HK1193763A - Oral composition - Google Patents

Abstract

Provided is an oral composition into which an egg antibody can be contained stably and which can prevent or ameliorate oral diseases such as dental caries and a periodontal disease. The oral composition is characterized by comprising at least one component selected from the group consisting of a lipase, a protease and an egg antibody, citric acid, and a metal salt of citric acid. The total content of the lipase, the protease and the egg antibody is preferably 0.001 to 10 wt%. It is preferred that the relationship represented by the following formula: 0.005 <= A/B <= 1, wherein A [wt%] represents the content of citric acid and B [wt%] represents the content of the metal salt of citric acid, is fulfilled. The oral composition according to the present invention preferably contains a polyglycerin fatty acid ester or an amino-acid-type amphoteric activator as a surfactant. The oral composition according to the present invention preferably contains a collagen.

Description

Oral composition

Technical Field

The present invention relates to oral compositions.

Background

The cause of caries is adhesion of tartar (plaque). It has been pointed out in connection with oral hygiene that removal or prevention of adhering tartar is important, i.e. that adhesion of tartar is prevented. Tartar formation is due to the enzyme produced by streptococcus mutans(s), glucosyltransferase, which synthesizes viscous and insoluble glucan with which streptococcus mutans adheres strongly to the surface of the teeth, using sucrose as a substrate.

In addition, such adhesion of tartar is also an important cause of periodontal disease, such as inflammation of the periodontal tissues, which is manifested as redness and swelling of the gingiva, periodontitis, or pyorrhea with radiculitis.

In order to prevent or improve such oral diseases such as dental caries and periodontal disease, oral compositions containing egg antibodies, enzymes, and the like have been developed (see, for example, patent documents 1 and 2).

However, the conventional oral composition cannot stably mix egg antibodies or enzymes, and thus it is difficult to continuously and sufficiently prevent adhesion of tartar. Therefore, conventional oral compositions do not sufficiently prevent or improve dental caries or periodontal disease.

Documents of the prior art

Patent document

Patent document 1: japanese patent application laid-open No. 2641228

Patent document 2: japanese patent application laid-open No. 2001-181163

Disclosure of Invention

Problems to be solved by the invention

The purpose of the present invention is to provide an oral composition which can stably mix egg antibodies or enzymes and prevent or improve oral diseases such as dental caries and periodontal disease.

Means for solving the problems

This object is achieved by the following (1) to (8) of the present invention.

(1) An oral composition comprising at least 1 selected from the group consisting of lipase, protease and egg antibody; citric acid; and a metal citrate.

(2) The composition for oral cavity according to (1), wherein the total amount of the protease and the egg antibody is 0.001 to 10 wt%.

(3) The oral composition according to the above (1) or (2), wherein when the amount of the citric acid is A [ wt% ]andthe amount of the metal citrate is B [ wt% ], the relationship of 0.005. ltoreq. A/B.ltoreq.1 is satisfied.

(4) The oral composition according to any one of the above (1) to (3), wherein when the amount of citric acid mixed is A [ wt% ], and the total amount of the protease and the egg antibody mixed is C [ wt% ], the relationship of 0.0005. ltoreq.A/C.ltoreq.10000 is satisfied.

(5) The oral composition according to any one of the above (1) to (4), wherein the ratio of B/C.ltoreq.10000 is 0.005. ltoreq.B/C, where B represents the mixing amount of the metal citrate and C represents the total mixing amount of the lipase, the protease and the egg antibody.

(6) The oral composition according to any one of the above (1) to (5), further comprising a polyglycerin fatty acid ester or an amino acid-based amphoteric surfactant as a surfactant.

(7) The oral composition according to any one of the above (1) to (6), further comprising collagen.

(8) The oral composition according to any one of the above (1) to (7), wherein the salt concentration in the oral composition is 0.1 to 20%.

Effects of the invention

According to the present invention, there can be provided an oral composition which can stably contain an antibody or an enzyme from an egg and prevent or improve an oral disease such as dental caries or periodontal disease.

Detailed Description

Suitable embodiments of the oral composition of the present invention will be described in detail below.

Further, the oral composition of the present specification comprises: toothpaste, toothpaste powder, liquid toothpaste, lozenge, tablet, cream, ointment, patch, mouthwash, chewing gum, and the like.

The oral composition of the present invention is used for inhibiting tartar formation and preventing oral diseases, and is characterized by comprising at least 1 selected from the group consisting of lipase, protease and egg antibody; citric acid; and a metal citrate.

In order to prevent or improve oral diseases such as dental caries and periodontal disease, oral compositions containing egg antibodies have been developed. However, in the conventional oral composition, the egg antibody or enzyme cannot be stably mixed, so that it is difficult to prevent or improve dental caries or periodontal disease.

