IP Library Granted Patent US 7,034,006
Granted Patent B2
US 7,034,006 · App. 09/756,765 · Granted Apr 25, 2006

Use of lipid conjugates in the treatment of disease

Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 7,034,006
App. No.
09/756,765
Granted
Apr 25, 2006
Kind
B2
Abstract

The invention provides novel methods for treating disease based upon the medicinal use of lipids and phospholipids covalently bound to physiologically acceptable monomers or polymers. Phosphatidylethanolamine moieties conjugated to physiologically acceptable monomers and polymers (PE conjugates) manifest an unexpectedly wide range of pharmacological effects, including stabilizing cell membranes; limiting oxidative damage to cell and blood components; limiting cell proliferation, cell extravasation and (tumor) cell migratory behavior; suppressing immune responses; and attenuating physiological reactions to stress, as expressed in elevated chemokine levels. The surprisingly manifold pharmacological properties of the PL-conjugates allow for the invention, disclosed herein, of novel methods for the treatment of a diverse range of disease states, including obstructive respiratory disease, including asthma; colitis and Crohn's disease; central nervous system insult, including blood brain barrier compromise, ischemic stroke, and multiple sclerosis; contact dermatitis; psoriasis; cardiovascular disease, including ischemic conditions and prophylaxis for invasive vascular procedures; cellular proliferative disorders, including anti-tumor vasculogenesis, invasiveness, and metastases; anti-oxidant therapy; hemolytic syndromes; sepsis; acute respiratory distress syndrome; tissue transplant rejection syndromes; autoimmune disease; viral infection; and hypersensitivity conjunctivitis. The therapeutic methods of the invention include administration of phosphatidylethanolamine bound to carboxymethylcellulose, heparin, hyaluronic acid, polyethylene glycol, and hemaccel. Disclosed herein are also new compounds comprised of phospholipid moieties bound to low molecular weight monomers and dimers, including mono- and disaccharides, carboxylated disaccharides, mono- and dicarboxylic acids, salicylates, bile acids, and fatty acids.

Claims (11)

1. A phosphatidylethanolamine conjugate according to the formula

wherein

R 1 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;

R 2 is a linear, saturated, mono-unsaturated, or poly-unsaturated, alkyl chain ranging in length from 2 to 30 carbon atoms;

Y is either nothing or a spacer group ranging in length from 2 to 30 atoms, wherein said spacer comprises —CO-alkylene-NH—, —CO-alkylene-CO— or a combination thereof; and

X is either a physiologically acceptable monomer, dimer, or oligomer, wherein n is unity, or a physiologically acceptable polymer, wherein n is a number from 1 to 1,000, wherein x is a glycosaminoglycan;

wherein if Y is nothing the phosphatidylethanolamine is directly linked to X via a carboxylic group.

2. The compound according to claim 1 wherein the glycosaminoglycan is hyaluronic acid, heparin, heparan sulfate, chondrotin sulfate, keratin, keratan sulfate, dermatan sulfate or a derivative thereof.

3. The compound according to claim 1 wherein the glycosamininoglycan is di- and trisaccharide unit monomers of glycosaminoglycans.

4. The compound according to claim 3 , wherein the chondrotin sulfate is chondrotin-6-sulfate, chondroitin-4-sulfate or a derivative thereof.

5. The compound according to claim 1 , wherein the glycosaminoglycan is hyaluronic acid.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 6, 2018
From: YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM, LTD
To: YEDGAR, SAUL
Reel/Frame 046006/0942 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 26, 2004
From: YEDGAR, SAUL; SHOSEYOV, DAVID; GOLOMB, GERSHON; REICH, REUVEN; GINSBURG, ISAAC; HIGAZI, ABD-AL-ROOF; LIGUMSKI, MOSHE; KRIMSKY, MIRON; OJCIUS, DAVID; YARD, BENITO ANTONIO; VAN DER WOUDE, FOKKO JOHANNES; SCHNITZER, EDIT
To: YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM
Reel/Frame 015182/0001 →
Continuity (3)
Provisional Application 6017490700 · Jan 10, 2000
Provisional Application 6017490500 · Jan 10, 2000
Related Publication 20020049183A1 · Apr 25, 2002