JP5067553B2 - Denture cleaning liquid composition - Google Patents

Description

  The present invention is a concentrated denture cleaning that is used after dilution, which exhibits excellent removal power and sterilization power for denture biofilms, is excellent in the sterilization power of denture immersion liquid, and has good storage stability The present invention relates to a liquid composition for use.

  In recent years, with the arrival of an aging society, the number of denture users tends to increase year by year. Denture users tend to accumulate food residue between the dentures and the oral mucosa and healthy teeth, and are placed in an environment in which oral microorganisms are more likely to propagate than healthy people.

  Denture stains include food residues, denture biofilms, tartar-like deposits, pigments and the like. Here, the denture biofilm is a biofilm in which oral microorganisms are fixed on the surface of the denture and aggregated together with products such as adhesive polysaccharides, saliva and serum components. Since this denture biofilm contains various microorganisms, denture stomatitis, halitosis and denture odor are generated, and with respect to partial denture, caries and periodontal disease of the remaining teeth are likely to occur.

  The microbiological characteristics of denture biofilms include a high proportion of Candida, but Candida is closely related to respiratory infections such as pulmonary candidiasis and aspiration pneumonia. Has been reported (see Non-Patent Documents 1 and 2). Therefore, it is important to keep the denture clean by removing the denture biofilm attached to the denture by daily care.

  As a method for removing the denture biofilm, there are mechanical removal by brushing and chemical removal by using a denture cleaning agent and a polishing agent. However, mechanical removal by brushing makes it difficult to completely remove the denture biofilm adhering to the narrow gap or denture surface. Therefore, it is effective to combine the two methods of mechanical removal and chemical removal. It is desirable as a safe care method.

  As denture cleaning agents marketed for the purpose of chemical removal, tablet-type and powder-type ones are mainly used. Generally, these detergents contain peroxides such as percarbonates and perborate, proteolytic enzymes (proteases), surfactants, chelating agents, etc. as cleaning ingredients. It uses a cleaning system that dissolves in water and removes the denture biofilm by the action of decomposing hydrogen peroxide and enzymes generated, and the action of surfactants and chelating agents. However, in such a cleaning system, a certain degree of bactericidal power is exhibited by the generated hydrogen peroxide, but the removal power against the denture biofilm is insufficient.

  In addition, the above-described solid type cleaning agent has a problem in that the amount used is adjusted according to the amount of liquid. In particular, tablet-type cleaning agents are packaged in a single unit, and the user is dissatisfied with the amount of use adjustment for cleaning partial dentures whose denture sizes vary greatly among users. Solid-type cleaning agents have such problems, while liquid preparations have the advantage of easy adjustment of the amount used. Furthermore, concentrated type preparations that are diluted with water according to the amount used at the time of use can reduce the volume of the container and reduce the volume of the container since it can be used only once compared with the case of using the stock solution preparation. And is advantageous in terms of storage space.

  However, the concentration-type preparation that is diluted with water at the time of use reduces the concentration of the ingredients depending on the mixing ratio of the preparation and water. The issue is whether to do this. Accordingly, there has been a demand for the development of a concentrated liquid composition that exhibits excellent removal power and sterilization power for denture biofilms with a concentrated liquid composition that is diluted with water at the time of use.

  Examples of components that remove denture biofilms and dental plaques include protease enzymes and surfactants, and biofilms can be effectively removed by using proteases and surfactants in combination. However, enzymes generally have low stability, and there is a problem that they are inactivated when stored for a long time in a liquid composition. In addition, depending on the type of surfactant used, the enzyme activity may be greatly reduced. Therefore, in order to maintain the quality as a product, it is important to use a surfactant that has little influence on enzyme stability in addition to excellent detergency. Nonionic surfactants are often used as surfactants with good enzyme stability.

  On the other hand, in order to exert a bactericidal power against denture biofilms, it is essential to add a bactericidal agent. However, surfactants such as nonionic surfactants that have a detergency or are incorporated to solubilize oily components such as fragrances reduce the effectiveness of the bactericide to incorporate the bactericide into micelles. There is a problem of end. In addition, in a composition containing an anionic surfactant such as sodium lauryl sulfate, when a cationic bactericidal agent is used, there is a problem that the efficacy of the bactericidal agent is lost because a complex is formed. For this reason, it becomes important to set the kind of surfactant and its blending amount so as not to inhibit the efficacy of the bactericide as much as possible.

  As described above, in order to obtain a concentrated denture cleaning liquid composition that exhibits excellent removal and bactericidal power against denture biofilms, it is essential to add protease and bactericides. It is important to select surfactants with excellent detergency and to determine the concentration and mass ratio during each use, but it is difficult to achieve satisfactory results with conventional technologies. there were.

  A liquid composition containing a protease and a nonionic surfactant is known (see Patent Document 1). However, since this liquid composition does not contain a bactericidal component, it does not exert bactericidal power and is used for denture cleaning. It is insufficient as a composition.

  Moreover, although many oral compositions containing a cationic bactericidal agent and a nonionic surfactant have been disclosed, the nonionic surfactant has a problem that the bactericidal agent is taken into the micelle and inactivated. . In order to solve such a problem, a technique for preventing inactivation of a cationic bactericidal agent has been disclosed (see Patent Documents 2, 3, and 4). However, these technologies select surfactants to achieve both the expression of bactericidal power against airborne bacteria and the solubilization of oily fragrances, and because of their weak cleaning power, The removal power against such strong dirt is extremely low.

  Furthermore, a composition that exhibits excellent bactericidal activity against a collection of microorganisms such as dental plaque has also been disclosed (see Patent Document 5), but the technology does not include protease as an essential component, There is no description about the blending amount, and sufficient removal power against strong dirt like a denture biofilm is not exhibited. As a result, it is difficult to satisfy both high sterilization power and removal power for a denture biofilm satisfactorily. Further, it does not relate to a concentrated type composition that is diluted at the time of use, and there is no description about improvement in appearance stability and protease stability of the composition.

  In addition, studies have been made to increase the cleaning power by adding a protease to a liquid containing a cationic bactericide (see Patent Documents 6 and 7), but the selected surfactant is used as a cleaning component for contact lenses. Therefore, the cleaning power cannot be exhibited against strong dirt such as denture biofilm. Furthermore, in Example 3, the concentration of the cationic bactericidal agent and the mass ratio of the nonionic surfactant to the cationic bactericidal agent cannot be sufficiently exhibited. Therefore, excellent sterilizing power is not exhibited even for denture biofilms.

