KR19980013946A - Oral composition of liquid type - Google Patents

Abstract

The present invention relates to an oral liquid composition which is characterized by containing grapefruit seed extract as an active ingredient and exhibits excellent periodontal disease prevention and treatment, tooth decay prevention and bad breath removal effect.

Description

Oral Liquid Composition

The present invention is characterized by containing grapefruit seed extract as an active ingredient, and relates to an oral liquid composition showing excellent effects in prevention and treatment of periodontal disease, prevention of tooth decay, and removal of bad breath.

Various oral diseases that may occur in the oral tissues are caused by plaques and numerous bacteria in the oral cavity. Clinical and pathological importance thereof has already been widely recognized and studied.

The plaque is a sticky film adhered to the surface of the teeth. It is composed of a dental bacterial membrane in which the oral bacteria are trapped in a network of glucose polymer dextran. When left without being removed, Lt; / RTI >

Dextran in the plaque is present in the strap Sat Lactococcus bonded to the mutans cell membrane or which by the enzyme glucosyl transferase raised secreted outside the cells of sugar in the diet at the same time, decomposed and synthesized into glucose and fructose and α ^1-3 Oral As a glucose polymer of? ^1-6 bond, it has sticky properties and is attached to the teeth. In the dextran thus produced, Streptococcus mythans continue to multiply and produce pyruvic acid through the action of glucose as a substrate. The resulting pyruvic acid is converted to lactic acid by lactate dehydrogenase and released to the outside of the cell to lower the pH in the plaque to an acidity of about 4.0 to 4.5, thereby dissociating hydroxyapatite, which is a component of the tooth, into phosphoric acid and calcium components And the tooth decay process.

In addition, the acidic environment in the plaque promotes the proliferation of periodontal disease bacteria, causing inflammation of the gums, and continues to develop into periodontal disease. Periodontal disease refers to the loss of teeth caused by gingivitis and hemorrhage, the formation of periodontal pockets, and the destruction of alveolar bone. These periodontal diseases are caused by bacterial colonization, bacterial perforation, and periodontal destruction Lt; / RTI > That is, the saliva protein in the saliva in the oral cavity is adsorbed on the dentin and cementum surfaces to form a coating, and bacteria such as streptococcus and actinomycetes grow on the surface of the coating to form a plaque. As time passes, the formed plaque migrates in the apical direction, and at the same time, anaerobic gram-negative bacteria such as bacteria and actinobacillus grow, and these bacteria, bacterial components, and bacterial products penetrate into the connective tissue through the gingival epithelium A periodontal pouch is formed. As a result of the metabolism of these bacteria, cytotoxins such as ammonia hydrogen sulfide and toxic amine are secreted into the periodontal tissue, and the upright tissue is destroyed by the toxin such as lipopolysaccharide which constitutes the cell wall or the cola secreted from bacteria and white blood cells The collagen of the periodontal tissue is decomposed by the enzymes such as genetics and the gingival recession occurs. At the same time, the active immunity of the extracellularly released active oxygen, prostaglandin, and luciferase by various actions of the humoral and cellular immune system stimulated by the bio- Cortriene, histamine, etc., causes periodontal disease.

On the other hand, bad breath is generally caused by acquired systemic disease, and protein and food residues in saliva are decomposed by microorganisms in the oral cavity, and the resulting amino acids are decomposed by demineralization enzymes and amino enzymes, It may also appear by producing a substance. As the bad breath inducing substance, volatile sulfides such as hydrogen sulfide and methyl mercaptan can be mentioned. In addition, aldehyde, fatty acid, ammonia, amines, pyridine and the like can be mentioned.

In ancient times, ancient Chinese used various herbal medicines for the prevention or treatment of oral diseases. Especially ancient Chinese used Inhin Tong, a medicinal herb for gingival inflammation and gingival bleeding, The Enishi used honey and the like. In the Middle Ages, opium and rose oil were used. In the 14th and 15th centuries, white wine and roasted salt were used. On the Asian side, Chinese medicine was used to prevent or treat various oral diseases.

As an effort to prevent periodontal diseases and tooth decay and halitosis, antibacterial agents such as chlorohexidine, quaternary ammonium compounds such as cetylpyridinium chloride, triclosan, and xanthine, which can sterilize bacteria present in the oral cavity, Antibiotics such as penicillin, enzyme inhibitors such as fluoride compounds such as sodium fluoride and sodium monofluorophosphate and dextranase which inhibit the demineralization of teeth or accelerate remineralization to prevent the occurrence of cavities have been used variously, Similarly, herbal medicine extracts have been studied in various ways and applied to products.

