JP2018177742A - Oral controlled-release composition and production method therefor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral controlled-release composition to be licked in a mouth so that a contained component can be melted into the mouth little by little while its flavor is being tasted; and a production method therefor.SOLUTION: An oral controlled release composition is obtained by: an ingredient mixing step of mixing ingredients, which include a high-intensity sweetener and a starchy ingredient comprising at least one modified starch selected from etherified starch, acetylated starch, etherified crosslinked starch and acetylated crosslinked starch, where the starchy ingredient content in the ingredients is 40 mass% or more in terms of a dry matter; a gelatinizing and shaping step of heating the mixture obtained in the ingredient mixing step to gelatinize the starchy ingredient and then shaping it into a prescribed shape, or for shaping the mixture into a prescribed shape and then heating it to gelatinize the starchy ingredient; and a drying step of drying the shaped product obtained through the gelatinizing and shaping step so that the water content is 20 mass% or less.SELECTED DRAWING: None

Description

  TECHNICAL FIELD The present invention relates to a composition for sustained release in the mouth, which can be released slowly and gradually by keeping the ingredients sweet and long without feeling completely soluble in the mouth, and a method for producing the composition.

  2. Description of the Related Art Conventionally, as products which can be melted and melted in the mouth, tablets such as throat cakes and tablets are known. However, conventional chewing and tablets can only stay in the mouth for only a few minutes, and can meet the requirement to dissolve the ingredients contained in chewing and tablets gradually over a longer period of time It was not.

  On the other hand, as a technique related to a sustained release preparation in which ingredients such as drugs are dissolved little by little in the body, Patent Document 1 below prepares a mixture by mixing starch glue and a drug so as to be homogeneous. It is described that the drug is embedded in a sustained release support in a capsule base by filling the mixture in a capsule base and lyophilizing the obtained capsule (paragraph (paragraph) See 0033).

  Also, US Pat. No. 6,095,099 is directed to at least one of producing granules for tableting and for capsule filling and / or further processing using injection molding technology as an adjuvant for direct tableting. A method of using a pharmaceutical dosage form, wherein said dosage form is a base whose properties are formed by extrusion, and which comprises at least one of starch, starch derivative and starch complex as basic components Said base comprising one and an active agent of at least one medicament, said dosage form being formed by extrusion to render said base amorphous or partially amorphous, The release of the active agent is modulated, and the dosage form comprises up to 50% by weight of the active agent of at least one pharmaceutical agent based on formulation, starch, starch derivative, and dip Forming a dry preparation by mixing with at least one of the complexes, and extruding the dry preparation using an extruder under conditions where the temperature of the orifice does not exceed 100 ° C. under standard pressure A method comprising the steps of: forming a base by obtaining: (see claim 1).

  Furthermore, Patent Document 3 listed below is a sustained release tablet containing a mixed compact of at least two dry powders, which comprises a powder of at least one pharmaceutical substance and a powder of a sustained release excipient, wherein The sustained release excipient is a chemical modification step in which the following steps are: (a) cross-linking and hydroxypropylation of highly amylose starch, and subsequently (b) gelatinization step, and then (c) sustained release by drying. The above-mentioned sustained release tablet is described, which further comprises a cross-linked high amylose starch prepared by the step of obtaining a powder of a sex excipient (see claim 1).

Unexamined-Japanese-Patent No. 2009-286759 Patent No. 5022086 Patent No. 5025066

  As described above, Patent Documents 1 to 3 describe that the gelatinized starch is dried to be a base of a sustained release preparation. However, there is no disclosure of such a product which is kept in the mouth for a long time while releasing it and releasing the contained ingredients little by little.

  Therefore, an object of the present invention is to provide a composition for dissection for oral cavity which can dissolve out the ingredients contained little by little in the mouth while tasting in the taste while simmering in the mouth and a method for producing the same is there.

  In order to achieve the above object, the composition for sustained oral release according to the present invention is a starch containing at least one modified starch selected from etherified starch, acetylated starch, etherified crosslinked starch, and acetylated crosslinked starch. The raw material and the high-sweetness sweetener are contained, and the starch in the starchy material is formed into a predetermined shape in a gelatinized state, and the content of the starchy material is 40% by mass or more in dry matter conversion The water content is 20% by mass or less.

