JP2550909B2 - Oral composition - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an oral composition capable of effectively preventing and treating dentin hyperesthesia.

[0002]

BACKGROUND OF THE INVENTION Dentin hypersensitivity is a name of a disease caused by clinical symptoms, which is caused by dental caries, abrasion, abrasion, or gingival recession. Due to such causes, the enamel or cement of the tooth disappears and the dentin is exposed, and the dentin is heated thermally, chemically,
It causes a very unpleasant pain transiently (excited pain) due to various external stimuli such as mechanical, physicochemical and electrical (e.g., induced pain). It is a temporary pain that is experienced when ingesting strong fruits, drinking cold water, brushing teeth, etc.
These pains adversely affect daily diet and oral hygiene.

The mechanism of pain development in dentin is that the above-mentioned induction factors such as electrical stimulation and chemical stimulation (1) directly stimulate nerves in the pulp through dentinal tubules in dentin. (2) In the dentinal tubules present in dentin, there is an idea that stimulation of these inducing factors moves the dentinal tubule fluid existing in the dentinal tubules to stimulate nerves. Currently, the idea of (2) is used.・ M.Branstrom [Karolinska ・
Institute], Hiroshi Horiuchi [Faculty of Dentistry, Tohoku University], Pashley [Georgia Pharmaceutical], B. Matthew [University of Bristol]
Supported by these scholars, the idea of (2) is the mainstream. That is, the number of dentinal tubules in human molars is about 20,000 on the enamel side and about 30,000 on the enamel side, and about 30,000 to 40,000 on the dental pulp side is about 3.0 μm in diameter. However, when the enamel or cementum disappears, external stimuli cause the movement of fluid in the dentinal tubule by adding to the surface of the exposed dentin, and the movement of this fluid excites the sensory nerves of the pulp, It is felt as pain.

Therefore, in order to alleviate, eliminate or prevent the pain of hyperesthesia, the entrance of this dentinal tubule is blocked,
It is effective to suppress and block the transmission of stimulation by narrowing.

Conventionally, as clinical treatments for this hypersensitivity of dentin, (a) a filling method which also serves to repair a defective enamel, (b) a corrosive agent, a hardening accelerator, an anti-inflammatory agent, 2 Method using patch such as dentin formation promoter, (c) 8%
An iontophoresis method using an aqueous solution of ZnCl ₂ or 1 to 2% NaF, (d) a method of covering or lining the pulp, (e) a method of demyelination or a root canal treatment, and the like are adopted.

[0006] Although some oral compositions for the purpose of preventing or treating dentin hypersensitivity have been proposed, most of the conventional oral compositions of this type are narrowed or occluded in dentinal tubules. That is, it was an indirect preventive and therapeutic technique that mainly utilizes the blunt action of nerves, rather than hindering the movement of the tubule fluid to stimulate the nerves in the dentinal tubules.

[0007]

SUMMARY OF THE INVENTION In view of the above circumstances, the inventors of the present invention have conceived dentin by constricting or occluding dentinal tubules in dentin without relying on an indirect technique utilizing the blunt action of nerves. As a result of intensive research on an oral composition capable of preventing and treating hypersensitivity, aluminum and carboxylic acid radicals are present in a dissolved state in the oral composition, and 1 mol of the aluminum root Orthophosphoric acid, glycerophosphoric acid, pyrophosphoric acid, tripolyphosphoric acid, hexametaphosphoric acid, phytic acid, ethane-1-hydroxy-1,1-diphosphonic acid, and these as the active ingredient of dentinal tubule stenosis occlusion with a molar ratio of acid roots of 6 or less Water-soluble phosphoric acid compound selected from sodium salt, potassium salt and ammonium salt is used in combination, or carboxylic acid other than aluminum and oxalic acid When and are contained in a dissolved state, and the molar ratio of carboxylic acid roots to 1 mole of aluminum roots is 6 or less, an oxalic acid compound is used in combination with the dentinal tubule stenosis-occluding active ingredient, and the pH of the composition is 5 or more. It was found that the effect of stenosis or occlusion of dentin tubules is high, and dentin hypersensitivity can be effectively prevented or treated.

