JP7570191B2 - Denture adhesives - Google Patents

Description

The present invention relates to a denture adhesive that has long-lasting adhesive power and allows for optimal replacement timing.

Denture adhesives are dental preparations that fix ill-fitting dentures that have become loose due to age-related alveolar ridge absorption and deformation to the palate mucosa, thereby compensating for functions such as occlusion, chewing, and speaking.

Currently commercially available denture adhesives are broadly divided into adhesive and sticky types based on the difference in the mechanism by which they fix dentures. Adhesive denture adhesives improve adhesion by filling the gap between the denture base and the oral mucosa, improving compatibility. On the other hand, sticky denture adhesives absorb moisture from the oral cavity and dentures and swell to exert high adhesive strength, increasing the retention of dentures, and are further classified into cream, powder, and tape types based on the product form (see Non-Patent Document 1).

In general, the adhesive strength of adhesive denture adhesives is superior to that of clingy types. Also, adhesive cream denture adhesives are non-aqueous preparations in which a water-swellable polymer such as carboxymethylcellulose is dispersed in an oily base such as petrolatum or liquid paraffin, and the water-swellable polymer swells when it comes into contact with saliva between the denture base and the oral mucosa, exerting adhesive strength and stabilizing the denture.

Hidekazu H. (2003) Type and Characteristics of Denture Adhesives., The Journal of Japan Prosthodontic Society 47(3): 474-483.

Conventional adhesive denture adhesives have an adhesive characteristic in which their adhesive strength gradually decreases after reaching a maximum value from the start of use. After reaching its maximum adhesive strength, it is desirable to replace the denture adhesive as soon as possible when its adhesive strength falls below the adhesive strength required to stably fix the denture. However, even if the adhesive strength falls below the adhesive strength required to stably fix the denture, the user does not immediately feel uncomfortable (such as the denture becoming loose), making it difficult for the user to recognize the appropriate time to replace the denture adhesive. Therefore, in order to optimize the replacement time of the denture adhesive, it is effective to shorten the period from when the adhesive strength falls below the adhesive strength required to stably fix the denture to when the adhesive strength falls to the point where the denture becomes loose and other discomfort occurs (i.e., to make the user feel the discomfort sooner after the adhesive strength falls below the adhesive strength required to stably fix the denture). However, in the conventional technology, no formulation technology has been developed that provides such adhesive properties while providing a sustained adhesive strength.

The object of the present invention is to provide a denture adhesive that has long-lasting adhesive power and can be replaced at an appropriate interval.

The present inventors conducted extensive research to solve the above problems and found that a denture adhesive containing a water-swelling polymer, polyethylene glycol with an average molecular weight of 200 to 600, and polyethylene glycol with an average molecular weight of 2,000 to 40,000 can maintain an adhesive strength sufficient to stably fix dentures for a long period of time, and the adhesive strength decreases in a short period of time from the point at which the adhesive strength falls below the level at which the dentures can be stably fixed to a sufficient degree until the adhesive strength decreases to a level at which the dentures become unsteady or other discomfort is caused, so that the adhesive strength is sustained, and once the adhesive strength falls below the level at which the dentures can be stably fixed to a sufficient degree, the user can be made aware of the discomfort at an early stage, and the user can be encouraged to change the dentures at an early stage from the point at which the adhesive strength falls below the level at which the dentures can be stably fixed to a sufficient degree. The present invention was completed based on this knowledge and through further research.

That is, the present invention provides the following aspects.
Item 1. A denture adhesive comprising (A) a water-swellable polymer, (B) a polyethylene glycol having an average molecular weight of 200 to 600, and (C) a polyethylene glycol having an average molecular weight of 2,000 to 40,000.
Item 2. The denture adhesive according to Item 1, further comprising (D) an oily base.
Item 3. The denture adhesive according to item 1 or 2, further comprising (E) a polyglycerol fatty acid ester.
Item 4. The denture adhesive according to any one of Items 1 to 3, wherein the component (A) is at least one member selected from the group consisting of carboxymethyl cellulose, alkyl vinyl ether/maleic anhydride copolymers, and salts thereof.
Item 5. The denture adhesive according to any one of Items 1 to 4, wherein the component (B) is Macrogol 400 and the component (C) is Macrogol 4000.
Item 6. A method for imparting adhesive properties to a denture adhesive that enable durability and optimization of replacement intervals, by incorporating (A) a water-swellable polymer, (B) polyethylene glycol having an average molecular weight of 200 to 600, and (C) polyethylene glycol having an average molecular weight of 2,000 to 40,000 into the denture adhesive.

