公开(公告)号：US06977083B1

公开(公告)日：2005-12-20

申请号：US09806639

申请日：1999-09-30

申请人： Doris Huebler ,  Guenter Kaufmann ,  Michael Oettel ,  Holger Zimmermann ,  Michael Dittgen ,  Sabine Fricke ,  Manfred Boese ,  Ralf Ladwig ,  Sven Claussen ,  Carsten Timpe

发明人： Doris Huebler ,  Guenter Kaufmann ,  Michael Oettel ,  Holger Zimmermann ,  Michael Dittgen ,  Sabine Fricke ,  Manfred Boese ,  Ralf Ladwig ,  Sven Claussen ,  Carsten Timpe

IPC分类号： A61F13/00 ,  A61K9/00

CPC分类号： A61K9/006

摘要： The method of making a bioadhesive tablet for controlling testosterone blood level, especially in elderly men suffering from partial androgen deficiency, includes spray-drying an alcoholic solution or suspension of testosterone and at least one testosterone ester, preferably in a ratio of 1:10 to 1:1.5, separately or together, with an organic polymer and optionally one or more auxiliary ingredient to form an active ingredient premix. Then various other auxiliary ingredients are mixed, as needed, with the active ingredient premix to form the bioadhesive tablet with an active ingredient layer and an adhesive layer. The active ingredient layer contains an effective amount of the active ingredient premix. The adhesive layer includes auxiliary ingredients including the bioadhesive polymer. The bioadhesive tablet may be buccally administered to provide a predetermined timed release profile of testosterone, advantageously varying according to a circadian rhythm.

摘要翻译： 制备用于控制睾酮血液水平的生物粘附片剂的方法，特别是在患有部分雄激素缺乏症的老年男性中，包括将睾酮和至少一种睾酮酯的醇溶液或悬浮液喷雾干燥，优选1:10至 1：1.5，分别或一起与有机聚合物和任选的一种或多种辅助成分形成活性成分预混物。 然后根据需要将各种其它辅助成分与活性成分预混合物混合以形成具有活性成分层和粘合剂层的生物粘附片剂。 活性成分层含有有效量的活性成分预混物。 粘合层包括辅助成分，包括生物粘附聚合物。 生物粘附片剂可以经口给药以提供睾酮的预定定时释放曲线，其有利地根据昼夜节律改变。

公开(公告)号：US6117450A

公开(公告)日：2000-09-12

申请号：US65863

申请日：1998-04-24

申请人： Michael Dittgen ,  Sabine Fricke ,  Carsten Timpe ,  Hagen Gerecke ,  Annette Eichardt

发明人： Michael Dittgen ,  Sabine Fricke ,  Carsten Timpe ,  Hagen Gerecke ,  Annette Eichardt

IPC分类号： A61K9/22 ,  A61K9/48 ,  A61K9/52 ,  A61P43/00 ,  A61K9/26 ,  A61K9/28

CPC分类号： A61K9/4808

摘要： The method of making a solid drug with controlled effective ingredient delivery for oral administration includes selecting a predetermined number of at least three of four compressed compositions containing an effective ingredient or effective ingredient combination defined by their release profile of effective ingredient and/or effective ingredient combination. The solid drug or medicinal preparation is formed according to known methods requiring only comparatively small apparatus expense and minimal time. Perorally administered solid drugs are made by this process which can provide widely varying pharmaceutically-required release profiles of effective ingredients or effective ingredient combinations, for example delayed release, uniformly maintained release or pulsatile release adjusted to fit a special rhythm.

摘要翻译： 制备具有受控制的有效成分递送用于口服给药的固体药物的方法包括选择预定数量的四种压缩组合物中的至少三种，其包含由有效成分和/或有效成分组合的释放曲线限定的有效成分或有效成分组合 。 固体药物或药物制剂根据已知的方法形成，只需要较小的装置费用和最少的时间。 通过该方法制备经口施用的固体药物，其可以提供有效成分或有效成分组合的广泛变化的药学需要的释放曲线，例如延迟释放，均匀保持的释放或脉动释放，以适应特殊的节律。

公开(公告)号：US06214377B1

公开(公告)日：2001-04-10

申请号：US08567294

申请日：1995-12-05

申请人： Michael Dittgen ,  Sabine Fricke ,  Thomas Gräser ,  Hermann Osterwald ,  Michael Oettel ,  Theodor Hermann Lippert

发明人： Michael Dittgen ,  Sabine Fricke ,  Thomas Gräser ,  Hermann Osterwald ,  Michael Oettel ,  Theodor Hermann Lippert

IPC分类号： A61K958

CPC分类号： A61K9/4875 ,  A61K9/4858 ,  A61K31/4045

摘要： The use of melatonin for the production of peroral pulsatile forms of medications assures the safeguard of an effective level of the medical substance of melatonin in the blood, and which realize a relatively short invasion phase with a controlled delivery in comparison to conventional forms of medication containing melatonin, and which simultaneously exclude the known side effects. A control of the delivery of the melatonin is effected which is associated with the precise adaptation to the illness episodes or the pain attacks of certain illnesses, which can be treated prophylactically and therapeutically with the active agent melatonin.

