KR100314789B1 - Toothpaste Composition for Curing Dental Caries and Inflammation of Oral Cavity - Google Patents

Abstract

The present invention is to prevent caries and oral inflammation containing spinolipid, spinolipide-fluoric acid complex or spinolipide-chloride complex of human lipid components having inhibitory effect against caries-causing bacteria and oral inflammation treatment and tartar removal effect It relates to a toothpaste composition for treatment.

Toothpaste composition prepared according to the present invention can be applied to the skin, teeth, oral cavity and vaginal mucosa of humans and animals, and especially to prevent dental caries or to protect the teeth from caries bacteria when the oral mucosa is damaged. It can be used as a material to help restore cell membranes.

In addition, spinolipid, spinolipide-fluoric acid complex, and spinolipide-chloride complex can be applied to the skin, teeth, oral cavity and vaginal mucosa of humans and animals, as the spinolipide itself has sufficient oral microbial inhibitory function. In particular, it can be used as a material to prevent dental caries or to protect the teeth from caries bacteria when the oral mucosa is damaged and to restore the cell membrane of the damaged oral mucosa.

Description

Toothpaste Composition for Curing Dental Caries and Inflammation of Oral Cavity

The present invention is to prevent caries and oral inflammation containing spinolipid, spinolipide-fluoric acid complex or spinolipide-chloride complex of human lipid components having inhibitory effect against caries-causing bacteria and oral inflammation treatment and tartar removal effect It relates to a toothpaste composition for treatment.

Dental caries are one of the long-standing diseases of humanity, and the incidence of dental caries is increasing as sugar is used as a daily sweetener. In addition, this disease was once a measure of civilization, but is one of the most prevalent cultural diseases in the world, and the incidence rate is gradually increasing in Korea as well as in developed countries. Tooth decay is an infectious disease accompanied by destruction of teeth. It is a multifactorial disease caused by the interaction of bacteria, food, and saliva in the dental plaque. Among the dental plaques, Streptococcus mutans (S. mutans) is the main causative organism and causes dental caries through adhesion, proliferation and acid production process on the tooth surface. In other words, S. mutans are insoluble glucans, which are fructose polymers from sucrose in food by glucosyltransferase (Gtase) produced by themselves after attaching to the coating of the tooth surface. ) Is synthesized. It is reported that this insoluble glucan is composed mostly of α-1,3 bonds. Synthetic glucan increases the binding between bacteria that grow on the tooth surface, and S. mutans attached to the tooth surface are located on the tooth surface and produce organic acids such as lactic acid during carbohydrate metabolism. Decalcification of enamel causes caries.

Dentalis lapis is a cause of tooth decay and the biggest cause of periodontitis. If the gums are limited to inflammation in the gums, it is gingivitis, and if the condition has already spread to the periodontal tissue, especially the alveolar bone, it is periodontitis. When plaque is calcified, it becomes calculus, which acts to accelerate the destruction. Bacterial plaques also cause gingivitis and chronic gingivitis causes periodontitis.

Recently, efforts have been made to separate anti-cavities from natural substances that can be easily accessed from the surroundings as a new strategy to solve tooth decay. For example, several kinds of tannin compounds with glucosyltransferase inhibitory activity were isolated from cacao bean and persimmon leaves, but these tannin compounds have almost all enzymatic actions as well as glucosyltransferase. Has been reported to inhibit nonspecifically and has many limitations in practical industrial applications. In addition, polyphenol compounds such as catechin in green tea and oolong tea have been found to have potent inhibitory activity against glucosyltransferase.

Therefore, in order to effectively prevent tooth decay, it is necessary to prevent tooth decay bacteria and at the same time strengthen the enamel of the tooth to prevent demineralization of the tooth caused by organic acids, and to prevent or treat ulcers caused by inflammation and wounds of the gums or treat them promptly to maintain healthy teeth. Will be.

The present inventors pay attention to the fact that the spin cycle feed is an antimicrobial substance and synthesized a fluorine-coupled spin cycle feed-fluoric acid complex to obtain a substance which can satisfy both the inhibition of caries-inducing bacteria and the acid poor solubility of the tooth surface by fluorine. Developed. In addition to this substance, spinolipide and spinolipide-chloride complexes also inhibit caries inducing bacteria and have excellent regenerating ability of the oral mucosa, which is not only an additive for the purpose of preventing caries, but also effective in healing oral inflammation. And developed the toothpaste composition.