  In the oral sustained release composition of the present invention, the content of the processed starch is preferably 30% by mass or more in terms of dry matter of the starch material.

  Moreover, it is preferable that the said modified starch is at least 1 sort (s) chosen from hydroxypropylated phosphoric acid crosslinking starch, acetylated starch, and hydroxypropylated starch.

  In addition, it is preferable that the penetration depth when the load reaches 5 kg is 1 mm or less by pressing at a penetration speed of 60 mm / min using a 1.5 mm diameter stainless steel cylindrical plunger with a rheometer.

  Furthermore, it is preferable to contain at least 1 sort (s) chosen from a gelling agent, a thickener, and insoluble dietary fiber.

  Furthermore, at least one selected from the above gelling agents, thickeners, and insoluble dietary fibers is agar, gelatin, xanthan gum, galactomannan, glucomannan, gellan gum, carrageenan, pectin, alginic acid, alginate, cellulose derivative Preferably, it is at least one selected from gum arabic, gati gum, pullulan, soybean polysaccharide, cellulose powder, microcrystalline cellulose, fermented cellulose, crushed bran, and chitin powder.

  The method for producing the composition for sustained oral release according to the present invention comprises a starchy material comprising at least one modified starch selected from etherified starch, acetylated starch, etherified crosslinked starch, and acetylated crosslinked starch, and Sweetness mixing step: A raw material mixing step of mixing a raw material containing a sweetness degree sweetener and having a content of the starchy raw material of 40% by mass or more in terms of dry matter, and a mixture obtained in the raw material mixing step A gelatinization / forming step of gelatinizing the raw material and molding it into a predetermined shape or molding the mixture into a predetermined shape and then heating it to gelatinize the starch raw material; And drying the molded product obtained through the molding process to a moisture content of 20% by mass or less.

  According to the present invention, since the starch material containing the specific modified starch is dried in the gelatinized state to have a water content of 20% by mass or less, it does not dissolve completely when placed in the mouth and is long. The sweetness can also be long-lasting, since it can be kept for a while and licked, and the elution of the high-sweetness sweetener retained in starch is gradually made. In addition, when a drug or functional food material is contained, it can be sustained-released in the mouth for a long time.

  The composition for sustained release in the oral cavity according to the present invention comprises a starchy material comprising at least one modified starch selected from etherified starch, acetylated starch, etherified crosslinked starch, and acetylated crosslinked starch, and high sweetness degree Containing at least

  Etherified starch, acetylated starch, etherified crosslinked starch, and acetylated crosslinked starch have the property of being resistant to aging when gelatinized. These starches are characterized in that when they are dried in a gelatinized state, they become hard and insoluble solids. For this reason, it can not be completely dissolved in the mouth, can stay for a long time and can be licked, and a solid material excellent in sustained release, in which the contained components are gradually eluted, can be provided. In addition, the modified starch which gelatinized the said modified starch further can also be used.

  In the present invention, it is more preferable to use at least one selected from hydroxypropylated phosphate cross-linked starch, acetylated starch, and hydroxypropylated starch among the above-mentioned modified starches. It is less soluble in the mouth and can enhance sustained release.

  In the present invention, starchy raw materials other than the above-mentioned modified starch may be included. Examples of such starch material include raw starch, crosslinked starch, oxidized starch, pregelatinized starch, dextrin and the like.

  In the oral sustained release composition of the present invention, the content of the starch material is 40% by mass or more in terms of dry matter, and preferably 60 to 99% by mass. If the content of the starchy material is less than 40% by mass in terms of dry matter, the solubility is high and the hardness is also low, so it is difficult to stay in the mouth for a long time while stirring.

