KR0179523B1 - Dentifrice composition for gingivitis curing - Google Patents

Abstract

The present invention relates to a dentifrice composition for treating gingivitis characterized by containing an extract of oriental and / or creation.

Description

[Title of the Invention]

Dentifrice composition containing oriental and creation extract for treating gingivitis

DETAILED DESCRIPTION OF THE INVENTION [

The present invention relates to a dentifrice composition containing a crude drug extract which inhibits the activity of collagenase enzyme which inhibits the production of prostaglandin (PGE ₂ ) for the treatment of gingivitis and decomposes collagen protein, which is a substrate of periodontal tissue.

Periodontal disease refers to the loss of teeth due to clinical gingival inflammation and hemorrhage, formation of periodontal pockets, and destruction of alveolar bone. The periodontal disease progresses to bacterial colony formation, bacterial periodontal tissue infiltration, and periodontal tissue destruction. First, saliva proteins in oral saliva are adsorbed on the dentin and cementum surfaces to form a film, As bacteria such as Streptococcus and Actinomyces grow, they form grags. As time goes by, these praes move in the apical direction and at the same time, Bacteriodes and Actinobacillus ), Such bacteria, germs, and bacterial products penetrate into the gingival connective tissue through the gingival epithelium, resulting in the formation of periodontal pockets. As a result of metabolism of these bacteria, toxic substances such as hydrogen sulfide, ammonia, And the cell wall component, lipopolysaccharide Collagen, which is a substrate of periodontal tissue, is degraded by enzymes such as collagen aids secreted from bacteria and leukocytes, resulting in gum recession, and at the same time stimulating the vital immune system to stimulate And various types of cytokines such as active oxygen released by extracellular secretion by various actions of the humoral and cellular immune system, Prostaglandins, Leukotriens, Histamine, Interleukins, (Cytokine) and causes gum inflammation and continue to prevent periodontal disease is progressing.

In order to prevent the development of periodontal disease, chlorhexidine gluconate, cetylpyridium chloride, sanguinarine and triacylglycerol, which can kill periodontal disease bacteria by short- Antibacterial agents such as Triclosan have been developed and applied to oral products such as toothpaste and toothpaste. However, the occurrence of gingival inflammation has not yet been fundamentally prevented.

Recently, efforts have been actively made to suppress gingival inflammation using herbal medicine extracts such as myrrh, epithelium bag, horse riding, green tea, licorice, gold, porcupineol, and gold europium in Korea. However, in the case of prostaglandins which play a crucial role in inducing gingivitis, And inhibit the activity of collagen AIDS that inhibits the formation of periodontal tissue. However, in most cases, plant extracts inhibiting the formation of plaque or inhibiting the formation of anti-bacterial, anti-inflammatory, astringent, hemostatic, It is the degree to prevent the occurrence of periodontal disease through the action of the same herbal medicine.

To date, the most widely used method for treating gingival inflammation has been to use a medicinal agent that inhibits the activity of collagen Azease, which degrades periodontal tissue, or inhibits the production of prostaglandin, a gingival inflammation-inducing substance.

U.S. Patent No. 52,308,895 A discloses that a periodontal disease-containing system capable of continuously delivering malodorous substances containing Tetracycline can be developed to treat periodontal disease by inhibiting the enzyme activity of collagenase that degrades periodontal tissue. EP 528468 A1 proposes that toothpastes and mouthwashes containing triclosan could be developed to inhibit the production of prostacyclin, a gingival inflammation inducing substance, to inhibit periodontal disease.

However, in the treatment of gingivitis, the pharmacological agent proposed in the prior patent does not have two functions of inhibiting the production of gingival inflammation-inducing substances and inhibiting the activity of periodontal enzymes, It is not only limited but it is a synthetic material, and there are many side effects when using it for a long time. In particular, tetracycline is usually administered 250 mg (1 tablet) four times a day and 1000 mg every day for 5 to 7 days. In general, it has been reported that tetracycline administration improves clinically and bacteriologically to a normal state, and it has been shown that tetracycline after day removal has a remarkably good effect. In a study of long-term low-dose studies, a daily dose of 1000 mg / day and 250 mg / day was administered once daily for 48 weeks. Clinically, the gingivitis was reduced, the migratory mucus was removed during the oral gingival recession, And the results are shown in Fig. However, when a low concentration of tetracycline is used over a long period of time, resistance to Gram-negative bacteria is frequently observed. These antibiotics are often present even when antibiotics are discontinued. Care should be taken when using antibiotics. Excessive vomiting, gastrointestinal pain, diarrhea, dental staining, and other complications are the limitations for pregnant women and children. .

