KR20120119904A - Edible composition for prevention of dental caries and periodontal disease by growth of bacteria in the mouth - Google Patents

Abstract

PURPOSE: An oral composition for preventing and treating dental caries due to breeding of the oral bacteria and periodontal diseases is provided to enhance antibacterial activity for Streptococcus mutants and/or Fusobacterium nucleatum. CONSTITUTION: An oral composition for preventing and treating dental caries due to breeding of the oral bacteria and periodontal diseases contains Bilberry, Vaccinium myrtillus L. which are uniformly dispersed inside an aqueous film substrate. The composition is manufactured into film, dentifrice, oral cavity cleaning solution, ointment, spray, dressing solution, coating material, dental floss, or preodontal pack. The Bilberry is uniformly dispersed inside the aqueous-soluble film material at the concentration of 0.2-0.5 mg / ml. The composition displays the antibacterial activity for Streptococcus mutans and/or Fusobacterium nucleatum.

Description

Oral composition for the prevention and treatment of dental caries and periodontal disease by proliferation of oral bacteria {Edible composition for prevention of dental caries and periodontal disease by growth of bacteria in the mouth}

The present invention relates to oral compositions for the prevention and treatment of dental caries and periodontal disease by the growth of oral bacteria.

One of the aspirations to live a healthier life, modern people not only want to have healthy teeth up to 80 years of age, but also wash their mouth after meals to reduce bad breath that can interfere with interpersonal relationships. Oral cleaning is performed to prevent dental caries, bad breath, and periodontitis caused by damage to the oral cavity and teeth caused by changes in the diet of modern people. Oral cleaning agents currently on the market use dental fluoride, benzetonium chloride, polyoxyethylene, polyoxypropylene polymer, cetylpyridinium chloride, sodium saccharin, sodium benzoate, etc. Prevent and cure. However, when swallowing these components, side effects such as vomiting, nervous breakdown, lethargy, diarrhea, etc., and fatal damage if swallowed excessively. So infants under 7 years of age limit the use of mouthwashes. In addition, studies have been published that damage the oral cavity after long-term use. In addition, antibiotics such as penicillin and erythromycin have been reported to play an effective role in combating the causative agents of dental plaque formation to prevent dental caries, but they have not been used in the clinic because resistance to antibiotics occurs during long-term use. Bad breath may be caused by an acquired disease, but in general, amino acids produced by decomposition of saliva proteins and food waste by microorganisms in the oral cavity are decomposed by dehydrating enzymes or amino enzymes, causing odors. To generate. Examples of bad breath-causing components include volatile sulfides (Volatile Sulfide Compounds), which include hydrogen sulfide (H 2 S), methyl mercaptan (CH ₃ SH), and dimethyl mercaptan (dimethyl mercaptan). , (CH ₃ ) 2 S], and methylmercaptan, in particular, is known as a major component of disgusting smell during bad breath.

Many mouthwashes currently used to prevent dental caries, bad breath, and periodontitis can sometimes be difficult or inconvenient depending on the situation in which oral cleaning should be performed. In your own home, you can use the usual mouthwashes, such as brushing, flushing, tongue cleaning, and gargle with a variety of devices and compositions, but not in homes, where bathroom equipment is insufficient, unavailable, or unsanitary. Not convenient Since brushing, flushing, tongue cleaning and gargling in public places are not socially acceptable in many cultures, a variety of less visible oral cleaning products have been developed. Such products include breathing, mouthwash gum and lozenges. But these too are not always socially acceptable. For example, chewing gum is explicitly prohibited in certain institutions such as schools and in certain countries such as Singapore. Gum and mint require long time use and may be undesirable, such as distracting the surroundings by causing the consumer to suck or chew. Also, mouse sprays, such as mouse washes, are usually packed in relatively expensive and complex metal canisters, which can clog pipes during use and are not environmentally friendly. Moreover, not being able to direct the spray will not only waste the product, but can also irritate the eyes, make the face sticky and stain the clothes. Therefore, an edible film has been proposed as a means for inconspicuous delivery of oral and respiratory cleansing formulations.

