An antiphlogistic-analgesic plaster comprising piroxicam and triacetin and/or triethyl citrate. The antiphlogistic-analgesic plaster of the invention is excellent in percutaneous absorption of piroxicam and hence has an excellent antiphlogistic and analgesic effect.

This application is filed under 35 USC 1.371 of PCT/JP92/01473 filed Nov. 
11, 1992. 
TECHNICAL FIELD 
The present invention relates to an antiphlogistic-analgesic plaster 
comprising piroxicam as an active ingredient, and more particularly to an 
antiphlogistic-analgesic plaster improved percutaneous absorption of 
piroxicam contained therein. 
BACKGROUND ART 
Piroxicam is a compound called by a chemical name of 
4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-di 
oxide and has an excellent antiphlogistic and analgesic effect. It has 
hence been widely used clinically at present. 
Piroxicam is mostly prepared in the form of an oral preparation and in the 
forms of a suppository and an ointment in extreme part. 
However, the oral preparation has involved a problem of side effects such 
as a disorder of the digestive tract. Although the side effects are 
somewhat reduced by the suppository compared with the oral preparation, 
the disorder of the digestive tract has been still recognized on the 
suppository. Moreover, these preparations have been difficult to 
effectively deliver their active ingredients to the diseased area. The 
ointment by which piroxicam can be topically applied has been proposed in 
order to remedy the above drawbacks involved in the oral preparation and 
suppository. However, this preparation has also been accompanied by 
drawbacks that its dose is inaccurate and its base ingredients adhere to 
clothes to smear them. 
A plaster is the most effective form for percutaneously administering the 
drug to deliver it to the diseased area Japanese Patent Application 
Laid-Open No 316314/1989 discloses that a plaster in which lornoxicam, 
tenoxicam, piroxicam or sulindac is incorporated exhibit higher 
antiphlogistic and analgesic effect compared with a plaster in which a 
non-steroidal antiphlogistic-analgesic drug such as indomethacin, 
diclofenac, flurbiprofen or ketoprofen is incorporated. However, its 
effect is insufficient and it also offers a problem of physical properties 
as a plaster. Therefore, it is unfit for use and hence not yet provided in 
the clinical field under circumstances. 
As described above, a satisfactory effect has not been successfully 
achieved even when piroxicam has been incorporated into a base for a 
plaster because its percutaneous absorption is poor. 
Therefore, it is an object of the present invention to provide a 
piroxicam-containing plaster excellent in percutaneous absorption of 
piroxicam. 
In view of the foregoing circumstances, the present inventors have carried 
out an extensive investigation. As a result, it has been found that 
triacetin and triethyl citrate have an effect of facilitating the 
percutaneous absorption of piroxicam, thus leading to completion of the 
present invention. 
DISCLOSURE OF THE INVENTION 
The present invention is directed to an antiphlogistic-analgesic plaster 
comprising piroxicam and triacetin and/or triethyl citrate.

BEST MODE FOR CARRYING OUT THE INVENTION 
In the plaster according to the present invention, the amount of piroxicam 
to be incorporated is preferably 0.05-5 wt. %. Besides, the amounts of 
triacetin and triethyl citrate to be incorporated are preferably each 
0.05-40 wt. %, particularly 0.5-10 wt. %. 
As base ingredients for the plaster according to the present invention, may 
be used base ingredients usually used. No particular limitation is imposed 
on such base ingredients. However, examples of the base ingredients 
usually used include water-soluble polymers such as sodium polyacrylate, 
polyacrylic acid, carboxyvinyl polymers, sodium carboxymethyl cellulose, 
polyvinyl alcohol and gelatin; glycols such as glycerin, propylene glycol 
and polyethylene glycol; cross-linking agents such as aluminum hydroxide, 
aluminum potassium sulfate and aluminum glycinate; purified water; 
inorganic powders such as kaolin and titanium oxide; pH adjustors such as 
citric acid and tartaric acid; surfactants such as polyoxyethylene 
sorbitan monooleate, sorbitan monooleate, polyoxyethylene monooleate and 
polyoxyethylene hydrogenated castor oil; and the like. Further, 
penetration enhancers, antiseptics, antifungal preservatives, 
antioxidants, flavorants colorants and the like may be added as needed. 
Of these, the water-soluble polymers, glycols, cross-linking agents, 
purified water, inorganic powders and surfactants are preferably 
incorporated in a base in proportions of 1-20 wt. % 1-50 wt. % 0.01-5 wt. 
% 10-90 wt. %, 0-20 wt. % and 0-20 wt. %, respectively. 
No particular limitation is imposed on the preparation process of the 
plaster according to the present invention. It is however prepared by a 
process in which a base is prepared from the above ingredients in 
accordance with a method known per se in the art, the base is spread on a 
backing material, and the surface of the spread base is covered with a 
protective film, or a process in which the above base is spread on a 
protective film, and the surface of the spread base is covered with a 
backing material to transfer the base to backing material. 
No particular limitation is imposed on the backing material so far as it is 
a woven fabric, nonwoven fabric, film or sheet having good flexibility. 