摘要翻译： 使用褪黑激素来生产口服脉搏形式的药物确保维持血液中褪黑激素的有效水平，并且与常规形式的药物相比，其具有受控递送的相对较短的入侵期 褪黑激素，同时排除已知的副作用。 对褪黑激素的输送进行控制，这与精神适应疾病发作或某些疾病的疼痛攻击有关，可以用活性剂褪黑激素进行预防和治疗。

公开(公告)号：US20050032756A1

公开(公告)日：2005-02-10

申请号：US10891729

申请日：2004-07-15

申请人： Michael Dittgen ,  Sabine Fricke ,  Herbert Hoffmann ,  Claudia Moore ,  Michael Oettel ,  Monika Oster Wald

发明人： Michael Dittgen ,  Sabine Fricke ,  Herbert Hoffmann ,  Claudia Moore ,  Michael Oettel ,  Monika Oster Wald

IPC分类号： A61K31/57 ,  A61K31/56

CPC分类号： A61K31/57 ,  A61K2300/00

摘要： A multistage preparation for contraception based on a combination of natural estrogen and synthetic gestogen is described. The preferred preparation contains estradiol valerate as the natural estrogen and dienogest or drospirenone as the synthetic gestogen. In comparison to conventional multistage preparations the multistage preparation according to the invention has a higher contraceptive reliability over the entire cycle, improved cyclic bleeding behavior and minimizes or prevents side effects, such as breast tension, headaches, depressive moods and libido changes.

摘要翻译： 描述了基于天然雌激素和合成gestogen的组合的用于避孕的多级制剂。 优选的制剂包含戊酸雌二醇作为天然雌激素和依诺孕酮或屈螺酮作为合成孕酮。 与常规多级制剂相比，根据本发明的多级制剂在整个循环中具有更高的避孕可靠性，改善的循环出血行为并且最小化或预防副作用，例如乳房张力，头痛，抑郁情绪和性欲改变。

公开(公告)号：US6133251A

公开(公告)日：2000-10-17

申请号：US738314

申请日：1996-10-25

申请人： Michael Dittgen ,  Sabine Fricke ,  Herbert Hoffmann ,  Claudia Moore ,  Michael Oettel ,  Monika Ostertag

发明人： Michael Dittgen ,  Sabine Fricke ,  Herbert Hoffmann ,  Claudia Moore ,  Michael Oettel ,  Monika Ostertag

IPC分类号： A61K31/565 ,  A61K31/57 ,  A61P15/00 ,  A61P15/18 ,  C07J1/00 ,  C07J7/00 ,  A61K31/56

CPC分类号： A61K31/57 ,  Y10S514/843

摘要： The combination preparation for contraception includes a first stage of 2 to 4 first stage daily dosage portions, a second stage of two groups of second stage daily dosage portions, a third stage of 2 to 4 third stage daily dosage portions and an additional stage of 2 to 4 additional stage daily dosage portions. The first stage daily dosage portion is an effective amount of natural estrogen, the second stage daily dosage portion is an effective amount of a combination of natural estrogen and natural or synthetic gestogen, the third stage daily dosage portion is another effective amount of natural estrogen and an additional stage daily dosage portion consists of a placebo. The first group of the second stage consists of 3 to 5 daily dosage portions and the second group, 13 to 17 daily dosage portions. More of the gestogen is included in the effective amount in the second group of the second stage than in the first group. The effective amount of the natural estrogen is constant in both the first and third stages, but smaller in the third stage than in the first stage.

摘要翻译： 用于避孕的组合制剂包括第一阶段的2至4个第一阶段每日剂量部分，第二阶段的两组第二阶段日剂量部分，第三阶段的2至4个第三阶段每日剂量部分和另外的阶段2 至4个额外的阶段日剂量部分。 第一阶段日剂量是天然雌激素的有效量，第二阶段日剂量是天然雌激素和天然或合成gestogen的组合的有效量，第三阶段日剂量是另一有效量的天然雌激素， 额外的阶段每日剂量部分由安慰剂组成。 第一组第一组由3〜5个日剂量组成，第二组为每日13〜17次。 第二组的第二组中有更多的gestogen包含在第一组中。 天然雌激素的有效量在第一和第三阶段都是恒定的，但在第三阶段中比在第一阶段更小。

