JPH06256177A - Antimicrobial composition and method for providing antimicrobial property - Google Patents

Abstract

PURPOSE:To obtain a composition consisting of a specific compound (salt) and a carrier, low in toxicity, capable of keeping skin, hair, etc., clean, excellent in keeping quality and useful for drinks and foods, cosmetics, medicines, etc. CONSTITUTION:The composition consists of (A) preferably >=1w/w% one or more compounds selected from 3-{4-hydroxy-3,5-bis(3-methyl-2-butenyl)phenyl}-2- propenoic acid, benzenepropanoic acid, 4-(2-carboxyethenyl)-2-(3-methyl-2-butenyl) phenyl ester and their salts and (B) a carrier such as vehicles. Furthermore, antimicrobial property is preferably provided to a material subjected to antimicrobial treatment by adding one kind of the component A to the material subjected to antimicrobial treatment in a concentration of the component A of >=16ppm.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel antibacterial composition and antibacterial method, and more particularly to 3- {4-hydroxy-
3,5-bis (3-methyl-2-butenyl) phenyl}
-2-propenoic acid, benzenepropanoic acid, 4- (2-carboxyethenyl) -2-
The present invention relates to an antibacterial composition and an antibacterial method containing, as an antibacterial component, at least one compound selected from (3-methyl-2-butenyl) phenyl ester and salts thereof.

[0002]

2. Description of the Related Art Antibacterial substances are used to improve the shelf life of foods and drinks, and to keep the skin clean. Conventionally, mainly chemical synthetic products such as benzoic acid, sorbic acid, dehydroacetic acid or salts thereof are used. Are used. However, these antibacterial substances are currently difficult to use because their side effects such as carcinogenicity are concerned and their use and usage are severely limited. On the other hand, antibiotics such as penicillin, streptomycin, and kanamycin are used as antibacterial substances to treat burns, cuts, infectious diseases, and the like.

However, there is a problem that excessive dependence on antibiotics causes the emergence of resistant bacteria, which in turn causes serious infections. Therefore, the highly safe antibacterial action derived from natural products has come to be reviewed. Those derived from these natural products generally have rare occurrence of resistant bacteria, have low toxicity as compared with their antibacterial effects, and have the advantage that they can be used with confidence.

However, the actual situation is that the individual antibacterial components contained in these substances have not always been elucidated. For example, the inventors of the present invention first reported that medicine and biology, Vol. 124 (5), 205-209 (19
Regarding the antibacterial action of Brazilian propolis reported in (92), the antibacterial action of propolis extract has been clarified, but the main body of the antibacterial substance contained therein has not been clarified. Therefore, it is desired to elucidate antibacterial substances derived from natural products and establish antibacterial compositions such as antibacterial agents having low toxicity and strong antibacterial action.

[0005]

DISCLOSURE OF THE INVENTION It is an object of the present invention to provide an antibacterial composition and an antibacterial method containing a compound having a low toxicity and a strong antibacterial action as an active ingredient.

[0006]

[Means for Solving the Problems] In order to achieve the above-mentioned object, the present inventors have focused their attention on the antibacterial substance contained in the propolis extract, and have continued to make earnest studies. As a result, the strong antibacterial action of Brazilian propolis extract is due to the fact that 3- {4-hydroxy-3,5-bis (3-methyl-2-butenyl) phenyl} -2-propenoic acid (3 -[4-Hydroxy-3,5-bis (3-methyl-2-butenyl) phen
yl] -2-propenoic acid [hereinafter referred to as compound (1). ] And benzenepropanoic acid 4-
(2-Carboxyethenyl) -2- (3-methyl-2-)
Butenyl) phenyl ester (Benzenpropanoic acid 4
-(2-carboxyethenyl) -2- (3-methyl-2-butenyl) phenyl e
ster [hereinafter referred to as compound (2). ] It was found that it was derived from. The present inventors have further researched on the basis of this new finding, and these compounds, antibacterial compositions containing at least one compound selected from these salts as an active ingredient, especially foods and drinks with improved storability, antibacterial The present invention has been completed by establishing an antibacterial method using such compounds, such as cosmetics and pharmaceuticals having an action.

That is, the present invention has the following gist. An antibacterial composition comprising at least one selected from compound (1), compound (2) and salts thereof, and a carrier. An antibacterial composition containing 1 w / w% or more of at least one selected from compound (1), compound (2) and salts thereof. The antibacterial composition, wherein the antibacterial composition is one selected from foods and drinks, cosmetics and pharmaceuticals. An antibacterial method for an antibacterial substance to be treated, wherein at least one selected from the compound (1), the compound (2) and a salt thereof is allowed to coexist with the substance to be antibacterial substance at a concentration of 16 ppm or more.

