TW201306883A - External plaster containing loxoprofen natrium - Google Patents

External plaster containing loxoprofen natrium Download PDF

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TW201306883A
TW201306883A TW101125028A TW101125028A TW201306883A TW 201306883 A TW201306883 A TW 201306883A TW 101125028 A TW101125028 A TW 101125028A TW 101125028 A TW101125028 A TW 101125028A TW 201306883 A TW201306883 A TW 201306883A
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acid
higher fatty
weight
fatty acid
lactic acid
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TWI526227B (en
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Kazuha Tani
Katsuyuki Inoo
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Teikoku Seiyaku Kk
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703Transdermal 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
    • A61K9/7038Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/192Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Rheumatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pain & Pain Management (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present inventino provides an external plaster containing loxoprofen natrium wherein percutaneous absorption to main medicine is high, formation of degradation products of tablet under storage can be suppressed, and stability is high. The external plaster has an adhesive layer which contains 0.1-10wt% of loxoprofen natrium and is set on support medium. The adhesive layer contains 5-30wt% of styrene-isoprene-styrene block copolymer, 10-50wt% of alicyclic saturated hydrocarbon resin, 0.1-1wt% of lactic acid and 5-15wt% of higher fatty acid and mixing ratio of the lactic acid and the higher fatty acid in lactic acid/higher fatty acid is 1/50-1/5 in the external plaster.

Description

含有洛索普洛芬鈉之外用貼附劑 Adhesive containing loxoprofen sodium

本發明係有關一種含有洛索普洛芬鈉之貼附劑,尤其係有關一種顯示優良藥物釋放性,且含有具備高製劑穩定性之洛索普洛芬鈉之油性外用貼附劑。 The present invention relates to a patch containing loxoprofen sodium, and more particularly to an oily topical patch which exhibits excellent drug release properties and contains loxoprofen sodium having high formulation stability.

洛索普洛芬鈉係一種作為苯基丙酸系非類固醇消炎鎮痛劑而顯示優良消炎‧鎮痛效果的藥物,自昔至今,無論是水性貼附劑、油性貼附劑,已對作為外用劑的製劑化進行研究,而既已市售有泥罨劑(販售名稱:Loxonin pap)、及硬膏劑(販售名稱:Loxonin tape)。 Loxoprofen sodium is a drug that exhibits excellent anti-inflammatory and analgesic effects as a non-steroidal anti-inflammatory analgesic agent for phenylpropionic acid. Since the past, it has been used as an external preparation for both aqueous and oil-based adhesives. The formulation was studied and commercially available as a loach (available under the trade name: Loxonin pap) and a plaster (available under the trade name: Loxonin tape).

在摻混有洛索普洛芬等非類固醇系消炎鎮痛藥的貼附劑中,已嚐試藉由添加克羅他命酮、吡咯啶酮類、高級脂肪酸及脂肪酸酯等溶解劑、或L-薄荷醇、薄荷油、及DL-樟腦等清涼劑來提升經皮吸收性。尤其在油性基劑中摻混洛索普洛芬鈉時,由於洛索普洛芬鈉為水溶性,如以改善對油性基劑的溶解性為目的,係常見將上述各成分與洛索普洛芬鈉共同摻混在一起之實例。然而,此等溶解劑、或清涼劑中造成皮膚刺激之原因的物質、或促進製品中之洛索普洛芬鈉的分解的成分甚多,而造成問題。 In the patch of a non-steroidal anti-inflammatory analgesic such as loxoprofen, an attempt has been made to add a dissolving agent such as crothedine, pyrrolidone, a higher fatty acid or a fatty acid ester, or L. - Cooling agents such as menthol, peppermint oil, and DL-camphor to enhance transdermal absorbability. Especially when loxoprofen sodium is blended in an oily base, since loxoprofen sodium is water-soluble, for the purpose of improving the solubility of the oily base, it is common to combine the above components with Losop An example of the incorporation of sodium phloem. However, such a dissolving agent, or a substance which causes skin irritation in a cooling agent, or a component which promotes decomposition of loxoprofen sodium in a product, causes a problem.

舉例而言,專利文獻1中記載一種將以洛索普洛芬為首的非類固醇系消炎鎮痛藥,使用松香酯衍生物作為溶解劑,與L-薄荷醇共同和貼附劑摻混而成的硬膏劑。且專利文獻2中記載一種以苯乙烯-異戊二烯-苯乙烯嵌 段共聚物為基底基劑,並摻混克羅他命酮的含有洛索普洛芬之貼附劑。前者其特徵在於使用本來大多用作賦黏樹脂的松香酯衍生物作為洛索普洛芬鈉的溶解劑,而後者的特徵在於使用克羅他命酮作為主藥溶解劑,惟松香酯有皮膚致敏作用,當貼附製劑時會有對皮膚產生不良副作用的可能性。而另一方面克羅他命酮會破壞貼附劑的物性,使黏著力降低等對貼附劑造成不良影響,因此摻混此等添加劑對於貼附製劑而言較為不佳。 For example, Patent Document 1 describes a non-steroidal anti-inflammatory analgesic drug comprising loxoprofen, which is prepared by mixing a rosin ester derivative as a dissolving agent with L-menthol and a patch. A plaster. And Patent Document 2 describes a styrene-isoprene-styrene embedded The segment copolymer is a base agent and is incorporated with a dose of a dose of a dose of a dose of a rosopron. The former is characterized in that a rosin ester derivative which is mostly used as a tackifying resin is used as a solubilizing agent for loxoprofen sodium, and the latter is characterized in that crotheter ketone is used as a main drug solubilizing agent, but rosin ester has a skin. Sensitization, when attached to the preparation, may have adverse side effects on the skin. On the other hand, crotheter ketone destroys the physical properties of the patch, and the adhesion is reduced, which adversely affects the patch. Therefore, the blending of these additives is not preferable for the patch preparation.

另外,專利文獻3中記載一種摻混有吡咯啶酮化合物的含有洛索普洛芬之貼附劑,惟吡咯啶酮化合物係與克羅他命酮同樣容易使製劑的物性惡化,且吡咯啶酮化合物中亦有揮發性高之成分,與貼附劑摻混時在保存中揮發,而有經皮吸收性降低的可能性。 Further, Patent Document 3 describes a loxoprofen-containing patch containing a pyrrolidone compound, and the pyrrolidone compound is as easy to deteriorate the physical properties of the preparation as the pyrrolidone, and the pyrrolidine The ketone compound also has a highly volatile component, which volatilizes during storage when blended with the patch, and has a possibility of lowering the transdermal absorbability.

