KR102207872B1 - Oral composition for preventation or treatment of oral disease - Google Patents

Abstract

The present invention relates to a composition for preventing or treating oral diseases. The composition for preventing or treating oral diseases according to an embodiment of the present invention can effectively prevent or treat tooth decay or periodontitis by inhibiting bacterial activity in the oral cavity, but is not highly toxic to the human body, thereby being able to be used for a long period of time, and being able to be applied in various formulations such as tablets, toothpaste, gargle liquid, oral patches, etc.

Description

Composition for preventing or treating oral diseases {ORAL COMPOSITION FOR PREVENTATION OR TREATMENT OF ORAL DISEASE}

The present invention relates to a composition for preventing or treating oral diseases.

Dental caries, also called caries, and periodontitis, such as periodontitis, which are also known as pungchi, are diseases with a very high incidence, and various diseases such as pain, masticatory dysfunction, destruction of periodontal tissue, bad breath and aching teeth. It causes clinical symptoms and is a major factor in causing tooth loss.

Tooth decay occurs mainly on the chewing surface of the tooth or the adjacent surface between the tooth and the tooth, and destroys the enamel surrounding the dentin, which exposes the dentin and the dentin tubules, causing the tooth to feel aching symptoms. This caries disease occurs mainly in the age group in which the enamel quality is not sufficiently strengthened from infancy to adolescence.

Pungchi (periodontitis), known as gum disease, occurs when the periodontal ligaments that connect teeth and alveolar bones are damaged, and as the ecosystem of oral microbes is disrupted by various causes, chronic inflammation of the underlying tissues continues, free radicals, inflammatory signaling substances, etc. The alveolar bone and periodontal ligaments under the periodontal tissue are absorbed by local over-concentration. Due to the damage of the alveolar bone and the periodontal ligament, the support for the teeth of the alveolar bone decreases, so that tooth mobility is increased, and the cementum surrounding the root of the tooth is exposed, causing a tooth ache. These periodontal diseases are mainly seen in adults after their 30s, but most of them are insensitive to this disease.

It is known that these cavities and air cavities are mainly caused by oral pathogens present in the oral cavity.

It is known that about 800 kinds of microorganisms are parasitic or symbiotic in human oral cavity. These microbial flora are controlled by enzymes secreted along with saliva, but because the inside of the oral cavity rich in nutrients and moisture is a good condition for the growth of microorganisms, the number of microorganisms can be greatly increased in plaque on the tongue or tartar on the tooth surface. .

As a method of inhibiting the proliferation of these oral pathogens, a therapy to remove plaque or calculus, which is the habitat of the germs, is known, and a therapy using an antibacterial agent acting on the pathogen itself or an antibiotic capable of sterilizing and bacteriostatic action Is known.

However, antibiotics are difficult to use for a long time because they can cause systemic side effects, such as allergies, and can cause resistant bacteria in the oral cavity or cause superinfection.

In addition, antimicrobial agents used in oral cleansers have not yet clearly revealed their effect on bacteria in the oral cavity, and in particular, there is controversy over the therapeutic effect of gum disease. There is a problem that may cause side effects.

The present specification is capable of effectively preventing or treating tooth decay, periodontitis, or gingivitis by inhibiting the bacterial activity in the oral cavity, but is not highly toxic to the human body, and can be used for a long period of time, tablets for oral use, toothpaste, gargle liquid, oral cavity It is intended to provide a composition for preventing or treating oral diseases that can be applied in various formulations such as patches.

The present specification is intended to provide a composition for preventing or treating oral diseases, including an extract of PerillaeFructus and 1,2,3-butanetriol.

According to an embodiment of the invention, the oral disease may include any one or more of bad breath, dental caries, gingivitis, and periodontitis.

And, the 1,2,3-butanetriol, (2S,3S)1,2,3-butanetriol, (2S,3R)1,2,3-butanetriol, (2R,3S)1 ,2,3-butanetriol, and (2R,3R)1,2,3-butanetriol may contain at least one selected from the group consisting of triol.

