Oral cavity-retentive composition, and oral composition or oral composition containing the same

Abstract

The purpose of the present invention is to provide an intraoral retention composition in which the reduction in the viscosity of an acidic polysaccharide caused by a protamine hydrolysate is suppressed.　The present invention relates to an intraoral retention composition containing: at least one compound selected from the group consisting of shellac and zein; a protamine hydrolysate; and an acidic polysaccharide. The protamine hydrolysate has a surface at least a portion of which is coated with the at least one compound selected from the group consisting of shellac and zein. The intraoral retention composition is obtained by mixing the protamine hydrolysate with the acidic polysaccharide.

Description

[Technical Field]

[0001] The present invention relates to an oral cavity-retentive composition and an oral composition or oral composition containing the same. More specifically, the present invention relates to a composition that has a long oral cavity retention time and an oral composition or oral composition containing the same. [Background technology]

[0002] Protamine degradation products obtained by hydrolysis of protamine are known to have antibacterial activity, and their application to oral candidiasis has been investigated (Patent Document 1). Attempts have been made to increase the retention of protamine degradation products in the oral cavity in order to effectively utilize the antibacterial activity of the protamine degradation products. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2018-177679 Summary of the Invention [Problem to be solved by the invention]

[0004] Patent Document 1 shows that the antibacterial activity of protamine degradation products is not impaired when neutral polysaccharides are used in combination to increase their retention in the oral cavity, but that the use of acidic polysaccharides causes them to react with and adsorb to the protamine degradation products, and that the use of xanthan gum in particular significantly impairs the antifungal activity of the protamine degradation products. For this reason, it has been thought that it is difficult to use acidic polysaccharides with protamine degradation products. [Means for solving the problem]

[0005] The present inventors investigated the application of acidic polysaccharides to protamine degradation products and found that the reaction of protamine degradation products with acidic polysaccharides not only reduced the antifungal activity described in Patent Document 1, but also significantly reduced the viscosity of the acidic polysaccharides, significantly impairing the oral retention of the protamine degradation products, making it even more difficult to utilize the combination of protamine degradation products and acidic polysaccharides. However, based on this finding, the present inventors discovered that coating protamine degradation products with at least one compound selected from the group consisting of shellac and zein can inhibit the reaction between the protamine degradation products and acidic polysaccharides, thereby suppressing the decrease in antibacterial activity of the protamine degradation products caused by the acidic polysaccharides and the decrease in viscosity of the acidic polysaccharides caused by the protamine degradation products, and have completed a composition containing protamine degradation products and acidic polysaccharides with improved oral retention.

[0006] An object of the present invention is to provide the compositions and production methods described below. Section 1. An oral cavity retention composition comprising at least one compound selected from the group consisting of shellac and zein, a protamine degradation product, and an acidic polysaccharide, wherein the protamine degradation product, at least a portion of whose surface is coated with at least one compound selected from the group consisting of shellac and zein, is mixed with the acidic polysaccharide. Section 2. Item 1. The oral cavity retentive composition according to Item 1, further comprising at least one selected from the group consisting of cinnamon and low molecular weight proanthocyanidins. Section 3. Item 3. The oral cavity retentive composition according to Item 1 or 2, comprising a protamine degradation product content of 0.1 to 80% by mass, at least one compound selected from the group consisting of shellac and zein content of 0.01 to 40% by mass, an acidic polysaccharide content of 1 to 90% by mass, a cinnamon content of 0.8% by mass or less, and a low-molecular-weight proanthocyanidin content of 8% by mass or less. Section 4. Item 4. The oral cavity retentive composition according to any one of Items 1 to 3, 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 5. Item 5. The oral cavity retentive composition according to any one of Items 1 to 4, which is in the form of granules or powder. Section 6. Item 6. The oral cavity retentive composition according to any one of Items 1 to 5, having an average particle size of 1 μm to 5000 μm. Section 7. Item 7. The oral cavity-retentive composition according to any one of Items 1 to 6, which is used as a material for producing an oral cavity composition or an oral composition. Section 8. An oral composition or oral composition containing the oral retention composition according to any one of Items 1 to 7. Section 9. Item 9. The oral composition or oral composition according to item 8, which is a food or oral care product. Section 10. A method for producing an oral cavity-retentive composition comprising at least one compound selected from the group consisting of shellac and zein, a protamine degradation product, and an acidic polysaccharide, the protamine degradation product being coated with at least one compound selected from the group consisting of shellac and zein and mixed with the acidic polysaccharide, Item 11. A production method comprising: Step 1: mixing a protamine degradation product with at least one compound selected from the group consisting of shellac and zein dissolved or dispersed in a solvent to coat the protamine degradation product; and Step 2: mixing the protamine degradation product coated with at least one compound selected from the group consisting of shellac and zein obtained in Step 1 with an acidic polysaccharide. Item 11. The method according to Item 10, wherein in step 2, the coated protamine degradation product and the acidic polysaccharide are mixed while adding aqueous ethanol. [Effects of the Invention]

[0007] The oral cavity-retaining composition of the present invention is able to maintain a continuously good oral hygiene environment because the antibacterial activity of the protamine degradation products is easily exerted and the oral cavity retention time is long. Furthermore, since the oral cavity-retaining composition of the present invention has a reduced harsh and astringent taste of the protamine degradation products, it can be suitably used in oral compositions (e.g., oral care products such as toothpaste, liquid toothpaste, mouthwash, and mouthwash, and other oral compositions that do not fall under the category of food, such as lozenges, chewable tablets, and gels) or oral compositions (e.g., orally ingested compositions (mainly foods) such as chewing gum, tablet candies, hard candies, soft candies, gummies, jellies, chewable tablets, and gels). [Brief explanation of the drawings]

[0008] [Figure 1] FIG. 1 is a graph showing the results of absorbance measurement in Test Example 6. DETAILED DESCRIPTION OF THE INVENTION

[0009] Unless otherwise specified, the symbols and abbreviations used in this specification should be understood to have the meanings commonly used in the technical field to which the present invention pertains, in accordance with the context of this specification.

[0010] As used herein, the phrase "comprising" is intended to encompass the phrases "consisting essentially of" and "consisting of."

[0011] As used herein, the phrase "antimicrobial activity" is intended to encompass the phrase "antibacterial activity" and the phrase "antifungal activity."

[0012] Unless otherwise specified, the steps, treatments, or operations described herein may be carried out at room temperature. In this specification, room temperature may mean a temperature of 10°C to 40°C.

[0013] Oral retention composition The oral cavity-retentive composition contains (1) a protamine degradation product, (2) at least one compound selected from the group consisting of shellac and zein (also referred to herein as a "coating compound"), and (3) an acidic polysaccharide. The protamine degradation product is coated with the coating compound, and the coated protamine degradation product (also referred to herein as a "coated protamine degradation product") is mixed with the acidic polysaccharide to form the oral cavity-retentive composition.

[0014] In the oral cavity-retentive composition, the protamine degradation products are used in the form of coated protamine degradation products coated with a coating compound, thereby inhibiting the reaction between the protamine degradation products and acidic polysaccharides in the oral cavity, thereby achieving the excellent effect of fully exerting both the antibacterial activity of the protamine degradation products and the retention function of the acidic polysaccharides. Therefore, the oral cavity-retentive composition allows the protamine degradation products to remain in the oral cavity for a longer period of time than when no coating compound is used, thereby allowing the effects of the protamine degradation products to be exerted in the oral cavity for a longer period of time.

[0015] Protamine Degradation Products In the oral cavity retention composition of the present invention, the protamine degradation product is coated with a coating compound, and the coated protamine degradation product is mixed with an acidic polysaccharide, thereby extending the retention time of the protamine degradation product in the oral cavity and allowing it to exert antibacterial activity for a longer period of time, without impairing the retention-imparting function of the acidic polysaccharide.

[0016] Protamine, the raw material for protamine degradation products, is a strongly basic protein that exists as nucleoprotamine bound to deoxyribonucleic acid in the sperm nuclei of fish such as salmon, herring, and trout. Depending on the raw material, it is called, for example, salmine (salmon) or clupein (herring), and although their structures differ slightly, either type of protamine can be used.

[0017] Methods for decomposing protamine include hydrolysis and physical cleavage (e.g., sonication). For example, hydrolysis using an acid, alkali, or protease can be used, and a combination of these methods can also be used. However, hydrolysis using a protease is preferred. More details are as follows.