The salt of the compound (1) and the salt of the compound (2) used in the present invention are each acceptable according to the mode of use (for example, in general, food hygiene, cosmetics, or pharmacologically acceptable). Specifically, sodium salts, calcium salts, copper salts and the like are exemplified.

The antibacterial composition according to the present invention is one which exhibits antibacterial properties against the composition itself (that is, a composition for preventing spoilage of the composition itself due to bacteria) and the composition. Then, it means a composition for antibacterial treatment of other substances, living bodies and the like.

The compound (1), the compound (2) and salts thereof used in the present invention are known compounds, and are synthesized synthetically by known means, or the compound (1), the compound (2) or salts thereof. It can be prepared by extraction from a plant or the like containing

As a method of preparing from natural products, a method of preparing from propolis or a method of preparing from stems of leaves of plants belonging to the family Asteraceae (for example, wormwood, etc.) [Phytochemistry, Vol. Two
5,2841-2855 (1986), Chemical Pharmaceutical Bulletin (Chemical P
pharmacological Bulletin) Vo
l. 36, 769-775 (1988)].
When prepared from these natural products, the compound (1), compound (2) and salts thereof used in the composition of the present invention do not necessarily have to be isolated as crystals, and they have an antibacterial action as an active ingredient. For example, an extract such as an extract that has been partially purified to such a degree that it can exert its activity may be used.

As the above-mentioned preparation method, a conventional extraction method, purification method or the like can be appropriately used. For example, first, a natural product (eg, propolis or foliage of Asteraceae) as a raw material is pulverized, extracted with a solvent such as alcohol (methanol, ethanol, etc.) or alcohol-water, and then concentrated by a conventional method. The obtained extract can be prepared by subjecting it to gel filtration column chromatography, reverse phase column chromatography and the like. The compound (1) may be prepared, for example, by the chemical synthesis method disclosed in JP-A-60-163841.

The antibacterial composition of the present invention comprises: an antibacterial composition comprising at least one selected from the compound (1), the compound (2) and salts thereof and a carrier (hereinafter referred to as antibacterial composition 1). ), And: An antibacterial composition (hereinafter referred to as antibacterial composition 2) containing at least 1 type selected from the compound (1), the compound (2) and salts thereof in an amount of 1 w / w% or more.

At least one compound selected from the compound (1), the compound (2) and salts thereof used in the antibacterial composition 1 may be a synthetic product, a pure product derived from a natural product, an extract or the like. Examples include crude products.

The carrier in the antibacterial composition 1 is added in order to give the composition an appropriate shape and properties. For example, in pharmaceuticals or cosmetics, a solvent (an aqueous solvent such as distilled water for injection, Organic solvents, etc.), excipients,
In foods and beverages, the base (ointment base, suppository base, etc.) is water, starch, gum base, seasoning (eg, vinegar,
Soy sauce, salt, etc.) and the like.

Compound (1) in the antibacterial composition 1,
The content of at least one compound selected from the compound (2) and salts thereof is usually 0.001 w as the total amount thereof.
/ W% or more, preferably 0.01 to 50 w / w%, more preferably 0.1 to 20 w / w%.

The antibacterial composition 2 contains at least one selected from the compound (1), the compound (2) and salts thereof in a total amount of 1 w / w% or more, preferably 2 w / w%.
As described above, more preferably 5 w / w% or more is contained.

Examples of the antibacterial composition 1 and the antibacterial composition 2 include food and drink, cosmetics and pharmaceuticals.

Antibacterial treatment of the substance to be antimicrobially treated by coexisting at least one selected from the compound (1), the compound (2) and salts thereof in an amount of 16 ppm or more, preferably 31 ppm or more. You can Coexistence means a state in which both the compound used in the present invention and the antibacterial substance to be treated are present, and specifically, for example, the compound is in contact with and mixed with the antibacterial substance to be treated.

The term "antimicrobial-treated product" as used herein is a concept that includes all products produced by bacteria, and examples thereof include foods and drinks, cosmetics, pharmaceuticals, etc. which will be described in detail later.

The antibacterial action of the compound (1), the compound (2) and salts thereof used in the present invention is particularly remarkable in filamentous fungi [eg Microsporum ].
Genus, Arusuroderuma (Arthroderma) genus, etc.], and bacteria [e.g. Bacillus (Bacillu
s ), Enterobacter ( Enterobacter)
r ) genus, Pseudomonas
Genus, Propionibac
terium ), Mycobacterium ( Mycoba
genus Cterium , Corynebacterium ( Coryn)
Escherichia ) etc.] and the like.

The minimum inhibitory concentration of the compound (1), the compound (2) and their salts varies depending on the bacterial species,
It is generally in the range of about 16 to 125 ppm.

