JP3443171B2 - 3-Lauroyl gallic acid and its ester derivatives - Google Patents

Description

Detailed Description of the Invention

[0001]

The present invention relates to a novel substance, 3-lauroyl gallic acid, which exhibits antibacterial action and antioxidant action and is useful as a preservative for cosmetics, detergents, edible oils and fats, engine oils, foods, pharmaceuticals and the like. It relates to the derivative. Furthermore, it is a natural plant that has no toxicity [Satakencia liukiuensis
H. E. MOORE, Jr. (Gulbia liuk
iuensis) Hatsushima] as a raw material, and relates to a highly safe natural antibacterial and / or antioxidant preservative.

[0002]

2. Description of the Related Art Generally, foods, cosmetics, and many other materials are extremely susceptible to microbial deterioration. It is also known that edible oils and fats for other uses undergo an oxidative effect of air on the oils and fats during storage to cause a bad deterioration, and further oxidization also produces harmful substances. Therefore, it is necessary to prevent them from the viewpoint of hygiene and effective use of resources.

As a method for preventing the deterioration by microorganisms,
Generally, antibacterial agents are used, but conventional synthetic antibacterial agents are highly toxic and have problems in safety and environmental protection. Recently, natural product antibacterial agents have been strongly demanded in the field of cosmetics as well as their use as pharmaceuticals. In particular, many synthetic products that have strong antibacterial activity are prone to skin troubles, and therefore there is a strong tendency to seek antibacterial agents for natural products with less skin irritation. In the food field, preparations using spice extract, magnolol, lysozyme, polylysine, bamboo extract, bamboo extract, etc. as natural product antibacterial agents have been developed, but they are satisfactory in terms of antibacterial spectrum and antibacterial activity. Very few things. Antioxidants are generally added as a method for preventing the oxidation of oils and fats. Dibutylhydroxytoluene (BHT) and butylhydroxyanisole (B), which are typical synthetic antioxidants in the fields of food and cosmetics.
There is a tendency to refrain from using HA), and there is a strong demand for safer natural product antioxidants.
Conventionally used natural product antioxidants are mainly tocopherols, spice extracts, licorice extracts and the like, but none of them have been satisfactory in terms of effects, aroma, taste, color tone and the like. Therefore, there has been no antibacterial and antioxidative preservative derived from a natural product which has both strong and stable antibacterial and antioxidative properties and is highly safe.

[0004]

DISCLOSURE OF THE INVENTION The object of the present invention is to show antibacterial action and antioxidative action and to be useful as a preservative for cosmetics, detergents, edible oils and fats, engine oils, foods, pharmaceuticals, etc.
It is to provide a novel substance, 3-laurolyl gallic acid and its ester derivatives. Further, the ester derivatives thereof and the 3-lauroyl gallic acid by extraction, especially Yaeyamayashi rhizomes are natural plant
It is to provide a method of manufacturing a composition . Furthermore, it is to provide an antibacterial agent and / or an antioxidant, which contains 3-lauroyl gallic acid or its ester derivative itself and an extract of rhizome of Yaeyama palm as an active ingredient.

[0005]

[Means for Solving the Problems] Yaeyama palm is a kind of so-called one kind of palm of the genus Palmae Yaeyama palm which grows on the Yaeyama Islands in Okinawa Prefecture. The roots are used in pickles and fish dishes in some private houses, and are known to have the effect of improving the shelf life of fish and improving the luster of pickles and fish. It is suggested that it is safe because it is edible. Therefore, the present inventor investigated whether or not the rhizome extract of Yaeyama palm was usable as an antibacterial agent or an antioxidant, and found that 3-lauroyl gallic acid and its ester derivative in the extract and the extracted components were examined. They found that they have a strong antibacterial action and antioxidant action, and completed the present invention.

That is, the present invention is based on the formula

[Chemical 3] And expression

[Chemical 4] The present invention provides 3-lauroyl gallic acid and its ester derivatives, which are compounds represented by Also, a step of extracting the rhizome of Yaeyama palm with a solvent to obtain an extract
And extract the extract with an acidic substance to extract the acidic substance
And a step of obtaining 3-lauroyl gallic acid and its
A method for producing a composition with an ester derivative is provided. Furthermore, 3-lauroyl gallic acid and its esthetics
Antimicrobial agents and / or antioxidants to the Le derivative as an active substance,
And an antibacterial agent and / or antioxidant containing an extract from the rhizome of Yaeyama palm as an active ingredient.

