KR0143191B1 - Compositions for preventwn and treatment of periodontal disease - Google Patents

Abstract

The present invention relates to a periodontal disease preventive and therapeutic agent composition containing a thick leaf extract and a ginkgo leaf extract as an active ingredient. Thick leaf x and ginkgo biloba X-containing composition according to the present invention exhibits an excellent effect of preventing and treating periodontal disease, as compared to conventional periodontal disease prevention and treatment.

Description

Periodontal disease prevention and treatment composition

The present invention relates to a composition for preventing and treating periodontal disease.

Periodontal disease is clinically gingival bleeding, swelling, formation of periodontal pockets and destruction of alveolar bone. The causes of periodontitis include local and systemic factors. When the plaque is mechanically accumulated in the periodontal sac, it becomes a habitat for bacteria present in the periphery. It gradually migrates into bacteria and multiplies deep into the periodontal sac. At this time, the toxins and all products of the proliferated anaerobic Gram-negative bacteria directly destroy tissues or stimulate the immune system, which causes inflammation and periodontal tissue destruction by various actions from the stimulated immune system.

As a defense mechanism, the function and immune response of polymorphonuclear leukocytes act as systemic factors.

However, antimicrobial and bacteriostatic action against anaerobic gram-negative bacteria, which are the underlying local disease, and the removal and destruction of damaged and lost periodontal tissues, which are toxic products of these bacteria, are important for the prevention and treatment of periodontal disease. It is known to be a key.

The prevention and treatment of periodontal disease has been conducted a lot of research since the 1920s, especially in Western countries have focused on the removal of plaque using antibiotics and chemotherapy.

These studies have been developed more actively since 1970, when the contours of periodontal pathogens among the bacteria in plaque have been identified, such as Listerin, a phenolic compound, Scofu, a quaternary ammonium compound, and ferritex, chlorhexidine. It is currently marketed in Gumi and imported and sold in Korea.

Listerin or scopu of the formulation is a chemotherapy agent with minor side effects, but it does not have the excellent effect of removing plaque and antibacterial effect. Peritex, a chlorhexidine preparation, exhibits very effective removal of plaque and antibacterial effects. Oral mucosal ulcers, exfoliative gingivitis, pigmentation, etc. appear, and long-term use has been reported to have side effects such as dry mouth.

Therefore, in order to express a perfect periodontal disease prevention and treatment effect, it was necessary to have an antimicrobial and bacteriostatic action against anaerobic gram-negative bacteria and to remove the inflammation and restore the destroyed and lost periodontal tissue. .

From this point of view, the present inventors showed selective antimicrobial activity against periodontal pathogens while researching herbal medicines useful for preventing and treating periodontal disease, while existing antibiotics or antimicrobial chlorhexidine, phenolic compound, listerin, and quaternary ammonium compound, Sco. This product is free from long-term use of balance, fungal expression, exfoliation of periodontal tissue and risk of carcinogenicity. It has been reported to have antibacterial activity against Streptococcus mutans, the causative agent of tooth decay. (Japanese Patent Application Publication No. Hei 2-17524), and the present inventors reported that the present invention has an excellent bactericidal action against the anaerobic Gram-negative bacteria Prevotella intermedia, one of the causative bacteria of periodontal disease (Korean Patent Application) No. 92-16516), the inhibitory effect of the extract and the collagenase has been reported (Bull, Tok) yo.Dent.Col., 2, 1991. 32 (1) .P.1-7), a causative agent for periodontal disease caused by the composition of ginkgo biloba extract (published in Korea) published by the present inventor with excellent tissue regeneration effect As a result of comparing and measuring the minimum inhibitory concentrations and the anti-inflammatory effect and tissue regeneration effect according to the gingival bleeding index, it is perfect periodontal effect by antimicrobial, bacteriostatic, anti-inflammatory and tissue regeneration effects superior to existing periodontal disease prevention and treatment It was confirmed that the disease can be prevented and treated effect has been completed the present invention.