更者,專利文獻4中記載一種摻混萜有烯樹脂或松香系樹脂的含有洛索普洛芬之貼附劑,惟本貼附劑中的松香系樹脂係如前述,為一種皮膚致敏成分,會對肌膚造成不良影響。 Further, Patent Document 4 describes a loxoprofen-containing patch which is blended with an oxime resin or a rosin-based resin, but the rosin-based resin in the patch is as described above and is a skin sensitizer. Ingredients can have an adverse effect on the skin.

專利文獻5中揭示一種摻混有0.1~3重量%之脂肪族羥酸、以及0.1~5重量%之高級脂肪酸的含有洛索普洛芬之外用貼附劑。該外用貼附劑其特徵在於組合摻混脂肪族羥酸與高級脂肪酸作為主藥的溶解劑,而作為脂肪族羥酸實質上係選擇蘋果酸、或檸檬酸。使用此等脂肪族羥酸時,洛索普洛芬的溶解性不充分,係為一種在經皮吸收性方面存有問題之貼附劑。 Patent Document 5 discloses a patch containing loxoprofen in an amount of 0.1 to 3% by weight of an aliphatic hydroxy acid and 0.1 to 5% by weight of a higher fatty acid. The external patch is characterized by a combination of an aliphatic hydroxy acid and a higher fatty acid as a main solvent, and an aliphatic hydroxy acid is substantially selected from malic acid or citric acid. When such an aliphatic hydroxy acid is used, the solubility of loxoprofen is insufficient, and it is a patch which has a problem in percutaneous absorption.

如上所述,在油性基劑中摻混洛索普洛芬鈉時,針對主藥之溶解劑的選擇便極為困難,因此,現況在於尚未開發出一種兼備主藥的經皮吸收性與主藥的穩定性的含有洛索普洛芬之硬膏劑。 As described above, when the loxoprofen sodium is blended in the oily base, the selection of the dissolving agent for the main drug is extremely difficult, and therefore, the present situation has not yet developed a transdermal absorbability and main drug having both the main drug. The stability of the loxoprofen-containing plaster.

先前技術文獻 Prior technical literature 專利文獻 Patent literature

專利文獻1 國際公開WO93/04677號 Patent Document 1 International Publication WO93/04677

專利文獻2 日本特開2004-43512號公報 Patent Document 2 Japanese Patent Laid-Open Publication No. 2004-43512

專利文獻3 日本特開2008-163017號公報 Patent Document 3 Japanese Patent Laid-Open Publication No. 2008-163017

專利文獻4 日本特開2008-214337號公報 Patent Document 4 Japanese Patent Laid-Open Publication No. 2008-214337

專利文獻5 日本特開2011-20997號公報 Patent Document 5 Japanese Patent Laid-Open No. 2011-20997

因此,本發明係用以解決上述課題,茲以提供一種在含有洛索普洛芬鈉之貼附劑中,顯示主藥之高經皮吸收性,且對於保存中的製劑可抑制分解生成物的生成之穩定性高的外用貼附劑為課題。 Therefore, the present invention has been made to solve the above problems, and it is intended to provide a high transdermal absorbability of a main drug in a patch containing loxoprofen sodium, and to inhibit decomposition products for a preparation for preservation. The topical patch with high stability of formation is a problem.

本發明人等為解決前述課題而致力進行多次研究的結果發現,藉由作成一種外用貼附劑,係於支持體上設置含有洛索普洛芬鈉的黏著劑層的外用貼附劑,其中該黏著劑層分別以特定量含有作為主基劑之苯乙烯-異戊二烯-苯乙烯嵌段共聚物、作為對皮膚安全性高的賦黏劑之脂環族飽和烴樹脂、作為主藥溶解劑之乳酸及高級脂肪酸,便可使洛索普洛芬鈉穩定溶解於黏著劑基劑中, 並於保持洛索普洛芬鈉的高穩定性下提升經皮吸收性,終至完成本發明。 In order to solve the above-mentioned problems, the present inventors have made a number of studies, and found that an external patch is provided on the support by an external patch containing an adhesive layer of loxoprofen sodium. The adhesive layer contains a styrene-isoprene-styrene block copolymer as a main component in a specific amount, and an alicyclic saturated hydrocarbon resin which is a highly safe agent for skin, as a main component. Lactoprofen sodium is stably dissolved in the adhesive base by the lactic acid and higher fatty acids of the drug dissolver. The transdermal absorbability is improved while maintaining the high stability of loxoprofen sodium, and the present invention is completed.

因此,以本發明而言,作為其基本形態,係一種外用貼附劑,係於支持體上設置含有0.1~10重量%之洛索普洛芬鈉的黏著劑層的外用貼附劑,其中該黏著劑層含有5~30重量%之苯乙烯-異戊二烯-苯乙烯嵌段共聚物、10~50重量%之脂環族飽和烴樹脂、0.1~1重量%之乳酸、及5~15重量%之高級脂肪酸,且乳酸與高級脂肪酸的摻混比例為乳酸/高級脂肪酸=1/50~1/5。 Therefore, in the present invention, as a basic form thereof, a topical patch is an external patch for which an adhesive layer containing 0.1 to 10% by weight of loxoprofen sodium is provided on a support, wherein The adhesive layer contains 5 to 30% by weight of a styrene-isoprene-styrene block copolymer, 10 to 50% by weight of an alicyclic saturated hydrocarbon resin, 0.1 to 1% by weight of lactic acid, and 5~ 15% by weight of higher fatty acid, and the blending ratio of lactic acid to higher fatty acid is lactic acid/higher fatty acid = 1/50 to 1/5.

具體而言,本發明係一種高級脂肪酸為選自異硬脂酸、肉豆蔻酸、棕櫚酸、硬脂酸、油酸、亞麻油酸、亞麻仁油酸、癸酸、月桂酸、己酸的1種或2種以上的外用貼附劑。 Specifically, the present invention is a higher fatty acid selected from the group consisting of isostearic acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linoleic acid, citric acid, lauric acid, and hexanoic acid. One or two or more external patches.

