KR101450098B1 - Composition for cleaning oral cavity containing fucoidan - Google Patents

Abstract

The present invention relates to a composition for oral cleansing comprising a fucoidan as an active ingredient or an antimicrobial composition for oral microorganisms. The fucoidan according to the present invention has an excellent antibacterial effect against various oral microbes and thus can be effectively used as a composition for oral cleaning or a composition for antimicrobial against oral microorganisms, And can be usefully used for prevention or treatment of diseases.

Description

TECHNICAL FIELD The present invention relates to a composition for oral cavity containing fucoidan as an active ingredient,

The present invention relates to a composition for oral cleansing comprising a fucoidan as an active ingredient or an antimicrobial composition for oral microorganisms.

The oral cavity is a place to provide energy to the human body, and its physical condition is immediately reflected. In particular, oral bacteria, which are the cause of oral diseases, invade blood vessels through the blood to reach other parts of the body and cause systemic diseases such as heart disease, stroke, diabetes, premature birth and low birth weight (Jin LJ, et al. Hong Kong Med J.9: 31-37 (2003), Pennisi E, Science, 307: 1899-1901 (2005), Xu P, et al., J Bacteriol. 189: 3166-3175 (2007)).

The teeth are minerals made of calcium phosphate. The diseases are mainly tooth decay and periodontal diseases. Cavities account for the majority of dental diseases, from children to adults, and the incidence is increasing. According to the Korean Dental Association, more than 90% of children experience dental caries and more than 80% of adults have gum disease. The main cause of these cavities is infection by microorganisms in the mouth, which is caused by the interaction of bacteria, food, and saliva. In other words, nutrients and moisture required for the development of oral bacteria are supplied by food, saliva, and saliva, and the environment in the oral cavity has a temperature (37 ° C) and pH (near neutrality) suitable for the development of microorganisms.

Streptococcus mutans and Prevotella intermedia are representative microorganisms causing periodontal disease. The microorganisms cause microbial metabolic processes that produce sucrose present in the food as glucose and fructose and form insoluble glucan (Glucan), which is a polymer of glucose, on the tooth surface. In this process, other microorganisms in the oral cavity attach to the tooth surface, forming a dental plaque. Lactic acid accumulated inside the formed plaque dissolves the enamel on the tooth surface, resulting in tooth decay. In addition, periodontal disease occurs due to the dissolution of the discomfort caused by the products of the growth of various bacteria.

To suppress tooth decay and periodontal disease, antimicrobial substances such as sodium bicarbonate (NaHCO ₃ ), triclosan (C ₁₂ H ₇ Cl ₃ O ₂ ), polyphosphate, sodium fluoride (NaF), vancomycin, Antibiotics such as chlorhexidine and spiramycin, or organic / inorganic fluorine have been used. However, the above methods are effective for preventing tooth decay, but their use is limited due to the disadvantage of vomiting, diarrhea, and antibiotic resistance. Especially, antibiotics are generally used for bacterial infectious diseases such as tooth decay and periodontitis, but antibiotics not only harm all the beneficial bacteria of the human body, but also cause the emergence of resistant bacteria, immunity of the patient, Such as anaphylaxis, and the like.

Currently, oral disease preventive agents and remedies are 1) bisbiguanide chlorhexidine, 2) sodium lauryl sulfate, a negative charge detergent, 3) dextrinase dextranase and mutanase; 4) essential oils such as thymol and eucalyptol; 5) quaternary ammonium compound cetylpyridinium chloride; Hexetidine, 6) phenolic triclosan, 7) organic or inorganic fluorine, 8) sugar substitute D-xylose, xylitol, D-sorbitol and the like. Bisbiguanide chlorhexidine is an antibiotic of positively charged detergents and is widely used in periodontal therapy to suppress Gram-negative bacteria. This inhibits the glucosyltransferase enzyme necessary for the accumulation of bacteria on the tooth surface and the phosphophenol pyruvate phosphotransferase enzyme necessary for metabolism. However, it is adsorbed on the surface of enamel or tartar to make it permanently brownish, and it also causes burning sensation or loss of appetite when used for a long time. Sodium lauryl sulfate, which is a negative charge detergent, is effective against Gram-positive bacteria but has a disadvantage that it is ineffective against Gram-negative bacteria. Enzymes such as dextrinase (α-1,6-glucosidase) and α-1,3-glucosidase were attempts to destroy the polysaccharide formed by plaque, but in In vitro , however, it is known that in vivo , it is impossible to penetrate into the gingiva itself due to the molecular character of the gingival matrix. Heterocyclic quaternary ammonium compound hexetidine has antibacterial and antifungal activity and thus has no effect on Gram-positive bacteria or Gram-negative bacteria. Therefore, it has not yet been commercialized. It has a disadvantage of inhibiting the action. Phenolic triclosan has a hydrophobic part and a hydrophilic part and has a broad antibacterial effect, but it has a disadvantage that it is difficult to be water-soluble. The method of inhibiting caries bacteria by organic or inorganic fluorine is now known to be the most widely used method, and it is known that fluoride inhibits demineralization and promotes remineralization, and it is evaluated that there is also an actual antibacterial effect. However, there is a problem in the purpose of prevention of dental caries because it can cause fluorosis in which white spots appear on teeth. D-xylose, xylitol and D-sorbitol, which are sugar substitutes, have been absorbed into the body, causing the caries-inducing bacteria not to be used for metabolism. However, diarrhea is caused by diarrhea at the same time There is a disadvantage.