公开(公告)号：US06884793B2

公开(公告)日：2005-04-26

申请号：US09950915

申请日：2001-09-12

申请人： Michael Dittgen ,  Sabine Fricke ,  Herbert Hoffmann ,  Claudia Moore ,  Michael Oettel ,  Monika Ostertag

发明人： Michael Dittgen ,  Sabine Fricke ,  Herbert Hoffmann ,  Claudia Moore ,  Michael Oettel ,  Monika Ostertag

IPC分类号： A61K31/565 ,  A61K31/57 ,  A61P15/00 ,  A61P15/18 ,  C07J1/00 ,  C07J7/00 ,  A61K33/56

CPC分类号： A61K31/57 ,  Y10S514/843 ,  A61K31/565 ,  A61K2300/00

摘要： The combination preparation for contraception includes from 2 to 4 first stage daily dosage portions each including an effective amount of at least one natural estrogen as sole active ingredient, from 16 to 22 second stage daily dosage portions each including an effective amount of a combination of at least one natural estrogen and at least one natural or synthetic gestogen as active ingredient; from 2 to 4 third stage daily dosage portions each including an effective amount of at least one natural estrogen as sole active ingredient; and from 2 to 4 final stage daily dosage portions containing a pharmaceutically acceptable placebo. The estrogen may be estradiol, an estradiol compound that is metabolized to estradiol when taken into the body, a conjugated equine estrogen or a phytoestrogen. The natural or synthetic gestogen can be natural progesterone or a synthetic gestogens, such as medroxyprogesterone acetate.

摘要翻译： 用于避孕的组合制剂包括2至4个第一阶段每日剂量部分，每个剂量部分包含有效量的至少一种天然雌激素作为唯一活性成分，16至22个第二阶段日剂量部分，每个包含有效量的组合 至少一种天然雌激素和至少一种天然或合成的Gestogen作为活性成分; 2至4个第三阶段每日剂量部分，每个包含有效量的至少一种天然雌激素作为唯一活性成分; 和含有药学上可接受的安慰剂的2至4个最终阶段每日剂量部分。 雌激素可以是雌二醇，当被摄入体内时被代谢为雌二醇的雌二醇化合物，共轭马雌激素或植物雌激素。 天然或合成的gestogen可以是天然孕酮或合成的gestogens，如醋酸甲羟孕酮。

公开(公告)号：US20070088010A1

公开(公告)日：2007-04-19

申请号：US11273426

申请日：2005-11-14

申请人： Doris Huebler ,  Sabine Fricke

发明人： Doris Huebler ,  Sabine Fricke

IPC分类号： A61K31/57 ,  A61K31/56

CPC分类号： A61K31/565 ,  A61K31/567 ,  A61K31/57 ,  A61K2300/00

摘要： The single-stage pharmaceutical preparation for oral therapy of dysfunctional uterine bleeding contains at least 21 separately packaged and individual administered daily dosage units in a single container. Each orally administered daily dosage unit contains a combination of ethinyl estradiol and dienogest in low dosage. Administration of this preparation results in a moderate proliferation of the endometrium with complete transformation and slight break-through bleeding in the hormone-free time interval.

摘要翻译： 用于口服功能障碍性子宫出血的单阶段药物制剂在单个容器中含有至少21个单独包装和单独施用的日剂量单位。 每个口服每日剂量单位含有低剂量的乙炔雌二醇和依诺孕酮的组合。 这种制剂的施用导致子宫内膜的适度增殖，在无激素时间间隔内完全转化和轻微的突破性出血。

公开(公告)号：US20090117184A1

公开(公告)日：2009-05-07

申请号：US12258817

申请日：2008-10-27

申请人： Sabine Fricke ,  Manuela Pfeifer ,  Claus Claussen ,  Ralf Ladwig ,  Beate Buerglen

发明人： Sabine Fricke ,  Manuela Pfeifer ,  Claus Claussen ,  Ralf Ladwig ,  Beate Buerglen

IPC分类号： A61K9/24 ,  A61K31/56 ,  A61K9/36

CPC分类号： A61K31/566 ,  A61K9/2054 ,  A61K9/2059

摘要： Gestagens, preferably dienogest, chlormadinone acetate or levonorgestrel, in combination with estrogens, for example ethinylestradiol, 17β-estradiol or estradiol valerate, and one or more pharmaceutically acceptable auxiliary agents/excipients provide lactose-free oral contraception.The possibility is provided of improving the prophylaxis for lactose intolerance concerning a possibly contributing factor and also in regard to the costly examinations for lactose intolerance.The invention is also suitable for long-term use.

