimulation and abnormality in an oral cavity were seen, and it was also confirmed that safety is high.

Another embodiment of the present invention will be described.
Example 2: Gel oral care composition
(weight%)
Sericin hydrolyzate aqueous solution (5% by weight) 5
Mukuroji peel extract 0.1
Glycerin 10
Propylene glycol 5
Sodium carboxymethylcellulose 5
Potassium chloride 0.12
Sodium chloride 0.084
Magnesium chloride 0.005
Citric acid 0.05
Sodium sulfite 0.05
Sodium benzoate 0.2
Ethyl paraoxybenzoate 0.05
Water remaining The pH of the resulting composition was 5.5.

Example 3: Liquid oral care composition
(weight%)
Sericin hydrolyzate aqueous solution (5% by weight) 5
Mukuroji peel extract 0.02
Glycerin 10
Potassium chloride 0.12
Sodium chloride 0.084
Magnesium chloride 0.005
Calcium chloride 0.015
Citric acid 0.05
Sodium citrate 0.02
Dipotassium hydrogen phosphate 0.05
Sodium sulfite 0.05
Sodium benzoate 0.2
Ethyl paraoxybenzoate 0.05
Water remaining The pH of the resulting composition was 5.5.

Claims (4)

  An oral care composition comprising a sericin hydrolyzate and a triterpenoid saponin. The composition for oral care according to claim 1, wherein the triterpenoid saponin is a plant extract containing a triterpenoid saponin .   The composition for oral care according to claim 2, wherein the plant extract containing a triterpenoid saponin is an extract of Mucurodi pericarp.   A Candida fungus growth inhibitor comprising sericin hydrolyzate and triterpenoid saponin as active ingredients.