WO2015129808A1 - ケトプロフェン含有パップ剤 - Google Patents
ケトプロフェン含有パップ剤 Download PDFInfo
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- WO2015129808A1 WO2015129808A1 PCT/JP2015/055616 JP2015055616W WO2015129808A1 WO 2015129808 A1 WO2015129808 A1 WO 2015129808A1 JP 2015055616 W JP2015055616 W JP 2015055616W WO 2015129808 A1 WO2015129808 A1 WO 2015129808A1
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- mass
- ketoprofen
- knitted fabric
- poultice
- cataplasm
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- 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
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K31/12—Ketones
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- 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
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- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- 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
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- 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
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
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- 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 ketoprofen-containing poultice.
- Non-steroidal anti-inflammatory analgesics such as ketoprofen have excellent anti-inflammatory and analgesic effects, so various forms such as patches, gels, creams, ointments, liniments, etc., such as poultices and plasters. It is contained in skin preparations as a medicinal ingredient.
- a transdermal preparation containing a non-steroidal anti-inflammatory analgesic agent which is a photosensitive compound, is used as an active ingredient, photosensitivity may rarely appear as a side effect.
- Skin irritation such as photosensitivity is an erythema with itchiness, rash, or irritation caused by exposure of a photosensitive compound such as ketoprofen to ultraviolet rays.
- a photosensitive compound such as ketoprofen
- a ketoprofen-containing tape preparation (see Patent Document 1) containing an ultraviolet absorbent having a high skin transferability, and a patch comprising a support subjected to an ultraviolet shielding process ( Attempts have been made to develop (see Patent Document 2). It is considered that the occurrence of side effects such as photosensitivity can be suppressed by suppressing the photodegradation of ketoprofen and suppressing the formation of a degradation product of ketoprofen.
- a poultice has a higher water content compared to a tape agent, so that the cooling effect is stronger.
- a cataplasm has a lower drug absorption rate than a tape agent.
- a means of increasing the content of ketoprofen in the poultice can be considered.
- increasing the ketoprofen content may increase the probability of side effects. Therefore, an object of the present invention is to provide a ketoprofen-containing cataplasm having an excellent pharmacological action and capable of suppressing the occurrence of side effects.
- the present inventors have examined a ketoprofen-containing cataplasm. As a result, the present inventors have found that the amount of ketoprofen permeated through the skin does not increase with a poultice that merely increases the content of ketoprofen in the conventional poultice composition. In addition, the present inventor can increase the ketoprofen content and blend propylene glycol so that the skin permeation amount of ketoprofen in the poultice can be equal to or more than the skin permeation amount of ketoprofen in the tape preparation. Found.
- BM-DBM 4-tert-butyl-4′-methoxydibenzoylmethane
- the present invention is a cataplasm comprising a support and a paste layer on the support, wherein the paste layer is 1.5 to 2.5 based on the total mass of the paste layer.
- a cataplasm comprising: wt% ketoprofen, 1.5-2.5 wt% 4-tert-butyl-4′-methoxydibenzoylmethane and 12-18 wt% propylene glycol.
- the plaster layer preferably further contains 12 to 18% by mass of D-sorbitol based on the total mass of the plaster layer.
- D-sorbitol enhances the effect of 4-tert-butyl-4'-methoxydibenzoylmethane and further suppresses photolysis of ketoprofen.
- the support is preferably a knitted fabric having a thickness of 450 to 650 ⁇ m.
- the skin permeability of ketoprofen is improved, an excellent pharmacological action can be achieved, and the expression of skin irritation and the like can be suppressed.
- ketoprofen-containing cataplasm which is an embodiment of the present invention will be described in detail below.
- skin symptom means skin irritation caused by ketoprofen and appearing as photosensitivity.
- the ketoprofen-containing poultice which is an embodiment of the present invention is a poultice comprising a support and a paste layer on the support, and the paste layer is based on the total mass of the paste layer.
- BM-DBM 4-tert-butyl-4′-methoxydibenzoylmethane
- a nonwoven fabric or a knitted fabric is preferable, and a nonwoven fabric or a knitted fabric having a predetermined elongation recovery rate is particularly preferable.
