JP6420101B2 - External application agent containing loxoprofen - Google Patents

Description

  The present invention relates to an external coating agent containing loxoprofen or a salt thereof.

As preparations to be applied to the skin, external preparations for skin are known, which are roughly classified into coating agents and patches.
Examples of the coating agent include an external solid agent (tick agent), an external liquid agent (liniment agent, lotion agent), an ointment, a cream agent, and a gel agent. Among these, the external solid agent is stored in an appropriate container. In this case, since the drug can be applied to the skin without staining hands and fingers, it is difficult to cause discomfort during use.
However, when formulating a solid preparation for external use using various drugs, problems often arise in the hardness and shape retention of the preparation. Although various studies have been made so far (Patent Documents 1 to 6), none of them is necessarily satisfactory in terms of hardness, shape retention, appearance transparency, and the like of the preparation.

  By the way, loxoprofen is a kind of phenylpropionic acid type non-steroidal anti-inflammatory analgesic (NSAID). As an external preparation for skin using this, it contains loxoprofen sodium hydrate, and it is a poultice and tape that has osteoarthritis, myalgia, swelling / pain after trauma, and anti-inflammatory / analgesic effects. Agents and gel agents are known (Patent Documents 7 to 9 and Non-Patent Document 1).

Japanese Patent Laid-Open No. 55-2645 JP-A-56-79619 JP-A-57-42613 JP-T 6-505245 JP 2003-176209 A JP 2004-161714 A JP 2002-128701 A JP 2004-43512 A International Publication No. 2006/048939

The 16th revision Japanese Pharmacopoeia Manual Sasakawa Shoten Co., Ltd. C-5359-5364

  An object of the present invention is to provide a loxoprofen-containing external coating agent that is excellent in appearance stability and is prevented from being discolored during high-temperature storage.

  As a result of intensive studies, the present inventor has used loxoprofen or a salt thereof in combination with an alkyl sulfate ester salt such as sodium lauryl sulfate to prevent discoloration even when stored under high temperature conditions, and to have excellent appearance stability. The present invention has been completed by finding that an external coating agent can be obtained.

That is, this invention provides the external application | coating agent containing the following components (A) and (B).
(A) Loxoprofen or a salt thereof (B) Alkyl sulfate ester salt

Moreover, this invention provides the discoloration inhibitor of the loxoprofen or its salt containing external application | coating agent containing an alkyl sulfate ester salt.
Furthermore, the present invention provides a shape retention agent for loxoprofen or a salt-containing external solid preparation containing an alkyl sulfate ester salt.

The external coating agent of the present invention has high commercial value because it hardly changes color even when stored under high temperature conditions and is excellent in appearance stability. Among these, when the external coating agent of the present invention is an external solid agent, it is not only excellent in appearance stability but also excellent in shape retention, and thus has a particularly high commercial value.
Moreover, the discoloration inhibitor of this invention is excellent in the discoloration suppression ability of a loxoprofen or its salt containing external application | coating agent.
Furthermore, the shape retention agent of the present invention is excellent in the shape retention ability of loxoprofen or a salt-containing external solid preparation.

<Component (A)>
The loxoprofen or a salt thereof contained in the external application agent of the present invention includes loxoprofen itself, a pharmaceutically acceptable salt of loxoprofen, and a solvate of these with water or alcohol. In the present invention, loxoprofen sodium hydrate (chemical name: Monosodium 2- [4-[(2-oxocyclopentyl) methyl] phenyl] propanoate dihydrate) is preferable.
Loxoprofen or a salt thereof is a known compound, and can be produced by a known method, or a commercially available product can be used.

  The content of loxoprofen or a salt thereof (in terms of loxoprofen sodium anhydrate) may be appropriately determined according to the desired anti-inflammatory analgesic effect, and is preferably 0.01 to 40 parts by mass in 100 parts by mass of the external application agent. 0.1-35 mass parts is more preferable, 0.5-25 mass parts is further more preferable, 0.5-15 mass parts is further more preferable, and 0.5-10 mass parts is especially preferable.

<Component (B)>
As the alkyl sulfate ester salt contained in the external coating agent of the present invention, for example, the following formula (1):
R—O—SO ₃ M (1)
(In the formula, R represents a linear or branched saturated or unsaturated hydrocarbon group having 8 to 22 carbon atoms, and M represents an alkali metal such as sodium, an alkaline earth metal such as magnesium, an ammonium ion, or (C2- or C3-hydroxyalkyl-substituted ammonium such as ethanolamine is shown.)
The alkyl sulfate ester salt represented by these is mentioned.