That is, it has been conventionally known to use aluminum chlorohydroallantoinate as a drug for treating hypersensitivity (US Pat. No. 3,541,451).
No. 3) is based on an evaluation method (evaluation of substance permeability of dentinal tubules) by Pashley et al., Which was adopted by the present inventors for investigating occlusive stenosis occlusion effect, as shown in Experimental Examples described later. If so, its effectiveness is small.

Further, a composition for oral cavity in which an aluminum compound is combined with a fluoride for the purpose of preventing tartar has been known (US Pat. No. 4,146,605), and citric acid or lactic acid may be added to the composition. However, the pH of this composition is 4.5 or less, and according to the study by the present inventors, as is clear from the experimental examples described later, at such low pH, dentinal tubule stenosis is occluded. It has no effect. Further, U.S. Pat. No. 3,651,207 discloses a mouthwash containing aluminum dihydroxyallantoinate, citric acid and tartaric acid, and further containing sodium monohydrogen phosphate. However, it is too little for citric acid and tartaric acid, and similarly, it has no hyperalgesic and blunting effect.

However, according to the results of the study by the present inventors,
Aluminum and a carboxylic acid radical, in particular a hydroxycarboxylic acid radical, in a specific molar ratio, that is, the latter 6 mol or less relative to the former 1 mol, preferably 0.3 / n to 6 / n mol (n is the number of carboxylic acid radicals in one molecule) The pH of the system is 5 or more, preferably 5 to 10, and further phosphoric acid, glycerophosphoric acid, pyrophosphoric acid, tripolyphosphoric acid, hexametaphosphoric acid, phytic acid, Ethane
When 1-hydroxy-1,1-diphosphonic acid and a sodium salt thereof, potassium salt, or a water-soluble phosphate compound selected from ammonium salt is blended, or a carboxylic acid radical other than oxalic acid is used as the carboxylic acid radical, When an oxalic acid compound was added to the composition, it surprisingly exhibited an excellent dentinal tubule stenosis occlusion effect, and was found to be extremely effective in the prevention and treatment of dentin hypersensitivity, which led to the present invention. Is.

Accordingly, the present invention contains an active ingredient of dentinal tubule stenosis obstruction which contains aluminum and carboxylic acid radicals in a dissolved state and has a molar ratio of carboxylic acid radicals to 1 mol of aluminum of 6 or less. phosphoric acid,
Glycerophosphoric acid, pyrophosphoric acid, tripolyphosphoric acid, hexametaphosphoric acid, phytic acid, ethane-1-hydroxy-
1,1-diphosphonic acid and a water-soluble phosphoric acid compound selected from these sodium salts, potassium salts and ammonium salts, and having a pH of 5 or more, and an oral composition and aluminum A dentin stenosis stenosis-occluding active ingredient containing a carboxylic acid root other than oxalic acid in a dissolved state and having a molar ratio of the carboxylic acid root to 1 mole of aluminum of 6 or less is added, and an oxalic acid compound is added. And a pH of 5 or more, an oral composition for hypersensitivity of dentin.

The oral composition according to the present invention is a toothpaste such as a toothpaste or a moisturized toothpaste, a liquid or gel coating agent, a mouthwash,
It is used as a dental floss, an oral band, etc., and contains carboxylic acid radicals in an amount of 6 mol or less per 1 mol of aluminum radicals in a dissolved state of aluminum and carboxylic acid radicals as active ingredients for dentinal stenosis stenosis. is there. The dissolved state is not limited to the case where all of the above components are solubilized in the oral composition, and also includes the case where the components are partially precipitated. Further, each of the above components may be solubilized as an ion alone or may be solubilized in a chelated form.

