JPH0984568A - Alcohol dehydrogenase inhibitor, bactericide, food manufacturing method and food - Google Patents

Abstract

(57) Abstract: An alcohol dehydrogenase inhibitor having high safety and an excellent alcohol dehydrogenase inhibitory activity, a bactericide that suppresses the decomposition of ethyl alcohol into acetaldehyde, and the production of acetaldehyde caused by ethyl alcohol A method for producing a suppressed food product and the food product are achieved. SOLUTION: Alcohol dehydrogenase inhibitor containing at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid as an active ingredient; from the group consisting of salts of hinokitiol, rutin, tannic acid and tannic acid. At least one chosen
And a fungicide characterized by containing ethyl alcohol; at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid,
A method for producing a food characterized by containing ethyl alcohol; a food comprising at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid, and ethyl alcohol.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an alcohol dehydrogenase inhibitor. The present invention also relates to fungicides. The present invention further relates to a method for producing a food product in which the production of acetaldehyde due to ethyl alcohol is suppressed, and the food product.

[0002]

Alcohol dehydrogenase (Alcohol
Dehydrogenase) is a metabolic enzyme that first acts on alcohol absorbed in the stomach and small intestine in vivo.
Alcohol becomes acetaldehyde by the action of this enzyme. Acetaldehyde is highly toxic and is known to cause sickness and hangover. Alcohol dehydrogenase is also known to exist widely in the living world such as insects, plant seeds and microorganisms as well as living organisms. In methanol poisoning, alcohol dehydrogenase produces toxic metabolites. Therefore, an inhibitor of this alcohol dehydrogenase has attracted attention, and methylpyrazoles have already been known as inhibitors (H. Theorell et al., Acta. Chem. Scand., 23, 255).
(1969); R. Dahlbom et al., Biochem. Biophys. Res. Comm.
un., 57 , 549 (1974)). However, these are synthetic and have problems with toxicity (RWFries
, J. Med. Chem., 22, 356 (1979)).

On the other hand, in the area of foods, it has become common to use ethyl alcohol for the purpose of preserving foods such as sterilization and bacteriostatic. However, when relatively strong alcohol dehydrogenase activity is present in the raw material such as raw buckwheat, there is a problem that ethyl alcohol decomposes into acetaldehyde and produces a foul odor. By inhibiting alcohol dehydrogenase, it is possible to reduce or eliminate the symptoms of sickness and hangover caused by drinking, and further prevent alcoholic liver damage. In the field of foods, it is considered to prevent the use of alcohol in foods, for example, the generation of acetaldehyde odor associated with ethanol sterilization. It has been reported that certain amino acids have an inhibitory action on alcohol dehydrogenase (Japanese Patent Laid-Open No. 61-50917, Japanese Patent Laid-Open No. 61-134313 and Japanese Patent Laid-Open No. 6-1161).
No. 44), it was not yet satisfactory. These amino acids are difficult to use because they are difficult to dissolve in alcohol.

[0004]

An object of the present invention is to provide an alcohol dehydrogenase inhibitor which is highly safe and has an excellent alcohol dehydrogenase inhibitory activity. Another object of the present invention is to provide a bactericide in which the decomposition of ethyl alcohol into acetaldehyde is suppressed. Another object of the present invention is to provide a method for producing a food product in which the production of acetaldehyde due to alcohol is suppressed, and the food product.

[0005]

[Means for Solving the Problems] In order to achieve the above object, the present inventors searched for an inhibitor of alcohol dehydrogenase from naturally occurring substances,
The inventors have found that hinokitiol, rutin, tannic acid and salts of tannic acid have a strong inhibitory effect on alcohol dehydrogenase, and have completed the present invention. Therefore, the present invention is an alcohol dehydrogenase inhibitor containing, as an active ingredient, at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid. The present invention also relates to a fungicide containing at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid, and ethyl alcohol. The present invention further comprises at least one member selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid,
It is a method for producing a food, which comprises blending ethyl alcohol. The present invention also relates to a food product containing ethyl alcohol and at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION Hinokitiol, which is also called lupusuricin, includes natural products and synthetic products. Natural products are made from Aomori Hiba, which is steam-treated to obtain Hiba oil,
From this, crude hinokitiol crystals are obtained. The crude hinokitiol crystals thus obtained are mixed crystals with β-drabulin (approximately 1: 1), but β-drabulin can be converted to hinokitiol by hydrogenation treatment.
In the present invention, both natural products and synthetic products can be used. Hinokitiol has long been known as a natural product having a wide spectrum of antibacterial spectrum, and is further known to have an inhibitory effect on enzymes related to browning (tyrosin hydroxylase inhibition, tyrosinase inhibition). Rutin can be obtained from a wide variety of plants, including buckwheat and buds of sage. As a function in the living body, it is said to have a vitamin P action which suppresses vascular permeability together with flavanone such as hesperidin, and is known to be used in a prescription used for improving bleeding tendency and hypertension. In addition, two types of rutin, water-soluble and water-insoluble, are known and commercially available, and either of them can be used in the present invention.