The 3-lauroyl gallic acid and its ester derivative ( hereinafter simply referred to as "derivative" ) of the present invention are
It is a novel compound that has not been published in the literature and can be produced by extracting the rhizome of Yaeyama palm. Specifically, it is obtained by drying the roots of Yaeyama palm, solvent-extracting this, and further extracting with an acidic substance. More specifically, the acidic substance extraction fraction was separated and fractionated by preparative HPLC chromatography, and the obtained fractions for each peak were dried and examined for antibacterial activity. Two recognized fractions were confirmed, and structural analysis of each colorless crystal revealed that one was 3-lauroyl gallic acid and the other was 3-lauroyl gallic acid ethyl ester. Further, a derivative can be chemically produced based on 3-lauroyl gallic acid.

For the structural analysis of the crystalline substance obtained by extracting the rhizome of Yaeyama palm, the molecular weight was investigated mainly by high-mass spectrum, ¹ H-NMR, ¹³ C-NMR and IR.
Was used to confirm the molecular structure.

The solvent used for producing 3-lauroyl gallic acid and its derivatives of the present invention may be any solvent commonly used for extracting plant components, but ethanol or ethyl acetate is preferably used. The alkaline solvent used for extracting the acidic substance is not particularly limited, but an aqueous sodium carbonate solution is preferably used.

The antibacterial agent and / or antioxidant of the present invention containing 3-lauroyl gallic acid or its derivative as an active substance may be purified 3-lauroyl gallic acid or 3-lauroyl gallic acid ethyl ester itself. Then 3-
It may be a mixture of plural selected from the group of lauroyl gallic acid and its derivatives, may be a crude fraction substance obtained by solvent-extracting the rhizome of Yaeyama palm, or a fraction substance obtained by further extracting this with an acidic substance. Good. 3 for each
-Contains lauroyl gallic acid or its derivatives. That is, an antibacterial agent and / or an antioxidant containing an extract of Yaeyama palm rhizome as an active ingredient is also added to the present invention.

[0011]

INDUSTRIAL APPLICABILITY The 3-lauroyl gallic acid and its derivatives of the present invention and the rhizome extract of Yaeyama palm exhibit strong antibacterial action and antioxidative action, and can be used for cosmetics, detergents, edible oils, engine oils, foods, pharmaceuticals, etc. It is useful as a preservative. Moreover, since it is a natural compound extracted from a plant that is not toxic, it is highly safe.

[0012]

【Example】

(Extraction operation of Yaeyama palm) Yaeyama palm native to Taketomi-cho, Yaeyama-gun, Okinawa was collected and used in July. To prepare the sample, dry roots are cut into small pieces, 10 volumes of ethanol is added, reflux extraction is performed for 15 hours, and filtration is performed. This operation was repeated twice, and the filtrates were combined and concentrated under reduced pressure to obtain a crude extract (F-1). Water was added to the obtained F-1,
Extraction was performed with ethyl acetate, and the water-soluble fraction and the ethyl acetate layer were separated. The water-soluble fraction was concentrated under reduced pressure to obtain an extract (F-2). A 10% Na ₂ CO ₃ aqueous solution was added to the ethyl acetate layer to separate it into a Na ₂ CO ₃ aqueous solution-soluble part and an ethyl acetate layer. . The alkali-soluble portion was neutralized with a 0.1 N HCl aqueous solution, extracted with ethyl acetate, dried over anhydrous Na ₂ SO ₄ , and the solvent was distilled off under reduced pressure to obtain an extract (F-3). A 0.1N NaOH aqueous solution was added to the acetic acid ethyl ester layer to separate into a NaOH aqueous solution-soluble portion and an acetic acid ethyl ester layer. The alkali-soluble portion was neutralized with a 0.1N HCl aqueous solution, extracted with ethyl acetate, dried over anhydrous Na ₂ SO ₄ , and the solvent was distilled off under reduced pressure to obtain an extract (F-4). A 0.1N HCl aqueous solution was added to the acetic acid ethyl ester layer to separate it into a HCl soluble portion and an acetic acid ethyl ester layer. HCl soluble part is 1
Neutralized with 0% Na ₂ CO ₃ aqueous solution, extracted with ethyl acetate and dried over anhydrous Na ₂ SO ₄ , the solvent was distilled off under reduced pressure,
An extract (F-5) was obtained. The acetic acid ethyl ester layer from which the HCl-soluble portion was removed was washed with water, dried over anhydrous Na ₂ SO ₄ , and the solvent was distilled off under reduced pressure to obtain an extract (F-6). The content% of each fraction is as follows for the dry sample. F-1: 4.30, F-2: 1.35, F-3: 0.6
3, F-4: 0.14, F-5: 0.72, F-6:
1.58