- the elongation recovery rate is a value measured according to “JIS L 1096: 2010 Fabric and knitted fabric test method”.
- Use of a nonwoven fabric or a knitted fabric having a predetermined elongation recovery rate is preferable because the support expands and contracts according to the movement of the application site when it is applied to a movable part such as a joint.
- the elongation recovery rate after 50% elongation may be 70 to 90%, or 73 to 98%.
- a knitted fabric When a knitted fabric is used as the support, for example, a knitted fabric that is processed into a cloth shape by gathering the stitches by round knitting, warp knitting, weft knitting, or the like can also be used.
- the knitted fabrics are roughly classified into weft knitted fabrics and warp knitted fabrics.
- Flat knitted fabrics (knitted fabric, jersey), rubber knitted fabric (rib knitted fabric), pearl knitted fabric (garter knitted fabric) And smooth knitting (double-sided knitting).
- Examples of the warp knitted fabric include denby knitting, bandai knitting, cord knitting, atlas knitting, and multi-axis insertion knitting. Any of these knitted fabrics is preferably used, but a flat knitted fabric is particularly preferred.
- the knitted fabric include a knitted fabric formed by combining one or more materials such as polyester, nylon, polypropylene, and rayon. Among them, polyethylene terephthalate having little interaction with a drug is used. A knitted fabric as a material is more preferable.
- the support is a knitted fabric or a nonwoven fabric
- the basis weight of the knitted fabric is preferably 80 to 150 g / m 2 , and more preferably 95 to 125 g / m 2 .
- the knitted fabric preferably has a 50% modulus (load at 50% elongation) of 2 to 8 N / 5 cm in the course direction and a 50% modulus in the wale direction of 2 to 12 N / 5 cm.
- the course direction and the wale direction in the knitted fabric will be described with reference to FIGS. 1 and 2.
- FIG. 1 is a perspective view showing a course direction and a wale direction in a weft knitted fabric
- FIG. 2 is a perspective view showing a course direction and a wale direction in a warp knitted fabric.
- the direction represented by X in FIGS. 1 and 2 is the course direction, which means the weft direction of the knitted fabric.
- 1 and 2 is the wale direction, which means the warp direction of the knitted fabric.
- the modulus is measured according to JIS L 1096: 2010. If the modulus is 50% modulus lower than 2 N / 5 cm in the course direction or the wale direction, the knitted fabric may extend when the plaster is applied, and the adhesive may soak into the knitted fabric. Further, if the 50% modulus of the knitted fabric is higher than 8 N / 5 cm in the course direction or 12 N / 5 cm in the wale direction, the stretchability is inferior, and it may be difficult to follow the stretching of the skin when applied to the bent portion.
- the 50% elongation modulus of the knitted fabric in the state where the 50% elongation modulus of the knitted fabric is wound into a roll before being cut into a size to be used as a support, it is 2 to 12 N / in the longitudinal direction (also referred to as the major axis direction). 5 cm and preferably 2 to 8 N / 5 cm in the lateral direction (also referred to as the minor axis direction or the width direction) (the method for measuring the 50% elongation modulus is according to JIS L 1096: 2010). If the 50% elongation modulus in at least one of the machine direction and the machine direction is lower than 2 N / 5 cm, the knitted fabric may be stretched when the plaster is applied, the adhesive soaks into the knitted fabric, and the function as a poultice may be reduced.
- the stretchability is inferior, and it may be difficult to follow the elongation of the skin when applied to the bent portion. .
- plaster of the present invention By spreading the plaster of the present invention on such a knitted fabric, it can be applied for a longer time.
- the support is preferably a rubber knitted double-sided knitted fabric, particularly preferably having a basis weight of 95 to 125 g / m 2 and a thickness of 450 to 650 ⁇ m.
- the rubber knitted fabric has basically no front and back because the front and back are knitted in the course direction.
- examples of the change structure of the rubber knitting include a single knitting knitting and a double knitting knitting.
- a rubber knitted fabric can be suitably used as a support from the viewpoint of excellent stretchability and improved anchoring properties of the pressure-sensitive adhesive layer.
