WO2018003965A1

WO2018003965A1 - Method for producing fumaric acid powder formulation

Info

Publication number: WO2018003965A1
Application number: PCT/JP2017/024108
Authority: WO
Inventors: 段王　保文; 克彦日野; 西本　友之
Original assignee: 株式会社林原
Priority date: 2016-07-01
Filing date: 2017-06-30
Publication date: 2018-01-04
Also published as: JPWO2018003965A1

Abstract

The present invention addresses the problem of providing a fumaric acid powder formulation which is excellent in powder flow property and rate of dissolution. To solve this problem, the present invention provides a fumaric acid powder formulation and a method for producing the same, wherein the fumaric acid powder formulation is characterized by: containing a fumaric acid, a hydrophilic non-ionic surfactant, and a non-reducing disaccharide or a sugar alcohol containing two or less sugars, the percent by mass thereof with respect to the fumaric acid being at least 0.5 but less than 10 in terms of anhydrous content; and in that the fumaric acid is coated with the hydrophilic non-ionic surfactant and the non-reducing disaccharide or the sugar alcohol containing two or less sugars.

Description

Method for producing powdered fumaric acid preparation

The present invention relates to a method for producing a powdered fumaric acid formulation containing fumaric acid as an active ingredient, and a powdered fumaric acid formulation obtained by the production method.

Fumaric acid is an organic acid that has the strongest acidity next to acetic acid and succinic acid, and its acidity is said to be about 1.5 times that of citric acid and malic acid widely used in fruit juice beverages. ing. In addition, acetic acid and succinic acid are volatile, while fumaric acid is non-volatile, and succinic acid is physiologically harmful, whereas fumaric acid is harmless. Furthermore, since fumaric acid is relatively inexpensive and has a strong sterilizing power, it has been widely used as a food additive such as a sour agent and a food preservative. However, fumaric acid has a very low solubility in water (the solubility in water at 25 ° C. is 0.63 g / 100 ml) and the dissolution rate is slow, so that it is difficult to disperse and dissolve in water in a short time. For this reason, the preparation of solution-form fumaric acid preparations such as acidulants, preservatives, and disinfectants containing fumaric acid as an active ingredient is usually inefficient and requires a lot of labor.

In order to improve this drawback, as a technique for improving the dissolution rate of fumaric acid in water, for example, Patent Document 1 proposes that a polyglycerin fatty acid ester is mixed and supported in a hydrophobic powder containing fumaric acid. ing. Patent Document 2 discloses a disinfecting detergent that improves the dissolution rate by coating fumaric acid particles with a hydrophilic nonionic surfactant. Further, Patent Document 3 discloses a fumaric acid preparation containing 2.5 to 10% by weight of a dextrose equivalent maltextrin wetting agent containing 75% by weight of a polysaccharide of trisaccharides or more based on fumaric acid. It is disclosed that it exhibits a high dissolution rate in cold water, and Patent Document 4 is characterized in that glucose or sucrose is blended as an auxiliary agent in an intimate mixture of finely powdered fumaric acid and a surfactant. Methods for producing fumaric acid-containing compositions with improved dissolution rates are disclosed respectively. However, according to the knowledge independently obtained by the present inventors, among the methods described in Patent Documents 1 to 4, the methods described in Patent Documents 1 and 2 are used to treat the surface of the fumaric acid particles with polyglycerol fatty acid ester or Since it coats with sucrose fatty acid ester etc., there exists a problem that the obtained fumaric acid formulation is easy to aggregate and solidify under the influence of these surfactant. On the other hand, in the method described in Patent Document 3, the dispersibility of the fumaric acid preparation is not sufficient, and in the method described in Patent Document 4, glucose or sucrose as an auxiliary agent is added to a mixture of powdered fumaric acid and a surfactant. It is necessary to mix saccharides such as at least 10% by mass or more with respect to fumaric acid, and since a relatively large amount of sugar is used with respect to fumaric acid, the content of fumaric acid in the preparation is reduced, and thus the sterilization effect, etc. There was a problem that the original effect of fumaric acid was reduced.

Japanese Patent Publication No.62-19146 JP 2003-147392 A Japanese Patent Publication No.57-54110 Japanese Patent Publication No.42-22184

The present invention has been made to solve the above-mentioned drawbacks of the prior art, exhibits excellent solubility in solvents such as water, is difficult to agglomerate and solidify in the manufacturing process, and is easy to prepare. It is another object of the present invention to provide a method for producing a powdered fumaric acid preparation that maintains the original effects of fumaric acid such as a sterilizing effect at a satisfactory level, and a powdered fumaric acid preparation obtained by the production method. To do.

In the process of examining the solution of the above problems, the present inventors have disclosed a method disclosed in Patent Document 1 or 2 in which the surface of fumaric acid particles is coated with a hydrophilic nonionic surfactant such as glycerin fatty acid ester. When a powdered fumarate formulation is prepared, the dissolution rate of the fumaric acid powder is improved, but the powdered fumaric acid formulation is agglomerated in the production process and the passage of the sieve is reduced, so that the workability in the production of the powdered formulation is reduced and the final product As a result, it was found that the yield of the powdered fumaric acid preparation was significantly reduced. Furthermore, when the present inventors coated the surface of fumaric acid particles with a hydrophilic nonionic surfactant and a saccharide according to the disclosure of Patent Document 4, the present inventors were excellent in powder flowability and water-soluble dispersion solubility. Although a powdered fumaric acid preparation can be obtained, it has been found that there is a new problem that has not been known so far that the entire composition solidifies and solidifies during the manufacturing process and places a heavy burden on the subsequent powdering process. . Based on these findings, further investigations were made, and the amount of carbohydrate added in the production of powdered fumaric acid preparations was adjusted to a range of 0.5% to less than 10% by weight in terms of anhydride relative to fumaric acid. Then, it discovered that a powdered fumaric acid formulation could be easily manufactured without solidifying a granular composition in the manufacturing process (drying process) of a formulation, and established the manufacturing method of this invention.

That is, the present invention is a method for producing a powdered fumaric acid preparation containing fumaric acid as an active ingredient,
(1) 0.5% by mass or more and less than 10.0% by mass of non-reducing disaccharide or disaccharide in terms of anhydride with respect to fumaric acid powder, hydrophilic nonionic surfactant and fumaric acid powder A sugar alcohol in the presence of a solvent to obtain a fumaric acid-containing wet mixture;
(2) The obtained fumaric acid-containing wet mixture is dried, and the fumaric acid-containing granular composition in which the fumaric acid particles are coated with a hydrophilic nonionic surfactant and a non-reducing disaccharide or a sugar alcohol less than a disaccharide. And (3) pulverizing and classifying the obtained fumaric acid-containing granular composition as necessary to obtain a powdered fumaric acid formulation;
The above-mentioned problems are solved by providing a method for producing a powdered fumaric acid preparation containing

Furthermore, this invention solves said subject by providing the powder fumaric acid formulation manufactured by said manufacturing method, The powder fumaric acid formulation manufactured by the said manufacturing method is solvent, such as water. The fumaric acid, which is an active ingredient, is contained at a concentration that provides a satisfactory level of the original action and effect of fumaric acid. Since it is hard to tie, it has the characteristic of stably maintaining fluidity as a powder even during storage and distribution.

According to the production method of the present invention, a powdered fumaric acid preparation having stable powder fluidity and an excellent dissolution rate is industrially produced while maintaining the original sterilizing effect of fumaric acid, which is an active ingredient, at a satisfactory level. Can be provided easily, in large quantities, and stably at low cost. The powdered fumaric acid preparation obtained by the production method of the present invention is a high-quality powdered fumaric acid preparation excellent in powder flowability and dissolution rate.

The present invention relates to a method for producing a powdered fumaric acid preparation containing fumaric acid as an active ingredient, which comprises the following steps (1) to (3):
(1) 0.5% by mass or more and less than 10.0% by mass of non-reducing disaccharide or disaccharide in terms of anhydride with respect to fumaric acid powder, hydrophilic nonionic surfactant and fumaric acid powder A sugar alcohol in the presence of a solvent to obtain a fumaric acid-containing wet mixture;
(2) The obtained fumaric acid-containing wet mixture is dried, and the fumaric acid-containing granular composition in which the fumaric acid particles are coated with a hydrophilic nonionic surfactant and a non-reducing disaccharide or a sugar alcohol less than a disaccharide. And (3) a step of pulverizing and classifying the obtained fumaric acid-containing granular composition as necessary to obtain a powdered fumaric acid preparation.

