JPH058169B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a stable external transdermal preparation containing ketoprofen, and more particularly to a stable external transdermal preparation characterized by incorporating an ultraviolet absorber into the external transdermal preparation containing ketoprofen. Furthermore, the present invention relates to a stable transdermal preparation for external use, which is characterized in that it contains an antioxidant, if necessary, in addition to the above. Ketoprofen is a non-steroidal anti-inflammatory and analgesic drug with excellent anti-inflammatory and analgesic effects.
It is a drug that is widely used in the treatment of rheumatoid arthritis, osteoarthritis, trauma, post-operative analgesia and inflammation, and other inflammatory diseases in various surgical fields in the form of oral preparations, suppositories, and injections. . However, in the above-mentioned formulation form, gastrointestinal,
Side effects such as liver and kidney damage occur, and problems remain with continued use. Therefore, research and development of external transdermal preparations such as ointments, gels, creams, poultices, and patches are being considered, but the stability of the preparation itself and the stability against the medicinal ingredient ketoprofen have not yet been investigated. At present, a satisfactory and stable external and transdermal preparation has not yet been completed. That is, it is clear that ketoprofen is stable with little change over time even if the tablet is left under sunlight, whereas the formulation form for topical transdermal use shows severe change over time and is extremely unstable. still,
The inventor investigated the cause of this problem and found that ketoprofen itself is extremely unstable to light.In tablet form, it is coated with many layers and is not easily affected by light. It was considered that this may be because the formulation is easily affected by light, either directly or indirectly. Also, due to the influence of this light, ketoprofen has a
It was also found that two by-products were produced: -ethyl-benzophenone and 3-acetylbenzophenone. However, these two by-products have a great influence on the stability, feeling of use, and coloring of the formulation.
It is also one of the causes of skin allergies. Therefore, the inventor of the present application has conducted extensive research in order to eliminate the above-mentioned drawbacks of the external transdermal preparation containing ketoprofen, and has finally completed the stable external transdermal preparation of the present invention. That is, an object of the present invention is to provide a stable external transdermal preparation containing ketoprofen. The present invention is capable of providing a ketoprofen-containing external preparation by incorporating an ultraviolet absorber such as a benzophenone derivative and, if necessary, an antioxidant.
This was completed based on the new finding that the photodecomposition of ketoprofen is specifically and significantly suppressed. However, the present invention provides topical transdermal preparations (e.g. ointments, gels, creams, etc.) containing ketoprofen.
Poultices, patches, suppositories, liniments, eye drops,
(including aerosols, etc.) with UV absorbers such as p-aminobenzoic acid derivatives, anthranilic acid derivatives, salicylic acid derivatives, cinnamic acid derivatives, benzophenone derivatives, coumarin derivatives, amino acid compounds, and other UV absorbers. It is characterized by: More specifically, p-aminobenzoic acid derivatives include p-aminobenzoic acid, various esters of p-aminobenzoic acid such as ethyl, propyl, butyl, isobutyl, monoglycerin, p-dimethylaminobenzoic acid and ethyl or Esters such as amino,
p-diethylaminobenzoic acid and esters such as ethyl or amyl, p-dimethylaminobenzoic acid 2
Examples of the anthranilic acid derivatives include ester derivatives of anthranilic acid, especially menthyl anthranilic ester. As the salicylic acid derivative, ester derivatives are preferable, and among them, salicylic acid menthyl, homomenthyl, ethylene glycol, glycerin, 2-ethylhexyl,
Various esters such as tributyl, porunyl, and phenyl, and triethanolammonium salt of salicylic acid are used as cinnamic acid derivatives such as cinoxate,
p-methoxycinnamic acid diethanolamine, p-methoxycinnamic acid 2-ethylhexyl ester, p-
Acetamide cinnamic acid isopropyl ester, etc.
Examples of benzophenone derivatives include 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2
-Hydroxy-4-methoxybenzophenone, 2
-Hydroxy-4-n-octoxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 4-phenylbenzophenone -2-carboxylic acid isooctyl ester, 2-hydroxybenzophenone, 2,4-dihydroxybenzophenone, 2,2'-4,4'-tetrahydroxybenzophenone and the like.
As a coumarin derivative, 7-ethylamino-4
-Methylcoumarin, 7,8-dihydroxycoumarin, 6,7-dihydroxycoumarin, 7-hydroxycoumarin, 4-methyl-7-hydroxycoumarin, etc. Amino acid compounds include urocanic acid, tryptamine derivatives, glutamic acid derivatives, etc. , and other ultraviolet absorbers include benzotriazole derivatives, imidazoline derivatives, pyrimidine derivatives, tetrazole derivatives, dioxane derivatives, furan derivatives, pyrone derivatives, camphor derivatives, nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, shikonin or vitamin B ₆
Examples include derivatives and the like. Note that benzophenone derivatives are particularly preferred as the ultraviolet absorber to be blended. Furthermore, in the present invention, in addition to the above-mentioned ultraviolet absorber, an antioxidant can be added to the external transdermal preparation containing ketoprofen, if necessary. Examples of antioxidants include ascorbic acid stearate, sodium ascorbate, and tocopherol (e.g., α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol).
d-form, l-form, dl-form of tocopherol, etc.) and their ester derivatives, nordihydroguaiaretic acid, dibutylhydroxytoluene, butylhydroxyanisole, tert-butylhydroquinone gallic acid ester (esters of ethyl, propyl, isoamyl, etc.) , 1-oxo-3-methyl-4-
Examples include isopropylbenzene. By blending the antioxidant in combination with an ultraviolet absorber, the photodecomposition of ketoprofen can be further suppressed, and a very stable external transdermal preparation can be obtained. Next, the blending amount will be described. The amount of ultraviolet absorber is 0.01 per 100% by weight of each topical transdermal preparation.
-5% by weight, preferably 0.1-1% by weight. In addition, the total amount of antioxidants in each topical transdermal preparation is 100%.
0.01 to 5% by weight, preferably 0.05% by weight
~1% by weight is blended. As detailed above, the present invention provides external transdermal preparations containing ketoprofen as an active ingredient, such as ointments, gels, creams, poultices, patches,
It is characterized by incorporating the above-mentioned ultraviolet absorber and, if necessary, an antioxidant into suppositories, liniments, eye drops, aerosols, etc., thereby achieving the above-mentioned object of the present invention. It is something. Here, formulation examples of the present invention will be shown for each of the above-mentioned external transdermal preparations. First, the ointment will be explained. The ointment base is selected from those known or commonly used, and includes, for example, higher fatty acids or their esters (e.g., adipic acid, myristic acid, palmitic acid, stearic acid, oleic acid, adipic acid ester, myristic acid ester, palmitic acid ester, diethyl sebacate, hexyl laurate, cetyl isooctanoate, etc.), waxes (e.g.
spermaceti, beeswax, ceresin, etc.), surfactants (e.g., polyoxyethylene alkyl ether phosphate, etc.), higher alcohols (e.g., cetanol, stearyl alcohol, cetostearyl alcohol, etc.), silicone oil (e.g., dimethylpolysiloxane) , methylphenylpolysiloxane, glycolmethylpolysiloxane, silicone glycol copolymer, etc.), hydrocarbons (e.g., hydrophilic petrolatum, white petrolatum, purified lanolin, liquid paraffin, etc.), water, absorption enhancers (e.g., propylene carbonate,
diisopropyl adipate, crotamiton, Azon, etc.), moisturizers (e.g. glycerin, propylene glycol, butylene glycol, sorbitol, etc.), anti-rash agents, other additives (e.g. salicylic acid, methyl salicylate, glycol salicylate, l-menthol, camphor, peppermint oil, etc.)
