Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Patent
1996-05-02
1999-01-12
Kishore, Gollamudi S.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
424456, 424489, 514937, 514941, A61K 914, A61K 948, A61K 9127
Patent
active
058583980
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/US94/12351 filed Nov. 3, 1994.
BACKGROUND OF THE INVENTION
The present invention relates generally to pharmaceutical compositions comprising microparticles suspended in micelle. More particularly, the microparticles comprise at least one pharmaceutically-active agent, at least one water soluble or miscible phospholipid, at least one lipid soluble or miscible phospholipid, at least one water soluble or miscible sterol, at least one non-ionic surfactant having an HLB value of about 15 or greater, and at least one non-ionic surfactant having an HLB value of about 6 or less, and the microparticles are suspended in micelle in at least one water soluble or miscible fatty acid having a chain length of C.sub.14 or less. This invention also relates to a method of preparing such compositions, methods of therapeutically treating various illnesses and conditions with such compositions, and methods of delivery of such compositions to human beings.
By binding a pharmaceutically-active agent (e.g. insulin) in accordance with this invention, enhanced bioavailability and bioactivity results from the bound pharmaceutically-active agent. For example, after oral or transdermal administration of the embodiment of this invention where insulin is the pharmaceutically-active agent, the composition is channeled into the liver, where the initially protected insulin is gradually released, mimicking an endogenously secreted insulin as found in human beings. An exogenous insulin, for example, has been successfully delivered by routes other than parenteral injection. The compositions of this invention may be applied by rectal, buccal, sublingual, intranasal, intrapulmonic, ocular or by other means of administration for management of disorders, for example diabetes mellitus. The compositions may be delivered selectively, after parenteral infusion, oral, transdermal, or other means of administration to achieve precise targeting of the pharmaceutically active agent to a given organ or tissues as a slow, controlled release-dosage formulation. The invention may be useful for, but not limited to, delivering pharmaceutically-active agents which include peptides (e.g. insulin), glycoproteins (e.g. erythropoietin), organic and inorganic chemicals (e.g. glyburide or steroids), herbals (e.g. vinca alkaloids), and other materials useful as pharmaceutically active agents.
For example, diabetes mellitus is a chronic disorder affecting carbohydrate, fat and protein metabolism. It is generally characterized by high blood sugar level (hyperglycemia) and sugar in urine (glycosurea) from a defective or deficient insulin secretory response. In the United States, over 10 million people are diagnosed as diabetics and this figure is increasing annually at a rate of about 6%. Two major variants of the disease exist. For about 10% of diabetics, the disease onsets as a juvenile insulinopenic diabetes requiring daily injection of insulin (referred to herein as insulin dependent diabetics or IDDM). The majority of diabetics are adult-onsetting diabetics (referred to herein as non-insulin dependent or NIDDM) for whom oral antihyperglycemics may be introduced to control hyperglycemia and glycosurea. Such compounds include chlorpropamide, tolbutamide (the first generation group of sulfonylureas), glyburide and glipizide (the second generation group). The sulfonylureas are believed to stimulate the beta cells of the pancreas, causing secretion of an endogenous insulin, and are also known to reduce hepatic production and to increase peripheral muscular utilization of glucose.
Ultimately, however, sulfonylureas will become less effective and eventually totally ineffective in lowering blood sugar in many long-term NIDDM patients, thus requiring injections of insulin as well, which causes restoration of the bioactivity of the sulfonyl urea (e.g. glyburide). According to one embodiment of the present invention, insulin-containing compositions of this invention, glyburide-containing compositions of this invention, and their combination m
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Isomed Inc.
Kishore Gollamudi S.
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