More specifically, filamentous fungi that cause skin infections, for example, Microsporum .
Genus and, for Arusuroderuma (Arthroderma) genus, minimum inhibitory concentration is about 16 ppm, thus the antimicrobial composition of the present invention is athlete's foot treatment, it can be advantageously used as antimicrobial compositions such as skin cosmetics.

Further, by rotting food, bacteria causing food poisoning, for example Bacillus (Bacillus) genus Enterobacter (Enterobacter) genus, the minimum inhibitory concentration of about 16 to 63 ppm, thus the present invention The above antibacterial composition can be advantageously used as an antibacterial composition for improving the preservability of food and drink.

Furthermore, it causes wound infection, dandruff,
For bacteria that cause skin diseases such as acne, for example, the genus Pseudomonas and the genus Propionibacterium , the minimum growth inhibitory concentration is about 31 to 125 ppm.
Therefore, the antibacterial composition of the present invention can be advantageously used as an antibacterial composition for wound healing agents, skin cosmetics and the like.

In addition, the genus Mycobacterium which causes tuberculosis and Corynebacterium which causes diphtheria ( Corynebacterium)
m ), the minimum growth inhibitory concentration is about 31 to 63 ppm. Therefore, the antibacterial composition of the present invention is advantageous as an antibacterial composition for treating and preventing infectious diseases such as tuberculosis and diphtheria. Can be used for

The antibacterial composition of the present invention comprises the compound (1),
It suffices that at least one selected from the compound (2) and salts thereof exhibit an antibacterial action. In other words, it is desirable that the minimum growth inhibitory concentration of these active ingredients be maintained when the action is exhibited. . Usually, the concentration is preferably 16 to 125 ppm, or higher.

The antibacterial composition of the present invention can be advantageously used in combination with other known antibacterial substances, if necessary.

The shape of the antibacterial composition of the present invention can be selected appropriately according to the purpose and may be liquid, paste or solid. Further, if necessary, at least one selected from the compound (1), the compound (2) and salts thereof, as well as other materials such as an excipient, a stabilizer, a bulking agent, an emulsifier, a solvent, a coloring agent, a flavoring agent. It is also advantageous to add a seasoning or the like.

It is also possible to mix at least one selected from the compound (1), the compound (2) and salts thereof with anhydrous maltose, cyclodextrin or the like to give a solid antibacterial composition, or to dissolve it in water. The antibacterial composition in the form of a solution or a paste may be advantageously dissolved in a solvent.

In order to improve the storability of foods and drinks by containing at least one selected from compound (1), compound (2) and salts thereof, the range of 1 ppm or more, preferably 16 to 500 ppm is preferable. is there. Examples of food and drink include agricultural products such as vegetable juice, tofu, bean paste, nut paste, starch paste, and flour dough,
Seafood products such as sardine paste, fish sausage, kamaboko, chikuwa, livestock products such as whey, fresh cream, cheese, ham, sausage, seasonings such as miso, soy sauce, sauce, betara pickles, Senmai pickles, cabbage pickles, etc. Pickles, boiled beans, potato salad, side dish such as kelp rolls, fertilizer, rice cakes,
It can be advantageously used for improving the preservability of various foods and drinks such as Japanese confectionery such as jelly, Western confectionery such as bread, custard cream, waffle, chewing gum and chocolate. Here, the food and drink is a concept including feeds and feeds for domestic animals such as livestock, poultry and fish.

In the case of cosmetics, it is possible not only to improve the preservability of the cosmetics themselves, but also to keep the skin, hair, oral cavity, etc., clean, for example, compound (1), compound (2) and those At least one selected from the above-mentioned salts is usually 10 ppm or more, preferably 50 to 5,0.
It is preferable to contain it in the range of 00 ppm. As the cosmetics, for example, bath agents, shampoos, rinses, nail polishes, emulsions, hair creams, hair lotions, hair tonics, toothpastes, lipsticks, lip balms, mouth fresheners, and breath fresheners can be used.

In the case of a drug, not only the storage property of the drug itself can be improved, but also the preventive and therapeutic effects of the infectious disease in the affected area can be exerted, and the compound (1), the compound (2) and salts thereof can be used. It is preferable that at least one selected from the above is contained in an amount of usually 100 ppm or more, and preferably 500 to 1,000,000 ppm. Examples of medicinal products include mouthwashes for treating and preventing periodontal disease, tooth decay, stomatitis, halitosis, troches, granules dissolved in the oral cavity, tablets, film-like drugs, food poisoning such as fever, diarrhea, and vomiting, infectious diseases. It can also be advantageously used as an internal medicine for the treatment of various infectious diseases, an external ointment for preventing infection of cuts, burns, ulcers, etc. and promoting healing, as well as nasal drops, suppositories, injections and the like.

