Oral preparations containing chicory dietary fiber or cassava starch

Abstract

According to one embodiment of the present invention, there is provided an oral preparation comprising an adhesive layer containing an adhesive polymer; and an efficacy layer providing at least one of functions of suppressing bad breath, promoting saliva secretion, and antibacterial properties, wherein the adhesive polymer comprises at least one selected from the group consisting of a mixture of cassava starch from which linamarin has been removed and chicory dietary fiber.

Description

[Technical Field]

[0001] The present invention relates to a preparation for the oral mucosa which comprises an adhesive layer containing a mixture of chicory dietary fiber or cassava starch from which linamarin has been removed, and an efficacy layer containing an active ingredient for removing or alleviating bad breath, and relates to an oral preparation which is less irritating to the oral mucosa and has excellent adhesive strength. [Background technology]

[0002] Bad breath refers to an unpleasant odor emanating from the mouth. While it does not cause pain to patients, it can occur during breathing, talking, and chewing, negatively impacting interpersonal relationships. This can lead to feelings of psychological atrophy and hinder normal social life, causing significant inconvenience to patients. While less than 10% of cases of bad breath are caused by digestive disorders such as the stomach or intestines, approximately 90% of cases are caused by gram-negative anaerobic bacteria that break down food proteins remaining in the mouth, oral cells, or proteins in saliva, producing volatile sulfur compounds (VSCs) such as hydrogen sulfide (H2S), methyl mercaptan (CH3SH), and dimethyl sulfide ((CH3)2S).

[0003] Environmental conditions that commonly cause bad breath include poor oral hygiene due to food remaining between teeth or in dental appliances such as dentures, oral inflammatory diseases such as periodontitis and tonsillitis, and an increase in bacteria that cause bad breath in the mouth due to factors that reduce saliva secretion such as smoking, sleep, fasting, and xerostomia.As a result, methods of improving bad breath include removing causes of reduced saliva secretion such as smoking, as well as taking saliva secretion-promoting ingredients, neutralizing VSCs, and suppressing the activity of bacteria that cause bad breath.

[0004] Xylitol, known as a sugar substitute, inhibits the acid production and energy acquisition of Streptococcus mutans (S. mutans), and is known to not only reduce S. mutans but also promote saliva secretion.2+ ) and copper ions (Cu 2+ ), some metal ions are also S 2- and CH3S - It is known to have the effect of preventing the formation of VSCs due to its strong binding ability to sulfides such as P. gingivalis, Fusobacterium nucleatum, Tannerella forsythia, Prevotella intermedia, and Prevotella nigrescens. 2+ Some metal ions, such as CI, are known to have antibacterial effects in addition to their VSC-neutralizing effects. Therefore, products containing these ingredients to reduce bad breath are known, and it is known that the effects are enhanced when active ingredients for antibacterial and saliva-enhancing properties are continuously released from the oral cavity.

[0005] As a result, various products containing active ingredients for improving oral health have been developed in the form of gums, candies, and other forms, designed to release the active ingredients in the oral cavity over a long period of time. However, these sustained-release periods, ranging from 5 to 15 minutes, are generally insufficient. As an alternative, formulations containing adhesive ingredients such as carboxymethyl cellulose (CMC), carbopol (Polyacrylic acid), and polyvinyl pyrrolidone (PVP) have been developed. These patch or tablet-type products adhere to specific locations in the oral cavity for extended use. However, CMC, carbopol, and PVP are synthetic adhesive polymers that are known to irritate the oral mucosa through ionic interactions with the oral mucosa, potentially causing mucosal pain during use. Another alternative is gum arabic, a natural adhesive polymer. However, this natural polymer still contains carboxyl groups (COOH groups) and therefore presents the problem of ionic interactions with the oral mucosa.

[0006] Furthermore, when a water film is formed on the mucosa under conditions of high saliva secretion, the interaction between the adhesive polymer and the mucosa is reduced, making fixation difficult. In response to this, there is a demand for a formulation that uses a polymer that does not undergo ionic interactions and has an adhesive layer that has high adhesive strength to the oral mucosa even under conditions of high saliva secretion.

[0007] In light of this background, the present inventors have proposed a double-layered formulation comprising an adhesive layer formulation containing chicory dietary fiber or cassava starch (tapioca), an adhesive layer formulation containing silica, and an adhesive layer containing an active ingredient for eliminating or alleviating bad breath. Specifically, the present invention uses chicory dietary fiber or cassava starch as an adhesive polymer component, which does not contain a carboxyl group (-COOH) and exhibits adhesive strength without ionic interaction with the oral mucosa. This provides an improved formulation with similar or superior adhesive strength to commonly known adhesive polymers and reduces the irritation to the oral mucosa caused by prolonged use of adhesive formulations for suppressing or alleviating bad breath. Furthermore, when silica is used as an excipient in the adhesive layer of a double-layered tablet, it can exhibit high adhesive strength to the oral mucosa, unlike other excipients, and provides a formulation with improved tablet strength. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] Annika Borde et al., Journal of Colloid and Interface Science 341(2010)255-260 Summary of the Invention [Problem to be solved by the invention]

[0009] An object of the present invention is to provide an oral preparation which has excellent adhesive strength and low irritation to the oral mucosa, and which includes an adhesive layer containing at least one selected from the group consisting of a mixture of cassava starch from which linamarin has been removed and chicory dietary fiber, and an efficacy layer which provides at least one of the functions of suppressing bad breath, promoting saliva secretion, and antibacterial properties.

[0010] Another object of the present invention is to provide an oral adhesive composition comprising a polymer containing at least one selected from the group consisting of a mixture of cassava starch from which linamarin has been removed and chicory dietary fiber, as an oral adhesive. [Means for solving the problem]

[0011] This will be explained in detail as follows. Meanwhile, each description and embodiment disclosed in the present invention also applies to each other description and embodiment. That is, all combinations of various elements disclosed in the present invention belong to the scope of the present invention. Furthermore, the following specific description is not considered to limit the category of the present application.

