JP2018517715A - エステトロールを含有する口腔内崩壊錠 - Google Patents
エステトロールを含有する口腔内崩壊錠 Download PDFInfo
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- JP2018517715A JP2018517715A JP2017563337A JP2017563337A JP2018517715A JP 2018517715 A JP2018517715 A JP 2018517715A JP 2017563337 A JP2017563337 A JP 2017563337A JP 2017563337 A JP2017563337 A JP 2017563337A JP 2018517715 A JP2018517715 A JP 2018517715A
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- estetrol
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- UDSFVOAUHKGBEK-CNQKSJKFSA-N testosterone undecanoate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCCCCCCCC)[C@@]1(C)CC2 UDSFVOAUHKGBEK-CNQKSJKFSA-N 0.000 description 1
- 229960000746 testosterone undecanoate Drugs 0.000 description 1
- 150000003515 testosterones Chemical class 0.000 description 1
- WZDGZWOAQTVYBX-XOINTXKNSA-N tibolone Chemical compound C([C@@H]12)C[C@]3(C)[C@@](C#C)(O)CC[C@H]3[C@@H]1[C@H](C)CC1=C2CCC(=O)C1 WZDGZWOAQTVYBX-XOINTXKNSA-N 0.000 description 1
- 229960001023 tibolone Drugs 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000001720 vestibular Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000036266 weeks of gestation Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A61K31/00—Medicinal preparations containing organic active ingredients
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Abstract
Description
国際公開第2002/094275号は、女性のリビドーを増強する方法におけるエステトロールの使用について記載されており、前記方法は、前記女性に有効量のエステトロールを投与することを含む。経口投与は適切な投与様式として言及されている。この特許出願は、国際公開第2002/094276号と同じエステトロール錠剤について記載されている。
国際公開第2003/041718号は、哺乳動物に対するホルモン補充法におけるエステトロールの使用について記載されており、前記方法は、哺乳動物に、低エストロゲン症の症状を予防又は治療するために有効な量のエステトロール及びプロゲストゲン成分を経口投与することを含む。この特許出願は、国際公開第2002/094279号と同じエステトロール錠剤について記載されている。
体積中位径(volume median diameter)が10μm〜400μmの担体粒子を形成するステップ、
少なくとも水60重量%、エステトロール成分1〜40重量%、及び任意選択で1種又は複数の他の薬学的に許容される成分0〜40重量%を含有する水性液体を生成するステップ、
上記水性液体1重量部を上記担体粒子0.5〜20重量部と混合して湿潤粒子を形成するステップ、
上記湿潤粒子から水を除去して担持粒子を形成するステップ、
任意選択で、上記担持粒子を1種又は複数の錠剤化賦形剤と混合するステップ、及び
上記担持粒子又は担持粒子と1種又は複数の錠剤化賦形剤の上記混合物を固形投与単位に形成するステップ
を含む方法によって入手可能である。
体積中位径が10μm〜400μmの担体粒子を形成するステップ、
少なくとも水60重量%、エステトロール成分1〜40重量%、及び任意選択で1種又は複数の他の薬学的に許容される成分0〜40重量%を含有する水性液体を生成するステップ、
上記水性液体1重量部を上記担体粒子0.5〜20重量部と混合して湿潤粒子を形成するステップ、
