KR101344803B1 - Oral care composition comprising extract of machilus thunbergii and sequestering agent - Google Patents

Abstract

The present invention relates to an oral composition comprising a thick extract and a metal ion sequestrant. The oral composition is excellent in inhibiting and removing the production of biofilm, which is the main cause of tooth corrosion, tartar formation, bad breath formation and gum disease, and effectively maintain and improve oral health by preventing and improving bad breath removal and gum disease. It has an effect to make.

Description

ORAL CARE COMPOSITION COMPRISING EXTRACT OF MACHILUS THUNBERGII AND SEQUESTERING AGENT}

The present invention relates to a composition for oral hygiene comprising a thick extract and a metal ion sequestrant.

Oral health or normal function and condition is very important to the daily life of all human beings, seriously impairing the quality of life in the event of an abnormality. The most influential factors associated with oral health factors are the erosion or tooth decay of the teeth, gum or periodontal disease, and the development of unpleasant mouth odors. The root cause is formed by oral pathogens. It is a biofilm. These pathogens also exist as a solution such as saliva when they are not attached to the surface of the oral cavity, and can be easily removed with gargle or drink intake, so there is little chance of causing diseases in the oral cavity. However, these pathogens are attached to the oral surface for effective survival, forming a biofilm. Once the biofilm is formed, the protection against external physical and chemical stimuli is significantly increased, so it is not only difficult to remove by general physical methods, but also by using a highly toxic antimicrobial agent or a large amount of antimicrobial agent. Can be. When left unattended, the biofilm becomes thicker and stronger, forming calculus, and becomes a habitat for numerous bacteria, causing various oral diseases. As a representative method for preventing such a process, physical methods such as scaling in the dentist have been recommended, and their effects have been verified. However, due to the hassle, fear, and economics of dental visits, they are usually not well managed. However, the removal of biofilm and calculus by brushing is limited, and a large number of populations are exposed to oral diseases. Accordingly, products containing components that sterilize caries and periodontitis, such as chlorohexidine, cetylpyridinium chloride, triclosan and the like, have been developed and popularized. However, these synthetic antibiotics, when used for a long time, not only irritate the oral mucosa, but also destroy normal bacteria, thereby increasing resistance to oral pathogens, and have a large side effect on the human body such as damaging tooth pigmentation and taste. Chlorohexidine, a representative antimicrobial agent used in mouthwashes, has been shown to show shock symptoms, and especially when there is an oral wound, it is reported to be more dangerous. Accordingly, the use of plant-derived antimicrobial agents has recently increased, and examples thereof include thymol, eucalyptol, menthol, epigallocatechin gallate, and xylitol. Although used, the effect is limited.

Streptococcus bacteria that are present at the bottom of the biofilm form lactic acid using sugars present in the oral cavity, and the lactic acid corrodes the enamel of the tooth and causes tooth decay. In addition, when plaque develops, P.gingivalis bacteria present in the gums generate irritating compounds and cause various inflammations in the gum tissue. In addition, biofilms made of anaerobic bacteria that live under the tongue break down proteins that remain in the oral cavity, generating sulfur or amine compounds, causing bad breath, causing discomfort.

According to Non-Patent Document 1, formation of a biofilm includes an initial attachment step of attaching bacteria to the surface of oral tissue and a co-adhesion step of forming a massive bond between bacteria and bacteria over several weeks. Is made of. The first stage occurs over a week, with almost entirely Streptococcus bacteria attached. The second stage occurs over several weeks, and more than 700 species of bacteria can be involved, but P. gingivalis is known to be involved. In addition, it is known that the presence of certain proteins that mediate adhesion in both the initial and interadhesion steps enables the formation of biofilms. Therefore, the effect of the existing antimicrobial component is limited because the attachment step is not effectively prevented, the antimicrobial component is mainly used to remove only the bacteria present in the three-dimensional solution, so that in the case of the already produced biofilm does not penetrate inside the biofilm surface only This is because it produces only a temporary effect. Therefore, a high concentration or strong antimicrobial component is required, and accordingly, disadvantages such as increased toxicity, loss of taste, and increased resistance of bacteria to the human body occur. Therefore, the product using the existing ingredients not only prevent the public from sufficiently preventing and removing the production of the biofilm by the usual method (such as the use of gargle and mouthwash 1-2 times a day). Side effects make it difficult to economically, conveniently, fundamentally and safely maintain or improve oral health as a preventive measure.

