Apparatus for removing chemotherapy compounds from blood

• US 10,098,997 B2
• Filed: 07/17/2017
• Issued: 10/16/2018
• 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:
  US15/651,141
• Publication Number:
  US 20180028740A1
• Time in Patent Office: 456 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 filter apparatus for removing small molecule chemotherapy agents from blood 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.

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

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

4. A filter apparatus 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

.

5. A filter apparatus 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

.

6. A filter apparatus according to claim 1, wherein the carbon cores have a percent of microporous pores that represents between about 18% to about 28% of the pore volume.

7. A filter apparatus according to claim 1, wherein the carbon cores have an MBET surface area of between about 1825 m²/g to about 2058 m²/g.

8. A filter apparatus according to claim 1, wherein the carbon cores have a DFT surface area of between about 1483 m²/g to about 1778 m²/g.

9. A filter apparatus according to claim 1, wherein the housing is a filter cartridge.

10. A filter apparatus according to claim 9, wherein the small molecule chemotherapy agent is melphalan hydrochloride and the filter apparatus has an extraction efficiency of greater than 98% for removing melphalan hydrochloride from blood using a filter cartridge in an in vitro system where blood flow through the filter cartridge is at about 250 mL/min.

11. A filter apparatus according to claim 9, wherein the small molecule chemotherapy agent is melphalan hydrochloride and the filter apparatus has an extraction efficiency of between about 95% and about 98% for removing melphalan hydrochloride from blood using a filter cartridge in an in vitro system where blood flow through the filter cartridge is at about 500 mL/min.

12. A filter apparatus according to claim 9, wherein the small molecule chemotherapy agent is melphalan hydrochloride and the filter apparatus has an extraction efficiency of greater than about 95% for removing melphalan hydrochloride from blood using a filter cartridge in an in vitro system.

13. A filter apparatus according to claim 9, wherein the small molecule chemotherapy agent is doxorubicin and the filter apparatus has an extraction efficiency of greater than about 95% for removing doxorubicin from blood using a filter cartridge in an in vitro system where blood flow through the filter cartridge is at about 250 mL/min.

14. A filter apparatus according to claim 9, wherein the small molecule chemotherapy agent is topotecan and the filter apparatus has an extraction efficiency of greater than about 89% for removing topotecan from blood using a filter cartridge in an in vitro system where blood flow through the filter cartridge is at about 250 mL/min.

15. A filter apparatus according to claim 1, wherein the hemocompatible polymer coated carbon cores contained within the housing are coated with a semipermeable polymer, the semipermeable polymer comprised of material selected from the group consisting of cellulose, a methacrylate polymer, and combinations thereof.

16. A filter apparatus according to claim 15, wherein the semipermeable polymer coating is a methacrylate selected from the group consisting of polymethylmethacrylate (PMMA), polyethylmethacrylate (PEMA), polyhydroxyethyl-methacrylate (PHEMA) and combinations thereof.

17. A filter apparatus according to claim 16, wherein the semipermeable polymer coating is polyhydroxyethyl-methacrylate (PHEMA).

18. A filter apparatus according to claim 16, wherein weight:

weight ratio of carbon to methacrylate is between 52;

1 to 25;

1.

19. A filter apparatus for removing small molecule chemotherapy agents from blood comprising a housing having an inlet and an outlet, an extraction media comprising hemocompatible polymer coated carbon contained within the housing, wherein the carbon cores have a pore volume of about 1.68 cc/g to about 2.17 cc/g and an MBET surface area of between about 1825 m²/g to about 2059 m²/g.

20. A filter apparatus according to claim 19, wherein the DFT surface area is between about 1483 m²/g and about 1778 m²/g.