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1. 发明申请

WO2016196113A1 METHODS OF REDUCING OR PREVENTING INTIMAL DAMAGE CAUSED BY MECHANICAL STIMULATION OF ENDOTHELIAL CELLS 审中-公开
标题翻译：降低或预防机械刺激内皮细胞引起的实体损伤的方法
公开(公告)号：WO2016196113A1
公开(公告)日：2016-12-08
申请号：PCT/US2016/034066
申请日：2016-05-25
申请人： UNIVERSITY OF MARYLAND, BALTIMORE , THE USA AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS , REMEDY PHARMACEUTICALS, INC.
发明人： SIMARD, J., Marc , JACOBSON, Sven
IPC分类号： A61K38/00 , C12N15/11 , A61K48/00 , A61K39/395 , A61K31/175 , A61K31/18
CPC分类号： C12N15/1138 , A61K31/05 , A61K31/132 , A61K31/196 , A61K31/64 , A61P9/00 , C12N2310/11 , C12N2310/315
摘要： Embodiments of the disclosure encompass methods and/or compositions for ameliorating or preventing intimal damage caused by mechanical stimulation of endothelial cells. The damage may be caused by use of a device within an artery, vein, or capillary of an individual, such as to remove a thrombus, an embolus or an atherosclerotic plaque in the vessel. Treatment and prevention embodiments concern therapeutically effective amounts of one or more antagonists of the SUR1- TRPM4 channel that is upregulated upon the mechanical stimulation.
摘要翻译：本公开的实施方案包括用于改善或预防由内皮细胞的机械刺激引起的内膜损伤的方法和/或组合物。损伤可能是由于使用个体的动脉，静脉或毛细血管内的装置，例如去除血管中的血栓，栓塞或动脉粥样硬化斑块引起的。治疗和预防实施方案涉及治疗有效量的在机械刺激时上调的SUR1-TRPM4通道的一种或多种拮抗剂。

2. 发明申请

WO2008046014A1 TREATMENT OF ALZHEIMER'S DISEASE USING COMPOUNDS THAT REDUCE THE ACTIVITY OF NON-SELECTIVE CA++- ACTIVATED ATP-SENSITIVE CATION CHANNELS REGULATED BY SUR1 RECEPTORS 审中-公开
标题翻译：使用化合物治疗ALZHEIMER的疾病，降低由SUR1受体调节的非选择性CA ++活化的ATP敏感通道的活性
公开(公告)号：WO2008046014A1
公开(公告)日：2008-04-17
申请号：PCT/US2007/081128
申请日：2007-10-11
申请人： REMEDY PHARMACEUTICALS, INC. , JACOBSON, Sven , ANG, Robert
发明人： JACOBSON, Sven , ANG, Robert
IPC分类号： A01N47/34 , A61K31/175
CPC分类号： A61K31/175
摘要： NSC antagonists are disclosed as useful in the treatment of dementia, in delaying the onset of dementia, and in the prevention of dementia. Dementia so treated may be, for example, Alzheimer's Disease (AD). NSC antagonists for treating dementia such as AD may be administered alone, a) in combination with other drugs used for treating dementia, b) in combination with drugs that stabilize or increase blood plasma glucose levels, or with both a) and b). Pharmaceutical compositions, dosage forms, and methods for using the same are disclosed, which include NSC antagonists, NSC antagonists combined with dementia drugs, NSC antagonists combined with glucose-level stabilizing or enhancing drugs, or combinations of these. Dosage forms may be designed to provide stable plasma levels for extended periods of time. Exemplary pharmaceutical compositions include compositions including glibenclamide and memantine; glibenclamide and donepezil; tolbutamide and memantine; tolbutamide and donepezil; and these compositions further including glucagon and/or glucose.
摘要翻译：公开了用于治疗痴呆，延缓痴呆发病以及预防痴呆的NSC拮抗剂。如此治疗的痴呆可以是例如阿尔茨海默病（AD）。用于治疗痴呆症如AD的NSC拮抗剂可以单独施用，a）与用于治疗痴呆的其他药物组合，b）与稳定或增加血浆葡萄糖水平的药物组合，或同时使用a）和b）。公开了药物组合物，剂型和使用该组合物的方法，其包括NSC拮抗剂，与痴呆药物联合的NSC拮抗剂，与葡萄糖水平稳定化或增强药物联合的NSC拮抗剂或它们的组合。剂量形式可以设计成在长时间内提供稳定的血浆水平。示例性药物组合物包括组合物，包括格列本脲和美金刚; 格列本脲和多奈哌齐; 甲苯磺丁脲和美金刚; 甲苯磺丁脲和多奈哌齐; 并且这些组合物还包括胰高血糖素和/或葡萄糖。

