WO2011049058A1 - ジクロフェナクナトリウム含有水性貼付剤 - Google Patents
ジクロフェナクナトリウム含有水性貼付剤 Download PDFInfo
- Publication number
- WO2011049058A1 WO2011049058A1 PCT/JP2010/068311 JP2010068311W WO2011049058A1 WO 2011049058 A1 WO2011049058 A1 WO 2011049058A1 JP 2010068311 W JP2010068311 W JP 2010068311W WO 2011049058 A1 WO2011049058 A1 WO 2011049058A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- diclofenac sodium
- plaster
- crotamiton
- water
- sodium
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- the present invention relates to a transdermal absorption-type aqueous patch containing diclofenac sodium as an active ingredient. More specifically, the present invention relates to a diclofenac sodium-containing transdermal absorption-type aqueous patch having excellent dissolution stability of diclofenac sodium, excellent initial drug release rate, and sustained drug release.
- nonsteroidal anti-inflammatory analgesics have been formulated for percutaneous absorption and are widely used for various inflammatory diseases such as rheumatoid arthritis, osteoarthritis, osteoarthritis, and back pain.
- diclofenac sodium has been widely used in clinical settings as an oral preparation or suppository because it has an excellent anti-inflammatory analgesic action.
- various side effects such as gastrointestinal disorders appear.
- an external preparation for percutaneously absorbing diclofenac sodium has been studied.
- an external patch can efficiently and continuously be treated because the drug dosage can be controlled and the drug can be directly transferred to the affected area immediately below the patch.
- diclofenac sodium is very poorly soluble in water and oil components, and it is not only difficult to prepare a patch in which diclofenac sodium is completely dissolved in the preparation, but an excessive amount of diclofenac sodium solubilizer is added.
- a completely dissolving type patch was prepared, it was difficult to store in a dissolved state for a long period of time without crystals being precipitated in the patch.
- Patent Document 1 listed below proposes a patch having enhanced transdermal absorbability by adding crotamiton and weakly acidic fatty acid to diclofenac sodium to make the drug free.
- the diclofenac sodium may be reduced to reduce the stability of diclofenac sodium, and the percutaneous absorption of the drug is not sufficient.
- Patent Document 2 proposes a patch that has a transdermal absorption efficiency that is composed of a drug layer containing diclofenac sodium and a base layer not containing diclofenac sodium and has little change over time. After the preparation and spreading of the base layer and the base layer separately, a bonding process is required, and there are problems in the complexity of process management, economic efficiency, and the like.
- Patent Document 3 proposes an absorption promoter comprising diclofenac sodium, l-menthol and propylene glycol, and an aqueous patch containing a hydrophilic base mainly composed of a water-soluble polymer.
- the solubility of diclofenac sodium is low, the drug may crystallize during long-term storage, and the transdermal absorbability of the drug is not sufficient.
- Patent Document 4 proposes that l-menthol and pyrrolidones (at least one of pyrrolidone or a derivative thereof) are blended as a transdermal absorption enhancer of diclofenac sodium, but diclofenac in an aqueous patch is proposed.
- the solubility of sodium is low, the drug may crystallize during long-term storage, and the transdermal absorbability of the drug is not sufficient.
- An object of the present invention is to provide an aqueous patch excellent in dissolution stability and transdermal absorbability of diclofenac sodium. That is, it is to provide an aqueous patch in which no drug crystals are observed in the plaster even when stored for a long time, the initial drug release rate is excellent, and the drug release is sustained.
- crotamiton / diclofenac sodium is 8.0 or less for clotamiton and diclofenac sodium which hardly dissolves alone in water.
- a mixed solution of crotamiton / water / diclofenac sodium mixed at a blending ratio of (water + crotamiton) / diclofenac sodium in the range of 3.0 to 20.0 is unexpectedly soluble in diclofenac sodium. It was found that a uniform diclofenac sodium complete solution (hereinafter referred to as diclofenac sodium main drug solution according to the present invention) can be prepared. Therefore, by blending this mixed solution in an aqueous patch, no dissolution of crystals in the plaster, excellent dissolution stability of diclofenac sodium, excellent initial drug release rate, and sustained drug release It became possible to obtain a patch.
- the present invention provides a uniform mixed solution obtained by mixing crotamiton / diclofenac sodium at 8.0 or less and (water + crotamiton) / diclofenac sodium in a mixing ratio of 3.0 to 20.0.
- a uniform mixed solution obtained by mixing crotamiton / diclofenac sodium at 8.0 or less and (water + crotamiton) / diclofenac sodium in a mixing ratio of 3.0 to 20.0.
- FIG. 6 is a graph showing the relationship between the permeation rate of diclofenac sodium permeating through the skin of the hairless rat of Experimental Example 3 and time.
- the amount of diclofenac sodium, which is an active ingredient of the aqueous patch of the present invention, in the paste is 0.1 to 5% by weight, preferably 0.5 to 2.5% by weight. If the blending amount is less than 0.1%, the pharmacological effect thereof is inferior, which is not preferable. Conversely, if the blending amount exceeds 5% by weight, diclofenac sodium crystals are likely to precipitate, and the physical properties of the preparation deteriorate.
- the blending amount of crotamiton in the plaster is 1.5 to 5% by weight, preferably 2 to 4% by weight. If the amount is less than 1.5% by weight, a uniform mixed solution cannot be prepared with diclofenac sodium / water / crotamiton, the solubility of diclofenac sodium in the plaster is lowered, and the initial percutaneous absorption is insufficient. It becomes. On the other hand, if it exceeds 5% by weight, the compatibility with other ingredients will be worsened, and clotamiton oozes out on the surface of the plaster, resulting in the release of diclofenac sodium and a decrease in the adhesive strength of the preparation, resulting in good formulation properties. It becomes difficult to maintain for a long time.
- water is an essential component for preparing diclofenac sodium main drug solution, and also a necessary component as a solubilizing agent such as a water-soluble polymer that is a paste component of an aqueous patch.
- the water for preparing the main drug solution of diclofenac sodium according to the present invention is blended in the range of 0.5 to 20%, preferably 1 to 10%, based on the weight of the paste. If this amount is out of this range, a uniform diclofenac sodium main drug solution cannot be prepared.
- the amount of water used for dissolving the plaster component including the amount of water previously contained in the compounding component.
- the amount of water contained in the 20% polyacrylic acid aqueous solution is the plaster composition and diclofenac. It is formulated in consideration of the balance with the amount of water used for preparing sodium, but is 20 to 50% by weight, preferably 30 to 45% by weight, based on the weight of the paste.
- the total weight of water with respect to the plaster is 20 to 70%, preferably 30 to 60% by weight.
