Vestar, Inc.

Allergan, Inc.

Eric A Forssen

Patrick Michael Hughes

Ester Fernandez-Salas

Joseph Francis

Terrence J Hunt

David C Rupp

Ron S Broide

Gary Shimizu

Pharmaceutical formulations comprising a clostridial derivative and a permeabilizing agent for intravesical instillation are disclosed.

Formulations of biologics for intravesical instillation

Compositions comprising phospholipid-encapsulated vesicles of active ingredient and triglyceride are described. In a preferred embodiment the vesicles are composed of a hexamethylmelamine active ingredient, with trilaurin or trimyristin as the triglyceride and a mixture of distearoylphosphatidylcholine, distearoylphosphatidylglycerol and cholesterol in the phospholipid outer layer. Preferably the molar ratios of active ingredient: triglyceride: DSPC: CHOL:DSPG will be from about 1:4:2:1:0 to about 1:4:1:1:1. Glycerol may be added to the carrier phase to reduce agglomeration. The composition may be used to deliver otherwise aqueous-insoluble agents to humans or animals to treat, for example, tumors.

Phospholipid delivery vehicle for aqueous-insoluble active ingredients

Novel liposome-entrapped cationic, lipophilic drug compositions, e.g., anthracycline antineoplastic agent compositions, and multistep entrapment/loading procedures for preparing them are disclosed. These procedures involve forming liposomes from phospholipids, such as distearoyl phosphatidylcholine or a similar long chain fatty acid diester phospholipid, to be loaded with the drug, e.g., daunorubicin or doxorubicin, in aqueous medium in the presence of an acid, e.g., an organic acid which can be monofunctional pyranosidyl acid such as lactobionic acid, adding the drug, and then adding a base such as calcium carbonate whose cations cannot pass through the vesicles' bilayers to charge neutralize the organic acid anions in the external aqueous phase and induce the acid anions in the internal aqueous phase to become neutralized by attracting the cationic, lipophilic drug.

Multiple step entrapment/loading procedure for preparing lipophilic

Formulations consisting of phospholipid bilayer membrane particles made from mixtures of anionic and neutral phospholipids encapsulating anthracycline anti-neoplastic agents, suspended in a low ionic strength aqueous phase, are described. In a preferred embodiment, the particles are in the form of vesicles which comprise daunorubicin, distearoyl phosphatidylglycerol and distearoyl phosphatidylcholine, the mol ratio of daunorubicin to distearoyl phosphatidylglycerol is at least about 1:1.25, and the suspending medium is an aqueous lactose solution containing a small amount of base.

Growing community of inventors

La Canada, CA, United States of America

Eric A Forssen