  A concentrated liquid composition containing a protease and a bactericidal agent has also been studied (see Patent Documents 8 and 9), but in this proposal, the mass ratio of the nonionic surfactant to the cationic bactericidal agent is within the range described. In this case, although a good sterilizing power is exhibited, the cleaning power is insufficient, and thus the effect of removing the denture biofilm is weak. Moreover, in order to exhibit the bactericidal power, the bactericidal agent is mix | blended in high concentration, As a result, the fall of enzyme activity occurs and the removal power will fall remarkably. That is, such a technique has a problem that it is difficult to achieve both sterilization and removal.

  In addition, a two-component type cleaning solution in which a cleaning solution containing a nonionic surfactant and a protease is diluted with a diluting solution containing an ionic antibacterial agent has been studied (see Patent Document 10). However, this technology relates to cleaning for contact lenses, and within the scope of the contents described, it cannot exert sufficient cleaning power and sterilizing power against strong dirt such as denture biofilm. . In addition, when the technique is applied to cleaning dentures, a large amount of dilution solution is required. For this reason, it is inconvenient for the user in terms of use, carrying, and storage space.

  Furthermore, it has been difficult for a concentrated liquid composition diluted during conventional use to maintain good temporal stability during both high temperature storage and low temperature storage.

  As described above, in the conventional technology, a concentrated denture cleaning liquid composition having excellent removal power and sterilization power for denture biofilms, excellent antiseptic power of denture immersion liquid, and good storage stability. It was difficult to get.

JP 2002-327199 A JP-A-4-173728 JP 7-215830 A Japanese Patent No. 3660169 JP-A-11-255629 JP 2000-273489 A Special table 2001-114624 gazette JP-T-2003-530447 Japanese translation of PCT publication No. 2003-529612 Japanese Patent No. 3697294 Prosthetic Journal 43: 636-639, 1999. Nihon University Dentistry 79,117-123,2005

  The present invention has been made in view of the above circumstances, and exhibits both excellent removal power and sterilization power for denture biofilms, and when immersed in dentures after dilution, is excellent in preservative power of denture soaking solution and preserved An object of the present invention is to provide a concentrated liquid type denture cleaning liquid composition that is also excellent in stability.

As a result of intensive studies to achieve the above object, the present inventors have formulated protease, a cationic bactericidal agent, and water in a concentrated denture cleaning liquid composition that is diluted with water and used, and Polyoxyethylene alkyl ether is selected as the nonionic surfactant, and among them, polyoxyethylene alkyl ether having an ethylene oxide average addition mole number of 12 to 18 and an alkyl group having 12 to 20 carbon atoms is selected and specified. By blending in proportions and diluting with water so that the concentrations of the polyoxyethylene alkyl ether and the cationic bactericidal agent are in a specific range, the protease is stably blended. Excellent bioremovability against biofilm and excellent biocidal power against denture biofilm It is possible to achieve both excellent removal power and sterilization power, and when the denture is immersed in the diluted solution after dilution with water, the denture soaking solution has high antiseptic power and good preservation. It has been found that it has stability, further good enzyme stability, and good appearance stability in high-temperature storage or low-temperature storage, and has led to the present invention.

In the present invention, when benzethonium chloride is used as the cationic fungicide (C), the bactericidal power against the denture biofilm can be further improved.
Furthermore, (E) The sterilizing power with respect to a denture biofilm can be strengthened more by mix | blending isopropylmethylphenol and / or thymol.
Furthermore, the content of (A) polyoxyethylene alkyl ether in the composition is 5 to 30% by mass, (D) the moisture content is 30 to 50% by mass, (F) polyol, (G) pH adjuster. And having a pH of 6.0 to 8.5 at 25 ° C., better storage stability, especially enzyme stability in the composition, and appearance stability during high or low temperature storage are further improved. Can be made.
In addition, when (G) phosphoric acid or a salt thereof is included as a pH adjusting agent, (B) protease / ((B) protease / () selected from (H) at least one chelating agent selected from citrate, edetate and water-soluble polyphosphate H) When the chelating agent is blended in a mass ratio of 1 to 10, the storage stability of the composition can be further improved.

  In addition, as described above, in the liquid composition for concentrated denture cleaning used by dilution in the prior art, the selected surfactant is not suitable for removing the denture biofilm, Therefore, it is difficult to solve the above-mentioned problems because the blending amount of the nonionic surfactant with respect to the cationic fungicide is unsuitable. Fully demonstrate its ability to achieve both excellent removal power and sterilization power for denture biofilms after dilution, and the denture soaking solution (diluted solution) has a high preservative power and can be stored at both high and low temperature storage. While it was difficult to obtain a product having excellent stability, the present inventors blended (A) to (D), and the blending ratio of (A) / (C) was a specific ratio. ,And By diluting with water so that the concentrations of A) and (C) are within a specific range, the denture biofilm exhibits both excellent removal power and bactericidal power, and antiseptic power of denture immersion liquid The liquid composition for denture cleaning of concentrated liquid type which is high and excellent in storage stability can be obtained.

Accordingly, the present invention provides the following denture cleaning liquid composition.
[ 1 ]
A concentrated denture cleaning liquid composition that is diluted with water and applied to a denture during use,
(A) polyoxyethylene alkyl ether having an ethylene oxide average addition mole number of 12 to 18 and an alkyl group having 12 to 20 carbon atoms,
(B) protease,
(C) a cationic fungicide,
(D) It contains water, (A) component / (C) component is 2-10 as mass ratio, and the density | concentration of (A) component is 0.01-0.5 mass% and (C) A denture cleaning liquid composition, which is diluted with water so that the concentration of the components is 0.005 to 0.1% by mass.
[2]
(A) The denture cleaning liquid composition as described in [1], wherein the blending amount of the component polyoxyethylene alkyl ether is 5 to 30% by mass of the entire composition.
[ 3 ]
(C) The liquid composition for denture cleaning according to [1] or [2], wherein the cationic disinfectant is benzethonium chloride.
[ 4 ]
Furthermore, (E) The liquid composition for denture cleaning according to [1], [2] or [3], which contains isopropylmethylphenol and / or thymol.
[ 5 ]
( D) The content of water is 30 to 50% by mass of the entire composition, and further contains (F) a polyol and (G) a pH adjuster, and the pH at 25 ° C. is 6.0 to 8.5. The denture cleaning liquid composition according to any one of [1] to [4] .
[ 6 ]
(G) the pH adjuster is phosphoric acid or a salt thereof, and (H) at least one chelating agent selected from citrate, edetate and water-soluble polyphosphate is used in combination; (H) The denture cleaning liquid composition according to [5] , wherein the mass ratio of the chelating agent is in the range of 1 to 10.

