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1. 发明授权

US08906410B2 Oral dosage form of 25-hydroxyvitamin D 有权
标题翻译： 25-羟基维生素D的口服剂型
公开(公告)号：US08906410B2
公开(公告)日：2014-12-09
申请号：US13848982
申请日：2013-03-22
申请人： Charles W. Bishop , Keith H. Crawford , Eric J. Messner
发明人： Charles W. Bishop , Keith H. Crawford , Eric J. Messner
IPC分类号： A61K31/593 , A61K9/16 , A61K9/48 , A61K31/592 , A61K9/00 , A61K47/26
CPC分类号： A61K31/593 , A61K9/00 , A61K9/0019 , A61K9/16 , A61K9/48 , A61K9/4808 , A61K9/4858 , A61K9/4866 , A61K9/4875 , A61K31/592 , A61K47/26
摘要： Methods and compositions for treating 25-hydroxyvitamin D insufficiency and deficiency in a patient are described herein. The method includes orally administering to the patient a delayed, sustained release formulation including a first ingredient selected from the group consisting of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, or a combination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, or it includes gradually administering to the patient a sterile intravenous formulation including a first ingredient selected from the group consisting of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, or a combination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3.
摘要翻译：本文描述了用于治疗患者的25-羟基维生素D不足和缺乏症的方法和组合物。该方法包括向患者口服给予延迟的持续释放制剂，其包括选自由25-羟基维生素D2,25-羟基维生素D3或25-羟基维生素D 2和25-羟基维生素D 3组合组成的组的第一成分，或其包括向患者逐渐施用无菌静脉内制剂，其包含选自由25-羟基维生素D2,25-羟基维生素D3或25-羟基维生素D 2和25-羟基维生素D 3组合组成的组的第一成分。

2. 发明授权

US08329677B2 Method of treating and preventing secondary hyperparathyroidism 有权
标题翻译：治疗和预防继发性甲状旁腺功能亢进的方法
公开(公告)号：US08329677B2
公开(公告)日：2012-12-11
申请号：US12305572
申请日：2007-06-21
申请人： Charles W. Bishop , Keith H. Crawford , Eric J. Messner , Martin P. Petkovich , Christian F. Helvig
发明人： Charles W. Bishop , Keith H. Crawford , Eric J. Messner , Martin P. Petkovich , Christian F. Helvig
IPC分类号： A61K31/59
CPC分类号： A61K31/593 , A61K9/48 , A61K31/59 , A61K31/592
摘要： The a method of treating elevated blood levels of iPTH by increasing or maintaining blood concentrations of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in a patient by administering, as necessary, both Vitamin D repletion and Vitamin D hormone replacement therapies, is disclosed. The blood concentrations of 25-hydroxyvitamin D are increased to and maintained at or above 30 ng/mL, and blood concentrations of 1,25-dihydroxyvitamin D are increased to or maintained within a patient's normal historical physiological range for 1,25-dihydroxyvitamin D without causing substantially increased risk of hypercalcemia, hyperphosphatemia or over suppression of plasma iPTH in the patient. The blood levels of 25-hydroxyvitamin D are maintained at or above 30 ng/mL between doses of Vitamin D repletion therapies, and the blood levels of 1,25-dihydroxyvitamin D are maintained in the patient's normal historical physiological range between doses of Vitamin D hormone replacement therapies. In one aspect, the disclosure includes methods wherein the blood concentration of 25-hydroxyvitamin D during treatment comprises predominantly 25-hydroxyvitamin D3, and/or wherein the method includes administering predominantly or solely 25-hydroxyvitamin D3 for 25-hydroxyvitamin D repletion and/or maintenance.
摘要翻译：通过根据需要施用维生素D补充剂和维生素D激素替代疗法，通过增加或维持患者的25-羟基维生素D和1,25-二羟基维生素D的血液浓度来治疗iPTH升高的血液水平的方法是披露 25-羟基维生素D的血液浓度增加并保持在30ng / mL以上，1,25-二羟基维生素D的血液浓度增加至1,25-二羟基维生素D的患者正常的历史生理范围内而不会导致患者高钙血症，高磷血症或过度抑制血浆iPTH的风险显着增加。在维生素D补充疗法的剂量之间，25-羟基维生素D的血液水平维持在或高于30ng / mL，1,25-二羟基维生素D的血液水平维持在维生素D剂量之间的患者正常的历史生理范围内激素替代疗法。一方面，本公开内容包括其中治疗期间25-羟基维生素D的血液浓度主要包含25-羟基维生素D3和/或其中所述方法包括主要或单独使用25-羟基维生素D补充的25-羟基维生素D3用于25-羟基维生素D补充和/或保养。