And, the composition for preventing or treating oral diseases, 1,2,3-butanetriol, about 0.0001 wt.% to about 0.250 wt.%, or about 0.0001 wt.% to about 0.150 wt%, or about 0.0005 It may be desirable to include in a concentration of wt.% to about 0.100 wt.%.

According to an embodiment of the invention, the magnetic element is perilla ( Perilla frutescens Britton var. acuta Kudo ) Seed or Perilla frutescens Britton var. crispa Decaisne ) may include any one or more of the seeds.

At this time, the perilla extract is water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, ethyl acetate, methylene chloride, n-hexane, hydrochloric acid, acetic acid, formic acid, diethyl ether, and cyclo It may be extracted using one or more solvents selected from the group consisting of hexane.

And, the perilla extract is extracted and concentrated in a ratio of about 10:1 to about 500:1, or about 50:1 to about 200:1, or about 60:1 to about 100:1 It may be desirable, and at the same time, the composition for preventing or treating oral diseases may contain a perilla extract extracted and concentrated in the above ratio at a concentration of about 0.15 mg/ml015 wt.% or less.

According to another embodiment of the invention, the composition for preventing or treating oral diseases, in addition to 1,2,3-butanetriol and perilla extract, is a water-soluble zinc salt, vitamin B group, vitamin C, and vitamin E. It may further include one or more additives selected from the group consisting of.

In this case, the additive may be included in a concentration of about 0.001 wt.% to about 10 wt.%.

Specifically, in the case of a water-soluble zinc salt, it may be included in an amount of about 0.001 wt.% to about 0.300 wt.%, and in the case of a vitamin B group, especially vitamin B12, it may be included in an amount of about 0.0001 wt.% to about 0.01 wt.%, Vitamin C may be contained in a concentration of about 0.11 wt.% to about 10 wt.%, and vitamin E in a concentration of about 0.01 wt.% to about 5 wt.%.

The composition for preventing or treating oral diseases according to an embodiment of the present invention, due to the above-described composition, Aggregatibacter actinomycetemcomitans ( Aggregatibacter actinomycetemcomitans ), Tannerella forsythia ( Tannerella forsythia ), Treponema Denticola ( Treponema denticola ), Prevotella nigrescens , Eubacterium nodatum ( Eubacterium nodatum ), Parvimonas micra , Eikenella corodens ( Eikenella) corrodens ), Campylobacter rectus , Fusobacterium nucleatum nucleatum ATCC 25586), Streptococcus sobrinus , Streptococcus salivarius GTC0215), Streptococcus anginasus FW73, Streptococcus mutans JCM5705), Prevotella Intermedia intermedia ATCC 25611), and Porphyromonas gingivalis ( Porphyromonas gingivalis W83, ATCC 33277 (F), FDC 381) can have antibacterial, bactericidal, or bacteriostatic activity against one or more bacteria selected from the group consisting of.

And, such a composition for preventing or treating oral diseases is one or more formulations selected from the group consisting of toothpaste, oral rinse, oral tablet, gum, candy, oral spray, oral ointment, oral varnish, and oral patch. It may be in a processed form.

In the present invention, terms such as first and second are used to describe various components, and the terms are used only for the purpose of distinguishing one component from other components.

In addition, terms used in the present specification are only used to describe exemplary embodiments, and are not intended to limit the present invention.

Singular expressions include plural expressions unless the context clearly indicates otherwise.

In the present specification, terms such as "comprise", "include" or "have" are used to describe implemented features, numbers, steps, components, or combinations thereof, and one or more other features, numbers, and steps , Components, combinations or additions thereof are not excluded.

The present invention will be described in detail below and exemplify specific embodiments, as various changes can be made and various forms can be obtained. However, this is not to limit the present invention to a specific form disclosed, it should be understood to include all changes, equivalents, and substitutes included in the spirit and scope of the present invention.