[0012] According to one embodiment of the present invention, there is provided an oral preparation comprising an adhesive layer containing an adhesive polymer; and an efficacy layer, wherein the adhesive polymer comprises at least one selected from the group consisting of a mixture of cassava starch with linamarin removed and chicory dietary fiber.

[0013] Furthermore, according to one embodiment of the present invention, there is provided an oral preparation in which the efficacy layer provides at least one function of suppressing bad breath, promoting saliva secretion, reducing plaque, reducing gingivitis, reducing periodontitis, alleviating periodontal disease, and alleviating dental caries.

[0014] According to one embodiment of the present invention, the oral preparation is provided in the form of a double-layered tablet.

[0015] According to another embodiment of the present invention, the adhesive layer further comprises silica as an excipient, and the oral preparation has any one dosage form selected from the group consisting of a breath freshener, a dry mouth relieving agent, a solid mouthwash, a solid toothpaste, and a sustained-release candy.

[0016] According to one embodiment of the present invention, there is provided an oral preparation containing the excipient in a weight ratio of 20 wt % to 40 wt % based on the total weight of the adhesive layer raw materials.

[0017] According to another embodiment of the present invention, there is provided an oral preparation, wherein the silica has a particle diameter of 1 nm to 50 μm.

[0018] According to one embodiment of the present invention, the functional layer contains copper ions (Cu 2+ ), zinc ions (Zn 2+ ) or tin ions (Sn 2+ The oral formulation further comprises any one or more of the group consisting of salts of

[0019] According to another embodiment of the present invention, there is provided an oral preparation, wherein the efficacy layer contains the breath odor suppressant in a weight ratio of 0.1 wt % to 5 wt % based on the total weight of the oral preparation.

[0020] According to another embodiment of the present invention, there is provided an oral preparation, wherein the efficacy layer contains a saliva promoter in a weight ratio of 50 wt % to 80 wt % based on the total weight of the efficacy layer.

[0021] According to another embodiment of the present invention, there is provided an oral preparation, wherein the adhesive layer is contained in a weight ratio of 2 wt % to 50 wt % of the total weight.

[0022] According to one embodiment of the present invention, there is provided an oral preparation, wherein the efficacy layer is contained in a weight ratio of 20 wt% to 85 wt% of the total weight.

[0023] According to one embodiment of the present invention, the oral preparation has a strength of 1000 gf or more and less than 4000 gf.

[0024] According to one embodiment of the present invention, the oral preparation further comprises a layer having one or more functions selected from the group consisting of surface coating, dissolution rate adjustment, strength adjustment, tooth surface polishing, whitening, and pH adjustment.

[0025] Furthermore, according to one embodiment of the present invention, there is provided an oral adhesive composition, which includes a polymer containing at least one selected from the group consisting of a mixture of cassava starch with linamarin removed and chicory dietary fiber, as an oral adhesive. [Effects of the Invention]

[0026] The oral adhesive composition of the present invention, which contains at least one selected from the group consisting of a mixture of cassava starch from which linamarin has been removed and chicory dietary fiber, reduces irritation to the oral mucosa and has excellent adhesive strength.

[0027] Furthermore, an oral preparation containing the oral adhesive composition has low irritation to the oral mucosa and exhibits high adhesive strength to the oral mucosa even in situations where saliva secretion is high, and is therefore highly usable. [Brief explanation of the drawings]

[0028] [Figure 1] 1 is an image of an oral preparation according to one embodiment of the present invention. [Figure 2] 1 is a schematic diagram showing a method for measuring the hydrophilicity of silica contained in an oral preparation according to an embodiment of the present invention. [Figure 3] 1 is an image of a test process for measuring adhesive strength of an oral preparation according to an embodiment of the present invention. [Figure 4] 1 is an image of a test process for measuring the strength of an oral preparation according to an embodiment of the present invention. [Figure 5] 1 is a graph comparing adhesive strength of oral preparations according to an embodiment of the present invention. [Figure 6] 1 is a graph comparing the VSC neutralization rate between the oral preparation according to one embodiment of the present invention with and without a breath odor suppressant. [Figure 7] 1 is a graph comparing the disintegration rates of oral preparations according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0029] The present invention will be described in more detail with reference to the following examples. These examples are intended to explain the present invention in more detail, but the scope of the present invention is not limited to these examples.

[0030] While the present invention may be modified in various ways and may take various forms, specific embodiments are shown by way of example in the drawings and described in detail herein, but it is to be understood that it is not intended to limit the invention to the particular forms disclosed, but rather to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present invention.

[0031] In describing the various drawings, like reference numerals are used to refer to like elements. In the accompanying drawings, the dimensions of structures are exaggerated for clarity of the present invention. Terms such as "first," "second," etc. are used to describe various elements, but the elements should not be limited by these terms. These terms are used only to distinguish one element from another. For example, a first element may be referred to as a "second element," and similarly, a second element may be referred to as a "first element," without departing from the scope of the present invention. A singular expression includes a plural expression unless the meaning clearly changes in the context.

[0032] In this application, the terms "comprise" or "have" and the like are intended to specify the presence of a feature, number, step, operation, component, part, or combination thereof described in the specification, and should be understood not to preclude the possibility of the presence or addition of one or more different features, numbers, steps, operations, components, parts, or combinations thereof. Furthermore, when a layer, film, region, plate, or other part is referred to as being "on" another part, this includes not only the case where it is "directly on" the other part, but also the case where there is another part between them.

[0033] Furthermore, in this specification, when a layer, film, region, plate, or other portion is said to be formed on another portion, the direction of formation is not limited to the upward direction, but also includes the lateral and downward directions. Conversely, when a layer, film, region, plate, or other portion is said to be "under" another portion, this does not only mean that it is "directly under" the other portion, but also includes the case where there is another portion between them.