3. 发明申请

US20090209501A1 METHOD OF TREATING AND PREVENTING SECONDARY HYPERPARATHYROIDISM 有权
标题翻译：治疗和预防继发性高血压病的方法
公开(公告)号：US20090209501A1
公开(公告)日：2009-08-20
申请号：US12305572
申请日：2007-06-21
申请人： Charles W. Bishop , Keith H. Crawford , Eric J. Messener , Martin P. Petkovich , Christian F. Helvig
发明人： Charles W. Bishop , Keith H. Crawford , Eric J. Messener , Martin P. Petkovich , Christian F. Helvig
IPC分类号： A61K31/59 , A61P5/14
CPC分类号： A61K31/593 , A61K9/48 , A61K31/59 , A61K31/592
摘要： The a method of treating elevated blood levels of iPTH by increasing or maintaining blood concentrations of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in a patient by administering, as necessary, both Vitamin D repletion and Vitamin D hormone replacement therapies, is disclosed. The blood concentrations of 25-hydroxyvitamin D are increased to and maintained at or above 30 ng/mL, and blood concentrations of 1,25-dihydroxyvitamin D are increased to or maintained within a patient's normal historical physiological range for 1,25-dihydroxyvitamin D without causing substantially increased risk of hypercalcemia, hyperphosphatemia or over suppression of plasma iPTH in the patient. The blood levels of 25-hydroxyvitamin D are maintained at or above 30 ng/mL between doses of Vitamin D repletion therapies, and the blood levels of 1,25-dihydroxyvitamin D are maintained in the patient's normal historical physiological range between doses of Vitamin D hormone replacement therapies. In one aspect, the disclosure includes methods wherein the blood concentration of 25-hydroxyvitamin D during treatment comprises predominantly 25-hydroxyvitamin D3, and/or wherein the method includes administering predominantly or solely 25-hydroxyvitamin D3 for 25-hydroxyvitamin D repletion and/or maintenance
摘要翻译：通过根据需要施用维生素D补充剂和维生素D激素替代疗法，通过增加或维持患者的25-羟基维生素D和1,25-二羟基维生素D的血液浓度来治疗iPTH升高的血液水平的方法是披露 25-羟基维生素D的血液浓度增加并保持在30ng / mL以上，1,25-二羟基维生素D的血液浓度增加至1,25-二羟基维生素D的患者正常的历史生理范围内而不会导致患者高钙血症，高磷血症或过度抑制血浆iPTH的风险显着增加。在维生素D补充疗法的剂量之间，25-羟基维生素D的血液水平维持在或高于30ng / mL，1,25-二羟基维生素D的血液水平维持在维生素D剂量之间的患者正常的历史生理范围内激素替代疗法。一方面，本公开内容包括其中治疗期间25-羟基维生素D的血液浓度主要包含25-羟基维生素D3和/或其中所述方法包括主要或单独使用25-羟基维生素D补充的25-羟基维生素D3用于25-羟基维生素D补充和/或保养

4. 发明授权

US06903083B2 Stabilized hydroxyvitamin D 有权
公开(公告)号：US06903083B2
公开(公告)日：2005-06-07
申请号：US10223986
申请日：2002-08-20
申请人： Joyce C. Knutson , Richard B. Mazess , Charles W. Bishop
发明人： Joyce C. Knutson , Richard B. Mazess , Charles W. Bishop
IPC分类号： A61K31/59 , A61K31/592 , A61K31/593 , A61P3/02 , C07C401/00
CPC分类号： C07C401/00 , A61K31/59
摘要： The invention provides a stabilized 1α-hydroxyvitamin D (“SHVD”) which is particularly well suited for pharmaceutical formulations.