[0007] Tannic acid is a tannin produced from quintet or gallate and is not a single compound, but pentagalloyl glucose (1,2,3,4,6-penta-O-galloyl-β-D-glu).
cose) or tetragalloyl glucose (1,2,3,6-
Tetra-O-galloyl-β-D-glucose) is the basic unit, and some of these galloyl groups are mainly a mixture of gallic acid and a structure having a depside bond with several gallic acids. There are many similar compounds, resulting in complex mixtures. It is widely used as a raw material for inks, dyes, antioxidants, and the like, and is known to be used as a tannic acid agent, a local astringent agent, and a hemostatic agent in combination with other pharmaceuticals for medicinal purposes. The salt of tannic acid used in the present invention may be any salt having an alcohol dehydrogenase inhibitory action, for example, sodium salt, potassium salt, calcium salt,
Examples thereof include magnesium salt, barium salt, tetrabutylammonium salt, albumin tannate, diphenhydramine tannate, and berberine tannate.

The hinokitiol, rutin, tannic acid and tannic acid salts used in the present invention are preferably highly pure, but may be of any practically low purity. These active ingredients are generally available on the market, and commercially available products may be used in the present invention. Hinokitiol, rutin, tannic acid and salts of tannic acid can be dissolved in alcohol. Hinokitiol, rutin and tannic acid are also extremely non-toxic.

The alcohol dehydrogenase inhibitor of the present invention may contain additives in addition to its active ingredients, hinokitiol, rutin, tannic acid and salts of tannic acid. The alcohol dehydrogenase inhibitor of the present invention is
It can be contained in foods and health foods. It can also be a component of food additives. The food to which the alcohol dehydrogenase inhibitor of the present invention is mixed is not particularly limited, and examples thereof include bread, noodles, confectionery, prepared foods and beverages. In particular, it is preferable that the food contains alcohol. As a method for incorporating the alcohol dehydrogenase inhibitor of the present invention into food, various addition methods such as mixing directly into food materials or dissolving in water added at the time of production can be adopted, and can be appropriately selected depending on the food. . The amount of the alcohol dehydrogenase inhibitor of the present invention added to food is 0.001 to 50 with respect to the food material such as raw noodles as an active ingredient, based on the powder.
% By weight, preferably 0.01 to 20% by weight,
More preferably, it is 0.01 to 5% by weight.

One use of the alcohol dehydrogenase inhibitor of the present invention is also a preventive agent for alcoholic liver injury. That is, the active ingredient of the alcohol dehydrogenase inhibitor of the present invention can be formulated with a suitable auxiliary agent to give an orally administrable prophylactic agent for alcoholic liver injury. Upon formulation, a diluent or excipient such as a filler, a bulking agent, a binder, a disintegrant, a surfactant, a lubricant, and the like which are usually used can be used. Various forms can be selected as the pharmaceutical preparation, for example, capsules,
Examples include tablets, pills, granules, fine granules, powders, liquids and the like. Examples of excipients include sucrose, lactose, starch,
Crystalline cellulose, mannite, light anhydrous silicic acid, magnesium aluminate, magnesium metasilicate magnesium aluminate, synthetic aluminum silicate, calcium carbonate, sodium hydrogencarbonate, calcium hydrogenphosphate, carboxymethylcellulose calcium, or a combination of two or more thereof. It can be added. As the lubricant, for example, magnesium stearate, talc, hydrogenated oil, etc. may be used alone or in combination.
More than one species can be added.

