Self-assembling peptide and polysaccharide complexes

Patent metadata

Field	Value
Publication number	US-9937265-B2
Application number	US-201414782961-A
Country	US
Kind code	B2
Filing date	Apr 8, 2014
Priority date	Apr 8, 2013
Publication date	Apr 10, 2018
Grant date	Apr 10, 2018

Abstract

Novel self-assembling peptide complexes comprising a charged peptide and a polysaccharide, methods of producing them and uses therefore are described. The novel self-assembling peptide complexes have particular utility in the restoration of biomechanical or biochemical function of a variety of biological tissues, for example and without limitation, in degenerated spinal discs, osteoarthritic joints, damaged cartilage, meniscus, ligaments, tendons, dental, ophthalmic and cardiovascular and blood vessel tissues. Methods of repairing and or restoring biomechanical or biochemical function of biological tissues and scaffolds for the support of cell growth are also described.

First claim

The invention claimed is:

1. A composition of matter comprising a self-assembling peptide complex, the complex comprising:
(i) at least one charged self-assembling peptide, the peptide comprising 11 amino acid residues and comprising a hydrophobic aromatic core, wherein the amino acids at positions 4 and 8 are phenylalanine (F) and the amino acid at position 6 is tryptophan (W); and
(ii) an oppositely or same charged polysaccharide,

wherein the peptide and polysaccharide are not covalently bonded together, and wherein the peptide and/or self-assembling peptide complex forms ribbons, fibrils, fibers or a three dimensional scaffold in a β-sheet tape-like substructure.

2. The composition according to claim 1 , wherein the self-assembling peptide is selected from the group consisting of P11-12 (SEQ ID NO:2), P11-8 (SEQ ID NO:1), P11-14 (SEQ ID NO: 3), P11-16 (SEQ ID NO: 4), P11-18 (SEQ ID NO:5), P11-28 (SEQ ID NO:8), P11-31 (SEQ ID NO:9), P11-32 (SEQ ID NO:10), P11-4 (SEQ ID NO:11), P11-9 (SEQ ID NO:12), P11-13 (SEQ ID NO:13), P11-15 (SEQ ID NO:14), P11-17 (SEQ ID NO:15), P11-29 (SEQ ID NO:20) and P11-30 (SEQ ID NO:21).

3. The composition according to claim 1 wherein the overall net charge on the peptide is +/−2, +/−4 or +/−6.

4. The composition of claim 1 , wherein:
the amino acid residues at both positions 5 and 7 of the peptide is ornithine (O) or glutamic acid (E); and
the amino acid residues at positions 1 and 2 on the peptide are the same or different but reversed at positions 10 and 11.

5. The composition according to claim 1 , wherein the self-assembling peptide is a positively charged peptide and is associated with a polysaccharide selected from the group consisting of glycosaminoglycan (GAG), oligosaccharide, mucopolysaccharide and dextran.

6. The composition according to claim 5 , wherein the polysaccharide is negatively charged and is a glycosaminoglycan (GAG) selected from the group consisting of chondroitin sulfate, dermatan sulfate, kertatan sulfate, hyaluronan, hyaluronic acid, heparin and heparan sulphate.

7. The composition according to claim 1 , wherein the self-assembling peptide complex is P11-12 (SEQ ID NO: 2): GAG, P11-8 (SEQ ID NO: 1): GAG, P11-14 (SEQ ID NO: 3): GAG, P11-16 (SEQ ID NO: 4): GAG, P11-18 (SEQ ID NO: 5): GAG, P11-28 (SEQ ID NO: 8) GAG, P11-31 (SEQ ID NO: 9): GAG, P11-32 (SEQ ID NO:10): GAG, P11-4 (SEQ ID NO:11):GAG, P11-9 (SEQ ID NO:12):GAG, P11-13 (SEQ ID NO:13):GAG, P11-15 (SEQ ID NO:14):GAG, P11-17 (SEQ ID NO:15):GAG, P1129 (SEQ ID NO:20):GAG or P11-30 (SEQ ID NO:21):GAG.

8. The composition according to claim 1 , wherein the self-assembling peptide is a positively charged peptide and is associated with a positively charged polysaccharide selected from the group consisting of chitosan and its derivatives and other cationic polysaccharides.

9. The composition according to claim 1 , wherein the self assembling peptide is negatively charged and is associated with a negatively charged polysaccharide selected from the group consisting of glycosaminoglycan (GAG), oligosaccharide, mucopolysaccharide and dextran.