5. 发明授权

US06211168B1 Methods for preparation and use of 1&agr;,24 (S)-dihydroxy vitamin D2 失效
标题翻译：制备和使用1α，24（S） - 二羟基维生素D2的方法
公开(公告)号：US06211168B1
公开(公告)日：2001-04-03
申请号：US08483371
申请日：1995-06-07
申请人： Charles W. Bishop , Ronald L. Horst , Glenville Jones , Nicholas J. Koszewski , Joyce C. Knutson , Robert M. Moriarty , Timothy A. Reinhardt , Raju Penmasta , Stephen Strugnell , Liang Guo , Sanjay K. Singhal , Lei Zhao
发明人： Charles W. Bishop , Ronald L. Horst , Glenville Jones , Nicholas J. Koszewski , Joyce C. Knutson , Robert M. Moriarty , Timothy A. Reinhardt , Raju Penmasta , Stephen Strugnell , Liang Guo , Sanjay K. Singhal , Lei Zhao
IPC分类号： A61K3159
CPC分类号： A61K31/59 , A61K31/592 , A61K45/06 , C07C401/00 , C07J9/00 , C07J71/0042 , A61K2300/00
摘要： 1&agr;,24(S)-Dihydroxy vitamin D2 which is useful as an active compound of pharmaceutical compositions for the treatment of disorders of calcium metabolism and for various skin disorders. The invention also includes preparation of synthetic 1&agr;,24(S)-dihydroxy vitamin D2 starting from ergosterol which is converted in six steps to 24-hydroxyergosterol. 24-Hydroxyergosterol is irradiated and thermally converted to 24-hydroxy vitamin D2 which is converted in six steps to 1&agr;,24(S)-dihydroxy vitamin D2. The syntheses also produced novel intermediates.
摘要翻译： 1α，24（S） - 二羟基维生素D2，其可用作用于治疗钙代谢紊乱和各种皮肤病症的药物组合物的活性化合物。本发明还包括从麦角甾醇开始合成的1α，24（S） - 二羟基维生素D2的制备，其从六步转化为24-羟基麦角固醇。 24-羟基麦角甾醇被照射并热转化成24-羟基维生素D2，其被六步转化为1α，24（S） - 二羟基维生素D2。综合也产生了新的中间体。

6. 发明授权

US5869473A Method for treating and preventing hyperparathyroidism 失效
标题翻译：治疗和预防甲状旁腺功能亢进的方法
公开(公告)号：US5869473A
公开(公告)日：1999-02-09
申请号：US907659
申请日：1997-08-08
申请人： Joyce C. Knutson , Richard B. Mazess , Charles W. Bishop
发明人： Joyce C. Knutson , Richard B. Mazess , Charles W. Bishop
IPC分类号： A61K31/59 , A61K31/66 , A61K33/00 , A61K33/06 , A61K33/16 , A61K33/22 , A61K38/23 , A61K31/595
CPC分类号： A61K31/59 , A61K31/592 , A61K31/66 , A61K31/714 , A61K33/00 , A61K33/06 , A61K33/16 , A61K33/22 , A61K38/23
摘要： A method for reducing or preventing elevated blood parathyroid hormone level in a human being suffering from hyperparathyroidism by administering a sufficient amount of 1.alpha.-OH vitamin D.sub.2, 1.alpha.-OH vitamin D.sub.4 or 1.alpha.,24(R)-(OH).sub.2 vitamin D.sub.4.
摘要翻译：通过给予足量的1α-OH维生素D2，1α-OH维生素D 4或1α，24（R） - （OH）2，减少或预防人甲状旁腺激素水平升高的方法维生素D4。