Patent document 1 relates to a gum for preventing and improving periodontal disease, and when using a natural herbal thickener alone or in combination as a chewing gum composition, inhibits the activity of prostaglandins, collagen degrading enzymes caused by inflammation, inhibits periodontal production The prevention and amelioration effect of a disease is disclosed. However, the preceding document is effective only on the surface of the biofilm that causes bad breath and periodontal (gum) disease, and does not penetrate the inside of the biofilm, thereby causing a problem in that the fundamental oral disease improvement effect is insufficient.

Domestic Patent Publication No. 2011-0011350

Rosan et al, Microbes and Infection 2000, 2: 1599-1607

Accordingly, the present inventors have tried to find a component or composition that can penetrate not only the surface of the biofilm but also the inside of the biofilm to exhibit an antimicrobial effect, and as a result, the metal ion blocking agent that has been used as a tartar formation inhibitor is Significantly lowered the defense against physicochemical stimuli to increase the biofilm suppression and elimination effect of the extract, the biofilm suppression and elimination effect is excellent, and bad breath removal and gingivitis improvement effect, through the efficacy test for the test product applied to this The present invention was completed by confirming its excellent practical value.

Accordingly, an object of the present invention is to provide an oral hygiene composition that can effectively maintain and improve oral health through the prevention of gum disease such as bad breath removal and gingivitis due to excellent microbial biofilm formation suppression and removal effect.

As means for solving the above problems,

Provides a composition for oral hygiene comprising a thick extract and a metal ion sequestrant as an active ingredient.

As another means for solving the above problems,

Provided is a toothpaste comprising a thick extract and a metal ion sequestrant as an active ingredient.

The composition for oral hygiene according to the present invention is excellent in inhibiting and removing the production of biofilm which is the main cause of tooth corrosion, tartar formation, mouth odor production and gum disease, and removing bad breath and preventing gum disease (gingivitis, etc.) And improving to effectively maintain and improve oral health. In addition, since it is composed of natural ingredients and is safe for the human body, it can be universally used for maintaining and improving oral health regardless of age.

The present invention relates to a composition for oral hygiene comprising a thick extract and a metal ion sequestrant as an active ingredient.

In the present invention, 'oral hygiene composition' refers to a composition for oral hygiene and / or application to the oral cavity having a prophylactic and / or therapeutic effect on oral diseases such as periodontitis and gingivitis. Including with the agent is characterized in that it has a better biofilm production suppression and removal, promote oral hygiene, and prevent and / or treat gum disease.

The groin is the hilus ( Machilus) It is a herb that is a skin of thunbergii ), and is known to be effective for red ginseng, ovulation, vomiting and diarrhea.

The thick gourd extract may be obtained by extracting various organs or parts, that is, leaves, flowers, fruits, stems, roots, branches and bark. The extract may include all extracts obtained by conventional extraction methods known in the art such as organic solvent extract, water extract extracted using water, supercritical extract. Preferably, the extract may be an extract obtained by extraction with water, an organic solvent, or a mixture thereof. The organic solvent may be used without limitation, those known in the art, specifically, lower alcohols such as methanol, ethanol, isopropyl alcohol, butanol; Polyhydric alcohols such as glycerol, ethylene glycol, propylene glycol and 1,3-butylene glycol; And hydrocarbon solvents such as petroleum ether, methyl acetate, ethyl acetate, benzene, hexane, methylene chloride, diethyl ether, dichloromethane, chloroform, and the like, or a mixture thereof.

The thick gourd extract may be used as it is, an extract in a liquid state by an extraction solvent, CO ₂ supercritical extraction, or diluted in a solvent, and may be used by powdering. The powdering may be carried out by conventional methods known in the art, such as vacuum drying, freeze drying, spray drying.

The extract of the present invention includes not only the aforementioned extraction solvent, but also an extract that has undergone a conventional purification process. Specifically, the extract of the present invention is purified after extraction with an extraction solvent, for example, chromatographic separation for separation according to membrane separation, size, charge, hydrophobicity or affinity using a filtration membrane having a cut-off value at a constant molecular weight. Purification process such as separation by may be carried out additionally.