In view of the above problems, the present inventors have made extensive studies, and as a result, citric acid and a metal citrate are mixed in an oral composition as described later together with an egg antibody or an enzyme. Accordingly, the present inventors have found that egg antibodies and enzymes are stably mixed as described below. As a result, the present inventors have found that an excellent prophylactic and ameliorating effect on oral diseases can be exerted.

The various components are described in detail below.

[ egg antibody ]

The egg antibody is obtained from an egg produced by a chicken immunized with an enzyme (antigen) produced by pathogenic bacteria of an oral disease, and has a function of inactivating an enzyme produced by pathogenic bacteria of an oral disease.

As described above, such egg antibodies have not been stably incorporated in oral compositions, and the above-mentioned functions deteriorate with time, and thus the prophylactic effect on oral diseases cannot be sufficiently exhibited. In the present invention, egg antibodies can be stably mixed by mixing egg antibodies with the oral composition together with the components described later, and the functions of egg antibodies can be stably exerted. As a result, it is possible to exert a prophylactic or ameliorating effect on oral diseases.

Examples of egg antibodies include: antibodies obtained from chicken eggs immunized with an antigen produced by an oral bacterium such as Streptococcus mutans or Porphyromonas gingivalis.

In particular, when an egg antibody obtained from an egg immunized with an enzyme produced by Streptococcus mutans is used, the following effects can be obtained.

Dental caries in oral diseases is generally caused by the oral bacteria Streptococcus mutans.

S. mutans produces membrane-bound glucosyltransferase in the oral cavity. The produced membrane-bound glucosyltransferase synthesizes an insoluble glucan having adhesiveness, using sucrose as a substrate.

By this synthesized glucan, Streptococcus mutans adheres strongly to the surface of the teeth, forming tartar. Dental caries is produced due to these dental calculus. In addition, the tartar stays in the oral cavity for a long time, and thereby periodontal diseases such as gingivitis and periodontitis occur.

Since the oral composition contains egg antibodies against the enzyme produced by Streptococcus mutans, it is effective in preventing adhesion of tartar to the surface of teeth. That is, the egg antibody inactivates enzymes produced by Streptococcus mutans, thereby inhibiting biofilm (tartar layer) formed by adhesion of tartar to the tooth surface, and reliably preventing dental caries and periodontal disease.

Among the enzymes produced by Streptococcus mutans, the enzyme acting as an egg antibody is preferably membrane-bound glucosyltransferase, which is an adhesion factor of Streptococcus mutans to teeth. Accordingly, adhesion of Streptococcus mutans to the tooth surface can be suppressed, and adhesion of tartar can be more effectively prevented. As a result, the occurrence of dental caries and periodontal disease can be prevented more effectively.

The egg antibody having a membrane-bound glucosyltransferase activity can be obtained by immunizing a chicken with a membrane-bound glucosyltransferase enzyme and preparing immunoglobulin from an egg produced by the chicken.

The immunoglobulin thus obtained acts as an antibody against an adhesion factor of Streptococcus mutans to teeth, and also inhibits the production of membrane-bound glucosyltransferase. As a result, glucan synthesis is inhibited, and tartar formation is effectively inhibited.

In addition, when such egg antibodies are used in combination with the components described later, the egg antibodies can be stably mixed in the oral composition and the activity of Streptococcus mutans can be more effectively inhibited. As a result, occurrence of oral diseases such as dental caries and periodontal disease can be effectively prevented.

In addition, the following effects can be obtained by using an egg antibody obtained from an egg immunized with an enzyme produced by porphyromonas gingivalis.

Porphyromonas gingivalis is anaerobic, a bacterium present in dental calculus. Moreover, the porphyromonas gingivalis produces a proteolytic enzyme called gingivalin. The enzyme destroys gum tissue and promotes inflammation of gum, thereby exacerbating periodontal disease.

The oral composition contains an antibody against (gingivanin), and is capable of inactivating an enzyme produced by porphyromonas gingivalis. This can suppress the worsening of gingivitis, and can more reliably and effectively prevent or improve the oral disease.

[ Lipase ]

Lipases are a generic term for enzymes that catalyze the hydrolysis of lipids with water, and are called three major digestive enzymes in combination with amylase and protease. The lipase is a hydrolytic enzyme for decomposing cell walls, lipid and sugar. Lipases are enzymes having a function of inhibiting the activity of oral bacteria by decomposing cell walls of oral bacteria, decomposing sugars utilized by oral bacteria, and the like.

In conventional oral compositions, it can be difficult to stably mix lipases. However, by using citric acid and a metal citrate in combination with lipase as in the present invention, lipase can be stably mixed in the oral composition.

Examples of lipases include: lipases derived from organs such as pig and lipases derived from microorganisms include, specifically, lipases derived from Pseudomonas and Bacillus.