  The denture cleaning liquid composition of the present invention is a concentrated type that is applied to dentures by diluting with water at the time of use, exhibiting excellent removal power and sterilization power against denture biofilm even when diluted, diluted at the time of use When dentures are soaked in a later dilution, the denture soaking solution has a high preservative power and is excellent in storage stability of the composition, and also in storage stability and enzyme stability during high-temperature storage and low-temperature storage. The denture biofilm of dentures can be effectively removed and sterilized by a chemical method, and the dentures can be kept clean.

Hereinafter, the present invention will be described in more detail. The denture cleaning liquid composition of the present invention is a concentrated denture cleaning liquid composition which is diluted with water at the time of use and applied to a denture, and comprises (A) ethylene It contains polyoxyethylene alkyl ether having an average oxide addition mole number of 12 to 18 and an alkyl group having 12 to 20 carbon atoms, (B) protease, (C) cationic fungicide, and (D) water. Furthermore, (E) isopropylmethylphenol and / or thymol, (F) polyol, (G) pH adjuster, etc. can be contained.

  In the present invention, as the nonionic surfactant, (A) polyoxyethylene alkyl ether having an ethylene oxide average addition mole number of 10 to 20 and an alkyl group having 12 to 20 carbon atoms is used.

  In this case, the alkyl group of the polyoxyethylene alkyl ether has 12 to 20 carbon atoms from the viewpoint of the removal power against the diluted biofilm, the bactericidal power and the antiseptic power of the denture soaking solution, or the stability of the composition. , Preferably 12 to 16, more preferably 12 or 14. Polyoxyethylene alkyl ethers may be used alone or in combination of two or more, and may be used alone or in combination with different carbon numbers. It may be used as a mixture of 12 and 14 carbon atoms. If the number of carbon atoms is less than 12, the surface activity is weak, so the removal power for denture biofilm is weak, and if it exceeds 20, the effectiveness of the cationic bactericidal agent is lowered, so the bactericidal power against denture biofilm and the denture soaking solution It is not preferable because the antiseptic power is weakened, the solubility is deteriorated, and the storage stability is remarkably lowered.

The ethylene oxide average addition molar number of polyoxyethylene alkyl ether, removal forces for denture biofilm after dilution, germicidal and antiseptic dentures immersion liquid, or whether the storage stability of the point of the composition et 12-18 and is a preferably 12 to 15. If the average added mole number is less than 10, the effectiveness of the cationic bactericidal agent is reduced, so that the bactericidal power against denture biofilm and the preservative power of denture soaking solution are weakened, and the solubility is weakened so that the storage stability and dilution are reduced. There is a possibility that the usability at the time may be lowered, and if it exceeds 20, the removal power for the denture biofilm is lowered, which is not preferable.

  Examples of such polyoxyethylene alkyl ethers include polyoxyethylene lauryl ether (EO average addition mole number 15), polyoxyethylene myristyl ether (EO average addition mole number 15), and polyoxyethylene alkyl (C12,14) ether. (EO average added mole number 15) and the like can be used, and one of these can be used alone or in combination of two or more, and polyoxyethylene lauryl ether (EO average added mole number 15) is particularly preferable. Used for. These polyoxyethylene alkyl ethers can be obtained from, for example, Japan Emulsion Co., Ltd. or Lion Chemical Co., Ltd.

The blending amount of the polyoxyethylene alkyl ether of component (A) is based on the entire composition from the viewpoint of bactericidal power, removal power and antiseptic power of denture soaking solution for denture biofilm after dilution, or stability of the composition. 2 to 50% (mass%, the same shall apply hereinafter) is preferable. If the blending amount is less than 2%, the removal ability to the diluted biofilm may not be satisfactorily exhibited. If the blending amount exceeds 50%, the stability of the protease in the composition is inhibited, and the diluted biofilm is diluted. In some cases, the removal power against the water is reduced. Moreover, the effect of the cationic bactericidal agent after dilution may be inhibited and the bactericidal power with respect to a denture biofilm and the preservative power of denture immersion liquid may fall.
From the standpoint of improving the storage stability of the composition and the stability of the protease, the blending amount of the polyoxyethylene alkyl ether as the component (A) is preferably 5 to 30%, particularly 8 to 15%. Is more preferable. When the blending amount is less than 5%, when oil-soluble fragrances or bactericides are blended, the stability at low and high temperatures may be lowered, and problems in appearance stability may occur. In some cases, the stability under low temperature storage is lowered, which is not preferable from the viewpoint of appearance stability, and the stability of the protease may be lowered.

  Next, examples of the (B) protease used in the present invention may include microorganism-derived proteases, plant-derived proteases, animal-derived proteases, and the like, and are not particularly limited. A microorganism-derived protease that can be produced is preferable, and an alkaline protease exhibiting high activity in a washing solution is particularly preferably used. A protease preparation can also be used as the protease. Here, the protease preparation includes propylene glycol, glycerin, boric acid, calcium and the like as a stabilizer other than protease, and water as a base. Specific examples include Evalase 16L, Sabinase 16L, Cannase, Clearlens Pro (Novozymes), Purefect L, Alkaline Protease GL440 (GENENCOR), Properase L (GENENCOR), etc. Among them, Evalase 16L and Savinase 16L are mentioned. preferable. The titer of Evalase 16L is 16 EPU / g or more, usually 16-20 EPU / g. Moreover, the titer of sabinase 16L is 16 KNPU / g or more, usually 16 to 20 KNPU / g.

