KR20030083162A - Composition for oral care - Google Patents

Abstract

The present invention relates to a composition for promoting oral hygiene, and more specifically, oral hygiene, oral hygiene, gingivitis, periodontal disease prevention and alleviation, including oral hygiene enhancement, including tocotrienol, astaxanthin, or a mixture thereof as an active ingredient. It relates to a composition for.

Description

Composition for promoting oral hygiene {COMPOSITION FOR ORAL CARE}

[Industrial use]

The present invention relates to a composition for promoting oral hygiene, and more particularly, to a composition for promoting oral warfare having an excellent effect of inhibiting the generation of free radicals and nitric oxide for the purpose of preventing and alleviating periodontal and intraoral inflammation.

[Prior art]

In the process of developing oral inflammation, especially periodontitis, first, saliva proteins in the oral saliva are adsorbed on the dentin and chalky surfaces to form a film, and Streptococcus and Actinomyces mainly on the surface of the film. When bacteria, such as) grow, they form plaques, and when some of the plaques move toward the root end and become anaerobic conditions, anaerobic Gram-negative bacteria such as porphyromonas and Actinobacillus grow. Cells such as hydrogen sulfide, ammonia, and amines that are toxic to the periodontal tissue that are formed and secreted as a result of the metabolism of bacteria in the periodontal pocket by the formation of periodontal pockets through the gingival epithelium through the gingival epithelium. Tissues are directly destroyed by endotoxins such as toxins and lipopolysaccharide, a cell wall component, and are inflamed or secreted outside the cell by various actions of humoral and cellular immune systems stimulated by these toxins. Active oxygen, nitric oxide, prostagladins, Leukotriens, histamine, and interleukins, Tumor Necrosis Factor α Gum inflammation is caused by cytokines and the like, and collagenase secreted from bacteria and blood cells Is a matrix of collagen in the periodontal tissue is decomposed by the enzyme it occurs when gum recession continuing to leave it proceeds to periodontal disease.

Currently, the most widely used method for treating plaque and gingivitis is U.S. Patent No. 5,356,615, which has developed an oral product using triclosan to show excellent effects on inhibiting plaque formation. No. 5,571,501 has also shown the efficacy of triclosan on the bactericidal effect of oral microorganisms, and in clinical preventive dentistry (Clinical Preventive Dentistry vol / 14 (16), 1992), triclosan is used to inhibit plaque formation and prevent periodontal disease. To provide effects and the like. European Patent No. 528468 A1 proposed a method of treating periodontal disease by developing a toothpaste and a mouthwash containing triclosan to inhibit the production of periodontal disease by inhibiting the production of prostaglandins, which cause the periodontal disease. . However, triclosan is highly cytotoxic, so there is a high risk of side effects in long-term use, and expression of resistant strains may also be a problem.

In order to solve the problems of the prior art as described above, an object of the present invention is to provide a composition for promoting oral hygiene excellent in the function of inhibiting active oxygen and nitric oxide production.

Another object of the present invention is to provide a composition for promoting oral hygiene excellent gingivitis prevention and relief function.

In order to achieve the above object, the present invention provides a composition for promoting oral hygiene, comprising a tocotrienol, astaxanthin, or a mixture thereof.

More specifically, the content of tocotrienol, astaxanthin, or a mixture thereof in the composition for promoting oral hygiene of the present invention is preferably 0.0001 to 2% by weight.

Hereinafter, the present invention will be described in detail.

In order to solve the conventional problems and to prevent and alleviate oral inflammation in the oral cavity, the inventors focus on using a substance capable of inhibiting the production of free radicals and nitric oxide, which are the most important inflammatory inducing substances, Among the antioxidant vitamins, tocotrienol and astaxanthin were found to be effective, and clinical trials of oral hygiene compositions containing them in patients with oral diseases showed that the plaque removal, gingivitis and the prevention and treatment of periodontal disease. It was confirmed that the efficacy for the excellent to complete the present invention.

Tocotrienol (tocotrienol) used as an active ingredient in the present invention is present in four kinds in nature, is a kind of vitamin E contained in rice bran and palm oil, 40 to 60 times more antioxidant than the main component of the existing vitamin E tocopherol Have activity.

In addition, astaxanthin used as an active ingredient in the present invention is a carotenoid-based natural pigment contained in many shellfish such as crab, shrimp, salmon, trout, and the like, which is red when heated in crustaceans. The antioxidant activity of the astaxanthin is better than β-carotene, 100 to 500 times stronger than vitamin E.