[0018] In acid or alkali hydrolysis, protamine is heated under strong acid or alkali conditions under which peptides of the desired size (length) are obtained, and then neutralized to obtain peptides of the desired size (length).

[0019] Deionized water is added to protamine, and sodium hydroxide or hydrochloric acid is added to adjust the pH to a pH at which enzymatic activity is obtained, preferably the optimal pH. The reaction solution is heated to a temperature at which enzymatic activity is obtained, preferably the optimal temperature for the enzyme, and then the enzyme is added and the enzymatic reaction is carried out with stirring. After completion of the reaction, the reaction solution is heated to 80-100°C for 5-60 minutes for heat inactivation, and the pH is adjusted to a neutral range. The reaction solution is then lyophilized to obtain a protamine hydrolysate. The hydrolytic enzyme reaction is preferably carried out until an arginine-rich peptide consisting of approximately 5-14 amino acid residues is obtained, and then stopped by heat inactivation of the enzyme.

[0020] Each component contained in the protamine hydrolysate obtained as described above can be used as an active ingredient in an oral retention composition. Therefore, the protamine hydrolysate can be used, for example, in the following forms: (1) The reaction solution after the enzyme was inactivated by heating and the pH was adjusted. (2) Lyophilized product of the reaction mixture (3) A preparation obtained by removing enzyme proteins from the reaction solution or freeze-dried product. (4) A preparation obtained by converting the peptide in the reaction solution, lyophilized product, or preparation into a desired salt form.

[0021] Examples of proteolytic enzymes that can be used for hydrolysis in the present invention include enzymes produced by the genus Bacillus (e.g., Bacillus subtilis, Bacillus thermoproteolyticus, Bacillus licheniformis, etc.), enzymes produced by the genus Aspergillus (e.g., Aspergillus oryzae, Aspergillus niger, Aspergillus melleus, etc.), enzymes produced by the genus Rhizopus (e.g., Rhizopus niveus, Rhizopus derema, etc.), and enzymes produced by the genus Bacillus (e.g., Rhizopus niger, Rhizopus derema, etc.). Examples of enzymes that can be used include enzymes produced by bacteria such as cereals (e.g., cereals containing glutamic acid), pepsin, pancreatin, and papain. These enzymes can be used alone or in combination of two or more. Proteolytic enzymes are classified into endopeptidases, which specifically recognize and cleave the internal sequence of proteins, and exopeptidases, which cleave one or two amino acid residues at a time from the end. Therefore, various peptide chains can be produced by combining endopeptidases and exopeptidases as needed. When hydrolyzing with an enzyme, 0.001 to 10% by mass of the enzyme is added to the substrate, and the pH of the solution is adjusted to the optimal pH for the enzyme used.

[0022] The peptides contained in the protamine hydrolysate can be used as active ingredients of oral retention compositions in the form of salts with inorganic or organic acids or inorganic or organic bases, as needed. The acid or base can be selected depending on the intended use of the salt. However, considering applications in pharmaceuticals, foods, cosmetics, oral hygiene products, etc., the following pharmaceutically acceptable salts are preferred. Examples of acid addition salts include hydrochlorides, nitrates, sulfates, methanesulfonates, p-toluenesulfonates, salts with dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, maleic acid, and fumaric acid, and salts with monocarboxylic acids such as acetic acid, propionic acid, and butyric acid. Inorganic bases suitable for forming salts of the peptide compounds obtained by the present invention include hydroxides, carbonates, and bicarbonates of ammonia, sodium, lithium, calcium, magnesium, aluminum, and the like. Examples of salts with organic bases include mono-, di-, or tri-alkylamine salts such as methylamine, dimethylamine, and triethylamine, mono-, di-, or tri-hydroxyalkylamine salts, guanidine salts, and N-methylglucosamine salts. The protamine hydrolysate of the present invention also includes protamine hydrolysates in which peptide components have been converted into salt forms.

[0023] Examples of peptides obtainable by hydrolysis of protamine include peptides classified into the following categories (1) to (6). (1) A peptide or a salt thereof consisting of the amino acid sequence of SEQ ID NO: 1, represented by Ile Arg Arg Arg Arg Pro Arg Arg. (2) A peptide or a salt thereof consisting of the amino acid sequence of SEQ ID NO: 2 represented by Ser Arg Arg Arg Arg Arg Arg Gly Gly Arg Arg Arg Arg Arg. (3) A peptide or a salt thereof consisting of the amino acid sequence of SEQ ID NO: 3 represented by Val Ser Arg Arg Arg Arg Arg Arg Gly Gly Arg Arg Arg Arg Arg. (4) A peptide or a salt thereof consisting of an amino acid sequence in which 1 to 6 amino acids are deleted from the amino acid sequence of SEQ ID NO: 1. (5) A peptide or a salt thereof consisting of an amino acid sequence in which 1 to 4 amino acids are deleted from the amino acid sequence of SEQ ID NO: 3. (6) A peptide or a salt thereof, wherein the deletion sequence of SEQ ID NO: 3 consists of the amino acid sequence represented by Arg Arg Arg Arg Arg Arg Gly Gly Arg Arg Arg Arg Arg (SEQ ID NO: 4), Arg Arg Arg Arg Arg Gly Gly Arg Arg Arg Arg (SEQ ID NO: 5), or Arg Arg Arg Arg Gly Gly Arg Arg Arg Arg (SEQ ID NO: 6).

[0024] Two or more protamine degradation products (preferably protamine hydrolysates) having different compositions can also be mixed and used.

[0025] The content of the protamine degradation product in the oral cavity-retentive composition can be, for example, 0.1% to 80% by mass, 1% to 80% by mass, or preferably 0.5% to 40% by mass, relative to 100% by mass of the total mass of the composition. When the content is within this range, the protamine degradation product is more likely to exert its antibacterial activity in the oral cavity for a long period of time while maintaining a pleasant flavor.

[0026] Coating Compound The coating compound is at least one compound selected from the group consisting of shellac and zein. Coating a protamine degradation product with the coating compound to form a coated protamine degradation product is thought to inhibit the reaction between the protamine degradation product and the acidic polysaccharide, and thus, despite the presence of the protamine degradation product and the acidic polysaccharide, the protamine degradation product exhibits the antibacterial activity and retention-imparting function of the acidic polysaccharide. In the present invention, the coating compound is sufficient as long as it coats the protamine degradation product; therefore, components constituting the oral cavity-retentive composition other than protamine may also be coated with the coating compound.

[0027] As used herein, "coated" refers to a state in which part or all of the surface of an object to be coated (e.g., a protamine digestion product, etc.) is covered with a film (e.g., a film containing a coating compound, etc.). Coating also encompasses a state in which the object to be coated is contained in a film, 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 when part or all of the acidic polysaccharide is coated with aqueous ethanol containing a protamine digestion product and shellac, the protamine digestion product is still considered to be shellac-coated if part or all of the surface of the protamine digestion product is covered with shellac.

[0028] The degree of coating of the protamine degradation product may be that achievable by a typical granulation method, and does not necessarily require 100% of the surface of the object 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, or 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 using imaging analysis techniques based on X-ray CT, infrared spectroscopy, or near-infrared spectroscopy.

[0029] Shellac is preferred as the coating compound because of its high drying efficiency. Shellac is used as a glossing agent, masking agent, and coating agent in the fields of food, quasi-drugs, etc., and these can also be used in the present invention.

[0030] Zein is used as a coating agent in the fields of food, medicine, etc., and can also be used in the present invention.

[0031] The content of the coating compound in the oral cavity-retentive composition can be, for example, 0.01% to 40% by mass, preferably 0.01% to 20% by mass, and more preferably 0.05% to 8% by mass, relative to 100% by mass of the total mass of the composition. When the content is within this range, the retention of the protamine degradation product in the oral cavity is good.

[0032] acidic polysaccharide The acidic polysaccharide has the function of imparting oral retention to the protamine degradation product. The acidic polysaccharide is mixed with the coated protamine degradation product to form an oral retention composition. By mixing the acidic polysaccharide with the coated protamine degradation product, it is possible to suppress adverse effects on the function of the protamine degradation product of imparting oral retention (e.g., viscosity).

