KR20020044855A - Oral compositions containing xanthorrhizol as an inhibitor of reactive oxygen species and nitric oxide for dental hygiene - Google Patents

Abstract

PURPOSE: An oral care composition containing as an effective composition xanthorrhizol having an excellent action for inhibiting the formation of active oxygen and nitric oxide inducing gum disease is provided which is effective in removal of plague and the treatment and prevention of gingivitis and periodontal disease. CONSTITUTION: This oral hygiene composition contains 0.001 to 3% by weight of a xanthorrhizol composition and additionally 0.001 to 2% by weight of ursodeoxycholic acid as an inflammation inhibitor, based on the total weight of the composition. This oral hygiene composition is a toothpaste or oral ointment.

Description

Oral hygiene containing xanthorrhizol as an inhibitor of reactive oxygen species and nitric oxide for dental hygiene

The present invention confirms that xantholizole, which is one of essential oil components, has an excellent effect of inhibiting the generation of free radicals and nitric oxide, which are mediators of gum disease.

It relates to an oral product composition containing xantholisol as an active ingredient that promotes oral hygiene through one effect.

In the process of caries and periodontal disease, first, saliva proteins in the oral saliva are adsorbed on the dentin and chalky surface to form a film. The surface of the film is mainly composed of Streptococcus and Actinomyces and Actinomyces. As the same bacteria grow, they form plaques, and as time passes, calcium and phosphorus in the saliva are adsorbed to form tartar, and at the same time, enamel and dentin are demineralized by organic acids secreted from these bacteria. As the plaque moves toward the root end, anaerobic Gram-negative bacteria such as Porphyromonas and Actinobacillus grow, and these bacteria, bacterial components, and bacterial products penetrate into the gingival connective tissue through the gingival epithelium. Periodontal pockets are formed and these bacteria metabolism results in poisonous sulfur water The secretion of cell toxins such as bovine, ammonia, and toxic amines, as well as the direct destruction of tissues by endotoxins such as lipopolysaccharide, a cell wall component, or stimulation of the biological immune system, Free radicals secreted extracellularly by various actions of the cellular immune system, nitric oxide, prostaglandins, leukotriens, histamine, and interleuckins, tumer nicrosis factor Gum inflammation is caused by several types of cytokines such as alpha (Tumour Necrosis Factor α), and collagen, a substrate of periodontal tissue, is degraded by enzymes such as collagenase secreted from bacteria and leukocytes. This happens, and if left unattended will progress to periodontal disease.

Chlorohexidine gluconate, Cetylpyridium chloride, Triclosan, which can kill periodontal disease bacteria with short-term exposure, in an effort to prevent the occurrence of tooth decay and periodontal disease. And antimicrobial agents such as Sanguinarine (Sanguinarine) has been developed and applied to oral products such as dentifrice and toothpaste, but the occurrence of dental caries and periodontal disease has not yet prevented fundamentally.

Therefore, in recent years, efforts have been actively made to suppress tooth decay and periodontal disease by using herbal extracts such as myrrh, baekbaekpi, horse riding, green tea, licorice, golden, pogongyoung, and gold and silver coins. It prevents the occurrence of periodontal disease through abstract effects such as anti-inflammatory, convergence, hemostasis, and blood circulation.

At present, the most widely used method for treating plaque and gingivitis is US published patent US NO. 5356615 has developed an oral product using triclosan and has shown that it has an excellent effect on inhibiting plaque formation. 5571501 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), the use of triclosan inhibits plaque formation and periodontal disease. European Patent No. 528468 A1 has developed a toothpaste and a mouthwash containing triclosan to inhibit periodontal disease by inhibiting the production of prostaglandins, which cause periodontal disease. After confirming that, the method of treating periodontal disease was suggested. However, in the case of triclosan is highly cytotoxic, there is a high risk of side effects in long-term use, and the expression of resistant strains may also be a problem.

Thus, the present inventors can inhibit the production of free radicals and nitrogen oxides, which are the most important of inflammation-causing substances for the prevention and treatment of gum disease, and have particularly hydrophobic properties among natural products such as safe herbal medicines and plant extracts having excellent penetration effects. Extensive research has been conducted to identify the essential medicinal ingredients in essential oils, confirming that oils extracted from the roots of Curcuma xanthorrhiza have the highest efficacy and that the oils are known to have excellent antibacterial effects. Fitoterapia 71 (2000) 321-323) Xanthorrhizol, Xanthorrhizol, and the purchase of patients with oral disease in clinical trials results in plaque removal, gingivitis and periodontal disease prevention and treatment It was confirmed that the efficacy for the excellent to complete the present invention.

