Oral retention components

Abstract

The purpose of the present invention is to provide an oral retention composition in which a decrease in viscosity of an acidic polysaccharide due to a functional substance is inhibited even when the functional substance is basic.　The present invention pertains to an oral retention composition that contains at least one compound selected from the group consisting of shellac and zein, a functional substance, and an acidic polysaccharide, and in which the functional substance is covered with the at least one compound selected from the group consisting of shellac and zein, and is mixed with the acidic polysaccharide.

Description

Technical Field

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[0001] The present invention relates to an intraoral retention composition, and an oral composition or an oral composition containing the same. More specifically, it relates to a composition having a long retention time in the oral cavity, and an oral composition or an oral composition containing the same.

Background Art

[0002] Functional substances for application in the oral cavity for the purpose of improving the oral environment (for example, antibacterial action (bactericidal and / or bacteriostatic) against oral resident bacteria, cariogenic bacteria, etc.) are known. For example, it is known that protamine degradation products have an antifungal effect against Candida albicans, which is an oral resident bacterium (Patent Document 1).

[0003] However, in the oral cavity that is constantly washed with saliva and exudate, functional substances are likely to be lost. Therefore, attempts have been made to retain functional substances in the oral cavity for a longer time in order to extract more actions of functional substances on the oral cavity. For example, it has been reported that the liquid oral care composition obtained by dissolving powders of catechin and xanthan gum in water has a gradually increasing catechin concentration upon contact with model saliva (Patent Document 2).

Prior Art Documents

[0006] The inventors have found that even if the functional substance is at least one selected from the group consisting of basic substances and polyphenols, the decrease in viscosity of acidic polysaccharides caused by the functional substance can be suppressed, and the retention time in the oral cavity is extended. The present invention was completed based on these findings.

[0007] One objective of the present invention is to provide the compositions and manufacturing methods listed in the following items. Item 1 An oral cavity retention composition comprising at least one compound selected from the group consisting of shellac and zein, a functional substance, and an acidic polysaccharide, wherein the functional substance coated with at least one compound selected from the group consisting of shellac and zein is mixed with the acidic polysaccharide. Section 2 The oral cavity retention composition according to claim 1, wherein the acidic polysaccharide is at least one selected from the group consisting of carrageenan, hyaluronic acid, xanthan gum, sodium alginate, pectin, and gum arabic. Section 3 The oral cavity retention composition according to claim 1 or 2, wherein the functional substance is at least one selected from the group consisting of basic substances, polyphenols, and lactic acid bacteria. Section 4 The oral cavity retention composition according to any one of claims 1 to 3, wherein the basic substance has an amino group and the polyphenols have two or more hydroxyl groups bonded to an aromatic ring. Section 5 The oral cavity retention composition according to any one of claims 1 to 3, wherein the basic substance is at least one selected from the group consisting of protamine hydrolysate, arginine, lysine, glucosamine, spermine, spermidine, putrescine, piperine, and chitosan. Section 6 The oral cavity retention composition according to any one of claims 1 to 3, wherein the polyphenols are at least one selected from the group consisting of chlorogenic acid, quercetin, resveratrol, tannic acid, caffeic acid, caffeic acid phenethyl ester, hydroxytyrosol, oleuropein, gallic acid, eugenin, catechin, daidzein, procyanidin, theaflavin, polyphenol-containing plant extract, propolis, champignon extract, syringin, and eleuthroside E. Section 7 An oral retention composition according to any one of claims 1 to 6, having the form of granules, powder, or tablets. Section 8 An oral cavity retention composition according to any one of items 1 to 7, wherein the average particle size is 1 μm to 400 μm. Section 9 An oral retention composition according to any one of claims 1 to 8, for use as a material for manufacturing an oral composition or an oral composition. Section 10 An oral composition or oral composition containing an oral retention composition as described in any of items 1 to 9. Section 11 An oral composition or oral composition as described in item 10, which is a food, oral care product, pet food, pharmaceutical, or quasi-drug. Section 12 An oral composition as described in item 11, which is a food for suppressing bad breath. Section 13 An oral composition according to item 12, which is a food for suppressing bad breath while wearing a mask or a food for suppressing bad breath upon waking. Section 14 An oral composition according to item 11, which is a food for flavor retention or a food for flavor masking. Section 15 A method for producing an oral retention composition containing at least one compound selected from the group consisting of shellac and zein, a functional substance, and an acidic polysaccharide, wherein the functional substance coated with at least one compound selected from the group consisting of shellac and zein is mixed with the acidic polysaccharide, Step 1 of mixing at least one compound selected from the group consisting of shellac and zein dissolved or dispersed in a solvent with a functional substance to coat the functional substance, and Step 2 of mixing the functional substance coated with at least one compound selected from the group consisting of shellac and zein obtained in Step 1 with an acidic polysaccharide, The manufacturing method including. Item 16 The production method according to item 15, wherein in step 2, the functional substance and the acidic polysaccharide are mixed while adding ethanol or hydrous ethanol having an ethanol concentration of 50% to 99% (v / v).

Advantages of the Invention

[0008] According to the present invention, the oral retention of the functional substance is improved. Further, according to the present invention, the action of reducing the viscosity of the acidic polysaccharide by the functional substance can be suppressed. According to the present invention, the reaction between the functional substance and the acidic polysaccharide can be suppressed. According to the present invention, a method for producing an oral retention composition can be provided.

Brief Description of the Drawings

[0009] [Figure 1] FIG. 1 is a graph showing the results of absorbance measurement in Test Example 8. [Figure 2] FIG. 2 is a graph showing the test results of Test Example 14. [Figure 3] FIG. 3 is a graph showing the test results of Test Example 15. [Figure 4] FIG. 4 is a graph showing the test results of Test Example 16.

Modes for Carrying Out the Invention

[0010] Symbols and abbreviations in this specification can be understood in the context of this specification and in the meaning commonly used in the technical field to which the present invention pertains, unless otherwise specifically limited.

[0011] In this specification, the term "comprising" is used with the intention of including the terms "consisting essentially of" and "consisting of".

[0012] The processes, treatments, or operations described in this specification can be carried out at room temperature, unless otherwise specified. In this specification, room temperature can mean a temperature of 10°C to 40°C.

[0013] Oral retention composition The oral retention composition contains (1) a functional substance, (2) at least one compound selected from the group consisting of shellac and zein (also referred to as "coating compound" in this specification), and (3) an acidic polysaccharide. The functional substance is coated with the coating compound, and the coated functional substance (also referred to as "coated functional substance" in this specification) is mixed with the acidic polysaccharide to form the oral retention composition.

[0014] The oral retention composition may have a function in the oral cavity such that the functional substance stays longer compared to the case where the acidic polysaccharide is not used and the functional substance is not coated with the coating compound. For this reason, the oral retention composition can be used to allow the functional substance to stay in the oral cavity for a longer time, so as to exert the action of the functional substance in the oral cavity for a long time.

[0015] functional substances The functional substance can be a substance having oral functionality, that is, a property of exerting the function of the functional substance on the living body by being present in the oral cavity. In the oral retention composition of the present invention, the functional substance is coated with the coating compound, and by mixing the coated functional substance with the acidic polysaccharide, the retention time in the oral cavity is prolonged, and its function can be exerted for a longer time, and the function of imparting retention of the acidic polysaccharide is not significantly impaired. The functional substance can be used alone or in combination of two or more.

[0016] Functional substances may be substances that have functions such as preventing or suppressing periodontal disease, gingivitis, dental caries, bad breath, dry mouth, or depression. For this reason, functional substances may have, for example, bactericidal action, bacteriostatic action, biofilm formation inhibitory action, anti-inflammatory action, immunomodulatory action, tissue regeneration promoting action, etc., and preferably bactericidal action, biofilm formation inhibitory action, etc.

[0017] In one embodiment, at least one selected from the group consisting of basic substances (basic functional substances), polyphenols, and lactic acid bacteria may be used as the functional substance. Normally, when acidic polysaccharides are mixed with basic functional substances, polyphenols, or lactic acid bacteria, their retention-enhancing function is greatly reduced. However, in the present invention, the reduction in retention-enhancing function can be suppressed by coating the functional substance with a coating compound.

[0018] Basic substances are, for example, functional substances having an amino group. Basic substances may include peptides such as protamine hydrolysates, amino acids such as arginine, amino sugars such as glucosamine, amino group-containing polysaccharides such as chitosan, and polyamines such as spermine. Examples of basic substances include protamine hydrolysates, arginine, lysine, glucosamine, chitosan, spermine, spermidine, putrescine, piperine, organic compounds containing divalent cations (calcium, magnesium, iron, etc.), and inorganic compounds containing divalent cations (calcium, magnesium, iron, etc.). Preferably, the basic substance is at least one selected from the group consisting of protamine hydrolysates, arginine, lysine, glucosamine, and chitosan; more preferably, at least one selected from the group consisting of protamine hydrolysates, arginine, lysine, glucosamine, and chitosan; and particularly preferably, at least one selected from the group consisting of arginine, lysine, glucosamine, and chitosan.