- the rubber knitting may be a circular knitting or a flat knitting. Rubber knitted fabrics tend to have excellent lateral stretchability. Moreover, when the thickness of the knitted fabric is within the above range, the stretchability and flexibility of the poultice are more excellent.
- a poultice using such a knitted fabric as a support can be applied for a longer time.
- the plaster liquid is spread on the knitted fabric, it is preferably spread so that the range in which the plaster enters the knitted fabric is in the range of 23 to 40% of the thickness direction of the knitted fabric.
- the penetration of the plaster in the knitted fabric is within the above range, moisture in the plaster liquid does not ooze out from the surface opposite to the surface in contact with the plaster layer of the support.
- the poultice obtained by spreading by the above method exhibits an ODT (occlusive dressing technique) effect, thereby further improving the skin permeability of ketoprofen and the skin transferability of BM-DBM.
- the plaster layer according to this embodiment is an aqueous plaster containing ketoprofen, BM-DBM, and propylene glycol.
- the mass of the plaster layer of the poultice is preferably 320 to 650 g / m 2 , and more preferably 380 to 550 g / m 2 .
- the mass of the plaster layer is 320 to 650 g / m 2 , the fit is good and the adhesion for a longer period can be improved. If the mass of the plaster layer is within the above range, the thickness of the entire poultice can be reduced.
- the thickness of the plaster layer according to this embodiment is preferably 0.4 to 1.0 mm, more preferably 0.5 to 0.8 mm, and preferably 0.6 to 0.7 mm. Further preferred.
- the thickness of the plaster layer according to the present embodiment may be 0.2 to 1.0 mm, 0.3 to 0.8 mm, or 0.4 to 0.7 mm. Also good. Even if the thickness of the entire poultice is 1.0 mm or less, it is easy to follow the skin, and the difference in height due to the thickness of the poultice becomes small when applied to the skin. It tends to be difficult to peel off.
- ketoprofen means a compound represented by the chemical formula (1) or a pharmaceutically acceptable salt thereof.
- Ketoprofen exists in two optical isomers, R-form and S-form.
- the ketoprofen according to the present embodiment may use either one of the optical isomers, or may be used by mixing two kinds of optical isomers in an arbitrary ratio.
- ketoprofen examples include inorganic salts such as sodium salt, potassium salt and calcium salt; amine salts such as monoethanolamine and diethanolamine.
- the ketoprofen content is 1.5 to 2.5% by mass and 1.8 to 2.2% by mass based on the mass of the entire plaster layer. It is preferable.
- BM-DBM 4-tert-butyl-4′-methoxydibenzoylmethane
- the content of BM-DBM is 1 to 5% by mass, preferably 1 to 3% by mass, based on the mass of the entire plaster layer. It is more preferably 5 to 2.5% by mass.
- the content of BM-DBM is 1% by mass or more, photodecomposition of ketoprofen due to irradiation with light such as ultraviolet rays can be suppressed.
- the content of propylene glycol is 5 to 20% by mass, preferably 10 to 20% by mass, based on the mass of the entire plaster layer, and preferably 12 to 18%. More preferably, it is more preferably 14 to 16% by mass.
- the content of propylene glycol is 5% by mass or more, the skin transferability of BM-DBM can be enhanced while exhibiting the pharmacological effect of ketoprofen.
- the propylene glycol content is 10% by mass or more, the skin transferability of BM-DBM can be further enhanced while exhibiting the pharmacological effect of ketoprofen.
- the ketoprofen-containing poultice according to this embodiment may further contain D-sorbitol.
- the content of D-sorbitol is 10 to 20% by mass, preferably 12 to 18% by mass, based on the total mass of the plaster layer. It is more preferable that it is 16 mass%.
- the content of D-sorbitol is 10% by mass or more, the skin transferability of BM-DBM can be further enhanced while exhibiting the pharmacological effect of ketoprofen.
- Other components may be further added to the paste layer.
- other components include pressure-sensitive adhesives, water-soluble polymers, solubilizers, antioxidants, humectants, cooling agents, inorganic powders, coloring agents, and flavoring agents.
- the pressure-sensitive adhesive is not particularly limited as long as it can increase the adhesion of the poultice, and those generally known to those skilled in the art can be used.