The denture adhesive of the present invention has excellent durability because it can maintain an adhesive strength (e.g., 15 kPa) sufficient to stably fix dentures for a long period of time.

Furthermore, the denture adhesive of the present invention has a short period of time from when its adhesive strength falls below a level sufficient to stably fix the denture (e.g., 15 kPa) to when its adhesive strength falls to a level at which the denture becomes loose or otherwise uncomfortable (e.g., less than 5 kPa), so that the user can be made aware of the need to replace the denture at an early stage from when its adhesive strength falls below a level sufficient to stably fix the denture, thereby enabling the user to optimize the replacement time.

1 shows the configuration of the sample holder and pressure-sensitive shaft attached to the rheometer used in Test Example 1. A is a top view of the sample holder, B is a cross-sectional view of the sample holder, and C is a schematic diagram of the pressure-sensitive shaft in a state where it is connected to a load detection unit.

1. Denture adhesive The denture adhesive of the present invention is characterized by being a non-aqueous denture adhesive, containing a water-swellable polymer (sometimes referred to as component (A)), polyethylene glycol having an average molecular weight of 200 to 600 (sometimes referred to as component (B)), and polyethylene glycol having an average molecular weight of 2,000 to 40,000 (sometimes referred to as component (C)). The denture adhesive of the present invention will be described in detail below.

[(A) Water-swellable polymer]
The denture adhesive of the present invention contains a water-swellable polymer, which swells upon contact with saliva and plays a role in increasing adhesive strength.

The type of water-swellable polymer used in the present invention may be any polymeric compound that exhibits the property of swelling when in contact with water, such as carboxymethyl cellulose, alkyl vinyl ether/maleic anhydride copolymer, hydroxyethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, alginic acid, guar gum, tragacanth gum, karaya gum, locust bean gum, agar, gum arabic, carrageenan, etc.

Among the water-swellable polymers, the alkyl vinyl ether/maleic anhydride copolymer is a copolymer obtained by polymerizing an alkyl vinyl ether monomer and maleic anhydride. The alkyl group bonded to the alkyl vinyl ether constituting the copolymer is preferably a lower alkyl group, specifically an alkyl group having 1 to 8 carbon atoms, preferably an alkyl group having 1 to 6 carbon atoms, more preferably an alkyl group having 1 to 3 carbon atoms, and even more preferably a methyl group. Specific examples of the alkyl vinyl ether/maleic anhydride copolymer include methyl vinyl ether/maleic anhydride copolymer (methoxyethylene/maleic anhydride copolymer), ethyl vinyl ether/maleic anhydride copolymer, divinyl ether/maleic anhydride copolymer, propyl vinyl ether/maleic anhydride copolymer, and isobutyl vinyl ether/maleic anhydride copolymer.
The water-swellable polymer may be in the form of a salt. The salt of the water-swellable polymer may be any suitable salt depending on the type of the water-swellable polymer. For example, in the case of a salt of carboxymethylcellulose, alkali metal salts such as sodium salt and potassium salt, preferably sodium salt, may be mentioned. In addition, in the case of a salt of an alkyl vinyl ether/maleic anhydride copolymer, alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, zinc salt, strontium salt, and mixed salts containing two or more of these, preferably mixed salts containing both sodium salt and calcium salt may be mentioned.

Among these water-swellable polymers, preferred are carboxymethyl cellulose, alkyl vinyl ether/maleic anhydride copolymers, and salts thereof.

These water-swellable polymers may be used alone or in combination of two or more.