  (B) The amount of protease is appropriately adjusted depending on the titer, etc., but from the viewpoint of the removal power and bactericidal power of the diluted biofilm after biodilution, or the storage stability of the composition, 0.1 to 5.0%, particularly 0.5 to 2.0% is preferable. Especially when Evalase 16L or Savinase 16L is used, 0.5 to 2.% is considered from the viewpoint of storage stability of the composition. 0% is preferable, and 0.5 to 1.2% is more preferable. If it is less than 0.1%, the removal power and sterilization power for the denture biofilm after dilution may not be satisfactorily exhibited, and if it exceeds 5.0%, there are problems in appearance stability such as occurrence of orientation in the composition. May occur.

  Examples of the cationic fungicide (C) used in the denture cleaning liquid composition of the present invention include bisguanides such as chlorhexidine hydrochloride and chlorhexidine gluconate, and quaternary ammonium compounds such as benzethonium chloride, benzalkonium chloride and cetylpyridinium chloride. Among them, quaternary ammonium compounds, particularly benzethonium chloride, benzalkonium chloride, and cetylpyridinium chloride are preferable, and benzethonium chloride is particularly preferable in terms of bactericidal power against denture biofilms. Such cationic fungicides can be used alone or in combination of two or more.

  (C) The blending amount of the cationic fungicide is preferably 0.2 to 10%, particularly preferably 1.0 to 5.0% with respect to the entire composition, and if less than 0.2%, the blending effect is satisfactorily exhibited. In some cases, high bactericidal power for diluted biofilm after dilution may not be obtained. If it exceeds 10%, the stability of protease in the composition may be inhibited, and the removal power for diluted biofilm after dilution may be reduced. There is. In addition, the stability of the composition under high temperature storage deteriorates and discoloration may occur, which may be undesirable from the viewpoint of appearance stability.

  Furthermore, in the liquid composition of the present invention, the mass ratio of (A) polyoxyethylene alkyl ether and (C) cationic bactericide is from the viewpoint of sterilization, removal power and bactericidal power against the denture biofilm after dilution ( A) / (C) is the range of 2-10, Preferably it is the range of 2-6, More preferably, it is the range of 3-5. If the mass ratio of (A) / (C) is less than 2, the removal power for the denture biofilm after dilution is weak, and if it exceeds 10, incorporation of the cationic bactericide into the micelle increases, resulting in dilution. Sufficient bactericidal power against the later denture biofilm and sufficient antiseptic power in the denture soaking solution will not be exhibited.

  The denture cleaning liquid composition of the present invention is obtained by blending (D) water, and the water content (water content) is a composition in terms of sterilizing power and removing power against the denture biofilm after dilution. Although it can be 30 to 97% based on the total amount, the water content is 30 to 50%, especially 35 to 45%, particularly from the viewpoint of the stability of the protease in the composition and the appearance stability during low-temperature storage. It is preferable that If the water content is less than 30%, insoluble matter may precipitate when the composition is stored at low temperature, which may be undesirable from the viewpoint of appearance stability. If it exceeds 50%, the stability of the protease in the composition is satisfactory. May not be obtained. In this case, the water content of the composition includes water contained in each component such as a glycerin liquid blended in the composition.

  The denture cleaning liquid composition of the present invention is a concentrated type preparation that is used after dilution, and the denture can be cleaned by immersing the denture in a diluted solution obtained by diluting with water such as tap water or purified water. However, in this case, the dilution ratio of the denture cleaning liquid composition with water is from 5 to 500 times, particularly from 25 to 200 times, especially from 50 to 200 times, from the viewpoint of usability and solubility. Dilution is preferred.

  In the denture cleaning liquid composition of the present invention, the diluted solution diluted at the above dilution rate can be used as a denture immersion solution, and in this case, the concentration of each component in the diluted solution is diluted so as to be in the following range. In particular, in the present invention, the concentration of the component (A) in the diluent is 0.01 to 0.5%, and the concentration of the component (C) is 0.005 to 0.1%. It is effective to dilute the composition with water so as to achieve excellent removal power and sterilization power for denture biofilms and high antiseptic power in denture immersion liquid.

The concentration of each component during use will be described in further detail below.
(A) The concentration in the diluting solution when polyoxyethylene alkyl ether is used (after diluting) is 0.01% of the total diluting solution in terms of removal power against the denture biofilm, sterilizing power, and antiseptic power of the denture soaking solution. It is -0.5%, Preferably it is 0.05-0.3%, More preferably, it is 0.08-0.15%. When the concentration after dilution is less than 0.01%, the removal power and sterilization power for the denture biofilm are insufficient, and when it exceeds 0.5%, the sterilization power for the denture biofilm and the antiseptic power of the denture soaking solution are reduced. Is not preferred because

  (B) When using protease (after dilution), the concentration in the dilute solution is particularly when Evalase 16L or Sabinase 16L is used from the viewpoint of removal power against denture biofilm, sterilization power and antiseptic power of denture soaking solution. Is preferably 0.001 to 0.02% of the whole diluted solution, and more preferably 0.005 to 0.015%. If it is less than 0.001%, the removal power and sterilization power against the denture biofilm are insufficient, and if it exceeds 0.02%, the effect of the cationic biocide is reduced, and the bactericidal power against the denture biofilm and the antiseptic of the denture soaking solution May reduce power.

  (C) The concentration in the diluted solution at the time of use (after dilution) of the cationic disinfectant is 0.005 to the entire diluted solution from the viewpoint of the removal power against the denture biofilm, the sterilizing power, and the antiseptic power of the denture soaking solution. It is 0.1%, preferably 0.01 to 0.05%, more preferably 0.02 to 0.04%. If it is less than 0.005%, sufficient bactericidal power against the denture biofilm and preservative power in the immersion liquid will not be exhibited, and if it exceeds 0.1%, the action of protease is inhibited, so that sufficient removal power to the denture biofilm is sufficient. Cannot be demonstrated.

  Moreover, the mass ratio in the diluted solution at the time of use (after dilution) of (B) protease and (C) cationic fungicide is the point of the bactericidal power against denture biofilm, the removal power, and the antiseptic power of the denture immersion liquid. In particular, when Evalase 16L or Sabinase 16L is used, (B) / (C) is preferably in the range of 0.2 to 2, particularly in the range of 0.3 to 1.0. More preferred. If the mass ratio of (B) / (C) is less than 0.2, the cationic bactericidal agent may inhibit the protease and the removal power against the denture biofilm may be reduced. Inhibiting the effect of the cationic bactericidal agent may reduce the bactericidal power against denture biofilms and the preservative power in the denture soaking solution.