- the blending amount is less than 20% by weight, the paste viscosity becomes too high, and the workability during production deteriorates.
- the adhesive strength of the preparation becomes too strong, pain occurs when it is peeled off and skin irritation occurs, which is not preferable.
- composition ratio of the main drug solution of diclofenac sodium according to the present invention is such that crotamiton / diclofenac sodium is 8.0 or less and (water + crotamiton) / diclofenac sodium is in the range of 3.0 to 20.0. is there. If each component deviates from this composition ratio, a uniform diclofenac sodium main drug solution cannot be prepared.
- the plaster component constituting the aqueous patch is not particularly limited as long as it is a plaster component used in producing a general aqueous patch, for example, a water-soluble polymer, a humectant, an excipient, a stable An agent, a crosslinking agent, an antioxidant, a cooling agent, a warming stimulant, and the like can be added.
- water-soluble polymer examples include gelatin, hydrolyzed gelatin, polyacrylic acid, sodium polyacrylate, partially neutralized polyacrylic acid, starch polyacrylate, polyvinyl alcohol, polyvinyl pyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose. Hydroxyethyl cellulose, methyl cellulose, carmellose sodium, carboxyvinyl polymer, methoxyethylene maleic anhydride copolymer, N-vinylacetamide copolymer, xanthan gum, gum arabic, etc. can be used alone or in combination of two or more. In particular, it is particularly preferable to use polyacrylic acid, a polyacrylic acid partial neutralized product, and carmellose sodium in combination.
- humectant for example, concentrated glycerin, D-sorbitol solution, 1,3-butylene glycol, dipropylene glycol, polyethylene glycol and the like can be used alone or in combination of two or more.
- excipient for example, kaolin, titanium oxide, silicic anhydride, zinc oxide, bentonite and the like can be used alone or in combination of two or more.
- edetate, tartaric acid, citric acid, sodium bisulfite, diisopropanolamine and the like can be used alone or in combination of two or more.
- the crosslinking agent include dry aluminum hydroxide gel, synthetic aluminum silicate, dihydroxyaluminum aminoacetate, synthetic hydrotalcite, magnesium aluminate metasilicate, magnesium silicate, and other polyvalent metal compounds. It can be used in combination of the above.
- antioxidant for example, tocopherol acetate, ascorbic acid, butylhydroxytoluene, tocopherol and the like can be used alone or in combination of two or more.
- refreshing agent include mint oil, dl-camphor, d-borneol and the like, and these may be used alone or in combination of two or more.
- warm stimulants include capsicum-derived substances such as red pepper powder, red pepper extract, red pepper tincture, capsaicin, dihydroxycapsaicin, capsaicin analogs such as capsinoid, nonyl acid vanillylamide, nicotinic acid benzyl, and these are used alone. May also be used in combination of two or more.
- the pH of the plaster component composition according to the present invention is preferably in the range of pH 3.5 to 7.0, more preferably in the range of pH 4.0 to 6.0 from the viewpoint of skin irritation.
- the diclofenac sodium aqueous patch of the present invention is prepared by preparing diclofenac sodium, which is the main ingredient, into the diclofenac sodium main drug solution according to the present invention, and then blending it into other plaster compositions of the aqueous patch. If it is not specifically limited, it can manufacture with a well-known manufacturing method.
- a diclofenac sodium aqueous patch can be formed by spreading a plaster composition having the above-described configuration on a support and coating the plaster composition surface with a plastic film as necessary. .
- plastic film covering the surface of the plaster composition a single layer or a composite film of polyethylene, polypropylene, polyester, polyvinyl chloride can be used. Further, these surfaces are treated with silicone, corona discharge treatment, uneven treatment, plasma. What gave the process etc. can be used.
- the support examples include porous bodies such as polyethylene, polypropylene, polyvinyl chloride, polyester, nylon, and polyurethane, foams, woven fabrics, and nonwoven fabrics, and plastic films or sheets and porous bodies, foams, woven fabrics, and nonwoven fabrics. Laminated products can be used.
- Example 1S indicates diclofenac sodium main drug solution according to the present invention used for experiments, etc.
- those without “S” are as follows.
- the patch as the final preparation of the present invention containing the diclofenac sodium main drug solution according to the present invention is shown.
- Example 1 Diclofenac sodium 10.0 g and purified water 10.0 g were added to crotamiton 20.0 g and uniformly stirred and dissolved to prepare a diclofenac sodium main drug solution (corresponding to Example 1S) according to the present invention.
- a solution A was prepared by stirring and dispersing 30 g of kaolin in 150 g of 70% D-sorbitol solution. Further, 250 g of concentrated glycerin, 40 g of carmellose sodium, 50 g of partially neutralized polyacrylic acid, 20.0 g of hydroxypropylcellulose, and 0.6 g of dihydroxyaluminum aminoacetate were stirred and dispersed to prepare solution B.
- Liquid A 200.0 g of 20% polyacrylic acid aqueous solution, diclofenac sodium main agent liquid according to the present invention, 0.8 g of sodium edetate, 191.6 g of purified water, and liquid B were sequentially added and kneaded until uniform. Further, 8.0 g of polyvinyl alcohol and 5.0 g of tartaric acid were dispersed uniformly in the water-containing gel. Finally, 2.5 g of l-menthol, 1.0 g of methylparaben, and 0.5 g of propylparaben were dissolved in 10.0 g of 1,3-butylene glycol, and this dissolved solution was made uniform in the previously prepared hydrous gel. To obtain a plaster for a patch. The plaster was spread on a polyester nonwoven fabric, and the plaster surface was covered with a polypropylene film to form an aqueous patch.
- Example 2 Diclofenac sodium 10.0 g and purified water 60.0 g were added to 20.0 g of crotamiton and uniformly stirred and dissolved to prepare a diclofenac sodium main drug solution (corresponding to Example 2S) according to the present invention.
- Solution A was prepared by stirring and dispersing 30 g of kaolin and 5.0 g of titanium oxide in 150 g of 70% D-sorbitol solution.
- liquid B was prepared by stirring and dispersing 250.0 g of concentrated glycerin, 40.0 g of carmellose sodium, 50.0 g of partially neutralized polyacrylic acid, 20.0 g of hydroxypropylcellulose, and 0.6 g of dihydroxyaluminum aminoacetate. .