更具體而言,本發明係一種高級脂肪酸為單獨異硬脂酸、或異硬脂酸與肉豆蔻酸的組合、或異硬脂酸、肉豆蔻酸與棕櫚酸的組合的外用貼附劑。 More specifically, the present invention is a topical patch of a higher fatty acid of isostearic acid alone, or a combination of isostearic acid and myristic acid, or a combination of isostearic acid, myristic acid and palmitic acid.

本發明所提供之外用貼附劑藉由作成一種外用貼附劑,係於支持體的單面上設置含有洛索普洛芬鈉的黏著劑層的外用貼附劑,其中該黏著劑層使用作為主基劑之苯乙烯-異戊二烯-苯乙烯嵌段共聚物、及作為對皮膚安全性高的賦黏劑之脂環族飽和烴樹脂,進一步分別以特定量摻混屬針對作為主藥之洛索普洛芬鈉的溶解劑的乳酸及高級脂肪酸,便可使洛索普洛芬鈉穩定溶解於黏著劑基劑中,而能夠提供一種習知貼附劑中未能達成之兼 備高經皮吸收性與主藥穩定性的含有洛索普洛芬鈉之外用貼附劑。 The external patch provided by the present invention is provided as an external patch, and is provided on the one surface of the support with an external patch containing an adhesive layer of loxoprofen sodium, wherein the adhesive layer is used. a styrene-isoprene-styrene block copolymer as a main base, and an alicyclic saturated hydrocarbon resin as a tackifier having high skin safety, further blended in a specific amount with each other as a main The lactic acid and higher fatty acid of the loxoprofen sodium dissolving agent can stabilize the dissolution of loxoprofen sodium in the adhesive base, and can provide a conventional adhesive which cannot be achieved. A patch containing loxoprofen sodium for high transdermal absorbability and main drug stability.

尤其是針對乳酸、以及作為高級脂肪酸之單獨異硬脂酸、異硬脂酸與肉豆蔻酸的組合、或異硬脂酸、肉豆蔻酸與棕櫚酸的組合,設為乳酸/高級脂肪酸=1/50~1/5之範圍,藉此即可顯示極為良好的溶解性、以及經皮吸收性。 In particular, for lactic acid, as a combination of isostearic acid, isostearic acid and myristic acid as a higher fatty acid, or a combination of isostearic acid, myristic acid and palmitic acid, it is set as lactic acid/higher fatty acid=1 The range of /50~1/5 can show extremely good solubility and transdermal absorbability.

本發明所提供之外用劑中,作為外用貼附劑中之主藥的洛索普洛芬鈉的摻混量只要可製劑化,則未特別限定,較佳為相對於製劑總重量,能以0.1~10重量%,更佳為,能以0.5~6重量%之範圍摻混。 In the external preparation of the present invention, the amount of the loxoprofen sodium to be used as the main drug in the external patch is not particularly limited as long as it can be formulated, and it is preferred to use the total weight of the preparation. 0.1 to 10% by weight, more preferably, it can be blended in the range of 0.5 to 6% by weight.

製劑中的洛索普洛芬鈉含量若低於0.1重量%時經皮吸收性不充分,而大於10重量%時,不僅損及貼附劑的物性,於成本方面亦屬不利而不佳。 When the content of loxoprofen sodium in the preparation is less than 0.1% by weight, the transdermal absorbability is insufficient, and when it is more than 10% by weight, not only the physical properties of the patch are impaired, but also the disadvantage in terms of cost.

本發明之外用貼附劑中,作為基劑成分之苯乙烯-異戊二烯-苯乙烯嵌段共聚物(以下稱為「SIS」)係發揮賦予黏著劑層黏著性,同時將各成分保持於黏著劑中的作用。 In the external patch of the present invention, the styrene-isoprene-styrene block copolymer (hereinafter referred to as "SIS") as a base component serves to impart adhesion to the adhesive layer while maintaining the components. The role in the adhesive.

SIS的摻混量係將其他成分的摻混量納入考量來摻混,通常摻混5~30重量%,較佳摻混10~25重量%。上述摻混量若低於5重量%時,基劑的凝聚力或保形性降低。另外,上述摻混量大於30重量%時則會導致黏著力降低、膏體不均勻、及製造步驟中的作業性下降而不佳。 The blending amount of the SIS is blended in consideration of the blending amount of the other components, and is usually blended in an amount of 5 to 30% by weight, preferably 10 to 25% by weight. When the blending amount is less than 5% by weight, the cohesive force or shape retention of the base is lowered. On the other hand, when the blending amount is more than 30% by weight, the adhesion is lowered, the paste is not uniform, and the workability in the production step is not deteriorated.

本發明之外用貼附劑中摻混於基劑中的脂環族飽和烴樹脂係作為賦黏劑使用。 The alicyclic saturated hydrocarbon resin blended in the base with the patch of the present invention is used as a tackifier.

脂環族飽和烴樹脂對皮膚的安全性高,而且其極性低,因此與洛索普洛芬鈉、以及其他摻混成分的反應性低,由提升製劑中之洛索普洛芬鈉的穩定性觀點而言亦屬較佳之賦黏劑。 The alicyclic saturated hydrocarbon resin has high skin safety and low polarity, so it has low reactivity with loxoprofen sodium and other admixtures, and is stable by the improvement of loxoprofen sodium in the preparation. From a sexual point of view, it is also a preferred adhesive.

就此種脂環族飽和烴樹脂而言,具體可例舉Alcon P100、Alcon P90、Alcon P115等(皆為商品名:荒川化學工業製)。 Specific examples of such an alicyclic saturated hydrocarbon resin include Alcon P100, Alcon P90, and Alcon P115 (all of which are trade names: manufactured by Arakawa Chemical Industries, Ltd.).

本發明之外用貼附劑中的脂環族飽和烴樹脂的摻混量只要可製劑化則未特別限制,係以較佳為相對於製劑總重量,以10~50重量%之範圍摻混為佳。更佳為15~40重量%。 The blending amount of the alicyclic saturated hydrocarbon resin in the external patch of the present invention is not particularly limited as long as it can be formulated, and is preferably blended in an amount of 10 to 50% by weight based on the total weight of the preparation. good. More preferably 15 to 40% by weight.