The dose can be appropriately adjusted depending on the administration route, administration frequency, symptoms, body weight, age and the like. Usually, at least one selected from the compound (1), the compound (2), and a salt thereof is about 0.
A dosage in the range of 001 to 5 grams is preferred.

The production examples, experimental examples and examples of the present invention will be described below, but the present invention is not limited by these descriptions.

[0036]

[Manufacturing example / Experimental example]

Production Example 1 1. Method for Preparing Compound (1) 153.3 parts by weight of a propolis original mass produced in Brazil was crushed with a triobender and extracted with ethyl acetate. Methanol was added to the extract and the resulting precipitate was removed by centrifugation.
The solvent was removed on a rotary evaporator and methanol was added. The resulting precipitate was again removed by centrifugation, the solvent was removed by a rotary evaporator, and methanol was added to obtain an extract. As a solid, 63.9 parts by weight was obtained.

Next, column chromatography was performed using silica gel 60 G650 (manufactured by Katayama Chemical Co., Ltd.). Charge 35 parts by weight of extract as a solid,
The mixture was eluted with a mixed solvent of hexane and ethyl acetate while applying a gradient. Hexane / ethyl acetate = 59/41
The fraction eluted at 57/43 and 2.2 parts by weight as a solid substance were collected.

Next, this fraction was separated into Sephadex LH-2
It was subjected to column chromatography with 0 (Pharmacia). Methanol was used as the eluent and the elution was carried out with SV 0.16. When the fraction near the elution position of 1.1 volume / carrier volume was concentrated, crystals were precipitated. The crystals were washed with hexane to obtain 0.28 part by weight of a standard product.

The physicochemical properties of this preparation were investigated. (1) Melting point 95 ° C. (2) Elemental analysis measurement value C = 75.85% H = 8.39% O
= 16.39% Calculated value C = 75.97% H = 8.05% O
= 15.98% (Molecular formula: C ₁₉ H ₂₄ O ₃ ) (3) Molecular weight 300.40

(4) Ultraviolet absorption Measured by dissolving in methanol. The results are shown in Fig. 1. As is clear from FIG. 1, 204, 219, 235, 31
It has an absorption maximum at 3 nanometers. This is JP 60
It was in agreement with the value of the present compound shown in -163841.

(5) Infrared absorption spectrum 1.5 mg of the standard and 200 mg of dry KBr were mixed to prepare tablets, and the infrared absorption spectrum was measured. The result is shown in Figure 2.
Shown in. As apparent from FIG. 2, 3440cm ^-1, 3
000-2500 cm ^-1 (br), 1670 cm ^-1 , 1
It has absorption at 625 cm ^-1 , 1595 cm ^-1 and so on. These values are 3440 cm ⁻¹ , 2800-2500c, which are the values of the present compound disclosed in JP-A-60-163841.
m ^-1 (br), 1680 cm ^-1 , 1628 cm ^-1 , 15
It coincided with 99 cm ^-1 .

(6) Hydrogen nuclear magnetic resonance analysis ( ¹ H-NM
R) Dissolved in deuterated chloroform and measured at 500 MHz. The following 22 hydrogen signals were observed. 7.69 pp
m (1H, d, J = 15.9Hz), 7.20ppm
(2H, s), 6.29ppm (1H, d, J = 15.9Hz),
5.31ppm (2H, brt), 3.35ppm
(4H, br d), 1.79 ppm (6H, s),
1.78ppm (6H, s) This value is Chemical Pharmaceuti
cal Bulletin, Vol. 36,769-7
75 measurements of the compound measured in aceton-d _6, which shows the (1988), 7.69ppm (1H,
d, J = 17 Hz), 7.15 ppm (2H, br
s), 6.23 ppm (1H, d, J = 17 Hz),
5.28 ppm (2H, br t), 3.33 ppm
(4H, m), 1.78 ppm (12H, s).

(7) Chemical Structure From these results, this compound was identified as 3--
It was identified as [4-hydroxy-3,5-bis (3-methyl-2-butenyl) phenyl] -2-propenoic acid. The chemical structure of this compound is shown in the following formula (1).

[0044]

[Chemical 1]

Production Example 2 1. Preparation method of compound (2) A fraction obtained by silica gel column chromatography of Production Example 1 and eluted with hexane / ethyl acetate = 55/45 to 52/48, 2.5 parts by weight as a solid was prepared.
It was subjected to column chromatography with Sephadex LH-20 in the same manner. Fractions near the elution position of 1.0 volume / carrier volume were collected. Furthermore, fractionation was performed by reverse phase high performance liquid chromatography. Methanol / eluent
Water / acetic acid = 900/100 / 0.01 was used. The fraction was concentrated to give 0.058 part by weight of crystals.

