Derivatized hyperbranched polyglycerols

Patent metadata

Field	Value
Publication number	US-10071160-B2
Application number	US-201615388676-A
Country	US
Kind code	B2
Filing date	Dec 22, 2016
Priority date	Mar 1, 2010
Publication date	Sep 11, 2018
Grant date	Sep 11, 2018

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, wherein the ratio of alkyl chains to glycerol units is greater at a center of the core compared to a periphery of the core; 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), polyethylene glycol (PEG), or a combination thereof, and the at least one functional group comprises —NH 2 or —NH 3 + .

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 1 , wherein the hyperbranched polyglycerol comprises from about 1 to about 100 moles of the at least one functional group per mole of the hyperbranched polyglycerol.

4. The hyperbranched polyglycerol according to claim 1 , wherein the hyperbranched polyglycerol comprises from about 1 to about 40 moles of the at least one functional group per mole of the hyperbranched polyglycerol.

5. The hyperbranched polyglycerol according to claim 1 , wherein the hyperbranched polyglycerol comprises from about 5 to about 40 moles of the at least one functional group per mole of the hyperbranched polyglycerol.

6. The hyperbranched polyglycerol according to claim 1 , wherein the hyperbranched polyglycerol comprises from about 5 to about 15 moles of the at least one functional group per mole of the hyperbranched polyglycerol.

7. The hyperbranched polyglycerol according to claim 1 , wherein the hyperbranched polyglycerol comprises from about 1 to about 200 moles of the at least one hydrophilic substituent per mole of the hyperbranched polyglycerol.

8. The hyperbranched polyglycerol according to claim 1 , wherein the hyperbranched polyglycerol comprises from about 1 to about 100 moles of the at least one hydrophilic substituent per mole of the hyperbranched polyglycerol.

9. The hyperbranched polyglycerol according to claim 1 , wherein the hyperbranched polyglycerol comprises from about 1 to about 40 moles of the at least one hydrophilic substituent per mole of the hyperbranched polyglycerol.

10. The hyperbranched polyglycerol according to claim 1 , wherein the hyperbranched polyglycerol comprises from about 10 to about 40 moles of the at least one hydrophilic substituent per mole of the hyperbranched polyglycerol.

11. The hyperbranched polyglycerol according to claim 1 , wherein the hyperbranched polyglycerol comprises from about 10 to about 30 moles of the at least one hydrophilic substituent per mole of the hyperbranched polyglycerol.

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

13. The hyperbranched polyglycerol according to claim 1 , wherein the core comprises hyperbranched polyglycerol derivatized with C 8 alkyl chains.

14. The hyperbranched polyglycerol according to claim 1 , wherein the core comprises hyperbranched polyglycerol derivatized with C 10 alkyl chains.

15. The hyperbranched polyglycerol according to claim 1 , wherein the at least one hydrophilic substituent comprises MePEG and PEG.

16. The hyperbranched polyglycerol according to claim 1 , wherein the at least one hydrophilic substituent comprises PEG.

17. The hyperbranched polyglycerol according to claim 1 , wherein the at least one hydrophilic substituent comprises MePEG.

18. The hyperbranched polyglycerol according to claim 1 , wherein the at least one functional group comprises —NH 2 .

19. The hyperbranched polyglycerol according to claim 1 , wherein the at least one functional group comprises —NH 3 + .

20. The hyperbranched polyglycerol according to claim 1 , further comprising a biologically active moiety selected from the group consisting of docetaxel, paclitaxel, valrubicin, vinblastine, mitomycin, cisplatin, methotrexate, doxorubicin, epirubicin, gemcitabine, everolimus, suramin, and combinations thereof.

21. A pharmaceutical composition comprising a hyperbranched polyglycerol according to claim 20 and a pharmaceutically acceptable carrier.

22. A method of treating a cancer in a subject in need thereof, the method comprising administering a hyperbranched polyglycerol according to claim 20 to the subject, wherein the administering is effective to treat a cancer in the subject, wherein the cancer is a bladder cancer.

23. The method according to claim 22 , wherein the cancer is non-muscle invasive bladder cancer.

24. The method according to claim 22 , wherein the administering comprises intravesical administration of the hyperbranched polyglycerol.

25. The method according to claim 22 , wherein the subject is a human.

26. 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 20 to the patient, wherein the administering is effective to increase uptake of the biologically active moiety by the biological tissue of the patient.

27. 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 20 to the patient, wherein the administering is effective to increase permeability of the biological tissue of the patient to the biologically active moiety.

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

29. A pharmaceutical composition comprising a hyperbranched polyglycerol according to claim 1 and a biologically active moiety selected from the group consisting of docetaxel, paclitaxel, valrubicin, vinblastine, mitomycin, cisplatin, methotrexate, doxorubicin, epirubicin, gemcitabine, everolimus, suramin, and combinations thereof.

30. The pharmaceutical composition according to claim 29 , further comprising a pharmaceutically acceptable carrier.

31. The pharmaceutical composition according to claim 29 , wherein the biologically active moiety is docetaxel.

32. The pharmaceutical composition according to claim 29 , wherein the biologically active moiety is paclitaxel.

33. The pharmaceutical composition according to claim 29 , wherein the combination of moieties is methotrexate, vinblastine, and doxorubicin, or methotrexate, vinblastine, doxorubicin and cisplatin.

34. The pharmaceutical composition according to claim 29 , 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.

35. The pharmaceutical composition according to claim 29 , wherein the hyperbranched polyglycerol comprises from about 1 to about 40 moles of the at least one functional group per mole of the hyperbranched polyglycerol.

36. The pharmaceutical composition according to claim 29 , wherein the hyperbranched polyglycerol comprises from about 5 to about 15

Assignees

• Univ British Columbia
• Centre For Drug Res And Development

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

• A61K9/0034

  Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants · CPC title

• C08G65/48

  Polymers modified by chemical after-treatment · CPC title