For example, in Japanese Patent Laid-Open No. 55-120,509, herbal medicine extracts such as bone cucumber, mulberry leaf, oilseed oil, lotus root, and lavender are used. In Japanese Patent Publications 57-5641 and 57-85319, 87-268613 and 60-75418 in Japanese Patent Application No. 60-75418 in order to obtain a bacteriostatic effect in the oral cavity by blending sage or rosemary.

However, all of the ingredients used in the above-described prior arts have a problem that the continuous oral antimicrobial inhibitory effect is so weak that the effect of prevention and treatment of periodontal disease, prevention of tooth decay and removal of bad breath is weak and the usability is poor when applied to a product have.

Accordingly, the present inventors have carried out numerous studies and experiments to solve the above-mentioned conventional problems, and as a result, they have found that not only the inactivating agent of the gonococci, the causative agent of periodontitis, but also the germicidal effect against the cavities are excellent, Has been used as an active ingredient of an oral composition, it has been found that it exhibits excellent effects in inhibiting bacteria in the oral cavity, preventing periodontal disease, preventing tooth decay, and removing bad breath. Hereinafter, the configuration of the present invention will be described in detail.

The present invention relates to an oral composition characterized by containing grapefruit seed extract as an active ingredient.

The grapefruit seed extract contains natural ascorbic acid, naringin, and tocopherol in a large amount and has excellent antimicrobial and antioxidant properties. It is a natural extract that inhibits the production of toxic and degenerated products. When it is absorbed into the body, It is safe for human body without any risk of toxicity due to accumulation in the body.

In particular, ascorbic acid, which accounts for 45% of the grapefruit seed extract, forms a hydrogen radical as a reducing agent of metal ions, which inhibits the enzymatic activity distributed in the cell membrane and weakens the cell membrane function, thereby inhibiting the cell respiration of the microorganism. It acts to suppress normal growth. In other words, the use of grapefruit seed extract can inhibit microbial sterilization by inhibiting cell membrane weakness and cell respiration.

The antioxidant is an active oxidative radical that is involved in the chain reaction in the maintenance process or in the active radicals that participate in the formation of the hydro-paroxyside, While at the same time it is antioxidant by its action mechanism which is stabilized by resonance, that is, it is converted into a low activity radical. The mechanism of action of these antioxidants is represented by the reaction scheme as follows.

The major antimicrobial substances contained in grapefruit seed extract are naringin and citral. Naringin is a component of flavonoids known as vitamin P, which is present in many of the ripe grapefruit seeds and shells. Naringen has a bitter taste, and its molecular formula can be represented by C ₂₇ H ₃₂ O ₁₄ .2H ₂ O, and its chemical structure is shown in the following chemical formula 1.

Citral is present in many citrus fruits and exists naturally as two isomers of geranial (citral a) and neral (citral b) of structure (a) below.

The grapefruit seed extract used as an active ingredient in the oral composition according to the present invention may be those prepared by a conventional method known in the art to which the present invention belongs. Preferably, grapefruit pulp is removed and the separated seeds are collected Dried, and then pulverized and extracted with glycerol as a solvent (for example, DF-100, purchased from the Korea Microorganism Research Institute, Inc.) for 6 to 8 hours at 121 ° C. The composition of the present invention contains 0.005 to 1.0% by weight, preferably 0.01 to 0.5% by weight of the grapefruit seed extract as described above. When the content of the grapefruit seed extract is less than 0.005% by weight, sufficient effect can not be expected. It is very difficult to apply the composition to a product because of its inherent odor and taste, which gives a displeasure such as a strong taste when used, and in particular, when it is applied to a liquid composition, there is a problem that the component is precipitated due to its preparation characteristics.

Meanwhile, the oral composition according to the present invention may further exhibit a better effect by containing the green tea extract in addition to the grapefruit seed extract. The green tea extract may be one prepared by a conventional method known in the art to which the present invention belongs have. Preferably, 4 to 30 parts of ethanol and purified water are added to 1 part of the oil fraction of the dry distillate obtained by vacuum distillation of green tea leaves under the conditions of 150 to 250 DEG C and 20 to 40 mmHg to prepare a solution state .

The green tea extract is a natural compound mainly containing tannin and polyphenol derivatives. In the Japanese Society of Textile Engineers (Vol.40, No.3, 1987), polyphenol derivatives of three-dimensional structure present in green tea extract, It is described that the odor is removed by covering the molecule or atom which is represented. Green tea extract mainly contains components such as caffeine, organic acid, amino acid, (+) - catechin and saccharides. Among these components, (+) - catechin having a three- Which is the most common cause of halitosis.