The physicochemical properties of this preparation were investigated. (1) Melting point 99 ° C. (2) Elemental analysis measured value C = 75.14% H = 6.59% (3) Molecular weight FD / MS; M / z = 364 (molecular formula is C ₂₃ H ₂₄ O ₄ , molecular weight 364.44, C =
The calculated values were 75.80%, H = 6.64%, and O = 17.56%. )

(4) Ultraviolet absorption Measured by dissolving in methanol. The results are shown in Fig. 3. As is clear from FIG. 3, the absorption maximum is at 208,278 nanometers.

(5) Infrared absorption spectrum 1 mg of the standard and 200 mg of dry KBr were mixed to form a tablet.
The infrared absorption spectrum was measured. The results are shown in Figure 4.
You As is clear from FIG. 4, 3450 cm^-1(B
r), 2920 cm^-1, 3100-2800cm^-1(B
r), 1750 cm ^-1, 1690cm^-1, 1635cm
^-1Have absorption in etc.

(6) Hydrogen nuclear magnetic resonance analysis ( ¹ H-NM
R) Dissolved in deuterated chloroform and measured at 500 MHz. The following signals for 23 hydrogen atoms were observed. 7.73 ppm (1 H, d, J = 16.0 Hz), 7.
40ppm (1H, dd), 7.39ppm (1H,
s), 7.31 ppm (2H), 7.27 ppm (2
H), 7.24 ppm (1H), 6.97 ppm (1
H, d, J = 8.3 Hz), 6.38 ppm (1H,
d, 16.0 Hz), 5.18 ppm (1H, br
t, J = 7.3, 1.4 Hz), 3.14 ppm (2
H, br d, J = 7.3 Hz), 3.09 ppm (2
H, t, J = 7.8, 7.4 Hz), 2.92 ppm
(2H, t, J = 8.0, 7.4Hz), 1.75pp
m (3H, s), 1.67ppm (3H, s)

These values are Phytochemistr
y, Vol. 25, 2841-2855 (1986)).
7.6, the measured value of the methyl ester of the present compound,
3ppm (1H, d, J = 16Hz), 7.35ppm
(1H, dd, J = 2, 8.5Hz), 7.34ppm
(1H, brs), 7.15-7.3ppm (5H,
m), 6.93 ppm (1 H, d, J = 8.5 Hz),
6.33ppm (1H, d, 16Hz), 5.17pp
m (1H, tqq, J = 7, 1Hz), 3.13ppm
(2H, br d, J = 7Hz), 3.08ppm (2
H, br t), 2.91 ppm (2H, br t),
1.74ppm (3H, br s), 1.66ppm
(3H, br s), 3.79 ppm (OMe, s)
And, except for the signal of the methoxyl group.

(7) Chemical Structure This compound is a known compound, benzenepropanoic acid 4- (2-carboxyethenyl) -2- (3).
-Methyl-2-butenyl) phenyl ester. The chemical structure of this compound is shown in the following formula (2).

[0052]

[Chemical 2]

Experimental Example 1 Antibacterial activity The antibacterial activity of the compounds (1) and (2) isolated in Production Example 1 and Production Example 2 against various microorganisms was determined by the minimum inhibitory concentration (MIC) of the Japanese Society of Chemotherapy. Measurement method (C
hemotrapy, Vol. 29, 76-79 (1
987), Vol. 27,559-560 (197)
9)) was measured.

The following 20 strains were used. (A) Bacillus cereus IFO 3466 ( b) Bacillus subtilis ATCC 6633 (c) Corynebacterium equi IFO 3730 (d) Micrococcus luteus IAM 1099 (e) Micrococcus lysodeikticus IFO 3333 (f) Pseudomonas aeruginosa IFO 3453 (g) Mycobacterium phlei JCM 5865 T (H) Mycobacterium smegmatis JCM 5866 ^T (i) Staphylococcus aureus ATCC 6538P (j) Staphylococcus epidermidis ATCC 12228 (k) Enterobacter r aerogenes IFO 3321 (l) Flavobacterium meningosepticum IFO 12535 (m) Thermoactinomyces intermedius JCM 3312 T (n) Propionibacterium acnes JCM 6425 T (o) Bifidobacterium adolescentis JCM 1275 T (p) Bifidobacterium longum JCM 1217 T (q) Kloeckera apiculata JCM 5947 (R) Saccharomyces cerevisiae IFO 0214 (s) Arthroderma benhamiae JCM 1885 (t) Microsporum gypseum IFO 8231

The test maximum concentrations of the compound (1) and the compound (2) were 250 μg / ml, and 2-fold serial dilutions were performed to prepare test agar plates. The test agar plate is (a)
(L) is Sensitive Disc Agar-N (Nissui),
(Q) to (t) are potato dextrose agar (Dif
(manufactured by N. Co.), (m) tryptosoya agar medium (manufactured by Nissui), and (n) to (p) used modified GAM agar medium (manufactured by Nissui).