[0034] According to one embodiment of the present invention, there is provided an oral preparation comprising an adhesive layer containing an adhesive polymer; and an efficacy layer, wherein the adhesive polymer comprises at least one selected from the group consisting of a mixture of cassava starch with linamarin removed and chicory dietary fiber.

[0035] Furthermore, according to one embodiment of the present invention, there is provided an oral preparation in which the efficacy layer provides at least one function of suppressing bad breath, promoting saliva secretion, reducing plaque, reducing gingivitis, reducing periodontitis, alleviating periodontal disease, and alleviating dental caries.

[0036] The adhesive ingredients used in the prior art, such as carboxymethyl cellulose (CMC), carbopol (Polyacrylic acid), and polyvinyl pyrrolidone (PVP), are synthetic adhesive polymers that have the problem of causing mucosal pain due to ionic interactions with the oral mucosa. Another alternative natural adhesive polymer, gum arabic (Acacia gum), also contains a carboxyl group (-COOH), which does not resolve the issue of ionic interactions with the oral mucosa. In contrast, the natural adhesive polymers included in the oral preparation according to one embodiment of the present invention, a mixture of cassava starch with linamarin removed and chicory dietary fiber, do not contain a carboxyl group (-COOH) and therefore do not undergo ionic interactions with the oral mucosa. These natural adhesive polymers have similar or superior adhesive strength to commonly known adhesive polymers, thereby reducing the irritation to the oral mucosa caused by prolonged use of adhesive preparations for the purpose of suppressing or alleviating bad breath.

[0037] Furthermore, the dissolution rate of the oral preparation according to one embodiment of the present invention can be adjusted. The oral preparation may be provided in the form of an effervescent tablet using sodium bicarbonate (NaHCO3) and citric acid, and may further contain a hydrophilic ingredient such as salt or sugar. To delay the dissolution rate, the content of a binder may be increased, and the oral preparation according to one embodiment of the present invention can be used for 1 hour to a maximum of 4 hours.

[0038] According to one embodiment of the present invention, the oral preparation may be in the form of a double-layer tablet.

[0039] FIG. 1 is an image of an oral preparation according to one embodiment of the present invention.

[0040] Referring to Figure 1, the oral preparation includes an adhesive layer containing an adhesive polymer and an efficacy layer that provides functions such as suppressing bad breath, promoting saliva secretion, antibacterial properties, etc. The oral preparation may be configured as a double layer as shown in Figure 1, but is not limited thereto.

[0041] The diameter of the oral preparation according to one embodiment of the present invention may be 5 mm to 16 mm, preferably 7 mm to 14 mm, and more preferably 9 mm to 12 mm, and the thickness may be 2 mm to 6 mm, preferably 2.5 mm to 5 mm, and more preferably 3 mm to 4 mm. If the diameter is 5 mm or less, the small size may make it inconvenient to use, and if it is 16 mm or more, many parts may slip off the gums, making it difficult to attach. Furthermore, if the thickness is 2 mm or less, the strength may be low and chipping may occur, making tableting difficult, and if it is 6 mm or more, the thickness may be too thick, causing inconvenience to use.

[0042] The raw materials for the adhesive layer may comprise 0.5% to 60% by weight of the total double layer, preferably 1% to 55%, and more preferably 2% to 50% by weight, and may include adhesive polymers, excipients, binders, lubricants, etc.

[0043] The "adhesive polymer" used is a mixture of chicory dietary fiber or cassava starch (tapioca) from which linamarin has been removed.

[0044] Chicory dietary fiber is a substance extracted from chicory plants (roots, etc.) through enzymatic or hot water treatment, and contains inulin and oligofructose, which are polysaccharides that cannot be broken down by human digestive enzymes and have a degree of polymerization of 2 to 60. A representative raw material is Orafti GR from Beneo (Germany).

[0045] Cassava starch is starch extracted from cassava roots. It is a white powder rich in amylopectin, with linamarin removed. Representative raw materials include Tapioca starch from Sanguan Wongse Industries (Thailand). Linamarin is a cyanogenic glucoside found in the leaves and roots of plants such as cassava, lima beans, and flax. It is a glycoside compound containing a hydrocyanic acid residue and is a type of plant toxin. While stable and harmless to the human body, hydrolysis produces cyanide, making it toxic. While it is typically found in inedible parts of the plant and in some edible parts, cassava contains significant amounts in its roots and leaves. In contrast, this invention removes linamarin from cassava starch, eliminating the risk of dietary exposure to linamarin.

[0046] The adhesive polymer may comprise 0.5% to 80% by weight, preferably 10% to 70%, and more preferably 20% to 60% of the total weight of the adhesive layer ingredients. Binders for adjusting the adhesive strength of the adhesive polymer and increasing the binding strength of the adhesive layer may include one or more of gelatin, alginate, pectin, starch, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, polyvinyl acid, carboxymethyl cellulose, etc., and may be included in an amount within the total amount of the adhesive layer excluding the adhesive polymer, excipients, pH adjusters, lubricants, etc.

[0047] According to one embodiment of the present invention, the adhesive layer further contains silica as an excipient, and the oral preparation may have any one dosage form selected from the group consisting of breath fresheners, xerostomia relief agents, solid mouthwashes, solid toothpastes, and sustained-release candy preparations. The "excipient" may include calcium carbonate (CaCO3), calcium sulfate (CaSO4), calcium phosphate (CaPO4), starch, etc., which are commonly used in tablets. However, silica may also be included to strengthen the strength of the double-layered preparation and improve the adhesive strength of the adhesive layer under conditions of high saliva content. Here, silica refers to silica particles with hydrophilic surfaces, including precipitated silica, fumed silica, and colloidal silica, during the manufacturing process.