  Examples of the alkyl sulfate ester salt in the present invention include lauryl sulfate ester salt, tetradecyl sulfate ester salt, hexadecyl sulfate ester salt, octadecyl sulfate ester salt and the like. In the present invention, from the viewpoint of appearance stability, lauryl sulfate ester salt is preferable, and sodium lauryl sulfate is more preferable.

The content of the alkyl sulfate ester salt may be appropriately determined according to the appearance stability or the like in the external coating agent, and is preferably 0.01 to 40 parts by mass, preferably 0.1 to 35 parts by mass in 100 parts by mass of the external coating agent. Part is more preferable, 0.25 to 25 parts by mass is further preferable, 0.3 to 20 parts by mass is further more preferable, 0.35 to 10 parts by mass is further more preferable, and 0.4 to 7 parts by mass is even more preferable. 0.5 to 5 parts by mass is preferable.
Moreover, as mass ratio [(B) / (A)] of (A) loxoprofen or its salt (in terms of loxoprofen sodium anhydrate) and (B) alkyl sulfate ester salt, 0.01-10 is included. Preferably, 0.1-7 are more preferable, 0.5-5 are more preferable, and 1-3 are especially preferable.

The external coating agent of the present invention is prepared by adding components (A) and (B) to components (C) and (described later) as necessary, based on the known methods described in the 16th revised Japanese Pharmacopoeia General Rules for Preparations. D) It can be manufactured by mixing with other commonly used formulation additives, dissolving or dispersing, and solidifying as desired.
Examples of the dosage form of the external coating agent of the present invention include an external solid agent (tic agent), an external liquid agent (liniment agent, lotion agent), an ointment, a cream agent, a gel agent, etc. Considering the feeling of use such as stickiness and spreadability that leads to discomfort during coating and rubbing, and good shape retention, a solid preparation for external use is more preferable. As specifically disclosed in Examples below, when the external coating agent of the present invention is an external solid agent, it is excellent in shape retention as well as appearance stability, and therefore has a particularly high commercial value. In addition, as a base of the external solid agent, a soap gel base is preferable.

<Ingredient (C)>
The external coating agent of the present invention may contain a saturated higher fatty acid salt (hereinafter sometimes referred to as component (C)) as a base. The saturated higher fatty acid salt can be suitably used as a base when the dosage form of the external coating agent is used as a solid agent.
The saturated higher fatty acid salt is preferably one having 12 to 22 carbon atoms. Examples include laurate, myristate, pentadecanoate, palmitate, margarate, stearate, isostearate, arachidate, behenate, etc., and these may be used alone Two or more kinds may be used in combination. Among these, those having 14 to 22 carbon atoms are more preferable, specifically, palmitate, myristate, stearate and isostearate are preferable, and stearate and isostearate are more preferable. It is done.
Moreover, as such a salt, inorganic salts, such as aluminum salt, potassium salt, sodium salt, magnesium salt, are preferable, and sodium salt is especially preferable.
Specific examples of the saturated higher fatty acid salt include sodium myristate, potassium myristate, sodium palmitate, aluminum stearate, potassium stearate, sodium stearate, magnesium stearate, sodium isostearate and the like. More preferred is sodium stearate.

  When a saturated higher fatty acid salt is used, a saturated higher fatty acid, preferably a compound having 12 to 22 carbon atoms, and a compound (such as potassium hydroxide or sodium hydroxide) that dissociates a cation that forms a salt with this compound is saturated. Higher fatty acid salts may be formed. A soap base or a medicinal soap containing a saturated higher fatty acid salt (such as a sodium salt of a saturated higher fatty acid) may also be used.

As content of the saturated higher fatty acid salt in an external application agent, 0.1-70 mass parts is preferable in 100 mass parts of external application agents, 0.5-40 mass parts is more preferable, and 1-30 mass parts is further. Preferably, 5-20 mass parts is more preferable, 5-15 mass parts is further more preferable, and 5-10 mass parts is especially preferable.
In addition, the mass ratio [(C) / (A)] of (A) loxoprofen or a salt thereof (in terms of loxoprofen sodium anhydride) and (C) a saturated higher fatty acid salt is 0.5 to 25. Preferably, 1 to 25 is more preferable, 3 to 15 is more preferable, and 5 to 10 is particularly preferable. When the mass ratio [(C) / (A)] is in such a range, and the dosage form of the external application agent is an external solid agent, appropriate hardness is given as the external solid agent.