Hereinafter, the present invention will be described in detail.

According to an aspect of the present invention, there is provided a composition for preventing or treating oral diseases, comprising a perilla extract and 1,2,3-butanetriol.

Oral cleaners that are generally used include a fluorine-based compound that can have an antibacterial effect against tooth decay, but can be combined with a calcium component of teeth to make teeth hard; Penicillin, erythromycin, or tetracycline antibiotics; Antibacterial agents such as chlorhexidine; By including alcohol-based compounds such as ethanol, it exhibits an antibacterial effect against bacteria in the oral cavity.

However, fluorine-based compounds are highly toxic, and when swallowed, human side effects such as fluoridation and indigestion may occur, and in the case of antibiotics, resistant bacteria may appear, and chlorhexidine-based antimicrobial agents may also affect the human body. It is highly toxic to teeth and can cause pigmentation of teeth and oral tissues.

The inventors of the present invention, after repeating research to compensate for the disadvantages of the conventional oral formulations that were commonly used as described above, when using a mixture of perilla extract and 1,2,3-butanetriol, While having the effect of inhibiting the growth of bacteria in the oral cavity, there is little toxicity to the human body, so it can be used for a long time, and it has been found that it can be applied in various formulations such as oral tablets, toothpaste, gargle liquid, and oral patches. Was completed.

Perilla is a perennial plant of the Lamiaceae family of the mosquito plant native to China, and is also called perilla or lobule, and recently, the ingredients contained in perilla leaves, that is, perilla leaf, have excellent antioxidant effects, anti-inflammatory effects, and anticancer activity in the human body. It is known to show, and many studies are being conducted.

Perilla seeds are seeds of perilla, and contain a large amount of unsaturated fatty acids. In addition to the above-described effects such as inflammation suppression, antioxidant effect, and anti-cancer effect in the human body, perilla is active, and plays a role in increasing phagocytosis. It is known to do.

Meanwhile, 1,2,3-butantriol (1,2,3-butantriol) may be represented by the following formula.

In other words, 1,2,3-butanetriol is a form in which a hydroxy group is continuously bonded to carbon positions 1,2,3 of the basic skeleton of butane (normal-butane), and thus carbons 2 and 3 A stereogenic center is formed at the position, and accordingly, (2S,3S)1,2,3-butanetriol, (2S,3R)1,2,3-butanetriol, (2R,3S)1,2, 3-butanetriol, and (2R,3R)1,2,3-butanetriol, can have a total of 4 kinds of optical isomers.

These four types of optical isomers do not seem to show a significant difference between each compound in the effect of inhibiting the growth of bacteria in the oral cavity of the human body. Therefore, the composition for preventing or treating oral diseases according to an embodiment of the present invention, 1,2,3-butanetriol, (2S,3S)1,2,3-butanetriol, (2S,3R) 1,2,3-butanetriol, (2R,3S)1,2,3-butanetriol, and at least one selected from the group consisting of (2R,3R)1,2,3-butanetriol, 2,3-butanetriol may be included, and all of them may be included.

The composition for preventing or treating oral diseases according to an aspect of the present invention includes an extract of perilla and 1,2,3, -butanetriol at the same time, as described above, the antimicrobial that the two substances have individually uniquely Or it is possible to obtain a so-called synergy effect in which the sterilization effect is greatly increased.

At this time, the composition for preventing or treating oral diseases may contain 1,2,3-butanetriol in an amount of about 0.0001 wt.% to about 0.250 wt.%, and the lower limit thereof is about 0.0001 wt.% or more. , Or about 0.01mM or more, and its upper limit is about 25mM or less, or about 0.250 wt.% or less, or about 0.150 wt.% or less, or about 12.5mM or less, or about 0.100 wt.% or less, or about 10mM or less I can.

If the concentration of 1,2,3-butanetriol is too low, the inhibitory effect of bacterial activity in the oral cavity decreases, which may not be suitable for use in preventing or treating oral diseases, and the concentration of 1,2,3-butanetriol When is too high, due to toxicity to human cells, it may not be suitable for use in preventing or treating oral diseases.

