TW200536547A - Film-shaped medicament for oral administration, containing estriol - Google Patents
Film-shaped medicament for oral administration, containing estriol Download PDFInfo
- Publication number
- TW200536547A TW200536547A TW094114391A TW94114391A TW200536547A TW 200536547 A TW200536547 A TW 200536547A TW 094114391 A TW094114391 A TW 094114391A TW 94114391 A TW94114391 A TW 94114391A TW 200536547 A TW200536547 A TW 200536547A
- Authority
- TW
- Taiwan
- Prior art keywords
- drug
- estriol
- active substance
- film
- polymer
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 59
- 229960001348 estriol Drugs 0.000 title claims abstract description 38
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- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 title claims abstract description 36
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Classifications
-
- 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
-
- 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
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- 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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- 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
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- 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
- A61P5/30—Oestrogens
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Physiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
Description
200536547 九、發明說明： 【發明所屬之技術領域】 本發明係.職齡，其細口服域，並欲用於、 黏膜(tra__al)投藥雌三醇且/或至少—種其醫藥可接受 醋類，單獨或與至少一種助孕素(gestagen)組合。 本發明進一步關於雌三醇且/或至少一種其醫藥可接受
ί類’早獨或與至少—御料組合，胁製魏狀、口服投 樂之用於治療更年期疾病之藥物之用途。 【先前技術】 /女的停、_(更軸)為生命巾區分受孕期及不可能再 生月日^期之躺。更年期之特徵在於卵巢荷㈣製造的持續降 二Γΐ相關讀期亦會減少並最終停止。在更年期開始， 攻助讀含讀降低’縣幾年後祕製造少量雌性素， 直到身體完全停趟造這些荷賴。 ’、 、生一、Ί改又期間’約8()%婦女會發生疾病。荷爾蒙製 :退^器官賴。其中為皮_、變薄及鬆他、肌張 至掉叆、關節痛及肌肉痛，組織中水分批 出增加，其造成乳居纟山热 、、'朋|、、陰道乾燥及搔癢、較常陰道發
膀胱發炎、及漏尿，與骨量降低(骨質疏鬆症）。/ 4FLACCUS/05001TW/HF 5 200536547 器官疾病會伴隨神經與血管(neurovegetative)疾病,如熱 潮紅、發汗、睡眠中斷、眩暈、心跳加速或頭痛。這些症狀決 定更年期疾病的狀況約2至3年。 此外’亦會發生精神疾病。其中為焦慮、易怒及好爭論、 内在壓力、情緒不佳、神經質、心情起伏及憂營、疲勞及缺乏 動機、健忘、♦注力降低、性慾改變。當此個體已習慣荷爾蒙 缺乏時，這些疾病通常會再減輕。 受到與更年期相關之疾病影響之婦女中有30至4〇%覺得 相當輕微，受影響者巾有挪其精神及⑽賴非常強烈， 且其中5%有關的婦女甚至暫時無法工作。 在所謂的荷爾蒙替代療法(贿)中，係投藥雌性素盘助孕 償铜蒙不足及治療與更年期細之赫。用 女祕後之更袖疾病及用於·料疏鬆症及心 吕疾病切爾_代療法的優點已充分證明。 然而，荷«替代祕亦林 性。其中最常見的副作㈣⑽…作用务生之可肥 …、7形成增加、血拴風險增加、得