  In the present invention, the high sweetness degree sweetener is not particularly limited, and examples thereof include sucralose, acesulfame potassium, aspartame, stevia extract, neotame, saccharin, saccharin sodium, glycyrrhizinic acid and salts thereof, thaumatin, licorice extract, α- It is possible to use at least one selected from the group consisting of glucosyl transferase-treated stevia, enzyme-treated licorice, enzyme-degraded licorice, advantame, and lacantha extract. Among these, in particular, sucralose, acesulfame potassium, aspartame, stevia extract, neotame, α-glucosyltransferase-treated stevia is preferably employed. These high intensity sweeteners are mixed with the starchy material and elute little by little as the starchy material dissolves in the mouth. Therefore, sweetness can be given over a long time. Although the content of the high sweetness degree sweetener is not particularly limited in the oral sustained release composition of the present invention, it is usually preferable that it is 0.05 to 5% by mass in terms of dry matter.

  It is preferable that the composition for sustained-release oral cavity of this invention contains at least 1 sort (s) chosen from a gelatinizer, a thickener, and an insoluble dietary fiber as raw materials other than the above.

  As a gelling agent and / or thickener, for example, agar, gelatin, xanthan gum, galactomannan, glucomannan, gellan gum, carrageenan, pectin, alginic acid, alginate, cellulose derivative, carboxymethylcellulose, locust bean gum, gum arabic, At least one selected from gati gum, pullulan, soybean polysaccharide and the like is preferably employed. Here, as a cellulose derivative, carboxymethylcellulose sodium, hydroxypropylcellulose, hydroxypropyl methylcellulose, hydroxypropylethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, ethylcellulose, methylcellulose and the like can be mentioned. By containing a gelling agent and / or a thickener, it is possible to prevent stickiness during molding and to improve shape retention. Moreover, in the state which the composition for oral sustained release dried and solidified, the fragility of solidified material can be improved, and even if it bites in a mouth, it can be made hard to fall apart. Although the content of the gelling agent and / or the thickener is not particularly limited in the oral sustained release composition of the present invention, in general, it is preferably 0.05 to 7% by mass in terms of dry matter.

  As the insoluble dietary fiber, for example, at least one selected from cellulose powder, microcrystalline cellulose, fermented cellulose, ground bran, chitin powder and the like can be preferably used. By containing the insoluble dietary fiber, it is possible to enhance the shape retention property at the time of molding, and to control the water absorbability after being dried and solidified. Although the content of the insoluble dietary fiber in the composition for sustained release in the oral cavity of the present invention is not particularly limited, in general, it is preferably 0.5 to 40% by mass in terms of dry matter.

  Since the composition for sustained release in the oral cavity of the present invention can stay in the mouth for a long time and dissolve the contained ingredients gradually, it is possible to release it in the mouth little by little. It is suitable for containing an ingredient that exerts an action.

  Such components include, but are not limited to, for example, menthol, menthol, cineolementone, methyl salicylate, spearmint oil, peppermint oil, refreshing agents such as peppermint oil and peppermint oil, herbal extracts, plum extracts, cullin extract and the like In addition to extracts which improve throat discomfort, vitamins, antioxidants, caffeine, minerals, carbohydrates, pH adjusters, anti-inflammatory agents and the like can be mentioned.

  The composition for sustained release in the oral cavity of the present invention can contain an acidulant, a flavor, a pigment, a carbohydrate, a water-soluble dietary fiber, a fat and oil, a protein, an emulsifier, a seasoning and the like as a raw material other than the above. In addition to food materials, materials for pharmaceuticals and cosmetics can also be contained.

  The oral sustained release composition of the present invention can be produced, for example, by the following production method. That is, an appropriate amount of water is added to the above-described raw materials and mixed (mixing step). In this case, the gelling agent and / or the thickener and the like are preferably mixed with other raw materials in a state of being mixed with water and heated in advance. The water content of the mixture thus obtained varies depending on the method of subsequent gelatinization / forming step and drying step, but usually 10 to 70% by mass is preferable, and 15 to 60% by mass is more preferable.

  Next, the mixture thus obtained is molded into a predetermined shape and heated to gelatinize the contained starchy material, or after heating the mixture to gelatinize the contained starchy material , And molded into a predetermined shape (gelatinization / molding process).

