Collagen-related peptides and uses thereof
AssigneeAdvanced Technologies and Regenerative Medicine, LLC
InventorsWilliam A. Kinney, Mabel Alarnino Cejas, Bruce E. Maryanoff, Thomas Matalenas, Chunlin Yang
Life of this patent
Estimating the term…
Abstract
The present invention relates to a collagen-related polypeptide (CRP) having hydrophobic amino acid groups at the N- and C-termini capable of non-covalent self-assembly into collagen mimetic triple helices and fibrils thereof and the synthesis, methods of use and compositions thereof.
Claims37
A composition comprised of a collagen-related peptide of Formula (I):
- B-(Z)m-X
- wherein
- Z is selected from the group consisting of Gly-Pro-J, Pro-J-Gly and J-Gly-Pro;
- J is selected from the group consisting of Hyp, fPro, mPro and Pro;
- m is an integer selected from 8, 9, 10, 11, 12, 13, 14 or 15;
- and,
- B and X are independently selected from the group consisting of F5-Phe, Phe wherein the phenyl ring is mono or disubstituted with fluoro, chloro, bromo, hydroxyl, methyl or CF3, Tyr, 3,4-(OH)2-Phe, MeO-Tyr, phenylglycine, 2-naphthyl-Ala, 1-naphthyl-Ala, Trp, Cha, Chg, Met, Leu, Ile and Val,
- wherein the composition is in the form of a foam, a powder, a fiber, or a film, wherein the composition comprises a plurality of said collagen-related peptides, wherein the collagen-related peptides are present in the form of a plurality of collagen-related peptide trimers, and wherein the collagen-related peptide trimers are homotrimers or heterotrimers.
A composition comprised of
- (a) a collagen-related peptide of Formula (I):
- B-(Z)m-X
- wherein
- Z is selected from the group consisting of Gly-Pro-J, Pro-J-Gly and J-Gly-Pro;
- J is selected from the group consisting of Hyp, fPro, mPro and Pro;
- m is an integer selected from 8, 9, 10, 11, 12, 13, 14 or 15;
- and,
- B and X are independently selected from the group consisting of F5-Phe, Phe wherein the phenyl ring is mono or disubstituted with fluoro, chloro, bromo, hydroxyl, methyl or CF3, Tyr, 3,4-(OH)2-Phe, MeO-Tyr, phenylglycine, 2-naphthyl-Ala, 1-naphthyl-Ala, Tip, Cha, Chg, Met, Leu, Ile and Val;
- and
- (b) a substrate,
- wherein the composition comprises a plurality of said collagen-related peptides, wherein the collagen-related peptides are present in the form of a plurality of collagen-related peptide trimers, and wherein the collagen-related peptide trimers are homotrimers or heterotrimers.
A gel comprised of:
- a) a collagen-related peptide of Formula (I):
- B-(Z)m-X
- wherein
- Z is selected from the group consisting of Gly-Pro-J, Pro-J-Gly and J-Gly-Pro;
- J is selected from the group consisting of Hyp, fPro, mPro and Pro;
- m is an integer selected from 8, 9, 10, 11, 12, 13, 14 or 15;
- and,
- B and X are independently selected from the group consisting of F5-Phe, Phe wherein the phenyl ring is mono or disubstituted with fluoro, chloro, bromo, hydroxyl, methyl or CF3, Tyr, 3,4-(OH)2-Phe, MeO-Tyr, phenylglycine, 2-naphthyl-Ala, 1-naphthyl-Ala, Trp, Cha, Chg, Met, Leu, Ile and Val;
- and
- b) a gelling agent, wherein the collagen-related peptide is present in the gel in an amount, based upon the total weight of the gel, from about 0.1 mg/ml to about 10 mg/mL
- wherein the composition comprises a plurality of said collagen-related peptides, wherein the collagen-related peptides are present in the form of a plurality of collagen-related peptide trimers, and wherein the collagen-related peptide trimers are homotrimers or heterotrimers.