- an acrylate resin emulsion such as poly (methyl acrylate / 2-ethylhexyl acrylate) can be used.
- Ultrazol W-50 (trade name, manufactured by Aika Kogyo Co., Ltd.) ) Ultrasol series, Primal N-580NF (manufactured by Nippon Acrylic Chemical Co., Ltd., trade name), etc., and Nicazole TS-620 (Nihon Carbide Industries Co., Ltd., trade name) etc.
- blends BM-DBM of this embodiment can raise adhesiveness further by mix
- the water-soluble polymer is not particularly limited as long as it can retain moisture in the poultice, and those generally known to those skilled in the art can be used.
- Examples of the water-soluble polymer include sodium polyacrylate, partially neutralized polyacrylic acid, polyacrylic acid, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene oxide, polyvinyl methacrylate, sodium alginate, hydroxypropylcellulose, sodium carboxymethylcellulose, Examples thereof include methylcellulose and carrageenan, and one kind may be used alone, or two or more kinds may be used in combination.
- gelatin or polyvinyl alcohol is preferable.
- the content of the water-soluble polymer is preferably 1 to 40% by mass based on the mass of the entire plaster layer.
- the solubilizer is not particularly limited as long as it can dissolve a drug.
- examples thereof include crotamiton; N-methylpyrrolidone; polyalkylene glycol such as polyethylene glycol and polybutylene glycol; isopropyl myristate, diethyl adipate, poly
- fatty acid esters such as oxyalkylene sorbitan fatty acid esters.
- the content of the dissolving agent is preferably 0 to 30% by mass based on the mass of the entire plaster layer.
- antioxidants examples include phenol derivatives such as butylhydroxyanisole, dibutylhydroxytoluene, thymol, propyl gallate, tocopherol and its ester derivatives, ascorbic acid and its ester derivatives.
- the content of the antioxidant is preferably 0 to 10% by mass based on the mass of the entire plaster layer.
- the moisturizing agent is not particularly limited as long as it can suppress the evaporation of moisture from the paste layer over time.
- the humectant include polyhydric alcohols such as concentrated glycerin, ethylene glycol, polyethylene glycol, liquid paraffin, 1,3-propanediol (propylene glycol) and 1,4-butanediol (butylene glycol).
- polyhydric alcohols such as concentrated glycerin, ethylene glycol, polyethylene glycol, liquid paraffin, 1,3-propanediol (propylene glycol) and 1,4-butanediol (butylene glycol).
- One of these humectants may be used alone, or two or more thereof may be used in combination.
- concentrated glycerin is preferable.
- the content of the humectant is preferably 0 to 60% by mass based on the mass of the entire plaster layer.
- Examples of the refreshing agent include thymol, l-menthol, dl-menthol, l-isopulegol, and preferably 1-menthol.
- the content of the refreshing agent is preferably 0 to 15% by mass based on the mass of the entire plaster layer.
- the poultice may have a release liner.
- the release liner is laminated on the surface opposite to the support with respect to the plaster layer. When the release liner is provided, it is possible to suppress a decrease in the water content of the paste layer during storage, and to reduce adhesion of dust and the like to the paste layer.
- the material of the release liner is not particularly limited, and a liner generally known to those skilled in the art can be used.
- a liner generally known to those skilled in the art can be used.
- examples of the material include polyethylene, polypropylene, polybutylene, polyethylene terephthalate, rayon, polyurethane, fine paper, and cellulose derivatives, and one kind may be used alone. Two or more kinds may be used in combination.
- a material for the release liner a polypropylene film is preferable.
- the release liner may be embossed. When the release liner is embossed, it becomes difficult to shift laterally.
- the thickness of the release liner is preferably 20 to 100 ⁇ m.
- the poultice may be stored inside the pouch.
- a decrease in the water content of the paste layer can be suppressed, and adhesion of dust and the like to the paste layer can be reduced.
- Ketoprofen, BM-DBM and propylene glycol, and if necessary, D-sorbitol and other components are mixed and stirred for a certain time to obtain a paste.
- the obtained plaster is uniformly spread on the release liner so that the plaster mass per sheeting agent (14 cm ⁇ 10 cm) is a predetermined mass, the support is further laminated immediately, Prepare a poultice.
