JPH06247847A - Plaster - Google Patents

Abstract

PURPOSE:To provide a flurbiprofen-containing external plaster having improved drug releasability and percutaneous absorbability. CONSTITUTION:This invention provides a plaster containing flurbiprofen produced by coating a matrix containing O/W type emulsion consisting of flurbiprofen, at least one kind of liquid oil selected from a group of polycarboxylic acid polyalkyl esters and crotamiton, at least one kind of oil selected from a group of squalane, silicone and liquid paraffin, a hydrophilic surfactant and water.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a flurbiprofen-containing patch which is excellent in drug release and percutaneous absorption and is stable in preparation.

[0002]

Fulbiprofen is officially known as 2- (2
- fluoro-4-biphenylyl) propionic acid [molecular weight _C 15 _H 13 _FO 2: 244.26] in compounds called the properties is a white crystalline powder, methyl alcohol, ethyl alcohol, acetone, ether, chloroform, etc. It is known that it is easily soluble in the solvent and almost insoluble in water. The present compound is an excellent non-steroidal anti-inflammatory analgesic, and clinically, rheumatoid arthritis, arthritis, osteoarthritis, shoulder periarthritis, tendonitis, pulpitis,
It is widely used for the treatment of muscle pain, back pain, tennis elbow, inflammation and swelling after surgery and after trauma. However, when flurbiprofen is orally administered, side effects such as gastrointestinal disorders, gastrointestinal system, hepatic disorder, and renal disorder become a problem, and it may occur in patients with peptic ulcers and patients with severe liver disorder and renal disorder. The fact is that its use is restricted. In the field of orthopedics, an external preparation of flurbiprofen is mainly used as a method for directly applying to the affected area with the purpose of reducing such side effects. For external use, liquids, ointments, creams, etc. have been developed.
Both of these dosage forms also have the problem that when they are applied to the skin, they easily peel off from the affected area due to contact with clothes, etc., and the required amount of drug is not absorbed sufficiently, and clothes are soiled as a result of being scraped off by clothes. there were. In order to eliminate these drawbacks, a patch containing flurbiprofen has been developed in recent years.

Therefore, as a method of administering flurbiprofen as a patch, as shown in JP-A-56-154413, a solution of flurbiprofen in a terpene or higher fatty acid ester solution, a nonionic surfactant and water is used. A patch consisting of an oil-in-water emulsion and an aqueous base has been developed.

[0004]

However, when the present inventors prepared a flurbiprofen-containing patch by a conventional method, the terpene or higher fatty acid ester used as the flurbiprofen dissolving agent was flurbiprofen. The solubility of biprofen is not so large, and drug crystals are deposited with the passage of time, resulting in insufficient release of flurbiprofen from the patch and transdermal absorbability. Therefore, when the present inventors emulsified a liquid oil having a high solubility of flurbiprofen, that is, using at least one liquid oil selected from the group consisting of polycarboxylic acid polyalkyl esters and crotamiton, crystals were precipitated. Although the drawbacks were improved, the emulsion stability deteriorated, and the drug could not be blended stably in such a patch.

[0005] Therefore, the present inventors have conducted extensive studies to develop a patch having good formulation stability and excellent flurbiprofen release and transdermal absorbability. Emulsifies flurbiprofen under specific conditions,
By dispersing this emulsion in the plaster, crystals were not deposited, and a flurbiprofen-containing patch having excellent emulsion stability could be obtained. Moreover, the obtained flurbiprofen-containing patch was found not only to be excellent in drug release and percutaneous absorption, but also to be persistent and stable in its properties, thus completing the present invention. It was

[0006]

That is, according to the present invention, at least one liquid oil component selected from the group consisting of (i) flurbiprofen, (ii) polycarboxylic acid polyalkyl ester and crotamiton, (iii) ) A flurbiprofen-containing O / W emulsion containing at least one oil selected from the group consisting of squalane, silicone and liquid paraffin, (iv) a hydrophilic surfactant, and (v) water is used as a patch. Disclosed is a flurbiprofen-containing patch, which is dispersed in a plaster.