[0019] Protamine is a strongly basic protein that exists as a nucleoprotamine bound to deoxyribonucleic acid in the sperm nuclei of fish such as salmon, herring, and trout. Protamine hydrolysates can be produced by degrading protamine by hydrolysis, physical cleavage (e.g., sonication), etc. Hydrolysates obtained by enzymatic hydrolysis of protamine are preferred. Details of protamine hydrolysates and methods for producing protamine hydrolysates are described in Patent Document 1, and the same applies in this specification.

[0020] Organic compounds containing divalent cations (calcium, magnesium, iron, copper, etc.) include heme iron, calcium pantothenate, calcium gluconate, and zinc gluconate. Organic mixtures include zinc yeast, selenium yeast, manganese yeast, and chromium yeast, which can be used individually or in combination of two or more.

[0021] Inorganic compounds containing divalent cations (such as calcium, magnesium, iron, and copper) include magnesium chloride, calcium hydroxide, calcium acetate, calcium carbonate, iron oxide, magnesium sulfate, zinc sulfate, and calcium silicate, which can be used individually or in combination of two or more.

[0022] Polyphenols may be substances having two or more hydroxyl groups bonded to an aromatic ring. Polyphenols may have antibacterial, bad breath suppressing, and anti-inflammatory effects. Polyphenols may have antibacterial, bad breath suppressing, and anti-inflammatory effects in the oral cavity. Examples of polyphenols include polyphenol compounds, lignan compounds, propolis, finely ground polyphenol-containing plants, and polyphenol-containing extracts obtained by extracting plants with hot water and / or organic solvents (e.g., methanol, ethanol, acetone, etc.). They can be used individually or in combination of two or more.

[0023] Examples of polyphenol compounds include chlorogenic acid, quercetin, resveratrol, tannic acid, caffeic acid, caffeic acid phenethyl ester, hydroxytyrosol, oleuropein, gallic acid, eugenin, daidzein, procyanidin, theaflavin, catechins (catechin, epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, etc.), anthocyanidins (cyanidin, delphinidin, etc.), morin, taxifolin, and manniflavanone. Preferably, polyphenol compounds include chlorogenic acid, quercetin, resveratrol, tannic acid, catechins, anthocyanidins, caffeic acid, gallic acid, eugenin, procyanidin, and theaflavin, with chlorogenic acid, quercetin, resveratrol, tannic acid, catechins, and anthocyanidins being more preferred. Polyphenol compounds can be used individually or in combination of two or more.

[0024] Examples of lignan compounds include syringin (eleutroside B), eleutroside E, dehydrodiconiferyl alcohol, dihydrodehydrodiconiferyl alcohol, syringaresinol, pinoresinol, epoxylioniresinol, lioniresinol, lariciresinol, secoisolariciresinol, matairesinol, sesamin, sesaminol, sesamolinol, etc., with syringin (eleutroside B) and eleutroside E being preferred. Lignan compounds can be used individually or in combination of two or more.

[0025] Plants containing polyphenols may be plants containing polyphenol compounds. Examples of plants containing polyphenols include tea (green tea, black tea, bitter tea, etc.), blackcurrant, coffee beans, guava, blueberries, apples, persimmons, lychees, chestnuts, grapes, cacao, Garcinia, Eleutherococcus senticosus, etc., and they can be used individually or in combination of two or more.

[0026] The plant extract containing polyphenols may be an extract obtained by extracting the polyphenol-containing plant with hot water, an organic solvent, etc., and is preferably a hot water extract, methanol extract, ethanol extract, aqueous methanol extract, aqueous ethanol extract, etc. Examples of plant extracts containing polyphenols include tea (green tea, black tea, Kuding tea, etc.) extract, blackcurrant extract, raw coffee bean extract, guava extract (preferably leaf extract), blueberry extract (preferably leaf extract), olive extract (preferably leaf extract), lychee extract, sword bean extract, bamboo grass extract, etc. Preferably, green tea extract, blackcurrant extract, raw coffee bean extract, guava extract (preferably leaf extract), blueberry extract (preferably leaf extract), Eleutherococcus senticosus extract, etc. The plant extract containing polyphenols can be used individually or in combination of two or more.

[0027] The polyphenols may be at least one selected from the group consisting of chlorogenic acid, quercetin, resveratrol, tannic acid, caffeic acid, caffeic acid phenethyl ester, hydroxytyrosol, oleuropein, gallic acid, eugenin, catechin, daidzein, procyanidin, theaflavin, polyphenol-containing plant extracts, propolis, champignon extract, syringin, and eleuthroside E.

[0028] Lactic acid bacteria can be live or dead. Lactic acid bacteria can be in any form, but solid or powder form is preferred, and powder form is more preferred.

[0029] In one embodiment, the functional substance is at least one selected from the group consisting of protamine hydrolysate, arginine, lysine, glucosamine, chitosan, chlorogenic acid, quercetin, resveratrol, tannic acid, catechins, anthocyanidins, caffeic acid, gallic acid, eugenin, procyanidins, theaflavins, syringin, eleuthroside E, lactic acid bacteria, tea extract, blackcurrant extract, green coffee bean extract, guava extract (preferably leaf extract), blueberry extract (preferably leaf extract), olive extract (preferably leaf extract), lychee extract, sword bean extract, and bamboo grass extract.

[0030] In other embodiments, the functional substance is at least one selected from the group consisting of protamine hydrolysates, arginine, lysine, glucosamine, chitosan, chlorogenic acid, quercetin, resveratrol, tannic acid, catechins, anthocyanidins, syringin, eleuthroside E, lactic acid bacteria, green tea extract, blackcurrant extract, green coffee bean extract, guava extract (preferably leaf extract), and blueberry extract (preferably leaf extract).

[0031] The content of the functional substance in the oral cavity retention composition can be, for example, 0.1% to 80% by mass, 0.1% to 50% by mass, etc., relative to the total mass of the composition, preferably 1% to 40% by mass, and preferably 1% to 20% by mass. When the content is within this range, the retention of the functional component in the oral cavity is good.

[0032] Coating compound The coating compound is at least one compound selected from the group consisting of shellac and zein. By coating a functional substance with the coating compound to form a coated functional substance, the functional substance is less likely to impair the retention-granting function of acidic polysaccharides. In the present invention, the coating compound only needs to coat a functional substance such as a protamine hydrolysate, and in addition, components constituting the oral cavity retention composition other than the functional substance may also be coated with the coating compound.

[0033] In this specification, "coating" refers to a state in which part or all of the surface of an object to be coated (e.g., a functional substance, etc.) is covered with a coating (e.g., a coating containing a coating compound, etc.). Furthermore, coating also includes embodiments in which the object to be coated is contained within the coating, such as when an acidic polysaccharide or other component is coated using a liquid containing the object to be coated and the coating compound. For example, even if part or all of an acidic polysaccharide is coated with ethanol or aqueous ethanol containing protamine hydrolysate and shellac, if part or all of the surface of the protamine hydrolysate is covered with shellac, it falls under the category of shellac-coated protamine hydrolysate.

[0034] The degree of coating can be as achievable by a general granulation method, and it is not necessary for 100% of the surface of the functional material to be coated with the coating compound. The degree of coating can be, for example, 50% or more, 60% or more, 70% or more, 80% or more, 85% or more, 90% or more, 95% or more, preferably 97% or more, more preferably 98% or more, even more preferably 99% or more, and particularly preferably 100%. The degree of coating can be determined by image analysis using X-ray CT. The details of the determination method are as follows. Since X-ray CT measurement can visualize the surface and interior of a material and output it as a 3D image, the surface state of the material after coating can be clarified by measuring the material before and after coating. First, the material before coating is measured with X-ray CT and a 3D image is output. Next, a 3D image is output in the same way for the coated material. The area of ​​the differing parts, i.e., the coated part, is calculated by software by comparing the two images. The coating rate is calculated by dividing this area by the total area of ​​the material.

[0035] Shellac is preferred as the coating compound due to its high drying efficiency. Shellac is used as a gloss enhancer, masking agent, coating agent, etc. in fields such as food and quasi-drugs, and can also be used in the present invention.

[0036] Zein is used as a coating agent in fields such as food and pharmaceuticals, and it can also be used in the present invention.

[0037] The content of the coating compound in the oral cavity retention composition can be, for example, 0.001% to 40% by mass, 0.001% to 25% by mass, 0.01% to 20% by mass, 0.01% to 15% by mass, etc., relative to the total mass of the composition, preferably 0.001% to 10% by mass, and more preferably 0.01% to 8% by mass. When the content is within this range, the retention of the functional components in the oral cavity is good. Furthermore, the content of the coating compound can be, for example, 0.1 to 50 parts by mass, 1 to 40 parts by mass, etc., relative to 100 parts by mass of the functional substance, preferably 1 to 30 parts by mass, and more preferably 1 to 20 parts by mass.

[0038] acidic polysaccharide Acidic polysaccharides have the function of imparting oral retention properties to functional substances. Acidic polysaccharides are mixed with coating functional substances to form oral retention compositions. By mixing acidic polysaccharides with coating functional substances, adverse effects on the function of the functional substance that imparts oral retention properties (e.g., viscosity) can be suppressed.