The present invention is to prevent caries and oral inflammation containing spinolipid, spinolipide-fluoric acid complex or spinolipide-chloride complex of human lipid components having inhibitory effect against caries-causing bacteria and oral inflammation treatment and tartar removal effect Toothpaste composition for treatment

Spinolipide consists of phytospinosine, spinosine, and spinganine, which are precursors of ceramides, which are known to be important ingredients in preventing skin loss and restoring damaged skin layers. Recently it has been known to act as an antibiotic to maintain.

It was found that this function acts not only on the skin but also on the oral mucosa and has a significant effect on the healing of wounds caused by oral inflammation or ulcers. In addition, the mechanism of preventing tooth decay of fluorine combined with spin cycle feed is briefly summarized as follows.

The mechanisms by which fluoride prevents tooth decay can be summarized in the following three ways.

1) Fluoride combines with hydroxyapatite, the main component of dental hard tissue, to form fluoride apatite that is poorly soluble in acid.

2) Fluoride provides a good condition for depositing inorganic salts such as calcium phosphate on the surface of teeth in saliva containing inorganic salts in the free state.

3) Fluoride acts on the enzyme furnace to prevent tooth decay. However, there is a slight difference in response depending on the concentration of fluoride in the dental hard tissue. In other words, at high concentrations of more than 100 ppm of fluorine, it reacts with dental hard tissue first to form calcium fluoride (CaF2). As time passes, calcium fluoride is decomposed again, and some of the fluorine derived therefrom is separated, but some of the To form. However, when low concentration of fluorine less than 100ppm reacts with dental hard tissue, it does not form calcium fluoride, but forms fluorophosphate directly, imparting poor solubility to acid of tooth. Deposition of fluorine is more likely to occur on the tooth surface of the caries than on a healthy tooth surface. In particular, fluoride is deposited in large amounts at the initial site of caries, forming fluorite apatite, which effectively serves to cure caries.

Therefore, the present inventors pay attention to the fact that spinolipide is an antibacterial and anti-inflammatory substance, and synthesized a fluorine-coupled spinolipide-fluoric acid complex to inhibit the decay-causing bacteria and to treat oral inflammation and acid-solubility of tooth surface by fluorine. At the same time, it was developed a material that can satisfy the same, and proved that the material has sufficient use as a preventive material for caries prevention and oral disease.

Hereinafter, the present invention will be described in detail with reference to examples of the present invention. However, these examples are only for the understanding of the present invention, and do not limit the scope of the present invention in any sense.

EXAMPLE

Example 1 Spinolipid-Fluronic Acid Complex and Spinolipid-Chloride Composite

Example 1-1 Method for Preparing Phytospingosin-Fofluorate Complex (F-PS)

Concentrated phytospingosin in chloroform ethanol (1: 1) solution and concentrated hydrofluoric acid

The solution is added slowly to neutralize the pH to 7. After stirring for 30 minutes, acetone is added to the reaction solution, and the resulting precipitate is filtered. This filtrate was dried to afford the desired material.

Example 1-2 Spingosin-Fluoro-Compound (F-SS) Manufacturing Method

A spinocin-fluoric acid complex was prepared in the same manner as in Example 1-1, except that spingosin was used instead of phytospingosin.

Example 1-3 Spinganine-Fluronate Complex (F-SN) Manufacturing Method

A spinganine-fluoric acid complex was prepared in the same manner as in Example 1-1, except that spinganine was used instead of phytospinosine.

Example 1-4 Preparation Method of Phytospingosin-chloride Complex (Cl-PS)

After dissolving phytospingosin in chloroform ethanol (1: 1) solution, neutralize the pH to 7 by slowly adding concentrated hydrochloric acid (HCl) solution. After stirring for 30 minutes, acetone is added to the reaction solution, and the resulting precipitate is filtered. This filtrate was dried to afford the desired material.

[Example 1-5] Spingosin-chloride complex (Cl-SS) manufacturing method

A spingosin-chloride complex (Cl-SS) was prepared in the same manner as in Example 1-4 except that spingosin was used instead of phytospingosin.

