Acid resistant powder, food product, and method for producing acid resistant powder

Abstract

To provide an acid resistant powder excellent in processing stability, storage stability, pressure resistance, and bile acid resistance.SOLUTION: An acid-resistant powder contains primary coated particles, which are coated with a primary coating material (B) as a continuous phase including powder particles of a core material (A) and secondary coated particles having a structure where the primary coated particles are coated with a secondary coating material (C) as a single nucleus. The core material (A) contains a powder (A1) that includes viable bacteria with a bulk density of 0.2 to 0.7 and an excipient (A2) with a bulk density of 0.7 to 1.0, the primary coating material (B) contains lipids with a melting point of 40°C to 70°C, the secondary coating material (C) contains lipids with a melting point of 40°C to 100°C, an average particle diameter of the primary coated particles is between 50 μm and 500 μm, and the average particle diameter of the secondary coated particles relative to the average particle size of the primary coated particles is 1.05 to 2.0 times.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present invention relates to an acid-resistant powder comprising coated particles that contain a powder containing live bacteria as a core substance, a food product, and a method for producing the acid-resistant powder. [Background technology]

[0002] Live bacteria such as bifidobacteria and lactic acid bacteria suppress the proliferation of bad bacteria in the intestines and improve the intestinal flora, thereby exerting beneficial effects on the host. In addition, the live bacteria have an intestinal regulating effect, such as improving constipation and diarrhea. In recent years, these live bacteria have been known as probiotics and are food materials used in foods for specified health uses. However, these live bacteria cannot fully exert their effects unless they reach the intestinal tract after oral ingestion without being killed by gastric acid, bile acid, etc. Therefore, acid-resistant and enteric coatings have been invented to deliver bifidobacteria and lactic acid bacteria alive to the intestinal tract and exert their effects.

[0003] For example, Japanese Patent Application Laid-Open No. 5-186335 (Patent Document 1) and Japanese Patent Application Laid-Open No. 5-186336 (Patent Document 2) propose a method for producing an enteric granulated product using lactic acid bacteria and an excipient. In these methods, dry lactic acid bacteria powder, an excipient, and zein are mixed, and oil melted at 40°C is added to the mixture, stirred, extrusion granulated, and then a zein solution or palm oil melted at 40°C is sprayed to obtain an enteric granulated product. Specifically, this method obtains granulated products with a length of 1.5 to 2 mm using an extrusion granulator equipped with a screen with a hole size of 0.8 mm, and the obtained enteric granulated products have a cylindrical shape with a diameter of about 0.8 mm and a length of 1.5 to 2 mm. The methods for producing enteric coated granules described in Patent Documents 1 and 2 can impart resistance to digestive fluids to live bacteria, but the bacteria are killed rapidly during the process of adding molten oil and fat and extrusion granulation, and the number of remaining bacteria after production tends to be low. Therefore, the number of bacteria in the preparation is low, and there is a risk that the value of the enteric coated preparation will be halved. In addition, the particles produced by the extrusion granulation method are large, making them unsuitable for use as powders for tableting such as pellets and tablets. In addition, large particles make it difficult to add them to soft capsules, etc., and there is a problem that the powder is not very versatile as a powder that provides resistance to live bacteria in digestive fluids.

[0004] In addition, JP 2020-174667 A (Patent Document 3) proposes a method for producing protein-polysaccharide double-coated lactic acid bacteria using a protein hydrolysate. This method involves adding a specific polysaccharide to lactic acid bacteria cultured in a specific medium containing a protein hydrolysate, followed by freeze-drying. However, this production method needs to be applied from the time of culturing the lactic acid bacteria, and there is a problem that resistance cannot be imparted later to widely distributed live bacteria, making it less versatile.

[0005] In addition, live bacteria such as lactic acid bacteria and bifidobacteria are often used in tablet or chewable health foods and tablet confectioneries. However, these live bacteria are weak against the impact during tableting, and there is a problem that the survival rate of live bacteria is low when the tablet is made. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Publication No. 5-186335 [Patent Document 2] Japanese Patent Application Publication No. 5-186336 [Patent Document 3] JP 2020-174667 A Summary of the Invention [Problem to be solved by the invention]

[0007] In light of this background, firstly, there is a demand for reducing the death of live bacteria when powdered raw materials containing live bacteria such as lactic acid bacteria and bifidobacteria are processed into acid-resistant powders (processing stability). Secondly, there is a demand for suppressing the death of live bacteria during storage of this acid-resistant powder (storage stability). When the acid-resistant powder is compressed into tablets, there is a demand for suppressing the death of live bacteria due to the pressure during tableting (pressure resistance). In addition, there is a demand for suppressing the death of live bacteria when they come into contact with gastric acid (acid resistance) and when they come into contact with intestinal fluids (bile acid resistance) so that the live bacteria are delivered alive to the intestines after ingestion.

[0008] An object of the present invention is to provide an acid-resistant powder which is excellent in processing stability, storage stability, pressure resistance, acid resistance, and bile acid resistance. [Means for solving the problem]

[0009] As a result of intensive research into solving the above problems, the present inventors have found that the above problems can be solved by primary coated particles having a specific average particle size, each of which contains a powder containing live bacteria and an excipient having a specific bulk density as multiple cores and is coated with a primary coating material containing a lipid with a specific melting point, and the primary coated particles are coated with a secondary coating material containing a lipid with a specific melting point, each of which has a specific average particle size, and have thus completed the present invention. That is, the present invention is as follows: [1] to [6].