- Liquid A 200.0 g of 20% polyacrylic acid aqueous solution, diclofenac sodium main agent liquid according to the present invention, 0.8 g of sodium edetate, 136.6 g of purified water, and liquid B were sequentially added and kneaded until uniform. Further, 8.0 g of polyvinyl alcohol and 5.0 g of tartaric acid were dispersed uniformly in the water-containing gel. Finally, 2.5 g of l-menthol, 1.0 g of methylparaben, and 0.5 g of propylparaben were dissolved in 10.0 g of 1,3-butylene glycol, and this solution was made uniform in the previously prepared hydrous gel. To obtain a plaster for a patch. The plaster was spread on a polyester nonwoven fabric, and the plaster surface was covered with a polypropylene film to form an aqueous patch.
- Example 3 Diclofenac sodium 10.0 g and purified water 20.0 g were added to crotamiton 40.0 g and uniformly stirred and dissolved to prepare a diclofenac sodium main drug solution (corresponding to Example 3S) according to the present invention.
- a solution A was prepared by stirring and dispersing 30.0 g of kaolin in 150.0 g of 70% D-sorbitol solution.
- liquid B was prepared by stirring and dispersing 250.0 g of concentrated glycerin, 40.0 g of carmellose sodium, 50.0 g of partially neutralized polyacrylic acid, 30.0 g of hydroxypropylcellulose, and 0.6 g of dihydroxyaluminum aminoacetate. .
- Liquid A 200.0 g of 20% polyacrylic acid aqueous solution, diclofenac sodium main agent liquid according to the present invention, 0.8 g of sodium edetate, 151.6 g of purified water, and liquid B were sequentially added and kneaded until uniform. Further, 8.0 g of polyvinyl alcohol and 5.0 g of tartaric acid were dispersed uniformly in the water-containing gel. Finally, 2.5 g of l-menthol and 1.5 g of methylparaben were dissolved in 10.0 g of 1,3-butylene glycol, and the resulting solution was dispersed uniformly in the previously prepared hydrous gel. A paste was obtained. The plaster was spread on a polyester nonwoven fabric, and the plaster surface was covered with a polyester film to form an aqueous patch.
- Example 4 Diclofenac sodium 10.0 g and purified water 20.0 g were added to 20.0 g of crotamiton and uniformly dissolved by stirring to prepare a diclofenac sodium main drug solution (corresponding to Example 4S) according to the present invention.
- a solution A was prepared by stirring and dispersing 30.0 g of kaolin in 150.0 g of 70% D-sorbitol solution.
- liquid B was prepared by stirring and dispersing 250.0 g of concentrated glycerin, 40.0 g of carmellose sodium, 50.0 g of partially neutralized polyacrylic acid, 20.0 g of hydroxypropylcellulose, and 0.4 g of dihydroxyaluminum aminoacetate. .
- a solution 200.0 g of 20% polyacrylic acid aqueous solution, diclofenac sodium main agent solution according to the present invention, 0.4 g of sodium edetate, 182.2 g of purified water and B solution were sequentially added and kneaded until uniform. Further, 8.0 g of polyvinyl alcohol and 5.0 g of tartaric acid were dispersed uniformly in the water-containing gel. Finally, 2.5 g of l-menthol, 1.0 g of methylparaben, and 0.5 g of propylparaben were dissolved in 10.0 g of 1,3-butylene glycol, and this dissolved solution was made uniform in the previously prepared hydrous gel. To obtain a plaster for a patch. The plaster was spread on a polyester nonwoven fabric, and the plaster surface was covered with a polypropylene film to form an aqueous patch.
- Example 1S Diclofenac sodium main drug solution (Example 1S) of Example 1 was removed by stirring 10.0 g of purified water added at the time of preparation, and diclofenac sodium main drug solution in which diclofenac sodium was undissolved (Comparative Example 1S). Equivalent).
- the subsequent production method was the same as in Example 1, and a plaster for patch was obtained. The plaster was spread on a polyester nonwoven fabric, and the plaster surface was covered with a polyester film to form an aqueous patch.
- Comparative Example 2 Remove 20.0 g of crotamiton added at the time of preparation of diclofenac sodium main drug solution of Example 1 (Example 1S), and increase 20.0 g of purified water instead, and stir to disperse diclofenac sodium in an undissolved state.
- Diclofenac sodium main drug solution (corresponding to Comparative Example 2S) was prepared.
- the subsequent production method was the same as in Example 1, and a plaster for patch was obtained. The plaster was spread on a polyester nonwoven fabric, and the plaster surface was covered with a polypropylene film to form an aqueous patch.
- Diclofenac sodium 10.0 g was added to 30.0 g of propylene glycol and uniformly stirred and dissolved to prepare a diclofenac sodium main drug solution (corresponding to Comparative Example 9S).
- 180.0 g of concentrated glycerin, 40.0 g of carmellose sodium, 20.0 g of partially neutralized polyacrylic acid, 20.0 g of sodium polyacrylate, 1.5 g of magnesium aluminate metasilicate, 0.2 g of dry aluminum hydroxide gel Liquid A was prepared by stirring and dispersing.
- Solution A 250.0 g of 70% D-sorbitol solution, diclofenac sodium main agent solution, 0.5 g of sodium edetate, and 390.8 g of purified water were sequentially added and kneaded until uniform. Furthermore, 40.0 g of polyvinyl alcohol and 3.0 g of tartaric acid were dispersed uniformly in the water-containing gel. Finally, 2.5 g of l-menthol, 1.0 g of methylparaben, and 0.5 g of propylparaben were dissolved in 10.0 g of 1,3-butylene glycol, and this dissolved solution was made uniform in the previously prepared hydrous gel. To obtain a plaster for a patch. The plaster was spread on a polyester nonwoven fabric, and the plaster surface was covered with a polyester film to form an aqueous patch.
- Liquid A was prepared by stirring and dispersing 250.0 g of concentrated glycerin, 40.0 g of carmellose sodium, 60.0 g of sodium polyacrylate, 5.0 g of hydroxypropylcellulose, and 1.2 g of dihydroxyaluminum aminoacetate.
- Solution A 2.5 g of l-menthol, 1.0 g of methylparaben, 0.5 g of propylparaben, 80.0 g of 20% polyacrylic acid aqueous solution, 10.0 g of diisopropanolamine, 180.0 g of 70% D-sorbitol solution, diclofenac sodium
- the main chemical solution, 0.8 g of sodium edetate, and 308.0 g of purified water were sequentially added and kneaded until uniform.
- 13.0 g of polyvinyl alcohol and 3.0 g of tartaric acid were dispersed uniformly in the water-containing gel described above to obtain a plaster for a patch.
- the plaster was spread on a polyester nonwoven fabric, and the plaster surface was covered with a polyester film to form an aqueous patch.
- Diclofenac sodium 10.0 g was added to 20.0 g of N-methyl-2-pyrrolidone and uniformly dissolved by stirring to prepare a diclofenac sodium main drug solution (corresponding to Comparative Example 11S).
