JP2009143831A - Oral composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an oral composition which does not cause condensation, precipitation and the like and uniformly comprises lysozyme or its salt while stably maintaining its activity. <P>SOLUTION: The oral composition comprises (a) lysozyme or its salt, (b) at least one anionic water-soluble polymer selected from a carboxymethyl cellulose salt, xanthan gum and carrageenan, and (c) at least one water-soluble metal salt selected from the group consisting of a magnesium salt, a calcium salt, and a zinc salt. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an oral composition, and in particular, relates to an oral composition in which condensation, precipitation, or the like does not occur, lysozyme or a salt thereof is uniformly blended, and its activity is stably maintained.

  Lysozyme is a mucopolysaccharide hydrolase, and exhibits a bactericidal (lytic) action against inflamed microorganisms by its mucopolysaccharide hydrolyzing action, and has a strong anti-inflammatory action. Therefore, lysozyme is effective in the prevention and treatment of both infectious and non-infective inflammation, and plays a very important role in the prevention, progression prevention and treatment of oral diseases, especially periodontal diseases such as alveolar pyorrhea. It is used in various internal medicines and external preparations.

  Examples of such preparations include various products such as dentifrices and mouthwashes for application in the oral cavity, particularly to soft tissues in the oral cavity (eg, oral mucosa, tongue, gums, salivary glands, palate, etc.). Considering the ease of application and the retention of the preparation, an ointment-like preparation that can be applied with a finger or the like is most desirable.

  In this regard, various studies have been made on lysozyme-blended oral compositions in order to increase the activity of lysozyme and / or prevent the decrease in the activity of lysozyme, and various patents have been disclosed.

  For example, Patent Document 1 (Japanese Patent Laid-Open No. 52-54037), Patent Document 2 (Japanese Patent Laid-Open No. 52-90638) include sodium halide salts, and Patent Document 3 (Japanese Patent Laid-Open No. 02-264711). Dihydrogen phosphate, Patent Document 4 (Japanese Patent Laid-Open No. 03-157322), Patent Document 5 (Japanese Patent Laid-Open No. 03-157323), and Patent Document 6 (Japanese Patent Laid-Open No. 03-167115) have specific interfaces. An oral composition in which an active agent and lysozyme coexist is disclosed. Patent Document 7 (Japanese Patent Laid-Open No. 06-329523) discloses an oral composition in which lysozyme is mixed with hydroxyethyl cellulose and sodium alginate.

  However, these oral compositions all relate to preparations centering on dentifrices and mouthwashes, and when this is simply used for ointment-like preparations, the appearance properties may deteriorate or in some cases. Causes aggregation and precipitation. This is because lysozyme reacts with ionic components such as commonly used anionic surfactants such as sodium lauryl sulfate and anionic water-soluble polymers such as sodium carboxymethylcellulose, sodium alginate, and carrageenan. It is thought that it affects the appearance properties and causes aggregation and precipitation. In addition, regarding the composition for oral cavity, it has not been clarified whether lysozyme is actually blended uniformly in the entire composition.

Therefore, as a result of various studies to solve these problems, the present inventors have found a technique in which aggregation and precipitation do not occur and lysozyme is uniformly blended in the composition while maintaining its activity stably. Furthermore, the inventors have found that this can be used for all oral compositions including ointment-like preparations, and have completed the present invention.
JP 52-54037 A JP 52-90638 A Japanese Patent Laid-Open No. 02-264711 Japanese Patent Laid-Open No. 03-157322 Japanese Patent Laid-Open No. 03-157323 Japanese Patent Laid-Open No. 03-167115 Japanese Patent Laid-Open No. 06-329523

  An object of the present invention is to easily provide an oral composition in which lysozyme or a salt thereof is uniformly blended in a composition without causing condensation, precipitation, or the like while maintaining activity stably.