Curcuma xanthorrhiza is traditionally known for its efficacy in gastrointestinal and liver diseases, anticancer activity, dysentery, fever, hemorrhoids and constipation. Major ingredients include Sesquiterpenoids such as α-curcumene, β-curcumene, arturmenone, xanthorrhizol, germacrone, β-sesquiphellandrene, curzerenone, α-turmerone and β-turmerone. (JP2000-136141A).

Hereinafter, a detailed description of the present invention is as follows.

The xantholizole used in the present invention is preferably used in an amount of 0.001 to 3% by weight based on the total composition, and for the synergistic effect on the inhibitory effect of the active oxygen and nitric oxide production of xantholisol It is preferred to use with antibacterial agents such as (Triclosan) and Cetylpyridium chloride or anti-inflammatory agents such as Ursodeoxycholic acid and bamboo salt, the content of each of 0.001 to 2% by weight It is preferable to use.

Xanthol azole is difficult to use at the concentration of less than 0.0001% by weight of the anti-freezing effect of biofilm plaque and antibacterial effect on oral bacteria through infiltration, when it exceeds 3% by weight.

The present invention prevents and treats gingival inflammation and periodontal disease through the promotion of oral hygiene and inhibition of the production of free radicals and nitric oxide by applying xantholisol as an active ingredient to conventional ingredients such as oral toothpaste, mouthwash, oral ointment. It relates to a composition for. As another component of this invention, it mix | blends using the appropriate amount of the component normally used according to the kind of composition for oral cavity, and a use purpose. For example, the toothpaste composition of the present invention can be prepared by the following method.

Abrasive ingredients include calcium monohydrogen phosphate, precipitated silica, silica gel, sodium bicarbonate, calcium carbonate, hydrous alumina, insoluble sodium phosphate, sodium pyrophosphate, etc. Sodium fluoride and sodium monofluoride phosphate may be mixed or used alone as a fluorine compound which promotes remineralization of the tooth and strengthens the tissue of the tooth. The content is suitably 0.01 to 2.0% by weight. It is not suitable as an oral preparation because the content is ineffective at a concentration of 0.01% by weight or less and exceeds 2.0% by weight because it may affect the safety of the human body.

Wetting agents are used to maintain the dentifrice composition and prevent drying. Such wetting agents include glycerin, sorbitol solution, polyethylene glycol and propylene glycol, and are used alone or in combination of two or more. In addition, it is a binder used to maintain the shape of the toothpaste by combining the liquid and solid components of the toothpaste component and to ensure the stability, mainly natural or such as sodium carginate or calcium salt, sodium carboxymethylcellulose, xanthan gum, acacia gum or Synthetic polymer is used and its amount is 0.1 -5 wt%. The foaming agent complements the cleaning action of the abrasive and not only penetrates the medicament to the areas where the toothbrush is hard to reach, but also generates bubbles to increase the sensation of teeth, aids in the cleaning action, speeds up the dispersion and penetration of the drug, By reducing the interfacial tension, foreign matter in the oral cavity easily falls. Commonly used foaming agents are anionic surfactants such as sodium lauryl sulfate and sodium alkyl sulfate, and auxiliary nonionic surfactants such as polyoxyethylene, polyoxypropylene, copolymers, polyoxyethylene sorbitan fatty acids, alkanolamide fatty acid esters and sucrose Fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acid esters and polyoxyethylene castor cured oil derivatives are used. The amount of foaming agent is preferably 0.5 to 5% by weight of anionic or nonionic surfactants alone or in combination of two or more.