- 180.0 g of concentrated glycerin, 40.0 g of carmellose sodium, 20.0 g of partially neutralized polyacrylic acid, 20.0 g of sodium polyacrylate, 1.5 g of magnesium aluminate metasilicate, and 0.2 g of dry aluminum hydroxide gel Liquid A was prepared by stirring and dispersing.
- Solution A 250.0 g of 70% D-sorbitol solution, diclofenac sodium main agent solution, 0.5 g of sodium edetate, and 400.8 g of purified water were successively added and kneaded until uniform. Furthermore, 40.0 g of polyvinyl alcohol and 3.0 g of tartaric acid were dispersed uniformly in the water-containing gel. Finally, 2.5 g of l-menthol and 1.5 g of methylparaben were dissolved in 10.0 g of 1,3-butylene glycol, and the solution was dispersed uniformly in the previously prepared hydrous gel. A paste was obtained. The plaster was spread on a polyester nonwoven fabric, and the plaster surface was covered with a polyester film to form an aqueous patch.
- Comparative Example 12 20.0 g of oleic acid and 20.0 g of crotamiton were added to 10.0 g of diclofenac sodium and uniformly stirred and dissolved to prepare a diclofenac sodium main drug solution (corresponding to Comparative Example 12S).
- a solution A was prepared by stirring and dispersing 30.0 g of kaolin in 150.0 g of 70% D-sorbitol solution.
- liquid B was prepared by stirring and dispersing 250.0 g of concentrated glycerin, 40.0 g of carmellose sodium, 50.0 g of partially neutralized polyacrylic acid, 20.0 g of hydroxypropylcellulose, and 0.4 g of dihydroxyaluminum aminoacetate. .
- Liquid A 200.0 g of 20% polyacrylic acid aqueous solution, diclofenac main agent liquid, 0.4 g of sodium edetate, 182.2 g of purified water, and liquid B were sequentially added and kneaded until uniform. Further, 8.0 g of polyvinyl alcohol and 5.0 g of tartaric acid were dispersed uniformly in the water-containing gel. Finally, 2.5 g of l-menthol, 1.0 g of methylparaben, and 0.5 g of propylparaben were dissolved in 10.0 g of 1,3-butylene glycol, and this solution was made uniform in the previously prepared hydrous gel. To obtain a plaster for a patch. The plaster was spread on a polyester nonwoven fabric, and the plaster surface was covered with a polypropylene film to form an aqueous patch.
- Tables 2 and 3 show the prescription list of this example and the comparative example, respectively.
- Example 3 the relationship between the skin permeation rate of diclofenac sodium permeated through the skin of hairless rats and time is shown in FIG.
- Examples 1 to 4 were found to be preparations excellent in the stability of the preparation and the skin permeability of the drug.
- the comparative example in the storage test after production, crystals were precipitated in the preparations of Comparative Examples 1-2 and 9-11.
- Comparative Example 10 when the results of Experimental Example 6 were considered together, Not only was it precipitated, but the diclofenac sodium drug itself had a low stability. Further, it was found that Comparative Examples 1 to 2, 9, 11, and 12 were inferior in the skin permeability of the drug as compared with each Example.
- an aqueous patch excellent in dissolution stability and transdermal absorbability of diclofenac sodium can be provided.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
特に外用貼付剤は、薬物投与量をコントロールできるとともに貼付部直下の患部に薬物を直接移行させることができるため、効率よく持続的に治療することが可能である。しかしながら、ジクロフェナクナトリウムは、水や油性成分への溶解性が極めて悪く、ジクロフェナクナトリウムを製剤中で完全溶解させた貼付剤を作製することが困難であるだけではなく、ジクロフェナクナトリウム溶解剤等の過量添加により完全溶解型の貼付剤を作製しても、貼付剤中に結晶が析出することなく溶解状態で長期間保存することが難しいものであった。また、ジクロフェナクナトリウムの溶解性が高い油性成分を水性貼付剤中に高濃度に配合すると他の成分との相溶性が悪くなり、相分離が起きやすくなり、長期間安定的に保存することが不可能となる。加えてジクロフェナクナトリウムの経皮吸収性は一般的に低いため、これらの問題を改善すべく従来より種々の検討や工夫が行われてきたが、上記問題点が解決された製剤は得られていないのが現状である。
