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1.发明授权Compositions comprising a GPR109 ligand for treating disorders of the digestive tract and/or cancer 有权包含用于治疗消化道和/或癌症疾病的GPR109配体的组合物公开(公告)号：US08309534B2
公开(公告)日：2012-11-13
申请号：US12599923
申请日：2008-05-15
摘要： Pharmaceutical compositions containing an effective amount of a ligand for GPR109 to decrease intracellular cAMP levels of a subject in combination with an effective amount of a DNA methyl transferase inhibito to reduce or inhibit downregulation of GPR109 in the intestinal epithelial cells of the subject relative to a control are provided. It has been discovered that ligands for GPR109 can be used to treat one or more symptoms of cancer, inflammatory disorders, and diarrhea. Representative CPR109 ligands include, but are not limited to butyrate, β-hydroxybutyrate, nicotinic acid, acifran, and octanoate. Suitable DNA methyl transferase inhibitors include 5-azacytidine, 5-aza-2′-deoxytidine, 1-β-D-arabinfarnosyl-5-azacytosine and dihydro-5-azacytidine. Typically, the compositions are formulated to achieve a GPR109 ligand serum blood level of about 1 to about 1000 μM. The compositions are useful for the treatment of one or more symptoms of cancer. Preferred cancers that can be treated using the disclosed compositions include, but are not limited to colon cancer, breast cancer and leukemia. Methods for treating cancer, inflammatory disorders, and diarrhea are also provided.
摘要翻译： 含有有效量的GPR109配体的药物组合物与有效量的DNA甲基转移酶组合减少受试者的细胞内cAMP水平，抑制该对象的肠上皮细胞中GPR109的下调，相对于对照组 被提供。 已经发现，用于GPR109的配体可用于治疗癌症，炎性疾病和腹泻的一种或多种症状。 代表性的CPR109配体包括但不限于丁酸盐，β-羟基丁酸盐，烟酸，丙酸盐和辛酸盐。 合适的DNA甲基转移酶抑制剂包括5-氮杂胞苷，5-氮杂-2'-脱氧胆碱，1- [b-D-阿拉伯非糖苷基-5-氮胞嘧啶和二氢-5-氮杂胞苷。 通常，配制组合物以实现约1至约1000μM的GPR109配体血清血浆水平。 该组合物可用于治疗癌症的一种或多种症状。 可以使用所公开的组合物治疗的优选癌症包括但不限于结肠癌，乳腺癌和白血病。 还提供了治疗癌症，炎性疾病和腹泻的方法。
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2.发明申请Compositions Comprising a GPR109 Ligand For Treating Disorders of the Digestive Tract and/or Cancer 有权包含用于治疗消化道和/或癌症疾病的GPR109配体的组合物公开(公告)号：US20100137236A1
公开(公告)日：2010-06-03
申请号：US12599923
申请日：2008-05-15
摘要： Pharmaceutical compositions containing an effective amount of a ligand for GPR109 to decrease intracellular cAMP levels of a subject in combination with an effective amount of a DNA methyl transferase inhibito to reduce or inhibit downregulation of GPR109 in the intestinal epithelial cells of the subject relative to a control are provided. It has been discovered that ligands for GPR109 can be used to treat one or more symptoms of cancer, inflammatory disorders, and diarrhea. Representative CPR 109 ligands include, but are not limited to butyrate, β-hydroxybutyrate, nicotinic acid, acifran, and octanoate. Suitable DNA methyl transferase inhibitors include 5-azacytidine, 5-aza-2′-deoxytidine, 1-β-D-arabinfαmosyl-5-azacytosine and dihydro-5-azacytidine. Typically, the compositions are formulated to achieve a GPR 109 ligand serum blood level of about 1 to about 1000 μM. The compositions are useful for the treatment of one or more symptoms of cancer. Preferred cancers that can be treated using the disclosed compositions include, but are not limited to colon cancer, breast cancer and leukemia. Methods for treating cancer, inflammatory disorders, and diarrhea are also provided.
