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1. 发明公开

EP3150255A1 COMPOSITIONS AND METHODS FOR BONE FORMATION AND REMODELING 审中-公开
标题翻译： ZUSAMMENSETZUNGEN UND VERFAHREN ZUR KNOCHENBILDUNG UND -UMFORMUNG
公开(公告)号：EP3150255A1
公开(公告)日：2017-04-05
申请号：EP16000780.3
申请日：2005-05-18
申请人： Enzo Therapeutics, Inc. , Zhang, Yazhou , Liu, Peng , Li, Xiaofeng , Zhang, Jie , Shan, Jufang , Engelhardt, Dean
发明人： Enzo Therapeutics, Inc. , Zhang, Yazhou , Liu, Peng , Li, Xiaofeng , Zhang, Jie , Shan, Jufang , Engelhardt, Dean
IPC分类号： A61P19/00 , A61P19/08 , A61P19/10 , A61K31/00 , G01N33/68 , A61K38/16
CPC分类号： G01N33/6893 , A61K38/00 , G01N33/6887 , G01N2500/00 , G01N2800/10 , G01N2800/108
摘要： The mechanism by which the high bone mass (HBM) mutation (G171V) of the Wnt coreceptor LRP5 regulates the canonical Wnt signaling was investigated. The mutation was previously shown to reduce Dkk protein-1-mediated antagonism, suggesting that the first YWTD repeat domain where G171 is located may be responsible for Dkk protein-mediated antagonism. However, we found that the third YWTD repeat, but not the first repeat domain, is required for DKK1-mediated antagonism. Instead, we found that the G171V mutation disrupted the interaction of LRP5 with Mesd, a chaperon protein for LRP5/6 molecules on the cell surface. Although the reduction in the level of cell surface LRP5 molecules led to a reduction in Wnt signaling in a paracrine paradigm, the mutation did not appear to affect the activity of coexpressed Wnt in an autocrine paradigm. Together with the observation that osteoblast cells produce autocrine canonical Wnt, Wnt7b, and that osteocytes produce paracrine Dkkl, we believe that the G171V mutation may cause an increase in Wnt activity in osteoblastls by reducing the numnber of targets for paracrine Dkkl to antagonize without affecting the activity of autocrine Wnt.
摘要翻译：研究了Wnt共同受体LRP5的高骨量（HBM）突变（G171V）调节规范Wnt信号传导的机制。以前显示突变以减少Dkk蛋白-1介导的拮抗作用，表明G171位于第一个YWTD重复结构域可能是Dkk蛋白介导的拮抗作用的原因。然而，我们发现第三个YWTD重复，但不是第一个重复结构域，是DKK1介导的拮抗作用所必需的。相反，我们发现G171V突变破坏了LRP5与Mesd的相互作用，Mesd是细胞表面上LRP5 / 6分子的伴侣蛋白。尽管细胞表面LRP5分子水平的降低导致旁分泌范例中Wnt信号传导的降低，但突变似乎并不影响共表达的Wnt在自分泌范式中的活性。连同观察到成骨细胞产生自分泌标准Wnt，Wnt7b，并且该骨细胞产生旁分泌Dkk1，我们认为G171V突变可能通过减少旁分泌Dkk1靶向拮抗的目标数量而引起成骨细胞中Wnt活性的增加，而不影响成骨细胞自分泌Wnt的活性。

2. 发明公开

EP2846748A1 SHEET AND LIQUID COMBINATION SYSTEMS FOR DERMAL DELIVERY OF LIDOCAINE, DICLOFENAC, AND OTHER DRUGS 审中-公开
标题翻译：电影和液体组合的系统FOR利多卡因，双氯芬酸和其它药剂的真皮递送
公开(公告)号：EP2846748A1
公开(公告)日：2015-03-18
申请号：EP13787145.5
申请日：2013-05-08
申请人： Zhang, Jie
发明人： Zhang, Jie
IPC分类号： A61F13/02
CPC分类号： A61K9/703 , A61K31/167 , A61K31/192 , A61K31/196 , A61K31/445
摘要： A system for dermal delivery of lidocaine, bupivacaine, diclofenac, or ketoprofen is provided which comprises at least two components, for example, a sheet of a solid and flexible material, and a vehicle liquid comprising a solvent and optionally other ingredients. A drug, selected from group consisting of lidocaine, bupivacaine, diclofenac, and ketoprofen, can be impregnated in the sheet or contained in the vehicle liquid. These two components can be stored separately and joined either shortly before or at the time of application. To use the system, the vehicle liquid may be applied either on the target skin area or on the sheet, and the sheet may then be applied on the target skin area so that the vehicle liquid is positioned between the sheet and the skin and brought into contact with the ingredients impregnated in the sheet.