従って、この混合溶液を水性貼付剤に配合することにより、膏体中に結晶を認めることなく、ジクロフェナクナトリウムの溶解安定性に優れ、初期その薬物放出速度が優れるとともに、その薬物放出も持続する水性貼付剤を得ることが可能となった。
本発明の水性貼付剤の有効成分であるジクロフェナクナトリウムの膏体中の配合量は、0.1~5重量%であり、好ましくは、0.5~2.5重量%である。配合量が0.1%未満であるとその薬理効果が劣るので好ましくなく、逆に配合量が5重量%を超えるとジクロフェナクナトリウムの結晶が析出しやすくなり、また製剤の物性が悪化する。
膏体に対する水の総重量は20~70%であり、好ましくは30~60重量%の範囲で配合する。配合量が70重量%を超えた場合、膏体粘度の低下による保形性悪化及びべとつき現象が見られる。また、粘着力が著しく低下し、貼付部位への接着性が十分に得られず好ましくない。他方、配合量が20重量%未満では、膏体粘度が高くなりすぎて製造時の作業性が悪化する。また、製剤の粘着力が強くなりすぎるために剥がす時に痛みが生じたりして皮膚刺激が生じ好ましくない。
賦形剤としては例えば、カオリン、酸化チタン、無水ケイ酸、酸化亜鉛、ベントナイト等を単独又は2種以上の組み合わせで用いることができる。
架橋剤としては例えば、乾燥水酸化アルミニウムゲル、合成ケイ酸アルミニウム、ジヒドロキシアルミニウムアミノアセテート、合成ヒドロタルサイト、メタケイ酸アルミン酸マグネシウム、ケイ酸アルミン酸マグネシウムなどの多価金属化合物等を単独又は2種以上の組み合わせで用いることができる。
清涼化剤は、ハッカ油、dl-カンファ、d-ボルネオール等が挙げられ、それらを単独で用いても2種以上を併用して用いてもよい。
また、本発明に係る膏体成分組成のpHは、皮膚刺激性の点からpH3.5~7.0の範囲が好ましく、pH4.0~6.0の範囲がより好ましい。
<薬物の溶解性試験>
ジクロフェナクナトリウム/クロタミトン/精製水を所定の比率で混合した各ジクロフェナクナトリウム主薬液中のジクロフェナクナトリウムの溶解性を目視で観察した(実施例1~11(S)及び比較例1~12(S))。結果をそれぞれ表1-1及び表1-2に示す。
クロタミトン20.0gにジクロフェナクナトリウム10.0g及び精製水10.0gを加えて均一に攪拌溶解し、本発明に係るジクロフェナクナトリウム主薬液(実施例1Sに相当)を調製した。70%D-ソルビトール液150gにカオリン30gを攪拌分散させてA液を調製した。また、濃グリセリン250g、カルメロースナトリウム40g、ポリアクリル酸部分中和物50g、ヒドロキシプロピルセルロース20.0g、ジヒドロキシアルミニウムアミノアセテート0.6gを攪拌分散させてB液を調製した。A液、20%ポリアクリル酸水溶液200.0g、本発明に係るジクロフェナクナトリウム主薬液、エデト酸ナトリウム0.8g、精製水191.6g、B液を順次添加して均一になるまで練合した。更にポリビニルアルコール8.0g、酒石酸5.0gを先ほどの含水ゲル中に均一になるように分散した。最後に1,3-ブチレングリコール10.0gにl-メントール2.5g、メチルパラベン1.0g、プロピルパラベン0.5gを溶解した後、この溶解液を先に調製した含水ゲル中に均一になるように分散し、貼付剤用膏体を得た。この膏体をポリエステル不織布上に展延し、膏体表面をポリプロピレンフィルムで被覆することにより水性貼付剤を成形した。
クロタミトン20.0gにジクロフェナクナトリウム10.0g及び精製水60.0gを加えて均一に攪拌溶解し、本発明に係るジクロフェナクナトリウム主薬液(実施例2Sに相当)を調製した。70%D-ソルビトール液 150gにカオリン30g、酸化チタン5.0gを攪拌分散させてA液を調製した。また、濃グリセリン250.0g、カルメロースナトリウム 40.0g、ポリアクリル酸部分中和物50.0g、ヒドロキシプロピルセルロース20.0g、ジヒドロキシアルミニウムアミノアセテート0.6gを攪拌分散させてB液を調製した。A液、20%ポリアクリル酸水溶液200.0g、本発明に係るジクロフェナクナトリウム主薬液、エデト酸ナトリウム0.8g、精製水136.6g、B液を順次添加して均一になるまで練合した。更にポリビニルアルコール8.0g、酒石酸5.0gを先ほどの含水ゲル中に均一になるように分散した。最後に1,3-ブチレングリコール10.0gにl-メントール 2.5g、メチルパラベン1.0g、プロピルパラベン0.5gを溶解した後、この溶解液を先に調製した含水ゲル中に均一になるように分散し、貼付剤用膏体を得た。この膏体をポリエステル不織布上に展延し、膏体表面をポリプロピレンフィルムで被覆することにより水性貼付剤を成形した。
クロタミトン40.0gにジクロフェナクナトリウム10.0g及び精製水20.0gを加えて均一に攪拌溶解し、本発明に係るジクロフェナクナトリウム主薬液(実施例3Sに相当)を調製した。70%D-ソルビトール液150.0gにカオリン30.0gを攪拌分散させてA液を調製した。また、濃グリセリン250.0g、カルメロースナトリウム 40.0g、ポリアクリル酸部分中和物50.0g、ヒドロキシプロピルセルロース30.0g、ジヒドロキシアルミニウムアミノアセテート 0.6gを攪拌分散させてB液を調製した。A液、20%ポリアクリル酸水溶液200.0g、本発明に係るジクロフェナクナトリウム主薬液、エデト酸ナトリウム0.8g、精製水151.6g、B液を順次添加して均一になるまで練合した。更にポリビニルアルコール8.0g、酒石酸 5.0gを先ほどの含水ゲル中に均一になるように分散した。最後に1,3-ブチレングリコール10.0gにl-メントール 2.5g、メチルパラベン1.5gを溶解した後、この溶解液を先に調製した含水ゲル中に均一になるように分散し、貼付剤用膏体を得た。この膏体をポリエステル不織布上に展延し、膏体表面をポリエステルフィルムで被覆することにより水性貼付剤を成形した。
クロタミトン20.0gにジクロフェナクナトリウム10.0g及び精製水20.0gを加えて均一に攪拌溶解し、本発明に係るジクロフェナクナトリウム主薬液(実施例4Sに相当)を調製した。70%D-ソルビトール液150.0gにカオリン30.0gを攪拌分散させてA液を調製した。また、濃グリセリン250.0g、カルメロースナトリウム40.0g、ポリアクリル酸部分中和物50.0g、ヒドロキシプロピルセルロース 20.0g、ジヒドロキシアルミニウムアミノアセテート0.4gを攪拌分散させてB液を調製した。A液、20%ポリアクリル酸水溶液200.0g、本発明に係るジクロフェナクナトリウム主薬液、エデト酸ナトリウム0.4g、精製水182.2g、B液を順次添加して均一になるまで練合した。更にポリビニルアルコール8.0g、酒石酸5.0gを先ほどの含水ゲル中に均一になるように分散した。最後に1,3-ブチレングリコール10.0gにl-メントール2.5g、メチルパラベン1.0g、プロピルパラベン0.5gを溶解した後、この溶解液を先に調製した含水ゲル中に均一になるように分散し、貼付剤用膏体を得た。この膏体をポリエステル不織布上に展延し、膏体表面をポリプロピレンフィルムで被覆することにより水性貼付剤を成形した。
実施例1のジクロフェナクナトリウム主薬液(実施例1S)調製時に添加していた精製水10.0gを抜いて攪拌し、ジクロフェナクナトリウムが未溶解の状態で分散しているジクロフェナクナトリウム主薬液(比較例1Sに相当)を調製した。その後の作製方法は実施例1と同じとし、貼付剤用膏体を得た。この膏体をポリエステル不織布上に展延し、膏体表面をポリエステルフィルムで被覆することにより水性貼付剤を成形した。
実施例1のジクロフェナクナトリウム主薬液(実施例1S)調製時に添加していたクロタミトン20.0gを抜き、かわりに精製水を20.0g増量して攪拌し、ジクロフェナクナトリウムが未溶解の状態で分散しているジクロフェナクナトリウム主薬液(比較例2Sに相当)を調製した。その後の作製方法は実施例1と同じとし、貼付剤用膏体を得た。この膏体をポリエステル不織布上に展延し、膏体表面をポリプロピレンフィルムで被覆することにより水性貼付剤を成形した。