製劑中之脂環族飽和烴樹脂的摻混量若低於10重量%時,黏著力弱,而發生貼附中剝離等問題,而摻混大於50重量%時,製劑的黏著力反而過強,發生皮膚刺激性變高等問題而不佳。 When the blending amount of the alicyclic saturated hydrocarbon resin in the preparation is less than 10% by weight, the adhesion is weak, and peeling or the like occurs in the attachment, and when the blending is more than 50% by weight, the adhesion of the preparation is excessively strong. Problems such as high skin irritation are not good.

本發明中,乳酸為一種對洛索普洛芬鈉極為優良的溶解劑,係一種藉由將其摻混而能夠使洛索普洛芬鈉穩定溶解於黏著基劑中,並顯示優良經皮吸收促進效果的成分。 In the present invention, lactic acid is a very excellent dissolving agent for loxoprofen sodium, which is capable of stably dissolving loxoprofen sodium in an adhesive base by blending it, and exhibits excellent percutaneousness. A component that absorbs the promoting effect.

然而,乳酸為一種另一方面會與洛索普洛芬鈉反應產生分解生成物,而使製劑的穩定性降低的添加劑。因此,相對於製劑總重量,本發明之外用貼附劑中的乳酸的摻混量係以0.1~1.0重量%,較佳為0.1~0.8重量%,更佳為0.2~0.6重量%之範圍摻混為佳。乳酸的摻混量若低於0.1重量%時,無法使洛索普洛芬鈉充分溶解於黏著 基劑中,而發生製劑的經皮吸收性下降、或保存中之製劑中的主藥結晶析出等,反之乳酸的摻混量大於1.0重量%時,則來自乳酸的分解生成物增加,以致製劑的穩定性降低。 However, lactic acid is an additive which, on the other hand, reacts with loxoprofen sodium to produce a decomposition product, thereby lowering the stability of the preparation. Therefore, the blending amount of lactic acid in the external patch of the present invention is in an amount of 0.1 to 1.0% by weight, preferably 0.1 to 0.8% by weight, more preferably 0.2 to 0.6% by weight, based on the total weight of the preparation. Mixed is better. When the blending amount of lactic acid is less than 0.1% by weight, the loxoprofen sodium cannot be sufficiently dissolved in the adhesive. In the base, the transdermal absorbability of the preparation is lowered, or the main drug crystals are precipitated in the preparation during storage, and when the blending amount of the lactic acid is more than 1.0% by weight, the decomposition product derived from lactic acid is increased, so that the preparation is increased. The stability is reduced.

本發明之外用貼附劑中,係與上述乳酸共同摻混高級脂肪酸來確保作為對洛索普洛芬鈉之溶解劑的功能。本發明中,藉由在製劑中摻混較多量的高級脂肪酸,可抑制乳酸所衍生之分解生成物的增加而不會降低製劑的經皮吸收性。 In the external patch of the present invention, a higher fatty acid is blended with the above lactic acid to secure a function as a solubilizing agent for loxoprofen sodium. In the present invention, by adding a large amount of a higher fatty acid to the preparation, an increase in the decomposition product derived from lactic acid can be suppressed without lowering the transdermal absorbability of the preparation.

就此種高級脂肪酸而言,係可例示異硬脂酸、肉豆蔻酸、棕櫚酸、硬脂酸、油酸、亞麻油酸、亞麻仁油酸、癸酸、月桂酸、己酸等,可組合使用其1種或2種以上,惟本發明中特別適合使用異硬脂酸、肉豆蔻酸、及棕櫚酸。 In the case of such a higher fatty acid, isostearic acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linseed oleic acid, citric acid, lauric acid, caproic acid, etc. may be combined. One type or two or more types are used, but isostearic acid, myristic acid, and palmitic acid are particularly preferably used in the present invention.

製劑中之高級脂肪酸的摻混量為5~15重量%,較佳為6~10重量%,更佳為6~8重量%。高級脂肪酸的摻混量若低於5重量%時,製劑中的洛索普洛芬鈉未能充分溶解,且來自乳酸的分解生成物增加。又,高級脂肪酸的摻混量大於15重量%時,非但製劑的物性降低,亦發生皮膚刺激性等問題而不佳。 The blending amount of the higher fatty acid in the preparation is 5 to 15% by weight, preferably 6 to 10% by weight, more preferably 6 to 8% by weight. When the blending amount of the higher fatty acid is less than 5% by weight, the loxoprofen sodium in the preparation is not sufficiently dissolved, and the decomposition product derived from lactic acid is increased. Further, when the blending amount of the higher fatty acid is more than 15% by weight, the physical properties of the preparation are lowered, and problems such as skin irritation are also poor.

本發明所提供之外用貼附劑中,為兼具主藥的經皮吸收性與主藥的穩定性,其特徵在於組合較微量的乳酸、與較多量的高級脂肪酸而予以摻混於製劑中。 The external patch provided by the present invention has both the transdermal absorbability of the main drug and the stability of the main drug, and is characterized in that a small amount of lactic acid is combined with a relatively large amount of higher fatty acid and blended into the preparation. .

乳酸、或高級脂肪酸的摻混量係如上所述,惟,再者,可明瞭較佳將乳酸與高級脂肪酸的摻混比例調整成一定範圍。 The blending amount of lactic acid or higher fatty acid is as described above, but it is also clear that the blending ratio of lactic acid and higher fatty acid is preferably adjusted to a certain range.

本發明之外用貼附劑中,乳酸與高級脂肪酸的摻混比例為乳酸/高級脂肪酸=1/50~1/5,較佳為1/30~1/5,更佳為1/30~1/15。乳酸的摻混比若低於1/50時,經皮吸收性降低,乳酸的摻混比高於1/5時,則在保存中之製劑中來自乳酸的分解生成物的生成增加,以致藥物的穩定性降低。 In the external patch of the present invention, the blending ratio of lactic acid to higher fatty acid is lactic acid/higher fatty acid = 1/50 to 1/5, preferably 1/30 to 1/5, more preferably 1/30 to 1 /15. When the blending ratio of lactic acid is less than 1/50, the transdermal absorbability is lowered, and when the blending ratio of lactic acid is higher than 1/5, the production of the decomposition product derived from lactic acid is increased in the preparation for preservation, so that the drug is caused. The stability is reduced.