4FLACCUS/05001TW/HF 200536547 到子宮内膜癌之風險增加、感覺乳房緊繃、體重增加、噍心 黑色素沉殿及斑點形成。 此外’連續投藥荷爾蒙活化雌性素會促進陰道上皮細胞择 生’並提高子宮内膜過度增生之風險。 θ • 考慮到與連續投藥雌二醇相關之缺點，已提出使用雌三 醇’其幾乎不引起子宮内膜增生，取代荷爾蒙替代療法架構中 之雌二醇。雌三醇((⑽⑽-雌留-1，3,5(1〇)-三稀_3，16,17_三醇) 為雌性素代謝之最終代謝產物及中間代謝產物，通常主要在尿 液中。身為雌二醇的代謝物，雌三醇的荷爾蒙效果亦實質上小 於雌二醇。然而，當以衣錠、膠囊或錠劑之形式口服投藥時， 雌二醇在肝臟中因形成制萄糖贿化物衍生物而快速去活 • 化。目此，只有投藥雌三_量的丨至2%會以生物有效性形 式進入血液循環中。因此，已發現口服投藥雖三醇時，每曰 2mg (2mg/day)之㈣對於避免陰道萎縮及有效於治療熱潮 紅、睡眠中斷及數種其他與更年期相關之問題為最佳 。因相對
回剤里(2mg/day)之投藥，亦有發生例如噁心及乳房疼痛之副 作用之可能性。 4FLACCUS/05001TW/HF 200536547 。/為服彳x藥之替代方式，亦測試雌三醇之陰道投藥，以 抑低’賴維持_全身性_之翻蒙投藥量。較小劑量另 具有對雌性素調節之肝舰較小偏差讀點。_陰道投藥證 月車乂服才又藥有效’因陰道内投藥之雌三醇開始快速被吸收， 且因此原耻_於局雜與全雜翻料代療法，但陰道 皮、、、胞之肖化’發生於長期施用並對雌三醇之吸收具有負面 籲效果b妨礙雌二醇之陰道施用。此外，雌三醇之陰道投藥不 被原發病患接受。 除了陰道投藥之外，在EP 〇 63〇 248 +已描述雖三醇之經 皮投藥亦適用於治療更年期骨質疏鬆症。然而，非常高的雖三 醇置(12mg/24hr)必須連續經皮投藥於雄性個體，以達到相當於 雕性循環(50至350μΕ/πι1)中雌性荷_蒙生理濃度之游離雌三 _ 醇血清含量，必須考慮為缺點。 除此之外，經皮投藥雌三醇應會造成雌三醇之大量穩定血 液含量5其確實對骨質有正面效果，但亦促進對子宮黏膜之不 必要作用。
4FLACCUS/05001TW/HF 8 200536547 【發明内容】 ，目此本發明之目的為提供一種用於投藥雌三醇之藥物，其 . 係、以σ服投藥並_於治療更年期且/或停經後疾病，且其盡 量避免前述已知的口服投藥形式的缺點。 其驚訴地發現此目的可藉由單層或多層、包含雕三醇且/ 籲或至少-種雌三醇之醫討接受g旨類之膜狀藥物而達到。 【實施方式】 一醇之適合醫藥可接受醋類為，例如，雌三醇三醋酸、 雌三醇三丙酸、雌三醇各醋酸、雌三醇.醋酸、雖三醇_16，口— 二醋酸、雌三醇-3，17-二硫酸、雌三醇_16，17_二硫酸、雌三醇 -3-硫酸、雌三醇-17-硫酸、雌三醇各半琥珀酸或雌三醇_16，17一 ^ 半琥珀酸。 雌二醇且/或雌二醇之醫藥可接受酯類可視需要與至少一 種助孕素組合包含於此膜狀藥物中。
根據本發明之膜狀藥物可使雌三醇且/或雌三醇之醫藥可 接受酯類，經黏膜吸收及經由口腔黏膜舌下或口内施用藥物， 4FLACCUS/05001TW/HF 9 200536547 案例中助讀可另包含於此藥物巾。包含於膜狀藥物令之一 或夕種此雜物質係因麵的伽造成從膜狀_巾釋放，並 接著可經由π腔黏膜吸收。以此方式，可避免所謂的「初次通 、D、％、」Άπ服投藥快速去活化的原因。由本發 f三醇且/或雌三_旨類之齡，械於雌三醇已知= 技藥^式可因此降低至低於2mg/24h，較佳為至約 (W24h卩翻與π服或經皮投藥雌三醇之賺高劑量相 此外’口内或舌下投藥雌三醇並無觀察到口腔黏膜有盘於 陰道投藥雌性素情觀察_陰道上皮細胞層增生及角^或 類似之改變。 • 陰道中這些改變可能為所觀察到的事實的原因，以相同處 理及劑量，雌三醇在錢㈣含量麵三醇赌道制一段時 間後會可測量地降低，但經由口腔黏膜之經黏膜投藥則不會。 因此，即使在長期使用之案例中，在作為投藥部位之口腔黏曰膜 應不會有不必要的吸收情況顯示變壞的改變，只要使用根據本 發明之膜狀藥物進行治療更年期疾病。