[0039] Examples of acidic polysaccharides include carrageenan, hyaluronic acid, xanthan gum, sodium alginate, pectin, and gum arabic, which can be used individually or in combination of two or more. Preferred acidic polysaccharides are carrageenan, hyaluronic acid, xanthan gum, and sodium alginate, while more preferred acidic polysaccharides are carrageenan, hyaluronic acid, gum arabic, and sodium alginate. Among these, carrageenan and sodium alginate are particularly preferred because they can extend the retention time of the functional substance in the oral cavity.

[0040] The content of acidic polysaccharides in the oral cavity retention composition can be, for example, 0.1% to 90% by mass, 1% to 90% by mass, 0.1% to 60% by mass, 1% to 60% by mass, etc., relative to the total mass of the composition, and preferably 1% to 30% by mass. A content within this range is preferable because it can lengthen the oral cavity retention time of the functional substance.

[0041] The oral cavity retention composition may contain excipients in addition to the coating functional substance and acidic polysaccharides. When the oral cavity retention composition is made into granules, tablets, or finely ground products, it is preferable to include excipients because this improves moldability.

[0042] The average particle size (D50) of the oral cavity retention composition can be, for example, 1 μm to 5000 μm, 1 μm to 400 μm, etc., preferably 10 μm to 1000 μm, more preferably 50 μm to 400 μm, and particularly preferably 1 μm to 400 μm. The average particle size is determined by the method described in the <Method for Measuring Particle Size> section of the Examples.

[0043] Excipients can be appropriately selected from those usable in fields such as food, pharmaceuticals, and quasi-drugs, depending on the shape, application, granulation method, etc. The amount of excipient used should be the amount necessary to form the desired shape, etc., but for example, per 1 mass of the total of the functional substance, coating compound and acidic polysaccharide, the amount can be 90 parts or less, 80 parts or less, 70 parts or less, 0.001 to 90 parts, 0.001 to 80 parts, 0.001 to 70 parts, 0.01 to 90 parts, 0.01 to 80 parts, 0.01 to 70 parts, etc.

[0044] The oral retention composition is preferably in the form of granules, powder, or tablets, with granules and powder being more preferred. When these forms are taken or ingested as granular tablets, powders, tablets, orally disintegrating tablets, effervescent tablets, capsules, etc., they are referred to as oral retention compositions, and oral products and oral products containing oral retention compositions of these forms are referred to as oral compositions and oral compositions, respectively. For example, oral compositions and oral compositions can generally function as products even without containing an oral retention composition, but they may be supplemented with an oral retention composition in anticipation of its function in the oral cavity and its retention within the oral cavity.

[0045] Oral retention compositions can be used as materials for manufacturing oral compositions or oral compositions. Oral compositions or oral compositions can be manufactured by applying methods commonly used for the manufacture of oral compositions or oral compositions to the oral retention compositions and other materials used in the oral compositions or oral compositions. For example, oral retention compositions in granular form can be used in the manufacture of chewing gum, candy, gummies, etc., containing the oral retention compositions in granular form.

[0046] Oral composition Examples of oral compositions include oral care products such as granules, toothpaste, oily ointments, and film preparations; pharmaceuticals (such as lozenges); quasi-drugs (such as lozenges); and compositions applied to the mouth that are not contained in food, such as chewable tablets. Preferably, these are granules, lozenges, and chewable tablets. Uses of oral compositions include suppressing bad breath, prolonging flavor, and masking flavors. Examples of bad breath suppression uses include suppressing bad breath while wearing a mask and suppressing bad breath upon waking.

[0047] The content of the oral cavity retention composition in the oral composition can be appropriately selected according to the product form, usage form, final concentration of the functional substance, etc., and it is not necessarily appropriate to uniformly define a range, but for example it can be 0.1% to 50% by mass, 0.1% to 40% by mass, 1% to 50% by mass, 1% to 40% by mass, 0.1% to 30% by mass, and preferably 1% to 30% by mass, more preferably 1% to 20% by mass.

[0048] Oral compositions can be obtained by adding oral retention compositions to known oral compositions, or by substituting some or all of the components of known oral compositions with oral retention compositions. There are no particular limitations, but they can be manufactured by appropriately modifying the manufacturing method of known oral compositions.

[0049] Oral composition Examples of oral compositions include oral ingestible compositions (mainly foods) such as chewing gum, hard candy, soft candy, gummies, jelly, chewable tablets, and ramune candy. Preferably, these are foods that are not swallowed immediately but remain in the oral cavity for a certain period of time, and foods that are expected to have functional substances adhere to the teeth or gums when chewed, such as chewing gum, hard candy, soft candy, and gummies. Uses of oral compositions include suppressing bad breath, prolonging flavor, and masking flavors. Examples of bad breath suppression uses include suppressing bad breath while wearing a mask and suppressing bad breath upon waking.

[0050] The content of the oral retention composition in the oral composition can be appropriately selected depending on the product form, usage, and final concentration of the functional substance of the oral composition, and it is not necessarily appropriate to define a uniform range, but for example it can be 0.1% to 50% by mass, 0.1% to 40% by mass, 1% to 50% by mass, 1% to 40% by mass, 0.1% to 30% by mass, 0.5% to 20% by mass, and preferably 1% to 30% by mass, more preferably 1% to 20% by mass.

[0051] Oral compositions can be obtained by adding oral retention compositions to known oral compositions, or by substituting some or all of the components of known oral compositions with oral retention compositions. There are no particular limitations, but they can be produced by appropriately modifying the manufacturing methods of known oral compositions (especially food products).

[0052] Method for manufacturing oral cavity retention composition A method for producing an oral cavity retention composition comprising at least one compound selected from the group consisting of shellac and zein, a functional substance, and an acidic polysaccharide, wherein the functional substance coated with at least one compound selected from the group consisting of shellac and zein is mixed with the acidic polysaccharide, is: Step 1 involves mixing at least one compound selected from the group consisting of shellac and zein, which are dissolved or dispersed in a solvent, with a functional substance to coat the functional substance, and The process includes step 2, in which a functional substance coated with at least one compound selected from the group consisting of shellac and zein obtained in step 1 is mixed with an acidic polysaccharide.

[0053] In step 1, the functional substance is coated with a coating compound. For example, the coating compound can be dissolved or dispersed in a solvent and mixed with the functional substance. If necessary, the liquid component can be removed after mixing to obtain the coated functional substance.

[0054] The amount of coating compound used can be, for example, 0.1 to 50 parts by mass, 1 to 40 parts by mass, etc., per 100 parts by mass of the functional substance, preferably 1 to 30 parts by mass, and more preferably 1 to 20 parts by mass.

[0055] Water, ethanol, and aqueous ethanol can be used as solvents, with ethanol and aqueous ethanol being preferred. For example, aqueous ethanol with an ethanol concentration of 60% to 99% (v / v), preferably 60% to 95% (v / v), and more preferably 80% to 90% (v / v) can be used. The amount of solvent used can be, for example, 5 to 40 parts by mass, preferably 10 to 30 parts by mass, per 1 part by mass of the coating compound.

[0056] When the coating compound is shellac, ethanol is preferred as the solvent due to its ease of solubility. When the coating compound is zein, aqueous ethanol with an ethanol concentration of 60% to 99% (v / v) is preferred, and aqueous ethanol with an ethanol concentration of 80% to 90% (v / v) is more preferred, due to its ease of solubility.

[0057] The mixing method is not limited as long as the coating compound coats the surface of the functional material, but examples include dry granulation and wet granulation, with wet granulation being preferred. After mixing, the liquid component may be removed. Examples of removal methods include hot air drying (25°C to 100°C) and vacuum drying.

[0058] In step 2, a functional substance coated with at least one compound selected from the group consisting of shellac and zein obtained in step 1 is mixed with an acidic polysaccharide. Excipients may be added as needed.

[0059] The amount of acidic polysaccharide used can be, for example, 0.1 to 50 parts by mass, preferably 1 to 30 parts by mass, per 1 part by mass of the coating functional material.

[0060] The mixing method can be any known method applicable to the shape of the oral cavity retention composition, depending on its shape. For example, one method involves mixing and stirring the coating functional substance with powdered acidic polysaccharides, and then adding alcohol such as ethanol or aqueous alcohol such as aqueous ethanol to granulate the mixture. Mixing the functional substance and acidic polysaccharides while adding aqueous alcohol (preferably dropwise) is preferable in terms of mixing efficiency.

[0061] The alcohol can be, for example, ethanol, methanol, etc., and is preferably ethanol. The aqueous alcohol can be, for example, aqueous ethanol, aqueous methanol, etc., and is preferably aqueous ethanol. The alcohol concentration of the aqueous alcohol can be, for example, 50% to 99%, 50% to 95% (v / v), etc., preferably 70% to 95% (v / v), and more preferably 80% to 90% (v / v). [Examples]

[0062] The following describes in more detail one embodiment of the present invention by reference to examples, but the present invention is not limited to these. In the examples, "mass%" means "%(w / w)" unless otherwise specified. The following materials were used in the examples.

