KR102649635B1 - Oral composition comprising policresulen - Google Patents

Abstract

The present invention relates to an oral composition containing polycresulene, which uses an oral tissue astringent to increase the retention and/or adsorption of polycresulene in the oral cavity and improve the effect of polycresulene. Therefore, the composition according to the present invention is excellent in preventing plaque formation and alleviating inflammation in periodontitis and gingivitis.

Description

Oral composition comprising policresulen}

The present invention relates to an oral composition containing polycrezulene. More specifically, it relates to a composition for oral use, particularly for improving oral hygiene, in which polycrezulene has further improved effects of preventing plaque formation and alleviating periodontitis and gingivitis.

Plaque formed by oral bacteria in the oral cavity can be said to be the primary cause of oral diseases such as cavities and gingivitis.

In Korean Patent Publication No. 10-2015-0066756, the formation of a biofilm called a biofilm or biofilm can be suppressed by applying polycrezulene into the oral cavity through a composition for inhibiting biofilm formation containing polycrezulene, and through this, It is disclosed that plaque formation in the oral cavity can be suppressed without destroying the normal bacterial ecosystem.

However, as a result of the present inventors' research, it was found that the effect of oral compositions containing polycresulene did not last for a long time, and therefore, research was needed to maintain this effect.

Republic of Korea Patent Publication No. 2001-0069757 (Published on July 25, 2001) Republic of Korea Patent Publication No. 10-2015-0066756 (published on June 17, 2015)

Therefore, the problem to be solved by the present invention is to provide an oral composition containing polycrezulene, especially an oral hygiene composition, with a longer duration of effect or improved effect.

Another problem to be solved by the present invention is to provide a method for increasing the duration of the effect of polycresulene or improving the effect of polycresulene.

Another problem to be solved by the present invention is to provide a composition that can extend the duration of the effect of polycresulene or improve the effect of polycresulene and/or a kit containing such a composition.

In order to solve the above problems, the present invention provides the technical idea that the duration of effect of policresulen can be increased or the effect can be improved by using an oral tissue astringent.

First, as a result of the present inventors' research, it was confirmed that it is difficult for polycrezulene, a water-soluble substance, to remain in the oral cavity for a long time due to the characteristics of the oral environment, making it difficult for polycrezulene to continuously exert its effect in the oral cavity. Therefore, it remains in the oral mucosa or gums. Meanwhile, a technology was needed to enable polycrezulene to continuously maintain its pharmacological action. While carrying out various studies to solve the problems in the prior art as described above, the present inventors found that when an oral tissue astringent was included in a composition containing polycrezulene, the oral adsorption of polycrezulene was improved, and the oral bio-absorption was continuously improved. The present invention was completed by confirming that it had an excellent effect in suppressing film formation. However, the present invention is not limited to this mechanistic speculation.

Accordingly, the present invention provides an oral composition, particularly a composition for improving oral hygiene, containing (a) polycresulen and (b) an oral tissue astringent.

The present invention also provides an oral composition containing polycrezulene, particularly a composition for improving oral hygiene, which includes an oral tissue astringent for the purpose of enhancing the effect of polycrezulene.

The present invention also provides a method for enhancing the effect of polycresulene, characterized in that an oral tissue astringent is applied intraorally simultaneously with or before the application of polycresulene. Through these methods, oral hygiene can be further improved.

The present invention also provides an oral kit comprising (a) a composition containing polycrezulene, and (b) a composition containing an oral tissue astringent for enhancing the effect of polycresulene.

The present invention also provides a composition for enhancing the effect of polycrezulene, which includes an oral tissue astringent as an active ingredient.

In the present invention, the 'oral composition' or 'oral hygiene composition' has the effect of preventing plaque formation and/or improving oral hygiene and/or preventing and/or treating oral diseases such as periodontitis and gingivitis by inhibiting the formation of biofilm. It may refer to a composition for application to the oral cavity, and by including polycrezulene together with an oral tissue astringent, which is an efficacy enhancing substance, the retention and/or adsorption of polycrezulene in the oral cavity is increased, resulting in better inhibition of biofilm formation. The desired effect can be achieved more excellently.