Further, as a corrigent and a flavoring agent, sweeteners such as table salt, saccharin, sugar, mannitol, orange oil, licorice extract, citric acid, glucose, menthol, eucalyptus oil, malic acid, etc., flavors, colorants, preservatives. Etc. may be contained. Adjuvants such as suspending agents and wetting agents can include, for example, coconut oil, olive oil, sesame oil, peanut oil, calcium lactate, safflower oil, soybean phospholipids, and the like. As the surfactant, for example, one kind or two or more kinds of esters, polyethylene glycol derivatives, sorbitan fatty acid esters and the like can be added. Further, in order to impart stability and acid resistance to the active ingredient for long-term storage and to completely maintain the drug effect, if a formulation is further provided with a pharmaceutically acceptable film, excellent stability is obtained. It can be an alcohol dehydrogenase inhibitor. Examples of the film-forming substance include cellulose acetate phthalate (CAP) as a resistance to the induction of carbohydrates such as cellulose and saccharides, and methyl acrylate / methacrylic acid as polyvinyl derivatives such as acrylic acid copolymers and dibasic acid monoesters. Examples thereof include copolymers and methyl methacrylate / methacrylic acid copolymers. Further, when coating the above-mentioned film-forming substance, the properties of the film-forming agent can be improved by adding various additives for preventing adhesion of the agents during the coating operation, in addition to a commonly used coating agent such as a plasticizer. It can improve or make the coating operation easier.

The active ingredient of the alcohol dehydrogenase inhibitor of the present invention can be formulated into various dosage forms by a conventional method using the additives as described above. The proportion of the active ingredient in the preventive agent for alcoholic liver damage may be changed to some extent depending on the dosage form, but is usually 0.01 to 15.0% by weight. The administration method is not particularly limited,
It can be appropriately selected according to the patient's age, other conditions, disease states, and various preparation forms. The dose may vary depending on the administration method, patient age, symptoms, etc., but 0.5 to 5,000 mg per day is suitable as the active ingredient.

The present invention also relates to hinokitiol, rutin,
The present invention is directed to a bactericide characterized by containing ethyl alcohol and at least one selected from the group consisting of tannic acid and salts of tannic acid. That is, the alcohol dehydrogenase inhibitory action of the above-mentioned active ingredient can suppress the decomposition of ethyl alcohol into acetaldehyde and maintain the bactericidal action.
The fungicide of the present invention is made by adding the above-mentioned active ingredient to an aqueous solution containing ethyl alcohol in an amount of 60 to 90%. The content of at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid in the fungicide of the present invention is 1 to 50 per ml.
0 mg is suitable, preferably 10-200 mg. The subject to which the fungicide of the present invention is applied is not particularly limited, and examples thereof include foods such as raw noodles. In particular, it is preferably used for raw buckwheat etc. where the raw material has a relatively strong alcohol dehydrogenase activity, and the production of acetaldehyde is suppressed, and it is possible to reduce or eliminate the acetaldehyde odor which has been a difficult point in the past. The sterilization treatment with the disinfectant of the present invention may be carried out by a conventional method such as spraying the improved sterilizing alcohol on the object or immersing the object in the improved sterilizing alcohol.

The present invention also relates to hinokitiol, rutin,
The present invention is directed to a method for producing a food, which comprises blending at least one selected from the group consisting of tannic acid and salts of tannic acid with ethyl alcohol. As one embodiment of the method for producing a food according to the present invention, sterilization treatment with the above-mentioned bactericide can be mentioned in the production of food. As another embodiment, at the time of producing a food, at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid is directly mixed into the food material or dissolved in water to be used. It is possible to add them appropriately by a method such as adding, and separately sterilize with sterilizing ethanol. The amount of at least one selected from the group consisting of hinokitiol, rutin, tannic acid, and salts of tannic acid to be mixed with foods can be appropriately changed depending on the amount of alcohol used in foods, but food materials such as raw noodles can be used. In the case of
~ 50% by weight is suitable, preferably 0.001-20
%, More preferably 0.01 to 5% by weight.