[ protease ]

The protease refers to a general term for enzymes that hydrolyze peptide bonds of polypeptides (generally 100 residues are less than full, and the molecular weight is small) or proteins (generally 100 residues or more, and the molecular weight is large) in which amino acids are linked by peptide bonds in a chain.

There are a number of proteins contained in dental calculus. Proteases have a function of decomposing and removing these proteins. By containing protease in the oral composition, tartar can be effectively removed.

Conventional oral compositions have difficulty in stably mixing proteases. However, by using citric acid and a citric acid metal salt in combination with a protease as in the present invention, the protease can be stably mixed in the oral composition.

Examples of proteases include: examples of the protease include neutral protease produced by a bacterium belonging to the genus Bacillus (BacIllus) (NoVa), alkaline protease (NoVa), protease Esperase (NoVa), protease Savinase (NoVa), protease Nagare (Rex chemical Co., Ltd.), protease API-21 (Showa Denko K.K.), protease Prozyme produced by a filamentous bacterium belonging to the genus Aspergillus (AspergIllus) (Prozyme, Japan pharmaceutical Co., Ltd.), and Serratia protease produced by a bacterium belonging to the genus Serratia (Serratia). In addition, there may be enumerated, for example: papain from fruit, bromelain, etc. In addition, for example, a culture solution isolated from soil or the like to a protease-producing strain can be used.

The total amount of the egg antibody, lipase and protease is preferably 0.001 to 10wt%, more preferably 0.05 to 5 wt%. Thus, the movement of bacteria in the oral cavity can be more surely suppressed. On the contrary, if the total amount is less than the lower limit value, the amount of the antibody retained in the oral cavity is insufficient, and it is difficult to sufficiently suppress the activity of bacteria in the oral cavity. On the other hand, if the total amount exceeds the upper limit value, the effect corresponding to the content cannot be sufficiently obtained.

[ citric acid and citric acid metal salt ]

The oral composition of the present invention contains citric acid and a metal citrate.

Citric acid and metal citrate are components that contribute to the stable mixing of the egg antibody, lipase and protease in the oral composition. By containing citric acid and a metal citrate in this manner, the functions of egg antibodies, lipase and protease can be stably exerted. As a result, it is possible to prevent or improve oral diseases such as dental caries and periodontal disease. The following reasons are considered.

The egg antibody contains many amino acids, and has a three-dimensional structure due to electrostatic force caused by amino acid charges. However, this construction is fragile and is greatly affected by moisture, temperature, pH, and salt concentration. Therefore, it is considered that by adding citric acid and a citric acid metal salt to the oral composition, the optimum pH and salt concentration for egg antibodies and the like can be adjusted, and a stable three-dimensional structure is formed.

Examples of the metal citrate salts include: sodium citrate, potassium citrate, calcium citrate, magnesium citrate, copper citrate, and the like.

The amount of citric acid is preferably 0.005 to 10wt%, more preferably 0.01 to 5 wt%. In this way, egg antibodies, lipase and protease can be stably mixed in the oral composition more efficiently.

The amount of the metal citrate to be mixed is preferably 0.05 to 10wt%, more preferably 0.1 to 5wt%, and still more preferably 0.2 to 1 wt%. In this way, egg antibodies, lipase and protease can be stably mixed in the oral composition more efficiently.

When the amount of citric acid to be mixed is A [ wt% ] and the amount of metal citrate to be mixed is B [ wt% ], the relationship of 0.005. ltoreq. A/B. ltoreq.1 is preferably satisfied, and the relationship of 0.01. ltoreq. A/B. ltoreq.0.5 is more preferably satisfied. By satisfying such a relationship, the egg antibody, lipase and protease can be stably mixed in the oral composition more effectively. In particular, the stability of the egg antibody can be obviously improved.

Further, when the amount of citric acid to be mixed is A [ wt% ] and the total amount of lipase, protease and egg antibody to be mixed is C [ wt% ], the relationship of 0.0005. ltoreq.A/C.ltoreq.10000 is preferably satisfied, and the relationship of 0.002. ltoreq. A/C.ltoreq.2000 is more preferably satisfied. By satisfying such a relationship, the egg antibody, lipase and protease can be stably mixed in the oral composition more effectively. In particular, the stability of the egg antibody can be obviously improved.

In addition, when the amount of the metal citrate is B [ wt% ], and the total amount of the lipase, the protease and the egg antibody is C [ wt% ], the relationship of 0.005. ltoreq. B/C.ltoreq.10000 is preferably satisfied, and the relationship of 0.01. ltoreq. B/C.ltoreq.2000 is more preferably satisfied. By satisfying such a relationship, the egg antibody, lipase and protease can be stably mixed in the oral composition more effectively. In particular, the stability of the egg antibody can be obviously improved.