  The denture cleaning liquid composition of the present invention contains the components (A) to (D) as described above, and is particularly used at the time of use (dilution) to enhance the bactericidal power against the denture biofilm after dilution. In the case where the concentration of the (C) cationic fungicide in the latter) is 0.01% or less, or in the case where the concentration of (A) the polyoxyethylene alkyl ether is 0.2% or more, (A) / (C) When the mass ratio is 7 or more, (E) isopropylmethylphenol and / or thymol can be further blended as a fungicide in addition to the (C) cationic fungicide. These isopropylmethylphenol and thymol may be blended singly or in combination of two.

In the case of blending the component (E), the total blending amount of the fungicide of the component (E) is from the viewpoint of the enhancement of bactericidal power against the diluted biofilm and the appearance stability during storage at high and low temperatures of the composition. It is preferable to set it as 0.5 to 2.0% of the whole composition, especially 0.8 to 1.5%. If it is less than 0.5%, the effect of enhancing the bactericidal power against denture biofilms is weak, and if it exceeds 2.0%, discoloration during high-temperature storage may occur remarkably, and appearance stability during low-temperature storage may deteriorate. It may not be preferable.
Further, when the component (E) is blended, the concentration in the diluting solution at the time of use (dilution) of the fungicide of the component (E) is preferably 0.001 to 0.1%, 0.005 More preferably, it is -0.05%. If it is less than 0.001%, the effect of enhancing the sterilizing power against denture biofilms is weak. If it exceeds 0.1%, the solution becomes cloudy upon dilution, or denture material (resin) changes due to repeated soaking of dentures. It may happen.

  The denture cleaning liquid composition of the present invention can further contain (F) a polyol and (G) a pH adjusting agent in order to enhance the storage stability of the entire composition.

  Examples of the (F) polyol used in the present invention include 1,3-butylene glycol, glycerin, propylene glycol, ethylene glycol, polypropylene glycol, polyethylene glycol, and sugar alcohols such as erythritol and sorbitol. Among these, glycerin, propylene glycol, and polyethylene glycol are preferably used from the viewpoint of protease stability, and glycerin is particularly preferable. These polyols may be used alone or in combination of two or more.

When blending (F) polyol, the blending amount of (F) polyol in the composition of the present invention is not particularly limited, but is preferably 20 to 60% in total with respect to the total amount of the composition in terms of protease stability. 30 to 50% is more preferable. If it is less than 20%, the stability of the protease may decrease, and if it exceeds 60%, the appearance stability during low-temperature storage may be deteriorated.
Furthermore, when mix | blending (F) polyol, it is preferable that the density | concentration in the dilution liquid at the time of use of (F) polyol (at the time of dilution) is 0.04 to 12%.

  The composition of the present invention has a pH at 25 ° C. of 6.0 to 8.5, preferably 6.5 to 8.0, from the viewpoint of appearance stability and protease stability, and preferably 7.0 to 7 .8 is more preferable. If the pH at 25 ° C. is less than 6.0, the stability of the protease is low, and if it exceeds 8.5, discoloration of the high-temperature storage product may occur remarkably, resulting in poor appearance stability, and soaking dentures. The denture material (resin) may be altered by repeated operations. In addition, (G) pH adjuster can be mix | blended as a means of pH adjustment as needed. Examples of the pH adjuster in this case include sodium hydroxide, hydrochloric acid, phosphoric acid or a salt thereof, citric acid or a salt thereof, sodium carbonate, sodium bicarbonate, boric acid or a salt thereof. Among these, it is preferable to use sodium hydroxide, hydrochloric acid, phosphoric acid or a salt thereof, citric acid or a salt thereof. Examples of the phosphate include sodium monohydrogen phosphate, potassium monohydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, trisodium phosphate and the like. Examples of the citrate include sodium citrate, calcium citrate, and tripotassium citrate. The blending amount of these pH adjusters only needs to be able to adjust the pH to the above range.

From the viewpoint of protease stability and appearance stability, in the case where phosphoric acid or a salt thereof such as sodium monohydrogen phosphate or sodium dihydrogen phosphate is blended as a pH adjuster, (H) citrate, edet Preferably, at least one chelating agent selected from acid salts and water-soluble polyphosphates is used in combination. By including a chelating agent selected from citrate, edetate and water-soluble polyphosphate, when (B) protease, especially Evalase 16L or Sabinase 16L is used, (B) contained in the protease raw material It can prevent that calcium, phosphoric acid, or its salt react, and an insoluble matter precipitates, and it becomes a problem on an external appearance.
As a chelating agent, for example, sodium citrate, sodium edetate (EDTA-2Na), sodium tripolyphosphate, etc. can be blended, and sodium citrate is particularly remarkable in terms of protease stability and appearance stability during storage at high and low temperatures. It is more preferably used because of its superiority. In addition, about citrate, you may mix | blend for any purpose of a pH adjuster and a chelating agent.
In this case, when phosphoric acid or a salt thereof is blended as a pH adjuster, the blending amount is 0.1 to 1. of the entire composition from the viewpoint of pH stability, protease stability and appearance stability of the composition. 0% is preferable, and 0.2 to 0.5% is more preferable. If it is less than 0.1%, the pH stability is lowered, and as a result, the stability of the protease may be lowered. If it exceeds 1.0%, orientation and discoloration may occur during storage at high or low temperatures.
Moreover, when mix | blending (H) chelating agent, the compounding quantity is 0.1-1.0% of the whole composition from the point of stability of protease, and external appearance stability, 0.2-0. 5% is more preferable. If it is less than 0.1%, the effect of suppressing the occurrence of orientation during storage at high and low temperatures may be low, and if it exceeds 1.0%, the stability of the protease may be reduced.

  In addition, when blending (H) chelating agent, the mass ratio of (B) protease to (H) chelating agent in the composition ((B ) / (H)) is preferably in the range of 1-10, more preferably in the range of 2-5. If it is less than 1, the protease stability may be lowered, and if it is more than 10, orientation and the like may occur during storage at high and low temperatures and appearance stability may be lowered.

