JP6809675B2 - Method for Producing Immediate Oral Granules Containing Plant Extract - Google Patents

Description

The present invention relates to a method for producing instantly soluble granules in the oral cavity containing a bitter plant extract such as turmeric extract.

Ingredients that are orally ingested in the form of foods and drinks, feeds, pharmaceuticals, quasi-drugs, etc. may contain components that exhibit unpleasant tastes such as bitterness, pungent taste, sourness, and astringency. Plant extracts are also examples of such ingredients, but since plant extracts are bitter in most cases, they are often taken in tablets or granulated products dissolved in water. In addition, since plant extracts generally contain sugars, they are viscous and become bulky and heavy powders even when powdered. Therefore, when a plant extract is used, there is a peculiar problem that the granulation load is large and it is difficult to granulate.

So far, various techniques have been developed for preparations that do not cause an unpleasant taste such as bitterness in the oral cavity. For example, in Patent Documents 1 and 2, an unpleasant taste component such as granules is coated with a coating layer containing fats and oils, proteins, etc. to suppress its elution, and the coating contains an unpleasant taste component and is high. Immediately soluble granules that make it difficult to feel an unpleasant taste by containing a savory substance such as a sensitive sweetener are described. However, these quick-dissolving granules have a complicated manufacturing process for coated granules, are costly, and are not satisfactory in terms of productivity and economy.

Patent Document 3 describes kneading in order to eliminate an increase in viscosity and mechanical resistance during kneading and granulation when granulating by extruding and granulating using a highly viscous raw material such as a plant extract. It has been proposed to knead using water and ethanol containing menthol as the liquid, but the solubility and bitterness of the produced granules in the mouth have not been investigated.

In Patent Document 4, by molding granules having a specific particle size, unpleasant flavors such as bitterness and astringency of off-flavor components are masked even if the granules have a material-specific flavor that is easily felt directly on the tongue. , A method for producing fast-disintegrating granules having excellent drinking comfort and flavor during drinking is described. However, as the off-taste component, only three components, glucosamine, chondroitin, and enzyme-treated rutin, are targeted, and plant extracts are not targeted.

In Patent Document 5, erythritol and sugar are used as excipients, and by setting the particle size of the granules within a certain range, even if they are put directly into the mouth, they are immediately dissolved in a small amount of saliva, and the swallowing property is good. Granules are listed. However, there is no mention of eliminating the unpleasant taste of the drug contained in the granules.

Patent Document 6 describes that the unpleasant taste such as bitterness of a drug is improved by adding a sugar alcohol having a specific heat of solution and a pH adjuster in combination. Tranexamic acid is used as a drug. It is a target, not a plant extract.

Japanese Patent No. 5756727 Japanese Patent No. 5909040 Japanese Patent No. 4803969 Japanese Patent No. 5270893 Japanese Patent No. 3435109 Japanese Patent No. 4346817

Therefore, an object of the present invention is to provide a method for producing granules of a plant extract that is difficult to granulate, which dissolves immediately in the oral cavity, is less bitter, and can be easily taken without water. ..

As a result of diligent research to solve the above problems, the present inventors used sugar alcohol and starch as a base material in the production of granules containing a plant extract, and determined the amount of water used in the kneading process. By blending the raw materials so that the water content of the powder mixture after kneading is within a predetermined range by reducing it as much as possible, extruded granules can be easily performed without increasing the viscosity during kneading of the powder mixture. We have found that bulky granules can be obtained with excellent meltability in the mouth, without bitterness, and have completed the present invention.

That is, the present invention includes the following inventions.
(1) The powder mixture after kneading includes a step of adding an aqueous medium to the powder mixture containing the plant extract, sugar alcohol and starch and kneading the mixture, and a step of extruding and granulating the powder mixture after kneading. A method for producing instantly soluble granules in an oral cavity containing a plant extract, which comprises a water content of more than 5.1% by weight and less than 8.9% by weight.
(2) The production method according to (1), wherein the content of the plant extract in the instantly soluble granules in the oral cavity is 10% by weight or more.
(3) The production method according to (1) or (2), wherein the plant extract is turmeric extract and / or zedoary extract.
(4) The production method according to any one of (1) to (3), wherein the mixing ratio of sugar alcohol and starch is 1: 1 to 5: 1 by weight.
(5) The production method according to any one of (1) to (4), wherein the sugar alcohol is powdered reduced maltose and the starch is cornstarch.
(6) The production method according to any one of (1) to (5), wherein the immediately soluble granules in the oral cavity can be taken without water.
(7) The production method according to any one of (1) to (6), wherein the aqueous medium is water, ethanol, or a mixed solution of water and ethanol.