[ other ingredients ]

The oral composition of the present invention may contain the following components in addition to the above components.

(collagen)

The oral composition of the present invention may further contain collagen.

Collagen is a component contributing to stable mixing of the egg antibody, lipase and protease in the oral composition. By using citric acid and a metal citrate in combination with collagen, stable mixing of egg antibody, lipase and protease in the oral composition can be further promoted, and the functions of egg antibody, lipase and protease can be stably exerted. As a result, it is possible to more effectively prevent or improve oral diseases such as dental caries and periodontal disease.

Examples of collagen include: fibrous collagens such as collagen types I to III and collagen type V; type IV collagen, non-fibrillar collagen of types VI to VIII, and the like; or hydrolyzed collagen (collagen polypeptide) obtained by hydrolyzing these collagens with an acid or an enzyme, water-soluble collagen (atelocollagen), gelatin, and the like.

Among them, when hydrolyzed collagen is used, the egg antibody, lipase and protease can be stably mixed in the oral composition more effectively, and the functions of the egg antibody, lipase and protease can be stably exerted. As a result, the oral disease can be more effectively prevented or improved.

The hydrolyzed collagen is a collagen contained in a large amount in skins of fish, cattle, pigs, and the like, and is hydrolyzed with an acid, a base, and the like to be a small molecule, thereby being a high-purity protein which is easily absorbed in the body. The collagen may be derived from fish (such as skin and scale), mammalian collagen such as bovine and porcine, or collagen derived from other sources such as chicken. The species of fish is not limited, and examples thereof include: salmon, trout, cod, mackerel, horse mackerel, sea bream, tilapia, weever, herring, carp, crucian, etc. The hydrolyzed collagen obtained may be used as a solution, or a concentrated solution may be used by concentrating the solution as necessary, or a solid may be used by volatilizing all the liquid in the solution.

Gelatin is a component having a molecular weight of several tens to several hundreds of thousands, which is obtained by decomposing collagen and refining it.

The amount of collagen is preferably 0.01 to 10wt%, more preferably 0.1 to 5 wt%. In this way, the egg antibody, lipase and protease can be stably mixed in the oral composition more effectively, and the functions of the egg antibody, lipase and protease can be stably exerted. As a result, the oral disease can be more effectively prevented or improved.

In addition, when the total amount of egg antibody, lipase and protease is C [ wt% ]andthe amount of collagen is D [ wt% ], the relationship of 0.001. ltoreq. D/C.ltoreq.10000 is preferably satisfied, and more preferably, the relationship of 0.02. ltoreq. D/C.ltoreq.100 is satisfied. In this way, the egg antibody, lipase and protease can be stably mixed in the oral composition more effectively.

In addition, in the oral composition of the present invention, various components may be mixed in accordance with the dosage form in addition to the above components. For example, when the oral composition of the present invention is applied to toothpaste, abrasives, humectants, binders, foaming agents (surfactants), sweeteners, preservatives, flavor components, medicinal components other than the above, and the like may be mixed.

Examples of the abrasive include: silica abrasives such as silica gel, precipitated silica, pyrogenic silica, hydrous silicic acid, zeolite, aluminum silicate, zirconium silicate, etc., and abrasives such as dibasic calcium phosphate dihydrate, dibasic calcium phosphate anhydride, calcium pyrophosphate, trimagnesium phosphate, tricalcium phosphate, aluminum hydroxide, alumina, light calcium carbonate, heavy calcium carbonate, magnesium carbonate, zirconium silicate, synthetic resin abrasives, etc., may be used in combination of 1 or 2 or more.

The amount of the polishing agent to be mixed is not particularly limited, but is preferably 3 to 60wt%, more preferably 10 to 45 wt%.

Examples of wetting agents are: 1 or 2 or more kinds of polyhydric alcohols such as glycerin, condensed glycerin, diglycerin, sorbitol, maltitol, dipropylene glycol, propylene glycol, 1, 3-butylene glycol, and xylitol can be used in combination.

The amount of the wetting agent is not particularly limited, but is preferably 1 to 60wt%, more preferably 5 to 50 wt%.

Examples of the binder include: carrageenan (iota, lambda, kappa), alginic acid, sodium alginate, propylene glycol alginate, calcium-containing sodium alginate, potassium alginate, calcium alginate, ammonium alginate and other alginate salts and derivatives thereof, xanthan gum, guar gum, gelatin, agar, sodium carboxymethylcellulose, sodium hydroxyethylcellulose, sodium polyacrylate and the like, and 1 or 2 or more of them can be used in combination.

The amount of the binder is not particularly limited, but is preferably 0.1 to 5.0wt%, more preferably 0.5 to 3.0 wt%.