較佳之乳酸與高級脂肪酸的組合為乳酸與異硬脂酸、或乳酸、與異硬脂酸及肉豆蔻酸。更佳為乳酸、與異硬脂酸、肉豆蔻酸及棕櫚酸的組合。 A preferred combination of lactic acid and higher fatty acid is lactic acid and isostearic acid, or lactic acid, isostearic acid and myristic acid. More preferably, it is a combination of lactic acid, isostearic acid, myristic acid and palmitic acid.

本發明之外用貼附劑中所摻混的軟化劑係指與其他基劑成分相溶性佳,並可賦予基劑柔軟性者,具體可例舉聚異丁烯、液態聚異戊二烯、聚丁烯、羊毛脂、蓖麻油、杏仁油、橄欖油、茶子油、桃核油、落花生油、加工油、增效劑油、及流動石蠟等,其中較佳為聚丁烯、及流動石蠟。 The softening agent blended in the external patch of the present invention means that it is compatible with other base components and can impart flexibility to the base, and specifically, polyisobutylene, liquid polyisoprene, polybutadiene Alkene, lanolin, castor oil, almond oil, olive oil, tea oil, peach kernel oil, groundnut oil, processing oil, synergist oil, and mobile paraffin, among which polybutene and mobile paraffin are preferred.

此等軟化劑可分別單獨使用,惟亦可組合、摻混2種以上。軟化劑的摻混量亦考量到摻混於製劑中的其他液態成分的摻混量,惟通常為10~75重量%,較佳為15~50重量%。 These softeners may be used alone or in combination of two or more. The blending amount of the softening agent is also considered to be a blending amount of other liquid components blended in the preparation, but it is usually 10 to 75% by weight, preferably 15 to 50% by weight.

本發明所提供之外用貼附劑中,係以摻混L-薄荷醇作為清涼劑為佳。然而,由於L-薄荷醇本身可能在製劑中與作為分子內具有羧酸基之非類固醇系消炎鎮痛劑的洛索普洛芬鈉反應而生成分解生成物(L-薄荷醇酯體),若大量摻混時則有伴隨其量,分解生成物(L-薄荷醇酯體)的生成量亦增加之傾向。又摻混過多L-薄荷醇時,皮膚 所感受之冰冷感過強,因人而異亦有感到不適的情況。因此本發明之外用貼附劑中的L-薄荷醇的摻混量為0.1~10重量%,更佳為0.5~5重量%。 In the external patch provided by the present invention, it is preferred to blend L-menthol as a cooling agent. However, since L-menthol itself may react with loxoprofen sodium which is a non-steroidal anti-inflammatory analgesic having a carboxylic acid group in the preparation, a decomposition product (L-menthol ester) is formed in the preparation, if When a large amount is blended, the amount of the decomposition product (L-menthol ester body) is also increased. When blended with too much L-menthol, the skin The cold feeling that I feel is too strong, and I feel uncomfortable because of people. Therefore, the blending amount of L-menthol in the external patch of the present invention is 0.1 to 10% by weight, more preferably 0.5 to 5% by weight.

此外,本發明之外用貼附劑中,為抑制所述分解生成物的增加,亦可摻混多價金屬鹽。尤其是針對來自乳酸的分解生成物,摻混甘胺酸鋁係屬有效。上述多價金屬鹽係以0.001~5重量%之範圍摻混,較佳為0.005~3重量%。 Further, in the external patch of the present invention, in order to suppress an increase in the decomposition product, a polyvalent metal salt may be blended. In particular, for the decomposition product derived from lactic acid, it is effective to blend aluminum glycinate. The polyvalent metal salt is blended in the range of 0.001 to 5% by weight, preferably 0.005 to 3% by weight.

本發明之外用貼附劑的黏著劑層中,還可視需求摻混溶解劑、其他吸收促進劑。對於此等溶解劑或吸收促進劑,可例示肉豆蔻酸異丙酯、癸二酸二乙酯、癸二酸二異丙酯、己二酸二異丙酯、棕櫚酸異丙酯等脂肪酸酯、丙二醇、聚乙二醇、丁二醇、及丙三醇等多元醇、N-甲基-2-吡咯啶酮、1-乙基-2-吡咯啶酮、5-甲基-2-吡咯啶酮、N-辛基-2-吡咯啶酮等吡咯啶酮化合物、克羅他命酮、其他各種界面活性劑等。 In the adhesive layer of the external patch of the present invention, a solvent and other absorption enhancers may be blended as needed. Examples of such a dissolving agent or an absorption enhancer include fatty acid such as isopropyl myristate, diethyl sebacate, diisopropyl sebacate, diisopropyl adipate, and isopropyl palmitate. Polyols such as esters, propylene glycol, polyethylene glycol, butanediol, and glycerol, N-methyl-2-pyrrolidone, 1-ethyl-2-pyrrolidone, 5-methyl-2- Pyrrolidone compounds such as pyrrolidone and N-octyl-2-pyrrolidone, crotheter ketone, various other surfactants, and the like.