The amount of flurbiprofen in the flurbiprofen-containing patch of the present invention is generally 0.02 to 3.0% by weight, preferably 0.05 based on the total amount of the plaster. ~ 2.0 wt%, more preferably 0.1
~ 1.5 wt% is preferred. If the content of flurbiprofen is too small, the pharmacological effect will be poor, which is not preferable. On the contrary, if the content of flurbiprofen is too large, a large amount of the oil (ii) that dissolves flurbiprofen will be used, resulting in poor usability. However, since it is not inapplicable, it is possible to add a large amount.

The polycarboxylic acid polyalkyl ester compounded in the flurbiprofen-containing patch of the present invention need only be liquid. Generally, total carbon number is 10
Ester of 25, which has two or more carboxyl groups and which is aliphatically or aromatically bonded to an aliphatic, araliphatic or aromatic polycarboxylic acid and a linear or branched alcohol Is. When a polycarboxylic acid having 3 or more carboxyl groups is used, a polycarboxylic acid polyalkyl ester partially having a free carboxyl group can be used, and the incompletely esterified polycarboxylic acid polyalkyl ester can be used. Mixtures of esters and fully esterified polycarboxylic acid polyalkyl esters can be used. Specific examples of the ester include those having a total carbon number of 12 to
Adipic acid dialkyl ester of 22, total carbon number 13
~ 23 dialkyl pimelic acid ester, total carbon number is 1
Suberic acid dialkyl ester having 4 to 24, azelaic acid dialkyl ester having 13 to 21 carbon atoms, sebacic acid dialkyl ester having 14 to 22 carbon atoms, and phthalic acid dialkyl ester having 14 to 24 carbon atoms (however, The alkyl group may be linear or branched, and the alkyl groups of dialkyl may be the same or different) and the like. Of these, particularly preferred representative examples are dibutyl phthalate, diisobutyl phthalate, diethyl phthalate, diethyl sebacate, dibutyl sebacate, diisopropyl azelate, diisopropyl adipate, dibutyl adipate, diisobutyl adipate, and the like. , And can be used alone or as an arbitrary mixture.

At least one liquid oil component selected from the group consisting of polycarboxylic acid polyalkyl esters and crotamiton to be blended with the flurbiprofen-containing patch of the present invention is generally 0 in the whole plaster. .0
The amount is 2 to 10% by weight, preferably 0.1 to 8% by weight, more preferably 0.5 to 6% by weight. These liquid oils are good solvents for flurbiprofen, and the compounding amount of the polycarboxylic acid polyalkyl ester and crotamiton should be an amount that dissolves flurbiprofen when preparing a flurbiprofen-containing patch. Is required,
If this amount is too small, flurbiprofen will be precipitated, which is not preferable, and conversely, if it is too large, usability will not be good, which is not preferable.

At least one oil component selected from the group consisting of squalane, silicone and liquid paraffin to be incorporated into the flurbiprofen-containing patch according to the present invention is generally flurbiprofel to the entire plaster. 1/20 times to 8 times, preferably 1/15 times the total amount of at least one liquid oil selected from the group consisting of phen, polycarboxylic acid polyalkyl ester and crotamiton.
Double amount to 5 times amount, more preferably 1/10 times amount to 3 times amount. If the content of such oil is too small, the stability of the flurbiprofen-containing O / W emulsion deteriorates. On the contrary, if the content is too large, crystals of flurbiprofen are precipitated, which is not preferable. These can be used alone or as an arbitrary mixture.

The hydrophilic surfactant compounded in the flurbiprofen-containing patch of the present invention is not particularly limited,
It is preferable that the HLB is 10 or more. The hydrophilic surfactant may be any of a nonionic surfactant, an ionic surfactant and an amphoteric surfactant, and these can be used alone or as an arbitrary mixture. As the nonionic surfactant, polyoxyalkylene-based, polyglycerin fatty acid ester, tween-based, sugar ester, etc., and as the ionic surfactant, fatty acid soap, alkyl sulfonate, ether phosphate, basic Examples include fatty acid salts of amino acids, triethanolamine soap, alkyl quaternary ammonium salts and the like, and amphoteric surfactants include betaine, aminocarboxylic acid salts and the like. Furthermore,
Also used are hydrophilic surfactants derived from natural products such as saponins, phospholipids, glycopeptides, soybean proteins, egg yolk proteins and the like.