  In the denture cleaning liquid composition of the present invention, the effects of the present invention, i.e., removal power and sterilization power for denture biofilm, antiseptic power of denture soaking solution, storage stability, etc., are not affected depending on the purpose. Other components than the above can be blended. Other optional components include, for example, fragrances, solvents other than polyols, colorants, cationic bactericides, other bactericides other than isopropylmethylphenol and thymol, and (A) nonionic surfactants other than polyoxyethylene alkyl ethers. Agents and the like.

  As perfumes, spearmint oil, peppermint oil, anise oil, eucalyptus oil, winter green oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, Natural flavors such as lime oil, lavender oil, rosemary oil, laurel oil, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, cinnamon bark oil, and menthol, Menthone, Carvone, Ethylbutyrate, Vanillin, Ethylmaltol, Anethole, Methyl salicylate, Synamic aldehyde, Cineol, Eugenol, Ethylvanillin, Maltol, Limonene, Citronellol, Linalol, Linalyl acetate, Menthyl acetate, Pine , Octyl aldehyde, citral, pregon, carbyl acetate, anisaldehyde, ginger oleoresin, creosole, dl-camphor, etc., single flavors, ethyl acetate, allylcyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycy Known fragrances used in oral compositions such as single fragrances such as dating, undecalactone, hexanal, ethyl alcohol, propyl alcohol, butanol, isoamyl alcohol and / or various blended fragrances including natural fragrances can be used. .

  In the denture cleaning liquid composition of the present invention, a refreshing feeling can be imparted by blending a fragrance, and the user can more comfortably clean the denture or feel a refreshing feeling when the denture is attached. it can. It is preferable to blend 1 to 4% of the fragrance from the viewpoint of refreshing feeling and appearance stability. When the blending amount is less than 1%, the refreshing feeling and the refreshing feeling may be insufficient when the denture is mounted. If it exceeds 4%, for example, even if 30% of polyoxyethylene alkyl ether is blended, good appearance stability may not be maintained, or discoloration of a high-temperature storage product may occur remarkably.

  In addition to the (F) polyol, ethanol can be preferably added to the composition of the present invention as a solvent in order to dissolve hardly soluble components such as oil-soluble fragrances and isopropylmethylphenol. It is preferable to mix | blend ethanol 4-20% in a composition, and it is more preferable in it being 6-12%. When ethanol is blended in this concentration range, perfumes, oil-soluble components such as isopropylmethylphenol and thymol are easily dissolved, and the stability of the protease is not inhibited.

  As colorants, Red No. 2, Red No. 3, Red No. 225, Red No. 226, Yellow No. 4, Yellow No. 5, Yellow No. 205, Blue No. 1, Blue No. 2, Blue No. 201, Blue No. 204, Green No. 3 etc. Legal dye, caramel dye, safflower dye, gardenia dye, cochineal dye, anato dye, mica titanium, titanium oxide and the like.

  In the present invention, in addition to the above (C) cationic fungicide, (E) isopropylmethylphenol and / or thymol, as other fungicides, triclosan, benzoic acid or a salt thereof, salicylic acid or an ester thereof or a salt thereof, Parabens, phenol and the like can be used.

  In the present invention, in addition to the polyoxyethylene alkyl ether (A), which is the main surfactant, other surfactants such as nonionic surfactants can be blended, such as polyoxyethylene hydrogenated castor oil. Sugar alcohol fatty acid esters such as ethylene fatty acid esters and sucrose fatty acid esters, alkylol amide, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxy Ethylene glycerin fatty acid ester, polyoxyethylene glycol fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene polyoxypropylene glycol, lauric acid mono- or diethanolamide Fatty acid diethanol amides, can be blended polyoxyethylene alkyl phenyl ether. The blending amount of these other surfactants is usually preferably 0 to 2%, particularly preferably 0 to 1% of the whole composition.

  Moreover, there is no restriction | limiting in particular as a container which accommodates this invention composition, Usually, it can be filled and used for the container currently applied to the composition for oral cavity. Specifically as such a container, a polyethylene layer, an ethylene methacrylic acid copolymer layer, a polyethylene terephthalate layer, an aluminum layer, a glass vapor deposition layer, a polyvinyl alcohol layer, an ethylene vinyl alcohol copolymer layer, an acrylonitrile copolymer layer, Laminate containers made of paper, recycled plastic layers, etc., or polyethylene containers, polyethylene terephthalate containers, polypropylene containers, etc. can be used. Tube containers, dispensers containers with mechanical or differential pressure, film packaging containers such as pillow packaging, etc. Various containers usually used as the composition can be used. A polyethylene terephthalate container is preferable.

  In order to wash dentures with the concentrated denture cleaning liquid composition of the present invention, for example, the composition of the present invention is put in a container such as a cup, and the composition is diluted with tap water or purified water to obtain a diluted solution. It is only necessary to prepare and soak the denture overnight, and after soaking, the denture can be taken out and rinsed with water before being mounted. It is more effective to remove the dirt lightly with a toothbrush or the like and then immerse the denture in the diluent.

  EXAMPLES Hereinafter, although an experimental example, an Example, and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples,% means mass% unless otherwise specified. The blending amounts in Tables 1, 3, and 5 indicate pure component equivalents for the components (A), (C), and (F). Moreover, since the sodium hydroxide mix | blended as a pH adjuster in Table 1, 3 is trace amount, the compounding quantity was considered to be zero and (D) moisture content was computed.