又,本發明之外用貼附劑中,只要不造成其他影響,還可使用一般外用製劑所使用的各種基劑成分。以所述基劑成分而言並未特別限定,惟可例舉如丁基橡膠、聚異丁烯、天然橡膠、聚異戊二烯橡膠等橡膠系彈性體;聚乙烯吡咯啶酮、聚乙烯醇、聚丙烯酸等水溶性高分子;乙基纖維素、羥丙基纖維素、羥丙基甲基纖維素等纖維素衍生物、無水矽酸、輕質無水矽酸等矽化合物、二丁基羥基甲苯、新戊四醇-四[3-(3,5-二-三級丁基-4-羥苯基)丙酸酯]、生育酚乙酸酯、抗壞血酸等抗氧化劑;氧化鋅、 氧化鋁、二氧化鈦、氧化矽類、氧化鎂、氧化鐵、硬脂酸鋅等無機填充劑等。更可視需求添加防腐劑、清涼劑、殺菌劑、香味料、著色劑等。 Further, in the external patch for use in the present invention, various base ingredients used in general external preparations can be used as long as they do not cause other effects. The base component is not particularly limited, and may, for example, be a rubber-based elastomer such as butyl rubber, polyisobutylene, natural rubber or polyisoprene rubber; polyvinylpyrrolidone or polyvinyl alcohol; Water-soluble polymer such as polyacrylic acid; cellulose derivative such as ethyl cellulose, hydroxypropyl cellulose or hydroxypropyl methyl cellulose; anthracene compound such as anhydrous citric acid, light anhydrous citric acid, dibutyl hydroxytoluene , neopentyl alcohol-tetrakis[3-(3,5-di-tri-butyl-4-hydroxyphenyl)propionate], tocopherol acetate, ascorbic acid and other antioxidants; zinc oxide, An inorganic filler such as alumina, titania, cerium oxide, magnesium oxide, iron oxide or zinc stearate. Preservatives, cooling agents, bactericides, flavoring agents, coloring agents, etc. may be added as needed.

就外用貼附劑之支持體而言,可例舉薄膜、不織布、織布、及不織布與薄膜的層壓複合體等。就此等支持體的材料而言,可例舉聚乙烯、聚丙烯、聚氯乙烯、聚酯、聚對苯二甲酸乙二酯、尼龍、聚胺基甲酸酯、嫘縈、聚丙烯腈、聚苯乙烯、聚萘二甲酸乙二酯等。 The support for the external patch may, for example, be a film, a nonwoven fabric, a woven fabric, or a laminate composite of a nonwoven fabric and a film. The material of the support may, for example, be polyethylene, polypropylene, polyvinyl chloride, polyester, polyethylene terephthalate, nylon, polyurethane, hydrazine, polyacrylonitrile, Polystyrene, polyethylene naphthalate, and the like.

外用貼附劑所使用之剝離襯墊可採用聚對苯二甲酸乙二酯、聚丙烯、紙等,聚對苯二甲酸乙二酯尤佳。為使剝離力最佳化,剝離襯墊可視需求實施矽處理。 The release liner used for the external patch may be polyethylene terephthalate, polypropylene, paper, etc., and polyethylene terephthalate is particularly preferred. In order to optimize the peel force, the release liner can be treated as needed.

[實施例] [Examples]

以下,舉出實施例對本發明更具體地進行說明,惟本發明並不受以下實施例所限定。 Hereinafter, the present invention will be more specifically described by way of examples, but the present invention is not limited by the following examples.

實施例1: Example 1:

將SIS(QUINTAC 3570C;日本ZEON製)、脂環族飽和烴樹脂(Alcon P-100;荒川化學工業製)、聚丁烯(HV-300F;日本石油製)、流動石蠟(HICALL M-352;KANEDA製)、BHT(二丁基羥基甲苯)之各成分於氮氣環境下加熱攪拌而溶解。次之,在前述黏著劑中添加主藥洛索普洛芬鈉、L-薄荷醇、乳酸、異硬脂酸、棕櫚酸、及肉豆蔻酸,進一步攪拌混合來調製黏著劑。 SIS (QUINTAC 3570C; manufactured by ZEON, Japan), alicyclic saturated hydrocarbon resin (Alcon P-100; manufactured by Arakawa Chemical Industries Co., Ltd.), polybutene (HV-300F; manufactured by Nippon Petroleum Co., Ltd.), and liquid paraffin (HICAL L M-352; Each component of BANE (dibutylhydroxytoluene) and BHT (dibutylhydroxytoluene) were heated and stirred under a nitrogen atmosphere to be dissolved. Next, the main drug loxoprofen sodium, L-menthol, lactic acid, isostearic acid, palmitic acid, and myristic acid are added to the above-mentioned adhesive, and further stirred and mixed to prepare an adhesive.

將調製之黏著劑塗覆於經矽處理之聚對苯二甲酸乙二酯薄膜上,形成約150μm之黏著劑層。在所得之黏著劑層上層壓支持體之聚酯製織布,而得到本發明之外用貼附劑。 The prepared adhesive was applied to a tantalum-treated polyethylene terephthalate film to form an adhesive layer of about 150 μm. A polyester woven fabric of a support is laminated on the obtained adhesive layer to obtain a patch for external use of the present invention.

各成分的摻混量係示於表1。 The blending amount of each component is shown in Table 1.

實施例2~6: Embodiments 2 to 6:

根據下述表1所示之組成,依循實施例1之製法,得到實施例2~6之各外用貼附劑。 According to the composition shown in Table 1 below, each of the external application patches of Examples 2 to 6 was obtained according to the method of Example 1.

比較例1~9: Comparative Examples 1~9:

根據下述表2及3所示之組成,依循實施例1之製法,得到比較例1~9之各外用貼附劑。 According to the compositions shown in the following Tables 2 and 3, each of the external use patches of Comparative Examples 1 to 9 was obtained according to the method of Example 1.

再者,於後述之試驗例中,就比較例10而言,係使用市售之含有洛索普洛芬之硬膏劑。 Further, in the test examples described later, in the case of Comparative Example 10, a commercially available plaster containing loxoprofen was used.

試驗例1:人體貼附殘留試驗 Test Example 1: Human body attached residue test

在知後同意下,將實施例2~4與比較例1~3之製劑分別沖切成3×4cm大小,將各製劑貼附於受驗者的背部24小時,再將製劑剝離、回收後,萃取各製劑中所殘留的洛索普洛芬鈉,以HPLC測定該藥物量。由測定自貼附0小時(未貼附)之製劑的洛索普洛芬藥物量,減去各個殘留藥物量來計算各製劑的藥物消失量。其結果係示於表4及表5。 The preparations of Examples 2 to 4 and Comparative Examples 1 to 3 were each punched into a size of 3 × 4 cm, and the preparations were attached to the back of the subject for 24 hours, and then the preparation was peeled off and recovered. The loxoprofen sodium remaining in each preparation was extracted, and the amount of the drug was determined by HPLC. The amount of drug disappearance of each preparation was calculated by measuring the amount of loxoprofen drug from the preparation which was attached for 0 hours (unattached), and subtracting the amount of each residual drug. The results are shown in Tables 4 and 5.

