公开(公告)号：US5855905A

公开(公告)日：1999-01-05

申请号：US841719

申请日：1997-04-30

申请人： Michael Oettel ,  Siegfried Golbs ,  Michael Dittgen ,  Carsten Timpe ,  Thomas Graser ,  Doris Hubler

发明人： Michael Oettel ,  Siegfried Golbs ,  Michael Dittgen ,  Carsten Timpe ,  Thomas Graser ,  Doris Hubler

IPC分类号： A61K31/565

CPC分类号： A61K31/565

摘要： A compound preparation for the treatment of hypogonadal men and men with hypophyseal diseases. This invention relates to compound preparations containing biogenous or synthetic androgens and biogenous or synthetic estrogens that are used for the treatment of imbalances of the testosterone metabolism in old age, of hypogonadal men, and of men with hypophyseal diseases. These compound preparations are present in various galenic formulations such as ointments, gels, sprays, TTS systems, tablets, lozenges, capsules, and suppositories. These preparations are used to treat the fluctuations of the testosterone metabolism occurring in old age and with certain diseases such as hypophyseal diseases (adenoma), hypogonadism and/or metabolic syndrome, to maintain the balance between androgens and estrogens found in young and healthy men in ill and/or elderly men as well. The preparations for treating these imbalances are suitable for oral, parenteral, percutaneous, sublingual or rectal administration depending on their galenic form. Thus, unphysiological changes in steroid-converting enzymes such as aromatases and reductases are avoided, which considerably improves the outcome of the therapy.

摘要翻译： 用于治疗性腺功能减退的男性和男性的复方制剂。 本发明涉及包含生物或合成雄激素和生物或合成雌激素的化合物制剂，其用于治疗老年睾酮代谢失调，性腺机能不良男性和具有垂体浸润性疾病的男性的不平衡。 这些复合制剂存在于各种盖仑制剂如软膏，凝胶剂，喷雾剂，TTS系统，片剂，锭剂，胶囊和栓剂中。 这些制剂用于治疗老年发生的睾酮代谢的波动，以及诸如垂体疾病（腺瘤），性腺机能减退和/或代谢综合征等某些疾病，以维持年轻和健康男性发现的雄激素和雌激素之间的平衡 生病和/或老年男子。 用于治疗这些不平衡的制剂适用于口服，肠胃外，经皮，舌下或直肠给药，取决于其盖仑形式。 因此，避免类固醇转化酶如芳香酶和还原酶的非生理变化，这显着改善了治疗的结果。

公开(公告)号：US06225299B1

公开(公告)日：2001-05-01

申请号：US09219660

申请日：1998-12-23

申请人： Siegfried Golbs ,  Michael Oettel ,  Michael Dittgen ,  Thomas Graser ,  Christoph Luderschmidt

发明人： Siegfried Golbs ,  Michael Oettel ,  Michael Dittgen ,  Thomas Graser ,  Christoph Luderschmidt

IPC分类号： A61K3156

CPC分类号： A61K31/56 ,  A61K8/63 ,  A61Q7/00 ,  Y10S514/859 ,  Y10S514/864

摘要： The pharmaceutical composition, especially for treating skin with seborrhea, Acne vulgaris and androgonically conditioned alopecia, contains a hormonal agent including the gestogen, dienogest, or a combination of dienogest and an estrogen, as active ingredient. Methods for treatment of this type of skin condition include topical application of the composition including the dienogest which results in an outstanding sebosuppression, a drastic reduction of androstandiol glucuronide and a moderate competitive blockage of androgen receptor sites. Galenic formulations are described which limit and/or prevent the permeation of the active ingredient through the skin. The pharmaceutical preparation including the dienogest and conventional dermatologically acceptable carrier and auxiliary substances in the described galenic formulation advantageously provides a drastic reduction in androstandiol glucuronide and moderate androgen receptor blockage without passing through the skin barrier so that systemic effects including side reactions are substantially prevented.

摘要翻译： 药物组合物，特别是用于治疗皮脂溢，皮肤寻常痤疮和阴道调理性脱发的皮肤，含有激素剂，包括睾酮，依那诺或二烯酸和雌激素的组合作为活性成分。 用于治疗这种类型皮肤病症的方法包括局部应用组合物，其包括引起明显的抑制作用的替奈格明，葡萄糖醛酸葡萄糖醛酸葡聚糖和葡萄糖醛酸葡聚糖的剧烈降低以及雄激素受体位点的适度竞争性阻断。 描述了限制和/或防止活性成分渗透皮肤的Galenic制剂。 在所述盖仑制剂中包含地那烯酸和常规皮肤病学可接受的载体和辅助物质的药物制剂有利地提供了葡萄糖醛酸葡萄糖醛酸葡萄糖苷和中和雄激素受体阻断物的急剧降低，而不会通过皮肤屏障，从而基本上防止包括副反应的全身效应。

公开(公告)号：US5910493A

公开(公告)日：1999-06-08

申请号：US714463

申请日：1996-09-16

申请人： Siegfried Golbs ,  Michael Oettel ,  Michael Dittgen ,  Thomas Graser ,  Christoph Luderschmidt