The hydrophilic surfactant compounded in the flurbiprofen-containing patch of the present invention is generally 0.02 to 5% by weight, preferably 0.05 to 3% by weight based on the total amount of the plaster.
It is blended in a proportion of wt%, more preferably 0.1 to 2 wt%. If the blending amount of the hydrophilic surfactant is too small, the emulsion cannot be stably emulsified. Conversely, if the blending amount is too large, usability such as stickiness deteriorates, stability becomes poor due to interaction with the plaster, and skin irritation occurs. This is not preferable because it increases the property.

The amount of water to be added to the flurbiprofen-containing patch of the present invention may be any amount as long as it can form an O / W emulsion, and is generally 1 with respect to the entire plaster.
The amount is 5 to 90% by weight, preferably 30 to 70% by weight, and more preferably 40 to 60% by weight.

The flurbiprofen-containing O / W type emulsion to be incorporated in the flurbiprofen-containing patch of the present invention generally has a dosage form in which it is uniformly distributed in the plaster, but it is not uniform. It is also possible to use a dosage form in which the drug is distributed so that it acts more selectively at a specific site.

In addition, the flurbiprofen-containing patch of the present invention may appropriately contain commonly used components in addition to the above components. For example, glycerin, diglycerin, triglycerin, propylene glycol, 1,3-butylene glycol, dipropylene glycol, polyethylene glycol, sorbitol, glucose, fructose,
It is preferable to blend a polyhydric alcohol such as maltose, xylitol, erythritol, threitol, mavit and mannitol from the viewpoint of production and stability.

In preparing the flurbiprofen-containing O / W type emulsion in the flurbiprofen-containing patch of the present invention, it can be easily prepared with a normal homomixer, but if necessary, a polytron homogenizer, A pressure emulsifying machine such as an ultrasonic emulsifying machine, a Manton-Gaulin homogenizer, or a microfluidizer may be used. In addition, the prepared flurbiprofen-containing O / W
The emulsion particle size of the type emulsion is not particularly limited, but 1
About 10 to 10 μm is good, preferably about 1 to 5 μm, and more preferably 1 to 3 μm.

The flurbiprofen-containing patch of the present invention is produced by dispersing the flurbiprofen-containing O / W emulsion in a plaster of the patch and spreading it on a support.

The plaster of the flurbiprofen-containing patch of the present invention is not particularly limited, and a water-soluble polymer generally used as a base of the patch is appropriately used. As the water-soluble polymer used in the plaster of the patch of the present invention,
For example, sodium polyacrylate, ammonium polyacrylate, potassium polyacrylate, monoethanolamine polyacrylate, diethanolamine polyacrylate, triethanolamine polyacrylate, sodium carboxymethyl cellulose, carboxymethyl cellulose, carboxymethyl amylose, gelatin, polyvinyl Pyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, sodium alginate, ammonium alginate, propylene glycol alginate, casein, carrageenan, gum arabic, tragacanth gum, xanthan gum, karaya gum, locust bean gum, dextrin, hydroxypropylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, methylcellulose , Heaven, soluble starch, mannan, pectin, methyl vinyl ether-maleic anhydride copolymer, methoxyethylene-maleic anhydride copolymer, acrylic acid-styrene copolymer, acrylic acid-methacrylic acid amide copolymer, butyl acrylate -Methacrylic acid copolymer, styrene-methacrylic acid copolymer and the like,
These can be used by appropriately selecting any one kind or two or more kinds.