In addition, the green tea extract has an excellent anti-inflammatory and antibacterial activity, has an excellent cell protection action, has an excellent anti-aging effect on the skin, has an anti-cancer effect and anti-mutagenic effect on animal cancer cells and has an angiotensin- Inhibits platelet aggregation, and acts to lower blood pressure by relaxing platelets. In addition, there is an effect of inhibiting arteriosclerosis by decreasing the concentration of blood cholesterol.

In the present invention, when the green tea extract is used together with the grapefruit seed extract, the content of the green tea extract is in the range of 0.01 to 5.0% by weight, preferably 0.05 to 1.0% by weight based on the whole composition. The use of less than 0.01% by weight or more than 5.0% by weight may cause the same problems as in the grapefruit seed extract. The mixing ratio of the grapefruit seed extract and the green tea extract is preferably 1: 5 to 1: 100 in terms of the weight ratio, and the effect can not be expected if it is used in other ranges.

In addition, the oral composition of the present invention can be used as an adjuvant for the prevention of cavities such as sodium fluoride, sodium fluorophosphate, fluoride amine, tin fluoride and xylitol, bactericides such as chlorhexidine, cetylpyridium chloride and triclosan, An antiinflammatory agent such as anthraquinone, aminocaproic acid, tranexamic acid, and tocopherol acetate, dextrinase, an antioxidant, an antioxidant, an antioxidant, an antioxidant, an antioxidant, an antioxidant, , Enzymes such as glucose oxidase, glucoamylase,?,? -Amylase, lactoperoxidase, lysozyme, and the like.

Hereinafter, the composition of each composition of the present invention will be described in more detail.

The oral liquid composition, for example a saliva solution or a spray, according to the present invention is prepared using ingredients as described below in addition to the above-mentioned active ingredient and adjuvant active substance. At this time, as essential ingredients, ethanol, wetting agent, surfactant, sweetening agent, refreshing agent, perfume can be mentioned.

The oral liquid composition is usually prepared by mixing two phases, which can be divided into an alcohol portion and a purified water portion, in which various components are respectively dissolved in a dissolvable portion. Ethanol is used in the alcohol part to dissipate flavors and preservatives that give a cooling sensation when the product is used and does not dissolve in water. Generally, the higher the ethanol content, the better the emulsifying power of the perfume. And stimulates the oral mucous membrane, it is used in the range of 5 to 50.0% by weight, preferably 8.0 to 40% by weight.

A wetting agent is used to give stability and sweetness and a little viscosity of the product, and examples thereof include glycerin, sorbitol, amorphous sorbitol, propylene glycol and the like. Of these, glycerin or amorphous sorbitol is preferred. The amount of the wetting agent to be used is generally from 3.0 to 40.0% by weight, preferably from 5 to 25% by weight.

The surfactant is used as a solubilizing agent for solubilizing a perfume or the like in water, and usually a polyoxyethylene polyoxypropylene copolymerized polymer, polyoxyethylene hydrogenated castor oil, high alkyl acetates and polyoxyethylene derivatives of sorbitan fatty acid esters are used , Preferably polyoxyethylene hydrogenated castor oil or polyoxyethylene polyoxypropylene copolymerized polymer is used. The amount is 0.1 to 5.0% by weight, preferably 0.5 to 3.0% by weight.

In addition, fragrances and sweeteners are used to improve the feeling of use. Examples of the fragrance include a fragrance oil, a menthol, a spearmint oil, a carban, an anise oil, an anthole, an eucalyptus oil, an eucalyptol (1 0.01 to 4.0% by weight, preferably 0.1 to 2.0% by weight, of at least one material selected from among clove oil, eugenol, wintergreen oil, methyl salicylate, cinnamon oil and cinnamic aldehyde %. As the sweetening agent, lactose, sorbitol, aspartame, xylitol, sodium saccharin and the like can be used. In general, 0.001 to 0.3% by weight of sodium saccharin is used.

A cooling agent is used for improving the feeling of exhilaration and persistence. As the refreshing agent, 0.01 to 10.0% by weight of at least one substance selected from the group consisting of mentyllactate, menthyl glycol carbonate, menthyl propylene glycol carbonate, and menthone glycerol acetal is used .