4FLACCUS/05001TW/HF 200536547 根據本發日狀膜狀投藥形式為小厚度之藥物。這些膜狀藥 物的厚度為_mm至5mm，較佳為⑽3麵至3麵，特佳 為〇.〇5mm至2mm，及非常佳為〇.lmm至lnim。發明藥物的 面積為0.5至2(W之間；較佳地，面積量為i至1〇咖2。 單一藥物的形狀可不同。其可為圓形、擴圓形、三角形、 方形或多角形。 根據本發明之獻藥物亦稱為「㈣⑽㈣」。其在吸收 水分後可符合π蹄賴不酬表面。❹卜，娜本發明之膜 狀藥物可為可凝膠化或可膨脹。 在較佳實施例中，本發明臈狀藥物製劑在施用前已為圓滑 的，並可從唾液吸收水分。 根據本發明之膜狀藥物製劑之活性物質含量為〇·5至 40%-wt ’較佳為丨至30Vwt，及特佳為5至2〇%_加。 此膜狀藥物係由含聚合物(p〇lymer_c〇ntaining)層組成或包 含至少-層含聚合物層，該含聚合物層係作為潍物質貯存
4FLACCUS/05001TW/HF 11 200536547 處。此層包含綠_，対在麵 =物貯存撕之娜 為20至70〇/〇-wt，特佳為3〇至·糾。 土 適用於製造作輕性物f貯存處之層 聚乙_、聚乙稀峨酮、聚醋酸♦聚乙二醇、= t騎合Γ、聚胺甲酸⑽、聚丙烯酸、聚__旨、聚两埽 酉夂甲酉曰、聚(甲基乙稀基乙时稀二酸肝).、殿粉街生物、 天然膠質、褐藻膠、果谬及明膠、聚三葡萄糖、膠質形成蛋白 聚氨基葡萄糖、_、_精、紅藻膠、三仙膠、山羊刺_、 右旋歸、及纖維素靴物例如乙基纖維素、誠乙基纖維 素、丙基纖維素、羧基甲基纖維素、Na_羧基甲基纖維素、声 丙基纖維素、麵基甲基纖維素、經丙基乙基纖維素、醋酸纖 維素所組成之群組。 鐵 此聚合物可單獨或與另一種組合，以製備根據本發明之荜 物，其具有所需性質例如附著、釋放或分解性。 ’、 在其最簡單的實補t ’本發麵絲物係由單聚合物層 組成。其他實施例侧於具有雙_或多層結構之職藥物，^
4FLACCUS/05001TW/HF 200536547 •此射至少—層包含活性物質。若這些實施例之層之多層包含 種活性物質，這些層可因其活性物質含量及其活性物質 、且及在其聚合倾成，使細著性且/或分触可不同。 根據本剌之祕可料含—或多種_域技術者已 知的非活化(inactive)成分。這些非活化成分可選自一或多個下 •歹憐組：乳化劑，其包含聚乙氧基去水山梨醇脂肪酸醋、聚乙 乳基脂肪醇及㈣脂；增塑劑，其包含聚乙二醇、丙三醇及其 他多元醇、高級醇例如十二醇、十一醇或八醇、山梨醇、甘露 醇及其他糖醇、凝膠右泛醇及三酸甘油脂；填充劑，其包含高 y刀散度的二氧化矽、二氧化鈦、氧化鋅、白堊及澱粉；增色劑； 甜味劑及調味劑；濕潤劑；防腐劑；pH調節劑及抗氧化劑； 刀解促進劑；增強雌二醇經由黏膜吸收之通透促進劑例如脂肪 φ酉夂及脂肪酸醋、多價醇例如丙二醇、生育醇、或揮發油例如薄 荷醇。 這些非活化成分比例相對於藥物總重量可合計達到6〇 % °較佳地，非活化成分部分為5至4〇%-wt。藉由加入一或 多種上述之非活化成分，熟習該項技術者可運用對所含活性物 貝、膜狀藥物之化學及物理性質之影響，以使，例如，所需的
4FLACCUS/05001TW/HF 200536547 彈性、黏膜附著性、膨脹性或分解性與擴散性可調整。 根據較佳貫施例，此膜狀藥物可使長效活性物質慢慢地 延遲釋放。此活性物質較佳為釋放持續4小時期間，特佳為持 ，6小時期間，及非常佳為持續8小時期間。藉由每曰一次在 T 6小叫·或8小日守内脈衝式釋放活性物質，其有可能在 # ❿要治療之中框神經系統、陰道上皮細胞及泌尿道組織中產生 功放’而不引發在胚胎學具有相同來源之陰道或泌尿道之萎 縮。 脈衝式投討’例如’有祕改善子錄道分裂。在此 方面’根據本發明之藥物可增加雌三醇及雌三醇之麵在治療 更年期疾病之組織特異性。 在根據本發明之藥物之另一較佳實施例中，此活性物質係 j24小時錢長_釋放。因此有可能翻大滅定血液含 置’因其在骨頭之較佳功效，特別適用於治療骨質疏鬆症。
為了達到雙衫層藥物之延遲活性物質槪，此含活性物 質聚合物層中至少_層具有延遲釋放活性物質。 4FLACCUS/05001TW/HF 200536547 為了達到延遲活性物質職，此酿_難可調配成緩 慢溶解或緩慢分賴，其僅在數小日植完全分解或完全溶解。 較佳為其僅在4小喊完全分解或完全轉，特佳為僅在6 ㈣後完全分解或完全溶解’及非f佳為僅在M、時後或甚至 僅在24小時後。 • 土根據—較佳實施例，本發明之膜狀藥物為黏膜附著的。特 佳為僅有黏_著表面之實補。其可使此騎製劑在施用期 間黏住口腔黏膜，且此活性物質可在施用部位經由口腔黏膜直 接吸收。 ' 在特佳實施例中’此黏膜附著藥物在黏膜附著表面的另一
面具有活性物質不可通透之層’因此在施用於口腔黏膜時，有 可能達到方向性活性物質釋放。 一用於Π服投藥之職藥物，其包含雌三醇且/或至少一種 雌三醇之醫财接受s旨類’可另包含至少—種來自助孕素之群 、且之雜^，其在制此藥物咖樣為經麵投藥，因此在使 用雌二醇與至少—種助孕素之组合之荷躲替代療种，僅必 須給予單一藥物製劑。