Policresulene used in the present invention is also called Albothyl or Polilen, and has the structure of the following formula 1, and the chemical formula is (C ₉ H ₈ O ₄ S) _n . .

Preferably, in Formula 1, n is 1 to 3, and more preferably, n is 3.

Since polycrezulene of the present invention is highly soluble in water, it exists dissolved rather than precipitated in oral compositions such as toothpaste containing excessive water.

In the present invention, it is clear that the oral tissue astringent serves to increase the retention and/or adsorption of polycrezulene, but it may play other additional roles in addition to this role, and the present invention provides polycrezulene as an oral tissue astringent. It is not limited to a particular theoretical mechanism of retention and/or adsorption enhancement.

The oral tissue astringent of the present invention may be a halogen compound, a sulfate compound, a carbonate compound, a phosphate compound, or a mixture thereof containing cations such as sodium, potassium, calcium, and magnesium.

Specifically, the oral tissue astringent is sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium sulfate, potassium sulfate, sodium bicarbonate, sodium carbonate, potassium phosphate monobasic, potassium phosphate dibasic, potassium phosphate tribasic, sodium phosphate monobasic, and potassium phosphate monobasic. It may be one or more selected from the group consisting of sodium phosphate, sodium phosphate tribasic, and sodium saccharin.

The sodium chloride may be included in the form of salt containing sodium chloride, for example, bamboo salt, bamboo salt, sun-dried salt, refined salt, formulation salt, or pharmacopoeial salt, etc., and preferably may be contained in the form of bamboo salt. there is.

Among various oral tissue astringents, the form of bamboo salt is especially preferable in terms of cleansing feeling, lasting cleanliness, flavor, and overall satisfaction during actual use.

Among the sodium chlorides used in the present invention, bamboo salt is a general term for salt using bamboo. For example, it is bamboo salt synthesized through a fire method using bamboo and salt mentioned in Korean Patent Registration No. 85705, which produces cells. Shiki makes bamboo salt by repeatedly processing bamboo, which produces cells, and salt, which sterilizes and prevents decay, at high heat in a kiln to melt and solidify the salt. In addition to sodium, bamboo salt manufactured in this way contains a lot of minerals such as potassium, calcium, magnesium, and iron. In the case of bamboo salt, it contains similar amounts of minerals and ions as bamboo salt. The various mineral components and sodium chloride components contained in bamboo salt or bamboo salt have an especially excellent astringent effect on the oral mucosa when brushing teeth. As convergence occurs, the swollen cells contract, and at this time, polycrezulene in the oral mucosa converges to oral tissue, and it is presumed that the remaining polycrezulene continues to exert medicinal efficacy. However, the present invention is not limited to this theoretical mechanism.

In the oral composition according to the present invention or the composition for promoting the retention or adsorption of polycrezulene in the oral cavity, the content of polycrezulene is preferably 0.0005 to 2% by weight relative to the total weight of the composition for various purposes of the present invention, and 0.0001 to 1% by weight. % is more preferred, and 0.001 to 0.1% by weight is even more preferred. In addition, the content of the oral tissue astringent in the composition according to the present invention is preferably 0.1 to 5% by weight, more preferably 0.2 to 4% by weight, and even more preferably 0.3 to 3% by weight for various purposes of the present invention.

When the content of polycrezulene is less than 0.0005% by weight relative to the total weight of the composition, the effect of inhibiting biofilm formation is minimal, making it difficult to achieve the practical purpose of the present invention, and when it is more than 2% by weight, it may cause irritation and surgical wounds. There is a problem.