Edible film is easy to carry and can be easily taken without water, without having to save the place and environment, so it is a good medium to deliver drugs to elderly patients who cannot take pills abroad or to children who do not like syrup-type drugs. Is getting. The use of edible films is very versatile because a variety of substances can be formulated in edible films, from drugs to food. Methods for administering physiologically active substances such as cold medicines, vitamins, and appetite reducing agents have been developed through edible films and are also being developed as a means for administering drugs to pets.

Examples of applying such an edible film include Korean Patent Publication No. 10-2001-0075347 described for a rapidly dissolving oral consumption film, Korean Patent Publication No. 10-2005-0048056, described for an oral consumption film composition, Korean Patent Laid-Open Publication No. 10-2005-0055808, which describes a method for preparing an edible film containing polyphenol extracted from green tea, and a Korean Patent Publication, which discloses a film for preventing and removing bad breath and a film forming composition for producing the same. Korean Patent Publication No. 10-2005-0029905, Korean Patent Publication No. 10-2008-0023873 described for the oral consumable film.

Edible film is a product that has a great potential in the use as described above, the situation that needs to be applied to the edible film by finding and developing a good antimicrobial activity against bacteria causing oral diseases (such as bad breath, periodontitis, dental caries). .

An object of the present invention is Streptococcus ( Streptococcus) which is the causative agent of dental caries mutans ) and / or Fusobacterium nucleatum , a representative cause of periodontal disease, to provide an oral composition exhibiting an antimicrobial activity.

In order to achieve the above object, the present invention citric acid, malic acid, vitamin C, cinnamon (cinnamon), cinnamic aldehyde (Cinnamic Aldehyde), grape flavor, glycerin fatty acid esters (Glycerin Esters of Fatty Acids), propolis (propolis) And oral composition for the prevention and treatment of dental caries by proliferation of Streptococcus mutans , characterized in that the single or two or more selected from the group consisting of golden extract is uniformly dispersed in the water-soluble film substrate. To provide.

In addition, the present invention citric acid, malic acid, vitamin C, cinnamon flavor, cinnamic aldehyde, peppermint oil, peppermint flavor, coffee powder, lemon oil, sorbitan fatty acid ester (Sorbitan Esters of Fatty Acids), bilberry (Bilberry), chitosan, Prevention of periodontal disease by proliferation of Fusobacterium nucleatum , characterized in that the single or two or more selected from the group consisting of chacatechin, propolis and golden extract is uniformly dispersed inside the water-soluble film substrate And oral compositions for treatment.

Hereinafter, the present invention will be described in detail.

The present invention comprises citric acid, malic acid, vitamin C, cinnamon (cinnamon), Cinnamic Aldehyde, grape scent, glycerin fatty acid ester (Glycerin Esters of Fatty Acids), propolis (propolis) and golden extract from the group Provided is an oral composition for the prevention and treatment of dental caries caused by the propagation of Streptococcus mutans , characterized in that the selected single or two or more are uniformly dispersed in the water-soluble film substrate.

In a specific embodiment of the present invention, the malic acid, vitamin C, cinnamon (cinnamon), cinnamic aldehyde (Cinnamic Aldehyde), grape scent, glycerin fatty acid ester (Glycerin Esters of Fatty Acids), propolis (propolis) and golden extract Showed antimicrobial activity against Streptococcus mutans, and the highest inhibitory rate for inhibition of growth of Streptococcus mutans was glycerin fatty acid ester at 50% and 90% inhibition rate. And gold extracts were also found to exhibit a significantly higher inhibition rate of IC ₉₀ below 1 (see Table 2). In addition, Glycerin Esters of Fatty Acids among these substances have previously been reported to exhibit antimicrobial activity against Streptococcus mutans. Thus, it can be usefully used for the prevention and treatment of dental caries due to the proliferation of Streptococcus mutans.

Oral compositions of the present invention include pharmaceutical compositions, oral cleaning compositions and food compositions, and may be specifically formulated into a film, toothpaste, mouthwash solution, ointment, spray, dressing solution, coating agent, dental floss or periodontal bag. .

