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1. 发明授权

US06143910A Methods for preparation and use of 1.alpha., 24(S) -dihydroxy vitamin D2 有权
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：US06143910A
公开(公告)日：2000-11-07
申请号：US211984
申请日：1998-12-14
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： A23K1/16 , A61K31/59 , A61P3/02 , A61P3/14 , A61P17/00 , A61P19/08 , A61P35/00 , C07C401/00 , C07J9/00 , C07J71/00
CPC分类号： C07J9/00 , A61K31/59 , C07C401/00 , C07J71/0042
摘要： 1.alpha.,24(S)-Dihydroxy vitamin D.sub.2 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.alpha.,24(S)-dihydroxy vitamin D.sub.2 starting from ergosterol which is converted in six steps to 24-hydroxyergosterol. 24-Hydroxyergosterol is irradiated and thermally converted to 24-hydroxy vitamin D.sub.2 which is converted in six steps to 1.alpha.,24(S)-dihydroxy vitamin D.sub.2. The syntheses also produced novel intermediates.
摘要翻译： 1α，24（S） - 二羟基维生素D 2，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。将24-羟基麦角固醇照射并热转化成24-羟基维生素D 2，其以6步转化为1α，24（S） - 二羟基维生素D 2。综合也产生了新的中间体。

2. 发明授权

US5789397A Methods for preparation and use of 1A,24(S)-dihydroxy vitamin D2 失效
标题翻译：制备和使用1A，24（S） - 二羟基维生素D2的方法
公开(公告)号：US5789397A
公开(公告)日：1998-08-04
申请号：US485184
申请日：1995-06-07
申请人： Charles W. Bishop , Glenville Jones , Ronald L. Horst , Nicholas J. Koszewski , Joyce C. Knutson , Raju Penmasta , Robert M. Moriarty , Stephen Strugnell , Timothy A. Reinhardt , Liang Guo , Sanjay K. Singhal , Lei Zhao
发明人： Charles W. Bishop , Glenville Jones , Ronald L. Horst , Nicholas J. Koszewski , Joyce C. Knutson , Raju Penmasta , Robert M. Moriarty , Stephen Strugnell , Timothy A. Reinhardt , Liang Guo , Sanjay K. Singhal , Lei Zhao
IPC分类号： A61K31/59 , A61K45/06 , C07C401/00 , C07J9/00 , C07J71/00
CPC分类号： A61K31/59 , A61K31/592 , A61K45/06 , C07C401/00 , C07J71/0042 , C07J9/00
摘要： 1.alpha.,24(S)-Dihydroxy vitamin D.sub.2 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.alpha.,24(S)-dihydroxy vitamin D.sub.2 starting from ergosterol which is converted in six steps to 24-hydroxyergosterol. 24-Hydroxyergosterol is irradiated and thermally converted to 24-hydroxy vitamin D.sub.2 which is converted in six steps to 1.alpha.,24(S)-dihydroxy vitamin D.sub.2. The syntheses also produced novel intermediates.
摘要翻译： 1α，24（S） - 二羟基维生素D 2，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。将24-羟基麦角固醇照射并热转化成24-羟基维生素D 2，其以6步转化为1α，24（S） - 二羟基维生素D 2。综合也产生了新的中间体。

3. 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。

4. 发明授权

US5786348A Methods for preparation and use of 1.alpha.,24(S)-dihydroxy vitamin D.sub.2 失效
标题翻译：使用1α，24（S） - 二羟基维生素D2的方法
公开(公告)号：US5786348A
公开(公告)日：1998-07-28
申请号：US477930
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： A61K31/59 , A61K45/06 , C07C401/00 , C07J9/00 , C07J71/00
CPC分类号： A61K31/59 , A61K31/592 , A61K45/06 , C07C401/00 , C07J71/0042 , C07J9/00
摘要： 1.alpha.,24(S)-Dihydroxy vitamin D.sub.2 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.alpha.,24(S)-dihydroxy vitamin D.sub.2 starting from ergosterol which is converted in six steps to 24-hydroxyergosterol. 24-Hydroxyergosterol is irradiated and thermally converted to 24-hydroxy vitamin D.sub.2 which is converted in six steps to 1.alpha.,24(S)-dihydroxy vitamin D.sub.2. The syntheses also produced novel intermediates.
摘要翻译： 1α，24（S） - 二羟基维生素D 2，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。将24-羟基麦角固醇照射并热转化成24-羟基维生素D 2，其以6步转化为1α，24（S） - 二羟基维生素D 2。综合也产生了新的中间体。

