JP2016502993A - ゲル組成物 - Google Patents
ゲル組成物 Download PDFInfo
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- JP2016502993A JP2016502993A JP2015547061A JP2015547061A JP2016502993A JP 2016502993 A JP2016502993 A JP 2016502993A JP 2015547061 A JP2015547061 A JP 2015547061A JP 2015547061 A JP2015547061 A JP 2015547061A JP 2016502993 A JP2016502993 A JP 2016502993A
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- polycarbophil
- skin
- pharmaceutical
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Abstract
Description
1から5重量%の含有量のポリカルボフィルと、
4から8重量%の含有量のポリビニルピロリドンと、
1から10重量%の含有量のグリセリンと、
20から40重量%の含有量のプロピレングリコールと
を含み、ここで、
ポリビニルピロリドン:ポリカルボフィルの重量比は、1:1から4:1であり、
グリセリン:ポリカルボフィルの重量比は、1:1から2:1であり、
プロピレングリコール:ポリカルボフィルの重量比は、8:1から20:1である、
組み合わせを提供する。
から作製され、CAS番号9003−39−8を有する水溶性ポリマーとして理解されなくてはならない。重合反応を終了させる機構は、ほぼあらゆる分子量の可溶性ポリビニルピロリドンを生成することを可能にする。異なる鎖長は異なる粘度で産出する。伝統的に、重合度はK値によって特徴付けられ、これは、本質的に、水溶液における粘度の関数である(例証的な非限定的例:K−15、K−25、K−30、K−60及びPVP K−90)。
ポリカルボフィル:3重量%と、
ポリビニルピロリドン:6重量%と、
グリセリン:2重量%と、
プロピレングリコール:30重量%と、
トロメタモール:3重量%と
を含むものである。
[式中、「溶質」は活性成分である]。
すべての構成要素を、市販の精密てんびんで秤量した。次いで、メントール結晶をモルタル吹き付けし、その後、これをかき混ぜながら、プロピレングリコールに溶解した。溶液を沈殿容器に組み込み、かき混ぜながら、アシクロビルを組み込んだ。
A)材料及び方法
A.1.美容整形によるヒト女性腹部由来の皮膚膜を使用した。分裂皮膚(およそ500p.m)は皮節を用いて調製されたものであり、角質層、表皮、及び真皮の一部を含む。拡散セルにおいて使用するための皮膚片(暴露面積の直径10mm)を、押抜き具で生成した。皮膚片を顕微鏡スライドガラスに挟み、−15℃で凍結した。調製した分裂皮膚の厚さを、二枚の顕微鏡スライドガラスプレパラートに挟んで測定した。
二つの異なる製剤を試験した:製剤1(実施例1)及び基準としてゾビラックスを選んだ。
分析を実施するまで、すべての試料を凍結した。
アシクロビルの量が皮膚において決定される図1において、本発明の組成物が投与された場合に実質的な累積効果があることが観察できる。実際に、10及び24時間では、皮膚表面上で利用可能なアシクロビルの量は、基準製剤を適用した場合に取得される量と比較して著しく高いことが示されている。
これは、本発明の組み合わせが、(a)薬物のバイオアベイラビリティには悪影響を及ぼさないが、対照的に、実質的な薬物バイオアベイラビリティを保証し、(b)前記薬物がより長期間に皮膚に残り(これは、累積効果等を説明する)、(c)悪条件(皮膚リンス等)下であっても、基準組成物で利用可能なものの少なくとも二倍の活性成分の量を保証する、基準組成物よりも良好な生体接着プロファイルを示し、(d)薬物が体循環に至らない、マトリックスを提供することを意味する。
アシクロビルは、安全性プロファイルが十分に確立された、広く知られている物質である。しかしながら、本発明の組み合わせの安全性プロファイルを確認するために、一連の安全性研究及び調節耐性を製剤1(この項においては、「試験生成物」とも称する)で実施し、そのうち、単回用量でのウサギにおける真皮耐性研究、反復用量でのウサギにおける真皮耐性研究、及び単回用量でのウサギにおける眼の耐性研究は以下に含まれる。
A)目標
この研究の目的は、ウサギの結膜嚢における単回用量適用後の、製剤1の眼の耐性を評定すること(刺激/腐食試験)であった。
初期試験(刺激/腐食):ニュージーランドウサギの右目の結膜嚢に、0.1mLの試験生成物の単回適用を受けさせた。左目は未治療とし、コントロールとして役立てた。