For the plaster of the flurbiprofen-containing patch of the present invention, the same cross-linking agent as in a general plaster is used. Preferred crosslinking agents include polyvalent metal salts, such as aluminum hydroxide, aluminum chloride,
Aluminum compounds such as aluminum sulfate, aluminum nitrate, aluminum acetate, sodium aluminate, aluminum glycinate and chlorohydroxyaluminum, magnesium compounds such as magnesium hydroxide, magnesium chloride, magnesium sulfate, magnesium carbonate and magnesium nitrate, calcium hydroxide, carbonic acid. Calcium compounds such as calcium, calcium nitrate, calcium chloride, calcium gluconate, calcium lactate, calcium citrate, and pantothenate, potassium alum, sodium alum, aluminum alum,
Examples include alums such as iron alum, antacids containing aluminum and magnesium, and any one or more of these can be appropriately selected and used.

In addition to the above, the flurbiprofen-containing patch of the present invention includes, for example, kaolin, talc, bentonite, titanium oxide, calcium bicarbonate, silicic acid anhydride, zinc oxide for maintaining water retention and shape retention. Powders such as silica, silica, and alumina can be added. These may be used alone or in combination of two or more.

In the flurbiprofen-containing patch of the present invention, various components used in pharmaceuticals and cosmetics, that is, as necessary, within a range not impairing the effects of the present invention, that is,
Antiseptic, antioxidant, pH adjuster, chelating agent, fragrance,
Coloring agents, water-soluble agents, oil-soluble agents, absorption promoters and the like are used as appropriate.

As the support for the flurbiprofen-containing patch of the present invention, for example, any of woven fabric such as flannel and lint cloth, non-woven fabric and knitted fabric can be used. Further, the fibers forming the woven cloth, the non-woven cloth and the knitted cloth may be natural fibers such as cotton or synthetic fibers such as polyolefin, polyester and nylon. If necessary, a liner made of a suitable material may be attached to the surface of the drug holding layer for the purpose of protecting the layer by preventing water evaporation.

The patch obtained by the present invention has a temperature of -5 ° to 5 °.
It is stable in a wide temperature range of 0 ° C., does not become stiff on the low temperature side, does not cause crystallization of the drug, and does not collapse or sag on the high temperature side. Even with the passage of time, there is no exudation of the plaster on the non-woven fabric side,
No change was observed in the peelability of the film, the adhesiveness of the plaster, the flexibility and the shape retention.

[0024]

EXAMPLES Next, the present invention will be described in more detail with reference to examples, but it goes without saying that the scope of the present invention is not limited to these examples. In the following examples, "%" means "% by weight" unless otherwise specified.

Example 1 (Formulation) (1) Flurbiprofen 1% (2) Diethyl sebacate 4.3 (3) Squalane 1.2 (4) Polyoxyethylene (60 mol) hydrogenated castor oil 1.2 (5) Concentrated glycerin 5.0 (6) Gelatin 1.2 (7) Polyvinylpyrrolidone K-90 0.3 (8) Methylparaben Appropriate amount (9) d-sorbitol liquid 35 (10) Aluminum hydroxide 0.2 (11) ) Urea 1.1 (12) Sodium edetate Suitable amount (13) Citric acid Suitable amount (14) Hibiswako 104 ^R 0.27 (15) Sodium polyacrylate 0.25 (16) Carboxymethyl cellulose sodium 1.9 (17) Kaolin 1.6 (18) Purified water Remaining amount (manufacturing method) Component (2) is added to component (1) and dissolved by heating to add component (3) to room temperature. Cooling the oil phase was prepared.
Next, appropriate amounts of the component (4) and the component (18) were added to the component (5) and dissolved by heating, and cooled to room temperature to prepare an aqueous phase.
Next, a homomixer treatment was carried out while adding the oil phase to the aqueous phase, and if necessary, an appropriate amount of component (18) was added to prepare a flurbiprofen-containing O / W emulsion.
Next, a proper amount of the component (18) is added to the component (6), the component (7),
Component (8), Component (9), Component (10), Component (1
1), the component (12) and the component (13) were added and dissolved by heating, and the rest of the component (18) was mixed with the component (14), the component (15), the component (16) and the component (17). In addition, in addition to stirring and dissolving, the flurbiprofen-containing O / W type emulsion prepared in advance is further added, and they are sufficiently mixed until they are homogeneous. The obtained plaster is spread on a non-woven fabric at 1000 g / m ² , and a liner made of siliconized polyethylene terephthalate is attached and cut into a desired size. As a result, 1 m of flurbiprofen
A flurbiprofen-containing external patch containing g / cm ² is obtained.