Moreover, the following were used as each component of a raw material.
Polyoxyethylene (POE) lauryl ether (EO (ethylene oxide) average addition mole number 15);
Made by Nippon Emulsion Co., Ltd. (trade name Emarex 715)
Polyoxyethylene alkyl (C12,14) ether (EO average addition mole number 15);
Lion Chemical Co., Ltd. (brand name Leox CC-150-90, 90% product)
Polyoxyethylene lauryl ether (EO average addition mole number 25) (comparative product);
Nikko Chemicals Co., Ltd. (trade name Nikkor BL-25)
Polyoxyethylene behenyl ether (EO average addition mole number 10) (comparative product);
Made by Nippon Emulsion Co., Ltd. (Brand name Emarex BHA-10)
Polyoxyethylene hydrogenated castor oil (EO average added mole number 60) (comparative product);
Nikko Chemicals Co., Ltd. (trade name HCO-60)
Alkyl (C12,14) glycoside (comparative product); manufactured by Henkel (trade name Plantacare 1200UP)
Protease; manufactured by Novozymes (trade name Evalase 16L)
Manufactured by Novozymes (trade name Sabinase 16L)
Benzethonium chloride; Sankyo Lifetech Co., Ltd. (trade name: Highamine)
Cetylpyridinium chloride; benzalkonium chloride manufactured by Wako Pure Chemical Industries, Ltd .; chlorhexidine hydrochloride manufactured by Nippon Oil &Fats; alkyl chloride (C12,14) diaminoglycine manufactured by Wako Pure Chemical Industries, Ltd. (comparative product);
Product made by Sanyo Chemical Co., Ltd. (Brand name Levon LAG-40, 40% product)
Photosensitive element 201 (comparative product); manufactured by Koseisha (trade name: Pionin)
Isopropyl methylphenol; Osaka Chemical Co., Ltd. thymol; Osaka Kasei Co., Ltd. glycerin; Sakamoto Pharmaceutical Co., Ltd. (85% product)
Propylene glycol; 70% sorbite solution from Showa Denko KK; Erythritol manufactured by Towa Kasei Kogyo Co., Ltd .; Sodium monohydrogen phosphate and sodium dihydrogen phosphate manufactured by Mitsubishi Chemical Foods Co., Ltd .; Quen manufactured by Taihei Chemical Industrial Co., Ltd. Sodium edetate manufactured by Iwata Chemical Co., Ltd .; product manufactured by Lion Co., Ltd. (trade name Disolvin NA2)
Sodium tripolyphosphate; other optional components manufactured by Taihei Chemical Industry Co., Ltd .; all use Japanese Pharmacopoeia or quasi-drug material standards.

Examples and comparative examples
Preparations of the compositions shown in Tables 1, 3 and 5 below (prepared denture cleaning liquid composition) were prepared by the following manufacturing method, and the following methods were used to remove denture biofilm, disinfecting power, and preservative power of denture soaking solution. Storage stability was evaluated. The results are shown in Tables 2, 4, 5, and 6.

<Production method>
(1) A phase was prepared by mixing and dissolving water-soluble components such as a cationic bactericide, polyol, and protease in purified water. A pH adjuster was added if necessary.
(2) Ethanol and polyoxyethylene alkyl ether heated and melted were mixed to prepare B phase. In the case of addition, oil-soluble components such as fragrance, isopropylmethylphenol, and thymol were added.
(3) The B phase was added to and mixed with the A phase while stirring to obtain a denture cleaning liquid composition.

<PH measurement method>
The value after 3 minutes at 25 ° C. with a pH meter (manufactured by Toa Denpa Kogyo Co., Ltd., HM-30V) and a pH electrode (manufactured by Toa Denpa Kogyo Co., Ltd., GST-5421C) for the blended product transferred to a glass container. Was measured.

<Preparation of sample solution>
In order to achieve the dilution ratios shown in Tables 2, 4, and 6 in the following Tables 1, 3, and 5 (liquid compositions for denture cleaning), they were diluted with tap water. This diluted solution was used as a sample solution in the following Test Examples 1 to 3. The volume of the sample solution (diluted solution) used for the test was 1.8 mL.

Test Example 1 Removal power test for denture biofilm In order to verify the removal power of the denture cleaning liquid composition of the present invention for a denture biofilm, a denture biofilm model was created and evaluated in vitro.

<Denture biofilm model creation method>
A 1 × 1 cm polymerized acrylic plate was placed in a 24-well plate, and 0.5 mL of a 0.5% mucin solution and 0.5% albumin solution mixture was placed there and allowed to stand at 37 ° C. for 1 hour. After 1 hour, the mucin albumin solution was removed. Next, 50 μL each of a bacterial solution (turbidity OD = 1.0 at 660 nm) collected from precultured Candida albicans (Candida albicans IFO1594) and Streptococcus mutans (Streptococcus mutans ATCC25175) and dispersed in PBS And allowed to stand at 37 ° C. for 2 hours. Thereafter, 1.8 mL of tributicase soy broth (TSB) medium was added and cultured at 37 ° C. for 20 hours to prepare a denture biofilm. After 20 hours, the medium was removed from the well, and 1 mL of water was added for washing, and the operation of removing water was repeated twice.

<Removal power test>
The denture biofilm model prepared by the above method was placed in a new 24-well plate and immersed in 1.8 mL of the sample solution overnight. The next day, the plate was shaken to remove the broken denture biofilm, the sample solution was removed, and washing with 1 mL of water was repeated twice. The acrylic plate was transferred to a test tube, and the biofilm was peeled and dispersed in water with ultrasound and vortex, and the turbidity (OD = 660 nm) was measured (OD sample). As a control, turbidity (OD control) was similarly measured for a biofilm immersed in water overnight, and the denture biofilm removal rate was calculated according to the following formula. This test was measured 3 times, the average value was calculated | required, and the removal power with respect to a denture biofilm was evaluated by the following reference | standard.
Removal rate (%) = {(OD control−OD sample) / OD control} × 100

<Evaluation criteria>
Denture biofilm removal rate 80% or more: ◎
〃 60% -79%: ○
５０ 50% ~ 59%: △
未 満 Less than 50%: ×
The results are shown in Tables 2, 4 and 6.

Test Example 2 Bactericidal power test for denture biofilm A denture biofilm model was created and verified in vitro to verify the bactericidal power of the liquid composition for denture cleaning of the present invention to microorganisms in the denture biofilm. It was.

<Bactericidal test>
Put the denture biofilm model created by the above method into a new 24-well plate, soak it overnight in 1.8 mL of sample solution, shake the plate the next day to remove the broken biofilm, remove the sample solution and wash with water Was repeated twice. The acrylic plate was transferred to a test tube, the biofilm was peeled and dispersed in PBS with ultrasound and vortex, and then diluted serially with PBS. After 100 μL of each diluted solution was smeared on tributicase soy agar (TSA) medium and cultured at 37 ° C. for 4 days, the number of colonies was counted as the number of remaining bacteria, and the bactericidal effect was evaluated according to the following evaluation criteria. The number of colonies was similarly measured for a biofilm immersed in water overnight as a control. This test was performed twice, the average value was calculated | required, and the bactericidal power with respect to a denture biofilm was evaluated by the following evaluation criteria.