[0033] Examples of acidic polysaccharides include carrageenan, hyaluronic acid, xanthan gum, sodium alginate, pectin, gum arabic, etc., and these may be used alone or in combination. Preferred acidic polysaccharides are carrageenan, hyaluronic acid, xanthan gum, sodium alginate, etc., and more preferred acidic polysaccharides are carrageenan, hyaluronic acid, sodium alginate, etc. Among these, carrageenan and sodium alginate are particularly preferred because they can prolong the retention time of protamine degradation products in the oral cavity.

[0034] The content of the acidic polysaccharide in the oral cavity-retentive composition can be, for example, 0.1% to 90% by mass, 1% to 90% by mass, 0.1% to 60% by mass, or 1% to 60% by mass, relative to 100% by mass of the total mass of the composition, and is preferably 1% to 60% by mass. A content within this range is preferred in that it can prolong the oral cavity retention time of the protamine degradation products.

[0035] cinnamon In one embodiment, the oral cavity-retentive composition contains cinnamon. The inclusion of cinnamon is preferable in that the antifungal effect is improved. Cinnamon may be a spice containing cinnamaldehyde, an aromatic aldehyde having a phenylpropanoid skeleton, as a fragrance component. As the cinnamon, for example, cinnamon powder, cinnamon oil, cinnamon powder, or cinnamon extract can be used. Alternatively, cinnamaldehyde chemically synthesized or purified from natural products, or a composition containing cinnamaldehyde (e.g., cinnamaldehyde-containing flavor, cinnamaldehyde-containing oil, etc.) can also be used. As the cinnamon, the above-mentioned examples can be used alone or in combination of two or more.

[0036] The cinnamon may be uncoated, may be coated with a coating compound, or may be coated with other coating compounds (e.g., hydroxypropyl methylcellulose, hydroxypropyl cellulose, pullulan, gelatin, etc.). When the cinnamon is coated with a coating compound, it may be coated together with the protamine degradation product, may be coated separately from the protamine degradation product, or may be contained in the coating film formed by the coating compound.

[0037] The content of cinnamon in the oral cavity-retentive composition can be, for example, 0.8% by mass or less, 0.6% by mass or less, 0.4% by mass or less, 0.001% to 0.8% by mass, 0.001% to 0.6% by mass, 0.001% to 0.4% by mass, 0.005% to 0.8% by mass, 0.005% to 0.6% by mass, etc., and preferably 0.005% to 0.4% by mass, relative to 100% by mass of the total mass of the composition. When the content is within this range, good antibacterial activity is achieved.

[0038] Low molecular weight proanthocyanidins In one embodiment, the oral cavity-retentive composition contains low molecular weight proanthocyanidins. The inclusion of low molecular weight proanthocyanidins is preferable because it improves antifungal effects. Low molecular weight proanthocyanidins may be those whose main component is a low molecular weight monomer, dimer, or trimer proanthocyanidin. Oligonol (registered trademark), commercially available from Amino Up Chemical Co., Ltd. (Sapporo, Hokkaido), is a preferred low molecular weight proanthocyanidin. Oligonol is a chemically reduced molecular weight form of high molecular weight proanthocyanidin, a type of polyphenol contained in lychee fruit. Other low molecular weight proanthocyanidins that can be used include Pycnogenol (registered trademark, Hofer Research Ltd.) and Flavangenol (registered trademark, Toyo Shinyaku Co., Ltd.). Other low molecular weight proanthocyanidins that can be used include acacia bark extract, grape seed extract, pine bark extract, lychee fruit extract, and wine. The above-mentioned low molecular weight proanthocyanidins can be used alone or in combination of two or more.

[0039] The low molecular weight proanthocyanidin may be uncoated, may be coated with a coating compound, or may be coated with other coating compounds (e.g., hydroxypropylmethylcellulose, hydroxypropylcellulose, pullulan, gelatin, etc.). When the low molecular weight proanthocyanidin is coated with a coating compound, it may be coated together with the protamine degradation product, may be coated separately from the protamine degradation product, or may be contained in the coating film formed by the coating compound.

[0040] The content of low molecular weight proanthocyanidin in the oral cavity-retentive composition can be, for example, 8% by mass or less, 6% by mass or less, 4% by mass or less, 0.01% by mass to 8% by mass, 0.01% by mass to 6% by mass, 0.01% by mass to 4% by mass, 0.05% by mass to 8% by mass, 0.05% by mass to 6% by mass, etc., and preferably 0.05% by mass to 4% by mass, relative to 100% by mass of the total mass of the composition. When the content is within this range, good antibacterial activity is achieved.

[0041] The oral cavity-retentive composition may contain an excipient in addition to the coated protamine degradation product and acidic polysaccharide. It is preferable to contain an excipient because this improves moldability when the oral cavity-retentive composition is formed into granules or tablets. The excipient may be one that can be used in the fields of food, oral care products, pharmaceuticals, etc. Examples of excipients include, but are not limited to, crystalline cellulose, partially pregelatinized starch, starch, lactose, maltose, maltitol, xylitol, erythritol, sorbitol, mannitol, trehalose, carboxymethylcellulose, carboxymethylcellulose calcium, methylcellulose, agar, hydroxypropyl cellulose, hydroxypropylmethylcellulose, pullulan, and psyllium.

[0042] The excipient may be selected as appropriate from those usable in the fields of food, pharmaceuticals, quasi-drugs, etc., depending on the shape, application, granulation method, etc. The amount of excipient used may be any amount necessary for forming into the desired shape, etc., and may be, for example, 90 mass parts or less, 80 mass parts or less, 70 mass parts or less, 0.001 to 90 mass parts, 0.001 to 80 mass parts, 0.001 to 70 mass parts, 0.01 to 90 mass parts, 0.01 to 80 mass parts, 0.01 to 70 mass parts, etc., per 1 mass part of the total of the protamine degradation product, coating compound, and acidic polysaccharide.

[0043] The method for producing an oral cavity-retentive composition comprises at least one compound (coating compound) selected from the group consisting of shellac and zein, a protamine degradation product, and an acidic polysaccharide, and the protamine degradation product coated with at least one compound selected from the group consisting of shellac and zein is mixed with the acidic polysaccharide, The method includes 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 protamine degradation product to coat the protamine degradation product, and step 2 of mixing the protamine degradation product coated with at least one compound selected from the group consisting of shellac and zein obtained in step 1 with an acidic polysaccharide.

[0044] The oral cavity-retentive composition can be produced, for example, by mixing at least one compound selected from the group consisting of shellac and zein dissolved or dispersed in a solvent (e.g., ethanol, aqueous ethanol, etc.) with a protamine degradation product to coat and dry the protamine degradation product, mixing the coated protamine degradation product with an acidic polysaccharide or an aqueous solution thereof, and dry or wet granulating the mixture; however, the coated protamine degradation product may be in either a solid dispersion state or a solution dispersion state, and the production method is not limited thereto.

[0045] In step 1, a protamine degradation product is coated with a coating compound by mixing the protamine degradation product with a solution in which the coating compound is dissolved or dispersed in a solvent, and removing the liquid component after mixing as necessary to obtain a coated functional material.

[0046] The amount of the coating compound used can be, for example, 0.1 to 50 parts by mass, 1 to 40 parts by mass, preferably 1 to 30 parts by mass, and more preferably 1 to 20 parts by mass, per 100 parts by mass of the functional substance.

[0047] The solvent can be water, ethanol, or aqueous ethanol, with ethanol and aqueous ethanol being preferred. The aqueous ethanol can have an ethanol concentration of, for example, 60 to 99% (v / v), preferably 80 to 90% (v / v). The amount of solvent used can be, for example, 5 to 40 parts by mass, and preferably 10 to 30 parts by mass, per part by mass of the coating compound.

[0048] When the coating compound is shellac, the solvent is preferably ethanol in terms of ease of dissolving shellac. When the coating compound is zein, the solvent is preferably aqueous ethanol with an ethanol concentration of 60% to 99% (v / v), more preferably aqueous ethanol with an ethanol concentration of 80% to 90% (v / v), in terms of ease of dissolving zein.

[0049] The coating method is not limited as long as the coating compound can coat the surface of the protamine degradation product, but examples include dry granulation and wet granulation, with wet granulation being preferred. After coating, the liquid component may be removed. Examples of removal methods include hot air drying (25°C to 100°C) and vacuum drying.

[0050] In step 2, the protamine degradation product 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. At this time, an excipient may be mixed, if necessary.