<The manufacturing method of the powder fumaric acid formulation of this invention>
The outline of the method for producing the powdered fumaric acid preparation of the present invention will be described below. To the fumaric acid powder, a hydrophilic nonionic surfactant and a non-reducing disaccharide or a sugar alcohol less than a disaccharide are added in the presence of a solvent. By mixing uniformly, the fumaric acid particles are coated with a hydrophilic nonionic surfactant and a non-reducing disaccharide or a sugar alcohol less than a disaccharide, and then dried to remove the solvent, and the resulting granules This is a method for producing a powdered fumaric acid preparation by pulverizing and classifying the composition as necessary.

In the production method of the present invention, commercially available fumaric acid powder can be used as the raw material. Commercially available fumaric acid powder is usually a white crystalline powder, has no odor, and has a strong acidity. As the commercially available fumaric acid powder, for example, trade name “Fumaric acid” sold by Nippon Shokubai Co., Ltd., trade name “Fumaric acid” sold by Fuso Kogyo Co., Ltd. can be used. The particle size of fumaric acid used as the active ingredient of the preparation is not particularly limited, but the smaller the particle size, the better the water dispersibility and dissolution rate. Therefore, when the particle size of commercially available fumaric acid as a raw material is relatively large, it is preferable to pulverize in advance and adjust the particle size of fumaric acid to usually 150 μm or less, desirably 75 μm or less. When the particle size of fumaric acid exceeds 150 μm, the dissolution rate in water tends to decrease.

As the surfactant added to the fumaric acid powder in the production method of the present invention, a nonionic surfactant is preferable, and the surface of the fumaric acid particles is coated to improve the dispersibility and dissolution rate of fumaric acid in water. Therefore, a hydrophilic nonionic surfactant is more preferable than a lipophilic nonionic surfactant. Examples of hydrophilic nonionic surfactants include sucrose fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, and polyglycerin fatty acid esters. Especially, polyglycerin fatty acid esters are highly effective in improving the fumaric acid dissolution rate. Is preferred. As the hydrophilic nonionic surfactant, a hydrophilic / lipophilic balance (hereinafter abbreviated as “HLB”). HLB takes a value from 0 to 20, and the closer to 0, the more lipophilic. It is preferable to use a hydrophilic nonionic surfactant having an HLB in the range of 14 to 18, preferably using a hydrophilic nonionic surfactant having a range of 14 to 18. The advantage that the effect of improving the dissolution rate of fumaric acid in water is the highest is obtained. In addition, since the above-mentioned hydrophilic nonionic surfactants are all safe substances designated as food additives, the powder fumaric acid preparation of the present invention obtained, for example, for foods can be obtained even if it is added. It also has the advantage of not hindering its use as a disinfectant cleaning agent.

In the production method of the present invention, the amount of the hydrophilic nonionic surfactant used for coating the fumaric acid particles is not particularly limited as long as the dispersibility and dissolution rate of fumaric acid in water are improved. In terms of anhydride, it is usually 0.1 to 3.0% by mass, preferably 0.3 to 1.0% by mass, more preferably about 0.5% by mass. The greater the amount of hydrophilic nonionic surfactant added, the better the effect of improving the dissolution rate of the powdered fumaric acid preparation, and a sufficient effect is usually obtained at 0.1% by mass or more. On the other hand, if the addition amount is too large, the fumaric acid particles are liable to aggregate, so the addition amount of the hydrophilic nonionic surfactant is preferably 3.0% by mass or less.

In the production method of the present invention, examples of the saccharide used for coating the fumaric acid particles include a non-reducing disaccharide or a sugar alcohol having a disaccharide or less. Among the non-reducing disaccharides or the sugar alcohols below the disaccharide, trehalose, sorbitol, and maltitol are preferable from the viewpoint of improving the cohesiveness and sieving ability of the powdered fumaric acid preparation. By using trehalose, sorbitol or maltitol, the dissolution rate of fumaric acid in the powdered fumaric acid preparation in water can be improved, and the cohesiveness and sieving ability of the powdered fumaric acid preparation can be improved. Here, since trehalose, sorbitol and maltitol all have no reducing aldehyde group and have low reactivity, there is also an advantage that the obtained powdered fumaric acid preparation is difficult to be colored.

In the production method of the present invention, the addition amount of the non-reducing disaccharide or the disaccharide or less sugar alcohol used for coating the fumaric acid particles is usually 0.5% by mass or more in terms of anhydride with respect to fumaric acid. The content is preferably less than 10.0% by mass, and more preferably 1.0 to 5.0% by mass. When the addition amount of non-reducing disaccharide or sugar alcohol less than disaccharide is 10.0% by mass or more, the fumaric acid particles coated with the hydrophilic nonionic surfactant and the saccharide in the production process are blocked. It is easy to solidify and solidify, making it difficult to pulverize, and there is a disadvantage that the work efficiency in production is reduced. Moreover, when the addition amount of non-reducing disaccharide or sugar alcohol less than disaccharide is less than 0.5% by mass, it is difficult to obtain the effect of improving the cohesiveness and sieving ability of the powdered fumaric acid preparation.

In the production method of the present invention, the solvent used to obtain the fumaric acid-containing wet mixture is particularly limited as long as it dissolves a hydrophilic nonionic surfactant and a non-reducing disaccharide or a sugar alcohol having a disaccharide or less. However, in consideration of using the obtained powdered fumaric acid preparation as a sterilizing detergent for foods, it is preferable to use water or ethyl alcohol, and more preferably water.

In the production method of the present invention, the amount of the solvent to be used is not particularly limited as long as it is an amount capable of dissolving the added hydrophilic nonionic surfactant and the non-reducing disaccharide or the sugar alcohol less than the disaccharide. Usually, it is preferably 50% by mass or more and more preferably 80% by mass or more with respect to the acid. When the amount of the solvent used is less than 50% by mass, the fluidity of the fumaric acid-containing wet mixture during mixing is significantly reduced, and a large load is imposed on the mixing operation, so that uniform mixing becomes difficult and workability is poor. This is not desirable. On the other hand, if the amount of solvent used is too large, it takes a lot of time and energy in the process of drying the fumaric acid-containing wet mixture and removing the solvent. 300 mass% or less is preferable, and 200 mass% or less is more preferable.

In the production method of the present invention, a fumaric acid powder is mixed with a hydrophilic nonionic surfactant solution and a non-reducing disaccharide or a sugar alcohol solution of a disaccharide or less, and then the solvent is removed to obtain fumaric acid powder particles. It is coated with a hydrophilic nonionic surfactant and a non-reducing disaccharide or a sugar alcohol less than the disaccharide. At this time, if the particle size of the fumaric acid powder to be used is too large, before adding and mixing the hydrophilic nonionic surfactant and the non-reducing disaccharide or the sugar alcohol less than the disaccharide, use a mixer or the like in advance. It is preferable to grind to about 150 μm or less, more preferably about 75 μm or less.

The step of mixing a hydrophilic nonionic surfactant and a non-reducing disaccharide or a sugar alcohol of a disaccharide or less with fumaric acid powder in the presence of a solvent is performed by simultaneously mixing these three in the presence of a solvent. The fumaric acid powder may be mixed with a nonionic disaccharide or a sugar alcohol having a disaccharide or less in the presence of an appropriate amount of solvent, and then further mixed with a hydrophilic nonionic surfactant. Is more preferable. As a result, the surface of the fumaric acid particles is first coated with a non-reducing disaccharide or a sugar alcohol less than the disaccharide, and further coated with a hydrophilic nonionic surfactant. The effect of improving the dissolution rate is improved.

In the production method of the present invention, the step of mixing the fumaric acid powder, the hydrophilic nonionic surfactant and the non-reducing disaccharide or the sugar alcohol of the disaccharide or less in the presence of a solvent is performed by any means. Although it may be sufficient and it does not restrict | limit in particular, For example, it can carry out using the suitable mixing means widely used in this field, such as a blender, a homogenizer, a whisk, a paste mixer, a kneader, an extruder, a mixing stirrer. The conditions at the time of mixing are not particularly limited as long as the fumaric acid powder particles are coated with a hydrophilic nonionic surfactant and a non-reducing disaccharide or a sugar alcohol of a disaccharide or less, and heating conditions as necessary It can also be mixed below.