Here, aluminum and carboxylic acid radicals are
It may be given as aluminum carboxylate, or
Aluminum compounds and carboxylic acids that do not contain rubonic acid groups
Or, the salts other than the aluminum salt are blended separately.
May be given by doing. In this case, the carboxylic acid
Luminium includes aluminum lactate and gluconate
Monocarbo such as aluminum and aluminum glycolate
Aluminum acid salt, aluminum malonate, glutaric acid
Aluminum, aluminum malate, aluminum tartrate
Aluminum dicarboxylates such as um and aluminum citrate
Normal salts and salts of aluminum tricarboxylates such as um
Anomalous salts such as basic aluminum (abnormals)
Alt) and the like. Also, these carboxylic acids
Aluminum compounds other than aluminum include Al
(NH_Four) (SO_Four)₂, AlCl₃, AlF₃, [Al
(OH)₂Cl]_x, Al (NO₃)₃, KAl (S
O _Four)₂, NaAl (SO_Four)₂, Al₂(SO_Four)₃, Al
(SiF₆)₃Soluble aluminum compounds such as
Further, as the carboxylic acid and its salt, the above-mentioned mono,
Di, tricarboxylic acid and its alkali metal salts are used
it can. In the present invention, two kinds of these compounds are used.
The above may be used in combination.

Among the compounds having a carboxylic acid group described above, a compound having a hydroxycarboxylic acid group is particularly preferable, and a hydroxymonocarboxylic acid compound such as lactic acid, glycolic acid or gluconic acid is particularly preferable.

In the present invention, the above-mentioned aluminum and carboxylic acid radicals are mixed in a dissolved state at a ratio of 6 mol or less of carboxylic acid radicals to 1 mol of aluminum. In this case, particularly 6 carboxylic acid radicals to 1 mol of aluminum are mixed. / N or less (where n is the number of carboxylic acid radicals in one molecule. That is, in the case of monocarboxylic acid, n =
1, n = 2 in the case of dicarboxylic acid, n = 3 in the case of tricarboxylic acid), and more preferably 0.3 / n to 6 /
It is preferable that the number of moles is n. More preferably, it is 0.7 to 5, especially 1 to 4 in the case of monocarboxylic acid, 0.2 to 2.5 in the case of dicarboxylic acid, especially 0.3 to 2, and 0.1 to 2 in the case of tricarboxylic acid, and particularly It is 0.2 to 1.5 mol.

The content of aluminum is not necessarily limited, but solubilized aluminum is 0.0% of the total composition.
It is preferably 1 to 10% (weight%, the same applies hereinafter), and particularly preferably 0.1 to 5%.

In the present invention, in addition to aluminum and carboxylic acid radical, a specific water-soluble phosphoric acid compound is further added, whereby the preventive and therapeutic effects of dentin hypersensitivity can be further improved.

As the phosphoric acid compound, water-soluble orthophosphoric acid, glycerophosphoric acid, pyrophosphoric acid, tripolyphosphoric acid, hexametaphosphoric acid, phytic acid, ethane-1-
Hydroxy-1,1-diphosphonic acid and one or more selected from sodium salt, potassium salt and ammonium salt thereof are used. In addition, these phosphate compounds are also contained in the oral composition in a dissolved state, and the content of the solubilized compound is 0.01 to 0.01% of the entire composition.
It is preferably set to 10%, particularly 0.1 to 5%.

In the present invention, a carboxylic acid compound is blended as described above, and a hydroxycarboxylic acid compound is preferable as the carboxylic acid compound. In this case, the carboxylic acid compound other than the oxalic acid compound is used. By using a carboxylic acid compound together with an oxalic acid compound, the same effect as in the case of blending the above specific water-soluble phosphoric acid compound can be obtained. Therefore, an oxalic acid compound and a carboxylic acid other than the oxalic acid compound can be obtained. It is also effective to use an acid compound, especially a hydroxycarboxylic acid compound in combination.