Example 2 (Formulation) (1) Flurbiprofen 3% (2) Crotamiton 4.8 (3) Diisopropyl adipate 5.5 (4) Liquid paraffin 4.5 (5) Polyoxyethylene (55 Mol) stearic acid 2.5 (6) sodium cetyl sulfate 0.1 (7) 1,3-butylene glycol 5.2 (8) gelatin 2.5 (9) methylparaben suitable amount (10) d-sorbitol solution 27.5 (11) Aluminum glucinate 0.18 (12) Urea 0.8 (13) Sodium hexametaphosphate (14) Succinic acid (15) Hibiswako 105 ^R 0.25 (16) Sodium polyacrylate 0.35 (17) Sodium carboxymethyl cellulose 3.1 (18) Purified water Remaining amount (manufacturing method) Component (2) was added to component (1). (3) was added heated and dissolved to component (4) In addition, to prepare an oil phase cooled to room temperature. Next, appropriate amounts of the component (5), the component (6), and the component (18) were added to the component (7) and dissolved by heating, and cooled to room temperature to prepare an aqueous phase. Next, a homomixer treatment was carried out while adding the oil phase to the aqueous phase, and if necessary, an appropriate amount of the component (18) was added to the mixture to obtain flurbiprofen-containing O / O.
A W type emulsion was prepared. Next, the components (18), (8), (9), (10), and (1) are added in appropriate amounts.
1), component (12), component (13) and component (14) were added and dissolved by heating, and this was added to the rest of component (18) as component (15), component (16) and component (17). Is added and stirred and dissolved, and further, a flurbiprofen-containing O / W type emulsion prepared in advance is added and thoroughly mixed until uniform. The obtained plaster is spread on a non-woven fabric at 1000 g / m ² , and a liner made of siliconized polyethylene terephthalate is attached and cut into a desired size. This gives 3mg of flurbiprofen
The external patch containing flurbiprofen containing / cm ² is obtained.

Example 3 (Formulation) (1) Flurbiprofen 0.5% (2) Dibutyl phthalate 2.1 (3) Olive oil 0.5 (4) Squalane 0.2 (5) Liquid paraffin 0 .8 (6) Decaglycerin monooleate 1.2 (7) Propylene glycol 4.8 (8) Sodium alginate 0.9 (9) Methylparaben Appropriate amount (10) d-sorbitol liquid 37 (11) Aluminum chloride 0.04 (12) Sodium hexametaphosphate Suitable amount (13) Lactic acid Suitable amount (14) Hibiswako 104 ^R 0.14 (15) Ammonium polyacrylate 0.94 (16) Carboxymethyl cellulose 2.3 (17) Purified water Remaining amount (Production method) Add component (2) to component (1), dissolve by heating, add component (3), component (4), and component (5), and cool to room temperature. To prepare an oil phase. Next, appropriate amounts of the component (6) and the component (17) were added to the component (7), and the mixture was heated and dissolved, and cooled to room temperature to prepare an aqueous phase. Next, a homomixer treatment is carried out while adding the oil phase to the water phase, and if necessary, an appropriate amount of the component (17) is added to the mixture to obtain flurbiprofen-containing O / O.
A W type emulsion was prepared. Next, the component (8), the component (9), the component (10), and the component (1
1), the component (12) and the component (13) were added and dissolved by heating, and this was stirred and dissolved by adding the component (14), the component (15) and the component (16) to the rest of the component (17). In addition to the above, a previously prepared flurbiprofen-containing O / W type emulsion is added and mixed thoroughly until uniform. 1000 g / m of the obtained paste on a non-woven fabric
² A liner made of polyethylene terephthalate which has been spread and siliconized is attached and cut into a desired size. This gives a flurbiprofen-containing external patch containing flurbiprofen at 0.5 mg / cm ² .