- the back skin of the hairless mouse was peeled off, and attached to a flow-through cell (0.785 cm 2 ) in which warm water at 37 ° C. was circulated around the outer periphery with the dermis side facing the receptor layer side.
- the cataplasm of Reference Example 1 or Comparative Example 1 was applied to the stratum corneum side, and sampling was performed at a rate of 0.8 mL / hour every 4 hours from the time of application to 24 hours later. In this test, physiological saline was used as the receptor layer.
- tape preparations of Comparative Example 2 and Reference Examples 2 to 8 were prepared by the methods well known to those skilled in the art using the components shown in Tables 2 and 3.
- a skin permeability test was conducted in the same manner using the tapes of Comparative Example 2 and Reference Examples 2 to 8 instead of the cataplasm.
- a woven fabric was used as the support, and the mass of the plaster layer was 1 g / 70 cm 2 .
- “SIS block copolymer” means a styrene-isoprene-styrene block copolymer
- “SBR rubber” means a styrene-butadiene copolymer.
- Table 4 shows the cumulative skin permeation amount ( ⁇ g / cm 2 ) of ketoprofen from the time of application to 24 hours after application of the cataplasm of Reference Example 1 and Comparative Example 1.
- the cataplasm of Comparative Example 1 had a smaller cumulative skin permeation amount than the tape of Comparative Example 2.
- the cataplasm of Reference Example 1 and Comparative Example 1 showed the same amount of cumulative skin permeation. Therefore, even when the ketoprofen content of the cataplasm of the comparative example 1 was increased, it became clear that the cumulative skin permeation amount did not increase.
- Hairless mouse skin permeability test (2) After mixing the components described in Table 5, the mixture was stirred for a certain time to obtain a paste liquid. The obtained paste liquid was uniformly spread on a release liner so that the paste mass per sheet (14 cm ⁇ 10 cm) of the poultice was 7 g, and then a non-woven fabric was immediately laminated to obtain Reference Example 9 And the cataplasms of Comparative Examples 3-7 were prepared. In preparing each cataplasm, the mass of the paste layer was 7 g / 140 cm 2 . The cumulative skin permeation amount was calculated in the same manner as in the hairless mouse skin permeability test (1) for the obtained cataplasm of Reference Example 9 and Comparative Examples 3 to 7 and the tape of Comparative Example 2.
- Table 6 shows the cumulative skin permeation amount ( ⁇ g / cm 2 ) of ketoprofen from the time of application to 24 hours after application for the cataplasm of Reference Example 9 and Comparative Examples 3 to 7 and the tape of Comparative Example 2. It was.
- the 24-hour cumulative skin permeation amount of ketoprofen was higher than the 24-hour cumulative skin permeation amount of ketoprofen when the tape agent of Comparative Example 2 was used.
- the cumulative skin permeation amount could not be measured.
- Example 2 After applying the poultice of Example 1 to the back skin of guinea pigs for 4 hours, the poultice was peeled off. The skin of the site to which the patch was applied was cut out, the skin piece was extracted with methanol, and the concentration of ketoprofen and BM-DBM ( ⁇ g / cm 2 ) in the obtained skin piece using high performance liquid chromatography (HPLC) was calculated. Further, the same operation was performed for the tape preparation containing 2% by mass of ketoprofen (Comparative Example 2), and the concentrations of ketoprofen and BM-DBM were calculated.
- HPLC high performance liquid chromatography
- Table 8 shows the concentrations of ketoprofen and BM-DBM for the cataplasm of Example 1 and the tape of Comparative Example 2.
- the intradermal concentration of ketoprofen when using the cataplasm of Example 1 was comparable to that when using the tape of Comparative Example 2.
- the intradermal concentration of BM-DBM when the cataplasm of Example 1 was used was higher than that when the tape of Comparative Example 2 was used. Therefore, it can be said that the cataplasm of Example 1 is superior to the tape of Comparative Example 2 in BM-DBM skin migration.
- Table 9 shows the average skin reaction score obtained according to the evaluation criteria of Sato et al.
