JPWO2013035850A1 - 経皮吸収製剤 - Google Patents
経皮吸収製剤 Download PDFInfo
- Publication number
- JPWO2013035850A1 JPWO2013035850A1 JP2013532677A JP2013532677A JPWO2013035850A1 JP WO2013035850 A1 JPWO2013035850 A1 JP WO2013035850A1 JP 2013532677 A JP2013532677 A JP 2013532677A JP 2013532677 A JP2013532677 A JP 2013532677A JP WO2013035850 A1 JPWO2013035850 A1 JP WO2013035850A1
- Authority
- JP
- Japan
- Prior art keywords
- adhesive layer
- drug
- weight
- containing adhesive
- fatty acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 66
- 238000010521 absorption reaction Methods 0.000 title claims description 28
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- -1 fatty acid salt Chemical class 0.000 claims abstract description 58
- 239000012790 adhesive layer Substances 0.000 claims abstract description 50
- 229940079593 drug Drugs 0.000 claims abstract description 46
- 239000003814 drug Substances 0.000 claims abstract description 46
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 43
- 239000000194 fatty acid Substances 0.000 claims abstract description 43
- 229930195729 fatty acid Natural products 0.000 claims abstract description 43
- 229960003530 donepezil Drugs 0.000 claims abstract description 38
- 150000003839 salts Chemical class 0.000 claims abstract description 10
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- 229920002725 thermoplastic elastomer Polymers 0.000 claims description 18
- 150000004665 fatty acids Chemical class 0.000 claims description 17
- 229920000346 polystyrene-polyisoprene block-polystyrene Polymers 0.000 claims description 15
- 229940057995 liquid paraffin Drugs 0.000 claims description 14
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 claims description 12
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- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 3
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 3
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Abstract
Description
薬物含有粘着層が、ドネペジルまたはその塩、および高級脂肪酸塩を含有することを特徴とする経皮吸収製剤。
[2] 高級脂肪酸の炭素数が、12以上30以下である上記[1]に記載の経皮吸収製剤。
[3] 薬物含有粘着層が、高級脂肪酸ナトリウムを含有する上記[1]または[2]に記載の経皮吸収製剤。
[4] 薬物含有粘着層が、熱可塑性エラストマーおよび流動パラフィンを含有し、
薬物含有粘着層中の流動パラフィンの含有量が、熱可塑性エラストマー100重量部に対して、300重量部超1500重量部以下であり、