動物を同定し、個々のケージに分けた。順応期間の後、初期試験を始め、このために、本発明人らは、投与の24時間前に拡大鏡及び懐中電灯を使用して、第一の動物の目の検査を進めた。1と同定された動物の右目の結膜嚢に、0.1mLの試験生成物の単回適用用量を受けさせた。下まぶたを眼球の外側にそっと引くことによって、生成物を適用した。適用したら、材料損失を防止するために、眼瞼を一緒に約一秒間保持した。左目は未治療とし、コントロールとして役立てた。腐食又は重度の刺激の兆候の非存在下で、本発明人らは確認試験を実施し、このために、本発明人らは、上述したのと同じ様式で、他二匹の動物の研究(2及び3のラベル付き)を同時に進めた。
生存率/死亡率:毎日、投与後3日間。
動物の重量:動物の到着まで、開始時及び屠殺前、PNT−BT−502として。
全身症状:投与の前後、及びその後3日間毎日。
眼の腐食を、初期試験の一部として、生成物の適用直後、並びに1、24、48及び72時間後に評価した。眼の腐食は、存在−非存在の観点から、貫通又は著しい角膜潰瘍、潰瘍又は結膜の壊死、瞬膜の壊死、眼内出血(hemorrhage)、48時間持続するグレード4の角膜混濁及び72時間持続するグレード2の光に対する虹彩の無反応として、不可逆的とみなされる病変と評定された。
眼内刺激を、研究の3匹の動物について(初期及び確認アッセイ)、生成物適用の1、24、48及び72時間後に評定した。異常の非存在下では、可逆性を研究する必要はなく、治療の72時間後に研究を終えた。
H.1.生存率/死亡率及び全身症状:試験生成物が投与された動物のいずれにおいても、致死性は記録されなかった。実験動物は、全体的な状態において変性を示さなかった。
製剤1は、刺激性でないとして分類された。
A)目標:1mL/120cm2(8.3μL/cm2)、1日4回、最大10日間の真皮反復用量適用後の、ウサギにおける試験生成物の局部耐性を、1、5及び10日目における耐性評価とともに評定すること。さらに、取得された耐性データに対する製剤ビヒクルの影響を評価するために、研究には、治療群と並行して、試験生成物のビヒクルを受けた動物群の包含を含めた。
分配
二つの群(n=12)、−治療及びビヒクル−の、24匹のニュージーランド雄ウサギ。各群を、四つの亜群(n=3)−a、b、c及び逆転−に分割した。
1mL/120cm2(8.3μL/cm2)の試験生成物の、1日4回の真皮適用(2.5時間±15分の範囲)。適用は、120cm2(体内組織の約10%)の剃毛した領域に為された。適用回数は亜群によって決定し、各動物について、治療の開始日を0日目とみなした。
亜群a:1日のみの投与(0日目)。
亜群b:5日間毎日の投与(0から4日目まで)。
亜群c:10日間毎日の投与(0から9日目まで)。
亜群逆転:10日間毎日の投与(0から9日目まで)。
・治療群及びビヒクル群(亜群a、b及びc):最後の投与後最大16時間
・治療群及びビヒクル群(亜群逆転):最後の投与後最大72時間
動物を同定し、12匹の動物からなる二つの群:治療群及びビヒクル群に分けた。今度は、各群を、それぞれ3匹の動物によって形成される四つの亜群−a、b、c及び逆転−に分割した。動物小屋を個別化した。
生存率/死亡率:毎日
全身症状:動物挙動を、投与期間中毎日モニターした。研究には、全身状態、活動、体位、皮膚の色、目、粘液性膜の評価、並びに発作、振戦、下痢及び立毛の存在/非存在を含めた。
動物の重量:動物の到着時、開始時及び屠殺前。
1mL/120cm2の量で、1日4回適用、10日間にわたる試験生成物の真皮適用は、非刺激性であり、完全に安全であった。
A)目標:この研究の目的は、ウサギにおける、無傷な皮膚への単回適用用量後の、試験生成物の皮膚真皮耐性(刺激/腐食)を評価することであった。
初期試験(刺激/腐食):ニュージーランドウサギには、各投与領域についておよそ6cm2の体内組織上に、該動物の背領域に経真皮的に適用される試験生成物(治療領域)及びそのビヒクル(ビヒクルコントロール領域)両方の単回0.5mL用量を受けさせた。暴露期間は4時間であった。72時間以内の腐食の兆候の非存在下で、本発明人らは、下記の試験(確認試験)の実現を進めた。
動物を同定し、個々のケージに分けた。順応期間の後、初期試験を始め、このために、本発明人らは、適用のおよそ24時間前に、第一の動物の背部を慎重に剃毛した。
生存率/死亡率:毎日、投与後3日間。
動物の重量:動物の到着まで、開始時及び屠殺前。
全身症状:投与の前後、及びその後3日間毎日。
皮膚腐食を、初期試験の一部として、包帯の除去後、並びに1、24、48及び72時間後に評価した。反応物を、存在−非存在の観点から、潰瘍、出血、及び出血性構成要素を伴う痂皮化について評価した。
皮膚刺激を、研究(初期及び確認試験)の3匹の動物について、包帯の除去の1、24、48及び72時間後に評価した。変化が観察されなかったため、研究期間を延長する必要はなかった。
実験段階を終了させたら、動物を、事前に鎮静し、致死注射によって犠牲にした。
H.1.生存率/死亡率及び全身症状:試験生成物が投与された動物のいずれにおいても、致死性は記録されなかった。実験動物は、全体的な状態において変性を示さなかった。