Examples of the foaming agent (surfactant) include: sodium lauryl sulfate, sodium lauryl sarcosinate, sodium alkyl sulfosuccinate, sodium coconut oil fatty acid monoglyceride sulfonate, sodium α -olefin sulfonate, N-acyl amino acid salts such as N-glutamic acid, 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazoline betaine, maltitol fatty acid esters, sucrose fatty acid esters, polyglycerol fatty acid esters, fatty acid diethanolamides, polyoxyethylene sorbitan monolaurate, polyoxyethylene hardened castor oil, polyoxyethylene fatty acid esters, and the like, and 1 or 2 or more thereof may be used in combination.

As described above, when the polyglycerin fatty acid ester and/or the amino acid-based amphoteric surfactant are used, the egg antibody, the lipase and the protease can be stably mixed in the oral composition more effectively, and the functions of the egg antibody, the lipase and the protease can be stably exerted. As a result, the oral disease can be more effectively prevented or improved.

The polyglycerin fatty acid ester is preferably an ester of polyglycerin and a fatty acid having 12 to 16 carbon atoms. In this way, the egg antibody, lipase and protease can be stably mixed in the oral composition more effectively, and the functions of the egg antibody, lipase and protease can be stably exerted. As a result, the oral disease can be more effectively prevented or improved.

The amount of the foaming agent (surfactant) to be mixed is not particularly limited, but is preferably 0.1 to 10.0wt%, more preferably 0.5 to 5.0 wt%.

In addition, when the total amount of egg antibody, lipase and protease is C [ wt% ]andthe amount of foaming agent is E [ wt% ], the relationship of E/C0.01. ltoreq.10000 is preferably satisfied, and the relationship of E/C0.1. ltoreq.100 is more preferably satisfied. Thus, the egg antibody, lipase and protease can be stably mixed in the oral composition more effectively.

Examples of sweeteners are: saccharin sodium, aspartame, trehalose, stevioside, stevia extract, p-methoxycinnamaldehyde, neohesperidin dihydrochalcone, perillaseed, etc., and 1 or more than 2 of them can be used in combination.

The amount of the solubilizer is not particularly limited, but is preferably 0.005 to 5.0wt%, more preferably 0.01 to 3.0 wt%.

Examples of preservatives are: methyl paraben, ethyl paraben, propyl paraben, butyl paraben and other parabens, sodium benzoate, phenoxyethanol, alkyl diamino ethyl glycine hydrochloride, can be used in combination of 1 or more than 2.

The amount of the preservative agent is preferably 0.005 to 5.0wt%, more preferably 0.01 to 3.0wt%, depending on the kind of the preservative agent.

Examples of perfume ingredients are: 1-menthol, anethole, menthone, eucalyptol, limonene, carvone, methyl salicylate, ethyl butyrate, eugenol, thymol, cinnamaldehyde, trans-2-hexenal, etc., and 1 or 2 or more thereof may be used in combination. These components may be blended in the form of a single product, or may be blended with essential oils containing them. In addition to the above-mentioned perfume components, perfume components such as fatty alcohols or esters thereof, terpenoids, phenol ethers, aldehydes, ketones, lactones, and essential oils may be blended as long as the effects of the present invention are not impaired.

The amount of the perfume component to be mixed is not particularly limited, but is preferably 0.02 to 2wt%, more preferably 0.05 to 1.5 wt%.

The pharmaceutical ingredients can be listed as: monofluorophosphate, sodium fluoride, potassium fluoride, sodium monofluorophosphate, polyethylene glycol, polyvinylpyrrolidone, zeolite, hinokitiol, chlorhexidine salt, cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, dequalinium chloride, triclosan, isopropylmethylphenol, bisabolol, ascorbic acid and/or a derivative thereof, tocopheryl acetate, epsilon-aminocaproic acid, tranexamic acid, aluminum hydroxyallantoin, aluminum lactate, dihydrocholesterol, glycyrrhetinic acid, glycyrrhetate, copper chlorophyllin salt, sodium azulene sulfonate, dextranase, pyridoxine hydrochloride, zeolite and the like, and 1 or 2 or more of them can be used in combination.

The oral composition may contain, in addition to the above components, pigments such as cyan No. 1, pigments such as titanium oxide, antioxidants such as dibutylhydroxytoluene, dry tea distillate, and flavoring agents such as sodium glutamate.

The salt concentration of the oral composition is preferably 0.1 to 20%, more preferably 0.5 to 15%. Thus, the egg antibody, lipase and protease can be stably mixed in the oral composition more effectively.

Here, the salt concentration refers to the total concentration of salt contained in the oral composition.

The oral composition of the present invention comprising the above-mentioned components in combination can be prepared by a conventional method, and the preparation method is not particularly limited. In particular, it is preferable to add the egg antibody and collagen in a state of being dissolved in water to the oral composition. As a result, the egg antibody function can be more stably exhibited, and the occurrence of oral diseases can be more effectively prevented or suppressed.

