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1. 发明申请

US20070238703A1 1alpha-Hydroxy-2-(3'-Hydroxypropylidene)-19-Nor-Vitamin D Compounds with a 1,1-Dimethylpropyl Side Chain 有权
标题翻译：具有1,1-二甲基丙基侧链的1α-羟基-2-（3'-羟基亚丙基）-19-维生素D化合物
公开(公告)号：US20070238703A1
公开(公告)日：2007-10-11
申请号：US11697430
申请日：2007-04-06
申请人： Hector F. DeLuca , Agnieszka Glebocka , Rafal R. Sicinski , Lori A. Plum , Margaret Clagette-Dame
发明人： Hector F. DeLuca , Agnieszka Glebocka , Rafal R. Sicinski , Lori A. Plum , Margaret Clagette-Dame
IPC分类号： A61K31/695 , A61K31/59 , C07C401/00
CPC分类号： C07C401/00 , C07F7/1804
摘要： This invention discloses 1α-hydroxy-2-(3′-hydroxypropylidene)-19-nor-vitamin D compounds with a 1,1-dimethylpropyl side chain, and pharmaceutical uses therefor. These compounds exhibit pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. These compounds also have little, if any, calcemic activity and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as renal osteodystrophy. These compounds may also be used for the treatment or prevention of obesity.
摘要翻译：本发明公开了具有1,1-二甲基丙基侧链的1-羟基-2-（3'-羟基亚丙基）-19-去甲维生素D化合物及其制药用途。这些化合物在阻止未分化细胞的增殖并诱导其分化为单核细胞方面表现出显着的活性，从而证明其用作抗癌剂并用于治疗皮肤疾病如牛皮癣以及皮肤病症如皱纹，松弛皮肤，皮肤干燥，皮脂分泌不足。这些化合物也具有很少（如果有的话）钙活性，因此可用于治疗人体中的自身免疫性疾病或炎性疾病以及肾性骨营养不良。这些化合物也可用于治疗或预防肥胖症。

2. 发明授权

US07214671B2 Use of 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3 for the prophylaxis of bone diseases 有权
标题翻译：使用2-亚甲基-19-nor-20（S）-1α，25-二羟基维生素D 3用于预防骨疾病
公开(公告)号：US07214671B2
公开(公告)日：2007-05-08
申请号：US10782337
申请日：2004-02-19
申请人： Hector F. DeLuca , Lori A. Plum , Margaret Clagette-Dame
发明人： Hector F. DeLuca , Lori A. Plum , Margaret Clagette-Dame
IPC分类号： A61K31/59 , A61K31/592 , A61K31/593 , A61K401/00
CPC分类号： A61K31/593 , A61K31/59
摘要： This invention provides pharmaceutical uses for 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3. This compound is characterized by high bone calcium mobilization activity demonstrating preferential activity on bone. This results in a novel therapeutic agent for the treatment and prophylaxis of diseases where bone formation is desired, particularly osteoporosis. This compound also increases both breaking strength and crushing strength of bones evidencing use in conjunction with bone replacement surgery such as hip and knee replacements, as well as use by normal subjects when high bone mass is desired.
摘要翻译：本发明提供2-亚甲基-19-去甲-20（S）-1α，25-二羟基维生素D 3 N的药用。该化合物的特征在于高骨钙动员活性，表现出骨优先活性。这导致用于治疗和预防需要骨形成的疾病，特别是骨质疏松症的新型治疗剂。这种化合物还增加骨骼的断裂强度和破碎强度，这些骨骼与骨替代手术如髋关节和膝关节置换术一起使用，以及在需要高骨质量时由正常受试者使用。

