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1. 发明授权

US06977083B1 Bioadhesive tablet containing testosterone/testosterone ester mixtures and method for producing a predetermined testosterone time-release profile with same 失效
标题翻译：含有睾酮/睾酮酯混合物的生物粘附片剂和用于产生具有相同的预定睾酮时间释放特性的方法
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。

2. 发明授权

US5855905A Compound preparation for the treatment of hypogonadal men and men with hypophyseal diseases 失效
标题翻译：复方制剂治疗性腺功能减退的男性和男性患有垂体病
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。

3. 发明申请

US20050032756A1 Multistage preparation for contraception based on natural estrogens 审中-公开
标题翻译：基于天然雌激素的避孕多步骤准备
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。

4. 发明授权

US6133251A Combination compound for contraception based on natural estrogen 失效
标题翻译：基于天然雌激素的避孕组合化合物
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。

5. 发明授权

US06214377B1 Melatonin for the production of a peroral pulsatile form of medication 失效
标题翻译：褪黑激素用于产生口服脉搏形式的药物
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。

6. 发明授权

US06884793B2 Combination preparation for contraception based on natural estrogens 失效
标题翻译：基于天然雌激素的避孕组合制剂
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。

7. 发明授权

US06225299B1 Hormonal agent for skin treatment 失效
标题翻译：皮肤治疗激素剂
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。

8. 发明授权

US5910493A Hormonal agent for skin treatment 失效
标题翻译：皮肤治疗激素剂
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。

9. 发明授权

US07053077B1 Use of biogenic estrogen sulfamates for hormone replacement therapy 有权
标题翻译：使用生物源性雌激素氨基磺酸盐治疗激素替代疗法
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。

10. 发明授权

US5614213A Use of estriol for treatment of climacteric osteoporosis 失效
标题翻译：使用雌三醇治疗更年期骨质疏松症
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。

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