The obtained composition such as a dentifrice can be used by being filled in an aluminum tube, a laminate tube, a glass deposition tube, a plastic bottle, an aerosol container, or the like.

The oral composition of the present invention is described above, but the present invention is not limited thereto. For example, the oral composition of the present invention may contain any functional ingredient in addition to the above-mentioned ingredients.

Examples

Hereinafter, specific embodiments of the present invention will be described.

(example 1)

A toothpaste as an oral composition is prepared by using the following components (unit: wt%) in an amount of 1 to 11.

Furthermore, as the egg antibody, immunoglobulin prepared from an egg produced by a chicken immunized with membrane-bound glucosyltransferase of Streptococcus mutans was used. In addition, toothpaste was prepared according to the usual method except that the egg antibody was dissolved in water together with hydrolyzed collagen and added.

(examples 2 to 10)

Toothpaste was prepared in the same manner as in example 1, except that the mixing amounts of egg antibody, citric acid and metal citrate were changed as shown in table 1.

(example 11)

As the egg antibody, an immunoglobulin prepared from eggs produced from chickens immunized with gingivalis of porphyromonas gingivalis was used, hydrolyzed collagen was changed to gelatin, 2-alkyl-N-carboxymethyl-N-hydroxyethyl betaine was used instead of polyglycerol monolaurate as a surfactant, and the mixture was mixed in the amount shown in table 1, and toothpaste was prepared in the same manner as in example 1.

(example 12)

The following components (unit: wt%) are used to prepare toothpaste.

Furthermore, as the egg antibody, immunoglobulin prepared from an egg produced by a chicken immunized with membrane-bound glucosyltransferase of Streptococcus mutans was used. In addition, the egg antibody and the hydrolyzed collagen are dissolved in water and then added, and other ingredients are prepared into toothpaste according to the conventional method.

(example 13)

The following components (unit: wt%) are used to prepare toothpaste.

In addition, the lipase and the hydrolyzed collagen are dissolved in water and added, and other ingredients are made into toothpaste according to the conventional method.

(examples 14 to 22)

Toothpaste was prepared in the same manner as in example 13, except that the mixing amounts of lipase, citric acid and metal citrate were changed as shown in table 2.

(example 23)

The following components (unit: wt%) are used to prepare toothpaste.

In addition, protease and hydrolyzed collagen are dissolved in water and added, and other ingredients are made into toothpaste according to the conventional method.

(examples 24 to 32)

Toothpaste was prepared in the same manner as in example 23, except that the mixing amounts of lipase, citric acid and metal citrate were changed as shown in table 2.

Comparative example 1

Toothpaste was prepared in the same manner as in example 1 above, except that citric acid was not mixed in the toothpaste.

Comparative example 2

Toothpaste was prepared in the same manner as in example 1, except that citric acid was not mixed in the toothpaste and the surfactant shown in table 1 was used.

Comparative example 3

Toothpaste was prepared in the same manner as in example 1 above, except that citric acid and sodium citrate were not mixed in the toothpaste, and a surfactant as shown in table 1 was used.

Comparative example 4

Toothpaste was prepared in the same manner as in example 13 above, except that citric acid was not mixed in the toothpaste.

Comparative example 5

Toothpaste was prepared in the same manner as in example 13, except that citric acid was not mixed in the toothpaste and the surfactant shown in table 2 was used.

Comparative example 6

Toothpaste was prepared in the same manner as in example 13 above, except that citric acid and sodium citrate were not mixed in the toothpaste and a surfactant as shown in table 2 was used.

Comparative example 7

Toothpaste was prepared in the same manner as in example 23 above, except that citric acid was not mixed in the toothpaste.

Comparative example 8

Toothpaste was prepared in the same manner as in example 23, except that citric acid was not mixed in the toothpaste and the surfactant shown in table 2 was used.

Comparative example 9

Toothpaste was prepared in the same manner as in example 23 above, except that citric acid and sodium citrate were not mixed in the toothpaste and a surfactant as shown in table 2 was used.

The types and amounts of egg antibodies and enzymes, the amounts of citric acid, sodium citrate and sodium chloride, and the types and amounts of collagen and surfactants in examples and comparative examples are shown in tables 1 and 2. In the table, immunoglobulin prepared from eggs produced by chickens immunized with membrane-bound glucosyltransferase of streptococcus mutans is used as an egg antibody, and is represented by X; immunoglobulin prepared from an egg produced by a chicken immunized with gingivalis of porphyromonas gingivalis was used as an egg antibody, which is represented as Y; the lipase is represented by L; the protease is represented by P; adding water to decompose collagen into a; gelatin is b; polyglycerol monolaurate is A; the sodium lauroamphoacetate is B; the 2-alkyl-N-carboxymethyl-N-hydroxyethyl betaine is C.

