Apparatus for removing chemotherapy compounds from blood

• US 10,369,264 B2
• Filed: 09/10/2018
• Issued: 08/06/2019
• 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:
  US16/127,008
• Publication Number:
  US 20190001044A1
• Time in Patent Office: 330 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 kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject, comprising:

a double balloon catheter;

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.

2. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 1, wherein the carbon cores have a particle diameter of about 0.45 mm to about 1.15 mm.

3. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 1, wherein the apparent density of carbon cores is about 0.19 g/cc to about 0.2 g/cc.

4. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject 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 kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject 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 kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 1, further comprising a catheter for providing access to a hepatic artery and/or a sheath or return catheter for returning blood to a patient after the blood has been filtered to reduce the amount of chemotherapeutic agent in the blood.

7. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 1, wherein the small molecule chemotherapeutic agent is melphalan hydrochloride.

8. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 1, wherein the filter apparatus comprises one or more filter cartridges.

9. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 1, wherein the filter apparatus comprises a dual filter cartridge wherein the dual filter cartridge comprises filter cartridges arranged in parallel.

10. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 1, wherein the hemocompatible polymer coated carbon cores contained within the housing are coated with a semipermeable polymer coating comprised of material selected from the group consisting of cellulose, a methacrylate polymer, and combinations thereof.

11. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 10, wherein the semipermeable polymer coating is a methacrylate selected from the group consisting of polymethylmethacrylate (PMMA), polyethylmethacrylate (PEMA), polyhydroxyethyl-methacrylate (PHEMA) and combinations thereof.

12. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 11, wherein the semipermeable polymer coating is polyhydroxyethyl-methacrylate (PHEMA).

13. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 1, wherein the subject is a human.

14. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 1, further comprising the small molecule chemotherapeutic agent melphalan hydrochloride.

15. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a liver of a patient, comprising:

an isolation-aspiration catheter which comprises two balloons, and

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 polymer coated carbon cores wherein the carbon cores have a pore volume of about 1.68 cc/g to about 2.17 cc/g.

16. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a liver of a patient according to claim 15, further comprising a chemotherapeutic agent selected from melphalan, doxorubicin, 5-fluorouracyl 5-FU, floxuridine FURD, cisplatin, oxaliplatin, topotecan, mytomycin C, cyclophosphamide, methotrexate, vincristine, Bleomycin, FAMT, or combinations thereof.

17. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a liver of a patient according to claim 15, further comprising melphalan hydrochloride.

18. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a liver of a patient according to claim 15, further comprising an extracorporeal circuit.

19. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a liver of a patient according to claim 15, further comprising an infusion catheter.

25. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a liver of a patient according to claim 15, wherein the carbon cores have a particle diameter of about 0.45 mm to about 1.15 mm.

26. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 15, wherein the apparent density of carbon cores is about 0.19 g/cc to about 0.2 g/cc.

27. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 15, wherein the carbon cores have a median microporous diameter (D50, micro) of between about 9.3 Å

to about 10.5 Å

.

28. A kit of parts capable of being assembled for delivering a small molecule chemotherapeutic agent to a subject according to claim 15, wherein the carbon cores have a median mesoporous diameter (D50,meso) of between about 30 Å

to about 156 Å

.

20. A system comprising a circuit of catheters for delivering a high concentration of a small molecule chemotherapeutic agent to a subject in need of treatment while minimizing systemic exposure to the small molecule chemotherapeutic agent, comprising:

a catheter inserted percutaneously into the inferior vena cava of a patient in need of treatment, the catheter comprising a hemo-compatible tube having a cranial end and a caudal end, the hemo-compatible tube defining a main lumen for outflowing blood, two balloons, fixedly spaced apart about the hemo-compatible tube and bonded thereto for inflation thereabout, one being contiguous to the cranial end, and the balloons, when inflated, having a size sufficient to block the flow of blood in a vein or artery into which the first catheter is designed to be inserted;

fenestrations in the hemo-compatible tube between the balloons to the main lumen;

second and third lumina within the hemo-compatible tube, the second lumen connecting to one of the balloons and the third lumen connecting to the other of the balloons, or other expandable devices, for effecting inflation or deflation of the balloons, the cranial end of the hemo-compatible tube effectively blocking inflow of blood, and

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 polymer coated carbon cores have a pore volume of about 1.68 cc/g to about 2.17 cc/g, wherein the filter apparatus is capable of being connected via a connector to the first catheter and a flow machine for pumping the blood from the subject through the filter apparatus, and a sheath or return catheter for returning blood removed from the patient back to the patient after filtration.

21. A system according to claim 20, wherein the carbon cores have a particle diameter of about 0.45 mm to about 1.15 mm.

22. A system according to claim 20, wherein the apparent density of carbon cores is about 0.19 g/cc to about 0.2 g/cc.

23. A system according to claim 20, wherein the carbon cores have a median microporous diameter (D50, micro) of between about 9.3 Å

to about 10.5 Å

.

24. A system according to claim 20, wherein the carbon cores have a median mesoporous diameter (D50,meso) of between about 30 Å

to about 156 Å

.