[go: up one dir, main page]

CN1141168A - 由糖衣控释的类固醇 - Google Patents

由糖衣控释的类固醇 Download PDF

Info

Publication number
CN1141168A
CN1141168A CN96104096A CN96104096A CN1141168A CN 1141168 A CN1141168 A CN 1141168A CN 96104096 A CN96104096 A CN 96104096A CN 96104096 A CN96104096 A CN 96104096A CN 1141168 A CN1141168 A CN 1141168A
Authority
CN
China
Prior art keywords
sugar
coat
microcrystalline cellulose
sterin
hormones
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
Application number
CN96104096A
Other languages
English (en)
Other versions
CN1106839C (zh
Inventor
R·J·巴康
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wyeth LLC
Original Assignee
American Home Products Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=23473354&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN1141168(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by American Home Products Corp filed Critical American Home Products Corp
Publication of CN1141168A publication Critical patent/CN1141168A/zh
Application granted granted Critical
Publication of CN1106839C publication Critical patent/CN1106839C/zh
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

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
    • A61K31/565—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
    • A61K31/566—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 having an oxo group in position 17, e.g. estrone
    • 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
    • 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
    • A61K31/567—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 substituted in position 17 alpha, e.g. mestranol, norethandrolone
    • 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
    • A61K31/568—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 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • 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
    • A61K31/568—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 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • A61K31/569—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 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone substituted in position 17 alpha, e.g. ethisterone
    • 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
    • A61K31/57—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
    • 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
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • 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
    • A61K9/20—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
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • 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)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Endocrinology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