It is preferable that it is selected from. The ointment of the present invention can be obtained by blending the medicinal ingredient ketoprofen into each of the above bases, and further adding an ultraviolet absorber, which is a feature of the present invention, or an antioxidant, if necessary. It is something. Next, one example of the production of an ointment will be described for reference. Higher fatty acid ester 5-15% by weight, surfactant 1-10% by weight, ketoprofen 0.1-10% by weight,
Mix 0.01 to 5% by weight of an ultraviolet absorber or 0.01 to 5% by weight of an antioxidant if necessary at room temperature or under heating,
Add 4-10% by weight of waxes and 50-90% by weight of hydrocarbons, heat or melt by heating, and keep at 50-100°C. After all ingredients become a transparent solution, mix uniformly with a homomixer. Thereafter, the ointment of the present invention is obtained by lowering the temperature to room temperature while stirring. It goes without saying that the above-mentioned production example is merely an example, and that it can be produced by known or similar methods and formulations. Furthermore, the order of blending each compound is not particularly limited. (Hereinafter, this is common to the formulation examples and manufacturing examples of various preparations.) Next, the gel agent will be described. The gel base is selected from various known or commonly used bases, including lower alcohols (e.g. ethanol,
isopropyl alcohol, etc.), water, gelling agent (e.g., carboxyvinyl polymer, hydroxyethyl cellulose, hydroxypropyl cellulose,
methylcellulose, ethylcellulose, carboxymethylcellulose, propylene glycol alginate, etc.), neutralizing agents (e.g., triethanolamine, diisopropanolamine, sodium hydroxide, etc.), surfactants (e.g., sorbitan sesquioleate, sorbitan trioleate, sorbitan monooleate, sorbitan monostearate, sorbitan monolaurate, polyethylene glycol monostearate, polyoxyethylene nonyl phenyl ether, polyoxyethylene cetyl ether, polyoxyethylene lauryl ether, etc.), absorption enhancers (e.g. propylene carbonate) ,
diethyl sebacate, diisopropyl adipate, crotamiton, Azon, propylene glycol, etc.), anti-rash agents, and other additives (e.g., salicylic acid, methyl salicylate, glycol salicylate, l-menthol, camphor, pepper oil, etc.). The gel of the present invention can be obtained by adding ketoprofen, a medicinal ingredient, to each of the above bases, and adding an ultraviolet absorber or, if necessary, an antioxidant as appropriate. Here, one example of producing a gel agent will be shown. (A) Add 0.5 to 5% by weight of a gelling agent to 55% by weight or less of water to swell, while (B) 0.1 to 10% of ketoprofen.
% by weight and 0.01 to 5% by weight of ultraviolet absorber, or 0.01 to 5% by weight of antioxidant if necessary, are dissolved or suspended in a dissolving agent, and this is further added to glycols 40% by weight.
The gel of the present invention can be prepared by dissolving it in a mixture of 60% by weight or less of lower alcohol and 60% by weight or less of lower alcohol, then adding (B) to (A), adding a neutralizing agent, and adjusting the pH to 4 to 7. agent is obtained. Next, creams will be described. The cream base is selected from various known or commonly used bases, including higher fatty acid esters (e.g.
myristic acid ester, palmitic acid ester,
diethyl sebacate, hexyl laurate, cetyl isooctanoate, etc.), lower alcohols (e.g., ethanol, isopropanol, etc.), carbohydrates (e.g., liquid paraffin, squalane, etc.), polyhydric alcohols (e.g., propylene glycol, 1,3-butylene) glycol, etc.), higher alcohol (e.g. 2
-hexyldecanol, cetanol, 2-octyldodecanol, etc.), emulsifiers (e.g. polyoxyethylene alkyl ethers, fatty acid esters,
polyethylene glycol fatty acid ester, etc.), preservatives (e.g. paraoxybenzoic acid ester), absorption enhancers (e.g. propylene carbonate, diethyl sebacate, diisopropyl adipate, crotamiton,
anti-inflammatory agents, and other additives (eg, salicylic acid, methyl salicylate, glycol salicylate, l-menthol, camphor, peppermint oil, etc.). The cream of the present invention can be obtained by adding ketoprofen, a medicinal ingredient, to each of the above bases, and further adding an ultraviolet absorber or, if necessary, an antioxidant. In addition, in order to make a gel-like cream with properties intermediate between a cream and a gel, a gelling agent (e.g. carboxyvinyl polymer,
Hydroxyethyl cellulose, hydroxypropyl cellulose, ethyl cellulose, carboxymethyl cellulose, etc.) and a neutralizing agent (e.g. diisopropanolamine, triethanolamine, sodium hydroxide, etc.) are added to adjust the pH value to 4 to 8, preferably 5 to 6.5. By doing so, the gel-like cream of the present invention can be obtained. One example of manufacturing a gel cream is shown below. (A) 0.1-10% by weight of ketoprofen, 0.01-5% by weight of ultraviolet absorber, or 0.01% of antioxidant if necessary
~5% by weight is dissolved in a mixture of 25% by weight or less of higher fatty acid ester and 40% by weight or less of lower alcohol,
Furthermore, 0.5% by weight or less of a preservative and 5% by weight or less of an emulsifier are added. On the other hand, (B) 0.5 to 5% by weight of gelling agent in water
The gel-like cream of the present invention is obtained by adding (B) to (A) and uniformly emulsifying it with a homomixer, and then adding a neutralizing agent after emulsification to adjust the pH value to 4 to 8. is obtained. Next, we will discuss poultices. Poultice bases, such as thickeners (e.g. synthetic water-soluble polymers such as sodium polyacrylate, polyacrylic acid, poval, polyvinylpyrrolidone, polyethylene oxide, polyvinyl methacrylate, natural products such as gum arabic, starch, gelatin, etc.) Methyl cellulose, hydroxypropyl cellulose, alginic acid, sodium alginate, ammonium alginate, sodium carboxymethyl cellulose, etc.), wetting agents (e.g., urea, glycerin, propylene glycol, butylene glycol, sorbitol, etc.), fillers (e.g., kaolin, zinc oxide, talc) , titanium, bennite, epoxy resins, organic acids (citric acid, acharitic acid, maleic acid, maleic anhydride, succinic acid, etc.), calcium, magnesium, aluminum, etc.), water, solubilizing agents (e.g. propylene carbonate, crotamiton, diisopropyl adipate, etc.), tackifiers (e.g. rosin, ester gum,
polybutene, polyacrylic acid ester, etc.), anti-rash agents (e.g. diphenhydramine hydrochloride, chlorpheniramine maleate, glycyrrhizic acid, dexamethasone, betamethasone, fluocinolone acetonide, etc.), other additives (e.g. salicylic acid,
Methyl salicylate, glycol salicylate, l-
Ketoprofen, a medicinal ingredient, is added to each base selected from menthol, camphor, nonylic acid vanillylamide, thymol, chili pepper extract, peppermint oil, Azone, etc.), and further UV absorbers or antioxidants are added as needed. By blending, the poultice of the present invention can be obtained. Next, one example of manufacturing a poultice will be shown. (A) 0.1 to 10% by weight of ketoprofen, 0.01 to 5% by weight of ultraviolet absorber, or 0.05% of antioxidant if necessary
~5% by weight is mixed and dissolved with 0.5~8% by weight of a solubilizing agent to form a homogeneous solution. Next, (B) 5 to 20% by weight of a thickener, preferably 10 to 15% by weight, is mixed and dissolved in 5 to 40% by weight of a wetting agent and 10 to 80% by weight of water, and 20% by weight of a filler is mixed and dissolved.