In the production method of the present invention, fumaric acid powder, a hydrophilic nonionic surfactant, and a non-reducing disaccharide or a sugar alcohol less than a disaccharide are mixed, and then the solvent is dried and removed from the wet mixture. The step of making the acid-containing granular composition may be carried out by any means and is not particularly limited, but examples thereof include spray drying, drum drying, reduced pressure drying, heat drying, freeze drying and the like. Can be carried out using any appropriate means widely used. Although the drying conditions vary depending on the type of solvent, etc., when the solvent is, for example, water, it is desirable to remove it by drying under reduced pressure by heating to about 70 to 100 ° C. in order to reduce cost and increase efficiency.

The production method of the present invention includes a step of pulverizing the fumaric acid-containing granular composition obtained by drying, if necessary. That is, if the particle size of the obtained fumaric acid-containing granular composition satisfies the particle size conditions required for a powdered fumaric acid formulation, the fumaric acid-containing granular composition obtained by drying is directly used as a powdered fumaric acid formulation. However, when the particle size of the obtained fumaric acid-containing granular composition is larger than the particle size required for the powdered fumaric acid preparation, it may be appropriately pulverized. The pulverizing means is not particularly limited, and can be performed using appropriate pulverizing means widely used in the field such as a mortar, a mill, a fine pulverizer, and an atomizer. Incidentally, when the addition amount of the non-reducing disaccharide or the sugar alcohol below the disaccharide to the fumaric acid powder is 10% by mass or more in terms of anhydride, the entire fumaric acid-containing granular composition is solidified (blocked). However, in the production method of the present invention, since the amount of the saccharide added is small, such a problem relating to pulverization does not occur.

Furthermore, the production method of the present invention includes a step of classifying the fumaric acid-containing granular composition obtained by drying or a pulverized product thereof as necessary, and adjusting the particle size distribution required for the powdered fumaric acid preparation. Yes. The classifying means is not particularly limited, and can be performed using appropriate classifying means widely used in the field such as a wire mesh, a test sieve, a vibration sieve, and an ultrasonic vibration sieve. Since the dispersibility and dissolution rate of fumaric acid in water are also related to the particle size of the preparation, the particle size is usually adjusted to 500 μm or less, preferably 300 μm or less by classification.

<Powdered fumaric acid formulation of the present invention>
The present invention is a powdered fumaric acid preparation produced by the production method of the present invention described above, that is, fumaric acid particles are coated with a hydrophilic nonionic surfactant and a non-reducing disaccharide or a sugar alcohol less than a disaccharide. It is also related to powdered fumaric acid preparation, and the powdered fumaric acid preparation corresponds to the addition ratio of various compounds in the production method, and is 0.5% by mass or more and less than 10.0% in terms of anhydride with respect to fumaric acid. % Non-reducing disaccharides or sugar sugars less than or equal to disaccharides.

As described above, the powdered fumaric acid preparation of the present invention is in a form in which a crystalline powder of fumaric acid is coated with a hydrophilic nonionic surfactant and a specific amount of a non-reducing disaccharide or a sugar alcohol less than a disaccharide. It is the formulation characterized by this.

In the powdered fumaric acid preparation of the present invention, other components such as a chelating agent, a thickening agent, an emulsifying agent, a fragrance, a coloring agent, and the like can be appropriately blended as necessary. In addition, other edible disinfectants can be added to the powdered fumaric acid preparation of the present invention. Examples of other edible sterilizing agents include sodium hypochlorite, sodium chlorite, high-grade salty powder, and hydrogen peroxide.

In the powdered fumaric acid preparation of the present invention, an organic acid other than fumaric acid, a derivative thereof, or a salt thereof can be used in appropriate combination. Examples of organic acids other than fumaric acid include citric acid, malic acid, tartaric acid, succinic acid, lactic acid, acetic acid, propionic acid, sorbic acid, benzoic acid, ascorbic acid, and the like. Specifically, glycosyl derivatives, acylated derivatives, phosphorylated derivatives and the like can be mentioned, and examples of salts thereof include sodium salts, potassium salts, magnesium salts, calcium salts, ammonium salts and the like. In particular, from the viewpoint of improvement of antibacterial activity and / or expansion of antibacterial targets, a combination of fumaric acid and citric acid, malic acid, tartaric acid and ascorbic acid is preferable, and a combination of ascorbic acid or a derivative thereof or a salt thereof is particularly preferable. . The amount of an organic acid other than fumaric acid, a derivative thereof, or a salt thereof is preferably more than an equivalent amount, and more preferably twice or more the amount of fumaric acid. If the amount of the organic acid other than fumaric acid, its derivative or their salt is equal to or less than that, it is not desirable because the effect of improving the antibacterial activity and / or expanding the antibacterial target is reduced. On the other hand, if the amount of the organic acid other than fumaric acid to be combined, the derivative thereof or the salt thereof is too large, the effect of improving the cohesiveness and sieving property of the powdered fumaric acid preparation is difficult to be obtained. 20 times or less is preferable and 12 times or less is more preferable.

An organic acid other than fumaric acid, a derivative thereof or a salt thereof in the method for producing a powdered fumaric acid preparation containing fumaric acid as an active ingredient described above;
(1) 0.5% by mass or more and less than 10.0% by mass of non-reducing disaccharide or disaccharide or less in terms of anhydride with respect to fumaric acid powder, hydrophilic nonionic surfactant and fumaric acid Mixing the sugar alcohol in the presence of a solvent to obtain a fumaric acid-containing wet mixture;
(2) The obtained fumaric acid-containing wet mixture is dried, and the fumaric acid-containing granular composition in which the fumaric acid particles are coated with a hydrophilic nonionic surfactant and a non-reducing disaccharide or a sugar alcohol less than a disaccharide. And (3) pulverizing and classifying the obtained fumaric acid-containing granular composition as necessary to obtain a powdered fumaric acid formulation;
For example, in the step (1), it may be added and mixed with other components, and in the step (2), a wet mixture before or during drying, Or it can mix with the granular composition after drying, and, in the process of (3), it can be mixed before, during or after pulverization or classification. Furthermore, you may make it mix the powdered fumaric acid formulation manufactured through the process of (1) thru | or (3), organic acids other than fumaric acid, its derivative (s), or those salts. The organic acid other than fumaric acid, its derivative, or salt thereof may be mixed at the same time at any one of the timings described above, or may be mixed at two or more timings divided into two or more. .

The intended use of the powdered fumaric acid preparation of the present invention is not particularly limited, but as it is or after being dispersed, dissolved and diluted, and further containing an alcohol such as ethanol, an antibacterial agent, etc. It can be used as a sour agent, a preservative, a sterilizing detergent, or as a detergent for tanks and lines in foods and food factories, and can also be used as a general sterilizing detergent. . *

When the powdered fumaric acid preparation of the present invention is used as a sterilizing detergent for foods, it is usually dispersed and dissolved uniformly in water or warm water, and the concentration of fumaric acid is preferably 0.05 to 1% by mass, More preferably, it is used as a treatment liquid of about 0.1 to 0.5% by mass. When the concentration of the treatment liquid is less than 0.05% by mass, it is difficult to obtain the intended sterilizing effect. In addition, when the concentration of the treatment liquid is too high, the food has a strong acidity and may deteriorate the flavor. The treatment liquid for the sterilization detergent for food can be used as a treatment liquid for sterilization of food materials such as vegetables, fruits, seafood, and meat. *

For example, when the powdered fumaric acid preparation of the present invention is used for processing foodstuffs of vegetables, fruits, seafood, meat, etc., the powdered fumaric acid preparation of the present invention has a concentration of 0.05-1 mass as the fumaric acid concentration. Bacteria are sterilized by immersing the ingredients in a treatment solution that is dispersed and dissolved to about%. Immersion time is appropriately set according to the purpose. For example, in the case of vegetables such as cabbage, about 30 seconds to 10 minutes, in the case of seafood such as squid, octopus and shrimp, about 10 seconds to 10 minutes, in the case of meat such as chicken, pork, and beef Soak and disinfect for about 60 minutes. Specifically, in the case of vegetables, the washed and cut vegetables are immersed in the treatment solution for a short time, and then rinsed with water for cooking. Thus, even when used for the sterilization of foods including vegetables, the sanitary detergent for food obtained by dissolving the powdered fumaric acid preparation of the present invention is fumaric acid which is recognized as a food additive. As the main component, it is extremely safe and at the same time exerts extremely strong sterilizing power against food poisoning bacteria such as Escherichia coli, Pseudomonas aeruginosa, Salmonella, etc., vegetables, fruits, seafood, meat, etc. It can be used effectively for the purpose of preventing the occurrence of food poisoning caused by food.

Hereinafter, based on various experiments, the production method of the powdered fumaric acid formulation according to the present invention and the powdered fumaric acid formulation obtained by the production method will be described in more detail.