The present invention relates to a composition for preventing and treating periodontal disease, which contains the thick leaf extract and the ginkgo leaf extract as active ingredients.

The latex extract used in the present invention was extracted from the latex and used as the main ingredient Magnolol (Magnolol) of 5.0% or more, Honokiol (1.0% or more), and the ginkgo leaf extract of France Bupo-Ipsen (Beufour-Ipsen) Standardized ginkgo biloba extract manufactured by Co., Ltd.) was used as a raw material (Batch No. EGB761) containing more than 24% as total Ginkgo heterosides.

The combination composition of the thick gourd extract and ginkgo biloba extract of the present invention may be added with conventional pharmaceutical excipients, and may be prepared in the form of tablets, ointments, toothpastes, solutions (gagle), sprays. For example, it can be included alone in a dentifrice composition, and can be mixed with a conventional carrier and formulated as an ointment or solution to be used as a prophylactic and therapeutic agent for periodontal disease. The composition of the present invention may also further contain at least one other agent.

It can also be included in conventional gargles to rinse your mouth after brushing your teeth, or spray it onto the periodontal disease by packing it in a compressed container with a propellant, and incorporating it in the dentifrice component to continuously prevent and treat periodontal disease for a long time. You can also get In such formulations, the mixing ratio of the ginkgo biloba extract and the thick extract may vary widely, and there is a slight difference depending on the drug difference between the external preparation and the internal preparation, but preferably 1: 1 to 10 (weight ratio), in particular Preferably it is 1: 1-6 (weight ratio). If the combination ratio of ginkgo biloba extract and thick leaf extract exceeds 1:10, the therapeutic effect is worsened. If the ratio is lower than 1: 1, there is no synergistic effect by the combination.

The effective content range of the combination of thick pepper x and ginkgo leaf x in the whole composition may vary depending on the purpose of use, but if the concentration is too low, the effect drops sharply. Drop, and the stability of the formulation can be reduced, and the synergistic effect of increasing the content is also reduced, so in the case of tablets it is 10 to 500 mg, preferably 30 to 250 mg per tablet, and the ointment is 0.1 to 10.0% by weight, preferably 0.2 to 5.0% by weight, more preferably 0.3 to 2.0% by weight, and toothpaste, liquid or spray is 0.05 to 5.0% by weight, preferably 0.1 to 2.0% by weight, more preferably 0.3 to 1.0% by weight.

Hereinafter, the present invention will be described in detail with reference to Examples, which are not intended to limit the present invention.

Experimental Example 1 Preparation of Thick X from Thick

100 g thick slices were cut thinly, extracted twice with 1.5 L of 75% ethanol in a water bath at 60 ° C., filtered, and the filtrate was concentrated to obtain X 20 g. This extract was used as the standard for the thick extract extract.

Experimental Example 2: Pharmacological Activity Test of Thick Gum and Ginkgo Bilum Extracts

Experimental Example 1) Antimicrobial Activity Test of Periodontal Pathogens of Thick Gum and Ginkgo Bilum Compositions

Eight standard strains of periodontal pathogens purchased from ATCC in the United States, NCTC in the UK, and the College of Dentistry at New York State University were used. The standard strains were anaerobic Gram-negative bacteria Porphyromonas gingivalis W50, Prevotella intermedia 25611, Veillonella dispar 17745, and the breathable Gram-negative bacterium ginggivala Capnocytophaga gingivalis 33596, Sputigena 33612, Actinobacilluctinomycetemcomitans Y4, Gram-positive bacteria Actinomyces viscosus 15987 naeslundii) 12104 was selected and the minimum inhibitory concentration (MIC) was calculated for each bacterium using agar medium dilution.

The medium used at this time was tryticase soy agar agar blood medium, and chlorhexidine diglucose, which is known as a hickax x and ginkgo biloba extract, alone and in combination (Hakax: Ginkgo biloba x = 4: 1) and control, respectively. Dilute each component twice with Nate, Listerine, and Myrrh, inoculate one of the eight strains into the medium, and incubate for 3 to 5 days in an anaerobic and 10% carbon dioxide incubator As a result of comparative experiments to confirm the presence or absence, the minimum bacterial growth inhibition concentration (MIC) is shown in Table 1 below.