一种用于压缩药物片剂的糖衣组合物，它含有糖、负荷剂量的激素类固醇和类固醇释放速率控制量的微晶纤维素。

Description

由糖衣控释的类固醇
过去的三十年中，人们在确认药物从药物片剂中控释速率的方法上已付出了许多努力。将赋形剂掺入药片核芯中以控制其溶解，并由此控制药物的吸收。用聚合物包衣片剂或球以提供药物的缓慢、扩散控释或特定位点释放。
含有多种药物片剂和用胶囊包裹的球状剂型也已有制备，其中的药物从混合物或分离的片层或小球形式存在。这些药物被用来提供多种功能或提供协同作用。常规治疗表明那些使用不止一种不同但可配伍的活性药物情况下，这类片剂特别有用。例如，利尿剂与抗高血压剂一起使用，促孕剂与雌激素联合使用。
根据本发明，提供一种压缩的、糖衣的、含有两种或更多种药理学活性的药物片剂。该压缩片剂可含赋形剂以使药剂快速或缓慢释放。该糖衣中含有治疗量的激素类固醇和激类固醇控释量的微晶纤维素。存在于该片剂核心的药剂可以包括任何常规与激类固醇联合使用的药剂。该糖衣片也可以像通常那样最后进行着色包衣和磨光。
该片剂核芯的内含物在某种意义上与糖衣无关，在压片剂崩解和药的成分溶解发生之前，该糖衣及其中所含的激类固醇就溶解了。因此该核芯片剂的配方中采用的成份可以包括可药用的水溶性和或水不溶性组分，诸如乳糖、磷酸钙、淀粉、碳酸钙、葡萄糖、山梨醇、甘露醇、微晶纤维素、蔗糖、聚乙烯吡咯烷酮、甲基纤维素、羧甲基纤维素、藻酸盐、羟丙基纤维素、羟丙基甲基纤维素、乙基纤维素、交联羧甲基纤维素钠、淀粉羟乙酸钠、硬脂酸镁，硬脂酸、聚乙二醇、十二烷基磺酸钠、烟化二氧化硅、滑石粉等。
含有激素类固醇的糖衣还含有类固醇释放速率控制量的微晶纤维素，在某些情况下，还含有有助于糖衣应用的聚乙烯吡咯烷酮。
该片剂核芯通过压缩类固醇相容的药物和其它可药用赋形剂的混合物来制备，该混合物优选成颗粒的。该片剂核芯可以有不可塑的或可塑的密封包衣，用以修饰核芯所含药物的释放特性，或防止它们受潮和/或氧化。
本发明提供一种改进的压缩片剂，其中除含有一种或多种与外部糖衣中的类固醇在药学上相容的药物的常规内部片剂核芯以外，还有糖衣，该糖衣中含占糖衣重量约0.1％～20％的激素类固醇；占糖衣重量约0.1％～3％的微晶纤维素；占糖衣重量约0％～5％的聚乙烯吡咯烷酮；和糖。以单位剂量为基准，该片剂的负荷糖衣层中含有约0.05mg～50mg，优选约0.1～30mg的激素类固醇。如果需要，可在包封带有类固醇的糖衣层之前的密封包衣层外包覆一惰性的填充糖内包衣层。该含有惰性填料的亚层糖衣可用含约7.5％～1 5％微晶纤维素的蔗糖制成。该外层糖衣可含有制片剂领域常用的着色剂诸如在二氧化钛或一级、二级或灰色钛。如果需要，该着色剂可以作为单独的包衣层施加在外层糖衣上。最后磨光完成片剂制备。
用于涉及本说明书的糖衣制备的糖是糖产品，诸如从甜菜中甘蔗原料或者经淀粉、糖化物或多糖转化原料得的蔗糖都适于片剂包衣。目前优选的糖是蔗糖。
已知激素类固醇从糖衣中的释放可通过限量的微晶纤维素来控制，徽晶纤维素的量为糖衣重量的约0.1％～3％。在糖衣中使用这样少量的微晶纤维素与这种赋形剂作为压缩辅助剂或加速片剂核芯分解的应用不同。在后者情况下，微晶纤维素的浓度可高达15％Wt至30％Wt。
适于加入本发明糖衣配方的激素类固醇的实例包括：乙酸甲羟孕酮、乙基羟基二降孕甾烯炔酮、甲地妊娠素、二甲去氢孕酮、雌二醇、乙炔雌二醇、乙炔雌二醇三甲醚、雌酮、双烯雌酚、己雌酚、己烯雌酚、孕酮、desogestrel、肟炔诺酮、羟孕酮、甲基睾酮、乙基雌烯三醇、去氢甲睾酮、氧甲氢龙、三甲孕酮等。
为说明在不存在和存在微晶纤维素时体外类固醇溶解速率的控制，下列是说明性实施例，但不限制本发明。实施例1
用无孔的或有孔的包衣盘将含有下述固体的糖衣包在片剂核芯上：
蔗糖，NF                   87％
聚乙烯吡咯烷酮             3％
乙酸甲羟孕酮，USP          10％
根据<711>USPXX，P.959(1980)测定类固醇的溶解速率，用装置2，在50rpm溶解在37℃ 0.54％十二烷基磺酸钠水溶液中，重复试验六次(方法A)。CV表示以百分比表示的这些试验之间的变化系数。
时间(分)      释放的类固醇的百分比(CV％)
  5                  93(5.2)
 10                  94(5.3)
 30                  95(5.3)
 60                  95(5.4)
120                  95(5.4)实施例2
用USP装置1在100rpm将用上述相同方法及相同糖衣包衣的片剂溶于37℃ 0.13％十二烷基磺酸钠的0.1NHCL溶液中，试验六次(方法B)。这一研究的结果如下：
时间(分)       释放的类固醇的百分比(CV％)
   5                 83(6.0)
   10                85(5.8)
   30                85(6.2)
   60                85(6.1)
  120                85(6.2)实施例3
用相同方法及相同成分的糖包衣的其它片剂在37℃、0.12％十二烷基磺酸钠0.1N HCL溶液中使用SOTAXD issotest装置以5.7ml/分流速进行经流溶解试验(方法C)。三次试验的结果分别是：
时间(分)    释放的类固醇的百分比(CV％)
  30             90.9(2.9)
  60             94.2(3.0)
  90             95.3(2.9)
 120             96.0(3.0)
 210             97.4(3.0)
 300             98.9(3.6)
通过这些体外研究，清楚地表明在这里作为典型激素类固醇的甲羟孕酮从糖衣中释放得非常迅速。实施例4
为了比较及详细说明本发明糖衣意想不到的性质，用含有下列固体的糖衣包衣片剂核芯：
蔗糖，NF             86.5％
微晶纤维素            0.5％
PVP                   3.0％
乙酸甲羟孕酮，USP    10.0％
使用含微晶纤维素的糖包衣的片剂及方法A进行试验，得到三次实验的体外溶解数据：
时间(分)        释放的类固醇的百分比(CV％)
  5                     19.5(49.5)
