JPH08268854A - Composition for oral cavity - Google Patents

Abstract

PURPOSE: To obtain a composition used for oral cavities, containing an acidic non-steroidal antiinflammatory agent, a cationic antimicrobial agent, a tetracy cline antibiotic and an inorganic acid, prevented from the discoloration of the composition, and effective for preventing and treating periodontitis, halitosis, etc. CONSTITUTION: A composition used for oral cavities containing an acidic non- steroidal antiinflammatory agent (e.g. ibuprofen and/or flurbiprofen), at least one kind of cationic antimicrobial agent (e.g., cetylpyridinium chloride and/or chlorhexidine salt), and a tetracycline antibiotic contained is further compounded with at least one kind of organic acid or its derivative (e.g., citric acid) in an amount of 0.001-2wt.% based on the whole amount of the composition. The acidic non-steroidal antiinflammatory agent, the cationic antimicrobial agent and the tetracycline antibiotic are contained in amounts of 0.01-5wt.%, 0.001-5wt.% and 0.01-5wt.%, respectively. The composition may further suitably be compounded with an abrasive agent, a thickening agent, a flavor, a sweetener, a wetting agent, etc., and subsequently prepared into a dentifrice, a mouth wash, a troche, a chewing gum, a paste for oral cavities, etc.

Description

Detailed Description of the Invention

[0001]

The present invention relates to an oral composition,
More specifically, an oral composition excellent in the effect of preventing and treating periodontal disease, halitosis, etc. even if it contains an acidic non-steroidal anti-inflammatory agent and a cationic fungicide or a tetracycline antibiotic. It is about.

[0002]

2. Description of the Related Art Acidic non-steroidal anti-inflammatory agents have a strong anti-inflammatory effect and have been tried to be applied to oral compositions in the past (Japanese Patent Laid-Open Nos. 60-61524 and 52-3.
No. 8030), and is effective for treating and preventing periodontal diseases such as gingivitis and periodontitis.

On the other hand, cationic bactericides having strong bactericidal and antibacterial effects and tetracycline antibiotics are also used.
It is said to be effective for periodontal diseases such as gingivitis and periodontitis, and oral diseases such as caries and bad breath.

Therefore, the present inventors have blended an acidic non-steroidal anti-inflammatory drug with a cationic bactericidal agent or a tetracycline antibiotic to have an excellent effect on oral diseases such as periodontal disease, caries and bad breath. The presenting oral composition was examined.

However, according to the study by the present inventor,
When an acidic non-steroidal anti-inflammatory agent and a cationic bactericidal agent or a tetracycline antibiotic are mixed in an oral composition at the same time, there is a problem that discoloration occurs when stored at high temperature and the property becomes unstable. found.

[0006]

SUMMARY OF THE INVENTION The present invention has been made by paying attention to the problems of the prior art as described above.
Its purpose is to prevent discoloration of an oral composition containing an acidic non-steroidal anti-inflammatory agent and a cationic bactericidal agent or a tetracycline antibiotic and to provide an oral composition having stable properties.

[0007]

The composition for oral cavity of the present invention, which has been able to solve the above-mentioned problems, comprises an acidic non-staloid anti-inflammatory agent and at least one or more cationic bactericides,
It is characterized in that an oral composition containing a tetracycline antibiotic is blended with at least one organic acid or a derivative thereof.

[0008]

The present inventor can prevent discoloration and can be stably blended when it contains an acidic non-steroidal anti-inflammatory agent, at least one or more cationic bactericides, and tetracycline antibiotics. Various studies were conducted on the composition of the product. As a result, they have surprisingly found that discoloration can be prevented in the presence of an organic acid or its derivative, and have completed the present invention.