From the viewpoint of more suitably providing adhesive properties that ensure durability of adhesive force and appropriate replacement timing, a suitable example of the water-swellable polymer used in the present invention is a combination of carboxymethylcellulose and/or its salt with alkyl vinyl ether/maleic anhydride copolymer and/or its salt. When carboxymethylcellulose and/or its salt with alkyl vinyl ether/maleic anhydride copolymer and/or its salt are used in combination, the ratio is not particularly limited, but for example, 10 to 240 parts by weight, preferably 30 to 220 parts by weight, more preferably 50 to 200 parts by weight of alkyl vinyl ether/maleic anhydride copolymer and/or its salt per 100 parts by weight of carboxymethylcellulose and/or its salt.

The content of component (A) in the denture adhesive of the present invention is, for example, 30 to 75% by weight, preferably 35 to 70% by weight, and more preferably 40 to 65% by weight, of the total amount of component (A).

[(B) Polyethylene glycol having an average molecular weight of 200 to 600]
The denture adhesive of the present invention comprises polyethylene glycol having an average molecular weight of 200-600.

The average molecular weight of the polyethylene glycol used as component (B) may be 200 to 600, but from the viewpoint of more optimally providing adhesive properties that ensure durability of adhesive strength and appropriate replacement timing, it is preferably 300 to 500, more preferably 350 to 450, and even more preferably 380 to 420. In the present invention, the average molecular weight of the polyethylene glycol used as component (B) is a value determined by the method described in the average molecular weight test prescribed in the "Macrogol 400" column of each monograph on pharmaceuticals in the 17th Revised Japanese Pharmacopoeia.

A suitable example of polyethylene glycol to be used as component (B) is macrogol 400.

The content of component (B) in the denture adhesive of the present invention is, for example, 10 to 50% by weight, preferably 15 to 45% by weight, and more preferably 20 to 40% by weight.

[(C) Polyethylene glycol having an average molecular weight of 2,000 to 40,000]
The denture adhesive of the present invention contains polyethylene glycol having an average molecular weight of 2000 to 40000. By using the aforementioned components (B) and (C) in combination, i.e., by using two types of polyethylene glycol with different average molecular weights in combination, it is possible to enhance the durability of adhesive strength while also providing the effect of making it easier to recognize when it is time to replace the denture adhesive.

The average molecular weight of the polyethylene glycol used as component (C) may be 2,000 to 40,000, but from the viewpoint of more optimally providing adhesive properties that ensure durability of adhesive strength and appropriate replacement timing, it is preferably 2,500 to 30,000, more preferably 2,500 to 25,000, and even more preferably 2,600 to 20,000. In the present invention, the average molecular weight of the polyethylene glycol used as component (C) is a value determined by the method described in the average molecular weight test prescribed in the "Macrogol 400" column of each monograph on pharmaceuticals in the 17th Revised Japanese Pharmacopoeia.

Suitable examples of polyethylene glycols used as component (C) include macrogol 4000, macrogol 6000, and macrogol 20000.

The content of component (C) in the denture adhesive of the present invention is, for example, 0.5 to 10% by weight, preferably 0.5 to 8% by weight, and more preferably 1 to 5% by weight.

In addition, in the denture adhesive of the present invention, the ratio of component (B) to component (C) is, for example, 2 to 15 parts by weight, preferably 3 to 13 parts by weight, and more preferably 4.5 to 11 parts by weight of component (C) per 100 parts by weight of component (B).

[(D) Oily base]
When the denture adhesive of the present invention is made into a cream type, it contains an oily base (sometimes referred to as component (D)).

The type of oily base is not particularly limited, but examples include hydrocarbon oils, higher alcohols, ester oils, higher fatty acids, vegetable oils, animal oils, silicone oils, etc. Among these, hydrocarbon oils are preferred.

Specific examples of hydrocarbon oils include liquid paraffin (light liquid paraffin, heavy liquid paraffin), petrolatum (white petrolatum, yellow petrolatum), gelled hydrocarbons (Plastibase, etc.), polybutene, hydrogenated polyisobutene, squalane, squalene, etc. Among these hydrocarbon oils, preferred is liquid paraffin, and more preferred is light liquid paraffin.

These oily bases may be used alone or in combination of two or more.

