公开(公告)号：US5652221A

公开(公告)日：1997-07-29

申请号：US335015

申请日：1994-11-07

申请人： Joseph Larner ,  John Price ,  Thomas Picariello ,  Laura Huang

发明人： Joseph Larner ,  John Price ,  Thomas Picariello ,  Laura Huang

IPC分类号： C07H15/04 ,  A61K31/70 ,  A61K31/7028 ,  A61K31/7034 ,  A61P3/08 ,  C07H15/207 ,  C07H17/04

CPC分类号： C07H17/04 ,  C07H15/207 ,  Y10S514/866

摘要： A synthetic insulin mimetic compound is disclosed. Small synthetic amines of disaccharides, such as 2-deoxy-2-amino-galactopyranosyl pinitol are shown to mimic the action of insulin and to modulate its action.

摘要翻译： 公开了合成的胰岛素模拟化合物。 二恶烷的小合成胺，例如2-脱氧-2-氨基 - 吡喃半乳糖基肉豆蔻糖显示模拟胰岛素的作用并调节其作用。

公开(公告)号：US6093697A

公开(公告)日：2000-07-25

申请号：US902338

申请日：1997-07-29

申请人： Joseph Larner ,  John Price ,  Thomas Piccariello ,  Laura Huang

发明人： Joseph Larner ,  John Price ,  Thomas Piccariello ,  Laura Huang

IPC分类号： C07H15/04 ,  A61K31/70 ,  A61K31/7028 ,  A61K31/7034 ,  A61P3/08 ,  A61P3/10 ,  C07H15/207 ,  C07H17/04 ,  C07H15/00

CPC分类号： C07H17/04 ,  C07H15/207 ,  Y10S514/866

摘要： Compounds are disclosed which have the formula (I) ##STR1## wherein R.sub.1 -R.sub.2 are each independently selected from the group consisting of: (a) a hydrogen atom; and (b) a lower alkyl group, straight or branched chain, having 1 to 8 carbon atoms; or R.sub.1 -R.sub.2 and the nitrogen atom to which they are bonded may together form a heterocyclic group; R.sub.3 -R.sub.10 are each independently selected from the group consisting of: (a) a hydrogen atom; (b) an alkyl group, straight or branched chain, having 1 to 24 carbon atoms; (c) a cycloalkyl group having 3 to 10 carbon atoms; (d) an alkenyl group, straight or branched chain, having 2 to 24 carbon atoms; (e) a cycloalkenyl group having 4 to 10 carbon atoms and one or more non-adjacent double bonds; (f) an aryl group having 6 to 10 carbon atoms; (g) an aralkyl group having 7 to 34 carbons atoms; (h) a heteroaryl group having 4 to 9 carbon atoms and at least one heteroatom selected from the group consisting of oxygen, nitrogen and sulfur; (i) a carboxyalkyl group, straight or branched chain, having 2 to 24 carbon atoms; (j) a carboxyaryl group having 7 to 34 carbon atoms; and (k) a heterocyclic group having 2 to 9 carbon atoms and at least one heteroatom selected from the group consisting of oxygen, sulfur and nitrogen; or any adjacent two of R.sub.3 -R.sub.10 may together form a cycloalkyl group or heterocyclic group; and X.sub.1 and X.sub.2 are each independently selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom. Pharmaceutical compositions containing these compounds and the use thereof for the treatment of disorders of glucose metabolism are also disclosed.

摘要翻译： 公开了具有式（I）的化合物，其中R 1 -R 2各自独立地选自：（a）氢原子; 和（b）具有1至8个碳原子的直链或支链的低级烷基; 或R 1 -R 2和它们所键合的氮原子可以一起形成杂环基; R3-R10各自独立地选自：（a）氢原子; （b）具有1至24个碳原子的直链或支链烷基; （c）碳原子数3〜10的环烷基; （d）具有2至24个碳原子的直链或支链烯基; （e）具有4-10个碳原子和一个或多个不相邻双键的环烯基; （f）具有6〜10个碳原子的芳基; （g）碳原子数为7〜34的芳烷基; （h）具有4至9个碳原子的杂芳基和至少一个选自氧，氮和硫的杂原子; （i）具有2至24个碳原子的直链或支链的羧基烷基; （j）具有7至34个碳原子的羧基芳基; 和（k）具有2至9个碳原子的杂环基和至少一个选自氧，硫和氮的杂原子; 或R 3 -R 10任意相邻的两个可以一起形成环烷基或杂环基; X 1和X 2各自独立地选自氧原子，硫原子和氮原子。 还公开了含有这些化合物的药物组合物及其用于治疗葡萄糖代谢紊乱的用途。

