Apparatus for removing chemotherapy compounds from blood
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.
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 m 2 /g to about 2058 m 2 /g.
8. The filter apparatus according to claim 1 , wherein the carbon cores have a density functional theory surface area of between about 1483 m 2 /g to about 1778 m 2 /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 m 2 /g to about 2059 m 2 /g.
20. The filter apparatus according to claim 19 , wherein the carbon cores have a density functional theory surface areabetween about 1483 m 2 /g and about 1778 m 2 /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.