The acidic non-steroidal anti-inflammatory agent used in the present invention may be either a free one or a pharmaceutically acceptable acid addition salt. For example, as the phenylacetic acid type, diclofenac sodium, fenbufen, etc.,
As the indoleacetic acid type, indomethacin, acemethacin, sulindac, etc., as the propionic acid type, ibuprofen, flurbiprofen, planoprofen, ketoprofen, etc., as the anthranilic acid type, phenacetin, acetaminophen, mefenamic acid, etc. Among them, arylpropionic acid anti-inflammatory agents are preferable, and ibuprofen and flurbiprofen are particularly preferable. The content of these should be appropriately determined according to the dosage form of the composition, the type of drug, etc., but when ibuprofen and / or flurbiprofen are used, the total amount of the composition is It is preferably 0.01 to 5% by weight, more preferably 0.05 to 1
It is contained in the range of% by weight.

As the cationic bactericide according to the present invention,
Quaternary ammonium salt type cationic bactericides or biguanide type bactericides are preferable, and examples of the quaternary ammonium salt type cationic bactericides include benzethonium chloride, cetylpyridinium chloride, benzethonium chloride, and the like, and chlorhexidine hydrochloride and glucon as biguanide type bactericides. Examples thereof include chlorhexidine acid, and preferred examples include cetylpyridinium chloride, chlorhexidine hydrochloride, and chlorhexidine gluconate. The amount of the cationic bactericide added is preferably 0.001 with respect to the entire composition.
˜5% by weight, more preferably 0.01 to 0.1% by weight.

The tetracycline antibiotic used in the present invention is a free pharmaceutically acceptable salt,
Any derivative may be used, and examples thereof include tetracycline, tetracycline hydrochloride, and tetracycline phosphate complex salt, and the amount thereof is preferably 0.01 to 5% by weight, more preferably 0.0 to 5% by weight, based on the entire composition.
It is mixed in the range of 5 to 2% by weight.

The cationic bactericide and the tetracycline antibiotic according to the present invention can be blended alone or in combination of two or more.

The organic acid or its derivative of the present invention includes
Carboxylic acid or a derivative thereof is preferable, for example, citric acid, isopropyl citrate, calcium citrate, iron citrate, triethyl citrate, sodium dihydrogen citrate, disodium citrate, ammonium citrate, ammonium iron citrate, etc. Examples thereof include malic acid salts such as citrate, malic acid, sodium malate, and diisostearyl malate, and more preferably citric acid, sodium citrate, malic acid, and sodium malate. The content of the organic acid or its derivative is preferably 0.001 to 2% by weight, more preferably 0.01 to 1.0% by weight, based on the entire composition. 0.0
If the amount is less than 01% by weight, discoloration cannot be prevented, and if the amount exceeds 2% by weight, the taste and the like become poor.

The oral composition according to the present invention is a toothpaste such as toothpaste, powder toothpaste, liquid toothpaste, a liquid mouth freshener such as mouthwash, a solid mouth freshener such as troche, chewing gum,
Applicable as an oral pasta and the like, and in the oral composition of the present invention, if necessary, an appropriate component is selected according to its type such as an abrasive, a viscosity adjusting agent, a flavor, a sweetener, a wetting agent, etc. , Blended.

For example, in the composition for oral cavity, dibasic calcium phosphate dihydrate and anhydride, monobasic calcium phosphate, tribasic calcium phosphate, disodium phosphate, monosodium phosphate, citric acid monohydrate. And anhydrate, trisodium citrate, disodium citrate, dl-malic acid, dl-sodium malate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina,
One or more of silicic acid anhydride, silica, silica gel, aluminosilicate, aluminum silicate, insoluble sodium metaphosphate, magnesium triphosphate, calcium sulfate, polymethylmethacrylate, bentonite, zirconium silicate, etc. are blended. obtain.

In the case of paste or gel such as toothpaste, or composition such as ointment, as a binder, carrageenan, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl hydroxyethyl cellulose, hydroxypropyl methyl cellulose, Cellulose derivatives such as hydroxypropyl cellulose, alkali metal alginates such as sodium alginate, propylene glycol alginate, xanthan gum, tragacanth gum, karaya gum, gums such as gum arabic, polyvinyl alcohol, polyvinyl acetate, sodium polyacrylate, carboxyvinyl polymer, polyvinyl Synthetic binders such as pyrrolidone, silica gel, aluminum silica gel, vinyl Gum, inorganic binder such as one including laponite or two or more can be formulated.