[0063] Carrageenan: SATIAGUM MM30; Unitech Foods Co., Ltd. Protamine hydrolysate: HAP100; Maruha Nichiro Corporation. This is a hydrolysate of protamine hydrochloride (product name: Protamine, Maruha Nichiro Corporation) derived from chum salmon milt, produced by bromelain (Amano Enzyme Co., Ltd.), and contains four basic peptides. Arginine: L-arginine; Ajinomoto Co., Inc. Glucosamine: MSM60; Bioactives Japan Co., Ltd. Chitosan: Koyo Chitosan FM-80; Koyo Chemical Co., Ltd. N-acetylglucosamine: Bio-NAG; BHN Corporation Propolis: Propolis extract powder; Nippon Beekeeping Co., Ltd. Royal Jelly: Royal Jelly FD Powder; Nakahara Co., Ltd. Green tea extract (green tea extract powder): Theafran 30A; Ito En Co., Ltd., Sunphenon 90S; Taiyo Kagaku Blackcurrant extract (blackcurrant extract powder): Active Blackcurrant Extract 35; Tama Chemical Co., Ltd. Coffee bean extract (green coffee bean extract powder): Phytopharma Co., Ltd. Blueberry extract (blueberry leaf extract powder): Bizen Kasei Co., Ltd. Guava extract (guava leaf extract powder): Bizen Kasei Co., Ltd. Chlorogenic acid: 08416-14; Nacalai Tesque Co., Ltd. Tannic acid: 40001-32; Kanto Chemical Co., Ltd. Quercetin: P0042; Tokyo Chemical Industry Co., Ltd. Resveratrol: Fujifilm Wako Pure Chemical Corporation Shellac: Gifu Shellac Co., Ltd. Zein (corn hydrolysate): Kobayashi Zein DP-N; Kobayashi Fragrance Co., Ltd. HPMC (Hydroxypropyl Methylcellulose): Metholose SE-06; Shin-Etsu Chemical Co., Ltd. Hyaluronic acid: Hyaluronic acid RV; Nippon Shinyaku Co., Ltd. Xanthan gum: Bistop; San-Ei Gen Co., Ltd. Sodium alginate: Sodium alginate I-1; Kimika Co., Ltd. Crystalline cellulose: FD-F20; Asahi Kasei Corporation, VIVAPUR101; Sucralose: Sunsweet 200; San-Ei Gen FFI Co., Ltd. Aspartame: Pal Sweet; Ajinomoto Co., Inc. Xylitol: Xylitol; Mitsubishi Corporation Foodtech Co., Ltd. Lactitol: Lactitol MC; Mitsubishi Corporation Foodtech Co., Ltd. Eleutherococcus senticosus extract powder: UKOGIN; Bizen Kasei Co., Ltd. Epigallocatechin gallate standard; Fujifilm Wako Pure Chemical Corporation Syringin: Purity 95% or higher; CAYMAN CHEMICAL COMPANY Eleuthroside E: Purity 98% or higher; Sigma-Aldrich Spermidine: Purity 95% or higher; Fujifilm Wako Pure Chemical Corporation Fine-particle silicon dioxide: Silopage 720; Fuji Silicia Chemical Co., Ltd. Calcium stearate: Eika Shoji Lactic acid bacteria powder: L8020 lactic acid bacteria powder; Bizen Kasei Co., Ltd.

[0064] Test Example 1: Viscosity Change of Acidic Polysaccharides by Functional Substances The viscosity of acidic polysaccharides is important for their retention in the oral cavity. The viscosity of acidic polysaccharides was measured and evaluated as follows. Measurement device: An inclined surface was created by tilting an 18cm x 32cm plastic plate at a 10° angle to the horizontal plane using a protractor. Measurement: 300 μL of the sample was dropped onto a designated point on an inclined surface, and the distance the sample had traveled (advance distance) was measured after 3 minutes. Samples: An aqueous solution containing 1% by mass of an acidic polysaccharide was used as the control sample, an aqueous solution containing a predetermined amount of a functional substance and an acidic polysaccharide (1% by mass of acidic polysaccharide) was used as the uncoated sample, and an aqueous solution containing a predetermined amount of a functional substance and an acidic polysaccharide coated with a coating compound (1% by mass of acidic polysaccharide) was used as the coated sample. Evaluation method: The progress distance (mm) of the control sample was set to D0, the progress distance (mm) of the uncoated sample to D1, and the progress distance (mm) of the coated sample to D2. The relative progress (RD) was calculated using the following formula. Relative progress (RD) = (D2 - D0) / (D1 - D0) When RD < 1.0, it indicates that the viscosity reduction of the acidic polysaccharide aqueous solution caused by the functional substance was suppressed by the coating. When RD > 1.0, it indicates that the viscosity reduction of the acidic polysaccharide aqueous solution caused by the functional substance was promoted by the coating. When RD = 1.0, it indicates that the viscosity of the acidic polysaccharide aqueous solution did not change with or without the coating. Results with an RD value greater than 0.9 were evaluated as "-" because the viscosity reduction could not be suppressed or was only slightly suppressed, and results with an RD value of 0.9 or less were evaluated as "○" because the viscosity reduction was suppressed.

[0065] Control samples, uncoated samples, and coated samples were prepared as follows and used to evaluate the viscosity of carrageenan aqueous solutions. The results are shown in Table 1. Acidic polysaccharides were dissolved in water to prepare a 1% by mass aqueous solution, which was used as a control sample. Separately, the same solution as the control sample was prepared, and the functional substance was added and mixed at a concentration of 0.75% by mass (0.68% by mass in the case of protamine hydrolysate). The resulting solution was used as the uncoated sample. Separately, ethanol in which shellac was dissolved at a concentration of 25% by mass was added dropwise to the powdered functional substance. The amount of shellac added was such that the amount of shellac was 10% by mass relative to the mass of the functional substance. After thorough mixing, the mixture was dried in a dryer at 50°C to prepare a granular coated functional substance. The amount of coated functional substance with a functional substance concentration of 0.75% by mass (0.68% by mass in the case of protamine hydrolysate) was mixed with 20 g of the same solution as the control sample (1% by mass aqueous solution of acidic polysaccharides) to obtain the solution which was used as the coated sample.

[0066] [Table 1]

[0067] Protamine hydrolysates The viscosity of carrageenan decreased significantly upon mixing with uncoated protamine hydrolysate (D1-D0 in Example 1 was 17 mm), showing a significant decrease compared to the original viscosity of carrageenan. Patent Document 1 suggested that carrageenan and protamine hydrolysate reacted and adsorbed, and that xanthan gum, an acidic polysaccharide similar to carrageenan, also reacted and adsorbed with protamine hydrolysate, resulting in a decrease in the antibacterial activity of the protamine hydrolysate. However, it had not shown that changes in the viscosity of acidic polysaccharides occurred, making this a new finding.

[0068] On the other hand, when the protamine hydrolysate coated with shellac was evaluated, the change in viscosity was reduced (the D2-D0 value in Example 1 was 4 mm), and it was close to the viscosity of carrageenan itself. The RD value was less than 0.9, suggesting that the shellac coating inhibited the reaction and adsorption between the protamine hydrolysate and carrageenan. Since Patent Document 1 confirms antibacterial activity with neutral polysaccharides that have low adsorption rates, it was considered that the inhibition of reaction and adsorption by shellac coating sufficiently reduces the inhibition of the antibacterial activity of the protamine hydrolysate by acidic polysaccharides, and also sufficiently suppresses the decrease in viscosity of acidic polysaccharides.

[0069] Basic functional substances Next, the basic substances arginine, glucosamine, and chitosan also reduced the viscosity of carrageenan (D1-D0 in Examples 2-4 was 16-19 mm), suggesting that they reacted with carrageenan in a similar manner to protamine hydrolysates. On the other hand, N-acetylglucosamine (a neutral compound), a derivative of glucosamine, did not cause a change in the viscosity of carrageenan (D1-D0 in Comparative Example 1 was 1 mm). These results clearly indicate that basic compounds react with carrageenan and reduce its viscosity.

[0070] In samples containing arginine, glucosamine, or chitosan coated with shellac, the decrease in viscosity was reduced, similar to Example 1, and the viscosity was close to the intrinsic properties of carrageenan (D2-D0 was 3 or 4 mm in Examples 2-4). The RD value was less than 0.9, indicating that shellac coating inhibited the reaction and adsorption of basic functional substances with carrageenan. It was considered that the inhibition of reaction and adsorption by shellac coating sufficiently reduced the inhibition of biofilm formation inhibitory activity of functional substances by acidic polysaccharides, and also sufficiently suppressed the decrease in viscosity of acidic polysaccharides. On the other hand, the RD value of N-acetylglucosamine was 1, indicating no reactivity with carrageenan.

[0071] Plant extracts, propolis, and royal jelly Green tea extract, blackcurrant extract, coffee bean extract, guava extract, blueberry extract, and propolis reduced the viscosity of carrageenan, similar to basic functional substances (D1-D0 in Examples 5-10 ranged from 16-35 mm), suggesting they reacted with carrageenan in the same way as protamine hydrolysates. On the other hand, royal jelly had an RD value of 1, and there was almost no difference between D1 and D0, suggesting it did not react with carrageenan.

