公开(公告)号：US06812362B2

公开(公告)日：2004-11-02

申请号：US10268155

申请日：2002-10-10

申请人： Nnochiri N. Ekwuribe ,  Kenneth D. James, Jr.

发明人： Nnochiri N. Ekwuribe ,  Kenneth D. James, Jr.

IPC分类号： C07C25550

CPC分类号： C07C253/30 ,  C07C315/04 ,  C07C317/46 ,  C07C255/60

摘要： Methods of synthesizing an acylanilide include contacting a compound having the structure of Formula I: with a compound having the structure of Formula II: under conditions sufficient to provide a compound having the structure of Formula III: and treating the compound of Formula III under conditions sufficient to provide an acylanilide. The compound of Formula III may be addition reacted with a compound having the structure of Formula IV: R5—X1—R6—R7   Formula IV under conditions sufficient to provide an acylanilide having the structure of Formula V:

摘要翻译： 合成酰基酰苯胺的方法包括使具有式I结构的化合物与具有式II结构的化合物接触：在足以提供具有式III结构的化合物的条件下：在足够的条件下处理式III化合物 以提供酰基苯胺。 式III的化合物可以与具有式IV结构的化合物反应：在足以提供具有式V结构的酰基酰苯胺的条件下：

公开(公告)号：US5359030A

公开(公告)日：1994-10-25

申请号：US59701

申请日：1993-05-10

申请人： Nnochiri N. Ekwuribe

发明人： Nnochiri N. Ekwuribe

IPC分类号： A61K38/00 ,  A61K9/107 ,  A61K9/48 ,  A61K38/04 ,  A61K38/11 ,  A61K38/21 ,  A61K38/22 ,  A61K38/23 ,  A61K38/26 ,  A61K38/27 ,  A61K38/28 ,  A61K38/35 ,  A61K38/43 ,  A61K38/44 ,  A61K38/46 ,  A61K38/48 ,  A61K47/48 ,  A61K49/00 ,  A61P3/10 ,  A61P5/50 ,  C07K1/107 ,  C07K14/00 ,  C07K14/62 ,  C08G65/26 ,  C08G69/10 ,  C08G69/40 ,  C08G81/02 ,  C08L71/02 ,  C12N9/96 ,  C07K7/40 ,  C07K7/36 ,  C07K17/08 ,  C08H1/00

CPC分类号： C12N9/96 ,  A61K47/48169 ,  A61K47/48215 ,  A61K9/1075 ,  C07K1/1077 ,  C07K14/62 ,  A61K38/00 ,  A61K9/4858

摘要： A stabilized conjugated peptide complex comprising a peptide conjugatively coupled to a polymer including lipophilic and hydrophilic moieties, wherein the peptide may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, and papain. In a particular aspect, the invention comprises an insulin composition suitable for parenteral as well as non-parenteral administration, preferably oral or parenteral administration, comprising insulin covalently coupled with a polymer including (i) a linear polyalkylene glycol moiety and (ii) a lipophilic moiety, wherein the insulin, the linear polyalkylene glycol moiety and the lipophilic moiety are conformationally arranged in relation to one another such that the insulin in the composition has an enhanced in vivo resistance to enzymatic degradation, relative to insulin alone. One, two, or three polymer constituents may be covalently attached to the insulin molecule, with one polymer constituent being preferred. The conjugates of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications, and the peptide and polymer may be covalently coupled to one another, or alternatively may be associatively coupled to one another, e.g., by hydrogen bonding or other associative bonding relationship.

摘要翻译： 稳定的共轭肽复合物，其包含与包含亲脂性和亲水部分的聚合物共轭偶联的肽，其中所述肽可以例如选自胰岛素，降钙素，ACTH，胰高血糖素，生长抑素，生长激素，生长因子，甲状旁腺激素，促红细胞生成素 ，下丘脑释放因子，催乳素，促甲状腺激素，内啡肽，脑啡肽，加压素，非天然存在的阿片样物质，超氧化物歧化酶，干扰素，天冬酰胺酶，精氨酸酶，精氨酸脱胺酶，腺苷脱氨酶，核糖核酸酶，胰蛋白酶，糜蛋白酶和木瓜蛋白酶。 在一个特定方面，本发明包括适于肠胃外和非肠胃外给药的胰岛素组合物，优选口服或非肠道给药，其包含与聚合物共价偶联的胰岛素，所述聚合物包括（i）线性聚亚烷基二醇部分和（ii）亲脂性 部分，其中胰岛素，线性聚亚烷基二醇部分和亲脂性部分相对于彼此构象地排列，使得组合物中的胰岛素相对于单独的胰岛素具有增强的体内抗酶降解性。 一个，两个或三个聚合物组分可以共价连接到胰岛素分子上，其中一种聚合物成分是优选的。 本发明的缀合物有用地用于治疗和非治疗，例如诊断，应用，并且肽和聚合物可以彼此共价偶联，或者可以彼此相互偶联，例如通过氢 键合或其他缔合键合关系。