The cells cultured in the growth medium were streaked on a test plate with a platinum wire loop and inoculated. (A) to (f) and (q) and (r) at 27 ° C. for 1 day, (g) to (l) at 37 ° C. for 1 day, (h) at 55 ° C. for 1 day, and (n) to (P)
Anaerobically at 37 ° C for 2 days, (s) and (t) at 27 ° C for 3 days
After the day culture, the judgment was made. The results are shown in Table 1.

[0057]

[Table 1]

As is clear from the results shown in Table 1, the compounds (1), (2) and salts thereof, which are the active ingredients of the present invention, have antibacterial activity against various microorganisms. In particular, the genus Microsporum , Arthroderm
a genus, Bacillus genus, Corynebacterium
ium , Micrococcus , Pseudom
genus onas, genus Enterobacter , Mycob
It has an effective antibacterial activity against microorganisms of the genera Actium , Staphylococcus and Thermoactinomyces . Mi , a dermatophyte
It is effective against the genus Crosporum and the genus Arthroderma and can be used as a remedy for athlete's foot. Ba
genus Cillus, genus Micrococcus , Ente
genus robobacter and Staphylococcus
It is effective against food spoilage bacteria such as s genus and bacteria caused by food poisoning, and can be used, for example, as a preservative for various foods. Pse
It is effective against the genus udomonas and can be used, for example, in wound healing. It is also effective against the genus Propionibacterium and can be used, for example, for the treatment of skin diseases.
It is effective against the acid-fast bacterium Mycobacterium genus and Corynebacterium genus close to the diphtheria bacterium, and can be used for infectious diseases such as tuberculosis and diphtheria. On the other hand, Bifidobacterium
The antibacterial action against the genus m is extremely weak, and it selectively acts on food poisoning bacteria, intestinal spoilage bacteria, etc., so that it can be used as, for example, an intestinal regulating agent.

Experimental Example 2 Acute toxicity A compound (1) prepared by the method of Production Example 1 was orally administered to 7-week-old dd mice, and an acute toxicity test was conducted. No examples were seen.
Therefore, the toxicity of this compound (1) is extremely low. In addition, when this test was performed using the compound (2) prepared by the method of Production Example 2, the same result was obtained and it was found that the toxicity was extremely low.

[0060]

EXAMPLES Examples of the present invention will be described below. Example 1 Antibacterial agent 80 parts by weight of 5 parts by weight of the compound (1) obtained by the method of Production Example 1 was added.
It was dissolved in 95 parts by weight of v% ethanol to obtain a liquid antibacterial agent. The product is advantageously used as an antibacterial agent in antibacterial compositions such as foods and drinks, cosmetics and pharmaceuticals.

Example 2 Antibacterial agent 75 parts by weight of 2 parts by weight of the compound (2) obtained by the method of Production Example 2 was added.
It was dissolved in 98 parts by weight of v% isopropyl alcohol to obtain a liquid antibacterial agent. This product is advantageously used as an antibacterial agent in an antibacterial composition such as foods and drinks, cosmetics and pharmaceuticals as in Example 1.

Example 3 Antibacterial agent 50 parts by weight of the antibacterial agent obtained by the method of Example 1 were mixed with 45 parts by weight of 5 w / w% glycerin, and the mixture was adjusted to pH 7.4 with 1N disodium phosphate. A liquid antibacterial agent was obtained. The product is advantageously used as an antibacterial agent in antibacterial compositions such as foods and drinks, cosmetics and pharmaceuticals.

Example 4 Antibacterial agent 80 v / v% of 1 part by weight of the compound (1) obtained by the method of Production Example 1 and 1 part by weight of the compound (2) obtained by the method of Production Example 2 were used.
It was heated and dissolved in 9 parts by weight of ethanol, mixed with 8 parts by weight of β-cyclodextrin powder, and dried under reduced pressure to obtain a powdery antibacterial agent. This product is advantageously used as an antibacterial agent in an antibacterial composition such as foods and drinks, cosmetics and pharmaceuticals as in Example 1.

