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    Combination therapy for treatment of erectile dysfunction
    1.
    发明授权
    Combination therapy for treatment of erectile dysfunction 失效
    联合治疗勃起功能障碍

    公开(公告)号：US06747063B2

    公开(公告)日：2004-06-08

    申请号：US09177711

    申请日：1998-10-23

    申请人： Michael A. Adams ,  Jeremy P. W. Heaton ,  Donald H. Maurice

    发明人： Michael A. Adams ,  Jeremy P. W. Heaton ,  Donald H. Maurice

    IPC分类号： A61K31557

    CPC分类号： A61K31/34 ,  A61K31/198 ,  A61K31/21 ,  A61K31/295 ,  A61K31/5377 ,  A61K38/063 ,  A61K45/06

    摘要： In the field of treatment of erectile dysfunction there is disclosed a novel therapy in which the actions of an agent or agents, produce a combination of effects to induce effective erection (and avoid priapism) while reducing or entirely avoiding pain. The method taught combines a first action of an agent which is to antagonize a drug-induced pain stimulus within nociceptive nerves of penile tissue with a second action of either the same agent or of a second agent, which enhances, synergistically, smooth muscle relaxation. The synergism allows for at least an equivalent effect of smooth muscle relaxation to be obtained at significantly lower doses of a smooth muscle relaxing agent such as PGE1 which in standard therapy is also in 40-45% of cases pain-inducing at doses which achieve effective erection. Thus in an anatomical site where nociceptive tissue is in close proximity to one or more effector systems, the method enhances the effector system while reducing nociception in the nociceptive tissue which nociception would be caused by an agent such as PGE1 which is used to trigger the effector system.

    摘要翻译： 在治疗勃起功能障碍的领域中，公开了一种新颖的治疗方法，其中药剂或药剂的作用产生组合的作用以诱导有效勃起（并避免阴茎异常勃起），同时减少或完全避免疼痛。 所述方法结合了药剂的第一作用，其是在相同药剂或第二药剂的第二作用下拮抗阴茎组织伤害性神经内的药物诱发的疼痛刺激，其增强，协同地平滑肌肉松弛。 协同作用允许在明显较低剂量的平滑肌松弛剂（例如PGE1）下获得平滑肌松弛的至少等效效果，其在标准治疗中也是在实现有效的剂量下疼痛诱导的40-45％的病例 勃起。 因此，在伤害感受性组织紧邻一个或多个效应系统的解剖部位中，该方法增强效应系统，同时减少伤害感受器官组织中的伤害感受，其中伤害感受会由用于触发效应物的PGE1 系统。

    Methods for the normalization of sexual response and amelioration of long term genital tissue degradation
    3.
    发明授权
    Methods for the normalization of sexual response and amelioration of long term genital tissue degradation 失效
    性反应正常化和改善长期生殖器组织降解的方法

    公开(公告)号：US06403605B1

    公开(公告)日：2002-06-11

    申请号：US09086630

    申请日：1998-05-29

    申请人： Jeremy P. W. Heaton ,  Michael A. Adams

    发明人： Jeremy P. W. Heaton ,  Michael A. Adams

    IPC分类号： A61K3144

    CPC分类号： A61K31/137 ,  A61K31/00 ,  A61K31/405 ,  A61K31/473 ,  A61K31/48 ,  A61K31/498 ,  A61K31/506

    摘要： The present invention provides, in one embodiment, a method of normalizing the timing of sexual response in a mammal comprising the administration of an amount of a central nervous system sexual response initiator in an amount sufficient to produce genital vasodilation but less than the amount required to produce effective vasocongestive arousal. The method is applicable not only to adjusting or normalizing the timing of sexual response in humans, but in the breeding of valuable commercial animals such as horses, cattle, sheep, swine and the like and domesticated pets such as dogs and go cats. In an alternative embodiment, the present invention provides a method for the prophylactic treatment of long-term tissue degradation in the genital organs comprising the administration to a mammal of a central nervous system sexual response initiator in an amount sufficient to produce genital vasodilation but less than the amount required to produce effective vasocongestive arousal. The preferred central nervous system sexual response initiator is apomorphine or a pharmaceutically acceptable acid addition salt thereof.