The present inventors have disclosed in Patent Documents 1 and 2 that the solubility is improved by coating the surface of fumaric acid particles with a nonionic surfactant (hydrophilic nonionic surfactant) exhibiting hydrophilicity. The following preliminary experiments were conducted to confirm the disclosed prior art.

<Preliminary experiment 1: Effect of addition of hydrophilic nonionic surfactant on solubility of powdered fumaric acid preparation>
(1) Summary Various hydrophilic nonionic surfactants having different HLBs were added to fumaric acid, and the influence of each on the solubility of the powdered fumaric acid preparation was examined.
(2) Experimental method (a) Preparation of test sample To 3.0 g of fumaric acid powder (trade name “fumaric acid (fine powder)”, purity of 99.0% by mass or more, sold by Fuso Chemical Industry Co., Ltd.), various hydrophilic nonions Surfactants, specifically, polyglycerin fatty acid ester (trade name “Poem J-0021”, HLB 15.5, sold by Riken Vitamin Co., Ltd.), sucrose fatty acid ester (trade name “Ryoto Sugar Ester”, HLB16 0.0, sold by Mitsubishi Chemical Foods Co., Ltd.), polyglycerin fatty acid ester (trade name “Ryoto Polyglycerate L-7D”, HLB17, sold by Mitsubishi Chemical Foods Co., Ltd.), sucrose fatty acid ester (trade name “DK Ester SS”) , HLB16.0, sold by Daiichi Kogyo Seiyaku Co., Ltd.), or polyoxyalkyl branched decyl ester (trade name “Neugen X L-1000 ”, HLB19.3, sold by Daiichi Kogyo Seiyaku Co., Ltd.) 5 mL of an aqueous solution having a concentration of 3 mg / mL was added and mixed, and then the wet mixture was spread on a tray and a hot-air circulating dryer And dried at 70 ° C. for 15 hours. Next, each fumaric acid-containing granular composition obtained was pulverized in a mortar, and then a sieve having an opening of 500 μm (trade name “THE IIDA TESTING SIEVE” manufactured by Iida Manufacturing Co., Ltd. The test samples 2 to 6 of powdered fumaric acid preparations coated with various hydrophilic nonionic surfactants having different HLB values were obtained. A test sample 1 was prepared by only adding a hydrophilic nonionic surfactant to the fumaric acid powder used as a raw material and passing through a sieve having an opening of 500 μm. The obtained test samples 2 to 6 each contain 0.5% by mass of various hydrophilic nonionic surfactants with respect to fumaric acid.

(A) Solubility test About each powder fumaric acid formulation obtained above, after weighing each test sample into a 20 mL beaker so that it may become 30 mg as a fumaric acid, 10 mL of pure waters were added, and it stirred for 2 minutes And filtered through a 0.22 μm pore filter. Next, after each filtrate was diluted 10 times with pure water, the absorbance at a wavelength of 280 nm of the diluted solution was measured, and a 10-fold diluted solution of an aqueous solution in which 30 mg of fumaric acid was completely dissolved in 10 mL of pure water was separately obtained. The absorbance at a wavelength of 280 nm was taken as 100%, and the relative fumaric acid dissolution rate (%) of each test sample was relatively evaluated. That is, the percentage of the value (Y) at the wavelength 280 nm of the 10-fold diluted solution of each test sample with respect to the absorbance value (X) at the wavelength 280 nm of the standard fumaric acid aqueous solution of 0.15 mg / mL {(Y / X) × 100} was determined and taken as the relative fumaric acid dissolution rate. The results are shown in Table 1. It has been confirmed that under the conditions tested, the influence of the addition of various hydrophilic nonionic surfactants on the absorbance at a wavelength of 280 nm is negligible.

As shown in Table 1, in the test sample 1 in which only the process of passing a 500 μm sieve through the fumaric acid powder was performed, the relative fumaric acid dissolution rate with respect to the control in which the fumaric acid powder was completely dissolved was as low as 82.0%. It was confirmed that stirring for 2 minutes did not sufficiently dissolve (dissolution rate was slow). On the other hand, the powdered fumaric acid preparations (test samples 2 to 6) to which various hydrophilic nonionic surfactants were added and coated were shown to have a relative fumaric acid solubility of 97.0% or more. It was confirmed that the addition of the nonionic surfactant has the effect of improving the dissolution rate of fumaric acid. In addition, the HLB value of the hydrophilic nonionic surfactant did not significantly affect the dissolution rate within the tested range, but among the hydrophilic nonionic surfactant, HBL was 15.5 and Since the test samples 2 and 4 to which the polyglycerin fatty acid ester of 17.0 was added showed a relative fumaric acid dissolution rate of 100%, the HBL is preferably in the range of about 14.0 to 18.0, In addition, among the same hydrophilic nonionic surfactants, it was considered that polyglycerol fatty acid ester is more effective in improving dissolution rate than sucrose fatty acid ester and polyoxyalkyl branched decyl ester.

Although it was confirmed that the dissolution rate of the powdered fumaric acid preparation (test samples 2 to 6) in water was improved by adding a hydrophilic nonionic surfactant, these preparations (test samples 2 to 6) Were easily aggregated, and it was difficult to obtain a sufficient amount of test sample that passed through a sieve having an opening of 500 μm in the test sample preparation step (a). Therefore, the following sieve passability test was performed in order to objectively evaluate the sieve passability of the test samples 2 to 6.

(C) Screenability test A part of the test samples 1 to 6 obtained in (a) above is stored at room temperature for 3 days, 3 g each is weighed on a 500 μm sieve, and the sieve is vortex mixer (SCIENTIFIC). INDUSTRIES, "MODEL G560") was used to shake for 30 seconds at the strength of the scale 5, the weight of each test sample that passed through the sieve was measured, and the sieve permeability was evaluated. That is, with respect to the weight (A) of the original sample, the percentage {(B / A) × 100} occupied by the weight (B) of each test sample that passed through the sieve was obtained and calculated as the sieve passing percentage (%). Table 2 shows the evaluation of the calculated passage rate of each test sample in the following three stages:
+++: sieve passing rate after shaking for 30 seconds 50% or more;
++: sieve passage rate after shaking for 30 seconds 25 to less than 50%;
+: Sieve passing rate after shaking for 30 seconds is less than 25%.

As shown in Table 2, test sample 1 in which only fumaric acid powder is passed through a 500 μm sieve and test samples 2 to 6 which are powdered fumaric acid preparations to which various hydrophilic nonionic surfactants are added. In each case, the sieve passing rate after shaking for 30 seconds was less than 25% (+), and the sieve passing ability was extremely low.

<Preliminary experiment 2: Effect of addition amount of polyglycerol fatty acid ester on dissolution rate improvement of powdered fumaric acid preparation>
Subsequently, using polyglycerin fatty acid ester (HLB17), which was confirmed in the preliminary experiment 1 to be excellent in the dissolution rate improvement effect, the effect of the addition amount of the hydrophilic nonionic surfactant on the dissolution rate improvement of fumaric acid Further, the following preliminary experiment was conducted.

(1) Outline By examining various addition amounts of polyglycerin fatty acid ester (HLB17) to fumaric acid powder, the influence of the addition amount of polyglycerin fatty acid ester on the dissolution rate improvement of the powdered fumaric acid preparation was examined.
(2) Experimental method (a) Preparation of test sample To 3.0 g of fumaric acid powder (trade name “fumaric acid (fine powder)”, purity 99.0% by mass or more, sold by Fuso Chemical Industry Co., Ltd.), polyglycerin fatty acid ester An aqueous solution having a concentration of 0.006, 0.3, 0.6, 3, 6, 18, 30, or 42 mg / mL (trade name “Ryoto-Polyglyceride L-7D”, HLB17, sold by Mitsubishi Chemical Foods Corporation) 5 mL of any of the above was mixed to prepare a wet mixture, and then the wet mixture was spread on a tray and dried by heating at 70 ° C. for 15 hours in a hot air circulating dryer. Thereafter, the dried product was pulverized in a mortar, passed through a sieve having an opening of 500 μm, and various powdered fumaric acid preparations (test samples 7 to 14) coated with polyglycerin fatty acid ester were obtained. In addition, the obtained test samples 7 thru | or 14 are polyglycerol fatty acid ester 0.001, 0.05, 0.1, 0.5, 1.0, 3.0, 5 with respect to fumaric acid, respectively. 0.0 and 7.0% by mass.