[0072] In samples containing plant extracts or propolis coated with shellac, the decrease in viscosity was reduced, similar to Example 1, and the viscosity was close to the intrinsic properties of carrageenan (D2-D0 for Examples 5-10 was 2-7 mm). The RD value was less than 0.9, indicating that shellac coating inhibited the reaction and adsorption between plant extracts and propolis and carrageenan. It was considered that the inhibition of reaction and adsorption by shellac coating sufficiently reduced the inhibition of the antibacterial activity of functional substances by acidic polysaccharides, and also sufficiently suppressed the decrease in viscosity of acidic polysaccharides. On the other hand, the RD value of N-acetylglucosamine was 1, indicating no reactivity with carrageenan.

[0073] Plant extracts generally contain polyphenols, and the five extracts examined are known to be rich in catechins, anthocyanins, chlorogenic acid, and tannic acid. Propolis is also known to contain many flavonoids, which are polyphenols. Royal jelly, on the other hand, is a bee secretion like propolis, but does not contain flavonoids. The fact that substances relatively rich in polyphenols, such as plant extracts and propolis, react with carrageenan and reduce its viscosity is a first-of-its-kind finding. It is thought that polyphenol compounds react with carrageenan to cause a decrease in viscosity.

[0074] Test Example 2: Viscosity Change of Acidic Polysaccharides by Polyphenol Compounds Chlorogenic acid, tannic acid, quercetin, and resveratrol were prepared as polyphenol compounds, and their effects on the viscosity of carrageenan were measured to evaluate their reactivity.

[0075] The measuring apparatus, measurement, control sample, and D0 were the same as in Test Example 1. A methanol aqueous solution containing a polyphenol compound was prepared by dissolving the polyphenol compound in an aqueous methanol solution (methanol concentration 50% by mass), and this solution was made up to 1 mg / mL. 200 μL of this solution was added to 20 g of the same solution as the control sample (a 1% by mass aqueous carrageenan solution) and mixed uniformly, and the resulting solution was used as the uncoated sample. Furthermore, a solution obtained in the same manner as the uncoated sample, except that the methanol aqueous solution containing the polyphenol compound was replaced with a 50% (v / v) methanol aqueous solution, was used as the methanol sample. Evaluation method: The progress distance (mm) of the control sample was set to D0, the progress distance (mm) of the uncoated sample to D1, and the progress distance (mm) of the methanol sample to D1M. The reactivity index (RI) of polyphenol compounds and carrageenan was calculated using the following formula. Reactivity index (RI) = (D1 - D0) / (D1M - D0)

[0076] In this test system, since an aqueous solution is added, a certain decrease in viscosity occurs due to the dilution effect. Therefore, the above determination method was adopted to detect the change in viscosity caused by the polyphenol-based compound. The ±10% of the RI value was set as the error range (that is, 0.9 - 1.1 of the RI value is the error range).

[0077] When RI > 1.1, it indicates that the viscosity of carrageenan has decreased due to the polyphenol-based compound. When 0.9 ≤ RI ≤ 1.1, it indicates that there is no change in the viscosity of carrageenan due to the polyphenol-based compound. When RI < 0.9, it indicates that the viscosity of carrageenan has increased due to the polyphenol-based compound. The results are shown in Table 2.

[0078]

Table 2

[0079] In the solution of the polyphenol-based compound (uncoated sample), when 50% aqueous methanol solution was added (methanol sample), a greater decrease in viscosity was caused, so the calculated RI values were 2.5 - 4.1. Since these polyphenol-based compounds reduce the viscosity of the carrageenan aqueous solution even at an addition amount of only 10 ppm, and the plant extract is rich in chlorogenic acid, tannic acid, quercetin, resveratrol and their derivatives, it is considered that not only the plant extracts in which the reaction with carrageenan was confirmed in Test Example 1 but also other plant extracts containing polyphenols react with carrageenan and reduce the viscosity.

[0080] Test Example 3: Viscosity Change of Acidic Polysaccharides by Coated Polyphenol Compounds Using chlorogenic acid, tannic acid, quercetin, and resveratrol, which were found by Test Example 2 to react with carrageenan and reduce its viscosity, the inhibitory effect of shellac coating on the reaction was tested.

[0081] Each compound was dissolved in a 50% methanol aqueous solution and made up to a concentration of 10 mg / mL. 50 g of a 10% by mass dextrin aqueous solution (Pinex #100, Matsutani Chemical) was added to 20 mL of the resulting aqueous solution and mixed uniformly. The mixture was then freeze-dried to prepare powders containing each compound (coated functional substances). These powders were mixed with 20 g of a 1% by mass carrageenan aqueous solution to obtain uncoated samples. Separately, an ethanol solution was prepared by dissolving the coated compound in 25% by mass using the same solution as the uncoated samples. To the same solution as the prepared uncoated samples, the prepared ethanol solution was added dropwise in an amount of shellac equal to 10% by mass of the functional substance mass. After thorough mixing, the solution was dried in a 50°C dryer to prepare granular coated functional substances. A coating of the coated functional substance was prepared by mixing an amount of the coated functional substance equal to 0.75% by mass with 20 g of the same solution as the target sample (1% by mass acidic polysaccharide aqueous solution).

[0082] Using the obtained samples, D0, D1, and D2 were measured in the same manner as in Test Example 1, and the RD values ​​were calculated. The results are shown in Table 3.

[0083] [Table 3]

[0084] The polyphenol compounds reacted with carrageenan, reducing the viscosity of the solution (D1-D0 was 25-34 mm). However, coating with shellac suppressed this viscosity reduction, resulting in an RD value of less than 0.9, indicating that the reaction with carrageenan was inhibited. These results are similar to those obtained when using plant extracts in Examples 5-10. Therefore, it is considered that coating the plant extract inhibited the action of the polyphenol compounds in the plant extract on carrageenan, thereby inhibiting the reaction with carrageenan.

[0085] From the above, it was concluded that the viscosity reduction inhibitory effect of coating compounds on acidic polysaccharides is not limited to the examples tested above, but can also be obtained with basic functional substances, polyphenol compounds, plant extracts containing polyphenol compounds, secretions containing flavonoids such as propolis, and substances containing these.

[0086] Test Example 4: Concentration and Type of Coating Compound D0, D1, D2, and RD were determined in the same manner as in Test Example 1, except that the concentration of shellac relative to the mass of the functional substance was changed. The shellac concentrations were 1, 5, 10, and 20% by mass relative to the mass of the protamine hydrolysate. In addition, the coated compound was changed to zein or HPMC, and the ethanol solution in which the coated compound was dissolved at 25% by mass was changed to an 80% (v / v) aqueous ethanol solution in which zein or HPMC was dissolved at 25% by mass, except that D0, D1, D2, and RD were determined in the same manner as in Test Example 1. The functional substance used was protamine hydrolysate at 0.68% by mass, as in Test Example 1. The results are shown in Table 4.

[0087] [Table 4]

[0088] Coating the protamine hydrolysate with 1% by mass of shellac also suppressed the decrease in viscosity of the carrageenan aqueous solution containing the protamine hydrolysate (RD was 0.6 in Example 15). The decrease in viscosity was suppressed in a manner dependent on the amount of shellac added (Examples 15-18). Furthermore, since the RD values ​​for all of Examples 15-18 were less than 0.9, it was found that shellac has an effect of inhibiting the reaction with carrageenan in the range of at least 1-20% by mass of the functional substance.

[0089] Furthermore, coating with zein resulted in an RD value of less than 0.9 (Example 19), confirming that the reaction between protamine hydrolysate and carrageenan was inhibited. In contrast, coating with HPMC promoted the reduction in carrageenan viscosity, and the RD value became greater than 1.1 (Comparative Example 7). HPMC coating was thought to reduce the oral cavity retention of carrageenan.

[0090] Test Example 5: Types of Acidic Polysaccharides The effect of shellac coating on the viscosity of the acidic polysaccharide was measured after substituting carrageenan with other acidic polysaccharides. The procedure was the same as in Test Example 1, except that carrageenan was replaced with hyaluronic acid, xanthan gum, or sodium alginate. The results are shown in Table 5.

[0091] [Table 5]

[0092] The acidic polysaccharides hyaluronic acid, xanthan gum, and sodium alginate reacted with protamine hydrolysates, reducing the viscosity of 1% aqueous solutions. The viscosity reduction for hyaluronic acid and sodium alginate was similar to that of carrageenan (D1-D0 was 17 mm in Example 1) (D1-D0 was 16 or 14 mm in Examples 20 and 22), but xanthan gum showed a particularly large decrease in viscosity (D1-D0 was 43 mm in Example 21). On the other hand, coating with shellac significantly suppressed the viscosity reduction, similar to the case of carrageenan (RD values ​​for Examples 20-22 were 0.3-0.5). It was considered that coating with shellac is effective in suppressing the viscosity reduction of acidic polysaccharides other than carrageenan and the resulting decrease in oral retention.

