USE OF HEPARIN AND CARBOHYDRATES TO TREAT CANCER

• US 20150111849A1
• Filed: 12/09/2014
• Published: 04/23/2015
• Est. Priority Date: 06/13/2012
• Status: Active Grant

• Current Assignee: ExThera Medical Corporation
• Original Assignee: ExThera Medical Corporation
• Inventors: LARM, OLLE, MCCREA, KEITH, WARD, ROBERT
• Granted Patent: US 11,266,772 B2
• Time in Patent Office: Days
• US Class Current: 514/56
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61M 1/34 Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 2202/0478 Heparin
• CPC Class Codes: A61M 2202/07 Proteins
• CPC Class Codes: A61M 2205/3334 Measuring or controlling the flow rate
• CPC Class Codes: A61M 2205/7545 for solid matter, e.g. microaggregates

Abstract

The method is described as the removal of mediators that contribute to the pathogenesis of cancer from blood by contacting the blood with a solid, essentially non-micro-porous substrate which has been surface treated with heparin, heparan sulfate and, optionally, other molecules or chemical groups (the adsorbent media or media) having a binding affinity to the mediator, and wherein the size of the interstitial channels within said substrate are balanced with the amount of interstitial substrate surface area such that high flow rates of blood past said substrate creates a flow transport that is characterized by convection transport more than Brownian diffusion transport.

Claims

1. A method for removing cancer mediators and/or circulating cancerous cells from the blood comprising:

contacting blood from a patient with a solid substrate coated with heparin and/or other carbohydrates.

4. The method of claim 1, wherein the one or more cancer mediators are selected from the group consisting of circulating growth factors that contribute to angiogenesis of tumors, circulating cytokines that contribute to angiogenesis, circulating heparanases that degrade heparan sulfate segments on endothelial cell walls that can lead to tumor cell invasion, and circulating fibrin or thrombin that leads to venous thromboembolism.

5. The method of claim 4, wherein the one or more cancer mediators are selected from the group consisting of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), IL-8, heparanases, pro-uPA (pro-urinary plasminogen activator protein), plasminogen, and thrombin.

6. The method according to any one of claims 1-5, wherein said contacting blood from a patient is conducted during and/or after surgery to remove a tumor.

2. A method of treating cancer progression by removing cancer mediators from mammalian blood comprising contacting mammalian blood with a solid substrate coated with heparin and/or other carbohydrates.

3. A method of treating cancer comprising:

removing cancer mediators and/or circulating cancer cells from blood of a mammal that has undergone surgery, wherein the cancer mediators and/or circulating cancer cells have been generated by the surgery, by contacting the mammalian blood with a solid substrate coated with heparin and/or other carbohydrates, and returning the blood to the mammal.

7. A device for the removal of one or more cancer mediators in the blood comprising:

a solid substrate in a container, said solid substrate having one or more polysaccharide adsorbents on the surface thereof with a binding affinity for the one or more cancer mediators, wherein said substrate is sufficiently rigid such that blood does not pass through pores in said substrate, and wherein the size of the interstitial pore size between individual portions of said substrate and the amount of interstitial substrate surface area is such that when blood is in flow contact with said substrate at a linear flow velocity through said device of at least about 24 cm/min, said one or more cancer mediators binds to said one or more polysaccharide adsorbents to separate from said blood and the flow transport of said blood past said substrate is by convection transport more than Brownian diffusion transport.

8. The device of claim 7, wherein said substrate comprises a packed column of non-porous rigid beads or particles, a column packed with a rigid reticulated foam, a column packed with a rigid monolithic bed of sintered beads or other sintered solid media with internal flow channels, a column packed with woven or non-woven rigid fabric, a column packed with a rigid yarn or optionally hollow monofilament fibers, a spiral wound cartridge, or a combination of at least two members selected from the group consisting of beads, rigid reticulated foam, sintered beads, fabric, yarn and monofilament.

9. The device according to claim 8, wherein the solid substrate comprises polyethylene beads coated with one or more polysaccharides.

10. The device according to claim 9, wherein at least one of said polysaccharides is selected from the group consisting of heparin, heparan sulphate, hyaluronic acid, salicylic acid, carbohydrates with mannose sequences, and chitosan.