 10             29.9(32.8)
 30             50.0(23.0)
 60             61.6(19.5)
120             74.2(19.2)
实施例5
用另外的以上述相同方法制备的由含微晶纤维素的糖包衣的片剂采用方法B进行六次试验，所得数据如下：
时间(分)       释放的类固醇的百分比(CV％)
  5                  2.3(34.4)
 10                  8.2(27.0)
 30                  17.9(16.1)
 60                  26.5(13.6)
120                  32.7(16.6)实施例6
采用方法C，用糖衣中含微晶纤维素的片剂进行三次试验，所得数据如下：
时间(分)        释放的类固醇的百分比(CV％)
  30                  2.8(34.4)
  60                  4.1(24.8)
  90                  5.1(22.3)
 120                  6.4(22.3)
 210                 11.0(19.4)
300             14.3(11.0)
这些数据清楚地表明，糖衣中的少量微晶纤维素(糖衣固体重量的0.5％时)可明显延迟激素类固醇的释放。实施例7
制备糖衣片剂，其中糖衣含有0.0％、0.5％或2％的微晶纤维素与3.0％聚乙烯吡咯烷酮、10.0％乙酸甲羟孕酮和蔗糖结合。这些片剂给禁食的四条警犬喂食，在0、0.5、1、1.5、2、3、5、8、12、16和24小时测定类固醇的血浆水平。数据结果用曲线表示，计算的24小时期间的曲线下面积(AUC)并测定到达最大血浆浓度的时间如下：
微晶纤维素％  AUC(0～24小时)   tmax(hr)      Cmax
                 ng×hr/ml                  (ng/ml)
    0.0            345           0.6         37.8
    0.5            294           1.0         36.9
    2.0            294           1.1         24.6
由这些狗的体内数据明显看出，当糖衣中微晶纤维素的浓度从0.0增至0.5％至2.0％，激素类固醇的生物利用率出现了明显的变化。这样，掺入糖衣中的激素类固醇的释放速率就可以由掺入糖衣中的非常少量的微晶纤维素来控制。实施例8
制备糖衣片，其中糖衣含有0.25％、0.5％或0.8％的微晶纤维素与0.5％聚乙烯吡咯烷酮、5.0％乙酸甲羟孕酮和蔗糖结合。在37C的的0.54％十二烷基磺酸钠溶液中用USP崩解装置(USPXX，<201>，p958)(1980)对这些片剂进行体外溶解试验。所得试验数据如下：
溶解的乙酸甲羟孕酮的百分比(CV％)时间(分)   0.25％微晶纤维素   0.5％微晶纤维素   0.8％微晶纤维素15          97.8(5.2)            72.6(9.5)        32.4(15.2)30          98.8(5.3)            89.9(6.3)        62.8(8.2)45          99.3(5.2)            95.2(5.6)        76.6(6.9)60          99.1(5.2)            98.3(5.7)        84.8(6.6)90          99.9(5.3)           100.9(6.0)        94.4(6.9)120         100.3(5.6)           102.4(5.3)        98.0(7.1)
对这些剂型也进行了人体生物利用度测定研究。这些剂型以交换(cross-over)设计施用于十二例健康女性。在0.5、1、1.5、2、2.5、3、4.5、6、8和12小时采集血样，分析血浆中的乙酸甲羟孕酮。所得数据如下：微晶纤维素  AUC(0～12小时)   tmax(hr)    Cmax(ng/ml)0.25％     26.0±14.3*    2.9±1.3     4.24±3.00.5％      25.8±10.5      3.2±1.2     3.88±1.870.8％      13.2±4.0       3.9±1.6     1.99±0.73*平均值±1标准偏差
体外溶解和人体内生物利用度数据清楚地表明激素类固醇药物的释放特性和生物利用度是由糖衣中的微晶纤维素浓度控制的。实施例9
将蔗糖基质中含有5mg二甲去氢孕酮、0.4％微晶纤维素和0.5％聚乙烯吡咯烷酮的糖衣包于密封的并用糖包衣的片剂核芯上。使用USPXX的<711>，p959(1980)描述的溶解测试方法，用装置2，在37℃ 50r.p.m，900ml 0.54％十二烷基磺酸钠进行测试来比较这种剂型与含5mg，二甲去氢孕酮的快速崩裂压缩片剂的体外溶解情况。所得数据如下：
释放的二甲去氢孕酮的平均百分比(CV％)
时间(分)    常规快速崩片    糖衣中含二甲去氢孕酮
                                  的糖衣片
   15          95(2.0)            6(11.2)
   30          95(2.9)            11(6.9)
   45          97(1.6)            15(6.4)
   60          97(1.9)            18(6.6)
  120          98(1.9)            25(6.2)
结果表明当激素掺入含0.4％的微晶纤维素的糖衣中时大大降低了二甲去氢孕酮溶解。
本发明优选的实施方案是压缩片剂，其中的片剂核芯含有单位剂量的雌激素化合物或其混合物，含量为0.1mg～5mg，更优选为约0.3mg～2.5mg，与稳定的赋形剂压助剂和填充剂结合，最理想的是结合于片剂核芯的雌激素包括自然发生结合的雌激素产品，如已知的PremarinR.在压缩处上的糖衣上包覆另外一层糖衣，该糖衣含有约1mg～50mg，优选1.5mg～30mg的乙酸甲羟孕酮，再加上着色包衣，最后是磨光包衣。