公开(公告)号：US5122603A

公开(公告)日：1992-06-16

申请号：US320484

申请日：1989-03-08

申请人： Joseph Larner ,  Alison Kennington ,  Laura Huang ,  Tsung Y. Shen

发明人： Joseph Larner ,  Alison Kennington ,  Laura Huang ,  Tsung Y. Shen

IPC分类号： G01N33/50 ,  A61K31/70 ,  A61K35/407 ,  A61K49/00 ,  A61P3/08 ,  A61P43/00 ,  C07K1/14 ,  C07K1/16 ,  C07K1/18 ,  C07K1/22 ,  C07K14/00 ,  C07K14/47 ,  G01N30/88 ,  C07K15/00 ,  A01N57/00 ,  C12N9/88

CPC分类号： C07K14/47 ,  Y10S514/866

摘要： A method for purifying two distinct insulin mediators to substantial homogeneity, and relative purity values above 80%, comprises adsorption on first anion exchange resin and subsequently on a chelex cation exchange resin column. The chelex resin ion exchange column substantially increases the activity of the recovered mediator. Following purification, the already treated fraction is subjected to three successive thin layer chromatography purification steps, the last giving, in the presence of ninhydrin stain, a characteristic salmon-color spot, which is indicative of the presence of the mediator. This process can also be used as a screening process, the absence of the salmon-colored spot being indicative of the diabetic state. Structure information on the insulin mediators obtained is given.

摘要翻译： 一种用于纯化两种不同胰岛素介质以达到基本均匀的方法，并且相对纯度值高于80％的方法包括在第一阴离子交换树脂上吸附，随后在Chelex阳离子交换树脂柱上进行吸附。 衣壳树脂离子交换柱显着增加了回收的介体的活性。 纯化后，已经处理的级分经过三次连续的薄层色谱纯化步骤，最后在茚三酮染色剂存在下给出特征性鲑鱼色斑，这表明存在介体。 该过程也可用作筛选过程，没有鲑鱼色斑点指示糖尿病状态。 给出了获得的胰岛素介质的结构信息。

公开(公告)号：US20060258754A1

公开(公告)日：2006-11-16

申请号：US11386150

申请日：2006-03-22

申请人： Joseph Larner ,  John Price ,  Michael Brownlee ,  Manasses Fonteles

发明人： Joseph Larner ,  John Price ,  Michael Brownlee ,  Manasses Fonteles

IPC分类号： A61K31/075

CPC分类号： A61K31/05 ,  A61K31/085 ,  A61K31/09

摘要： A composition, either as a nutritional supplement or pharmaceutical, for the treatment of oxidative stress, endothelial dysfunction and related disease states which comprises administration of D-chiroinositol (DCI) congeners, acting as an antioxidant or glucose uptake promoter and metabolic normalizer, is disclosed. A composition of treating oxidative stress comprising administration of DCI is also disclosed. The administration of DCI derivatives comprises administering to the whole animal a dose in an amount sufficient to normalize blood glucose and triglycerides and to ameliorate endothelial dysfunction. The administration can be an oral, injectable, intranasal, or patch dosage forms. DCI is found in the food chain and has been shown to be very safe in large doses and, therefore, the amounts sufficient to achieve the desired therapeutic antioxidant effect will be low relative to the amounts reaching toxic levels. Therefore, DCI can be administered orally as a prophylactic nutritional supplement.

摘要翻译： 公开了作为营养补充剂或药物用于治疗氧化应激，内皮功能障碍和相关疾病状态的组合物，其包括施用作为抗氧化剂或葡萄糖摄取促进剂和代谢规范化酶的D-二羟基肌醇（DCI）同系物， 。 还公开了包含施用DCI的治疗氧化应激的组合物。 DCI衍生物的施用包括向整个动物施用足以使血糖和甘油三酯正常化并改善内皮功能障碍的剂量。 给药可以是口服，可注射，鼻内或贴剂剂型。 DCI在食物链中发现，并且已被证明在大剂量下非常安全，因此，足以达到所需治疗性抗氧化作用的量相对于达到毒性水平的量将低。 因此，DCI可以口服给药作为预防性营养补充剂。

公开(公告)号：US4446064A

公开(公告)日：1984-05-01

申请号：US218075

申请日：1980-12-19

申请人： Joseph Larner ,  Kang Cheng ,  Gail Galasko

发明人： Joseph Larner ,  Kang Cheng ,  Gail Galasko

IPC分类号： A61K35/34 ,  C07G7/00

CPC分类号： A61K35/34 ,  Y10S530/841

摘要： An insulin mediator substance produced by the process comprising: contacting muscle tissue with insulin; deproteinizing the muscle tissue; removing the major nucleotides from the deproteinized muscle tissue; chromatographing the so-treated product on a Sephadex G-25 column using 0.05 N formic acid; and recovering the fraction wherein the major 230-nm absorbance peak corresponds with the ninhydrin-positive peak.

