KR20020001915A - Oral hygiene compositions containing hydroxytyrosol - Google Patents

Abstract

PURPOSE: A composition for the promotion of oral hygiene and oral health containing hydroxytyrosol as one of oliver oil components of Olea europaea extracts is provided, which can be used for the inhibition of bacterial plaque accumulation on teeth and prevention and treatment of diseases of dental cavity and periodontium. CONSTITUTION: A composition to improve buccal hygiene contains 0.001 to 3 parts by weight of hydroxytyrosol and 0.01 to 3 parts by weight of tetrasodium pyrophosphate(TSPP) or citric acid as a metal blocking agent. In experiments, the composition exhibits excellent effects on inhibiting plaque accumulation and alleviating gingivitis.

Description

Oral hygiene compositions containing hydroxytyrosol

The present invention relates to a composition for promoting oral hygiene containing hydroxytyrosol for the prevention and treatment of oral diseases, and more specifically, inhibiting plaque formation, caries and periodontal disease by containing hydroxytyrosol as an active ingredient. It relates to a composition for promoting oral hygiene that can effectively prevent and treat.

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 adsorb and form tartar, and at the same time, the enamel and dentin are demineralized by organic acids from these bacteria, while some plaques As it 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, causing periodontal pockets. Hydrogen sulfide, a cancer that forms and metabolizes these bacteria The secretion of humoral and cellular immune systems by direct secretion of endotoxins such as lipopolysaccharide, a cell wall component, and secretion of toxins in cells such as nia and toxic amines. Prostaglandins, free radicals secreted extracellularly by several actions

), Leukotriens, Histamine, and Interleukin

gum inflammation caused by various types of cytokines such as ckins, and Tumor Necrosis Factor α, and substrates of periodontal tissues by enzymes such as collagenase secreted from bacteria and leukocytes. Phosphorus collagen is broken down and gum retraction occurs, and if left unattended, it progresses to periodontal disease.

In an effort to prevent the development of tooth decay and periodontal disease, antimicrobial agents such as chlorohexidine gluconate, cetylpyridium chloride, trichloro acid and Sanguinarine can kill periodontal disease bacteria with short exposure. Although it has been applied to oral products such as dentifrice and toothpaste, the occurrence of caries and periodontal disease has not been fundamentally prevented yet.

Recently, in Korea, 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, gold, 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.

Currently, the most widely used method for treating plaque and gingivitis is U.S. Patent No. 5,356,615, which suggests that an oral product using triclosan is effective in suppressing plaque formation. U.S. Patent No. 5,571,501 In this issue, triclosan has been shown to be effective in the bactericidal effect of oral microorganisms. Clinical Preventive Dentistry vol. (16), 1992, and others have also been shown to use triclosan to inhibit plaque formation and prevent periodontal disease. I suggest that. European Patent No. 528468A1 describes a method for treating periodontal disease by developing toothpaste and oral cleaning agent containing Triclosan, which can suppress periodontal disease by inhibiting the production of prostaglandin, which is a periodontal disease-causing agent. Presented. However, triclosan is highly cytotoxic, so there is a high risk of side effects when used for a long time, and expression of resistant strains may be a problem.

Thus, in order to find a natural antibacterial agent that is safe even for long-term use and has excellent efficacy against resistant strains, it was first discovered in 1928 and has been widely used as a natural preservative in food such as milk and cheese for a long time. Publication Nos. WO 89/12399, WO 93/11738 and WO 94/12150 propose a method for improving oral hygiene by adding an adduct that can increase the antibacterial action of niacin and niacin. However, it is impossible to cure periodontal disease occurring in diabetic patients who progress regardless of the presence of bacteria only by improving the antimicrobial effect. In addition, Tetracycline, an antibiotic, has a high risk of side effects when used for a long time. Side effects such as vomiting, pain in the gastrointestinal tract, diarrhea, and tooth coloring are very frequent. Resistant strain expression may also be a problem.