Add up to % by weight to make a uniform mixture. Then (A)
Add to (B) and mix to obtain a homogeneous mixture. After spreading and coating this mixture on a support using the usual method,
By applying a release coating thereon, the poultice of the present invention is obtained. Note that the support is appropriately selected from stretchable or non-stretchable fabrics, nonwoven fabrics, nonwoven paper, etc., and the release coating is appropriately selected from polyethylene, polypropylene, polyvinyl chloride, polyester, polyvinylidene chloride, silicone-treated paper, etc. . Next, we will discuss the patch. The base material for the patch is a known polymer base (e.g., acrylic compositions that are copolymers with vinyl monomers such as methacrylic acid esters, acrylonitrile, vinyl acetate, and vinyl propionate, silicone resins, polyamides, etc.). isoprene rubber, polyisobutylene rubber, natural rubber, acrylic rubber, styrene-butadiene-styrene block copolymer, styrene-isoprene-styrene block copolymer, etc.), oils and fats or higher fatty acids (e.g. almond oil, olive oil, camellia oil, bursick oil, rattan oil, oleic oil, liquid paraffin, polybutene, etc.), tackifiers (e.g., rosin, rosin-modified maleic acid, hydrogenated rosin ester, etc.), anti-rash agents, and other additives to the base. substances (e.g. salicylic acid, methyl salicylate, glycol salicylate, dl-camphor, l
- Menthol, thymol, nonylic acid vanillylamide, capsicum tincture, peppermint oil, crotamiton, peppermint oil, Eizon, etc.) are added as necessary, then the medicinal ingredient ketoprofen is added, and then a UV absorber or as necessary. Add an antioxidant as appropriate and apply it to a stretchable or non-stretchable support (e.g. polypropylene, polyester, polyvinylidene chloride, polyacrylic, polyurethane, rayon, cotton, ethylene-vinyl acetate copolymer, cloth, non-woven fabric) The adhesive patch of the present invention can be obtained by spreading and applying the adhesive onto a nonwoven paper, etc., and then attaching a release coating thereon. The patch can be easily manufactured according to a known method, and the composition is such that the medicinal ingredient in a known cooling or warming patch is 0.1% ketoprofen.
The adhesive patch of the present invention can be obtained by substituting 10% by weight of the ultraviolet absorber and further adding 0.01 to 5% by weight of an ultraviolet absorber or, if necessary, 0.01 to 5% by weight of an antioxidant. Next, let's talk about suppositories. As the base for suppositories, conventionally known suppository bases, that is, lipophilic bases,
An appropriate selection is made from among water-soluble bases and emulsion bases. In addition, additives that may be added as necessary include local anesthetics, bactericidal agents, antihistamines, local astringents, sulfur agents, antibiotics, scar treatment agents, surfactants, vitamins, herbal medicine extracts, bile acids, Preservatives, excipients, absorption enhancers, amino acids, etc. are used. The base for suppositories is selected from, for example, synthetic oil-based bases such as cocoa butter, hydrogenated coconut oil, and hydrogenated coconut oil, and water-soluble bases such as polyethylene glycols, monolene, Twin, and Pluronic. Ketoprofen, a medicinal ingredient in the drug
0.1-10% by weight, UV absorber 0.01-5% by weight,
Furthermore, the ketoprofen-containing suppository preparation of the present invention can be obtained by blending 0.01 to 5% by weight of an antioxidant, if necessary. Next, liniment agents will be described. The liniment agent of the present invention contains 10 to 70% by weight of alcohols (e.g., monohydric alcohols such as ethanol, propanol, isopropanol, polyhydric alcohols such as polyethylene glycol, propylene glycol, butylene glycol, etc.), 55% by weight or less of water, Fatty acid esters (e.g. various esters of adipic acid, sebacic acid, myristic acid, etc.) 60% by weight or less, surfactants (e.g. polyoxyethylene alkyl ether) 10% by weight or less, medicinal ingredient ketoprofen 0.1-10% by weight % and further UV absorber
The liniment agent of the present invention can be obtained by blending 0.01 to 5% by weight and, if necessary, 0.01 to 5% by weight of an antioxidant. The above formulation examples and manufacturing examples are merely examples, and the liniment agent of the present invention can of course be obtained by a known liniment manufacturing method. Also, in the formulation, the liniment agent of the present invention can be easily obtained by replacing the medicinal ingredient of a known liniment agent with ketoprofen and adding an ultraviolet absorber thereto. In addition, in the liniment agent of the present invention, a neutralizing agent for pH adjustment, a viscosity imparting agent such as methyl cellulose, carboxyvinyl polymer, hydroxypropyl cellulose, anti-rash agent, or other additives (e.g. salicylic acid, salicylic acid Methyl, glycol salicylate, l-menthol, camphor, pepper oil, capsicum extract, nonylic acid vanillylamide, thymol, crotamiton, Azon, propylene carbonate, diisopropyl adipate, etc.) can also be blended. Furthermore, eye drops and aerosols of the present invention can also be obtained by blending 0.01 to 5% by weight of an ultraviolet absorber or, if necessary, 0.01 to 5% by weight of an antioxidant. can. It should be noted that conventionally known methods for producing these are sufficient, and the composition of the present application can be modified by replacing the medicinal ingredient in the known formulation with ketoprofen, and adding an ultraviolet absorber or an antioxidant as necessary. The said formulation of the invention can be obtained. As detailed above, the present invention is characterized by incorporating an ultraviolet absorber and, if necessary, an antioxidant into a topical transdermal preparation containing ketoprofen, and according to the present invention, the active ingredient is Since it can prevent photodecomposition of ketoprofen, it has the following effects. 1. Degradation products generated due to the influence of light are significantly suppressed. 2. The coloring prevention effect is remarkable. 3. Side effects such as itching, rash, and other skin allergies are significantly alleviated. 4. Skin toxicity due to skin absorption is reduced. 5. Side effects such as skin damage caused by light irradiation are significantly alleviated. 6. The preparation remains stable even after long-term storage, does not deteriorate in quality, and always maintains its original feel when used. Now, to explain the prior art related to the present invention, there is no example in the world where an ultraviolet absorber or, if necessary, an antioxidant was added to a topical transdermal preparation containing ketoprofen, or where such was suggested. The inventor of this application was the first to incorporate this for the purpose of stabilization. EXAMPLES Hereinafter, test examples will be shown to further explain the effects of the present invention described above, and examples will be shown to further specifically explain the present invention. Test Example 1 Gels containing 0%, 0.1%, 0.2%, 0.5%, and 1.0% by weight of 2-hydroxy-4-methoxybenzophenone were obtained by the method described in Example 1.
After applying a thin layer of these gels to a glass plate,
The sample was left in a place where it could be sufficiently exposed to direct sunlight, and the amount of ketoprofen remaining after 8 hours was measured by liquid chromatography. The results are shown in Table 1.

【table】

[Table] Test Example 2 Gel of Example 1 described later and 2-hydroxy- produced by the same method as described in Example 1
Gels containing no 4-methoxybenzophenone were placed in transparent glass containers and exposed to sunlight, and the degree of coloration was observed after 1, 3, 5, and 7 days. The results are shown in Table 2.

[Table] Test Example 3 Cinoxate, 2,2'-dihydroxy-4-methoxybenzophenone, methyl anthranilate, 2-hydroxy-4-methoxybenzophenone, Various ointments containing 1.0% by weight of various UV absorbers such as 2-ethylhexyl p-dimethylaminobenzoate, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, and phenyl salicylate, 2-hydroxy-4-methoxy An ointment containing 1.0% by weight each of benzophenone and γ-tocophenol and an ointment containing no ultraviolet absorber or antioxidant were obtained.
These were left indoors at room temperature (in a place not exposed to direct sunlight) for one week, and then the remaining amount of ketoprofen was measured by liquid chromatography.
The results are shown in Table 3.

[Table] Test Example 4 Various formulations containing 0%, 0.1%, 0.2%, 0.5%, and 1.0% by weight of 2-hydroxy-4-methoxybenzophenone were obtained by the method shown in Examples. These preparations were applied or pasted on a glass plate, left in a place where it could be sufficiently exposed to direct sunlight, and the residual rate (%) of ketoprofen after 8 hours was measured by liquid chromatography. The results are shown in Table 4.