Glycerin Esters of Fatty Acids are esters and derivatives of fatty acids and glycerin or polyglycerin, but they are insoluble in water but in organic solvents such as alcohol, ethyl acetate, ether, and chloroform. Additives used to uniformly disperse liquids or solids that do not mix well with each other in liquids are used in margarine, milk beverages, ice cream, cakes, biscuits, bread, etc., in addition to emulsifiers. The glycerin fatty acid ester has not been reported to exhibit antimicrobial activity against Streptococcus mutans, IC ₅₀ and IC ₉₀ value of 0.008 and 0.159 mg / ㎖, respectively, 0.01 to 0.2 mg / inside the water-soluble film substrate of the present invention It is preferable to be contained uniformly dispersed in a concentration of ml.

Golden extract is the main ingredient of golden (黄 芩, Scutellariae Radix), and it is extracted incidentally including licorice for the sweetness effect, the gold belongs to Lamiaceae, native to northern China in East Asia, imported as medicinal plants It is a naturalized plant grown in herbalist farms everywhere, and is often grown in fields. In the herbal medicine, golden is dried roots. In spring or autumn, the roots are dug up, scrape off the husks and rotten genus, rinse in water, dry in the sun, and use it as a medicinal herb. The root is yellow so it is called golden. The gold is involved in the treatment of diseases associated with fever, anger, fever associated with symptoms such as thirst, coughing and sputum and humidity-related diseases associated with diarrhea, stuffy chest or painful urination. The golden extract has not been reported to exhibit antimicrobial activity against Popiromonas gingivalis, IC ₅₀ and IC ₉₀ values of 0.129 and 0.651 mg / ml, respectively, 0.1 to 0.7 mg in the water-soluble film substrate of the present invention. It is preferable that it is contained uniformly dispersed at a concentration of / ml.

In addition, the present invention citric acid, malic acid, vitamin C, cinnamon flavor, cinnamic aldehyde, peppermint oil, peppermint flavor, coffee powder, lemon oil, sorbitan fatty acid ester (Sorbitan Esters of Fatty Acids), bilberry (Bilberry), chitosan, Prevention of periodontal disease by proliferation of Fusobacterium nucleatum , characterized in that the single or two or more selected from the group consisting of chacatechin, propolis and golden extract is uniformly dispersed inside the water-soluble film substrate And oral compositions for treatment.

In a specific embodiment of the present invention, the citric acid, malic acid, vitamin C, cinnamon flavor, cinnamic aldehyde, peppermint oil, peppermint flavor, coffee powder, lemon oil, sorbitan esters of Fatty Acids, bilberry (Bilberry) ), Chitosan, chacatechin, propolis and golden extract show antimicrobial activity against Peugeot bacterium nucleatum, and the highest inhibition rate against the growth of Peugeot bacterium nucleatum is 50% and 90% It was found to be catechin, and cinnamon, cinnamic aldehyde and sorbitan fatty acid ester were also found to exhibit a significantly higher IC ₉₀ inhibition rate of 0.2 or less (see Table 3). In addition, tea catechin or sorbitan fatty acid esters (Sorbitan Esters of Fatty Acids) of the above has not been reported to exhibit antimicrobial activity against the Peugeot bacterium nucleotum. Thus, it can be usefully used for the prevention and treatment of periodontal disease by the proliferation of Peugeot bacterium nucleatum.

Oral compositions of the present invention include pharmaceutical compositions, oral cleaning compositions and food compositions, and may be specifically formulated into a film, toothpaste, mouthwash solution, ointment, spray, dressing solution, coating agent, dental floss or periodontal bag. .