Therefore, the present inventors pay attention to the fact that prag is a kind of biofilm to remove plaque, which is the root cause of these diseases, for prevention and treatment of caries, gingivitis and periodontal disease. In addition, as a result of extensive research on essential oils having hydrophobic properties among natural products such as safe herbal medicines and plant extracts with excellent penetration into Virofilm, the leaves of Oliver tree (Olea europaea) Taking into account this particular resistance to bacterial infections, we investigated whether hydroxytyrosol, a component of Oliver oil, has a bactericidal effect through biofilm penetration. As a result, hydroxytyrosol not only has excellent antibacterial effect against oral bacteria but also excellent sterilization effect through penetration of biofilm, and clinical trial results of patients with oral disease resulted in plaque, gingivitis and periodontal disease. It has been found that the efficacy for prevention and treatment is excellent and the present invention has been completed.

The present invention relates to a composition for enhancing oral hygiene, characterized in that it contains hydroxyl tyrosol as an active ingredient.

Oliver tree, also called Olea europaea, was one of the important tree crops in Palestine. Olive fruits were pickled and squeezed and used more valuablely. Olive oil (olive oil) has been used in a variety of dishes and was also used as oil for lanterns. It has been used as a skin ointment in a dry Mediterranean climate. The components of olive oil include palmitine, stearin, oleine, linoleine, oleuropein and hydroxytyrosol. Recently, oleuropein and hydroxytai Rosol is known to prevent lung cancer by inhibiting the production of free radicals due to its excellent antioxidant activity.

In the composition for promoting oral hygiene of the present invention, hydroxytyrosol is preferably contained in an amount of 0.001 to 3 weight based on the total composition. When the content of hydroxytyrosol is less than 0.001 weight, antimicrobial effect on oral bacteria cannot be expected through biofilm penetration, and when it exceeds 3 weight, it is difficult to use because it affects the properties of oral products.

Oral hygiene-promoting composition of the present invention can be used in combination with a metal suture, such as tetrasodium pyrophosphate (TSPP), or citric acid for a synergistic effect on the antimicrobial effect of hydroxytyrosol. The content of the metal blocking agent is preferably used by mixing 0.01 to 1 weight, respectively.

The present invention is a composition for improving oral hygiene and inhibiting plaque formation, preventing and treating gingivitis and periodontal disease by applying hydroxytyrosol as an active ingredient to conventional ingredients such as toothpaste, oral cleaning agent, oral ointment, which are oral products. It is about. The other component of the present invention is formulated using an appropriate amount of the carrier component usually used according to the type and purpose of the composition for oral cavity. These carrier components may include abrasives, agonists, wetting agents, binders, foaming agents, fragrances, sweeteners, pH buffers and the like.

For example, the toothpaste composition of the present invention can be prepared by the following method.

As an abrasive component, 1-90 weights of calcium monohydrogen phosphate, precipitated silica, silica gel, sodium bicarbonate, calcium carbonate, hydrous alumina, insoluble sodium metaphosphate, sodium pyrophosphate, etc. are mixed and used. In addition, as a fluorine compound which is an agent that promotes remineralization of teeth and strengthens the tissues of teeth, sodium fluoride and sodium monofluorophosphate may be mixed or used alone, and its content is suitably 0.01 to 2.0 weight. If the content of the fluorine compound is less than 0.01 weight is not expected enough effect, if it exceeds 2.0 weight is not suitable for oral preparations because it may affect the safety of the human body.

Wetting agent is used to maintain the condition of toothpaste composition and to prevent drying. Such humectants include glycerin, sorbitol solution, polyethylene glycol and propylene glycol, and are used alone or in combination of two or more by 20-60 weight. In addition, a binder is used to combine the liquid and solid components of the toothpaste component to maintain the form of the toothpaste and to ensure stability. As a binder, natural or synthetic high molecular weight materials such as sodium carginate, calcium salt, carboxymethyl cellulose sodium, xanthan gum, and acacia gum are mainly used. The foaming agent complements the cleaning action of the abrasive and not only penetrates the drug to the areas where the toothbrush is hard to reach, but also generates bubbles to increase the brushing feeling, helps 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. The most commonly used foaming agents are anionic surfactants such as sodium lauryl sulfate and sodium alkyl sulfate, and secondary nonionic surfactants are polyoxyethylene, polyoxypropylene, copolymers, polyoxyethylene sorbitan fatty acids, alkanolamide fatty acid esters, 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 alone or in combination of two or more kinds of anionic or nonionic surfactants.

