SN-38 loaded iron crosslinked micelle and methods thereof

• US 10,143,689 B2
• Filed: 02/08/2018
• Issued: 12/04/2018
• Est. Priority Date: 02/08/2017
• Status: Active Grant

• Current Assignee: Intezyne Technologies
• Original Assignee: Intezyne Technologies
• Inventors: Sill, Kevin N., Carie, Adam
• Primary Examiner(s): Valenrod, Yevgeny
• Application Number:
  US15/892,216
• Publication Number:
  US 20180228796A1
• Time in Patent Office: 299 Days
• Field of Search: 514283
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention provides SN-38 compositions for treating cancer.

Claims

1. A composition comprising SN-38, iron, and multiblock copolymer of Formula I:

2. The composition according to claim 1, wherein said composition further comprises a cryoprotectant.

3. The composition according to claim 2, wherein the cryoprotectant is trehalose.

4. The composition according to claim 2, further comprising at least one of 7-ethyl camptothecin, 10-hydroxy camptothecin, and 10-hydroxy-7-methyl camptothecin.

5. The composition according to claim 4, wherein the 7-ethyl camptothecin is between about 0.0001 and about 0.04 weight percent of the composition, the 10-hydroxy camptothecin is between about 0.00005 and about 0.02 weight percent of the composition, and the 10-hydroxy-7-methyl camptothecin is between about 0.00005 and about 0.02 weight percent of the composition.

6. The composition according to claim 1, wherein:

the SN-38 is between about 1.60 and about 1.77 weight percentage of the composition,

the iron is between about 1.01 and about 1.52 weight percentage of the composition; and

the multiblock copolymer of Formula I is between about 39.9 and about 48.7 weight percentage of the composition.

7. The composition according to claim 2, wherein:

the SN-38 is between about 0.5 and about 2.5 weight percentage of the composition;

the iron is between about 0.01 and about 5 weight percentage of the composition;

the multiblock copolymer of Formula I is between about 20 and about 60 weight percentage of the composition; and

the cryoprotectant is between about 20 and about 80 weight percentage of the composition.

8. The composition according to claim 3, wherein:

the SN-38 is between about 0.5 and about 2.5 weight percentage of the composition;

the iron is between about 0.01 and about 5 weight percentage of the composition;

the multiblock copolymer of Formula I is between about 20 and about 60 weight percentage of the composition; and

the trehalose is between about 20 and about 80 weight percentage of the composition.

9. A method for treating a cancer, in a patient in need thereof, comprising administering to the patient the composition according to claim 1.

10. The method according to claim 9, wherein the cancer is selected from pancreatic, lung, gastroesophageal, colorectal cancer, or gastrointestinal cancer, or breast.

11. The composition according to claim 6, wherein said composition further comprises a cryoprotectant.

12. The composition according to claim 11, wherein the cryoprotectant is trehalose.

13. The composition according to claim 11, further comprising at least one of 7-ethyl camptothecin, 10-hydroxy camptothecin, and 10-hydroxy-7-methyl camptothecin.

14. The composition according to claim 13, wherein the 7-ethyl camptothecin is between about 0.0001 and about 0.04 weight percent of the composition, the 10-hydroxy camptothecin is between about 0.00005 and about 0.02 weight percent of the composition, and the 10-hydroxy-7-methyl camptothecin is between about 0.00005 and about 0.02 weight percent of the composition.

15. The method according to claim 9, wherein administration at a dose of 4 mg/m² to a patient in need thereof achieves a C_max of SN-38 of about 100 to about 1,000 ng/mL.

16. The method according to claim 9, wherein administration at a dose of 4 mg/m² to a patient in need thereof achieves an AUC of SN-38 of about 400 to about 4,000 ng*h/mL.