According to the method of the present invention, it is possible to produce granules containing a plant extract that dissolves immediately in the oral cavity, is less likely to cause bitterness, and can be easily taken without water. The method of the present invention is excellent in productivity and economy because it does not require a coating step for masking bitter substances and does not use any special raw material.

FIG. 1 shows micrographs of the granules of Examples 1 to 6 and Comparative Example 2.

The method for producing instantly soluble granules in the oral cavity containing the plant extract of the present invention includes a step of adding an aqueous medium to a powder mixture containing the plant extract, sugar alcohol and starch and kneading the granules, and a powder after kneading. It comprises a step of extruding and granulating the mixture, and is characterized in that the water content of the powder mixture after kneading is more than 5.1% by weight and less than 8.9% by weight. The orally rapidly dissolving granules produced by this method dissolve immediately in the presence of saliva even when taken without water, so that they can be easily taken anywhere and at any time.

The "plant extract" used in the present invention includes zedoary (purple turmeric), autumn turmeric, spring turmeric (curcuma cona), swertia japonica, gentiana, grapefruit, tea, onion, buckwheat, persimmon, soybean, coffee, strawberry, sesame, and parsley. , Clara, Kihada, Nigaki, Daidai, Hop, Cacao and other plant extracts. These plant extracts may be used alone or in admixture of two or more. In particular, extracts of one or more plants selected from the group consisting of zedoary, autumn turmeric, and spring turmeric are preferable.

In the present invention, the "plant extract" refers to an extract obtained from a part or all of the plant body of the above-mentioned plant (for example, a part normally ingested for foods, pharmaceuticals, etc.) or all of the extraction solvent. Examples of the extraction solvent include water, hot water, a hydrophilic organic solvent, and a mixed solvent of water and a hydrophilic organic solvent. Alcohol, water, and a mixed solvent of alcohol and water are preferable, and ethanol is preferable as the alcohol. When a mixed solvent of water and a hydrophilic organic solvent is used, the mixing ratio of water and the hydrophilic organic solvent is not particularly limited, but for example, the weight ratio is preferably in the range of 10:90 to 90:10, and 20:80 to 50. A range of: 50 is more preferred. In the present invention, this plant extract is used in the form of powder. The powder of the plant extract can be prepared by subjecting the solvent phase obtained by the above extraction to a treatment such as concentrated drying, spray drying, freeze drying and the like.

Examples of the "sugar alcohol" used in the present invention include powdered reduced maltose (maltitol), reduced lactose (lactitol), sorbitol, xylitol, erythritol, mannitol, isomartitol, trehalose, palatinose, reduced starch saccharified product and the like. These sugar alcohols may be used alone or in combination of two or more. Among these sugar alcohols, powdered reduced maltose is preferable in that it is easily dissolved in water, has higher water absorption than the plant extract, and does not become sticky even if it absorbs water during kneading.

Examples of the "starch" used in the present invention include cornstarch, wheat starch, rice starch, potato starch, sweet potato starch, tapioca starch, and ester-etherified crosslinked products, oxides, and partially decomposed products thereof. These starches may be used alone or in combination of two or more. Among these starches, the particles are fine and the particle size is uniform, so the fluidity is good, the slippage during extrusion granulation is good, the gelatinization temperature is high, and even if it is kneaded with a liquid raw material and granulated. Cornstarch is preferable in that it does not easily increase in viscosity and that it has a plastic flow viscosity with little spinnability even if the viscosity increases.