In addition, flavors and sweeteners are used to control the hot or somewhat bitter taste. The fragrance is mainly used in the natural flavors peppermint and spearmint oil, and 0.1 to 1 weight in toothpaste. As the sweetener, synthetic or natural non-fermentable sugars are mainly used. Examples of the sweeteners include sodium saccharin, aspartame, lactose, maltose, xylitol, and the like. A suitable sweetener is preferably 0.05 to 1 weight of a saccharin sweetener. Do.

And as a buffer for adjusting the pH of the toothpaste composition may be used alkali metal salts of phosphate, especially sodium monophosphate, dibasic sodium phosphate, sodium triphosphate, phosphoric acid, hydrochloric acid, sodium hydroxide and sodium pyrophosphate and pyrophosphate. 0.01 to 0.5% by weight of paraoxybenzoic acid methyl, benzoic acid, sodium benzoate, salicylic acid or the like, which is generally licensed for food and medicine, to prevent contamination of microorganisms that may occur during the manufacture and use of toothpaste compositions. use.

The composition for promoting oral hygiene and inhibiting plaque formation, gingivitis, and periodontal disease of the present invention is generally applied using an appropriate amount of ingredients used in the product and using hydroxytyrosol as an active ingredient as an active ingredient. Let's do it.

The composition for promoting oral hygiene according to the present invention includes a toothpaste (oral detergent), an oral ointment or a mouthwash. Mouthwashes are liquid compositions for oral use, and containers and formulations are ferns and sprays.

Hereinafter, examples and experimental examples of compositions for improving oral hygiene and inhibiting trag formation, preventing and treating gingivitis and periodontal disease, which describe the present invention in detail.

(1) Experimental Example 1.

(1-1) Test subject group

(Unit: weight)

Experimental group Hydroxytyrosol Citric acid () One - 0.1 2 0.001 3 0.001 0.1 4 0.01 5 0.01 0.1 6 0.05 7 0.05 0.1 8 0.1 9 0.1 0.1 10 One 11 One 0.1 12 3 13 3 0.1 14 5 15 5 0.1

(1-2) The bactericidal effect of oral microorganisms of the present invention drug (experimental group 1 to 15).

Experiments include Actinomyces viscosus ATCC 15987 and Candida albicans ATCC 10231 and Streptococcus mutans ATCC 10449 and Actinobacillus Actinomycetactitans (Actinobacillu)

s actinomycetum comitans) ATCC 33384 and Porphyromonasgingi

valis) Five strains of ATCC 381 were used.

Actinomysis biscusus ATCC 15987 and Candida albicans ATCC 10231 were incubated in YM medium (glucose 10 g / L, yeast extract 3 g / L, malt extract 3 g / L, bactopeptone 5 g / L). Caucus mutans ATCC 10449 was incubated in TH medium (Todd Hewitt broth 30g / L, sucrose 50g / L), Actinobacillus actinomycetumcomitans ATCC 33384 and Porphyromonas gingivalis ATCC 381 are thioglycolate Incubated in Medium. The incubation temperature was incubated in an anaerobic incubator at 26 ° C by Actinomyces Viscosus ATCC 15987, 37 ° C for Candida albicans ATCC 10231 and Streptococcus mutans ATCC 10449, 37 ° C for Actinobacillus actinomycetumcomitans ATCC 33384 and Porphyromonas gingivalis ATCC 381. The cells were cultured in an anaerobic incubator.

The bactericidal test was carried out after subculture of these strains, three times in 24 hours pre-cultivation, and inoculated 1 × 10 ⁶ strains after adding 0.1 ml of the experimental drug to 9.9 ml of each appropriate experimental group. After incubation for 18 hours, the bacterial count was measured by colony count using agar dilution method.