上記湿潤粒子から水を除去して担持粒子を形成するステップ、
任意選択で、上記担持粒子を1種又は複数の錠剤化賦形剤と混合するステップ、及び
上記担持粒子又は担持粒子と1種又は複数の錠剤化賦形剤の上記混合物を固形投与単位に形成するステップ
を含む。
体積中位径が10μm〜400μmの担体粒子を形成するステップ、
少なくとも水60重量%、エステトロール成分1〜40重量%、及び任意選択で1種又は複数の他の薬学的に許容される成分0〜40重量%を含有する水性液体を生成するステップ、
上記水性液体1重量部を上記担体粒子0.5〜20重量部と混合して湿潤粒子を形成するステップ、
上記湿潤粒子から水を除去して担持粒子を形成するステップ、
任意選択で、上記担持粒子を1種又は複数の錠剤化賦形剤と混合するステップ、及び
上記担持粒子又は担持粒子と1種又は複数の錠剤化賦形剤の上記混合物を固形投与単位に形成するステップ
を含む方法によって得られる。
体積中位径が10μm〜400μmの担体粒子を形成するステップ、
少なくとも水60重量%、エステトロール成分1〜40重量%、及び任意選択で1種又は複数の他の薬学的に許容される成分0〜40重量%を含有する水性液体を生成するステップ、
上記水性液体1重量部を上記担体粒子0.5〜20重量部と混合して湿潤粒子を形成するステップ、
上記湿潤粒子から水を除去して担持粒子を形成するステップ、
任意選択で、上記担持粒子を1種又は複数の錠剤化賦形剤と混合するステップ、及び
上記担持粒子又は担持粒子と1種又は複数の錠剤化賦形剤の上記混合物を固形投与単位に形成するステップ
を含む前記方法に関する。
下記溶出試験は、口腔内崩壊性投与単位の溶出挙動を試験するために適用することができる。
パドル及びバスケット溶出試験器バンケルVK7010(VanKel VK7010)又はVK7025、オートサンプラーVK8000、1000mL溶出試験器用ベッセル、及び多孔性ミクロンフィルター(35ピン)
10,000mLのメスフラスコに脱イオン水(demineralised water)9,000mLを移す。
68.05gのKH2PO4及び8.96gのNaOHを加え、すべてが溶解するまで上記溶液を撹拌する。
上記溶液を混合し、必要であれば、NaOH又はリン酸を用いてpHを6.8に調整し、脱イオン水を用いて体積を調整する。
溶出媒体900mLをパドル装置の各ベッセルに移す。
装置を組み立て、上記媒体を37±0.5℃に加温し、温度計を取り外す。
パドルの回転を開始する前に6個のベッセルの底にそれぞれ1個の錠剤を置く。
直ちにパドルの回転を開始する。
50rpmの撹拌速度を用いる。
完全な溶出プロファイルのため、5、10、20、30、45、60、75、及び90分後に溶出試験器用ベッセルからサンプル5mLを採取する。溶出媒体の表面とパドルブレードの先端の間の中間で、ベッセル壁から10mm以上離れた位置からサンプルを採取する。取り除かれた溶出媒体の体積分は、新たな溶出媒体で置き換えない。
サンプル中のエステトロール濃度は、基準としてエステトロール原液を用いたHPLCによって確定された。
1.15gのNH4H2PO4(10mM)を脱イオン水1,000mLに移して溶解し、リン酸を用いてpHを3.0に調整する。
クォータナリ溶媒送達システム、容量可変インジェクター、温度制御オートサンプラー、カラム恒温槽、及びフォトダイオードアレイ検出器2996(すべてWaters)から成るアライアンス2695(Alliance2695)分離モジュール
分析カラム:シンメトリーC18(Symmetry C18)、3.9×150mm、dp=5μm(Waters製)
ガードカラム:セキュリティーガード(Security guard)カラムC18、4x3mm(Phenomenex)
流量:1.0mL/分
検出:UV@280nm
カラム温度:30℃
オートサンプラー温度:10℃
注入量:100μL
実行時間:12分
エステトロール一水和物の粒径分布は、マルバーンマスターサイザーマイクロプラス(MALVERN MASTERSIZER MICROPLUS)レーザー粒径分析器を用いて実施する。
エステトロール一水和物1g及びトリオレイン酸ソルビタン1gをフラスコ内に量り取る。
n−ヘキサン1Lを加え、室温で少なくとも1時間混合する。
0.45μmフィルターを通して濾過する。
サンプル100mgを25mLビーカーに入れる。
分散媒を数滴加える。
ガラス棒で慎重に混合し、粉末を十分に懸濁させる。
分散媒10mLを加える。
サンプル分散ユニットの速度3000〜3500rpmで分析を実施する。
粒径測定は、同じ分散を用いて3回実施する。最終的な結果は、3回の検出結果を平均して得られる。
舌下錠は、下記の手順によって調製する。
舌下錠は、下記の手順及び図1に示される手順によって調製する。
無作為化、非盲検、二期間、クロスオーバー、薬物動態試験を実施し、80mgの錠剤1個で投与されたエステトロール10mgの舌下バイオアベイラビリティと、エステトロール10mgを含有する83mgの錠剤に含有されたエステトロールの経口アベイラビリティを比較した。これらの錠剤は、絶食状態の女性健常者に舌下及び経口投与された。