10. The composition according to claim 9 , wherein the negatively charged polysaccharide is a glycosaminoglycan (GAG) selected from the group consisting of chondroitin sulfate, dermatan sulfate, kertatan sulfate, hyaluronan, hyaluronic acid, heparin and heparan sulphate.

11. The composition according to claim 1 , wherein the self-assembling peptide is negatively charged and is associated with a positively charged polysaccharide selected from the group consisting of chitosan and its derivatives and other cationic polysaccharides.

12. The composition of claim 1 wherein the self-assembling peptide complex has an elastic modulus in the range 1 to 400,000 Pa.

13. The composition according to claim 1 , wherein the self-assembling peptide complex is in a gel, fluid, semi-solid, hydrogel, viscous solution, Newtonian fluid solution, aerogel, visco-elastic solid, xerogel, surface coating, film or a non-woven fabric.

14. The self-assembling peptide complex of claim 1 , further comprising a bioactive peptide sequence attached on either or both of the peptide termini.

15. A kit comprising:
(i) an injectable charged polysaccharide, and
at least one injectable self-assembling peptide selected from the group comprising wherein the self-assembling peptide is selected from the group consisting of P11-12 (SEQ ID NO:2), P11-8 (SEQ ID NO:1), P11-14 (SEQ ID NO: 3), P11-16 (SEQ ID NO: 4), P11-18 (SEQ ID NO:5), P11-28 (SEQ ID NO:8), P11-31 (SEQ ID NO:9), P11-32 (SEQ ID NO: 10), P11-4 (SEQ ID NO:11), P11-9 (SEQ ID NO:12), P11-13 (SEQ ID NO:13), P11-15 (SEQ ID NO:14), P11-17 (SEQ ID NO:15), P11-29 (SEQ ID NO:20) and P11-30 (SEQ ID NO:21);
wherein upon injection of the polysaccharide and the peptide a peptide complex is formed that has an elastic modulus in the range 1 to 400,000 Pa, the kit optionally further including a set of written instructions.

16. The kit according to claim 15 , further comprising a syringe comprising two barrels, wherein a first barrel comprises the polysaccharide and a second barrel comprises the peptide and the first and the second barrels are adapted to be in fluid communication when the peptide and polysaccharide are ejected from the syringe to allow mixing of the peptide and polysaccharide.

17. A method of preparing a self-assembling peptide complex, comprising:
mixing the composition of claim 1 with a negatively charged polysaccharide in a selected ratio so as to form a gel.

18. The method according to claim 17 , wherein the composition is present in a saline solution.

19. The method according to claim 17 , wherein mixing the charged self-assembling peptide and the polysaccharide comprises simultaneous injection into a recipient directly to the point at which it is desired to form a gel in situ.

20. The method according to claim 17 , wherein mixing the charged self-assembling peptide comprises injection to an appropriate site before or after injection of the polysaccharide.

21. An injectable biomaterial composition comprising a self-assembling peptide complex, the complex comprising:
(i) at least one charged self-assembling peptide comprising 11 amino acids residues and having a hydrophobic aromatic core wherein the amino acid at positions 4 and 8 are phenylalanine (F) and the amino acid at position 6 is tryptophan (W); and
ii) an oppositely or same charged polysaccharide, wherein the peptide and polysaccharide are not covalently bonded together, and wherein the peptide and/or self-assembling peptide complex forms ribbons, fibrils, fibers or a three dimensional scaffold in a β-sheet tape-like substructure.

22. The biomaterial composition according to claim 21 , wherein the composition forms a gel, semi-solid, hydrogel, viscous solution, visco-elastic solid, xerogel, surface coating or film at the site where it has been injected.

23. A personal care product, tissue reconstruction device, scaffold for tissue engineering or an adjunct for ophthalmology procedures comprising the self-assembling peptide complex of claim 1 .

24. A method of repairing or replacing or restoring the nucleus pulposus of a disc, comprising administering the self-assembling peptide complex according to claim 1 into an area of the nucleus pulposus of a disc that requires treatment.

25. The method according to claim 24 , wherein the self-assembling peptide complex has shear elastic and viscous mo

Assignees

• Univ Leeds Innovations Ltd

Inventors

• Ingham Eileen
• Wilcox Ruth Karen
• Aggeli Amalia
• Miles Danielle Elizabeth

Classifications

• A61P19/00

  Drugs for skeletal disorders · CPC title

• A61M5/19

  having more than one chamber {, e.g. including a manifold coupling two parallelly aligned syringes through separate channels to a common discharge assembly (surgical glue applicators A61B17/00491)} · 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

• A61K31/728

  Hyaluronic acid · CPC title

• C07K7/06

  having 5 to 11 amino acids · CPC title