<Evaluation criteria>
The number of colonies was measured and evaluated by the number of bacteria reduced with respect to the control (water).
Reduced number of bacteria = control (water) number of bacteria−number of sample treated bacteria 0 to 10: ×
11 to 100: △
101-1000: ○
1001-: ◎
The results are shown in Tables 2, 4 and 6.

Test Example 3 Preservative Strength Test In order to verify the preservative power during denture immersion in the diluted solution of the denture cleaning liquid composition of the present invention, a denture biofilm model was created and evaluated in vitro.

<Preservation test>
The denture biofilm model prepared by the above method is placed in a new 24-well plate, immersed in 1.8 mL of the sample solution overnight, and 40 μL of the immersion solution is collected the next day. Diluted 100 times. 100 μL of the diluted solution was smeared on an SCDLP agar medium and cultured at 37 ° C. for 4 days, and the number of colonies was counted as the number of remaining bacteria. This test was performed twice, the average value was calculated | required, and the preservative power in denture immersion was evaluated by the following evaluation criteria.

<Evaluation criteria>
The number of colonies was measured and evaluated based on the number of grown bacteria.
0: ◎
1 to 50: ○
51-300: △
301-: ×
The results are shown in Tables 2, 4 and 6.

  From the results of Table 2, the denture cleaning liquid composition of the present invention has a concentration of 0.01 to 0.5% when (A) polyoxyethylene alkyl ether is used, and (C) when a cationic fungicide is used. The concentration of (A) the polyoxyethylene alkyl ether to the cationic fungicide (C) is in the range of 2-10, In particular, when it was in the range of 2 to 5, it was found that the denture biofilm was excellent in removal power / sterilization power and denture immersion liquid preservative power. On the other hand, from the results of Table 4, when any of the essential components of the present invention is not included, (A) polyoxyethylene alkyl ether and (C) cationic fungicide are used (dilute). When the concentration of the polyoxyethylene alkyl ether with respect to the cationic disinfectant is outside the predetermined range, the removal power / bactericidal power against denture biofilm, denture It has been found that sufficient effects are not exhibited in any of the preservative power of the immersion liquid.

Test Example 4 Storage Stability Test Next, the storage stability of the denture cleaning liquid composition was evaluated by the following method for the blended products (denture cleaning liquid composition) shown in Table 5. Moreover, the removal power and sterilization power with respect to a denture plaque and the antiseptic power after being immersed in a dilution liquid were evaluated similarly to the above. The results are shown in Table 5.

<Evaluation Method> Appearance Stability About 40 g of the sample (formulated product) was stored in a 50 mL transparent PET container for 1 month under high temperature (50 ° C.) and low temperature (−10 ° C.) conditions. The sample after storage was allowed to stand at room temperature for 1 day, and then the appearance change (precipitate / liquid separation / discoloration) was evaluated. Enzyme activity was measured and storage stability was evaluated.

<Evaluation criteria>
No change is observed in any of precipitate, liquid separation and discoloration: ◎
Slight changes are observed in any of the items of sediment, liquid separation, and discoloration, but there is no problem: ○
Changes are observed in any of the items of sediment, liquid separation, and discoloration: △
Changes are observed in any of precipitates, liquid separation, and discoloration: ×
The results are shown in Table 5.

<Evaluation Method> Enzyme Stability About 20 g of the sample (formulated product) was stored in a 20 mL glass vial at 40 ° C. for 1 month. The sample after storage was allowed to stand at room temperature for 1 day, and then enzyme activity was measured to evaluate storage stability. As a method for measuring enzyme activity, peptidyl p-nitroaniline was used as a substrate, and the increase rate of p-nitroaniline released by hydrolysis was determined by measuring the absorbance at 405 nm.

<Evaluation criteria>
Residual rate of enzyme after storage at 40 ° C for 1 month 80% or more: ◎
７０ 70% -79%: ○
５０ 50% -69%: △
〃 49% or less: ×
The results are shown in Table 5.

  From the results of Table 5, the denture cleaning liquid composition of the present invention is excellent in appearance stability and enzyme stability at the time of high-temperature storage and low-temperature storage of the blended product before dilution, and (A) polyoxyethylene alkyl ether 5 to 30%, (D) 30% to 50% moisture composition, (F) polyol, (G) pH adjuster, pH 6.0 to 8.5, appearance stability The enzyme stability was found to be excellent. Further, when the mass ratio of (B) protease / (H) chelating agent was 1 to 10, the appearance stability was further improved. Furthermore, from the results of Table 6, it was confirmed that the denture cleaning liquid composition of the present invention was excellent in removal power / sterilization power for the denture biofilm after dilution and antiseptic power of the denture soaking solution.

Claims (6)

A concentrated denture cleaning liquid composition that is diluted with water and applied to a denture during use,
(A) polyoxyethylene alkyl ether having an ethylene oxide average addition mole number of 12 to 18 and an alkyl group having 12 to 20 carbon atoms,
(B) protease,
(C) a cationic fungicide,
(D) It contains water, (A) component / (C) component is 2-10 as mass ratio, and the density | concentration of (A) component is 0.01-0.5 mass% and (C) A denture cleaning liquid composition, which is diluted with water so that the concentration of the components is 0.005 to 0.1% by mass. The liquid composition for denture cleaning according to claim 1, wherein the blending amount of the polyoxyethylene alkyl ether as the component (A) is 5 to 30% by mass of the whole composition. (C) The liquid composition for denture cleaning according to claim 1 or 2, wherein the cationic disinfectant is benzethonium chloride. Furthermore, the liquid composition for denture cleaning of Claim 1 , 2, or 3 containing (E) isopropyl methyl phenol and / or thymol. ( D) The content of water is 30 to 50% by mass of the entire composition, and further contains (F) a polyol and (G) a pH adjuster, and the pH at 25 ° C. is 6.0 to 8.5. The liquid composition for denture cleaning according to any one of claims 1 to 4 . (G) the pH adjuster is phosphoric acid or a salt thereof, and (H) at least one chelating agent selected from citrate, edetate and water-soluble polyphosphate is used in combination; (H) The denture cleaning liquid composition according to claim 5 , wherein the mass ratio of the chelating agent is in the range of 1 to 10.