摘要翻译： 通过该方法产生的胰岛素介体物质包括：使肌肉组织与胰岛素接触; 去蛋白肌肉组织; 去除脱蛋白肌肉组织中的主要核苷酸; 使用0.05N甲酸在Sephadex G-25柱上色谱处理如此处理的产物; 并回收其中主要的230nm吸收峰对应于茚三酮正峰的级分。

公开(公告)号：US5428066A

公开(公告)日：1995-06-27

申请号：US304806

申请日：1994-09-12

申请人： Joseph Larner ,  Alison Kennington ,  Laura C. Huang

发明人： Joseph Larner ,  Alison Kennington ,  Laura C. Huang

IPC分类号： A23L1/09 ,  A61K31/047 ,  A61K31/045

CPC分类号： A61K31/047 ,  A23L29/37 ,  Y10S514/866

摘要： A method of treating a cluster of diseases associated with elevated blood sugar levels comprising the administration of a dietary supplement of chiro-inositol. Chiro-inositol is an essential element for the synthesis of an insulin-directed mediator apparently responsible for the activation of pyruvate dehydrogenase-phosphatase. Disease conditions commonly associated with insulin-resistance, such as hypertension, lactic acidosis, obesity, coronary artery disease, and the like, are treated by administration of sufficient chiro-inositol to meet normal metabolic levels.

摘要翻译： 一种治疗与升高的血糖水平相关的一系列疾病的方法，其包括给予一种膳食补充的肌醇肌醇。 肌醇是合成明显负责丙酮酸脱氢酶 - 磷酸酶活化的胰岛素导向介体的重要元素。 通常通过施用足够的肌醇以满足正常的代谢水平来治疗通常与胰岛素抵抗相关的疾病状况，例如高血压，乳酸性酸中毒，肥胖，冠状动脉疾病等。

公开(公告)号：US5427956A

公开(公告)日：1995-06-27

申请号：US953708

申请日：1992-09-30

申请人： Alison S. Kennington ,  Joseph Larner

发明人： Alison S. Kennington ,  Joseph Larner

IPC分类号： C12Q1/26 ,  G01N33/53 ,  G01N33/66 ,  G01N24/00 ,  G01N33/49 ,  G01N33/493

CPC分类号： C12Q1/26 ,  G01N33/5308 ,  G01N33/66 ,  Y10S436/811 ,  Y10S436/815 ,  Y10T436/203332 ,  Y10T436/24

摘要： An enhanced quantitative assay for chiro-inositol concentration can be used to determine insulin-resistance, or a predisposition to the development of insulin-resistance, in type I and type II diabetics. Spot urine or serum samples reflecting concentrations of chiro-inositol below about 1.0 micrograms/ml in urine or 0.1 micrograms/ml in serum are indicative of a predisposition to the development of insulin-resistance, while concentrations below about 0.3 micrograms/ml or 0.03 micrograms/ml in serum are associated with actual insulin-resistance symptoms. The assay can be employed for patient diagnosis, insulin therapy monitoring, and family screening.

摘要翻译： 在I型和II型糖尿病患者中，可以使用增强的肌醇浓度的定量分析来确定胰岛素抵抗或胰岛素抵抗发展的倾向。 反映尿液浓度低于约1.0微克/毫升的尿液或血清中0.1微克/毫升血清样本的尿样或血清样本表明胰岛素抵抗发展的倾向，而浓度低于约0.3微克/毫升或0.03微克 / ml在血清中与实际的胰岛素抵抗症状相关。 该测定可用于患者诊断，胰岛素治疗监测和家庭筛查。

