JPH045222A - Crude drug extract for oral cavity and composition for oral cavity containing the same as active ingredient - Google Patents

Abstract

PURPOSE:To obtain a crude drug extract for the oral cavity useful for preventing periodontosis by extracting a crude drug selected from Psoraleae Semen, Pyrola japonica Klenze, Curcumae Rhizoma, Akebiae Caulis, Euphorbie Lathyridis Semen, Benincasae Semen and Pruni Cortex with methanol, ethanol and water. CONSTITUTION:Psoraleae Semen, Pyrola japonica Klenze, Curcumae Rhizoma, Akebiae Caulis, Euphorbie Lathyridis Semen, Benincasae Semen and Pruni Cortex are used as a crude drug and extracted with methanol and then ethanol, further water as extracting solvents at ambient temperature to 55 deg.C. The resultant extracts are then mixed and the methanol and ethanol are distilled away. The residue is subsequently fractionated with ethyl acetate and water by liquid- liquid partition. Furthermore, the obtained water fraction is extracted and fractionated with butanol and the ethyl acetate fraction is extracted and fractionated with hexane and methanol. Thereby, the objective crude drug extract is obtained. The resultant extract has selective antimicrobial activity against causative bacteria of periodontosis with low danger for microbial substitution even in prolonged administration for a long period.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to an oral crude drug extract for the purpose of preventing periodontal diseases and an oral composition containing this as an active ingredient.

[Conventional technology]

Periodontal diseases such as gingivitis and periodontitis are caused by oral anaerobic bacteria that live in dental plaque and gingival sulcus, such as Bacteroidesgin.
givaLis, Capnocytophaga o
chracea, Fuso-bacterturn
It is an infectious disease caused by NucLeatum, etc.
It has become clear that bactericides are effective in preventing periodontal disease.

[Problem to be solved by the invention] However, today, synthetic disinfectants such as chlorhexidine hydrochloride and cetylpyridinium chloride are known to have a preventive effect on periodontal disease and are widely used around the world. There are disadvantages such as it may cause Therefore, in Japan, the compounding ratio in daily-used oral care products such as toothpaste is limited to a low concentration of about 100 ρpIIl, which poses the problem that sufficient effects cannot be obtained.

[Means to solve the problem]

Therefore, the present inventors focused on crude drugs that have been used in Japan for a long time, are well known for their safety, and are also known to have a certain degree of antibacterial activity, and evaluated their antibacterial effects against periodontal disease-causing bacteria. conducted extensive research to uncover its potential as a periodontal disease preventive agent.

As a result, out of 17 types of herbal medicines, extracts of specific fractions obtained by solvent extraction of 7 types of herbal medicines were found to have characteristic antibacterial activity against periodontal disease-causing bacteria, leading to the completion of the present invention.

That is, in the present invention, a herbal medicine selected from bone fat, deer hoof grass, Ukin, Mikdong, Zizuizi, winter melon, and cherry bark is first extracted with methanol, then ethanol, and then water at a temperature ranging from room temperature to 55°C. The respective extracts were mixed at a temperature selected from fractions and ethyl acetate fractions were obtained;
The water fraction was subjected to liquid-liquid extraction fractionation using butanol to obtain a butanol fraction and a water fraction, and the ethyl acetate fraction was further subjected to liquid-liquid partitioning with hexane and a 90% aqueous methanol solution after distilling off the ethyl acetate. When extracted and fractionated into hexane and methanol fractions, methanol and hexane fractions of bone fat, methanol and hexane fractions of deer hoof grass, and water and butanol fractions of Ugane. From the methanol fraction and hexane fraction, the methanol fraction of Kidori, the hexane fraction of cassava, the butanol fraction, methanol fraction, and hexane fraction of winter melon, and the methanol fraction and hexane fraction of cherry bark. The present invention provides one or more oral crude drug extracts selected from the group consisting of: and oral compositions containing these oral crude drug extracts as active ingredients.

The extract for the oral cavity of the present invention uses skeletal fat, deer grass, ugane, woody grass, tsuzuizhi, winter melon, or cherry bark as herbal medicines, and is shown in Figure 1.
Various fractions are obtained by solvent extraction according to the procedure shown in , and an active extract is obtained. The temperature for solvent extraction and fractionation operations is selected in the range from room temperature to 55°C.

methanol fraction and hexane fraction of bone graft obtained by such operation, methanol fraction and hexane fraction of deer hoof grass,
Water fraction, butanol fraction, methanol fraction, and hexane fraction of Ugane, methanol fraction of Kidori, hexane fraction of Tsuizuki, butanol fraction, methanol fraction, hexane fraction of winter melon, and cherry blossoms. Antibacterial activity is observed in the methanol and hexane fractions of the skin.

