JPS6324489B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a cariogenic fungus growth inhibitor, and more specifically, a cariogenic fungus growth inhibitor containing a hydrophilic organic solvent extract of nikuduku (nikumame) and/or mulberry bark as an active ingredient. It relates to growth inhibitors. Dental caries is generally referred to as tooth decay, and its causes are thought to be as follows. Sucrose contained in food becomes sticky polysaccharide under the action of certain oral bacteria, which makes it easier for the bacteria to adhere to the teeth, forming dental plaque, which is a nest for bacteria.
Here, bacteria break down sugars and produce acids, which demineralize the tooth enamel surface and advance caries. If caries progresses further, it will develop into alveolar pyorrhea. Various proposals have been made so far as means to prevent caries, such as antibiotics,
There are methods to use disinfectants, etc., methods to use cell wall lytic enzymes, and methods to exterminate oral bacteria using Japanese and Chinese medicine. Streptococcus mutans is a bacteria that causes dental caries.
Streptococcus sanguis ( S.
Sanguis), Streptococcus michiis ( S.
mitis), but the main one is Streptococcus miutans. Many drugs, both synthetic and natural, have been reported to inhibit the growth of Streptococcus miutans. However, there are major problems with the use of conventional antibiotics. For example, it has been pointed out that antibiotics can disturb the flora of intestinal bacteria if swallowed, and very few antibiotics have reached the stage of practical use. One of the reasons for this is that when these antibacterial agents are actually used, they kill or weaken the functions of bacteria necessary for the human body. In view of this situation, the present inventor conducted intensive research to find a substance that inhibits the growth of Streptococcus miutans and does not have antibacterial properties against intestinal bacteria. We have discovered that a hydrophilic organic solvent extract of mulberry bark and/or mulberry bark can achieve the above object, and based on this knowledge, we have completed the present invention. Nikuduku (meat beans) are the seeds of the Nikuzuku family, with the aril and seed coat removed, and are widely cultivated in tropical regions and are often used as a spice. Mulberry bark is the root bark of mulberry or its congener plants, which belong to the Moraceae family, and is a type of Chinese herbal medicine produced mainly in Japan and China. The above plants may be used alone or in combination of two or more. Furthermore, these plants are usually used in the form of crushed products or powder. Hydrophilic organic solvents used in the present invention include lower alcohols such as methanol and ethanol;
Glycols such as ethylene glycol and propylene glycol, ketones such as acetone, and tetrahydrofuran are preferred, and in the case of raw materials with a high fat content, an appropriate amount of water can be added as necessary to use as a water-containing organic solvent. The extraction method from the above plants may be any commonly used method, such as immersing the raw material plant in an organic solvent or a water-containing organic solvent for a long time at room temperature, heating at a temperature below the boiling point of the organic solvent, There are methods such as performing extraction while stirring and filtering to obtain the extract. Depending on the mode of use, the extract may be used as it is, or may be partially concentrated and used, or after concentration, it may be washed with hexane, water, etc. to remove the inert part to obtain a concentrated purified product, and this may be used. It can be used by dissolving or suspending it in an appropriate solvent. The caries growth inhibitor of the present invention may be used alone or in combination of two or more, and other agents may be added as necessary. Generally, it is preferable to use it as an additive to chewing gum, candy, troches, candy, etc. that can stay in the mouth for a certain period of time, but the caries growth inhibitor of the present invention hardly loses its effectiveness due to surfactants. It can also be used in mouth cleansers such as toothpaste and mouthwash. The applicable concentration of the caries growth inhibitor of the present invention may be determined by considering factors such as effective concentration and dilution in the mouth. Generally, when used in a mouth cleanser, it is desirable to use it at a slightly higher concentration since the contact time between the agent and bacteria is relatively short. Susceptibility tests for various bacteria were conducted as follows. Streptococcus miutans RIMD3125001 strain (hereinafter referred to as Bacillus myutans) was used as the cariogenic bacterium, and Bacteroides microfusus IPCR 1009 strain (hereinafter referred to as Bacterium microfusus) was used as an aerobic intestinal bacterium. ) and Escherichia coli ATCC
We selected Bifidobacterium adolescentis strain 10798 (hereinafter referred to as B. coli) as an obligate anaerobic bacterium.