[0010] [1] An acid-resistant powder comprising primary coated particles in which powder particles of a core substance (A) are encapsulated as multiple nuclei and coated with a primary coating material (B) as a continuous phase, and secondary coated particles having a structure in which the primary coated particles are coated with a secondary coating material (C) as a single nucleus, The core material (A) comprises a powder (A1) containing live bacteria having a bulk density of 0.2 to 0.7 and an excipient (A2) having a bulk density of 0.7 to 1.0; The primary coating material (B) contains a lipid having a melting point of 40°C to 70°C, The secondary coating material (C) contains a lipid having a melting point of 40°C to 100°C, The average particle size of the primary coated particles is 50 μm to 500 μm, The acid-resistant powder is characterized in that the ratio of the average particle size of the secondary coated particles to the average particle size of the primary coated particles (average particle size of secondary coated particles / average particle size of primary coated particles) is 1.05 to 2.00. [2] a mass ratio of the core material (A) to a total mass of the core material (A) and the primary coating material (B) is 0.65 to 0.90; The acid-resistant powder according to [1], wherein a mass ratio of the primary coated particles (B) to a total mass of the primary coated particles and the secondary coating material (C) is preferably 0.60 to 0.85. [3] The acid-resistant powder according to [1] or [2], characterized in that it is preferable that the average particle size is 50 μm to 500 μm, the viable cell survival rate after an acid resistance test is 32% or more, and the viable cell survival rate after a bile acid resistance test is 15% or more. [4] The acid-resistant powder according to any one of [1] to [3], which is preferably for tableting. [5] A food product comprising the acid-resistant powder according to any one of [1] to [4]. [6] A method for producing an acid-resistant powder according to any one of [1] to [4], A step of mixing the core material (A) and the primary coating material (B) to obtain the primary coated particles; A method for producing an acid-resistant powder, comprising: a step of mixing the primary coated particles with a powdered secondary coating material (C) to obtain the secondary coated particles. Effect of the Invention

[0011] According to the present invention, it is possible to provide an acid-resistant powder in which the death of live bacteria is reduced when a powdered raw material containing live bacteria is processed into an acid-resistant powder (processing stability), the death of live bacteria is suppressed during storage of this acid-resistant powder (storage stability), when the acid-resistant powder is compressed into tablets, the death of live bacteria due to the pressure during tableting is suppressed (pressure resistance), and the death of live bacteria is suppressed when coming into contact with gastric acid (acid resistance) and when coming into contact with intestinal fluids (bile acid resistance) so that the live bacteria are delivered to the intestines alive after ingesting. [Brief description of the drawings]

[0012] [Figure 1] FIG. 2 is a schematic explanatory diagram showing the structure of a primary coated particle constituting the acid-resistant powder of the present invention. [Diagram 2] FIG. 2 is a schematic explanatory diagram showing the structure of a secondary coated particle constituting the acid-resistant powder of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] In this specification, when a preferred numerical range (e.g., mass %) is described stepwise, each lower limit and upper limit can be independently combined. For example, in the description "preferably 10 or more, more preferably 20 or more, and preferably 100 or less, more preferably 90 or less," "preferably lower limit: 10" and "more preferably upper limit: 90" can be combined to "10 or more and 90 or less."

[0014] [Acid-resistant powder] The acid-resistant powder of the present invention is an acid-resistant powder comprising primary coated particles which encapsulate powder particles of a core substance (A) as multiple nuclei and are coated with a primary coating material (B) as a continuous phase, and secondary coated particles which have a structure in which the primary coated particles serve as single nuclei and are coated with a secondary coating material (C), characterized in that the core substance (A) comprises a powder (A1) containing live bacteria having a bulk density of 0.2 to 0.7 and an excipient (A2) having a bulk density of 0.7 to 1.0, the primary coating material (B) comprises a lipid having a melting point of 40°C to 70°C, the secondary coating material (C) comprises a lipid having a melting point of 40°C to 100°C, the average particle diameter of the primary coated particles is 50 μm to 500 μm, and the average particle diameter of the secondary coated particles relative to the average particle diameter of the primary coated particles (average particle diameter of secondary coated particles / average particle diameter of primary coated particles) is 1.05 to 2.0.

[0015] FIG. 1 shows a schematic diagram of the structure of a primary coated particle constituting the acid-resistant powder of the present invention, and FIG. 2 shows a schematic diagram of the structure of a secondary coated particle contained in the acid-resistant powder of the present invention. 1, primary coated particle 10 is a coated granule in which core substance (A) is encapsulated as multiple nuclei inside primary coating material (B) which is a continuous phase. Although not shown, core substance (A) contains powder (A1) containing live bacteria having a bulk density of 0.2 to 0.7 and excipient (A2) having a bulk density of 0.7 to 1.0. 2, the secondary coated particle 20 has a structure in which the primary coated particle 10 serves as a single core and is coated with a particulate secondary coating material (C). By using the particulate secondary coating material (C), it is possible to produce the secondary coated particle 20 having the primary coated particle 10 as a single core. The presence of a single primary coated particle 10 within the secondary coated particle 20 makes the secondary coated particle 20 less likely to crumble under pressure during compression molding, and pressure resistance is more effectively exhibited.