Accordingly, the present inventors have found that, by using a scientific method such as a method for measuring the activity of collagen aids for decomposing periodontal tissues and a method for quantifying prostaglandins causing gingival inflammation, it is possible to inhibit the activity of collagen aids or inhibit the production of prostaglandins A dentifrice composition to which oriental and plant extracts are added to inhibit the production of gingival inflammation-inducing substances and inhibit the activity of periodontal enzymes is excellent in the treatment of gingival inflammation And the present invention has been completed.

The present invention relates to a dentifrice composition characterized by containing an extract of oriental and / or creation.

In the present invention, atractylodes japonica Koidzumi, a rootstock of Asterylodes japonica Koidzumi, distributed in China, China, Shanxi, etc., has an irregularly curved columnar shape of 3-10 cm in length and 10-25 mm in diameter, It is a dark tan. The cross section is almost circular and has thinning point by pale brown to reddish brown discharge. It is known to have pharmacological action such as dryness, diuretic, perspiration, sedation, hypoglycemic action, and tonic action. The main ingredients of the creation include Hinesol, β-Eudesmol, Elemol, Atractylodin and β-Selinene.

The fragrance used in the present invention is a resin obtained by scratching the cortex of Boswellia Carterii Birdwood and related plants (Olive and Bu-rseraceae), and is spherical or uneven in length of 5-30 mm. Outer surface is pale yellow- It has various colors such as yellowish white or red and gray. It has a white fine powder on its surface. It is translucent, has a smell of aroma, has a little taste, is mucinous, has pharmacological action, analgesic action and antituberculous action. have. The main ingredients of the frankincense include Boswellic acid, Olibanoresene, Boswelidinic acid, Pinene.

Hereinafter, a method for producing sulfur and herbal medicine extracts used in the present invention will be described. First, dried herbal medicines were shredded and powdered, and 500 g of 95% ethanol was added to 50 g of powder, followed by immersion extraction for 3 days. Then, the extract was filtered using No. 1 watt mann (No. 1) Lt; / RTI > According to the present invention, it is suitable to use sulfur and / or herbal medicine extracts in a dentifrice composition by mixing 0.01 to 10% by weight, preferably 0.1 to 5% by weight. When the content of the herbal extract is less than 0.01 wt%, the effect or effect on the gingival inflammation can not be expected. If the content is more than 10 wt%, the safety of the product is deteriorated.

The dentifrice composition according to the present invention may be prepared by mixing one or more kinds of abrasive components, for example, calcium monohydrogenphosphate, precipitated silica, silica gel, sodium bicarbonate, calcium carbonate, hydrated alumina, insoluble sodium metaphosphate, sodium pyrophosphate, Preferably 1-90% by weight, and preferably 20-60% by weight of potassium monohydrogenphosphate, hydrated silica and calcium carbonate, alone or in combination.

The dentifrice composition according to the present invention uses a fluorine compound as a medicinal agent for enhancing re-calcification of a tooth to strengthen the tissue of a tooth. As the fluorine compound, sodium fluoride and sodium monofluorophosphate are used singly or in combination, and the content thereof is suitably from 0.01 to 2.0% by weight. When the content of the fluorine compound is 0.01 wt% or less, the effect is not sufficient. When the content is more than 2.0 wt%, the safety of the human body may be adversely affected.

Wetting agents are used to maintain the condition of the dentifrice composition and prevent drying. Examples of such a wetting agent include glycerin, sorbitol solution, polyethylene glycol and propylene glycol, and they are used alone or as a mixture of two or more thereof in an amount of 20 to 60% by weight. In addition, a binding agent is used to combine the liquid and the solid component in the toothpaste ingredient to maintain the toothpaste shape and secure the stability. As the binder, a natural or synthetic high molecular substance such as sodium cargate or calcium salt, carboxymethyl cellulose sodium, xanthan gum, acacia gum and the like is used, and its content is 0.1-5 wt%. The foaming agent complements the cleaning action of the abrasive. It also penetrates the hard to reach areas where the toothbrush is hard to reach. It also acts to increase the brushing sensation by generating bubbles. It also helps the cleaning action and accelerates the dispersion and penetration of the active ingredient By reducing the interfacial tension, the foreign substance in the oral cavity easily falls. As the foam agent mainly used, anionic surfactants such as sodium lauryl sulfate and sodium alkylsulfate are used, and also nonionic surfactants such as polyoxyethylene, polyoxypropylene, copolymer, polyoxyethylene hardened castor oil, polyoxyethylene sorbitan fatty acid, Alkanolamide fatty acid esters, sucrose fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene fatty acid esters and polyoxyethylene castor oil hardened oil derivatives. The amount of the foaming agent used is preferably 0.5 to 5% by weight of an anionic or nonionic surfactant alone or in combination of two or more thereof.