- UVA (+) means that UVA was irradiated
- UVA ( ⁇ ) means that UVA was not irradiated.
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Abstract
Description
ケトプロフェン、BM-DBM及びプロピレングリコール、必要に応じてD-ソルビトール及びその他の成分を混合して、一定時間撹拌して膏体を得る。得られた膏体を、パップ剤(14cm×10cm)1枚当たりの膏体質量が所定の質量となるように、剥離ライナー上に均一に展延した後、直ちに支持体をさらに積層させて、パップ剤を調製する。
表1に記載の成分を混合した後、一定時間、撹拌して膏体を得た。得られた膏体を、パップ剤(14cm×10cm)1枚当たりの膏体質量が10gとなるように、剥離ライナー上に均一に展延した後、直ちに不織布をさらに積層させて、参考例1及び比較例1のパップ剤を調製した。なお、参考例1及び比較例1のパップ剤を調製するにあたり、膏体層の質量は、10g/140cm2とした。また、表1中、各成分の含有量は、膏体層全体の質量を基準とした含有量(質量%)で示した。
ヘアレスマウス背部皮膚を剥離し、真皮側をレセプター層側に向け、37℃の温水を外周部に循環させたフロースルーセル(0.785cm2)に装着した。角質層側に参考例1または比較例1のパップ剤を貼付し、0.8mL/時間の速さで、貼付時から24時間後までの4時間ごとにサンプリングを行った。本試験では、レセプター層として生理食塩水を使用した。
また、表2及び表3に記載の成分を用いて、当業者に周知の方法により、比較例2及び参考例2~8のテープ剤を調製した。パップ剤の代わりに比較例2及び参考例2~8のテープ剤を用いて、同様の操作により、皮膚透過性試験を行った。なお、比較例2及び参考例2~8のテープ剤を調製するにあたり、支持体として織布を使用し、膏体層の質量は、1g/70cm2とした。表2及び表3中、「SISブロック共重合体」とは、スチレン-イソプレン-スチレンブロック共重合体を意味し、「SBRゴム」とは、スチレン-ブタジエン共重合体を意味する。
表5に記載の成分を混合した後、一定時間、撹拌して膏体液を得た。得られた膏体液を、パップ剤1枚(14cm×10cm)当たりの膏体質量が7gとなるように、剥離ライナー上に均一に展延した後、直ちに不織布をさらに積層させて、参考例9及び比較例3~7のパップ剤を調製した。なお、各パップ剤を調製するにあたり、膏体層の質量は、7g/140cm2とした。
得られた参考例9及び比較例3~7のパップ剤、ならびに、比較例2のテープ剤について、ヘアレスマウス皮膚透過性試験(1)と同様にして、累積皮膚透過量をそれぞれ算出した。
表7に記載の成分を混合した後、一定時間、撹拌して膏体を得た。得られた膏体を、剥離ライナー上に均一に展延した後、直ちに不織布をさらに積層させて、実施例1のパップ剤を調製した。なお、実施例1のパップ剤を調製するにあたり、膏体層の質量は、7g/140cm2とした。また、アクリレート樹脂エマルジョン1として、ウルトラゾールW-50(アイカ工業(株)製、商品名)を使用し、アクリレート樹脂エマルジョン2として、ニカゾールTS-620(日本カーバイド工業(株)製、商品名)を使用した。
実施例1のパップ剤をモルモットの背部皮膚に4時間適用した後、パップ剤を剥離した。パップ剤を適用した部位の皮膚を切り取り、皮膚片をメタノールで抽出し、高速液体クロマトグラフィー(HPLC)を用いて、得られた皮膚片中のケトプロフェン及びBM-DBMの濃度(μg/cm2)を算出した。また、ケトプロフェンを2質量%含むテープ剤(比較例2)についても、同様の操作を行い、ケトプロフェン及びBM-DBMの濃度を算出した。
表7に記載の成分を混合した後、一定時間、撹拌して膏体を得た。得られた膏体を、剥離ライナー上に均一に展延した後、直ちに不織布をさらに積層させて、実施例2~8のパップ剤を調製した。なお、実施例2~8のパップ剤を調製するにあたり、膏体層の質量は、10g/140cm2とした。
得られたパップ剤のうち、実施例1、2について、モルモットを用いたAdjuvant and strip法(佐藤ら、西日本皮膚科,42,831-837(1980))を一部変更し、光感作性試験を行った。
すなわち、ハートレー系白色雌モルモット(一群6匹)の頚背部を除毛し、当該頚背部の2cm×2cmの正方形領域の4隅に、実施例1、2のパップ剤または比較例2のテープ剤を貼付し(光感作処置)、1時間後に長波長紫外線(以下、「UVA」ともいう、照射エネルギー:10J/cm2)を照射した。この光感作処置を、5日間連続して施した。光感作処置の開始日から3週間後に、当該モルモットの腰背部を除毛し、光感作処置を施した部位とは異なる2cm×2cmの正方形領域の4隅に、実施例1、2のパップ剤または比較例2のテープ剤を貼付し、1時間後にUVA(照射エネルギー:10J/cm2)を照射した(光惹起処置)。UVA照射時から24時間後及び48時間後の皮膚反応(紅斑及び浮腫)を、上記佐藤らの基準に従い評価した。