  As a result of intensive studies to solve the above problems, the present inventors have added 0.5 to 10% by weight of a water-soluble metal salt in addition to lysozyme or a salt thereof and an anionic water-soluble polymer. The inventors have found that a composition in which lysozyme or a salt thereof is blended stably and uniformly in a composition without causing aggregation or precipitation can be produced, and the present invention has been completed.

That is, this invention provides the composition for oral cavity of the following items 1 and 2 especially.
Item 1. An oral composition comprising the following (a) to (c):
(A) lysozyme or a salt thereof (b) at least one anionic water-soluble polymer selected from the group consisting of carboxymethylcellulose salt, xanthan gum and carrageenan (c) selected from the group consisting of magnesium salt, calcium salt and zinc salt 0.5 to 10% by weight of at least one water-soluble metal salt
Item 2. Item 2. The oral composition according to Item 1, wherein the water-soluble metal salt is at least one selected from the group consisting of magnesium chloride, calcium chloride, calcium lactate and zinc gluconate.

  According to the present invention, it is possible to easily provide an oral composition in which lysozyme or a salt thereof is uniformly blended in the composition while maintaining activity stably without causing condensation or precipitation. Moreover, since the activity of lysozyme is stably maintained, the composition for oral cavity can be preferably used for prevention, progression prevention, and treatment of oral diseases, particularly periodontal diseases such as alveolar pyorrhea. Furthermore, since aggregation and precipitation do not occur, there is no discomfort to the user in appearance and touch during use, and no inconvenience occurs during manufacture and use.

  Hereinafter, the present invention will be described in more detail.

  The oral composition according to the present invention is an oral composition containing lysozyme or a salt thereof, a specific anionic water-soluble polymer and a water-soluble metal salt.

  Lysozyme is usually obtained by extraction and purification from egg white of chicken eggs according to a general method. Moreover, it can obtain from Eisai Food Chemical Co., Ltd. or Kewpie Co., Ltd. as a commercial item (all are brand names "lysozyme chloride"). Examples of the lysozyme salt include lysozyme chloride. If the amount of lysozyme or a salt thereof used in the present invention is too small, a sufficient addition effect cannot be obtained, and adding more than necessary is economically disadvantageous. Therefore, the addition amount is generally 0.05 to 5.0% by weight, preferably 0.25 to 2.5% by weight, more preferably 0.25 to 1.5% by weight, based on the total amount of the composition. is there.

  The anionic water-soluble polymer blended in the oral composition according to the present invention is preferably carboxymethyl cellulose salt, xanthan gum and carrageenan. Among these, carboxymethylcellulose salt is preferable, and examples of the salt include sodium salt, potassium salt, and calcium salt. Among these, sodium salt of carboxymethylcellulose is particularly preferable. Moreover, the compounding amount of the anionic water-soluble polymer is preferably 0.01 to 10% by weight, more preferably 0.05 to 5% by weight, more preferably 0.5 to It is further preferably 2.5% by weight, and more preferably 1 to 2% by weight.

  The water-soluble metal salt to be blended in the composition for oral cavity according to the present invention is preferably a water-soluble polyvalent metal salt, and particularly preferably water-soluble polyvalent metal salts of magnesium salt, calcium salt and zinc salt. Specifically, magnesium chloride, trimagnesium phosphate, magnesium sulfate, magnesium citrate, magnesium gluconate, calcium chloride, calcium gluconate, calcium lactate, calcium pantothenate, calcium dihydrogen phosphate, calcium propionate, calcium acetate , Calcium bromide, calcium glycerophosphate, zinc chloride, zinc gluconate, zinc paraphenolsulfonate, zinc sulfate, zinc acetate and the like, and magnesium chloride, calcium chloride, calcium lactate and zinc gluconate are particularly preferable. By using these water-soluble metal salts, not only the occurrence of aggregation and precipitation can be suppressed, but also the pharmaceutical properties such as shape retention and spinnability can be improved. The amount of the water-soluble metal salt is preferably 0.5 to 10% by weight, more preferably 1 to 5% by weight, and 1 to 2.5% by weight based on the total amount of the composition. More preferably it is.