Further, pastes, gels, ointments of toothpaste,
In the production of a liquid oral composition, as a viscous agent, one or more of sorbit, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylit, maltite, lactit and the like are used. It may be blended.

Further, the oral composition of the present invention has a carbon number of a fatty acid group such as a water-soluble salt of an alkyl sulfate ester such as sodium lauryl sulfate, higher fatty acid sodium, sodium lauryl monoglyceride sulfonate and sodium coconut monoglyceride sulfonate. Is 10-18
Higher fatty acid monoglyceride sulfonate water-soluble salt, higher fatty acid sodium monoglyceride monosulfate, olein sulfonate, paraffin sulfonate, fatty acid mono or diethanolamide such as lauric acid mono- or diethanolamide, stearyl monoglyceride, sucrose mono- or dilaurate fatty acid Sucrose fatty acid ester having 12 to 18 carbon atoms, lactose fatty acid ester, lactitol fatty acid ester, maltitol fatty acid ester, polyoxyethylene sorbitan monolaurate, polyoxyethylene hardened castor oil, about 60 mol of ethylene glycol Added sorbitan monostearate, polymer of ethylene oxide and propylene oxide, and polyoxyethylene polyoxypropylene monolaurate Rue - it can be formulated such derivatives, such as ether nonionic surfactant, one or more surfactants of the double-sided surface active agents such betaines.

Further, the oral composition of the present invention includes p-hydroxymethyl benzoate, p-hydroxyethyl benzoate, p-hydroxypropyl benzoate, sodium benzoate, lower fatty acid monoglyceride and the like. Preservatives, titanium dioxide, ethanol, liquid paraffin, pigments, and other components may be added, and for example, in the case of toothpaste, the above-mentioned desired components may be produced by kneading with an appropriate amount of water. Also, when other oral compositions are produced, they can be produced according to a conventional method using appropriate components that are usually used.

In the present invention, as an active ingredient, an enzyme such as dextranase, amylase, protease, mutanase, lysozyme, lytic enzyme (ricenzyme), alkali such as sodium monofluorophosphate, potassium monofluorophosphate, etc. Metal monofluorophosphate, sodium fluoride, stannous fluoride and other fluorides,
One or more kinds of active ingredients such as aluminum chlorhydroxylantoin, dihydrocholesterol, glycyrrhizinate, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, caropeptide, water-soluble inorganic phosphate compound may be blended.

[0021]

EXAMPLES Next, the present invention will be described in more detail by showing experimental examples and examples, but the present invention is not limited to these, and changes and modifications can be made without departing from the spirit of the above and the following. All that is included in the technical scope of the present invention.

Experimental Example 1 A mouthwash was prepared according to a conventional method according to the formulations shown in Tables 1 to 5. Stability was evaluated by visually observing the change in color tone of the obtained mouthwash at the initial stage and at 55 ° C. for 2 weeks. The change in color tone was evaluated according to the following criteria. The results are shown in Tables 1 to 5.

(Evaluation Criteria) A: No change B: Slightly colored B: Colored yellow B: Colored brown

[0024]

[Table 1]

[0025]

[Table 2]

[0026]

[Table 3]

[0027]

[Table 4]

[0028]

[Table 5] As is clear from Tables 1 to 5, formulations containing only ibuprofen and a cationic fungicide or a tetracycline antibiotic (chlorhexidine gluconate, cetylpyridinium chloride, minocycline hydrochloride) (Comparative Examples 1 and 6,
In 11), discoloration was observed. In addition, discoloration of the mouthwash was also observed for the formulations containing the phosphate (Comparative Examples 2-5, 7-10, 12, 13). On the other hand, in Examples 1 to 40, the discoloration of the composition was prevented by adding citric acid or malic acid, and the composition was stabilized. In Examples 1 and 9, 18, 26, and 34, citric acid or malic acid was contained, but a slight discoloration was observed because the blending amount was lower than the effective amount.