(A) Solubility test The above-mentioned various powdered fumaric acid preparations were subjected to the same solubility test as described in (I) of Preliminary Experiment 1: (2), and the relative fumaric acid dissolution rates of test samples 7 to 14 (%) Was calculated. The results are shown in Table 2.

As shown in Table 3, the relative fumaric acid dissolution rate is improved as the amount of the polyglycerin fatty acid ester to be mixed increases, and the amount becomes 1.0% by mass or more (test samples 11 to 14) with respect to fumaric acid. It was confirmed that the dissolution rate was improved to the extent of complete dissolution in water by stirring for 2 minutes.

Also in this preliminary experiment, it was confirmed that the powdered fumaric acid preparation aggregates when polyglycerin fatty acid ester is added. That is, as the amount of polyglycerin fatty acid ester increases, the degree of aggregation of fumaric acid particles tends to increase, and the permeability of the powder when using a sieve having an opening of 500 μm is reduced. It was experienced that the recovery of the fumaric acid formulation was significantly reduced. Although details are omitted, when the obtained test samples 7 to 14 were subjected to the same sieving test as in Preliminary Experiment 1, all of the sieving rates after shaking for 30 seconds were less than 25% (+). It was evaluated and the sieve passing ability was remarkably low.

From the results of Preliminary Experiments 1 and 2 above, when fumaric acid particles are coated with a hydrophilic nonionic surfactant such as polyglycerin fatty acid ester, the fumaric acid dissolution rate is improved, but powder fumaric acid particles are agglomerated in the production process. As a result, it was found that the passage of the sieve was lowered, and the workability in the production process and the recovery rate of the powdered fumaric acid preparation were significantly lowered. In addition, the cohesiveness of the powdered fumaric acid particles is also expressed in the process of storage and distribution of the powdered fumaric acid preparation, and there is a concern that the fluidity of the powdered fumaric acid preparation may be lost. These findings are new findings uniquely found by the present inventors.

<Experiment 1: Effect of sugar type on sieve passability of powdered fumaric acid preparation blended with polyglycerol fatty acid ester>
Based on the above new findings, the following experiments were conducted in order to achieve both improvement in dissolution rate and improvement in aggregation and solidification.
(1) Summary Various sugars were added to a powdered fumaric acid preparation containing a certain amount of polyglycerin fatty acid ester, and the effects of the type of sugar on the sieve passability of the powdered fumaric acid preparation were compared.
(2) Experimental method (a) Preparation of test sample To 20.0 g of fumaric acid powder (trade name “fumaric acid (fine powder)”, purity 99.0% by mass or more, sold by Fuso Chemical Industry Co., Ltd.), polyglycerin fatty acid ester 1 g of an aqueous solution with a concentration of 10% by mass (trade name “Ryoto-polyglycerate L-7D”, HLB17, sold by Mitsubishi Chemical Foods Co., Ltd.), various carbohydrates with a concentration of 10% by mass in terms of anhydride, specifically, Glucose (reagent grade, sold by Wako Pure Chemical Industries, Ltd.), sucrose (reagent grade, sold by Wako Pure Chemical Industries, Ltd.), trehalose (trade name "Treh", sold by Hayashibara Corporation), sorbitol (reagent grade, Wako Pure Chemical Industries, Ltd.) Industrial Co., Ltd.), Maltitol (reagent grade, Wako Pure Chemical Industries Ltd. sale), Maltose (trade name “San Mart (Green)”, Hayashibara Co., Ltd. sale), Lactose (Reagent grade) Wako Pure Chemical Industries, Ltd.), or 10 g of any aqueous solution containing a partially decomposed starch (trade name “Paindex # 1”, Matsutani Chemical Industry Co., Ltd.) at a concentration of 10% by mass in terms of anhydride. After adding 25.1 g of pure water and mixing for 3 minutes using a blender, the resulting wet mixture was dried by heating in a hot air circulating dryer at 70 ° C. for 20 hours, and various drying I got a thing. Thereafter, the dried product was pulverized in a mortar and then passed through a sieve having an opening of 500 μm to obtain a powdered fumaric acid formulation (test samples 15 to 22) coated with various sugars together with a polyglycerin fatty acid ester. The various powdered fumaric acid preparations (test samples 15 to 22) obtained contain 0.5% by mass of various carbohydrates in terms of anhydride with respect to fumaric acid.

(Ii) Screening test The various powdered fumaric acid preparations described above were subjected to the same screening test as described in (c) of Preliminary Experiment 1: (2), and the screening properties of each test sample were obtained. ,evaluated. The results are shown in Table 4.

As shown in Table 4, the fumaric acid powder is obtained by adding and mixing a certain amount of polyglycerin fatty acid ester and various sugars, and coating the fumaric acid particles with polyglycerin fatty acid ester and various sugars. Compared with the powdered fumaric acid preparation obtained by coating only the control surfactant (polyglycerin fatty acid ester), the powdered fumaric acid preparations (test samples 15 to 22) are improved in passing through the sieve. It was confirmed that Regarding the sieving ability, there is a difference between sugars, and non-reducing disaccharide trehalose (test sample 17), sugar alcohol sorbitol (test sample 18) below disaccharide, and maltitol (test sample 19). ) Was evaluated as “++++: sieve passing rate after shaking for 30 seconds, 50% or more”, and particularly excellent sieve passing ability was exhibited.

Furthermore, in order to confirm the influence of the added amount of sugar on the sieve passability of the powdered fumaric acid preparation, the following experiment was conducted using trehalose which showed particularly excellent sieve passability in Experiment 1.

<Experiment 2: Effect of added amount of sugar on sieving ability of powdered fumaric acid preparation>
(1) Outline A test sample was prepared in the same manner as in Experiment 1 except that trehalose was selected as the carbohydrate to be blended and the amount of trehalose added was varied. The effect on sieve passage was compared.
(2) Experimental method (a) Preparation of test sample To 20.0 g of fumaric acid powder (trade name “Fumaric acid (fine powder)”, sold by Fuso Chemical Co., Ltd.), polyglycerin fatty acid ester (trade name “Ryoto-polyglycerester” L-7D ”, HLB17, sold by Mitsubishi Chemical Foods Co., Ltd.) 1 g of an aqueous solution with a concentration of 10% by mass, 0.1, 0.2, 0.6, 1.0, 2.0, 4 in terms of anhydride 10 g of any of 10.0, 10.0, 20.0, 40.0 or 60.0% by mass of a trehalose aqueous solution is added, and the total amount of water including the amount of water in the aqueous solution is 35.0 g ( After adding pure water so that it may become 175 mass% with respect to fumaric acid, it mixes for 3 minutes using a blender, and heats the obtained wet mixture in a hot-air circulation type dryer at 70 degreeC for 20 hours. To obtain various dried products . Thereafter, the dried product was pulverized in a mortar and then passed through a sieve having an opening of 500 μm to obtain a powdered fumaric acid preparation (test samples 23 to 32) in which fumaric acid particles were coated with polyglycerin fatty acid ester and trehalose. The various powdered fumaric acid preparations (test samples 23 to 32) obtained were obtained by adding trehalose to fumaric acid in terms of anhydrides of 0.05, 0.1, 0.2, 0.3, 0, respectively. .4, 0.5, 1.0, 2.0, 5.0, 10.0, 20.0, and 30.0 mass%. In addition, as a comparison for confirming the coating effect of carbohydrates, fumaric acid powder and polyglycerin fatty acid ester are mixed in the above quantity ratio in the presence of water, and fumaric acid particles are coated only with polyglycerin fatty acid ester. First, a mixture powder (comparative sample) of powdered fumaric acid and trehalose powder coated with fumaric acid only with a polyglycerin fatty acid ester was prepared by first preparing the mixed powder and mixing it as a powder.

(I) Screenability test In addition to the above-mentioned various powdered fumaric acid preparations (test samples 23 to 32 and comparative samples), fumaric acid powder as a raw material as control 1, fumaric acid powder and polyglycerin fatty acid ester as control 2 The mixture was subjected to the same sieving test as described in Preliminary Experiment 1: (2) (c), and the fumaric acid sieving ability of each sample was evaluated. The results are shown in Table 5.

As shown in Table 5, in the powdered fumaric acid preparation (test samples 23 to 32) prepared by coating fumaric acid particles with polyglycerin fatty acid ester and trehalose, the addition amount of trehalose was 0.05 to 0.05 with respect to fumaric acid. In the case of 0.3% by mass (test samples 23 to 25), the effect of improving the cohesiveness was not observed, and the passing rate of the sieve was as low as less than 25% by mass (+) or less than 50% by mass (++). On the other hand, when the amount of trehalose added is 0.5 to 5.0 mass (test samples 26 to 29), the sieve passing rate of the powdered fumaric acid preparation is improved to 50 mass% or more (+++), and the cohesiveness is improved. The effect was recognized.