Sorbitan Esters of Fatty Acids are white to yellow brown liquid or powder and waxy substances with strong dispersion stability. They are used as a single product, but are mainly used as mixed emulsifiers. There is no special usage standard. In the manufacturing method, sorbitol is heated to 150 ° C. to 152 ° C., dehydrated, and then maintained at 160 ° C. to 165 ° C. to obtain sorbitan. Mixing 0.5% of wheat flour in the manufacture of shortening for bread and cake slows down the bread and improves the quality of oil dispersion, uniformity of bubbles, volume increase, etc. To keep the dispersion even and prevent it from sticking to the teeth. In addition, the mixing of the dough can be facilitated, and the expansion can be good, and the aging can be prevented from cracking. The sorbitan fatty acid ester has not been reported to exhibit antimicrobial activity against Streptococcus mutans, IC ₅₀ and IC ₉₀ values of 0.054 and 0.087 mg / ml, respectively, 0.05 to 0.1 mg in the water-soluble film substrate of the present invention. It is preferable that it is contained uniformly dispersed at a concentration of / ml.

Bilberry; Vaccinium myrtillus L. ) has been used as a food ingredient for centuries, has been tasted and nutritious, and is still used in the manufacture of jams, pies, syrups and beverages. Pharmaceutically, it has been used for the treatment of diarrhea and hemorrhoids, and has a pronounced astringent effect to treat inflammation of the mouth and mucous membranes. The bilberry has not been reported to exhibit antimicrobial activity against Popiromonas gingivalis, IC ₅₀ and IC ₉₀ values of 0.246 and 0.447 mg / ml, respectively, 0.2 to 0.5 mg / inside the water-soluble film substrate of the present invention It is preferable to be contained uniformly dispersed in a concentration of ml.

Tea catechin is a white or pale yellow to dark brown powder or liquid with a characteristic odor. Chacatechin is obtained by extracting and purifying the stem or leaves of the tea tree with water or ethanol, or by hydrothermal extraction and decomposition with methanol or ethyl acetate. The catechins include epicatechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, gallocatechin gallate, and the like, and are known as tea flavor components. It is also used as a food additive that is used as an antioxidant to prevent food from deteriorating, and it has antibiotic properties because it plays a role in dividing a special step during the DNA replication process of bacteria. The chacatechin has not been reported to exhibit antimicrobial activity against Peugeot bacterium nucleatum, IC ₅₀ and IC ₉₀ values of 0.0264 and 0.0373 mg / ml, respectively, 0.02 to 0.04 mg in the water-soluble film substrate of the present invention. It is preferable that it is contained uniformly dispersed at a concentration of / ml.

The film composition of the present invention is the causative agent of dental caries Streptococcus mutans ( Streptococcus mutans ) and / or Fusobacterium nucleatum , a representative causative agent of periodontal disease, exhibits excellent antimicrobial activity, which is useful for the prevention and treatment of dental caries and / or periodontal disease caused by the growth of the bacterium. Can be.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

< Example  1> Use strain  And culture conditions

The strain used in this experiment was Streptococcus musos ) and Fusobacterium nucleatum , a representative cause of periodontal disease, were used from the Oral Biochemistry Laboratory of the College of Dentistry, Chosun University.

When culturing Streptococcus mutans, incubated for 1 to 2 days at 37 ° C. in anaerobic conditions (CO ₂ 5%, H ₂ 5%, N ₂ 90%), and cultured in a single medium. Inoculation was incubated for 6 hours at 37 ° C. in anaerobic conditions. Solid medium was added with 90 g / l MS (mitis salivarius) agar, 5 g / l yeast extract, 4 ml / l of 0.025% resazurin and 200 g / l sucrose, followed by heating. After melting and autoclaving to about 45 ~ 46 ℃, 1% tellurite phosphate (Potassium tellurite) 1 ㎖ / ℓ, 0.5 ㎎ / ㎖ Bacitracin 1 ㎖ / ℓ were made. Liquid medium was prepared by adding 37 g / l of brain heart infusion (BHI) broth and 5 g / l of yeast extract, followed by autoclavation.

Peugeot bacterium nucleatum cultured in solid medium, incubated for 2 to 3 days at 37 ℃, anaerobic conditions (CO ₂ 5%, H ₂ 5%, N ₂ 90%) and then picked the strain formed from a single colony liquid Inoculated to the medium and incubated for 13 hours at 37 ℃ anaerobic. The solid medium was 10 g / l of Tryptic soy broth (TSB), 5 g / l of yeast extract, 2 g / l of glucose, 0.2 g / l of L-tryptophan, 20 g / l of Bacto-agar After autoclaving to about 45-46 ° C., 50 ml / l of sheep blood, 2 mg / ml Erythromycin 2 ml / l, 1.25 µg / ml, crystal violet 4 ml / It was made to be l. The liquid medium was autoclaved with 28.4 g / l of Schaedler broth and 2 ml / l of erythromycin when the temperature was about 45-46 ° C.