Claims (4)
- 支持体と、前記支持体上に膏体層を備えるパップ剤であって、
前記膏体層は、前記膏体層の全質量を基準として、1.5~2.5質量%のケトプロフェン、1.5~2.5質量%の4-tert-ブチル-4’-メトキシジベンゾイルメタン及び12~18質量%のプロピレングリコールを含む、パップ剤。 - 前記膏体層は、前記膏体層の全質量を基準として、12~18質量%のD-ソルビトールをさらに含む、請求項1に記載のパップ剤。
- 前記支持体は、厚みが450~650μmである編布である、請求項1に記載のパップ剤。
- 前記支持体は、厚みが450~650μmである編布である、請求項2に記載のパップ剤。
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US15/121,534 US9707194B2 (en) | 2014-02-27 | 2015-02-26 | Ketoprofen-containing poultice |
JP2016505295A JP6182257B2 (ja) | 2014-02-27 | 2015-02-26 | ケトプロフェン含有パップ剤 |
BR112016017949-8A BR112016017949B1 (pt) | 2014-02-27 | 2015-02-26 | Emplastro de gel contendo cetoprofeno |
EP15754904.9A EP3111932B1 (en) | 2014-02-27 | 2015-02-26 | Ketoprofen-containing poultice |
CN201580007148.0A CN105960234A (zh) | 2014-02-27 | 2015-02-26 | 含有酮洛芬的巴布剂 |
ES15754904T ES2724483T3 (es) | 2014-02-27 | 2015-02-26 | Emplasto que contiene ketoprofeno |
KR1020167020788A KR101852701B1 (ko) | 2014-02-27 | 2015-02-26 | 케토프로펜 함유 폴티스 |
SG11201606199SA SG11201606199SA (en) | 2014-02-27 | 2015-02-26 | Ketoprofen-containing poultice |
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WO2019006437A1 (en) * | 2017-06-30 | 2019-01-03 | Midas Green Technologies, Llc | ENHANCED APPROPER IMMERSION COOLING SYSTEM |
KR102022336B1 (ko) * | 2019-03-12 | 2019-09-18 | 주식회사 우신라보타치 | 국소 통증 완화 카타플라즈마 패치 |
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PH12016501469B1 (en) | 2016-08-22 |
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SG11201606199SA (en) | 2016-09-29 |
EP3111932B1 (en) | 2019-04-03 |
EP3111932A1 (en) | 2017-01-04 |
US9707194B2 (en) | 2017-07-18 |
KR101852701B1 (ko) | 2018-04-26 |
KR20160126981A (ko) | 2016-11-02 |
ES2724483T3 (es) | 2019-09-11 |
US20160361281A1 (en) | 2016-12-15 |
EP3111932A4 (en) | 2017-09-13 |
BR112016017949A2 (ja) | 2017-08-08 |
MY179230A (en) | 2020-11-02 |
CN105960234A (zh) | 2016-09-21 |
TWI630930B (zh) | 2018-08-01 |
BR112016017949B1 (pt) | 2023-02-07 |
PH12016501469A1 (en) | 2016-08-22 |
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