< evaluation >

[ Stable Mixed evaluation of egg antibody ]

With respect to the toothpastes obtained in examples 1 to 12 and comparative examples 1 to 3, 1g each of the immediately prepared toothpaste and the toothpaste kept at 40 ℃ for 6 months was suspended in 9mL of Phosphate Buffered Saline (PBS) to obtain a solution. The solution was placed in an incubator at 37 ℃ for 15 minutes. Then, 10mL of chloroform was added to the solution to obtain a mixed solution. After the mixture was placed in an incubator at 37 ℃ for 15 minutes, the mixture was centrifuged for 20 minutes to separate an aqueous phase. The aqueous portion was used as the experimental sample solution. A solution of 100. mu.L/well of the test sample was added to the ELISA plate having the immobilized antigen adsorbed thereon. The ELISA plate was left standing at 25 ℃ for 1 hour to react the antigen and antibody. After the reaction, the ELISA plate was washed 5 times with PBS-T. Subsequently, 100. mu.L of peroxidase-conjugated anti-chicken IgG antibody was added to the ELISA plate as a secondary antibody, and the antigen-antibody reaction was carried out at 25 ℃ for 30 minutes. Thereafter, the ELISA plate was washed 6 times with PBS-T. Next, a substrate solution prepared from 20mg of phenylenediamine and 10. mu.L of hydrogen peroxide was added to 50mL of a 0.2M phosphate-0.1M sodium citrate buffer (pH 5.0) to obtain a mixture. Then, the mixture was reacted at 25 ℃ for 20 minutes.The reaction was stopped by adding 100. mu.L of 3N sulfuric acid solution to the mixture. After completion of the reaction, the absorbance (OD) of the obtained reaction solution was measured₄₉₀) Antibody values were obtained. The ratio of the antibody value obtained using the toothpaste stored at 40 ℃ for 6 months to the antibody value obtained using the immediately prepared toothpaste was used as the residual rate of egg antibodies, and the residual rate was evaluated on the following 4-point scale.

A: the residual rate of the egg antibody is more than 80 percent

B: the residual rate of the egg antibody is more than 70 percent and less than 80 percent

C: the residual rate of the egg antibody is more than 50 percent and less than 70 percent

D: egg antibody survival rate of 50% less than

[ Stable Mixed evaluation of Lipase ]

With respect to the toothpastes obtained in examples 13 to 22 and comparative examples 4 to 6, 5.0g of each of the immediately prepared toothpaste and the toothpaste kept at 40 ℃ for 6 months was suspended in 10ml of 0.1M phosphate buffer (pH 7.0) to obtain a solution. Next, the suspension was centrifuged for 5 minutes to separate, and the supernatant was obtained. To 1mL of the supernatant was added 2mL of 0.1M phosphate buffer (pH 7.0) to obtain mixture A. The mixture A was heated in a 37 ℃ thermostat for 5 minutes. Then, 3mL of olive oil emulsion preheated at 37 ℃ for 5 minutes was added to the mixture A to obtain a mixture B. The mixture B was stirred and mixed at 37 ℃ for 30 minutes. Then, 20mL of a mixed solution of acetone and ethanol having an equal volume was added to the mixed solution B to prepare an experimental solution.

In contrast to the above, with respect to the toothpastes obtained in examples 13 to 22 and comparative examples 4 to 6, 5.0g of each of the immediately prepared toothpaste and the toothpaste kept at 40 ℃ for 6 months was suspended in 10mL of 0.1M phosphate buffer solution (pH 7.0) to obtain a solution. Next, the suspension was centrifuged for 5 minutes to separate, and the supernatant was obtained. To 1mL of the supernatant was added 2mL of 0.1M phosphate buffer (pH 7.0) to obtain mixture C. Then, 20mL of a mixed solution of acetone and ethanol of equal volume was added to the mixed solution C and mixed well. Then, 3mL of olive oil emulsion was added to the mixed solution C to obtain a mixed solution D. The mixture D was stirred and mixed at 37 ℃ for 30 minutes to prepare a control solution.

To the experimental solution and the control solution, 3 drops of phenolphthalein solution were added, and titration was performed with 0.1N sodium hydroxide solution. The lipase titer (unit/g) was determined by the following equation. The lipase titer obtained using the toothpaste stored at 40 ℃ for 6 months was evaluated as the ratio of the lipase titer to that obtained using the immediately prepared toothpaste as the residual ratio of the lipase titer on the following 4-step scale.

Lipase titer [ units/g ] ═ 400 × (a-b) ]/3

Wherein, a: titration amount (mL) of test solution, b: control solution titration amount (mL).

