JPH0769851A - Composition for oral cavity - Google Patents

Abstract

PURPOSE:To obtain a composition for oral cavity having excellent inhibitory effect on absorption of alveolar bone due to endotoxin of periodontal pathogenic bacterium and effective in preventing and treating a periodontal disease. CONSTITUTION:This composition for oral cavity is obtained by combinedly using one or two or more kinds of nonsteroidal anti-inflammatory agents and minocycline hydrochloride.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention relates to Polyphyromonas gingivalis, which is the main cause of periodontal disease.
nas gingivalis) and Actinobacillus
Actinomycetemcomitance (Actinobacill)
lus actinomycetemcomitan
The present invention relates to a composition for oral cavity which has an excellent inhibitory effect on alveolar bone resorption by bacterial endotoxin such as s).

[0002]

BACKGROUND OF THE INVENTION Periodontal disease is known as Porphyromonas gingivalis.
And Actinobacillus actinomyc
It is a disease of periodontal tissue caused by periodontopathic bacteria such as etemcomitans. The plaque formed by this periodontopathic bacterium causes inflammation of periodontal tissues, gingiva and periodontal ligament, which eventually causes resorption of alveolar bone,
It is a disease that eventually causes teeth to fall out.

Conventionally, plaque suppression and anti-inflammatory agents by anti-plaque agents have been used for the prevention and treatment of periodontal tissue inflammation. Further, as an alveolar bone absorption inhibitor, flurbiprofen (J. Periodont. Res. 1988.
(23) 166-169), indomethacin (J. Pe)
riodont. Res. 1982. (17) 90-1
It has been reported to have an effect on non-steroidal anti-inflammatory agents such as (00), and JP-A-60-61524 describes that ibuprofen and flurbiprofen have an alveolar bone resorption inhibitory effect. ing.

However, the effect of inhibiting alveolar bone resorption at the actual use concentration of these drugs is not sufficient, and the use of these drugs at high concentrations may cause a false harmful effect on the oral mucosa. Therefore, it is desired to further enhance the alveolar bone resorption inhibiting effect of these non-steroidal anti-inflammatory agents.

[0005]

Means and Actions for Solving the Problems The present inventors have
As a result of intensive studies to improve the alveolar bone resorption inhibitory effect of the nonsteroidal anti-inflammatory drug, by combining the nonsteroidal anti-inflammatory drug with minocycline hydrochloride,
Despite the fact that minocycline hydrochloride itself does not have an alveolar bone resorption inhibitory effect, a synergistic effect is exhibited by the combined use of both, and it was found that the alveolar bone resorption inhibitory effect of a non-steroidal anti-inflammatory agent is further enhanced, and the present invention was completed. It is a thing.

The present invention will be described in more detail below. The oral composition of the present invention comprises one or more non-steroidal anti-inflammatory agents and minocycline hydrochloride as active ingredients for inhibiting alveolar bone resorption. Contains, pasta for the oral cavity,
Ointment, mouthwash, periodontal pocket, patch,
It can be prepared and applied in a dosage form such as toothpaste.

Examples of the non-steroidal anti-inflammatory agent include the following types, which may be used alone or in combination of two or more. 1. Aniline anti-inflammatory agents: acetaminophen, tolfemic acid, phenacetin, phenylacetylglycine dimethylamide 2. Anthranilic acid drugs: diclofenac sodium, mefenamic acid, flufenamic acid, aluminum flufenamic acid, floctafenin, meclofenamic acid 3. Phenylacetic acid anti-inflammatory agents: alclofenac, ibuprofen, naproxen, flurbiprofen, ketoprofen, fenbufen, sodium afenac 4. Salicylic acid anti-inflammatory agents: aspirin, aspirin aluminum, aspurin DL-lysine, etenzamid,
4. Choline salicylate, salicylamide, sodium salicylate, sazapyrine, glycol salicylate 5. Pyrazolone anti-inflammatory agents: aminopyrine, antipyrine, isopropylantipyrine, oxyphenbutazone, clofezone, ketophenylbutazone, sulpirine, phenylbutazone 6. Basic anti-inflammatory agent: tinoridine hydrochloride, benzydamine hydrochloride, mepyrizole, tiaramid hydrochloride, perisoxal citrate 7. Other anti-inflammatory agents: indomethacin, acemethacin, graphenin, diphenylmethylaminoethane hydrochloride, tolmetin sodium, bucolome, pentazocine, acetylcholine chloride, tramadol hydrochloride, dimethothiazine mesylate, methiazinate, protidic acid, sulindac, pranoprofen, miglenin, Fenoprofen calcium, piroxicam, febrazone, fenthiazac, emorfazone, buprenorphine hydrochloride, diphenylsal, thiaprofenic acid, oxaprozin, butorphanol tartrate, lobenzarituto disodium, loxoprofen sodium, eptazocine hydrobromide,
Sodium hyaluronate, tenoxicam

In the present invention, the content of the non-steroidal anti-inflammatory agent is 0.01 to 10% by weight based on the whole composition,
Particularly, 0.1 to 2% by weight is suitable. The amount of minocycline hydrochloride added is 0.01 to 10 relative to the total composition.
%, Especially 0.1 to 5% by weight is preferred.