3. 发明授权

US07718636B2 Use of 2-methylene-19-nor-20(S)-1alpha,25dihydroxy vitamin d3 to inhibit mammary tumor 有权
标题翻译：使用2-亚甲基-19-nor-20（S）-1α，25二羟基维生素d3抑制乳腺肿瘤
公开(公告)号：US07718636B2
公开(公告)日：2010-05-18
申请号：US11472125
申请日：2006-06-21
申请人： Hector F. DeLuca , Lori A. Plum , Margaret Clagette-Dame
发明人： Hector F. DeLuca , Lori A. Plum , Margaret Clagette-Dame
IPC分类号： A61K31/59 , C07C401/00
CPC分类号： A61K31/593
摘要： This invention provides pharmaceutical uses for 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3. Administration of this compound increases the life expectancy of human beings, especially elderly human beings. In particular, it increases the survival rate of females lacking estrogen, especially post-menopausal females, and reduces mortality resulting from spontaneous development of malignant tumors in both males and females.
摘要翻译：本发明提供2-亚甲基-19-去甲-20（S）-1α，25-二羟基维生素D3的药用。这种化合物的施用增加了人类，特别是老年人的预期寿命。特别是增加女性缺乏雌激素，特别是绝经后女性的生存率，并降低男性和女性恶性肿瘤自发发生的死亡率。

4. 发明授权

US07259143B2 Method of extending the dose range of vitamin D compounds 有权
标题翻译：延长维生素D化合物剂量范围的方法
公开(公告)号：US07259143B2
公开(公告)日：2007-08-21
申请号：US10235244
申请日：2002-09-05
申请人： Hector F. DeLuca , John W. Pike , Nirupama Shevde , Lori A. Plum , Margaret Clagette-Dame
发明人： Hector F. DeLuca , John W. Pike , Nirupama Shevde , Lori A. Plum , Margaret Clagette-Dame
IPC分类号： A61K38/00 , A61K31/59
CPC分类号： A61K31/565 , A61K31/593 , A61K45/06 , A61K2300/00
摘要： Inhibitors of bone calcium resorption are administered to allow high doses of vitamin D compounds or mimetics to be given with the intent of treating non-calcium related diseases such as cancer, psoriasis, and autoimmune disease without the dangers of calcification of kidney, heart, and aorta. Inhibitors of bone calcium resorption include the bis-phosphonates, OPG (osteoprotegerin) or the soluble RANKL (receptor activator of NF-κB ligand) receptor known as sRANK (soluble RANK which is the protein expressed by the NF-κB gene), and function to block the availability of calcium from bone thereby preventing hypercalcemia and the resulting calcification of soft tissues. Thus, high doses of 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3), its analogs, prodrugs, or mimetics can be utilized with minimal risk to a patient. Specifically, alendronate is shown to block the bone calcium mobilization activity of both 1,25-(OH)2D3 and its very potent analog, 2-methylene -19-nor-(20S)-1α,25-dihydroxyvitamin D3.
摘要翻译：施用骨钙吸收抑制剂以允许给予高剂量的维生素D化合物或模拟物，其目的是治疗非钙相关疾病如癌症，牛皮癣和自身免疫性疾病，而不会引起肾，心脏和主动脉。骨钙吸收抑制剂包括称为sRANK（可溶性RANK，由NF-κB基因表达的蛋白质）的双膦酸盐，OPG（骨保护素）或可溶性RANKL（NF-κB配体的受体活化剂）受体）和功能以阻止骨骼中钙的供应，从而防止高钙血症和软组织的钙化。因此，高剂量的1α，25-二羟基维生素D 3 N（1,25-（OH）2 N 3），其类似物，前药，或者模拟物可以以最小的风险使用于患者。具体地说，阿仑膦酸被显示阻断1,25-（OH）2 N 3 N 3及其非常有效的类似物2-亚甲基-19-二酮的骨钙动员活性，（20S）-1α，25-二羟基维生素D 3。