[Table] Example 1 Carboxyvinyl polymer [HIBIS Wako
104: manufactured by Wako Pure Chemical Industries, Ltd.] were swollen in 25 parts of purified water. To this was added 40 parts of ethyl alcohol, 2 parts of diisopropyladipate, and 3 parts of ketoprofen.
A solution containing 1 part and 0.5 part of 2-hydroxy-4-methoxybenzophenone was added and stirred. Furthermore,
To this, add 2 parts of hydroxypropyl cellocase dissolved in 15 parts of propylene glycol and stir, then add 2.5 parts of diisopropanolamine dissolved in 8 parts of purified water, and stir thoroughly until the whole is homogeneous. I received an anti-inflammatory analgesic gel. Example 2 Carboxyvinyl polymer [Hibis Wako
104: manufactured by Wako Pure Chemical Industries, Ltd.] 1.5 parts was swollen in 25.1 parts of purified water. To this, 20 parts of ethyl alcohol, 10 parts of propylene carbonate, 1 part of ketoprofen, and 2-
A solution containing 0.2 part of hydroxy-4-methoxybenzophenone was added and stirred. Further, 2 parts of hydroxypropyl cellulose dissolved in 30 parts of propylene glycol was added and stirred, and then 0.2 parts of triethanolamine dissolved in 10 parts of purified water was added and stirred thoroughly until the mixture was uniformly coated to extinguish the flame. Obtained analgesic gel. Example 3 Carboxyvinyl polymer [Hibis Wako
104: manufactured by Wako Pure Chemical Industries, Ltd.] 2.5 parts was swollen in 21 parts of purified water. A solution of 5 parts of ketoprofen and 1.0 part of 2,4-dihydroxybenzophenone (generic name: benzoresorcinol) dissolved in 40 parts of ethyl alcohol and 3 parts of diisopropyl adipate was added and stirred. Furthermore, 1 part of hydroxypropyl cellulose dissolved in 15 parts of 1,3-butylene glycol was added and stirred, then 3 parts of diisopropanolamine dissolved in 8.5 parts of purified water was added, and the mixture was stirred until the whole was homogeneous. The mixture was stirred to obtain an anti-inflammatory analgesic gel. Example 4 Carboxyvinyl polymer [Hibis Wako
104: manufactured by Wako Pure Chemical Industries, Ltd.] was swollen in 21 parts of purified water. A solution of 43 parts of ethyl alcohol and 3 parts of diisopropyl adipate, 2 parts of ketoprofen, 0.5 part of 2-hydroxy-4-methoxybenzophenone, and 1.0 part of γ-tocopherol was added and stirred. Furthermore, 2 parts of hydroxypropyl cellulose dissolved in 16 parts of propylene glycol was added, and after stirring, 2.5 parts of diisopropanolamine dissolved in 7 parts of purified water was added.
The mixture was sufficiently stirred until the whole was homogeneous to obtain an anti-inflammatory analgesic gel. Example 5 Carboxyvinyl polymer [Hibis Wako
104: manufactured by Wako Pure Chemical Industries, Ltd.] 2.5 parts was swollen in 18 parts of purified water. A solution prepared by dissolving 3 parts of ketoprofen and 0.5 part of 2-hydroxy-4-methoxybenzophenone in 43 parts of ethanol and 3 parts of crotamiton was added and stirred. Furthermore, 1 part of hydroxypropylcellulose dissolved in 15 parts of 1,3-butylene glycol was added and stirred, then 3 parts of diisopropanolamine dissolved in 10.8 parts of purified water was added, and further 0.2 parts of butylhydroxyanisole was added.
The mixture was stirred thoroughly until the mixture was homogeneous to obtain an anti-inflammatory and analgesic gel. Example 6 Carboxyvinyl polymer [Hibis Wako
104: manufactured by Wako Pure Chemical Industries, Ltd.] was swollen in 25 parts of purified water. Add to this 40 parts of ethanol, 10 parts of propylene glycol, 1 part of ketoprofen, and 2-
A solution containing 0.5 part of hydroxy-4-methoxybenzophenone was added and stirred. Next, a solution of 1.1 parts of diisopropanolamine dissolved in 21.4 parts of purified water was added and thoroughly stirred until the whole was homogeneous to obtain an anti-inflammatory and analgesic gel. Example 7 Carboxyvinyl polymer [Hibis Wako
104: manufactured by Wako Pure Chemical Industries, Ltd.] 2.2 parts was swollen in 30 parts of purified water. Add to this 35 parts of ethyl alcohol, 3 parts of diisopropyladipate, and 3 parts of ketoprofen.
A solution containing 0.5 parts of 2-hydroxy-4-methoxybenzophenone and 0.1 parts of dibutylhydroxytoluene was added and stirred. Furthermore, hydroxypropylcellulose 1
After adding 3 parts of diisopropanolamine dissolved in 13 parts of propylene glycol and stirring, add 3 parts of diisopropanolamine dissolved in 9.2 parts of purified water and stir thoroughly until the whole was homogeneous to obtain a digestive analgesic gel. . Example 8 7 parts of ketoprofen was dissolved in 52 parts of ethanol, and 1 part of 2-hydroxy-4-methoxybenzophenone was added thereto. Next, 40 parts of diisopropyl adipate was added, and the mixture was sufficiently stirred to make the whole mixture uniform, thereby obtaining an anti-inflammatory and analgesic liniment agent. Example 9 1 part of ketoprofen was dissolved in 38 parts of ethanol, and 0.5 part of 2-hydroxy-4-methoxybenzophenone, 12 parts of propylene glycol,
0.8 parts of methyl cellulose and 2 parts of diethyl sebacate were added and thoroughly stirred and dispersed. A solution prepared by dissolving 0.07 parts of potassium hydroxide in 45.63 parts of purified water was added to this while stirring, and the mixture was stirred until the whole was homogeneous to obtain an anti-inflammatory and analgesic liniment agent. Example 10 3 parts of ketoprofen was dissolved in 40 parts of ethanol, and 1 part of 2,4-dihydroxybenzophenone (generic name: benzoresorcinol), 10 parts of butylene glycol, 2 parts of diethyl sebacate,
0.8 part of methyl cellulose was added and thoroughly stirred and dispersed. Add 0.07 part of potassium hydroxide to this and purified water.
A solution dissolved in 43.13 parts was added with stirring, and the mixture was sufficiently stirred until the whole was homogeneous to obtain an anti-inflammatory and analgesic liniment agent. Example 11 2 parts of ketoprofen were dissolved in 49 parts of ethanol, and 0.6 parts of 2-hydroxy-4-methoxybenzophenone and 30 parts of diisopropyl adipate were dissolved therein.
1 part of γ-tocopherol and 1.5 parts of hydroxypropylcellulose were added and dispersed with stirring.Furthermore, 15.9 parts of water was added thereto and stirred until the whole was homogeneous to obtain an anti-inflammatory and analgesic liniment agent. Example 12 Ketoprofen 0.5 parts, propylene glycol
After adding 20 parts of acetone and 20 parts of ethyl alcohol to 10 parts, 0.2 parts of 2-hydroxy-4-methoxybenzophenone, 10 parts of polyethylene glycol monolaurate (10E.O.), and 0.5 parts of crotamiton, and dissolving the ketoprofen, water was added. 10 parts were added, and ethanol was further added to make the total amount 100 parts to obtain an anti-inflammatory and analgesic liniment agent. Example 13 After adding 1 part of ketoprofen, 0.5 part of 2-hydroxy-4-methoxybenzophenone, 1 part of γ-tocopherol, 1 part of crotamiton, and 10 parts of polyethylene glycol 400, and further adding 50 parts of ethanol to dissolve the ketoprofen, Add 5 parts of water,
Add isofropyl alcohol to bring the total volume to 100.