[0048] The excipient may be contained in an amount of 1 wt% to 60 wt%, preferably 10 wt% to 50 wt%, and more preferably 20 wt% to 40 wt% of the total weight of the adhesive layer raw materials. If the excipient is contained in an amount less than 1 wt% of the total weight of the adhesive layer raw materials, the strength-enhancing effect and the adhesive force-enhancing effect under conditions with a lot of saliva may be small, and if the excipient is contained in an amount exceeding 50 wt%, a large amount of dust may occur, making it difficult to mix during the tableting process.

[0049] 2 is a schematic diagram showing a method for measuring the hydrophilicity of silica contained in an oral preparation according to one embodiment of the present invention. Here, hydrophilicity refers to a substance in which, when a silica particle is positioned at the horizontal interface between water and oil (a water-immiscible solvent), and a tangent is drawn at the point where the interface meets the silica particle, the angle between the tangent and water at the interface is between 0 and 90 degrees, preferably between 5 and 85 degrees, and more preferably between 10 and 80 degrees.

[0050] The diameter of the silica particles is 1 nm to 50 μm, preferably 1.5 nm to 40 μm, and more preferably 2 nm to 30 μm. If the diameter of the silica particles is less than 1 nm, handling is difficult due to dust during production, and bonding strength is weakened. If the diameter is 50 μm or more, the strength and adhesive strength are reduced.

[0051] Lubricants can be added during manufacturing to facilitate the compression and refinement discharge processes. Examples of lubricant materials include calcium stearate, magnesium stearate, stearic acid, sodium stearyl fumarate, and talc. The lubricant content is 0.1% to 10%, preferably 0.3% to 7%, and more preferably 0.5% to 5%, of the adhesive layer material. If the lubricant content exceeds 10% of the adhesive layer material, the adhesive strength may decrease, and if it is less than 0.1%, friction may cause difficulties during refinement.

[0052] The ingredients of the efficacy layer should account for 10% to 95% of the total weight of the double layer, preferably 15% to 90%, more preferably 20% to 85%, and even more preferably 50% to 70%, and may include, but are not limited to, bad breath suppressants, saliva secretion stimulants, excipients, binders, lubricants, etc. If the weight of the efficacy layer exceeds 90% of the total weight of the double layer, adhesive strength may decrease, and if it is less than 10%, efficacy may be insufficient.

[0053] The functional layer may be composed of multiple layers instead of one layer. When the functional layer is composed of multiple layers, each functional layer may perform a different function, or layers performing the same function may be separated.

[0054] According to one embodiment of the present invention, the efficacy layer contains copper ions (Cu 2+ ), zinc ions (Zn 2+ ) or tin ions (Sn 2+ The oral formulation further comprises any one or more of the group consisting of salts of

[0055] "Breath odor suppressant" refers to a component that has a VSC-neutralizing effect or an antibacterial effect against VSC-producing bacteria. 2- and CH3S - This refers to the inhibition of the volatilization of VSCs due to the strong ionic bonding force with sulfides such as P. gingivalis, F. nucleatum, T. forsythus, P. intermedia, P. nigrescens, etc., which produce VSCs.

[0056] As a breath odor suppressant, copper ions (Cu 2+ ), zinc ions (Zn 2+ ), tin ions (Sn 2+) and one or more salts thereof containing ions such as hydroxybenzoates, etc., and the amount is preferably 0.01% to 10%, more preferably 0.05% to 7%, and even more preferably 0.1% to 5%, based on the raw materials of the efficacy layer, and is preferably contained within the recommended daily intake standard.

[0057] The bad breath suppressant, copper ions (Cu 2+ ), zinc ions (Zn 2+ ), tin ions (Sn 2+ ), S 2- and CH3S - The strong binding force to sulfides such as zinc ions (Zn 2+ Oral preparations containing ) exhibit antibacterial effects.

[0058] An oral preparation containing the breath odor suppressant releases the active ingredient continuously in the oral cavity, thereby enhancing its effectiveness.

[0059] The copper ions (Cu 2+The salts of Copper Acetylmethionate, Copper Acetyl Tyrosinate Methylsilanol, Copper Ascorbyl Phosphate Succinoyl Tripeptide-34, Copper Aspartate, Copper Carbonate Hydroxide, Copper Chlorophyll, Copper Chloride, Copper Citrate, Copper DNA, Copper Gluconate, Copper Heptapeptide-14 Pantothenate, Copper (Lysinate / Prolinate), Copper Palmitoyl Heptapeptide-14 The compound may comprise at least one selected from the group consisting of copper heptapeptide-14, copper PCA, copper PCA methylsilanol, copper picolinate, copper sulfate, copper tetrapeptide-52 dimer, copper tripeptide-1, copper tripeptide-34 copper HCl, copper tripeptide-1 palmitamide, disodium EDTA-copper, and the like.

[0060] The zinc ions (Zn 2+) Salts include Zinc Acetate, Zinc Adenosine Triphosphate, Zinc Adenosine Triphosphate Hydroxide, Zinc Ascorbate, Zinc Ascorbate Hydroxide, Zinc Aspartate, Zinc Borate, Zinc Carbonate, Zinc Carbonate Hydroxide, Zinc Carboxydecyl Trisiloxane, Zinc Chloride, Zinc Chloride Hydroxide, Zinc Citrate, Zinc Coceth Sulfate, Zinc Coco-Sulfate, Zinc Cysteinate, Zinc Dibutyldithiocarbamate Dibutyldithiocarbamate, Dimethicone PEG-25 Zinc Phthalate, Dimethicone PEG-8 Zinc Succinate, Zinc DNA, Zinc Formaldehyde Sulfoxylate, Zinc Glucoheptonate, Zinc Gluconate, Zinc Glutamate, Zinc Glycinate, Zinc Glycinate Salicylate, Zinc Glycyrrhetinate, Zinc Hydrolyzed Collagen, Zinc Hydrolyzed Hyaluronate, Zinc IndoleacetateHydroxide, Zinc Lactate, Zinc Laurate, Zinc Magnesium Aspartate, Zinc Myristate, Zinc Neodecanoate, Zinc Nitrate, Zinc Oxide, Zinc Palmitate, Zinc Palmitoyl Nonapeptide-14, Zinc PCA, Zinc Pentadecene Tricarboxylate, Zinc Peroxide, Zinc Phenolsulfonate, Zinc Picolinate, Zinc Pyrithione, Zinc Ricinoleate, Zinc Rosinate The present invention may include at least one selected from the group consisting of zinc rosinate, zinc salicylate, zinc stearate, zinc undecylenate, zinc undecylenoyl hydrolyzed wheat protein, and the like.