In the present invention, when the thick extract of the biofilm is loosened by the metal ion sequestrant, penetrates to the inside of the biofilm to increase the biofilm suppression and removal effect and has an excellent antibacterial effect, and the total composition is 100 parts by weight. 0.01 to 1.0 parts by weight, more preferably 0.03 to 0.5 parts by weight. If the content is less than 0.01 parts by weight, the antimicrobial activity does not appear, if it exceeds 1.0 parts by weight oral irritation and stability is not good because it is not preferable.

In the composition of the present invention, the metal ion sequestrant is a substance that inhibits tartar formation by chelating metal ions having an important effect on the formation of tartar, and a phosphate-based compound is preferable. Specifically, sodium phosphate and monosodium phosphate (Monosodium phosphate), disodium phosphate, trisodium phosphate, sodium tripholyphosphate, sodium hexametaphosphate, tetrasodium pyrophosphate, tetrasodium pyrophosphate It may be one or more selected from the group consisting of phosphate (Sodium acid pyrophosphate). The use of such phosphate compounds significantly lowers the protection against external physical and chemical stimuli and loosens the structure of the biofilm. The metal ion sequestrant in the present invention contains 0.1 to 10.0 parts by weight, more preferably 0.5 to 4.0 parts by weight based on 100 parts by weight of the total composition. If the content is less than 0.1 parts by weight, the ability to inhibit tartar formation is weak, and if it exceeds 10.0 parts by weight, it is not preferable because the feeling such as taste at the time of brushing may be poor and irritation may occur.

Oral hygiene compositions according to the present invention, such as abrasives, wetting agents, binders, foaming agents, sweetening agents, pH adjusting agents, caries preventive agents, flavoring agents, purified water, etc., for proper formulation and formulation stability, enhancement of the desired effect, enhancement of preference. It may further contain one or more additives selected from the group consisting of.

The abrasive is selected from the group consisting of precipitated silica, silica gel, zirconium silicate, calcium monohydrogen phosphate, calcium monohydrogen phosphate, hydrous alumina, hard calcium carbonate, heavy calcium carbonate, calcium pyrophosphate, insoluble methacrylate and aluminum silicate. As mentioned above, it can use 1-60 weight part with respect to 100 weight part of total compositions.

The wetting agent may be used in an amount of 10 to 60 parts by weight based on 100 parts by weight of one or more selected from the group consisting of concentrated glycerin, glycerin, aqueous sorbitol solution, amorphous sorbitol solution, polyethylene glycols, and propylene glycol.

The binder is sodium carboxymethyl cellulose, carrageenan, xanthan gum, hydroxyethyl cellulose, hydroxypropylmethylcellulose, hydroxypropyl cellulose, guar gum, gellan gum, carbomer, pectin, polyvinylpyrrolidone, carboxyvinyl poly At least one selected from the group consisting of sodium alginate and laponite, preferably sodium carboxymethylcellulose or xanthan gum, and may be used in an amount of 0.5 to 2.0 parts by weight based on 100 parts by weight of the total oral composition.

As the foaming agent, anionic and nonionic surfactants such as sodium sulfate, sodium lauryl sulfate, sucrose fatty acid ester, and sorbitan fatty acid ester may be used in an amount of 0.5 to 5.0 parts by weight based on 100 parts by weight of the total oral composition.

The sweetener is at least one selected from the group consisting of saccharin sodium, sucralose, maltitol, aspartame, erythritol, xylitol and licoriceic acid, preferably sodium saccharin, and may be used in an amount of 0.05 to 3 parts by weight based on 100 parts by weight of the total composition. have.

The preservative may be at least one selected from the group consisting of benzoic acid, methylparaben, propylparaben and sodium benzoate, preferably paraoxybenzoic acid ester, and may be used at 0.05 to 0.3 parts by weight based on 100 parts by weight of the total oral composition.

