Apparatus for removing chemotherapy compounds from blood

• US 10,569,004 B2
• Filed: 06/12/2019
• Issued: 02/25/2020
• Est. Priority Date: 11/07/2011
• Status: Active Grant

• Current Assignee: Delcath Systems, Inc.
• Original Assignee: Delcath Systems, Inc.
• Inventors: Johnston, Daniel S., Chammas, Jacques, Appling, William M., Barton, Samantha J.
• Primary Examiner(s): Mellon, David C
• Application Number:
  US16/439,620
• Publication Number:
  US 20190290823A1
• Time in Patent Office: 258 Days
• 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 1/3406 Physical characteristics of the filtrate, e.g. urea
• CPC Class Codes: A61M 1/3615 Cleaning blood contaminated by local chemotherapy of a body part temporarily isolated from the blood circuit
• CPC Class Codes: A61M 1/3687 Chemical treatment A61M1/3675 takes precedence
• CPC Class Codes: A61M 2205/3306 Optical measuring means
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61M 2210/1071 Liver; Hepar
• CPC Class Codes: B01J 20/20 comprising free carbon; comprising carbon obtained by carbonising processes
• CPC Class Codes: B01J 20/261 obtained by reactions only involving carbon to carbon unsaturated bonds macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F
• CPC Class Codes: B01J 20/28011 Other properties, e.g. density, crush strength
• CPC Class Codes: B01J 20/28066 being more than 1000 m2/g
• CPC Class Codes: B01J 20/28076 being more than 1.0 ml/g
• CPC Class Codes: B01J 20/28078 Pore diameter
• CPC Class Codes: B01J 20/3078 Thermal treatment, e.g. calcining or pyrolizing
• CPC Class Codes: B01J 20/3204 Inorganic carriers, supports or substrates
• CPC Class Codes: B01J 20/327 Polymers obtained by reactions involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3293 Coatings on a core, the core being particle or fiber shaped, e.g. encapsulated particles, coated fibers
• CPC Class Codes: C01B 32/354 After-treatment
• CPC Class Codes: C01B 32/372 Coating; Grafting; Microencapsulation

Abstract

A filter apparatus for removing small molecule chemotherapy agents from blood is provided. The filter apparatus comprises a housing with an extraction media comprised of polymer coated carbon cores. Also provided are methods of treating a subject with cancer of an organ or region comprising administering a chemotherapeutic agent to the organ or region, collecting blood laded with chemotherapeutic agent from the isolated organ, filtering the blood laden with chemotherapeutic agent to reduce the chemotherapeutic agent in the blood and returning the blood to the subject.

Claims

1. A method of treating a subject with cancer of the liver, comprising:

isolating blood flow out of the liver;

administering a chemotherapeutic agent arterially to the isolated liver;

collecting blood laden with the chemotherapeutic agent from the isolated liver;

filtering the blood laden with the chemotherapeutic agent with a filter apparatus comprising a housing having an inlet and an outlet, an extraction media comprising hemocompatible polymer coated carbon cores contained within the housing, wherein the carbon cores have a pore volume of about 1.68 cc/g to about 2.17 cc/g, to provide filtered blood, and

returning the filtered blood to the subject.

2. A method according to claim 1, wherein the carbon cores have a particle diameter of about 0.45 mm to about 1.15 mm.

3. A method according to claim 1, wherein the apparent density of the carbon cores is about 0.19 g/cc to about 0.2 g/cc.

4. A method according to claim 1, wherein the apparent density of the carbon cores is less than 0.2 g/cc.

5. A method according to claim 1, wherein the carbon cores have a median microporous diameter (D_{50, micro}) of between about 9.3 Å

to about 10.5 Å

.

6. A method according to claim 1, wherein the carbon cores have a median mesoporous diameter (D_50,meso) of between about 30 Å

to about 156 Å

.

7. A method according to claim 1, wherein the chemotherapeutic agent is melphalan hydrochloride.

8. A method according to claim 1, wherein the housing is a filter cartridge and the filter apparatus achieves an extraction efficiency of greater than 98% for removing melphalan hydrochloride from blood in an in vitro system where blood flow through the filter cartridge is at a rate of about 250 ml/min.

9. A method according to claim 8, wherein the extraction efficiency of greater than 98% for removing melphalan hydrochloride from blood is achieved where blood flow rate through the filter cartridge is at a rate of about 500 ml/min or less.

10. A method according to claim 1, wherein the chemotherapeutic agent is doxorubicin.

11. A method according to claim 1, wherein the filter apparatus comprises one or more filter cartridges.

12. A method of treating a cancer in a liver of a patient in need of treatment, comprising:

introducing a first catheter into a femoral artery to provide access to a region of proper hepatic artery;

guiding the first catheter to within the region of the proper hepatic artery for delivering melphalan hydrochloride;

inserting an isolation-aspiration catheter having two balloons fixedly spaced apart into the femoral vein and guiding the isolation-aspiration catheter into the inferior vena cava;

inflating the two balloons to block normal venous outflow of blood from the liver to isolate the liver;

delivering a dose of melphalan hydrochloride to the liver via the first catheter within the region of the proper hepatic artery over a period of from about 15 minutes to about 45 minutes;

collecting melphalan-laden blood as it exits the liver between the two inflated balloons, fixedly spaced apart, of the isolation-aspiration catheter;

passing the melphalan-laden blood through a filter apparatus at a rate of between about 250 ml/min and about 1000 ml/min, wherein the filter apparatus comprises a housing having an inlet and an outlet, an extraction media comprising hemocompatible polymer coated carbon cores contained within the housing, and wherein the carbon cores have a pore volume of about 1.68 cc/g to about 2.17 cc/g, and

returning blood that has passed through the filter apparatus and has been filtered to the patient.

13. A method according to claim 12, wherein returning blood that has passed through the filter apparatus and has been filtered to the patient comprises passing the blood through a third catheter that is placed in the patient'"'"'s internal jugular vein.

14. A method according to claim 12, wherein the carbon cores have a particle diameter of about 0.45 mm to about 1.15 mm.

15. A method according to claim 12, wherein the apparent density of the carbon cores is about 0.19 g/cc to about 0.2 g/cc.

16. A method according to claim 12, wherein the apparent density of the carbon cores is less than 0.2 g/cc.

17. A method for delivering a small molecule chemotherapeutic agent to a selected organ, or section of an organ, of a mammalian subject while restricting systemic exposure of the mammalian subject to the small molecule chemotherapeutic agent, comprising:

placing one or more catheters within venous vasculature which drains the organ, or section of an organ, at least one of the catheters having two or more expandable members;

isolating the organ, or section of the organ, by occluding flow of blood within the venous vasculature which drains the organ, or section of the organ, by inflating the expandable members;

delivering the small molecule chemotherapeutic agent to the isolated organ or isolated section of the organ;

perfusing the small molecule chemotherapeutic agent to perfuse within the isolated organ, or section of an organ, for a period of time sufficient to provide a therapeutic effect;

removing blood from the isolated organ, or section of the organ, the blood comprising the small molecule chemotherapeutic agent, and

filtering the blood to remove the small molecule chemotherapeutic agent by passing the blood through a filter apparatus comprising a housing having an inlet and an outlet, an extraction media comprising hemocompatible polymer coated carbon cores contained within the housing, wherein the carbon cores have a pore volume of about 1.68 cc/g to about 2.17 cc/g.

18. A method according to claim 17, wherein the carbon cores have a particle diameter of about 0.45 mm to about 1.15 mm.

19. A method according to claim 17, wherein the apparent density of the carbon cores is about 0.19 g/cc to about 0.2 g/cc.