[0051] The amount of acidic polysaccharide used can be, for example, 0.1 to 50 parts by mass, and preferably 1 to 30 parts by mass, per 1 part by mass of the protamine degradation product.

[0052] The mixing method may be a known method applicable to the shape of the oral cavity-retentive composition, depending on the shape of the composition. For example, a method may be used in which the coated protamine degradation product and the powdered acidic polysaccharide are mixed and stirred, and then an alcohol such as ethanol or a water-containing alcohol such as water-containing ethanol is added to granulate the mixture. Mixing the protamine degradation product and the acidic polysaccharide while adding (preferably dropwise) the water-containing alcohol is preferred in terms of kneading efficiency. The alcohol may be, for example, ethanol, methanol, etc., and is preferably ethanol. The hydrous alcohol may be, for example, hydrous ethanol, hydrous methanol, etc., and is preferably hydrous ethanol. The alcohol concentration of the hydrous alcohol is, for example, 50% to 99%, 50% to 95% (v / v), preferably 70% to 95% (v / v), and more preferably 80% to 90% (v / v).

[0053] The oral cavity-retentive composition is preferably in the form of granules, powder, or tablet, with granules and powder being more preferred. When these forms are ingested as granule tablets, powders, tablets, orally disintegrating tablets, effervescent tablets, capsules, etc., they are considered oral cavity-retentive compositions. Oral products and oral products incorporating these oral cavity-retentive compositions are called oral compositions and oral compositions, respectively. For example, oral compositions and oral compositions generally exist without the oral cavity-retentive composition, but the oral cavity-retentive composition is added to these compositions in order to utilize the oral cavity's functions and retention in the oral cavity. The average particle size (D50) of the oral cavity-retentive composition can be, for example, 1 μm to 5,000 μm, preferably 10 μm to 1,000 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.

[0054] The oral cavity-retentive composition can be used as a material for producing an oral cavity composition or an oral composition. The oral cavity-retentive composition or oral composition can be produced by applying a method commonly used for producing an oral cavity composition or an oral composition to the oral cavity-retentive composition and other materials used in the oral cavity-retentive composition. For example, a granular oral cavity-retentive composition can be used to produce chewing gum, candy, etc. containing the granular oral cavity-retentive composition.

[0055] Oral composition Examples of oral compositions include oral care products such as toothpaste, and compositions that are not contained in food and are applied to the oral cavity, such as lozenges, chewable tablets, and gels.

[0056] The content of the oral cavity-retaining composition in the oral composition can be selected appropriately depending on the product form, usage form, final content concentration of the protamine degradation product, etc. of the oral composition, and it is not necessarily appropriate to uniformly specify a range, but it can be, for example, 0.1% by mass to 50% by mass, and preferably 0.5% by mass to 20% by mass.

[0057] The oral composition can be obtained by adding an oral retention composition to a known oral composition, or by replacing some or all of the components constituting the known oral composition with an oral retention composition.The oral composition can be produced, without particular limitation, by appropriately modifying the manufacturing method of a known oral composition.

[0058] Oral Composition Oral compositions include orally ingested compositions (mainly foods) such as chewing gum, candy tablets, hard candy, soft candy, gummies, jellies, chewable tablets, gels, etc. Preferred are foods that are not immediately swallowed but are maintained in the oral cavity for a certain period of time, and foods that are expected to cause protamine degradation products to adhere to the teeth or gums when chewed, such as chewing gum, hard candy, soft candy, gummies, etc.

[0059] The content of the oral cavity-retentive composition in the oral composition can be selected appropriately depending on the product form, usage form, final content concentration of the protamine degradation product, etc. of the oral composition, and it is not necessarily appropriate to uniformly specify a range, but it can be, for example, 0.1% by mass to 50% by mass, and preferably 0.5% by mass to 20% by mass.

[0060] The oral composition can be obtained by adding an oral retention composition to a known oral composition, or by replacing some or all of the components constituting the known oral composition with an oral retention composition.The oral composition can be produced, without particular limitation, by appropriately modifying the manufacturing method of a known oral composition (especially food).

[0061] Methods for incorporating an oral cavity-retaining composition into an oral composition include, for example, coating the oral cavity-retaining composition on the surface of a food core, or mixing or kneading the composition into the food. When the oral cavity-retaining composition is used as a coating layer, the amount of the oral cavity-retaining composition is preferably 80% by mass or less, more preferably 60% by mass or less, from the standpoint of texture and taste, and even more preferably 40% by mass or less, from the standpoint of excellent texture and taste. When the oral cavity-retaining composition is used for mixing or kneading, the amount of the oral cavity-retaining composition is preferably 50% by mass or less, more preferably 30% by mass or less, from the standpoint of moldability and taste, and even more preferably 10% by mass or less, from the standpoint of excellent moldability and taste. The amount of the oral cavity-retaining composition referred to here refers to the ratio of the weight of the oral cavity-retaining composition to the total weight of the food containing the oral cavity-retaining composition. [Example]

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

[0063] Protamine hydrolysate: HAP100; Maruha Nichiro Co., Ltd. This is a hydrolysis product of protamine hydrochloride (trade name: Protamine, Maruha Nichiro Co., Ltd.) derived from chum salmon milt with bromelain (Amano Enzyme Co., Ltd.), and contains basic peptides. Shellac (coating compound): Gifu Shellac Co., Ltd. Zein (corn hydrolyzate) (coating compound): Kobayashi Zein DP-N; Kobayashi Fragrance Co., Ltd. Carrageenan (acidic polysaccharide): SATIAGUM MM30; Unitech Foods Co., Ltd. Hyaluronic acid (acidic polysaccharide): Hyaluronic acid RV; Nippon Shinyaku Co., Ltd. Xanthan gum (acidic polysaccharide): Bistop; San-ei Gen Co., Ltd. Sodium alginate (acidic polysaccharide): Sodium alginate I-1; Kimika Co., Ltd. Lychee extract (low molecular weight proanthocyanidin): Oligonol; Amino Up Chemical Co., Ltd. Cinnamon powder (cinnamon): Cinnamon powder; S&B Foods Co., Ltd. HPMC (hydroxypropyl methylcellulose) (excipient): Metrose SE-06; Shin-Etsu Chemical Co., Ltd. Microcrystalline cellulose (excipient): Ceolus FD-F20; Asahi Kasei Corporation

[0064] Test Example 1: Viscosity change of acidic polysaccharides by protamine degradation The viscosity of the acidic polysaccharide is important for retention in the oral cavity. The viscosity of the acidic polysaccharide was measured and evaluated as follows. Measurement device: An 18cm x 32cm plastic plate was tilted at 10° to the horizontal using a protractor to create an inclined plane. Measurement: 300 μL of sample was dropped onto a predetermined point on the inclined surface, and the distance traveled by the sample (progression distance) was measured after 3 minutes had passed. Samples: A control sample was an aqueous solution containing 1% by mass of acidic polysaccharides; an uncoated sample was an aqueous solution containing a mixture of a predetermined amount of protamine degradation products and acidic polysaccharides (1% by mass of acidic polysaccharides); and a coated sample was an aqueous solution containing a mixture of a predetermined amount of protamine degradation products and acidic polysaccharides coated with a coating compound (1% by mass of acidic polysaccharides). Evaluation method: The progress distance (mm) of the control sample was defined as D0, the progress distance (mm) of the uncoated sample as D1, and the progress distance (mm) of the coated sample as 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 decrease in viscosity of the acidic polysaccharide aqueous solution caused by the protamine degradation product was suppressed by coating. When RD>1.0, it indicates that the decrease in viscosity of the acidic polysaccharide aqueous solution caused by the protamine degradation product was promoted by coating. When RD=1.0, it indicates that the viscosity of the acidic polysaccharide aqueous solution is unchanged with or without coating. Results where the RD value was greater than 0.9 were evaluated as "-" because the viscosity decrease could not be suppressed or could only be suppressed slightly, and results where the RD value was 0.9 or less were evaluated as "○" because the viscosity decrease was suppressed.