Accordingly, the present inventors have made efforts to develop a substance having no antitumor effect and selective antimicrobial activity against harmful oral microorganisms. As a result, it has been confirmed that fucoidan has excellent antimicrobial activity against various oral microorganisms.

Domestic Patent Application Number: 10-2001-7004043

It is an object of the present invention to provide a composition for oral cleaning comprising fucoidan as an active ingredient.

It is still another object of the present invention to provide a composition for antimicrobial use for oral microorganisms containing fucoidan as an active ingredient.

It is still another object of the present invention to provide a pharmaceutical composition for preventing or treating periodontal disease comprising fucoidan as an active ingredient.

It is still another object of the present invention to provide a food composition for preventing or ameliorating periodontal disease comprising fucoidan as an active ingredient.

In order to achieve the above object, the present invention provides a composition for oral care comprising fucoidan as an active ingredient.

The present invention also provides an antimicrobial composition for oral microorganisms comprising fucoidan as an active ingredient.

The present invention also provides a pharmaceutical composition for preventing or treating periodontal disease comprising fucoidan as an active ingredient.

The present invention also provides a food composition for preventing or ameliorating periodontal disease comprising fucoidan as an active ingredient.

The fucoidan according to the present invention has an excellent antibacterial effect against various oral microbes and thus can be effectively used as a composition for oral cleaning or a composition for antimicrobial against oral microorganisms, And can be usefully used for prevention or treatment of diseases.

Figure 1 shows that when combined with fucoidans and antibiotics, Streptococcus mutans mutans ) through the time-kill curve.
Figure 2 is when used in combination with antibiotics and fucoidan (fucoidan), Streptococcus sanggwi varnish (Streptococcus sanguinis ) through the time-kill curve.
Figure 3 shows that when antibiotics were used in combination with fucoidan, Streptococcus < RTI ID = 0.0 > sobrinus ) through a time-kill curve.
4 is a diagram illustrating through a fucoidan (fucoidan) and when used in combination with antibiotics, Streptococcus Lahti time kill curves for antibiotic activity for (Streptococcus ratti).
Figure 5 shows that, when fucoidans and antibiotics were used in combination, Streptococcus criceti ) through a time-kill curve.
Figure 6 shows that when combined with fucoidan and antibiotics, Streptococcus godoni gordonii ) through the time-kill curve.
Figure 7 shows that when combined with fucoidan and antibiotics, Streptococcus anginosus ) through a time-kill curve.
Figure 8 shows that when fucoidans and antibiotics were used in combination, actinobacillus actinobacillus ( Actinobacillus < RTI ID = 0.0 > actinomycetemcomitans ) through a time-kill curve.
Figure 9 shows that when combined with fucoidans and antibiotics, Fusobateria < RTI ID = 0.0 > nucleatum ) through a time-kill curve.
Figure 10 shows that when fucoidans and antibiotics were used together, Prevotella intermedia ) through a time-kill curve.
Figure 11 shows that when combined with fucoidans and antibiotics, Porphylomonas < RTI ID = 0.0 > gingivalis ) through a time-kill curve.
.