When the oral herbal extract of the present invention is used as a preparation, the amount of the herbal drug extract in the oral cavity is at least 100 ppm when the product is used in a normal way.
However, in the case of oral compositions such as dentifrices, the oral cavity is usually washed with water after use, so it is desirable to add a large amount.

Moreover, in the oral composition of the present invention, active ingredients and raw materials used in ordinary oral compositions such as dentifrices, mouthwashes, and chewing gums can be used in combination. For example, active ingredients include sodium fluoride, sodium monofluorophosphate, allantoin, tranexamic acid, vitamin E, salt, chlorhexidine salt, cetylpyridinium salt, lysozyme, dextranase, mutanase, protease, amylase, lipase, glycyrrhizinate, etc. can be mentioned. Raw materials include abrasives such as aluminum hydroxide, calcium carbonate, zeolite, and calcium pyrophosphate. Examples of the binder include birch carrageenan, lambda carrageenan, guar gum, sodium polyacrylate, methyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose. As surfactants, polyoxyethylene polyoxypropylene copolymer, polyoxyethylene fatty acid ester, sorbitol fatty acid ester,
Examples include sodium acylglutamate, sucrose fatty acid ester, and the like.

[Examples] The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples.

Example 1 (Method for producing crude drug extract) Various crude drugs shown in Tables 1 to 5 were extracted by the method shown in FIG. 1, and the extraction solvent was leaked to obtain an extract.

(Preparation method of culture medium for antibacterial activity test) The above-mentioned extract was dissolved in deionized water, and those that were sparingly soluble in water were dissolved in the nonionic surfactant "Triton X100J".
Wako Pure Chemical Industries, Ltd.) was added and dispersed, and the pore size was 0.4.
The final concentration of the filter is 1.
00 pp- to the agar medium. The agar medium used was GAM agar medium (manufactured by Hinaga Pharmaceutical Co., Ltd.) containing 1x defibrinated sheep blood.

(Test strain) Bacteroides gingivalis (A
TCC33277) ; Causative bacteria of adult periodontitis.

Capnocytophaga och, racea
(ATCC33596); Causative bacteria of periodontitis.

Fusobacteria nucLeatua (
ATCC2558); causative bacteria of periodontitis.

5treptococcus ttrutans (A
TCC25175) ; Bacteria that causes tooth decay. It also causes early gingivitis.

Actinoayces viscosus (ATC
C15987) ; Causative bacteria of early gingivitis.

(Bacterial liquid preparation) The test bacterial strain was cultured anaerobically at 37°C for 24 hours in CAM broth (manufactured by Hinaga Pharmaceutical Co., Ltd.) to a bacterial concentration of 10" CFII (Col.
onyforming unit) /d was obtained. This bacterial solution was added to 40mM phosphate buffer (p)l=7.0)
Repeat dilution 10 times using
．． A bacterial solution of 105 CFU/hard was prepared.

(Determination of antibacterial activity) The above-mentioned bacterial solution 5111 was inoculated onto the above-mentioned CAM agar medium using an inoculator (20 locations: 5 bacterial species x 4 concentrations/plate). Thereafter, the cells were cultured anaerobically at 37°C for 24 hours. All operations and cultivation were carried out using anaerobic glove boxes (anaerobic mixed gas CO
z:Hz:hh=10:10:80).

After culturing, the degree of bacterial growth was visually determined, and those in which no bacterial growth was observed were considered effective.

At this time, since samples with high antibacterial activity are effective even when the concentration of the inoculated bacterial species is high, it is possible to judge the strength of the antibacterial activity of the test crude drug extract. So 10'CFU
Effective at /- concentration ◎, 10'CPU/d! The strength of the antibacterial activity was expressed as ○ if it was effective at a concentration of , Δ if it was effective at a concentration of 105CPtl/d, and × if it was ineffective at a concentration of 10'CFtl/d. Tables 1 to 5 show the antibacterial activity of extracts of various herbal medicines against bacteria.

・; Not tested; Not tested; Not tested; Not tested; Not tested (determination results of antibacterial activity) Strong antibacterial activity was observed in the fraction and Kidori's methanol fraction, but no activity was observed in the water fraction.

Strong antibacterial activity against C. ochγacea was observed in the water, butanol, and hexane fractions of Ugan, and in the butanol, methanol, and hexane fractions of winter melon.

