Drug-loaded ganglioside micelle and the preparation method and use thereof

Patent metadata

Field	Value
Publication number	US-10039713-B1
Application number	US-201815871300-A
Country	US
Kind code	B1
Filing date	Jan 15, 2018
Priority date	Mar 14, 2017
Publication date	Aug 7, 2018
Grant date	Aug 7, 2018

Abstract

The present application belongs to the field of biopharmaceutical technology and particularly relates to a drug-loaded ganglioside micelle and a method for preparing and use thereof. The present application provides a use of GM1 or a derivative thereof as a carrier material of nano drug delivery system. The blood brain barrier is a key barrier to intracranial drug delivery. The nano drug delivery system provides a powerful tool for non-invasive intracranial combined administration and has important clinical significance. Without introducing other carrier materials, long-circulating modifying materials and nerve repair drugs, the drug-loaded ganglioside micelle prepared by using GM1 or a derivative thereof as a carrier material of nano drug delivery system can achieve nerve injury repair and intracranial combined administration by penetrating the blood-brain barrier. The drug-loading ganglioside micelle in the present application is expected to provide a new perspective and method for improving clinical treatment.

First claim

What is claimed is:

1. A method comprising:
obtaining a first solution of Ganglioside M1 (GM1), II 3 —N-acetylneuraminosylgangliotetraosyl-D-erythro-1,3-dihydroxy-2-2dichloroacetylamide-4-trans-octadacene (LIGA20), N-acetyl sphingosine (LIGA4) or d-eritro 1, 3-dihydroxy-2-dichloroacetylamide-4-trans-octadecene (PKS3);
obtaining a second solution of a drug;
obtaining a mixed solution by mixing the first solution and the second solution; and
obtaining drug-loaded ganglioside micelles by dialyzing the mixed solution.

2. The method according to claim 1 , wherein the drug is selected from the group consisting of a drug for treating an intracranial disease and a drug for treating a central nervous system disease.

3. The method according to claim 2 , wherein the drug for treating an intracranial disease or the drug for treating a central nervous system disease is selected from the group consisting of an intracranial antitumor drug, an antidepressant, an antiepileptic drug, a drug against a neurodegenerative disease, a drug against an intracranial hematoma and a drug against blood pressure.

4. The method according to claim 1 , wherein the drug comprises doxorubicin (DOX) or curcumin (CUR).

5. The method according to claim 1 , wherein obtaining the mixed solution comprises incubation at a temperature between 2° C. and 8° C.

6. The method according to claim 1 , wherein dialyzing the mixed solution is at a temperature between 2° C. and 8° C.

7. The method according to claim 1 , wherein a molar ratio of GM1 to the drug is between 2:1 and 20:1.

8. The method of claim 1 , further comprising incubating the first solution at a temperature between 2° C. and 8° C. for a time period between 22 hours and 26 hours.

9. The method of claim 1 , further comprising centrifuging the first solution for a time period between 25 minutes and 35 minutes.

10. The method of claim 1 , further comprising filtering the first solution.

11. The method according to claim 1 , wherein dialyzing the mixed solution is for a duration between 22 hours and 26 hours.

12. The method according to claim 5 , wherein the incubation is for a duration between 22 hours and 26 hours.

13. A micelle comprising:
an enclosure comprising Trisialoganglioside-GT1b (GM1), LIGA20, N-acetyl sphingosine or d-eritro 1,3-dihydroxy-2-dichloroacetylamide-4-trans-octadecene; and
a drug in the enclosure.

14. The micelle of claim 13 , wherein the drug comprises doxorubicin (DOX) or curcumin (CUR).

15. The micelle of claim 13 , wherein a molar ratio of GM1 to the drug is between 2:1 and 20:1.

16. The micelle of claim 13 , wherein the drug is selected from the group consisting of a drug for treating an intracranial disease and a drug for treating a central nervous system disease.

17. The micelle of claim 16 , wherein the drug for treating an intracranial disease or the drug for treating a central nervous system disease is selected from the group consisting of: an intracranial antitumor drug, an antidepressant, an antiepileptic drug, a drug against a neurodegenerative disease, a drug against an intracranial hematoma and a drug against blood pressure.

Assignees

• Univ Chongqing

Inventors

• Wang Yazhou
• Zou Dan
• Yin Tieying
• Wang Guixue

Classifications

• A61K31/12

  Ketones · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K9/1075 Primary

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/65

  Tetracyclines · CPC title