プロピレングリコール30.0gにジクロフェナクナトリウム10.0gを加えて均一に攪拌溶解し、ジクロフェナクナトリウム主薬液(比較例9Sに相当)を調製した。濃グリセリン180.0g、カルメロースナトリウム40.0g、ポリアクリル酸部分中和物 20.0g、ポリアクリル酸ナトリウム20.0g、メタケイ酸アルミン酸マグネシウム1.5g、乾燥水酸化アルミニウムゲル0.2gを攪拌分散させてA液を調製した。A液、70%D-ソルビトール液250.0g、ジクロフェナクナトリウム主薬液、エデト酸ナトリウム0.5g、精製水390.8gを順次添加して均一になるまで練合した。更にポリビニルアルコール40.0g、酒石酸3.0gを先ほどの含水ゲル中に均一になるように分散した。最後に1,3-ブチレングリコール10.0gにl-メントール2.5g、メチルパラベン1.0g、プロピルパラベン0.5gを溶解した後、この溶解液を先に調製した含水ゲル中に均一になるように分散し、貼付剤用膏体を得た。この膏体をポリエステル不織布上に展延し、膏体表面をポリエステルフィルムで被覆することにより水性貼付剤を成形した。
ラウロマクロゴール20.0gにジクロフェナクナトリウム10.0g及びアジピン酸ジイソプロピル10.0g、クロタミトン5.0gを加えて均一に攪拌溶解し、ジクロフェナクナトリウム主薬液(比較例10Sに相当)を調製した。濃グリセリン250.0g、カルメロースナトリウム40.0g、ポリアクリル酸ナトリウム60.0g、ヒドロキシプロピルセルロース5.0g、ジヒドロキシアルミニウムアミノアセテート1.2gを攪拌分散させてA液を調製した。A液、l-メントール2.5g、メチルパラベン1.0g、プロピルパラベン0.5g、20%ポリアクリル酸水溶液80.0g、ジイソプロパノールアミン10.0g、70%D-ソルビトール液180.0g、ジクロフェナクナトリウム主薬液、エデト酸ナトリウム0.8g、及び精製水308.0gを順次添加して均一になるまで練合した。更にポリビニルアルコール13.0g、酒石酸3.0gを先ほどの含水ゲル中に均一になるように分散し、貼付剤用膏体を得た。この膏体をポリエステル不織布上に展延し、膏体表面をポリエステルフィルムで被覆することにより水性貼付剤を成形した。
N-メチル-2-ピロリドン20.0gにジクロフェナクナトリウム10.0gを加えて均一に攪拌溶解し、ジクロフェナクナトリウム主薬液(比較例11Sに相当)を調製した。濃グリセリン180.0g、カルメロースナトリウム40.0g、ポリアクリル酸部分中和物20.0g、ポリアクリル酸ナトリウム20.0g、メタケイ酸アルミン酸マグネシウム1.5g、乾燥水酸化アルミニウムゲル0.2gを攪拌分散させてA液を調製した。A液、70%D-ソルビトール液250.0g、ジクロフェナクナトリウム主薬液、エデト酸ナトリウム0.5g、精製水400.8gを順次添加して均一になるまで練合した。更にポリビニルアルコール40.0g、酒石酸3.0gを先ほどの含水ゲル中に均一になるように分散した。最後に1,3-ブチレングリコール10.0gにl-メントール2.5g、メチルパラベン1.5gを溶解した後、この溶解液を先に調製した含水ゲル中に均一になるように分散し、貼付剤用膏体を得た。この膏体をポリエステル不織布上に展延し、膏体表面をポリエステルフィルムで被覆することにより水性貼付剤を成形した。
ジクロフェナクナトリウム10.0gにオレイン酸20.0gとクロタミトン20.0gを加えて均一に攪拌溶解し、ジクロフェナクナトリウム主薬液(比較例12Sに相当)を調製した。70%D-ソルビトール液150.0gにカオリン30.0gを攪拌分散させてA液を調製した。また、濃グリセリン250.0g、カルメロースナトリウム40.0g、ポリアクリル酸部分中和物 50.0g、ヒドロキシプロピルセルロース20.0g、ジヒドロキシアルミニウムアミノアセテート0.4gを攪拌分散させてB液を調製した。A液、20%ポリアクリル酸水溶液200.0g、ジクロフェナク主薬液、エデト酸ナトリウム0.4g、精製水182.2g、B液を順次添加して均一になるまで練合した。更にポリビニルアルコール8.0g、酒石酸5.0gを先ほどの含水ゲル中に均一になるように分散した。最後に1,3-ブチレングリコール10.0gにl-メントール 2.5g、メチルパラベン1.0g、プロピルパラベン0.5gを溶解した後、この溶解液を先に調製した含水ゲル中に均一になるように分散し、貼付剤用膏体を得た。この膏体をポリエステル不織布上に展延し、膏体表面をポリプロピレンフィルムで被覆することにより水性貼付剤を成形した。
<膏体中のジクロフェナクナトリム結晶の析出有無の確認>
実施例1~4、比較例1~2、9~11及び12について20℃の条件下で24時間放置した後と40℃の条件下で2ヶ月放置した後の膏体中のジクロフェナクナトリウム結晶の析出有無を偏光顕微鏡にて観察した。観察した結果を表4に示す。
<薬物のラット皮膚透過性試験>
実施例1~4及び比較例1~2、9~11及び12について、ヘアレスラット皮膚を用いてジクロフェナクナトリウムの皮膚透過性を評価した。ヘアレスラット背部皮膚を剥離し、真皮側をレセプター層側にして、37℃の温水を外周部に循環させたフランツ型セル(1.77cm2, 10mL)に装着した。角質層側に製剤を貼付し、レセプター層にはpH7.4のリン酸緩衝溶液(PBS)を用いて、経時的にレセプター溶液のサンプリングを行った。各時間毎にサンプリングされたレセプター溶液について、高速液体クロマトグラフ法により透過したジクロフェナクナトリウム量を定量した。得られたデータより単位時間かつ単位面積当たりの皮膚透過速度を算出し、実施例1~4及び比較例1~2、9~11及び12の2時間目及び24時間目の皮膚透過速度を求めた結果を表5に示す。
また本実施例3と比較例9~11については、ヘアレスラットの皮膚を透過したジクロフェナクナトリウムの皮膚透過速度と時間との関係を図1に示す。
<製剤中の薬物安定性>
実施例1~4及び比較例1~2、9~11及び12より得られたジクロフェナクナトリウム水性貼付剤を遮光性の気密容器に入れ、温度40℃の条件下で1ヶ月及び2ヶ月間保存した。各測定日に保存条件下から取り出し、メタノール加熱還流抽出を行った。十分に冷却後、抽出液を液体クロマトグラフィー法にて測定し、製剤中のジクロフェナクナトリウム濃度を測定した結果を表6に示す。
Claims (5)
- ジクロフェナクナトリウム含有水性貼付剤において、クロタミトン/ジクロフェナクナトリウムの配合比率が8.0以下で、かつ(水+クロタミトン)/ジクロフェナクナトリウムの配合比率が3.0~20.0の範囲で混合して得られるジクロフェナクナトリウムの均一な混合溶液を膏体に配合してなる該ジクロフェナクナトリウム含有水性貼付剤。
- 膏体重量当たり5%を越えないジクロフェナクナトリウムと5%を越えないクロタミトンを含有してなるジクロフェナクナトリウム含有水性貼付剤において、クロタミトン/ジクロフェナクナトリウムの配合比率が8.0以下で、かつ(水+クロタミトン)/ジクロフェナクナトリウムの配合比率が3.0~20.0の範囲で混合して得られるジクロフェナクナトリウムの均一な混合溶液を膏体に配合してなる該ジクロフェナクナトリウム含有水性貼付剤。
- クロタミトン配合量が膏体重量当たり1.5~5%である請求項1又は2に記載のジクロフェナクナトリウム含有水性貼付剤。
- クロタミトン、ジクロフェナクナトリウム及び水を、クロタミトン/ジクロフェナクナトリウムの配合比率が8.0以下で、かつ(水+クロタミトン)/ジクロフェナクナトリウムの配合比率が3.0~20.0の範囲で混合し、ジクロフェナクナトリウムの均一な混合溶液を得、次いでこの溶液に常法により他の膏体成分を配合し、そして得られた膏体組成物(膏体)を支持体上に展延することを特徴とするジクロフェナクナトリウム含有水性貼付剤の製造法。
- クロタミトン、ジクロフェナクナトリウム及び水を、クロタミトン/ジクロフェナクナトリウムの配合比率が8.0以下で、かつ(水+クロタミトン)/ジクロフェナクナトリウムの配合比率が3.0~20.0の範囲で混合し、ジクロフェナクナトリウムの均一な混合溶液を得、次いでこの溶液に常法により他の膏体成分を配合し、膏体重量当たり5%を越えないジクロフェナクナトリウムと5%を越えないクロタミトンを含有してなる膏体組成物を得、これを支持体上に展延することを特徴とするジクロフェナクナトリウム含有水性貼付剤の製造法。
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2010309050A AU2010309050B2 (en) | 2009-10-23 | 2010-10-19 | Aqueous Patches Containing Diclofenac Sodium |
CA2778009A CA2778009C (en) | 2009-10-23 | 2010-10-19 | Aqueous patches containing diclofenac sodium |