[0016] The average particle diameter of the primary coated particles 10 is 50 μm to 500 μm. The lower limit is preferably 100 μm or more. The upper limit is preferably 400 μm or less, more preferably 300 μm or less. When the average particle diameter is less than 50 μm, the surface area of ​​the primary coated particles becomes large and sufficient coating with the secondary coating material cannot be achieved, so that acid resistance and bile acid resistance cannot be obtained. When the average particle diameter is more than 500 μm, the secondary coating material is easily peeled off, and the coating state of the secondary coated particles becomes poor, so that acid resistance, bile acid resistance, and processing stability cannot be obtained. In addition, when the primary coated particles are formed, the particles are grown large in a dissolved state, so that the stability of the useful components during processing is reduced.

[0017] The average particle diameter of the secondary coated particles 20 is not particularly limited, but is, for example, 50 μm to 500 μm. The lower limit is preferably 100 μm or more. The upper limit is preferably 400 μm or less, and more preferably 300 μm or less. When the average particle diameter is less than 50 μm, the particle diameter of the primary coated particles is also less than 50 μm, and as described above, sufficient coating with the secondary coating material cannot be achieved, and acid resistance and bile acid resistance cannot be obtained. When the average particle diameter exceeds 500 μm, the secondary coating material is easily peeled off, and the coating state of the secondary coated particles deteriorates, making it impossible to achieve acid resistance, bile acid resistance, and processing stability.

[0018] The ratio of the average particle size of the secondary coated particles 20 to the average particle size of the primary coated particles 10 (average particle size of secondary coated particles / average particle size of primary coated particles) is 1.05 to 2.00. The upper limit is preferably 1.60 or less, and more preferably 1.40 or less. When this ratio exceeds 2.00, the secondary coated particles are composed of multiple primary coated particles as cores, and therefore acid resistance, bile acid resistance, processing stability, and pressure resistance are not obtained. When this ratio is less than 1.05, the secondary coated layer does not have a sufficient thickness or the primary coated particles are broken into small particles, and therefore processing stability, pressure resistance, acid resistance, and bile acid resistance are not obtained.

[0019] In the primary coated particles, the mass ratio of the core substance (A) to the primary coating material (B) is not particularly limited, but for example, the mass ratio of the core substance (A) to the total mass of the core substance (A) and the primary coating material (B) is preferably 0.65 to 0.90. The lower limit is more preferably 0.70 or more, and most preferably 0.75 or more. The upper limit is more preferably 0.85 or less. When the mass ratio is 0.65 or more, the content of the core substance (A) can be increased. On the other hand, when the mass ratio is 0.90 or less, the content of the primary coating material (B) increases, and there is an effect of improving the coating performance.

[0020] In the primary coated particles, the mass ratio of the powder (A1) containing live bacteria with a bulk density of 0.2 to 0.7 and the excipient (A2) with a bulk density of 0.7 to 1.0 in the core material (A) is not particularly limited, but for example, when the mass of the powder (A1) containing live bacteria is taken as 1, the mass of the excipient (A2) is preferably 1 to 100. The lower limit is more preferably 2 or more. The upper limit is more preferably 50 or less, even more preferably 20 or less, and most preferably 10 or less. When the mass ratio is 1 or more, there is an effect of improving the coating performance. Also, when it is 100 or less, the content of live bacteria can be increased.

[0021] In the secondary coated particles, the mass ratio of the primary coated particles to the secondary coating material (C) is not particularly limited, but for example, the mass ratio of the primary coated particles (B) to the total mass of the primary coated particles and the secondary coating material (C) is preferably 0.60 to 0.85. The lower limit is more preferably 0.65 or more, and most preferably 0.70 or more. The upper limit is more preferably 0.80 or less. When the mass ratio is 0.60 or more, the content of the core substance (A) contained in the primary coated particles can be increased. Also, when the mass ratio is 0.85 or less, the content of the secondary coating material (C) increases, and there is an effect of improving the coating performance.

[0022] The processing stability of the acid-resistant powder of the present invention is, for example, such that the viable cell survival rate in the processing stability test of the present invention is 70% or more, preferably 80% or more, and more preferably 90% or more.

[0023] The acid resistance of the acid-resistant powder of the present invention is, for example, such that the viable cell survival rate in the acid resistance test of the present invention is 10% or more, preferably 20% or more, more preferably 30% or more, even more preferably 32% or more, and most preferably 35% or more.

[0024] The bile acid resistance of the acid-resistant powder of the present invention is, for example, such that the viable cell survival rate in the bile acid resistance test of the present invention is 5% or more, preferably 10% or more, and more preferably 15% or more.

[0025] The pressure resistance of the acid-resistant powder of the present invention is, for example, such that the viable cell survival rate in the pressure resistance test of the present invention is 75% or more, preferably 85% or more, and more preferably 95% or more.

[0026] The storage stability of the acid-resistant powder of the present invention is, for example, such that the viable cell survival rate in the storage stability test of the present invention is 50% or more, preferably 60% or more, and more preferably 70% or more.

[0027] The oil content of the acid-resistant powder of the present invention is not particularly limited, but is preferably, for example, 20 to 60% by mass or more. The lower limit is more preferably 25% by mass or more, and most preferably 30% by mass or more. The upper limit is more preferably 50% by mass or less, even more preferably 45% by mass or less, and most preferably 40% by mass or less. The oil content is measured according to the "ether extraction method". When the oil content is high, the acid-resistant powder has excellent water repellency, and therefore has the effect of excellent storage stability. When the oil content is low, the content of live bacteria can be increased.