[Example 1-6] Spinganine-chloride Complex (Cl-SN) Preparation Method

A spinganine-chloride complex (Cl-SS) was prepared in the same manner as in Example 1-4 except that spinganine was used instead of phytospinosine.

The composition prepared according to the present invention can be applied to the skin, teeth, oral cavity and vaginal mucosa of humans and animals, and especially to prevent tooth caries or to protect the teeth from caries bacteria when the oral mucosa is damaged and the cell membrane of damaged oral mucosa. Can be used as a substance to aid in the restoration of.

In addition, spinolipid, spinolipide-fluoric acid complex, and spinolipide-chloride complex can be applied to the skin, teeth, oral cavity and vaginal mucosa of humans and animals, as the spinolipide itself has sufficient oral microbial inhibitory function. In particular, it can be used as a material to prevent dental caries or to protect the teeth from caries bacteria when the oral mucosa is damaged and to restore the cell membrane of the damaged oral mucosa.

The amount of spinolipide added is preferably 0.1% to 10% by weight depending on the formulation. When used as a spin cycle feed complex, the spin cycle feed-fluoric acid complex is preferably added to the composition within the range of 0.1 to 5% by weight for the purpose of suppressing oral harmful microorganisms such as caries bacteria and increasing acid solubility of the tooth surface. Do.

Spinolipide and spinolipide chloride complex preferably contains 1 to 10% by weight in the toothpaste composition for the purpose of inhibiting harmful bacteria in the oral cavity, and when not used as a hydrofluoric acid complex, sodium fluoride and monofluoride as a source of fluorine It is preferable that at least one selected from sodium phosphate and tin fluoride contains 0.1 to 1% by weight.

Other components used in the toothpaste composition of the present invention is suitable for containing 3 to 50% by weight of calcium monohydrogen phosphate, hydrous alumina, hard calcium carbonate, calcium pyrophosphate, silica gel and the like as an abrasive, polyethylene glycol, as a wetting agent, One or more of propylene glycol, sorbitol, ziitol and glycerin may be selected to contain 1 to 40% by weight.

As the foaming agent, anionic and nonionic surfactants such as sodium lauryl sulfate, sucrose fatty acid ester and polyoxyethylene-cured castor oil may be used alone or in combination of two or more, and 0.5 to 5% by weight may be used.

As the additive used in small amounts, sweeteners, pH adjusting agents, preservatives, coloring agents, binders and the like which are commonly used in toothpaste can be added, and one or two or more kinds of caries preventive agents, tartar preventive agents and medicinal components can be used.

For example, sodium saccharate, aspartame, stevioside, etc. can be used as a sweetening agent, and sodium phosphate, trisodium phosphate, citric acid, sodium citrate, tartaric acid, etc. as a pH adjuster,

Preservatives include methyl paraoxybenzoate, propyl paraoxybenzoate, sodium benzoate and the like. Examples of the binder include sodium carboxymethyl cellulose, carrageenan, xanthan gum, polyvinylpyrrolidone, sodium alginate, and other gums.

Sodium fluoride, sodium monofluorophosphate, tin fluoride, and the like may be used as the caries prevention agent, and sodium pyrophosphate, potassium pyrophosphate, zinc chloride, zinc citrate, etc. may be used as the tartar prevention agent.

As a medicinal component, it can be used individually or in mixture of 2 or more of allantoin chlorohydroxy aluminate, amino capronic acid, chlorohexidine, tocopherol acetate, pyridoxine hydrochloride.

The procedure for preparing the functional toothpaste containing the spinolipid as in Example 2-1 is to disperse the carboxymethylcellulose sodium, xanthan gum, sodium saccharate, phytospingosin hydrofluoric acid complex in the glycerin as a humectant, and dilute with purified water The mixture was first mixed at, followed by adding calcium hydrogen dihydrogen phosphate as an abrasive and then mixing the mixture secondly. Finally, the dentifrice composition was completed by adding a foaming agent sodium lauryl sulfate and a flavor and tertiary mixing.

As a control of the toothpaste composition of the present invention, the toothpaste composition without addition of the spin ring lipid was compared as a conventional technique (Comparative Example 2-1).