The food to which the method for producing a food of the present invention is applied is not particularly limited, but is suitable for the production of noodles, and particularly suitable for the production of raw buckwheat. For example, in producing raw buckwheat, when making dough with buckwheat flour and water, at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid is blended to prepare a raw buckwheat noodle band, Then, sterilizing ethanol is sprayed. Further, at the time of preparation of the dough for confectionery containing flour as a main component, at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid is mixed, and after heating treatment such as baking or steaming, It can be treated with sterilizing ethanol. In this way, the production of acetaldehyde from ethyl alcohol can be suppressed, and the acetaldehyde odor, which has been a difficulty in the past, can be eliminated. As another embodiment of the method for producing a food of the present invention, in the production of a food using ethyl alcohol as a food material, at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid is blended. It can be mentioned. In this case, at least one selected from the group consisting of hinokitiol, rutin, tannic acid, and salts of tannic acid, and ethyl alcohol can be blended separately, and the ethyl alcohol used can be hinokitiol, rutin, tannic acid, and tannin. It is also possible to dissolve the acid salts before blending.

The present invention also relates to hinokitiol, rutin,
The present invention is directed to a food characterized by containing at least one selected from the group consisting of tannic acid and salts of tannic acid and ethyl alcohol. The food of the present invention is not particularly limited and includes a wide range, but specifically includes bread, noodles, confectionery, prepared foods, beverages, and the like, preferably noodles, particularly raw buckwheat. The food of the present invention is obtained, for example, by blending at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid, and ethyl alcohol at an appropriate stage in the production process of various foods. The blending of the ethyl alcohol includes blending as a food material and sterilization treatment with sterilizing ethanol. The food of the present invention is also obtained by performing a sterilization treatment with the above-described bactericide of the present invention in the process of producing various foods. In the food of the present invention, the content of at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid can be appropriately changed depending on the amount of ethyl alcohol used in the food, For example, in the case of raw noodles, about 0.001 to 50% by weight with respect to the powder is suitable, preferably 0.001 to 20% by weight, more preferably 0.01 to 5% by weight.

The present invention will be described in more detail with reference to test examples and examples.

[Test example]

Assay of alcohol dehydrogenase inhibitory activity of hinokitiol, rutin and tannic acid The reaction solution below (reaction solution 1.5 ml + enzyme 10 μl + sample)
Alcohol dehydrogenase inhibitory activity was assayed by the curve of absorbance increase when time-scanned at 30 ° C. and OD 340 nm for 20 minutes. [Reaction solution] 0.1M TRIS-HCl (pH 8.0) 10 ml 0.013M β-nicotinamide adenine dinucleotide 1.5 ml 1.8v / v% ethanol 0.5 ml [Enzyme] Alcohol dehydrogenase (Boehringer
127540) × 1,000 diluted solution As a result, IC50 of each sample was as shown in Table 1 below.

[0018]

[Table 1] ──────────────────────── Specimen IC50 (μg / ml) ──────────────── ───────── Hinokitiol 23.9 Rutin 81.1 Water-soluble rutin 105.8 Tannic acid 25.0 ────────────────────────

[0019]

Example 1 Raw buckwheat production and acetaldehyde inhibitory effect Raw buckwheat of test groups 0 to 16 was produced with various formulations shown in Table 2 below. In test sections 1 to 8, noodle-shaped raw buckwheat was sprayed with a bactericide (70% ethyl alcohol) containing tannic acid, hinokitiol or rutin, and left in a closed container at 37 ° C for 3 hours. Then, the amount of acetaldehyde generated was measured with a gas detector (manufactured by Gastec Co., Ltd.). In test groups 9 to 16, after adding and kneading either tannic acid, hinokitiol or rutin, sterilizing ethanol (ethyl alcohol 70%) was sprayed on noodles-shaped raw buckwheat, and test groups 1 to 8 The amount of acetaldehyde generated was measured in the same manner as in. The inhibition rate (%) of the generated acetaldehyde in each test section was determined. The results are shown in Table 3 below.
The inhibition rate (%) of the generated acetaldehyde was calculated by the following formula. [(Amount generated in test plot 0-Amount generated in each test plot 1-16) / Amount generated in test plot 0] x 100

[0020]