<Component (D)>
The external application agent of the present invention may contain an alcohol (hereinafter also referred to as component (D)) as a base.
The component (D) alcohol means an alcohol other than the component (E) terpenes to be described later excluding those having an alcoholic hydroxyl group.
The alcohol is roughly classified into a monohydric alcohol and a polyhydric alcohol, and one kind may be used alone, or two or more kinds may be used in combination.
Examples of the monohydric alcohol include methanol, ethanol, methanol-modified alcohol, propanol, isopropanol, butanol, isobutanol, octaacetyl sucrose-modified alcohol, phenylethyl alcohol, phenylethyl alcohol-modified alcohol, and the like. Among these, ethanol, methanol-modified alcohol, octaacetyl sucrose-modified alcohol, phenylethyl alcohol, phenylethyl alcohol-modified alcohol and the like are preferable.

  The polyhydric alcohol has a plurality of alcoholic hydroxyl groups, specifically, dihydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, and polyoxyethylene polyoxypropylene glycol. A trihydric alcohol such as glycerin; a sugar alcohol such as erythritol, sorbitol, and mannitol; Among these, propylene glycol, 1,3-butylene glycol, polyethylene glycol, and glycerin are preferable, and a combination of one or more selected from the group consisting of propylene glycol, 1,3-butylene glycol, and polyethylene glycol and glycerin is particularly preferable.

When the component (D) alcohol is contained, the content thereof is usually 10 to 90 parts by weight, preferably 15 to 85 parts by weight, more preferably 20 to 80 parts by weight, in 100 parts by weight of the external coating agent. 30-70 mass parts is still more preferable.
In addition, when the component (D) alcohol is included, (A) Loxoprofen or a salt thereof (in terms of loxoprofen sodium anhydrate) and (D) the mass ratio of the content of the alcohol [(D) / (A)] Is preferably 90 to 90, more preferably 15 to 85, still more preferably 20 to 80, and even more preferably 30 to 70, from the viewpoint of imparting appropriate hardness to the solid preparation for external application. Is particularly preferred.

  Examples of other preparation additives described above include oils such as diisopropyl adipate, crotamiton, squalane, squalene, diethyl sebacate, castor oil, isopropyl palmitate, isopropyl myristate, cetyl myristate, myristyl myristate; sucrose fatty acid Surfactants such as ester, sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyglycerin fatty acid ester, lauromacrogol, polyoxyethylene cetyl ether; higher alcohols such as oleyl alcohol and lauryl alcohol; PH adjusting agents such as hydrochloric acid, sodium acetate hydrate, tartaric acid, sodium tartrate, sodium hydroxide, sodium carbonate hydrate, sodium lactate, sodium malate; Agents and the like. These may be used alone or in combination of two or more.

Examples of the antioxidant include sodium nitrite, ascorbic acid, L-ascorbic acid stearate, sodium hydrogen sulfite, alpha thioglycerin, sodium edetate, erythorbic acid, cysteine hydrochloride, dry sodium sulfite, and citric acid hydrate. , Potassium dichloroisocyanurate, dibutylhydroxytoluene, sodium thioglycolate, sodium thiomalate, natural vitamin E, tocopherol, d-δ-tocopherol, tocopherol acetate, concentrated mixed tocopherol, ascorbic acid palmitate, sodium pyrosulfite, Butylhydroxyanisole, 1,3-butylene glycol, benzotriazole, pentaerythrityl-tetrakis [3- (3,5-di-t-butyl-4-hydroxypheny ) Propionate], propyl gallate, 2-mercaptobenzimidazole, and malic acid. Among them, sodium nitrite, sodium hydrogen sulfite, dibutylhydroxytoluene, natural vitamin E, tocopherol, d-δ-tocopherol, tocopherol acetate, sodium pyrosulfite, butylhydroxyanisole, 1,3-butylene glycol, sodium pyrosulfite, etc. preferable.
When the antioxidant is contained in the external application agent of the present invention, the content thereof may be appropriately determined according to the type of the antioxidant, etc., but 0.01 to 50 mass in 100 parts by mass of the external application agent. Part is preferable, 0.02 to 10 parts by mass is more preferable, and 0.03 to 2 parts by mass is further preferable.