In addition, flavors and sweeteners are used to control the bitter or somewhat bitter taste. The flavoring is mainly used in the natural flavors of peppermint and spearmint oil, 0.1 to 1% by weight in toothpaste. The sweeteners are mainly synthetic or natural non-fermentable sugars, and the representative ones are saccharin sodium, aspartame, lactose, maltose, xylitol, and the like, and suitable sweeteners are preferably 0.05 to 1% by weight of saccharin sweeteners. Do. As the buffer for adjusting the pH of the toothpaste composition, alkali metal salts of phosphoric acid, particularly sodium phosphate, dibasic sodium phosphate, sodium triphosphate, phosphoric acid, hydrochloric acid, sodium hydroxide, sodium pyrophosphate and pyrophosphate may be used. . 0.01 to 0.5% by weight of paraoxybenzoic acid methyl, benzoic acid, sodium benzoate, salicylic acid or the like, which is generally approved for use in foods and medicines, to prevent contamination of microorganisms that may occur during the manufacture and use of toothpaste compositions. % use.

Another composition for improving oral hygiene, gingivitis and periodontal disease prevention and treatment of the present invention is characterized by using an appropriate amount of the component used in the product and using xanthosol as an active ingredient as an active ingredient.

Hereinafter, examples and experimental examples of the composition for preventing and treating gingivitis and periodontal disease, which specifically describe the present invention.

Experimental Example 1.

Subject

The following are experimental results for explaining the present invention in detail.

Test subject group (unit: weight%) Experimental group Xantholyzol Triclosan Ursodeoxycholic acid One - 2 0.001 3 0.3 4 0.01 5 0.001 0.01 6 0.001 0.3 7 0.01 8 0.01 0.01 9 0.1 10 0.1 0.01 11 One 12 One 0.3 13 2 14 2 0.01

Superoxide Formation Inhibitory Effect

Venous blood collected using citric acid as an anticoagulant from a healthy adult without centrifugation was centrifuged at 1200 rpm for 10 minutes, and then the leukocyte concentrate was recovered first, and then diluted 1: 1 with RPMI 1640 medium. After 12 ml of Ficoll-Paque was added to a 50 ml centrifuge tube, 30 ml of diluted blood was carefully added to form a middle layer, followed by centrifugation at 1600 rpm for 30 minutes, and then the upper layer containing serum was removed. After carefully diluting the middle layer, three times of RPMI 1640 medium was added, centrifuged at 800 rpm for 10 minutes, the supernatant was discarded, 10 ml of RPMI 1640 medium was added, gently pipetted, and centrifuged at 800 rpm for 10 minutes. The supernatant is then discarded and pipetted with HBSS (HANKS 'BALANCED SALT SOLUTION) buffer, followed by 24-well flocculation of human mononuclear leukocytes. Sites 10 ⁶ cell / well to be dispensed and 0.45ml of 95% air, 5% CO _2, aseptically under 100% humidity After incubation for 2 hours, the FMLP (N-Formyl-Met- Leu-Phe) 10 - ^After stimulating the cells by 0.05ml to 6M and incubating for 15 minutes at 37 ℃, 0.1ml cytochrome C to 80μM, 0.1ml Superoxide dismutase to 30μg, Add 0.1ml of medicinal system to proper concentration, add HBSS (HANKS 'BALANCED SALT SOLUTION) to add 0.9ml of the total reaction solution, keep warm at 37 ℃ for 10 minutes, and then cultured Zymosan A (Zymosan A) ) 0.1ml is added to a final concentration of 1.3mg / ml and kept at 37 ° C for 90 minutes while shaking.Then, the reaction is stopped for 10 minutes at 4 ° C, centrifuged at 4 ° C, 1500rpm for 10min, and then the supernatant is removed. The optical density is measured at 550nm and the amount of superoxide anion produced is calculated by All.

ΔO.D. = (B-D)-(A-C) = (B + C)-(D + A)

A B C D Mononuclear leukocytes 0.5ml 0.45ml 0.5ml 0.45ml Cytochrome C 0.1ml 0.1ml 0.1ml 0.1ml SOD - - 0.1ml 0.1ml FMLP 0.05ml 0.05ml ZYMOSAN - 0.1ml - 0.1ml Experimental group - 0.1ml - Reaction solution 0.4ml 0.2ml 0.3ml 0.2ml total 1.00ml 1.00ml 1.00ml 1.00ml

(A, B, C, D means each absorbance measured in the composition)

Experiment result

Experimental group One 2 3 4 5 6 7 8 9 10 11 12 13 14 Superoxide (%) 100 50 0 40 35 0 30 15 20 10 15 0 10 5

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

In the above experimental results, the experimental group 1 was found to have no superoxide inhibitory effect, whereas in the experimental groups 2, 7, 9, 11, and 13, the xantholisol showed an excellent superoxide inhibitory effect as the concentration was increased. In combination with ursodeoxycholic acid, synergistic effects on the inhibition of superoxide production were observed. In addition, trichromic acid was unable to measure the superoxide production inhibitory effect due to cytotoxicity.

