Apparatus for removing chemotherapy compounds from blood

• US 9,707,331 B2
• Filed: 11/07/2012
• Issued: 07/18/2017
• Est. Priority Date: 11/07/2011
• Status: Active Grant

• Current Assignee: Delcath Systems, Inc.
• Original Assignee: Delcath Systems, Inc.
• Inventors: Barton, Samantha J., Johnston, Daniel S., Chammas, Jacques, Appling, William M.
• Primary Examiner(s): Mellon, David C
• Application Number:
  US13/671,549
• Publication Number:
  US 20130116658A1
• Time in Patent Office: 1,714 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; and

an extraction media contained within the housing and comprising carbon cores and a polymer that coats the carbon cores,

wherein the carbon cores each have a pore volume of about 1.68 cc/g to about 2.17 cc/g,

wherein the polymer that coats the carbon cores consists of a material selected from the group comprising cellulose, a methacrylate polymer, or combinations thereof, and

wherein the apparent density of the carbon cores with the polymer that coats the carbon cores is less than about 0.2 g/cc.

2. The 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. The filter apparatus according to claim 1, wherein the apparent density of the carbon cores with the polymer that coats the carbon cores is about 0.19 g/cc to about 0.2 g/cc.

4. The 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. The 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. The filter apparatus according to claim 1, wherein microporous pores comprise between about 18% to about 28% of the pore volume of the carbon cores.

7. The filter apparatus according to claim 1, wherein the carbon cores have a multiple point Brunauer, Emmett and Teller surface area of between about 1825 m²/g to about 2058 m²/g.

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

9. The filter apparatus according to claim 1, wherein the housing includes a hemocompatible filter cartridge.

10. The 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 the filter cartridge in an in vitro system where blood flow through the filter cartridge is at about 250 mL/min.

11. The 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 the filter cartridge in an in vitro system where blood flow through the filter cartridge is at about 500 mL/min.

12. The 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 the filter cartridge in an in vitro system.

13. The 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 the filter cartridge in an in vitro system where blood flow through the filter cartridge is at about 250 mL/min.

14. The 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 the filter cartridge in an in vitro system where blood flow through the filter cartridge is at about 250 mL/min.

15. The filter apparatus according to claim 1, wherein the polymer that coats the carbon cores is a semipermeable polymer.

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

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

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

weight ratio of carbon to methacrylate is between 52;

1 to 25;

1.

19. The filter apparatus according to claim 1, wherein the carbon cores have a multiple point Brunauer, Emmett and Teller surface area of between about 1825 m²/g to about 2059 m²/g.

20. The filter apparatus according to claim 19, wherein the carbon cores have a density functional theory surface areabetween about 1483 m²/g and about 1778 m²/g.

21. The filter apparatus according to claim 19, wherein the carbon cores have an apparent density between about 0.185 g/cc to about 0.195 g/cc.

22. The filter apparatus according to claim 1 or 19, 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.

23. The filter apparatus according to claim 1, wherein the carbon cores are generally spherical.

24. A filter apparatus comprising:

a housing having an inlet and an outlet; and

an extraction media contained within the housing and configured to remove melphalan hydrochloride from blood, the extraction media comprising polymer coated carbon cores,

wherein the polymer coated carbon cores have an apparent density of less than 0.2 g/cc and an extraction efficiency of greater than 98% for removing melphalan hydrochloride from blood.

25. The filter apparatus according to claim 24, wherein the polymer coated carbon cores have a pore volume of about 1.68 cc/g to about 2.19 cc/g.

26. The filter apparatus according to claim 24, wherein the polymer coated carbon cores are generally spherical.

27. A filter apparatus for removing melphalan having a concentration less than 15,000 ng/mL from blood, comprising:

one or more filter cartridges comprising an extraction media contained within the one or more filter cartridges and comprising polymer coated carbon cores,

wherein the polymer coated carbon cores have a pore volume of about 1.68 to about 2.19 cc/g and an apparent density of less than about 0.2 g/cc, and

wherein the filter apparatus has an extraction efficiency for melphalan of greater than 98% when blood flows through the filter apparatus at a rate of 500 ml/L or less.

28. The filter apparatus according to claim 27, wherein the one or more filter cartridges comprises two filter cartridges.

29. The filter apparatus according to claim 28 wherein the two filter cartridges are parallel to each other and flow is split such that fluid passes through the two filter cartridges in parallel.

30. The filter apparatus according to claim 27, wherein the polymer coated carbon cores are generally spherical.