  The gelatinization method of the starch material is not particularly limited, and for example, heating by steaming, hot water, heater, oven, autoclave, microwave or the like, pressure heating in an extruder, or the like can be adopted.

  In addition, as a forming method, for example, filling forming into a forming die, rolling forming with a roller, extrusion forming, or the like can be adopted. Moreover, after shaping | molding by said means, you may cut to a desired magnitude | size. The forming shape is not particularly limited, but various shapes such as a sheet shape, a plate shape, a hexahedron shape, a disk shape, a spherical shape, a triangular pyramid shape and the like can be adopted.

  Next, the water content is 20% by mass or less, preferably 18% by mass or less, and more preferably 16% by mass or less, in such a manner that the formed starch material is formed into a predetermined shape and gelatinized. Let dry. Although the drying method is not particularly limited, for example, means such as hot air drying, freeze drying, blast drying, far infrared heating drying, dehumidifying air drying, sun drying, reduced pressure drying, indirect heating drying, microwave heating drying, etc. is adopted. be able to. In addition, since it is high temperature at the time of extrusion when heat-pressing and extruding with an extrusion molding apparatus, moisture evaporates and is dried simultaneously with extrusion, and it is also possible to make water content 20 mass% or less . Thus, by drying the starchy raw material in a gelatinized state, a solid material having high hardness and which is difficult to dissolve can be obtained.

  The composition for sustained release in the oral cavity of the present invention thus obtained is a starchy raw material comprising at least one modified starch selected from etherified starch, acetylated starch, etherified crosslinked starch, and acetylated crosslinked starch. Sweetness and sweetness are contained, the starch in the starch material is formed into a predetermined shape in a gelatinized state, the content of the starch material is 40% by mass or more in dry matter conversion, and the water content is Is 20% by mass or less.

  The hardness of the oral sustained release composition of the present invention is not particularly limited, but preferably the penetration depth is 1 mm or less when the load measured by the following hardness measurement method reaches 5 kg.

[How to measure hardness]
Using a rheometer, a 1.5 mm diameter stainless steel cylindrical plunger was pressed at a penetration speed of 60 mm / min to measure the penetration depth when the load reached 5 kg.

  The solubility of the oral sustained release composition of the present invention is also not particularly limited, but the solubility measured by the following method is preferably 60 or less, more preferably 40 or less.

[Method of measuring solubility]
The composition for oral sustained release is cut into 1 cm square, and the weight (A) of one cut tablet is measured. After immersing in 200 ml of 40 ° C. water for 60 minutes, it is sandwiched between filter paper and allowed to stand for 2 minutes to drain, and then the weight (B) is measured. Furthermore, while lightly pressing the particles against the filter paper, the surface is rubbed with the filter paper, the swollen part of the particle surface is removed, and the weight (C) is measured. The solubility is calculated by the following equation.
Solubility = {(B-C) / A} x 100
The composition for sustained release of the present invention thus obtained can be eluted over a long period of time while being put in the mouth and being stirred. In addition, since the high sweetness degree sweetener dissolves little by little and remains until the end, the sweetness can be kept feeling even if it is kept in the mouth for a long time. In addition, the active ingredients contained in the oral sustained release composition, such as refreshing agents, extracts for improving throat discomfort, drugs, functional foods, etc., are eluted over a long time, and their actions, for example, If it is a refreshing agent, refreshing feeling etc. can be maintained over a long time.

  In the present invention, “long time period” of the time for dissolving the composition for sustained release in the mouth while stirring it in the mouth preferably means 10 minutes or more, more preferably 20 minutes or more.

  Hereinafter, although the example of the present invention is mentioned and explained, the present invention is not limited to these examples.

<Example of experiment>
40 parts of water was added to 60 parts of each starch shown in Table 1, and after sufficient kneading at normal temperature, it was formed into a 6 mm thick sheet. The molded product was heated with a steamer for 15 minutes, allowed to cool at normal temperature, and then dried at 70 ° C. for 18 hours. The dried product was left to stand at room temperature for 1 day for evaluation.

  The evaluation was carried out with respect to visual uniformity and shape (flatness, cracking) and sensory. At the time of sensory evaluation, it was possible to continue giving up without making any and 20 minutes or more. The results are shown in Table 1.