[0028] Each component of the present invention will be described in detail below. [Powder containing live bacteria (A1)] The powder (A1) containing live bacteria of the core material (A) of the present invention is not particularly limited as long as it is a powder containing live bacteria. Examples of live bacteria include bifidobacteria and lactic acid bacteria.

[0029] The powder (A1) containing the live bacteria of the core material (A) has a bulk density of 0.2 to 0.7. It is preferably 0.3 or more, more preferably 0.4 or more, and most preferably 0.5 or more. When the bulk density is less than 0.2, the effect of improving the acid resistance and bile acid resistance cannot be obtained even if the present invention is applied. When the bulk density is more than 0.7, the acid resistance and bile acid resistance can be obtained without applying the present invention. The average particle size of the powder (A1) containing the live bacteria of the present invention is not particularly limited as long as it is within the range in which the effects of the present invention are exhibited, but is preferably, for example, 10 to 200 μm. As an upper limit, it is more preferably 150 μm or less, even more preferably 100 μm or less, and most preferably 80 μm or less. When the average particle size of the core material (A) is small, there is an advantage that the size of the primary coated particles can be easily adjusted.

[0030] [Powder (A2)] The excipient (A2) of the core substance (A) of the present invention has a bulk density of 0.7 to 1.0. It is preferably 0.7 to 0.9, and more preferably 0.75 to 0.85. If the bulk density is less than 0.7 and more than 1.0, the effect of improving bile acid resistance of the present invention cannot be obtained. The average particle size of the excipient (A2) of the present invention is not particularly limited as long as it is within the range in which the effects of the present invention can be obtained, but the average particle size is preferably 20 μm to 200 μm, more preferably 30 μm to 150 μm, and most preferably 40 μm to 100 μm. If the average particle size is less than 20 μm and more than 200 μm, the effect of improving acid resistance and bile acid resistance of the present invention cannot be obtained. Examples of the excipient (A2) include powders of lactose, starch, calcined starch, white sugar, maltitol, sorbitol, dextrin, trehalose, crystalline cellulose, etc., but other substances whose particle size or bulk density has been adjusted by processing such as pulverization or granulation, or by sieving or classification, may also be used. The powder (A1) containing live bacteria of the present invention has a bulk density of 0.2 to 0.7, and is a light powder compared to the excipient (A2), while the excipient (A2) has a bulk density of 0.7 to 1.0, and is a heavy powder compared to the powder (A1) containing live bacteria. When the core material (A) of the present invention is only the powder (A1) containing live bacteria, the particle size of the primary coated particles varies, the efficiency of the secondary coating decreases, the coating performance of the secondary coated particles does not reach the target, and the effect of improving acid resistance and bile acid resistance is not sufficiently obtained. However, by primary coating the powder (A1) containing live bacteria of the present invention together with the excipient (A2), that is, the excipient (A2) which is heavy compared to the powder (A1) containing live bacteria having a bulk density of 0.7 to 1.0, the particle size of the primary coated particles can be made uniform, the efficiency of the secondary coating is improved, the coating performance of the secondary coated particles is improved, and the acid resistance and bile acid resistance can be improved.

[0031] [Primary covering material (B)] The primary coating material (B) of the present invention contains an edible lipid having a melting point of 40° C. to 70° C. The lower limit of the melting point of the lipid in the primary coating material (B) is preferably 50° C. or higher, more preferably 55° C. or higher. When the melting point of the lipid in the primary coating material (B) is 40° C. or higher, the coating performance is improved, and the pressure resistance and acid resistance are excellent. On the other hand, when the melting point of the lipid in the primary coating material (B) is 70° C. or lower, the primary coating material (B) can be softened without exposing the core substance (A) to high temperatures during the formation of the primary coated particles.

[0032] The lipid of the primary covering material (B) may be any lipid having a melting point of 40° C. to 70° C., and examples thereof include fatty acid esters, higher alcohols, and waxes, and one or more of these may be used. Examples of fatty acid esters include triglycerides, which are typical edible fats and oils, and have a structure in which three molecules of fatty acid are ester-bonded to glycerin, and originate from, for example, soybean oil, rapeseed oil, cottonseed oil, rice oil, corn oil, sesame oil, peanut oil, sunflower oil, safflower oil, camellia oil, olive oil, coconut oil, palm oil, palm kernel oil, cacao butter, perilla oil, perilla oil, lard, beef tallow, chicken oil, whale oil, and fish oil. The melting point is adjusted by transesterification, hydrogenation, or the like. Other fatty acid esters include so-called emulsifiers, such as glycerin fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, sucrose fatty acid esters, and lecithin. Examples of higher alcohols include linear or branched alcohols having 20 to 36 carbon atoms. Specific examples include eicosanol (20 carbon atoms), docosanol (26 carbon atoms), octacosanol (28 carbon atoms), triacontanol (=myricyl alcohol, 30 carbon atoms), and hexatriacontanol (36 carbon atoms). Examples of waxes include carnauba wax, candelilla wax, and rice wax.

[0033] The lipid of the primary coating material (B) may be in powder form or in liquid form melted by heating. When using a lipid of the powdered primary coating material (B), primary coated particles can be formed quickly and easily by spraying the liquid primary coating material (B) onto the mixed core substance (A).