    摘要翻译： 在一个实施方案中，本发明提供了使哺乳动物的性反应时间正常化的方法，其包括以足以产生生殖器血管舒张的量施用一定量的中枢神经系统性反应引发剂，但小于 产生有效的血管舒张功能。该方法不仅适用于调整或正常化人类性反应的时间，而且适用于马，牛，绵羊，猪等有价值的商业动物的养殖，驯养宠物如狗和 在替代实施方案中，本发明提供了用于预防性治疗生殖器官中的长期组织降解的方法，包括以足以产生生殖器血管舒张的量向哺乳动物施用中枢神经系统性反应引发剂 但少于产生有效的血管舒张功能所需的量 中枢神经系统性反应引发剂是阿朴吗啡或其药学上可接受的酸加成盐。

    Method and compositions for the treatment or amelioration of female sexual dysfunction
    4.
    发明授权
    Method and compositions for the treatment or amelioration of female sexual dysfunction 失效
    用于治疗或改善女性性功能障碍的方法和组合物

    公开(公告)号：US06395744B1

    公开(公告)日：2002-05-28

    申请号：US09336088

    申请日：1999-06-18

    申请人： Michael A. Adams ,  Jeremy P. W. Heaton

    发明人： Michael A. Adams ,  Jeremy P. W. Heaton

    IPC分类号： A61K3144

    CPC分类号： A61K9/0056 ,  A61K31/4045 ,  A61K31/405 ,  A61K31/472 ,  A61K31/473 ,  A61K31/48 ,  A61K31/485 ,  A61K31/506 ,  A61K31/565 ,  A61K38/11 ,  A61K38/12 ,  A61K49/0004 ,  A61K2300/00

    摘要： The present invention provide a method of treating sexual dysfunction in a female, including the vasculogenic symptoms of delayed vaginal engorgement, diminished vaginal lubrication, pain or discomfort with intercourse (dyspareunia), diminished vaginal sensation, diminished vaginal orgasm, diminished clitoral sensation or diminished clitoral orgasm, or of combating vaginal pain by stimulating peripheral pelvic nerve release of nitric oxide (NO). The method comprises administering to a female in need of such treatment a therapeutically effective amount of a compound which acts on a mid-brain pathway to increase blood flow to the ilio-hypogastric-pudendal artery bed and stimulate the release of nitric oxide (NO) from peripheral NANC nerve cells. The preferred compound for the method of this invention is apomorphine or one of its pharmaceutically acceptable salts, esters, or pro-drugs. Alternatively, the apomorphine is co-administered with an apomorphine-potentiating amount of an androgen, preferably testosterone either prior to, or concomitantly with, the administration of the apomorphine.

    摘要翻译： 本发明提供了一种治疗女性性功能障碍的方法，其中包括延迟性阴道充盈的血管发生症状，阴道润滑减轻，性交疼痛或不适（性交痛），阴道感觉减退，阴道性高潮减退，阴蒂感或减少的阴蒂 通过刺激一氧化氮（NO）的周围骨盆神经释放来抵抗阴道疼痛。 该方法包括向需要这种治疗的女性施用治疗有效量的作用于中脑途径的化合物，以增加血液流向髂下腹部阴道动脉床并刺激一氧化氮（NO）的释放， 从外周神经细胞NANC。 本发明方法的优选化合物是阿朴吗啡或其药学上可接受的盐，酯或前药之一。 或者，阿扑吗啡在阿朴吗啡的施用之前或同时伴随阿朴吗啡增强量的雄激素，优选睾酮共同施用。

    Methods for remodeling neuronal and cardiovascular pathways
    8.
    发明授权
    Methods for remodeling neuronal and cardiovascular pathways 失效
    重建神经元和心血管途径的方法