由各表所示之結果可確認,作為本發明之外用貼附劑的各實施例之製劑相較於各比較例,藥物消失量高,亦即為經皮吸收性高之製劑。 From the results shown in the respective tables, it was confirmed that the preparations of the respective examples of the externally applied patch of the present invention have a higher amount of drug disappearance than the comparative examples, that is, a preparation having high transdermal absorbability.

試驗例2:人體角質內藥物量測定試驗 Test Example 2: Test for measuring the amount of drug in human keratin <試驗方法> <Test method>

在知後同意下,將實施例1及比較例10(市售品)之各供試製劑(2.5×2.5cm)貼附於受驗者的背部。貼附24小時後,將製劑剝離,並以角質剝離用膠帶剝離各供試製劑之剝離部位(以下稱為「剝離部位」)的角質,來採取角質。以甲醇萃取所得角質中的洛索普洛芬鈉,並藉由HPLC測定法來測定其量。其結果係示於表6。 Each test preparation (2.5 x 2.5 cm) of Example 1 and Comparative Example 10 (commercial product) was attached to the back of the subject with the consent of the latter. After the attachment for 24 hours, the preparation was peeled off, and the keratin of the peeled portion (hereinafter referred to as "peeling portion") of each test preparation was peeled off with a tape for keratin peeling to take keratin. The loxoprofen sodium in the resulting keratin was extracted with methanol and determined by HPLC assay. The results are shown in Table 6.

由以上結果可確認,本發明之實施例1之外用貼附劑係顯示與市售之含有洛索普洛芬之硬膏劑(比較例10)同等、或其以上之經皮吸收性。 From the above results, it was confirmed that the external patch of Example 1 of the present invention showed transdermal absorbability equivalent to or higher than that of a commercially available plaster containing loxoprofen (Comparative Example 10).

試驗例3:小鼠皮膚穿透性試驗 Test Example 3: Mouse skin penetration test

為探討實施例1~6、及比較例2~10之外用貼附劑的主藥釋放性,而實施使用無毛小鼠之in vitro小鼠皮膚穿透性試驗。 In order to investigate the main drug release properties of the patching agents other than Examples 1 to 6 and Comparative Examples 2 to 10, the skin penetration test of in vitro mice using hairless mice was carried out.

將8~10週大之無毛小鼠的背部皮膚剝離,以真皮側作為受體層側,予以裝接於外周部有37℃之溫水循環的Franz型槽(Franz cell)(開口面積:1.77cm2)。其次,在 皮膚的角質層側貼附各貼附劑,使用作為受體液之PBS(pH7.4)溶液,以2.25mL/hr的速度對受體液進行採樣90分鐘,再藉由高效液相層析法測定採取液中的藥物濃度。 The back skin of 8 to 10 weeks old hairless mice was peeled off, and the dermis side was used as the receptor layer side, and was attached to a Franz cell having a warm water circulation of 37 ° C in the outer periphery (opening area: 1.77) Cm 2 ). Next, attach the patch to the stratum corneum side of the skin, and use the PBS (pH 7.4) solution as the acceptor solution to sample the receptor solution at a rate of 2.25 mL/hr for 90 minutes, followed by a high-performance liquid layer. The concentration of the drug in the solution is determined by an analytical method.

另外,由其結果算出穩定狀態(試驗開始後第18~24小時)的皮膚穿透速度(Flux:μg/cm2/hr)。 Further, from the results, the skin penetration rate (Flux: μg/cm 2 /hr) in a steady state (18 to 24 hours after the start of the test) was calculated.

其結果係示於表7。此外,flux值係以相對於比較例10的flux比表示。 The results are shown in Table 7. Further, the flux value is expressed by the flux ratio with respect to Comparative Example 10.

Flux比=(各實施例及比較例之穩定狀態下的flux值/(比較例10之穩定狀態下的flux值) Flux ratio = (flux value in steady state of each of the examples and comparative examples / (flux value in steady state of Comparative Example 10)

由以上結果可確認,各實施例之外用貼附劑係顯示與市售之含有洛索普洛芬之硬膏劑(比較例10)同等、或其以上之經皮吸收性。 From the above results, it was confirmed that the patching agent other than the examples showed the same transdermal absorbability as or equivalent to the commercially available loxoprofen-containing plaster (Comparative Example 10).

另一方面,比較例2、3、及5~9之外用貼附劑比起比較例10,經皮吸收性大幅劣化。 On the other hand, in Comparative Examples 2, 3, and 5 to 9, the patch was significantly deteriorated in transdermal absorbability as compared with Comparative Example 10.

試驗例4:穩定性試驗(分解生成物的定量試驗) Test Example 4: Stability test (quantitative test of decomposition product)

針對實施例1~4、實施例6、比較例4及比較例5之各製劑,於60℃之保存條件下,測定1個月之保存期間內的保存試料中的分解生成物。進一步針對實施例1與實施例4之各製劑,同樣對3個月之保存期間內的保存試料中的分解生成物量進行測定。試料之調製法及HPLC測定條件係如下所示。 With respect to each of the preparations of Examples 1 to 4, Example 6, Comparative Example 4, and Comparative Example 5, the decomposition product in the stored sample during the storage period of one month was measured under the storage conditions of 60 °C. Further, in each of the preparations of Example 1 and Example 4, the amount of decomposition product in the stored sample during the storage period of 3 months was measured in the same manner. The preparation method of the sample and the HPLC measurement conditions are as follows.

此外,在本穩定性試驗中,係特別測定來自乳酸的分解生成物。以下所示之HPLC測定條件中,設洛索普洛芬鈉的保持時間為1時之相對保持時間1.55~1.60所檢測出的分解生成物(以下稱為「分解生成物1」)、及相對保持時間1.65~1.70所檢測出的分解生成物(以下稱為「分解生成物2」)係來自乳酸的主要分解生成物。對於供予試驗之各製劑中的分解生成物的定量結果係示於表8,尤其關於實施例1、及比較例4的定量結果,係分別將分解生成物1的定量結果示於第1圖、分解生成物2的定量結果示於第2圖。 Further, in the present stability test, a decomposition product derived from lactic acid was specifically measured. In the HPLC measurement conditions shown below, the decomposition product (hereinafter referred to as "decomposition product 1") and relative relative to the relative retention time of 1.55 to 1.60 when the retention time of loxoprofen sodium is 1 is set. The decomposition product (hereinafter referred to as "decomposition product 2") detected by the holding time of 1.65 to 1.70 is a main decomposition product derived from lactic acid. The quantitative results of the decomposition products in the respective preparations for the test are shown in Table 8, and in particular, the quantitative results of Example 1 and Comparative Example 4 are shown in Fig. 1 for the quantitative results of the decomposition product 1 respectively. The quantitative result of the decomposition product 2 is shown in Fig. 2 .