[0065] A control sample, an uncoated sample, and a coated sample were prepared as follows and used to evaluate the viscosity of the carrageenan aqueous solution. The results are shown in Table 1. A 1% by mass aqueous solution of acidic polysaccharides was prepared as a control sample. Separately, a liquid identical to the control sample was prepared, to which 0.68% by mass of protamine degradation products were added and mixed. The resulting liquid was used as a non-coated sample. Separately, an ethanol solution containing 25% by mass of shellac was added dropwise to the powdered protamine degradation product in an amount equivalent to 10% by mass of the protamine degradation product in terms of shellac content. After thorough mixing, the mixture was dried in a dryer at 50°C to prepare coated protamine degradation products in granular form. A 1% by mass aqueous solution of acidic polysaccharides was mixed with 20 g of the same liquid as the control sample (20 g of the same liquid as the control sample), resulting in a 0.68% by mass protamine degradation product. The resulting liquid was used as a coated sample.

[0066] [Table 1]

[0067] Protamine Degradation Products The viscosity of carrageenan (Reference Example 1; D0 was 15 mm) was significantly reduced by mixing with uncoated protamine hydrolysates (Comparative Example 1; D1 was 31 mm). Patent Document 1 suggests that carrageenan reacted with and adsorbed onto protamine hydrolysates, and that xanthan gum, which is an acidic polysaccharide like carrageenan, also reacted with and adsorbed onto protamine hydrolysates, resulting in a decrease in the antibacterial activity of the protamine hydrolysates. However, this was a new finding, as it did not demonstrate that the viscosity of acidic polysaccharides changed.

[0068] On the other hand, when protamine degradation products coated with shellac were evaluated, the change in viscosity was reduced (Example 1; D2 was 18 mm) and was close to the original viscosity of carrageenan (Reference Example 1; D0 was 15 mm). The RD value of Example 1 was less than 0.9, which suggests that the shellac coating was able to inhibit the reaction and adsorption of the protamine degradation products with carrageenan. Since Patent Document 1 confirms the antibacterial activity of neutral polysaccharides with low adsorption rates, it is believed that the inhibition of reaction and adsorption by the shellac coating sufficiently reduces the inhibition of the antibacterial activity of the protamine degradation products by acidic polysaccharides and also sufficiently suppresses the decrease in viscosity of the acidic polysaccharides.

[0069] Test Example 2: Concentration and type of coating compound DO, D1, D2, and RD were determined in the same manner as in Test Example 1, except that the concentration of shellac relative to the amount of protamine degradation product was changed. The shellac concentrations were 1, 5, 10, and 20% by mass relative to the mass of the protamine degradation product. In addition, DO, D1, D2, and RD were determined in the same manner as in Test Example 1, except that the coating compound was changed to zein or HPMC, and the ethanol solution in which the coating compound was dissolved at 25% by mass was replaced with aqueous ethanol in which zein or HPMC was dissolved at 25% by mass and the ethanol concentration was 80% (v / v). The results are shown in Table 2.

[0070] [Table 2]

[0071] Coating the protamine hydrolyzate with 1% by mass of shellac suppressed the decrease in viscosity of the carrageenan aqueous solution containing the protamine hydrolyzate (Example 2; RD was 0.6). The decrease in viscosity was suppressed depending on the amount of shellac added (Examples 2 to 5). Furthermore, since the RD values ​​for all of Examples 2 to 5 were less than 0.9, it was confirmed that shellac was effective in inhibiting the reaction with carrageenan in the range of at least 1 to 20% by mass of the protamine hydrolyzate.

[0072] Furthermore, coating with zein reduced the RD value to less than 0.9 (Example 6), confirming that the reaction between protamine degradation products and carrageenan was inhibited. In contrast, coating with HPMC promoted a decrease in the viscosity of carrageenan, resulting in an RD value of greater than 1.1 (Comparative Example 2). It was thought that HPMC coating reduced the retention of carrageenan in the oral cavity.

[0073] Test Example 3: Types of acidic polysaccharides Carrageenan was replaced with other acidic polysaccharides, and the effect of shellac coating on the viscosity of the acidic polysaccharides was measured. The same procedures as in Test Example 1 were carried out except that carrageenan was replaced with hyaluronic acid, xanthan gum, or sodium alginate. The results are shown in Table 3.

[0074] [Table 3]

[0075] The acidic polysaccharides hyaluronic acid, xanthan gum, and sodium alginate reacted with protamine degradation products to reduce the viscosity of 1% aqueous solutions. The viscosity reductions for hyaluronic acid and sodium alginate (D1-D0 in Examples 7 and 9 were 16 or 14 mm) were comparable to those for carrageenan (D1-D0 in Example 1 was 16 mm), but xanthan gum showed a particularly large viscosity reduction (D1-D0 in Example 8 was 43 mm). On the other hand, coating with shellac significantly suppressed the viscosity reduction, as in the case of carrageenan (RD values ​​in Examples 7 to 9 were 0.3 to 0.5). Shellac coating was considered effective in suppressing the viscosity reduction of acidic polysaccharides other than carrageenan and, as a result, suppressing the reduction in oral retention.

[0076] Test Example 4: Amount of acidic polysaccharides Granule preparations were prepared according to the formulations shown in Table 4. The values ​​in Table 4 are in mass %.

[0077] [Table 4]

[0078] Ethanol containing 25% shellac by mass was added dropwise to the protamine degradation product. The amount of shellac added was 10% by mass relative to the protamine degradation product. After thorough mixing, the mixture was dried in a dryer at 50°C. The dried product was sieved through a No. 60 sieve (250 μm mesh size) to obtain granules that passed through the sieve (coated granules). The coated granules were mixed with carrageenan and crystalline cellulose while adding dropwise aqueous ethanol containing 90% ethanol (v / v). The mixture was dried in a dryer at 50°C. The dried product was sieved through a No. 60 sieve (250 μm mesh size). The granules that passed through the sieve were subjected to evaluation. Granules containing uncoated protamine degradation product (uncoated granules) were also prepared in the same manner, except that the coated granules were replaced with protamine degradation product.

[0079] A liquid obtained by mixing 1 g of coated or uncoated granules with 20 g of water was used as a sample, and the progress distance was measured in the same manner as in Test Example 1. The coated granules of Examples 10, 11, and 12 had a smaller progress distance (D1) than the uncoated granules of Comparative Examples 3, 4, and 5, respectively. This confirmed that coating a functional substance with shellac can suppress a decrease in viscosity. Note that although the carrageenan content in Comparative Example 3 and Example 10 is small at 1% by mass, because crystalline cellulose is not soluble in water, the viscosity developed by the addition of water can be evaluated as viscosity due to carrageenan.

[0080] Test Example 5: Particle size of granule formulation Granule formulations were prepared in the same manner as in Test Example 4 using the formulations with high concentrations of protamine degradation products shown in Table 5. However, sieves No. 30 (mesh size: 500 μm) and No. 60 (mesh size: 250 μm) were used, and the progress distance was measured in the same manner as in Test Example 1 for two sets of granules: those that passed through the No. 30 sieve but not the No. 60 sieve (Example 13), and those that passed through the No. 60 sieve (Example 14). Furthermore, precise particle size measurements were performed on the granules of Examples 13 and 14. The values ​​in Table 5 are in mass%. The particle size measurement results are shown in Table 6.

[0081] [Table 5]

[0082] <Method for measuring particle size> Particle size was measured using the equipment and measurement conditions shown below. The measurement principle was a wet laser diffraction / scattering method. During measurement, laser light was detected using the transmission method, and particle size was calculated assuming a particle refractive index of 1.81 and sample type of non-spherical particles. Equipment: Microtrac MT3200II (Microtrac Bell Co., Ltd.) Measurement solvent: isopropanol (refractive index of solvent is 1.38) Measurement time: 10 seconds

[0083] [Table 6]

[0084] The results of 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 that of the granules that passed through, with the D50 value, which can be considered as the average particle size, differing by more than four times. Meanwhile, the progress distance (D1) of the samples of Examples 13 and 14 was shorter than that of the sample of Comparative Example 6, confirming that the reactivity of the protamine degradation product with carrageenan was reduced. Furthermore, the relative progress RD (RD value using the sample of Comparative Example 6 as the control sample) of the samples of Examples 13 and 14 was the same, with no difference observed between them.

[0085] From the above, at least within the D50 range of 78.3 to 362.5 μm, there was no difference in the effect of shellac coating on inhibiting the reaction between protamine hydrolysates and carrageenan depending on the particle size. Furthermore, even when the protamine hydrolysate content was as high as 40%, shellac coating was effective in suppressing the decrease in carrageenan viscosity.

