Hepatocyte Directed Vesicle delivery system

• US 4,603,044 A
• Filed: 05/03/1984
• Issued: 07/29/1986
• Est. Priority Date: 01/06/1983
• Status: Expired due to Term

• Current Assignee: Calfee, Halter & Griswold LLP
• Original Assignee: Technology Unlimited Incorporated
• Inventors: Geho, W. Blair, Lau, John R.
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Brookes, Anne
• Application Number:
  US06/606,714
• Time in Patent Office: 817 Days
• Field of Search: 428/402.2, 424/178, 424/38, 424/9, 424/1.1, 436/829
• US Class Current: 424/450
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 8/14 Liposomes; Vesicles
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61Q 11/00 Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
• CPC Class Codes: Y10S 436/829 Liposomes, e.g. encapsulation
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

Abstract

A targeted drug delivery system which has specificity for hepatobiliary receptors, which are the specialized metabolic cells of the liver. Hereinafter, this will be referred to as a Hepatocyte Directed Vesicle, or abbreviated as HDV. This preferred directed delivery system utilizes a bipolar lipid for the majority of its vesicle membrane structure.

The targeting material, which is only a minor constituent of a targeted vesicle system, has a specificity for hepatobiliary receptors of the liver. The Hepatocyte Directed Vesicle is then attracted to the receptor, and the vesicle releases its pharmacological cargo.

This disclosure specifies that the attachment of the targeting material, or molecule, to the vesicle is preferably done by first providing a connector molecule, having a portion inserted into the wall of the vesicle, by reason of being lipophilic, and a portion which is hydrophilic and is projected from the vesicle wall.

The target, by connector molecules, are tied together to extend or project the target molecule a distance from the vescile wall.

Any chemical molecule capable of circulating in the bloodstream of a warm-blooded animal and attracted to the hepatobiliary receptors will serve as a target substance for this invention.

This invention is in the discovery of a unique and unprecedented result of directing a vesicle containing a pharmacological load to the hepatobiliary receptors.

Claims

1. A composition of matter for internal administration in the therapeutic treatment of a warm-blooded animal comprising:

a first component which is a drug or diagnostic agent, said first component being encapsulated in or associated with;

a second component which comprises lipid membrane structures in the form of vesicles or liposomes; and

a third component which is a molecule having a fatty substituent attached to the vesicle wall and a target substituent selected from the class consisting of those chemicals which are classed biologically as biliary attracted chemicals.

2. A composition of matter as defined in claim 1 wherein the third component target substituent is a substituted iminodiacetate complex.

3. A composition of matter as defined in claim 1 wherein the third component is two substantially identical substituents joined by a bridge molecule.

4. A composition of matter as defined in claim 1 wherein the third component is two substituted iminodiacetate complex molecules joined by a bridge molecule.

5. The method of preparing a composition of matter for delivering a dose of hepatic therapeutic chemical, comprising incorporating said chemical with a lipid vesicle and connecting a chemical target molecule to the vesicle, said target molecule having preferential affinity for the hepatobiliary receptors.

6. A composition of matter for internal administration in the delivery of an effective dose of a chemical to the liver of a warm-blooded animal, comprising:

a lipid vesicle defined by bipolar wall and containing a pharmacological cargo intended for internal utilization by the liver; and

a compound consisting of a lipophilic substituent held in the wall of the vesicle and joined by a connector molecule to a target substituent selected from the class consisting of those chemicals which are classed biologically as biliary attracted.

7. A composition of matter for therapeutic treatment of a warm-blooded animal, comprising:

a composite structure of a lipid vesicle, and a target moiety;

said target moiety having a physical structure of a fatty substituent attached to the vesicle wall and a target substituent oriented in three-dimensional space extended away from the membrane surface;

said target substituent selected from the class consisting of those chemicals which are classed biologically as having a high affirmity for hepatobiliary receptors.