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1. 发明授权

US06902741B1 Laminates containing an active substance transdermal system 有权
标题翻译：含有活性物质透皮系统的层压体
公开(公告)号：US06902741B1
公开(公告)日：2005-06-07
申请号：US09913112
申请日：2000-02-08
申请人： Detlef Grawe , Peter Hoesel , Wilfried Fischer
发明人： Detlef Grawe , Peter Hoesel , Wilfried Fischer
IPC分类号： A61K9/14 , A61K9/70 , A61K31/568 , A61P5/24 , A61F13/02 , A61L15/16
CPC分类号： A61K9/7053 , A61K9/146
摘要： The transdermal system includes a sex hormone-containing adhesive matrix, which contains inclusions of a sex hormone in a hydrophilic non-crosslinked polymer in dissolved or dispersed form. The inclusions have a concentration of 20 to 90 percent by weight of the sex hormone, which is more than 50 percent by weight amorphous. The hydrophilic non-crosslinked polymer can be polyvinylpyrrolidone, methylcellulose, ethylcellulose or hydroxyethylcellulose. The adhesive matrix can be a polyisobutylene, ethylene-vinyl-acetate copolymer or a polystyrene-butadiene block copolymer.
摘要翻译：透皮系统包括含有性激素的粘合剂基质，其在溶解或分散形式的亲水性非交联聚合物中含有性激素的夹杂物。夹杂物的浓度为性激素的20〜90重量％，超过50重量％的非晶体。亲水性非交联聚合物可以是聚乙烯吡咯烷酮，甲基纤维素，乙基纤维素或羟乙基纤维素。粘合剂基质可以是聚异丁烯，乙烯 - 乙酸乙烯酯共聚物或聚苯乙烯 - 丁二烯嵌段共聚物。

2. 发明授权

US07192942B2 Process for production of crystals of 11μ-benzaldoxim-estra-4,9-diene derivatives, crystals obtained thereby and pharmaceutical preparations containing them 有权
标题翻译：制备11M-亚苄基肟 - 雌-4,9-二烯衍生物的晶体的方法，由此获得的晶体和含有它们的药物制剂
公开(公告)号：US07192942B2
公开(公告)日：2007-03-20
申请号：US10417559
申请日：2003-04-17
申请人： Detlef Grawe , Hagen Gerecke , Peter Hoesel , Annette Eichardt , Sabine Gliesing , Uwe Mueller
发明人： Detlef Grawe , Hagen Gerecke , Peter Hoesel , Annette Eichardt , Sabine Gliesing , Uwe Mueller
IPC分类号： A61K31/56 , C07J1/00
CPC分类号： C07J41/0083 , A61K9/14
摘要： The process for making crystals of a 11 β-benzaldoxim-estra-4,9-diene derivative having an average particle size of from 3 μm to 25 μm and a maximum particle size of 100 μm, includes subjecting a supersaturated solution containing a special 11β-benzaldoxim-estra-4,9-diene derivative of formula (I) to a wet milling by a wet milling apparatus while crystallizing, In order to obtain a primary particle suspension. Crystals obtained according to this process and pharmaceutical preparations containing them are also described and are part of the invention.
摘要翻译：制备平均粒度为3μm〜25μm，最大粒径为100μm的11β-苯甲醛肟 - 雌-4,9-二烯衍生物的晶体的方法包括使含有特殊的11beta的过饱和溶液 - 苯甲醛 - 雌-4,9-二烯衍生物在结晶时通过湿式研磨装置进行湿法研磨，以获得初级颗粒悬浮液。还描述了根据该方法获得的晶体和含有它们的药物制剂，并且是本发明的一部分。