[0086] Test Example 6: Oral Retention Viscosity is related to adhesiveness in the oral cavity. The retention in the oral cavity of the granule formulations of Example 14 and Comparative Example 6 was evaluated. The intensity of the ninhydrin reaction shown by saliva was considered to represent the amount of peptides derived from protamine degradation products (residual amount of protamine degradation products).

[0087] Before the test, saliva was collected as a blank sample. Then, 100 mg of the protamine degradation product alone and the granule formulations (250 mg) of Example 14 and Comparative Example 6, each equivalent to 100 mg of the protamine degradation product, were administered onto the tongue, and saliva was collected over time while the formulations were gently spread in the oral cavity.

[0088] <Measurement of residual amount of protamine degradation products> 500 μL of collected saliva, 5.5 mL of purified water, and 1 mL of 0.2% (w / w) ninhydrin solution were mixed in a test tube, and the test tube was then heated in hot water for 10 minutes. The test tube was centrifuged and the supernatant was collected. The absorbance of the supernatant was measured at 570 nm, and the value obtained by subtracting the value of the blank sample was used to determine the absorbance intensity of the peptides contained in the protamine digest. The results are shown in Figure 1.

[0089] For both the sample of Example 14 and the sample of Comparative Example 6, the amount of residual protamine degradation products (absorbance intensity) reached a maximum 2 minutes after oral administration. The absorbance intensity at this time was designated 1, and the absorbance intensities obtained from samples collected at other times are shown in Figure 1 as relative values. In the case of protamine degradation products alone, the presence of protamine degradation products was not confirmed in the saliva sample collected 8 minutes later, indicating a retention time of 5 to less than 8 minutes. In contrast, the retention time for the granule formulation of Example 14 was 30 to less than 35 minutes, and the retention time for the granule formulation of Comparative Example 6 was 10 to less than 12 minutes. This confirms that shellac coating significantly extended the retention time of the protamine degradation products in the oral cavity. Furthermore, as shown in Test Example 5, it was confirmed that the viscosity derived from the acidic polysaccharide was maintained at a high level in the granules of Example 14 compared to Comparative Example 6, and it was therefore believed that the oral residence time could be extended by suppressing the decrease in viscosity. Therefore, it was strongly suggested that the oral residence time of the protamine degradation products of the compositions of the examples in which the suppression of the decrease in viscosity was confirmed would be longer than that of the uncoated compositions.

[0090] Test Example 7: Oral retention composition further containing cinnamon and lychee extracts The formulations shown in Table 7 (for Examples 15 and 16) were prepared using a pharmaceutical preparation machine. The protamine hydrolyzate, lychee extract, and cinnamon powder were placed in a stirring granulator (HIGH SPEED MIXER, FUKAE POWTEC). While stirring (agitator rotation speed: 300 rpm, chopper rotation speed: 1200 rpm), a 25% by weight ethanol solution of shellac was added dropwise. The mixture was then dried using a fluidized-bed dryer (FLOW COATER, Freund Corporation). The drying was continued at room temperature for 5 minutes, followed by an inlet air temperature of 90°C until the exhaust air temperature reached 60°C. Finally, the inlet air temperature was returned to room temperature, and the exhaust air temperature reached 47°C. The granules were classified using a No. 60 sieve, and the remaining granules were crushed using a bench mill. The entire amount was passed through a sieve to obtain shellac-coated granules.

[0091] The coated granules, a portion of the crystalline cellulose, and carrageenan were mixed using a stirring granulator while aqueous ethanol with an ethanol concentration of 90% (w / w) was added dropwise to prepare a wet granule. The granules were dried using a fluidized bed dryer as follows: after operating at room temperature for 3 minutes, drying was continued at an intake temperature of 95°C until the exhaust temperature reached 60°C, and finally drying was continued at room temperature until the exhaust temperature reached 47°C. The granules were classified using a No. 60 sieve, and the remaining granules were crushed using a bench mill, and the entire amount was passed through the sieve.

[0092] The citrus flavor was mixed with crystalline cellulose and allowed to adsorb, then mixed with the above-mentioned granules in a vinyl bag and passed through a No. 60 sieve again. No loss was observed during this process, and this mixed granule (Example 15) was subjected to particle size distribution measurement and sensory evaluation. A portion was also subjected to a fine grinding mill to obtain a fine powder (Example 16), whose particle size distribution was measured, and its oral retention was evaluated using the ninhydrin reaction in the same manner as in Test Example 6.

[0093] [Table 7]

[0094] <Fine grinding conditions> Equipment: CO-JET SYSTEMα MARK-III (Seishin Enterprise Co., Ltd.) Setting value: Sample feed speed 0.4g / min Fluid pressure: P.NOZZLE PRESSURE 7.4 kPa G.Nozzle Pressure 7.4 kPa Yield: 90% (90g of crushed material was obtained from 100g of raw material)

[0095] The yields in the step of coating the contents with shellac and the step of further wet granulating the coated granules were 93.6% and 97.6%, respectively, demonstrating good productivity. The results of particle size distribution measurement are shown in Table 8. The particle sizes of the granules prepared using a pharmaceutical preparation machine (Example 15) and the handmade granules (Table 6, Example 14) were comparable. When fine pulverization was performed, the value of the cumulative 50% particle size, which is the average particle size, was smaller, confirming that the particle size was further reduced (Example 16).

[0096] [Table 8]

[0097] Analysis of the amount of peptide remaining in saliva using the ninhydrin reaction revealed that peptides derived from the protamine digestion product remained in the oral cavity for 25 minutes before pulverization (Example 15) and for 30 minutes after pulverization (Example 16) (Table 8). Because the retention time of the protamine digestion product itself is approximately 8 minutes (Figure 1), the retention time of the protamine digestion product was increased by the granules of Examples 15 and 16. From the above, it was confirmed that oral retention can be improved not only when protamine hydrolysates are mixed with various ingredients such as lychee extract, cinnamon powder, and flavourings.

[0098] Test Example 8: Effects on total oral bacterial count, tongue coating index, and hydrogen sulfide concentration The finely pulverized material obtained in Example 16 was kneaded in an ordinary chewing gum base containing no functional ingredients in an amount of 2.9% by mass to obtain a granular chewing gum preparation. The subjects were five healthy adults. Immediately before ingesting the chewing gum, the evaluation items (oral cavity Total bacterial count , Degree of tongue coating Next, one piece of chewing gum (containing 43.7 mg of finely ground material) was chewed for 15 minutes, and the evaluation items were measured again. The total number of bacteria was measured using a bacteria counter manufactured by PHC, the Tongue Coating Index was visually scored by a dentist, and the hydrogen sulfide concentration was measured using OralChroma manufactured by NISSHA FIS. The total bacterial count (average) before intake was 1.35 x 10 7 cfu / mL, and after ingestion, it was 0.574 × 10 7 cfu / mL, and a reduction in the total number of bacteria was confirmed. The Tongue Coating Index (average value) was 85.6% before ingestion and 62.2% after ingestion, confirming a reduction in tongue coating. The hydrogen sulfide concentration (average value) was 36 ppb before ingestion and 22 ppb after ingestion, confirming a decrease in hydrogen sulfide, i.e., a reduction in bad breath.

[0099] Application examples of oral retention compositions to foods In the following examples, the same granules as in Example 14 were used as the oral retention granules containing protamine degradation products. The granules were added to food by one of the following methods: <Sugar coating method> The food was coated using soft sugar coating. Soft sugar coating is a type of sugar coating in which sugar syrup is prepared using sugar and starch syrup as the main ingredients, and the sugar syrup and optional powder are alternately applied to a core material. The moisture content of the sugar coating layer is 10% or less, and the optional powder is dispersed within the sugar coating layer. As mentioned above, sugar and starch syrup are generally used as the sugar for the sugar coating syrup, but other carbohydrates can also be used. <Direct mixing and kneading into food> This is a method in which any powder is mixed or kneaded into the food to disperse the powder throughout the food.

[0100] Example 17: Application to the sugar coating layer of coated chewing gum Commercially available strawberry-flavored chewing gum (a typical chewing gum containing no functional ingredients) was molded into spheres with a unit weight of 1.0 g to obtain chewing gum cores. 47 parts of sugar, 24 parts of enzyme-saccharified starch syrup, and 29 parts of dissolving water were mixed and heated to dissolve. A small amount of strawberry flavoring was added and mixed to obtain a sugar-coated syrup with a sugar content of 65% by mass. The cores were placed in a rotating onion-shaped coating pan, and the syrup and oral retention granules containing protamine degradation products were alternately poured over the cores in several batches to obtain a coated chewing gum with a unit weight of 1.1 g containing 8% by mass of protamine degradation product-containing granules and a sugar coating rate of 9%. The chewing gum preparation obtained in this manner exhibited reduced astringency and harshness inherent to protamine degradation products, providing a chewing gum with excellent texture and taste.