[0034] [Secondary covering material (C)] The secondary coating material (C) of the present invention contains an edible lipid having a melting point of 40°C to 100°C. The lower limit of the melting point of the lipid of the secondary coating material (C) is preferably 50°C or higher, more preferably 55°C or higher, and even more preferably 60°C or higher. On the other hand, the upper limit of the melting point of the lipid of the secondary coating material (C) is preferably 90°C or lower, more preferably 80°C or lower, and even more preferably 75°C or lower. When the melting point of the lipid of the secondary coating material (C) is high, the secondary coating materials (C) are less likely to adhere to each other when the primary coating particles and the secondary coating material (C) are mixed, and are more likely to be arranged on the surfaces of the primary coating particles. On the other hand, when the melting point of the lipid of the secondary coating material (C) is lowered, the primary coating particles collide with each other when the primary coating particles and the secondary coating material (C) are mixed, so that the secondary coating material (C) arranged on the surfaces of the primary coating particles spreads, thereby improving the coating performance.

[0035] The lipid of the secondary coating material (C) may be any lipid having a melting point of 40° C. to 100° C., and examples thereof include fatty acid esters, higher alcohols, and waxes, and one or more of these may be used. Examples of fatty acid esters include triglycerides, which are typical edible fats and oils, and have a structure in which three molecules of fatty acid are ester-bonded to glycerin, and originate from, for example, soybean oil, rapeseed oil, cottonseed oil, rice oil, corn oil, sesame oil, peanut oil, sunflower oil, safflower oil, camellia oil, olive oil, coconut oil, palm oil, palm kernel oil, cacao butter, perilla oil, perilla oil, lard, beef tallow, chicken oil, whale oil, and fish oil. The melting point is adjusted by transesterification, hydrogenation, or the like. Other fatty acid esters include so-called emulsifiers, such as glycerin fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, sucrose fatty acid esters, and lecithin. Examples of higher alcohols include linear or branched alcohols having 20 to 36 carbon atoms. Specific examples include eicosanol (20 carbon atoms), docosanol (26 carbon atoms), octacosanol (28 carbon atoms), triacontanol (=myricyl alcohol, 30 carbon atoms), and hexatriacontanol (36 carbon atoms). Examples of waxes include carnauba wax, candelilla wax, and rice wax.

[0036] The lipid of the secondary coating material (C) is in powder form. By using the lipid of the powdered secondary coating material (C), the secondary coating material (C) adheres to the surface of the primary coated particle, and a secondary coated particle having the primary coated particle as a single nucleus can be formed. If the lipid of the secondary coating material (C) in liquid form is used, the secondary coating material (C) becomes a coated granule containing the primary coated particles as multiple nuclei with the secondary coating material (C) as a continuous phase, and the effect of the present invention cannot be obtained.

[0037] The average particle size of the lipid in the secondary coating material (C) is preferably, for example, 5 to 100 μm. The upper limit is more preferably 80 μm or less, further preferably 60 μm or less, and most preferably 40 μm or less. When the average particle size of the lipid in the secondary coating material (C) is smaller, the secondary coating material (C) is densely arranged on the surface of the primary coating particles, thereby improving the coating performance.

[0038] [Processing method (manufacturing method)] The method for producing an acid-resistant powder containing secondary coated particles of the present invention includes, for example, a step of mixing the core material (A) and the primary coating material (B) to obtain the primary coated particles, and a step of mixing the primary coated particles and a powdery secondary coating material (C) to obtain the secondary coated particles. More specifically, a powder (A1) containing live bacteria as the core material (A) and an excipient (A2) are put into a stirring layer, and a lipid as the primary coating material (B) is separately melted at a temperature higher than the melting point and prepared in a liquid state. Then, while mixing and stirring the core material (A), the liquid primary coating material (B) is sprayed into the stirring layer. At this time, the temperature of the primary coating material (B) drops below the melting point and solidifies, so that the powder (A1) containing live bacteria as multiple core materials (A) and the excipient (A2) are both bound to the primary coating material (B) and granulated, and primary coated. Next, the lipid of the secondary coating material (C) is added to the primary coated particles in the stirring layer and put in, and secondary coating is performed by high-speed stirring. At this time, the lipid powder collides with the lipid of the primary coating material (B) on the surface of the primary coated particle and adheres to it, and by repeating this process, a secondary coating layer is formed, completing the secondary coated particle. The secondary coating is preferably performed at a temperature lower than the melting point of the lipid of the secondary coating material (C). Under these conditions, the primary coated particles and the secondary coating material are stirred at high speed to cause the powder particles to collide with each other, and the lipid of the secondary coating material is layered around the primary coated particles, forming a coating. EXAMPLES

[0039] The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited thereto.

[0040] (Examples 1 to 19, Comparative Examples 1 to 9) Acid-resistant powders were prepared according to the following methods for preparing primary coated particles and secondary coated particles. The obtained acid-resistant powders were evaluated for "survival rate of viable bacteria after processing" (processing stability), "survival rate of viable bacteria after storage" (storage stability), "survival rate of viable bacteria after tableting" (pressure resistance), "survival rate of viable bacteria after acid resistance test" (acid resistance), and "survival rate of viable bacteria after bile acid resistance test" (bile acid resistance), and the evaluation results are shown in Tables 1, 2, and 3.