The oral tissue astringent is added for the purpose of the present invention, such as increasing the adsorption and residual effect of polycrezulene. If the content is less than 0.1% by weight based on the total weight of the composition, the oral adsorption and residual effect are weak, 5 If the weight percent is exceeded, not only will the effect of increasing the content be minimal, but salty, fishy, and astringent tastes may appear due to excessive addition of salt. As a result of a sensory evaluation conducted by the present inventors on about 10 men and women, consumer preference was very low when the amount exceeded 5% by weight.

The composition of the present invention may be provided in various forms such as toothpaste, mouthwash, mouthwash, oral spray, gum, oral ointment, and oral patch. Depending on the form, type, and purpose of use of the composition, an appropriate amount of abrasives, wetting agents, binders, foaming agents, sweeteners, preservatives, medicinal agents, fragrances, acidity regulators, whitening agents, etc. can be used. That is, in addition to the ingredients mentioned above, the composition according to the present invention also contains an abrasive, a wetting agent, a binder, a foaming agent, a sweetener, and medicinal properties in order to formulate an oral composition appropriately, formulate stability, enhance the desired effect, and enhance the preference for use. It may additionally contain one or more additives selected from the group consisting of agents, fragrances, purified water, etc.

When the formulation containing the composition for improving oral hygiene of the present invention or the composition for improving retention/adsorption of polycrezulene in the oral cavity is a toothpaste composition, abrasives, wetting agents, binders, foaming agents, sweeteners, medicinal agents, flavorings, acidity regulators and whitening agents It may further include one or more additives selected from the group consisting of.

The abrasive is at least one selected from the group consisting of calcium monohydrogen phosphate, precipitated silica, calcium carbonate, hydrous alumina, kaolin, and sodium bicarbonate, preferably calcium monohydrogen phosphate and/or precipitated silica, and is used in an amount of 5 to 50% based on the total weight of the composition. It can be used as weight percent.

The humectant is at least one selected from the group consisting of glycerin, sorbitol, amorphous sorbitol solution, propylene glycol, polyethylene glycol, and xylitol, preferably sorbitol solution, for example, 20 to 60% by weight based on the total weight of the composition. You can use it.

The binders include sodium carboxymethylcellulose, carrageenan, xanthan gum, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, guar gum, gellan gum, carbomer, pectin, polyvinylpyrrolidone, carboxyvinylpoly. and at least one selected from the group consisting of sodium alginate and laponite, preferably sodium carboxymethyl cellulose, and can be used, for example, in an amount of 0.5 to 2% by weight based on the total weight of the composition.

Examples of the foaming agent include anionic surfactants such as sodium lauryl sulfate and sodium lauryl sarcosinate; Nonionic surfactants made of sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene/polyoxypropylene copolymer, etc.; Or at least one selected from amphoteric surfactants such as cocoaidopropyl betaine, preferably sodium lauryl sulfate, and can be used in an amount of 0.5 to 5% by weight based on the total weight of the composition.

The sweetener is one or two or more selected from the group consisting of sucralose, maltitol, aspartame, erythritol, and licorice acid, preferably sucralose, and can be used in an amount of 0.05 to 0.3% by weight based on the total weight of the composition.

The medicinal agents include sodium fluoride, sodium fluorophosphate, stannic fluoride, amine fluoride, chlorhexidine, aminocaproic acid, dipotassium glycyrrhizinate, tranexamic acid, allotoin, caproic acid, polyphosphates, enzymes, and herbal extracts. At least one selected from the group consisting of, preferably sodium fluoride, can be used in an amount of 0.1 to 0.3% by weight based on the total weight of the composition.

The above flavoring agent is used by mixing an appropriate amount of natural flavoring agents such as peppermint oil, spearmint oil, etc., and synthetic flavoring agents such as menthol and carbonate. Preferably, an appropriate amount of anise oil is mixed with the flavoring material mixed in a certain ratio. The content of fragrance can be 0.5 to 3% by weight based on the total weight of the composition.

