Derivatized hyperbranched polyglycerols

Patent metadata

Field	Value
Publication number	US-9561278-B2
Application number	US-201514868148-A
Country	US
Kind code	B2
Filing date	Sep 28, 2015
Priority date	Mar 1, 2010
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

Abstract

Herein are provided derivatized hyperbranched polyglycerols (“dHPGs”). The dHPG comprises a core comprising a hyperbranched polyglycerol derivatized with C 1 C 20 alkyl chains and a shell comprising at least one hydrophilic substituent bound to hydroxyl groups of the core, wherein the hyperbranched polyglycerol comprises from about 1 to about 200 moles of the at least one hydrophilic substituent. The dHPGs are for use as agents for the delivery of a drug or other biologically active moiety to the urinary tract, the digestive tract, the airways, the vaginal cavity and cervix and the peritoneal cavity to treat indications such as cancer, which may be useful in the treatment of or the manufacture of a medicament, in the preparation, of a pharmaceutical composition for the treatment of cancer, as a pre-treatment or co-treatment to improve drug uptake in a tissue. Furthermore, there are provided methods of making dHPGs.

First claim

What is claimed is:

1. A hyperbranched polyglycerol comprising:
a core comprising hyperbranched polyglycerol derivatized with C 8 alkyl chains, C 10 alkyl chains, or a combination thereof; and
a shell comprising at least one hydrophilic substituent and at least one functional group, wherein the at least one hydrophilic substituent comprises methoxypolyethylene glycol (MePEG) and the at least one functional group comprises —NH 2 .

2. The hyperbranched polyglycerol according to claim 1 , wherein the hyperbranched polyglycerol comprises from about 1 to about 200 moles of the at least one functional group per mole of the hyperbranched polyglycerol.

3. The hyperbranched polyglycerol according to claim 2 , wherein the hyperbranched polyglycerol comprises from about 30 to about 100 moles of the at least one functional group per mole of the hyperbranched polyglycerol.

4. The hyperbranched polyglycerol according to claim 2 , wherein the hyperbranched polyglycerol comprises about 37 moles of the at least one functional group per mole of the hyperbranched polyglycerol.

5. The hyperbranched polyglycerol according to claim 1 , wherein the core comprises hyperbranched polyglycerol derivatized with a combination of C 8 alkyl chains and C 10 alkyl chains.

6. The hyperbranched polyglycerol according to claim 1 , wherein the ratio of alkyl chains to glycerol units is greater at a centre of the core compared to a periphery of the core.

7. The hyperbranched polyglycerol according to claim 1 , further comprising a biologically active moiety.

8. The hyperbranched polyglycerol according to claim 7 , wherein the biologically active moiety is a hydrophobic drug.

9. The hyperbranched polyglycerol according to claim 7 , wherein the biologically active moiety is a taxane or derivative thereof.

10. The hyperbranched polyglycerol according to claim 9 , wherein the taxane or derivative thereof is docetaxel or a derivative thereof.

11. The hyperbranched polyglycerol according to claim 9 , wherein the taxane or derivative thereof is paclitaxel or a derivative thereof.

12. The hyperbranched polyglycerol according to claim 7 , wherein the biologically active molecule is selected from the group consisting of valrubicin, vinblastine, mitomycin, cisplatin, methotrexate, doxorubicin, epirubicin, gemcitabine, everolimus, suramin, and analogs thereof.

13. The hyperbranched polyglycerol according to claim 7 , wherein the biologically active moiety is a combination of moieties.

14. The hyperbranched polyglycerol according to claim 13 , wherein the combination of moieties is methotrexate, vinblastine and doxorubicin (M-VAC), or M-VAC and cisplatin.

15. A pharmaceutical composition comprising the hyperbranched polyglycerol according to claim 7 and a pharmaceutically acceptable carrier.

16. A method of treating a cancer in a subject in need thereof, the method comprising administering a pharmaceutical composition according to claim 15 to the subject, wherein the administering is effective to treat a cancer in the subject, wherein the cancer is a bladder cancer.