[0041] (About ingredients) The raw materials used in the examples are as follows. In the present invention, the average particle size is measured using a laser diffraction particle size distribution analyzer "SALD-2100" (manufactured by Shimadzu Corporation). The melting point in the present invention is measured in accordance with the Standard Methods for the Analysis of Fats, Oils and Related Materials, "2.2.4.2 Melting Point (Slip Melting Point)." In the present invention, the bulk density is defined as the loose bulk density (g / cm 3 ) and is calculated by pouring an excess of sample into a 100 mL cylindrical container until it overflows, and then measuring the mass of the powder when the excess powder is scraped off from the top of the container.

[0042] <Powder containing live bacteria (A1)> Bifidobacteria A: "Bifidobacteria Powder BB536" (Morinaga Milk Industry Co., Ltd.), average particle size 29.0 μm, bulk density 0.64 Bifidobacteria B: "Bifidobacteria M63" (Morinaga Milk Industry Co., Ltd.), average particle size 26.0 μm, bulk density 0.62 Lactic acid bacteria A: average particle size 35.2 μm, bulk density 0.45

[0043] <Excipient (A2)> "Maltitol" (Mitsubishi Corporation Life Sciences Co., Ltd.) crushed material, average particle size 55.5 μm, bulk density 0.79 "Maltitol" (Mitsubishi Corporation Life Sciences Co., Ltd.) ground product, average particle size 80.3 μm, bulk density 0.71 "ST Starch C" (manufactured by Nippon Starch Chemical Co., Ltd.), average particle size 16.9 μm, bulk density 0.61 "KC Flock" (manufactured by Nippon Paper Industries Co., Ltd.), average particle size 48.0 μm, bulk density 0.34

[0044] <Primary covering material (B)> Hardened rapeseed oil: (NOF Corp.), melting point 67°C Hardened palm oil: (NOF Corp.), melting point 57°C Hardened rapeseed oil 1: (NOF Corp.), melting point 50°C Hardened palm oil: (NOF Corp.), melting point 42°C Carnauba wax: (manufactured by Toa Kasei Co., Ltd.), melting point 86°C

[0045] <Secondary coating material (C)> The lipids described below were powdered by spray cooling or pulverization, and then subjected to secondary pulverization until the average particle size became 50 μm or less, to prepare secondary coating materials. Hardened rapeseed oil: (NOF Corp.), melting point 67°C, average particle size 6.8μm Hardened palm oil: (NOF Corporation), melting point 57°C, average particle size 14.6μm Glycerol fatty acid ester: (manufactured by Danisco Japan Co., Ltd.), melting point 62°C, average particle size 18.2 μm Hardened palm oil: (NOF Corporation), melting point 42°C, average particle size 42.5μm Rice wax: (manufactured by Toa Kasei Co., Ltd.), melting point 78°C, average particle size 14.5 μm Hardened rapeseed oil 2: (NOF Corp.), melting point 36°C, average particle size 40.4μm

[0046] (Regarding the production of acid-resistant powder) The primary coated particles and secondary coated particles constituting the acid-resistant powders of the Examples and Comparative Examples were prepared as follows. [Preparation method of primary coated particles] In Example 1, 50 g of powder (A1) "Bifidobacterium BB536" containing live bacteria as the core material (A) and 250 g of crushed excipient (A2) "maltitol" (average particle size 55.5 μm, bulk density 0.79) were put into a high-speed stirring mixer. While stirring the high-speed stirring mixer, the primary coating material (B) of extremely hardened rapeseed oil was adjusted to a melting point of +10°C and melted, and 75 g of this was sprayed inside the high-speed stirring mixer to coat the core material (A) with the primary coating material (B). Next, the product was cooled to a product temperature of 20°C in the high-speed stirring mixer to obtain the primary coated particles of Example 1.

[0047] [Preparation method of secondary coated particles] 125 g of rapeseed hardened oil, which is the secondary coating material (C), was added to the primary coated particles of Example 1 in a high-speed stirring mixer. Stirring and mixing were performed with the jacket temperature of the high-speed stirring mixer cooled, and the secondary coating material was attached to the surface of the primary coated particles in a powder state. By continuing to stir and mix further, the powder of the secondary coating material was evenly distributed on the surface of the primary coated particles, and the secondary coated particles of Example 1 were prepared.

[0048] In Examples 2 to 19 and Comparative Examples 1 to 9, the primary coated particles and secondary coated particles were prepared according to the formulations in Tables 1 to 3. Moreover, Examples 2 to 10, 12 to 18 and Comparative Examples 1, 3 to 4, and 8 to 9 were prepared under the same production conditions as Example 1.

[0049] In Example 11, the stirring speed was decreased and the spray speed of the primary coating material (B) was increased so that the particle diameter of the primary coated particles would be large when preparing the primary coated particles. In Comparative Example 2, the core material (A) was not primarily coated, and only the secondary coating was performed in the same manner as in Example 1. In Comparative Example 5, the stirring speed was increased and the spray speed of the primary coating material (B) was decreased so that the particle diameter of the primary coated particles would be small when preparing the primary coated particles. In Comparative Example 6, the stirring speed was decreased and the spray speed of the primary coating material (B) was increased so that the particle diameter of the primary coated particles would be large when preparing the primary coated particles. In Comparative Example 7, the secondary coated particles were prepared by warming and melting the secondary coating material (C) at a melting point +10°C and spraying it onto the primary coated particles. Other than that, the secondary coated particles were prepared under the same manufacturing conditions as in Example 1. The secondary coated particles thus obtained were used as acid-resistant powder and were evaluated.