An anti-inflammatory and analgesic liniment agent was obtained. Example 14 Ketoprofen 2 parts, 2,2-dihydroxy-
8-acetylated sucrose-denatured alcohol was added to 0.7 parts of 4-methoxybenzophenone, 15 parts of polyethylene glycol monolaurate (10E.O.), 2 parts of crotamiton, and 4 parts of diisopropyl adipate to make a total volume of 100 parts, and the mixture was made to eliminate inflammation. Analgesic liniment was obtained. Example 15 1 part ketoprofen, 10 parts propylene glycol
After adding 70 parts of ethanol to 1 part and 0.5 part of 2-hydroxy-4-methoxybenzophenone to dissolve ketoprofen, 5 parts of water were added, and then ethanol was added to make the total amount 100 parts to obtain an anti-inflammatory and analgesic liniment agent. . Example 16 1 part of ketoprofen, 0.5 parts of 2-hydroxy-4-methoxybenzophenone, 10 parts of diethyl sebacate, 5 parts of spermaceti, 2 parts of sodium polyoxyethylene lauryl ether phosphate, white petrolatum
81.45 parts and 0.05 parts of butyl paraoxybenzoate were mixed, heated and melted, and kept at 40 to 100°C. After the mixture became a transparent molten liquid, it was mixed using a homomixer so that the entire mixture became uniform. Thereafter, the mixture was cooled to room temperature while stirring to obtain an oil-based anti-inflammatory and analgesic ointment. Example 17 3 parts of ketoprofen, 1 part of 2-hydroxy-4-methoxybenzophenone, 1 part of γ-tocopherol, 10 parts of diethyl sebacate, 5 parts of spermaceti, 4 parts of sodium polyoxyethylene lauryl ether phosphate, white petrolatum 75.95 parts and 0.05 parts of butyl paraoxybenzoate were mixed. Below, Example 16
An anti-inflammatory analgesic ointment was obtained in the same manner as above. Example 18 1 part of ketoprofen, 2,2-dihydroxy-
0.5 parts of 4-methoxybenzophenone, 10 parts of isopropyl myristate, 4 parts of spermaceti, 2 parts of sodium polyoxyethylene lauryl ether phosphate,
82.5 parts of white petrolatum was mixed. Below, Example 16
An anti-inflammatory analgesic ointment was obtained in the same manner as above. Example 19 5 parts of ketoprofen, 1 part of 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 10 parts of diethyl sebacate, 5 parts of spermaceti, 5 parts of sodium polyoxyethylene lauryl ether phosphate
1 part, 73.95 parts of white petrolatum, and 0.05 part of butyl paraoxybenzoate. Thereafter, an anti-inflammatory and analgesic ointment was obtained in the same manner as in Example 16. Example 20 (A): 1 part of ketoprofen, 2-hydroxy-4-
Methoxybenzophenone 0.5 parts, stearyl alcohol 4 parts, liquid paraffin 4 parts, cetanol 4 parts
15 parts of white petrolatum, 2 parts of polyoxyethylene cetyl ether, 0.2 parts of methyl paraoxybenzoate
The parts were mixed and heated to melt and kept at 40-100°C. On the other hand, (B): 69.3 parts of water was kept at 40 to 100°C, and the melted solution of (A) was added to (B), and the mixture was stirred and mixed with a homomixer until the whole was homogeneous to emulsify. After emulsification, the mixture was cooled to room temperature with thorough stirring to obtain an emulsion-based anti-inflammatory analgesic ointment. Example 21 (A): 3 parts of ketoprophene, 1 part of 2,2'-dihydroxy-4-methoxybenzophenone, 1 part of γ-tocopherol, 10 parts of cetostearyl alcohol,
5 parts of liquid paraffin, 10 parts of white vaseline, 2.5 parts of polyoxyethylene lauryl ether, and 0.2 parts of methyl paraoxybenzoate were mixed and melted by heating.
It was kept at 40-100℃. On the other hand, (B): 67.3 parts of water was maintained at 40 to 100°C, and the melted solution of (A) was added to (B), and the mixture was stirred and mixed with a homomixer until the whole was homogeneous to emulsify. After emulsification, the mixture was cooled to room temperature with thorough stirring to obtain an emulsion-based anti-inflammatory analgesic ointment. Example 22 (A): 5 parts of ketoprofen, 0.8 parts of 2hydroxy-4-methoxybenzophenone-5-sulfonic acid,
Mix 4 parts of cetanol, 4 parts of stearyl alcohol, 15 parts of white petrolatum, 4 parts of liquid paraffin, 2 parts of polyoxyethylene cetyl ether, and 0.2 parts of methyl paraoxybenzoate, and heat and melt to give a
It was kept at ℃. On the other hand, (B): Keep 65 parts of water at 40-100°C, add the melted solution of (A) to (B), stir and mix with a homomixer until the whole becomes homogeneous, and emulsify. After emulsification, the mixture was cooled to room temperature with thorough stirring to obtain an emulsion-based anti-inflammatory analgesic ointment. Example 23 (A): 1 part of ketoprofen, 0.8 part of cinoxate,
Di-tert-butylhydroxytoluene 0.5 parts, cetanol 4 parts, white petrolatum 10 parts, liquid paraffin 7 parts, polyoxyethylene oleyl ether 2 parts
0.2 parts of methyl paraoxybenzoate,
Heat to melt and keep at 40-100℃. On the other hand, (B): Keep 74.5 parts of water at 40 to 100°C, add the melted solution of (A) to (B), stir and mix with a homomixer until the whole becomes homogeneous, and emulsify. After emulsification, the mixture was cooled to room temperature with thorough stirring to obtain an emulsion-based anti-inflammatory analgesic ointment. Example 24 Carboxyvinyl polymer [Carbopol 940
(manufactured by Gutsudoritsuchi Chemical Co., Ltd.)] was swollen in 65 parts of water. On the other hand, 10 parts of isopropyl myristate, 5 parts of ethanol, and 0.8 parts of 2-hydroxy-4-methoxybenzophenone were mixed, and 3 parts of ketoprofen was dissolved therein.
1 part of MYS-40 (manufactured by Nikko Chemicals) and 0.2 part of methyl paraoxybenzoate were mixed. This was added to the water-swollen carboxyvinyl polymer and uniformly emulsified using a homomixer. After emulsification, add 3 parts of coconut oil fatty acid diethanolamide to 11 parts of water.
The solution was added to the mixture and thoroughly stirred until the whole was uniformly mixed to obtain an anti-inflammatory analgesic cream. Example 25 Carboxyvinyl polymer [HIBIS Wako 104
(manufactured by Wako Pure Chemical Industries)] was swollen in 55 parts of water.
On the other hand, 10 parts of isopropyl palmitate, 10 parts of diethyl sebacate, 0.2 parts of 2,2'-dihydroxy-4-methoxybenzophenone and 0.5 parts of γ-tocopherol were mixed, and 1 part of ketoprofen was dissolved therein. , 2 parts of polyoxyethylene cetyl ether [Nitsukol BC-20TX (manufactured by Nikko Chemicals)], 10 parts of propylene carbonate, and 0.2 parts of methyl paraoxybenzoate were mixed. This was added to the water-swollen carboxyvinyl polymer and uniformly emulsified using a homomixer. After emulsification,
A solution of 0.1 part of sodium hydroxide dissolved in 10 parts of water was added and thoroughly stirred until the whole was homogeneous to obtain an anti-inflammatory analgesic cream. Example 26 1 part of ketoprofen was suspended in 5 parts of glycerin, and carboxyvinyl polymer [Carbopol] was suspended in 5 parts of glycerin.