  Furthermore, the ratio of the anionic water-soluble polymer and the water-soluble metal salt to be blended in the oral composition according to the present invention is such that the ratio by weight to the total amount of the composition is anionic water-soluble polymer / water-soluble metal. The salt is preferably 0.01 to 10, more preferably 0.05 to 5, and further preferably 0.1 to 2.

  The water-soluble component according to the present invention is not particularly limited, but is preferably one in which 0.1% by weight or more dissolves in water at 60 ° C. or higher.

  Although pH of the composition for oral cavity which concerns on this invention is not specifically limited unless the effect of this invention is impaired, In order to improve the stabilization of lysozyme activity more, it is preferable that it is pH5-pH7.

  The composition for oral cavity according to the present invention can be used, for example, by applying with a finger or the like as an ointment-like preparation, or putting it on a toothbrush as a dentifrice. Therefore, it can be used by squeezing out from a container such as a tube, or scooping out a container such as a bottle or can with a finger.

  The composition for oral cavity according to the present invention comprises, for example, ointment preparation, toothpaste, gel, pasta, dentifrice (toothpaste, liquid dentifrice, liquid dentifrice, etc.), mouthwash, jelly according to conventional methods. Ordinary dosage forms such as formulations and gums can be obtained. The ointment-like preparation mentioned here refers to a so-called ointment, and includes an oily ointment, an emulsion ointment, a water-soluble ointment and the like. The oral composition according to the present invention is preferably an ointment-like preparation, and among them, a water-soluble ointment is particularly preferable.

  In the composition for oral cavity according to the present invention, other base components are not particularly limited as long as the effects of the present invention are not impaired, and those usually used for this type of composition can be blended. For example, in the case of ointment-like preparations, wetting agents, flavoring agents, active agents, sweeteners, preservatives, coloring agents, pH adjusting agents, stabilizers, flavoring agents, astringents, thickeners, other medicinal properties An agent or the like is appropriately blended. In the case of toothpaste, abrasives, wetting agents, flavoring agents, activators, sweeteners, preservatives, colorants, pH adjusters, stabilizers, flavoring agents, astringents, thickeners, other Medicinal agents and the like are appropriately blended.

  Specifically, as a wetting agent, ethanol, glycerin, sorbit, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, palatinit, etc. alone or in combination It can mix | blend in combination. The normal amount of wetting agent is 5 to 70% by weight.

  Flavoring agents include menthol, anethole, carvone, eugenol, limonene, peppermint oil, spearmint oil, wintergreen, methyl salicylate, cionel, thymol, clove oil, eucalyptus oil, rosemary oil, sage oil, lemon oil, orange oil, Osimene oil, citronellol, methyl eugenol and the like can be mentioned. These flavoring agents can be blended alone or in combination of two or more. The usual compounding quantity of a flavoring agent is 0.05 to 5 weight%.

  Activating agents include sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, N-acyl glutamates such as sodium N-palmitoyl glutamate, sucrose fatty acid esters, maltose fatty acid esters, sugar fatty acid esters such as lactose fatty acid esters, poly Oxyethylene alkyl ethers, alkyl glucosides, fatty acid alkanolamides, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid esters, Fatty acid monoglyceride, N-alkyldiaminoethylglycine such as N-lauryldiaminoethylglycine, N-myristyldiethylglycine, - alkyl -N- carboxymethyl ammonium betaine surfactants such as lauryl dimethylamino acetic acid betaine. These surfactants can be blended singly or in combination of two or more, and the blending amount is usually 0.1 to 10% by weight.