3. 发明授权

US06290931B1 Homogeneous preformulations containing high concentrations of steroids, for producing low-dose solid and semi-solid pharmaceutical preparations 失效
标题翻译：含有高浓度类固醇的均质预制品，用于生产低剂量固体和半固体药物制剂
公开(公告)号：US06290931B1
公开(公告)日：2001-09-18
申请号：US09319802
申请日：1999-06-10
申请人： Detlef Grawe , Peter Hoesel , Peter Moellmann , Carsten Timpe , Michael Dittgen , Klaus Matthey
发明人： Detlef Grawe , Peter Hoesel , Peter Moellmann , Carsten Timpe , Michael Dittgen , Klaus Matthey
IPC分类号： A61K912
CPC分类号： A61K31/569 , A61K9/1623 , A61K9/1676 , A61K31/567 , A61K31/575
摘要： A homogeneous steroid-containing preformulation for production of solid and semi-solid pharmaceutical preparations containing a uniform constant dosage of at least one steroid in a range from 0.001 to 1 percent by weight is described. This steroid-containing preformulation contains of from 0.001 to 50 percent by weight of the at least one steroid. The homogeneous steroid-containing preformulation is made by a method including dissolving the at least one steroid in a solvent to form a dispersant; dispersing an adjuvant consisting of adjuvant particles in the dispersant in a mass ratio of the adjuvant to the at least one steroid of 1:1 to 1000:1 to form a suspension; and creating a spray-mist of the suspension so as to evaporate and remove the solvent from the suspension and thus to form a dried particulate which includes steroid-containing particles. The droplets in the spray mist have a droplet diameter greater than a mean diameter of the adjuvant particles. The maximum particle size of the dried particulate forming the steroid-containing preformulation is increased by less than 30 percent in comparison to an average particle size of the adjuvant particles.
摘要翻译：描述了用于生产固体和半固体药物制剂的均匀类固醇预制剂，其含有0.001至1重量％范围内的至少一种类固醇的均匀恒定剂量。该含类固醇的预制剂含有0.001至50重量％的至少一种类固醇。通过包括将至少一种类固醇溶解在溶剂中以形成分散剂的方法制备含均匀类固醇的预配制剂; 将助剂颗粒组成的佐剂以佐剂与至少一种类固醇的质量比为1:1至1000:1分散在分散剂中以形成悬浮液; 并产生悬浮液的喷雾，从而从悬浮液中蒸发除去溶剂，从而形成包含类固醇颗粒的干燥颗粒。喷雾中的液滴的液滴直径大于辅助颗粒的平均直径。与佐剂颗粒的平均粒径相比，形成含类固醇的预制剂的干燥颗粒的最大粒度增加小于30％。

4. 发明授权

US08324412B2 Method for preparing 4-[17β-methoxy-17α-methoxymethyl-3-oxoestra-4,9-dien-11β-yl]benzaldehyde (E)-oxime (asoprisnil) 有权
标题翻译：制备4- [17β-甲氧基-17α-甲氧基甲基-3-氧代雌-4,9-二烯-11β-基]苯甲醛（E） - 肟（asoprisnil）的方法，
公开(公告)号：US08324412B2
公开(公告)日：2012-12-04
申请号：US12987850
申请日：2011-01-10
申请人： Detlef Grawe , Sabine Gliesing , Hagen Gerecke , Peter Hoesel , Uwe Mueller , Thomas Michel , Robert Eilers , Uwe Knabe , Bernd Erhart , Michael Mosebach , David Voigtlaender , Ulf Tilstam , Jürgen Jacke , Klaus Bahl , Ulf Bohlmann , Dieter Wehmeier , Michael Sander
发明人： Detlef Grawe , Sabine Gliesing , Hagen Gerecke , Peter Hoesel , Uwe Mueller , Thomas Michel , Robert Eilers , Uwe Knabe , Bernd Erhart , Michael Mosebach , David Voigtlaender , Ulf Tilstam , Jürgen Jacke , Klaus Bahl , Ulf Bohlmann , Dieter Wehmeier , Michael Sander
IPC分类号： C07J1/00
CPC分类号： C07J3/00 , Y10T428/2982
摘要： The present invention relates to a method for the reliable and reproducible preparation of 4-[17β-methoxy-17α-methoxymethyl-3-oxoestra-4,9-dien-11β-yl]benzaldehyde (E)-oxime (asoprisnil) on the pilot and manufacturing scale. Asoprisnil, which is prepared by this method, is distinguished by a very good physical stability and is therefore particularly suitable for the manufacture of solid pharmaceutical forms (tablets, coated tablets, etc.).
摘要翻译：本发明涉及一种可靠和可重复制备4- [17-甲氧基-17α-甲氧基甲基-3-氧代雌-4,9-二烯-11-基]苯甲醛（E） - 肟（asoprisnil）的方法，在试点和制造规模上。通过该方法制备的麻醉药具有非常好的物理稳定性，因此特别适用于制备固体药物形式（片剂，包衣片剂等）。