940 (manufactured by Gutsudoritsuchi Chemical Co.) 1 part, purified water
After adding 89.1 parts and stirring to swell, 0.4 parts of diisopropanolamine was added to form a gel. 3 parts of medium chain fatty acid triglyceride (ODO, manufactured by Nisshin Oil Co., Ltd.) and 0.5 part of 2-hydroxy-4-methoxybenzophenone were added and mixed to this to obtain an anti-inflammatory analgesic cream. Example 27 (A): 1 part of ketoprofen to 1 part of peppermint oil 50-80
It was dissolved by heating to ℃. In this, stearic acid 5
5 parts of cetanol, 15 parts of liquid paraffin, 3 parts of white petrolatum, 2 parts of polyoxyethylene sorbitan monostearate, 0.6 parts of sorbitan monostearate, and 0.05 parts of propyl paraoxybenzoate, and the mixture was heated on a water bath for about 50 to 50 parts. The mixture was heated to 80°C and mixed. On the other hand, (B) 0.05 part of methyl paraoxybenzoate, 2
-Hydroxy-4-methoxybenzophenone 0.5
1 part, 3 parts of a 10% triethanolamine aqueous solution, 0.1 part of sodium lauryl sulfate, and 63.7 parts of purified water were heated to 50 to 80°C on a water bath and dissolved. (B) was added to the (A) solution, thoroughly stirred, and then cooled to obtain an anti-inflammatory analgesic cream. Example 28 (A): Mix 20 parts of glycerin monostearate and 4 parts of polyoxyethylene glyceryl monooleate, stir while keeping at 50 to 70°C, and add 5 parts of ketoprofen and butyl hydroxyanisole.
0.02 parts and 1 part of 2-hydroxy-4-methoxybenzophenone were added and mixed well. On the other hand, (B): 0.15 parts of methyl paraoxybenzoate was dissolved in 62.83 parts of purified water, and 7 parts of glycerin was added. The oil layer of (A) was added little by little to (B) and thoroughly stirred until the whole was homogeneous to obtain an anti-inflammatory analgesic cream. Example 29 A mixture of 1 part of ketoprofen, 0.5 parts of 2-hydroxy-4-methoxybenzophenone, and 10 parts of isopropyl myristate, further swollen with 5 parts of ethanol, 1.5 parts of carboxyvinyl polymer in 50 parts of purified water, and A solution of 1 part of oxyethylene (55) monostearate dissolved in 10 parts of purified water was added and thoroughly stirred until uniform. Thereafter, 3 parts of coconut oil fatty acid diethanolamide dissolved in 10 parts of purified water and 8 parts of purified water were added, and the mixture was sufficiently stirred until the whole was homogeneous to obtain an anti-inflammatory analgesic cream. Example 30 (A): Put 5 parts of gelatin, 10 parts of sorbitol, 7 parts of kaolin, and 44 parts of purified water into a mixer and heat to about 50-60°C.
to obtain a uniform dispersion. Add to this 25 parts of glycerin prepared in advance, 3 parts of sodium polyacrylate, and carboxymethyl cellulose.
3.5 parts of the dispersion liquid was added and stirred and mixed to obtain a uniform kneaded product. (B): 1 part of crotamiton, 0.5 part of 2-hydroxy-4-methoxybenzophenone, and 1 part of ketoprofen were mixed and stirred while heating on a water bath to obtain a uniform solution. Next, (B) was added to (A) and stirred to obtain a uniform mixture. Apply this to a thickness of 2 mm using a spreading machine.
Thereafter, it was covered with a polypropylene film and cut into a desired size to obtain an anti-inflammatory and analgesic poultice. Example 31 46.5 parts of purified water, 8 parts of gelatin, 10 parts of aluminum silicate, and 3.5 parts of polyvinyl alcohol were placed in a mixer and dissolved at about 50 to 60°C to obtain a uniform dispersion. A dispersion of 25 parts of glycerin and 3 parts of carboxymethyl cellulose prepared in advance was added to this and stirred and mixed to obtain a uniform kneaded product.
Next, 3 parts of ketoprofen and 1 part of 2-hydroxy-4-methoxybenzophenone were added to this mixture and mixed with stirring to obtain a uniform kneaded product. This was applied to a thickness of 1 mm using a spreading machine, then covered with a polyethylene film and cut into desired sizes to obtain an anti-inflammatory and analgesic poultice. Example 32 (1) Ketoprofen 1 part (2) Gelatin 6 parts (3) Polyvinyl alcohol 1 part (4) Sodium polyacrylate 3 parts (5) Carboxyvinyl polymer 5 parts (6) 2-Hydroxy-4-methoxy Benzophenone 0.5 parts (7) Glycerin 44.5 parts (8) Water 39 parts Total 100 parts The above components were mixed in the same manner as described in Examples 30 and 31, and then spread on a support and digested. Analgesic poultice was obtained. Example 33 (1) Ketoprofen 2 parts (2) Polyacrylic acid 4 parts (3) Aluminum sulfate 1 part (4) Glycerin 24 parts (5) Gelatin 4 parts (6) 2,2'-dihydroxy-4-methoxybenzo Phenone 1 part (7) Water 64.0 parts Total 100 parts The above components were mixed in the same manner as described in Examples 30 and 31, and then spread on a support to obtain an anti-inflammatory and analgesic poultice. Example 34 (1) Sodium polyacrylate 1 part (2) Triethanolamine 1 part (3) Tween 80 70 parts (4) Propylene glycol 8 parts (5) Ketoprofen 5 parts (6) 2-hydroxy-4-methoxy Benzophenone 2 parts (7) Water 13 parts Total 100 parts The above components were mixed in the same manner as described in Examples 30 and 31, and then spread on a support to obtain an anti-inflammatory and analgesic poultice. . Example 35 (1) Ketoprofen 0.5 parts (2) Peppermint oil 3 parts (3) 2,2'-dihydroxy-4-methoxybenzophenone 0.5 parts (4) Glycol salicylate 3 parts (5) Kaolin 52 parts (6) Glycerin 41 parts Total 100 parts The above components were mixed in the same manner as described in Examples 30 and 31, and then spread on a support to obtain an anti-inflammatory and analgesic poultice. Example 36 (1) Ketoprofen 1 part (2) Benzyl alcohol 1 part (3) Polysorbate 80 2 parts (4) 2-Hydroxy-4-methoxybenzophenone 0.5 part (5) Zinc oxide 8 parts (6) Polyethylene glycol 400 3 parts (7) Gelatin 3 parts (8) Sodium polyacrylate 1 part (9) Sorbiturate solution (70%) 15 parts (10) Glycerin 10 parts (11) Carboxyvinyl polymer 1 part (12) Sodium carboxymethyl cellulose 2 Part (13) Purified water 52.5 parts Total 100 parts The above components were mixed in the same manner as described in Examples 30 and 31, and then spread on a support to obtain an anti-inflammatory and analgesic poultice. Example 37 Polyethylene glycol monostearate 2.35
85.15 parts of medium chain fatty acid triglyceride was added to 7 parts of bleached beeswax, and the mixture was heated to about 60 to 70°C to dissolve and mix. Add 5 parts of ketoprofen and 0.5 part of 2-hydroxy-4-methoxybenzophenone to this,
The mixture was further heated to 75 to 85°C and completely dissolved while stirring. Immediately after dissolution, the solution was rapidly cooled to around 40°C, defoamed while maintaining the same temperature, and then filled into capsules using a soft gelatin capsule filling machine to obtain an anti-inflammatory and analgesic suppository. Example 38 Add 80 parts of medium-chain fatty acid triglyceride to 5 parts of polyethylene glycol 400, 8 parts of bleached beeswax, and 3.49 parts of sorbitan sesquioleate to make a mixture of about 60~
The mixture was heated to 70°C and dissolved and mixed. Add to this 3 parts of ketoprofen, 0.5 parts of 2-hydroxy-4-methoxybenzophenone, and dibutylhydroxytoluene.