Example 4 (Formulation) (1) Flurbiprofen 1.5% (2) Dibutyl sebacate 5.2 (3) Panacet 875 ^R 1.7 (4) Liquid paraffin 2.1 (5) Poly Oxyethylene (80 mol) hydrogenated castor oil 1.6 (6) 1,3-butylene glycol 4.6 (7) Gelatin 0.9 (8) Polyvinyl alcohol 1.7 (9) Methylparaben Appropriate amount (10) d-sorbitol Liquid 32.5 (11) potassium alum 0.09 (12) sodium edetate proper amount (13) citric acid proper amount (14) sodium polyacrylate 0.42 (15) carboxymethylamylose 2.8 (16) purified water residue Amount (Production method) The component (2) was added to the component (1) and dissolved by heating to add the components (3) and (4), and the mixture was cooled to room temperature to prepare an oil phase. Next, the component (6) is added to the component (5) and the component (1
An appropriate amount of 6) was added and dissolved by heating, and the mixture was cooled to room temperature to prepare an aqueous phase. Next, a homomixer treatment was carried out while adding the oil phase to the aqueous phase, and an appropriate amount of the component (16) was added if necessary to prepare a flurbiprofen-containing O / W emulsion. Next, the component (7) is added to an appropriate amount of the component (16),
Component (8), Component (9), Component (10), Component (1
1), component (12), and component (13) were added and dissolved by heating, and this was added to the rest of component (16), which was dissolved by stirring with component (14) and component (15). further,
Add the previously prepared flurbiprofen-containing O / W emulsion and mix thoroughly until uniform. The obtained plaster is spread on a non-woven fabric at 1000 g / m ² , and a liner made of siliconized polyethylene terephthalate is attached and cut into a desired size. This gives a flurbiprofen-containing external patch containing flurbiprofen at 1.5 mg / cm ² .

Example 5 (Formulation) (1) Flurbiprofen 0.3% (2) Diisopropyl adipate 1.8 (3) Liquid paraffin 0.7 (4) dl-camphor 0.2 (5) Poly Oxyethylene (55 mol) Stearic acid 0.1 (6) Polyoxyethylene (60 mol) hydrogenated castor oil 0.15 (7) Dipropylene glycol 5.1 (8) Gum arabic 0.3 (9) Methylparaben Appropriate amount ( 10) d-sorbitol liquid 33.5 (11) magnesium nitrate 0.05 (12) sodium hexametaphosphate suitable amount (13) tartaric acid suitable amount (14) Hibiswako 105 ^R 0.2 (15) sodium polyacrylate 0.24 ( 16) Sodium carboxymethyl cellulose 3.1 (17) Talc 2.5 (18) Purified water Remaining amount (Production method) Component ( ) To component (2) was heated and dissolved by adding component (3), the component (4), was cooled to room temperature was added a component (5) to prepare an oil phase. Next, appropriate amounts of the component (6), the component (7), and the component (19) were added to the component (8) and dissolved by heating, and cooled to room temperature to prepare an aqueous phase. Next, a homomixer treatment was carried out while adding the oil phase to the aqueous phase, and an appropriate amount of the component (19) was added if necessary to prepare a flurbiprofen-containing O / W emulsion. Next, the component (9), the component (10), and the component (1
1), the component (12), the component (13) and the component (14) are added and dissolved by heating, and this is added to the rest of the component (19) as the component (15), the component (16), the component (17), Ingredient (18)
Is added and stirred and dissolved, and further, a flurbiprofen-containing O / W type emulsion prepared in advance is added and thoroughly mixed until uniform. The obtained plaster was spread on a non-woven fabric at 1000 g / m ^2, and a siliconized polyethylene terephthalate liner was attached.
Cut to desired size. This gives a flurbiprofen-containing external patch containing flurbiprofen at 0.3 mg / cm ² .