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

The fucoidan of the present invention is a kind of polysaccharide and is composed of a small amount of galactose, xylose, mannose and glucuronic acid while L-fucose has a skeleton of? -1,2 or? -1,3 bonds have. Generally, it has a molecular weight of 20 kDa to 170 kDa, and it is a viscous polymer. It is mainly contained in mucous of mollusk such as sea cucumbers, abalone, squid, or brown algae such as seaweed or sea tangle. The fucoidan of the present invention can be obtained by using commercially available or extracting it.

The fucoidan according to the present invention has excellent antibacterial activity against oral microorganisms, i.e., cariogenic bacterial strains and periodontopathogenic bacterial strains. In addition, the fucoidan exhibits an antibiotic-merge effect on oral microorganisms when used in combination with an antibiotic. The kind of the antibiotic is not limited, but is preferably ampicillin or gentamicin.

As described above, the fucoidan according to the present invention has an excellent antibacterial effect against various oral microbes, and thus can be effectively used as a composition for oral cleaning or a composition for antimicrobial against oral microorganisms. Which can be used for preventing or treating periodontal disease.

The present invention provides a composition for oral cleaning comprising fucoidan as an active ingredient.

The composition for oral cleaning according to the present invention is not particularly limited in its formulation, and specific examples may include formulations such as toothpaste, mouthwash, mouthwash, gum, candy, mouth spray, mouthwash, and the like.

When the oral cleaning composition of the present invention is a toothpaste formulation, it may contain an abrasive, a wetting agent, a binder, a foaming agent, a sweetener, a pH adjusting agent, a preservative, a medicinal ingredient, a fragrance, a brightener, a colorant and a solvent. The toothpaste may also be applied to conventional ointment (paste) tubes as formulations and packaging of the final product.

Examples of the abrasive include precipitated silica, silica gel, zirconium silicate, calcium monohydrogenphosphate, calcium monohydrogenphosphate anhydrous, hydrated alumina, light calcium carbonate, heavy calcium carbonate, calcium pyrophosphate, insoluble metaphosphate and aluminum silicate. The abrasive component may be added alone or in admixture of 5 to 60% by weight based on the total weight of the composition. The particle size of the abrasive varies depending on the kind, but it is preferable to use an abrasive having an average particle size of 20 mu m or less.

The wetting agent is an essential ingredient for making ointment formulations. It prevents drying and solidification of the toothpaste when exposed to air, provides gloss to the surface of the toothpaste, and also acts to sweeten the toothpaste according to the kind. Examples of the humectant include concentrated glycerin (98%), glycerin (85%), sorbitol aqueous solution (70%), amorphous sorbitol aqueous solution (70%), xylitol, polyethylene glycols and propylene glycol, May be added alone or in admixture of two or more in an amount of 40 to 70% by weight based on the total weight of the composition.

The binder serves to prevent separation of the solid powder component and the liquid component, and is an essential component in toothpaste for ointment. As the binder, any kind of water-soluble polymer can be used. Commonly used components include carboxymethylcellulose sodium derived from cellulose, carrageenan extracted from seaweed, and xanthan gum obtained from metabolism of microorganisms. The binder component may be added alone or in admixture of two or more in an amount of 0.1 to 5% by weight, preferably 0.1 to 2% by weight based on the total weight of the composition.

The foaming agent enhances the sensation of use of the product, assists in the cleaning action, accelerates the dispersion and penetration of other active ingredients, and reduces the interfacial tension, thereby easily releasing foreign substances in the oral cavity. As the foaming agent, mainly anionic surfactant sodium lauryl sulfate is used, and depending on the characteristics of the formulation, a copolymer of nonionic surfactant polyoxyethylene polyoxypropylene (poloxamer), polyoxyethylene hardened castor oil, poly Oxyethylene sorbitan fatty acid esters and the like. The foaming agent may be added in an amount of 0.1 to 2% by weight based on the total weight of the composition.

As the sweetening agent, saccharin sodium, aspartame, stevioside, xylitol, licorice acid, etc. may be used alone or in a mixture of two or more thereof in an amount of 0.05 to 5% by weight based on the total weight of the composition.

Examples of the pH regulator include sodium phosphate, disodium phosphate, trisodium phosphate, sodium pyrophosphate, sodium citrate, citric acid, tartaric acid and the like. Examples of the preservative include paraoxyanthine methylate (methylparaben), paraoxybenzoate, Sodium may be used alone or in admixture of two or more.