0.01 part was added, and the mixture was further heated to 75 to 85°C and completely dissolved with stirring. Hereinafter, an anti-inflammatory and analgesic suppository was obtained in the same manner as described in Example 37. Example 39 4.5 parts of camphor, 4 parts of menthol, 3 parts of ketoprofen, and 1 part of 2-hydroxy-4-methoxybenzophenone were dissolved in 32.5 parts of ethanol, 26 parts of water was added thereto, and the mixture was filled into an aerosol container. Then, a stock solution was prepared by adding 4 parts of talc, 13 parts of dimethyl ether and liquefied petroleum gas as a propellant.
After press-fitting the mixture with 12 parts, the stem hole diameter is 0.4
mmφ valve hole diameter 0.6mmφ paper tap diameter 0.4mm
A φ valve was attached, and then a button with a mechanical break-up with a hole diameter of 0.4 mm was attached to obtain an anti-inflammatory and analgesic aerosol. Example 40 4.5 parts of camphor, 0.4 parts of diphenhydramine, 4.5 parts of menthol, 1 part of ketoprofen, 0.5 parts of 2-hydroxy-4-methoxybenzophenone and 1 part of γ-tocopherol were dissolved in 30.1 parts of ethanol, and the mixture was dissolved in 30.1 parts of ethanol. An aerosol container was filled with 24 parts of water, and then a mixture of 25 parts of dimethyl ether and 9 parts of liquefied petroleum gas was injected under pressure. Hereinafter, an anti-inflammatory analgesic aerosol was obtained in the same manner as described in Example 39. Example 41 Ketoprofen 0.1 part 2-hydroxy-4-methoxybenzophenone
0.05 parts White petrolatum 10 parts Liquid paraffin 89.85 parts Total amount 100 parts The above ingredients were stirred until uniform to obtain an anti-inflammatory analgesic eye drop. Example 42 Ketoprofen 0.5 parts Boric acid 1.6 parts Borax Appropriate amount 2-Hydroxy-4-methoxybenzophenone
0.1 part water Total remaining amount 100 parts The above ingredients were stirred until homogeneous to obtain an anti-inflammatory and analgesic eye drop with a pH of 7.4. Example 43 Ketoprofen sodium 0.5 part 2-hydroxy-4-methoxybenzophenone Arginine 0.1 part IN Hydrochloric acid 0.32 part Water Appropriate amount Total amount 100 parts The above ingredients were stirred until uniform, pH 7.4
Anti-inflammatory analgesic eye drops were obtained. Example 44 12 parts of styrene-isoprene-styrene teleblock copolymer (Califlex TR1107, manufactured by Shell Chemical Co., Ltd.), 12 parts of styrene-isoprene-styrene radial teleblock copolymer (Solprene μ18,
(manufactured by Philips Petroleum) 8 parts, hydrogenated rosin ester (Ester Gum H, manufactured by Arakawa Chemical) 12 parts
3 parts rosin-modified maleic acid resin (Malquido No. 2-N, manufactured by Arakawa Chemical), 57.5 parts liquid paraffin (Crystal 355, manufactured by Etsuso Standard Oil)
of this solution (approx.
150°C) to about 120°C, 5 parts of ketoprofen and 2.5 parts of 2-hydroxy-4-methoxybenzophenone were added and mixed to make it homogeneous. Spread this onto a non-woven fabric using a spreading machine to a thickness of approximately 50μ.
After spreading, the mixture was covered with release paper treated with mold release and cut into a desired size to obtain an anti-inflammatory and analgesic patch. Example 45 22.5 parts of styrene-isoprene-styrene teleblock copolymer (Califlex TR1107, manufactured by Shell Chemical Co., Ltd.), liquid paraffin (manufactured by Wako Pure Chemical Industries, Ltd.)
43.5 parts, hydrogenated rosin ester (ester gum H,
Arakawa Chemical Co., Ltd.) 28 parts was dissolved in a nitrogen gas stream, and after cooling this melt (approximately 150℃) to approximately 120℃,
5 parts of ketoprofen and 1 part of 2-hydroxy-4-methoxybenzophenone were added and mixed until homogeneous. This was spread to a thickness of about 50 μm on a non-raised cloth support using a spreading machine, and then covered with a polyethylene film and cut into a desired size to obtain an anti-inflammatory and analgesic patch. Example 46 20 parts of styrene-isoprene-styrene teleblock copolymer (Califlex TR1107, manufactured by Ciel Chemical Co., Ltd.), liquid paraffin (Crystal 355,
40 parts of Etsuso Standard Co., Ltd.), 12 parts of hydrogenated rosin ester (Ester Gum H, Arakawa Chemical Co., Ltd.), and 18 parts of rosin-modified maleic acid resin (Marquid No. 2-N, Arakawa Chemical Co., Ltd.) were dissolved in a nitrogen gas stream. After cooling this melt (about 150°C) to about 120°C, 5 parts of ketoprofen, 1 part of 2-hydroxy-4-methoxybenzophenone and 4 parts of γ-tocopherol were added and mixed to make a homogeneous mixture. did. This was spread on a cloth to a thickness of about 90 μm using a spreading machine, and then covered with a release-treated polypropylene film and cut into a desired size to obtain an anti-inflammatory and analgesic patch. Example 47 22 parts of styrene-isoprene-styrene teleblock copolymer (Califlex TR1107, manufactured by Ciel Chemical Co., Ltd.), liquid paraffin (Crystal 355,
42 parts (manufactured by Etsuso Standard Co., Ltd.) and 27.5 parts of hydrogenated rosin ester (Ester Gum H, manufactured by Arakawa Chemical) were dissolved in a nitrogen gas stream, and this melt (approximately 150°C) was dissolved.
After cooling to about 120℃, 5 parts of ketoprofen,
Adding 1.5 parts of 2,2-dihydroxy-4-methoxybenzophenone and 2 parts of γ-tocopherol;
Mixed until homogeneous. Use a spreading machine to spread this onto release paper to a thickness of 50μ, and after cooling, the thickness becomes 60μ.
The mixture was transferred onto a polyethylene film and cut into a desired size to obtain an anti-inflammatory and analgesic patch. Example 48 28.5 parts of styrene-isoprene-styrene radial teleblock copolymer (Solprene 418, manufactured by Phillips Petroleum Company), 37.5 parts of liquid paraffin (Crystal 355, manufactured by Esso Standard Oil Company), hydrogenated rosin ester (ester gum) H, manufactured by Arakawa Chemical) and 6 parts of rosin-modified maleic acid resin (Marquid No. 2-N, manufactured by Arakawa Chemical) were dissolved in a nitrogen gas stream, and this melt (approximately 150°C) was dissolved.
After cooling to about 120℃, add 4 parts of ketoprofen,
2-Hydroxy-4-methoxybenzophenone 1
part was added and mixed to make it homogeneous. This was spread on a nonwoven fabric to a thickness of approximately 50 μm using a spreading machine, and then covered with a polypropylene film and cut into desired sizes to obtain an anti-inflammatory and analgesic patch. Example 49 25 parts of styrene-isoprene-styrene radial teleblock copolymer (Solprene 418, manufactured by Philips Petroleum Corporation), 2 parts of styrene-butadiene-styrene radial teleblock copolymer (Solpsan T-431, manufactured by Asahi Kasei Corporation) , 41.5 parts of liquid paraffin (Crystal 70, manufactured by Etsuso Standard Oil Co., Ltd.), 18.5 parts of hydrogenated rosin ester (Ester Gum H, manufactured by Arakawa Chemical Co., Ltd.), rosin-modified maleic acid resin (Marquido No. 2-N, manufactured by Arakawa Chemical Co., Ltd.)
