Claims for Patent: 9,855,216

Summary for Patent: 9,855,216

Title:	Targeted nano-liposome co-entrapping anti-cancer drugs
Abstract:	A liposomal composition includes at least two anti-tumor herbal drugs that are simultaneously co-encapsulated. Optionally, the liposomal composition is targeted by adding a monoclonal antibody is added to the liposomes.
Inventor(s):	Amoabediny; Ghasem (Tehran, IR), Ochi; Mohammad Mahdi (Tehran, IR), Rezayat; Seyed Mahdi (Tehran, IR), Akbarzadeh; Azim (Tehran, IR), Ebrahimi; Bahman (Tehran, IR)
Assignee:	Amoabediny; Ghasem (Tehran, IR) Ochi; Mohammad Mahdi (Tehran, IR) UNIVERSITY OF TEHRAN (Tehran, IR)
Application Number:	15/130,144
Patent Claims:	1. A liposome composition for the treatment of cancer, comprising: at least a phospholipid compound; cholesterol; and at least two herbal drugs, wherein: said at least two herbal drugs are co-encapsulated in the liposome composition, and one of the at least two herbal drugs is silibinin and another of the at least two herbal drugs is glycyrrhizic acid, the mass ratio of silibinin to glycyrrhizic acid is approximately 1:3, and the liposome comprises poly(ethylene glycol)-phospholipid conjugate (PEG-lipid). 2. The liposome composition of claim 1, wherein the at least one phospholipid compound comprises dipalmitoyl phosphatidyl choline (DPPC). 3. The liposome composition of claim 2, wherein the PEG-lipid is distearoyl-phosphatidylethanolamine-N-[methoxy(polyethene glycol)-2000 (DSPE-mPEG2000). 4. The liposome composition of claim 3, wherein the molar ratio of (DPPC):cholesterol:DSPE-mPEG2000 in the liposome is in the rang of about 7:3:5:0.3 to about 7:4:0.4. 5. The liposome composition of claim 1, wherein the weight ratio of silibinin:glycyrrhizic acid:lipid phase is in the range of about 1:3:7 to 1:3:11. 6. The liposome composition of claim 1, wherein the liposome composition has a negative zeta potential. 7. The liposome composition of claim 1, wherein said liposome composition has an average diameter of less than 50 nanometers. 8. A targeted liposome composition for the treatment of cancer comprising: at least one phospholipid compound; a poly(ethylene glycol)-phospholipid conjugate (PEG-lipid); cholesterol; at least one monoclonal antibody; and at least two herbal drugs co-encapsulated in the liposome composition, wherein: one of the at least two herbal drugs is silibinin, another one of the at least two herbal drugs is glycyrrhizic acid, and glycyrrhizic acid is present at approximately three times the mass of silibinin. 9. The targeted liposome composition of claim 8, wherein the at least two herbal drugs co-encapsulated in the liposome composition include a third member selected from the group consisting of isosilibinin, silichristin, silidanin, glycyrrhetinic acid and combinations thereof. 10. The targeted liposome composition of claim 8, wherein the targeted liposome composition has an average diameter of less than about 90 nanometers. 11. The targeted liposome composition of claim 8, wherein the monoclonal antibody is selected from the group consisting of anti-CD147, HAb18, anti-CD166, anti-CD20, anti-HER2, anti-VEGF-A, anti-EGFR and rituximab. 12. The targeted liposome composition of claim 8, wherein said monoclonal antibody is Hab18 monoclonal antibody. 13. The targeted liposome composition of claim 12, wherein the number of Hab18 monoclonal antibodies on the surface of the liposome is at least 6. 14. The targeted liposome composition of claim 8, wherein the at least one phospholipid comprises dipalmitoyl phosphatidyl choline (DPPC). 15. The targeted liposome composition of claim 8, wherein the PEG-lipid is distearoyl-phosphatidylethanolamine-N-[methoxy(polyethene glycol)-2000 (DSPE-mPEG2000). 16. The targeted liposome composition of claim 8, wherein the phospholipid component comprises dipalmitoyl phosphatidyl choline (DPPC), wherein the PEG-lipid is distearoyl-phosphatidylethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG), and wherein the molar ratio of (DPPC):cholesterol:DSPE-mPEG2000 in the liposome composition is in the range of about 7:3.5:0.3 to about 7:4:0.4. 17. The targeted liposome composition of claim 16, wherein the targeted liposome composition has a negative zeta potential. 18. A method of preparing the liposome composition of claim 1, the method comprising: mixing a lipid mixture with the at least two herbal drugs in a solvent; evaporating the solvent from a result of mixing the lipid mixture with the at least two herbal drugs to form a lipid film; hydrating the lipid film with an aqueous solvent to form multilamellar vesicles; and sonicating the multilamellar vesicles to form a co-encapsulated nano-liposome composition that simultaneously includes the at least two herbal drugs co-encapsulated. 19. The method of claim 18, wherein hydrating the lipid film with the aqueous solvent is performed in a buffer. 20. The method of claim 19, wherein the at least one phospholipid compound comprises dipalmitoyl phosphatidyl choline (DPPC). 21. The method of claim 20, wherein the PEG-lipid is distearoyl-phosphatidylethanolamine-N-[methoxy(polyethene glycol)-2000] (DSPE-mPEG2000). 22. The method of claim 21, wherein the specific molar ratio of DPPC:cholesterol:DSPE-mPEG2000 is in the range of about 7:3.5:0.3 to about 7:4:0.4. 23. The method of claim 18, wherein hydrating the lipid film with the aqueous solvent is performed in a buffer, and wherein the specific weight ratio of the at least two herbal drugs:the lipid mixture:the aqueous solvent in the buffer is in the range of about 1:2:7 to about 1:3:11. 24. The method of claim 18, further comprising: drying of the liposome composition. 25. A method for preparing the liposome composition of claim 10, the method comprising: mixing a lipid mixture with the at least two herbal drugs in a solvent; evaporating the solvent from a result of mixing the lipid mixture with the at least two herbal drugs to form a lipid film; hydrating the lipid film with an aqueous solvent to form multilamellar vesicles; sonicating the multilameral vesicles to form a co-encapsulated nano-liposome composition that simultaneously includes the at least two herbal drugs co-encapsulated; and adding the monoclonal antibody to the prepared liposome composition to form the targeted liposome composition. 26. The method of claim 25, wherein the monoclonal antibody is selected from the group consisting of anti: HER2, anti-VEGF-A, and anti-EGFR. 27. The method of claim 25, wherein the monoclonal antibody is Hab18 monoclonal antibody. 28. The method of claim 25, wherein the method provides a loading efficacy in a range of about 25% to about 70% for the at least two herbal drugs. 29. The method of claim 25, wherein the liposome composition has an average diameter of less than about 90 nanometers. 30. The method of claim 18, wherein the method provides a loading efficacy in a range of about 25% to about 70% for the at least two herbal drugs. 31. The method of claim 18, wherein the liposome composition has an average diameter of less than about 90 nanometers. 32. A method of treating cancer in an individual in need of liver cancer treatment comprising administering the liposome composition of claim 1 to said individual. 33. A method of treating liver cancer in an individual in need of liver cancer treatment comprising administering the liposome composition of claim 8 to said individual.

Details for Patent 9,855,216

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2035-05-27
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2035-05-27