In addition, spices and sweeteners are used to control bitterness or rather bitter taste. Peppermint and spearmint oil, which are natural fragrances, are mainly used as the fragrance, and 0.1 to 1 wt% of the fragrance is used in the toothpaste. Examples of the sweetener include synthetic or natural non-inactivating sugar, and typical examples thereof include sodium saccharin, aspartame, lactose, maltose, and xylitol. As a suitable sweetener, 0.05 to 1% by weight of a saccharin sweetener or the like is preferably used Do. And buffering agents for adjusting the pH of the dentifrice composition include alkali metal phosphate salts, in particular sodium primary phosphate, sodium secondary phosphate, sodium tertiary phosphate, citric acid and sodium citrate, phosphoric acid, sodium hydroxide, sodium pyrophosphate and pyrophosphate . However, the buffer used in the dentifrice composition according to the present invention is adjusted by adjusting pH to 5 to 8.0 by appropriately mixing two kinds of sodium phosphate, sodium phosphate dibasic and sodium phosphate dibasic. In order to prevent the contamination of microorganisms that may occur during the production and use of the dentifrice composition, 0.01-0.5 wt% of methylhydroxybenzoate, benzoic acid, benzoic sodium, salicylic acid and the like, which are generally allowed to be used in foods and medicines, use.

Hereinafter, the dentifrice composition of the present invention will be described with reference to examples, but the technical scope of the present invention is not limited thereto.

[Implementation and Comparative Example]

A dentifrice composition was prepared according to a conventional method with the composition ratios shown in Tables 1 to 5 below.

[Experimental Example 1: Inhibitory effect on collagen AIDS which is a decomposition factor of periodontal tissue of the toothpaste of the present invention (Examples 1 to 10)] [

The inhibitory effect on collagen AIDS, which is a decomposition factor of periodontal tissue, was tested as follows with the toothpaste of the present invention.

This test was performed to evaluate the effects of periodontal disease in the saliva and gingival crevicular fluid of patients with periodontal disease secreted from Bacteriodes gingivalis, polymorphonuclear leukocytes and neutrophils, Collagen is an experimental method that imitates the oral environment of the gingival recession caused by decomposition of collagen which is the substrate of periodontal tissue by the action of AIDS enzyme.

Add 100 μl of Azocoll solution, which is a 2% red collagen matrix, to each of 25 25 ml Eppendorf tubes. One Eppendorf tube is used as a blank and three tubes are purchased from Sigma. One collagen AIDS I standard enzyme solution (collagen decomposition activity: 315 unit / mg) was added at 10, 100, and 200 ppm. Sephacryl S- (100 μl of collagen Azease purified through 200 Chromatography), another tube was used as a control group, and each of the remaining tubes was filled with an experimental toothpaste (Examples 1 to 10) and a comparative group toothpaste (Comparative Examples 1 to 10) (0.05M Tris-HCl, 1 nM CaCl, pH 7.8) was added to the reaction solution in a total reaction volume of 500 (500 rpm) for 10 minutes. Added in μL The reaction was carried out at 37 ° C for 18 hours, and the Eppendorf tube was centrifuged at 10000 g for 5 minutes to precipitate undissociated collagen. The supernatant containing the degraded collagen was taken and absorbance was measured at 540 nm to prepare a standard activity curve The enzyme activity in the experimental group and the control group was evaluated by comparing the enzyme activity from the standard curve.

From the above test results, Examples 2 and 7 containing 0.01% of the production showed inhibition of the activity of the collagen Azease enzyme by 40%, while Examples 4 and 8 containing the production rate of 0.1% inhibited enzyme activity by 70% Examples 6 and 9 containing 1% of the production showed inhibition of enzyme activity by 90%, and Example 10 containing 5% showed inhibition of enzyme activity by 100%, indicating that only collagenase Lt; RTI ID = 0.0 > enzymatic activity. ≪ / RTI >

[Experimental Example ₂ : Inhibitory effect on the production of prostaglandin (PG ₂ ) in toothpastes of the present invention (Examples 1 to 10)] [

The inhibitory effect on the production of prostaglandin, which is a gingival inflammation inducing substance, with the toothpaste of the present invention was carried out as follows.