11 parts was dissolved in a stream of nitrogen gas, and this melt (approximately
150°C) to about 120°C, 1 part of ketoprofen and 1 part of 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid were added and mixed to make it homogeneous. This was spread on a raised cloth using a spreading machine to a thickness of approximately 90 μm, then covered with a polyethylene film and cut into desired sizes to obtain an anti-inflammatory and analgesic patch. Example 50 16 parts of styrene-isoprene-styrene radial teleblock copolymer (Solprene 418, manufactured by Philips Petroleum Co., Ltd.), 16 parts of styrene-butadiene-styrene radial teleblock copolymer (Solpsan T-414, manufactured by Nippon Elastomer Co., Ltd.)
1.5 parts of liquid paraffin (Crystal 70, manufactured by Etsuso Standard Oil Co., Ltd.), and 25 parts of rosin-modified maleic acid resin (Marquid No. 2-N, manufactured by Arakawa Chemical) were dissolved in a nitrogen gas stream, and this melt ( 150℃) to about 120℃, add 3 parts of ketoprofen, 1.5 parts of 2-hydroxy-4-methoxybenzophenone, 6.5 parts of l-menthol, and 5 parts of dl-camphor and mix to make a homogeneous mixture. And so. This was spread on a raised cloth using a spreading machine to a thickness of about 1 mm, and then the surface was covered with cellophane film and cut into a desired size to obtain an anti-inflammatory and analgesic patch. Example 51 21 parts of styrene-isoprene-styrene radial teleblock copolymer (Solprene 418, manufactured by Phillips Petroleum), 45.5 parts of liquid paraffin (manufactured by Wako Pure Chemical Industries, Ltd.), rosin-modified maleic acid resin (Marquid No. 2-N, Arakawa Chemical Co., Ltd.) 20 parts and hydrogenated rosin ester (Ester Gum H, Arakawa Chemical Co., Ltd.) 20 parts were dissolved in a nitrogen gas stream, and after cooling this melt (approximately 150°C) to approximately 120°C, ketoprofen 4 1 part, 3 parts of 2-hydroxy-4-methoxybenzophenone, and 4.5 parts of chili pepper extract were added.
Mixed until homogeneous. This was spread on a raised cloth using a spreading machine to a thickness of about 1 mm, and then the surface was covered with a polyethylene film and cut into a desired size to obtain an anti-inflammatory and analgesic patch. Example 52 35 parts of styrene-isoprene-styrene teleblock copolymer (Califlex TR-1107, manufactured by Ciel Chemical Co., Ltd.), liquid paraffin (Crystol-
355, manufactured by Etsuso Standard Co., Ltd.) 35 parts, hydrogenated rosin ester (Ester Gum H, manufactured by Arakawa Chemical) 16.5 parts
part of the solution in a nitrogen gas stream, and this melt (approximately
150℃) to about 120℃, and then
1 part, 2 parts of ketoprofen, 2-hydroxy-4-
1 part of methoxybenzophenone, 3 parts of γ-tocopherol, 3 parts of l-menthol, 1 part of dl-camphor
1 part and 0.5 part of thymol were added and mixed to make it homogeneous. This was applied onto a 25μ polyester film using a spreading machine. Thereafter, it was covered with release paper and cut into a desired size to obtain an anti-inflammatory and analgesic patch. Example 53 Carboxyvinyl polymer [Carbopol 940
(manufactured by Gutsudoritsuchi Chemical Co.)] 1 part was swollen in 61.3 parts of water. Meanwhile, 5 parts of crotamiton, 10 parts of 2-octyldodecanol, 5 parts of propylene glycol
3 parts of polyoxyethylene (20) cetyl ether [Nitsukol BC-20TX], and 2-hydroxy-4-methoxybenzophenone
0.5 part, 0.2 part of methyl paraoxybenzoate, and 3 parts of ketoprofen were added and heated to 70 to 80°C to dissolve. After cooling this to room temperature, it was added to the carboxyvinyl polymer swollen in water, and after uniformly emulsifying with a homomixer, a solution of 1 part of diisopropanolamine dissolved in 10 parts of water was added,
An anti-inflammatory analgesic cream was obtained by stirring thoroughly until the whole was homogeneous. Example 54 Carboxyvinyl polymer [Carbopol 940
(manufactured by Gutsudoritsuchi Chemical Co., Ltd.)] was swollen in 54.3 parts of water. On the other hand, difosopropyl sebacate 10
parts, 10 parts of 2-hexyldecanol, 5 parts of 1,3-butylene glycol, polyoxyethylene (60)
Mix 5 parts of hydrogenated castor oil [Nitsukol, HCO-60] with 0.5 part of 2-hydroxy-4-methoxybenzophenone and methyl paraoxybenzoate.
Add 0.2 parts and 3 parts of ketoprofen, 70-80
The mixture was heated and dissolved at ℃. After cooling this to room temperature,
Add it to the carboxyvinyl polymer swollen in water and homogeneously emulsify it with a homomixer, then add 1 part of diisopropanolamine dissolved in 10 parts of water and stir thoroughly until the whole becomes uniform. An anti-inflammatory analgesic cream was obtained. Example 55 Add 3 parts of ketoprofen to linalyl denatured alcohol
35 parts, to which were added 1 part of 2-hydroxy-4-methoxybenzophenone, 5 parts of polyoxyethylene oleyl ether, and 0.5 parts of peppermint oil.
Further, purified water was added to bring the total amount to 100 parts, and the mixture was sufficiently stirred until the whole was homogeneous to obtain an anti-inflammatory and analgesic liniment agent. Example 56 (A): 5 parts of gelatin, 10 parts of sorbitol, 3 parts of polyvinyl alcohol, 5 parts of kaolin, and 44.4 parts of purified water are placed in a mixer and dissolved at about 50 to 60°C to obtain a uniform dispersion. To this, 25 parts of glycerin, which had been prepared in advance, and 3 parts of sodium polyacrylate,
Methyl vinyl ether maleic anhydride copolymer 3
of the dispersion was added and stirred and mixed to obtain a uniform kneaded product. (B): 1 part of peppermint oil, 2-hydroxy-
0.5 part of 4-methoxybenzophenone and 0.1 part of ketoprofen are mixed while heating to obtain a uniform solution. Next, (B) was added to (A) and stirred to obtain a uniform mixture. Apply this to a thickness of 1 mm (stockinette fabric) using a spreading machine. Thereafter, it was covered with a polypropylene film and cut into desired sizes to obtain an anti-inflammatory and analgesic poultice.

Claims (1)

[Scope of Claims] 1. A stable external transdermal preparation containing ketoprofen, which comprises incorporating an ultraviolet absorber into the external transdermal preparation containing ketoprofen. 2. A stable external transdermal preparation containing ketoprofen, which is characterized in that it contains both an ultraviolet absorber and an antioxidant. 3. The ultraviolet absorber is a p-aminobenzoic acid derivative, an anthranilic acid derivative, a salicylic acid derivative,
The ketoprofen-containing external transdermal preparation according to claim 1 or 2, which comprises a cinnamic acid derivative, a benzophenone derivative, a coumarin derivative, and an amino acid compound. 4. The ketoprofen-containing external transdermal preparation according to claim 1 or 2, wherein the ultraviolet absorber is a benzophenone derivative. 5 The benzophenone derivative is 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 2
-Hydroxy-4-methoxybenzophenone, 2
-Hydroxy-4-n-octoxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 4-phenylbenzophenone Claim 3 consisting of -2-carboxylic acid-isooctyl ester, 2-hydroxybenzophenone, 2,4-dihydroxybenzophenone, 2,2'-4,4'-tetrahydroxybenzophenone Or the external transdermal preparation containing ketoprofen according to item 4.