In this case, examples of the oxalic acid compound include oxalic acid and its sodium salt, potassium salt, ammonium salt and the like, and one or more of these may be used, and their content in the oral composition. The amount of solubilized oxalate is 0.07-5%, especially 0.1-0.1%.
It is preferably 3%.

As the other components of the composition for oral cavity of the present invention, appropriate components are used depending on the type, purpose of use and the like.

For example, in the case of toothpaste, dibasic calcium phosphate dihydrate and anhydride, monobasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate, titanium oxide, alumina, hydrated alumina,
Precipitable silica, other silica-based abrasives, aluminum silicate, insoluble sodium metaphosphate, insoluble potassium metaphosphate, magnesium triphosphate, magnesium carbonate, calcium sulfate, bentonite, zirconium silicate, synthetic resin, etc. or Two or more kinds may be blended (the blending amount is usually 7 to 99%, and in the case of toothpaste, it is 10 to 50%, but an RDA value of about 10 to 100, particularly about 30 to 60, an abrasive, It is preferable to select the blending amount).

In the case of a paste-form oral composition such as toothpaste, a cellulose derivative such as carrageenan, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, carboxymethyl hydroxyethyl cellulose sodium, etc. as a binder.
Alkali metal alginates such as sodium alginate, propylene glycol alginate, xanthan gum, tragacanth gum, gums such as karaya gum and gum arabic, polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, polyvinyl pyrrolidone and other synthetic binders, gelling property One or two or more kinds of inorganic binders such as silica, gelling aluminum silica, bee gum, and laponite may be blended (the blending amount is usually 0.5 to 5%).

Further, in the production of toothpaste and other liquid or paste oral compositions, as a viscous agent, sorbit, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylit. , Maltite, lactit and the like may be blended alone or in combination (the blending amount is usually 10 to 70% in the case of toothpaste).

Further, water-soluble salts of higher alkyl sulfates having an alkyl group having 8 to 18 carbon atoms such as sodium lauryl sulfate and sodium myristyl sulfate, and water-soluble higher fatty acids such as hydrogenated coconut oil fatty acid monoglyceride sodium monosulfate. Monoglyceride monosulfate, alkylaryl sulfonate such as sodium dodecylbenzene sulfonate, higher alkyl sulfonate, higher fatty acid ester of 1,2-dihydroxypropane sulfonate, N-
Anionic activators such as substantially saturated higher aliphatic acylamides of lower aliphatic aminocarboxylic acid compounds such as sodium, potassium or ethanolamine salts of lauroyl, N-myristoyl or N-palmitoyl sarcosine, and alkyl groups such as lauroyl diethanolamide. Sucrose fatty acid ester, lactose fatty acid ester, lactitol fatty acid ester having 12 to 18 carbon atoms in fatty acid groups such as loylethanolamide, sucrose mono and dilaurate,
Maltitol fatty acid ester, stearic acid monoglyceride, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate,
Polyoxyethylene (10, 20, 40, 60, 80,
(100 mol) hydrogenated castor oil, a polymer of ethylene oxide and propylene oxide, and nonionic activity such as a condensation product of polyethylene oxide such as polyoxyethylene polyoxypropylene monolauryl ester with a fatty acid, a fatty alcohol, a polyhydric alcohol and polypropylene oxide. One or two or more kinds of surfactants (compounding amount usually 0 to 7%, preferably 0.2 to 5%) such as agents, betaine-based and amino acid-based amphoteric surfactants may be added.

The oral composition of the present invention further comprises saccharin sodium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartin, thaumatin, asparatyl phenylalanine methyl ester,
p-methoxycinnamic aldehyde, sucrose, lactose,
Sweeteners such as fructose and sodium cyclamate (0-1
%, Preferably 0.01 to 0.5%), p-hydroxymethylbenzoic acid, p-hydroxyethylbenzoic acid, p-hydroxypropylbenzoic acid, p-hydroxybutylbenzoic acid, sodium benzoate, Preservatives such as lower fatty acid monoglyceride, wintergreen oil, spearmint oil, peppermint oil, sassafras oil, clove oil, eucalyptus oil and other flavors, gelatin, peptone, arginine hydrochloride, albumin, casein, brightener, silicone, pigment, Other components may be blended, for example, in the case of toothpaste, it may be produced by kneading the desired components described above with an appropriate amount of water.