Examples of the active ingredient include a fluoride which forms a fluorine film on teeth and strengthens the acid (lactic acid, etc.), which is a metabolite of tooth decay, and aminocaproic acid, allantoin and allantoin derivatives and vitamins for preventing periodontal disease, Triclosan may be used singly or in combination of two or more for the purpose of promoting oral hygiene by inhibiting the propagation of harmful microorganisms in the mouth.

The flavoring agent may be selected from the group consisting of peppermint oil, spearmint oil, menthol, anethole, and the like. In addition, titanium dioxide may be used as the brightener. The pigment may be an edible pigment, purified water, .

The present invention also provides an antimicrobial composition for oral microorganisms comprising fucoidan as an active ingredient.

The antimicrobial composition according to the present invention means a substance capable of inhibiting or inhibiting the growth and life functions of a strain. The antimicrobial composition according to the present invention contains 0.1 to 50% by weight of fucoidan based on the total weight of the composition.

The antimicrobial composition of the present invention exhibits an antibacterial effect against oral microorganisms, and the oral microorganisms include cariogenic bacterial strains and periodontopathogenic bacterial strains, and preferably Streptococcus mutans ( Streptococcus mutans), Streptococcus sanggwi varnish (Streptococcus sanguinis ), Streptococcus sobrinus , Streptococcus ratti , Streptococcus criceti , Streptococcus anginosus , Streptococcus gordonii , Actinobacillus actinomycetemcomitans , Fusobacterium nucleatum , Prevotella, intermedia , Porphylomonas gingivalis ) and the like.

The present invention also provides a pharmaceutical composition for preventing or treating periodontal disease comprising fucoidan as an active ingredient.

The periodontal disease is a disease caused by oral microorganisms, and includes periodontitis, gingivitis, periodontal disease, alveolar bone disorder, alveolar bone osteoporosis, alveolar bone disorder, alveolar bone loss, alveolar bone remodeling disorder, bad breath, tooth decay and the like.

The composition for preventing or treating periodontal disease of the present invention may contain one or more known active ingredients having a therapeutic effect of periodontal disease together with fucoidan.

The composition for the prevention or treatment of periodontal disease of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the production of pharmaceutical compositions. In addition, it can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral preparations such as syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to a conventional method. Suitable formulations known in the art are preferably those as disclosed in Remington ' s Pharmaceutical Science, recently, Mack Publishing Company, Easton PA. Examples of carriers, excipients and diluents which may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The term "administering" as used herein is meant to provide any desired composition of the invention to a subject in any suitable manner.

The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the fucoidan of the present invention can be administered in an amount of 1 to 10,000 mg / kg per day. The composition may be administered once a day, or divided into several doses.

The pharmaceutical composition of the present invention may be administered to a subject in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers for the prevention or treatment of periodontal disease.

The present invention also provides a food composition for preventing or ameliorating periodontal disease comprising fucoidan as an active ingredient.

In the present invention, the term "health functional food" refers to a food having a biological control function such as prevention and improvement of disease, bio-defense, immunity, recovery of disease and aging inhibition. The fucoidan according to the present invention can be added to health functional foods for the purpose of preventing or improving periodontal disease.

When the composition of the present invention is used as a food additive, the composition can be added as it is or can be used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). In general, the composition of the present invention is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material, in the production of food or beverage. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

There is no particular limitation on the kind of the food. Examples of foods to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen and other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. The natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharine and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may comprise flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of such additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, preferred embodiments and production examples are provided to facilitate understanding of the present invention. However, the following Examples and Preparation Examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the Examples and Production Examples.

Example  1. Verification of antimicrobial activity against oral microorganisms

MIC / MBC (Minimum inbihitory concentration / minimum bactericidal concentration) assay was performed to confirm the antimicrobial activity of fucoidan against oral microorganisms. Fucoidan was purchased from Sigma, and amphicillin (Sigma) and gentamycin (Sigma) were each treated as a positive control.