試験生成物について算出された皮膚刺激指数(IIC)は、ゼロの値を有する。適用領域において、紅斑、浮腫又は他の反応の非存在が観察された。上記に従い、試験生成物は非刺激性として分類されると結論付けた。
Claims (15)
- 1から5重量%の含有量のポリカルボフィルと、
4から8重量%の含有量のポリビニルピロリドンと、
1から10重量%の含有量のグリセリンと、
20から40重量%の含有量のプロピレングリコールと
を含み、
ここで、
ポリビニルピロリドン:ポリカルボフィルの重量比は、1:1から4:1であり、
グリセリン:ポリカルボフィルの重量比は、0.5:1から2:1であり、
プロピレングリコール:ポリカルボフィルの重量比は、8:1から20:1である、
組み合わせ。 - ポリビニルピロリドン:ポリカルボフィルの前記重量比が2:1である、請求項1に記載の組み合わせ。
- グリセリン:ポリカルボフィル間の前記重量比が、0.5:1から1:1である、請求項1又は2に記載の組み合わせ。
- プロピレングリコール:ポリカルボフィルの前記重量比が10:1である、請求項1から3のいずれか一項に記載の組み合わせ。
- pH調節剤をさらに含む、請求項1から4のいずれか一項に記載の組み合わせ。
- 前記pH調節剤がトロメタモールである、請求項5に記載の組み合わせ。
- ポリカルボフィル:3重量%と、
ポリビニルピロリドン:6重量%と、
グリセリン:2重量%と、
プロピレングリコール:30重量%と、
トロメタモール:3重量%と
を含む、請求項1から6のいずれか一項に記載の組み合わせ。 - 請求項1から7のいずれか一項に記載の組み合わせを、(a)活性成分又は薬学的に若しくは獣医学的に許容されるその塩の治療有効量;並びに(b)他の適切な薬学的に若しくは獣医学的に許容される賦形剤及び/又は担体と共に含む、薬学的又は獣医学的組成物。
- ゲルの形態である、請求項8に記載の薬学的又は獣医学的組成物。
- 持続放出型のものである、請求項8から10のいずれか一項に記載の薬学的又は獣医学的組成物。
- 請求項8から10のいずれか一項に記載の薬学的又は獣医学的組成物を調製するための方法であって、下記の工程:
(a)前記活性成分又は薬学的に若しくは獣医学的に許容されるその塩を、プロピレングリコールとかき混ぜながら混合すること、
(b)前記ポリビニルピロリドンを添加すること、
(c)前記グリセリンを添加すること、
(d)前記ポリカルボフィルを添加すること、及び
(e)前記他の適切な薬学的に若しくは獣医学的に許容される賦形剤及び/又は担体を添加すること
を含む方法。 - 請求項1から7のいずれか一項に記載の組み合わせ、又は請求項8から10のいずれか一項に記載の薬学的若しくは獣医学的組成物と、支持体とを含む、キット。
- ゲル形成剤としての、請求項1から7のいずれか一項に記載の組み合わせの使用。
- 組み合わせを体内組織上に堆積させ、それにより、前記組織から水分を吸収し、前記体内組織の表面上にフィルムを形成することによる、フィルム形成剤としての、請求項1から7のいずれか一項に記載の組み合わせの使用。
- 医薬としての使用のための、請求項8から10のいずれか一項に記載の薬学的又は獣医学的組成物。
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JP2015547061A Active JP6382215B2 (ja) | 2012-12-17 | 2013-12-16 | ゲル組成物 |
Country Status (17)
Country | Link |
---|---|
US (1) | US9486403B2 (ja) |
EP (2) | EP2742932A1 (ja) |
JP (1) | JP6382215B2 (ja) |
KR (1) | KR102207658B1 (ja) |
CN (1) | CN104918605B (ja) |
AU (1) | AU2013363788B2 (ja) |
BR (1) | BR112015014180A8 (ja) |
CA (1) | CA2893656C (ja) |
ES (1) | ES2608794T3 (ja) |
HK (1) | HK1215197A1 (ja) |
MX (1) | MX349868B (ja) |
NZ (1) | NZ709219A (ja) |
PL (1) | PL2931255T3 (ja) |
PT (1) | PT2931255T (ja) |
RU (1) | RU2677892C2 (ja) |
WO (1) | WO2014095705A1 (ja) |
ZA (1) | ZA201504144B (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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EP3838243A1 (de) * | 2019-12-20 | 2021-06-23 | Paul Hartmann AG | Inkontinenzartikel mit ph-regulationsmittel |