At this time, the perilla extract is perilla, that is, water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, ethyl acetate, methylene chloride, n-hexane, hydrochloric acid, acetic acid, formic acid, from the seeds of perilla, It may be extracted using one or more solvents selected from the group consisting of diethyl ether and cyclohexane.

And, the perilla extract is extracted and concentrated in a ratio of about 10:1 to about 500:1, or about 50:1 to about 200:1, or about 60:1 to about 100:1 It may be desirable, and at the same time, the composition for preventing or treating oral diseases may contain a perilla extract extracted and concentrated in the above ratio at a concentration of about 0.015 wt.% or less, and about 0.0001 wt.% or more, Alternatively, it may be included in a concentration of 0.0005 wt.% or more to about 0.015 wt.% or less, or about 0.007 wt.% or less, or about 0.005 wt.% or less.

If the content of perilla extract or 1,2,3-butanetriol is too small, there may be a problem in which the synergistic effect of mixing with 1,2,3-butanetriol is insufficient. If the content of perilla extract or 1,2,3-butanetriol is too high, it may damage normal cells and inhibit cell viability.

According to another embodiment of the invention, the composition for preventing or treating oral diseases, in addition to 1,2,3-butanetriol and perilla extract, is a water-soluble zinc salt, vitamin B group, vitamin C, and vitamin E. It may further include one or more additives selected from the group consisting of.

The water-soluble zinc salt is a salt of zinc (Zn), specifically, for example, zinc oxide, zinc chloride (ZnCl ₂ ), zinc hydroxide (Zn (OH) ₂ ), zinc sulfate (ZnSO ₄ ), or glue Zinc conate and the like.

These water-soluble zinc salts can inhibit enzyme activity by binding to an enzyme used for energy metabolism by anaerobic bacteria in the oral cavity, which is the cause of periodontal disease and bad breath, and inhibit the action of MMP enzymes. For this reason, the composition for preventing or treating oral diseases containing a water-soluble zinc salt can have an antibacterial action of suppressing the survival and growth of anaerobic bacteria, and can obtain a protective effect of suppressing the destruction of periodontal tissue.

The vitamin B group may be a complex including B1, B2, B3, B5, B6, B7, B9, and B12, and in particular, the composition for preventing or treating oral diseases according to an embodiment of the present invention is, Among them, B6 and B12 may be included.

These B vitamins can strengthen the immune system and nervous system functions of the human body, promote metabolism, and help heal wounds and inflammations in the oral cavity.

Vitamin C, a water-soluble vitamin, also called ascorbic acid, is a representative antioxidant. It is generated during the antibacterial process of concentrated neutrophil cells and macrophages in the chronic inflammatory process, and can remove free radicals that can destroy periodontal tissue. For this reason, the composition for preventing or treating oral diseases containing vitamin C can obtain a gum protective effect.

Vitamin E is a fat-soluble vitamin, and refers to 4 types of tocotrienol components including alpha tocopherol, beta tocopherol, gamma tocopherol, and delta tocopherol, and alpha tocotrienol, beta tocotrienol, gammatocotrienol, and deltatocotrienol. .

When the composition for preventing or treating oral diseases according to an embodiment of the present invention contains the above-described vitamin E, it is generated during the antimicrobial process of concentrated neutrophil cells and macrophages in the chronic inflammatory process and can destroy periodontal tissue, It can remove free radicals and also promote collagen synthesis, helping to regenerate damaged oral tissues.

In this case, the additive may be included in a concentration of about 0.001 wt.% to about 10 wt.%.

Specifically, in the case of a water-soluble zinc salt, it may be included in an amount of about 0.001 wt.% to about 0.300 wt.%, and in the case of a vitamin B group, especially vitamin B12, it may be included in an amount of about 0.0001 wt.% to about 0.01 wt.%, Vitamin C may be contained in a concentration of about 0.11 wt.% to about 10 wt.%, and vitamin E in a concentration of about 0.01 wt.% to about 5 wt.%.