In addition, the amount of trehalose added to the fumaric acid was 0. 0 compared to the control fumaric acid powder (control 1) and the coating with only the surfactant (polyglycerin fatty acid ester) (control 2). When it became 3 mass% or more, it was confirmed that the sieve passability of a powder fumaric acid formulation improves. The effect increased as the amount of trehalose added increased. In addition, in the comparative sample obtained by coating the fumaric acid particles only with the polyglycerin fatty acid ester and then simply mixing the trehalose powder, the effect of improving the sieve passing amount was not confirmed.

When the amount of trehalose added was 10% by mass (test sample 30: indicated by “*” in Table 5), although the sieve passing property was improved and the coagulation improvement effect was observed, the test The degree of solidification of the dried product obtained in the sample preparation process became stronger, and powdering by pulverization became partly difficult. Furthermore, when the amount of trehalose added is 20% by mass or 30% by mass (test samples 31 and 32: indicated by “**” in Table 5), the dry matter obtained in the test sample preparation step is The block-shaped lump solidified and became extremely difficult to grind. From the above results, the agent prepared by adding 10% by mass or more of trehalose in terms of anhydride to fumaric acid becomes difficult to grind, and the workability in the manufacturing process of the powdered fumaric acid preparation is significantly reduced. It became clear to do.

Conventionally, for example, as shown in Patent Document 4, in order to improve the dissolution rate and stability of a powdered fumaric acid preparation, it has been essential to add a large amount of carbohydrate of 10% by mass or more. As described above, the present inventors have confirmed through experiments that in order to achieve both improvement in dissolution rate and improvement in cohesion, the amount of sugar alcohol less than the non-reducing disaccharide or disaccharide is as follows: Rather, the result was that a smaller amount of less than 10% by weight with respect to fumaric acid was better. This is a new finding that overturns conventional technical common sense.

Acetic acid is known as an organic acid generally used as a sterilizing detergent for foods, and acetic acid is generally known to act more effectively against gram-negative bacteria than gram-positive bacteria. (Japan Food Industry Association, Vol. 41, No. 10, pp. 687-701, 1994). Although the difference in the antibacterial activity is not clarified, it is due to the structural difference between the Gram-negative bacterium having two lipid membranes, the cell membrane and the outer membrane, and the Gram-positive bacterium having no outer membrane and a thick peptidoglycan layer. It is considered a thing. Therefore, the present inventors intended to improve antibacterial activity and / or expand antibacterial targets, and as a model experiment, conducted experiments combining fumaric acid and ascorbic acid. It was confirmed that there was a fungus effect. Therefore, the present inventors conducted the following experiment to confirm the influence of the difference in the concentration of ascorbic acid when fumaric acid and ascorbic acid were combined on the sterilizing action against Gram-positive bacteria.

<Experiment 3: Effect of combination of fumaric acid and ascorbic acid on sterilization effect against Gram-positive bacteria>
(1) Outline Effects of different concentrations of ascorbic acid on the combination of fumaric acid and ascorbic acid on the sterilization effect against Gram-positive bacteria when adding ascorbic acid solutions with different concentrations to a solution containing a certain amount of fumaric acid Compared.
(2) Experimental method (a) Preparation of test sample Fumaric acid powder (trade name “Fumaric acid (fine powder)”, sold by Fuso Chemical Industry Co., Ltd.) dissolved in pure water to a concentration of 0.3% by mass 1.5 mL of a separately prepared ascorbic acid aqueous solution having an ascorbic acid concentration of 0.6% by mass was mixed with 1.5 mL of the acid-containing aqueous solution to obtain a total of 3 mL of a mixed solution of fumaric acid and ascorbic acid (test sample 33). . The obtained mixed solution (test sample 33) contains fumaric acid at a concentration of 0.15% by mass and ascorbic acid at a concentration of 0.3% by mass. Subsequently, a mixed solution of two types of fumaric acid and ascorbic acid (test samples 34 and 35) (each 3 mL) in the same manner except that the concentration of the ascorbic acid aqueous solution to be mixed was changed to 1.8 or 3.6% by mass. ) The obtained mixed solution (test samples 34 and 35) contains fumaric acid at a concentration of 0.15% by mass and ascorbic acid at concentrations of 0.9 and 1.8% by mass, respectively. .

(A) Preparation of Bacterial Solution As Gram-positive bacteria, Staphylococcus aureus NBRC12732 strain, which is a causative bacterium such as food poisoning, was used. Saline was added to the freeze-dried ampoule of the test bacterium, and 1 platinum ear was inoculated into a slant of a nutrient agar medium and cultured at 37 ° C. for 24 hours. Subsequently, 1 platinum ear of the test bacteria grown on the slant medium was inoculated into an Erlenmeyer flask containing 100 mL of a nutrient broth liquid medium, and cultured at 37 ° C. for 15 hours to form a seed culture. The obtained seed culture solution was inoculated to 1.0% in an Erlenmeyer flask containing 100 mL of a new nutrient broth liquid medium, and cultured with shaking at 37 ° C. for 4 hours. After completion of the culture, 50 mL of the bacterial solution was centrifuged at 5,000 rpm for 5 minutes, the supernatant was removed, and after washing three times with phosphate buffered saline (PBS), Absorbance at a wavelength of 660 nm was measured, and PBS was added so that the number of bacteria was 5 × 10 ⁶ CFU / mL to prepare a bacterial solution.

(C) Disinfection test 3 mL of the above bacterial solution was added to 3 mL of each of the various test sample solutions (33 to 35), the fumaric acid concentration was 0.075% by mass, and the concentration of ascorbic acid was 0.15, 0.00. A solution containing 45% or 0.90% by mass is kept in a water bath at 30 ° C. for a predetermined time (1, 5, 10, 20 minutes), 1 mL is sampled at each time point, and 9 mL of PBS is used. 10-fold dilutions (10 ¹ × 10 ² times, 10 ³ fold, 10 ⁴ fold) to create a solution, dispensed into each sterilized Petri dish solution 1ml of the dilution series min, added nutrient agar 15mL Then, the cells were cultured at 37 ° C. for 18 hours, the number of colonies was counted, and the number of bacteria per mL was calculated. The results are shown in Table 6.

As shown in Table 6, in Control 1 (fumaric acid concentration 0.075%) and Control 2 (ascorbic acid concentration 0.90%), the number of bacteria at the start of treatment was 2.5 × 10 ⁶ CFU / mL. The bacterial counts after 5 minutes of treatment time are almost unchanged at 2.1 × 10 ⁶ CFU / mL and 2.3 × 10 ⁶ CFU / mL, respectively, and even after 20 minutes of treatment time, 1.9 respectively. Although a slight decrease in the number of bacteria was confirmed, such as × 10 ⁶ CFU / mL and 1.5 × 10 ⁶ CFU / mL, it was confirmed that none of these bacteria showed any sterilization effect. On the other hand, in a solution (test samples 33 to 35) having a fumaric acid concentration of 0.075% and an ascorbic acid concentration of 0.15 to 0.90% in combination of both, the number of bacteria after 5 minutes of treatment time is 7. 7 × 10 ⁵ CFU / mL, 4.0 × 10 ⁴ CFU / mL, 2.0 × 10 ⁴ CFU / mL, and apparent decrease in the number of bacteria from 1/3 to 1/125 from the number of bacteria at the start of treatment Was confirmed and the sterilization effect was recognized. The effect increased with increasing treatment time and ascorbic acid content. In solutions with ascorbic acid concentrations of 0.45% and 0.90% (test samples 34 to 35), the number of bacteria is less than 10 CFU / mL after 10 minutes of treatment time, confirming that the test bacteria are completely killed It was done.

Furthermore, the inventor conducted the following experiment in order to confirm the sterilization effect of the combination of fumaric acid and alcorbic acid against Gram-negative bacteria.