  From the results of Table 1, it was found that by using a modified starch which is not easily aged after solidification, a product having a good shape and texture can be obtained. On the other hand, in the sensory evaluation, it was unpleasant to stay in the mouth for a long time because of no flavor.

Examples 1-4
The raw materials were kneaded according to the composition shown in Table 2 and then formed into a 6 mm thick sheet. In Example 3, the solution in which agar was dispersed in advance was heated to form a solution, and the mixture was kneaded while keeping at 40 ° C. or higher, and the remaining mixture was kneaded at room temperature. The molded product was heated with a steamer for 15 minutes, allowed to cool at normal temperature, and then dried at 70 ° C. for 18 hours. The dried product was left to stand at room temperature for 1 day for evaluation.

  The evaluation was carried out on the formability of the dough when making the kneaded product into a sheet, and the shape of the product after drying (flatness, warp or not). The results are shown in Table 2.

  As shown in Table 2, Example 1 had some difficulty in molding and warpage was observed in the shape after drying, but in Examples 2 and 3, the fabric was well-assembled and the formability was good. The shape after drying was also flat and clean. By adding a thickener, the improvement of shaping | molding ability and the deformation | transformation suppression by drying were recognized. In addition, 0.5 g of the product obtained in each example was evaluated by sensory evaluation. In any of the examples, the hardness was maintained without melting completely in the mouth for 30 minutes or more, and by blending the high-sweetness sweetener, a slight sweetness was felt, and the flavor could be enjoyed.

<Examples 5 · 6 · 7, Comparative Examples 1 · 2 · 3>
After compounding with the composition shown in Table 3, it was formed into a 6 mm thick sheet. The molded product was heated in a steamer for 30 minutes, allowed to cool at normal temperature, and then dried at 70 ° C. for 18 hours. The plate-like dried product was sealed and allowed to stand at room temperature for 1 day for evaluation. The evaluation was performed by measuring the solubility and the hardness by the respective methods described above. The results are shown in Table 3.

  As a result, in Examples 5, 6 and 7, even after 60 minutes of immersion, a hard part was likely to remain, and the product before immersion was also hard. In Comparative Examples 1, 2 and 3, the water absorption from the product surface was increased by water immersion for 60 minutes, and the swelling ratio was high. Actually, in Examples 5, 6 and 7 the hardness was maintained even after 30 minutes or more and the hardness was maintained to a reasonable degree, but in Comparative Examples 1 and 2 it took less than 10 minutes. It became soft and melted from the surface, and Comparative Example 3 crumbled in about 15 minutes, and was of unsatisfactory quality. From the above, it was suggested that when the content of the starch material is less than 40%, the product is likely to absorb water and the hardness is lowered. Furthermore, it was shown that the content of the modified starch is more preferably 30% by mass or more in terms of dry matter in the starch material.

<Comparative Example 4, Examples 8 to 10>
To 100 parts of the modified starch (hydroxypropylated phosphoric acid cross-linked starch), 65 parts of water was added, and the mixture was kneaded and formed into a 7 mm thick sheet. The molded product was heated with a steamer for 20 minutes, allowed to cool at normal temperature, divided into four equal parts, and then dried at 70 ° C. After the drying time was 6, 8, 10 and 12 hours, the plate-like dried product was taken out, sealed, allowed to stand at normal temperature for 1 day, and the hardness was measured by the above-mentioned method. The results are shown in Table 4.

  As a result, all of Examples 8 to 10 exhibited high hardness, and Comparative Example 4 did not have sufficient hardness. When actually put into the mouth and evaluated, although Examples 8 to 10 did not dent or deform even if they bite the product lightly, Comparative Example 4 is dented if it bites light and is easily deformed. The It was shown that adjusting the moisture value to less than 20% can keep the shape for a long time in the mouth.

Examples 11 and 12
The composition shown in Table 5 was sufficiently kneaded at normal temperature and then formed into a 6 mm thick sheet. The molded product was heated with a steamer for 15 minutes, allowed to cool at normal temperature, and then dried at 70 ° C. for 18 hours.

