公开(公告)号：US06432939B1

公开(公告)日：2002-08-13

申请号：US09710427

申请日：2000-11-10

申请人： Michael Oettel ,  Jens Berlau ,  Wolfgang Römer ,  Gerhard Schreiber

发明人： Michael Oettel ,  Jens Berlau ,  Wolfgang Römer ,  Gerhard Schreiber

IPC分类号： A61K3156

CPC分类号： A61K31/569 ,  C07J53/00

摘要： This invention describes 17&agr;-hydroxy-4-androstene-3-one and its derivatives of the general formula I a method for producing these compounds and pharmaceuticals containing these compounds. The compounds according to the invention can be used for regulating spermatogenesis and for hormone replacement therapy in males by stimulating the inhibin-B secretion by the Sertoli cells. The increased inhibin-B concentration suppresses spermatogenesis in the testicles as it inhibits excretion by the hypophysis of follicle-stimulating hormone (FSH) that is essential in spermatogenesis.

摘要翻译： 本发明描述了用于制备这些化合物的17α-羟基-4-雄甾烯-3-酮及其衍生物及其衍生物，以及含有这些化合物的药物。 根据本发明的化合物可以通过刺激Sertoli细胞的抑制素-B分泌来用于调节男性的精子发生和激素替代疗法。 增加的抑制素-B浓度抑制睾丸中的精子发生，因为它抑制了在精子发生中必需的促卵泡激素（FSH）的垂体分泌。

公开(公告)号：US06172056B2

公开(公告)日：2001-01-09

申请号：US08646341

申请日：1996-05-09

申请人： Peter Droescher ,  Bernd Menzenbach ,  Kurt Ponsold ,  Bernd Undeutsch ,  Michael Oettel ,  Wolfgang Römer ,  G{umlaut over (u)}nter Kaufmann ,  Jens Schroeder

发明人： Peter Droescher ,  Bernd Menzenbach ,  Kurt Ponsold ,  Bernd Undeutsch ,  Michael Oettel ,  Wolfgang Römer ,  G{umlaut over (u)}nter Kaufmann ,  Jens Schroeder

IPC分类号： A61K3156

CPC分类号： A61K31/565 ,  A61K31/575

摘要： The method of prophylaxis and therapy of radical-mediated cell damage includes administering an effective amount of at least one steroid and at least one pharmaceutical adjuvant to a human being. The at least one steroid is selected from the group consisting of ent-estradiol, 17&agr;-estradiol, 8-dehydro-estradiol, 8-dehydro-17&agr;-estradiol, 8(14)-dehydroestradiol, 6,8-didehydro-17&agr;-estradiol, 6-dehydroestriol, 9(11)-dehydroestriol, 20-hydroxymethyl-3-hydroxy-19-norpregna-1,3,5(10)-triene, 14&agr;, 15&agr;-methylene-8-dehydroestradiol, 14&agr;, 15&agr;-methylene-estradiol, 2-hydroxy-estradiol-3-methyl ether, 3-hydroxy-1,3,5(10)-estratriene-17S-spirooxirane, 3-hydroxy-1,3,5(10),9(11)-estratetraene-17S-spirooxirane, and 14&bgr;,15&bgr;-methylene-8-dehydroestradiol. This method strongly inhibits changes in cells and tissues, such as lipid peroxidation and oxidation of low-density lipoprotein (LDL) cholesterol, triggered by reaction oxygen species, free oxygen radicals and other forms of radicals and thus reduces attendant irreversible membrane and endothelial damage.

摘要翻译： 预防和治疗自由基介导的细胞损伤的方法包括向人施用有效量的至少一种类固醇和至少一种药物佐剂。 所述至少一种类固醇选自雌二醇，17α-雌二醇，8-脱氢雌二醇，8-脱氢-17α-雌二醇，8（14） - 脱氢雌二醇，6,8-二脱氢-17α-雌二醇 ，6-脱氢三醇，9（11） - 脱氢三醇，20-羟甲基-3-羟基-19-去甲基-13,5（10） - 三烯，14α，15α-亚甲基-8-脱氢雌二醇，14α，15α-亚甲基 - 雌二醇，2-羟基 - 雌二醇-3-甲基醚，3-羟基-1,3,5（10） - 雌三烯-17S-螺环氧乙烷，3-羟基-1,3,5（10），9（11） -estratetraene-17S-螺环氧乙烷和14beta，15beta-亚甲基-8-脱氢雌二醇。 这种方法强烈地抑制细胞和组织的变化，例如由反应氧物质，游离氧自由基和其他形式的基团触发的低密度脂蛋白（LDL）胆固醇的脂质过氧化和氧化，从而减少伴随的不可逆膜和内皮损伤。