<Experiment 4: Effect of combination of fumaric acid and ascorbic acid on sterilization effect against gram-negative bacteria>
(1) Outline About the effect of the combination of fumaric acid and ascorbic acid and the difference in the concentration of ascorbic acid on the sterilization effect against Gram-negative bacteria by adding ascorbic acid solutions with different concentrations to a solution containing a certain amount of fumaric acid Compared.
(2) Experimental method (a) Preparation of test sample and bacterial solution Fumaric acid prepared by adding an ascorbic acid solution having a different concentration to a solution containing a certain amount of fumaric acid so as to have the same concentration as in Experiment 3. Ascorbic acid mixed solution (test samples 33 to 35) was used, and as gram-negative bacteria, Escherichia coli NBRC3301 strain was used as a gram-negative bacterium, and cultured under the same conditions as in Experiment 3. Centrifugation of 50 mL of the bacterial solution at a rotation speed of 5,000 rpm for 5 minutes, removing the supernatant, washing three times with phosphate buffered saline (PBS), and then absorbance at a wavelength of 660 nm Was measured, and PBS was added so that the number of bacteria was 5 × 10 ⁶ CFU / mL to prepare a bacterial solution.

(I) Bacteria-removal test The same treatment as in Experiment 3 was performed except that the holding time in a 30 ° C water bath was changed to 40 seconds (unmeasured only for Control 2) and 80 seconds, and the number of bacteria per mL was calculated. did. The results are shown in Table 7.

As shown in Table 7, in Control 2 (ascorbic acid concentration 0.90%), the number of bacteria after a treatment time of 80 seconds was 1 with respect to the number of bacteria 2.5 × 10 ⁶ CFU / mL at the start of treatment. Although a slight decrease in the number of bacteria was confirmed at 4 × 10 ⁶ CFU / mL, it was confirmed that the concentration did not show any sterilization effect. In contrast, in Control 1 (fumaric acid concentration: 0.075%), the number of bacteria after a treatment time of 40 seconds was confirmed to be 2.6 × 10 ⁵ CFU / mL, and the number of bacteria was further reduced. After 2 seconds, 9.8 × 10 ⁴ CFU / mL and a further decrease in the number of bacteria were confirmed, and the sterilization effect was confirmed. On the other hand, in a solution (test samples 33 to 35) having a fumaric acid concentration of 0.075% and an ascorbic acid concentration of 0.15 to 0.90% in combination of both, 2 × 10 ⁵ CFU / mL, 7.2 × 10 ⁴ CFU / mL, and 9.6 × 10 ⁴ CFU / mL, the apparent decrease in the number of bacteria, 1/20 to 1/35 from the number of bacteria at the start of treatment Was confirmed and the sterilization effect was recognized. At this concentration, as the treatment time increases, the sterilization effect is further exhibited, and the numbers of bacteria after the treatment time of 80 seconds are 9.3 × 10 ³ CFU / mL and 6.2 × 10 ³ CFU / mL, respectively. It was 4.4 × 10 ³ CFU / mL and a further decrease in the number of bacteria was confirmed.

From the results of the above experiments 3 and 4, by combining fumaric acid and ascorbic acid, it was possible to obtain a stronger sterilizing effect against gram-positive and gram-negative bacteria than when acting alone. It became clear that it increased as the content increased. These findings are new findings uniquely found by the present inventors.

Subsequently, a powdered fumaric acid preparation containing ascorbic acid was prepared by the method described in Example 5 described later, and a powdered fumaric acid preparation was separately prepared by the method described in Example 1, 4 was subjected to the same bactericidal effect comparison test. As a result, in Experiment 4 which shows the sterilization effect against Gram-negative bacteria, the powdered fumaric acid preparations prepared by the methods of Examples 1 and 5 were both confirmed as sterilization effects and effective as a sterilization detergent for foods. It was confirmed that. Furthermore, in Experiment 3 which observes the sterilization effect against Gram-positive bacteria, the powdered fumaric acid preparation prepared by the method of Example 1 did not show the sterilization effect, but was prepared by the method of Example 5 containing ascorbic acid. It was found that the powdered fumaric acid preparation showed an excellent sterilizing effect and a wide antibacterial effect.

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

<Powdered fumaric acid preparation>
200 parts by mass of commercially available fumaric acid powder (trade name “fumaric acid (fine powder)”, sold by Fuso Chemical Industry Co., Ltd.) was pulverized in a mortar, passed through a sieve having an opening of 500 μm, and adjusted to a particle size of 500 μm or less. On the other hand, polyglycerin fatty acid ester (trade name “Ryoto Polyglycerin L-7D”, HLB17, manufactured by Mitsubishi Chemical Foods Co., Ltd.) was added and dissolved in water to prepare 10 parts by mass of a 10% by mass aqueous solution. Moreover, trehalose (trade name “Treha”, sold by Hayashibara Co., Ltd.) was dissolved in water to prepare 20 parts by mass of a 50% by mass aqueous solution of trehalose. Put 199 parts by mass of the pulverized fumaric acid powder in a plastic container, add the polyglycerin fatty acid ester aqueous solution and the trehalose aqueous solution at the same time, add 331 parts by mass of pure water, and mix using a blender. A mixture was obtained. Next, the obtained wet mixture was spread on a tray, preliminarily dried by heating at 70 ° C. for 2 hours in a hot air circulating dryer, and after the loosened material was loosened, it was further cooled at 95 ° C. under a reduced pressure. Water was removed and dried by drying for 5 hours. The obtained dried product is pulverized in a mortar, passed through a sieve having an opening of 500 μm, and powdered fumarate containing 94.8% by mass of fumaric acid, 0.48% by mass of polyglycerin fatty acid ester, and 4.8% by mass of trehalose. An acid formulation was obtained.

In this product, the amount of sugar relative to fumaric acid is reduced to less than 10% by weight in terms of anhydride, and the agent does not harden into blocks during the manufacturing process (after drying), which hinders crushing It was a powder having the advantage of not being. Moreover, since this product is coated with fumaric acid using trehalose together with polyglycerin fatty acid ester, the phenomenon that hinders the aggregation of the resulting powdered fumaric acid preparation and classification with a sieve has been reduced. . Furthermore, since this product has improved the dissolution rate in water, it has an excellent property of easily preparing a sterilizing solution for foods.

<Powdered fumaric acid preparation>
First, an aqueous trehalose solution was mixed with a commercially available fumaric acid powder, then a polyglycerol fatty acid ester aqueous solution was mixed with the resulting mixture, and the same procedure as in Example 1 was performed except that the pure water added was changed to 181 parts by mass. A powdered fumaric acid preparation containing 94.8% by mass of fumaric acid, 0.48% by mass of polyglycerol fatty acid ester, and 4.8% by mass of trehalose was obtained.

In this product, the amount of sugar relative to fumaric acid is reduced to less than 10% by weight in terms of anhydride, and the agent does not harden into blocks during the manufacturing process (after drying), which hinders crushing It was a powder having the advantage of not being. Moreover, since this product coat | covers the fumaric acid using trehalose with polyglyceryl fatty acid ester, the phenomenon which becomes obstructive when the obtained powder aggregates and classifies with a sieve was also reduced. Furthermore, since this product has improved the dissolution rate in water, it has an excellent property of easily preparing a sterilizing solution for foods.
Incidentally, when subjected to the same solubility test as described in (b) of Preliminary Experiment 1: (2), the dissolution rate of this product in water was compared with the powdered fumaric acid preparation obtained in Example 1. It showed the property of complete dissolution in a short time.

<Powdered fumaric acid preparation>
As a saccharide covering the fumaric acid particles, sorbitol (“reagent”, sold by Wako Pure Chemical Industries, Ltd.) is used instead of trehalose, the amount of a 50 mass% aqueous solution of sorbitol is 15 parts by mass, and pure water to be added is 142. A powdered fumaric acid preparation containing the same treatment as in Example 1 except that the content was changed to 0.5 parts by mass, and containing 95.9% by mass of fumaric acid, 0.48% by mass of polyglycerol fatty acid ester, and 3.6% by mass of sorbitol. Got.

In this product, the amount of sugar relative to fumaric acid is reduced to less than 10% by weight in terms of anhydride, and the agent does not harden into blocks during the manufacturing process (after drying), which hinders crushing It was a powder having the advantage of not being. Moreover, since this product coat | covers the fumaric acid using sorbitol with polyglyceryl fatty acid ester, the phenomenon which becomes obstructive when the obtained powder aggregates and classifies with a sieve was also reduced. Furthermore, since this product has improved the dissolution rate in water, it has an excellent property of easily preparing a sterilizing solution for foods.

