JP2008505909A - 周期的プロゲスチンレジメン及びキット - Google Patents
周期的プロゲスチンレジメン及びキット Download PDFInfo
- Publication number
- JP2008505909A JP2008505909A JP2007520464A JP2007520464A JP2008505909A JP 2008505909 A JP2008505909 A JP 2008505909A JP 2007520464 A JP2007520464 A JP 2007520464A JP 2007520464 A JP2007520464 A JP 2007520464A JP 2008505909 A JP2008505909 A JP 2008505909A
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- Prior art keywords
- dosage unit
- daily dosage
- days
- progestin
- active agent
- 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
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- 230000000737 periodic effect Effects 0.000 title description 4
- -1 tanaproget Chemical class 0.000 claims abstract description 25
- PYVFWTPEBMRKSR-UHFFFAOYSA-N tanaproget Chemical compound CN1C(C#N)=CC=C1C1=CC=C(NC(=S)OC2(C)C)C2=C1 PYVFWTPEBMRKSR-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 15
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- 229960002985 medroxyprogesterone acetate Drugs 0.000 claims description 10
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 claims description 10
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Classifications
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/536—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with carbocyclic ring systems
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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- 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
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/34—Gestagens
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
NSP−989の活性を、標準プロゲスチンである2%トゥイーン80/0.5%メチルセルロース媒質中の酢酸メドロキシプロゲステロン(MPA)及びトリメゲストン(TMG)と共に3つの異なるラットモデルにおいてプロゲスチン活性に関して経口的に評価した。これらのモデルをこの実施例のパートA、B及びCにおいて述べる。
排卵阻害アッセイは、成体雌性ラットにおいて排卵を阻害する化合物の能力を測定する。この活性は避妊効果のために必須である。このアッセイにおいて、NSP−989は0.03mg/kgの平均ED100値を有し、一方TMG及びMPAはいずれも1mg/kgのED100値を有していた(n=2−3)。
プロゲステロン活性を測定するための2番目のラットモデルは、成体卵巣摘出ラットにおける子宮脱落膜化アッセイである。子宮支質細胞を分化した脱落膜細胞に変換するためにプロゲスチンが絶対的に必要であるので、プロゲステロン受容体アゴニストである化合物だけがこのモデルにおいて活性である。
PRアゴニスト活性についての3番目のモデルは、成体卵巣摘出ラット子宮C3モデルであった。このアッセイは、子宮上皮においてエストロゲン誘導のC3発現をブロックするプロゲスチンの能力を評価する。
上述したラットプロゲステロンモデルに加えて、ウサギ子宮内膜変化モデルにおける古典的プロゲステロンアッセイであるクラウベルクモデルでもNSP−989を評価した[McPhail MK, "The assay of progestin." J .Physiol. 1934; 83: 145-1567]。簡単に述べると、未成熟雌性ニュージーランド白色ウサギ(〜1kg体重)に17β−エストラジオール(E2)5μg/ウサギ/日を連続6日間皮下注射した。最後のE2注射の24時間後から、媒質単独又は試験化合物を連続5日間経口的に投与した。子宮重量の増加及び子宮内膜腺分枝(endometrial glandular arborization)(マクファイル(McPhail)指数)によってプロゲステロン活性を測定した。
21日レジメンでのNP−989の3つの用量、次いで7日間のプラセボ丸薬、及び比較物質(Mircetteの製品名で米国において市販されている、配合ステロイドOCデソゲストレル(DSG)150μg/20μgエチニルエストラジオールを21日間、次いで2日間のプラセボ丸剤、次に5日間のEE10μg)から成る、第2相における無作為化された二重盲検による多施設での用量設定試験を計画する。
群 処置
A NSP−989 100μgを21日間、続いてプラセボ丸剤を7日間
B NSP−989 200μgを21日間、続いてプラセボ丸剤を7日間
C NSP−989 300μgを21日間、続いてプラセボ丸剤を7日間