As a result of the above comparative experiments, the composition of the hubac x and ginkgo biloba extracts was inferior in antimicrobial activity to the chemotherapeutic agents chlorhexidine and listerine, but had a slightly superior antimicrobial activity compared to myrrh, a herbal drug used as an antimicrobial agent.

Experimental Example 2) Anti-inflammatory effect by gingival bleeding index and anti-mortar effect by plaque index

Healthy adults without gingivitis were selected regardless of gender, and the selected teeth were examined for maxillary and mandibular 6 anterior teeth. One week before the experiment, oral cleansing was performed so that the gingival hemorrhage index and plaque index were zero. Negative control group containing no drug in this study, Experimental group I (thickness x 0.4w / w%), Experimental group II (ginkgo leaf x 0.1w / w%), Experimental group III (thickness x 0.4w / w% and ginkgo leaf X 0.1w / w% combination composition), chlorhexidine preparations having the best anti-inflammatory effect and plaque removal effect currently commercialized as the positive control group (group containing 0.12% chlorhexidine). No brushing was allowed for 4 days and only the experimental cleaning agent was used.

Doses and regimens wash 10 ml of detergent three times a day after meals. The gingival hemorrhage index and plaque index were examined before and 5 days after the experiment, respectively. For the analysis of the experimental results, differences between the experimental groups were verified by two-way analysis of variance of 5% and 1% significance. The results of the gingival bleeding index study are shown in Table 2 and the results of the plaque index are shown in Table 3, respectively.

*: Significant differences in 95% confidence limits

*: Significant difference in 95% confidence limits

The anti-inflammatory effect of gingival hemorrhagic bleeding index showed similar effect to chlorhexidine, a chemotherapeutic chlorhexidine, and anti-chiropractic effect of gingival index was similar to or slightly lower than chlorhexidine. It has been shown that the combination of the bakbak x and ginkgo biloba extracts have an excellent anti-inflammatory effect and anti- plaque effect comparable to the chemotherapeutic chlorhexidine.

Experimental Example 3: Comparative experiment on the proliferation of gingival tissue cells

In order to determine the effect of the thick gourd and ginkgo biloba extract composition used in the present invention on the proliferation of gingival tissue cells, a chlorhexidine known as a combination of the hoo bak x, ginkgo biloba extract, hoo bak x and ginkgo biloba extract and a comparison Samples were prepared at concentrations of 100 μg / ml each. In this experiment, subcultured human fibroblasts were treated with 0.25% trypsin-EDTA solution and centrifuged to form cell suspensions with culture medium, followed by 10% FBS, 100 U / ml penicillin, and 100 µg / ml streptomycin. Minimum required medium was incubated by transferring 200 μl into the microplate wells. The next day the medium was changed and the second day the medium was removed and washed with HBSS (Hank's balanced salt solution), followed by adding 200 μl of the added medium to the sample, which was then incubated at 37 ° C., 5% CO ₂ , and 100% humidity for 24 hours. After the incubation was completed, 50 μl of 3- (4,5-dimethyltriazol-2-yl) -2,5-dimethyltriazolum bromide (hereinafter referred to as MTT) solution dissolved in physiological saline was added to each plate hole. After 4 hours of further incubation, the MTT solution was discarded, and 50 μl of dimethyl sulfoxide (DMSO) was added in order to dissolve the formazon crystals. After shaking the plate well, the absorbance was measured at 570 nm with an MOLECULAR DEVICES Co. USA. As a control, a minimum required medium culture plate hole without a sample added to each experiment was used. All experimental results were calculated as a percentage of the control group, and the results are shown in the following Table 4.