[0050] (Evaluation method for acid-resistant powder) <Method for measuring live bacteria> In the method for measuring the viable bacteria of the present invention, 100 mg of a specimen was added to 100 mL of physiological saline and homogenized to extract the viable bacteria. This solution was appropriately diluted, and 1 mL of the diluted solution was mixed with 20 mL of BL agar medium (manufactured by Nissui Pharmaceutical Co., Ltd.) and subjected to anaerobic culture (37°C, 72 hours). After the culture was completed, the number of viable bacteria per 1 g of specimen was calculated from the number of colonies that grew on the medium.

[0051] <Processing stability: survival rate of live bacteria after processing (survival rate after processing)> The survival rate of live bacteria after processing was calculated using the following formula and evaluated according to the following criteria. Viable bacteria count before processing: The viable bacteria count of the powder containing viable bacteria as the raw material is measured and multiplied by the blending ratio. Viable bacteria count after processing: Viable bacteria count of secondary coated particles produced by processing Processing survival rate (%) = Number of viable bacteria after processing / Number of viable bacteria before processing × 100 [Standards for processing survival rate] ◎: 90% or more, 〇: less than 90%, 80% or more, △: less than 80%, 70% or more, ×: less than 70%

[0052] <Storage stability: Viable bacteria survival rate after storage (storage survival rate)> (Storage stability test) The acid-resistant powder was sealed in an aluminum bag and subjected to a storage test for 6 months at 25° C. The survival rate of live bacteria after storage was calculated using the following formula and evaluated according to the following criteria. Preservation survival rate (%) = Number of viable bacteria after storage / Number of viable bacteria before storage × 100 [Criteria for survival rate] ◎: 70% or more, 〇: less than 70%, 60% or more, △: less than 60%, 50% or more, ×: less than 50%

[0053] <Pressure resistance: Viable bacteria survival rate after tableting (survival rate after tableting)> (Pressure resistance test) In the evaluation of pressure resistance of the present invention, tablets containing the acid-resistant powder of the Examples or Comparative Examples were prepared under the following blending composition and tableting conditions, and the viable cell count was measured before and after tableting. The viable cell count in the tablets was measured by crushing the tablets in a mortar to obtain a powder, which was used as a sample for the viable cell count measurement method. The lactose used was "Lactose" (manufactured by Leprino Foods), the starch used was "ST Starch P" (manufactured by Nippon Starch Chemical Co., Ltd.), the crystalline cellulose used was "Ceolas UF-702" (manufactured by Asahi Kasei Co., Ltd.), and the sucrose fatty acid ester used was "Lute-Sugar Ester S-370" (manufactured by Mitsubishi Chemical Co., Ltd.). The pressure resistance of the viable cell was evaluated by the following formula. Tablet survival rate (%) = Number of viable bacteria after tableting / Number of viable bacteria before tableting × 100 [Tablet survival rate criteria] ◎: 95% or more, 〇: less than 95%, 85% or more, △: less than 85%, 75% or more, ×: less than 75% [Tablet composition] Acid-resistant powder of the examples or comparative examples 10% by mass Lactose granules 68% by mass Starch 10% by mass Crystalline cellulose 10% by mass Sucrose fatty acid ester 2% by mass Total 100% by mass [Tableting conditions for tablet production] Model: Rotary tablet press Collect 12HU (manufactured by Kikusui Seisakusho Co., Ltd.) Tableting pressure: 15kN Pestle size: diameter 15mmφ Tablet weight: 1g

[0054] <Vitamin survival rate after acid resistance test (acid resistance survival rate)> (Acid resistance test) In the present invention, the acid resistance evaluation is carried out by placing 100 mL of a hydrochloric acid aqueous solution of pH 3.0 in a 200 mL capacity beaker and adjusting the temperature to 37°C. Next, 100 mg of secondary coated particles are added and stirred for 1 hour at 100 rpm with a magnetic stirrer. After stirring is completed, the mixture is neutralized with a sodium hydroxide aqueous solution of pH 13 and the viable cell count is measured. When calculating the viable cell count, the amount of the sodium hydroxide aqueous solution added is corrected. Acid resistance survival rate (%) = number of viable bacteria after acid resistance test / number of viable bacteria before acid resistance test × 100 [Acid resistance survival rate standard] ◎: 30% or more, 〇: less than 30%, 20% or more, △: less than 20%, 10% or more, ×: less than 10%

[0055] <Viable bacteria survival rate after bile acid resistance test (bile acid resistance survival rate)> (Bile acid tolerance test) In the present invention, the bile acid resistance was evaluated by placing 100 mL of 3 mM bile acid solution at pH 6.8 in a 200 mL beaker and adjusting the temperature to 37°C. Next, 100 mg of secondary coated particles were added and stirred for 3 hours at 100 rpm using a magnetic stirrer. After stirring, the mixture was neutralized with an aqueous sodium hydroxide solution and the viable cell count was measured. When calculating the viable cell count, the amount of the aqueous sodium hydroxide solution added was corrected. Bile acid resistance survival rate (%) = number of viable bacteria after bile resistance test / number of viable bacteria before bile resistance test × 100 [Criteria for bile acid resistance] ◎: 15% or more, 〇: less than 15%, 10% or more, △: less than 10%, 5% or more, ×: less than 5%