D デソゲストレル150μgを21日間、続いてプラセボ丸剤を2日間、続いてEE10μgを5日間。
Claims (22)
- (a)各々の1日投与単位が、プロゲスチンを含む作用薬の有効量を含有する、作用薬の1日投与単位を21から27日間投与する第1期、及び
(b)作用薬の有効量を投与しない1から7日間の第2期
を含む薬剤を、連続28日間にわたって投与する、妊娠可能年齢の雌性における避妊のために有用な薬剤を製造する上でのプロゲスチンの使用。 - プロゲスチンが、17−ヒドロキシプロゲステロンエステル、19−ノル−17−ヒドロキシプロゲステロンエステル、17α−エチニルテストステロン及びその誘導体、17α−エチニル−19−ノル−テストステロン及びその誘導体、ノルエチンドロン、酢酸ノルエチンドロン、二酢酸エチノジオール、ジドロゲステロン、酢酸メドロキシプロゲステロン、ノルエチノドレル、アリルエストレノール、リネストレノール、酢酸フインゲスタノール(fuingestanol acetate)、メドロゲストン(medrogestone)、ノルゲストリエノン(norgestrienone)、ジメチデローム(dimethiderome)、エチステロン、酢酸シプロテロン、レボノルゲストレル、dl−ノルゲストレル、d−17α−アセトキシ−13β−エチル−17α−a−エチニル−ゴン−4−エン−3−オンオキシム、酢酸シプロテロン、ゲストデン、デソゲストレル、エトノルゲストレル(etonorgestrel)、ノルゲスチメート、ノルエルゲストロミン、クロルマジノン、ジエノゲスト及びドロスピレノンから成る群より選択される、請求項1に記載の使用。
- 第2期に製薬上許容されるプラセボの1日投与単位を1から7日間送達する、請求項1から3のいずれか一項に記載の使用。
- 前記薬剤が、
a)21日分の1日投与単位の第1期;及び
b)7日分の経口的に及び製薬上許容されるプラセボの1日投与単位の第2期
を含む、請求項1から4のいずれか一項に記載の使用。 - 前記薬剤が
a)23日分の1日投与単位の第1期;及び
b)5日分の経口的に及び製薬上許容されるプラセボの1日投与単位の第2期
を含む、請求項1から4のいずれか一項に記載の使用。 - 前記薬剤が
a)25日分の1日投与単位の第1期;及び
b)3日分の経口的に及び製薬上許容されるプラセボの1日投与単位の第2期
を含む、請求項1から4のいずれか一項に記載の使用。 - 前記薬剤が、
a)27日分の1日投与単位の第1期;及び
b)1日分の経口的に及び製薬上許容されるプラセボの1日投与単位の第2期
を含む、請求項1から4のいずれか一項に記載の使用。 - プロゲスチンが5−(4,4−ジメチル−2−チオキソ−1,4−ジヒドロ−2H−ベンゾ[d][1,3]オキサジン−6−イル)−1−メチル−1H−ピロール−2−カルボニトリル(タナプロゲト)である、請求項1から8のいずれか一項に記載の使用。
- (a)各々の1日投与単位が、プロゲスチンを含む作用薬の有効量を含有する、21から27日分の作用薬の1日投与単位、及び
(b)前記1日投与単位のための1又はそれ以上の包装
を含む、連日経口投与に適合させた医薬上有用なキット。 - プロゲスチンが、17−ヒドロキシプロゲステロンエステル、19−ノル−17−ヒドロキシプロゲステロンエステル、17α−エチニルテストステロン及びその誘導体、17α−エチニル−19−ノル−テストステロン及びその誘導体、ノルエチンドロン、酢酸ノルエチンドロン、二酢酸エチノジオール、ジドロゲステロン、酢酸メドロキシプロゲステロン、ノルエチノドレル、アリルエストレノール、リネストレノール、酢酸フインゲスタノール、メドロゲストン、ノルゲストリエノン、ジメチデローム、エチステロン、酢酸シプロテロン、レボノルゲストレル、dl−ノルゲストレル、d−17α−アセトキシ−13β−エチル−17α−a−エチニル−ゴン−4−エン−3−オンオキシム、酢酸シプロテロン、ゲストデン、デソゲストレル、エトノルゲストレル、ノルゲスチメート、ノルエルゲストロミン、クロルマジノン、ジエノゲスト及びドロスピレノンから成る群より選択される、請求項10に記載の医薬上有用なキット。
- 1から7日分の製薬上許容されるプラセボの1日投与単位をさらに含む、請求項10から12のいずれか一項に記載の医薬上有用なキット。
- a)21日分の作用薬の1日投与単位;及び
b)7日分の経口的に及び製薬上許容されるプラセボの1日投与単位
を含む、請求項10から13のいずれか一項に記載の連日経口投与に適合させた医薬上有用なキット。 - a)23日分の作用薬の1日投与単位;及び
b)5日分の経口的に及び製薬上許容されるプラセボの1日投与単位
を含む、請求項10から13のいずれか一項に記載の連日経口投与に適合させた医薬上有用なキット。 - a)25日分の作用薬の1日投与単位;及び
b)3日分の経口的に及び製薬上許容されるプラセボの1日投与単位
を含む、請求項10から13のいずれか一項に記載の連日経口投与に適合させた医薬上有用なキット。 - a)27日分の作用薬の1日投与単位;及び
b)1日分の経口的に及び製薬上許容されるプラセボの1日投与単位
を含む、請求項10から13のいずれか一項に記載の連日経口投与に適合させた医薬上有用なキット。 - 前記1日投与単位が錠剤の形態である、請求項10から17のいずれか一項に記載の医薬上有用なキット。
- 前記1日投与単位が外用クリーム又はゲルの形態である、請求項10から17のいずれか一項に記載の医薬上有用なキット。
- 前記1日投与単位が、経皮、経粘膜又は経膣薬剤送達システムの中から選択される持続放出送達システムによって送達される、請求項10から17のいずれか一項に記載の医薬上有用なキット。
- プロゲスチンが5−(4,4−ジメチル−2−チオキソ−1,4−ジヒドロ−2H−ベンゾ[d][1,3]オキサジン−6−イル)−1−メチル−1H−ピロール−2−カルボニトリルである、請求項10から20のいずれか一項に記載のキット。
- 妊娠可能年齢の雌性に連続18から28日間、プロゲスチンから成る作用薬の有効量を含有する1日投与単位を送達し、続いて連続1から7日間、作用薬の有効量を前記被験者に送達しないことを含む、妊娠可能年齢の雌性における避妊の方法。
Applications Claiming Priority (3)
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US58604504P | 2004-07-07 | 2004-07-07 | |