< Example  2> Candidate Substances Prohibiting Oral Microbial Growth

Candidates for oral microbial proliferation inhibition of Table 1 were distributed from CLP Co., Ltd., and each material was dissolved in a suitable solvent and used in an experiment.

Candidate Substances for Oral Microbial Proliferation density H ₂ O 50% EtOH EtOH DMSO One Licorice extract 100 mg / ml 2 Cinnamon incense 500 mg / ml 3 Citric acid 500 mg / ml 4 Glycerin Fatty Acid Ester 500 mg / ml 5 Green tea extract 500 mg / ml 6 Lemon Oil 500 mg / ml 7 Lemon incense 500 mg / ml 8 Vitamin C 200 mg / ml 9 Malic acid 500 mg / ml 10 Sorbitan Fatty Acid Ester 500 mg / ml 11 Pine needle extract 500 mg / ml 12 Cinnamicaldehyde 500 mg / ml 13 Eucalyptus 500 mg / ml 14 Cherry Extract 500 mg / ml 15 Coffee powder 200 mg / ml 16 Coffee flavor 500 mg / ml 17 Peppermint Oil 500 mg / ml 18 Peppermint incense 500 mg / ml 19 Grape 500 mg / ml 20 Polysorbate 200 mg / ml 21 Oriental Medicine Complex (7 types including licorice) 500 mg / ml 22 Red Ginseng Extract 500 mg / ml 23 Red ginseng 500 mg / ml 24 Fennel Extract 500 mg / ml 25 Acerola 200 mg / ml 26 Bilberry 100 mg / ml 27 Chacatechin 100 mg / ml 28 Chitosan 100 mg / ml 29 Propolis 100 mg / ml 30 Golden extract 100 mg / ml 31 Raspberry 100 mg / ml 32 Hinoki Thiol 100 mg / ml 33 Curcumin 100 mg / ml 34 Lutein 100 mg / ml

< Example  3> Streptococcus To Mutans  Antimicrobial Effect of Korean Oral Microbial Inhibitors

Pre-sorted Streptococcus mutans were activated by passage three times in BHI liquid medium and used in the experiment. Antimicrobial activity evaluation was performed by investigating the inhibitory power by the liquid culture method.

The cultured cells were diluted to 5 × 10 ⁷ CFU / ㎖ of the final bacteria was inoculated in a liquid medium. Subsequently, after adding oral microbial growth inhibition candidates of Table 1 at the same concentration, and incubating for 3 hours at 37 ° C. in an anaerobic state, the liquid culture solution was measured for absorbance at 595 nm to inhibit growth by equation (1). %) Was calculated.

[S: absorbance of medium + strain + sample, C1: absorbance of medium + strain, C2: absorbance of medium + sample, M: absorbance of medium]

As a result of examining the antimicrobial activity, it was confirmed that oral microbial proliferation inhibitory substance containing citric acid of Table 2 has antimicrobial activity against Streptococcus mutans.

At the time have an IC _{50 (50%} inhibition capacity as described by examining the antimicrobial activity was added at different concentrations as a candidate the antimicrobial activity of the selected identified as described in "concentration range" column of Table 2, Table 2 Concentration) and IC ₉₀ (concentration with 90% inhibition).

Oral Microbial Proliferation Inhibitor MIC (Mg / ml) Range IC50 IC90 Citric acid ≤1-5 1.317 3.492 Malic acid ≤1-5 1.438 3.699 Vitamin C ≤2-10 3.726 7.956 Cinnamon incense ≤0.15-2.4 0.278 1.353 Cinnamicaldehyde ≤0.05-0.8 0.123 0.778 Grape ≤0.2-3.2 0.721 2.219 Glycerin Fatty Acid Ester ≤0.01-0.16 0.008 0.159 Propolis ≤0.025-0.4 0.067 0.3872 Golden extract ≤0.05-0.8 0.129 0.651

In other words, the highest inhibitory rate for the inhibition of growth of Streptococcus mutans was glycerin fatty acid esters when the inhibition rate was 50% and 90%, and the cinnamic aldehyde, propolis and golden extract were also lower than IC ₉₀ . It was found to exhibit a significantly higher inhibition rate.