In addition, the oral liquid composition according to the present invention may further contain a preservative, a buffer, a pigment, and the like. As a double preservative, 0.001 to 0.1% by weight of at least one substance selected from benzoic acid and sodium benzoate is used. As the buffer for adjusting the pH of the oral liquid composition, sodium phosphate monobasic, Sodium citrate, sodium citrate, tartaric acid and sodium tartrate, boric acid, phosphoric acid, hydrochloric acid, sodium hydroxide and the like are preferably used, but preferably one or more kinds of sodium phosphate and sodium phosphate are used in combination. In addition, pigments can also be used to enhance the commercial value of the oral liquid composition and to meet the intended use, and food colors are mainly used.

Meanwhile, when the dentifrice composition according to the present invention is manufactured, in addition to the above-mentioned active ingredient and auxiliary active ingredient, conventional ingredients constituting toothpaste such as abrasives, wetting agents, binders, foaming agents, sweeteners, preservatives, Lt; / RTI >

The abrasive may be calcium carbonate, calcium monohydrogenphosphate, precipitated silica, hydrated alumina. Silica gel, insoluble sodium metaphosphate and zirconium silicate is used in an amount of 20 to 70% by weight, preferably 35 to 55% by weight, based on the whole composition.

As the wetting agent, 20 to 60% by weight, preferably 20 to 50% by weight, of at least one substance selected from glycerin, sorbitol, amorphous sorbitol and polyethylene glycol is used.

As the binding agent, 0.1 to 3.0% by weight, preferably 0.5 to 2.0% by weight, of at least one substance selected from carrageenan, xanthan gum, carboxymethylcellulose sodium, carboxyvinyl polymer and sodium alginate is used.

Examples of the foaming agent include anionic surfactants such as sodium lauryl sulfate and sodium lauroyl sarcosinate, and nonionic surfactants such as sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, and polyoxyethylene polyoxypropylene copolymers. 0.5 to 5.0% by weight, preferably 0.5 to 2.5% by weight, of the material is used.

As a sweetening agent, 0.05 to 0.5% by weight of at least one substance selected from the group consisting of sodium saccharin, aspartame, acesulfame, stevioside and licorice acid is used. As the preservative, at least one selected from the group consisting of paraoxybenzoic acid ester, benzoic acid and sodium benzoate 0.05 to 0.25 wt% of the material is used.

As the pH adjusting agent, 0.02 to 1.5% by weight of at least one substance selected from phosphoric acid, sodium phosphate, citric acid, sodium citrate, succinic acid, sodium succinate, tartaric acid and sodium tartrate is used.

Examples of the flavor include flavoring agents used in ordinary toothpaste and substances used as food flavoring agents such as peppermint oil, menthol, spearmint oil, carbohydrate, anise oil, anitol, eucalyptus oil, 0.1 to 2.0% by weight of at least one substance selected from the group consisting of Lipitor (1,8-cineol), clove oil, eugenol, wintergreen oil, methyl salicylate, cinnamon oil, cinnamic aldehyde, By weight, preferably 0.5 to 1.5% by weight.

In addition, calcium glycerophosphate is used in an amount of 0.05 to 3.0% by weight, preferably 0.05 to 2.0% by weight, which is excellent in the remineralization effect in dentifrices, and has a disinfection and sterilization effect by a high osmotic action and suppresses edema and hemorrhage Sodium chloride may also be used. The cooling agent may be used in an amount of 0.01 to 10.0% by weight of at least one selected from the group consisting of mentyllactate, menthyl glycol carbonate, menthyl propylene glycol carbonate, and menthone glycerin acetal as refreshing agents. do.

Hereinafter, the present invention will be described more specifically based on the following examples and experimental examples. However, these examples are provided only for the understanding of the present invention, and the scope of the present invention is not limited to these examples in any sense.

Examples 1-14 and Comparative Example 1-3: Oral liquid composition

Oral liquid compositions having the compositions shown in Table 1 were prepared in a conventional manner.

Component composition ethanol Polyoxyethylene hardened castor oil Concentrated glycerin Benzoic acid Sodium saccharin Combination fragrance Sodium phosphate monobasic Grapefruit seed extract Green tea extract Purified water is added Example 1 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.005 - 100.0 2 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.010 - 100.0 3 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.050 - 100.0 4 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.100 - 100.0 5 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.500 - 100.0 6 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.010 0.100 100.0 7 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.050 0.100 100.0 8 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.100 0.100 100.0 9 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.010 0.500 100.0 10 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.050 0.500 100.0 11 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.100 0.500 100.0 12 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.010 1,000 100.0 13 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.050 1,000 100.0 14 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.100 1,000 100.0 Comparative Example 1 10.00 1.00 8.00 0.10 0.01 0.10 0.01 - - 100.0 2 10.00 1.00 8.00 0.10 0.01 0.10 0.01 0.001 - 100.0 3 10.00 1.00 8.00 0.10 0.01 0.10 0.01 1.100 - 100.0

Examples 15-28 and Comparative Example 4-6: Toothpaste composition

A dentifrice composition having the composition shown in Table 2 below was prepared according to a conventional method.