As cariogenic bacterial strains of oral microorganisms, Streptococcus mutans mutans ATCC (American Type Culture Collection) 25175, Streptococcus sanguinis ATCC 10556, Streptococcus sobrinus ATCC 27607, Streptococcus ratti ) KCTC (Korean Collection for Type Cultures) 3294, Streptococcus criceti ) KCTC 3292, Streptococcus anginosus ATCC 31412, Streptococcus gordonii) was used to ATCC 10558, periodontal disease causative agent (periodontopathogenic bacterial strains) as a liquid solution Martino Bacillus Martino Mai semtem Cormier Tansu (Actinobacillus actinomycetemcomitans ATCC 43717, Fusobacterium < RTI ID = 0.0 > nucleatum ATCC 10953, Prevotella intermedia ) ATCC 25611, Porphylomonas gingivalis ATCC 33277 was used. BHI (Brain-Heart Infusion) medium containing 1% yeast extract was used for cultivation of dental caries bacteria. For the cultivation of periodontal disease bacteria, 1 μg / ml hemine (hemin, Sigma, St. Louis, MO, USA) and 1 μg / ml menadione (BHI medium).

The antimicrobial activity of fucoidan was determined by anaerobic conditions, incubation at 37 ° C for 18 hours (condition anaerobic bacteria, facultative anaerobic bacteria) or 24 hours (microaerophilic bacteria) or 1-2 days (obligate anaerobic bacteria) Respectively. MICs indicate the minimum concentration at which the growth of the strain is inhibited when visually observed under the given growth conditions. The MIC ₅₀ s or MIC ₉₀ s indicates the minimum concentration at which the growth of the strain is inhibited by 50 or 90% it means. MBC means the minimum concentration of the culture medium of the plate culture medium in which colonization of the strain is not generated at all when the plate is stained. The MIC / MBC results are shown in Table 1.

Oral microorganism Fucoidan (mg / mL) Ampicillin
(ampicillin) Gentamicin
(gentamicin) MIC _{50 <} MIC _{90 <} MIC / MBC MIC / MBC (μg / mL) S. mutans
ATCC 25175 0.062 0.25 0.25 / 0.50 0.125 / 0.5 8/16 S. sanguinis
ATCC 10556 0.125 0.50 0.50 / 1.00 0.5 / 1 64/64 S. sobrinus
ATCC 27607 0.125 0.25 0.25 / 0.50 0.5 / 1 4/8 S. ratti
KCTC 3294 0.062 0.25 0.25 / 0.50 0.5 / 1 16/32 S. criceti
KCTC 3292 0.062 0.25 0.25 / 0.50 1/2 8/16 S. anginosus
ATCC 31412 0.125 0.25 0.25 / 0.50 1/2 32/32 S. gordonii
ATCC 10558 0.125 0.50 0.50 / 1.00 0.5 / 1 32/32 A. actinomycetemcomitans
ATCC 43717 0.125 0.50 0.50 / 1.00 64/64 4/8 F. nucleatum
ATCC 51190 0.062 0.25 0.25 / 0.50 2/4 2/4 P. intermedia
ATCC  49049 0.062 0.25 0.25 / 0.25 4/8 16/32 P. gingivalis
ATCC 33277 0.031 0.125 0.125 / 0.25 0.5 / 1 256/512

As shown in Table 1, it was confirmed that fucoidan has a strong antimicrobial effect against 11 kinds of dental caries bacteria or periodontal disease causative bacteria. Accordingly, it has been confirmed that fucoidan can be used as a composition for oral cleaning, a composition for antibacterial treatment for oral microorganisms, or a composition for preventing or treating periodontal disease caused by oral microorganisms.

Example  2. Checkerboard Verification of antibiotic effect of oral antibiotics against oral microorganisms

To confirm the antimicrobial activity of fucoidan against oral microorganisms, the Checkerboard method was used to confirm the effect of antibiotics (Ampicillin or Gentamycin) (Cha et al. 2007). Oral microorganisms were the same species as in Example 1 above.

More specifically, two different materials (fucoidan + ampicillin or fucoidan + gentamycin) were mixed in a cation-added Mueller-Hinton medium and then gradually diluted. After incubation at 37 ° C for 24 hours, the MIC was confirmed. The FIC (fractional inhibitory index) was calculated according to the conventional method (Cha et al., 2007; Lee et al., 2008), a synergistic value when the FIC value is 0.5 or less, Indifferent for 1 to 2 and antagonistic for 2 or more. The antibiotic combination effect on ampicillin or gentamycin is shown in Table 2 and Table 3, respectively.