The composition for preventing or treating oral diseases according to an embodiment of the present invention, due to the above-described composition, Aggregatibacter actinomycetemcomitans ( Aggregatibacter actinomycetemcomitans ), Tannerella forsythia ( Tannerella forsythia ), Treponema Denticola ( Treponema denticola ), Prevotella nigrescens , Eubacterium nodatum ( Eubacterium nodatum ), Parvimonas micra , Eikenella corodens ( Eikenella) corrodens ), Campylobacter rectus , Fusobacterium nucleatum nucleatum ATCC 25586), Streptococcus sobrinus , Streptococcus salivarius GTC0215), Streptococcus anginasus FW73), Streptococcus mutans JCM5705 Prevotella Intermedia intermedia ATCC 25611), and Porphyromonas gingivalis ( Porphyromonas gingivalis W83, ATCC 33277 (F), FDC 381) can have antibacterial, bactericidal, or bacteriostatic activity against one or more bacteria selected from the group consisting of.

Porphyromonas gingivalis W83, ATCC 33277 (F), FDC 381) is known as a pathogen that causes periodontitis, and Prevotella intermedia ATCC 25611 is known as a pathogen that causes gingivitis.

Fusobacterium nucleatum nucleatum ATCC 25586) is known as a common oral bacterium that is involved in ductal diseases in tooth decay or various gums. Recently, Fusobacterium nucleatum nucleatum ATCC 25586) is also known to promote the growth of colorectal cancer cells.

Streptococcus sobrinus , Streptococcus salivarius GTC0215, Streptococcus anginasus FW73 and Streptococcus mutans ( Streptococcus mutans JCM57) are representative bacteria that cause tooth decay. , In the past, dental caries caused by Streptococcus mutans JCM5705 was widely known, but recently, especially Streptococcus sobrinus , Streptococcus salivarius GTC0215, Streptococcus Streptococcus anginasus FW73 is known to play an important role in the progression of tooth decay. In particular, when two or more types of bacteria coexist in the oral cavity, the incidence of tooth decay is high and the progression rate is also known to be fast.

The composition for preventing or treating oral diseases according to an embodiment of the present invention has antibacterial, bactericidal, or bacteriostatic activity against the major pathogens of the above-described oral diseases, and due to this bacterial suppression effect, gum-related such as gingivitis and periodontitis It can effectively prevent or treat diseases or tooth-related diseases such as tooth decay.

And, such a composition for preventing or treating oral diseases is one or more formulations selected from the group consisting of toothpaste, oral rinse, oral tablet, gum, candy, oral spray, oral ointment, oral varnish, and oral patch. It may be in a processed form.

For example, when the composition for preventing or treating oral diseases of the present invention is a toothpaste formulation, it may include a fluorine compound, a wetting agent, an abrasive, a binder, a foaming agent, a flavoring agent, a sweetening agent, a coloring agent, a preservative, a solvent, a pH adjusting agent, and the like. .

When the composition for preventing or treating oral diseases of the present invention may contain water as a solvent, surfactants, excipients, coloring agents, spices, preservatives, stabilizers, and commonly used to formulate active ingredients, and It may include a pH adjusting agent and the like.

In addition, in the case of oral tablets, gums, candy, oral sprays, oral ointments, oral varnishes, and oral patches (film), etc., may have a form generally used in the technical field to which the present invention belongs, Depending on each formulation, it may also include additives generally used for preparing the formulation in the art to which the present invention belongs.

The composition for preventing or treating oral diseases of the present invention inhibits the activity of various kinds of bacteria present in the oral cavity, among others, pathogens that are the main cause of oral diseases, effectively preventing tooth decay, gingivitis, periodontitis, or While it can be treated, it is not highly toxic to the human body, so it can be used for a long time, and can be applied in various formulations such as oral tablets, toothpaste, gargle liquid, and oral patches.

