JPS5988419A - Stable medicinal pharmaceutical - Google Patents

Abstract

PURPOSE:The titled agent for external use, prepared by adding a sulfur compound forming specific ions to ''Indomethacin'', and having prevented coloring with time. CONSTITUTION:A stable medicinal ''Indomethacin'' pharmaceutical for external use, prepared by incorporating one or two or more sulfur compounds forming at least one ions selected from HSO<->3, SO<2->3 and S2O<2->5, e.g. sodium hydrogensulfite, with the ''Indomethacin''. The ''Indomethacin'' is a nonsteroidal anti- inflammatory and analgesic agent, and an ointment or solution for external use is used as an external agent for local administration due to the elimination of side effects for fear thereof in oral or suppository administration. The external agent is colored with time, and there is a fear for discoloration to brown. The addition of the sulfur compound as a stabilizer is found to prevent the coloring. The amount of the stabilizer to be added is suitably 0.01-0.5%.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a stable topical preparation of indomethacin.
071 )-3; -methoxy -2-metl
Ylinaole-3-acetic acid is a non-steroidal anti-inflammatory analgesic having the chemical name of ylinaole-3-acetic acid (molecular formula: 019H26, molecular weight: sw, n), and is currently widely used in clinical practice.

In order to eliminate the side effects of the conventional administration methods of indomethacin, such as oral administration and suppository administration, an ointment (1983-1983) has already been developed as an external preparation for direct local administration6.
/θzaza6) and external liquid (Tokkai Sho!; 6-36g//)
There is. However, since these use a base that dissolves indomethacin, although the color is yellow at the time of manufacture, there is a risk that the color will change over time and turn brown.

Therefore, the inventors of the present invention have conducted intensive studies on methods for preventing color discoloration of topical preparations of indomethacin, and have added various stabilizers known as antioxidants, but most of them lack effectiveness. While enough, quite surprisingly l
SO3-, so3.

It has been discovered that coloring can be prevented by adding seven or more selected sulfur compounds that generate 52o52- ions, and the present invention has been completed.

Examples of sulfur compounds include bisulfites (alkali metal bisulfite such as sodium bisulfite and potassium bisulfite, ammonium bisulfite), sulfites (alkali metal sulfites such as sodium sulfite and potassium sulfite, calcium sulfite, barium sulfite, etc.) (alkaline earth metal sulfites), pyrosulfites (alkali metal sulfites such as sodium pyrosulfite, potassium pyrosulfite, etc.), and the amount of these stabilizers added should be determined based on the stabilizing effect and safety. The section θ, 0/~θ, S is in charge up to ko.

The preparation of the present invention is an ointment, a liquid for external use, etc., which uses a base that dissolves indomethacin, and the stabilizer is dissolved in water and mixed into the remaining base. It is preferable to use

Next, the usefulness of the present invention will be explained with experimental examples.Example A stabilizer such as oil is added to a gel ointment containing indomethacin per y/y at a concentration of θ,/h. These ointments were filled into ointment tubes at 7θ2 and then stored at 56°C and observed for color changes.

In the table, the - mark indicates no discoloration, and the 0± mark indicates slight discoloration.

+ mark indicates discoloration.

Significant discoloration is observed in the 廿 seal. It means to do something.

The formula for the gel ointment used in this experiment is as follows.

Indomethacin 7g Propylene glycol / θ2 Polyethylene glycol monolaurate (/C1, O) / θ2 Diisopropyl adipate 21 Ethanol
Gujiisobutpanolamine
θ, 31 carboxyvinyl polymer /1 precision
Total amount of water produced/θθ1d2 Examples will be shown next, but the present invention is not limited to these.

Example/ Indomethacin/2 and crotamiton 3fl.

Polyethylene glycol θθA? , 2 g of pendinoalcohol, dissolved in acetylated 1 = sugar-modified 7 alcohol 3S2, carboxyvinyl diagram ■ rimer (Hibis Wako 7, Wako! Yaku@') 4 aqueous solution ρj1 was added and stirred. This diisopropanolamine θ, S2, sodium pyrosulfite θ, /1
After dissolving (adding) in purified water/θg, further purified water was added to make up the total volume, and the mixture was sufficiently stirred until the whole was homogeneous to obtain indomethacin gel ointment. Filled into a tube, Although it was stored at 56°C for 3 months, no color change was observed.

Example! Indomethacin gel ointment was prepared in the same manner as in Example except that sodium sulfite was used in place of sodium pyrosulfite in Example. The mixture was filled into tubes and stored at 50°C for 3 months, but no color change was observed.

Example 3 Indomethacin gel ointment was prepared in the same manner as in Example, except that sodium bisulfite was used instead of sodium pyrosulfite in Example.

Fill a tube and store at 5θ°C for 3 months.
However, no color change was observed.

= Examples Indomethacin/1 is dissolved in polyethylene glycol monolaurate (/θ, O,)/θ1, diisopropyl dipate, 5, isopropyl alcohol +201, and ethyl alcohol 302. In addition to this, diisobanolamine θ, 251',
After adding 0.71 g of sodium pyrosulfite dissolved in 10 f of purified water, further purified water was added to make the total amount /θθd to obtain a liquid preparation for indomethacin series. It was filled into a plastic container and stored at 56°C for 3 months, but no color change was observed.

Claims (1)

[Claims] 1) Indomethacin and ii) H3O3-, S0
3. Indomethacin topical preparation 0, characterized in that it contains one or more sulfur compounds that produce at least one ion selected from 52052-