For example, the oral hygiene composition or the composition for enhancing the adsorption of polycrezulene in the oral cavity includes 0.0005 to 2% by weight of polycrezulene and 0.1 to 5% by weight of sodium chloride based on the total weight of the composition, and 15 to 60% by weight of an abrasive as an additive. , 20 to 60% by weight of wetting agent, 0.5 to 20% by weight of binder, 0.5 to 5% by weight of foaming agent, 0.05 to 0.3% by weight of sweetener, 0.1 to 0.3% by weight of medicinal agent, 0.5 to 3% by weight of fragrance, and the balance of purified water. It could be.

The present invention provides an oral composition, particularly an oral hygiene composition, containing polycrezulene, which has a longer duration of effect or improved effect.

The present invention also provides a method for increasing the duration of the effect of polycresulene or improving the effect of polycresulene.

The present invention also provides compositions and/or kits containing such compositions that can extend (increase) the duration of effect of polycresulene or improve the effect of polycresulene.

As a result, the composition according to the present invention improves the residual power of polycrezulene in the oral cavity, has an excellent effect of preventing plaque formation, and has an effect of alleviating inflammation in periodontitis and gingivitis.

Figure 1 is a diagram showing the plaque index used to evaluate the results of Experimental Example 2. The “Turesky Modification of Quigley-Hein plaque index” commonly used in the art was used.
Figure 2 shows a questionnaire used in consumer evaluation of toothpastes according to one embodiment of the present invention.
Figure 3 shows the results of consumer evaluation of toothpastes according to one embodiment of the present invention.

Hereinafter, to aid understanding of the present invention, it will be described in detail through examples. However, the embodiments according to the present invention may be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

Example 1 to 11 and Comparative example 1 to 3

The toothpaste compositions of Examples 1 to 11 and Comparative Examples 1 to 3 were prepared with the ingredients and composition ratios shown in Table 1 below. Powder components such as sodium carboxymethyl cellulose were dispersed in the sorbitol solution, which is a wet component, purified water was added, and then mixed first in a mixer. Next, an abrasive such as precipitated silica and a medicinal agent were added and mixed.

Finally, sodium lauryl sulfate as a foaming agent and flavoring ingredients were added and mixed under vacuum to prepare a toothpaste composition.

division
(Unit: weight%) Example Comparative example One 2 3 4 5 6 7 8 9 10 11 One 2 3 Dental type silica 14 14 14 14 14 14 14 14 14 14 14 14 14 14 Sorbitol solution
(70%) 50 50 50 50 50 50 50 50 50 50 50 50 50 50 Sodium lauryl sulfate 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 Sucralose 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Carboxymethylcellulose One One One One One One One One One One One One One One sodium fluoride 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Spices One One One One One One One One One One One One - One Purified water Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount polycrezulene 0.001 0.01 0.1 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 - 0.01 - bamboo salt One One One 2 3 - - - - - - - - One sea salt - - - - - One - - - - - - - - pharmacopoeial salt - - - - - - One - - - - - - - sodium bicarbonate - - - - - - - One - - - - - - calcium chloride - - - - - - - - One - - - - - Sodium phosphate monobasic - - - - - - - - - One - - - - Sodium saccharin - - - - - - - - - 0.2 - - - -

Experimental Example 1. Measurement of detection of polycrezulene

After brushing the teeth of 10 male and female consumers in their 20s to 40s for 1 minute with the compositions of the Examples and Comparative Examples in Table 1 above, saliva was collected over time and the presence or absence of polycresulene was detected using liquid chromatography. It was measured using the method.