Strain matter MIC / MBC FIC / FBC FICI / FBCI result Exclusive absorption S. mutans
ATCC 25175 Fucoidan 0.25 / 0.50 0.062 / 0.125 0.25 / 0.25 0.5 / 0.5 Synergistic /
Synergistic Ampicillin 0.0625 / 0.25 0.0156 / 0.0625 0.25 / 0.25 S. sanguinis
ATCC 10556 Fucoidan 0.50 / 1.00 0.125 / 0.50 0.25 / 0.5 0.5 / 1.0 Synergistic /
Additive Ampicillin 0.25 / 1.0 0.0625 / 0.5 0.25 / 0.5 S. sobrinus
ATCC 27607 Fucoidan 0.25 / 0.50 0.062 / 0.125 0.25 / 0.25 0.5 / 0.75 Synergistic /
Additive Ampicillin 0.0156 / 0.0625 0.0039 / 0.0313 0.25 / 0.5 S. ratti
KCTC 3294 Fucoidan 0.25 / 0.50 0.062 / 0.125 0.25 / 0.25 0.5 / 0.5 Synergistic /
Synergistic Ampicillin 0.125 / 0.5 0.0313 / 0.125 0.25 / 0.25 S. criceti
KCTC 3292 Fucoidan 0.25 / 0.50 0.062 / 0.125 0.25 / 0.25 0.5 / 0.5 Synergistic /
Synergistic Ampicillin 0.0156 / 0.125 0.0039 / 0.0313 0.25 / 0.25 S. anginosus
ATCC 31412 Fucoidan 0.25 / 0.50 0.062 / 0.125 0.25 / 0.25 0.5 / 0.5 Synergistic /
Synergistic Ampicillin 0.0625 / 0.25 0.0156 / 0.0625 0.25 / 0.25 S. gordonii
ATCC 10558 Fucoidan 0.50 / 1.00 0.125 / 0.25 0.25 / 0.25 0.5 / 0.5 Synergistic /
Synergistic Ampicillin 0.0625 / 0.25 0.0156 / 0.0625 0.25 / 0.25 A. actionmycetemcomitans
ATCC 43717 Fucoidan 0.50 / 1.00 0.125 / 0.50 0.25 / 0.5 0.5 / 0.75 Synergistic /
Additive Ampicillin 8/16 2/4 0.25 / 0.25 F. nucleatum
ATCC 51190 Fucoidan 0.25 / 0.50 0.062 / 0.125 0.25 / 0.25 0.5 / 0.5 Synergistic /
Synergistic Ampicillin 2/4 0.5 / 1 0.25 / 0.25 P. intermedia
ATCC 49049 Fucoidan 0.25 / 0.25 0.062 / 0.125 0.25 / 0.5 0.5 / 0.75 Synergistic /
Additive Ampicillin 0.25 / 1 0.0625 / 0.25 0.25 / 0.25 P. gingivalis
ATCC 33277 Fucoidan 0.125 / 0.25 0.031 / 0.062 0.25 / 0.25 0.5 / 0.5 Synergistic /
Synergistic Ampicillin 0.5 / 1.0 0.125 / 0.25 0.25 / 0.25

