JPS59122422A - Anti-inflammatory analgesic gel for oral cavity - Google Patents

Abstract

PURPOSE:The titled pharmaceutical preparation not precipitating an active ingredient, not irritating oral cavity, having improved medicinal effect, obtained by blending a nonsteroid anti-inflammatory analgesic with a water-soluble high polymer compound of a gelatinizing agent, and, if necessary, a water-soluble basic substance, to give a gel component with specific pH. CONSTITUTION:A nonsteroid anti-inflammatory analgesic (e.g., diclofenac sodium, ketoprofen, etc.) of an active ingredient is blended with a water-soluble high polymer compound (e.g., MC, CMC-Na, etc.) of a gelatinizing agent, and, if necessary, a water-soluble basic substance, to give an anti-inflammatory agnalgesic gel for oral cavity of a gel component with 6-8pH. Triethanolamine, or alkali salt of hydroxide is preferable as the water-soluble basic substance, and its amount is an amount enought to dissolve water-soluble anti-inflammatory analgesic such as ketoprofen, fentizac, etc. The active ingredient will not precipitate even in the absence of an alcohol component, the gel has good spreadability to the mucosa and good medicinal effect, having no irritation in oral cavity.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an oral anti-inflammatory analgesic gel containing a non-steroidal anti-inflammatory analgesic.

Medications currently used for the oral cavity include oral preparations, lozenges, oral fresheners, and
Treatment agents for alveolar pyorrhea are known.

There are also liquid preparations that are soaked in cotton cloth and applied to the affected area for the purpose of pain relief from toothaches, etc., and hydrophilic ointments containing various anti-inflammatory agents, local anesthetics, sterilizing disinfectants, etc. for the purpose of anti-inflammatory and pain relief in the oral cavity.

In the case of toothache solutions, they usually contain ethanol, propylene gelcol, etc. as solvents for the analgesic active ingredients, and are applied directly to the cavity, but the solution may spill and contact the oral mucosa. There is a very strong irritation sensation upon contact. Therefore, if the alcohol content is reduced, crystals of the analgesic active ingredient will precipitate. An improved version of this has recently been developed that uses carbo-cow divinyl polymer to gel this liquid preparation so that it is less likely to come into contact with mucous membranes (Japanese Patent Application Laid-Open No. 139415/1983), but this preparation also does not come in direct contact with mucous membranes. In some cases, there is a strong stimulus as well.

- Hydrophilic ointments are not irritating, but because of their high oil content, they do not spread well to the oral mucosa, and are easily removed by saliva when applied to inflamed areas. Therefore, there is a drawback that sufficient absorption of the active ingredient is hindered and the expected medicinal efficacy cannot be obtained.

Instead of local administration, oral administration of anti-inflammatory analgesics may also be considered. However, when taken internally, the active ingredients exhibiting medicinal efficacy are absorbed from the gastrointestinal tract and circulated throughout the body, resulting in a low production rate reaching the diseased area, and it is therefore unlikely that sufficient medicinal efficacy can be expected. In addition, side effects such as gastrointestinal disorders may occur.

Under these circumstances, the inventors of the present invention have conducted various studies and have developed a preparation that does not use alcohol, does not cause crystallization of the active ingredient, and is sufficiently effective when applied directly to the affected area in the oral cavity. I found it.

Thus, the present invention provides a gel component of pT (6 to 8) consisting of a non-steroidal anti-inflammatory analgesic as an active ingredient, a water-soluble polymer compound as a gelling agent, and a water-soluble basic substance added as necessary. The present invention provides an anti-inflammatory analgesic gel for oral cavity characterized by the following.

The formulation of this invention has better spreadability to mucous membranes than conventional formulations. Therefore, it is not absorbed by the saliva, and the sufficient amount of non-steroidal anti-inflammatory and analgesic ingredients contained therein provides sufficient anti-inflammatory and analgesic efficacy to the affected area. Furthermore, it is an excellent formulation that does not cause irritation to the oral cavity, as it does not contain any alcohol components that might irritate the oral cavity.

Examples of non-steroidal anti-inflammatory analgesics as active ingredients used in the formulation include diclofenac sodium, flurbiprofen, ketoprofen, fentiazac, and the like. The compounding concentration of these nonsteroidal anti-inflammatory analgesics cannot be determined unambiguously because each has different effects, but preparations containing 0.1 to 10% by weight (all percentages hereinafter refer to weight%) desirable. Among these, 0.5 to 2% for diclofenac sodium, 1 to 4% for flurbiprofen, 1 to 5% for ketoprofen, and 3 to 7% for fentiazac are considered appropriate. Particularly preferred formulation concentrations are diclofenac sodium 1%, flurbiprofen 2%, ketoprofen 3% and fentiazac 5%.