Claims (25)
- 重量が30〜1,000mgの間である口腔内崩壊性固形医薬投与単位であって、エステトロール、エステトロールエステル、及びその組合せから選択されるエステトロール成分を少なくとも100μg含有し、前記固形投与単位は:
体積中位径が10μm〜400μmの担体粒子を形成するステップ、
少なくとも水60重量%、エステトロール成分1〜40重量%、及び任意選択で1種又は複数の他の薬学的に許容される成分0〜40重量%を含有する水性液体を生成するステップ、
前記水性液体1重量部を前記担体粒子0.5〜20重量部と混合して湿潤粒子を形成するステップ、
前記湿潤粒子から水を除去して担持粒子を形成するステップ、
任意選択で、前記担持粒子を1種又は複数の錠剤化賦形剤と混合するステップ、及び
前記担持粒子又は担持粒子と1種又は複数の錠剤化賦形剤の前記混合物を固形投与単位に形成するステップ
を含む方法によって得られる、口腔内崩壊性固形医薬投与単位。 - 前記投与単位の重量が40〜500mgの間である、請求項1に記載の口腔内崩壊性固形医薬投与単位。
- エステトロール成分を0.3〜100mg含有する、請求項1又は2に記載の口腔内崩壊性固形医薬投与単位。
- 前記エステトロール成分がエステトロールである、請求項1〜3のいずれか一項に記載の口腔内崩壊性固形医薬投与単位。
- 前記投与単位がマンニトールを少なくとも20重量%含有する、請求項1〜4のいずれか一項に記載の口腔内崩壊性固形医薬投与単位。
- 前記投与単位が、加工デンプン、架橋ポリビニルピロリドン、クロスカルメロース、及びその組合せから選択される崩壊剤を0.1〜20重量%含有する、請求項1〜5のいずれか一項に記載の口腔内崩壊性固形医薬投与単位。
- 医学的治療における使用又は女性ホルモン補充療法における使用であって、前記投与単位を舌下、頬側、又は唇下投与することを含む前記使用のための、請求項1〜6のいずれか一項に記載の固形投与単位。
- 請求項7に記載の使用であって、少なくとも1週間の期間に1日1回投与することを含む前記使用のための固形投与単位。
- 女性の避妊の方法であって、請求項1〜6のいずれか一項に記載の投与単位を舌下、頬側、又は唇下投与することを含む前記方法。
- 前記方法が少なくとも1週間の期間に1日1回投与することを含む、請求項9に記載の方法。
- 請求項1〜10のいずれか一項に記載の固形投与単位を製造する方法であって:
体積中位径が10μm〜400μmの担体粒子を形成するステップ、
少なくとも水60重量%、エステトロール成分1〜40重量%、及び任意選択で1種又は複数の他の薬学的に許容される成分0〜40重量%を含有する水性液体を生成するステップ、
前記水性液体1重量部を前記担体粒子0.5〜20重量部と混合して湿潤粒子を形成するステップ、
前記湿潤粒子から水を除去して担持粒子を形成するステップ、
任意選択で、前記担持粒子を1種又は複数の錠剤化賦形剤と混合するステップ、及び
前記担持粒子又は担持粒子と1種又は複数の錠剤化賦形剤の前記混合物を固形投与単位に形成するステップ
を含む前記方法。 - 前記担体粒子が、単糖類、二糖類、三糖類、C4〜C12糖アルコール、及びその組合せから選択される水溶性炭水化物を少なくとも30重量%含有する、請求項11に記載の方法。
- 前記担体粒子が、前記水溶性炭水化物を少なくとも50重量%含有する、請求項12に記載の方法。
- 水溶性炭水化物が、マルトース、フルクトース、スクロース、ラクトース、グルコース、ガラクトース、トレハロース、キシリトール、ソルビトール、エリスリトール、マルチトール、マンニトール、及びその組合せから選択される、請求項12又は13に記載の方法。
- 前記担体粒子がマンニトールを少なくとも20重量%含有する、請求項12〜14のいずれか一項に記載の方法。
- 前記担体粒子がラクトースを少なくとも10重量%含有する、請求項12〜15のいずれか一項に記載の方法。
- 前記水性液体が、50μm未満の体積中位径を有する分散したエステトロールを含有する、請求項12〜16のいずれか一項に記載の方法。
- 前記水性液体が前記エステトロール成分を1.5〜30重量%含有する、請求項12〜17のいずれか一項に記載の方法。
- 前記水性液体が、セルロース誘導体、アルファ化デンプン、ポリビニルアルコール、ポリビニルピロリドン、寒天、ゼラチン、グアーガム、アラビアゴム、アルギン酸塩、ポリエチレングリコール、グルコース、スクロース、ソルビトール、及びその組合せから選択される結合剤を0.5〜40重量%含有する、請求項12〜18のいずれか一項に記載の方法。
- 前記湿潤粒子が、高剪断造粒機、低剪断造粒機、又は流動層造粒機で、前記水性液体と前記担体粒子を混合することによって形成される、請求項12〜19のいずれか一項に記載の方法。
- 前記湿潤粒子が、前記水性液体と前記担体粒子を、1:0.8〜1:12の範囲内の重量比で混合することによって調製される、請求項12〜20のいずれか一項に記載の方法。