7. 发明授权

US5801164A Methods of treating osteoporosis prophylactically or therapeutically 失效
标题翻译：预防或治疗骨质疏松症的方法
公开(公告)号：US5801164A
公开(公告)日：1998-09-01
申请号：US480310
申请日：1995-06-07
申请人： Joyce C. Knutson , Charles W. Bishop , Robert M. Moriarty
发明人： Joyce C. Knutson , Charles W. Bishop , Robert M. Moriarty
IPC分类号： A61K8/60 , A61K8/67 , A61K31/59 , A61Q19/00 , C07C35/21 , C07C401/00
CPC分类号： A61K31/592 , A61K31/59 , A61K8/606 , A61K8/67 , A61Q19/00 , C07C35/21 , C07C401/00
摘要： Methods of treating osteoporosis prophylactically or therapeutically are disclosed. The method of treating osteoporosis includes administering to a patient suffering therefrom an effective amount to treat the osteoporosis of novel 1.alpha.-hydroxyvitamin D.sub.4 and novel analogues 1,25-dihydroxyvitamin D.sub.4 and 1,24-dihydroxyvitamin D.sub.4, the aforementioned compounds having lower toxicity as measured by an LD.sub.50 test in rats when compared to a corresponding vitamin D.sub.3 compound. The method of administering the compound is substantially without occurrence of hypercalcemia.
摘要翻译：公开了预防或治疗骨质疏松症的方法。治疗骨质疏松症的方法包括向患有其的患者施用有效量的治疗新型1α-羟基维生素D4和新型类似物1,25-二羟基维生素D4和1,24-二羟基维生素D4的骨质疏松症，上述具有较低毒性的化合物与相应的维生素D3化合物相比，通过LD50测试在大鼠中测量。施用化合物的方法基本上不发生高钙血症。

8. 发明授权

US5763428A Methods of treating skin disorders with novel 1a-hydroxy vitamin D.sub.4 compounds and derivatives thereof 失效
标题翻译：用新型1a-羟基维生素D4化合物及其衍生物治疗皮肤病症的方法
公开(公告)号：US5763428A
公开(公告)日：1998-06-09
申请号：US484342
申请日：1995-06-07
申请人： Joyce C. Knutson , Charles W. Bishop
发明人： Joyce C. Knutson , Charles W. Bishop
IPC分类号： A61K31/59 , A61K8/60 , A61K8/67 , A61P17/00 , A61P35/00 , A61Q19/00 , C07C35/21 , C07C401/00 , C07J9/00
CPC分类号： A61K8/606 , A61K31/59 , A61K31/592 , A61K8/67 , A61Q19/00 , C07C35/21 , C07C401/00 , C07J9/00
摘要： The disclosure is of methods of treating various skin disorders, including skin cancer, with compounds of novel 1.alpha.-hydroxy vitamin D.sub.4 and novel analogues, thereof, including 1,25 dihydroxy vitamin D.sub.4 and 1,24 dihydroxy vitamin D.sub.4. Novel 1.alpha.-hydroxy vitamin D.sub.4 compounds and compounds of novel analogues suitable for use in the treatment of such disorders are also disclosed herein.
摘要翻译：本公开是用新的1α-羟基维生素D4及其新型类似物，包括1,25二羟基维生素D4和1,24二羟基维生素D4的化合物治疗各种皮肤疾病（包括皮肤癌）的方法。本文还公开了新的1α-羟基维生素D 4化合物和适合用于治疗这种病症的新型类似物的化合物。

