Emisphere Technologies, Inc.

Novartis Ag

Michael M Goldberg

Ehud Arbit

Shingai Majuru

Simon David Bateman

Rajesh K Agarwal

Joseph Ault

Joseph Sikora

Joseph Zielinski

Kiran Chaudhary

Subash Patel

Rebecca F Yang

Moise Azria

JoAnne P Corvino

William Elliot Bay

Steven Minh Dinh

Puchun Liu

William Elliott Bay

Vivien Wong

Richat Abbas

Donald J Sarubbi

Nai Fang Wang

Shingal Majuru

Shingai Majura

T Cooper Woods

JoAnne P Russo

Mosise Azria

Joanne P Russo

Joseph Murray Ault

Joseph L Zielinski

Rebecca Fai-Ying Yang

The present invention provides a topical composition comprising (a) at least one delivery agent compound and (b) a cromoglycic acid compound. Methods of treatment, and methods of preparing the topical composition are also provided.

Topical cromolyn formulations

The present invention provides a composition (e.g., a pharmaceutical composition) comprising at least one delivery agent compound and glucagon. Preferably, the composition includes a therapeutically effective amount of glucagon and the delivery agent compound. The composition of the present invention facilitates the delivery of glucagon and increases its bioavailability compared to administration without the delivery agent compound.

Intraoral dosage forms of glucagon

Methods for treating impaired glucose tolerance and early and late stage diabetes in mammals, for prophylactically sparing &#x3b2;-cell function, aiding in preventing &#x3b2;-cell death, preventing the onset of overt diabetes in a mammal with type 2 diabetes, treating the current level of glycemic control dysfunction of a mammal with impaired glucose tolerance or diabetes, comprising orally administering insulin and a delivery agent that facilitates insulin absorption from the gastrointestinal tract at the time of or shortly before mealtime, e.g., within about 10 minutes prior to ingestion of a meal, on a chronic basis. The methods also comprise, in addition to administering a rapid-acting insulin to provide a first insulin peak, administering a slow acting insulin to provide a second insulin peak occurring at a later time but of a longer duration. These methods achieve improved glycemic control without the risks of hypoglycemia, hyperinsulinemia and weight gain and the need for frequent blood glucose monitoring that are normally associated with insulin therapy.

Oral insulin therapies and protocol

The inventors have discovered that the disodium salt of certain delivery agents has surprisingly greater efficacy for delivering active agents than the corresponding monosodium salt. Furthermore, the inventors have discovered that the disodium salts of these delivery agents form solvates with ethanol and hydrates with water. Preferred delivery agents include, but are not limited to, N-(5-chlorosalicyloyl)-8-aminocaprylic acid (5-CNAC), N-(10-[2-hydroxybenzoyl]amino)decanoic acid (SNAD), and sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC). The invention also provides methods of preparing the disodium salt, ethanol solvate, and hydrate and compositions containing the disodium salt, ethanol solvate, and/or hydrate.

Disodium salts, monohydrates, and ethanol solvates for delivering active agents

An oral dosage form comprises cromolyn sodium (sodium or disodium cromoglycate), and an acylated amino acid delivery agent.

Formulations for oral administration of cromolyn sodium

The inventors have discovered that the disodium salt of certain delivery agents has surprisingly greater efficacy for delivering active agents than the corresponding monosodium salt. Furthermore, the inventors have discovered that the disodium salts of these delivery agents form solvates with ethanol and hydrates with water. The delivery agents have the formula wherein

Pharmaceutical dosage forms for oral administration to a patient for the treatment of diabetes, comprising insulin and a delivery agent that facilitates insulin transport in a therapeutically effective amount to the bloodstream and that result in a lower incidence of vascular diseases associated with the repeated administration of insulin are disclosed. Also disclosed is a method of attenuating the undesirable incidence of diseases associated with chronic dosing of insulin is provided whereby the oral administration to a patient of insulin along with a suitable delivery agent that facilitates the absorption of insulin from the gastrointestinal tract of the patient in a therapeutically effective amount, for treatment of diabetes.

Oral insulin therapy

A method for protection of a mammal that has impaired glucose tolerance or early stage diabetes mellitus from developing overt or insulin dependent diabetes comprises administering an orally effective dose of a pharmaceutical formulation comprising insulin at nighttime, e.g., at or shortly before bedtime.

Night-time oral insulin therapy

Growing community of inventors

Englewood, NJ, United States of America

Michael M Goldberg