4FLACCI/S/05001TW/HF 15 200536547 根據本發明之膜狀藥物可以熟習該項技術者原則上已知 的方法製造，例如以包含聚合物、活性劑、及視需要非活化成 分及溶劑之液體塗佈惰性載體，例如藉由刮刀塗佈、喷霧或擠 壓之方式。由此獲仔之薄膜層為乾燥的。在多層膜案例中，一 或多次塗佈可以相同方式施用於已存在之薄膜層，或分別製備 並接著將其疊合。 用於口服投藥之本發明膜狀藥物，其包含雌三醇且/或至 夕、種雌二醇之醫藥可接受醋類，單獨或與至少一種助孕素組 合，可用於治療更年期疾病且/或荷爾蒙替代療法過程。 有利地，當使用根據本發明之藥物時，荷爾蒙替代療法或 更年期疾病之治療可藉由使用低於2mg/24h之雌三醇劑量進 行’較佳為使用約2〇〇pg/24h劑量之活性物質劑量。 特別地，脈衝式給藥雌三醇及其醫藥可接受酯類為每曰一 次持續4小時期間，較佳為6小時，或特佳為8小時，根據本 發明之藥物使其有可能，相較於經皮投藥，除了投藥較少劑 1，其亦可增加組織特異性。
4FLACCUS/05001TW/HF 16 200536547 【圖式簡單說明】無。 【主要元件符號說明】無。
4FLACCUS/05001TW/HF 17
Claims (1)
- 200536547 十、申請專利範圍： 1. -種用於口服投藥之膜狀藥物，特別為·口内加㈣ 投藥，概在於賴_物包含料雜㈣之雌三醇且/或 至少-雌三醇之«可接受g旨類，單獨或與至少—助孕素 (gestagen)組合。 鲁2.如請求項i所述之藥物’特徵在於該膜狀藥物由一含聚合 物（polym⑽ntaining)層組成，或包含至少一含聚合物層， 該含聚合物層包含-❹該活性物f，並作為活性物質之贿 處0 3. 如請求項2所狀藥物，·在於該雜熱具有雙層或 多層結構，與至少一層包含活性物質。 4. 如請求項2或3所述之藥物，在於該含聚合物層或至 少-層該含聚合物層使延遲活性物質釋放成為可能。 18 200536547 6·如^求項4所述之歸，特徵在於制狀藥物釋放該活性 物質持續24小時或以上之一期間。 7·如則^求項之任_所述之藥物，特徵在於賴狀藥物在 水性介質中為可凝膠化或可膨脹。 # 8.如別述請求項之任一所述之藥物，特徵在於該膜狀藥物在 水性介質中為緩慢溶解或緩慢分解。 9.如明求項8所述之藥物’特徵在於該膜狀藥物僅在4小時 後，較佳為僅在6小時後，特佳地僅在8小時後，或甚至僅在 24小時後完全分解或完全溶解。 籲ίο.如前料求狀任—所狀_，特徵在於釋放低於 ㈣飾之一活性物質劑量，較佳為約2(%g/24h。 11. 如前述請求項之任—所述之藥物，在於該膜狀藥物為 黏膜附著，或包含至少—黏膜附著表面。 12. 如請求項11所述之藥物，特徵在於賴__著表面之 4FLACCUS/05001TW/HF 19 200536547 層對於該雜崎為何通透的。 二恤於該含聚合 及特佳為心〜。 較料2™1， 14·如前述請求項之任一 越 有-活性物質人旦A 特徵在於顧狀藥物具 30%-wt，及 、s里為〇.5至4〇%哺，較佳為ι至 特佳為5至20%_wt。 15. 如根簡猶求項往—所叙藥物，概在於該藥物的 厗度為0.01mm至5難，較佳為〇 〇3咖至3麵特 〇.〇5mm至2麵，及非常佳為0.1mm至1咖。 16. -種雌三醇且/或至少—獅三醇之㈣可接受自旨類之用 途’用於製造以口服投藥及欲用於治療更年期疾病之-膜狀藥 物0 〆、 Π.如請求項16所述之崎，特徵在於該酿雜為如請求項 1至15項中任一所述之藥物。 、 4FLACCUS/05001TW/HF 20 200536547 18.—種如請求項1至15項中任一所述之藥物之用途，用於治 療更年期疾病。 21 4FLACCUS/05001TW/HF 200536547 七、指定代表圖： (一) 本案指定代表圖為：無。 (二) 本代表圖之元件符號簡單說明：無。八、本案若有化學式時，讀揭示最能顯示發明特徵的化學式：無。 4FLACCUS/05001TW/HF 4
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102004023984A DE102004023984A1 (de) | 2004-05-14 | 2004-05-14 | Filmförmiges, oral zu verabreichendes Arzneimittel, enthaltend Estriol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW200536547A true TW200536547A (en) | 2005-11-16 |
Family
ID=34977101
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW094114391A TW200536547A (en) | 2004-05-14 | 2005-05-04 | Film-shaped medicament for oral administration, containing estriol |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20070243217A1 (zh) |