Claims (7)

1、一种用于压缩药物片剂的糖衣组合物，它含有糖、负荷剂量的激素类固醇和类固醇释放速率控制量的微晶纤维素。
2、权利要求1的糖衣组合物，其中糖是蔗糖。
3、权利要求1的糖衣组合物，其中所述的激素类固醇是乙酸甲羟孕酮、乙基羟基二降孕甾烯炔酮、甲地妊娠素、二甲去氢孕酮、雌二醇、雌三醇、乙炔雌二醇、乙炔雌二醇三甲醚、雌酮、双烯雌酚、己雌酚、己烯雌酚、孕酮、desogestrel、肟炔诺酮、羟孕酮、炔诺酮、醋酸炔诺酮、18-甲炔诺酮、乙酸甲地孕酮、甲基睾酮、乙基雌烯三醇、去氢甲睾酮、氧甲氢龙、三甲孕酮。
4、权利要求1的糖衣组合物，它含蔗糖，约0.1％Wt-3％Wt的微晶纤维素、从0-约5％Wt的聚乙烯吡咯烷酮、约0.1％Wt-20％Wt的激素类固醇和水溶液。
5、一种压缩片剂，它包括含有结合的雌激素的片剂核芯和糖衣，其中所述的糖衣与激素类固醇和释放速率控制量的微晶纤维素结合。
6、权利要求5的压缩片剂，其中所述的片剂核芯含有约0.1mg-5.0mg结合的雌激素，并且所述的糖衣含有约1.0mg-50mg所述的激素类固醇。
7、权利要求5的压缩片剂，其中所述片剂核芯含有约0.3mg～2.5mg结合的雌激素，并且所述的糖衣含有约1.5mg～30mg乙酸甲羟孕酮。
CN96104096A 1995-01-17 1996-01-16 由糖衣控释的类固醇 Expired - Lifetime CN1106839C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US08/373,667 US5547948A (en) 1995-01-17 1995-01-17 Controlled release of steroids from sugar coatings
US373667 1995-01-17

Publications (2)

Publication Number Publication Date
CN1141168A true CN1141168A (zh) 1997-01-29
CN1106839C CN1106839C (zh) 2003-04-30

Family

ID=23473354

Family Applications (1)

Application Number Title Priority Date Filing Date
CN96104096A Expired - Lifetime CN1106839C (zh) 1995-01-17 1996-01-16 由糖衣控释的类固醇

Country Status (34)

Country Link
US (2) US5547948A (zh)
EP (1) EP0722720B1 (zh)
JP (1) JP3833292B2 (zh)
KR (1) KR100338581B1 (zh)
CN (1) CN1106839C (zh)
AR (1) AR002019A1 (zh)
AT (1) ATE185482T1 (zh)
AU (1) AU705879B2 (zh)
BR (1) BR9600100B1 (zh)
CA (1) CA2167254A1 (zh)
CO (1) CO4370096A1 (zh)
CZ (1) CZ286102B6 (zh)
DE (1) DE69604600T2 (zh)
DK (1) DK0722720T3 (zh)
EE (1) EE03802B1 (zh)
EG (1) EG23687A (zh)
ES (1) ES2137627T3 (zh)
FI (1) FI117592B (zh)
GR (1) GR3031920T3 (zh)
HU (1) HU223781B1 (zh)
ID (1) ID23996A (zh)
IL (1) IL116772A (zh)
IS (1) IS1878B (zh)
MY (1) MY115786A (zh)
NO (1) NO315307B1 (zh)
NZ (1) NZ280826A (zh)
PL (1) PL183330B1 (zh)
RU (1) RU2152207C1 (zh)
SI (1) SI0722720T1 (zh)
SK (1) SK280484B6 (zh)
TR (1) TR199600038A2 (zh)
TW (1) TW460301B (zh)
UA (1) UA37236C2 (zh)
ZA (1) ZA96301B (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100381117C (zh) * 1999-02-08 2008-04-16 Fmc有限公司 可食用的包衣组合物
CN116236453A (zh) * 2023-02-08 2023-06-09 江苏和汇医药科技有限公司 一种延长药品释放的糖包衣及其制备方法