The caries preventive agent is selected from the group consisting of sodium fluoride, sodium monofluorophosphate, tin fluoride, chlorohexidine, allantoin chlorohydroxy aluminate, aminocaproic acid, zinc chloride, pyridoxine hydrochloride, tocopherol acetate and enzymes As mentioned above, it can be used with 0.1-1.0 weight part with respect to 100 weight part of whole oral compositions.

As the fragrance, the fragrance may be used alone or mixed with peppermint oil, spearmint oil, menthol, and the like. The fragrance is applied similarly to the fragrance of the toothpaste, and the amount is 0.1 to 3.0 parts by weight based on 100 parts by weight of the total oral composition. Can be used.

As the pH adjuster, sodium phosphate, disodium phosphate, citric acid, triethanolamine and the like are used, and the content thereof is preferably 0.01 to 1.0 parts by weight based on 100 parts by weight of the total oral composition.

Oral hygiene composition of the present invention may include an active ingredient, water and other additives.

The composition for oral hygiene according to the present invention is not particularly limited in its formulation, and specific examples may include formulations such as toothpaste, mouthwash, mouthwash, gum, candy, mouth spray, mouthwash, and the like.

As described above, the present invention is very effective in inhibiting and removing the production of the biofilm by containing a metal ion blocker and a thick extract of the antimicrobial agent at the same time, exhibits bad breath removal and gingivitis improvement function, to maintain oral health safe to the human body and Since it exhibits an improvement effect, it can be very useful industrially.

Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples. However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the present invention is not limited to the following Examples and Experimental Examples.

Manufacturing example  1: thick pepper extract manufacturer

The dried thick gourd and shell were powdered and CO ₂ supercritical extraction under a temperature of 30 to 60 ° C. and a pressure of 10 to 30 mpa, and the extract was used after vacuum drying.

Example  1 to 6 and Comparative Example  1 to 6

Toothpaste compositions of Examples 1 to 6 and Comparative Examples 1 to 6 were prepared with the components and composition ratios shown in Table 1 below.

Powder components such as binders and sweeteners were dispersed in the humectant and purified water was added, followed by primary mixing in a mixer, and then an abrasive, a caries preventive agent, and an active ingredient were added thereto, followed by secondary mixing. Finally, a foaming agent, a pH adjuster (citric acid, triethanolamine), a flavoring agent was added and mixed in a vacuum to prepare a toothpaste composition with the components and composition ratios of Table 1 below.

Experimental Example  1: Prevention of Biofilm Production

It is as important as inhibiting biofilm production by the compositions prepared in the above examples and comparative examples. Thus, the composition was diluted with distilled water and used. The artificial needle was used by diluting 1% type III mucin (mucin from porcine stomach, Sigma-Aldrich) in adhesion buffer solution and sterilizing for 15 minutes at 121 ℃.

As a strain, Streptococcus mutans (ATCC25275), S. sanguis ATCC 10556, and Actinomyces viscosus KCCM 12074 were used to inoculate them. -species) inoculum solution was prepared. More specifically, each cultured bacteria were separated through a centrifuge (4500 rpm, 5 minutes), and then suspended again in PBS (phosphate-buffered saline, pH 7.2) at a concentration of 1 × 10 ⁶ CFU / ml. The inoculated cell solution contained the same concentration of each bacteria. Rukayadi and Hwang's methods were used to measure the biofilm production inhibitory activity of the compositions. More specifically, 0.5 ~ 50 ㎍ / ml of the sample in a 96 well polystyrene microplate in each well was incubated for 3 hours using a shaker at room temperature, and then dried in air. 20 μl of bacterial inoculum was added to the sample-coated 96 well plate, and the culture was filled to a total volume of 200 μl (final concentration 1 × 10 ⁵ CFU / ml) and incubated at 37 ° C. for 24 hours. After removing the remaining culture, 200 μl of 50 mM PBS was used to wash the cells that did not form the remaining biofilm. The cells on which the biofilm was formed were colored for 30 minutes using 0.4% crystal violet solution, and then the remaining solution was washed with distilled water. The colored cells were dissolved in 200 μl of 90% ethanol and the amount thereof was measured using absorbance (596 nm). The biofilm inhibitory effect of this sample was measured using the following Equation 1 and the results are shown in Table 2 below.