[0061] The tin ions (Sn 2+ ) is, and may contain, tin oxide, etc.

[0062] In addition to the above ingredients, the efficacy layer may further contain antibacterial ingredients such as chlorhexidine, cetylpyridinium chloride, triclosan, essential oils, chlorine dioxide, green tea catechins, hinokitiol, lactoferrin, lactoperoxidase, etc., to enhance the efficacy of the breath freshener. The antibacterial ingredients may be contained in an amount of 0.01% to 10%, preferably 0.05% to 7%, and more preferably 0.1% to 5%, based on the raw materials of the efficacy layer.

[0063] The "saliva secretion-promoting ingredient" is an ingredient that stimulates the salivary glands to promote saliva secretion, and may include sugars, sweeteners, ascorbic acid, malic acid, citric acid, etc., and preferably xylitol. The saliva secretion-promoting ingredient may be contained in an amount of 30% to 95%, preferably 40% to 90%, and more preferably 50% to 85%, based on the ingredients of the active layer.

[0064] Lubricants can be added to facilitate the compression and refinement ejection processes during manufacturing. Lubricant ingredients may include calcium stearate, magnesium stearate, stearic acid, sodium stearyl fumarate, and talc. The lubricant may be included in an amount of 0.1% to 10%, preferably 0.3% to 7%, and more preferably 0.5% to 5%, based on the ingredients of the active layer.

[0065] The functional layer may contain at least one binder selected from the group consisting of gelatin, alginate, pectin, starch, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, and polyvinyl acid. The binder may be contained in an amount of 0.1% to 20%, preferably 3% to 17%, and more preferably 5% to 15%, based on the ingredients of the functional layer.

[0066] In addition, sweeteners such as stevia or saccharin for enhancing taste, or flavorings such as peppermint oil or menthol for enhancing flavor may be added to the efficacy layer or the adhesive layer.

[0067] The oral preparation according to one embodiment of the present invention may have a strength of 1000 gf or more but less than 4000 gf. If the strength is less than 1000 gf, there is a risk of breakage during the manufacturing process or transportation, and if the strength is more than 4000 gf, it may be difficult to ingest.

[0068] The oral preparation according to one embodiment of the present invention may further include a layer performing one or more functions selected from the group consisting of surface coating, dissolution rate adjustment, strength adjustment, tooth surface polishing, whitening, and pH adjustment. The layer performing the function may be composed of multiple layers. [Example]

[0069] Experimental Example 1. Comparison of adhesive strength and strength of oral preparations using adhesive polymers Production Example 1. Production of Comparative Examples 1 to 4 and Examples 1 to 3 The common ingredients used in manufacturing the adhesive layer for strength measurement, namely, excipient, pH adjuster, binder, and lubricant, were all the same raw materials. The excipient was calcium carbonate (CaCO3), the pH adjuster was sodium bicarbonate (NaHCO3), the binder was hydroxypropyl methylcellulose (HPMC), and the lubricant was magnesium stearate.

[0070] The tablet manufacturing method was to mix the raw materials for each manufacturing example in a powder mixer for at least 30 minutes, then place 300 mg of the mixed raw materials in a circular mold with a diameter of 12 mm and press the mold with a hydraulic press (Qmesys, QM900A) at a pressure of 5 mPa to manufacture the tablets.

[0071] Experimental Example 1-1. Measurement of adhesive strength of oral preparations using adhesive polymers FIG. 3 is an image of a test process for measuring the adhesive strength of an oral preparation according to one embodiment of the present invention.

[0072] The adhesive strength was measured under normal conditions and under conditions with a lot of saliva. Under normal conditions, 0.5 g of water was removed using a micropipette to prevent the gel from drying, and under conditions with a lot of saliva, 0.5 g of water was not removed.

[0073] The adhesive strength of the prepared oral preparation samples was measured by referring to the literature (Annika Borde et al., Journal of Colloid and Interface Science 341 (2010) 255-260) and measuring the force required for the oral preparation to fall off the material using an oral mucosa simulation material.

[0074] First, 1% agarose gel was selected as the oral mucosa simulation material, and agarose equivalent to a 1% concentration was dissolved in distilled water at high temperature. 10 g of the resulting gel solution was placed in a 50 mm diameter Petri dish and allowed to harden at room temperature. Then, 0.5 g of water was added to the gel to prevent the surface of the gel from drying out.

[0075] Measurements were carried out using a texture analyzer (product name: Texture analyzer, manufacturer: TA instrument, model: TA.XT plus) and a 35 mm aluminum probe. After fixing the tablet to the probe tip with double-sided tape, a force of 50 gf was applied to the tablet for 30 seconds onto the surface of 1% agarose gel fixed to the ground. The force at the time of dropping was divided by the tablet area to calculate the force per unit area (g / mm 2 ) was measured to determine the adhesive strength of the sample. In order to improve the accuracy of the measurement, five samples were prepared for each preparation example, and the average of the measured adhesive strengths was recorded for each preparation example.

[0076] Experimental Example 1-2. Strength measurement of oral preparations made with adhesive polymers FIG. 4 is an image of a test process for measuring the strength of an oral preparation according to one embodiment of the present invention.

