Eli Lilly and Company

Other

Thermalin, Inc.

Thermalin Diabetes, Inc.

Bruce H Frank

Ronald E Chance

Allen H Pekar

John A Galloway

Michael Rosario DeFelippis

Shun Li

Michael Allen Dobbins

Dawn Marie Rebhun

Richard Dennis DiMarchi

Michael A Weiss

James E Shields

Henry Acken Havel

Michael R De Felippis

Thomas Hattier

Gregory Dubé

Richard William Berenson

Zhiqiang Chen

Jeffrey I Joseph

Jeffrey C Baker

Richard E Heiney

David N Brems

Diane L Bakaysa

Walker E Prouty

Mark R Walden

James H Anderson, Jr

Nancy D Carter

The present invention provides rapid-acting insulin and insulin analogue formulations. The invention further provides delivery devices, particularly infusion sets, which allow for the rapid absorption of insulin and insulin analogues, as well as other active agents. Methods of using the insulin and insulin analogue formulations as well as the insulin delivery devices for treating subjects with diabetes mellitus are also provided.

Rapid action insulin formulations and pharmaceutical delivery systems

The present invention provides rapid-acting insulin and insulin analog formulations. The invention further provides delivery devices, particularly infusion sets, which allow for the rapid absorption of insulin and insulin analogs, as well as other active agents. Methods of using the insulin and insulin analog formulations as well as the insulin delivery devices for treating subjects with diabetes mellitus are also provided.

The present invention provides a monomeric insulin analog formulation stabilized against aggregation in which the buffering agent is either TRIS or arginine. The stable formulations of the present invention are useful for treating diabetes, and are particularly advantageous in treatment regimes requiring lengthy chemical and physical stability, such as, in continuous infusion systems.

Stable insulin formulations

The present invention discloses various parenteral pharmaceutical formulations having a protracted effect, which comprise: a sterile aqueous suspension of about 20 U/mL to about 500 U/mL insulin analog, about 5 mg/mL to about 10 mg/mL sodium chloride, about 0.2 to about 2.0 mg/mL physiologically acceptable buffer, a zinc ion content of about 0.07 mg/mL to about 0.1 mg/mL, and a physiologically acceptable preservative at a pH of about 6.5 to about 7.8; such that less than 5% of the analog present in the suspension is in the dissolved state.

Monomeric insulin analog formulations

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.

Process for preparing insulin analogs

The present invention discloses various parenteral pharmaceutical formulations, which comprise a mixture of a monomeric insulin analog and insulin-NPH. The analog formulations provide a rapid onset and a prolonged duration of action.

Insulin analog formulations

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.

Insulin analogs modified at position 29 of the B chain

The present invention discloses a process of preparing a crystalline insulin analog. The process is useful in the purification and manufacture of Lys.sup.B28 Pro.sup.B29 -human insulin. Lys.sup.B28 Pro.sup.B29 -human insulin is useful in the treatment of diabetes.

Preparation of stable zinc insulin analog crystals

The present invention discloses a human insulin analog hexamer complex and formulations. More specifically, the present invention relates to various parenteral formulations, which comprise: human insulin analogs in a hexamer conformation, zinc ions, and at least three molecules of a phenolic derivative selected from the group consisting of m-cresol, phenol, or a mixture of m-cresol and phenol. The formulation provides a rapid onset of action.

This specification describes a process for converting a human insulin precursor to human insulin, which comprises treating such human insulin precursor with trypsin and carboxypeptidase B in an aqueous medium containing per mole of human insulin precursor from about 0.1 to about 10 moles of one or more metal ions of those metals having Atomic Numbers 21 to 34, 39 to 52, 57 to 84, and 89 to 92.

Process for transforming a human insulin precursor to human insulin

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.

Human proinsulin pharmaceutical formulations

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.

Pharmaceutical formulations comprising human insulin and human proinsulin

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.

Growing community of inventors

Indianapolis, IN, United States of America

Bruce H Frank