5. 发明授权

US06251883B1 Methods for preparation and use of 1&agr;,24(S)-dihydroxy vitamin D2 有权
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：US06251883B1
公开(公告)日：2001-06-26
申请号：US09211991
申请日：1998-12-14
申请人： Ronald L. Horst , Charles W. Bishop , Glenville Jones , Nicholas J. Koszewski , Joyce C. Knutson , Robert M. Moriarty , Timothy Reinhardt , Raju Penmasta , Stephen Strugnell , Liang Guo , Sanjay K. Singhal , Lei Zhao
发明人： Ronald L. Horst , Charles W. Bishop , Glenville Jones , Nicholas J. Koszewski , Joyce C. Knutson , Robert M. Moriarty , Timothy Reinhardt , Raju Penmasta , Stephen Strugnell , Liang Guo , Sanjay K. Singhal , Lei Zhao
IPC分类号： A01N4500
CPC分类号： A61K31/592 , A61K31/59 , 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

US6042855A Use of vitamin D, its metabolites and analogs to improve tenderness of meat and meat products 失效
标题翻译：使用维生素D及其代谢物和类似物来改善肉和肉制品的柔软度
公开(公告)号：US6042855A
公开(公告)日：2000-03-28
申请号：US883865
申请日：1997-06-27
申请人： Donald C. Beitz , Allen Trenkle , Frederick C. Parrish , Jayden L. Montgomery , Ronald L. Horst
发明人： Donald C. Beitz , Allen Trenkle , Frederick C. Parrish , Jayden L. Montgomery , Ronald L. Horst
IPC分类号： A23K1/16 , A23L1/318 , A23L1/30 , A01N45/00 , A21D6/00
CPC分类号： A23K20/174 , A23L13/72
摘要： A method of improving the tenderness of meat and meat products is described. The method includes administering excessive doses of vitamin D to meat producing animals prior to slaughter. The vitamin D causes greater calcium activated calpain activity which degrades certain myofibrillar proteins in the meat postmortem. The resulting meat has a significantly lower shear force in comparison to untreated meat.
摘要翻译：描述了改善肉和肉制品压痛的方法。该方法包括在屠宰之前向生产肉的动物施用过量的维生素D. 维生素D会导致更多的钙激活钙蛋白酶活性，这会降低肉类死后的某些肌原纤蛋白。与未经处理的肉相比，所得肉具有显着较低的剪切力。

7. 发明授权

US5560920A Calcium formulations for prevention of parturient hypocalcemia 失效
标题翻译：用于预防分娩低钙血症的钙制剂
公开(公告)号：US5560920A
公开(公告)日：1996-10-01
申请号：US418389
申请日：1995-04-07
申请人： Jesse P. Goff , Ronald L. Horst
发明人： Jesse P. Goff , Ronald L. Horst
IPC分类号： A23K1/16 , A23K1/175 , A23K1/18 , A61K9/00 , A61K31/19 , A23K1/00
CPC分类号： A61K9/0095 , A23K20/105 , A23K20/22 , A23K50/10 , A61K31/19
摘要： Calcium propionate treatments for milk fever (parturient paresis) have been formulated (1) with propylene glycol and either citric or phosphoric acid as a non-hardening paste and (2) with sodium chloride as a liquid drench. These compositions are particularly useful for treating this hypocalcemic disorder associated with the onset of lactation in dairy cows.
摘要翻译：已经用丙二醇和柠檬酸或磷酸作为非硬化糊剂（2）用氯化钠作为液体浸泡剂（1）配制了用于牛奶热（分娩麻痹）的丙酸钙处理。这些组合物特别可用于治疗与乳牛发生哺乳相关的这种低血糖病症。

8. 发明授权

US4929609A 25, 28-dihydroxyergocalciferol and 1,25,28-trihydroxyergocalciferol compositions thereof and their use in the treatment of hyperproliferative disease 失效
标题翻译： 25,28-二羟基麦角钙化醇和1,25,28-三羟基麦角钙化物组合物及其在治疗过度增殖性疾病中的用途
公开(公告)号：US4929609A
公开(公告)日：1990-05-29
申请号：US272170
申请日：1988-11-14
申请人： Andrew D. Batcho , Ronald L. Horst , Milan R. Uskokovic , Joseph L. Napoli
发明人： Andrew D. Batcho , Ronald L. Horst , Milan R. Uskokovic , Joseph L. Napoli
IPC分类号： C07C35/21
CPC分类号： C07C35/21
摘要： Compounds of the formula ##STR1## wherein R" is hydrogen or hydroxy, epimers at the 24-position of compounds of formula I, diastereomeric mixtures of compounds of formula I which are epimeric at the 24-position, and mixtures thereof, which are useful as agents for the treatment of psoriasis, and osteoporosis, are described.
摘要翻译：其中R“是氢或羟基的式I化合物，式I化合物24位的差向异构体，在24位差向异构的式I化合物的非对映体混合物及其混合物，其中描述了治疗牛皮癣和骨质疏松症的药物。