Based on the embodiments of the present invention will be presented a specific use. However, these examples are only for the understanding of the present invention, and do not limit the scope of the present invention in any sense.

Example 2: Toothpaste Composition Containing Spinolipids

Test Example 1 Caries Inhibition Experiment

Strains of oral microorganisms include caries-inducing bacteria, Streptococcus mutans, Streptococcus cricetus , Streptococcus rattus , and Streptococcus sobrinus. ) And gingivitis- inducing bacteria, Actinomyces viscosus . Streptococci on MS agar (Mitis-Salivarius) agar and Actinomyces on BHI agar medium at 37 ° C. and 1 on anaerobic chamber The cultures were anaerobic for 3 days. Each of these cultures was inoculated again in BHI broth and left to culture at 37 ° C. for 1 day, and these were used as precultures prior to the main culture. Antimicrobial test is to dissolve the spun complex of FRPs (F-PS, F-SS and F-SN) in distilled water and then sterilize it, add a certain amount to the sterilized BHI medium and mix well Aseptically dried. Here, 1.5 ml of each preculture was transferred to a small test tube and incubated in a predetermined amount in dried agar medium. As a counterpart of the glass spinolipide-fluoric acid complex, catechin (catechin), which is isolated from green tea, and cinnamic aldehyde, which is a phenolic material, were used. Spinolipids (PS, SS, SN) and spinolipide-chloride complexes (Cl-PS, Cl-SS, Cl-SN) and toothpaste compositions prepared as in Example 2-1 and Comparative Example 2-1 The experiment was conducted in the same manner.

As shown in Table 1 below, phytospinosine phosphate complex (F-PS) and spinosine phosphate complex (F-SS) showed relatively high antimicrobial activity against each strain, and spinganine phosphate complex (F-SN) did not reach this. However, it showed relatively high antimicrobial activity compared to catechin and phenolic cinnamic aldehyde. Each minimum inhibition concentration (MIC) was the same for each strain.

As shown in Table 1-2, the antimicrobial effect of the composition containing the spin cycle lipid fluoride complex showed a superior antibacterial effect than the composition of Comparative Example 2-1 containing no spin cycle lipid.

Test Example 2 Comparison of Acid Production and Plasma Formation Capacity of Streptococcus mutans

Streptococcus mutans , known as oral microorganisms that form plaque, are passaged three times in Brain heart Infusion broth and then tryptic soy broth is prepared. Was passaged at 37 ℃ for 48 hours. Each spin sound feed fluoride complexes (F-PS, F-SS, F-SN) were added to each of 30ppm, 60ppm, and 120ppm and incubated at 37 ° C for 48 hours to change the pH (the pH after incubation at initial pH). Minus decrease) to determine acid production. Spinolipide (PS, SS, SN) and spinolipide-chloride complex was added 60ppm each and incubated for 48 hours at 37 ℃ by measuring the pH change (reduction of pH after incubation at the initial pH) to determine the acid production capacity Measured.

In addition , the plaque (dental plaque) ability of the caries ( Streptococcus mutans) was compared by measuring the amount of deposits produced in the culture. In other words, 30ppm, 60ppm, 120ppm spin cyclic feed hydrofluoric acid complex (F-PS, F-SS, F-SN) was put in tryptic soy broth (tryptic soy broth) and incubated for 48 hours at 37 ℃, discard the culture medium 1ml After lightly rinsing the test tube wall with distilled water, 2 ml of 0.5N sodium caustic (0.5N-NaOH) solution was added to dissolve the amount of deposit on the test tube wall, and the absorbance was measured at 540 nm. Spinolipides (PS, SS, SN) and spinolipide-chloride complexes were added in tryptic soy broth at 60 ppm each, and Example 2-1 and Comparative Example 2-1 compositions at 1%. After incubating for 48 hours at 37 ℃, discarded the culture medium, lightly rinsed the test tube wall with 1ml of distilled water, 2ml of 0.5N-NaOH solution was added to dissolve the amount of deposits attached to the test tube wall was measured for absorbance at 540nm.