Also, in the case of producing other oral compositions, it can be produced in accordance with a conventional method using appropriate components usually used.

Furthermore, in the present invention, epsilon aminocaproic acid, tranexamic acid, dextranase, amylase, protease, mutanase, lysozyme, lytic enzyme, enzyme such as litec enzyme, sodium monofluorophosphate, potassium monofluorophosphate. Alkali metal monofluorophosphate, sodium fluoride, ammonium fluoride, fluorides such as stannous fluoride, chlorhexidine salts, dihydrocholesterol, glycyrrhetin salts, glycyrrhetinic acid, chlorophyll, caropeptide, vitamins, anticalculus agent, antibacterial One or two or more kinds of active ingredients such as known agents, antiplaque agents, and known sensitizers such as potassium nitrate may be blended.

The oral composition of the present invention can be prepared by appropriately selecting and using the above-mentioned components. In this case, the pH of the composition is
Is 5 or more, more preferably 5 to 10, still more preferably 6
It is necessary to adjust the pH to -8, and if the pH is low, the effect of preventing and treating hypersensitivity cannot be exhibited. Note that p
When H is adjusted, alkali hydroxides such as sodium hydroxide, sodium hydrogen carbonate and sodium carbonate, alkali hydrogen carbonate and alkali carbonate can be added as pH adjusters.

[0030]

INDUSTRIAL APPLICABILITY The composition for oral cavity of the present invention has a very high effect of occluding dentinal tubule stenosis and can effectively prevent and treat dentine hyperesthesia.

[0031]

EXAMPLES The present invention will be specifically described below by showing experimental examples and examples, but the present invention is not limited to the following examples.

[Experimental Example] Pashley
The degree of stenosis and occlusion of dentin tubules of dentin by various agents was evaluated using the device of y). Here, the hyperesthesia is caused by the nerve being stimulated by the movement of the dentinal tubule fluid existing in the dentinal tubule, and the Pashley device can directly measure the movement of the dentinal tubule fluid in vitro.

Specifically, a dentin disc obtained from a human tooth is incorporated into an apparatus, and when the Ringer's solution is fed under pressure, the amount of the local Ringer's solution passing through the dentinal tubule of the dentin disc is measured per unit time. Therefore, the degree of stenosis or occlusion of dentinal tubules is evaluated from the amount of Ringer's liquid passing through the dentin tubules per unit time before and after treating the dentin disc with a drug.

In this experiment, the drugs shown in Tables 1 and 2 were dissolved in water at the concentrations shown in the table,
Treatment was carried out by immersing a dentin disc in the one adjusted to a predetermined pH with NaOH. In this case, among the aluminum carboxylates having a high aluminum content, basic aluminum chloride [Al (OH) ₂
Cl] _x and carboxylic acid are used so that the carboxylic acid / Al has a predetermined molar ratio, and when the carboxylic acid content is large, carboxylic acid is added to aluminum carboxylate so that the carboxylic acid / Al has a predetermined molar ratio. It was

Tables 1 and 2 also show the results of the occluded dentinal stenosis obstruction effect of various drugs. The effect of occluding dentinal tubule stenosis was evaluated by the reduction rate obtained from the following.

[0036]

[Equation 1]

[0037]

[Table 1]

[0038]

[Table 2]

From the results in Tables 1 and 2, it was confirmed that the combined use of a specific water-soluble phosphoric acid compound or oxalic acid compound with aluminum carboxylate further improved the dentinal tubule stenosis effect.

