JPH0425923B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel cariogenic agent. More specifically, the present invention relates to a novel anti-caries agent containing embelin as an active ingredient, which inhibits plaque formation and acid production to prevent dental caries and periodontal disease.

Dental caries, generally referred to as tooth decay, is a disease that causes localized and progressive destruction of teeth, has an extremely high morbidity rate, and has become an important public health problem in modern times.

According to recent research results, dental caries is caused by the sucrose in food that is linked to certain oral streptococci, especially Streptococcus miutans.
This is thought to be due to the production of insoluble and sticky glucan (a polysaccharide consisting of D-glucose) through the action of glucosyltransferase derived from D-glucose (D-glucose). That is, due to the glucan produced as described above, bacterial cells adhere to the tooth surface and multiply to form dental moss, which is a nest of bacteria. This process is the first stage of dental caries, and then the bacteria in this tooth moss demineralizes the tooth tissue with the acid produced by sugar fermentation, and caries progresses.

Since the essence and cause of dental caries is an infectious disease, it is necessary to eradicate the oral streptococcus that causes caries in order to prevent it and prevent its progression.

Oral streptococci include Streptococcus mutans and Streptoccocus sanguis.
sunguis) and Streptococcus mitis, among which Streptococcus mutans has the strongest cariogenic progeny. That is, Streptoccus mutans is
The ability to adhere to tooth surfaces (requirement for sucrose), the bacterial agglutination reaction (induced by high molecular weight dextran), and the ability to produce lactic acid through sorbitol-mannite fermentation are known to be key characteristics, and these properties are extremely effective in inducing caries. Be heavily involved.

Conventionally, many studies have been conducted for the purpose of preventing caries, and the present inventors first focused on the medicinal efficacy and safety of Ayurvedic drugs, and used extracts of these drugs to prevent caries and prevent the progression of caries. He invented an anti-caries agent and filed an application in Japanese Patent Application No. 162090/1983.

However, since such Ayurvedic drugs are natural products, they have the disadvantage that even if they are made from the same plant species, their quality varies depending on the place of production, growth conditions, harvest time, storage method, etc. Therefore, if the active ingredients of extracts obtained from these herbal medicines have not been specified, it has been extremely difficult to avoid drug fluctuations.

In order to overcome this drawback, the present inventors have conducted further intensive research, identified ingredients that are effective in preventing caries, and obtained an excellent anti-caries agent with stable quality and medicinal efficacy.
The present invention has now been completed.

Below, the book will be explained in more detail.

Embelia ribes BURM., an Ayurvedic herbal medicine, has traditionally been used as a tapeworm repellent and a stomachic agent.・It was claimed in a patent application in 1982 that it has the effect of inhibiting the formation of dental plaque caused by Streptococcus mitis.
Although it is disclosed in No. 162090, the actual active ingredient remains unknown.

In order to identify the active ingredients of Enbelia ribus, the present inventors performed the following fractionation using Enasal, an Enbelia ribus plant, and examined the medicinal efficacy of each fraction.

Enasal was crushed in a mortar and extracted with methanol to obtain a methanol soluble component from the resulting methanol layer. Part of the methanol soluble content is dispersed in water and extracted with ethyl ether, water is removed from the aqueous layer to obtain the water soluble content, and then ethyl ether is removed from the ethyl ether layer to obtain the ethyl ether soluble content. Obtained. Furthermore, after dissolving a portion of the ethyl ether soluble content in petroleum benzine, the petroleum benzine layer was separated and removed to obtain a petroleum benzine soluble content. The insoluble matter (precipitate) obtained when petroleum benzine was dissolved was recrystallized with methanol to obtain light yellow crystals. The following tests were conducted on each fraction thus obtained to determine the activity of inhibiting tooth moss formation.

Streptococcus miteis OMZ 176(d) pre-cultured and diluted in a sterilized test tube, 0.1ml, 0.5M
Add 0.25 ml of 5% sucrose solution adjusted to pH 6.8 with phosphate buffer, 0.05 ml of the sample dissolved or suspended in methanol, and 2.10 ml of BHI solution medium to make an incubation mixture, and adjust the tilt angle.
Cultured overnight at 30° and 37°C.

The proliferated Streptococcus miteis forms a plaque that adheres to the test tube wall.
After culturing, the culture solution is decanted and washed with 3 ml of water.The test tube wall deposits are suspended in 3 ml of water and the turbidity at 550 μm is measured. This turbidity represents the degree of tooth moss formation, and the inhibition rate of tooth moss formation was determined for each sample using a sample to which only a solvent was added as a control.

When the inhibition rate of tooth moss formation was determined for the ethanol soluble content, water soluble content, ethyl ether soluble content, petroleum benzine soluble content, and light yellow crystals at concentrations of 15.63 to 1000 μg/ml, it was found that the water soluble content was Although it showed almost no activity, all other fractions showed clear activity. Especially in the case of light yellow crystals, it is 62.5μg/
It showed a remarkable inhibition rate of 100% in ml. This light yellow crystal was identified as embelin based on its shape, melting point, IR, and mass spectra. Furthermore, TLC analysis of each fraction using methanol and chloroform as developing solvents revealed that all fractions showing inhibitory activity contained embelin, and the strength of the inhibitory activity was proportional to the embelin content. I found out.

This shows that embelin is the main ingredient in Emberia ribus's dental moss formation inhibiting activity, and by incorporating embelin into caries agents, lower alcohol extracts or water-containing lower alcohol extracts of Emberia ribs can be added. As a result, it has become possible to provide a new and excellent caries agent.

Furthermore, the chemical structure is similar to embelin,
The present invention also includes anti-caries agents containing compounds such as rapanone and vilandin, which are said to exhibit embelin-like physiological activity.

Embelin and embelin-like substances to be incorporated into the caries agent of the present invention may be fractionated and purified products from Ayurvedic herbal medicines such as Embelia ribus, Enasal, Walagasahal, etc., or from plants of the Aperaceae family that also grow in Japan. .

Next, the present invention will be specifically explained with reference to formulation examples, but the present invention is not limited thereto.

Formulation Example 1 Toothpaste A toothpaste is obtained according to the following formulation using a conventional method. Note that the numerical values indicate parts by weight.

Dicalcium phosphate dihydrate...45 Carboxymethylcellulose...1.0 Glycerin...20 Sodium lauryl sulfate...1.5 Flavor...1.0 Artificial sweetener...0.1 Sodium fluoride...0.1 Emberin...0.2 Water...Remaining 100 Formulation Example 2 Lozenges Lozenges are obtained by the usual method according to the formulation shown below. Note that the numerical values indicate parts by weight.

Gum arabic...6.0 Fructose...20 Glucose...20 Maltose...30 Flavor...0.1 Artificial sweetener...0.1 Emberin...3.0 Water...Remaining 100 Combination example 3 Preparation tablets The following was prepared using the usual method. Tablets for swallowing are obtained according to the formulation shown in . Note that the numerical values indicate parts by weight.

Sodium diphosphate...15 Sodium hydrogen carbonate...55 Polyethylene glycol...3.0 Sodium monofluorophosphate...0.5 Flavor...4.0 Chlorhexidine...0.05 Citric acid...15 Ethanol...6.0 Emberin...1.0 100

Claims (1)

[Claims] 1. An anti-caries solvent characterized by containing Embelin as an active ingredient.