3. 发明公开

EP2413837A1 METHODS FOR TREATING MYOFASCIAL, MUSCLE, AND/OR BACK PAIN 审中-公开
标题翻译：方法肌筋膜，肌肉和背部疼痛治疗
公开(公告)号：EP2413837A1
公开(公告)日：2012-02-08
申请号：EP10759386.5
申请日：2010-04-01
申请人： Zhang, Jie , Crockett, Andrew , Rigby, Larry
发明人： Zhang, Jie , Crockett, Andrew , Rigby, Larry
IPC分类号： A61F2/00
CPC分类号： A61K9/0004 , A61F7/034 , A61F2007/0226 , A61F2007/0257 , A61F2007/0261 , A61K9/7084
摘要： The present disclosure is drawn to methods for treating myofascial pain, muscle pain, back pain, or combinations of these pains. Specifically, a method for treating myofascial pain, muscle pain, back pain, or combinations thereof includes the application of an analgesic system to a skin surface of a subject experiencing the pain and maintaining the analgesic system on the skin surface for a period of time of at least 30 minutes. The analgesic system applied to the skin surface can include a heating component and a local anesthetic formulation which includes at least one local anesthetic. The heating component can be capable of heating the skin surface to a temperature of 36 0C to 42 0C.

4. 发明公开

EP3741364A1 PHARMACEUTICAL COMPOSITION, PATCH AND MANUFACTURING METHOD THEREOF, ANALGESIC METHOD, AND APPLICATION 审中-公开
公开(公告)号：EP3741364A1
公开(公告)日：2020-11-25
申请号：EP19741485.7
申请日：2019-01-16
申请人： Zhang, Jie
发明人： Zhang, Jie
IPC分类号： A61K31/167 , A61K31/245 , A61K31/445 , A61K45/00 , A61K47/32 , A61P23/02
摘要： The present invention provides a pharmaceutical composition, a patch and a manufacturing method thereof, an analgesic method, and an application. The pharmaceutical composition comprises a single anesthetic active ingredient. The anesthetic active ingredient comprises a water-dissolving anesthetic active ingredient and an anesthetic active ingredient existing in an insoluble form. The mass percent content of the anesthetic active ingredient in the pharmaceutical composition is 2% or more. The mass percent content of the water-dissolving anesthetic active ingredient in the pharmaceutical composition is 1% or less. The anesthetic active ingredient comprises lidocaine, tetracaine, bupivacaine, articaine, cinchocaine, dibucaine, etidocaine, levobupivacaine, mepivacaine, prilocaine, ropivacaine, trimecaine, benzocaine or procaine. The pharmaceutical composition and the patch can provide continuous analgesia for 12-30 hours. The patch is resistant to a certain amount of external squeezing force, preventing a formulation layer covered by the same from being squeezed out, thereby maintaining the thickness of the formulation layer.

5. 发明公开

EP2637647A2 SHEET AND LIQUID COMBINATION SYSTEMS FOR DERMAL DRUG DELIVERY 审中-公开
标题翻译：电影和液体组合的系统用于皮肤-RELEASE
公开(公告)号：EP2637647A2
公开(公告)日：2013-09-18
申请号：EP11839487.3
申请日：2011-11-08
申请人： Zhang, Jie
发明人： Zhang, Jie
IPC分类号： A61K9/70
CPC分类号： A61F13/00063 , A61K9/7023
摘要： A dermal drug delivery system is provided which comprises at least two components, for example, a sheet of a solid and flexible material, and a vehicle liquid comprising a solvent and optionally other ingredients. A drug, which can be unstable in said solvent but needs the solvent for being delivered into the skin, can be impregnated in the sheet. Other ingredients, such as agents for fastening the drug on the sheet can also be impregnated in the sheet. These two components may be stored separately and joined either shortly before or at the time of application. To use the system, the vehicle liquid may be applied either on the target skin area or on the sheet, and the sheet may then be applied on the target skin area so that the vehicle liquid is positioned between the sheet and the skin and brought into contact with the ingredients impregnated in the sheet. After the sheet and the vehicle liquid are combined in this way, the ingredients in the sheet and in the vehicle liquid are joined to form a combined formulation that is capable of delivering a drug through the skin at a desired rate. The sheet may have low enough permeability to the solvent or its vapor to control the time it takes for the solvent to evaporate across the sheet. When an appropriate local anesthetic agent, such as a tetracaine, is the drug, some embodiments of the system can have wide applications in anesthesia and pain control.

6. 发明公开

EP2378873A1 METHOD OF TREATING NEUROPATHIC PAIN 有权转让
标题翻译：治疗神经性疼痛的方法
公开(公告)号：EP2378873A1
公开(公告)日：2011-10-26
申请号：EP10729463.9
申请日：2010-01-06
申请人： Zhang, Jie
发明人： Zhang, Jie
IPC分类号： A01N37/12 , A01N37/44 , A61K31/24
CPC分类号： A61K31/24 , A61K9/7015 , A61K31/167 , A61K47/32 , A61K2300/00
摘要： A method for treating subjects experiencing neuropathic pain is provided. The method involves the application of a solid-forming local anesthetic formulation to a skin surface of the subject experiencing the neuropathic pain and then maintaining the formulation on the skin surface for a period of time sufficient to allow itself to transdermally deliver the local anesthetic to the subject thereby providing relief from the neuropathic pain within about 45 minutes.
摘要翻译：提供了用于治疗经历神经性疼痛的受试者的方法。该方法涉及将形成固体的局部麻醉剂制剂施用于经历神经性疼痛的受试者的皮肤表面，然后将制剂维持在皮肤表面上一段时间，该时间足以使其自身经皮递送局部麻醉剂至因此受试者在约45分钟内提供了神经性疼痛的缓解。

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