The content of component (D) in the denture adhesive of the present invention is, for example, 1 to 15% by weight, preferably 2 to 10% by weight, and more preferably 4 to 10% by weight, of the total amount of component (D).

[(E) Polyglycerol fatty acid ester]
The denture adhesive of the present invention may contain a polyglycerol fatty acid ester (sometimes referred to as component (E)) if necessary. In particular, when the denture adhesive of the present invention contains a polyglycerol fatty acid ester together with an oily base, it is possible to further improve the durability of adhesive strength and the effect of making it easier to recognize when it is time to replace the denture adhesive.

Polyglycerol fatty acid esters are esters of fatty acids or their polymers with polyglycerol.

In polyglycerol fatty acid esters, the number of ester bonds (the number of fatty acids bonded per polyglycerol molecule) is, for example, 1 to 10, preferably 1 to 8, and more preferably 1 to 5.

The fatty acids constituting the polyglycerol fatty acid ester may be either saturated or unsaturated. The number of carbon atoms of the fatty acids constituting the polyglycerol fatty acid ester may be, for example, 8 to 30, preferably 12 to 22, and more preferably 12 to 18.

The degree of polymerization of the polyglycerin constituting the polyglycerin fatty acid ester (the number of glycerin bonds) is, for example, 2 to 12, preferably 5 to 12, more preferably 8 to 12, and even more preferably 10.

These polyglycerol fatty acid esters may be used alone or in combination of two or more.

Among polyglycerol fatty acid esters, from the viewpoint of more optimally providing adhesive properties that ensure long-lasting adhesive strength and appropriate replacement timing, at least one of polyglyceryl laurate and polyglyceryl pentaoleate is preferred, and a combination of polyglyceryl laurate and polyglyceryl pentaoleate is more preferred. When polyglyceryl laurate and polyglyceryl pentaoleate are used in combination, there are no particular limitations on the ratio between them, but examples include 1 to 250 parts by weight, preferably 10 to 250 parts by weight, more preferably 25 to 75 parts by weight of polyglyceryl pentaoleate per 100 parts by weight of polyglyceryl laurate.

The content of component (E) in the denture adhesive of the present invention is, for example, 1 to 10% by weight, preferably 2 to 8% by weight, and more preferably 3 to 5% by weight, of the total amount of component (E).

[Other ingredients]
In addition to the components described above, the denture adhesive of the present invention may contain, as necessary, excipients, emulsifiers other than component (E), humectants, pH adjusters, viscosity adjusters, plasticizers, preservatives, bactericides, dyes, fragrances, flavorings, refreshing agents, sweeteners, etc.

[Form, usage, etc.]
The denture adhesive of the present invention is preferably a non-aqueous preparation that is substantially free of water. Here, "substantially free of water" means that the denture adhesive is free of water except for water that is inevitably mixed in. This means that no water has been added.

The denture adhesive of the present invention may be in any form, such as cream type, powder type, or tape type, but is preferably in cream type.

The method of using the denture adhesive of the present invention is the same as that of conventional denture adhesives. For example, in the case of a cream type, it is sufficient to spread it thinly over the entire surface of the denture base (denture base) that comes into contact with the gums (or upper jaw) after removing moisture, and then attach it to the gums (or upper jaw). In the case of a powder type, it is sufficient to sprinkle a thin, uniform layer over the entire surface of the denture base (denture base) that comes into contact with the gums (or upper jaw) while it is slightly moist, shake off the excess powder, and then attach it to the gums (or upper jaw). In the case of a tape type, it is sufficient to apply it to the surface of the denture base (denture base) that comes into contact with the gums (or upper jaw) after removing moisture, and then attach it to the gums (or upper jaw).

2. Method for imparting adhesive properties The present invention provides a method for imparting adhesive properties to a denture adhesive that will last longer and optimize replacement intervals, by incorporating (A) a water-swellable polymer, (B) polyethylene glycol having an average molecular weight of 200 to 600, and (C) polyethylene glycol having an average molecular weight of 2,000 to 40,000 into the denture adhesive.