(Measurement of Antibacterial Activity) As the test strain, the following microorganisms were used for the antibacterial activity measurement. Bacteria Gram-positive bacterium Staphylococcus aureu
s FDA-209 (S. aureus) Bacillus subtilis ATCC-66
33 (B. subtilis) Gram-negative bacterium Escherichia coli IF
O-3301 (E. coli) Salmonella typhimurium IF
D-12529 (S. typhimurium) Pseudomonas aeruginosa IF
D-3080 (P. aeruginosa) Proteus vulgaris ATCC-133
15 (P. vulgaris) Fungus Candida albicans ATCC-188
04 (C. albicans) Aspergillus niger ATCC-66
275 (C. niger) Aspergillus oryzae IFO-53
75 (A. oryzae) Penicillium funiculosum A
TCC-9644 (P. funiculosum)

Bacteria are normal agar medium (meat extract 0.005 g / ml, peptone 0.01 g / ml, sodium chloride 0.05 g / ml, agar 0.015 g / m manufactured by Eiken).
1, pH 7.0), the fungus is Sabouraud medium (glucose 0.04 mg / ml, peptone 0.01 g /
ml, agar 0.015 g / ml, pH 6.5) and used as a medium for antibacterial test. Approximately 1 × 10 ⁵ inoculation of test bacteria
Cells were inoculated to give cells. Bacteria 4 at 37 ℃
The fungus was cultured for 8 hours at 25 ° C. for 5 days, and the presence or absence of colony formation was observed to determine the minimum inhibitory concentration (MIC). The pH was adjusted by adding 10% sodium carbonate and 1N hydrochloric acid and adjusting the pH to 7.0 using a pH meter.

(Measurement result of antibacterial activity) Table 1 shows the MIC measurement results of the respective fraction extracts F-1 to F-6 of Yaeyama palm which were fractionated according to the method described in the item (Measurement of antibacterial activity).

[Table 1]

Antibacterial activity was observed in F-1, F-3 and F-4. Since F-3 and F-4 are fractions obtained by further fractionating F-1, the active ingredient is considered to be present in the acidic fractions of these two. F-3 is S. aureu
s, P. vulgaris has a MIC of 0.5%, F
-4 is P. funiculosum was active at 0.5%, and F-3 was B. subtilis, E .; col
i, P. aeruginosa, C.I. albican
S.A. niger and P.N. funiculosum
On the other hand, F-4 is C.I. albicans, A .; night
r and A. It was found that MIC showed an activity of 1.0% against oryzae and that F-3 and F-4 had a relatively broad antibacterial spectrum.

Among the acidic fractions of the 70% ethanol extract of Yaeyama palm root, F-3 (10% Na ₂ CO ₃ aqueous solution-soluble portion) was subjected to preparative chromatography to fractionate each peak. After drying, S. aureus, E .; co
li, A. MIC was determined using a niger. As a result, one peak of each preparative fraction of the preparative HPLC chromatogram was S. aureus, E .; coli, A .; ni
A relatively strong antibacterial activity against ger was recognized.