1 is a graph showing the culture survival rate of human fibroblasts according to changes in 1,2,3-butanetriol concentration.
2 is a graph showing results of a cytotoxicity test and an antibacterial test for perilla extract and 1,2,3-butanetriol.
3 and 4 are graphs showing the inhibitory effect of 1,2,3-butanetriol on oral bacteria.

Hereinafter, the functions and effects of the invention will be described in more detail through specific embodiments of the invention. However, these embodiments are only presented as examples of the invention, and the scope of the invention is not determined thereby.

<Example>

1,2,3, -butanetriol was used by purchasing an optically isomeric racemic mixture, which is generally sold on the market. (Sigma Aldrich, Inc.)

Preparation of perilla extract

Perilla ( Perilla) sold at a commercial medicinal agent. frutescens (L.) Britton var. acuta Kudo ) seeds were purchased and used. (Purchased from: Gyeongdong Market Jiundang Oriental Pharmacy)

The magnetic element was pulverized to a size of about 1 mm to obtain a magnetic element powder.

About 30 g of the perilla powder was put in a constant temperature water bath, and about 300 ml of an extraction solution containing water, methanol, or ethanol was added thereto, followed by extraction at a temperature of about 50° C. for about 3 hours. The water bath was shaken once every about 30 minutes, and extraction was performed so that the perilla powder and methanol could be mixed.

(All experiments described below were all carried out for extracts prepared using the extraction solution containing water, methanol, or ethanol, and the average value was calculated and summarized.)

Using Whatman(R) qualitative filter papers (Grade 1, GE Healthcare Life Science, Seoul, Korea), the mixed solution contained in the constant temperature water tank was filtered.

The extract obtained through filtration is concentrated to a semi-solid state using a vacuum concentrator (RV10, IKA® Korea, Ltd., Seoul, Korea), and then dried in a dryer at about 60° C. for about 1 week, and then semi-solid granules. A dried extract in the form (dry extract) was obtained.

The dried extract was sealed and stored at -80°C. The amount of the dried extract obtained was about 0.318 g, and was extracted and concentrated in a ratio of about 94.3:1 compared to the perilla.

Cytotoxicity test: 1,2,3- Butanetriol

First, in order to investigate the biotoxicity of 1,2,3-butanetriol, culture survival experiments of human fibroblasts according to changes in 1,2,3-butanetriol concentration were performed.

The initial seeding density was set to 5000 cells/well based on 96 wells, and the culture conditions were as follows.

DMEM (Dulbecco's Modified Eagle Medium) + FBS (Fetal Bovine Serum) 10%; 37°C, 5% CO ₂ ;

12 hours after seeding, 1,2,3-butanetriol was treated at different concentrations to determine cytotoxicity, and 48 hours after 1,2,3-butanetriol treatment, Dojindo Cell Counting Kit- After dispensing 10 µl per well of 8 and incubating for 2 hours at 37°C, cell viability was measured at 450 nm Absorbance.

The measurement results are shown in FIG. 1.

FIG. 1 is a graph showing the culture survival rate of human fibroblasts according to changes in 1,2,3-butanetriol concentration, and the horizontal axis of FIG. 1 shows the concentration of treated 1,2,3-butanetriol in mM It is marked as.

Referring to Figure 1, it can be seen that the viability of the cells is not significantly lowered at a concentration of about 12.5mM or less, and it can be seen that the cell viability is about 50% at a concentration of about 25mM.

Cytotoxicity test: Perilla extract

In order to investigate the biotoxicity of perilla, a culture survival experiment of human fibroblasts according to the change in concentration of perilla extract was conducted.

The initial seeding density was set at 8000 cells/well based on 96 wells, and the culture conditions were as follows.