In the present invention, the "method of imparting adhesive properties to a denture adhesive that enable durability and optimization of replacement timing" refers to a method for endowing a denture adhesive with adhesive properties that enable it to maintain an adhesive strength (e.g., 15 kPa or more) that can stably fix dentures for a long period of time, and that also enables it to maintain an adhesive strength that can stably fix dentures for a short period of time after it falls below an adhesive strength (e.g., 15 kPa) that can stably fix dentures until it falls to an adhesive strength that causes discomfort such as undulation of the dentures (e.g., less than 5 kPa).

The types and contents of the components (A) to (C) used in this method, the types and contents of other components added, and the form of the denture adhesive are as described in the section "1. Denture adhesive" above.

The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these.

The sources of the main components used in the following examples and comparative examples are as follows:
Methoxyethylene/maleic anhydride copolymer sodium/calcium salt : ISP Japan
・Sodium carboxymethylcellulose : manufactured by Daiichi Kogyo Seiyaku Co., Ltd.
Macrogol 400 : Polyethylene glycol with an average molecular weight of 380 to 420
Macrogol 4000 : Polyethylene glycol with an average molecular weight of 2600 to 3800
Macrogol 6000 : Polyethylene glycol with an average molecular weight of 7300 to 9300
Macrogol 20000 : polyethylene glycol with an average molecular weight of 20000
Polyglyceryl laurate : A polyglycerol fatty acid ester in which one lauric acid is ester-bonded to polyglycerol with a degree of polymerization of 10.
Polyglyceryl pentaoleate : A polyglycerol fatty acid ester in which five oleic acids are ester-bonded to polyglycerol with a degree of polymerization of 10.

Test Example 1
Cream-type denture adhesives were prepared having the compositions shown in Table 1. The adhesive properties of each of the obtained denture adhesives were evaluated by the following method.

Using the sample holder and pressure-sensitive shaft shown below, the adhesive properties of the denture adhesive in the presence of water were evaluated with a rheometer.
<Sample holder>
A sample holder in which a cylindrical water tank 2 (inner diameter 50 mm) is fixed on a support 1, and a columnar table 3 (diameter 22 mm, made of a methacrylic resin plate conforming to the provisions of JIS K 6178-2: 2015) is further installed in the water tank. A in Fig. 1 shows a top view of the configuration of the sample holder, and B in Fig. 1 shows a cross-sectional view of the configuration of the sample holder.

<Pressure-sensitive axis>
A pressure-sensitive shaft having a circular base (a plunger with a diameter of 20 mm; made of a methacrylic resin plate conforming to the provisions of JIS K 6178-2: 2015). FIG. 1C shows a schematic diagram of the pressure-sensitive shaft 4 connected to the load detection unit 5.

Specifically, 0.1 g of denture adhesive was applied onto the table of the sample holder, and then 37°C distilled water was added to the water tank of the sample holder to immerse the denture adhesive in the distilled water. In this state, the support of the sample holder was fixed to the sample stage of the rheometer, and the sample stage was moved toward the pressure-sensitive shaft at a speed of 50 mm/min to press the denture adhesive against the circular base of the pressure-sensitive shaft. When the load reached 9.8 N, the sample stage was pulled in the opposite direction at a speed of 50 mm/min to record the maximum force applied to the pressure-sensitive shaft. The maximum force was divided by the area of the bottom surface of the circular base of the pressure-sensitive shaft to determine the force per unit area as the adhesive force (kPa). Immediately after the above operation, the same operation was performed again while the denture adhesive was still immersed in the distilled water. This operation was repeated until the adhesive force was less than 5 kPa.

Table 1 shows the "maximum adhesive strength," "number of operations until the adhesive strength reaches the maximum," "number of operations at which an adhesive strength of 15 kPa or more is observed," and "number of operations at which an adhesive strength of 5 kPa or more but less than 15 kPa is observed."