- 前記担持粒子の体積中位径が100〜4,000μmの範囲内である、請求項12〜21のいずれか一項に記載の方法。
- 前記錠剤化賦形剤が、加工デンプン、架橋ポリビニルピロリドン、クロスカルメロース、及びその組合せから選択される崩壊剤を、前記投与単位の重量に対して0〜15%含有する、請求項12〜22のいずれか一項に記載の方法。
- 前記1種又は複数の錠剤化賦形剤が、ラクトース、マンニトール、キシリトール、微結晶セルロース、デンプン、クロスカルメロースナトリウム、ポリビニルピロリドン、及びその組合せから選択される賦形剤を、前記錠剤化賦形剤の重量に対して少なくとも30%含有する、請求項12〜23のいずれか一項に記載の方法。
- 前記固形投与単位が直接圧縮又は圧縮成形によって形成される、請求項12〜24のいずれか一項に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP15172755 | 2015-06-18 | ||
EP15172755.9 | 2015-06-18 | ||
PCT/EP2016/064181 WO2016203044A1 (en) | 2015-06-18 | 2016-06-20 | Orodispersible tablet containing estetrol |
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JP2018517715A true JP2018517715A (ja) | 2018-07-05 |
JP2018517715A5 JP2018517715A5 (ja) | 2020-11-19 |
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JP (1) | JP6813150B2 (ja) |
CN (1) | CN107750157B (ja) |
CA (1) | CA2988362C (ja) |
CY (1) | CY1124052T1 (ja) |
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ES (1) | ES2877476T3 (ja) |
HK (1) | HK1254649A1 (ja) |
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JP2022513587A (ja) * | 2018-10-31 | 2022-02-09 | セントロ デ インヴェスティガティオネス エネルヘティカス メディオアンビエンタレス イ テクロノヒカス オーアー エメぺー (シエマット) | 造血幹細胞移植後の回復を実施および促進するための改善 |
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TWI801561B (zh) | 2018-04-19 | 2023-05-11 | 比利時商依思特拉私人有限責任公司 | 化合物及其用於緩解絕經相關症狀的用途 |
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ES2877476T3 (es) | 2021-11-16 |
US10888518B2 (en) | 2021-01-12 |
CA2988362C (en) | 2022-07-19 |
SI3310346T1 (sl) | 2021-07-30 |
CN107750157A (zh) | 2018-03-02 |
HRP20210555T1 (hr) | 2021-05-14 |
EP3310346A1 (en) | 2018-04-25 |
PT3310346T (pt) | 2021-04-22 |
RS61777B1 (sr) | 2021-06-30 |
PL3310346T3 (pl) | 2021-10-25 |
CN107750157B (zh) | 2021-07-13 |
CA2988362A1 (en) | 2016-12-22 |
HUE054551T2 (hu) | 2021-09-28 |
DK3310346T3 (da) | 2021-05-25 |
MD3310346T2 (ro) | 2021-06-30 |
JP6813150B2 (ja) | 2021-01-13 |
HK1254649A1 (zh) | 2019-07-26 |
US20180153801A1 (en) | 2018-06-07 |
LT3310346T (lt) | 2021-06-10 |
WO2016203044A1 (en) | 2016-12-22 |
MA44206B1 (fr) | 2021-04-30 |
MA44206A (fr) | 2018-04-25 |
EP3310346B1 (en) | 2021-03-24 |
CY1124052T1 (el) | 2022-05-27 |
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