[0093] Test Example 6: Amount of acidic polysaccharides Granular formulations were prepared according to the formulations shown in Table 6. The units of the values ​​in Table 6 are in mass percent.

[0094] [Table 6]

[0095] Ethanol in which shellac was dissolved at a concentration of 25% by mass was added dropwise to the protamine hydrolysate. The amount added was such that the shellac was 10% by mass relative to the protamine hydrolysate. After thorough mixing, the mixture was dried in a drying oven at 50°C, and the dried product was classified using a No. 60 sieve (mesh size 250 μm) to obtain the granules that passed through the sieve (coated granules). These coated granules were mixed with carrageenan and crystalline cellulose while adding aqueous ethanol with an ethanol concentration of 90% (v / v) dropwise, and the mixture was dried in a drying oven at 50°C. The dried product was classified using a No. 60 sieve (mesh size 250 μm), and the granules that passed through the sieve were used for evaluation. Granules containing uncoated protamine hydrolysate (uncoated granules) were also prepared in the same manner, except that the coated granules were replaced with protamine hydrolysate.

[0096] A sample was prepared by mixing 1 g of coated or uncoated granules with 20 g of water, and the distance traveled was measured in the same manner as in Test Example 1. The coated granules of Examples 23, 24, and 25 had smaller distance traveled (D1) than the uncoated granules of Comparative Examples 8, 9, and 10, respectively. This confirmed that coating functional substances with shellac can suppress viscosity reduction. Although the carrageenan content in Comparative Example 8 and Example 23 was a small 1% by mass, crystalline cellulose is insoluble in water, so the viscosity exhibited upon addition of water can be evaluated as viscosity due to carrageenan.

[0097] Test Example 7: Particle Size of Granular Formulations Granular formulations were prepared in the same manner as in Test Example 6 using formulations with high protamine hydrolysate concentrations as shown in Table 7. The units of the values ​​in Table 7 are mass percent. However, sieves No. 30 (mesh opening 500 μm) and No. 60 (mesh opening 250 μm) were used, and the progress distance was measured in the same manner as in Test Example 1 for two types of granules: those that passed through the No. 30 sieve but not the No. 60 sieve (Example 26) and those that passed through the No. 60 sieve (Example 27). In addition, precise particle size measurements were performed on the granules of Examples 26 and 27. The particle size measurement results are shown in Table 8.

[0098] [Table 7]

[0099] <Method for measuring particle size> Particle size was measured using the equipment and measurement conditions shown below. The measurement principle is a wet laser diffraction / scattering method. During measurement, laser light was detected using a transmission method, and the particle size was calculated assuming a particle refractive index of 1.81 and the sample type was non-spherical particles. Equipment: Microtrac MT3200II (Microtrac Bell Co., Ltd.) Measurement solvent: Isopropanol (solvent refractive index: 1.38) Measurement time: 10 seconds

[0100] [Table 8]

[0101] The results for the cumulative 10% particle size (D10), cumulative 50% particle size (D50), and cumulative 90% particle size (D90) showed that the particle size of the granules remaining on the No. 60 sieve was larger than the particle size of the granules that passed through, and the D50 value, which can be considered as the average particle size, differed by more than four times. On the other hand, the progress distance (D1) of the samples in Examples 26 and 27 was shorter than that of the sample in Comparative Example 11, confirming that the reactivity of protamine hydrolysate and carrageenan was reduced. Furthermore, the relative progress RD (RD value with the sample in Comparative Example 11 as the control sample) of the samples in Examples 26 and 27 were equal, and no difference was observed between the two.

[0102] Based on the above, at least within the D50 range of 78.3 to 362.5 μm, no difference was observed in the effect of shellac coating on inhibiting the reaction between protamine hydrolysates and carrageenan, regardless of particle size. Furthermore, even with a high protamine hydrolysate content of 40%, shellac coating was effective in suppressing the decrease in carrageenan viscosity.

[0103] Test Example 8: Oral cavity retention Viscosity is related to adhesion in the oral cavity. The retention of the granular formulations of Example 27 and Comparative Example 11 in the oral cavity was evaluated. The evaluation was based on the intensity of the ninhydrin reaction shown by saliva, which was considered to represent the amount of peptide derived from protamine hydrolysates (residual amount of protamine hydrolysates).

[0104] Saliva was collected before the test and used as a blank sample. Subsequently, 100 mg of protamine hydrolysate alone, and an amount equivalent to 100 mg of protamine hydrolysate (250 mg) of the granular formulations from Example 27 and Comparative Example 11 were administered onto the tongue, and saliva was collected over time while gently spreading the solution throughout the oral cavity.

[0105] <Measurement of residual protamine hydrolysates> 500 μL of collected saliva, 5.5 mL of purified water, and 1 mL of 0.2% (w / w) ninhydrin aqueous solution were mixed in a test tube, and the test tube was heated in hot water for 10 minutes. The test tube was centrifuged, and the supernatant was collected. The absorbance at 570 nm was measured from the supernatant, and the value obtained by subtracting the value shown for the blank sample was considered to be the absorbance intensity attributable to protamine degradation products. The results are shown in Figure 1.

[0106] In both the sample from Example 27 and the sample from Comparative Example 11, the amount of residual protamine hydrolysate (absorbance intensity) was maximum 2 minutes after administration to the oral cavity. The absorbance intensity at this time was set to 1, and the absorbance intensities obtained from samples taken at other times are shown as relative values ​​in Figure 1. In the case of protamine hydrolysate alone, the presence of protamine hydrolysate could not be confirmed in the saliva sample after 8 minutes, indicating that the residence time was between 5 and 8 minutes. On the other hand, the residence time of the granular formulation from Example 27 was between 30 and 35 minutes, and the residence time of the granular formulation from Comparative Example 11 was between 10 and 12 minutes. From this, it was confirmed that coating with shellac significantly extended the oral cavity residence time of protamine hydrolysate. Furthermore, as shown in Test Example 7, the viscosity reduction was suppressed in the granules of Example 27 compared to Comparative Example 11. This strongly suggests that the compositions of the examples in which the viscosity reduction was suppressed also resulted in a longer oral retention time for the functional substance compared to the case without coating.

[0107] Test Example 9: Viscosity Change of Acidic Polysaccharides by Eleutherococcus senticosus Extract Powder The viscosity of acidic polysaccharides was measured and evaluated in the same manner as in Test Example 1, except that Eleutherococcus senticosus extract powder was used as the functional substance.

[0108] [Table 9]

[0109] The Eleutherococcus senticosus extract powder reduced the viscosity of carrageenan, similar to Examples 1-10 (D1-D0 values ​​for Examples 5-10 were 16-35 mm), suggesting that it reacted with carrageenan in the same way as green tea extract, blackcurrant extract, coffee bean extract, guava extract, and blueberry extract. On the other hand, the shellac-coated Eleutherococcus senticosus extract powder showed reduced viscosity reduction, similar to Examples 1-9, and the viscosity approached the original properties of carrageenan (D2-D0 values ​​for Examples 5-10 were 2-7 mm). The RD value was less than 0.9, indicating that shellac coating inhibited the reaction and adsorption with carrageenan. It was also considered that the inhibition of reaction and adsorption by shellac coating sufficiently suppressed the decrease in viscosity of acidic polysaccharides. Eleutherococcus senticosus extract powder is rich in lignan compounds such as syringin (eleuthroside B) and eleuthroside E, coumarin compounds such as isofraxidin, and polyphenol compounds such as chlorogenic acid, and it is thought that these reacted with carrageenan, an acidic polysaccharide.

[0110] Test Example 10: Viscosity changes of acidic polysaccharides due to polyphenol compounds, lignan compounds, or basic substances. In the same manner as in Test Example 2, epigallocatechin gallate as a polyphenol compound, syringin and eleuthroside E as lignan compounds, and spermidine as a basic substance were prepared, and their effects on the viscosity of carrageenan were measured to evaluate their reactivity. However, for spermidine, an aqueous solution prepared by dissolving it in purified water was used as the sample. The results are shown in Table 10.

[0111] [Table 10]

[0112] In solutions (uncoated samples) containing the polyphenol compound epigallocatechin gallate, the lignan compounds syringin and eleuthroside E, and the basic substance spermidine, the calculated RI values ​​ranged from 1.5 to 4.4, indicating that a mere 10 ppm addition reduced the viscosity of the carrageenan aqueous solution. Epigallocatechin gallate is present in tea leaf extracts such as green tea, black tea, and oolong tea; syringin is abundant in plants of the genus Eleutherococcus senticosus, dandelion, Ilex rotunda, Polytrichum commune, and Saussurea; eleuthroside E is abundant in Eleutherococcus senticosus; and spermidine is abundant in soybeans, adzuki beans, shiitake mushrooms, button mushrooms, bell peppers, peas, pistachios, corn, wheat germ, blue cheese, cod roe, salmon roe, beef intestines, and chicken liver. It was thought that these extracts, as well as other plant extracts, would react with carrageenan and reduce viscosity, in addition to the plant extracts whose reaction with carrageenan was confirmed in Test Examples 1 and 9.