This preparation can be manufactured by separately preparing an aqueous solution containing a non-steroidal anti-inflammatory analgesic as an active ingredient and a gel paste containing a water-soluble polymer compound, and then mixing the two. Preferably, this formulation is approximately neutral.

Diclofenac sodium, a nonsteroidal anti-inflammatory analgesic, is water-soluble, and its 1% aqueous solution has a pH of 7. It is lO. A desired Fl agent can be obtained by adding a gel paste containing a water-soluble elevated compound to the solution to form a gel.

Flurbiprofen, ketoprofen, and fentiazac are insoluble in water, so they dissolve in purified water containing water-soluble base substances.

Examples of water-soluble basic substances include alkylamines such as methylamine, ethylamine, and propylamine, dialkylamines such as dimethylamine, diethylamine, and dipropylamine, trialkylamines such as trimethylamine, triethylamine, and tripropylamine, methanolamine, and ethanolamine. , alkanolamines such as propatoolamine, dialkanolamines such as dimetatoolamine, jetanolamine, dibrobanolamine, trialkanolamines such as trimethanolamine, triethanolamine, tripropateolamine, trimethylolamine, Organic amines such as and methylamine are suitable. In addition, inorganic bases such as ammonia, potassium hydroxide or sodium hydroxide aqueous solutions, or amino acids such as lysine and arginine can also be used.

Among these, particularly preferred water-soluble basic substances include triethanolamine and alkali hydroxide salts.

The water-soluble base substance may be used in an amount sufficient to dissolve the water-insoluble anti-inflammatory analgesics such as flurbiprofen, ketoprofen, and fentiazac. Adding too much will facilitate the dissolution of the anti-inflammatory and analgesic agent, but it is not preferable because pT (pT) will be biased toward the base side, increasing the process of adjusting I)H with acidic substances, and increasing the bitterness during use. Further, the amount of the water-soluble basic substance may be adjusted as appropriate depending on the type and amount of the non-steroidal anti-inflammatory agent used and the type of water-soluble basic substance used.

These solutions are gelled by adding a gel paste containing a water-soluble polymer compound, and the water-soluble polymer compound used is methylcellulose (
MO), carboxymethyl cellulose sodium salt (CIMO-Na) or potassium salt (OMO-K
), OMO salts such as carboxyvinyl polymer (OVP
) or two or more thereof are used. The MC used here has a degree of substitution (the number of hydroxyl groups etherified with a metoxyl group per nofusaccharide in cellulose) of 1.
Those listed in the Japanese Pharmacopoeia of ゜7 to 2.2 may be used. OMO
As a salt, for example, 0M0-Na has a degree of substitution (the number of hydroxyl groups etherified with hydroxyl groups per anhydrous glucose) in the range of 0.6 to 0.8, and is also listed in the Japanese Pharmacopoeia. It is fine to use the one that has been published. OVP is a hydrophilic polymer obtained by polymerizing acrylic acid as a main component, and is commercially available under the names of Carbobol from Gutdrich Chemical Co., Ltd. in the United States, Hivis Wako from Wako Pure Chemical Industries, etc. good.

The formulation can be prepared by adding 0.1 to 1O20% of one or more of the water-soluble polymer compounds listed above to a gel formulation and gelling it. Suitably the water-soluble polymer compound is 0.5 to 7%, preferably 1.0 to 5.0%.
can be used. Appropriate MO1OMO salt, OV
The amount of P used alone is 1-7% and 0.5-10%, respectively.
%, 0.5-5% is suitable.

Preferably, the amounts of MO% CMC salt and OVP used are 2.5 to 5%, 1 to 5%, and 1 to 3%, respectively.

A water-soluble polymer compound may be used in combination. When MO and OMO salt are used together, the total amount is 1 to 5% (MO0.5 to 5%,
OMO0.5-5%), MO and OVP (7) combined use total 1-5% (MO0.5-4%, OVP O.5-2
%), and when used together with OMCJ salt and ω-yo, a total of 1 to 5% (OM
O salt 0.5-5%, OVP O, 5-5%) are suitable.

When OVP is used in making a gel paste, it is desirable to neutralize it with the water-soluble base materials mentioned above to obtain the appropriate viscosity. Conveniently, the water-soluble basic substance used is the water-soluble basic substance used to dissolve non-steroidal anti-inflammatory drugs.

The viscosity of the resulting preparation is not particularly limited, but is 30,000 to 60,000 cp.
The degree would be appropriate.

In addition, the preparation of the present invention may have l-
Menthol, peppermint oil, bactericides, local anesthetics, and other agents usable in the field may be added.