For example, a woven fabric or nonwoven fabric from fibers of rayon, 
polyester, polyolefin, polyurethane or the like, polymer film, foamed 
sheet, or the like may be used. It is preferable to use a backing material 
having elasticity in all directions. An anchor coat may be applied to 
these backing materials as needed. 
The thus-obtained plaster of the present invention is stored in a tight 
container or the like. 
Examples 
The present invention will hereinafter be described by the following 
examples. 
Examples 1-5 
Plasters having their corresponding compositions shown in Table 1 were 
prepared. 
TABLE 1 
______________________________________ 
(wt. %) 
Example 1 2 3 4 5 
______________________________________ 
Piroxicam 0.25 0.25 0.25 0.25 0.25 
Glycerin 15.00 15.00 15.00 15.00 15.00 
Polyoxyethylene 
1.00 1.00 1.00 1.00 1.00 
hydrogenated castor 
oil 
Triacetin 0.50 2.00 4.00 -- -- 
Triethyl citrate 
-- -- -- 2.00 4.00 
Sodium carboxy- 
4.00 4.00 4.00 4.00 4.00 
methylcellulose 
Sodium polyacrylate 
5.00 5.00 5.00 5.00 5.00 
Gelatin 1.00 1.00 1.00 1.00 1.00 
Kaolin 4.00 4.00 4.00 4.00 4.00 
Aluminum glycinate 
0.15 0.15 0.15 0.15 0.15 
Tartaric acid 
2.30 2.30 2.30 2.30 2.30 
EDTA.2Na 0.10 0.10 0.10 0.10 0.10 
Purified water 
66.70 65.20 63.20 65.20 63.20 
Total 100.00 100.00 100.00 
100.00 
100.00 
______________________________________ 
(Preparation process) 
Triacetin or triethyl citrate was mixed in polyoxyethylene hydrogenated 
castor oil melted under heat in advance, to which piroxicam was added to 
stir the resultant mixture (A). Gelatin was dissolved in 40 g of purified 
water heated (B). Sodium carboxymethylcellulose, sodium polyacrylate and 
aluminum glycinate were dispersed in glycerin (C). The mixture (A), the 
solution (B), the dispersion (C), kaolin, tartaric acid, EDTA. 2Na and the 
remainder of purified water were intimately mixed with one another to 
obtain a base for an antiphlogistic-analgesic plaster. This paste was 
spread at an amount of 0.1 g/cm.sup.2 on a nonwoven fabric having weight 
of 100 g/cm.sup.2. The surface was then covered with a polyester film to 
obtain an antiphlogistic-analgesic plaster according to the present 
invention, which contained piroxicam in a proportion of 0.25 mg per 
cm.sup.2. 
Comparative Example 1 
A plaster was prepared in the same manner as in Example 1 except that 
triacetin was not added. 
Test Example 1 
The plasters obtained in Examples 1-5 and Comparative Example 1 were 
separately applied to the shaved back (30 cm.sup.2) of a male guinea pig 
(Hartley, aged 4 weeks, weight: 250-300 g) to collect blood through a 
cannule inserted in the jugular vein right before the application and upon 
elapsed time of 2, 4, 6 and 8 hours after the application, whereby the 
concentration of piroxicam in plasma was determined by a high performance 
liquid chromatogram to observe the concentration profile of piroxicam in 
plasma with time. The results are shown in FIG. 1. 
Example 6 
To 2 g of triethyl citrate, were added 0.25 g of piroxicam and 0.1 g of 
methyl para-hydroxybenzoate to intimately stir the resultant mixture (A). 
To 15 g of glycerin, were added 5 g of sodium polyacrylate and 0.2 g of 
aluminum glycinate to intimately stir the resultant mixture (B). Five 
grams of a carboxyvinyl polymer were dispersed in 60 g of purified water 
heated (C). To 10.35 g of purified water heated, were added 2 g of gelatin 
and 0.1 g of EDTA.multidot.2Na to dissolve them in the purified water (D). 
The mixture (A), the mixture (B), the dispersion (C) and the solution (D) 
were intimately mixed with one another to obtain a base for an 
antiphlogistic-analgesic plaster. This base was spread at an amount of 0.1 
g/cm.sup.2 on a nonwoven fabric having weight of 70 g/cm.sup.2. The 
surface was then covered with a polypropylene film to obtain an 
antiphlogistic-analgesic plaster according to the present invention, which 
contained piroxicam in a proportion of 0.25 mg per cm.sup.2. 
Comparative Example 2 
A plaster was prepared in the same manner as in Example 6 except that 
triethyl citrate was not added, and piroxicam and methyl 
para-hydroxybenzoate were added to glycerol. 
Test Example 2 
The plasters obtained in Example 6 and Comparative Example 2 were tested in 
the same manner as in Test Example 1. The results are shown in FIG. 2. 
INDUSTRIAL APPLICABILITY 
The antiphlogistic-analgesic plasters according to the present invention 
are excellent in percutaneous absorption of piroxicam and hence have an 
excellent antiphlogistic and analgesic effect.