    公开(公告)号：US06787553B2

    公开(公告)日：2004-09-07

    申请号：US10192281

    申请日：2002-07-09

    申请人： Michael A. Adams ,  Jeremy P. W. Heaton

    发明人： Michael A. Adams ,  Jeremy P. W. Heaton

    IPC分类号： A61K31519

    CPC分类号： A61K31/519 ,  A61K31/00 ,  A61K31/502 ,  A61K31/513 ,  A61K31/5575 ,  A61K45/06

    摘要： The present invention provides a method of administration of an agent which acts to remodel neuronal or vascular pathways for the long term management of sexual dysfunction in both males and females. In a preferred embodiment, the invention provides a method of ameliorating or reversing pathogenic vascular degradative modeling in the ilio-hypogastric-pudendal arterial bed and genitalia comprising administering to a human patient in need of such treatment a therapeutically effective amount of an anti-pressor agent. The anti-pressor agent comprises one or more compounds selected from the therapeutic classes of direct vasodilators such as hydralazine and NO donors, ACE inhibitors, angiotensin-II receptor antagonists, &agr;1-adrenergic receptor antagonists, &bgr;-adrenergic receptor antagonists, calcium channel blockers, and phosphodiesterase inhibitors. The anti-pressor agent may be co-administered with a diuretic compound, and is administered either chronically at low dose, or for short periods of time at doses higher than are typically used for the treatment of hypertension. In certain embodiments of the method of the invention, the anti-pressor agent is co-administered with a diuretic agent and/or prostaglandin-E1.

    摘要翻译： 本发明提供了一种用于改变神经元或血管途径以在男性和女性中长期治疗性功能障碍的药剂的给药方法。 在一个优选的实施方案中，本发明提供了一种改善或逆转髂腹下腹阴部动脉床和生殖器中的病原性血管降解模型的方法，包括向需要这种治疗的人类患者施用治疗有效量的抗压力剂 。 抗压剂包括一种或多种选自直接血管扩张剂如肼屈嗪和NO供体的治疗类别的化合物，ACE抑制剂，血管紧张素-II受体拮抗剂，α1-肾上腺素能受体拮抗剂，β-肾上腺素能受体拮抗剂，钙通道阻断剂， 和磷酸二酯酶抑制剂。 抗压剂可以与利尿剂共同施用，并且以低于通常用于治疗高血压的剂量以低剂量或长时间给药。 在本发明方法的某些实施方案中，抗压剂与利尿剂和/或前列腺素-E1共同施用。

    Microdose therapy
    10.
    发明授权
    Microdose therapy 失效
    微剂量治疗

    公开(公告)号：US06610652B2

    公开(公告)日：2003-08-26

    申请号：US10095654

    申请日：2002-03-08

    申请人： Michael A. Adams ,  Jeremy P. W. Heaton ,  James D. Banting

    发明人： Michael A. Adams ,  Jeremy P. W. Heaton ,  James D. Banting

    IPC分类号： A61K3800

    CPC分类号： A61K38/063 ,  A61K31/04 ,  A61K31/16 ,  A61K31/198 ,  A61K31/21 ,  A61K31/295 ,  A61K31/34 ,  A61K31/5377

    摘要： Methods for treating vascular conditions associated with localized imbalance in vascular tone, which are hypothesized to be largely due to elevated endothelin (ET) are provided. The methods involve administration of nitric oxide (NO), agents which are able to provide NO, such as NO donors, agents which activate guanyl cyclase, such as YC-1, or agents which prolong the actions of endogenous NO or cyclic guanosine monophosphate (cGMP; a 2nd messenger molecule), such as phosphodiesterase (PDE) inhibitors. According to the invention, such agents are administered in minimal doses or microdoses by any route known in the art, so as to provide dosages which are about one half to about one twentieth (½ to {fraction (1/20)}) of those known to induce vasodilation in “normal” circulations. The low doses of these agents effectively alleviate vascular conditions associated with a reduction in NO production or an attenuation of NO effect, by restoring balance in vascular tone while exerting almost no systemic effect in normal vasculature.

    摘要翻译： 提供了用于治疗与血管紧张度局部不平衡相关的血管病变的方法，其被假设主要是由于内皮素（ET）升高。 所述方法包括给予一氧化氮（NO），能够提供NO的试剂，例如NO供体，活化脯氨酸环化酶的试剂，例如YC-1，或延长内源性NO或环鸟苷酸单磷酸的作用的试剂 cGMP;第二信使分子），例如磷酸二酯酶（PDE）抑制剂。 根据本发明，通过本领域已知的任何途径，以最小剂量或微量剂量施用这些药剂，以提供已知诱导血管舒张的剂量的约一半至约二十分之一（1/2至1/20）的剂量 “正常”循环。 低剂量的这些药物通过恢复血管紧张度的平衡，同时在正常脉管系统中几乎没有全身作用，有效地缓解与NO产生减少或NO作用减弱相关的血管病症。