JPS5939824A - Water-soluble azulene pharmaceutical - Google Patents

Abstract

PURPOSE:The titled pharmaceutical, prepared by incorporating a water-soluble azulene with polyvinylpyrrolidone, stable even under high temperature or high humidity conditions, and capable of keeping the initial potency of the water-soluble azulene for a long term. CONSTITUTION:A water-soluble azulene pharmaceutical prepared by incorporating one pts.wt. water-soluble azulene, having a noticeable antiallergic, antiinflammatory and tissue regenerating action, etc., and expressed by the formula with 0.1pts.wt. or more preferably 0.5-30pts.wt., polyvinylpyrrolidone. Both are dissolved in a solvent and adsorbed on a suitable excipient to give a complex of the both, which is then formulated into a pharmaceutical according to the conventional technique of formulating the pharmaceutical. The water-soluble azulene in the above-mentioned pharmaceutical has no sublimative property but very rich stability and is capable of keeping the initial potency almost intact even after the lapse of one year.

Description

[Detailed description of the invention] The present invention relates to water-soluble azulene formulations.

As is well known, water-soluble azulene has been pharmacologically recognized to have anti-allergic effects, anti-inflammatory effects, tissue regeneration effects, and the like.

This water-soluble azulene is an essential oil component of chamomile that has been used as a medicine for a long time, and is a sulfonic acid derivative of azulene having a seven-membered ring structure. Its appearance is dark blue flake-like crystals, with a slightly pungent odor, but no taste, and is easily soluble in water, giving a pale blue-indigo solution.

However, when this water-soluble azulene is left at room temperature, 1
Sublimation occurs after 2 months, and a decrease in strength can be seen. As the humidity increases, sublimation becomes even faster.

In addition, it is unstable to acids, and when the H of the aqueous solution is reduced to 5 or less,
The color was immediately decolored and the decomposition of water-soluble azulene was observed.

In general, a method for stably formulating sublimable substances is to form clathrate compounds with β-cyclodextrin, etc., but according to experiments by Tetsu Inventor et al.
The clathrate compound with cyclodextrin does not have sufficient stability, and its yield is extremely poor at about 30 forms. In addition,
As a method for stabilizing the pond, light silicic anhydride (S i02
), but since water-soluble azulene is unstable in the low H range, this method cannot be applied.

In order to solve the above problem, the inventors of the present invention have conducted various studies, and coincidentally found that water-soluble azulene forms a complex with polyvinylpyrrolidone, thereby stabilizing it without impairing its pharmacological action. They discovered this and completed the present invention.

That is, the water-soluble azulene formulation of the present invention is characterized by containing polyvinylpyrrolidone, and the water-soluble azulene does not have sublimation properties and is extremely stable.
As shown in the examples below, the initial titer of 5 is maintained almost as it is even after one year.

The blending amount of polyvinylpyrrolidone in the y1 agent of the present invention is preferably 0.1 part by weight or more, and more preferably is 0.05 parts by weight or more. The stabilizing effect increases as the amount is increased, but sufficient stability can be obtained by adding up to 30 parts and 30 parts, and there is no need to add more.

The formulation of the present invention is prepared by dissolving water-soluble azulene and polyvinylpyrrolidone in a solvent, adsorbing it on a suitable excipient to obtain a complex of water-soluble azulene and polyvinylpyrrolidone, and then
It can be obtained by formulating according to conventional pharmaceutical techniques.

The solvent used is not particularly limited as long as it can dissolve water-soluble azulene and polyvinylpyrrolidone. Further, the excipient to be adsorbed may be any one used for pharmaceutical purposes. Advantageous forms of the solid preparation include powders, fine granules, granules, tablets, capsules, tablets, ointments, and the like.

Next, examples of the present invention will be explained in comparison with a control product.

Example 1 Water-soluble azulene 2y was mixed with ethanol and water (1:1) 2
Polyvinylpyrrolidone 6y is added to it and stirred to dissolve and form a compound. Next, the complex was adsorbed to lactose 992y as an excipient, and then extruded and granulated using a 0.8 mm screen.
After drying at 0°C for 24 hours, the mixture was ground with a needle to obtain granules.

Control example 1 2 g of water-soluble azulene was mixed with ethanol and water (1:I) 2
00+++r, add 6 ml of methyl cellulose, stir and dissolve, then add lactose 992 ml as an excipient.
Let it adsorb to y. Then, the mixture was extruded and granulated using a 0.8 mm screen, and after drying for 211 hours at Ao''C, it was needle-trunked to obtain a granule.

Example 2 Water-soluble azulene 6y was dissolved in 200 me of water, polyvinylpyrrolidone 12y was added, stirred and dissolved to form a 1ν complex, and then the complex was adsorbed on lactose 67°y and crystalline cellulose 132v as excipients. let Then, 0
．． Extrusion granulation using a 5 mm screen, 30°
Dry at C for 24 hours. To the obtained granules were added 450y of carboxymethyl cellulose as a disintegrant and 30g of magnesium stearate as a lubricant, and compression molded to give 3g per tablet.

mq tablets (diameter 9 mm) were obtained.

Control example 2 Water-soluble azulene 6! / is dissolved in 200 me of water, 12 g of carboxymethyl cellulose sodium is added thereto, and the mixture is stirred and dissolved. Then, lactose 670 as an excipient
After adsorption on y and crystalline cellulose 132y, 0
．． Extrusion granulation temperature 30°C using a 5 mm screen
Let dry for 24 hours. 50 parts of carboxymethyl cellulose as a disintegrant and 30 parts of magnesium stearate as a lubricant were added to the obtained granules, and 1
Lock 309 l! 7 tablets (diameter 9+++ m) were obtained.

Regarding the formulations of each example and control example listed in L, (A) left in a constant temperature bath at a temperature of 80°C for 6 hours, (B) a temperature of 4°C.
Each formulation was subjected to a test of being left for 12 months in a constant temperature and humidity ocean at 75% humidity, and changes over time in the stability (quantitative value) of each formulation were measured. The ending of the Sung Dynasty is shown in Tables 1 and 2.

This shows that the formulation of the present invention is stable even under high temperature or high humidity conditions, and the initial strength of water-soluble azulene is maintained over a long period of time.

Claims (1)

[Claims] -1) A water-soluble azulene formulation characterized in that 0.1 parts by weight or more of polyvinylpyrrolidone is blended with 1 part by weight of water-soluble azulene.