[0101] Examples 18 and 19: Application to sugar coating layer of coated chewing gum Coated chewing gums were obtained using the same process as in Example 17, with the formulations shown in Table 9 (referred to as Examples 18 and 19) in which orally retentive granules containing protamine degradation products were incorporated into a sugar coating layer. The chewing gum obtained in Example 18 had a somewhat stronger astringent and harsh taste of the protamine degradation products and a powdery texture compared to Example 17, but still had a good taste. The chewing gum obtained in Example 19 had reduced astringent and harsh taste, and was a chewing gum with good texture and taste.

[0102] [Table 9]

[0103] Example 20: Application to chewing gum A commercially available strawberry-flavored chewing gum (a typical chewing gum without functional ingredients) was mixed with 8% by mass of oral retention granules containing protamine hydrolysates and molded into spherical shapes with a unit weight of 1.1 g to obtain a chewing gum formulation. This chewing gum had reduced the astringency and harshness inherent to protamine hydrolysates, and exhibited good moldability and taste.

[0104] Examples 21 and 22: Chewing gum application Following the same process as in Example 20, chewing gum preparations were obtained by kneading orally retaining granules containing protamine degradation products with the formulations shown in Table 9 (referred to as Examples 21 and 22). The chewing gum obtained in Example 21 had a somewhat stronger astringency and harshness inherent to protamine degradation products than Example 20, making it difficult to mold, but it had a good taste. The chewing gum obtained in Example 22 had reduced astringency and harshness, and was a chewing gum with good moldability and taste.

[0105] Example 23: Application to the sugar coating layer of coated tablet confectionery To improve tableting suitability, 98 parts of sugar were prepared using a fluidized bed granulator. The granules were mixed with 1 part calcium stearate and 1 part lemon flavoring and compressed into tablets with a diameter of 13 mm, thickness of 5 mm, and unit weight of 1.0 g using a tablet press to obtain core tablets. 47 parts of sugar, 24 parts enzyme-saccharified starch syrup, and 29 parts dissolution water were mixed and heated to dissolve. A small amount of lemon flavoring was added and mixed to obtain a sugar-coated syrup with a sugar content of 65% by mass. The core was placed in a rotating onion-shaped coating pan, and the syrup and oral retention granules containing protamine degradation products were alternately poured over the granules several times to obtain coated tablets with a protamine degradation product-containing granule content of 8% by mass, a sugar coating rate of 9%, and a unit weight of 1.1 g. The resulting tablets exhibited reduced astringency and harshness inherent to protamine degradation products, providing a good texture and taste.

[0106] Examples 24 and 25: Application to the sugar coating layer of coated tablet confectionery Coated tablets were obtained using the same process as in Example 23, with the formulations shown in Table 10 (referred to as Examples 24 and 25) containing orally retentive granules containing protamine degradation products incorporated into the coating layer. The formulation obtained in Example 24 had a somewhat stronger astringent and harsh taste of the protamine degradation products and a powdery texture compared to Example 23, but the tablet had a good taste. The formulation obtained in Example 25 had reduced astringent and harsh taste, and was a tablet with good texture and taste.

[0107] Example 26: Application to tablet confectionery To improve tableting suitability, 90 parts of sugar were granulated using a fluidized bed granulator. Eight parts of oral retention granules containing protamine degradation products, one part of calcium stearate, and one part of lemon flavor were mixed with the granulated product, and the mixture was compressed in a tablet press to yield tablets with a diameter of 13 mm, a thickness of 5 mm, and a unit weight of 1.1 g. These tablets had reduced astringency and harshness inherent to protamine degradation products, and exhibited excellent moldability and flavor.

[0108] Example 27: Application to tablet confectionery To improve tableting suitability, 90 parts of the sugar alcohol erythritol were prepared using a fluidized bed granulator. Eight parts of oral retention granules containing protamine degradation products, one part calcium stearate, and one part lemon flavor were mixed with the granules, and the mixture was compressed in a tablet press to yield tablets 13 mm in diameter, 5 mm thick, and weighing 1.1 g. These tablets had reduced astringency and harshness inherent to protamine degradation products, resulting in sugar-free tablets with good formability and flavor.

[0109] Examples 28 and 29: Application to tablet confectionery Tablets containing protamine degradation products were mixed with oral retention granules in the formulations shown in Table 9 (referred to as Examples 28 and 29) in accordance with the same process as in Example 26 to obtain tablet candies. The tablet candies obtained in Example 28 had a somewhat stronger astringent and harsh taste than those obtained in Example 26, due to the protamine degradation products, making molding difficult, but they had a good taste. The tablet candies obtained in Example 29 had reduced astringent and harsh taste, and were easy to mold and had good taste.

[0110] Example 30: Application to the sugar coating layer of coated candy 60 parts sugar and 38 parts enzyme-saccharified starch syrup were dissolved in water and cooked in a vacuum oven at 130°C. After adding 2 parts citric acid and a small amount of orange flavoring, the mixture was molded into 1.0 g spheres, resulting in a hard candy core with a moisture content of 2.5%. 47 parts sugar, 24 parts enzyme-saccharified starch syrup, and 29 parts water were mixed together, heated to dissolve, and then a small amount of the remaining orange flavoring was added and mixed to produce a sugar-coated syrup with a sugar content of 65% by mass. The core was placed in a rotating onion-shaped coating pan, and the syrup and oral-retentive granules containing protamine degradation products were applied alternately in several batches to produce a coated candy with a protamine degradation product-containing granule content of 8% by mass, a sugar coating rate of 9%, and a unit weight of 1.1 g. This coated candy exhibited reduced astringency and harshness inherent to protamine degradation products, resulting in a tablet confection with excellent texture and taste.

[0111] Examples 31 and 32: Application to the sugar coating layer of coated candy Coated candies were obtained in which orally retentive granules containing protamine degradation products were incorporated into a sugar coating layer in the formulations shown in Table 9 (referred to as Examples 31 and 32) following the same process as in Example 30. The candy obtained in Example 31 had a somewhat stronger astringent and harsh taste of the protamine degradation products and a powdery texture compared to Example 30, but still had a good taste. The candy obtained in Example 32 had reduced astringent and harsh taste and was a candy with good texture and taste.

[0112] Example 33: Application to candy 52 parts of sugar and 38 parts of enzyme-saccharified starch syrup were dissolved in water and cooked in a vacuum oven at 130°C, after which 8 parts of oral retention granules containing protamine degradation product, 2 parts of citric acid, and a small amount of orange flavoring were added, mixed, and molded into spheres to obtain a hard candy with a moisture content of 2.5% and a unit weight of 1.1g. The candy kneaded with the protamine degradation product-containing granules had reduced astringency and harshness inherent to protamine degradation products, and was a candy with good moldability and taste.

[0113] Example 34: Application to candy 90 parts of reduced starch syrup, a sugar alcohol, was cooked in a vacuum oven at 145°C, and then 8 parts of oral retention granules containing protamine degradation product, 2 parts of citric acid, and a small amount of orange flavoring were added and mixed, and the mixture was molded into spheres to obtain a hard candy with a moisture content of 1.5% and a unit weight of 1.1g. The candy kneaded with the protamine degradation product-containing granules had reduced astringency and harshness inherent to protamine degradation product, and was a sugar-free candy with good moldability and taste.

[0114] Examples 35 and 36: Candy Application Candies were obtained by kneading oral retention granules containing protamine degradation products using the same process as in Example 33 and the formulations shown in Table 9 (referred to as Examples 35 and 36). The candy obtained in Example 35 had a somewhat stronger astringent and harsh taste due to the protamine degradation products than in Example 33, making it difficult to mold, but it was a candy with good taste. The candy obtained in Example 36 had reduced astringent and harsh taste, and was a candy with good moldability and taste.