薬物含有粘着層中の粘着付与剤の含有量が、10重量%以下(0重量%を含む)である、上記[1]〜[3]のいずれか一つに記載の経皮吸収製剤。
[5] 熱可塑性エラストマーが、スチレン系ブロック共重合体である上記[4]に記載の経皮吸収製剤。
[6] スチレン系ブロック共重合体が、スチレン−イソプレン−スチレンブロック共重合体である上記[5]に記載の経皮吸収製剤。
[7] 薬物含有粘着層が、粘着付与剤を含有しない上記[4]〜[6]のいずれか一つに記載の経皮吸収製剤。
[8] 薬物含有粘着層が、エステル系溶媒および/またはアルコール系溶媒を含有する上記[1]〜[7]のいずれか一つに記載の経皮吸収製剤。
[9] 薬物含有粘着層が、エステル系溶媒およびアルコール系溶媒を含有する上記[1]〜[7]のいずれか一つに記載の経皮吸収製剤。
まず下記表1に記載の量で、スチレン−イソプレン−スチレンブロック共重合体(「JSR SIS5002」、JSR社製)および流動パラフィン(「KAYDOL」、Sonneborn社製)をテトラヒドロフラン(THF)に溶解させて、スチレン−イソプレン−スチレンブロック共重合体等の溶液を調製した。次いで、下記表1に記載の量で、脂肪酸塩および塩酸ドネペジルをエステル系溶媒およびアルコール系溶媒に溶解させて、脂肪酸塩等の溶液を調製した。得られたスチレン−イソプレン−スチレンブロック共重合体等の溶液および脂肪酸塩等の溶液を混合することによって、粘着基剤の塗液を調製した。得られた粘着基剤の塗液を、乾燥後の薬物含有粘着層が300g/m2の量になるように、シリコーン処理したPETフィルム(剥離ライナー)に塗布した。粘着基剤を塗布した剥離ライナーを80℃のオーブンにて30分乾燥した後、得られた粘着層の表面にPETフィルム(支持体)をラミネートして積層シートを調製した。この積層シートを所望の大きさに裁断して、実施例1〜4および比較例1〜3の経皮吸収製剤を得た。なお、酢酸塩を用いた比較例3の経皮吸収製剤では、結晶析出が見られ、製剤形態が不良であった。
実施例1〜4および比較例1〜3の経皮吸収製剤を使用して、以下のようなin vitro皮膚透過試験を行った。雄性Wister系ラット(5週齢)の腹部抽出皮膚を縦型フランツ拡散セルに装着した。次いで、経皮吸収製剤を直径1.0cmの円形に打ち抜き、剥離ライナーを剥がして、拡散セルのラット皮膚に貼付した(n=3)。レセプター側には、エタノール−生理食塩水の混合溶液(エタノール量:10%)を用いて、一定時間後にラットの皮膚を透過するドネペジル量を高速液体クロマトグラフィー(HPLC)により測定した。測定結果(貼付24時間後のドネペジルの透過量)を、図1に示す。また、HPLCの測定条件を以下に示す:
<HPLC条件>
HPLCシステム:高速液体クロマトグラム(LC2010C) 株式会社島津製作所製
カラム:ODS、4.6mmφ×15cm、5μm
カラム温度:40℃
移動層:0.1%リン酸水溶液/メタノール/アセトニトリル/SDS=4/1/5/0.01(重量比)
検出波長:271nm
流量:0.7mL/min
実施例1の経皮吸収製剤を使用して、以下のようなin vivo皮膚透過試験を行った。実施例1の経皮吸収製剤を4cm×6cmにカットし、剥離ライナーを剥がして、雄性slc/HWY系へアレスラット(7週齢)5匹の背部に貼付した。貼付直後(0時間後)並びに3、6、9、24、48および72時間後に、ラットの頸静脈より採血し、採取した血液を遠心分離して、血漿を得た。得られた血漿中のドネペジル濃度を液体クロマトグラフィー・タンデム質量分析法(LC−MS/MS)にて測定した。測定結果を図2に示す。また、LC−MS/MSの測定条件を以下に示す:
<LC条件>
HPLCシステム:高速液体クロマトグラム(1200Series) Agilent Technologies社製
分析カラム:Atlantis dc18、2.1mmI.D.×150mm、5μm
カラム温度:40℃
移動層:メタノール/0.05%ギ酸溶液
流量:0.2mL/min
<MS/MS条件>
タンデム質量分析計:API4000、AB Sciex Pte社製
インターフェース:Turbo−V spray
イオン化法:ESI、正イオンモード
測定イオン:380.5(ドネペジル)、91.1(フラグメントイオン)
実施例3の経皮吸収製剤を使用して、以下のような皮膚一次刺激試験を行った。実施例3の経皮吸収製剤を2.5cm×2.5cmにカットし、剥離ライナーを剥がして、電気バリカンで除毛した雄性の白色ウサギ(Kbs:NZW)の背部に貼付した。24時間閉塞貼付した後に経皮吸収製剤を剥離し、剥離してから1、24、48および72時間後に、J.Pharmacol. Exp. Ther.82:377〜390に記載のDraize.J.H.らの方法によって、一次刺激指数P.I.I.値を算出し、皮膚刺激性を評価した。算出したP.I.I.値は1.4であり、実施例3の経皮吸収製剤は、弱い刺激物であると評価された。この結果から、本発明の経皮吸収製剤の皮膚刺激性は低いことが分かる。
Claims (9)
- 支持体、および支持体上に形成された薬物含有粘着層を有する経皮吸収製剤であって、