[Equation 1]

% Biofilm production prevention effect = (absorbance of 1-sample coated cells / absorbance of control cells) X 100

As a control, cells without coating the sample were used, and a concentration (IC ₅₀ ) indicating a 50% prophylactic effect was obtained.

sample 50% inhibition concentration of biofilm production
(IC ₅₀ , μg / ml) sample 50% inhibition concentration of biofilm production
(IC ₅₀ , μg / ml) Example 1 5.2 Comparative Example 1 > 50 Example 2 4.5 Comparative Example 2 > 50 Example 3 2.3 Comparative Example 3 25 Example 4 2.1 Comparative Example 4 21 Example 5 2.7 Comparative Example 5 23 Example 6 1.9 Comparative Example 6 18

Test Example  2: Evaluation of biofilm removal effect

Effective removal of biofilms already formed in the oral cavity is as important as inhibiting production in improving oral health. Therefore, the removal effect of the biofilm was measured for the composition prepared above. In order to measure the bacterial film removal effect on the prepared composition, various bacterial biofilms were coated on 96-well plates by Sepanovic's method as follows. 200 μl of artificial needles are added to each plate, incubated with gentle shaking for 3 hours at room temperature, and after removing the remaining unattached artificial needles, the plates are dried in air. 20 μl of bacterial inoculum was added to the plate and incubated at 37 ° C. for 24 hours using a BHI culture medium containing 3% sucrose to form a biofilm. After removing the remaining culture solution, cells which did not form the remaining biofilm were washed with 200 μl 50 mM PBS. Each cell was treated with a test or comparative sample at a concentration of 0.5-50 μg / mL and incubated for 1 hour. The cells on which the biofilm was formed were colored for 30 minutes using 0.4% crystal violet solution, and then the remaining solution was washed with distilled water. The colored cells were dissolved in 200 μl of 95% ethanol and measured using absorbance (596 nm). The biofilm removal activity of each sample was determined by comparing the absorbance before and after treatment.

The biofilm removal effect was calculated by Equation 2 below, and the concentration (IC ₅₀ ) representing the 50% removal effect was obtained and shown in Table 3 below.

&Quot; (2) "

% Biofilm removal effect = (1-absorbance of sample / absorbance of untreated sample) X 100

sample 50% removal concentration of biofilm
(IC ₅₀ , μg / ml) sample 50% removal concentration of biofilm
(IC ₅₀ , μg / ml) Example 1 6.3 Comparative Example 1 > 50 Example 2 4.1 Comparative Example 2 > 50 Example 3 2.5 Comparative Example 3 44 Example 4 1.9 Comparative Example 4 34 Example 5 3.1 Comparative Example 5 31 Example 6 2.0 Comparative Example 6 22

Test Example  3: Clinical Trials of Inhibiting Gingivitis in Toothpaste Compositions

1) Subject

Subjects were selected from 120 oral subjects with 30 oral examinations of 30 patients from ages 30 to 50 years of age. The clinical experiment on the gingival inflammation treatment effect of the toothpaste (prepared in Examples 1 to 6) and the comparative toothpaste (prepared in Comparative Examples 1 to 6) according to the present invention was performed by the following method.

2) Experiment Method

The test subjects were divided into two groups: the experimental group and the comparative group, which were trained to use three times a day after sleeping 2 hours after meals, and the toothpaste was performed to score the initial gingivitis index and to use each toothpaste composition. After 3 months and 6 months, oral examination was performed to check the gingivitis index. The gingivitis index is measured by inserting a periodontal probe into the gingival bulb and burning it around each tooth without applying force and measuring the bleeding state after 30 seconds. Recording resulted.

score Contents 0 point No bleeding state 1 point Normal bleeding state 2 points Glandular bleeding 3 points Interdental triangle bleeding 4 points Total gingival bleeding

The results of conducting a clinical experiment for the treatment of gingivitis with the dentifrice composition and the comparative composition according to the present invention are shown in Table 5 below.

division Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Early 1.01 1.03 1.07 1.03 1.03 1.03 1.02 1.08 1.01 1.03 1.09 1.11 1 week 1.21 1.11 1.14 1.07 1.07 1.07 1.05 1.21 1.11 1.31 1.21 1.22 1 month 1.30 1.26 1.36 1.21 1.21 1.21 1.18 1.25 2.21 2.67 2.27 2.31 2 months 1.62 1.49 1.47 1.45 1.53 1.43 2.46 2.86 310 3.21 3.22 3.32 3 months 1.49 1.34 1.35 1.34 1.39 1.43 3.19 3.21 3.81 3.11 3.32 3.32

As shown in the above clinical trial results, the toothpaste composition of the comparative example had no or little gingival inhibitory effect, and the toothpaste composition of Examples 1 to 6 was superior to the dentifrice effect of the toothpaste composition of Comparative Examples 1 to 6.