US60/586,045 | 2004-07-07 | ||
PCT/US2005/023955 WO2006014476A1 (en) | 2004-07-07 | 2005-07-06 | Cyclic progestin regimens and kits |
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JP2012214378A Division JP2013040181A (ja) | 2004-07-07 | 2012-09-27 | 周期的プロゲスチンレジメン及びキット |
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JP2008505909A true JP2008505909A (ja) | 2008-02-28 |
JP2008505909A5 JP2008505909A5 (ja) | 2008-08-21 |
JP5288796B2 JP5288796B2 (ja) | 2013-09-11 |
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JP2007520464A Expired - Fee Related JP5288796B2 (ja) | 2004-07-07 | 2005-07-06 | 周期的プロゲスチンレジメン及びキット |
JP2012214378A Pending JP2013040181A (ja) | 2004-07-07 | 2012-09-27 | 周期的プロゲスチンレジメン及びキット |
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JP2012214378A Pending JP2013040181A (ja) | 2004-07-07 | 2012-09-27 | 周期的プロゲスチンレジメン及びキット |
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US (3) | US20060009428A1 (ja) |
EP (1) | EP1773344A1 (ja) |
JP (2) | JP5288796B2 (ja) |
CN (2) | CN1980676A (ja) |
AR (1) | AR049707A1 (ja) |
AU (1) | AU2005269938A1 (ja) |
BR (1) | BRPI0512991A (ja) |
CA (1) | CA2571377C (ja) |
MX (1) | MXPA06014579A (ja) |
PA (1) | PA8638601A1 (ja) |
PE (1) | PE20060378A1 (ja) |
SV (1) | SV2006002165A (ja) |
TW (1) | TW200603813A (ja) |
WO (1) | WO2006014476A1 (ja) |
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JP2008539262A (ja) * | 2005-04-28 | 2008-11-13 | ワイス | ミクロ化タナプロゲットおよびこれを含む組成物 |
JP2011520799A (ja) * | 2008-05-06 | 2011-07-21 | ウニベルジテート デス ザールランデス | ヒトアルドステロン合成酵素cyp11b2の阻害剤 |
JP2013518908A (ja) * | 2010-02-08 | 2013-05-23 | プレーリー ファーマシューティカルズ、エルエルシー | 糖質コルチコイド感作物質としてのプロゲストーゲンの使用方法 |
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US11351122B1 (en) | 2010-07-28 | 2022-06-07 | Laboratorios Leon Farma Sa | Synthetic progestogens and pharmaceutical compositions comprising the same |
US10849857B2 (en) | 2010-07-28 | 2020-12-01 | Laboratorios Leon Farma Sa | Pharmaceutical compositions comprising active drugs, contraceptive kits comprising active drugs, and methods of administering the same |
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JP2019513709A (ja) | 2016-04-01 | 2019-05-30 | セラピューティックスエムディー インコーポレーテッドTherapeuticsmd, Inc. | ステロイドホルモン薬学的組成物 |
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- 2005-07-06 CA CA2571377A patent/CA2571377C/en not_active Expired - Fee Related
- 2005-07-06 WO PCT/US2005/023955 patent/WO2006014476A1/en active Application Filing
- 2005-07-06 AU AU2005269938A patent/AU2005269938A1/en not_active Abandoned
- 2005-07-06 PA PA20058638601A patent/PA8638601A1/es unknown
- 2005-07-06 SV SV2005002165A patent/SV2006002165A/es not_active Application Discontinuation
- 2005-07-06 US US11/174,592 patent/US20060009428A1/en not_active Abandoned