摘要翻译： 含有有效量的GPR109配体的药物组合物与有效量的DNA甲基转移酶组合减少受试者的细胞内cAMP水平，抑制该对象的肠上皮细胞中GPR109的下调，相对于对照组 被提供。 已经发现，用于GPR109的配体可用于治疗癌症，炎性疾病和腹泻的一种或多种症状。 代表性的CPR 109配体包括但不限于丁酸盐，β-羟基丁酸盐，烟酸，丙酸盐和辛酸盐。 合适的DNA甲基转移酶抑制剂包括5-氮杂胞苷，5-氮杂-2'-脱氧胞苷，1-＆bgr-D-阿拉伯呋喃糖基-5-氮胞嘧啶和二氢-5-氮杂胞苷。 通常，配制组合物以实现约1至约1000μM的GPR 109配体血清血浆水平。 该组合物可用于治疗癌症的一种或多种症状。 可以使用所公开的组合物治疗的优选癌症包括但不限于结肠癌，乳腺癌和白血病。 还提供了治疗癌症，炎性疾病和腹泻的方法。
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公开(公告)号：US08518989B2
公开(公告)日：2013-08-27
申请号：US13039661
申请日：2011-03-03
CPC分类号： A61K31/22 , A61K31/195 , A61K31/7076
摘要： Prodrugs made up of biologically-active short-chain fatty acids or derivatives thereof conjugated to neutral or cationic amino acids capable of intracellular transport by ATB0,+ are provided. The short-chain fatty acid or derivative thereof can be attached to the amino acid through a hydroxyl group of the amino acid to form a fatty acid ester of the amino acid, or it can be attached through the amino group of the amino acid to form a fatty-acid amide of the amino acid. Serine butyrate (O-butyryl serine) is a preferred prodrug. These prodrugs are useful for treatment of colon cancer, inflammatory bowel disease, ulcerative colitis, Crohn's disease, lung cancer, cervical cancer, and cancers resulting from metastases from primary colon cancer sites. Methods of delivering biologically-active short-chain fatty acids or derivatives thereof to cells in need of these molecules and methods of treating diseases using the prodrugs of this invention are also provided.
摘要翻译： 提供由生物活性短链脂肪酸或其与能够通过ATB0 +进行细胞内转运的中性或阳离子氨基酸缀合的其衍生物组成的前药。 短链脂肪酸或其衍生物可以通过氨基酸的羟基与氨基酸连接以形成氨基酸的脂肪酸酯，或者可以通过氨基酸的氨基连接形成 氨基酸的脂肪酸酰胺。 丁酸丁酯（O-丁酰丝氨酸）是优选的前药。 这些前药可用于治疗结肠癌，炎性肠病，溃疡性结肠炎，克罗恩病，肺癌，子宫颈癌和由原发性结肠癌部位转移引起的癌症。 还提供了将生物活性短链脂肪酸或其衍生物递送至需要这些分子的细胞的方法和使用本发明的前药治疗疾病的方法。
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公开(公告)号：US20090123388A1
公开(公告)日：2009-05-14
申请号：US11813343
申请日：2006-01-17
IPC分类号： A61K9/12 , C07C69/675 , A61K31/221 , A61P35/00 , C07H19/04 , A61K31/7052
CPC分类号： A61K31/22 , A61K31/195 , A61K31/7076
摘要： Prodrugs made up of biologically-active short-chain fatty acids or derivatives thereof conjugated to neutral or cationic amino acids capable of intracellular transport by ATB0,+ are provided. The short-chain fatty acid or derivative thereof can be attached to the amino acid through a hydroxyl group of the amino acid to form a fatty acid ester of the amino acid, or it can be attached through the amino group of the amino acid to form a fatty-acid amide of the amino acid. Serine butyrate (O-butyryl serine) is a preferred prodrug. These prodrugs are useful for treatment of colon cancer, inflammatory bowel disease, ulcerative colitis, Crohn's disease, lung cancer, cervical cancer, and cancers resulting from metastases from primary colon cancer sites. Methods of delivering biologically-active short-chain fatty acids or derivatives thereof to cells in need of these molecules and methods of treating diseases using the prodrugs of this invention are also provided.
摘要翻译： 提供由生物活性短链脂肪酸或其与能够通过ATB0 +进行细胞内转运的中性或阳离子氨基酸缀合的其衍生物组成的前药。 短链脂肪酸或其衍生物可以通过氨基酸的羟基与氨基酸连接以形成氨基酸的脂肪酸酯，或者可以通过氨基酸的氨基连接形成 氨基酸的脂肪酸酰胺。 丁酸丁酯（O-丁酰丝氨酸）是优选的前药。 这些前药可用于治疗结肠癌，炎性肠病，溃疡性结肠炎，克罗恩病，肺癌，子宫颈癌和由原发性结肠癌部位转移引起的癌症。 还提供了将生物活性短链脂肪酸或其衍生物递送至需要这些分子的细胞的方法和使用本发明的前药治疗疾病的方法。
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