JP2018108993A - 注腸剤 - Google Patents
注腸剤 Download PDFInfo
- Publication number
- JP2018108993A JP2018108993A JP2017253179A JP2017253179A JP2018108993A JP 2018108993 A JP2018108993 A JP 2018108993A JP 2017253179 A JP2017253179 A JP 2017253179A JP 2017253179 A JP2017253179 A JP 2017253179A JP 2018108993 A JP2018108993 A JP 2018108993A
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- JP
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- Prior art keywords
- enema
- budesonide
- weeks
- day
- administered
- 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.)
- Pending
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- 241000792859 Enema Species 0.000 title claims abstract description 71
- 239000007920 enema Substances 0.000 title claims abstract description 71
- 229940095399 enema Drugs 0.000 title claims abstract description 68
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 claims abstract description 74
- 229960004436 budesonide Drugs 0.000 claims abstract description 73
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 25
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Classifications
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- 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
- A61K9/0031—Rectum, anus
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
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Abstract
Description
[1] ブデソニドを有効成分とし、炎症性腸疾患の治療又は再燃予防のために、1回あたり1.5〜2.5mgのブデソニドを1日あたり2回、12週間投与されることを特徴とする、注腸剤。
[2] ブデソニドの投与量が1回あたり2.0mgである、前記[1]の注腸剤。
[3] 潰瘍性大腸炎又はクローン病の治療又は再燃予防のために投与される、前記[1]又は[2]の注腸剤。
[4] 泡沫状又は液状である、前記[1]〜[3]のいずれかの注腸剤。
[5] 1回あたり1.5〜2.5mgのブデソニドを1日あたり2回、6週間投与された時点において、治療反応が認められたが大腸粘膜治癒(内視鏡所見スコア0点)には至らなかった炎症性腸疾患の患者に対して、さらに1回あたり1.5〜2.5mgのブデソニドを1日あたり2回、6週間投与される、前記[1]〜[4]のいずれかの注腸剤。
[6] 前記[1]〜[5]のいずれかに記載の注腸剤で1回分あたり1.5〜2.5mgのブデソニドを含有する注腸剤を、14回分投与可能な注腸剤パッケージ。
[7] 前記[1]〜[5]のいずれかに記載の注腸剤で1回分あたり1.5〜2.5mgのブデソニドを含有する注腸剤を、14回分投与可能なように調製する、注腸剤パッケージの製造方法。
活動期潰瘍性大腸炎患者を対象に、プラセボを対照とした二重盲検比較試験によりブデソニド2mgを1日2回、6週間、直腸内投与した際の粘膜治癒率を主要評価項目としてブデソニドのプラセボに対する優越性を検証するとともに安全性を調べた。また、6週間投与にて治療反応が認められたが粘膜治癒には至らなかった患者を対象に、ブデソニド2mg1日2回を更に6週間継続投与(計12週間投与)した際の安全性及び有効性を調べた(治験番号:JapicCTI−142704)。
試験には、被験薬として、1回の噴射でブデソニド2mgを含む25mL(1.35g)の白色のクリーム状の泡沫が放出される定量噴射式の注腸用エアゾール剤(直腸泡沫剤)を用いた。当該注腸用エアゾール剤は、病変が直腸及びS状結腸に限局する活動期潰瘍性大腸炎の寛解導入治療薬として、ブデソニド2mgを1日1回の用法・用量で欧州において承認されたものである(商品名:Budenofalk 2mg/dose rectal foam、ドクターファルクファーマ社製)。
また、対照薬として、外観、重量等が被験薬と識別不能で、ブデソニドを含有しない定量噴射式注腸用エアゾール剤を用いた。
活動期の潰瘍性大腸炎患者を被験者とし、被験薬を1日2回投与する群(以下、ブデソニド投与群)及び対照薬を投与する群(以下、プラセボ群)に分けた。
被験薬又は対照薬を、1日2回(朝1回、及び夜1回)、なるべく排便後に直腸内投与した。1投与当たりの噴射回数は1回であり、投与期間は6週間とし、粘膜治癒(内視鏡所見スコアが0点)に至らなかった場合は12週間投与可能とし、評価前日の夜まで投与した。各群のブデソニド投与量は、1日2回群が4mg/日であり、プラセボ群が0mg/日であった。12週間投与した被験者はブデソニド投与群が20例、プラセボ群が18例であった。
各被験者について、投与開始前(0週目)、6週間投与時点、及び12週間投与時点において、大腸内視鏡検査を行い、MMDAIの内視鏡所見スコア(0=正常又は非活動性所見、1=軽症(発赤、血管透見像の減少)、2=中等症(著明に発赤、血管透見像の消失、脆弱、びらん)、3=重症(自然出血、潰瘍))を調べた。内視鏡所見スコアの判定は、試験実施医療機関の担当医師による評価と内視鏡中央判定委員会による評価の2つを実施した。試験実施医療機関の担当医師による評価は、試験に被験者を登録する際の判断と6週間投与時にさらに6週間投与を継続するかの判断に用いた。内視鏡中央判定委員会による評価は、有効性を評価するために用いた。表1から3に示す内視鏡所見スコアは内視鏡中央判定委員会による評価を示す。12週間投与した被験者の測定結果を表1に示す。また、プラセボ群の各被験者の6週目から12週目への内視鏡所見スコアの変化を表2に、ブデソニド投与群の各被験者の6週目から12週目への内視鏡所見スコアの変化を表3に、それぞれ示す。
Claims (7)
- ブデソニドを有効成分とし、炎症性腸疾患の治療又は再燃予防のために、1回あたり1.5〜2.5mgのブデソニドを1日あたり2回、12週間投与されることを特徴とする、注腸剤。
- ブデソニドの投与量が1回あたり2.0mgである、請求項1に記載の注腸剤。
- 潰瘍性大腸炎又はクローン病の治療又は再燃予防のために投与される、請求項1又は2に記載の注腸剤。
- 泡沫状又は液状である、請求項1〜3のいずれか一項に記載の注腸剤。
- 1回あたり1.5〜2.5mgのブデソニドを1日あたり2回、6週間投与された時点において、治療反応が認められたが大腸粘膜治癒(内視鏡所見スコア0点)には至らなかった炎症性腸疾患の患者に対して、さらに1回あたり1.5〜2.5mgのブデソニドを1日あたり2回、6週間投与される、請求項1〜4のいずれか一項に記載の注腸剤。
- 請求項1〜5のいずれか一項に記載の注腸剤で1回あたり1.5〜2.5mgのブデソニドを含有する注腸剤を、14回分投与可能な注腸剤パッケージ。
- 請求項1〜5のいずれか一項に記載の注腸剤で1回あたり1.5〜2.5mgのブデソニドを含有する注腸剤を、14回分投与可能なように調製する、注腸剤パッケージの製造方法。
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