The oral composition of the present invention may contain, in addition to the above-mentioned components, appropriate components depending on the kind of the intended composition in a usual dose.

For example, as the polymer, methyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl cellulose,
Alginic acid propylene glycol ester, pullulan,
Tragant gum, xanthan gum, chitosan, polyethylene oxide, polyvinylpyrrolidone, polyacrylic acid and polymethacrylic acid or salts thereof, gelatin, peptone, casein, collagen, albumin, carrageenan, gum arabic, karaya gum, carboxyvinyl polymer, Eudragit (E, L, SR, S, N
E), ethyl cellulose, cellulose acetate, polyvinyl acetal / dimethylamino acetate, cellulose acetate / dibutyl hydroxypropyl ether and the like can be blended.

As the oil component, higher alcohols such as liquid paraffin, paraffin, cetyl alcohol and stearyl alcohol, and fatty acid esters such as oleic acid and isopropyl myristate can be blended.

As the excipient, aluminum hydroxide, second
Calcium phosphate dihydrate, dibasic calcium phosphate
Anhydrate, monobasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate, insoluble sodium metaphosphate, amorphous silica, crystalline silica, aluminosilicate, aluminum oxide, tribasic magnesium phosphate, magnesium carbonate, magnesium sulfate, Titanium oxide, crystalline cellulose and the like are mixed.

As alcohols, lower alcohols such as ethanol, propyl alcohol, isopropyl alcohol, butanol and isobutanol, and ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol,
Polyhydric alcohols such as glycerin, 1,5-pentadiol, sorbit and polyethylene glycol are mixed.

As the surface active agent, a nonionic surface active agent such as sorbitan fatty acid ester, glycerin fatty acid ester, decaglycerin fatty acid ester, polyglycerin fatty acid ester, propylene glycol / pentaerythritol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxy. Ethylene glycerin fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkylphenyl ether, polyoxyethylene castor oil, hydrogenated castor oil, poly Oxyethylene lanolin, lanolin alcohol, beeswax derivative, polyoxyethylene alkylamine Fatty acid amides, polyoxyethylene alkylphenyl formaldehyde condensates, single chain length polyoxyethylene alkyl ethers, anionic alkyl sulfates, polyoxyethylene alkyl sulfates, N-
Acyl amino acid and its salt, N-acyl amino acid and its salt, N-acyl methyl taurine salt, polyoxyethylene alkyl ether acetate, alkyl sulfocarboxylate, α-olefin sulfonate, alkyl phosphate,
Polyoxyethylene alkyl ether phosphate, an alkylammonium, an alkylbenzylammonium salt as a cationic surfactant, and betaine acetate, imidazolinium betaine, lecithin, etc. as an amphoteric surfactant can be blended.

As sweeteners, saccharin sodium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartine, P-methoxycinnamic aldehyde, aspartame and the like can be added.

As fragrances, essential oils such as peppermint and spearmint, 1-menthol, carvone, eugenol,
Anethole etc. can be mixed.

As the stabilizer, vitamin C, vitamin E, sodium sulfite, sodium pyrosulfite, sodium hydrogen sulfite, butylhydroxytoluene, propyl gallate, butylhydroxyanisole and the like can be added.

The oral composition of the present invention may contain various medicinal components, for example, antibacterial agents such as chlorhexidine and triclosan, sodium fluoride, stannous fluoride, sodium monofluorophosphate and the like. Examples thereof include plaque formation inhibitors such as fluorine compounds, dextranase, mutanase and protease, and hemostatic agents such as tranexamic acid.

[0019]

INDUSTRIAL APPLICABILITY The oral composition of the present invention has an excellent inhibitory effect on alveolar bone resorption by endotoxin of periodontopathic bacteria, and is effective for the prevention and treatment of periodontal disease.

[0020]

EXAMPLES The effects of the present invention will be specifically described below with reference to experimental examples and examples, but the present invention is not limited to the following examples.