Inhibitory Effect on the Production of Nitrogen Chloride (NO)

First, when RAW 264.7 cells incubated in DMEM medium containing 10% fetal bovine serum were filled in a 10 cm diameter cell culture plate,

After 1 ml of 10 ⁶ cells / well was incubated for 24 hours under 95% air, 5% CO ₂ , and 100% humidity conditions, the experimental group was treated with 100 ppm concentration for 1 hour to induce the production of nitric oxide. In order to treat the E. coli lipopolysaccharide (Lipopolysaccharide) and interferon gamma to 1ppm and 100U respectively and incubated for 24 hours. Then, after mixing the media supernatant and the Greases reagent purchased from Sigma 1: 1 at 5 minutes, the optical density was measured at 540 nm, and a standard curve was prepared using the absorbance value of the standard solution. Calculate the amount of.

Experiment result

Experimental group One 2 3 4 5 6 7 8 9 10 11 12 13 14 Superoxide (%) 100 50 0 40 35 0 30 15 20 10 15 0 10 5

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

In the above experimental results, the experimental group 1 showed no effect of inhibiting nitric oxide production, whereas the experimental group 2, 7, 9, 11, and 13 showed that the xantholizole had an excellent effect of inhibiting the production of nitric oxide as the concentration increased. In combination with ursodeoxycholic acid, synergistic effects on inhibition of nitric oxide production were observed. As in the superoxide inhibitory effect experiments, triclosan could not measure the nitric oxide inhibitory effect due to cytotoxicity.

Experimental Example 2

The following is an example of a toothpaste composition as an Example and a comparative example for demonstrating this invention in detail. Plaque formation inhibitory effect experiment and gingival inflammation inhibitory effect experiment were performed using the toothpaste which added the experimental group of Experimental example 1. The manufacturing procedure of these toothpaste compositions is as follows.

Disperse powder components such as sodium carboxymethyl cellulose, saccharin, and preservative in wet sorbitol solution, dilute with purified water, and then mix in a mixer firstly, and then add abrasives and active ingredients such as calcium monohydrogen phosphate and mix It was. And finally, a toothpaste composition was prepared by adding a foaming agent sodium sulfate, stabilizers and flavoring ingredients and mixing under vacuum.

The test method is to first screen the subjects, explain the oral examination, and then divide 10 random subjects into each of the Examples and Comparative Examples and find the correct brushing method.

After education, oral examinations are performed to measure the Quigley-Hein Index modified by Turesky and the Gingival Bleeding Index (Loe-Silness Index). In addition, after the scaling of all the teeth in the experimental group, the control toothpaste was used for 2 weeks, followed by an oral examination, and the plaque index and the gingivitis index were initial values. Example Toothpaste and Comparative Example Toothpaste was distributed to each subject, and brushing was performed three times a day for six months in the same manner as usual, and oral examination was performed to score plaque index and gingivitis index. The experimental results were compared with the initial values of the experimental group and the score after 6 months, and the statistical significance was tested by T-test, respectively.

Examples 1 to 9 and Comparative Examples 1 to 3

(Unit: weight%) ingredient Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Example 9 Calcium dihydrogen phosphate 40.00 40.00 40.00 - - - - - - Calcium carbonate - - 30.00 30.00 30.00 - - - Precipitated silica - - - - - - 20.00 20.00 20.00 Sorbitol 25.00 25.00 25.00 25.00 25.00 25.00 - - - glycerin - - - - - - 25.00 25.00 45.00 Alkyl Sodium Sulfate 1.50 1.50 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 0.10 0.10 Methyl paraoxybenzoate 0.1 0.1 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 - - - Carrageenan - - - - - - 0.90 0.90 0.90 Triclosan 0.3 0.3 Ursodeoxycholic acid 0.01 0.01 0.1 Xantholyzol 0.001 0.01 0.1 One 2 0.1 0.1 0.1 0.1 Bamboo salt 2 2 2 Sodium fluoride 0.22 0.22 0.22 Sodium monofluorophosphate 0.76 0.76 0.76 0.76 0.76 0.76 - - - With purified water 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0