As a result of the above experiment, chlorhexidine showed about 55% cell proliferation inhibitory effect compared to the control group without adding the sample. About 30% showed a cell growth promoting effect, and the combination composition of ginkgo biloba X and hickak x (1: 4) showed a clear cell growth promoting effect of about 45%. In this regard, it was confirmed that the combination composition of the thick gourd and ginkgo biloba extracts had a great effect on the regeneration of tissue defects in the gingival tissue, connective tissue and periodontal ligament injury of the periodontal tissue.

On the other hand, the stability of ginkgo biloba extracts showed that the acute toxicity of ginkgo biloba extracts was LD ₅₀ (50% lethal dose) of 7,725 mg / kg orally in mice and 10,000 mg / kg orally in rats. Because it is kg, it is known as a very safe drug.

The combination composition of the thick leaf extract and the ginkgo leaf extract of the present invention can be prepared by conventional pharmaceutical methods, for example, in the form of tablets, ointments, toothpastes, solutions, sprays, and the combination ratio of the ginkgo leaf extract and the thick leaf extract is preferred. Preferably 1: 1 to 10 (weight ratio), particularly preferably 1: 1 to 6 (weight ratio), and examples of the compositions are as follows.

Example 1: Film coated tablets-1 tablet (600 mg)

Thick X 30mg

Ginkgo biloba X 30mg

Lactose 525mg

5 mg of hydroxypropyl cellulose

Magnesium Stearate 3mg

Glycerin 2mg

Hydroxypropylmethylcellulose 5mg

Prepared according to the conventional tablet manufacturing method, the dosage is 3 times a day, 1 tablet once.

Example 2: Film coated tablets-1 tablet (600 mg)

Thick X 200mg

Ginkgo biloba X 50mg

Lactose 335mg

5 mg of hydroxypropyl cellulose

Magnesium Stearate 3mg

Glycerin 2mg

Hydroxypropylmethylcellulose 5mg

Prepared according to the conventional tablet manufacturing method, the dosage is 3 times a day, 1 tablet once.

Example 3 Ointment (Value by Weight)

Carboxy Vinyl Polymer 7.00

Glycerol 30.00

Peppermint Oil 0.006

Propylene Glycol 30.00

Thick X 0.30

Ginkgo biloba X 0.05

Add distilled water to make 100

The composition is mixed with a conventional ointment manufacturing method to prepare an ointment and is often applied around the tooth with oral periodontitis to treat periodontitis or gingivitis.

Example 4 Ointment (Value by Weight)

Carboxyvinyl Polymer 7.00

Glycerol 30.00

Peppermint Oil 0.006

Propylene Glycol 30.00

Thick X 0.30

Ginkgo biloba X 0.05

Add distilled water to make 100

The composition is mixed with a conventional ointment preparation method to prepare an ointment, and is often applied around the tooth with oral periodontitis to treat periodontitis or gingivitis.

Example 5 Toothpaste (Numeric Value)

Alumina 25.00

Propylene Glycol 30.00

Carboxymethyl Cellulose Sodium 2.00

Aspartame 0.30

Sodium Lauryl Sulfate 1.00

Peppermint 0.50

Thick X 0.30

Ginkgo biloba X 0.05

Add distilled water to make 100

Toothpaste was prepared by mixing the composition by a conventional toothpaste manufacturing method, and gargled with toothpaste, thereby preventing and treating gingivitis and periodontitis.

Example 6 Toothpaste (Numeric Value)

Alumina 25.00

Propylene Glycol 30.00

Carboxymethyl Cellulose Sodium 2.00

Aspartame 0.30

Sodium Lauryl Sulfate 1.00

Peppermint 0.50

Thick X 0.60

Ginkgo biloba X 0.10

Add distilled water to make 100

Toothpaste may be prepared by mixing the composition by a conventional toothpaste manufacturing method, and gingivitis and periodontitis may be prevented and treated by brushing teeth using toothpaste.

Example 7 Solution (Weight Value)

Polyethylene Glycol 7.00

Ethanol 5.00

Peppermint Oil 0.06

Thick X 0.30

Ginkgo biloba X 0.05

Add distilled water to make 100

It was possible to prevent and treat gingivitis or periodontitis by mixing and dissolving the composition in a conventional liquid preparation method and adjusting the pH to 5.5 to prepare a solution and gargle with a mouthwash 2 to 3 times a day.