5. 发明授权

US07214670B2 Use of 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3 to increase the life expectancy of human beings 有权
标题翻译：使用2-亚甲基-19-nor-20（S）-1α，25-二羟基维生素D3来增加人的预期寿命
公开(公告)号：US07214670B2
公开(公告)日：2007-05-08
申请号：US10669990
申请日：2003-09-24
申请人： Hector F. DeLuca , Lori A. Plum , Margaret Clagette-Dame
发明人： Hector F. DeLuca , Lori A. Plum , Margaret Clagette-Dame
IPC分类号： A61K31/593 , A61K31/59 , A61K31/592 , C07C401/00
CPC分类号： A61K31/593
摘要： This invention provides pharmaceutical uses for 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3. Administration of this compound increases the life expectancy of human beings, especially elderly human beings. In particular, it increases the survival rate of females lacking estrogen, especially post-menopausal females, and reduces mortality resulting from spontaneous development of malignant tumors in both males and females.
摘要翻译：本发明提供2-亚甲基-19-去甲-20（S）-1α，25-二羟基维生素D 3 N的药用。这种化合物的施用增加了人类，特别是老年人的预期寿命。特别是增加女性缺乏雌激素，特别是绝经后女性的生存率，并降低男性和女性恶性肿瘤自发发生的死亡率。

6. 发明申请

US20050187201A1 Use of 2-methylene-19-nor-20(S)-1alpha,25-dihydroxyvitamin D3 for the prophylaxis of bone diseases 有权
标题翻译：使用2-亚甲基-19-nor-20（S）-1α，25-二羟基维生素D 3用于预防骨疾病
公开(公告)号：US20050187201A1
公开(公告)日：2005-08-25
申请号：US10782337
申请日：2004-02-19
申请人： Hector DeLuca , Lori Plum , Margaret Clagette-Dame
发明人： Hector DeLuca , Lori Plum , Margaret Clagette-Dame
IPC分类号： A61K31/59 , A61K31/593
CPC分类号： A61K31/593 , A61K31/59
摘要： This invention provides pharmaceutical uses for 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3. This compound is characterized by high bone calcium mobilization activity demonstrating preferential activity on bone. This results in a novel therapeutic agent for the treatment and prophylaxis of diseases where bone formation is desired, particularly osteoporosis. This compound also increases both breaking strength and crushing strength of bones evidencing use in conjunction with bone replacement surgery such as hip and knee replacements, as well as use by normal subjects when high bone mass is desired.
摘要翻译：本发明提供2-亚甲基-19-去甲-20（S）-1α，25-二羟基维生素D 3 N的药用。该化合物的特征在于高骨钙动员活性，表现出骨优先活性。这导致用于治疗和预防需要骨形成的疾病，特别是骨质疏松症的新型治疗剂。这种化合物还增加骨骼的断裂强度和破碎强度，这些骨骼与骨替代手术如髋关节和膝关节置换术一起使用，以及在需要高骨质量时由正常受试者使用。

7. 发明申请

US20050065123A1 Use of 2-Methylene-19-nor-20(S)-1alpha,25-dihydroxyvitamin D3 to increase the life expectancy of human beings 有权
标题翻译：使用2-亚甲基-19-nor-20（S）-1α，25-二羟基维生素D 3以增加人的预期寿命
公开(公告)号：US20050065123A1
公开(公告)日：2005-03-24
申请号：US10669990
申请日：2003-09-24
申请人： Hector DeLuca , Lori Plum , Margaret Clagette-Dame
发明人： Hector DeLuca , Lori Plum , Margaret Clagette-Dame
IPC分类号： A61K31/593 , A61P35/00 , A61P35/02 , A61P43/00 , A61K31/59
CPC分类号： A61K31/593
摘要： This invention provides pharmaceutical uses for 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3. Administration of this compound increases the life expectancy of human beings, especially elderly human beings. In particular, it increases the survival rate of females lacking estrogen, especially post-menopausal females, and reduces mortality resulting from spontaneous development of malignant tumors in both males and females.
摘要翻译：本发明提供2-亚甲基-19-去甲-20（S）-1α，25-二羟基维生素D3的药用。这种化合物的施用增加了人类，特别是老年人的预期寿命。特别是增加女性缺乏雌激素，特别是绝经后女性的生存率，并降低男性和女性恶性肿瘤自发发生的死亡率。

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