The above-mentioned powder mixture containing the plant extract, sugar alcohol and starch may contain other components. The other ingredients are those that are acceptable in the final form of foods and drinks, pharmaceuticals, etc., and are not particularly limited as long as they are orally ingestible, but for example, sweeteners, acidulants, vitamins, Examples include minerals and antioxidants. Further, if necessary, fragrances, pigments, preservatives and the like may be used.

Sweeteners include simple sugars (dextrose, fructose, xylose, galactose, etc.), disaccharides (sucrose, malt sugar, lactose, etc.), oligosaccharides (fructo-oligosaccharide, maltooligosaccharide, isomaltooligosaccharide, galactooligosaccharide, coupling sugar, etc.) ), High-fructose corn syrup (fructose-fructose syrup, fructose-fructose syrup, sugar-mixed isomerized sugar, etc.), high-sweetness sweeteners (sclarose, acesulfam potassium, somatin, stevia, aspartame, etc.) and the like.

Examples of the acidulant include organic acids such as citric acid, malic acid, tartaric acid, acetic acid, phytic acid, lactic acid, fumaric acid, succinic acid and gluconic acid, inorganic acids such as phosphoric acid, or sodium salts, potassium salts or salts thereof. Calcium salt and the like can be mentioned.

Examples of vitamins include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, vitamin K, niacin, inositol and the like.

Examples of minerals include calcium, magnesium, zinc, iron, potassium and the like.

Examples of the antioxidant include vitamin C, tocopherol (vitamin E), enzyme-treated rutin, catechin and the like.

In the method for producing instantly soluble granules in the oral cavity of the present invention, sugar alcohol and starch are used as a base material, and the raw materials are blended so that the water content of the powder mixture after kneading is within a predetermined range. It can be carried out by the process of manufacturing granules by granulation, that is, mixing of powder raw materials, liquid mixing (kneading) of a solution containing a binder (kneading liquid), extrusion granulation, drying, granulation, and sieving. .. Here, the "moisture content of the powder mixture after kneading" means the total amount of the water content of the powder raw material and the water content of the kneading liquid. The water content of the powder mixture after kneading may be more than 5.1% by weight and less than 8.9% by weight, but is preferably 6.1 to 8.0% by weight, preferably 7.1 to 8.0% by weight. % Is more preferable.

(Mixing of powder raw materials)
First, the plant extract, which is a powder raw material, sugar alcohol, starch, and other components are mixed. The method for mixing the powder raw materials may be any method as long as each component of the powder raw materials can be uniformly mixed. Examples of the mixing machine include a V-type mixer, a ribbon-type mixer, a container mixer, a high-speed stirring mixer and the like. The mixing temperature is not particularly limited, but is preferably 10 ° C to 35 ° C, more preferably 15 ° C to 25 ° C. The mixing time is also not particularly limited, but is preferably 0.5 to 5 minutes, more preferably 1 to 2 minutes. The plant extract is preferably 10% by weight or more based on the total amount of the immediately soluble granules in the oral cavity finally obtained. The mixing ratio of sugar alcohol and starch is not limited as long as the amount of starch is the same as or less than that of sugar alcohol in order to obtain a good granulated product. For example, sugar alcohol: starch by weight ratio. Is preferably 1: 1 to 5: 1, more preferably 1: 1 to 3: 1, and even more preferably 1: 1 to 2: 1. If starch is not contained, a granulated product cannot be formed. On the contrary, if sugar alcohol is not contained, the desired good solubility in the mouth cannot be obtained.

(Kneading)
Next, an aqueous medium is added as a kneading solution to the powder mixture in which the above powder raw materials are mixed, and the mixture is kneaded. Examples of the aqueous medium include water, ethanol, or a mixed solution of water and ethanol. When a mixed solution of water and ethanol (ethanol aqueous solution) is used, the mixing ratio is not limited and can be appropriately selected. Here, as the ethanol aqueous solution, alcohol preparation may be used in addition to a commercially available ethanol preparation. The sake spirit is not particularly limited as long as it is used for food. For example, there are those produced from natural raw materials containing starch and sugar by the fermentation action of yeast, or those containing these components, and fermented seasonings such as sake, shochu, wine, whiskey, brandy and other alcoholic beverages, and mirin. A liquid containing ethanol can be used, such as a material. The amount of the aqueous medium added to the powder mixture is not particularly limited as long as the water content of the powder mixture after kneading is within the above range. Further, a binder may be added to the above aqueous medium (kneading liquid) if necessary, and for example, monosaccharides, disaccharides, polysaccharides, celluloses, sugar alcohols, or two or more of these. Examples thereof include a mixture, and the present invention is not particularly limited as long as it is pharmaceutically acceptable. Further, the amount of addition is not particularly limited as long as it can be granulated. When a powdery binder is used, it may be added to the powder raw material.