<Experiment result>

Experimental group A.viscosus C.albicans S.mutans A.actinomycetum comitans P.gingivalis One 6 × 10 ⁸ 5 × 10 ⁹ 3 × 10 ⁹ 7 × 10 ⁷ 4 × 10 ⁷ 2 110 200 80 90 110 3 90 180 80 80 100 4 10 23 8 9 12 5 9 18 8 7 10 6 0 0 0 0 0 7 0 0 0 0 0 8 0 0 0 0 0 9 0 0 0 0 0 10 0 0 0 0 0 11 0 0 0 0 0 12 0 0 0 0 0 13 0 0 0 0 0 14 0 0 0 0 0 15 0 0 0 0 0

The antimicrobial effect of hydroxytyrosol In experimental results, the growth of microorganisms was suppressed in experimental groups 2 to 15, which indicates that the hydroxytyrosol oral microorganism has an excellent antimicrobial effect.

(1-3) Antimicrobial effect after 1 minute contact of the inventive agent (Experimental group 1 to 15)

0.1 ml of Streptococcus mutans ATCC 10449 bacterial suspension of 1.00 at 600 nm measured by spectrophotometer was added to 0.9 ml of the experimental group, contacted for 1 min, smeared on agar medium and emulsified for 48 hours at 37 ° C. Check the effectiveness of the bactericidal power.

<Experiment result>

Experimental group One 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Germ growth 0 X X X X X X X X X X X X X X

(Bacterial Growth: 0, Bacterial Death: X)

As a result of the sterilization test according to the one-minute contact time of the experimental group, the experimental group 1 showed no sterilizing effect, whereas the experimental groups 2 to 15 containing hydroxytyrosol had a strong sterilizing effect.

(1-4) Bactericidal Effect through Infiltration of Poloxamer Biofilm

First, in order to manufacture poloxamer biofilm, poloxamer F127 composed of di-block copolymer of polyethylene and polypropylene was dissolved in Todd Hewitt Broth medium, and 45.5ml of 30 solution was prepared. 1 ml of S. mutans 10449 culture, 2.5 ml of 50 sugar solution, 2 ml of 0.42,3,5-triphenyltetrazolium chloride (TTC) solution were mixed well and maintained at 4 ° C. for 3 hours and then placed in a 24-well plate. Harden by adding 0.5ml per well. In order to test the sterilization effect through biofilm permeation, 100 μl of a suitable concentration of test solution was added, and after 1 minute of treatment, the solution was removed and the growth of bacteria was observed after 48 hours of incubation.

<Experiment result>

Experimental group One 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Germ growth 0 X X X X X X X X X X X X X X

(Bacterial Growth: 0, Bacterial Death: X)

Results of the sterilization test through biofilm penetration according to the one minute contact time of the experimental group showed that the experimental group 1 had no sterilizing effect, whereas the experimental groups 2 to 15 containing hydroxytyrosol had a strong sterilizing effect through the biofilm penetration. appear.

(2) Experimental Example 2.

Experimental Example 1 using the toothpaste to which the experimental group was added to the plaque formation inhibitory effect and gingival inflammation inhibitory effect experiment was carried out. The manufacturing procedure of these toothpaste compositions is as follows.

Powder components such as sodium carboxymethyl cellulose, saccharin, and preservatives were dispersed in the sorbitol solution, which is a wet component, diluted with purified water, and then mixed in a mixer firstly, and then an abrasive and a medicament such as calcium hydrogen sulfide were added and mixed. . Finally, abrasives such as alkylsulphurium, which are foaming agents, and medicaments were added and mixed. And finally, the toothpaste composition was prepared by adding a foaming agent sodium sulfate, stabilizers, flavoring ingredients and mixing under vacuum.

The test method was to first select the subjects, explain the oral examination, and then divide the ten random subjects into each of the Examples and Comparative Examples, train the correct brushing method, and then perform the oral examination to perform the qualitative index (Quigley-Hein Index). modified by Turesky) and Gingival Bleeding Index (Loe-Silness Index). After the scaling of all the teeth in the experimental group, the control toothpaste was used for two weeks, followed by an oral examination. At this time, 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 the 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.