[Table 2] ──────────────────────────────────── Test zone Raw buckwheat noodle strips for sterilization Ethanol (70%) 0.5 ml No. Powdered water Sample Sample Ethyl alcohol content (g) (g) Content (mg) Content (mg) (ml) ──────────────── ───────────────────── 0 15 15 0 0 0.35 ----------------------- ------------------------------------------------ 1 15 15 0 Tannic acid 12.5 0.35 2 15 15 0 Tannic acid 50.0 0.35 3 15 15 0 Hinokitiol 12.5 0.35 4 15 15 0 Hinokitiol 50.0 0.35 5 15 15 0 Rutin 12.5 0.35 6 15 15 0 Rutin 50.0 0.35 7 15 15 0 Water soluble rutin 12.5 0.35 8 15 15 0 Water-soluble rutin 50.0 0.35 ---------------------------------------- ------------------------------- 9 15 15 Tannic acid 50.0 0 0.35 10 15 15 Tannic acid 150.0 0 0.35 11 15 15 Rutin 1.5 0 0.35 12 15 15 Chin 15.0 0 0.35 13 15 15 Rutin 150.0 0 0.35 14 15 15 Water-soluble rutin 1.5 0 0.35 15 15 15 Water-soluble rutin 15.0 0 0.35 16 15 15 Water-soluble rutin 150.0 0 0.35 ──────────── ────────────────────────

[0021]

[Table 3]

[0022]

Example 2 Production of Hot Cake 100 g flour, 1 g rutin, 50 g whole egg, 15 sugar
g, 3 g of baking powder, and 30 g of water were mixed to prepare a dough by a conventional method, and then baked on a hot plate to prepare a hot cake. This was sprayed with sterilizing ethanol (70% ethyl alcohol) and packed.

[0023]

Example 3 Tablet Confectionery and Tablets 150 g of yeast extract, 60 g of wheat extract, 60 g of DK-ester, 35 g of Avicel, 170 g of sorbitol, and 25 g of rutin were mixed by a conventional method with a mixer,
The tablets were compressed to produce confectionery and tablets.

Example 4 Bread flour 3 kg, hinokitiol 3 g, yeast 60 g,
Using 3 g of yeast food, 150 g of sugar, 60 g of salt, 150 g of shortening, 60 g of skim milk powder, and 2070 g of water, a dough was prepared by a conventional method, molded and baked to produce bread.

[0024]

[Example 5] Noodles Negative noodles were mixed and kneaded with 1% by weight of tannic acid, 34% by weight of water, 1% by weight of salt and 1% by weight of starch to semi-strong wheat flour, and then kneaded for 12 minutes. It was rolled several times by a machine and molded to obtain raw noodle bands and raw noodle strings of Chinese noodles.

Example 6 Biscuit 120 g flour, water-soluble rutin 1.2 g, sugar 35 g, shortening 15 g, whole egg powder 1.5 g, salt 1 g, sodium hydrogencarbonate 0.6 g, ammonium carbonate 0.75 g, water 2
Using 0 g, a dough was prepared by a conventional method and molded and baked to produce a biscuit.

[0025]

INDUSTRIAL APPLICABILITY The present invention provides an alcohol dehydrogenase inhibitor which is highly safe and has an excellent alcohol dehydrogenase inhibitory activity. The alcohol dehydrogenase inhibitor of the present invention is also useful as a preventive agent for alcoholic liver damage. By using the active ingredient of the alcohol dehydrogenase inhibitor of the present invention and ethyl alcohol as the bactericidal agent, the decomposition of alcohol into acetaldehyde can be suppressed and the bactericidal effect can be maintained. By including the active ingredient of the alcohol dehydrogenase inhibitor of the present invention in foods, it is possible to suppress the production of acetaldehyde, which causes malodor, in foods, especially foods using alcohol.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI Technical display location A23L 1/03 A23L 1/03 1/16 1/16 C 1/30 1/30 B Z 3 / 3508 3/3508 3/3544 3/3544 3/3562 3/3562 A61K 31/12 ADZ A61K 31/12 ADZ AED AED 31/70 ADQ 31/70 ADQ C12N 9/99 C12N 9/99 // (A01N 35 / 06 31:04) (A01N 65/00 31:04)

Claims (8)

[Claims] 1. An alcohol dehydrogenase inhibitor containing, as an active ingredient, at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid. 2. A bactericide containing at least one selected from the group consisting of hinokitiol, rutin, tannic acid, and salts of tannic acid, and ethyl alcohol. 3. A method for producing a food product, which comprises blending at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid with ethyl alcohol. 4. The method for producing a food according to claim 3, wherein the food is noodles. 5. The method for producing a food according to claim 4, wherein the noodles are fresh buckwheat. 6. A food containing at least one selected from the group consisting of hinokitiol, rutin, tannic acid and salts of tannic acid, and ethyl alcohol. 7. The food according to claim 6, which is noodles. 8. The food according to claim 7, which is raw buckwheat.