It has been confirmed that a denture adhesive with an adhesive strength of 15 kPa or more can sufficiently and stably fix the denture, and that when the adhesive strength falls below 15 kPa, there is no discomfort such as wobbling, but the fixation of the denture gradually becomes insufficient, and when the adhesive strength falls below 5 kPa, discomfort such as wobbling occurs. In addition, all of the denture adhesives used in the test had an adhesive strength of 15 kPa or more after the first operation, and when the operation was repeated, the adhesive strength increased over time, reached a maximum value, and then decreased, eventually becoming less than 5 kPa. In other words, the "number of operations at which an adhesive strength of 15 kPa or more was observed" correlates with the period during which an adhesive strength capable of sufficiently and stably fixing the denture can be maintained, and the "number of operations at which an adhesive strength of 5 kPa or more but less than 15 kPa was observed" correlates with the period from the point at which the denture cannot be sufficiently and stably fixed to the point at which discomfort such as wobbling occurs.

As a result, the denture adhesive containing a water-swelling polymer but not polyethylene glycol (Comparative Example 1) showed a small number of manipulations in which an adhesive strength of 15 kPa or more was observed, and a large number of manipulations in which an adhesive strength of 5 kPa or more but less than 15 kPa was observed. In contrast, the denture adhesives containing Macrogol 400, Macrogol 4000, Macrogol 6000, or Macrogol 20000 together with a water-swelling polymer (Examples 1 to 6) showed a large number of manipulations in which an adhesive strength of 15 kPa or more was observed, and a small number of manipulations in which an adhesive strength of 5 kPa or more but less than 15 kPa was observed. These denture adhesives had the property of maintaining an adhesive strength capable of stably fixing dentures for a long period of time, and of making it easy to recognize the time to replace the dentures at an early stage once the adhesive strength fell below the level at which the dentures could be sufficiently stably fixed.

1 Support 2 Water tank 3 Table 4 Pressure-sensitive shaft 5 Load detection unit

Claims (9)

A denture adhesive comprising: (A) a water-swellable polymer; (B) a polyethylene glycol having an average molecular weight of 200 to 600 ; ( C) a polyethylene glycol having an average molecular weight of 2,000 to 40,000 ; and (E) a polyglycerol fatty acid ester . 2. The denture adhesive according to claim 1 , wherein said component (A) is at least one member selected from the group consisting of carboxymethyl cellulose, alkyl vinyl ether/maleic anhydride copolymers, and salts thereof. (A) a water-swellable polymer, (B) a polyethylene glycol having an average molecular weight of 200 to 600, and (C) a polyethylene glycol having an average molecular weight of 2,000 to 40,000;
the component (A) is a combination of carboxymethyl cellulose and/or a salt thereof and an alkyl vinyl ether/maleic anhydride copolymer and/or a salt thereof,
A denture adhesive, wherein the component (C) is at least one selected from the group consisting of macrogol 4000, macrogol 6000, and macrogol 20000. The denture adhesive of claim 3 , further comprising (E) a polyglycerol fatty acid ester. 5. The denture adhesive according to claim 1, 2 or 4, wherein the degree of polymerization of the polyglycerin constituting the polyglycerin fatty acid ester is 5 to 12. The denture adhesive according to any one of claims 1 to 5 , further comprising (D) an oily base. A denture adhesive according to any one of claims 1 to 6 , wherein the component (B) is Macrogol 400 and the component (C) is Macrogol 4000. A method for imparting adhesive properties to a denture adhesive that will last longer and optimize replacement intervals by having the denture adhesive contain (A) a water-swellable polymer, (B) polyethylene glycol having an average molecular weight of 200 to 600 , ( C) polyethylene glycol having an average molecular weight of 2,000 to 40,000 , and (E) a polyglycerol fatty acid ester . A method for imparting adhesive properties to a denture adhesive that can provide long-lasting adhesive properties and optimize replacement intervals, comprising the steps of: (A) a water-swellable polymer; (B) a polyethylene glycol having an average molecular weight of 200 to 600; and (C) a polyethylene glycol having an average molecular weight of 2,000 to 40,000;
the component (A) is a combination of carboxymethyl cellulose and/or a salt thereof and an alkyl vinyl ether/maleic anhydride copolymer and/or a salt thereof,
The above method, wherein the component (C) is at least one selected from the group consisting of macrogol 4000, macrogol 6000, and macrogol 20000.