9. 发明授权

US5614513A Oral 1.alpha.-hydroxyprevitamin D 失效
标题翻译：口服1α-羟维生素D
公开(公告)号：US5614513A
公开(公告)日：1997-03-25
申请号：US485354
申请日：1995-06-07
申请人： Joyce C. Knutson , Charles W. Bishop , Charles R. Valliere
发明人： Joyce C. Knutson , Charles W. Bishop , Charles R. Valliere
IPC分类号： A61K9/20 , A61K9/28 , A61K9/50 , A61K31/59 , A61K31/593 , A61K31/66 , A61K33/24 , A61K38/23 , A61K47/38 , A61P3/00 , A61P3/14 , A61P17/06 , A61P19/08 , A61P43/00 , A01N45/00
CPC分类号： A61K31/593 , A61K31/59 , A61K31/592 , A61K31/66 , A61K31/70 , A61K33/24 , A61K38/23 , A61K9/5078
摘要： Method of increasing activated vitamin D blood level by administering orally a 1.alpha.-hydroxyprevitamin D or a delayed and sustained release formulation of activated vitamin D or a combination thereof. Both the previtamin D form and the delayed and sustained release activated vitamin D formulation increase vitamin D blood level without significant risk of hypercalcemia associated with other oral dosing of vitamin D forms.
摘要翻译：通过口服1α-羟基维生素D或活化的维生素D的延迟和持续释放制剂或其组合来增加活化的维生素D血液水平的方法。维生素D组合物和延迟释放激活的维生素D制剂都能增加维生素D血浆水平，而与其他口服维生素D形式相关的高钙血症并不具有显着的风险。

10. 发明授权

US5488120A 1.alpha.-hydroxy vitamin D.sub.4 and novel intermediates and analogues 失效
标题翻译： 1α-羟基维生素D4和新型中间体和类似物
公开(公告)号：US5488120A
公开(公告)日：1996-01-30
申请号：US296084
申请日：1994-08-24
申请人： Joyce C. Knutson , Charles W. Bishop , Robert M. Moriarty
发明人： Joyce C. Knutson , Charles W. Bishop , Robert M. Moriarty
IPC分类号： A61K31/59 , C07C35/21 , C07C401/00
CPC分类号： A61K31/592 , C07C35/21 , C07C401/00
摘要： Novel 1.alpha.-hydroxy Vitamin D.sub.4 and novel analogues, 1,25 dihydroxy Vitamin D.sub.4 and 1,24 dihydroxy Vitamin D.sub.4 which are useful for the treatment of disorders of calcium metabolism. Preparation of the novel 1.alpha.-hydroxy Vitamin D.sub.4 starts from ergosterol which is converted in six steps to 22,23-dihydroergosterol. 22,23-dihydroergosterol was irradiated to yield Vitamin D.sub.4 which was converted in four steps to 1.alpha.-hydroxy Vitamin D.sub.4 using a cyclovitamin procedure which produced the novel intermediates, Vitamin D.sub.4 tosylate, 3,5 cyclovitamin D.sub.4 and 1.alpha.-hydroxy cyclovitamin D.sub.4. 1,25 dihydroxy Vitamin D.sub.4 and 1,24 dihydroxy Vitamin D.sub.4 are isolated as biological products of the metabolism of novel 1.alpha.-hydroxy Vitamin D.sub.4 using cultured human liver cells.
摘要翻译：新型1α-羟基维生素D4和新型类似物，1,25二羟基维生素D4和1,24二羟基维生素D4，其可用于治疗钙代谢紊乱。新型1α-羟基维生素D4的制备从麦角甾醇开始，其以六步转化为22,23-二氢麦角甾醇。 22,23-二氢麦角甾醇被照射以产生维生素D4，其使用产生新的中间体维生素D4甲苯磺酸盐，3,5环维生素D4和1α-羟基环维生素D4的环维生素程序将其四步转化为1α-羟基维生素D4 。使用培养的人肝细胞，分离出1,25二羟基维生素D4和1,24二羟基维生素D4作为新型1α-羟基维生素D4代谢的生物学产物。

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