  Further, when malic acid and / or citric acid hydrate is used as an antioxidant, it is preferably used in combination with higher fatty acids such as myristic acid, palmitic acid, stearic acid, and isostearic acid. The content of malic acid and / or citric acid hydrate in the case of containing an antioxidant is preferably 0.1 to 3 parts by mass in 100 parts by mass of the external solid preparation, while the content of higher fatty acids is as follows. 0.1 to 5 parts by mass is preferable.

  Further, the external application agent of the present invention includes drugs other than loxoprofen or a salt thereof, for example, local irritation component, analgesic component, anti-inflammatory component, bactericidal / disinfecting component, astringent / protective component, blood circulation promoting component, antihistamine component, Herbal medicines etc. are mentioned, and these may contain 1 type, or 2 or more types.

Examples of the local stimulation component include capsaicin, terpenes, nonanoic acid vanillylamide, and the like.
Examples of the analgesic component include salicylic acid, glycol salicylate, and methyl salicylate.
Examples of the anti-inflammatory component include glycyrrhizic acid, glycyrrhetinic acid, dipotassium glycyrrhizinate and the like.
Examples of the sterilizing / disinfecting component include thymol. Examples of the astringent / protective component include zinc oxide.
Examples of the blood circulation promoting component include benzyl nicotinate, heparin-like substances, sodium polyethylene sulfonate, and the like.

Antihistamine components include, for example, azelastine hydrochloride, alimemazine tartrate, istipendil hydrochloride, iproheptin hydrochloride, epinastine hydrochloride, emedastine fumarate, carbinoxamine diphenyl disulfonate, carbinoxamine maleate, Clemastine fumarate, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, ketotifen fumarate, difeterol hydrochloride, difeterol phosphate, diphenylpyraline hydrochloride, diphenylpyraline theocrate , Diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, triprolysine hydrochloride, tripelenamine hydrochloride, tondilamine hydrochloride, phenetazine hydrochloride, promethazine hydrochloride, mequitazi , Methdilazine hydrochloride, main blanking hydro Linna Paji sills salts include emetine Das Chin fumarate salt.
Examples of herbal medicines include arnica, gold, yellow cocoon, yellow ream, dry cinnamon cinnamon, safflower, mountain lion, horse chestnut, salmon, wood tempura, salmon plum, and extracts thereof (extract, tincture, etc.). It is done.

<Ingredient (E)>
As described above, the external application agent of the present invention can contain various drugs. Among them, terpenes (hereinafter referred to as components (E) from the viewpoint of local stimulating action and shape retention based on analgesic and analgesic action. )).) Is preferably included. Terpenes are not particularly limited, and examples include monoterpenes and sesquiterpenes.
Examples of such terpenes include, for example, isoborneol, iron, osimene, carbeol, carbotanaseton, carbomenton, carvone, caren, caron, camphene, camphor, geraniol, sabinene, safranal, cyclocitral, citral, citronellal, citronellic acid, Citronellol, Cineol, Cymen, Silvestrene, Isotujol, Tujon, Terpineol, Terpinene, Terpinolene, Tricyclene, Nerol, Pinene, Pinoccamphorol, Pinol, Piperithenone, Ferrandral, Ferrandrene, Fentchen, Fentyl alcohol, Perillyl alcohol , Perylaldehyde, borneol, myrcene, menthol, menthone, yonor, yonon, linalool, limonene, etc. It may be used in combination thereof alone or. Among these, camphor, geraniol, citronellal, terpineol, borneol, menthol, limonene and the like are preferable, camphor and menthol are more preferable, and dl-camphor, l-menthol and dl-menthol are particularly preferable.

Moreover, when the said terpenes are contained in the external application | coating agent, you may use the essential oil containing the above terpenes.
Such essential oils include, for example, anise oil, ylang ylang oil, iris oil, fennel oil, orange oil, cananga oil, chamomile oil, kayap oil, caraway oil, kubeb oil, grapefruit oil, cinnamon oil, coriander oil, saffron oil Oil, salamander, perilla oil, citriodora oil, citronella oil, ginger oil, gingergrass oil, gingergrass oil, spearmint oil, mint oil, geranium oil, geranium oil, clove oil, turpentine oil, spruce oil , Neroli oil, basil oil, peppermint oil, palmarosa oil, pimento oil, petitgren oil, bay oil, peniroyal oil, henoposi oil, bergamot oil, bored rose oil, pepper oil, marjolan oil, mandarin oil, melissa oil, eucalyptus oil, lime Oil, lavender oil, linaloe oil, lemon , Lemongrass oil, rose oil, rosemary oil, Roman chamomile oil, and the like, may be used in combination thereof alone or.
Among these, ylang ylang oil, fennel oil, orange oil, chamomile oil, cinnamon oil, perilla oil, citronella oil, ginger oil, camphor oil, mint oil, geranium oil, clove oil, turpentine oil, spruce oil, neroli oil Mint oil, palmarosa oil, bergamot oil, eucalyptus oil, lavender oil, linaloe oil, lemon oil, rose oil, rosemary oil, roman chamomile oil, etc., camphor oil, mint oil, mint oil are more preferable, mint Oil is particularly preferred.