< Example  4> Peugeot bacterium Nucleatum  Antimicrobial Effect of Korean Oral Microbial Inhibitors

Peugeot bacterium nucleatum that had been distributed was activated by three passages in Schaedler broth liquid medium and used in the experiment. Antimicrobial activity evaluation was performed by investigating the inhibitory power by the liquid culture method.

The cultured cells were inoculated in a liquid medium by diluting the final cell number to 600 OD at 600 nm. Subsequently, after adding oral microbial growth inhibition candidates of Table 1 at a constant concentration, and incubated for 13 hours at 37 ℃, anaerobic state, the liquid culture solution was measured by absorbance at 595 nm to inhibit growth (Equation 1) %) Was calculated.

As a result of examining the antimicrobial activity, it was confirmed that oral microbial proliferation inhibitory substance containing citric acid of Table 3 has antimicrobial activity against Peugeot bacterium nucleum.

At the time have an IC _{50 (50%} inhibition capacity as described by examining the antimicrobial activity was added at different concentrations as a candidate the antimicrobial activity of the selected identified as described in "concentration range" column of Table 3, Table 3 Concentration) and IC ₉₀ (concentration with 90% inhibition).

Oral Microbial Proliferation Inhibitor MIC (Mg / ml) Range IC50 IC90 Citric acid ≤0.2-1 0.574 0.808 Malic acid ≤0.2-1 0.494 0.777 Vitamin C ≤0.6-3 1.519 2.197 Cinnamon incense ≤0.04-2 0.095 0.153 Cinnamicaldehyde ≤0.02-0.1 0.042 0.058 Peppermint Oil ≤0.08-0.4 0.121 0.345 Peppermint incense ≤0.16-0.8 0.182 0.656 Coffee powder ≤1-5 1.847 3.486 Lemon Oil ≤0.16-0.8 0.383 0.58 Sorbitan Fatty Acid Ester ≤0.025-0.125 0.054 0.087 Bilberry ≤0.1-0.5 0.246 0.447 Chitosan ≤0.05-0.8 0.11 0.765 Chacatechin ≤0.008-0.04 0.0264 0.0373 Propolis ≤0.06-0.3 0.185 0.285 Golden extract ≤0.24-0.32 0.273 0.31

In other words, the most inhibitory rate for the inhibition of the growth of Peugeot bacterium nucleatum was chacatechin at 50% and 90% inhibition rate, and cinnamon, cinnamic aldehyde and sorbitan fatty acid esters were IC ₉₀ It was confirmed that it exhibited a considerably high inhibition rate below 0.2.

As described above, candidate oral microbial inhibitors of Tables 2 and 3 showed antimicrobial activity, and in particular, glycerin fatty acid ester, cinnamon flavor, cinnamic aldehyde, propolis, chacatechin, sorbitan fatty acid ester, and golden extract were considerably. It was confirmed that even at low concentrations it effectively inhibits the growth of Streptococcus mutans or Peugeot bacterium nucleatum. Through this, the present invention can be effectively used for oral microbial inhibitors to remove dental caries, periodontal disease and bad breath.

Claims (3)

Oral composition for the prevention and treatment of periodontal disease by the proliferation of Fusobacterium nucleatum , characterized in that the bilberry (Bilberry) is uniformly dispersed in the water-soluble film substrate.
The composition of claim 1, wherein the composition is formulated into one selected from the group consisting of a film, a toothpaste, a mouthwash solution, an ointment, a spray, a dressing solution, a coating agent, a dental floss and a periodontal bag.
The composition of claim 1, wherein the bilberry is uniformly dispersed in the water-soluble film substrate at a concentration of 0.2 to 0.5 mg / ml.