Component composition Calcium carbonate Sorbitol solution Sodium alkyl sulfate Carboxymethylcellulose Sodium saccharin Paraoxybenzoic acid ester Combination fragrance Grapefruit seed extract Green tea extract Purified water is added Example 15 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.005 - 100.0 16 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.010 - 100.0 17 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.050 - 100.0 18 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.100 - 100.0 19 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.500 - 100.0 20 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.010 0.100 100.0 21 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.050 0.100 100.0 22 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.100 0.100 100.0 23 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.010 0.500 100.0 24 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.050 0.500 100.0 25 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.100 0.500 100.0 26 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.010 1,000 100.0 27 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.050 1,000 100.0 28 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.100 1,000 100.0 Comparative Example 4 40.00 25.0 2.00 1.00 0.10 0.10 1.00 - - 100.0 5 40.00 25.0 2.00 1.00 0.10 0.10 1.00 0.001 - 100.0 6 40.00 25.0 2.00 1.00 0.10 0.10 1.00 1.100 - 100.0

Experimental Example 1: Inhibition of plaque formation and organic acid production

The effect of the oral liquid composition according to the present invention on plaque formation and organic acid production inhibition was examined as follows.

This test method was developed based on the fact that plaque and organic acid produced by Streptococcus mutans, which is a causative organism of tooth decay, play the most important role in the progress of tooth decay and periodontal disease.

First, Streptococcus mutans 10449 was subcultured on a Brain Heart Infusion agar medium and inoculated with platinum nodal Todd Hewitt Broth and cultured at 37 ° C for one day. A glass rod having a diameter of 2 mm and a length of 70 mm was prepared and sterilized at 180 ° C for 2 hours, and the weight of the first glass rod was measured to five decimal places. The glass rod was placed in a test tube containing 10 ml of THB medium containing 1% by weight of sugar solution, 1 ml of the composition of Comparative Examples 1 to 3 and Examples 1 to 14 was added, and Streptococcus mutans 10449 was added to 100 Mu] L and incubated at 37 [deg.] C for 24 hours. The glass rod was taken out and dried at 37 캜 for one day, and its final weight was measured. The control group was a group to which the test solution was not added, and the degree of plaque formation was calculated by the following formula (1).

Experimental group (final glass rod weight - initial glass rod weight)

Unit: prag Formation (%) = ----------------------------------- x 100

Control (final glass rod weight - initial glass rod weight)

The degree of organic acid production was determined by measuring the pH of the cultured medium using a pH meter.

Meanwhile, the effect of inhibiting the formation of plaque and organic acid production of the dentifrice composition according to the present invention was also investigated in the same manner as described above. However, the compositions of Examples 15 to 28 and Comparative Examples 4 to 6 could not be used immediately, 1: 2 (composition: distilled water), and the mixture was thoroughly homogenized. After centrifugation at 1000 g for 10 minutes, 1 ml of the supernatant was used. Experimental results for each composition are shown in Tables 3 and 4 below.

Experimental group Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Example 9 Example 10 Example 11 Example 12 Example 13 Example 14 Comparative Example 1 Comparative Example 2 Comparative Example 3 Plaque 50 0 0 0 0 0 0 0 0 0 0 0 0 0 100 100 0 pH 5.5 7.5 7.4 7.5 7.6 7.4 7.5 7.5 7.6 7.5 7.5 7.6 7.6 7.5 4.1 4.3 7.6

Experimental group Example 15 Example 16 Example 17 Example 18 Example 19 Example 20 Example 21 Example 22 Example 23 Example 24 Example 25 Example 26 Example 27 Example 28 Comparative Example 4 Comparative Example 5 Comparative Example 6 Plaque 50 0 0 0 0 0 0 0 0 0 0 0 0 0 100 100 0 pH 5.3 7.5 7.4 7.6 7.5 7.3 7.4 7.4 7.5 7.4 7.4 7.5 7.5 7.6 4.2 4.1 7.4

As can be seen from the results of Tables 3 and 4, the compositions of Comparative Examples 1 and 4, which contain no grapefruit seed extract at all, and the compositions of Comparative Examples 2 and 5, which contain 0.001% by weight of the composition, And the compositions of Comparative Examples 3 and 6 containing 1.1 weight% of the grapefruit seed extract showed the maximum inhibitory effect on the formation of plaque and organic acid production. On the other hand, the compositions of Examples 1 and 15 containing 0.005% by weight of the grapefruit seed extract showed a 50% inhibition of plaque formation, whereas the compositions of Examples 2 to 14 and 16 to 28 containing 0.01% And it was confirmed that the grapefruit seed extract showed excellent effect on the formation of plaque and inhibition of organic acid production.