Strain matter MIC / MBC FIC FICI result Exclusive absorption S. mutans
ATCC 25175 Fucoidan 0.25 / 0.50 0.062 / 0.125 0.25 / 0.25 0.5 / 0.5 Synergistic /
Synergistic Gentamicin 1/4 0.25 / 1 0.25 / 0.25 S. sanguinis
ATCC 10556 Fucoidan 0.50 / 1.00 0.125 / 0.50 0.25 / 0.5 0.5 / 0.75 Synergistic /
Additive Gentamicin 8/32 2/8 0.25 / 0.25 S. sobrinus
ATCC 27607 Fucoidan 0.25 / 0.50 0.062 / 0.125 0.25 / 0.25 0.5 / 0.75 Synergistic /
Additive Gentamicin 16/32 4/16 0.25 / 0.5 S. ratti
KCTC 3294 Fucoidan 0.25 / 0.50 0.062 / 0.125 0.25 / 0.25 0.5 / 0.75 Synergistic /
Additive Gentamicin 4/8 1/4 0.25 / 0.5 S. criceti
KCTC 3292 Fucoidan 0.25 / 1.00 0.125 / 0.25 0.5 / 0.25 1.0 / 0.5 Additive /
Synergistic Gentamicin 4/16 2/4 0.5 / 0.25 S. anginosus
ATCC 31412 Fucoidan 0.25 / 0.50 0.062 / 0.125 0.25 / 0.25 0.5 / 0.5 Synergistic /
Synergistic Gentamicin 2/8 0.5 / 2 0.25 / 0.25 S. gordonii
ATCC 10558 Fucoidan 0.50 / 1.00 0.125 / 0.25 0.25 / 0.25 0.5 / 0.75 Synergistic /
Additive Gentamicin 16/32 4/16 0.25 / 0.5 A. actionmycetemcomitans
ATCC 43717 Fucoidan 0.50 / 1.00 0.125 / 0.50 0.25 / 0.5 0.75 / 0.75 Additive /
Additive Gentamicin 2/8 1/2 0.5 / 0.25 F. nucleatum
ATCC 51190 Fucoidan 0.25 / 0.50 0.062 / 0.125 0.25 / 0.25 0.5 / 0.75 Synergistic /
Additive Gentamicin 0.5 / 2 0.125 / 1 0.25 / 0.5 P. intermedia
ATCC 25611 Fucoidan 0.25 / 0.50 0.062 / 0.25 0.25 / 0.5 0.375 / 0.75 Synergistic /
Additive Gentamicin 32/64 4/16 0.125 / 0.25 P. gingivalis
ATCC 33277 Fucoidan 0.125 / 0.25 0.031 / 0.062 0.25 / 0.25 0.5 / 0.5 Synergistic /
Synergistic Gentamicin 256/512 64/128 0.25 / 0.25

As shown in Table 2, when fucoidan and ampicillin were used, the MIC value for dental caries bacteria was 0.025 mg / mL to 0.125 mg / mL, which was more than 4 times lower than that for single use, It was confirmed that the FICI value was synergistic to 0.5 or less. The MBC values of S. anginosus and S. sobrinus in dental caries were 0.125 mg / mL to 0.50 mg / mL, which was more than 4 times lower than that of single use, and the FICI value was 0.75-1.0 And it is confirmed that there is a partial additive effect. In addition, the MIC value for periodontal pathogens was also decreased by more than 4 times, and it was confirmed that the FICI value was synergistic to 0.5 or less. A. actinomycetaemcomitans among periodontal pathogens And P. intermedia was 0.125 mg / mL to 0.50 mg / mL, which was more than four times lower than that of single use, and an FICI value of 0.75 or less, with an additive effect Respectively.

In addition, as shown in Table 3, when fucoidan and gentamicin were used, the MIC value was reduced by more than 4 times for all oral microorganisms except S. criceti and A. actinomycetemcomitans , and the FICI value was increased to less than 0.5 (synergistic effect). In addition, S. mutans, S. criceti, S. anginosus, and MBC values for P. gingivalis has had a FBCI rises (synergistic) effect to less than 0.5, S. sanguinis, S. sobrinus, S. ratti, S. MBC values for gordonii , A. actinomycetemcomitans , F. nucleatum , and P. intermedia were found to have an additive effect with an FBCI of 0.75 or less.

From the above experimental results, it was confirmed that when fucoidan was used in combination with ampicillin or gentamycin against oral microorganisms, excellent antibiotic merge effect was obtained.

Example  3. Time-kill curve ( Time - kill curves ) On the antimicrobial activity of oral microorganisms

Time-kill curves were used to re-verify the antibiotic (ampicillin or gentamycin) incorporation effect of the antimicrobial activity of oral fucoidan against oral microorganisms identified in Example 2 above. Oral microorganisms were the same species as in Example 1 above.

More specifically, a tube containing Mueller-Hinton medium was treated with MIC ₅₀ antibiotics to give a final concentration of 5 to 6 × 10 ⁶ CFU / ml. The tubes were incubated at 37 ° C under anaerobic conditions and cultured at 0.5, 1, 2, 3, 4, 5, 6, 12 and 24 hours After culturing, the number of strains was measured. The results are shown in Figs.

As shown in Figures 1 to 11, Fucoidan is a member of Streptococcus mutans mutans), Streptococcus sanggwi varnish (Streptococcus sanguinis), Rhodococcus host tepto small debris Nurse (Streptococcus sobrinus , Streptococcus ratti , Streptococcus criceti), host tepto caucus should Gino Seuss (Streptococcus anginosus), Streptococcus your altitude (Streptococcus gordonii ), actinobacillus actinobacillus ( Actinobacillus &lt; RTI ID = 0.0 &gt; actinomycetemcomitans , Fusobacterium nucleatum , Prevotella intermedia, intermedia and Porphylomonas gingivalis were found to have an excellent antibiotic effect when combined with ampicillin or gentamycin.

