Chromatographic Media for Storage and Delivery of Therapeutic Biologics and Small Molecules

• US 20130189322A1
• Filed: 01/18/2013
• Published: 07/25/2013
• Est. Priority Date: 01/19/2012
• Status: Abandoned Application

• Current Assignee: Merck Millipore Ltd. (Merck & Co., Inc.)
• Original Assignee: Natrix Separations Inc.
• Inventors: Honeyman, Charles H., Ragheb, Amro, Chickosky, John A., McGlaughlin, Molly S.
• Application Number:
  US13/744,583
• Publication Number:
  US 20130189322A1
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: G01N 33/544 the carrier being organic

Abstract

Described are composite materials and methods of making and using them for the storage and delivery of unstable drugs or biologics. In certain embodiments, the composite material comprises a support member, comprising a plurality of pores extending through the support member; a macroporous cross-linked gel, comprising a plurality of macropores; a therapeutic agent; and a stabilizing agent.

Claims

1. A composite material, comprising:

a support member, comprising a plurality of pores extending through the support member;

a macroporous cross-linked gel, comprising a plurality of macropores;

a therapeutic agent; and

a stabilizing agent,

wherein the macroporous cross-linked gel is located in the pores of the support member;

and the average pore diameter of the macropores is less than the average pore diameter of the pores.

2. The composite material of claim 1, wherein the therapeutic agent is an antibody, a protein, or a virus.

3. The composite material of claim 1, wherein the therapeutic agent is a small molecule.

4. The composite material of claim 1, wherein the therapeutic agent is covalently bonded to the macroporous cross-linked gel.

5. The composite material of claim 1, wherein the therapeutic agent is adsorbed to or absorbed on the macroporous cross-linked gel.

6. The composite material of claim 1, wherein the composite material is substantially free from water.

7. The composite material of claim 1, wherein the stabilizing agent comprises a sugar, a polyalcohol, or a derivative of a sugar or a polyalcohol.

8. The composite material of claim 1, wherein the composite material further comprises a salt.

9. The composite material of claim 1, wherein the composite material is substantially stable at about 20°

C., about 25°

C., about 30°

C., about 35°

C., about 40°

C., about 45°

C., about 50°

C., about 55°

C., or about 60°

C.

10. The composite material of claim 1, wherein the mass ratio of the stabilizing agent to the therapeutic agent is about 10:

1, about 9;

1, about 8;

1, about 7;

1, about 6;

1, about 5;

1, about 4;

1, about 3;

1, about 2;

1, about 1;

1, about 1;

2, or about 1;

4.

20. A method of delivering a therapeutic agent to a subject in need thereof, comprising the step of:

contacting a composite material of claim 1 with a second solution, thereby dissociating the therapeutic agent from the composite material and forming a third solution; and

delivering the third solution to the subject.

21. The method of claim 20, wherein the second solution comprises a salt.

22. The method of claim 20, wherein the composite material is configured in a syringe, an intravenous line, or a vial.

23. The method of claim 20, wherein the third solution is delivered to the subject intravenously.

11. A method, comprising the steps of:

contacting a therapeutic agent with a composite material thereby forming a composite material with an associated therapeutic agent;

contacting the composite material with the associated therapeutic agent with a first solution, wherein the first solution comprises a stabilizing agent, thereby forming a stabilized composite material; and

substantially drying the stabilized composite material at a temperature for an amount of time, thereby substantially removing water from the stabilizing composite material.

12. The method of claim 11, wherein the concentration of the stabilizing agent in the first solution is about 5 wt %, about 10 wt %, about 15 wt %, about 20 wt %, about 30 wt %, about 40 wt %, or about 50 wt %.

13. The method of claim 11, wherein the first solution further comprises a buffer salt.

14. The method of claim 13, wherein the concentration of the buffer salt in the first solution is about 20 mM, about 30 mM, about 40 mM, about 50 mM, about 60 mM, about 70 mM, about 80 mM, about 90 mM, about 100 mM, about 110 mM, about 120 mM, about 130 mM, about 140 mM, about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, about 200 mM, about 210 mM, about 220 mM, about 230 mM, about 240 mM, or about 250 mM.

15. The method of claim 11, wherein the pH of the first solution is about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 7, about 7.5, or about 8.

16. The method of claim 11, wherein the composite material with the associated therapeutic agent is soaked in the first solution.

17. The method of claim 11, wherein the composite material with the associated therapeutic agent is contacted with the first solution for about 1 min., about 2 min., about 3 min., about 4 min., about 5 min., about 10 min., about 20 min., about 30 min., about 40 min., about 50 min., about 60 min., about 70 min, about 80 min., about 90 min., about 100 min., about 110 min., about 120 min., about 130 min., or about 140 min.

18. The method of claim 11, wherein the stabilized composite material is substantially dried for about 5 min., about 10 min., about 20 min., about 30 min., about 40 min., about 50 min., about 60 min., about 70 min., about 80 min., about 90 min., about 100 min., about 110 min., about 120 min., about 130 min., or about 140 min.

19. The method of claim 11, wherein the stabilized composite material is substantially dried at a temperature of about 20°

C., about 25°

C., about 30°

C., about 35°

C., about 40°

C., about 45°

C., about 50°

C., about 55°

C., or about 60°

C.