A: the lipase survival rate is more than 80 percent

B: the lipase survival rate is more than 70 percent and less than 80 percent

C: the lipase survival rate is more than 50 percent and less than 70 percent

D: the lipase survival rate is less than 50%

[ Stable Mixed evaluation of protease ]

With respect to the toothpastes obtained in examples 23 to 32 and comparative examples 7 to 9, 0.25g each of the immediately prepared toothpaste and the toothpaste kept at 40 ℃ for 6 months was suspended in 20mL of water to obtain a suspension. Then, the suspension was centrifuged for 5 minutes to separate, and the supernatant was obtained. To 1mL of the supernatant was added 4mL of 0.1mol/L phosphate buffer solution to obtain a mixture E. The mixture E was heated in a constant temperature water bath at 30 ℃ for 5 minutes. Subsequently, 4mL of a 0.1mol/L solution of p-toluenesulfonylarginine methyl ester hydrochloride preheated at 30 ℃ for 5 minutes was added to the mixture E to obtain a mixture F. After heating the mixture F at 30 ℃ for 5 minutes, the mixture F was rapidly filtered (membrane filter having a pore size of 0.45 μm). 0.4mL of a trichloroacetic acid solution (15 → 100) was added to 0.6mL of the obtained filtrate to stop the enzyme reaction. Thus, a mixed solution G was obtained. Subsequently, 0.2mL of a potassium permanganate solution (2 → 100) was added to the mixture G to obtain a mixture H. The mixture H was shaken and allowed to stand for 1 minute. After the contents were oxidized, 0.2mL of sodium bisulfite solution (1 → 10) was added to the mixture H to obtain a mixture I. And oscillating the mixed solution I to reduce the surplus potassium permanganate. Then, 8mL of a color-changing acid solution was added to the mixed solution I to obtain a mixed solution J. The mixture J was stirred well and heated rigorously in a boiling water bath for 15 minutes. Thereby coloring the mixture solution J. Mixture J was left at room temperature for 40 minutes. Then, the absorbance of mixture J at 580nm was measured using water as a control. A blank test was conducted in the same manner, and the protease titer [ unit/g ] was determined by the following equation. The ratio of protease titer obtained using a toothpaste stored at 40 ℃ for 6 months to the protease titer obtained using a toothpaste prepared immediately was used as the residual ratio of the protease titer, and the residual ratio was evaluated on the following 4-step scale.

Protease titer [ unit/g ] ═ a-b x 188

Wherein, a: absorbance of sample solution, b: absorbance of sample solution for blank test.

A: the residual rate of protease is more than 80%

B: the residual rate of protease is more than 70 percent and less than 80 percent

C: the residual rate of protease is more than 50% and less than 70%

D: the residual rate of protease is less than 50%

The results of the above evaluations are shown in tables 1 and 2 together.

As is clear from tables 1 and 2, any of the toothpastes obtained in the examples was able to stably mix lipase, protease and egg antibody.

In contrast, the toothpastes obtained in the respective comparative examples did not give satisfactory results.

Industrial applicability of the invention

The present invention provides an oral composition characterized by containing at least 1 selected from the group consisting of lipase, protease and egg antibody, citric acid, and a metal citrate. According to the present invention, there can be provided an oral composition which can prevent or improve oral diseases such as dental caries and periodontal disease by stably mixing egg antibodies or enzymes. Therefore, the present invention has industrial applicability.

Claims (8)

1. An oral composition comprising

At least 1 selected from the group consisting of lipase, protease, egg antibody;

citric acid; and

a metal salt of citric acid.

2. The oral composition according to claim 1, wherein the total amount of the protease and the egg antibody is 0.001 to 10 wt%.

3. The oral composition according to claim 1 or 2, wherein,

when the amount of citric acid to be mixed is A [ wt% ], and the amount of the metal citrate to be mixed is B [ wt% ], a relationship of 0.005. ltoreq. A/B. ltoreq.1 is satisfied.

4. The oral composition according to any one of claims 1 to 3, wherein,

when the mixing amount of the citric acid is A [ wt% ], and the total mixing amount of the protease and the egg antibody is C [ wt% ], a relationship of 0.0005. ltoreq. A/C.ltoreq.10000 is satisfied.

5. The oral composition according to any one of claims 1 to 4, wherein,

when the mixing amount of the metal citrate is B [ wt% ], and the total mixing amount of the lipase, the protease and the egg antibody is C [ wt% ], a relationship of 0.005. ltoreq. B/C.ltoreq.10000 is satisfied.

6. The oral composition according to any one of claims 1 to 5,

further contains a polyglycerin fatty acid ester or an amino acid amphoteric surfactant as a surfactant.

7. The oral composition according to any one of claims 1 to 6,

further contains collagen.

8. The oral composition according to any one of claims 1 to 7,

the salt concentration in the oral composition is 0.1-20%.