A peak having a relatively strong antibacterial activity was recrystallized from hexane to obtain a colorless crystal. Structural analysis of the crystalline material was performed. The molecular weight was investigated mainly by high-mass spectrum, and the molecular structure was confirmed using ¹ H-NMR, ¹³ C-NMR and IR. As a result, it was estimated that the substance having antibacterial activity in F-3 was 3-lauroyl gallic acid. Then, 3-lauroyl gallic acid ethyl ester obtained by synthesizing ethyl gallic acid and lauroyl chloride was added with KCl 50%.
When 3-lauroyl gallic acid was synthesized by hydrolysis with an acetone solution and was compared with that obtained from Yaeyama palm and the IR, MS, and NMR spectra were compared, the two were in perfect agreement, so the molecular structure was presumed. I confirmed that it was correct. This substance is a novel substance not described in the literature.

From the acidic fraction of the 70% ethanol extract of Yaeyama palm root, F-4 (0.1N NaOH aqueous solution-soluble portion) was subjected to preparative chromatography to fractionate each peak and after drying. , S. aureus, E .; co
li, A. MIC was determined using a niger. As a result, one peak of each preparative fraction of the preparative HPLC chromatogram was S. aureus, E .; coli, A .; ni
A relatively strong antibacterial activity against ger was recognized.

A peak having a relatively strong antibacterial activity was recrystallized from hexane to obtain a colorless crystal. Structural analysis of the crystalline material was performed. The molecular weight was investigated mainly by high-mass spectrum, and the molecular structure was confirmed using ¹ H-NMR, ¹³ C-NMR and IR. As a result, it was estimated that the substance having antibacterial activity in F-4 was 3-lauroyl gallic acid ethyl ester. Subsequently, the mixture of 3-lauroyl gallic acid ethyl ester, which was synthesized ethyl gallic acid and lauroyl chloride, with that obtained from Yaeyama palm, IR, MS,
When the NMR spectra were compared, they were completely in agreement, confirming that the molecular structure was not estimated correctly. This substance is a novel substance not described in the literature.

Among the acidic fractions of 3-lauroyl gallic acid, 3-lauroyl gallic acid ethyl ester, and the 70.degree. C. ethanol extracted extract of Yaeyama palm, F-3 and F-4.
Table 2 shows the antibacterial spectra of methyl paraoxybenzoate, benzoic acid and sorbic acid, which are widely used in the fields of pharmaceuticals, cosmetics and foods.

[Table 2]

Sorbic acid showed a relatively strong antibacterial activity against bacteria, and a slightly poorer antibacterial activity against yeast and fungi. Methyl paraoxybenzoate shows antibacterial activity against all Gram-positive bacteria, Gram-negative bacteria, yeasts and fungi, but shows stronger antibacterial activity against fungi. aer
Antibacterial activity against uginosa is weak. On the other hand, 3-lauroyl gallic acid showed antibacterial activity against Gram-positive bacteria, Gram-negative bacteria, yeasts and fungi. The bacterial P. vulgaris with MIC of 0.04%, twice that of sorbic acid, S. aureus shows the same antibacterial activity as 0.04%, and fungus C. albicans and A. It showed an antibacterial activity of 0.08% against niger, which was similar to that of methyl paraoxybenzoate. It was found that all 10 strains exhibited antibacterial activity against other bacteria, such as showing half the activity of the strongest of the three synthetic fungicides, and had a broad antibacterial spectrum.

Also, 3-lauroyl gallic acid ethyl ester is a bacterial S. aureus, E .; coli, S. t
yphimurium and P. Vulgaris, MICs are 0.32, 0.16, and 0.16, respectively.
% And an antibacterial activity similar to that of methyl paraoxybenzoate, S. Benzoic acid showed similar activity to typhimurium. In addition, B. subtili
In s, 0.32% was obtained, which was half the potency of benzoic acid or methyl paraoxybenzoate. C. in fungi. albica
0.04% in ns and twice as much as methyl paraoxybenzoate,
A. niger and P.I. They showed similar activities to funiculosum as 0.08% and 0.04%, respectively. In addition, A. It was found that oryzae also showed antibacterial activity in all 10 strains, such as 0.08%, which shows activity similar to that of methyl paraoxybenzoate, and has a broad antibacterial spectrum.

Further, among the acidic fractions of the 70% ethanol extract of Yaeyama palm root, F-3 and F-4 also showed strong antibacterial properties, which were similar to 3-lauroyl gallic acid and 3-lauroyl gallic acid ethyl ester, respectively. Showed a trend.