1) Test subject group

(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 Senruloose Sodium 1.00 1.00 1.00 1.00 1.00 1.00 - - - Carrageenan - - - - - - 0.90 0.90 0.90 Hydroxytyrosol - 0.001 0.01 0.05 0.1 0.5 One 3 5 Citric acid 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Sodium fluoride 0.22 0.22 0.22 Sodium monofluorophosphate 0.76 0.76 0.76 0.76 0.76 0.76 - - - By adding 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 1 Comparative Example 1 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 Hydroxytyrosol - - - Citric acid - - - Sodium fluoride 0.22 Sodium monofluorophosphate 0.76 0.76 By adding purified water 100.0 100.0 100.0

2) Experiment result

Plaque index

Experimental Toothpaste Group Initial value 3 months 6 months Example 1 1.73 2.54 2.89 Example 2 1.75 1.58 1.48 Example 3 1.73 1.63 1.02 Example 4 1.76 1.50 1.01 Example 5 1.71 1.57 1.02 Example 6 1.75 1.53 1.03 Example 7 1.78 1.53 1.00 Example 8 1.74 1.49 0.84 Example 9 1.77 1.45 0.75 Comparative Example 1 1.77 2.42 2.85 Comparative Example 2 1.74 2.23 2.93 Comparative Example 3 1.72 2.34 2.79

As a result of statistically significant difference test by measuring plaque index after using Examples 1 to 9 and Comparative Examples 1 to 3 for 6 months, it was confirmed that there was a significant effect in Examples 2 to 9 on the effect of inhibiting plaque formation. These results indicated that hydroxyl tyrosol was excellent in inhibiting plag formation in clinical trials.

2. Gingivitis Index

Experimental Toothpaste Group Initial value 3 months 6 months Example 1 1.43 1.36 2.24 Example 2 1.45 1.29 1.68 Example 3 1.47 1.31 1.07 Example 4 1.43 1.24 1.08 Example 5 1.45 1.23 0.98 Example 6 1.43 1.11 1.05 Example 7 1.46 1.22 1.03 Example 8 1.41 0.72 0.98 Example 9 1.42 0.73 1.02 Comparative Example 1 1.48 1.39 2.22 Comparative Example 2 1.48 1.36 2.24 Comparative Example 3 1.45 1.35 2.21

The results of statistically significant test by measuring the gingivitis index after using Examples 1 to 9 and Comparative Examples 1 to 3 for 6 months showed the most excellent effect in Examples 2 to 9 in the gingivitis mitigation effect. It was confirmed that there is a significant effect rather than 2,3, which indicates that hydroxyl tyrosol has an excellent effect on suppressing gingival inflammation.

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 Hydroxytyrosol 0.10 Citric acid 0.1 Sweetener 0.20 Spices 0.30 With purified water 100.0

Example 11. Mouthwash

(Unit: weight)

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

In Examples 10 to 11, the results were excellent in inhibiting plaque formation and reducing gingival inflammation.

The composition for promoting oral hygiene according to the present invention is not only excellent in the bactericidal effect against hydroxytyrosol, which is one of the Oliver oil components, which is a fundamental cause of tooth decay and periodontal disease, but also as a mother of progression of oral disease. It is a kind of bio film which is a kind of bio-film that has excellent penetration ability to prevent plaque formation, caries and periodontal disease effectively.

Claims (7)

Oral hygiene composition comprising a hydroxyl tyrosol as an active ingredient. The composition for enhancing oral hygiene according to claim 1, wherein the composition contains 0.001 to 3 wt% of hydroxyl tyrosol. The composition for enhancing oral hygiene according to claim 1, wherein the metal blocking agent contains 0.01 to 3 weights of tetrasodium pyrophosphate (TSPP) or citric acid. The composition for promoting oral hygiene according to any one of claims 1 to 3, wherein the composition for promoting oral hygiene is a toothpaste. The composition for promoting oral hygiene according to any one of claims 1 to 3, wherein the composition for improving oral hygiene is an oral ointment. The composition for promoting oral hygiene according to any one of claims 1 to 3, wherein the composition for promoting oral hygiene is an oral cleaning agent. 7. The composition for oral hygiene according to claim 6, wherein the mouthwash is a liquid composition for oral cavity, and the packaging container and formulation are fern and spray.