Test Example  4: bad breath removal effect experiment

Clinical experiments were performed on the bad breath removal effect using the oral composition comprising the compositions of Examples and Comparative Examples of Table 1, the results are shown in Table 6 below.

1) Experimental method

Fifty men and women without dental caries were selected and subjected to a cross-over test. Commercial garlic powder was dispersed in water, left to stand for 24 hours, and diluted to make the Halimeter measurement value of 700 ppb or more, and the diluent was used as a source of bad breath. Gargle was diluted with 15 ml of garlic powder for 30 seconds, and after 1 minute, the degree of bad breath was measured using a halimeter. After 1 minute, 5 minutes, and 30 minutes after brushing the teeth, the degree of bad breath was measured by a halimeter to determine whether the bad breath was continued. The results are shown in Table 6 below.

2) Experimental results

As shown in Table 6, the comparative example showed the persistence of bad breath suppression for 5 minutes after brushing, but after 30 minutes it was confirmed that almost no bad breath removal effect, indicating that the persistence of the bad breath suppression effect is insufficient. . On the other hand, in the case of Example it was confirmed that the persistence of the bad breath suppression effect is maintained at a high level even after 30 minutes. As shown in the above bad breath removal test results, the toothpaste composition of Examples 1 to 6 was superior to the bad breath removal effect compared to the toothpaste composition of Comparative Examples 1 to 6.

division
(Inhalation inhibition rate) Elapsed time after brushing 1 minute 5 minutes 30 minutes Example 1 85.1% 74.3% 65.1% Example 2 90.1% 81.5% 74.1% Example 3 93.2% 77.6% 69.8% Example 4 96.1% 88.7% 81.5% Example 5 92.5% 85.0% 74.2% Example 6 94.5% 90.2% 81.0% Comparative Example 1 65.0% 43.2% 22.1% Comparative Example 2 64.2% 42.1% 23.8% Comparative Example 3 68.5% 36.6% 34.3% Comparative Example 4 71.2% 41.6% 33.2% Comparative Example 5 69.1% 45.2% 38.2% Comparative Example 6 73.3% 54.2% 45.6%

Through the above four experiments, the toothpaste composition containing a metal ion sequestrant and a thick extract according to the present invention, the metal ion sequestrant significantly lowers the defense against physicochemical stimulation of the outside of the biofilm, thereby inhibiting the production of the biofilm of the thick extract. And it is believed to be excellent in effectively maintaining and improving oral health by increasing the removal effect and preventing and improving bad breath and gum disease.

Claims (8)

Thick pepper extract; And
At least one metal ion sequestrant selected from the group consisting of terrasodium pyrophosphate and sodium acid pyrophosphate
Gum disease, bad breath prevention and improvement composition comprising as an active ingredient.
The method of claim 1,
Composition for the prevention and improvement of gum disease, bad breath having an effect of inhibiting or removing the production of biofilm.
The method of claim 1,
The thick gourd extract is a gum disease, bad breath prevention and composition comprising 0.01 to 1.0 parts by weight based on 100 parts by weight of the total oral hygiene composition.
delete delete The method of claim 1,
The metal ion sequestrant is a gum disease, bad breath prevention and improvement composition comprising 0.1 to 10 parts by weight based on 100 parts by weight of the total oral hygiene composition.
Thick pepper extract; And
At least one metal ion sequestrant selected from the group consisting of terrasodium pyrophosphate and sodium acid pyrophosphate
Gum disease, bad breath prevention and improvement toothpaste containing as an active ingredient.
The method of claim 7, wherein
Toothpaste for preventing and improving gum disease, bad breath, having the effect of inhibiting or removing the production of biofilm.