In the composition for promoting oral hygiene of the present invention, the content of tocotrienol, astaxanthin, or a mixture thereof is preferably used in an amount of 0.0001 to 2% by weight based on the total composition. When the content of tocotrienol and astaxanthin is less than 0.0001% by weight, the effect of inhibiting the production of free radicals and nitrogen oxides cannot be expected. It is difficult to expect and affects the properties of the product, making it difficult to use.

At this time, in order to further improve the oral inflammation prevention effect of the composition, it is preferable to use an anti-inflammatory agent such as triclosan and cetylpyridium chloride or an anti-inflammatory agent such as ursodeoxycholic acid, the amount of ?? Preference is given to using in%.

The formulation of the composition for promoting oral hygiene of the present invention is preferably an oral product such as toothpaste, mouthwash, oral ointment.

In the composition for promoting oral hygiene of the present invention, the components other than tocotrienol and astaxanthin used as the active ingredient use an appropriate amount of a component that is commonly used according to the type and purpose of use of the above-described formulation. For example, in the composition for promoting oral hygiene of the present invention, the toothpaste composition can be prepared by the following method.

The toothpaste composition of the present invention includes an abrasive, a medicinal agent, a humectant, a binder, a foaming agent, a flavoring and sweetening agent, a buffer, and water together with the above-mentioned active ingredient tocotrienol or astaxanthin.

The abrasive component is one or more selected from the group consisting of calcium monohydrogen phosphate, precipitated silica, silica gel, sodium bicarbonate (heavy bath), calcium carbonate, hydrous alumina, insoluble sodium phosphate, and sodium pyrophosphate. The abrasive is used in an amount of 1 to 90% by weight.

In addition, the pharmacological agent serves to enhance the tissue of the tooth by promoting remineralization of the tooth. As said agonist, fluorine compounds, such as sodium fluoride and sodium fluorophosphate, can be mixed or used individually, It is preferable that the amount of ?? is 0.01 to 2.0 weight%. If the content of the drug is less than 0.01% by weight is not effective, if it exceeds 2.0% by weight is not suitable for oral preparations because it may affect the safety of the human body.

The humectant is used to maintain the state of the dentifrice composition and prevent drying. Such humectant is selected from the group consisting of glycerin, sorbitol liquid, polyethylene glycol, and propylene glycol. The content of the humectant is used in 20 to 60% by weight.

In addition, the binder is used to combine the liquid and solid components of the toothpaste component to maintain the form of the toothpaste and ensure stability. As the binder, natural or synthetic high molecular materials such as carginous sodium, calcium salt, carboxymethylcellulose sodium, xanthan gum, and acacia gum are used, and the amount of the binder is used in an amount of 0.1 to 5% by weight.

The foaming agent complements the cleaning action of the abrasive and penetrates the medicinal agent to the area which is difficult to reach the toothbrush, and also acts to increase the brushing by generating bubbles, and also helps the cleaning action and the dispersion of the drug and It speeds up penetration and decreases interfacial tension, which makes it easy to remove foreign substances in the oral cavity. As the foaming agent, anionic surfactants such as sodium lauryl sulfate and sodium alkyl sulfate are used, and auxiliary polyoxyethylene, polyoxypropylene copolymer, polyoxyethylene sorbitan fatty acid, alkanolamide fatty acid ester, sucrose fatty acid ester, polyoxy Nonionic surfactants, such as ethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, and polyoxyethylene castor hardened oil derivative, can be used. The amount of the foaming agent is preferably used in an amount of 0.5 to 5% by weight of anionic or nonionic surfactants alone or two or more.

In addition, flavors and sweeteners are used to control the bitter or somewhat bitter taste, which is mainly used in natural flavors peppermint and spearmint oil. The amount of the perfume is used in 0.1 to 1% by weight in the toothpaste composition. Sweeteners include synthetic or natural non-fermentable sugars and the like, and typical examples thereof include sodium saccharin, aspartame, lactose, maltose, xylitol, and the like. Preferably, saccharinartium is used. The content of the sweetener is preferably used in 0.05 to 1% by weight.

The buffer serves to adjust the pH of the dentifrice composition. As the buffer, alkali metal salts of phosphorous acid, particularly sodium monophosphate, sodium diphosphate, trisodium phosphate, phosphoric acid, hydrochloric acid, sodium hydroxide, sodium pyrophosphate and pyrophosphate may be used.

In addition, the present invention, in order to prevent the contamination of microorganisms that may occur during the manufacture and use of toothpaste composition, in general, methyl paraoxy benzoate, benzoic acid, sodium benzoate, salicylic acid, etc., which is licensed for use in food and medicines alone or Mixing may be used at 0.01 to 0.5% by weight.