US13/502,558 US9168235B2 (en) | 2009-10-23 | 2010-10-19 | Aqueous patches containing diclofenac sodium |
ES10824907.9T ES2457519T3 (es) | 2009-10-23 | 2010-10-19 | Pasta a base de agua que contiene diclofenaco sódico |
KR1020127011029A KR101727347B1 (ko) | 2009-10-23 | 2010-10-19 | 디클로페낙 나트륨 함유 수성 패치 |
EP10824907.9A EP2491924B8 (en) | 2009-10-23 | 2010-10-19 | Aqueous patches containing diclofenac-sodium |
CN2010800490585A CN102596195B (zh) | 2009-10-23 | 2010-10-19 | 含有双氯芬酸钠的水性贴剂 |
HK13101111.7A HK1173965A1 (en) | 2009-10-23 | 2013-01-25 | Aqueous patches containing diclofenac-sodium |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009-244518 | 2009-10-23 | ||
JP2009244518A JP5421063B2 (ja) | 2009-10-23 | 2009-10-23 | ジクロフェナクナトリウム含有水性貼付剤 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2011049058A1 true WO2011049058A1 (ja) | 2011-04-28 |
Family
ID=43900284
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2010/068311 WO2011049058A1 (ja) | 2009-10-23 | 2010-10-19 | ジクロフェナクナトリウム含有水性貼付剤 |
Country Status (11)
Country | Link |
---|---|
US (1) | US9168235B2 (ja) |
EP (1) | EP2491924B8 (ja) |
JP (1) | JP5421063B2 (ja) |
KR (1) | KR101727347B1 (ja) |
CN (1) | CN102596195B (ja) |
AU (1) | AU2010309050B2 (ja) |
CA (1) | CA2778009C (ja) |
ES (1) | ES2457519T3 (ja) |
HK (1) | HK1173965A1 (ja) |
TW (1) | TWI468192B (ja) |
WO (1) | WO2011049058A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014009793A1 (en) | 2012-07-11 | 2014-01-16 | Glycores 2000 S.R.L. | Diclofenac solution for external use |
WO2023180792A1 (en) | 2022-03-25 | 2023-09-28 | Glycores 2000 Srl | Topical pharmaceutical composition with anti-inflammatory and analgesic activity and uses thereof |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6449554B2 (ja) * | 2014-03-30 | 2019-01-09 | 小林製薬株式会社 | 外用医薬組成物 |
JP6580305B2 (ja) * | 2014-03-30 | 2019-09-25 | 小林製薬株式会社 | 外用医薬組成物 |
CN106770747A (zh) * | 2016-12-09 | 2017-05-31 | 广州迈达康医药科技有限公司 | 一种他克莫司制剂评价方法 |
CN108210929A (zh) * | 2016-12-21 | 2018-06-29 | 北京泰德制药股份有限公司 | 一种含有依托考昔的药物组合物及其制备方法 |
JP2020066592A (ja) * | 2018-10-24 | 2020-04-30 | 帝國製薬株式会社 | 水性貼付剤 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04217925A (ja) * | 1990-03-27 | 1992-08-07 | Nippon Saafuakutanto Kogyo Kk | 新規な解熱消炎鎮痛剤組成物 |
JPH0532544A (ja) | 1991-07-26 | 1993-02-09 | Ss Pharmaceut Co Ltd | ジクロフエナクナトリウム貼付剤 |
JPH06219940A (ja) * | 1993-01-27 | 1994-08-09 | Shiseido Co Ltd | 貼付剤 |
JPH0789853A (ja) | 1993-09-24 | 1995-04-04 | Shiseido Co Ltd | 貼付剤 |
JPH11222443A (ja) | 1997-11-11 | 1999-08-17 | Saitama Daiichi Seiyaku Kk | 経皮吸収促進組成物および経皮吸収製剤 |
WO2004071499A1 (ja) | 2003-02-12 | 2004-08-26 | Teika Pharmaceutical Co., Ltd. | ジクロフェナク含有貼付剤 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1249968A (en) * | 1984-04-05 | 1989-02-14 | Kazuo Kigasawa | Ointment base |
US6698162B2 (en) * | 2000-03-23 | 2004-03-02 | Teikoku Pharma Usa, Inc. | Methods of producing a terminally sterilized topical patch preparation |
KR20020012978A (ko) * | 2000-08-10 | 2002-02-20 | 이영길 | 진통소염 효과를 갖는 디클로페낙염을 함유 카타플라스마제 |
BRPI0210074B1 (pt) | 2001-05-31 | 2017-05-30 | Hisamitsu Pharmaceutical Co | emplastro de anti-inflamatórios não esteroidais percutaneamente absorvível, contendo sais de amônio, promotores de permeação e/ou agentes de solubilização em uma camada de substrato adesivo |
JP4157018B2 (ja) * | 2003-11-10 | 2008-09-24 | 久光製薬株式会社 | 消炎鎮痛貼付剤 |
JP4764337B2 (ja) * | 2004-04-23 | 2011-08-31 | 久光製薬株式会社 | 消炎鎮痛貼付剤 |
TWI414320B (zh) * | 2004-05-13 | 2013-11-11 | Hisamitsu Pharmaceutical Co | 含有非類固醇系消炎鎮痛劑之外用經皮製劑 |
JP4678532B2 (ja) | 2004-11-05 | 2011-04-27 | リードケミカル株式会社 | 非ステロイド消炎鎮痛薬を含有する非水系経皮吸収製剤 |
CN102698278B (zh) | 2006-12-06 | 2014-02-12 | 尼普洛外用药品株式会社 | 外用药物组合物及贴剂 |
-
2009
- 2009-10-23 JP JP2009244518A patent/JP5421063B2/ja active Active