[0077] The strength of the prepared oral preparations was measured using the crush test method. The prepared oral preparations were placed vertically on the ground (with the circular surface perpendicular to the ground) and the pressure (gf) applied per unit time was measured using a texture analyzer (product name: Texture analyzer, manufacturer: TA instrument, model: TA.XT plus) and a 35mm aluminum probe, and the strength was calculated from the maximum force measured at break. To increase the accuracy of the measurements, five samples were prepared for each preparation example and the average of the measured strengths was recorded as the strength of each sample.

[0078] [Table 1]

[0079] Referring to Table 1, the experimental results show that the dosage forms of Examples 1 to 3 have higher strength and adhesive power than the Comparative Example, and showed less decrease in adhesive power under conditions with a large amount of saliva.

[0080] Experimental Example 2: Comparison of strength and adhesiveness of oral preparations depending on excipients Production Example 2: Production of Comparative Examples 2, 5, 6 and Examples 4 to 7 The pH adjuster, binder, lubricant, and adhesive polymer, which are common ingredients in the manufacturing of the adhesive layer for strength measurement, were all made from the same raw materials. The pH adjuster was sodium bicarbonate (NaHCO3), the binder was hydroxypropyl methylcellulose (HPMC), the lubricant was magnesium stearate, and the adhesive polymer was carboxymethyl cellulose (CMC).

[0081] The oral preparation was manufactured by adding the raw materials to a powder mixer and mixing them for 30 minutes or more, and then placing 300 mg of the mixed raw materials in a circular mold with a diameter of 12 mm and applying a pressure of 5 mPa using a hydraulic press (Qmesys, QM900A).

[0082] The prepared oral preparations were stored in a container containing silica for drying without any additional drying process. Then, the strength and adhesive strength of each preparation were measured.

[0083] The experiment was carried out by measuring the strength and adhesive force of oral preparations to which different excipients were applied.

[0084] [Table 2]

[0085] Referring to Table 2, the experimental results show that the dosage forms of Examples 4 to 7 have higher strength and adhesive strength under general conditions and under conditions with a lot of saliva than Comparative Examples 1 and 5. In particular, when the size of the silica particles is 50 μm or more as in Comparative Example 6, the excipient did not exert any effect of enhancing strength or adhesive strength.

[0086] Experimental Example 3: Comparison of strength and adhesive power of oral preparations using chicory dietary fiber or linamarin-free cassava starch as adhesive polymers and silica as excipients Production Example 3: Production of Examples 8 and 9 The pH adjuster, binder, and lubricant, which are common ingredients in the manufacturing of the adhesive layer for strength measurement, were all the same raw materials, with sodium bicarbonate (NaHCO3) used as the pH adjuster, hydroxypropyl methylcellulose (HPMC) as the binder, and magnesium stearate as the lubricant.

[0087] The oral preparation was manufactured by adding the raw materials to a powder mixer and mixing them for 30 minutes or more. Then, 300 mg of the mixed raw materials were placed in a circular mold with a diameter of 12 mm and pressurized with a hydraulic press (Qmesys, QM900A) at a pressure of 5 mPa.

[0088] The prepared oral preparation was stored in a container containing silica for drying without any additional drying process, and then the strength and adhesive strength of each sample were measured.

[0089] The experiment was carried out in the same manner as in Experimental Example 1.

[0090] [Table 3]

[0091] Figure 5 is a graph comparing the adhesive strength of oral preparations according to an embodiment of the present invention. Referring to Figure 5 and Table 3, the experimental results show that Examples 8 and 9 have higher strength and adhesive strength than Comparative Example 1. In particular, when the excipient is changed to silica, both strength and adhesive strength are enhanced compared to Examples 1 and 2.

[0092] Experimental Example 4: Comparison of the degree of irritation to the oral mucosa by adhesive polymers Production Example 4: Production of Comparative Examples 7 to 10 and Examples 10 and 11 For comparison with each adhesive polymer, the comparative examples were carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP), Carbopol (Polyacrylic acid), and gum arabic, while the examples were chicory dietary fiber or cassava starch.

[0093] To confirm the degree of irritation to the oral mucosa, the experiment compared the degree of irritation using a cytotoxicity evaluation. For the cytotoxicity evaluation, V79-4 cells (Chinese Hamster, CCL of lung tissue fibroblast) were cultured for 24 hours, and then each adhesive polymer was diluted to an appropriate concentration (any concentration between 1% and 10%) in a solvent that allows dilution (medium (3% FBS), DPBS, DMSO). The medium was then treated with the undiluted solution or 1 / 100 concentration and cultured for 24 hours. The toxicity evaluation was then carried out by measuring absorbance using MTT reagent to determine cell viability. From the results, the IC50 (Half maximal inhibitory concentration), which indicates the concentration at which 50% of cells die, and the CTI (Cellular Toxicity Index) were calculated.

[0094] [Table 4]

[0095] Referring to Table 4, the IC50 values ​​of Examples 10 and 11 were relatively higher than those of Comparative Examples 7 to 10, indicating low toxicity, and thus it was confirmed that the CTI was extremely low.

[0096] Experimental Example 5. Zinc ion (Zn 2+ ) and copper ions (Cu 2+ Comparison of the oral preparation's bad breath improvement effect with the addition of Production Example 5. Production of Comparative Examples 11 and 12 and Examples 12 and 13 As shown in Table 5, the oral preparations used to evaluate the effectiveness in improving bad breath were manufactured using the same raw materials for the common ingredients of excipients, flavor enhancers, pH adjusters, binders, and lubricants. The top layer contained xylitol as an excipient, and the bottom layer contained calcium carbonate (CaCO3). The top layer contained sodium saccharin, L-menthol, and peppermint extract powder as flavor enhancers. The bottom layer contained sodium bicarbonate (NaHCO3) as a pH adjuster. The binder was hydroxypropyl methylcellulose (HPMC), and the lubricant was magnesium stearate.