This study was conducted to investigate the effects of prostaglandin (PGE ₂ ) induced by gingival fibroblasts on lipopolysaccharide, a cell wall component of Bacteria gingivalis, The preparation was completely homogenized by mixing the test toothpaste (Examples 1 to 10) and the comparative group of toothpastes (Comparative Examples 1 to 10) with distilled water at a ratio of 1: 2 by immunoassay of antigen-antibody, centrifuging at 5000 g for 10 minutes After the supernatant was treated, the inhibitory effect was compared and evaluated.

Specific test methods were as follows: 50 μl buffer (0.9% NaCl, 0.1% bovine serum albumin, 0.5% Kathon) was added to a blank well of a 96-well plate to which 1 g of anti- 50 μL of standard solution was added to the standard (0, 2.5, 5, 10, 20, 40, 80, 160, 320 pg) wells and the test toothpaste 1 to 10) and a comparative group of dentifrices (Comparative Examples 1 to 10) were added to the wells set in the Examples and Comparative Examples, and 50 μl of the antibody against PGE ₂ was added to all wells except blank wells the washing buffer (0.05% tween 20, then covering the freight held for one hour at 25 ℃ - 50㎕ of PGE ₂ conjugate (conjugate) peroxidase (peroxidase) was added to all wells except for the blank well and 96-well (PH7.5) and incubated at room temperature with 150 [mu] l of enzyme substrate (dissolved in 20% dimethylformamide 3, 3 ', 5, 5'-tetramethylbenzidine / hydrogen peroxide) was immediately added thereto, kept at 25 ° C. for 30 minutes, added with 100 μl of 1 M sulfuric acid, and then absorbance was measured at 450 nm with a microplate reader. The absorbance value (T) of the blank was divided by the absorbance value (B) of the blank, and then multiplied by 100, and expressed as a% value, and the following results were obtained.

From the above test results, Examples 1 and 7 containing 0.01% scent showed inhibition of PGE ₂ formation by 35% and 36%, and Examples 3 and 8 containing scent 0.1% inhibited PGE ₂ formation by 52% And Examples 5 and 9 containing 1% frankincense showed 67% and 69% inhibition of PGE ₂ production, and Example 10 containing 5% showed complete inhibition of PGE ₂ production, Which is an effective inhibitor of PGE ₂ production.

EXPERIMENTAL EXAMPLE 3 Clinical Experiments on the Efficacy and Effect of the Toothpaste of the Invention (Examples 1 to 10)

Clinical experiments for treating gingival inflammation with the toothpaste of the present invention were conducted as follows.

Subjects were divided into 10 groups of 30 to 50 years of age. The subjects were divided into 30 groups according to their gender, and 120 subjects were selected. Clinical experiments on the therapeutic effect of gingival inflammation of experimental toothpastes (Examples 1 to 10) containing divided frankincense or creation and comparative group toothpastes containing no frankincense or creation (Comparative Examples 1 to 10) were carried out by the following method Respectively.

After dividing the experimental group into the experimental group and the comparative group, oral health education and correct brushing method were taught, and the same control toothbrush was supplied to all the experimental groups and the initial gingival index was scored by performing the dental surface treatment, The gingivitis index was examined by oral examination after 1 week, 1 month, 3 months and 6 months. The gingival index was measured by inserting a peridental probe into the gingival station After 30 seconds of continuous probe around each tooth without applying force, the bleeding state was measured and the score was recorded by the following method.

As a result of the above clinical tests, the gingival inflammation treatment effect of the toothpaste according to the present invention, which inhibits the production of prostaglandin which induces gingival inflammation and inhibits the enzyme activity of collagenase which decomposes periodontal tissue, The efficacy was superior to those of Comparative Examples 1 to 10, which did not contain frankincense or creation until 6 months, and the gingivitis index of the comparative example was continuously increased over time after one month, Using the developed toothpaste, the occurrence of gingival inflammation was suppressed and the gingival index was maintained constant over time.

Claims (4)

Dentifrice composition characterized by containing an extract of oriental and / or oriental The dentifrice composition according to claim 1, which comprises 0.01 to 10% by weight of oriental and / or extractive extracts The dentifrice composition according to claim 1 or 2, further comprising 20 to 60% by weight of calcium hydrogenphosphate, precipitated silica and calcium carbonate as an abrasive. 3. The dentifrice composition according to claim 1 or 2, further comprising 0.01 to 2% by weight of sodium fluoride or sodium monofluorophosphate as a fluorine compound.