17. The method according to claim 16 , wherein the cancer is non-muscle invasive bladder cancer.

18. The method according to claim 16 , wherein the administering comprises intravesical administration of the pharmaceutical composition.

19. The method according to claim 16 , wherein the subject is a human.

20. A method of delivering a biologically active moiety to a biological tissue of a patient, the method comprising administering a hyperbranched polyglycerol according to claim 7 to the patient, wherein the administering is effective to increase uptake of the biologically active moiety by the biological tissue of the patient.

21. A method of increasing permeability of a biological tissue of a patient to a biologically active moiety, the method comprising administering a hyperbranched polyglycerol according to claim 1 to the patient, wherein the administering is effective to increase permeability of the biological tissue of the patient to the biologically active moiety.

22. A pharmaceutical composition comprising the hyperbranched polyglycerol according to claim 1 and a pharmaceutically acceptable carrier.

23. The pharmaceutical composition according to claim 22 , further comprising a biologically active moiety.

24. The pharmaceutical composition according to claim 23 , wherein the biologically active moiety is a hydrophobic drug.

25. The pharmaceutical composition according to claim 23 , wherein the biologically active moiety is a taxane or derivative thereof.

26. The pharmaceutical composition according to claim 25 , wherein the taxane or derivative thereof is docetaxel or a derivative thereof.

27. The pharmaceutical composition according to claim 25 , wherein the taxane or derivative thereof is paclitaxel or a derivative thereof.

28. The pharmaceutical composition according to claim 23 , wherein the biologically active molecule is selected from the group consisting of valrubicin, vinblastine, mitomycin, cisplatin, methotrexate, doxorubicin, epirubicin, gemcitabine, everolimus, suramin, and analogs thereof.

29. The pharmaceutical composition according to claim 23 , wherein the biologically active moiety is a combination of moieties.

30. The pharmaceutical composition according to claim 29 , wherein the combination of moieties is methotrexate, vinblastine and doxorubicin (M-VAC), or M-VAC and cisplatin.

31. A method of treating a cancer in a subject in need thereof, the method comprising administering a pharmaceutical composition according to claim 23 to the subject, wherein the administering is effective to treat a cancer in the subject, wherein the cancer is a bladder cancer.

32. The method according to claim 31 , wherein the cancer is non-muscle invasive bladder cancer.

33. The method according to claim 31 , wherein the administering comprises intravesical administration of the pharmaceutical composition.

34. The method according to claim 31 , wherein the subject is a human.

35. A method of pre-treating or co-treating a biological tissue to increase uptake of a drug by the biological tissue of a patient, the method comprising administering a pharmaceutical composition according to claim 22 to the patient before or during administration of the drug to the patient.

36. A method of delivering a biologically active moiety to a biological tissue of a patient, the method comprising administering a hyperbranched polyglycerol according to claim 1 and a biologically active moiety to the patient, wherein the administering is effective to increase uptake of the biologically active moiety by the biological tissue of the patient.

37. The method according to claim 36 , wherein the administering comprises pre-treating the biological tissue by administering the hyperbranched polyglycerol to the patient before administering the biologically active moiety to the patient.

38. The method according to claim 36 , wherein the administering comprises co-treating the biological tissue by administering the hyperbranched polyglycerol to the patient during administration of the biologically active moiety to the patient.

Assignees

• Univ British Columbia
• Centre For Drug Res And Dev

Inventors

• Burt Helen M
• Brooks Donald E
• Kizhakkedathu Jayachandran N
• Liggins Richard
• Guan Dechi
• Ye Lu
• Mugabe Clement
• So Alan
• Gleave Martin E
• Jackson John K
• Kainthan Rajesh Kumar

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P13/10

  of the bladder · CPC title

• C08G65/48

  Polymers modified by chemical after-treatment · CPC title

• C08G2650/54

  Polyglycerols · CPC title