公开(公告)号：US5183764A

公开(公告)日：1993-02-02

申请号：US870771

申请日：1992-04-21

申请人： Alison S. Kennington ,  Joseph Larner

发明人： Alison S. Kennington ,  Joseph Larner

IPC分类号： C12Q1/26 ,  G01N33/53 ,  G01N33/66

CPC分类号： C12Q1/26 ,  G01N33/5308 ,  G01N33/66 ,  Y10S436/811 ,  Y10S436/822 ,  Y10T436/203332

摘要： An enhanced quantitative assay for chiro-inositol concentration can be used to determine insulin-resistance, or a predeposition to the development of insulin-resistance, in type I and type II diabetics. Spot urine or serum samples reflecting concentrations of chiro-inositol below about 1.0 micrograms/ml in urine or 0.1 micrograms/ml in serum are indicative of a predisposition to the development of insulin-resistance, while concentrations below about 0.3 micrograms/ml or 0.03 micrograms/ml in serum are associated with actual insulin-resistance symptoms. The assay can be employed for patient diagnosis, insulin therapy monitoring, and family screening.

摘要翻译： 在I型和II型糖尿病患者中，可以使用增强的肌醇浓度的定量分析来确定胰岛素抵抗或胰岛素抵抗发展的预沉积。 反映尿液浓度低于约1.0微克/毫升的尿液或血清中0.1微克/毫升血清样本的尿样或血清样本表明胰岛素抵抗发展的倾向，而浓度低于约0.3微克/毫升或0.03微克 / ml在血清中与实际的胰岛素抵抗症状相关。 该测定可用于患者诊断，胰岛素治疗监测和家庭筛查。

公开(公告)号：US5124360A

公开(公告)日：1992-06-23

申请号：US672778

申请日：1991-03-21

申请人： Joseph Larner ,  Alison Kennington

发明人： Joseph Larner ,  Alison Kennington

IPC分类号： A23L1/30 ,  A23L1/09 ,  A61K31/00 ,  A61K31/045 ,  A61K31/047 ,  A61K36/00 ,  A61P3/00 ,  A61P3/08 ,  A61P3/10 ,  A61P43/00

CPC分类号： A61K31/047 ,  A23L29/37 ,  Y10S514/866

摘要： A dietary supplement for the therapeutic treatment of those exhibiting clinical symptoms of insulin-resistant type II diabetes, and preventing the development of clinical symptoms in those genetically predisposed to the development of such symptoms, is provided by the administration of a dietary supplement comprising D-chiro-inositol. The dietary supplement is preferably administered orally, in vitamin-like amounts.

摘要翻译： 一种膳食补充剂，用于治疗治疗表现出胰岛素抵抗型II型糖尿病临床症状的药物，并且预防在发生这些症状的基因中发生临床症状的发展是由含有D- 手性肌醇。 膳食补充剂优选以维生素样量的量口服给药。

公开(公告)号：US20060004096A1

公开(公告)日：2006-01-05

申请号：US10908800

申请日：2005-05-26

申请人： Joseph Larner

发明人： Joseph Larner

IPC分类号： A61K31/225

CPC分类号： A61K31/225

摘要： A composition, either as a nutritional supplement or pharmaceutical, for the treatment of oxidative stress, endothelial dysfunction and related disease states which comprises administration of D-chiroinositol (DCI) congeners, acting as an antioxidant or glucose uptake promoter and metabolic normalizer, is disclosed. A composition of treating oxidative stress comprising administration of DCI is also disclosed. The administration of DCI derivatives comprises administering to the whole animal a dose in an amount sufficient to normalize blood glucose and triglycerides and to ameliorate endothelial dysfunction. The administration can be an oral, injectable, intranasal, or patch dosage forms. DCI is found in the food chain and has been shown to be very safe in large doses and, therefore, the amounts sufficient to achieve the desired therapeutic antioxidant effect will be low relative to the amounts reaching toxic levels. Therefore, DCI can be administered orally as a prophylactic nutritional supplement.

摘要翻译： 公开了作为营养补充剂或药物用于治疗氧化应激，内皮功能障碍和相关疾病状态的组合物，其包括施用作为抗氧化剂或葡萄糖摄取促进剂和代谢规范化酶的D-二羟基肌醇（DCI）同系物， 。 还公开了包含施用DCI的治疗氧化应激的组合物。 DCI衍生物的施用包括向整个动物施用足以使血糖和甘油三酯正常化并改善内皮功能障碍的剂量。 给药可以是口服，可注射，鼻内或贴剂剂型。 DCI在食物链中发现，并且已被证明在大剂量下非常安全，因此，足以达到所需治疗性抗氧化作用的量相对于达到毒性水平的量将低。 因此，DCI可以口服给药作为预防性营养补充剂。