[0097] [Table 5]

[0098] The oral preparation was manufactured by adding the ingredients for the corresponding layer in the ratio shown in the table for each manufacturing example to a powder mixer and mixing for at least 30 minutes. 50 mg of the mixed ingredients for the lower layer were then placed in a circular mold with a diameter of 12 mm and flattened, and 300 mg of the ingredients for the upper layer were then added to the mold and manufactured using a hydraulic press (Qmesys, QM900A) at a pressure of 5 mPa.

[0099] The prepared oral formulations were stored in containers containing drying silica without any additional drying steps.

[0100] Experimental Example 5-1. Zinc ion (Zn 2+ ) and copper ions (Cu 2+ Comparison of VSC neutralizing effects of oral preparations with the addition of The experiment involved preparing oral preparations for improving bad breath and evaluating their VSC neutralizing effect. 100 μl of the odor source sample (containing approximately 1250 ppb of H2S and approximately 1000 ppb of MeSH) was placed in a sealed 10 ml headspace vial, and 1 g of a 25% tablet suspension, prepared by powdering tablets and dissolving them in purified water, was added. After allowing the mixture to stand for 3 minutes, the H2S and MeSH concentrations were measured using a breath odor analyzer (Oral Chroma, Abimedical, Abilit Corp.).

[0101] [Table 6]

[0102] 6 is a graph comparing the VSC neutralization rate of oral preparations according to an embodiment of the present invention with and without a breath freshener. Referring to FIG. 6 and Table 6, it can be seen that Examples 12 and 13 have a higher breath freshening effect than Comparative Examples 11 and 12.

[0103] Experimental Example 5-2. Zinc ion (Zn 2+ ) and copper ions (Cu 2+ Comparison of VSC neutralization rates under actual use conditions of oral preparations with the addition of After preparing the oral preparation, the VSC neutralization rate was measured under actual use conditions to evaluate its effectiveness in improving bad breath. 28 evaluators were randomly divided into four groups and given different samples, and then asked to take the oral preparation twice a day. The oral preparation for improving bad breath was taken for four weeks, and the VSC neutralization rate was measured each week, and the reduction rate of four types of bad breath-causing bacteria after four weeks was measured to evaluate its effectiveness in improving bad breath.

[0104] The H2S and MeSH concentrations were measured using a VSC breath odor measuring device (Oral chroma, Abimedical, Abilit Corp.) at week 0 of the experiment, and then measured at each week, and the neutralization rate was calculated using the following formula.

[0105]

number

[0106] [Table 7]

[0107] Referring to Table 7, Examples 12 and 13 showed higher VSC neutralization rates under actual use conditions than Comparative Examples 11 and 12. Therefore, it can be confirmed that Examples 12 and 13 have a higher breath odor improvement effect than Comparative Examples 11 and 12.

[0108] Experimental Example 5-3. Zinc ion (Zn 2+ ) and copper ions (Cu 2+ Comparison of the reduction rate of bad breath-causing bacteria under actual use conditions of oral preparations with the addition of After preparing the oral preparation, the reduction rate of bad breath-causing bacteria was measured under actual use conditions to evaluate the effectiveness of improving bad breath. The experiment to measure the reduction rate of bad breath-causing bacteria was carried out as follows. To conduct a quantitative evaluation of each oral bacterial strain at the beginning of the experiment, subjects gargled for one minute with an oral gargle (LG Household & Healthcare EasyPerio), and the oral microorganisms of the subjects were quantitatively analyzed using PCR analysis. Then, after taking the oral preparation for four weeks, subjects gargled for one minute with an oral gargle (LG Household & Healthcare EasyPerio), and the oral microorganisms of the subjects were quantitatively analyzed using PCR analysis. The reduction rate of bad breath-causing bacteria was then calculated using the following formula.

[0109]

number

[0110] [Table 8]

[0111] Referring to Table 8, Examples 12 and 13 showed a higher reduction rate of four types of bad breath-causing bacteria under actual use conditions than Comparative Examples 11 and 12. Therefore, it can be seen that Examples 12 and 13 have a higher bad breath-reducing effect than Comparative Examples 11 and 12.

[0112] Experimental Example 6: Evaluation experiment on the satisfaction level and oral irritation of oral preparations using adhesive polymers Production Example 6: Production of Comparative Examples 13 to 16 and Examples 12 and 13 The oral preparations for sensory evaluation were manufactured using the same common ingredients, including excipients, flavor enhancers, pH adjusters, binders, and lubricants. The top layer contained xylitol as an excipient, and the bottom layer contained calcium carbonate (CaCO3). The top layer alone contained sodium saccharin, L-menthol, and peppermint extract powder as flavor enhancers. The bottom layer alone contained sodium bicarbonate (NaHCO3) as a pH adjuster. Hydroxypropyl methylcellulose (HPMC) was used as a binder, and magnesium stearate was used as a lubricant.

[0113] The oral preparation was manufactured by adding the ingredients for the corresponding layer in the ratio shown in the table for each manufacturing example to a powder mixer and mixing for at least 30 minutes. 50 mg of the mixed ingredients for the lower layer were then placed in a circular mold with a diameter of 12 mm and flattened, and 300 mg of the ingredients for the upper layer were then added to the mold and manufactured using a hydraulic press (Qmesys, QM900A) at a pressure of 5 mPa.

[0114] The prepared oral formulations were stored in containers containing drying silica without any additional drying steps.

[0115] In the experiment, oral preparations for improving bad breath with different adhesive polymers were manufactured, and then evaluations were conducted on user satisfaction and oral irritation. Different types of samples were distributed to 30 evaluators, who were randomly divided into 6 groups, and they were instructed to take the oral preparations twice a day. After one week of use, sensory evaluations were conducted on the scent, taste, irritation, and pleasant sensation. Evaluations were given on a scale of 0 (minimum) to 5 (maximum), and the average of the subjects' responses was calculated to obtain a score for each item.