Example 41 In this example, a toothpaste was prepared according to a conventional method according to the following formulation.

Ingredients Ingredients (%) Chlorhexidine gluconate 1.0 Ibuprofen 0.1 Sodium citrate 0.5 Dicalcium phosphate 20.0 Sodium carboxymethyl cellulose 1.5 Sorbit solution 40.0 Polyoxyethylene hydrogenated castor oil 1.0 Saccharin sodium 0.1 Dipotassium glycyrrhizinate 0.05 Allantoin chlorhydroxyaluminum 0.05 Fragrance 0.8 Purified water balance 100.0 Total 100.0 When the change in color tone of the obtained toothpaste was evaluated by the above-mentioned method, good results were obtained.

Example 42 In this example, a toothpaste was prepared according to a conventional method according to the following formulation.

Ingredient content (%) Chlorhexidine hydrochloride 0.1 Flurbiprofen 0.5 Sodium citrate 0.01 Silicic anhydride 20.0 Sodium polyacrylate 0.6 Xanthan gum 0.2 Glycerin 40.0 Polyoxyethylene hydrogenated castor oil 1.0 Saccharin sodium 0.1 Lauroyl sarcosine sodium 0.5 Perfume 0.5 When the change in color tone of the resulting toothpaste was evaluated by the above method, good results were obtained.

Example 43 A liquid dentifrice was prepared according to a conventional method according to the following formulation.

Component content (%) Chlorhexidine gluconate 0.05 Ibuprofen 0.1 Sodium malate 0.5 Glycerin 30.0 Ethanol 5.0 Sodium polyacrylate 3.0 Polyoxyethylene hydrogenated castor oil 1.0 Saccharin sodium 0.01 Perfume 0.1 Purified water balance 100.0 Total liquid obtained When the change in the color tone of toothpaste was evaluated by the above method, good results were obtained.

[0035]

INDUSTRIAL APPLICABILITY According to the present invention, discoloration can be achieved by adding an organic acid or a derivative thereof to an oral composition containing an acidic non-steroidal anti-inflammatory agent and a cationic bactericide or a tetracycline antibiotic. The present invention has realized an oral composition capable of preventing the above-mentioned problems and achieving stabilization. The oral composition of the present invention, the anti-inflammatory effect and alveolar bone resorption inhibitory effect of acidic non-steroidal anti-inflammatory agent, and each cationic bactericidal agent, antibacterial effect of tetracycline antibiotics, bactericidal effect, etc. should be sufficiently exerted. Therefore, it is useful for treating and preventing oral diseases such as gingivitis, periodontitis, dental caries and bad breath.

Claims (9)

[Claims] 1. At least one selected from the group consisting of an acidic non-steroidal anti-inflammatory agent, a cationic bactericidal agent and a tetracycline antibiotic, and at least one selected from the group consisting of an organic acid or a derivative thereof. A composition for oral cavity, which comprises: 2. The oral composition according to claim 1, wherein the acidic non-steroidal anti-inflammatory agent is an arylpropionic acid anti-inflammatory agent. 3. The arylpropionic acid anti-inflammatory agent is ibuprofen and / or flurbiprofen.
The composition for oral cavity according to. 4. The oral composition according to claim 1, wherein the cationic bactericide is a quaternary ammonium salt type cationic bactericide and / or a biguanide bactericide. 5. The oral composition according to claim 4, wherein the quaternary ammonium salt type cationic bactericide is cetylpyridinium chloride. 6. The oral composition according to claim 4, wherein the biguanide fungicide is a chlorhexidine salt. 7. The oral composition according to claim 1, wherein the organic acid or its derivative is a carboxylic acid or its derivative. 8. The oral composition according to claim 7, wherein the carboxylic acid or its derivative is citric acid or its derivative, and malic acid or its derivative. 9. The compounding amount of the organic acid or its derivative is 0.001 to 2% by weight based on the whole composition.
Or the composition for oral cavity according to 8.