Experimental Example 2: Inhibitory effect on collagenase, periodontal ligase

The compositions of Examples 1 to 14 and Comparative Examples 1 to 3 were tested as follows to investigate the inhibitory effect on collagenase, a periodontal tissue degrading enzyme.

This study was conducted to investigate the effects of periodontal disease on the periodontal disease caused by periodontal disease (Bacteriods gingivalis), polymorphonuclear leukocytes and neutrophils. This is an experimental method in which the collagen of the periodontal tissue is decomposed by the action of the collagenase enzyme and the gingival recession occurs.

100 μl of a 2% red collagen substrate Azocoll solution was added to each of 25 25 ml Eppendorf tubes, one Eppendorf tube was used as a blank, The collagenase type I standard enzyme solution (collagen decomposition activity: 315 units / mg) was added at 10, 100 and 200 ppm. 100 μl of purely isolated collagenase enzyme was added to each of the remaining tubes through Sephacryl S-200 chromatography from saliva and gingival crevicular fluid of periodontal disease patients. One tube was used as a control group, and the remaining tubes (0.05 M Tris-HCl, 1 nM CaCl ₂ , pH 7.8) was added to 500 μl of the total reaction solution, and the mixture was incubated at 37 ° C in a thermostat Lt; / RTI > for 18 hours. The eppendorf tube was centrifuged at 10000 g for 5 minutes to precipitate the undegraded collagen and the supernatant containing the degraded collagen was taken and absorbance was measured at 540 nm to prepare a standard activity curve and the enzyme activity concentration from the standard curve The enzyme activities of the experimental group and the control group were compared and evaluated.

On the other hand, the compositions of Examples 15 to 28 and Comparative Examples 4 to 6 were also examined for the inhibitory effect on collagenase in the same manner as described above. However, in the case of the toothpaste formulation, Examples 15 to 28 and Comparative Examples 4 to 6 (Composition: distilled water). The mixture was completely homogenized and centrifuged at 1000 g for 10 minutes, and 100 μl of the supernatant was used. Experimental results for each composition are shown in Tables 5 and 6 below.

Experimental group Absorbance Enzyme Activity (%) Example 1 0.155 93.74 Example 2 0.157 96.50 Example 3 0.155 94.66 Example 4 0.156 94.64 Example 5 0.154 92.82 Example 6 0.076 43.11 Example 7 0.083 46.18 Example 8 0.07 40.64 Example 9 0.02 24.85 Example 10 0.03 27.42 Example 11 0.02 24.85 Example 12 0.01 22.53 Example 13 0.01 22.53 Example 14 0.01 22.53 Comparative Example 1 0.157 94.66 Comparative Example 2 0.155 96.50 Comparative Example 3 0.156 94.74

Experimental group Absorbance Enzyme Activity (%) Example 15 0.154 92.82 Example 16 0.156 94.66 Example 17 0.156 94.66 Example 18 0.155 93.74 Example 19 0.155 93.74 Example 20 0.076 43.11 Example 21 0.083 46.18 Example 22 0.07 40.64 Example 23 0.03 27.42 Example 24 0.03 27.42 Example 25 0.02 24.85 Example 26 0.01 22.53 Example 27 0.01 22.53 Example 28 0.01 22.53 Comparative Example 4 0.155 93.74 Comparative Example 5 0.157 94.66 Comparative Example 6 0.156 94.66

Note) Enzyme activity (%) = Enzyme activity of test group x 100 ÷ Enzyme activity of control group

As can be seen from the results of Tables 5 and 6, in the compositions of Comparative Examples 1 to 6 and Examples 1 to 5 and 15 to 19 containing no green tea extract, the inhibitory effect on the collagenase enzyme activity that decomposes periodontal tissue However, the compositions of Examples 6 to 14 and 20 to 28 containing green tea extract in the range of 0.1 to 1 wt% exhibit excellent inhibitory effect on enzyme activity, so that the green tea extract has an excellent effect for inhibiting collagenase enzyme activity .

EXPERIMENTAL EXAMPLE 3 Clinical Experiment on Efficacy and Effect of Each Composition

A total of 30 patients were randomly assigned to a group of 120 subjects who had gingival inflammation without dentition and who had dentition and who were 30 to 50 years old. Clinical experiments on the therapeutic effect of the compositions of Examples 1 to 14 and Comparative Examples 1 to 3 on the treatment of gingival inflammation were performed by dividing the subject group into 60 subjects by the following methods.