DMEM (Dulbecco's Modified Eagle Medium) 10%; + Fetal Bovine Serum (FBS) 1%; 37°C, 5% CO ₂ ;

12 hours after seeding, perilla extracts were treated at different concentrations to determine cytotoxicity. After 24 hours of treatment, 10 µl per well of Dojindo Cell Counting Kit-8 was dispensed at 37°C for 2 hours. After incubation, cell viability was measured at 450 nm Absorbance.

The measurement results are shown in FIG. 2. (Cell viability (-BT)))

Referring to FIG. 2, it can be seen that the viability of the cells is not significantly reduced at a concentration of about 0.10 mg/ml or less, or about 0.05 mg/ml or less.

Cytotoxicity test: Perilla extract+1,2,3- Butanetriol

In the'Cytotoxicity Test: Perilla Extract', the same experiment was conducted except that the concentration of butanetriol was added to be about 0.0625 mM, and cell viability was measured.

The measurement results are shown in FIG. 2. (Cell viability (+BT)))

Antibacterial test: 1,2,3- Butanetriol

In order to examine the inhibitory effect of 1,2,3-butanetriol alone on bacterial activity in plaque, bacterial strains were prepared as follows.

First, plaques from three study participants were collected and cultured for 24 hours in BHI medium (Brain Heart Infusion 4g / 160ml distilled water-DDW) to which 1 wt.% of sucrose was added.

From the above cultured strain, gDNA was extracted, and the bacteria were identified through PCR.

The identified bacterial species are shown in Table 1 below.

Fungal species Abbreviation Aggregatibacter actinomycetemcomitans Aa Porphyromonas gingivalis Pg Tannerella forsythia Tf Treponema denticola Td Fusobacterium nucleatum Fn Prevotella nigrescens Pn Streptococcus mutans Sm Prevotella intermedia Pi Eubacterium nodatum En Parvimonas micra Pm Eikenella corrodens Ec Total bacterial load Tb Campylobacter rectus Cr Streptococcus sobrinus Ss

Prepare 1 wt.% sucrose-added BHI medium (Brain Heart Infusion 4g / 160ml distilled water-DDW), sterilize it in a high-temperature and high-pressure autoclave, and then 1,2,3-butanetriol to each concentration. (1,2,3-BT) was dispensed to prepare 96 well microplates containing 180 µl of culture solution.

Here, 20 µl per well of the culture medium in which bacteria in plaque prepared above were proliferated were dispensed.

This microplate was placed in a Biotek Synergy 2 microplate reader and the temperature was adjusted to 37°C, and the absorption rate was measured at 600nm.

The measurement results are shown in FIG. 3.

Apart from the absorption rate measurement, gDNA was extracted from the well microplate after butane triol treatment, and the results confirmed through PCR are shown in FIG. 3.

3 and 4 are graphs showing the inhibitory effect of 1,2,3-butanetriol on oral bacteria.

Referring to FIG. 3, when 1,2,3-butanetriol is treated, it can be confirmed that bacterial proliferation is suppressed considerably. When 12 hours have elapsed after incubation, 1,2,3-butanetriol Compared to the case where ol is not treated, it can be clearly confirmed that the bacterial proliferation inhibitory effect is expressed at least about 10% or more and at most about 50%. Referring to FIG. 4, for each bacterial species, 1,2,3 -The effect of inhibiting the growth of butanetriol can be clearly confirmed.

Antibacterial test: Perilla extract

In order to examine the antibacterial properties of the perilla extract, bacterial strains were prepared as follows.

First, plaque from three study participants was collected, and about 0.01 g of plaque was added to BHI medium (Brain Heart Infusion 1.25g / 50ml distilled water-DDW) to which 5 wt.% of sucrose was added, and about 24 hours at about 37℃. During incubation.

This culture was diluted 1:10, inoculated into 96 wells, and treated with different concentrations of perilla extract in each well.

This was incubated again in an incubator at about 37° C. for about 24 hours, and then absorbance was measured under OD 600 nm conditions.