CN112023452B (zh) * | 2020-08-19 | 2022-02-11 | 肇庆领誉环保实业有限公司 | 一种生活污水处理用消泡剂及其制备方法 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07223938A (ja) * | 1994-02-09 | 1995-08-22 | Saitama Daiichi Seiyaku Kk | 貼付剤基剤 |
JP2002507561A (ja) * | 1998-03-23 | 2002-03-12 | ラボラトアール テラメックス | 全身作用を有する局所ホルモン組成物 |
EP1413292A1 (en) * | 2002-10-25 | 2004-04-28 | FARMAKA S.r.l. | Bioadhesive pharmaceutical compositions based on non-steroidal anti-inflammatory drugs |
WO2005074883A1 (en) * | 2004-01-29 | 2005-08-18 | Sinclair Pharmaceuticals Limited | Aqueous compositions containing mixtures of synthetic polymers and biopolymers, useful in the treatment of skin and mucosal tissues dryness, and suitable as vehicles of active ingredients |
JP2011121983A (ja) * | 2011-02-08 | 2011-06-23 | Access Pharmaceuticals Inc | 粘膜の疾患および障害の予防および処置のための液体製剤 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100234336A1 (en) * | 2005-11-14 | 2010-09-16 | Erning Xia | Ophthalmic Compositions |
NZ577020A (en) * | 2006-10-17 | 2012-05-25 | Nuvo Res Inc | Diclofenac gel containing dimethyl sulfoxide (dmso) |
CN102038672B (zh) * | 2009-10-10 | 2014-04-16 | 广东东阳光药业有限公司 | 一种用于治疗痤疮的药物组合物 |
EP2444067A1 (en) | 2010-10-20 | 2012-04-25 | Laboratorios Ojer Pharma S.L. | Anhydrous gel comprising mupirocin |
EP2654677B1 (en) * | 2010-12-22 | 2018-04-04 | Colgate-Palmolive Company | Oral care compositions |
-
2012
- 2012-12-17 EP EP12197473.7A patent/EP2742932A1/en not_active Withdrawn
-
2013
- 2013-12-16 US US14/652,565 patent/US9486403B2/en active Active
- 2013-12-16 KR KR1020157019130A patent/KR102207658B1/ko active IP Right Grant
- 2013-12-16 NZ NZ709219A patent/NZ709219A/en unknown
- 2013-12-16 MX MX2015007347A patent/MX349868B/es active IP Right Grant
- 2013-12-16 RU RU2015129081A patent/RU2677892C2/ru active
- 2013-12-16 JP JP2015547061A patent/JP6382215B2/ja active Active
- 2013-12-16 EP EP13815447.1A patent/EP2931255B1/en active Active
- 2013-12-16 WO PCT/EP2013/076677 patent/WO2014095705A1/en active Application Filing
- 2013-12-16 CN CN201380066241.XA patent/CN104918605B/zh active Active
- 2013-12-16 PL PL13815447T patent/PL2931255T3/pl unknown
- 2013-12-16 CA CA2893656A patent/CA2893656C/en active Active