摘要翻译： 孕激素，优选地那诺孕，乙酸氯地孕酮或左炔诺孕酮与雌激素联合，例如炔雌醇，17β-雌二醇或戊酸雌二醇和一种或多种药学上可接受的助剂/赋形剂，提供无乳糖的口服避孕药。 提供了改善对可能促成因子的乳糖不耐症的预防以及关于乳糖不耐症的昂贵检查的可能性。 本发明也适用于长期使用。

公开(公告)号：US20080038350A1

公开(公告)日：2008-02-14

申请号：US11762207

申请日：2007-06-13

申请人： Hagen Gerecke ,  Sabine Fricke ,  Ralf Ladwig ,  Herbert Wiesinger ,  Alexander Buske

发明人： Hagen Gerecke ,  Sabine Fricke ,  Ralf Ladwig ,  Herbert Wiesinger ,  Alexander Buske

IPC分类号： A61K31/56 ,  A61K9/28 ,  A61P15/18

CPC分类号： A61K31/56 ,  A61K9/14 ,  A61K9/2018 ,  A61K9/2059 ,  A61K9/2813 ,  A61K9/282 ,  A61K9/284 ,  A61K9/2853 ,  A61K9/2866 ,  A61K31/567 ,  A61K45/06

摘要： The peroral medication for prevention of conception contains as one active ingredient crystalline 17α-cyanomethyl-17β-hydroxyestra-4,9-dien-3-one (dienogest) at a daily dosage equal to or less than 2.0 mg and as another active ingredient 17α-ethinyl estradiol at a daily dosage of less than 0.030 mg, together with one or more pharmaceutically acceptable carriers. The active ingredient dienogest is contained in the medication in crystalline form with an average particle size of preferably 25 to 70 μm. The other active ingredient ethinyl estradiol is incorporated during granulation in micronized form or by spraying an ethanolic solution containing it.

摘要翻译： 用于预防受孕的口服药物含有等于或小于2.0mg的日剂量的作为一种活性成分的结晶17α-氰基甲基-17β-羟雌甾-4,9-二烯-3-酮（地诺孕司），作为另一活性成分17alpha - 乙烯基雌二醇，每日剂量小于0.030mg，以及一种或多种药学上可接受的载体。 活性成分二烯酸酯以结晶形式包含在平均粒度优选为25至70μm的药物中。 另外的活性成分乙炔雌二醇是以微粉化形式造粒或通过喷雾含有它的乙醇溶液而掺入的。

公开(公告)号：US20090117183A1

公开(公告)日：2009-05-07

申请号：US12258737

申请日：2008-10-27

申请人： Sabine Fricke ,  Manuela Pfeifer ,  Claus Claussen ,  Ralf Ladwig ,  Beate Buerglen

发明人： Sabine Fricke ,  Manuela Pfeifer ,  Claus Claussen ,  Ralf Ladwig ,  Beate Buerglen

IPC分类号： A61K9/24 ,  A61K31/566 ,  A61P15/18

CPC分类号： A61K31/566 ,  A61K9/2054 ,  A61K9/2059

摘要： The method produces a lactose-free oral contraceptive composition containing a combination of a gestagen and an estrogen together with one or more pharmaceutically acceptable auxiliary agents and/or excipients. The contraceptive composition is a tablet, powder, or capsule that contains the gestagen and estrogen, filler material such as microcrystalline cellulose and a binder such as hydroxypropylcellulose, but no lactose. Preferably the gestagen is dienogest, chlormadinone acetate, or levonorgestrel and the estrogen is ethinylestradiol, 17β-estradiol, or estradiol valerate. A method is provided for improving the prophylaxis of lactose intolerance in women taking oral contraceptives. The oral contraceptive preparations for a standard 28-day cycle or for long-term use contain at least 21 daily dose units of the gestagen and the estrogen in a low-dosage but without lactose and at most 7 daily dose units containing no active ingredient or a placebo.

摘要翻译： 该方法产生不含无乳糖的口服避孕药组合物，其含有孕激素和雌激素以及一种或多种药学上可接受的助剂和/或赋形剂的组合。 避孕组合物是含有孕激素和雌激素，诸如微晶纤维素和粘合剂如羟丙基纤维素但不含乳糖的填充材料的片剂，粉末或胶囊。 优选地，孕激素是依诺麦特，乙酸氯地孕酮或左炔诺孕酮，雌激素是炔雌醇，17β-雌二醇或戊酸雌二醇。 提供了一种改善口服避孕药妇女乳糖不耐症预防的方法。 标准28天循环或长期使用的口服避孕制剂含有低剂量但不含乳糖的孕激素和雌激素至少21个日剂量单位，并且最多含有不含活性成分的至多7个日剂量单位或 一个安慰剂