Comparative Example 1 (Formulation) (1) Flurbiprofen 1% (2) Mint oil 8 (3) Isopropyl myristate 4 (4) Sorbitan monooleate 3 (5) Polyoxyethylene sorbitan monooleate 3 (6) Gelatin 5 (7) Glycerin 23 (8) Citric acid Appropriate amount (9) Sodium polyacrylate 4 (10) Sodium carboxymethyl cellulose 3 (11) Kaolin 5 (12) Purified water Appropriate amount (Production method) To component (1) Component (2) and component (3) are added and dissolved, and then component (4), component (5) and component (12)
To a component (6), component (7), component (8), component (9), component (10), component ( 11) is added and mixed and added to the mixed and mixed mixture.
The obtained plaster is spread on a non-woven fabric at 1000 g / m ² , and a liner made of siliconized polyethylene terephthalate is attached and cut into a desired size. This gives a flurbiprofen-containing external patch containing flurbiprofen at 1 mg / cm ² .

[0031]

[Experimental Example] Next, it was confirmed that the flurbiprofen-containing patch according to the present invention is significantly stable in terms of formulation and superior in transdermal absorbability as compared with the conventional flurbiprofen-containing patch. It was confirmed by a test and an anti-inflammatory test and will be described below.

[Anti-inflammatory effect test] From a bruise edema inhibition test using rats, it was confirmed that there was a significant difference in transdermal absorbability due to the difference in the base. This test weighs 130g
Wistar rats were used as one group consisting of 8 rats. In addition, the paw volume was measured by the rat hindlimb footpad edema volume measuring device (Unicom).
Was measured using.

After measuring the volume of the right hind limb of each rat, a sample piece of about 2 cm ² was attached to the foot pad of the right hind limb, removed after 3 hours, and a 100 g weight was dropped from the height of 80 cm on the same site. This caused edema. Inflammation 1,
After the lapse of 2 and 3 hours, the paw volume was measured and the edema rate was calculated by the following formula. The preparations of Example 1 and Comparative Example 1 were used as samples, and the control group was treated with the drug-removed product of Example 1.

The above test results were as shown in FIG. All values are average values of 8 samples. As is clear from this result, it was revealed that the flurbiprofen-containing patch according to the present invention has a higher anti-inflammatory action than the conventional flurbiprofen-containing patch. Table 1 shows the results of comparison of the formulation stability of the flurbiprofen-containing patch of the present invention and the conventional flurbiprofen-containing patch.

[0035]

[Table 1]

[0036]

EFFECT OF THE INVENTION The flurbiprofen-containing patch according to the present invention is superior in formulation stability to the conventional flurbiprofen-containing patch, has no skin irritation, and is flurbiprofen. Not only is the releasability and transdermal absorbability of remarkably excellent, but also because this property is stable and stable, it has the advantage that the drug effect can be maintained for a long time. First, the formulation stability is stable with respect to time and temperature changes. For example, the flurbiprofen-containing external-use patches of Examples 1 to 5 according to the present invention are extremely stable even after 1 year has passed from the preparation, and there is no exudation of the plaster on the non-woven fabric side. No change was observed in peelability, adhesiveness, flexibility and shape retention of the plaster. Also, for the formulation that has been stored for 2 months under harsh conditions of -5 ° C and 50 ° C, crystallization of flurbiprofen and breakage of emulsion are not observed by observation with a polarizing microscope, and peelability, tackiness, flexibility The stability and shape retention were extremely stable with no change observed.

[Brief description of drawings]

FIG. 1 is a view showing the anti-inflammatory effect of the flurbiprofen-containing patches of Example 1 and Comparative Example 1.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Reference number within the agency FI Technical indication location A61L 15/44 (72) Inventor Takashi Suzuki 2-12-1, Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa Company Shiseido 2 Research Center (72) Inventor Yuko Matsutoya 4-15-33 Shibaura, Minato-ku, Tokyo Shibaura Shimizu Building Shiseido Co., Ltd.

Claims (1)

[Claims] 1. At least one liquid oil selected from the group consisting of (i) flurbiprofen, (ii) polycarboxylic acid polyalkyl ester and crotamiton,
(Iii) at least one oil selected from the group consisting of squalane, silicone and liquid paraffin;
v) A flurbiprofen-containing patch characterized in that a flurbiprofen-containing O / W type emulsion containing v) a hydrophilic surfactant and (v) water is dispersed in a plaster of a patch. Agent.