Moreover, when it contains terpenes, the content should just consider suitably according to the local irritation | stimulation action etc. based on the desired analgesic and analgesic action in an external application | coating agent, and 0.01 ~ 15 mass parts is preferable, 0.1-10 mass parts is more preferable, and 0.5-7 mass parts is further more preferable.
When terpenes are included, the mass ratio [(E) / (A)] of (A) loxoprofen or a salt thereof (in terms of loxoprofen sodium anhydrate) and (E) terpenes is 0. 0.01-15 is preferable, 0.1-10 is more preferable, and 0.5-7 is still more preferable.

  When terpenes have a hydroxyl group, from the viewpoint of suppressing ester formation between the hydroxyl group and the carboxy group of loxoprofen, metal carbonates such as urea, calcium carbonate and magnesium carbonate, sodium hydrogen sulfite, 2-mercaptobenzimidazole Etc. may be further contained. The content of these components in the case of containing them may be appropriately examined, but it is preferable to contain 0.5 to 3 parts by mass of urea in 100 parts by mass of the external coating agent. In this case, in particular, 0.01 to 3 parts by mass of metal carbonate is preferably contained, 0.01 to 2 parts by mass of sodium bisulfite is preferably contained, and 0.01 to 2 parts by mass of 2-mercaptobenzimidazole. It is preferable to contain a part.

  The external coating agent of the present invention is stored in a container, and it is preferable to use a sealed container as the container. Examples of the sealed container include a bottle, a jar bottle, a tube container, an extrusion type and a dial type lifting and lowering type container. The external solid agent is preferably an extrusion-type or dial-type lift-down type container from the viewpoint of use and storage.

  Since loxoprofen or a salt thereof exhibits an anti-inflammatory analgesic effect as a phenylpropionic acid-based non-steroidal anti-inflammatory analgesic, the external application agent of the present invention can be used as a medical drug or an OTC drug. It is extremely useful as an analgesic / anti-inflammatory agent. Applicable symptoms and diseases include osteoarthritis, shoulder periarthritis, tendon / tendonitis, peritonitis, humerus condyleitis, muscle pain, swelling / pain after trauma, shoulder stiffness, shoulder stiffness Pain, low back pain, joint pain, tendonitis, elbow pain, bruise, sprain, fracture pain, muscle fatigue and the like.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these Examples.

Test Example 1 Evaluation of discoloration inhibiting ability of alkyl sulfate ester salt 1
Samples A and B shown below were each prepared and stored at 60 ° C. for 1 month, and the appearance of the mixture in the sample was observed with the naked eye immediately before and after the start of storage. Existence) was evaluated. The results are shown in Table 1.

[Sample A]
Loxoprofen sodium hydrate (Japanese Pharmacopoeia Loxoprofen sodium hydrate) 2g and sodium lauryl sulfate 2g are mixed with sodium stearate 2g, which is the base of external solid preparation, to obtain a mixture and put into a glass bottle (2K standard bottle) And sample A was obtained. [Sample B]
Sample B was obtained in the same manner as Sample A except that no sodium lauryl sulfate was added.

  From the above test results, it became clear that the alkyl sulfate ester salt has the ability to suppress discoloration when loxoprofen or a salt thereof is stored under high temperature conditions.

Test Example 2 Evaluation of discoloration inhibiting ability of alkyl sulfate ester salt Part 2
Loxoprofen sodium hydrate, sodium stearate, and sodium lauryl sulfate were dissolved and suspended in a Briton-Robinson broad-area buffer solution so as to have the concentrations (w / v%) shown in Table 2, and diluted hydrochloric acid, 10% sodium hydroxide The pH was adjusted to 8.0 with an aqueous solution to obtain a solid preparation liquid for external use. 100 g of the obtained liquid for external solid preparation was filled in a transparent glass bottle and solidified at room temperature to obtain an external solid preparation filled in the glass bottle.
The appearance of the obtained external solid preparation was confirmed with the naked eye, and then stored at 60 ° C. for 1 month to evaluate the change in appearance (presence of discoloration) before and after storage. The results are shown in Table 2.