| EP (1) | EP1761242A2 (zh) |
| JP (1) | JP2007537178A (zh) |
| KR (1) | KR20070040753A (zh) |
| CN (1) | CN1997349A (zh) |
| AR (1) | AR048958A1 (zh) |
| AU (1) | AU2005244409A1 (zh) |
| BR (1) | BRPI0510855A (zh) |
| CA (1) | CA2566325A1 (zh) |
| DE (1) | DE102004023984A1 (zh) |
| IL (1) | IL179014A0 (zh) |
| MX (1) | MXPA06012890A (zh) |
| NO (1) | NO20065657L (zh) |
| RU (1) | RU2006140649A (zh) |
| TW (1) | TW200536547A (zh) |
| WO (1) | WO2005110358A2 (zh) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009101021A2 (en) * | 2008-02-13 | 2009-08-20 | Bayer Schering Pharma Aktiengesellschaft | Estradiol-containing drug delivery system |
| EA018330B1 (ru) * | 2008-02-13 | 2013-07-30 | Байер Интеллекчуал Проперти Гмбх | Система доставки лекарственного средства со стабилизирующим эффектом |
| KR20110020782A (ko) * | 2008-04-24 | 2011-03-03 | 이브스트라, 인코포레이티드 | 장용 폴리머 중에 분산된 프로게스토겐 및 에스트로겐을 포함하는 경구 피임약 제형 |
| US20110250274A1 (en) * | 2008-09-19 | 2011-10-13 | Shaked Ze Ev | Estriol formulations |
| DE102009007771B4 (de) * | 2009-02-05 | 2012-02-16 | Bayer Schering Pharma Aktiengesellschaft | Bukkales Applikationssystem, 17α-Estradiol enthaltend |
| KR102044515B1 (ko) * | 2019-08-20 | 2019-11-14 | 이영환 | 구강점막 부착력이 우수한 서방형 구강붕해용 필름 및 이의 제조방법 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2061672T3 (es) * | 1987-09-24 | 1994-12-16 | Jencap Research Ltd | Preparado hormonal y su uso. |
| HU218290B (en) * | 1992-03-21 | 2000-07-28 | Process for producing pharmaceutical compositions containing estriol which are applicable for treatment of climacteric osteoporosis | |
| DE19701949A1 (de) * | 1997-01-13 | 1998-07-16 | Jenapharm Gmbh | Transdermales therapeutisches System |
| DE19832169A1 (de) * | 1998-07-17 | 2000-01-27 | Jenapharm Gmbh | Lokal anwendbare pharmazeutische Präparate zur Prophylaxe und Therapie atrophischer Erscheinungen in der Mundhöhle |
| US6117446A (en) * | 1999-01-26 | 2000-09-12 | Place; Virgil A. | Drug dosage unit for buccal administration of steroidal active agents |