A composition comprised of:
- a) a collagen-related peptide of Formula (I):
- B-(Z)m-X
- wherein
- Z is selected from the group consisting of Gly-Pro-J, Pro-J-Gly and J-Gly-Pro;
- J is selected from the group consisting of Hyp, fPro, mPro and Pro;
- m is an integer selected from 8, 9, 10, 11, 12, 13, 14 or 15;
- and,
- B and X are independently selected from the group consisting of F5-Phe, Phe wherein the phenyl ring is mono or disubstituted with fluoro, chloro, bromo, hydroxyl, methyl or CF3, Tyr, 3,4-(OH)2-Phe, MeO-Tyr, phenylglycine, 2-naphthyl-Ala, 1-naphthyl-Ala, Trp, Cha, Chg, Met, Leu, Ile and Val;
- and
- b) at least one excipient.
A method of treating bleeding disorders in an individual in need thereof comprising using a collagen-related peptide of Formula (I):
- B-(Z)mX wherein
- Z is selected from the group consisting of Gly-Pro-J, Pro-J-Gly and J-Gly-Pro;
- J is selected from the group consisting of Hyp, fPro, mPro and Pro;
- m is an integer selected from 8, 9, 10, 11, 12, 13, 14 or 15;
- and,
- B and X are independently selected from the group consisting of F5-Phe, Phe wherein the phenyl ring is mono or disubstituted with fluoro, chloro, bromo, hydroxyl, methyl or CF3, Tyr, 3,4-(OH)2-Phe, MeO-Tyr, phenylglycine, 2-naphthyl-Ala, 1-naphthyl-Ala, Trp, Cha, Chg, Met, Leu, Ile and Val;
- in an amount effective for initiating platelet aggregation on a desired site in said individual.
A method of diagnosing bleeding disorders in an individual in need thereof comprising
- (a) combining a collagen-related peptide of Formula (I):
- B-(Z)m-X
- wherein
- Z is selected from the group consisting of Gly-Pro-J, Pro-J-Gly and J-Gly-Pro;
- J is selected from the group consisting of Hyp, fPro, mPro and Pro;
- m is an integer selected from 8, 9, 10, 11, 12, 13, 14 or 15;
- and,
- B and X are independently selected from the group consisting of F5-Phe, Phe wherein the phenyl ring is mono or disubstituted with fluoro, chloro, bromo, hydroxyl, methyl or CF3, Tyr, 3,4-(OH)2-Phe, MeO-Tyr, phenylglycine, 2-naphthyl-Ala, 1-naphthyl-Ala, Trp, Cha, Chg, Met, Leu, Ile and Val;
- with blood or plasma containing platelets from said individual to form a mixture;
- then
- (b) adding the mixture to a platelet aggregometer in order to evaluate platelet aggregation in said mixture.
A composition comprised of:
- (a) a collagen-related peptide of Formula (I):
- B-(Z)m-X
- wherein
- Z is selected from the group consisting of Gly-Pro-J, Pro-J-Gly and J-Gly-Pro;
- J is selected from the group consisting of Hyp, fPro, mPro and Pro;
- m is an integer selected from 8, 9, 10, 11, 12, 13, 14 or 15;
- and,
- B and X are independently selected from the group consisting of F5-Phe, Phe wherein the phenyl ring is mono or disubstituted with fluoro, chloro, bromo, hydroxyl, methyl or CF3, Tyr, 3,4-(OH)2-Phe, MeO-Tyr, phenylglycine, 2-naphthyl-Ala, 1-naphthyl-Ala, Trp, Cha, Chg, Met, Leu, Ile and Val;
- and
- (b) a pharmaceutically active agent.
A composition comprising a chemically defined three-dimensional polymer matrix supplemented with a collagen-related peptide of Formula (I):
- B-(Z)m-X
- wherein
- Z is selected from the group consisting of Gly-Pro-J, Pro-J-Gly and J-Gly-Pro;
- J is selected from the group consisting of Hyp, fPro, mPro and Pro;
- m is an integer selected from 8, 9, 10, 11, 12, 13, 14 or 15;
- and,
- B and X are independently selected from the group consisting of F5-Phe, Phe wherein the phenyl ring is mono or disubstituted with fluoro, chloro, bromo, hydroxyl, methyl or CF3, Tyr, 3,4-(OH)2-Phe, MeO-Tyr, phenylglycine, 2-naphthyl-Ala, 1-naphthyl-Ala, Trp, Cha, Chg, Met, Leu, Ile and Val.
Dependencies are inferred from the claim text.