<Powdered fumaric acid preparation>
Maltitol (trade name “Crystalline Maltitol”, sold by Mitsubishi Corporation Foodtech Co., Ltd.) is used as a carbohydrate covering the fumaric acid particles instead of trehalose, and the amount of 50% by weight aqueous solution of maltitol is 25 parts by mass. Furthermore, sucrose fatty acid ester (trade name “Ryoto Sugar Ester S-1670”, HLB16, manufactured by Mitsubishi Chemical Foods Co., Ltd.) is used as a hydrophilic nonionic surfactant, and the amount of 10% by mass aqueous solution of sucrose fatty acid ester A powdered fumaric acid preparation containing the same treatment as in Example 1 except that the amount of the fumaric acid was changed to 20 parts by mass and containing 93.2% by mass of fumaric acid, 0.94% by mass of sucrose fatty acid ester and 5.85% by mass of maltitol Got.

In this product, the amount of sugar relative to fumaric acid is reduced to less than 10% by weight in terms of anhydride, and the agent does not harden into blocks during the manufacturing process (after drying), which hinders crushing. It was a powder having the advantage of not being. Moreover, since this product coat | covers fumaric acid using maltitol with sucrose fatty acid ester, the phenomenon which becomes obstructive when the obtained powder aggregates and classifies with a sieve was also reduced. Furthermore, since this product has improved the dissolution rate in water, it has an excellent property of easily preparing a sterilizing solution for foods.

<Powdered fumaric acid preparation>
6 parts by weight of ascorbic acid (reagent grade, sold by Wako Pure Chemical Industries, Ltd.) is added to 1 part by weight of fumaric acid in the powdered fumaric acid preparation obtained in Example 1, and pulverized and mixed in a mortar. An open 500 μm sieve was passed through to obtain a powdered fumaric acid preparation containing an organic acid other than fumaric acid (ascorbic acid).

Although this product contains a relatively large amount of ascorbic acid, it covers the fumaric acid particles using trehalose together with the polyglycerin fatty acid ester. The phenomenon was reduced. Furthermore, since this product has improved the dissolution rate in water, it has an excellent property of easily preparing a sterilizing solution for foods.

<Powdered fumaric acid preparation>
3 parts by mass of ascorbic acid 2-glucoside (reagent grade, sold by Wako Pure Chemical Industries, Ltd.) is added to 1 part by mass of fumaric acid in the powdered fumaric acid preparation obtained in Example 1, and pulverized and mixed in a mortar. Then, it was passed through a sieve having an opening of 500 μm to obtain a powdered fumaric acid preparation containing an organic acid derivative (ascorbic acid 2-glucoside) other than fumaric acid.

This product contains a relatively large amount of ascorbic acid 2-glucoside, which is a derivative of ascorbic acid, but because the fumaric acid particles are coated with trehalose together with polyglycerin fatty acid ester, the resulting powder aggregates. The phenomenon that hinders classification with a sieve was reduced. Furthermore, since this product has improved the dissolution rate in water, it has an excellent property of easily preparing a sterilizing solution for foods.

<Vegetable sanitizer for vegetables>
The powdered fumaric acid preparation obtained in Example 2 was dissolved in pure water so as to have a fumaric acid concentration of 0.3% by mass to obtain a sterilizing detergent for vegetables. By immersing the cut vegetables in this sanitizing detergent for 30 seconds or more, the number of viable bacteria in the cut vegetables can be significantly reduced.

<Decontamination detergent for meat>
The powdered fumaric acid preparation obtained in Example 3 was dissolved in pure water so as to have a fumaric acid concentration of 0.5% by mass to obtain a sanitizing detergent for meat. By immersing the chicken cut into this sterilizing detergent at 25 ° C. for 60 minutes, the number of viable bacteria in chicken can be significantly reduced.

Comparative Example 1

<Powdered fumaric acid preparation>
The same treatment as in Example 1 was performed except that the addition amount of 50% by mass aqueous solution of trehalose was 50 parts by mass, 88.4% by mass of fumaric acid, 0.44% by mass of polyglycerol fatty acid ester, 11.1% by mass of trehalose. % Powdered fumaric acid formulation was obtained.

This product contains more than 10% by mass of saccharides relative to fumaric acid in terms of anhydride, and because the agent solidified into blocks during the manufacturing process (after drying), it became difficult to grind and work The property decreased significantly.

Comparative Example 2

<Powdered fumaric acid preparation>
A powder fumaric acid preparation containing 99.5% by weight of fumaric acid and 0.5% by weight of polyglycerol fatty acid ester was obtained except that a 50% by weight aqueous solution of trehalose was not added. .

In this product, the surface of the fumaric acid particles is only coated with polyglycerin fatty acid ester, which is a surfactant, and the fumaric acid dissolution rate itself is improved, but the powdered fumaric acid preparation is agglomerated in the manufacturing process. Thus, the passability of the sieve was lowered, and the workability in the production of the powdered fumaric acid preparation and the recovery rate of the preparation were significantly reduced.

As described above, according to the present invention, a powdered fumaric acid preparation excellent in powder flowability and dissolution rate can be easily produced. The powdered fumaric acid preparation obtained by the production method of the present invention is superior in powder fluidity, hard to solidify, easy to handle as a powdered preparation, and soluble in water, compared to conventional powdered fumaric acid preparations. Since (dissolution rate) is also good, it can be advantageously used in the food field as a sour agent, preservative, disinfectant and the like. The influence of the present invention on the world is so great that the industrial applicability of the present invention is extremely large.

Claims

A method for producing a powdered fumaric acid preparation containing fumaric acid as an active ingredient, comprising the following steps (1) to (3):
(1) 0.5% by mass or more and less than 10.0% by mass of non-reducing disaccharide or disaccharide or less in terms of anhydride with respect to fumaric acid powder, hydrophilic nonionic surfactant and fumaric acid Mixing the sugar alcohol in the presence of a solvent to obtain a fumaric acid-containing wet mixture;
(2) The obtained fumaric acid-containing wet mixture is dried, and the fumaric acid-containing granular composition in which the fumaric acid particles are coated with a hydrophilic nonionic surfactant and a non-reducing disaccharide or a sugar alcohol less than a disaccharide. And (3) a step of pulverizing and classifying the obtained fumaric acid-containing granular composition as necessary to obtain a powdered fumaric acid preparation.
In the step (1), a nonionic disaccharide or a sugar alcohol less than a disaccharide is mixed with fumaric acid in the presence of a solvent, and then a hydrophilic nonionic surfactant is added and mixed. The manufacturing method of the powdered fumaric acid formulation of Claim 1.
3. The method for producing a powdered fumaric acid preparation according to claim 1 or 2, wherein the non-reducing disaccharide is trehalose, and the sugar alcohol below the disaccharide is either sorbitol or maltitol.
The amount of the hydrophilic nonionic surfactant to be mixed in the step (1) is 0.1 to 3.0% by mass in terms of anhydride with respect to fumaric acid. A method for producing a powdered fumaric acid preparation according to any one of claims 1 to 3.
The method for producing a powdered fumaric acid preparation according to any one of claims 1 to 4, wherein the hydrophilic nonionic surfactant to be mixed in the step (1) is a polyglycerol fatty acid ester.
The method for producing a powdered fumaric acid preparation according to any one of claims 1 to 5, wherein the amount of the solvent used for mixing in the step (1) is 50% by mass or more based on fumaric acid.
In any one of the steps (1) to (3), an organic acid other than fumaric acid, a derivative thereof, or a salt thereof is further mixed, or an organic acid other than fumaric acid, A method for producing a powdered fumaric acid preparation according to any one of claims 1 to 6, wherein a derivative or a salt thereof is mixed.
Fumaric acid, hydrophilic nonionic surfactant, and non-reducing disaccharide or disaccharide or less sugar alcohol of 0.5% by mass or less and less than 10.0% by mass in terms of anhydride with respect to fumaric acid, A powdered fumaric acid formulation in which fumaric acid particles are coated with the hydrophilic nonionic surfactant and the non-reducing disaccharide or a sugar alcohol of a disaccharide or less.
The powdered fumaric acid preparation according to claim 8, wherein the non-reducing disaccharide is trehalose, and the sugar alcohol below the disaccharide is either sorbitol or maltitol.
The powdered fumaric acid preparation according to claim 8 or 9, wherein the content of the hydrophilic nonionic surfactant is 0.1 to 3.0 mass% with respect to fumaric acid.
The powdered fumaric acid preparation according to any one of claims 8 to 10, wherein the hydrophilic nonionic surfactant is a polyglycerin fatty acid ester.
The powdered fumaric acid preparation according to any one of claims 8 to 11, further comprising an organic acid other than fumaric acid.
The powdered fumaric acid preparation according to claim 12, wherein the organic acid other than fumaric acid is 2 to 12 times the mass of fumaric acid.
The powdered fumaric acid preparation according to claim 12 or 13, wherein the organic acid other than fumaric acid is ascorbic acid.