| DE19932603A1 (de) * | 1999-07-13 | 2001-01-25 | Gruenenthal Gmbh | Wirkstoffhaltiger Mehrschichtfilm aus in situ vernetzten hydrophilen Polymeren |
| PT1611892E (pt) * | 2000-01-18 | 2009-11-20 | Bayer Schering Pharma Ag | Composições farmacêuticas compreendendo drospirenona |
-
2004
- 2004-05-14 DE DE102004023984A patent/DE102004023984A1/de not_active Ceased
-
2005
- 2005-05-04 TW TW094114391A patent/TW200536547A/zh unknown
- 2005-05-06 BR BRPI0510855-1A patent/BRPI0510855A/pt not_active Application Discontinuation
- 2005-05-06 AU AU2005244409A patent/AU2005244409A1/en not_active Abandoned
- 2005-05-06 US US11/596,239 patent/US20070243217A1/en not_active Abandoned
- 2005-05-06 EP EP05747659A patent/EP1761242A2/de not_active Withdrawn
- 2005-05-06 RU RU2006140649/15A patent/RU2006140649A/ru not_active Application Discontinuation
- 2005-05-06 CA CA002566325A patent/CA2566325A1/en not_active Abandoned
- 2005-05-06 WO PCT/EP2005/004894 patent/WO2005110358A2/de not_active Ceased
- 2005-05-06 MX MXPA06012890A patent/MXPA06012890A/es unknown
- 2005-05-06 CN CNA2005800140311A patent/CN1997349A/zh active Pending
- 2005-05-06 KR KR1020067023835A patent/KR20070040753A/ko not_active Withdrawn
- 2005-05-06 JP JP2007512026A patent/JP2007537178A/ja active Pending
- 2005-05-13 AR ARP050101957A patent/AR048958A1/es unknown
-
2006
- 2006-11-02 IL IL179014A patent/IL179014A0/en unknown
- 2006-12-07 NO NO20065657A patent/NO20065657L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007537178A (ja) | 2007-12-20 |
| IL179014A0 (en) | 2007-03-08 |
| EP1761242A2 (de) | 2007-03-14 |
| US20070243217A1 (en) | 2007-10-18 |
| WO2005110358A3 (de) | 2007-03-15 |
| NO20065657L (no) | 2006-12-07 |
| DE102004023984A1 (de) | 2005-12-08 |
| CA2566325A1 (en) | 2005-11-24 |
| MXPA06012890A (es) | 2007-07-19 |
| WO2005110358A2 (de) | 2005-11-24 |
| CN1997349A (zh) | 2007-07-11 |
| AR048958A1 (es) | 2006-06-14 |
| AU2005244409A1 (en) | 2005-11-24 |
| RU2006140649A (ru) | 2008-05-27 |
| KR20070040753A (ko) | 2007-04-17 |
| BRPI0510855A (pt) | 2007-12-26 |
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