The initial gingivitis index was scored by subjecting the subjects divided into two groups: experimental group and control group, 2 hours after the meal and 4 times a day before sleep. After oral administration at 1 week, 1 month, 3 months and 6 months after oral administration, the gingivitis index was examined. The gingival index was measured by continuously inserting a periodontal probe into the gingival sulcus with no force applied, and after 30 seconds, the state of bleeding was measured and scored according to the criteria of Table 7 below .

The dentifrice compositions of Examples 15 to 28 and Comparative Examples 4 to 6 were also tested in the same manner, and the results are shown in Tables 8 and 9 below.

score Contents 0 point No bleeding state 1 point Petechial state 2 points Hemorrhage 3 points Triangle Bleeding 4 points Gingival hemorrhage

time Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Example 9 Example 10 Example 11 Example 12 Example 13 Example 14 Comparative example 1 Example 2 Example 3 Early 1.08 1.02 1.11 1.12 1.16 1.12 0.98 1.11 1.13 1.11 0.99 1.20 1.14 1.02 1.14 1.06 1.14 1 week 1.09 1.05 1.13 1.12 1.14 1.13 1.03 1.12 1.13 1.12 1.11 1.18 1.15 1.04 1.45 1.08 1.14 1 month 1.25 1.25 1.22 1.19 1.12 1.17 1.11 1.14 1.14 1.13 1.13 1.14 1.16 1.11 2.69 2.23 1.19 3 months 1.48 1.47 1.33 1.21 1.21 1.77 1.12 1.15 1.15 1.15 1.15 1.14 1.14 1.12 3.14 2.47 1.18 6 months 1.68 1.48 1.43 1.42 1.41 1.18 1.12 1.16 1.16 1.16 1.16 1.15 1.16 1.14 3.24 3.14 1.24

time Example 15 Example 16 Example 17 Example 18 Example 19 Example 20 Example 21 Example 22 Example 23 Example 24 Example 25 Example 26 Example 27 Example 28 Example 4 Example 5 Example 6 Early 1.06 1.01 1.10 1.11 1.14 1.11 0.99 1.12 1.13 1.12 1.07 1.18 1.12 1.03 1.15 1.05 1.13 1 week 1.07 1.04 1.13 1.12 1.15 1.13 1.04 1.14 1.15 1.14 1.13 1.19 1.15 1.05 1.43 1.06 1.13 1 month 1.24 1.24 1.20 1.17 1.12 1.16 1.12 1.13 1.13 1.12 1.11 1.13 1.16 1.13 2.67 2.22 1.19 3 months 1.46 1.47 1.31 1.21 1.20 1.74 1.13 1.14 1.15 1.17 1.13 1.15 1.13 1.15 3.12 2.46 1.17 6 months 1.66 1.46 1.42 1.40 1.41 1.17 1.11 1.13 1.14 1.15 1.13 1.12 1.14 1.13 3.23 3.13 1.24

Analysis of the results of the clinical tests of Tables 8 and 9 showed that the compositions of Comparative Examples 1 and 4, which contained no pharmaceutical active ingredient, had no inhibitory effect on gingival inflammation and that the composition of Comparative Examples 2 and 5 containing 0.001% by weight of grapefruit seed extract The compositions of Comparative Examples 3 and 6 containing 1.1% of the grapefruit seed extract showed excellent gingival inflammation inhibitory effect while the gingival inflammation inhibitory effect was not observed until 6 months later. The compositions of Examples 1 to 5 and 15 to 19 containing only the grapefruit seed extract in an amount of 0.005 to 0.50% by weight showed gingival inflammation inhibitory effects. Examples 6 to 14 in which the grapefruit seed extract and green tea extract were formulated together 20 to 28 compared to the gingival inflammation inhibiting effect of the composition. Therefore, it can be seen that the composition containing the grapefruit seed extract together with the green tea extract shows excellent efficacy in suppressing the formation of plaque and inhibiting the enzyme activity of collagenase, and the therapeutic effect lasts for 6 months.

Experimental Example 4: Clinical Comparative Experiment on Bad Breath Suppression Effect

85 men and women in their twenties who had no dental caries were selected and five subjects were selected for each oral liquid composition of Examples 1 to 14 and Comparative Examples 1 to 3 according to the present invention.