薬物含有粘着層が、ドネペジルまたはその塩、および高級脂肪酸塩を含有することを特徴とする経皮吸収製剤。 - 高級脂肪酸の炭素数が、12以上30以下である請求項1に記載の経皮吸収製剤。
- 薬物含有粘着層が、高級脂肪酸ナトリウムを含有する請求項1または2に記載の経皮吸収製剤。
- 薬物含有粘着層が、熱可塑性エラストマーおよび流動パラフィンを含有し、
薬物含有粘着層中の流動パラフィンの含有量が、熱可塑性エラストマー100重量部に対して、300重量部超1500重量部以下であり、
薬物含有粘着層中の粘着付与剤の含有量が、10重量%以下(0重量%を含む)である、請求項1〜3のいずれか一項に記載の経皮吸収製剤。 - 熱可塑性エラストマーが、スチレン系ブロック共重合体である請求項4に記載の経皮吸収製剤。
- スチレン系ブロック共重合体が、スチレン−イソプレン−スチレンブロック共重合体である請求項5に記載の経皮吸収製剤。
- 薬物含有粘着層が、粘着付与剤を含有しない請求項4〜6のいずれか一項に記載の経皮吸収製剤。
- 薬物含有粘着層が、エステル系溶媒および/またはアルコール系溶媒を含有する請求項1〜7のいずれか一項に記載の経皮吸収製剤。
- 薬物含有粘着層が、エステル系溶媒およびアルコール系溶媒を含有する請求項1〜7のいずれか一項に記載の経皮吸収製剤。
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US20130226112A1 (en) * | 2010-09-03 | 2013-08-29 | Medrx Co., Ltd. | Percutaneous absorbent and adhesive sheet for skin patch |
JP2016135744A (ja) * | 2013-05-08 | 2016-07-28 | 株式会社 ケイ・エム トランスダーム | 貼付剤 |
CN108778272A (zh) * | 2015-12-10 | 2018-11-09 | Km特兰斯达股份有限公司 | 经皮吸收制剂 |
EP3563843A4 (en) * | 2016-12-28 | 2019-12-11 | FUJIFILM Toyama Chemical Co., Ltd. | TOPICAL COMPOSITION |
CA3085342A1 (en) * | 2017-12-13 | 2019-06-20 | Corium, Inc. | Method for depot creation during transdermal drug delivery |
KR102024996B1 (ko) * | 2017-12-27 | 2019-09-25 | 동아에스티 주식회사 | 도네페질을 함유하는 치매 치료용 경피흡수제제 |
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WO2003032960A1 (fr) * | 2001-10-17 | 2003-04-24 | Hisamitsu Pharmaceutical Co., Inc. | Preparations pour absorption percutanee |
JP2005162616A (ja) * | 2003-11-28 | 2005-06-23 | Daio Paper Corp | メディカルシート |
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WO2011049038A1 (ja) * | 2009-10-21 | 2011-04-28 | 帝國製薬株式会社 | ドネペジル含有経皮吸収型製剤 |
WO2011074635A1 (ja) * | 2009-12-16 | 2011-06-23 | 後藤 武 | 抗認知症薬物の経皮吸収製剤 |
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WO2003032960A1 (fr) * | 2001-10-17 | 2003-04-24 | Hisamitsu Pharmaceutical Co., Inc. | Preparations pour absorption percutanee |
JP2005162616A (ja) * | 2003-11-28 | 2005-06-23 | Daio Paper Corp | メディカルシート |
WO2009066457A1 (ja) * | 2007-11-22 | 2009-05-28 | Medrx Co., Ltd. | 脂肪酸系イオン液体を有効成分とする外用剤組成物 |
WO2011049038A1 (ja) * | 2009-10-21 | 2011-04-28 | 帝國製薬株式会社 | ドネペジル含有経皮吸収型製剤 |
WO2011074635A1 (ja) * | 2009-12-16 | 2011-06-23 | 後藤 武 | 抗認知症薬物の経皮吸収製剤 |
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