Hereinafter, the present invention will be described with reference to the following Examples and Comparative Examples. However, these examples are only for illustrating the present invention, and the present invention is not limited thereto.

EXAMPLE

Experimental Example 1

(Active oxygen and nitric oxide production inhibitory effect test)

Toothpaste composition comprising the following ingredients as an active ingredient was prepared.

Active ingredient content by experimental group (unit: weight%) Experimental group Active ingredient Tocotrienol Astaxanthin 1 (control) - - 2 0.0001 - 3 - 0.0001 4 0.0005 - 5 - 0.0005 6 0.001 - 7 - 0.001 8 0.0005 0.0005 9 One - 10 - One 11 2 - 12 - 2

Experimental Example 1-1. Inhibitory effect on the formation of superoxide, a kind of active oxygen

Venous blood collected using citric acid as an anticoagulant from healthy adults without systemic diseases was centrifuged at 1200 rpm for 10 minutes, and then the leukocyte concentrate of the bilayer was recovered and diluted 1: 1 with RPMI 1640 medium. After 12 ml of Ficoll-Paque was added to a 50 ml centrifuge vessel, 30 ml of diluted blood was carefully added to make a double layer, centrifuged at 1600 rpm for 30 minutes, and then the upper layer containing serum was removed. Removed and recovered the layer containing monocytes. Three times 1640 medium was added thereto again, and centrifuged at 800 rpm for 10 minutes. Then, the supernatant was discarded, and 10 ml of RPMI 1640 medium was added again, and centrifuged at 800 rpm for 10 minutes, and the supernatant was discarded. After adding HBSS (HANK'S BALANCED SALT SOLUTION) buffer solution to the filtrate, 0.45 ml of human mononuclear leukocytes were dispensed to make 10 ⁶ cell / well in a 24-well plate, 95% air, 5% CO ₂ , 100% humidity. Incubated under conditions aseptically for 2 hours. Treated with 0.05 ml of FMLP (N-Formyl-Met-Leu-Phe) to 10 ^-6 M and incubated for 15 minutes at 37 ℃ to stimulate the cells and then 80 μM 0.1 ml of Cytochrome C, 0.1 ml of superoxide dismutase to 30 ㎍, 0.1 ml of the experimental group's medicinal system were added to the appropriate concentration, and the remaining total reaction solution was 0.9 ml. After adding HBSS to keep warm at 37 ℃ 10 minutes. Subsequently, 0.1 ml of the stimulating substance, phylated Zymosan A, was added to a final concentration of 1.3 mg / ml and kept at 37 ° C. for 90 minutes with shaking, followed by 10 minutes at 4 ° C. to stop the reaction. After centrifugation at 4 ° C. and 1500 rpm for 10 minutes, the supernatant was measured for optical density at 550 nm. The amount of superoxide anion produced was calculated by the following equation.

[Equation 1]

The experimental results for the above experiments are shown in Table 2 below.

(Unit:% = amount of superoxide produced in the experimental group x 100 ÷ amount of superoxide produced in the control group).

Experimental group Superoxide (%) 1 (control) 100 2 40 3 30 4 35 5 25 6 25 7 18 8 14 9 10 10 5 11 0 12 0

In the experimental results of Table 2, the control group was found to have no superoxide inhibitory effect, while in the experimental groups 1 to 12, both tocotrienol and astaxanthin were found to have excellent superoxide inhibitory effect as the concentration increased. In addition, synergistic effects were obtained even when both materials were used, showing an excellent synergistic effect on the inhibition of superoxide production.

Experimental Example 1-2. Inhibitory Effect on the Production of Nitric Oxide (NO)

When RAW 264.7 cells incubated in DMEM medium containing 10% fetal bovine serum were filled in a 10 cm diameter cell culture plate, they were dispensed in 1 ml so that 10 ⁶ cells / well were added to a 24-well plate. Incubate for 24 hours aseptically under air, 5% CO ₂ , 100% humidity conditions. The experimental group was treated at 100 ppm for 1 hour, and then treated with E. coli Lipopolysaccharide and interferon gamma to 1 ppm and 100 U, respectively, to induce the production of nitric oxide for 24 hours. Incubated. Optical density was measured at 540 nm after 5 minutes by mixing 1: 1 with the Griess reagent purchased from the media supernatant and Sigma. The amount of nitrogen oxide produced in the experimental group was calculated by preparing a standard curve based on the absorbance values of the standard solution.