After a certain amount of garlic (0.5 g) was masticated for 2 minutes to generate oral odor, 10 ml of the product was used for 30 seconds, and after 1 minute, 5 minutes, 10 minutes and 15 minutes, the amount of methyl mercaptan And the mouth was closed except when using the product to prevent mixing of the subject's breath with external air.

The volume of the sample was measured three times by gas chromatography (FPD) after taking 100 ml of the sample using a gas tighter syringe. To analyze only 1 ml of the sample, (Sampling Loop) was attached.

Chromosil 330 was used as a gas chromatographic column, a Teflon tube with a filling length of 6 ft and an outer diameter of 1/8 inch was used. The column temperature was adjusted to 70 ° C. and helium was used as a carrier gas at 20 ml / min Respectively. The percent reduction (%) of methyl mercaptan was measured for the dentifrice compositions of Examples 15 to 28 and Comparative Examples 4 to 6 in the same manner as above except that the composition was used for one minute. 10 and 11, respectively.

Reduction rate of methyl mercaptan (%) Time difference 1 minute 5 minutes 10 minutes 15 minutes Example 1 77.1 77.4 77.7 78.1 2 79.7 79.9 80.2 80.5 3 80.0 80.6 80.8 81.1 4 81.5 81.7 82.1 82.6 5 83.3 83.7 83.9 84.2 6 90.5 90.8 91.2 91.6 7 92.2 92.4 92.8 93.1 8 92.7 92.9 93.0 93.4 9 94.1 94.6 94.8 95.2 10 94.8 95.1 95.5 95.9 11 95.2 95.6 95.9 96.1 12 97.7 98.2 98.7 98.8 13 97.9 98.4 98.7 99.0 14 98.1 98.7 99.1 99.3 Comparative Example 1 61.2 61.9 62.1 62.5 2 69.1 69.4 69.7 70.1 3 85.7 86.1 86.4 86.9

Reduction rate of methyl mercaptan (%) Time difference 1 minute 5 minutes 10 minutes 15 minutes Example 15 80.2 80.6 80.8 81.1 16 81.6 81.9 82.3 82.5 17 82.5 82.7 83.2 83.7 18 83.3 83.7 83.9 84.2 19 85.5 85.8 86.0 86.4 20 90.7 90.9 91.3 91.7 21 92.5 92.8 93.0 93.3 22 92.9 93.1 93.4 93.6 23 94.2 94.5 94.8 95.1 24 94.8 95.1 95.5 95.9 25 95.1 95.5 95.9 96.2 26 97.8 98.1 98.5 98.8 27 98.1 98.4 98.8 99.0 28 98.7 99.1 99.3 99.5 Comparative Example 4 63.3 63.9 64.1 64.5 5 71.2 71.5 72.1 72.4 6 87.5 87.9 88.3 88.6

The results are shown in Tables 10 and 11. Table 10 and 11 show decreasing amounts of methylmercaptan generated during garlic chewing over time. As a result, the composition containing the grapefruit seed extract has a remarkable decrease in mercaptan, and in particular, And the effect is further increased. Therefore, it can be seen that oral liquid composition and dentifrice composition using a mixture of grapefruit seed extract and green tea extract can be very effectively used for removing bad breath. However, when the grapefruit seed extract is contained in an amount exceeding 1.0% by weight as in the compositions of Comparative Examples 3 and 6, it may give an unpleasant taste such as a strong browning taste in use.

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Claims (10)

A liquid composition for oral use characterized by containing grapefruit seed extract as an active ingredient. The composition according to claim 1, which contains 0.005 to 1.0% by weight of grapefruit seed extract. 3. The composition of claim 2 containing from 0.01 to 0.5% by weight of grapefruit seed extract. The composition according to any one of claims 1 to 3, which contains green tea extract. 5. The composition according to claim 4, which contains 0.01 to 5.0% by weight of green tea extract. 6. The composition according to claim 5, which comprises 0.05 to 1.0% by weight of green tea extract. 5. The composition of claim 4 wherein the grapefruit seed extract and green tea extract are in a weight ratio of 1: 5 to 1: 100. The method according to claim 1, further comprising the step of adding a reducing agent such as sodium fluoride, sodium fluorophosphate, fluoride amine, tin fluoride, xylitol, chlorohexidine, cetylpyridium chloride, triclosan, bamboo salt, , Glucosamine, gold, ebony, propolis, allantoin, aminocaproic acid, tranexamic acid, tocopheryl acetate, dextranase, glucose oxidase, glucoamylase,?,? - amylase, lactoperoxidase and lysozyme A composition comprising at least one adjuvant. The composition of claim 1, wherein the formulation is a saline solution. The composition of claim 1, wherein the formulation is a spray.