3. 发明申请

WO2009097443A3 LIQUID FORMULATIONS OF COMPOUNDS ACTIVE AT SULFONYLUREA RECEPTORS 审中-公开
标题翻译：化合物的液体配方在磺酰脲受体中有活性
公开(公告)号：WO2009097443A3
公开(公告)日：2009-12-10
申请号：PCT/US2009032455
申请日：2009-01-29
申请人： REMEDY PHARMACEUTICALS INC , JACOBSON SVEN MARTIN , CLARKE GILLIAN , MATHARU RAJINDER
发明人： JACOBSON SVEN MARTIN , CLARKE GILLIAN , MATHARU RAJINDER
IPC分类号： A61K9/08 , A61K31/64 , A61K47/10 , A61K47/34 , A61P3/10
CPC分类号： A61K31/64 , A61K9/0019 , A61K9/08 , A61K47/10 , A61K47/18 , A61K47/26
摘要： The invention provides liquid formulations of compounds that act at sulfonylurea receptors that are suitable for intravenous and intra-arterial infusion. Compounds active at a sulfonylurea receptor include glibenclamide, tolbutamide, repaglinide, nateglinide, meglitinide, midaglizole, LY397364, LY389382, glyclazide, and glimepiride. Liquid formulations may be concentrated solutions suitable for storage; may be diluted (e.g., dilution of 1 : 1 or 1 : 1.2) suitable for bolus injections, and may be further diluted (e.g., dilution of 1 : 10 or 1 : 20 or more) for intravenous and intra-arterial infusion over an extended period of time. For example, a liquid formulation may include at least about 0.05 mg/ml glibenclamide in a water-based solution including 40% polyethylene glycol 300, 10% Ethanol, 50% water, at about pH 9. The solution may include a buffer, and is suitable for storage in refrigerator or at room temperature. This solution may be diluted 1 : 1, or more (e.g., 1 :20) without precipitation of the glibenclamide.
摘要翻译：本发明提供了适用于静脉内和动脉内输注的磺酰脲受体的化合物的液体制剂。在磺酰脲受体中活性的化合物包括格列本脲，甲苯磺丁脲，瑞格列奈，那格列奈，麦格列奈，米格列齐，LY397364，LY389382，氯格列齐和格列美脲。液体制剂可以是适合储存的浓缩溶液; 可以稀释（例如，稀释1：1或1：1.2）适合于推注，并可进一步稀释（例如，稀释1:10或1:20或更高），用于静脉内和动脉内输注延长一段时间例如，液体制剂在包含40％聚乙二醇300,10％乙醇，50％水，约pH 9的水溶液中可包含至少约0.05mg / ml格列本脲。该溶液可包括缓冲液，和适用于冰箱或室温储存。该溶液可以以1:1或更多（例如1:20）稀释，而不会沉淀格列本脲。

4. 发明申请

WO2009097443A2 LIQUID FORMULATIONS OF COMPOUNDS ACTIVE AT SULFONYLUREA RECEPTORS 审中-公开
标题翻译：在磺酰脲类受体上具有活性的化合物的液体制剂
公开(公告)号：WO2009097443A2
公开(公告)日：2009-08-06
申请号：PCT/US2009/032455
申请日：2009-01-29
申请人： REMEDY PHARMACEUTICALS, INC. , JACOBSON, Sven, Martin , CLARKE, Gillian , MATHARU, Rajinder
发明人： JACOBSON, Sven, Martin , CLARKE, Gillian , MATHARU, Rajinder
IPC分类号： A61K9/08 , A61K31/64 , A61K47/10 , A61K47/34 , A61P3/10
CPC分类号： A61K31/64 , A61K9/0019 , A61K9/08 , A61K47/10 , A61K47/18 , A61K47/26
摘要： The invention provides liquid formulations of compounds that act at sulfonylurea receptors that are suitable for intravenous and intra-arterial infusion. Compounds active at a sulfonylurea receptor include glibenclamide, tolbutamide, repaglinide, nateglinide, meglitinide, midaglizole, LY397364, LY389382, glyclazide, and glimepiride. Liquid formulations may be concentrated solutions suitable for storage; may be diluted (e.g., dilution of 1 : 1 or 1 : 1.2) suitable for bolus injections, and may be further diluted (e.g., dilution of 1 : 10 or 1 : 20 or more) for intravenous and intra-arterial infusion over an extended period of time. For example, a liquid formulation may include at least about 0.05 mg/ml glibenclamide in a water-based solution including 40% polyethylene glycol 300, 10% Ethanol, 50% water, at about pH 9. The solution may include a buffer, and is suitable for storage in refrigerator or at room temperature. This solution may be diluted 1 : 1, or more (e.g., 1 :20) without precipitation of the glibenclamide.
摘要翻译：本发明提供了作用于适用于静脉内和动脉内输注的磺酰脲类受体的化合物的液体制剂。对磺酰脲受体具有活性的化合物包括格列本脲，甲苯磺丁脲，瑞格列奈，那格列奈，美格列奈，米格列唑，LY397364，LY389382，甘氨酰叠氮和格列美脲。液体制剂可以是适合储存的浓缩溶液; 可以被稀释（例如，1:1或1:1.2的稀释）适合于快速浓注，并且可以进一步稀释（例如1:10或1:20或更多的稀释）用于静脉内和动脉内输注延长一段时间。例如，液体制剂可以包含至少约0.05mg / ml格列本脲，所述基于水的溶液包含在约pH 9的40％聚乙二醇300,10％乙醇，50％水。该溶液可以包含缓冲剂，并且适合于在冰箱或室温下储存。该溶液可以1:1或更多（例如1:20）稀释而不沉淀格列本脲。