Families Citing this family (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5759577A (en) * 1995-01-17 1998-06-02 American Home Products Corporation Controlled release of steroids from sugar coatings
US5547948A (en) * 1995-01-17 1996-08-20 American Home Products Corporation Controlled release of steroids from sugar coatings
BE1009856A5 (fr) * 1995-07-14 1997-10-07 Sandoz Sa Composition pharmaceutique sous la forme d'une dispersion solide comprenant un macrolide et un vehicule.
WO1997004752A1 (en) * 1995-07-26 1997-02-13 Duramed Pharmaceuticals, Inc. Pharmaceutical compositions of conjugated estrogens and methods for their use
US6479475B1 (en) * 1996-07-26 2002-11-12 Wyeth Oral contraceptive
US6451778B1 (en) * 1996-07-26 2002-09-17 Wyeth Oral contraceptive
CA2230748C (en) * 1997-03-14 2010-08-03 American Home Products Corporation Rapamycin formulations for oral administration
DE19715594A1 (de) 1997-04-15 1998-10-22 Bayer Ag Analgetika-Kombination
ATE283687T1 (de) * 1997-06-13 2004-12-15 Wyeth Corp Rapamycin-formulierungen zur oralen verabreichung
US5985325A (en) * 1997-06-13 1999-11-16 American Home Products Corporation Rapamycin formulations for oral administration
US5997905A (en) * 1998-09-04 1999-12-07 Mcneil-Ppc Preparation of pharmaceutically active particles
US6723342B1 (en) 1999-02-08 2004-04-20 Fmc Corporation Edible coating composition
US6500462B1 (en) 1999-10-29 2002-12-31 Fmc Corporation Edible MCC/PGA coating composition
AT500063A1 (de) 1999-11-23 2005-10-15 Sandoz Ag Beschichtete tablettenkerne
FR2801218B1 (fr) * 1999-11-23 2001-12-28 Hoechst Marion Roussel Inc Compositions pharmaceutiques comprenant de la trimegestone, leurs procedes de preparation ainsi que le conditionnement primaire les renfermant
US7989436B2 (en) 2003-07-23 2011-08-02 Duramed Pharmaceuticals, Inc. Estrogenic compounds and pharmaceutical formulations comprising the same
US6660726B2 (en) 2000-03-10 2003-12-09 Endeavor Pharmaceuticals Estrogenic compounds, pharmaceutical compositions thereof, and methods of using same
US6855703B1 (en) 2000-03-10 2005-02-15 Endeavor Pharmaceuticals Pharmaceutical compositions of conjugated estrogens and methods of analyzing mixtures containing estrogenic compounds
US7459445B2 (en) * 2000-03-10 2008-12-02 Duramed Pharmaceuticals, Inc. Estrogenic compounds and topical pharmaceutical formulations of the same
US20010034340A1 (en) * 2000-03-20 2001-10-25 American Home Products Corporation Hormone replacement therapy
US6932861B2 (en) 2000-11-28 2005-08-23 Fmc Corporation Edible PGA coating composition
AU2002225763A1 (en) 2000-11-28 2002-06-11 Fmc Corporation Edible pga(propylene glycol alginate) coating composition
US6630166B1 (en) * 2001-02-12 2003-10-07 Watson Pharmaceuticals, Inc. Compositions for conjugated estrogens and associated methods
US7303763B2 (en) * 2001-02-12 2007-12-04 Watson Laboratories, Inc. Compositions for conjugated estrogens and associated methods
AU2002338277B2 (en) * 2001-03-16 2007-11-22 Wyeth Estrogen replacement therapy
NZ528373A (en) * 2001-03-16 2005-07-29 Wyeth Corp Hormone replacement therapy
UA77200C2 (en) 2001-08-07 2006-11-15 Wyeth Corp Antineoplastic combination of cci-779 and bkb-569
TW200306196A (en) * 2002-04-03 2003-11-16 Wyeth Corp Hormone replacement therapy
TW200306846A (en) * 2002-04-03 2003-12-01 Wyeth Corp Hormone replacement therapy
TW200306851A (en) * 2002-04-29 2003-12-01 Wyeth Corp Hormone replacement therapy
