公开(公告)号：US5514646A

公开(公告)日：1996-05-07

申请号：US57201

申请日：1993-05-05

Applicant: Ronald E. Chance ,  Richard D. DiMarchi ,  Bruce H. Frank ,  James E. Shields

Inventor： Ronald E. Chance ,  Richard D. DiMarchi ,  Bruce H. Frank ,  James E. Shields

IPC: A61K9/00 ,  A61K38/00 ,  C07K14/62 ,  A61K61/28

CPC classification number: C07K14/62 ,  C07K14/622 ,  A61K38/00 ,  A61K9/0043

Abstract: Analogs of human insulin modified at position 29 of the B chain thereof and, optionally, at other positions, have modified physico-chemical and pharmacokinetic properties and are useful in the treatment of hyperglycemia.

Abstract translation: 在其B链的29位和任选地在其它位置修饰的人胰岛素的类似物具有改变的物理化学和药代动力学性质，并且可用于治疗高血糖症。

公开(公告)号：US4421685A

公开(公告)日：1983-12-20

申请号：US262141

申请日：1981-05-11

Applicant: Ronald E. Chance ,  James A. Hoffmann

Inventor： Ronald E. Chance ,  James A. Hoffmann

IPC: C07K1/06 ,  C07K1/12 ,  C07C103/52 ,  C07G7/00

CPC classification number: C07K1/12 ,  C07K1/067

Abstract: Production of insulin or an insulin analog is provided by combination of an A-chain and a B-chain, which comprises bringing the S-sulfonated form of the A-chain, the S-sulfonated form of the B-chain, and a thiol reducing agent together in an aqueous medium under conditions which produce a mixture having (1) a pH of from about 8 to about 12, (2) a total protein concentration of from about 0.1 to about 50 milligrams per milliliter, and (3) an amount of thiol reducing agent which affords a total of from about 0.4 to about 2.5 --SH groups per each --SSO.sub.3.sup.- group present in the total amount of A- and B-chain S-sulfonates, and allowing formation of insulin or an insulin analog to occur by maintaining the mixture at a temperature of from about 0.degree. C. to about 25.degree. C. and in an environment which provides a source of oxygen.

Abstract translation: 通过A链和B链的组合提供胰岛素或胰岛素类似物的生产，其包括使S-链的S-磺化形式，S-链的S-磺化形式和硫醇 （1）pH为约8至约12，（2）总蛋白质浓度为约0.1至约50毫克每毫升的混合物的条件下，在水性介质中一起在水性介质中，和（3） 量的硫醇还原剂，其存在于A-和B-链S-磺酸盐的总量中的每个-SSO 3 - 基团总共为约0.4至约2.5个-SH基团，并且允许形成胰岛素或胰岛素类似物 通过将混合物保持在约0℃至约25℃的温度和在提供氧源的环境中进行。

公开(公告)号：US5700662A

公开(公告)日：1997-12-23

申请号：US465847

申请日：1995-06-06

Applicant: Ronald E. Chance ,  Richard D. DiMarchi ,  Bruce H. Frank ,  James E. Shields

Inventor： Ronald E. Chance ,  Richard D. DiMarchi ,  Bruce H. Frank ,  James E. Shields

IPC: A61K9/00 ,  A61K38/00 ,  C07K14/62 ,  C07K7/40 ,  A61K37/26

CPC classification number: C07K14/62 ,  C07K14/622 ,  A61K38/00 ,  A61K9/0043

Abstract: Recombinant processes for preparing insulin analogs modified at position 29 of the B-chain and, optionally, at other positions are claimed. The analogs produced using the claimed processes have modified physico-chemical properties and are useful in treating hyperglycemia.

Abstract translation: 要求保护用于制备在B链29位修饰的胰岛素类似物和任选地在其它位置的重组方法。 使用所要求保护的方法制备的类似物具有改变的物理化学性质并且可用于治疗高血糖症。

公开(公告)号：US4652548A

公开(公告)日：1987-03-24

申请号：US682204

申请日：1984-12-17

Applicant: Ronald E. Chance ,  Bruce H. Frank ,  John A. Galloway

Inventor： Ronald E. Chance ,  Bruce H. Frank ,  John A. Galloway

IPC: A61K38/28 ,  A61K37/26

CPC classification number: A61K38/28

Abstract: A pharmaceutical composition which comprises, in association with a pharmaceutically acceptable carrier, human insulin, human C-peptide, and human proinsulin, said human C-peptide being present in a molar ratio, human insulin to human C-peptide, of from about 1:4 to about 4:1, and said human proinsulin being present in a weight ratio, human insulin to human proinsulin, of from about 1:100 to about 100:1, is useful in treating diabetics and in promoting attainment of natural hormonal homeostasis, thereby preventing or substantially diminishing or retarding diabetic complications.

Abstract translation: 一种药物组合物，其包含与药学上可接受的载体结合的人胰岛素，人C肽和人胰岛素原，所述人C-肽以人胰岛素与人C肽的摩尔比计约为1 ：4至约4:1，并且所述人胰岛素原以约1:100至约100:1的重量比存在于人胰岛素原中，可用于治疗糖尿病并促进获得天然激素体内平衡 ，从而防止或显着减少或延缓糖尿病并发症。

公开(公告)号：US4654324A

公开(公告)日：1987-03-31

申请号：US682205

申请日：1984-12-17

Applicant: Ronald E. Chance ,  Bruce H. Frank ,  John A. Galloway

Inventor： Ronald E. Chance ,  Bruce H. Frank ,  John A. Galloway

IPC: A61K38/28 ,  A61K37/00

CPC classification number: A61K38/28

Abstract: A pharmaceutical composition which comprises human proinsulin in association with a pharmaceutically acceptable carrier is useful in controlling a diabetic condition and in promoting attainment of natural hormonal homeostasis, thereby preventing or substantially diminishing or retarding diabetic complications.

Abstract translation: 包含与药学上可接受的载体结合的人胰岛素原的药物组合物可用于控制糖尿病状况和促进天然激素体内平衡的实现，从而预防或显着减少或延缓糖尿病并发症。

公开(公告)号：US4652547A

公开(公告)日：1987-03-24

申请号：US682207

申请日：1984-12-17

Applicant: Ronald E. Chance ,  Bruce H. Frank ,  John A. Galloway

Inventor： Ronald E. Chance ,  Bruce H. Frank ,  John A. Galloway

IPC: A61K38/00 ,  A61K38/16 ,  A61K38/28 ,  A61K37/26

CPC classification number: A61K38/28

Abstract: A pharmaceutical composition which comprises, in association with a pharmaceutically acceptable carrier, human insulin and human proinsulin in a weight ratio, human insulin to human proinsulin, of from about 1:100 to about 100:1, is useful in treating diabetics and in promoting attainment of natural hormonal homeostasis, thereby preventing or substantially diminishing or retarding diabetic complications.

Abstract translation: 包含与药学上可接受的载体结合的人胰岛素和人胰岛素原的重量比为约1:100至约100:1的药物组合物可用于治疗糖尿病和促进 达到天然激素体内平衡，从而预防或显着减少或延缓糖尿病并发症。