Examples will be shown below. [Example 1] Toothpaste Propylene glycol 5% Carrageenan 2 Gelatin 0.3 Sorbit 15 Aluminum hydroxide 40 Sodium lauryl sulfate 0.5 Perfume 0.5 Sodium saccharin 0.05 Aluminum lactate 1.0 Potassium nitrate 5.0 Diphosphate Sodium 0.6 Sodium monofluorophosphate 0.76 Water balance 100.0% pH = 6.0 (adjusted with sodium hydroxide)

[Example 2] Toothpaste Propylene glycol 3% Xanthan gum 2 Glycerin 20 Alumina 10 Sodium lauryl sulfate 2.0 Perfume 0.3 Saccharin sodium 0.05 Aluminum citrate 3.5 Sodium pyrophosphate 1.0 Chlorhexidine gluconate 0 0.01 Water Residual 100.0% pH = 5.5 (adjusted with sodium hydroxide)

[Example 3] Mouthwash Glycerin 5.0% Sorbit 5.0 Ethanol 10 Saccharin sodium 0.15 Sodium lauryl sulfate 3.0 Perfume 0.5 Dye 0.01 Aluminum lactate 2.0 Disodium phosphate 0 .4 Water balance 100.0% pH = 7.0 (adjusted with potassium hydroxide)

[0043]

Example 4 Mouthwash pH = 6.5 (adjusted with potassium hydroxide)

Example 5 Oral band pH = 7 (adjusted with sodium hydroxide)

Example 6 Oral band pH = 7.5 (adjusted with sodium hydroxide) The oral band of the above example was prepared by dissolving each component in water to give 10
A 0 g solution was prepared, which was freeze-dried to remove water as much as possible and formed into a film.

Example 7 Coating agent pH = 7.0 (adjusted with sodium hydroxide)

[0048]

Claims (12)

(57) [Claims] 1. An dentinal tubule stenosis-occluding active ingredient containing aluminum and a carboxylic acid radical in a dissolved state and having a molar ratio of the carboxylic acid radical to 6 mol of aluminum is 6 or less, and orthophosphoric acid, Glycerophosphoric acid, pyrophosphoric acid, tripolyphosphoric acid, hexametaphosphoric acid,
Phytic acid, ethane-1-hydroxy-1,1-diphosphonic acid, and a water-soluble phosphoric acid compound selected from sodium salt, potassium salt, and ammonium salt thereof, and having a pH of 5 or more An oral composition for hypersensitivity of dentin. 2. A molar ratio of carboxylic acid radicals to 1 mol of aluminum is 0.3 / n to 6 / n (where n represents the number of carboxylic acid radicals in one molecule).
The composition according to the item. 3. The composition according to claim 1 or 2 having a pH of 5-10. 4. The composition according to any one of claims 1 to 3, wherein the carboxylic acid radical is a hydroxycarboxylic acid radical. 5. The composition according to claim 4, wherein the hydroxycarboxylic acid radical is a hydroxymonocarboxylic acid radical. 6. The composition according to claim 1, wherein the content of solubilized aluminum is 0.01 to 10% by weight based on the total weight of the composition. 7. An dentinal tubule stenosis-occluding active ingredient containing aluminum and a carboxylic acid radical other than oxalic acid in a dissolved state, and having a molar ratio of the carboxylic acid radical to 6 mol of aluminum is 6 or less, and An oral composition for hypersensitivity of dentin, which comprises an oxalic acid compound and has a pH of 5 or more. 8. A molar ratio of carboxylic acid radicals to 1 mol of aluminum is 0.3 / n to 6 / n (where n represents the number of carboxylic acid radicals in one molecule).
The composition according to the item. 9. The composition according to claim 7, which has a pH of 5 to 10. 10. The composition according to any one of claims 7 to 9, wherein the carboxylic acid radical is a hydroxycarboxylic acid radical. 11. The composition according to claim 10, wherein the hydroxycarboxylic acid radical is a hydroxymonocarboxylic acid radical. 12. The composition according to any one of claims 7 to 11, wherein the content of solubilized aluminum is 0.01 to 10% by weight based on the whole composition.