[0056] [Table 1-1] [Table 1-2]

[0057] [Table 2-1] [Table 2-2]

[0058] [Table 3-1] [Table 3-2]

[0059] In Examples 1 to 19, a powder (A1) containing live bacteria with a bulk density of 0.2 to 0.7 and an excipient (A2) with a bulk density of 0.7 to 1.0 were used as the core material (A), and a lipid with a melting point of 40°C to 70°C was used as the primary coating material (B) to form primary coated particles with an average particle size of 50 μm to 500 μm. The surfaces of the obtained primary coated particles were coated with a lipid with a melting point of 40°C to 100°C as the secondary coating material (C), and secondary coated particles were formed so that the average particle size of the secondary coated particles relative to the average particle size of the primary coated particles was 1.05 to 2.0, resulting in excellent results in all evaluations of processing stability, storage stability, pressure resistance, acid resistance, and bile acid resistance. In addition, the obtained acid-resistant powder had an average particle size of about 50 μm to 500 μm, so it was suitable as a raw material for other dosage forms such as tableting and soft capsules.

[0060] On the other hand, in Comparative Example 1, the primary coated particles were not coated with the secondary coating material (C), and therefore the effects of pressure resistance, acid resistance, and bile acid resistance were not obtained. Also, since the amount of the primary coating material (B) blended during the primary coating process was large, the particles were exposed to heat for a long time during the primary coating process, and therefore a tendency for processing stability to decrease was observed. In Comparative Example 2, since the primary coating process using the primary coating material was not performed, the coating with the secondary coating material was insufficient, and the effect of resistance to bile acidity was not obtained. In Comparative Example 3, a primary coating material with a high melting point was used, so that during coating with the primary coating material, live bacteria were killed by contact with the high-temperature primary coating material, and processing stability was poor. In Comparative Example 4, a lipid having a melting point of less than 40° C. was used as the secondary coating material, and therefore the effects of pressure resistance, acid resistance, and bile acid resistance were not obtained. In Comparative Example 5, the average particle size of the primary coated particles was less than 50 μm, so that the effects of acid resistance and bile acid resistance were not obtained. In Comparative Example 6, since the average particle size of the primary coated particles was more than 500 μm, the effects of processing stability, acid resistance, and bile acid resistance were not obtained. In Comparative Example 7, the secondary coating material was melted and the secondary coated particles were formed using the melted secondary coating material, so that the heat killed the live bacteria and the processing stability was reduced. Also, the ratio of the average particle size of the secondary coated particles to the average particle size of the primary coated particles exceeded 2.0, and a granulation product of the primary coated particles in which the secondary coating material was the continuous phase was formed, so that pressure resistance, acid resistance, and bile acid resistance were not obtained. In Comparative Examples 8 and 9, a powder having a low bulk density was used as the excipient (A2), and thus the coating performance was insufficient, and resistance to bile acidity was not obtained. [Industrial Applicability]

[0061] The acid-resistant powder of the present invention has a low mortality rate of live bacteria during processing such as coating, and can be endowed with excellent acid resistance and bile acid resistance, compared to powders containing live bacteria. Therefore, the acid-resistant powder of the present invention can be used as a raw material for enteric preparations such as foods (including health foods, functional foods, and foods for specified health uses), pharmaceuticals, quasi-drugs, and feed. Furthermore, the acid-resistant powder of the present invention has excellent storage stability and pressure resistance, and can therefore be suitably used as a raw material for tablets.

Claims

1. An acid-resistant powder comprising primary coated particles which contain powder particles of a core substance (A) as a plurality of nuclei and are coated with a primary coating material (B) as a continuous phase, and secondary coated particles which have a structure in which the primary coated particles are coated with a secondary coating material (C) as a single nucleus, The core material (A) comprises a powder (A1) containing live bacteria having a bulk density of 0.2 to 0.7 and an excipient (A2) having a bulk density of 0.7 to 1.0; The primary coating material (B) contains a lipid having a melting point of 40° C. to 70° C., The secondary coating material (C) contains a lipid having a melting point of 40° C. to 100° C., The average particle size of the primary coated particles is 50 μm to 500 μm, The ratio of the average particle size of the secondary coated particles to the average particle size of the primary coated particles (average particle size of the secondary coated particles / average particle size of the primary coated particles) is 1.05 to 2.

00.

2. a mass ratio of the core material (A) to a total mass of the core material (A) and the primary coating material (B) is 0.65 to 0.90; 2. The acid-resistant powder according to claim 1, wherein a mass ratio of the primary coated particles to a total mass of the primary coated particles and the secondary coating material (C) is 0.60 to 0.

85.

3. 3. The acid-resistant powder according to claim 1, wherein the average particle size is 50 μm to 500 μm, the viable cell survival rate after an acid resistance test is 32% or more, and the viable cell survival rate after a bile acid resistance test is 15% or more.

4. 3. The acid-resistant powder according to claim 1 or 2, which is for tableting.

5. A food product comprising the acid-resistant powder according to claim 1 or 2.

6. A method for producing the acid-resistant powder according to claim 1 or 2, A step of mixing the core material (A) and the primary coating material (B) to obtain the primary coated particles; A method for producing an acid-resistant powder, comprising: a step of mixing the primary coated particles with a powdery secondary coating material (C) to obtain the secondary coated particles.

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