-
2010
- 2010-10-14 TW TW99135070A patent/TWI468192B/zh active
- 2010-10-19 US US13/502,558 patent/US9168235B2/en active Active
- 2010-10-19 KR KR1020127011029A patent/KR101727347B1/ko active IP Right Grant
- 2010-10-19 CA CA2778009A patent/CA2778009C/en active Active
- 2010-10-19 EP EP10824907.9A patent/EP2491924B8/en active Active
- 2010-10-19 ES ES10824907.9T patent/ES2457519T3/es active Active
- 2010-10-19 AU AU2010309050A patent/AU2010309050B2/en active Active
- 2010-10-19 CN CN2010800490585A patent/CN102596195B/zh active Active
- 2010-10-19 WO PCT/JP2010/068311 patent/WO2011049058A1/ja active Application Filing
-
2013
- 2013-01-25 HK HK13101111.7A patent/HK1173965A1/xx unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04217925A (ja) * | 1990-03-27 | 1992-08-07 | Nippon Saafuakutanto Kogyo Kk | 新規な解熱消炎鎮痛剤組成物 |
JPH0532544A (ja) | 1991-07-26 | 1993-02-09 | Ss Pharmaceut Co Ltd | ジクロフエナクナトリウム貼付剤 |
JPH06219940A (ja) * | 1993-01-27 | 1994-08-09 | Shiseido Co Ltd | 貼付剤 |
JPH0789853A (ja) | 1993-09-24 | 1995-04-04 | Shiseido Co Ltd | 貼付剤 |
JPH11222443A (ja) | 1997-11-11 | 1999-08-17 | Saitama Daiichi Seiyaku Kk | 経皮吸収促進組成物および経皮吸収製剤 |
WO2004071499A1 (ja) | 2003-02-12 | 2004-08-26 | Teika Pharmaceutical Co., Ltd. | ジクロフェナク含有貼付剤 |
Non-Patent Citations (1)
Title |
---|
See also references of EP2491924A4 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014009793A1 (en) | 2012-07-11 | 2014-01-16 | Glycores 2000 S.R.L. | Diclofenac solution for external use |
WO2023180792A1 (en) | 2022-03-25 | 2023-09-28 | Glycores 2000 Srl | Topical pharmaceutical composition with anti-inflammatory and analgesic activity and uses thereof |
Also Published As
Publication number | Publication date |
---|---|
JP2011088862A (ja) | 2011-05-06 |
EP2491924A4 (en) | 2013-04-10 |
ES2457519T3 (es) | 2014-04-28 |
EP2491924A1 (en) | 2012-08-29 |
CN102596195B (zh) | 2013-10-30 |
KR20120093239A (ko) | 2012-08-22 |
EP2491924B8 (en) | 2014-06-11 |
US20120207814A1 (en) | 2012-08-16 |
CA2778009C (en) | 2016-08-30 |
AU2010309050B2 (en) | 2014-04-17 |
CA2778009A1 (en) | 2011-04-28 |
HK1173965A1 (en) | 2013-05-31 |
TW201124177A (en) | 2011-07-16 |
EP2491924B1 (en) | 2014-03-26 |
AU2010309050A1 (en) | 2012-05-10 |
TWI468192B (zh) | 2015-01-11 |
CN102596195A (zh) | 2012-07-18 |
US9168235B2 (en) | 2015-10-27 |
KR101727347B1 (ko) | 2017-04-14 |
JP5421063B2 (ja) | 2014-02-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2387394B1 (en) | Transdermal administration of tamsulosin | |
JP5421063B2 (ja) | ジクロフェナクナトリウム含有水性貼付剤 | |
JP5581080B2 (ja) | 外用貼付剤 | |
TW201609200A (zh) | 含水型貼劑 | |
JP6843622B2 (ja) | パップ剤 | |
KR101606950B1 (ko) | 케토프로펜리신염을 함유하는 수성 첩부제 | |
TWI803469B (zh) | 水性貼附劑 | |
KR101819249B1 (ko) | 케토프로펜 함유 수성 첩부제 | |
JPH0662401B2 (ja) | ケトプロフエン含有パツプ剤 | |
JP5319950B2 (ja) | 塩酸ブテナフィン含有水性貼付剤 | |
JP7228527B2 (ja) | ルパタジン含有貼付剤 | |
JP2001302503A (ja) | 貼付剤 | |
CN104367566A (zh) | 一种吲哚美辛巴布剂及其组合物 | |
JP2002029971A (ja) | インドメタシン水溶性貼付剤 | |
JP2002029970A (ja) | 貼付剤 | |
TW201332592A (zh) | 經皮吸收型製劑 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 201080049058.5 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 10824907 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2778009 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2010309050 Country of ref document: AU Ref document number: 13502558 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2010824907 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 20127011029 Country of ref document: KR Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2010309050 Country of ref document: AU Date of ref document: 20101019 Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 4387/CHENP/2012 Country of ref document: IN |