(Extruded granulation)
Next, the powder mixture after the kneading is extruded and granulated. Extruded granulation refers to granulating by adding water or a binding liquid and kneading the powder, and extruding the plasticized powder from a screen having a large number of holes or a die having a predetermined pore diameter with a screw, a roller, or the like. Extruded granulation is suitable for the method of the present invention in that granulated products can be produced smoothly and efficiently under low moisture conditions. Examples of the granulation machine include a front extrusion type granulator, a disc pelleter type granulator, a ring die type granulator, a basket type granulator, an oscillating type granulator, a cylinder type granulator, and the like. .. As for the conditions for extruded granules in the present invention, it is preferable to use extruded holes having a pore diameter of about 0.8 to 1.5 mm in order to obtain a bulk specific gravity of granules having good immediate solubility.

(Drying, sizing)
The granulated product can be dried by a usual drying method. Examples of the drying machine include a ventilation dryer, a vacuum dryer, a vacuum dryer, a fluidized bed dryer and the like. If desired, it can be sieved and sized with a sieve, a combil or the like after drying.

The orally rapidly soluble granules produced by the method of the present invention may be provided as a food product or as a pharmaceutical product for oral administration, but are preferably food products. In addition, the granules can be contained in a container or bag used as a container or bag for food or pharmaceuticals, and examples thereof include paper, plastic, glass, and metal containers and bags. Of these, a form (stick packaging, separate packaging, etc.) packaged for each oral intake (for example, about 1.5 g to 2 g) is preferable. The packaging material is not usually limited as long as it is used for foods and pharmaceuticals, but for example, a combination of aluminum foil, synthetic resin (polyethylene terephthalate, etc.), laminated paper, or the like can be used.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but these Examples do not limit the present invention.

The raw materials used in Examples and Comparative Examples are shown below.
Powder reduced maltose: "Resis fine powder" (manufactured by Mitsubishi Corporation Food Tech Co., Ltd., containing 99.5% maltitol)
Cornstarch: "Cornstarch" (manufactured by Sanwa Cornstarch Co., Ltd.)
Reduced maltose starch syrup: "Amarti syrup" (manufactured by Mitsubishi Corporation Food Tech Co., Ltd.)
Ethanol aqueous solution formulation: "Kohelsin" (manufactured by Mitsubishi Chemical Foods Co., Ltd., 70% ethanol)

(Examples 1 to 6, Comparative Examples 1 to 2)
1. 1. Preparation of test product Powder mixture of turmeric extract, gajutsu extract, powdered reduced maltose, corn starch, acidulant (citric acid), and sweetener (stevia) uniformly mixed in the formulation (% by weight) shown in Table 1. Was prepared. On the other hand, in the formulation (% by weight) shown in Table 1, a solution prepared by dissolving reduced maltose starch syrup (binder) as a liquid raw material in water and an aqueous ethanol solution (70%) was prepared, and this solution was used as a kneading solution to prepare the solution. The powder mixture was spray-added and kneaded. The powder mixture after kneading is extruded and granulated on a screen having a pore size of 1.3 mm using a granulator (Dalton Corporation, Multigran MG-55-1), and dried at an intake temperature of 60 ° C. for 10 minutes. The mixture was allowed to cool to prepare granules of a test product. In Examples 1 to 2 and Comparative Examples 1 and 2, the water content of the powder mixture after kneading is different by keeping the blending amount of the powder raw material constant and changing the blending amount of water in the liquid raw material. It was a product. Further, Examples 4 to 6 were test products in which the water content of the powder mixture after kneading was kept constant and the mixing ratio of powder-reduced maltose and cornstarch in the powder raw material was changed.