Strong antibacterial activity against F. nucLeatum was observed only in the methanol and hexane fractions of cherry bark.

None of the extracts was active against S. mutans and A. viscosus.

The antibacterial activity of the crude drug extract of the present invention is characterized by high selectivity. This point is effective in the sense that periodontal disease-causing bacteria can be selectively suppressed.

That is, since the above-mentioned periodontal disease-causing bacteria are resident bacteria in the oral cavity, it is necessary to constantly apply an antibacterial agent to suppress them. This is different from the fact that the bacteria that cause infectious diseases such as cholera and typhoid fever are endemic and can be eradicated by regular administration of antibiotics.

Therefore, if broad-spectrum antibiotics are used for a long period of time to suppress periodontal disease-causing bacteria, the balance that the hundreds of species of oral bacteria maintain through antagonistic and symbiotic relationships may be disrupted, leading to candidiasis and other problems. There is an increased risk of bacterial replacement. However, the higher the selectivity of the antimicrobial agent used, the less the risk of disrupting the balance of oral flora. That is, it can be said that the use of the crude drug extracts having selective antibacterial activity discovered by the present inventors, alone or in combination, is suitable for long-term use for the purpose of preventing periodontal disease.

Example 2 (dentifrice part 1) The following components were degassed and mixed to obtain a paste-like dentifrice.

(Weight %) Successive hexane fraction 0.1 Kidori methanol fraction Calcium dihydrogen phosphate for toothpaste Glycerin anhydrous silicate 70% Sorbitol solution Sodium carboxymethyl cellulose iota Carrageenan Sodium methyl parahen lauryl sulfate Flavor 0.2 40 .0 2.0 10.0 15.0 1.8 Example 3 (Dentifrice No. 2) The following components were degassed and mixed to obtain a transparent dentifrice.

Kiyari methanol fraction Winter melon butanol fraction Silicic anhydride (weight%) 0.5 0.5 25.0 glycerin 70% sorbitol solution carboxymethyl cellulose sodium Methylparahen sodium lauryl sulfate Incense 30.0 30.0 1.8 0.1 1.7 0.9 Example 4 (mouthwash) The following components were stirred and mixed to obtain a mouthwash.

(Weight%) Cherry bark methanol fraction 0.1 Sodium benzoate Ethanol Coloring agent Flavoring 0.5 10.0 Trace amount 0.3 Total 100.0% by weight Example 5 (Chewing gum) The following ingredients were heated and mixed. The mixture was stretched into a plate shape, cooled and solidified to obtain chewing gum.

Weight% Ugane hexane fraction 0.1 Deer hoof grass hexane fraction 0.1 Bone fat hexane fraction
0.1 gum hese
25.0 sugar
50.0 Corn syrup 24
．． 5

[Brief explanation of drawings]

FIG. 1 is a flowchart showing the procedure of fractionation operation for obtaining the oral herbal medicine extract of the present invention. (Effects of the Invention) The oral herbal medicine extract of the present invention has selective antibacterial activity against periodontal disease-causing bacteria, and has a low risk of bacterial replacement even when used continuously for a long period of time. In addition, by blending these extracts, products effective for preventing periodontal diseases such as dentifrices, mouth rinses, and chewing gums can be obtained.

Claims (1)

[Scope of Claims] 1. A herbal medicine selected from bone fat, deer foot grass, Ugan, Mikdong, Zizuizi, winter melon, and cherry bark is extracted with methanol, then ethanol, and then water as an extraction solvent from room temperature to 55%. Mix the extracts extracted at a temperature selected from between ℃ and distill off methanol and ethanol to obtain a crude extract,
This crude extract was further subjected to liquid-liquid partition extraction fractionation with ethyl acetate and water to obtain a water fraction and an ethyl acetate fraction, and the water fraction was further subjected to liquid-liquid partition extraction fractionation with butanol to obtain a butanol fraction. After distilling off the ethyl acetate, the ethyl acetate fraction was further subjected to liquid-liquid extraction fractionation with hexane and a 90% methanol aqueous solution to obtain a hexane fraction and a methanol fraction. Methanol fraction and hexane fraction of fat, methanol fraction and hexane fraction of deer hoof grass, water fraction, butanol fraction, methanol fraction, and hexane fraction of Ugane, methanol fraction of Kidori, etc. One or more crude drug extracts for the oral cavity selected from the group consisting of the hexane fraction of roe, the butanol fraction, methanol fraction, and hexane fraction of winter melon, and the methanol fraction and hexane fraction of cherry bark. 2. An oral composition comprising the oral crude drug extract according to claim 1 as an active ingredient.