  For Example 11, the product was cut to a weight of 2 g, and for Example 12, the product was cut to a weight of 10 g.

[Dissolution test of water-soluble substance · Example 11]
One of the products obtained in Example 11 was placed in 100 ml of warm water. Two sets of this were prepared. After 20 minutes and 1 hour, they were taken out of the hot water, respectively, and the water of the taken out sample was lightly taken, and it was put in 100 ml of normal temperature water stirred by a stirrer to measure pH 10 minutes.

  As a result, the 20-minute immersion product had a pH of 6.26 and the 1-hour immersion product had a pH of 6.36. In addition, the pH of normal temperature water before putting a product was 7.06. A 20-minute immersion product and a 1-hour immersion product both showed a slight sweetness and orange taste.

  Thus, the pH of the water at the time of measurement changed low at any time. This result indicates that citric acid, which is a water-soluble substance, is gradually released in water while being retained in the product.

[Dissolution test of fat-soluble substance, Example 12]
One of the products obtained in Example 12 was placed in 100 ml of hot water. Two sets of this were prepared. After 20 minutes and 1 hour, they were taken out of the hot water, and after taking a light sample by placing the taken sample on filter paper, the color difference was measured.

  As a result, after 20 minutes, L *: 59.57, a *: 28.26, b *: 41.66. After 40 minutes, L *: 61.51, a *: 26.14, b *: 38.75. And it was both deltaE = 4.91.

  Thus, from the numerical value change of color difference after 20 minutes and 1 hour, the sample changed from dark orange to bright orange. These show that the paprika pigment, which is a fat-soluble substance, was gradually released in water but was also retained in the product.

  From the test results of Examples 11 and 12 above, it was shown that the components contained in the product were gradually released while stirring in the mouth, regardless of water solubility or oil solubility.

Claims (7)

  A starchy material comprising at least one modified starch selected from etherified starch, acetylated starch, etherified crosslinked starch, and acetylated crosslinked starch, and a high-sweetness sweetener, wherein the starchy material is contained The starch is formed into a predetermined shape in a gelatinized state, and the content of the starch material is 40% by mass or more in terms of dry matter, and the water content is 20% by mass or less. Oral sustained release composition.   The composition for sustained release in the oral cavity according to claim 1, wherein the content of the processed starch is 30% by mass or more in terms of dry matter in the starch material.   The composition for sustained release in the oral cavity according to claim 2, wherein the modified starch is at least one selected from hydroxypropylated phosphate cross-linked starch, acetylated starch, and hydroxypropylated starch.   The penetration depth at a load of 5 kg is 1 mm or less when the load reaches 5 kg by pressing at a penetration speed of 60 mm / min using a 1.5 mm diameter stainless steel cylindrical plunger with a rheometer. The composition for oral sustained release according to any one of the above.   Furthermore, the composition for oral sustained release of any one of Claims 1-4 which contains at least 1 sort (s) chosen from a gelatinizer, a thickener, and insoluble dietary fiber.   At least one selected from the above gelling agents, thickeners and insoluble dietary fibers is agar, gelatin, xanthan gum, galactomannan, glucomannan, gellan gum, carrageenan, pectin, alginic acid, alginate, cellulose derivative, gum arabic The oral sustained release according to any one of claims 1 to 5, at least one selected from gati gum, pullulan, soybean polysaccharide, cellulose powder, microcrystalline cellulose, fermented cellulose, crushed bran, and chitin powder. Composition.   A starchy material comprising at least one modified starch selected from etherified starch, acetylated starch, etherified crosslinked starch, and acetylated crosslinked starch, and high intensity sweetener, containing the starchy material A raw material mixing step of mixing raw materials having an amount of 40% by mass or more in terms of dry matter and a mixture obtained in the raw material mixing step are heated to gelatinize the starchy raw material and then formed into a predetermined shape Alternatively, after forming the mixture into a predetermined shape, the mixture is heated to gelatinize the starch material, and the formed product obtained through the gelatinization / forming process and the gelatinization / forming process has 20 mass of water. And b) drying the composition so as to be less than 10%.