(Measurement of Antioxidant Property) To measure the antioxidant property,
Pork fat (produced by Ogawa Fragrance Co., Ltd.) was used as the base oil. The test oil was adjusted to 25 pp for 3-lauroyl gallic acid and 3-lauroyl gallic acid ethyl ester for lard.
F-3 and F-4 of the acidic fraction of 70% ethanol extract of Yaeyama palm root
Was added at 1% and tocopherol was added at 200 ppm, and the mixture was uniformly dispersed with a homogenizer. As the tocopherol, Emix 80 manufactured by Eisai Co., Ltd. was used.

Oven test In the oven test, 20 g of test oil was placed in a 200 ml beaker, covered lightly with aluminum foil, and placed on the middle wire mesh of an electric thermostat controlled at 60 ± 2 ° C. around a thermometer as a center. Then, each beaker was taken out daily and the peroxide value (POV) was measured.

(Results of Antioxidant Measurement) 3-Lauroyl gallic acid, 3-lauroyl gallic acid ethyl ester, and F-3 and F-4 and tocopherol were added to the acid fraction of the 70% ethanol extract of Yaeyama palm root. FIG. 1 shows the change with time in POV of each of the test oils tested in an oven test at 60 ± 2 ° C.

As shown in FIG . 1, as compared with no addition, 3-
Lauroyl gallic acid, 3-lauroyl ethyl gallate
Steal, 70% ethanol extract of Yayama palm root
F-3 and F-4, tocopherols of acidic fraction of
Suppresses the increase of POV, especially 3-lauroyl
Gallic acid, 3-lauroyl gallic acid ethyl ester, yam
Acidic fraction of 70% ethanol extract of edible palm root
Of these, F-3 and F-4 are compared to tocopherol
The increase in POV can be significantly suppressed.

[Brief description of drawings]

Fig. 1 Peroxide value (POV) of each test oil over time
It is a graph which shows change.

Continuation of the front page (56) References JP-A-6-211746 (JP, A) JP-A-4-295444 (JP, A) JP-A-54-134621 (JP, A) J. Antibact. Antifu ng. Agents, 1994, Vol. 22, No. 7, P411-415 J. Antibact. Antifu ng. Agents, 1994, Vol. 22, No. 6, P345-348 (58) Fields investigated (Int.Cl. ⁷ , DB name) C07C 69/353 C07C 69/86 C07C 67/56 C07C 67/29 C09K 15/08 A01N 37/36-37/40 CA (STN) REGISTRY (STN)

Claims (7)

(57) [Claims] 1. The formula: 3-lauroyl gallic acid, which is a compound represented by: 2. The formula: The ester derivative of 3-lauroyl gallic acid according to claim 1, which is represented by the formula (R in the formula is an alkyl group). 3. Yaeyama palm [Satakentia
liukiuensis H .; E. MOORE, Jr.
(Gulbia liukiuensis) Hatsu
represented by the above formula [Chemical formula 1], which comprises a step of extracting the rhizome of [Shima] with a solvent to obtain an extract, and a step of extracting the extract with an acidic substance to obtain an acidic substance extract fraction.
That 3-lauroyl gallate and the [formula 2] (wherein R d
It is a chill group. ) And a method for producing a composition with an ester derivative of 3-lauroyl gallic acid . Wherein the antimicrobial agent to the active substance at least one component selected from the group of ester derivative of claim 1, wherein the 3-lauroyl gallate and claim 2, wherein the 3-lauroyl gallate. 5. The 3-lauroyl gallic according to claim 1.
Acid and 3-lauroyl gallic acid according to claim 2
At least one component selected from the group of telluride derivatives
Quality antioxidants. 6. Yaeyama palm [Satakenti
a liukiuensis H .; E. MOORE, J
r. (Gulbia liukiuensis) Hat
sushima] rhizome extract as an active ingredient
Antibacterial agent. 7. Yaeyama palm [Satakentia ]
liukiuensis H .; E. MOORE, Jr.
(Gulbia liukiuensis) Hatsu
The extract from the rhizome of
Oxidant.