  As sweeteners, saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perilartine, thaumatin, asparatylphenylalanyl methyl ester, α-methoxycinnamic aldehyde, xylit, sucralose, xylitol, palatinose, palatinit, Erythritol, maltitol, etc. can be blended. These sweeteners can be blended alone or in combination of two or more. The usual amount of sweetener is 0.005 to 5% by weight, preferably 0.01 to 0.5% by weight.

  Examples of the preservative include parabens such as methyl paraben, ethyl paraben, propyl paraben, and butyl paraben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride.

  Examples of the colorant include legal dyes such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3, mineral dyes such as ultramarine blue, enhanced ultramarine blue, and bitumen, and titanium oxide.

  Examples of the pH adjuster include citric acid, phosphoric acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or a chemically possible salt thereof, sodium hydroxide, and the like. It can mix | blend individually or in combination of 2 or more types so that pH of a composition may be the range of 5-7. The normal amount of the pH adjuster is 0.01 to 2% by weight.

  Examples of the stabilizer include sodium edetate, sodium thiosulfate, sodium sulfite, sodium chloride, calcium lactate, lanolin, triacetin, castor oil, magnesium sulfate and the like.

  Examples of the corrigent include tea extract, tea dry distillation solution, propolis extract, sodium glutamate and the like.

  Examples of astringents include baking soda and aluminum lactate.

  As a thickener, in addition to the carboxymethylcellulose salt used in the present invention, cellulose derivatives such as hydroxypropylcellulose, hydroxypropylmethylcellulose, and hydroxyethylcellulose; in addition to xanthan gum used in the present invention, gums such as tragacanth gum, karaya gum, gum arabic, and gellan gum , Synthetic binders such as polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, polyvinylpyrrolidone, inorganic binders such as thickening silica, aluminum silica gel, bee gum, sodium alginate, pectin, soybean polysaccharide, sodium chondroitin sulfate, It is also possible to add sodium hyaluronate or the like. These thickeners can be blended alone or in combination of two or more. The normal blending amount of the thickener is 0.01 to 20% by weight.

  Other medicinal agents include: fluorine compounds such as sodium fluoride, sodium monofluorophosphate, stannous fluoride; enzymes such as dextranase, mutanase, amylase, protease, lytic enzyme (Litech Enzyme); tranexamic acid, ε-aminocaproic acid, aluminum chlorohydroxy allantoin, allantoin, dihydrocholesterol, glycyrrhizic acid, glycyrrhetinic acid, bisabolol, isopropylmethylphenol, glycerophosphoric acid, chlorophyll, copper gluconate, sodium chloride, water-soluble inorganic phosphate compound, chlorhexidine salts, triclosan , Cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride; vitamins such as acetic acid-dl-α-tocopherol, pyridoxine acetate, ascorbic acid or salts thereof Kinds: plant extracts such as thyme and urgon are listed. These medicinal agents can be blended alone or in combination of two or more.

  As abrasives, dicalcium phosphate dihydrate and anhydrous, calcium phosphate, tricalcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, anhydrous silicic acid, silica gel, aluminum silicate, insoluble sodium metaphosphate Tertiary magnesium phosphate, magnesium carbonate, calcium sulfate, polymethyl methacrylate, bentonite, zirconium silicate, hydroxyapatite, synthetic resin, and the like can be used. These abrasives may be used alone or in combination of two or more. The normal compounding amount of the abrasive is 5 to 50% by weight.

  As other bases, alcohols, silicon, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane and the like can be added.

  In addition, what is necessary is just to let the compounding quantity of these arbitrary components be the quantity of the grade mix | blended with the normal composition for oral cavity, as long as the effect of this invention is not prevented.

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not limited to the following Example. In addition, the compounding quantity in each example shows weight%, unless there is a prescription | regulation.