The measurement results are indicated only as detection or non-detection (detection (O), non-detection (X)) of polycrezulene in Table 2 below.

division Example Comparative example One 2 3 4 5 6 7 8 9 10 11 One 2 3 Elapsed time Immediately after O O O O O O O O O O O X O X 5 minutes O O O O O O O O O O O X X X 10 minutes O O O O O O O O O O O X X X 30 minutes O O O O O O O O O O O X X X

As shown in Table 2, it was confirmed that polycrezulene was continuously detected in the experimental results up to 30 minutes after brushing teeth, but in the toothpaste of Comparative Example 2, it was detected immediately after brushing teeth, but due to dilution and ingestion by saliva. Therefore, it was confirmed that it was not detected even after 5 minutes immediately after brushing teeth. In other words, it was confirmed that the residual power of polycrezulene increased significantly when used simultaneously with an oral tissue astringent.

Experiment example 2. polycrezulene and bamboo salt-containing toothpaste Tooth surface bacterial film formation inhibitory effect

<Experiment method>

Adult men and women aged 20 to 65 years old with at least 20 existing natural teeth were asked to use Example 2 and Comparative Examples 1 to 2 in Table 1 for 4 weeks, and then initially and after 4 weeks, the biofilm index was measured in the following manner. It was evaluated by score. All 20 or more natural teeth present in the study subjects' mouths were evaluated by dividing them into 6 planes (buccal-mesial, buccal-central, buccal-distal, lingual-mesial, lingual-central, and lingual-distal). At this time, crowns equipped with fixed orthodontic devices or in which the entire tooth surface was restored were excluded. To evaluate the index to evaluate the inhibition of dental plaque formation, plaque was stained using a plaque staining reagent, and the Turesky Modification of Quigley-Hein plaque index (PI) was evaluated by one examiner based on Figure 1 and the following criteria. .

0 points = no plaque at all

1 point = If the plaque is not connected and forms an island

2 points = If there is plaque in the form of a line along the gingival margin

3 points = If there is plaque in the cervical 1/3 area

4 points = Plaque on 2/3 of the crown

5 points = When plaque covers almost the entire crown

PI = sum of total scores / total number of teeth inspected

<Experiment results>

The plaque index measurement results are shown in Table 3 below. As shown in Table 3 below, when comparing the results after 4 weeks of using toothpaste, the toothpaste in Comparative Example 1 increased by 5.6% compared to the initial period, decreased by 2.7% in the toothpaste in Comparative Example 2, and decreased by 4.6% in the toothpaste in Example 2. In addition, among the study subjects, the effectiveness rate confirmed that the plaque index after 4 weeks of toothpaste use was the same or decreased than before toothpaste use was 58% of the toothpaste users in Comparative Example 2 and 82% of the toothpaste users in Example 2. Through this, it can be seen that the oral composition containing polycresulene and bamboo salt results in a synergistic increase in its function through various causes (for example, increased adsorption of polycresulene in the oral cavity).

Toothpaste group n Baseline
Mean (standard deviation) 4 weeks later
Mean (standard deviation) P-value Comparative Example 1 25 3.09(0.41) 3.24(0.34) < 0.001 Comparative Example 2 26 3.29(0.37) 3.20(0.46) Example 2 22 3.30(0.41) 3.13(0.35)

Experiment example 3. polycrezulene and Oral tissue astringent Consumer evaluation of toothpaste containing

Consumer sensory evaluation of toothpaste containing polycrezulene and oral tissue astringent was conducted in the following manner.

Experimental subjects: 30 adult male and female volunteers in their 20s to 40s were publicly recruited.

Experimental method: Test subjects were given new toothpaste every week and were asked to use only that toothpaste and evaluate their feeling of use through a survey.

Experimental toothpaste: Examples 2 and 6 to 11 of Table 1 above were provided as experimental toothpastes. All compositions used the same fragrance and color to prevent likes and dislikes due to fragrance and color.

Survey items: Evaluated using a consumer evaluation questionnaire as shown in Figure 2.

The results are shown in Figure 3 below. As shown in Figure 3, the consumer evaluation results showed that the composition of Example 2 had the highest satisfaction in terms of cleansing feeling, continuation of neatness, flavor, and overall satisfaction.