5. 发明申请

WO2017062765A1 METHODS OF TREATING INJURIES OR CONDITIONS RELATED TO CNS EDEMA 审中-公开
标题翻译：治疗与CNS EDEMA相关的伤口或病症的方法
公开(公告)号：WO2017062765A1
公开(公告)日：2017-04-13
申请号：PCT/US2016/055988
申请日：2016-10-07
申请人： REMEDY PHARMACEUTICALS, INC.
发明人： JACOBSON, Sven Martin
IPC分类号： A61K31/64
CPC分类号： A61K31/64 , A61K31/166 , A61K31/451
摘要： The present technology is related to reducing or treating neurological swelling and related conditions with SUR1-TRPM4 channel inhibitors. In some embodiments, the methods include: reducing late neurological deterioration or preventing death, reducing cerebral midline shift, reducing the degree of disability in a subject, counteracting blood glucose levels in a subject receiving a SUR1-TRPM4 channel inhibitor, preventing brain swelling, monitoring liver enzyme activity along with treating injury or conditions related to CNS edema, or monitoring cardiac activity along with treating injury or conditions related to CNS edema.
摘要翻译：本技术涉及减少或治疗SUR1-TRPM4通道抑制剂的神经肿胀和相关病症。在一些实施方案中，所述方法包括：减少晚期神经系统恶化或预防死亡，减少脑中线移位，降低受试者的残疾程度，抵消接受SUR1-TRPM4通道抑制剂的受试者的血糖水平，防止脑肿胀，监测肝酶活性以及与CNS水肿有关的损伤或病症，或监测心脏活动以及与CNS水肿相关的损伤或病症。

6. 发明申请

WO2012012347A3 METHODS OF INTRAVENOUS ADMINISTRATION OF GLYBURIDE AND OTHER DRUGS 审中-公开
公开(公告)号：WO2012012347A3
公开(公告)日：2012-01-26
申请号：PCT/US2011/044397
申请日：2011-07-18
申请人： REMEDY PHARMACEUTICALS, INC. , JACOBSON, Sven, Martin
发明人： JACOBSON, Sven, Martin
IPC分类号： A61K31/64 , A61K9/20 , A61K9/22 , A61P9/00 , A61P25/00
摘要： Methods of administering glyburide, or other drug, are disclosed. The novel methods disclosed herein include intravenous methods of administering glyburide, or other drug, over periods of more than an hour, preferably over periods of about 72 hours. The novel methods include administering a bolus of glyburide, or other drug, followed by a first continuous infusion administration of glyburide, or other drug; and optionally a second or further bolus administration of glyburide, or other drug, and/or a second or further continuous infusion administration of glyburide, or other drug. These methods are effective to rapidly achieve a desired level of glyburide, or other drug, and to provide a substantially steady level of glyburide, or other drug, over a desired period of time. The methods disclosed herein may be useful for treating a subject in need of treatment for, e.g., acute stroke (ischemic and hemorrhagic), traumatic brain injury (TBI), spinal cord injury (SCI), myocardial infarction (MI), shock (including hemorrhagic shock), organ ischemia, and ventricular arrhythmias. These methods provide for the rapid achievement and maintenance of therapeutic glyburide, or other drug, plasma levels over an extended period of time, and further avoid excessive levels of drug and so avoid possible drug side-effects.