Example 5 Lactic Acid Beverage 10 parts by weight of skim milk powder were sterilized by heating at 80 ° C. for 20 minutes, cooled to 40 ° C., 0.3 parts by weight of a starter were added thereto, and fermented at about 37 ° C. for 10 hours. . Then, after homogenizing this, 5 parts by weight of lactosucrose syrup (trade name: Dairy Fruit Oligo, sold by Hayashibara Shoji Co., Ltd.),
Add 1 part by weight of sucrose and 2 parts by weight of isomerized sugar syrup,
Sterilized by keeping at 70 ° C. This was cooled, 0.1 part by weight of the liquid antibacterial agent obtained by the method of Example 1 was added, and bottled to obtain a product. This product has a good balance of flavor, sweetness and sourness,
It is a high-quality lactic acid beverage with improved stability.

Example 6 1 part by weight of waxy waxy starch was mixed with 1.2 parts by weight of water, and while being gelatinized with heating, 1.5 parts by weight of sucrose and crystalline β-maltose (produced by Hayashibara Co., Ltd., 0.7 parts by weight of registered trademark Sanmalto), 0.3 parts by weight of starch syrup, and 0.01 parts by weight of the liquid antibacterial agent obtained by the method of Example 3 are mixed, and thereafter, molded and packaged in accordance with a conventional method to obtain a fertilizer. Manufactured. This product is a Japanese confectionery that has a good flavor and mouthfeel, has an improved shelf life, and has stable quality.

Example 7 Chewing gum 3 parts by weight of a gum base was melted by heating to a softening degree,
To this, 4 parts by weight of sucrose and 3 parts by weight of maltose powder were added, and 0.02 of the liquid antibacterial agent obtained by the method of Example 1 was added thereto.
Mix parts by weight with an appropriate amount of colorant and fragrance, and according to a conventional method,
The product was obtained by kneading with a roll, molding and packaging.
This product is a chewing gum with good texture and flavor. In addition, this product is a chewing gum that exhibits an antibacterial effect in the oral cavity and can prevent bad breath and tooth decay.

Example 8 Bath agent 21 parts by weight of DL-sodium lactate, 8 parts by weight of sodium pyruvate, 10 parts by weight of the liquid antibacterial agent obtained by the method of Example 3 and 35 parts by weight of ethanol, 26 parts by weight of purified water and A bath agent was manufactured by mixing with an appropriate amount of a coloring agent and a fragrance.
This product is suitable not only for preventing skin infection but also as a skin beautifying agent. It may be diluted 100 to 10,000 times with hot water for bathing before use. Further, this product can be advantageously used by diluting it with face-washing water, lotion, etc., as in the case of hot water for bathing.

Example 9 Emulsion 0.5 parts by weight of polyoxyethylene behenyl ether, 1 part by weight of polyoxyethylene sorbitol tetraoleate, 1 part by weight of lipophilic glyceryl monostearate, 0.5 parts by weight of pyruvic acid, 0 of behenyl alcohol. 0.5 parts by weight, 1 part by weight of avocado oil, 1 part by weight of the liquid antibacterial agent obtained by the method of Example 2 and an appropriate amount of vitamin E were dissolved by heating according to a conventional method, and 1 part by weight of L-sodium lactate,
5 parts by weight of 1,3-butylene glycol, 0.1 part by weight of carboxyvinyl polymer and 85.3 parts by weight of purified water were added and emulsified by applying a homogenizer. Further, an appropriate amount of perfume was added and mixed by stirring to produce an emulsion. . This product not only prevents skin infections, but can also be used advantageously as a sunscreen, skin beautifying agent, and skin lightening agent.

Example 10 Antibacterial Cream 2 parts by weight of polyoxyethylene glycol monostearate, 5 parts by weight of self-emulsifying glyceryl monostearate,
10 parts by weight of the liquid antibacterial agent obtained by the method of Example 1, 1 part by weight of liquid paraffin, and 10 parts by weight of glyceryl trioctanoate were dissolved by heating according to a conventional method, and 2 parts by weight of L-lactic acid,
5 parts by weight of 1,3-butylene glycol and purified water 54
An antibacterial cream was produced by adding parts by weight, emulsifying the mixture with a homogenizer, adding an appropriate amount of a flavor and stirring and mixing.
As an antibacterial cream, this product can be advantageously used not only for preventing skin infection but also as a sunscreen, a skin beautifying agent, a skin lightening agent and the like.

Example 11 Toothpaste Formulation Dibasic calcium phosphate 45.0% Pullulan 2.9% Sodium lauryl sulfate 1.5% Glycerin 20.0% Polyoxyethylene sorbitan laurate 0.5% Sorbitol 10.0% Maltitol 7.0% Powdered antibacterial agent obtained by the method of Example 4 0.1% Water 13.0% The above materials were mixed according to a conventional method to obtain a toothpaste. This product has antibacterial activity and is convenient for preventing bad breath and tooth decay.