<試料之調製法> <Measurement method of sample>

茲將各製劑沖切成5×7cm大小,添加四氫呋喃(以下稱為「THF」),並利用超音波萃取及振盪機進行萃取。用THF使所得之萃取液達100mL,而作成萃取液。取3mL之該萃取液,使用40%乙腈定量至50mL,再利用膜濾器(0.45μm)進行過濾,將所得之液作為供試試料。 Each preparation was die-cut into a size of 5 × 7 cm, tetrahydrofuran (hereinafter referred to as "THF") was added, and extraction was carried out by ultrasonic extraction and a shaker. The resulting extract was made up to 100 mL with THF to prepare an extract. 3 mL of this extract was taken and quantified to 50 mL using 40% acetonitrile, and then filtered using a membrane filter (0.45 μm), and the obtained liquid was used as a test material.

<HPLC測定條件> <HPLC measurement conditions>

管柱:Unison UK-C18(3×150mm) Column: Unison UK-C18 (3×150mm)

移動相:乙腈:水:磷酸=400:600:1 Mobile phase: acetonitrile: water: phosphoric acid = 400:600:1

流速:0.5mL/分鐘 Flow rate: 0.5mL/min

波長:223nm Wavelength: 223nm

注入量:10μL Injection volume: 10μL

由表8、第1圖及第2圖所示之結果可知,相對於比較例4之製劑中來自乳酸的分解生成物的生成量經時性地明顯增加,本發明之實施例1之製劑中則可大幅抑制分解生成物的生成。 As a result of the results shown in Table 8, FIG. 1 and FIG. 2, the amount of the decomposition product derived from lactic acid in the preparation of Comparative Example 4 was significantly increased with time, and in the preparation of Example 1 of the present invention. The generation of the decomposition product can be greatly suppressed.

[產業上可利用性] [Industrial availability]

根據本發明,可提供一種含有洛索普洛芬鈉、顯示優良藥物釋放性,且含有具備高穩定性之洛索普洛芬鈉的油性外用貼附劑。 According to the present invention, there is provided an oily topical patch containing loxoprofen sodium which exhibits excellent drug release properties and contains loxoprofen sodium having high stability.

本發明所提供之貼附劑係一種含有洛索普洛芬鈉之消炎鎮痛外用製劑,係有用於預防、治療例如退化性關節炎、慢性類風濕性關節炎、腰痛、肩關節周圍炎、腱鞘炎、腱周圍炎、肱骨外上髁炎(網球肘等)、肌肉痛、外傷後的腫脹、疼痛等。 The patch provided by the present invention is an anti-inflammatory analgesic external preparation containing loxoprofen sodium, which is used for preventing and treating, for example, degenerative arthritis, chronic rheumatoid arthritis, low back pain, periarthritis of the shoulder, tenosynovitis. , around the sputum, sacral epicondylitis (tennis elbow, etc.), muscle pain, swelling after trauma, pain and so on.

第1圖 係表示本發明之試驗例4之分解生成物1的定量結果的圖。 Fig. 1 is a graph showing the quantitative results of the decomposition product 1 of Test Example 4 of the present invention.

第2圖 係表示本發明之試驗例4之分解生成物2的定量結果的圖。 Fig. 2 is a view showing the quantitative result of the decomposition product 2 of Test Example 4 of the present invention.

Claims (3)

一種外用貼附劑,係於支持體上設置含有0.1~10重量%之洛索普洛芬鈉的黏著劑層的外用貼附劑,其中該黏著劑層含有5~30重量%之苯乙烯-異戊二烯-苯乙烯嵌段共聚物、10~50重量%之脂環族飽和烴樹脂、0.1~1重量%之乳酸、及5~15重量%之高級脂肪酸,且乳酸與高級脂肪酸的摻混比例為乳酸/高級脂肪酸=1/50~1/5。 A topical patch for external application of an adhesive layer containing 0.1 to 10% by weight of loxoprofen sodium, wherein the adhesive layer contains 5 to 30% by weight of styrene- Isoprene-styrene block copolymer, 10 to 50% by weight of alicyclic saturated hydrocarbon resin, 0.1 to 1% by weight of lactic acid, and 5 to 15% by weight of higher fatty acid, and lactic acid mixed with higher fatty acid The mixing ratio is lactic acid/higher fatty acid = 1/50 to 1/5. 如申請專利範圍第1項之外用貼附劑,其中高級脂肪酸為選自異硬脂酸、肉豆蔻酸、棕櫚酸、硬脂酸、油酸、亞麻油酸、亞麻仁油酸、癸酸、月桂酸、己酸的1種或2種以上。 The applicator is used in addition to the first item of the patent application, wherein the higher fatty acid is selected from the group consisting of isostearic acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linoleic acid, and citric acid. One or more of lauric acid and caproic acid. 如申請專利範圍第1或2項之外用貼附劑,其中高級脂肪酸為單獨異硬脂酸、或異硬脂酸與肉豆蔻酸的組合、或異硬脂酸、肉豆蔻酸與棕櫚酸的組合。 A patching agent is used in addition to the first or second aspect of the patent application, wherein the higher fatty acid is isostearic acid alone, or a combination of isostearic acid and myristic acid, or isostearic acid, myristic acid and palmitic acid. combination.
TW101125028A 2011-07-13 2012-07-12 External plaster containing loxoprofen natrium TWI526227B (en)

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EP4311547A1 (en) 2021-03-04 2024-01-31 Teikoku Seiyaku Co., Ltd. Loxoprofen-containing adhesive patch and method for manufacturing same
JP7558545B1 (en) 2023-05-26 2024-10-01 株式会社 雪の元本店 Loxoprofen-containing topical skin preparation

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