7. 发明申请

WO2012012347A2 METHODS OF INTRAVENOUS ADMINISTRATION OF GLYBURIDE AND OTHER DRUGS 审中-公开
标题翻译：甘油三酯和其他药物的静脉内给药方法
公开(公告)号：WO2012012347A2
公开(公告)日：2012-01-26
申请号：PCT/US2011044397
申请日：2011-07-18
申请人： REMEDY PHARMACEUTICALS INC , JACOBSON SVEN MARTIN
发明人： JACOBSON SVEN MARTIN
IPC分类号： A61K31/64 , A61K9/20 , A61K9/22 , A61P9/00 , A61P25/00
CPC分类号： A61K9/0019 , A61K31/17 , A61K31/18 , A61K31/64
摘要： Methods of administering glyburide, or other drug, are disclosed. The novel methods disclosed herein include intravenous methods of administering glyburide, or other drug, over periods of more than an hour, preferably over periods of about 72 hours. The novel methods include administering a bolus of glyburide, or other drug, followed by a first continuous infusion administration of glyburide, or other drug; and optionally a second or further bolus administration of glyburide, or other drug, and/or a second or further continuous infusion administration of glyburide, or other drug. These methods are effective to rapidly achieve a desired level of glyburide, or other drug, and to provide a substantially steady level of glyburide, or other drug, over a desired period of time. The methods disclosed herein may be useful for treating a subject in need of treatment for, e.g., acute stroke (ischemic and hemorrhagic), traumatic brain injury (TBI), spinal cord injury (SCI), myocardial infarction (MI), shock (including hemorrhagic shock), organ ischemia, and ventricular arrhythmias. These methods provide for the rapid achievement and maintenance of therapeutic glyburide, or other drug, plasma levels over an extended period of time, and further avoid excessive levels of drug and so avoid possible drug side-effects.
摘要翻译：公开了施用格列本脲或其他药物的方法。本文公开的新颖方法包括施用格列本脲或其它药物的静脉注射方法，时间长于一小时，优选约72小时。所述新方法包括施用大剂量的格列本脲或其他药物，然后连续输注给予格列本脲或其他药物; 和任选地第二次或进一步推注格列本脲或其他药物，和/或第二次或进一步连续输注给予格列本脲或其它药物。这些方法有效地快速达到期望水平的格列本脲或其他药物，并且在期望的时间段内提供基本上稳定的格列本脲或其他药物水平。本文公开的方法可用于治疗需要治疗的受试者，例如急性中风（缺血性和出血性），创伤性脑损伤（TBI），脊髓损伤（SCI），心肌梗死（MI），休克（包括出血性休克），器官缺血和室性心律失常。这些方法提供了在长时间内快速获得和维持治疗性格列本脲或其他药物血浆水平，并进一步避免过量的药物，从而避免可能的药物副作用。

8. 发明申请

WO2009073711A1 IMPROVED FORMULATIONS AND METHODS FOR LYOPHILIZATION AND LYOPHILATES PROVIDED THEREBY 审中-公开
标题翻译：改进的柠檬酸和柠檬酸的配方和方法
公开(公告)号：WO2009073711A1
公开(公告)日：2009-06-11
申请号：PCT/US2008/085384
申请日：2008-12-03
申请人： REMEDY PHARMACEUTICALS, INC. , JACOBSON, Sven, Martin
发明人： JACOBSON, Sven, Martin
IPC分类号： A61K9/16 , A61K9/20 , A61K31/175
CPC分类号： A61K9/1682 , A61K9/0019 , A61K9/1611 , A61K9/1623 , A61K9/19 , A61K31/175 , A61K31/451 , A61K31/64 , Y10S514/96
摘要： The present invention provides compositions, methods for lyophilizing compounds and making pharmaceutical compositions, and kits providing solutions and lyophilized formulations of compounds. The compositions, methods, and kits are particularly useful in pharmaceutical applications involving therapeutic agents that have low solubility at low pH and medium pll values. Certain embodiments provide methods for lyophilizing compounds in liquid solutions, which include the steps of: a) preparing aqueous solutions of a compound of interest in the absence of buffer; b) adjusting the pH to high values of pH in order to increase the solubility of the compound of interest; and c) frecze-drying the solution to provide a lyophilized solid composition. Aqueous solutions including buffer are also disclosed. Lyophilized formulations, including micronized and non-micronized powders, are provided.
摘要翻译：本发明提供组合物，冻干化合物和制备药物组合物的方法，以及提供化合物溶液和冻干制剂的试剂盒。组合物，方法和试剂盒特别适用于涉及在低pH值和中等pll值下具有低溶解度的治疗剂的药物应用。某些实施方案提供了在液体溶液中冻干化合物的方法，其包括以下步骤：a）在不存在缓冲液的情况下制备目的化合物的水溶液; b）将pH调节至高的pH值，以增加目标化合物的溶解度; 和c）对溶液进行自由干燥以提供冻干的固体组合物。还公开了包括缓冲液的水溶液。提供冻干制剂，包括微粉化和非微粉化粉末。

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