SOLID FORM AND METHOD FOR PREPARING THE SAME

• US 20140187591A1
• Filed: 04/26/2013
• Published: 07/03/2014
• Est. Priority Date: 12/28/2012
• Status: Active Grant

• Current Assignee: Industrial Technology Research Institute
• Original Assignee: Industrial Technology Research Institute
• Inventors: SHEN, Hsin-Hsin, LIOU, Yu-Bing, CHEN, Chin-Fu, LIN, Li-Hsin, HUANG, Hsiu-Hua, CHAO, Ying-Hsueh, HUNG, Chih-Bing, HSIEH, Meng-Yow, CHEN, Miao-Tzu
• Granted Patent: US 9,084,822 B2
• Time in Patent Office: Days
• US Class Current: 514/355
• 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 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L

Abstract

The disclosure provides a solid form and a method for preparing the same. The solid form consists essentially of a biodegradable copolymer and an amide-containing compound. The biodegradable copolymer is semi-crystalline due to the dipole-dipole interaction between the biodegradable copolymer and the urea. The method for preparing the above solid form includes: dissolving a biodegradable copolymer and an amide-containing compound in water at a first temperature, obtaining a solution; cooling the solution at a second temperature to form a solid mixture; and the solid mixture is subjected to a freeze-drying process at a third temperature.

Claims

1. A solid form, consisting essentially of:

a biodegradable copolymer; and

an amide-containing compound, wherein the biodegradable copolymer is semi-crystalline due to the dipole-dipole interaction between the biodegradable copolymer and the amide-containing compound

2. The solid form as claimed in claim 1, wherein the amide-containing compound comprises

3. The solid form as claimed in claim 1, wherein the biodegradable copolymer comprises a di-block or tri-block copolymer prepared from a hydrophobic polymer and a hydrophobic polymer via copolymerization.

4. The solid form as claimed in claim 3, wherein the hydrophilic polymer comprises polyethylene glycol (PEG), or methoxy-poly(ethylene glycol) (mPEG).

5. The solid faint as claimed in claim 3, wherein the hydrophobic polymer comprises poly(lactide-co-glycolide) (PLGA), poly(propionic-co-lactic (PPLA), poly(valeric-co-lactic) (PVLA), or poly(caproic-co-lactic (PCLA).

6. The solid form as claimed in claim 1, wherein the biodegradable copolymer has a structure represented by Formula (I) or Formula (II):

A-B-BOX-B-A 

 

Formula (I); and

B-A-B-(BOX-B-A-B)_n-BOX-B-A-B 

 

Formula (II)

wherein A comprises a hydrophilic polyethylene glycol polymer, B comprises a hydrophobic polyester polymer, BOX is a bifunctional group monomer of 2,2′

-Bis(2-oxazoline) and used for coupling the blocks A-B or B-A-B, and a is an integer and the same or more than 0.

7. The solid form as claimed in claim 6, wherein the A comprises polyethylene glycol (PEG), or methoxy-poly(ethylene glycol) (mPEG).

8. The solid form as claimed in claim 6, wherein the B comprises poly(lactide-co-glycolide) (PLGA), poly(propionic-co-lactic (PPLA), poly(valeric-co-lactic) (PVLA), or poly(caproic-co-lactic (PCLA).

9. The solid form as claimed in claim 1, wherein the weight ratio of the biodegradable copolymer is 52-83 wt %, and the weight ratio of the amide-containing compound is 17-48 wt %, based on the weight of the solid form.

10. The solid form as claimed in claim 1, wherein the solid form is completely dissolved in water within 5 min.

11. A method for preparing a solid faint, comprising:

dissolving a biodegradable copolymer and an amide-containing compound in water at a first temperature, obtaining a solution;

cooling the solution at a second temperature to form a solid mixture; and

the solid mixture is subjected to a freeze-drying process at a third temperature.

12. The method as claimed in claim 11, wherein the first temperature is from 1 to 10°

C.

13. The method as claimed in claim 11, wherein the second temperature is from −

15 to −

60°

C.

14. The method as claimed in claim 11, wherein the third temperature is from −

15 to −

40°

C.

15. The method as claimed in claim 11, wherein the biodegradable copolymer comprises a di-block or tri-block copolymer prepared from a hydrophobic polymer and a hydrophobic polymer via copolymerization.

16. The method as claimed in claim 15, wherein the hydrophilic polymer comprises polyethylene glycol (PEG), or methoxy-poly(ethylene glycol) (mPEG).

17. The method as claimed in claim 15, wherein the hydrophobic polymer comprises poly(lactide-co-glycolide) (PLGA), poly(propionic-co-lactic (PPLA), poly(valeric-co-lactic) (PVLA), or poly(caproic-co-lactic (PCLA).

18. The method as claimed in claim 11, wherein the biodegradable copolymer has a structure represented by Formula (I) or Formula (II):

A-B-BOX-B-A 

 

Formula (I); and

B-A-B-(BOX-B-A-B)_n-BOX-B-A-B 

 

Formula (II)

wherein A comprises a hydrophilic polyethylene glycol polymer, B comprises a hydrophobic polyester polymer, BOX is a bifunctional group monomer of 2,2′

-Bis(2-oxazoline) and used for coupling the blocks A-B or B-A-B, and n is an integer and the same or more than 0.

19. The method as claimed in claim 18, wherein the A comprises polyethylene glycol (PEG), or methoxy-poly(ethylene glycol) (mPEG).

20. The method as claimed in claim 18, wherein the B comprises poly(lactide-(PLGA), poly(propionic-co-lactic (PPLA), poly(valeric-co-lactic) (PVLA), or poly(caproic-co-lactic (PCLA).

21. The method as claimed in claim 11, wherein the weight ratio of the biodegradable copolymer is 52-83 wt %, and the weight ratio of the amide-containing compound is 17-48 wt %, based on the weight of the biodegradable copolymer and the amide-containing compound.

22. The method as claimed in claim 11, wherein the amide-containing compound comprises