- 2005-07-06 MX MXPA06014579A patent/MXPA06014579A/es active IP Right Grant
- 2005-07-06 PE PE2005000783A patent/PE20060378A1/es not_active Application Discontinuation
- 2005-07-06 CN CNA2005800227796A patent/CN1980676A/zh active Pending
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- 2005-07-06 AR ARP050102805A patent/AR049707A1/es unknown
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Cited By (15)
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US8450312B2 (en) | 2005-04-28 | 2013-05-28 | Wyeth Llc | Micronized tanaproget, compositions, and methods of preparing the same |
US8513240B2 (en) | 2005-04-28 | 2013-08-20 | Wyeth Llc | Micronized tanaproget and compositions containing same |
JP2008539262A (ja) * | 2005-04-28 | 2008-11-13 | ワイス | ミクロ化タナプロゲットおよびこれを含む組成物 |
JP2014205684A (ja) * | 2005-04-28 | 2014-10-30 | ワイス・エルエルシー | ミクロ化タナプロゲットおよびこれを含む組成物 |
JP2012255000A (ja) * | 2005-04-28 | 2012-12-27 | Wyeth Llc | ミクロ化タナプロゲットおよびこれを含む組成物 |
JP2012254999A (ja) * | 2005-04-28 | 2012-12-27 | Wyeth Llc | ミクロ化タナプロゲットを含む組成物 |
JP2008539256A (ja) * | 2005-04-28 | 2008-11-13 | ワイス | ミクロ化タナプロゲット、組成物およびその調製方法 |
JP2014205683A (ja) * | 2005-04-28 | 2014-10-30 | ワイス・エルエルシー | ミクロ化タナプロゲットを含む組成物 |
US8343965B2 (en) | 2005-04-28 | 2013-01-01 | Wyeth Llc | Compositions containing micronized tanaproget prepared by wet granulation |
JP2008539264A (ja) * | 2005-04-28 | 2008-11-13 | ワイス | ミクロ化タナプロゲットを含む組成物 |
JP2013006840A (ja) * | 2005-04-28 | 2013-01-10 | Wyeth Llc | ミクロ化タナプロゲット、組成物およびその調製方法 |
US8772271B2 (en) | 2005-04-28 | 2014-07-08 | Wyeth Llc | Micronized tanaproget, compositions, and methods of preparing the same |
US8791109B2 (en) | 2005-04-28 | 2014-07-29 | Wyeth Llc | Compositions containing micronized tanaproget prepared by wet granulation |
JP2011520799A (ja) * | 2008-05-06 | 2011-07-21 | ウニベルジテート デス ザールランデス | ヒトアルドステロン合成酵素cyp11b2の阻害剤 |
JP2013518908A (ja) * | 2010-02-08 | 2013-05-23 | プレーリー ファーマシューティカルズ、エルエルシー | 糖質コルチコイド感作物質としてのプロゲストーゲンの使用方法 |
Also Published As
Publication number | Publication date |
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AU2005269938A1 (en) | 2006-02-09 |
US20140094458A1 (en) | 2014-04-03 |
SV2006002165A (es) | 2006-05-09 |
AR049707A1 (es) | 2006-08-30 |
US8604027B2 (en) | 2013-12-10 |
BRPI0512991A (pt) | 2008-04-22 |
JP2013040181A (ja) | 2013-02-28 |
US20060009428A1 (en) | 2006-01-12 |
PA8638601A1 (es) | 2006-07-03 |
WO2006014476A1 (en) | 2006-02-09 |
JP5288796B2 (ja) | 2013-09-11 |
MXPA06014579A (es) | 2007-03-01 |
PE20060378A1 (es) | 2006-06-02 |
CA2571377C (en) | 2014-03-25 |
US20100292198A1 (en) | 2010-11-18 |
CN1980676A (zh) | 2007-06-13 |
TW200603813A (en) | 2006-02-01 |
CA2571377A1 (en) | 2006-02-09 |
CN104208067A (zh) | 2014-12-17 |
EP1773344A1 (en) | 2007-04-18 |
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