Example 8 Solution (Values in Weight)

Polyethylene Glycol 5.00

Ethanol 5.00

Peppermint Oil 0.06

Thick x 0.60

Ginkgo biloba X 0.10

Add distilled water to make 100

It was possible to prevent and treat gingivitis or periodontitis by mixing and dissolving the composition in a conventional liquid preparation method and adjusting the pH to 5.5 to prepare a solution and gargle with a mouthwash 2 to 3 times a day.

[Example 9]: Atomizer (value in weight%)

Thick X 0.30

Ginkgo biloba X 0.05

Trichloromonofluoromethane 40.00

Dichlorodifluoromethane 45.00

Peppermint Oil 0.15

Ethanol 6.00

Polyethylene Glycol 8.40

The composition was mixed by a conventional spray preparation method and filled and packed in a compression container spray spray application to the periodontal disease site from time to time to prevent and treat periodontal disease.

Example 10 Spray (Numerical Value by Weight)

Thick x 0.60

Ginkgo biloba X 0.10

Trichloromonofluoromethane 40.00

Dichlorodifluoromethane 45.00

Peppermint Oil 0.15

Ethanol 6.00

Polyethylene Glycol 8.40

The composition was mixed by a conventional spray preparation method and filled and packed in a compression container spray spray application to the periodontal disease site from time to time to prevent and treat periodontal disease.

Example 11 Stability Test of Samples

In order to determine the stability of the samples prepared in Examples 1 to 10 ginkgo biloba extract content of the sample according to the content test method of Ginkgo biloba extract terms of the National Institutes of Health, 365nm of the UV detector by high performance liquid chromatography (HPLC) method In the analysis, the thickness of magnolol and honokiol was analyzed by high-performance liquid chromatography (HPLC) at 254 nm of the UV detector, and the results are shown in Table 5 below.

Storage condition

-Test material: The samples prepared in Examples 1 to 10 were put in a glass bottle or a compression container, sealed with a cap, and then placed in a cardboard box.

-Storage condition: 40 ℃ (± 1 ℃)

However, the spraying agents of Examples 9 and 10 were stored at room temperature.

Measurement time: Immediately after manufacture, after 2 months, after 4 months, after 6 months

-Test item: Gingcoflavone glycoside content of Ginkgo biloba extract,

Contents of Magnool and Honokiol in Thick X

Claims (11)

A periodontal disease prevention and treatment composition comprising a composition comprising a ginkgo leaf extract and a thick leaf extract in a ratio of 1: 1 to 10 by weight. The composition of claim 1 wherein the formulation is a tablet, ointment, toothpaste, liquid or spray. The composition of claim 2, wherein the formulation is a tablet. 4. A composition according to claim 3, wherein the composition contains 10 to 500 mg of a combination of ginkgo biloba extract and thick leaf extract per unit tablet. 5. A composition according to claim 4, wherein the composition contains 30 to 250 mg of a combination of ginkgo biloba extract and thick leaf extract per unit tablet. The composition according to claim 2, which is an ointment formulation which contains 0.1 to 10.0% by weight of the combination of ginkgo biloba extract and thick pepper extract per unit formulation. 7. A composition according to claim 6, wherein the composition comprises 0.2 to 5.0% by weight of a combination of ginkgo biloba extract and thick pepper extract per ointment unit preparation. The composition according to claim 2, wherein the composition is a toothpaste, liquid or spray formulation containing 0.05 to 5.0% by weight of the combination of ginkgo biloba extract and thick leaf extract per unit formulation. The composition according to claim 8, wherein the composition contains 0.1 to 2.0% by weight of the combination of ginkgo biloba extract and thick rim extract per dentifrice solution or spray unit formulation. The composition of claim 1, wherein the weight ratio of the ginkgo biloba extract and the thick vine extract is 1: 1 to 6. The composition of claim 1 further containing at least one other agent.