TW200400040A (en) * 2002-05-17 2004-01-01 Wyeth Corp Hormone replacement therapy
RU2224517C1 (ru) * 2002-10-09 2004-02-27 Открытое акционерное общество "Ирбитский химико-фармацевтический завод" Способ получения противомикробного лекарственного средства
US6992075B2 (en) * 2003-04-04 2006-01-31 Barr Laboratories, Inc. C(14) estrogenic compounds
EP1622623A4 (en) * 2003-04-11 2009-03-18 Barr Lab Inc METHOD FOR THE ADMINISTRATION OF ESTROGENIC AND TESTED
EP1673071A1 (en) * 2003-09-29 2006-06-28 Novo Nordisk Femcare AG Improved stability of progestogen formulations
ES2623363T3 (es) * 2004-06-07 2017-07-11 Wyeth Llc Revestimientos de azúcar y procedimientos para su obtención
JP2008513584A (ja) * 2004-09-23 2008-05-01 エフ エム シー コーポレーション 被覆組成物
WO2006084082A1 (en) * 2005-02-03 2006-08-10 Duramed Pharmaceuticals, Inc. Compositions of unconjugated estrogens and methods for their use
AR054806A1 (es) * 2005-06-29 2007-07-18 Wyeth Corp Formulaciones de estrogenos conjugados y bazedoxifeno
WO2008058074A2 (en) * 2006-11-07 2008-05-15 Wyeth Sugar coatings and methods therefor
JP2010511062A (ja) * 2006-11-29 2010-04-08 ワイス エルエルシー エストロゲン／ｓｅｒｍおよびエストロゲン／プロゲスチン二層錠剤
WO2012120365A1 (en) 2011-03-07 2012-09-13 Aurobindo Pharma Limited Stable pharmaceutical composition comprising ethinyl estradiol
EP2709597A2 (en) * 2011-05-13 2014-03-26 Emotional Brain B.V. Drug delivery system
CA2856520C (en) 2011-11-23 2021-04-06 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US9301920B2 (en) 2012-06-18 2016-04-05 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US10806740B2 (en) 2012-06-18 2020-10-20 Therapeuticsmd, Inc. Natural combination hormone replacement formulations and therapies
US20150196640A1 (en) 2012-06-18 2015-07-16 Therapeuticsmd, Inc. Progesterone formulations having a desirable pk profile
US10806697B2 (en) 2012-12-21 2020-10-20 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US20130338122A1 (en) 2012-06-18 2013-12-19 Therapeuticsmd, Inc. Transdermal hormone replacement therapies
US10537581B2 (en) 2012-12-21 2020-01-21 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10471072B2 (en) 2012-12-21 2019-11-12 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US11246875B2 (en) 2012-12-21 2022-02-15 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US10568891B2 (en) 2012-12-21 2020-02-25 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
US9180091B2 (en) 2012-12-21 2015-11-10 Therapeuticsmd, Inc. Soluble estradiol capsule for vaginal insertion
US11266661B2 (en) 2012-12-21 2022-03-08 Therapeuticsmd, Inc. Vaginal inserted estradiol pharmaceutical compositions and methods
EP2970839B1 (en) * 2013-03-15 2017-02-22 Monosol, LLC Water-soluble film for delayed release
US10808210B2 (en) 2013-03-15 2020-10-20 Monosol, Llc Water-soluble film for delayed release
MX2016014281A (es) 2014-05-22 2017-02-22 Therapeuticsmd Inc Formulaciones y terapias de reemplazo de combinación de hormonas naturales.
US10328087B2 (en) 2015-07-23 2019-06-25 Therapeuticsmd, Inc. Formulations for solubilizing hormones
WO2017173044A1 (en) 2016-04-01 2017-10-05 Therapeuticsmd Inc. Steroid hormone compositions in medium chain oils
MX2018011705A (es) 2016-04-01 2019-06-10 Therapeuticsmd Inc Composicion farmaceutica de hormona esteroide.
US11633405B2 (en) 2020-02-07 2023-04-25 Therapeuticsmd, Inc. Steroid hormone pharmaceutical formulations