[0113] Test Example 11: Concentration and Type of Coating Compound Except for using green tea extract as the functional substance and specifying the type and concentration of the coating compound as shown in Table 11 below, D0, D1, D2, and RD were determined in the same manner as in Test Example 4. The results are shown in Table 11.

[0114] [Table 11]

[0115] Coating the green tea extract with 1% by mass of shellac suppressed the decrease in viscosity of the carrageenan aqueous solution, and the decrease in viscosity was suppressed in a manner dependent on the amount of shellac added (Examples 29-32). These results demonstrate the reproducibility of the results in Test Example 4, confirming that shellac inhibits the reaction with carrageenan in the range of at least 1-30% by mass relative to the functional substance. Furthermore, coating with zein resulted in an RD value of less than 0.9 (Example 34), confirming that the reaction between the green tea extract and carrageenan was inhibited, thus demonstrating the reproducibility of the zein coating effect.

[0116] Test Example 12: Types of Acidic Polysaccharides The effect of shellac coating on the viscosity of acidic polysaccharides was measured under the same conditions as in Test Example 5, except for those shown in Table 12 below. The results are shown in Table 12.

[0117] [Table 12]

[0118] The acidic polysaccharides hyaluronic acid, xanthan gum, and sodium alginate reacted with green tea extract, reducing the viscosity of the 1% aqueous solution. On the other hand, coating with shellac significantly suppressed the decrease in viscosity, similar to the case with carrageenan. Therefore, coating with shellac was effective in suppressing the decrease in viscosity of acidic polysaccharides other than carrageenan, and consequently suppressing the decrease in oral retention. Furthermore, the results of Test Example 5 were also reproducible.

[0119] Test Example 13: Relationship between the amount of acidic polysaccharides and granule hardness Granule preparations were prepared according to the formulations shown in Table 13. The units of the values ​​in Table 13 are grams (g). Ethanol in which shellac was dissolved at a concentration of 25% by mass was added dropwise to the green tea extract. The amount added was such that the shellac was 15% by mass relative to the green tea extract. After thorough mixing, the mixture was dried in a dryer at 50°C, and the dried material was classified using a No. 60 sieve (mesh size 250 μm) to obtain granules that passed through the sieve (coated granules). These coated granules were mixed with carrageenan, and aqueous ethanol with an ethanol concentration of 90% (v / v) was added dropwise at a rate of 40% by mass of the carrageenan amount while further mixing. Subsequently, granulation was performed by extrusion using a stainless steel mesh with a diameter of 1 mm, and the mixture was dried in a dryer at 50°C to prepare granules (Examples 37-40, Comparative Example 16). Similarly, granulation was performed by extrusion using green tea extract that was not coated with shellac to prepare granules (Comparative Examples 17-20). These granules were subjected to the granule strength tests described below.

[0120] [Table 13]

[0121] <Granule Strength Test> All prepared granules (Examples 37-41, Comparative Examples 16-20) were sieved using a 710 μm diameter sieve to remove powder particles smaller than 710 μm, and the granules remaining on the sieve were collected. 5 g of these granules were then placed on a 710 μm diameter sieve, and a forced impact was applied using an electromagnetic sieve vibrator (Retshc AS200 CONTROL) (intensity: 1.5 mm / g, time: 5 minutes). The percentage of particles remaining on the sieve was then calculated. Since particles smaller than 710 μm were removed beforehand, a high percentage of remaining particles indicates high granule strength. The results are shown in Table 14, in %.

[0122] [Table 14]

[0123] The results from Comparative Examples 16-20 showed that the retention rate decreased as the proportion of carrageenan increased, indicating that the granules tended to become brittle. On the other hand, in Examples 37-41, the retention rate was high, indicating that the decrease in granule strength was suppressed. This study revealed that coating with shellac increased the strength of granules prepared together with acidic polysaccharides. This phenomenon had not been reported before and was a new finding. If the granule strength is weak, it can crumble due to vibration during the manufacturing process, and the resulting fine powder can get caught in machinery and packaging materials, causing manufacturing problems; therefore, higher strength is desirable. From this experiment, it was found that the amount of acidic polysaccharide used should preferably be 1 to 30 times the amount of the functional substance, and more preferably 1 to 20 times.

[0124] Test Example 14: Oral Retention Test Using Green Tea Extract Table 15 shows the formulations of tablets with a unit weight of 1000 mg. In Comparative Example 21 and Example 42, tablets were prepared with a total batch weight of 200 g. In Comparative Example 21, the respective raw materials were mixed, and a φ15 mm punch was attached to a rotary tablet press (Kikusui Seisakusho, CLEAN PRESS 19K). Tablets were compressed to a tablet weight of 1000 mg and a rotary rotation speed of 35 rpm. The hardness of the resulting tablets was 10 kgf or more. In Example 42, a zein ethanol solution (80% aqueous solution of ethanol) was added dropwise to green tea extract and lactitol, and the mixture was uniformly mixed by stirring in a high-speed mixer (Fukae Pawtech, LFS-GS-1J) at an agitator rotation speed of 300 rpm and a chopper rotation speed of 1200 rpm. Subsequently, the mixture was dried using a fluidized bed granulator (Freund Industrial Co., FLO-5A) with hot air at room temperature to 90°C, then crushed using a household mill, and classified using a No. 30 sieve (mesh size 600 μm) to obtain granules (coated granules) that passed through the sieve. Carrageenan, HPMC, sorbitol, fine silicon dioxide, and calcium stearate were added and mixed to obtain a powder for tableting. The obtained powder was compressed into tablets in the same manner as in Comparative Example 21 to obtain tablets with a hardness of 10 kgf or more.

[0125] [Table 15]

[0126] <Oral cavity retention test> The test was conducted with three healthy volunteers. First, they rinsed their mouths three times with water held in their mouths, and then saliva at the start (0 minutes) was sampled as a blank sample. Subsequently, they each held one of the tablets of Comparative Example 21 and Example 42 in their mouths, chewed them within 1 minute, and sampled saliva at 10, 20, and 30 minutes later. To evaluate the green tea extract contained in this saliva, a 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity test was conducted to verify the residual property in the oral cavity. In this test, since the saliva at 0 minutes has no DPPH radical scavenging activity and the green tea extract has DPPH radical scavenging activity, the fact that the collected saliva has DPPH radical scavenging activity means that the green tea extract remains in the saliva.

[0127] <DPPH Radical Scavenging Activity Test> First, a 1 mM DPPH / methanol solution was prepared in the dark. This solution was diluted with 50% acetonitrile so that the absorbance at 517 nm was 0.65. 25 μl of 50% acetonitrile was added to 1475 μl of this diluted DPPH / methanol solution, and the mixed solution was used as a blank solution. Subsequently, 100 μl of the sampled saliva and 100 μl of acetonitrile were added and mixed using a vortex mixer. Then, ultrasonic treatment was performed for about 30 seconds, followed by centrifugation at 5000 G for 5 minutes. 25 μl of the supernatant was used as a sample solution, and 1475 μl of the above-mentioned diluted DPPH / methanol solution was mixed using a vortex mixer. After mixing, the reaction was carried out in the dark for 30 minutes, and the absorbance at 517 nm was measured using a spectrophotometer (U-2900 manufactured by Hitachi High-Technologies Corporation), and the radical scavenging ability was calculated by the following formula.

[0128]

Number

[0129] The results are shown in Figure 2. When comparing Comparative Example 21 and Example 42, Example 42 showed higher radical scavenging ability, resulting in more green tea extract remaining in the oral cavity. It also exhibited higher retention performance than Comparative Example 21, with strong retention in the oral cavity confirmed even after 30 minutes.

[0130] Test Example 15: Verification of bad breath suppression using green tea extract 1 The bad breath suppression effect was verified using the tablets described in Comparative Example 21 and Example 42 above. Changes in bad breath were evaluated by quantitatively analyzing the total amount of volatile sulfur compounds in exhaled breath using Breastron XP (manufactured by Shin-Cosmos Electric). The experimental details are described below.

[0131] <Verification experiment on bad breath suppression> Five healthy volunteers were prohibited from consuming garlic-containing foods the day before the experiment, and on the day of the experiment, they were prohibited from consuming beverages such as coffee and tea, as well as smoking, before the test. First, they gargled three times with water, then wore masks, and the change in bad breath over one hour was measured. After that, they each placed tablets of Comparative Example 21 and Example 42 in their mouths, chewed them within one minute, and continued their normal daily activities while wearing masks. After ingesting the test substances, they were prohibited from eating or drinking, and volatile sulfur compounds in their exhaled breath were quantified every 30 minutes. The results are shown in Figure 3.

[0132] The group that did not take the supplement showed a higher rate of change, indicating a worsening of bad breath over time while wearing a mask. While taking the tablets in Comparative Example 21 slightly suppressed the worsening of bad breath, Example 42 suppressed it even more effectively. As mentioned above, the tablets in Example 42 exhibited the retention of green tea extract in the oral cavity, and it is thought that this suppressed the worsening of bad breath.