[0116] [Table 9]

[0117] Referring to Table 9, as a result of the sensory evaluation, Comparative Examples 13 to 16 and Examples 12 to 13 received similar scores in terms of aroma, taste, and pleasant sensation, but in terms of low irritation, Examples 12 and 13 received higher scores than Comparative Examples 13 to 16, indicating that Examples 12 and 13 provide a lower irritation than Comparative Examples 13 to 16.

[0118] Experimental Example 7: Measurement of the disintegration rate of oral preparations using adhesive polymers Production Example 7: Production of Examples 14 and 15 and Production of Comparative Example 17 The oral preparation used in Comparative Example 17 for measuring the disintegration rate was a product that dissolves after adhering to the oral mucosa (Oracoat Xylimelts, product usage time (dissolution rate): 1-4 hours in the daytime, 4-8 hours at night). In addition, to match the mass of one tablet of Comparative Example 17 (approximately 700 mg), Example 14 has the same composition as Example 12, and Example 15 has the same composition as Example 13, but 100 mg of adhesive layer raw material and 600 mg of active layer raw material were used during tableting. In contrast, as shown in Table 9, the same raw materials were used for the common ingredients in the manufacturing process, including excipients, flavor enhancers, pH adjusters, binders, and lubricants. The top layer used xylitol as an excipient, and the bottom layer used calcium carbonate (CaCO3). The top layer alone used sodium saccharin, L-menthol, and peppermint extract powder as flavor enhancers. The bottom layer alone used sodium bicarbonate (NaHCO3) as a pH adjuster. Hydroxypropyl methylcellulose (HPMC) was used as a binder, and magnesium stearate was used as a lubricant.

[0119] The oral preparation was manufactured by adding the ingredients for each layer in the ratio shown in Table 9 to a powder mixer and mixing for 30 minutes or more. 100 mg of the mixed adhesive layer ingredients were then placed in a circular mold with a diameter of 12 mm and flattened, and 600 mg of the upper layer ingredients were then added to the mold and pressed at 5 mPa using a hydraulic press (Qmesys, QM900A).

[0120] The prepared oral formulations were stored in containers containing drying silica without any additional drying steps.

[0121] In the experiment, oral preparations for improving bad breath with different adhesive polymers were prepared and their disintegration rates were measured. Each of Examples 14, 15, and Comparative Example 17 was placed in a tea bag, and the disintegration rate was measured in 100 g of distilled water at 37°C. After 1 hour, 2 hours, and 4 hours for each preparation, the tea bag was removed from the bag and dried in an oven at 60°C for 24 hours, after which its weight was measured and the disintegration rate was calculated using the following formula:

[0122]

number

[0123] [Table 10]

[0124] Figure 7 is a graph comparing the disintegration rates of oral preparations according to examples of the present invention. Referring to Table 10 and Figure 7, the disintegration rate evaluation results show similar disintegration rates to Comparative Example 17. It can be seen that Examples 14 and 15 disintegrate somewhat more slowly than Comparative Example 17, and are somewhat superior in sustained release properties, whereby the active ingredient is released later and the effect is sustained.

[0125] Although the present invention has been described above with reference to preferred embodiments, it will be understood by those skilled in the art or those with ordinary knowledge in the art that various modifications and variations can be made to the present invention without departing from the spirit and technical scope of the present invention as set forth in the claims below.

[0126] Therefore, the technical scope of the present invention should not be limited to the contents described in the detailed description of the specification, but should be defined by the claims.

Claims

1. an adhesive layer comprising an adhesive polymer; and an efficacy layer; The adhesive polymer includes at least one selected from the group consisting of a mixture of cassava starch from which linamarin has been removed and chicory dietary fiber; Oral preparations.

2. The oral preparation according to claim 1, wherein the efficacy layer provides at least one of the functions of suppressing bad breath, promoting saliva secretion, reducing plaque, reducing gingivitis, reducing periodontitis, alleviating periodontal disease, and alleviating dental caries.

3. The oral formulation of claim 1 , wherein the oral formulation is in the form of a double-layered tablet.

4. The adhesive layer further comprises silica as an excipient, The oral preparation according to claim 1, wherein the oral preparation has any one dosage form selected from the group consisting of a breath freshener, a dry mouth relieving agent, a solid mouthwash, a solid toothpaste, and a sustained-release candy.

5. The oral preparation according to claim 4, wherein the excipient is contained in an amount of 20 wt % to 40 wt % by weight of the adhesive layer raw materials.

6. The oral preparation according to claim 4, wherein the silica has a particle diameter of 1 nm or more and 50 μm or less.

7. The efficacy layer contains copper ions (Cu ２＋ ), zinc ions (Zn ２＋ ) or tin ions (Sn ２＋ 2. The oral preparation according to claim 1, further comprising at least one salt selected from the group consisting of:

8. 8. The oral preparation according to claim 7, wherein the efficacy layer contains the breath odor suppressant in a weight ratio of 0.1 wt % to 5 wt % based on the total weight of the layer.

9. 2. The oral preparation according to claim 1, wherein the efficacy layer contains the saliva promoter in a weight ratio of 50 wt % to 80 wt % based on the total weight of the efficacy layer.

10. The oral preparation according to claim 1, wherein the adhesive layer is contained in a weight ratio of 2 wt % to 50 wt % of the total weight.

11. The oral preparation according to claim 1, wherein the efficacy layer is contained in a weight ratio of 20 wt % to 85 wt % of the total weight.

12. The oral preparation according to claim 1, wherein the oral preparation has a strength of 1000 gf or more and less than 4000 gf.

13. The oral preparation according to claim 1, further comprising a layer that performs one or more functions selected from the group consisting of surface coating, dissolution rate adjustment, strength adjustment, polishing of the tooth surface, whitening, and pH adjustment.

14. An oral adhesive composition comprising a polymer containing at least one selected from the group consisting of a mixture of cassava starch from which linamarin has been removed and chicory dietary fiber, as an oral adhesive.

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