Example 12 To 500 parts by weight of ointment maltose powder, 20 parts by weight of the liquid antibacterial agent obtained by the method of Example 1 and 33 parts by weight of ethanol were added and mixed, and further 200 parts by weight of a 10 w / w% pullulan aqueous solution was added. In addition, the mixture was mixed to obtain an ointment for treating wounds, which has a proper extension and shows adhesiveness. This product exerts not only antibacterial action but also the action of maltose to supply energy to cells, so that the healing period is shortened and the wound surface is healed neatly. In addition, this product exhibits an antibacterial action and is used to promote the treatment of wounds such as cuts, burns and stomatitis. Furthermore, the product can be advantageously used as a suppository for treating infectious diseases for rectum, vagina, etc. by filling and molding it into a soft capsule or the like.

Example 13 Tablets: 5 parts by weight of maltose powder, 5 parts by weight of lactosucrose powder and 5 parts by weight of the powdered antibacterial agent obtained by the method of Example 4 were uniformly mixed and, according to a conventional method, a diameter of 12 mm and a 20R punch were used. Tablets were obtained by using. The product can be advantageously used as a sublingual tablet for treating oral infections such as stomatitis and periodontal disease, and a tablet for internal use for treating digestive system infections such as food poisoning.

Example 14 Injectable solution The liquid antibacterial agent obtained by the method of Example 1 was purified and filtered according to a conventional method to be pyrogen-free, and this solution became 500 mg of the compound (1) in a 20 ml ampoule. Thus, it was lyophilized and sealed to prepare an injection. If desired, this injection can be mixed with other vitamins, minerals, etc., dissolved or suspended in distilled water for injection at the time of use, and administered intramuscularly or intravenously. As an antibacterial agent, wound healing, treatment of infectious diseases, etc. Can be used to advantage.

[0074]

INDUSTRIAL APPLICABILITY The compound (1), the compound (2) and salts thereof well inhibit the growth of harmful bacteria and can be advantageously used as an antibacterial agent. The antibacterial composition of the present invention, for example, has a high preservability as an aspect of foods and drinks, has a high preservability as an aspect of cosmetics, and has an action of keeping skin, hair and the like clean, as an aspect of a pharmaceutical product It is effectively used for the treatment and prevention of various infectious diseases.

[Brief description of drawings]

FIG. 1 is a diagram showing an ultraviolet absorption spectrum of compound (1).

FIG. 2 is a diagram showing an infrared absorption spectrum of compound (1).

FIG. 3 is a diagram showing an ultraviolet absorption spectrum of compound (2).

FIG. 4 is a diagram showing an infrared absorption spectrum of compound (2).

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Office reference number FI technical display location A61K 7/40 7252-4C 31/215 ADB 9283-4C 35/64 ACK 7431-4C C07C 59/52 8930-4H 69/017 8018-4H

Claims (6)

[Claims] 1. 3- {4-hydroxy-3,5-bis (3-methyl-2-butenyl) phenyl} -2-propenoic acid, benzenepropanoic acid
4- (2-carboxyethenyl) -2- (3-methyl-
An antibacterial composition comprising at least one selected from 2-butenyl) phenyl ester and salts thereof and a carrier. 2. 3- {4-hydroxy-3,5-bis (3-methyl-2-butenyl) phenyl} -2-propenoic acid, benzenepropanoic acid
4- (2-carboxyethenyl) -2- (3-methyl-
An antibacterial composition containing 1 w / w% or more of at least one selected from 2-butenyl) phenyl ester and salts thereof. 3. 3- {4-Hydroxy-3,5-bis (3-methyl-2-butenyl) phenyl} -2-propenoic acid, benzenepropanoic acid
4- (2-carboxyethenyl) -2- (3-methyl-
2-butenyl) phenyl esters and their salts are
The antibacterial composition according to claim 1 or 2, which is derived from propolis. 4. The antibacterial composition according to claim 1, wherein the antibacterial composition is one type selected from foods and drinks, cosmetics and pharmaceuticals. 5. 3- {4-Hydroxy-3,5-bis (3-methyl-2-butenyl) phenyl} -2-propenoic acid, benzenepropanoic acid
4- (2-carboxyethenyl) -2- (3-methyl-
The content of at least one selected from 2-butenyl) phenyl ester and salts thereof is 16 to 1.00.
An amount selected from the range of 50,000 ppm.
The antibacterial composition described. 6. 3- {4-hydroxy-3,5-bis (3-methyl-2-butenyl) phenyl} -2-propenoic acid, benzenepropanoic acid
4- (2-carboxyethenyl) -2- (3-methyl-
An antibacterial method for an antibacterial substance to be treated, wherein at least one selected from 2-butenyl) phenyl ester and a salt thereof is allowed to coexist with the antibacterial substance to be treated at a concentration of 16 ppm or more.