Next, the present invention will be explained in more detail with reference to Examples.
' Example 1 Flurbiprofen 2f was mixed with triethanolamine 1.8
The mixture was added to 40 g of purified water containing f and stirred to dissolve. −
20g of 4% aqueous solution of 10,000 OVP (Carboball 940)
and 25 g of MOIO% aqueous solution were uniformly mixed, and 1 g of triethanolamine was added while stirring to prepare a gel paste. The previously prepared flurbiprofen solution was added to this gel paste, purified water was further added to make a total amount of 100 g, and the mixture was sufficiently stirred to obtain a preparation. The viscosity of the obtained formulation was 4
1000 cp, pH was 7.20.

Example 2 Flurbiprofen 2f and triethanolamine 1.4
It was added to 40 g of purified water containing 5 g and stirred to dissolve it.

-10,000 MC-Na 10% aqueous solution 35. 20g of purified water
Mix and stir evenly to prepare a gel paste.

The previously prepared flurbiprofen solution was added to this gel paste, and purified water was further added to make a total of 100 g of teeth, and the mixture was sufficiently stirred to obtain a preparation. The viscosity of the obtained formulation was 6000
0 cp, pH was 7.21.

Example 3 Ketoprofen 3f in 10% sodium hydroxide aqueous solution 5
．． 0. The mixture was added to 40 p of purified water containing 100 g of water and stirred to dissolve. 19 g of a 4% aqueous solution of -10,000 OVP (Carbopol 940) and 24.5 g of a MOIO% aqueous solution were uniformly mixed, and 3.0 g of a 10% aqueous solution of sodium hydroxide was further stirred.
41 was added to prepare a gel paste. The previously prepared ketoprofen solution was added to this gel paste, purified water was further added to make a total volume of 100 f/ml, and the mixture was sufficiently stirred to obtain a preparation. The viscosity of the obtained formulation was 40,000 Cp, pT (6
．． It was 65.

Example 4 5 g of Fentiazac was mixed with 2.9 g of triethanolamine.
The mixture was added to 40 y of purified water containing 100% of the total amount of water and stirred to dissolve. -10,000 cvp (Carbopol 940) 4% aqueous solution 40g
and 5 f of purified water are uniformly mixed and stirred, and 3.32 g of triethanolamine is further added while stirring to prepare a gel paste. To this gel paste, the previously prepared fenthiazac solution was added, and purified water was further added to make a total amount of 100 g, and the mixture was sufficiently stirred to obtain a preparation.

The resulting formulation had a viscosity of 30,000 cp and a pH of 7.
It was 71.

Example 5 Diclofenac sodium ly was dissolved in 40 g of purified water with stirring. -10,000 MONO% aqueous solution 407 and purified water 1
A gel paste was prepared by uniformly mixing and stirring 0y. A diclofenac sodium solution was added to this gel paste, purified water was further added to make a total volume of 100 y, and the mixture was thoroughly stirred to obtain a preparation. The viscosity of the obtained formulation was 33000 c
p, pH was 6.72.

Example 6 Change over time The change over time of the preparation obtained in Example 4 was investigated. The preparation was incubated at 40°C, 150°C and 60°C for 4 hours.
After being left for 5 and 90 days, the non-steroidal anti-inflammatory analgesic was detected by liquid chromatography, and the detection rate was calculated with the detection value directly related to the formulation as 100%. The results are shown in the table below. No decomposition of the main component of the non-steroidal anti-inflammatory analgesic gel according to the present invention was observed, and there was no change in properties such as viscosity or shape of the preparation.

-13--14

Claims (1)

[Scope of Claims] 1. A gel component with a pH of 6 to 8 consisting of a non-steroidal anti-inflammatory analgesic as an active ingredient, a water-soluble polymer compound as a gelling agent, and a water-soluble basic substance added as necessary. An anti-inflammatory analgesic gel for the oral cavity. 2. The gel preparation according to claim 1, wherein the non-steroidal anti-inflammatory analgesic is diclofenac sodium, flurbiprofen, ketoprofen or fentiazac. 3. The gel agent according to claim 1, wherein the water-soluble polymer compound is one or a mixture of 2N or more of methylcellulose, carboxymethylcellulose salt, or carboxyvinyl polymer. 4o non-steroidal anti-inflammatory analgesics are flurbiprofenine,
The gel according to claim 1 or 2, which contains a water-soluble basic substance such as ketoprofen or fentiazac. 5. The gel agent according to claim 1 or 3, wherein the water-soluble polymer compound is a carboxyvinyl polymer and contains a water-soluble basic substance. 6. The gel agent according to claim 1, wherein the water-soluble basic substance is a tertiary alkanolamine or an alkali hydroxide salt. 7. The gel according to claim 2, which contains 0.1 to 10% by weight of a non-steroidal anti-inflammatory analgesic. 8. The gel according to claim 3, which contains 0.5 to 7% by weight of a water-soluble polymer compound.