Experimental results for this experiment are shown in Table 3 below.

(Unit:% = amount of nitric oxide produced in the experimental group x 100 ÷ amount of nitric oxide produced in the control group)

Experimental group Nitric Oxide (%) 1 (control) 100 2 32 3 35 4 28 5 25 6 21 7 22 8 12 9 6 10 5 11 0 12 0

In the results of Table 3, the control group was found to have no effect of inhibiting the production of nitric oxide, whereas the experimental groups 1 to 12 were found to have an excellent effect of inhibiting the production of nitric oxide as the concentration increased as in the superoxide production inhibition experiment. There was no significant difference between tocotrienol and astaxanthin, but the effect tended to increase.

Examples 1-5 and Comparative Examples 1-2

(Preparation of Toothpaste Composition)

A toothpaste composition (Examples 1 to 5) and a conventional toothpaste composition (Comparative Examples 1 to 2) of the present invention were prepared using the components shown in Table 4 as main components. Then, plaque formation inhibitory effect experiment and gingival inflammation formation inhibitory effect experiment were performed.

(Unit: weight%) Example 1 Example 2 Example 3 Example 4 Example 5 Comparative Example 1 Comparative Example 2 Tocotrienol 0.01 - 0.1 - 0.05 - - Astaxanthin - 0.01 - 0.1 0.05 - - Calcium carbonate 30.00 30.00 30.00 30.00 30.00 30.00 30.00 Sorbitol 25.00 25.00 25.00 25.00 25.00 25.00 25.00 Alkyl Sodium Sulfate 1.50 1.50 1.50 1.50 1.50 1.50 1.50 Saccharin Sodium 0.10 0.10 0.10 0.10 0.10 0.10 0.10 Methyl paraoxybenzoate 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Carboxymethyl Cellulose Sodium 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Triclosan 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Orthodeoxycholic acid 0.01 0.01 0.01 0.01 0.01 - 0.01 Sodium monofluorophosphate 0.76 0.76 0.76 0.76 0.76 0.76 0.76 Purified water Remaining amount Remaining amount Remaining amount Remaining amount Remaining amount Remaining amount Remaining amount

Experimental Example 2. Clinical Effect on Inhibitory Effect of Gingivitis Formation

This experiment was conducted after screening the oral examination by screening the subjects, each of the subjects randomly divided into 10 subjects in each of Examples 1 to 4 and Comparative Examples 1 to 2 and then trained the correct brushing method. An oral examination of the subject was performed to determine the gingivitis index (Gringival Bleeding Index, Loe-Silness Index). Then, after scaling the entire teeth of the experimental group, the control toothpaste was used for two weeks, followed by an oral examination, and the gingivitis index was set as an initial value. Toothpaste prepared in Examples and Comparative Examples were distributed to each subject and the brushing was performed three times a day for 6 months in the same manner as usual, and then oral examination was performed to score the gingivitis index. Experimental results were statistically tested by T-test (T-test) by comparing the initial value of the experimental group and the score after 6 months, respectively, and the results are shown in Table 5 below.

Gingivitis index Initial value 3 months 6 months Example 1 1.45 1.29 1.10 Example 2 1.47 1.31 1.07 Example 3 1.43 1.14 1.02 Example 4 1.45 1.10 0.98 Example 5 1.43 1.11 0.99 Comparative Example 1 1.48 1.39 1.30 Comparative Example 2 1.48 1.32 1.22

In Table 5, after using Examples 1 to 5 and Comparative Examples 1 to 2 for 6 months, the gingivitis index was measured and statistically significant. As a result, the gingivitis alleviation effect was compared. Examples 1 to 5 were compared. It was confirmed that there is a significant effect for Examples 1 and 2, and particularly excellent effects were shown in Examples 3 to 5. These results indicate that tocotrienol and astaxanthin are excellent in inhibiting gingival inflammation.

As described above, the present invention may include a tocotrienol and astaxanthin as an active ingredient to provide an oral hygiene promotion and gingival inflammation, periodontal disease prevention and alleviation excellent composition for oral hygiene.

Claims (3)

In the composition for promoting oral hygiene, Tocotrienol, astaxanthin, or a composition for promoting oral hygiene comprising a mixture thereof. The method of claim 1, Oral hygiene-promoting composition, characterized in that the content of the tocotrienol, astaxanthin, or a mixture thereof is 0.0001 to 2% by weight. The method of claim 1, Oral hygiene-promoting composition, wherein the formulation of the composition for promoting oral hygiene, oral hygiene or oral ointment.