  It was revealed that even when the external solid preparation of Example 1 was stored under severe high temperature conditions, no discoloration occurred and the appearance stability was excellent.

  From the above results, it was revealed that the external coating agent containing loxoprofen or a salt thereof and an alkyl sulfate ester salt hardly changes color even after storage under high temperature conditions and is excellent in appearance stability. Moreover, it became clear that the alkyl sulfate ester salt is useful as a discoloration suppressing agent for an external coating agent containing loxoprofen or a salt thereof.

Test Example 3 Evaluation of Alkyl Sulfate Ester Salt Shape Retention Capacity In the above external solid preparation of Example 1 and the external solid preparation of Example 1, sodium lauryl sulfate was not added (hereinafter referred to as “Comparative Example 1”). .) Each 50 mL was stored at room temperature for 3 days, and the volume reduction (mL) after storage was measured. As a result, the external solid preparation of Comparative Example 1 was reduced in volume by 0.8 mL from the external solid preparation of Example 1. Turned out to be.

  From the above test results, it was revealed that when the external coating agent containing loxoprofen or a salt thereof and an alkyl sulfate ester salt is an external solid agent, volume reduction is suppressed and the shape retention is excellent. Moreover, it became clear that the alkyl sulfate ester salt is useful as a shape-retaining agent for an external solid preparation containing loxoprofen or a salt thereof.

Production Examples 1-5
By an ordinary method, an external solid preparation (tic agent) containing the components and amounts (% by mass) shown in Table 3 was produced.

Production Example 6 (Cream)
A cream containing the following components in 100 mg was produced by a conventional method.
Loxoprofen sodium hydrate 1.13mg
Sodium lauryl sulfate 2mg
dl-Camphor 4mg
Nonanoic acid vanillylamide 0.12mg
Polyvinyl alcohol 0.2mg
Carboxyvinyl polymer 0.8mg
Sodium edetate aqueous solution 1mg
Sodium bisulfite 0.1mg
Octyldodecyl myristate 8mg
Diisopropyl adipate 5mg
Glycerol monostearate 2mg
Sorbitan monostearate 0.5mg
1 mg polyoxyethylene sorbitan monostearate
Paraben 0.2mg
Polyoxyethylene sorbitan monostearate 0.1mg
Sodium hydroxide 0.1mg
Purified water total amount 100mg

Production Example 7 (Gel)
By a conventional method, a gel (gel cream) containing the following components in 100 mg was produced.
Loxoprofen sodium hydrate 1.13mg
Sodium lauryl sulfate 1mg
l-Menthol 2mg
Polyvinyl alcohol 0.2mg
Salicylic acid glycol ester 2mg
Carboxyvinyl polymer 1mg
Glycerin 10mg
Octyldodecanol 9mg
Glycerol monostearate 0.5mg
Polyoxyl stearate 0.5mg
Isopropyl myristate 5mg
Lauro Macrogol 1.5mg
Triethanolamine 1mg
Purified water total amount 100mg

  ADVANTAGE OF THE INVENTION According to this invention, the loxoprofen containing external coating agent which is excellent in external appearance stability can be provided. Since the external application agent of the present invention contains loxoprofen which is a kind of NSAID, it is effective for, for example, osteoarthritis, myalgia and swelling / pain after trauma, as well as anti-inflammatory / analgesic symptoms. It can be suitably used as a medicine.

Claims (7)

An external coating agent containing the following components (A) and (B) , wherein the dosage form is an external solid agent .
(A) Loxoprofen or a salt thereof (B) Alkyl sulfate ester salt   The external application agent according to claim 1, wherein component (A) is loxoprofen sodium hydrate.   The external coating agent according to claim 1 or 2, wherein the component (B) is a lauryl sulfate ester salt.   The external coating agent according to any one of claims 1 to 3, wherein the component (B) is sodium lauryl sulfate.   Furthermore, the external application | coating agent of any one of Claims 1-4 containing a component (C) saturated higher fatty acid salt.   The external coating agent according to claim 5, wherein the component (C) is a saturated higher fatty acid salt having 12 to 22 carbon atoms.   The external application agent according to claim 5 or 6, wherein the component (C) is a stearate.