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1. 发明授权

US06323311B1 Synthesis of insulin derivatives 有权
标题翻译：胰岛素衍生物的合成
公开(公告)号：US06323311B1
公开(公告)日：2001-11-27
申请号：US09400942
申请日：1999-09-22
申请人： Feng Liu , Sung Wan Kim , Miroslav Baudys
发明人： Feng Liu , Sung Wan Kim , Miroslav Baudys
IPC分类号： A61K3828
CPC分类号： C07K14/62 , A61K38/00 , A61K47/60 , Y02P20/55
摘要： A method for the “one-pot” synthesis of insulin derivatives wherein insulin is modified at the &agr;-amino group of the PheB1 residue is described. The method comprises protecting the &agr;-amino group of the GlyA1 residue and the &egr;-amino group of the LysB29 residue by reaction of insulin with a cyclic anhydride of a dicarboxylic acid in the presence of a tertiary amine. The protected insulin is then reacted with an activated hydrophilic compound, preferably an activated polyethylene glycol, resulting in a conjugate of the hydrophilic compound coupled to the PheB1 residue of insulin. The protecting groups are then removed from the conjugate under mild acidic conditions, and the resulting insulin derivative can be purified by conventional methods. Monosubstituted insulin derivatives wherein polyethylene glycol or derivatives thereof or glycosides are coupled to the PheB1 residue of insulin are also described.
摘要翻译：描述了在PheB1残基的α-氨基处修饰胰岛素的“一锅”合成胰岛素衍生物的方法。该方法包括在叔胺存在下，通过胰岛素与二羧酸的环状酸酐的反应来保护GlyA1残基的α-氨基和LysB29残基的ε-氨基。然后将受保护的胰岛素与活化的亲水化合物，优选活化的聚乙二醇反应，得到与胰岛素的PheB1残基偶联的亲水性化合物的缀合物。然后在温和的酸性条件下将保护基团从缀合物中除去，所得到的胰岛素衍生物可以通过常规方法纯化。还描述了其中聚乙二醇或其衍生物或糖苷偶联至胰岛素的PheB1残基的单取代胰岛素衍生物。

2. 发明授权

US5726154A Stabilization and oral delivery of calcitonin 失效
标题翻译：降钙素的稳定和口服递送
公开(公告)号：US5726154A
公开(公告)日：1998-03-10
申请号：US671870
申请日：1996-06-28
申请人： Miroslav Baudys , Sung Wan Kim
发明人： Miroslav Baudys , Sung Wan Kim
IPC分类号： A61K38/23 , A61K38/00 , A61K38/02 , A61K38/30 , C07K5/00
CPC分类号： A61K38/23
摘要： Compositions and methods for stabilization and oral delivery of human calcitonin are described. An aqueous liquid composition for stable storage of human calcitonin comprises an aqueous mixture of SDS and an organic acid. An nonaqueous liquid composition for stable storage of human calcitonin comprises about 90-100% by volume of a mixture of C.sub.8 /C.sub.10 mono- and di-glycerides and about 0-10% by volume of a polar, nonaqueous solvent. Both of these stabilized human calcitonin formulations provided significant intestinal absorption of calcitonin.
摘要翻译：描述了人类降钙素稳定和口服递送的组合物和方法。用于稳定储存人降钙素的水性液体组合物包括SDS和有机酸的水性混合物。用于稳定储存人降钙素的非水液体组合物包含约90-100体积％的C8 / C10单甘油酯和二甘油酯的混合物和约0-10体积％的极性非水溶剂。这两种稳定的降钙素制剂都能提供显着的降钙素吸收。

3. 发明申请

US20060159657A1 Formulations of lymphokines and method of use thereof for local or both local and systemic control of proliferative cell disorders 审中-公开
标题翻译：淋巴因子的制剂及其用于局部或局部和全身控制增殖性细胞病症的方法
公开(公告)号：US20060159657A1
公开(公告)日：2006-07-20
申请号：US11386156
申请日：2006-03-21
申请人： Kirk Fowers , Gaylen Zentner , Miroslav Baudys , Maria Jurek , Wolfram Samlowski
发明人： Kirk Fowers , Gaylen Zentner , Miroslav Baudys , Maria Jurek , Wolfram Samlowski
IPC分类号： A61K38/20 , A61K9/14
CPC分类号： A61K38/2013 , A61K9/0019 , A61K9/0024 , A61K47/10 , A61K47/34 , C08G63/664 , C08G2261/126 , C08L71/02 , C08L2203/02
摘要： Therapeutic formulations comprising an effective amount of IL-2 or other lymphokine and a biodegradable polymeric carrier having reverse gelation properties and the methods of use thereof for local or both local and systemic control of proliferative cell disorders is disclosed. The formulation can be administered intratumorally/peritumorally and forms an IL-2 containing depot. The IL-2-containing depot provides for continuous, prolonged release of IL-2 sufficient to stimulate the production of cytotoxic T lymphocytes which function both locally and systemically, without causing unacceptable side effects.
摘要翻译：公开了包含有效量的IL-2或其它淋巴因子和具有反向凝胶化特性的可生物降解的聚合物载体的治疗剂型及其用于局部或局部和全身控制增殖性细胞病症的方法。该制剂可以肿瘤内/周围给药并形成含IL-2的贮库。含IL-2的贮存库提供足够的IL-2连续延长释放，以足以刺激局部和全身功能的细胞毒性T淋巴细胞的产生，而不引起不可接受的副作用。

4. 发明授权

US06465694B1 Method for preparation of polyethylene glycol aldehyde derivatives 有权
标题翻译：聚乙二醇醛衍生物的制备方法
公开(公告)号：US06465694B1
公开(公告)日：2002-10-15
申请号：US09830470
申请日：2001-06-04
申请人： Miroslav Baudys , Feng Liu , Sung Wan Kim
发明人： Miroslav Baudys , Feng Liu , Sung Wan Kim
IPC分类号： C07C4310
CPC分类号： C07K1/1077 , C07C45/38 , C07C47/198 , C07C213/02 , C07C227/18 , C07C229/26 , C07C241/02 , C07C319/12 , C08G65/324 , C07C323/25 , C07C217/28 , C07C217/42 , C07C243/14
摘要： Aldehyde derivatives of polyethylene glycols and methods of making thereof are disclosed. These aldehyde derivatives can be used to make polyethylene glycol-hydrazines, polyethylene glycol-thiols, polyethylene glycol amines, and branched polyethylene glycols. PEG aldehyde derivatives or other functional PEG derivatives prepared from PEG aldehydes are useful for protein conjugation and surface modification.
摘要翻译：公开了聚乙二醇的醛衍生物及其制备方法。这些醛衍生物可用于制备聚乙二醇 - 肼，聚乙二醇 - 硫醇，聚乙二醇胺和支链聚乙二醇。由PEG醛制备的PEG醛衍生物或其它功能性PEG衍生物可用于蛋白质缀合和表面改性。

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