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：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：US5693628A

公开(公告)日：1997-12-02

申请号：US309175

申请日：1994-09-20

申请人： Gerd Schubert ,  Gunther Kaufmann ,  Lothar Sobeck ,  Michael Oettel ,  Walter Elger ,  Anatoli Kurischko

发明人： Gerd Schubert ,  Gunther Kaufmann ,  Lothar Sobeck ,  Michael Oettel ,  Walter Elger ,  Anatoli Kurischko

IPC分类号： A61K31/56 ,  A61K31/565 ,  A61P13/02 ,  A61P15/00 ,  A61P35/00 ,  C07J41/00 ,  C07J75/00 ,  C07J1/00

CPC分类号： C07J41/0094 ,  C07J41/0083

摘要： This invention relates to new 11-benzaldoxime-estra-diene derivatives of the general formula I ##STR1## and their pharmaceutically acceptable salts, a method for their production, and pharmaceuticals containing such compounds. The compounds described show strong antigestagenic effects combined with reduced glucocorticoid activity.

摘要翻译： 本发明涉及通式I（I）的新的11-苯甲醛肟 - 雌二烯衍生物及其药学上可接受的盐，其制备方法和含有这些化合物的药物。 所描述的化合物显示出强的抗前体效应以及糖皮质激素活性降低。

公开(公告)号：US20060142257A1

公开(公告)日：2006-06-29

申请号：US11356012

申请日：2006-02-17

申请人： Eberhard Nieschlag ,  Axel Kamischke ,  Michael Oettel ,  Alexander Ruebig ,  Ekkerhard Schillinger ,  Ursula-Friederike Habenicht

发明人： Eberhard Nieschlag ,  Axel Kamischke ,  Michael Oettel ,  Alexander Ruebig ,  Ekkerhard Schillinger ,  Ursula-Friederike Habenicht

IPC分类号： A61K31/56

CPC分类号： A61K31/56

摘要： A formulation for male contraception comprising a progestin possessing both estrogenic and androgenic properties is remarkably effective for spermatogenesis suppression in males. The progestin Norethisterone (NET), particularly its derivatives Norethisterone acetate and Norethisterone enanthate in sufficient doses induce oligozoospermia or azoospermia in males. Formulations further comprising an androgen, such as a testosterone derivative such as a testosterone ester, particularly testosterone undecanoate, are especially effective male contraceptive formulations.

公开(公告)号：US07053077B1

公开(公告)日：2006-05-30

申请号：US09744574

申请日：1999-05-13

申请人： Walter Elger ,  Pekka Lähteenmäki ,  Matti Lehtinen ,  Gudrun Reddersen ,  Holger Zimmermann ,  Michael Oettel ,  Sigfrid Schwarz

发明人： Walter Elger ,  Pekka Lähteenmäki ,  Matti Lehtinen ,  Gudrun Reddersen ,  Holger Zimmermann ,  Michael Oettel ,  Sigfrid Schwarz

IPC分类号： A61K31/56

CPC分类号： A61K31/566 ,  A61K31/565 ,  A61K31/57 ,  Y10S514/874 ,  A61K2300/00

摘要： The invention relates to the use of biogenic estrogen sulfamates for the oral discontinuous application for hormone replacement therapy (HRT). The discontinuous administration takes place in intervals ranging from 2 to 40 days. The invention also provides the additional application of gestagens, preferably continuously in the form of an implant or in the form of an intrauterine releasing system (IUD). Estrone sulfamate, estradiol sulfamate or an N-acyl sulfamate of estrone, estradiol or estriol having up to 7 C-atoms in the acyl chain, or a combination comprised of two or more of said active ingredients are used as biogenic estrogen sulfamates.

摘要翻译： 本发明涉及用于激素替代治疗（HRT）的口服不连续应用的生物源性雌激素氨基磺酸盐的用途。 不连续给药时间间隔为2至40天。 本发明还提供了孕妇的额外应用，优选连续地以植入物的形式或以子宫内释放系统（IUD）的形式。 氨基磺酸氨基磺酸酯，氨基磺酸雌二醇酯或酰基链中具有至多7个C原子的雌酮，雌二醇或雌三醇的N-酰基氨基磺酸酯或由两种或更多种所述活性成分组成的组合物用作生物来源的雌激素亚磺酸盐。

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：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。