Experiment example 4. polycrezulene and Oral tissue astringent Evaluation of antibacterial activity of toothpaste containing

Consumer sensory evaluation of toothpaste containing polycrezulene and oral tissue astringent was conducted in the following manner.

Strains: Streptococcus mutans (ATCC 25175), Porphyromonas gingivalis (ATCC 49417), Prevotella nigrescens (ATCC 25261), Fusobacterium nucleatum (ATCC 25586) was used. The strain was subcultured in Brain Heart Infusion (BHI: Difco, USA) liquid medium for the first and second rounds, then inoculated into the same medium and cultured in an anaerobic incubator at 37°C for 72 hours before use. The medium was used by adding menadion (50ng/ml) and hemin (4ug/ml) to BHI.

Experimental method: Examples 2 and 6 to 11 of Table 1 were diluted in BHI liquid medium to adjust the final concentration to 10% and further incubated with 3 × 10 ⁵ CFU/ml of bacteria for 3 minutes. Afterwards, the culture medium was sequentially diluted and cultured on solid medium for an additional 48 hours, and the resulting CFU (Colony Forming Unit) was examined. All experimental groups were repeated three times.

The results are shown in Table 4 below. As a result of a comparison test of antibacterial activity against oral microorganisms used in the experiment, it was found that the composition of Example 2 had the highest antibacterial activity, as shown in Table 4 below.

division S. mutans P. gingivalis P. nigrescens F. nucleatum Early 3×10 ⁵ 3×10 ⁵ 3×10 ⁵ 3×10 ⁵ Example 2 100 or less 100 or less 100 or less 100 or less Example 6 2.0×10 ³ 2.2×10 ³ 3.0×10 ³ 3.0×10 ³ Example 8 100 or less 1.0×10 ³ 1.2×10 ³ 1.3×10 ³ Example 9 1.2×10 ³ 1.0×10 ³ 2.0×10 ³ 2.0×10 ³ Example 10 1.8×10 ³ 1.0×10 ³ 1.6×10 ³ 2.0×10 ³ Example 11 2.0×10 ³ 2.2×10 ³ 2.2×10 ³ 2.3×10 ³

Claims (9)

An oral composition containing policresulen and an oral tissue astringent. In the oral composition containing policresulen,
An oral composition comprising an oral tissue astringent for enhancing the effect of polycrezulene. The oral composition according to claim 2, wherein the oral tissue astringent is used to increase retention or adsorption of polycresulene. The oral tissue astringent according to any one of claims 1 to 3, wherein the oral tissue astringent is sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium sulfate, potassium sulfate, sodium bicarbonate, sodium carbonate, potassium phosphate monobasic, potassium phosphate dibasic, An oral composition comprising at least one selected from the group consisting of potassium triphosphate, sodium phosphate monobasic, sodium phosphate dibasic, sodium phosphate tribasic, and sodium saccharin. The oral composition according to claim 4, wherein the sodium chloride is contained as bamboo salt, bamboo salt, sea salt, refined salt, formulation salt, or pharmacopoeial salt. The oral composition according to claim 5, wherein the composition contains bamboo salt. The method according to any one of claims 1 to 3, wherein the composition contains 0.0005 to 2% by weight of polycrezulene based on the total weight of the composition; And an oral composition comprising 0.001 to 5% by weight of an oral tissue astringent. (a) a composition containing polycrezulene, and
(b) a composition containing an oral tissue astringent for enhancing the effect of polycrezulene.
Oral kit containing: The method of claim 8, wherein the oral tissue astringent is sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium sulfate, potassium sulfate, sodium bicarbonate, sodium carbonate, potassium phosphate monobasic, potassium phosphate dibasic, potassium phosphate tribasic, sodium phosphate monobasic. , an oral kit comprising at least one selected from the group consisting of sodium phosphate dibasic, sodium phosphate tribasic, and sodium saccharin.