2. 2. Evaluation method (1) Sensory evaluation Each test product was subjected to sensory evaluation by 10 panelists. The panelists took each test product and evaluated "melting in the mouth" and "bitterness" on a scale of 1 to 10 (10 points for good melting in the mouth and 10 points for bitterness), and the average value of the evaluation points was calculated. ..

(2) Evaluation of granulation property The granulation property of each test product was evaluated by the granulator load (A: current value).

(3) Measurement of granule disintegration rate and bulk specific gravity Granule disintegration rate (seconds) is an index of solubility and was measured according to the 17th revised Pharmacopoeia 6.09 Disintegration Test Method of the Japanese Pharmacopoeia. Further, the bulk specific gravity (g / cc) is an index of whether or not the granules are porous and bulky, and means a weight value per unit volume (loose bulk specific gravity) of the granules in a non-tapping state. Specifically, the granules of the test product are placed in a stationary cup with an internal volume of 100 cc, the granules protruding above the cup are weighed with a blade, and the measured value is divided by the capacity of the cup (100 cc). I asked for it. For the disintegration rate and bulk specific gravity of the granules, the average value of three measurements was calculated for each test product.

(4) Microscopic observation of granules The granules were observed using a scanning electron microscope (manufactured by Hitachi High-Technologies Corporation).

3. 3. Results The test results are shown in Table 1. In the table, "-" indicates that the granules could not be granulated and the granules were not evaluated. In addition, FIG. 1 shows scanning electron micrographs of the granules of each test product (excluding Comparative Example 1 which could not be granulated).

As shown in Table 1, the test products (Examples 1 to 6) having a water content of 6.1 to 8.0% by weight of the powder mixture after kneading were granules having good melting in the mouth and less bitterness. On the other hand, in the test product having the same water content of 5.1% by weight (Comparative Example 1), the water content was too small to apply a granulation load and granules could not be formed, and the same water content However, in the test product of 8.9% by weight (Comparative Example 2), the granules were hard and did not melt in the mouth, resulting in bitterness. From these results, it can be said that the water content of the powder mixture after kneading is more than 5.1% by weight and less than 8.9% by weight in a preferable range.

Regarding the mixing ratio of powdered reduced maltose and cornstarch in the powder raw material, the test products (Examples 4 to 6) in which the amount of cornstarch was equal to or less than that of powdered reduced maltose had good melting in the mouth and less bitterness. It was a granule.

As can be seen from the photomicrograph of FIG. 1, the test products (Examples 1 to 6) having a water content of 6.1 to 8.0% by weight after kneading were porous and bulky granules. .. On the other hand, the test product (Comparative Example 2) having the same water content of 8.9% by weight had a smooth surface, was not porous, and was a bulky granule.

According to the method of the present invention, it is possible to produce plant extract-containing granules that are immediately dissolved by saliva in the oral cavity and can be taken without water. Therefore, the present invention can be used in the field of manufacturing pharmaceuticals and supplements.

Claims (7)

It includes a step of adding an aqueous medium to a powder mixture containing a plant extract, sugar alcohol and starch and kneading, a step of extruding and granulating the powder mixture after kneading , and a step of drying the granulated product . Immediately soluble granules containing a plant extract, characterized in that the water content of the powder mixture after kneading and before drying of the granules is greater than 5.1% by weight and less than 8.9% by weight. Manufacturing method. The production method according to claim 1, wherein the content of the plant extract in the instantly soluble granules in the oral cavity is 10% by weight or more. The production method according to claim 1 or 2, wherein the plant extract is turmeric extract and / or zedoary extract. The production method according to any one of claims 1 to 3, wherein the mixing ratio of sugar alcohol and starch is 1: 1 to 5: 1 by weight. The production method according to any one of claims 1 to 4, wherein the sugar alcohol is powdered reduced maltose and the starch is cornstarch. The production method according to any one of claims 1 to 5, wherein the orally immediately soluble granules can be taken without water. The production method according to any one of claims 1 to 6, wherein the aqueous medium is water, ethanol, or a mixed solution of water and ethanol.

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