JPS58201710A - Anti-inflammatory paste preparation for oral cavity - Google Patents

Abstract

PURPOSE:An amfenac preparation that contains at least one selected from magnesium oxide, basic magnesium carbonate and calcium carbonate in such an amount as the compound causes no effect on the amfenac salt, thus causing no discoloration and decomposition with time. CONSTITUTION:A salt such as sodium, potassium or alkaline earth metal salt of amfenac, its chemical name is 2-amino-3-benzoylbenzeneacetate, is combined with at least one selected from magnesium oxide, basic magnesium carbonate or calcium carbonate in such an amount as the salt causes no effect on the amfenac, e.g., about 0.1-1 time the amount of the amfenac to give the objective paste. The addition of magnesium oxide or the like causes no color change of the amfenac from yellow to orangish red and decomposition into 7-benzoyl-2- oxyindole to give a stabilized preparation.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a stable intracavitary amfenac paste formulation.

Amfenac is a non-steroidal anti-inflammatory analgesic with the chemical name 2-amino-3-benzoylbenzene acetate. Amfenac salts are sodium salts,
It is either a potassium salt, an alkaline earth metal salt, or a mixture of two or more salts.

In basic tests, it has shown excellent anti-inflammatory effects, and clinically it has been highly evaluated for its effectiveness in treating rheumatoid arthritis, osteoarthritis, etc., and its usefulness as a capsule has been fully proven. Furthermore, in the field of dentistry, basic tests have revealed that intraoral administration of paste preparations is effective against pain, inflammation, etc. after tooth extraction.

Oral paste preparations can be manufactured using known methods, such as white petrolatum, plastibase, and sodium carboxymethyl cellulose as paste bases, according to the "Preparation Guidelines" (published by Yakuji Nippo).

Manufactured using liquid paraffin. For example, it has been found that indomethacin, a type of anti-inflammatory substance, can be used as a paste with this composition. However, when an oral paste preparation containing amfenac salts was manufactured using the known formulation shown in Table 1 and stored at room temperature for one year, the yellow color derived from amfenac salts in the paste preparation changed to orange-red. Analysis by thin layer chromatography confirmed that 7-penzoyl-2-oxindole was produced by decomposition of amfenac salts. As described above, when Amfenac paste preparations are manufactured by conventional known methods, it is difficult to formulate them due to the formation of decomposition products and changes in appearance due to discoloration.

In order to solve this problem, the present inventors have conducted extensive research and found that one or more selected from magnesium oxide, basic magnesium carbonate, and calcium carbonate is added to Amfenac salts in an amount that does not exhibit medicinal efficacy. They discovered that it is possible to produce a stable formulation that does not change color or decompose over time.

The present invention was completed based on this knowledge.

These additives are typically added to Amfenac salts at 0.
It is desirable to add 1 to 1 times the amount. The safety of these additives has been confirmed by the Japanese Pharmacopoeia.

Next, Examples will be shown to concretely demonstrate the method of the present invention and its effects.

Example 1゜For the basic formulation of the oral paste preparation shown in Table 1, that is, the formulation based on a known manufacturing method, the substances shown in the first column of Table 2 and the substances shown in the second column as various stabilizers were added. After adding and mixing the indicated amount and filling it into an aluminum tube, 60
After heating at ℃ for one month, the appearance of the contents was observed and thin layer chromatography was performed.

For thin layer chromatography, the developing solvent is a mixture of dimethyl acetate, ethanol, and 10% ammonia water (3:1:1).
The test was carried out under the test conditions of a thin plate Nijiri Gel F 254 (manufactured by Merck & Co., Ltd.).

Regarding the above test results, changes in appearance and column 4 in Table 2,
The column indicates the presence or absence of the decomposition product 7-penzoyl-2-oxindole.

Table 1: Table 2: Composition per 1g of oral paste preparation Ichiro From the results in Table 2, it is clear that it is magnesium oxide.

Calcium carbonate was found to have a stabilizing effect, while sodium carbonate and potassium carbonate had no stabilizing effect. Since this stabilizing effect is observed only in oxides and carbonates of divalent alkaline earth metals, it is presumed that the effect is based on weak chelate formation.

Example 2 Regarding magnesium oxide, which has a strong stabilizing effect as revealed in Example 1, the amount to be added was investigated in detail. 1st
Add and mix magnesium oxide in the amount shown in the second column of Table 3 to the basic composition of the oral paste preparation shown in the table, fill it in an aluminum tube, and then store it at 6°C for 1 month and at room temperature for 3 days.
Regarding the results of storage and testing for one year, the third column shows changes in appearance, and the fourth column shows the presence or absence of decomposed products by thin layer chromatography.

From Table 3, by adding 3 mg or more of magnesium oxide to 30 mg of amfenac sodium,
It has been found that an oral paste preparation that is completely stable over time can be obtained.

Example 3 Stabilizing effect when two or more types of stabilizers are added Table 4, Table 1I to the basic formulation of oral paste formulation in Table 1
The stabilizer shown in I was added and mixed in the amount shown in column 2, filled into an aluminum tube, stored at room temperature for 3 years, and tested. Column 3 shows changes in appearance, and column 4 shows thinness. The presence or absence of decomposition products was shown by layer chromatography.

From Table 4 w44, the stabilizing effect of the combined use of magnesium oxide, basic magnesium carbonate, and calcium carbonate was observed.

From the results of Examples 1 to 3, it was found that magnesium oxide, basic magnesium carbonate,
It has been found that by adding at least one type of calcium carbonate, a preparation that is extremely stable over time can be produced.

Patent applicant: Meiji Seika Co., Ltd. Agent: Ito Nada (and 2 others) 0

Claims (1)

[Claims] A stable amfenac paste preparation for intracavitary use, characterized by containing at least one selected from magnesium oxide, basic magnesium carbonate, and calcium carbonate in an amount that does not exhibit medicinal efficacy in amfenac salts.