[0133] Test Example 16: Verification of bad breath suppression using green tea extract 2 The effectiveness of the tablets described in Comparative Example 21 and Example 42 in suppressing morning breath was verified. For the evaluation of bad breath, the total amount of volatile sulfur compounds in exhaled breath was quantitatively analyzed using Breastron XP (manufactured by Shin-Cosmos Electric). The experimental details are described below.

[0134] <Verification experiment on bad breath suppression> One healthy volunteer was prohibited from consuming garlic-containing foods, coffee, tea, and other stimulants on the evening of the experiment. They brushed their teeth one hour before bedtime, and volatile sulfur compounds were measured immediately after bedtime, one hour later. After six hours of sleep, they woke up and their volatile sulfur compounds were measured again immediately. Similarly, after measuring volatile sulfur compounds before bedtime, they ingested either the tablet from Comparative Example 21 or Example 42, chewed it within one minute, and slept for six hours. Their volatile sulfur compounds were measured again after waking up. The results are shown in Figure 4.

[0135] The results for the group that did not take the tablets show the degree of worsening of bad breath before and after waking up. In Comparative Example 21, tablet intake slightly suppressed the worsening of bad breath, but in Example 42, tablet intake further suppressed the worsening of bad breath upon waking. As mentioned above, the tablets in Example 42 exhibit the retention of green tea extract in the oral cavity, but since the amount of saliva during sleep is very small, it is thought that the retention was further enhanced, suppressing the worsening of bad breath for a longer period of time.

[0136] Test Example 17: Sweetness Persistence Test Using Sweeteners Table 16 shows the formulation of a granular preparation with a unit weight of 100 mg. Based on this formulation, the granular preparations for Examples 43, 44, and 45 were prepared with a total amount of 200 g. An ethanol solution of zein (an 80% aqueous solution of ethanol) was added dropwise to sucralose, aspartame, and xylitol, respectively, and the mixtures were uniformly mixed by stirring in a high-speed mixer at an agitator speed of 300 rpm and a chopper speed of 1200 rpm. After that, the mixtures were dried with hot air at room temperature to 90°C using a fluidized bed granulator (Freund Industrial Co., FLO-5A), crushed using a household mill, and classified using a No. 60 sieve (mesh opening of 250 μm) to obtain the granules (coated granules) that passed through the sieve. Carrageenan and HPMC were added to these granules and the mixtures were uniformly mixed by stirring in the same high-speed mixer as described above. Subsequently, the granules were dried using a fluidized bed granulator (Freund Industrial Co., FLO-5A) with hot air at room temperature to 90°C, then ground using a household mill, and classified using a No. 60 sieve (mesh size 250 μm). The powder that passed through the sieve was obtained. The obtained granules were subjected to the following sensory tests. In addition, the sweetener itself was subjected to sensory tests as comparative examples 22, 23, and 24.

[0137] [Table 16]

[0138] <Sensory Testing> Five healthy volunteers were instructed to refrain from consuming beverages such as coffee and tea, and from smoking, before the study. The study was conducted with these volunteers. Granules containing sucralose or aspartame (Examples 43 and 44) ​​and sweeteners containing comparative examples 22 and 23 were placed on the tongue in amounts corresponding to a 20 mg intake of sucralose or aspartame. Granules containing xylitol (Example 45) and sweeteners containing xylitol (Comparative Example 24) were placed on the tongue in amounts corresponding to a 100 mg intake of xylitol. After ingestion, participants were instructed to behave normally, refrain from eating or drinking during this time, and self-report the time at which they no longer perceived sweetness. This time was recorded. The results are shown in Table 17.

[0139] As shown in Table 17, all examples resulted in a longer-lasting sweetness perception compared to the comparative examples, which were sweeteners themselves. The granular formulations in Examples 43-45 were coated with zein, a coating agent, and the carrageenan extended their retention in the oral cavity, which is thought to have contributed to the longer-lasting sweetness perception. The differences in duration are thought to be due to the sweetness threshold of each sweetener; for example, the threshold for sucralose has been reported to be 0.2 mg / L, suggesting that the lower the taste threshold, the longer the perception of sweetness will last. Similar effects are thought to be observed with other sweeteners, such as thaumatin, curculin, monellin, monatin, miraculin, stevia, glycyrrhizin, neotame, advantame, acesulfame potassium, and saccharin, and it is also thought that they may have a prolonged effect on other tastes, such as saltiness, spiciness, sourness, and umami.

[0140] [Table 17]

[0141] Test Example 18 The degree of bitterness was evaluated using the tablets from Example 42 and Comparative Example 21. The evaluation method is described below.

[0142] <Method for evaluating bitterness> Five healthy volunteers were instructed to refrain from consuming beverages such as coffee and tea, and from smoking, before the test. After gargling with water, they placed the samples in their mouths, chewed them, and evaluated the degree of bitterness sensorily. The samples were one tablet of Example 42 (1000 mg; equivalent to 28.6 mg of green tea extract), one tablet of Comparative Example 21 (1000 mg; equivalent to 28.6 mg of green tea extract), and green tea extract (28.6 mg powder). Each person tested all samples and assigned a score to each. The tests were conducted in the following order: Example 42 tablet, Comparative Example 21 tablet, and green tea extract. The scoring criteria were as follows: The average of the scores from five people was calculated. 1: I hardly taste any bitterness. 2: I can taste a slight bitterness. 3: I taste bitterness 4: I feel a strong bitterness. 5: I feel a very strong bitterness.

[0143] The results are shown in Table 18. The score for Comparative Example 21 was lower compared to the green tea extract raw material itself. This was thought to be due to the masking of bitterness by the sweetness of sorbitol (excipient) used in tablet formation. On the other hand, the score for Example 42 was even lower, becoming half the score compared to the green tea extract raw material itself. This clearly shows that Example 42 has a bitterness masking effect. Although this test evaluated bitterness masking, it is thought that similar masking of saltiness, sourness, astringency, and spiciness is also possible.

[0144] [Table 18]

[0145] Test Example 19: Manufacturing Example of Chewable Tablets (Example 46) Tablets were manufactured in the same manner as in Example 42, except that the amounts of raw materials used were as shown in Table 19, and green tea extract and lactitol were replaced with L8020 lactic acid bacteria powder and xylitol, respectively. The hardness of the obtained tablets was 10 kgf or more, which was sufficient. No problems were observed in terms of manufacturability. [Table 19]

Claims

1. An oral retention composition for retaining a functional substance in the oral cavity, comprising at least one compound selected from the group consisting of shellac and zein, a functional substance, and an acidic polysaccharide, wherein the functional substance coated with at least one compound selected from the group consisting of shellac and zein is mixed with the acidic polysaccharide, and the average particle size is 1 μm to 400 μm.

2. The oral cavity retention composition according to claim 1, wherein the acidic polysaccharide is at least one selected from the group consisting of carrageenan, hyaluronic acid, xanthan gum, sodium alginate, pectin, and gum arabic.

3. The oral cavity retention composition according to claim 1 or 2, wherein the functional substance is at least one selected from the group consisting of basic substances, polyphenols, and lactic acid bacteria.

4. The oral cavity retention composition according to claim 3, wherein the basic substance has an amino group and the polyphenols have two or more hydroxyl groups bonded to an aromatic ring.

5. The oral cavity retention composition according to claim 3, wherein the basic substance is at least one selected from the group consisting of protamine hydrolysates, arginine, lysine, glucosamine, spermine, spermidine, putrescine, piperine, and chitosan.

6. The oral cavity retention composition according to claim 3, wherein the polyphenols are at least one selected from the group consisting of chlorogenic acid, quercetin, resveratrol, tannic acid, caffeic acid, caffeic acid phenethyl ester, hydroxytyrosol, oleuropein, gallic acid, eugenin, catechin, daidzein, procyanidin, theaflavin, polyphenol-containing plant extract, propolis, champignon extract, syringin, and eleuthroside E.

7. An oral retention composition according to any one of claims 1 to 6, having the form of granules, powder, or tablets.

8. An oral cavity retention composition according to any one of claims 1 to 7, for use as a material for manufacturing an oral composition or an oral composition.

9. An oral composition or oral composition containing the oral cavity retention composition according to any one of claims 1 to 8.

10. The oral composition or oral composition according to claim 9, which is a food, oral care product, pet food, pharmaceutical, or quasi-drug.

11. An oral composition or oral composition according to claim 10, which is a food for suppressing bad breath.

12. The oral composition or oral composition according to claim 11, which is a food for suppressing bad breath while wearing a mask or a food for suppressing bad breath upon waking.

13. The oral composition or oral composition according to claim 10, which is a food for sustaining flavor or a food for masking flavor.

14. A method for producing an oral cavity retention composition according to claim 1, Step 1 involves mixing at least one compound selected from the group consisting of shellac and zein dissolved or dispersed in a solvent with a functional substance to coat the functional substance, and A method for producing functional substances, comprising step 2 of mixing a functional substance coated with at least one compound selected from the group consisting of shellac and zein obtained in step 1 with an acidic polysaccharide.

15. The manufacturing method according to claim 14, wherein in step 2, a functional substance and an acidic polysaccharide are mixed while adding ethanol or aqueous ethanol with an ethanol concentration of 50% to 99% (v / v).

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