Hereinafter, a pharmaceutical composition containing the composition of the present invention and a preparation example of a health functional food will be described, but the present invention is not intended to be limited but is specifically described .

Formulation example  1. Preparation of Oral Cleansing Composition

1-1. For oral use Gaggle  Produce

0.1 to 1.0 g of fucoidan

5 to 10 g of xylitol

Ethyl alcohol 5-15 g

Sorbitol 5 to 15 g

10 to 100 mg of saccharin sodium

Sodium monofluorophosphate 500 to 1000 mg

Sodium lauryl sulfate 100-200 mg

Polysorbate 20 100 to 1000 mg

Pepaminite flavor 10 to 100 mg

Sodium benzoate 10-100 g

Pigment amount

Purified water is added to make 100 g.

1-2. Paste phase  Manufacture of toothpaste

Fucoidan 1 mg

Aluminum hydroxide 47 mg

Sodium fluorophosphate 0.76㎎

5 mg of glycerin

40 mg of sorbitol solution

0.7 mg of carboxymethylcellulose sodium

4 mg of silicon dioxide

2 mg of sodium lauryl sulfate

Methylparaben 0.15 mg

1 mg flavoring

0.4 mg of titanium dioxide

Sodium saccharin 0.2 mg

Purified water balance

Formulation example  2. Preparation of pharmaceutical compositions

2-1. Sanje  Produce

Fucoidan 20 mg

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

2-2. Manufacture of tablets

Fucoidan 10 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

2-3. Preparation of capsules

Fucoidan 10 mg

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

2-4. Injection preparation

Fucoidan 10 mg

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na ₂ HPO ₄ 2H ₂ O 26 mg

(2 ml) per 1 ampoule in accordance with the usual injection preparation method.

2-5. Liquid  Produce

Fucoidan 20 mg

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

Formulation example  3. Preparation of food composition

3-1. Manufacture of health food

Fucoidan 100 mg

Vitamin mixture quantity

Vitamin A acetate 70 μg

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

Vitamin B12 0.2 μg

Vitamin C 10 mg

Biotin 10 μg

Nicotinic acid amide 1.7 mg

Folic acid 50 μg

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

3-2. Health drink  Produce

Fucoidan 100 mg

Vitamin C 15 g

Vitamin E (powder) 100 g

19.75 g of ferrous lactate

3.5 g of zinc oxide

Nicotinic acid amide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3g

Water quantification

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The solution thus prepared was filtered and sterilized in a sterilized 2 liter container, It is used in the production of the health beverage composition of the invention.

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (9)

Fucoidan; And an antibiotic selected from the group consisting of ampicillin, gentamicin, and a mixture thereof, as an active ingredient, and has an antibacterial activity against oral microorganisms.
delete delete The oral cleaning composition according to claim 1, wherein the oral cleaning composition is at least one selected from the group consisting of toothpaste, mouthwash, mouthwash, gum, candy, mouth spray, mouthwash, and the like.
delete The oral microorganism according to claim 1, wherein the oral microorganism is selected from the group consisting of Streptococcus mutans , Streptococcus sanguinis , Streptococcus sobrinus , Streptococcus ratti , Streptococcus criceti , Streptococcus anginosus , Streptococcus gordonii , Actinobacillus actinomycetemcomitans , Fusobacterium nucleatum , Pseudomonas aeruginosa, , Prevotella intermedia , and Porphylomonas gingivalis . The composition for oral care according to claim 1, wherein the composition is selected from the group consisting of Porphyromonas gingivalis , Prevotella intermedia , and Porphyromonas gingivalis .
A pharmaceutical composition for preventing or treating periodontal disease comprising fucoidan as an active ingredient.
The method of claim 7, wherein the periodontal disease is one or more diseases selected from the group consisting of stomatitis, gingivitis, periodontitis, alveolar bone disorder, alveolar bone disorder, alveolar bone disorder, alveolar bone loss, alveolar bone remodeling disorder, A pharmaceutical composition for preventing or treating diseases.
A food composition for preventing or improving periodontal disease comprising fucoidan as an active ingredient.

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