[0115] Example 37: Application to sugar coating layer of coated gummies 38 parts sugar, 46 parts starch syrup, 11 parts gelatin, and 4.5 parts gum arabic were dissolved by heating, concentrated under reduced pressure, and then homogenized by adding 0.5 parts citric acid and a small amount of cola flavoring. A certain amount was filled into a starch mold using a filling machine, dried, de-powdered, and oiled to obtain granular gummy candy cores with a moisture content of 8% and a unit weight of 1.0 g. Further, 47 parts sugar, 24 parts enzyme-saccharified starch syrup, and 29 parts dissolving water were mixed, dissolved by heating, and a small amount of cola flavoring was added and mixed to obtain a sugar-coated syrup with a sugar content of 65% by mass. The core was placed in a rotating onion-shaped coating pan, and the syrup and oral retention granules containing protamine degradation products were poured alternately several times to obtain coated gummy candies with a protamine degradation product-containing granule content of 8% by mass, a sugar coating rate of 9%, and a unit weight of 1.1 g. The coated gummy preparation obtained in this manner had reduced astringency and harshness of the protamine degradation products, and was a gummy candy with good texture and taste.

[0116] Examples 38 and 39: Application to sugar coating layer of coated gummies Following the same process as in Example 37, coated gummies were obtained in which orally retentive granules containing protamine degradation products were incorporated into a sugar coating layer using the formulations shown in Table 10 (referred to as Examples 38 and 39). The gummies obtained in Example 38 had a somewhat stronger astringent and harsh taste due to the protamine degradation products and a powdery texture compared to Example 37, but still had a good taste. The gummies obtained in Example 39 had reduced astringent and harsh taste and were good in both texture and taste.

[0117] Example 40: Application to gummies 30 parts sugar, 46 parts starch syrup, 11 parts gelatin, and 4.5 parts gum arabic were dissolved by heating and concentrated under reduced pressure. Then, 8 parts of oral retention granules containing protamine degradation products, 0.5 parts citric acid, and a small amount of cola flavoring were added and homogenized. A fixed amount was filled into a starch mold using a filling machine, dried, de-powdered, and oiled to obtain granular gummy candies with a moisture content of 8% and a unit weight of 1.1 g. The gummy candy formulation kneaded with the protamine degradation product-containing granules thus obtained had reduced astringency and harshness associated with the protamine degradation products, and exhibited excellent moldability and flavor.

[0118] Examples 41 and 42: Application to gummies Following the same process as in Example 40, gummy formulations were obtained by kneading orally retaining granules containing protamine degradation products with the formulations shown in Table 9 (referred to as Examples 41 and 42). The gummy formulation obtained in Example 41 had a somewhat stronger astringent and harsh taste due to the protamine degradation products than Example 40, making it difficult to mold, but it had a good taste. The gummy formulation obtained in Example 42 had reduced astringent and harsh taste, and was a gummy that was easy to mold and had good taste.

[0119] The compositions of the simple mixtures (powder) containing protamine degradation products blended in Comparative Examples 7 to 10 are shown in Table 10. Each raw material was simply mixed and subjected to testing.

[0120] [Table 10]

[0121] Comparative Example 7 A coated chewing gum was obtained in the same manner as in Example 17, except that a simple mixture containing protamine degradation products (see Table 10 for composition) was used instead of the orally retentive granules containing protamine degradation products, with a blending amount of the mixture of 8% by mass, a sugar coating rate of 9%, and a unit weight of 1.1 g. The chewing gum preparation thus obtained had a strong astringent and harsh taste inherent to the protamine degradation products, and was undesirable in terms of flavor.

[0122] Comparative Example 8 A tablet formulation containing 8% by mass of a simple mixture containing protamine degradation products (see Table 10 for composition) was obtained in the same manner as in Example 26, except that the orally retentive granules containing protamine degradation products were replaced with the mixture. The tablet formulation thus obtained had a strong astringent and harsh taste inherent to the protamine degradation products, and was undesirable in flavor.

[0123] Comparative Example 9 Using the same process as in Example 30, a coated candy was obtained with the formulation shown in Table 11 (referred to as Comparative Example 9), with a simple mixture containing protamine degradation products (see Table 10 for composition) at 90% by mass, a sugar coating rate of 92%, and a unit weight of 12.5 g. The candy obtained in this manner had a very powdery texture and exhibited the strong astringency and harshness inherent to protamine degradation products, resulting in an undesirable flavor.

[0124] Comparative Example 10 Using the same process as in Example 40, a granular gummy candy was obtained with the formulation shown in Table 11 (referred to as Comparative Example 10), in which the simple mixture containing protamine degradation products (see Table 10 for composition) was blended in an amount of 60% by mass, the moisture content was 8%, and the unit weight was 1.1 g. The gummy candy obtained in this manner had very hard properties, making it extremely difficult to mold, and had a strong astringent and harsh taste, resulting in an undesirable flavor.

[0125] The food compositions and evaluation results of Examples 17 to 42 and Comparative Examples 7 to 10 are summarized in Tables 9 and 11. The amounts of oral retentive granules and simple mixtures in the tables are in mass %, and the unit of unit weight is g. The amounts of oral retentive granules, simple mixtures, and sugar coating ratios shown in Tables 9 and 11 are values ​​calculated using the following formulas.

[0126]

number

[0127] Furthermore, for Examples 17 to 42 and Comparative Examples 7 to 10, five panelists evaluated the astringency, harshness, taste, texture, and moldability using absolute evaluation, and the results selected by three or more panelists are shown in Tables 9 and 11 as follows. <Astringency> "◎": Almost no bitterness "○": Slightly bitter, but does not impair the flavor "×" Strong astringency <Bitter taste> "◎" Almost no bitter taste "○": A slightly bitter taste, but it doesn't affect the flavor. "×": Strong bitter taste <taste> "◎": A refreshing and pleasant taste "○" Good taste "X": Unpleasant taste <Texture> "◎": Not powdery and has a good texture "○": Slightly powdery but has a good texture "X": Powdery texture, not desirable <Moldability> "◎" Easy to mold "○": Slightly difficult to mold, but moldable "X" Difficult to mold

[0128] [Table 11]

[0129] It was found that all of the foods containing the oral retention granules obtained in Examples 17 to 42 had reduced astringency and harshness, excellent moldability, and good texture and taste compared to those obtained in Comparative Examples 7 to 10, and it was found that the taste was improved by converting protamine degradation products into oral retention granules.

Claims

1. An oral cavity retention composition comprising at least one compound selected from the group consisting of shellac and zein, a protamine degradation product, and an acidic polysaccharide, wherein the protamine degradation product, at least a portion of whose surface is coated with at least one compound selected from the group consisting of shellac and zein, is mixed with the acidic polysaccharide.

2. The oral cavity-retentive composition according to claim 1, further comprising at least one selected from the group consisting of cinnamon and low molecular weight proanthocyanidins.

3. An oral retention composition according to claim 1 or 2, having a protamine degradation product content of 0.1 to 80% by mass, a content of at least one compound selected from the group consisting of shellac and zein of 0.01 to 40% by mass, a content of acidic polysaccharides of 1 to 90% by mass, a cinnamon content of 0.8% by mass or less, and a low molecular weight proanthocyanidin content of 8% by mass or less.

4. An oral retention composition according to any one of claims 1 to 3, 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.

5. The oral cavity-retentive composition according to any one of claims 1 to 4, which is in the form of granules or powder.

6. An oral retention composition according to any one of claims 1 to 5, having an average particle size of 1 μm to 5000 μm.

7. The oral cavity-retentive composition according to any one of claims 1 to 6, which is used as a material for manufacturing an oral cavity composition or an oral composition.

8. An oral composition or oral composition comprising the oral retention composition according to any one of claims 1 to 7.

9. 10. The oral or oral composition of claim 8, which is a food or oral care product.

10. A method for producing an oral cavity-retentive composition comprising at least one compound selected from the group consisting of shellac and zein, a protamine degradation product, and an acidic polysaccharide, the protamine degradation product being coated with at least one compound selected from the group consisting of shellac and zein and mixed with the acidic polysaccharide, A production method comprising: Step 1, in which at least one compound selected from the group consisting of shellac and zein dissolved or dispersed in a solvent is mixed with a protamine degradation product to coat the protamine degradation product; and Step 2, in which the protamine degradation product 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.

11. The method according to claim 10, wherein in step 2, the coated protamine degradation product and the acidic polysaccharide are mixed while adding aqueous ethanol.

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