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB844772A (en) * 1956-04-19 1960-08-17 Pfizer & Co C Granular pharmaceutical compositions and process for preparing same
GB888631A (en) * 1959-02-24 1962-01-31 Upjohn Co Improvements in or relating to oral therapeutic compositions comprising steroids
FR1396710A (fr) * 1964-06-15 1965-04-23 Diwag Chemische Fabriken G M B Procédé pour la fabrication de charges ou supports perfectionnés et produits obtenus
US3980766A (en) * 1973-08-13 1976-09-14 West Laboratories, Inc. Orally administered drug composition for therapy in the treatment of narcotic drug addiction
US4154820A (en) * 1976-02-23 1979-05-15 Akzona Incorporated Compositions containing alkali metal sulfate salts of conjugated estrogens and antioxidants as stabilizers
US4248856A (en) * 1979-07-10 1981-02-03 American Home Products Corporation Sustained release pharmaceutical compositions
US4309404A (en) * 1979-08-09 1982-01-05 American Home Products Corporation Sustained release pharmaceutical compositions
US4309405A (en) * 1979-08-09 1982-01-05 American Home Products Corporation Sustained release pharmaceutical compositions
US4327076A (en) * 1980-11-17 1982-04-27 Life Savers, Inc. Compressed chewable antacid tablet and method for forming same
US4425339A (en) * 1981-04-09 1984-01-10 Syntex (U.S.A.) Inc. Treatment of menopausal symptoms
US4415546A (en) * 1981-05-12 1983-11-15 Janakiraman Ramachandran Biologically active analogs of ACTH and radioimmuno assay therefor
US4390531A (en) * 1981-08-10 1983-06-28 Syntex Pharmaceuticals International Ltd. Method of contraception using peak progestogen dosage
US4415547A (en) * 1982-06-14 1983-11-15 Sterling Drug Inc. Sustained-release pharmaceutical tablet and process for preparation thereof
JPS604120A (ja) * 1983-06-22 1985-01-10 Shionogi & Co Ltd 作用持続型ピナシジル製剤
US4826831A (en) * 1983-08-05 1989-05-02 Pre Jay Holdings Limited Method of hormonal treatment for menopausal or post-menopausal disorders involving continuous administration of progestogens and estrogens
GB8403360D0 (en) * 1984-02-08 1984-03-14 Erba Farmitalia Pharmaceutical compositions
US4716041A (en) * 1984-02-10 1987-12-29 A/S Alfred Benzon Diffusion coated multiple-units dosage form
GB8414221D0 (en) * 1984-06-04 1984-07-11 Sterwin Ag Unit dosage form
SE8404467D0 (sv) * 1984-09-06 1984-09-06 Ferrosan Ab Controlled-release medical preparations
US4755386A (en) * 1986-01-22 1988-07-05 Schering Corporation Buccal formulation
US5208225A (en) * 1986-02-27 1993-05-04 Warner-Lambert Company Compositions containing fixed combinations
GB8705083D0 (en) * 1987-03-04 1987-04-08 Euro Celtique Sa Spheroids
US4927816A (en) * 1987-08-20 1990-05-22 Ester George C Formulae and methods for sublingual ingestion of natural progesterone
US5108995A (en) * 1987-09-24 1992-04-28 Jencap Research Ltd. Hormone preparation and method
IT1227626B (it) * 1988-11-28 1991-04-23 Vectorpharma Int Farmaci supportati aventi velocita' di dissoluzione aumentata e procedimento per la loro preparazione
US5073374A (en) * 1988-11-30 1991-12-17 Schering Corporation Fast dissolving buccal tablet
DK469989D0 (da) * 1989-09-22 1989-09-22 Bukh Meditec Farmaceutisk praeparat
JP2542122B2 (ja) * 1990-04-18 1996-10-09 旭化成工業株式会社 球状核、球形顆粒およびその製造方法
US5316772A (en) * 1990-12-19 1994-05-31 Solvay & Cie, S.A. (Societe Anonyme) Bilayered oral pharmaceutical composition with pH dependent release
US5223268A (en) * 1991-05-16 1993-06-29 Sterling Drug, Inc. Low solubility drug-coated bead compositions
JP3722294B2 (ja) * 1993-02-23 2005-11-30 ワーナー−ランバート・コンパニー 実質的にアルコールを含有しない医薬組成物の製造方法
ZA949929B (en) * 1993-12-23 1995-08-23 Akzo Nobel Nv Sugar-coated pharmaceutical dosage unit.
US5547948A (en) * 1995-01-17 1996-08-20 American Home Products Corporation Controlled release of steroids from sugar coatings