ingredient Comparative Example 1 Comparative Example 2 Comparative Example 3 Calcium dihydrogen phosphate 40.00 - Calcium carbonate - 30.00 Precipitated silica - - 20.00 Sorbitol 25.00 25.00 glycerin - - 25.00 Alkyl Sodium Sulfate 1.50 1.50 1.50 Saccharin Sodium 0.10 0.10 0.10 Methyl paraoxybenzoate 1.00 1.00 1.00 Carboxymethyl Cellulose Sodium 1.00 1.00 - Carrageenan - 0.90 Triclosan 0.3 Ursodeoxycholic acid 0.01 Xantholyzol - - - Bamboo salt 2 Sodium fluoride 0.22 Sodium monofluorophosphate 0.76 0.76 With purified water 100.0 100.0 100.0

Experiment result

Gingivitis index Experimental Toothpaste Group Initial value 3 months 6 months Example 1 1.43 1.36 1.80 Example 2 1.45 1.29 1.68 Example 3 1.47 1.31 1.07 Example 4 1.43 1.14 1.08 Example 5 1.45 1.10 0.98 Example 6 1.43 1.11 1.04 Example 7 1.46 1.12 1.03 Example 8 1.41 1.10 0.98 Example 9 1.42 1.05 1.02 Comparative Example 1 1.48 1.39 2.52 Comparative Example 2 1.48 1.36 1.86 Comparative Example 3 1.45 1.35 1.98

As a result of statistically significant difference test by measuring the gingivitis index after using Examples 1 to 9 and Comparative Examples 1 to 3 for 6 months, the most excellent effect was found in Examples 1 to 9 in the gingivitis relief effect, and Comparative Example 1 , 2, 3 were found to have a significant effect, and these results indicate that xanthosol is effective in inhibiting gingival inflammation, and the use of trichromic acid or ursodeoxycholine acid in combination increases the suppression of gingival inflammation. Showed an effect.

Example 10. Gum Ointment

(Unit: weight%) ingredient content(%) Glycerin Monolauryl 3.00 Oleic Alcohol 5.00 Polyethylene glycol 15.00 White waserine 3.00 N-palmitic glutamate monosodium 0.50 Hydroxy ethyl cellulose 5.00 Tocopherol Acetate 0.10 Xantholyzol 0.10 Citric acid 0.1 Sweetener 0.20 Spices 0.30 With purified water 100.0

Example 11. Mouthwashes

(Unit: weight%) ingredient content(%) ethanol 10.00 Polyoxyethylene Polyoxypropylene Copolymer 1.00 Concentrated glycerin 15.00 Saccharin Sodium 0.01 Xantholyzol 0.1 Citric acid 0.1 Sodium fluoride 0.23 Spices 0.30 With purified water 100.00

Also in Examples 10-11, the result which was excellent in the gingivitis relief effect was obtained.

As can be seen from the above Examples, Experimental Examples and Comparative Examples, the composition of the present invention contains xantholisol having an active oxygen and nitric oxide production inhibitory effect as an active ingredient to remove plaque, gingivitis and periodontal disease Excellent efficacy in the prevention and treatment of

Claims (7)

Oral hygiene composition comprising xantholizole having an active oxygen and nitric oxide production inhibitory effect as an active ingredient. The composition for oral hygiene according to claim 1, wherein the xantholizole is contained in an amount of 0.001 to 3% by weight based on the total amount of the composition. The composition for oral hygiene according to claim 2, further comprising 0.001 to 2% by weight of ursodeoxycholic acid as an anti-inflammatory agent, based on the total weight of the composition. The composition for oral hygiene according to claim 2 or 3, further comprising 0.01 to 1% by weight of trichromic acid as an antimicrobial agent, based on the total weight of the composition. The composition for oral hygiene according to claim 2 or 3, wherein the composition for oral hygiene is a toothpaste. The composition for oral hygiene according to claim 2 or 3, wherein the composition for oral hygiene is an oral ointment. The composition for oral hygiene according to claim 2 or 3, wherein the composition for oral hygiene is an oral cleaning agent which is a liquid composition for oral cavity.