5. 发明申请

US20110257142A1 METHOD FOR PREPARING 4-[17BETA-METHOXY-17ALPHA-METHOXYMETHYL-3-OXOESTRA-4,9-DIEN-11-BETA-YL]BENZALDEHYDE (E)-OXIME (ASOPRISNIL) 有权
标题翻译：制备4- [17-甲氧基-17α-甲氧基甲基-3-氧杂环丙烷-4,9-二烯-11-β-YL]苯甲醛（E）-OXIME（ASOPRISNIL）
公开(公告)号：US20110257142A1
公开(公告)日：2011-10-20
申请号：US12987850
申请日：2011-01-10
申请人： Detlef Grawe , Sabine Gliesing , Hagen Gerecke , Peter Hoesel , Uwe Mueller , Thomas Michel , Robert Eilers , Uwe Knabe , Bernd Erhart , Michael Mosebach , David Voigtlaender , Ulf Tilstam , Jürgen Jacke , Klaus Bahl , Ulf Bohlmann , Dieter Wehmeier , Michael Sander
发明人： Detlef Grawe , Sabine Gliesing , Hagen Gerecke , Peter Hoesel , Uwe Mueller , Thomas Michel , Robert Eilers , Uwe Knabe , Bernd Erhart , Michael Mosebach , David Voigtlaender , Ulf Tilstam , Jürgen Jacke , Klaus Bahl , Ulf Bohlmann , Dieter Wehmeier , Michael Sander
IPC分类号： A61K31/56 , A61P43/00 , C07J3/00
CPC分类号： C07J3/00 , Y10T428/2982
摘要： The present invention relates to a method for the reliable and reproducible preparation of 4-[17β-methoxy-17α-methoxymethyl-3-oxoestra-4,9-dien-11β-yl]benzaldehyde (E)-oxime (asoprisnil) on the pilot and manufacturing scale. Asoprisnil, which is prepared by this method, is distinguished by a very good physical stability and is therefore particularly suitable for the manufacture of solid pharmaceutical forms (tablets, coated tablets, etc.).
摘要翻译：本发明涉及一种可靠和可重复制备4- [17-甲氧基-17α-甲氧基甲基-3-氧代雌-4,9-二烯-11-基]苯甲醛（E） - 肟（asoprisnil）的方法，在试点和制造规模上。通过该方法制备的麻醉药具有非常好的物理稳定性，因此特别适用于制备固体药物形式（片剂，包衣片剂等）。

6. 发明授权

US07148212B2 Process for production of steroid crystals, steroid crystals obtained thereby and pharmaceutical preparations containing them 有权
标题翻译：类固醇晶体的生产方法，由此获得的类固醇晶体和含有它们的药物制剂
公开(公告)号：US07148212B2
公开(公告)日：2006-12-12
申请号：US10417557
申请日：2003-04-17
申请人： Detlef Grawe , Hagen Gerecke , Peter Hoesel , Annette Eichardt , Sabine Gliesing , Uwe Mueller
发明人： Detlef Grawe , Hagen Gerecke , Peter Hoesel , Annette Eichardt , Sabine Gliesing , Uwe Mueller
IPC分类号： A61K31/56 , C07J1/00
CPC分类号： C07J1/0085
摘要： The process for making steroid crystals having a predetermined average particle size of from 1 μm to 25 μm and a maximum particle size that does not exceed a predetermined maximum value of 100 μm, includes subjecting a supersaturated solution containing a steroid to a wet milling by wet milling apparatus while crystallizing, in order to obtain a primary particle suspension. Crystals obtained according to this process and pharmaceutical preparations containing them are also described.
摘要翻译：具有预定平均粒径为1〜25μm，最大粒径不超过规定的最大值为100μm的类固醇晶体的方法包括使含有类固醇的过饱和溶液通过湿法湿法研磨研磨装置结晶，以获得初级颗粒悬浮液。还描述了根据该方法获得的晶体和含有它们的药物制剂。

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