The measurement results are summarized in FIG. 2. (Bacterial viability (-BT)

Referring to FIG. 2, when the perilla extract is added, it can be clearly confirmed that the growth of bacteria is greatly reduced. In particular, in the section of more than about 0.00 mg/ml to about 0.05 mg/ml, the growth of bacteria according to the concentration gradient It can be clearly seen that sex is greatly influenced.

Antibacterial test: Perilla extract +1,2,3-butanetriol

In the'antibacterial test: Perilla extract', the same experiment was conducted except that the concentration of butanetriol was added to be about 0.0625 mM, and the degree of decrease in the growth properties of the bacteria was measured.

The measurement results are summarized in FIG. 2. (Bacterial viability (+BT)

Referring to FIG. 2, when 1,2,3-butanetriol is added even in a very small amount to the perilla extract, the perilla extract is used alone due to a synergistic effect while almost no toxicity to normal normal cells. It can be clearly confirmed that the growth of bacteria is further lowered than when the concentration is greater than about 0.00 mg/ml and less than about 0.0503 mg/ml, and it can be clearly confirmed that bacterial growth is greatly influenced by the concentration gradient.

Claims (10)

In the pharmaceutical composition for the prevention or treatment of oral diseases, comprising a perilla (Peirllae Fructus) extract and 1,2,3-butanetriol,
The oral disease, including any one or more of halitosis, dental caries, gingivitis, and periodontitis, oral disease prevention or treatment pharmaceutical composition.
delete The method of claim 1,
The 1,2,3-butanetriol, containing 0.0001 wt.% to 0.250 wt.% concentration, oral disease prevention or treatment pharmaceutical composition.
The method of claim 1,
The perilla ( Perilla frutescens Britton var. acuta Kudo ) seeds or wrinkled lobules ( Perilla frutescens Britton var. crispa Decaisne ) containing any one or more of the seeds, oral disease prevention or treatment pharmaceutical composition.
The method of claim 1,
The perilla extract is composed of water, methanol, ethanol, propanol, isopropanol, butanol, acetone, ether, ethyl acetate, methylene chloride, n-hexane, hydrochloric acid, acetic acid, formic acid, diethyl ether, and cyclohexane from perilla. Extracted using one or more solvents selected from the group, oral disease prevention or treatment pharmaceutical composition.
The method of claim 1,
The perilla extract is a perilla extract extracted and concentrated in a ratio of 10:1 to 500:1;
The perilla extract is contained in a concentration of 0.15 mg / ml015 wt.% or less, oral disease prevention or treatment pharmaceutical composition.
The method of claim 1,
Water-soluble zinc salt, vitamin B group, vitamin C, and further comprising one or more additives selected from the group consisting of vitamin E, oral disease prevention or treatment pharmaceutical composition.
The method of claim 7,
The additive is contained in a concentration of 0.001 wt.% to 10 wt.%, oral disease prevention or treatment pharmaceutical composition.
The method of claim 1,
Aggregatibacter actinomycetemcomitans ( Aggregatibacter actinomycetemcomitans ), Tannerella forsythia , Treponema denticola ( Treponema denticola ), Prevotella nigrescens ( Prevotella nigrescens ), Eubacterium no Eubacterium nodatum , Parvimonas micra , Eikenella corrodens , Campylobacter rectus , Fusobacterium nucleatum ATCC 25586, Strepto Streptococcus sobrinus , Streptococcus salivarius GTC0215, Streptococcus anginasus FW73, Streptococcus mutans JCM5705, Streptococcus mutans JCM5705 Prevotella intermedia ATCC 25611), and Porphyromonas gingivalis (Pharphyromonas gingivalis W83, ATCC 33277 (F), FDC 381) having antibacterial activity against at least one bacteria selected from the group consisting of, oral disease prevention or treatment pharmaceutical Ever composition.
The method of claim 1,
Oral tablets, oral sprays, oral ointments, oral varnishes, and having one or more formulations selected from the group consisting of oral patches, oral disease prevention or treatment pharmaceutical composition.

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