As a result, the pH decrease of the medium to which the spincyclic hydrofluoric acid complex (F-PS, F-SS, F-SN) was added was very small, especially in the 120 ppm group. In addition, the concentration of polymer attached to the wall of the test tube was significantly lower in absorbance of the spinolipide fluoride complex-added group than the control group. In addition, the comparison with the composition showed that the caries preventive effect of Example 2-1 containing the spin cycle feed is significantly higher than Comparative Example 2-1 (see Table 2).

Test Example 3: Bacto Snyder agar test using Lactobacillus acidophilus

Lactobacillus acidophilus , known as a major bacterium, which forms an acid to corrode teeth, was passaged twice in MRS broth to isolate cells. Bacto Snyder agar, which can be used to determine the amount of acid produced by the addition of indicators, was prepared using free spinolipide-fluoric acid complex, spingolipide and spingolipide-chloride complex and Example 2-1 and Comparative Example 2- Prepared by adding only the concentration of the composition of 1 and then inoculated cells were mixed quickly. Color changes were observed after 24, 48, and 72 hours after the agar was solidified in the upright position.

As a result, it can be seen that the color change decreases according to the concentration of the spinolipide-fluoric acid complex.

Therefore, the spinolipid-fluoric acid complex was judged to have the ability of inhibiting oral microorganisms, thereby inhibiting the production of acid which corrodes the teeth, thereby confirming the ability to prevent tooth decay. In addition, it was shown that the composition of Example 2-1 has a superior ability to prevent tooth decay than Comparative Example 2-1 (see Table 3 below).

Experimental Example 4: Measurement of the healing effect of oral mucosal ulcers

Experimental animals used male hamsters of about 80g body weight. Hamsters were anesthetized with ether and then injected into a micro-syringe with 1 μl of 20% acetic acid under the mucous membrane of the left cheek pocket of the mouth. 100 μl of 0.1%, 0.2%, and 0.5% of free spinolipid-fluoric acid complexes were applied to the wound site using a syringe for oral administration three times a day for 10 days from the day after the first day of acetic acid administration. A certain amount was applied. On the day after the last administration, the hamster was killed with ether and the oral mucosa containing the ulcer site was collected and soaked in a 10% formalin solution. The mucosal skin was developed on a glass plate and the ulcer area was measured to calculate the treatment rate. The spin loop feed and the spin loop feed-chloride complex were coated with 0.5 μl of 100 μl, and the composition of Example 2-1 and Comparative Example 2-1 were also applied by 100 mg.

As a result, it can be seen that not only the free spinolipide-fluoric acid complex but also the spinolipide and spinolipide chloride complexes have a significant wound healing promoting effect on wound healing of the oral mucosa compared to the control group. In addition, the composition of Example 2-1 showed superior wound healing than Comparative Example 2-1 (see Table 5 below).

Toothpaste composition prepared according to the present invention can be applied to the skin, teeth, oral cavity and vaginal mucosa of humans and animals, and especially to prevent dental caries or to protect the teeth from caries bacteria when the oral mucosa is damaged. It can be used as a material to help restore cell membranes.

In addition, spinolipid, spinolipide-fluoric acid complex, and spinolipide-chloride complex can be applied to the skin, teeth, oral cavity and vaginal mucosa of humans and animals, as the spinolipide itself has sufficient oral microbial inhibitory function. In particular, it can be used as a material to prevent dental caries or to protect the teeth from caries bacteria when the oral mucosa is damaged and to restore the cell membrane of the damaged oral mucosa.

Claims (4)

A dentifrice composition for preventing tooth decay and suppressing oral inflammation, comprising: a spinolipid as an active ingredient. The toothpaste composition of claim 1, wherein the spinolipid is selected from the group consisting of phytospinosine, spinosine and spinganine. The method according to any one of claims 1 to 3, wherein the spin ring feed is a phytospingosin-fluoric acid complex, spingosin-fluoric acid complex, spinganine- complexed with hydrofluoric acid or hydrochloric acid (HCl) Toothpaste composition for caries prevention and oral inflammation characterized in that it is selected from the group consisting of hydrofluoric acid complex, phytospinosine-chloride complex, spingosin-chloride complex, spinganine-chloride complex. The toothpaste composition according to any one of claims 1 to 3, wherein the spinolipid is contained in the toothpaste composition at 0.1% by weight to 10% by weight.