- 2013-12-16 ES ES13815447.1T patent/ES2608794T3/es active Active
- 2013-12-16 AU AU2013363788A patent/AU2013363788B2/en active Active
- 2013-12-16 PT PT138154471T patent/PT2931255T/pt unknown
- 2013-12-16 BR BR112015014180A patent/BR112015014180A8/pt not_active Application Discontinuation
-
2015
- 2015-06-09 ZA ZA2015/04144A patent/ZA201504144B/en unknown
-
2016
- 2016-03-22 HK HK16103319.0A patent/HK1215197A1/zh unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07223938A (ja) * | 1994-02-09 | 1995-08-22 | Saitama Daiichi Seiyaku Kk | 貼付剤基剤 |
JP2002507561A (ja) * | 1998-03-23 | 2002-03-12 | ラボラトアール テラメックス | 全身作用を有する局所ホルモン組成物 |
EP1413292A1 (en) * | 2002-10-25 | 2004-04-28 | FARMAKA S.r.l. | Bioadhesive pharmaceutical compositions based on non-steroidal anti-inflammatory drugs |
WO2005074883A1 (en) * | 2004-01-29 | 2005-08-18 | Sinclair Pharmaceuticals Limited | Aqueous compositions containing mixtures of synthetic polymers and biopolymers, useful in the treatment of skin and mucosal tissues dryness, and suitable as vehicles of active ingredients |
JP2011121983A (ja) * | 2011-02-08 | 2011-06-23 | Access Pharmaceuticals Inc | 粘膜の疾患および障害の予防および処置のための液体製剤 |
Also Published As
Publication number | Publication date |
---|---|
KR20150095898A (ko) | 2015-08-21 |
RU2677892C2 (ru) | 2019-01-22 |
HK1215197A1 (zh) | 2016-08-19 |
NZ709219A (en) | 2019-06-28 |
AU2013363788A1 (en) | 2015-07-09 |
ZA201504144B (en) | 2017-03-29 |
EP2931255A1 (en) | 2015-10-21 |
BR112015014180A2 (pt) | 2017-07-11 |
JP6382215B2 (ja) | 2018-08-29 |
PL2931255T3 (pl) | 2017-06-30 |
PT2931255T (pt) | 2017-01-04 |
CN104918605B (zh) | 2017-09-15 |
RU2015129081A (ru) | 2017-01-25 |
KR102207658B1 (ko) | 2021-01-26 |
MX2015007347A (es) | 2015-09-10 |
CN104918605A (zh) | 2015-09-16 |
WO2014095705A1 (en) | 2014-06-26 |
BR112015014180A8 (pt) | 2019-10-22 |
EP2931255B1 (en) | 2016-10-19 |
MX349868B (es) | 2017-08-17 |
US20150343066A1 (en) | 2015-12-03 |
CA2893656A1 (en) | 2014-06-26 |
ES2608794T3 (es) | 2017-04-17 |
EP2742932A1 (en) | 2014-06-18 |
US9486403B2 (en) | 2016-11-08 |
CA2893656C (en) | 2020-11-03 |
AU2013363788B2 (en) | 2016-06-23 |
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