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100381117C (zh) * 1999-02-08 2008-04-16 Fmc有限公司 可食用的包衣组合物
CN116236453A (zh) * 2023-02-08 2023-06-09 江苏和汇医药科技有限公司 一种延长药品释放的糖包衣及其制备方法

Also Published As

Publication number Publication date
FI960210L (fi) 1996-07-18
CZ286102B6 (cs) 2000-01-12
IL116772A0 (en) 1996-05-14
BR9600100A (pt) 1998-01-27
IS1878B (is) 2003-06-20
SK4996A3 (en) 1997-04-09
AU705879B2 (en) 1999-06-03
EG23687A (en) 2007-05-13
KR960028919A (ko) 1996-08-17
RU2152207C1 (ru) 2000-07-10
IS4318A (is) 1996-07-18
NO960191L (no) 1996-07-18
SK280484B6 (sk) 2000-02-14
IL116772A (en) 1999-08-17
PL312336A1 (en) 1996-07-22
CZ12896A3 (en) 1996-08-14
HU223781B1 (hu) 2005-01-28
HUP9600090A2 (en) 1996-12-30
AU4098296A (en) 1996-07-25
NO315307B1 (no) 2003-08-18
ZA96301B (en) 1997-07-15
CO4370096A1 (es) 1996-10-07
DE69604600D1 (de) 1999-11-18
BR9600100B1 (pt) 2009-01-13
NZ280826A (en) 1996-12-20
ATE185482T1 (de) 1999-10-15
NO960191D0 (no) 1996-01-16
MY115786A (en) 2003-09-30
TR199600038A2 (tr) 1996-08-21
EE9600002A (et) 1996-08-15
ID23996A (id) 1996-07-25
EP0722720B1 (en) 1999-10-13
US5547948A (en) 1996-08-20
TW460301B (en) 2001-10-21
DE69604600T2 (de) 2000-02-24
EE03802B1 (et) 2002-08-15
JPH08231436A (ja) 1996-09-10
FI117592B (fi) 2006-12-15
FI960210A0 (fi) 1996-01-16
SI0722720T1 (en) 1999-12-31
DK0722720T3 (da) 2000-01-03
US5759576A (en) 1998-06-02
JP3833292B2 (ja) 2006-10-11
ES2137627T3 (es) 1999-12-16
CN1106839C (zh) 2003-04-30
CA2167254A1 (en) 1996-07-18
HUP9600090A3 (en) 1997-05-28
HK1009935A1 (zh) 1999-06-11
PL183330B1 (pl) 2002-06-28
UA37236C2 (uk) 2001-05-15
AR002019A1 (es) 1998-01-07
EP0722720A1 (en) 1996-07-24
KR100338581B1 (ko) 2002-11-23
GR3031920T3 (en) 2000-03-31

Similar Documents

Publication Publication Date Title
CN1106839C (zh) 由糖衣控释的类固醇
CN1149982C (zh) 类固醇从糖衣中的控制释放
AU2021203265B2 (en) Orodispersible dosage unit containing an estetrol component
KR100857344B1 (ko) 피임약으로서의 사용을 위한 에티닐에스트라디올과드로스피렌온의 약학적 조합
KR102164693B1 (ko) 드로스피레논을 포함하는 약학적 조성물 및 피임용 키트
EP3310345B1 (en) Orodispersible tablet containing estetrol
CN1064810A (zh) 低剂量的干药物制剂
PL198425B1 (pl) Kompozycja farmaceutyczna zawierająca eplerenon oraz zastosowanie eplerenonu
RU2482853C2 (ru) Фармацевтическая композиция, способ ее получения и многофазный фармацевтический препарат для ингибирования овуляции у млекопитающего
CN1870981A (zh) 结合雌激素组合物以及相关方法
CN1500478A (zh) 延迟固体口服避孕药或终止妊娠药溶解的剂型及其应用
KR102210982B1 (ko) 드로스피레논을 포함하는 약학적 조성물 및 피임용 키트
JP2005529929A (ja) プロゲスターゲン投与単位
EP1958628A1 (en) Combination of immediately liberated drospirenone with a modified releasing formulation containing 8-prenylnaringenin for use in oral contraception and hormone replacement therapy
EP1900359A1 (en) Oral modified release formulations containing drospirenon and 8-prenylnaringenin for use in female contraception
HK1254650B (zh) 含雌四醇组分的口腔分散剂量单位
HK1254486B (zh) 含雌四醇的口腔分散片剂
HK1254486A1 (zh) 含雌四醇的口腔分散片剂
HK1254649A1 (zh) 含雌四醇的口腔分散片剂
HK1254649B (zh) 含雌四醇的口腔分散片剂
HK1003870B (zh) 控制类固醇自糖衣中释放
MXPA97000515A (en) Controlled release of steroids from azu coatings

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
REG Reference to a national code

Ref country code: HK

Ref legal event code: GR

Ref document number: 1022115

Country of ref document: HK

CX01 Expiry of patent term

Granted publication date: 20030430

EXPY Termination of patent right or utility model