Experimental Example A mouse skull was used as a substitute for the alveolar bone. That is, the skulls of newborn BALB / c mice (around 5 days old) were excised and divided into 2 parts,
24 hours CO _{2 in} ml of α-MEM cell culture medium
Cultured in an incubator. After that, one of the divided skulls was Actinobacillus ac
Transfer to a medium (LPS group) containing endotoxin (LPS, 1 μg / ml each) separated and prepared from the Tinomycetemcomitans Y-4 strain, and to the other skull, the same amount of endotoxin and each concentration of a nonsteroidal anti-inflammatory drug were added. The cells were transferred to a medium containing minocycline hydrochloride (drug-treated group). Then C
After culturing for 48 hours in an O ₂ incubator, the culture solution was collected, and Ca ²⁺ released in the culture solution was measured using Ciba Corning 550. The results are shown in Table 1. The results show the bone resorption inhibitory effect of each drug, with the group in which the mouse skull was added only with endotoxin (LPS) as a control group.

[0022]

[Table 1]

From the results shown in Table 1, it is recognized that when minocycline hydrochloride and a nonsteroidal anti-inflammatory agent are used in combination, they act synergistically to give an excellent bone resorption inhibiting effect.

Examples will be shown below. [Example 1] Mouthwash Ethanol 10.0% Glycerin 10.0% P.I. O. E (60) Hydrogenated castor oil 5.0% Saccharin sodium 0.2% Minocycline hydrochloride 2.0% Diclofenac sodium 1.0% Fragrance 0.2% Purified water Residual 100.0%

[Example 2] Pasta for oral cavity Liquid paraffin 15.0% Glycerin 15.0% Sodium benzoate 0.1% Methylparaben 0.2% Cetanol 5.0% Microcrystalline wax 10.0% Paraffin wax 5. 0% Sorbitan monostearate 4.0% Minocycline hydrochloride 1.5% Flurbiprofen 0.8% Perfume 0.4% Purified water Residual total 100.0%

[Example 3] Pasta for oral cavity Liquid paraffin 24.0% Sorbit 14.0% Sodium benzoate 0.1% Cetanol 5.0% Microcrystalline wax 10.0% Paraffin wax 5.0% Hydroxypropyl cellulose 1.5% Minocycline hydrochloride 0.5% Indomethacin 0.5% Fragrance 1.0% Purified water Residual 100.0%

Example 4 Oral Pasta Cetanol 15.0% Squalane 15.0% Silica Anhydrous 5.0% P. O. E (20) Hydrogenated castor oil 2.0% Hydroxypropyl cellulose 1.5% Sorbitan monooleate 2.0% Minocycline hydrochloride 1.0% Mefenamic acid 1.0% Perfume 1.0% Purified water Residual 100. 0%

[Example 5] Pasta for oral use Plastibase 87.0% Sorbitan monooleic acid 10.0% Minocycline hydrochloride 2.0% Ibuprofen 1.0% Total 100.0%

Example 6 Toothpaste Dicalcium Phosphate 45.0% Carboxymethyl Cellulose 1.0% Carrageenan 1.0% Glycerin 15.0% Propylene Glycol 2.0% Sodium Lauryl Sulfate 1.0% Lauryl Diethanolamide 0.5% Minocycline hydrochloride 2.0% Diclofenac sodium 1.0% Sodium benzoate 0.1% Sodium saccharin 0.1% Perfume 1.0% Purified water Residual total 100.0%

[Example 7] Toothpaste Precipitable silica 25.0% Sorbit 25.0% Glycerin 25.0% Polyvinylpyrrolidone 1.0% Lauroyl polyglycerin ester 1.0% P.I. O. E (60) Sorbitan monolaurate 0.5% Ethyl paraoxybenzoate 0.1% Saccharin sodium 0.2% Sodium fluoride 0.05% Minocycline hydrochloride 0.5% Flurbiprofen 1.0% Purified water Residual total 100.0%

Example 8 Periodontal pocket insertion agent Hydroxypropyl cellulose 92.0% Glycerin 5.0% Minocycline hydrochloride 0.5% Flurbiprofen 0.3% Total 100.0%

[Example 9] Patch Adhesive layer Polyacrylic acid 53.0% Hydroxypropylmethylcellulose phthalate 10.0% Hydroxypropylcellulose 29.0% Polyethylene glycol 400 5.0% Minocycline hydrochloride 2.0% Flurubi Profene 1.0% Total 100.0% Support layer Ethylcellulose 67.0% Castor oil 33.0% Total 100.0%

Claims (1)

[Claims] 1. An oral composition comprising one or more non-steroidal anti-inflammatory agents in combination with minocycline hydrochloride.