<Preparation of composition>
Water and methyl paraben were added to various metal salts, heated to 60 to 70 ° C., and stirred for 5 to 10 minutes until dissolved. Next, concentrated glycerin and various anionic water-soluble polymers were added, and the mixture was stirred for 5 minutes at 3000 rpm with a homomixer (M2-f, manufactured by Tokushu Kika Kogyo Co., Ltd.). Further, water and lysozyme chloride were added, and the mixture was stirred with a homomixer at 3000 rpm for 5 minutes to prepare a water-soluble ointment.

<Performance evaluation of composition>
In each example, the cohesiveness and appearance properties of the produced compositions were evaluated.

Aggregation property It was visually evaluated whether or not aggregation occurred (including a state where a plurality of granular materials were produced). The evaluation criteria are as follows.
○: No aggregation was observed ×: Aggregation occurred

Appearance properties In consideration of the fact that the composition is used as a composition for oral cavity, the occurrence of aggregation / precipitation, color, and the like were comprehensively evaluated by visual observation. The evaluation criteria are as follows.
1: Appearance property is very good 2: Appearance property is good 3: Appearance property is bad

  Below, the table | surface which described the compounding quantity at the time of composition preparation and the result of the performance evaluation of a composition is shown. In addition, the numerical value about the component in a table | surface represents the compounding quantity in weight%.

  As shown in Table 1, from the results of Examples, 1-2% of an anionic water-soluble polymer selected from the group consisting of sodium carboxymethylcellulose, xanthan gum and carrageenan, and magnesium chloride, calcium chloride, calcium lactate and The composition containing 0.5 to 10% of at least one water-soluble metal salt selected from the group consisting of zinc gluconate was confirmed to have no aggregation and good appearance properties.

  On the other hand, from the results of Comparative Examples 1 to 4, it was confirmed that when the concentration of the water-soluble metal salt was 0.1% or less, condensation occurred and the appearance properties were poor. Moreover, from the results of Comparative Examples 5 to 11, it was confirmed that sodium alginate was unsuitable as an anionic water-soluble polymer. Further, from the results of Comparative Examples 12 to 14, it was confirmed that condensation occurred and the appearance properties were poor when calcium hydrogen phosphate, calcium carbonate, or aluminum lactate was used as the metal salt.

  As described above, it was found that the effect of the composition for oral cavity according to the present invention was exhibited for the first time by blending a specific anionic water-soluble polymer and a specific water-soluble metal salt with specific concentrations. .

<Evaluation of lysozyme activity in the composition>
The activity of lysozyme chloride in the compositions of Examples 1 and 4 and Comparative Example 2 was measured. The composition was prepared the day before the measurement, and was measured according to the lysozyme hydrochloride quantification method of the Japanese Pharmacopoeia Standards for Pharmaceutical Ingredients. The measurement was performed by collecting samples from three points of the same composition.
The results are shown below. A graph of the results is shown in FIG.

  As shown in Table 2, the lysozyme activity of the composition containing 10% magnesium chloride (Example 1) and the composition containing 1% (Example 4) was maintained at almost 100%. Furthermore, the standard deviations were both as low as 0.7, and it was found that lysozyme was blended almost uniformly in the composition. On the other hand, in the composition to which no magnesium chloride was added (Comparative Example 2), the lysozyme activity was reduced by about 10%, and the standard deviation was 8.0. It was.

  Below, the formulation example of the composition for oral cavity which concerns on this invention is described.

The measurement result of lysozyme activity in the composition of Examples 1 and 4 and Comparative Example 2 is graphed.

Claims (2)

An oral composition comprising the following (a) to (c):
(A) lysozyme or a salt thereof (b) at least one anionic water-soluble polymer selected from the group consisting of carboxymethylcellulose salt, xanthan gum and carrageenan (c) selected from the group consisting of magnesium salt, calcium salt and zinc salt 0.5 to 10% by weight of at least one water-soluble metal salt The oral composition according to claim 1, wherein the water-soluble metal salt is at least one selected from the group consisting of magnesium chloride, calcium chloride, calcium lactate and zinc gluconate.

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