9. 发明申请

US20150250803A1 USE OF VITAMIN D GLYCOSIDES AND SULFATES FOR TREATMENT OF DISEASE 审中-公开
标题翻译：维生素D糖尿病和硫酸盐治疗疾病的使用
公开(公告)号：US20150250803A1
公开(公告)日：2015-09-10
申请号：US14707162
申请日：2015-05-08
申请人： Jesse P. Goff , Ronald L. Horst
发明人： Jesse P. Goff , Ronald L. Horst
IPC分类号： A61K31/593 , A61K47/48
CPC分类号： A61K31/593 , A61K31/592 , A61K31/7032 , A61K31/7034 , A61K45/06 , A61K47/549 , A61P35/00 , A61P37/02 , Y02A50/475 , Y02A50/481 , A61K2300/00
摘要： Methods of treating vitamin D-sensitive diseases without inducing severe forms of hypercalcemia. The methods comprise administering biologically inert vitamin D prodrugs. The vitamin D prodrugs have a vitamin D-drug moiety and a pro moiety, wherein the pro moiety is selected from the group consisting of a glycone moiety and a sulfate moiety. The vitamin D prodrugs are activated by enzymes at target tissues or cells that cleave the pro moiety from the vitamin D drug moiety, freeing the vitamin D-moiety from the pro moiety in the vicinity of the target tissues or cells. The methods of the invention prevent large, acute, systemic increases in the free form of the vitamin D-drug moiety that would otherwise lead to hypercalcemia. The methods can be used to treat hyperproliferative, autoimmune, or infectious diseases throughout the body, including the intestine. Compositions of the vitamin D prodrugs useful in the described methods are also disclosed.
摘要翻译：治疗维生素D敏感性疾病而不引起严重形式的高钙血症的方法。所述方法包括施用生物惰性的维生素D前药。维生素D前药具有维生素D-药物部分和亲部分，其中前部分选自糖基部分和硫酸酯部分。维生素D前药通过在靶组织或细胞上被酶激活，所述细胞从维生素D药物部分切割原部分，从目标组织或细胞附近的亲部分释放维生素D部分。本发明的方法防止维生素D-药物部分的游离形式的大量急性系统性增加，否则会导致高钙血症。该方法可用于治疗全身，包括肠道的过度增生，自身免疫或感染性疾病。还公开了在所述方法中有用的维生素D前药的组合物。

10. 发明申请

US20110152207A1 USE OF VITAMIN D GLYCOSIDES AND SULFATES FOR TREATMENT OF DISEASE 审中-公开
标题翻译：维生素D糖尿病和硫酸盐治疗疾病的使用
公开(公告)号：US20110152207A1
公开(公告)日：2011-06-23
申请号：US12977303
申请日：2010-12-23
申请人： Jesse P. Goff , Ronald L. Horst
发明人： Jesse P. Goff , Ronald L. Horst
IPC分类号： A61K31/70 , A61P1/00 , A61P3/10 , A61P25/00 , A61P37/00 , A61P35/00 , A61P31/04
CPC分类号： A61K31/593 , A61K31/592 , A61K31/7032 , A61K31/7034 , A61K45/06 , A61K47/549 , A61P35/00 , A61P37/02 , Y02A50/475 , Y02A50/481 , A61K2300/00
摘要： Disclosed are methods of treating vitamin D-sensitive diseases without inducing severe forms of hypercalcemia. The methods comprise administering biologically inert vitamin D prodrugs. The vitamin D prodrugs have a vitamin D-drug moiety and a pro moiety, wherein the pro moiety is selected from the group consisting of a glycone moiety and a sulfate moiety. The vitamin D prodrugs are activated by enzymes at target tissues or cells that cleave the pro moiety from the vitamin D-drug moiety, freeing the vitamin D-moiety from the pro moiety in the vicinity of the target tissues or cells. In some versions, the vitamin D-drug moiety is an active vitamin D drug that has direct therapeutic effects at target sites. In other versions, the vitamin D-drug moiety is an inactive vitamin D drug that regulates the production and/or turnover of an active vitamin D drug and, therefore, abundance of the active vitamin D drug at the target site. The methods of the invention prevent large, acute, systemic increases in the free form of the vitamin D-drug moiety that would otherwise lead to hypercalcemia. The methods can be used to treat hyperproliferative, autoimmune, or infectious diseases throughout the body, including the intestine. Compositions of the vitamin D prodrugs useful in the described methods are also disclosed.
摘要翻译：公开了治疗维生素D敏感性疾病而不诱发严重形式的高钙血症的方法。所述方法包括施用生物惰性的维生素D前药。维生素D前药具有维生素D-药物部分和亲部分，其中前部分选自糖基部分和硫酸酯部分。维生素D前药通过在靶组织或细胞上被酶激活，所述细胞从维生素D-药物部分切割该部分，从靶组织或细胞附近的亲部分释放出维生素D部分。在某些版本中，维生素D药物部分是一种活性维生素D药物，在目标部位具有直接的治疗作用。在其他版本中，维生素D-药物部分是无活性维生素D药物，其调节活性维生素D药物的生产和/或更替，因此在目标部位的活性维生素D药物的丰度。本发明的方法防止维生素D-药物部分的游离形式的大量急性系统性增加，否则会导致高钙血症。该方法可用于治疗全身，包括肠道的过度增生，自身免疫或感染性疾病。还公开了在所述方法中有用的维生素D前药的组合物。

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