发明人： Siegfried Golbs ,  Michael Oettel ,  Michael Dittgen ,  Thomas Graser ,  Christoph Luderschmidt

IPC分类号： A61K8/63 ,  A61Q5/00 ,  A61Q7/00 ,  A61Q19/00 ,  A61K31/56

CPC分类号： A61K31/567 ,  A61K8/63 ,  A61Q19/00 ,  A61Q5/00 ,  A61Q7/00 ,  Y10S514/859 ,  Y10S514/864

摘要： The pharmaceutical composition, especially for treating skin with seborrhea, Acne vulgaris and androgonically conditioned alopecia, contains a hormonal agent including the gestogen, dienogest, or a combination of dienogest and an estrogen, as active ingredient. Methods for treatment of this type of skin condition include topical application of the composition including the dienogest which results in an outstanding sebosuppression, a drastic reduction of androstandiol glucuronide and a moderate competitive blockage of androgen receptor sites. Galenic formulations are described which limit and/or prevent the permeation of the active ingredient through the skin. The pharmaceutical preparation including the dienogest and conventional dermatologically acceptable carrier and auxiliary substances in the described galenic formulation advantageously provides a drastic reduction in androstandiol glucuronide and moderate androgen receptor blockage without passing through the skin barrier so that systemic effects including side reactions are substantially prevented.

摘要翻译： 药物组合物，特别是用于治疗皮脂溢，皮肤寻常痤疮和阴道调理性脱发的皮肤，含有激素剂，包括睾酮，依那诺或二烯酸和雌激素的组合作为活性成分。 用于治疗这种类型皮肤病症的方法包括局部应用组合物，其包括引起明显的抑制作用的替奈格明，葡萄糖醛酸葡萄糖醛酸葡聚糖和葡萄糖醛酸葡聚糖的剧烈降低以及雄激素受体位点的适度竞争性阻断。 描述了限制和/或防止活性成分渗透皮肤的Galenic制剂。 在所述盖仑制剂中包含地那烯酸和常规皮肤病学可接受的载体和辅助物质的药物制剂有利地提供了葡萄糖醛酸葡萄糖醛酸葡萄糖苷和中和雄激素受体阻断物的急剧降低，而不会通过皮肤屏障，从而基本上防止包括副反应的全身效应。

公开(公告)号：US5614213A

公开(公告)日：1997-03-25

申请号：US295723

申请日：1994-08-31

申请人： Walter Elger ,  Birgitt Schneider ,  Michael Oettel ,  Michael Ernst ,  Doris Hubler ,  Michael Dittgen

发明人： Walter Elger ,  Birgitt Schneider ,  Michael Oettel ,  Michael Ernst ,  Doris Hubler ,  Michael Dittgen

IPC分类号： A61K9/06 ,  A61K9/70 ,  A61K31/565 ,  A61P3/02 ,  A61P19/10 ,  A61P43/00 ,  A61F13/00

CPC分类号： A61K9/7084 ,  A61K31/565 ,  Y10S514/969

摘要： The invention relates to the use of estriol as the sole active ingredient for the production of a transdermal medicament which continuously releases the active ingredient for the treatment of climacteric osteoporosis. It has been shown according to the invention that estriol, which has up until now been thought ineffective for the treatment of climacteric osteoporosis, develops strong anti-osteoporotic effectiveness upon continuous transdermal application.

摘要翻译： PCT No.PCT / EP93 / 00636 Sec。 371日期1994年8月31日 102（e）日期1994年8月31日PCT 1993年3月18日PCT公布。 出版物WO93 / 18774 日期1993年9月30日本发明涉及使用雌三醇作为唯一活性成分用于生产连续释放用于治疗更年期骨质疏松症的活性成分的透皮药物。 根据本发明已经显示，直至现在被认为对治疗更年期性骨质疏松症无效的雌三醇在连续经皮施用时发挥强烈的抗骨质疏松效果。

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：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％。

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：US6063404A

公开(公告)日：2000-05-16

申请号：US124577

申请日：1998-07-29

申请人： Carsten Timpe ,  Michael Dittgen ,  Detlef Grawe ,  Jochen Schumacher ,  Holger Zimmermann ,  Herbert Hoffmann

发明人： Carsten Timpe ,  Michael Dittgen ,  Detlef Grawe ,  Jochen Schumacher ,  Holger Zimmermann ,  Herbert Hoffmann

IPC分类号： A61K9/00 ,  A61K9/20 ,  A61K47/30 ,  A61K47/38 ,  A61K9/44

CPC分类号： A61K9/006 ,  A61K9/2072 ,  A61K9/2086

摘要： This invention relates to a bioadhesive tablet containing at least one bioadhesive adjuvant and at least one lubricant, with at least one surface of the tablet comprising concentric or parallel, straight and/or curved depressions, and to a method for producing the bioadhesive tablets as well as to pharmaceuticals in the form of the bioadhesive tablets.

摘要翻译： 本发明涉及包含至少一种生物粘附剂佐剂和至少一种润滑剂的生物粘附片剂，片剂的至少一个表面包含同心或平行的直的和/或弯曲的凹陷部分，以及用于生产生物粘附片剂的方法 关于生物粘附片形式的药物。

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。