We selected ATCC 15705 strain (hereinafter referred to as Bacterium adolescentis) and used these as test microorganisms, and proceeded with the search for target substances using the growth or growth inhibition of each microorganism as an indicator. The sample (extracted, concentrated and purified product) was added to a heart infusion agar medium, and P. myutans was punctured and transplanted thereto, cultured at 37°C for 72 hours, and those that showed no growth were treated as anti-Myutans active substances. did. A sample was similarly added to a heart infusion agar plate medium with the same composition, inoculated with Microfusus bacteria and Coli bacteria, and cultured for 72 hours at 37°C under aerobic conditions. Those with growth were considered to have passed. . In addition, the sample was similarly added to a heart infusion agar medium with the same composition, and B. adolescentis was punctured and transplanted to this, and cultured for 72 hours at 37°C under anaerobic conditions.Those that showed growth passed the test. And so. That is, a sample that inhibited the growth of B. mutans at the same concentration, while allowing growth without affecting intestinal bacteria, was used as the cariogenic bacteria growth inhibitor of the present invention. Although the substance of the caries growth inhibitor according to the present invention is still unknown, it has a major feature of being insoluble in hydrocarbon solvents such as hexane, although it is soluble in hydrophilic solvents. . Next, the present invention will be explained in more detail with reference to Examples. 500 ml of 50% methanol was added to 100 g of the coarsely ground product described in Example 1, and extraction was performed with stirring at 65° C. for 8 hours. After extraction, it was filtered, and methanol and water were distilled off from the filtrate to obtain a concentrate. Add warm water to this concentrate
50 ml was added and washed with stirring to remove water-soluble substances. After repeating this operation three times, 50ml of n-
Hexane was added, the mixture was stirred and washed, and hexane-soluble components were extracted and removed. Repeat this operation three times,
2.3 g of a brown, slightly viscous oil was obtained. 10 ml of propylene glycol was added to 0.5 g of this oil and heated to prepare a caries growth inhibitor (hereinafter referred to as sample). Chewing gum can be made by mixing this sample with a chewing gum base. As a result of measuring the antibacterial properties using B. mutans as a test bacterium, the growth of the bacterium could be completely inhibited for 72 hours by adding 0.2% of this sample (1/10000 concentration). Next, Microfuusus bacteria and Coli bacteria were inoculated onto a heart infusion agar plate medium supplemented with 0.2% of this sample and cultured at 37°C for 72 hours, and growth was observed in both cases. In addition, B. adolescentis was punctured into a heart infusion agar medium supplemented with 0.2% of this sample, and cultured for 72 hours in an anaerobic culture tank at 37°C. As a result, growth of the bacteria was observed. Example 2 500 ml of 50% aqueous acetone was added to 100 g of mulberry bark powder, and extraction was performed with stirring at 65° C. for 8 hours. After filtration, the extract was concentrated under reduced pressure. The concentrate was extracted and washed three times with 50 ml of n-hexane, and then concentrated to dryness again under reduced pressure to obtain 0.8 g of a brown viscous solid.
0.25 g of this solid was dissolved in 5 ml of 50% ethanol to prepare a caries growth inhibitor. This sample can be added to mouthwash liquid to form a product. When antibacterial properties were measured in the same manner as in Example 1, the growth of B. myutans was completely inhibited at a concentration of 1/10000. Regarding intestinal bacteria, 1/
No growth inhibition was observed even at a concentration of 5,000.

Claims (1)

[Claims] 1. A caries growth inhibitor containing a hydrophilic organic solvent extract of mulberry bark and/or mulberry bark as an active ingredient.