Linkage of agents to body tissue using microparticles and transglutaminase

• US 6,958,148 B1
• Filed: 07/21/2000
• Issued: 10/25/2005
• Est. Priority Date: 01/20/1998
• Status: Expired due to Fees

• Current Assignee: Pericor Science, Inc.
• Original Assignee: Pericor Science, Inc.
• Inventors: Green, Howard, Djian, Philippe, Compton, Bruce J., Corey, George D.
• Primary Examiner(s): Naff, David M.
• Application Number:
  US09/620,783
• Time in Patent Office: 1,922 Days
• Field of Search: 424/94.5, 424/94.63, 424/401, 424/59, 435/16, 435/177, 435/193, 514/2, 530/403, 530/812
• US Class Current: 424/94.5
• CPC Class Codes: A61K 2800/412 Microsized, i.e. having sizes between 0.1 and 100 microns
• CPC Class Codes: A61K 2800/57 Compounds covalently linked to a(n inert) carrier molecule, e.g. conjugates, pro-fragrances
• CPC Class Codes: A61K 2800/94 Involves covalent bonding to the substrate
• CPC Class Codes: A61K 8/11 Encapsulated compositions
• CPC Class Codes: A61K 8/64 Proteins; Peptides; Derivatives or degradation products thereof
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: C07K 17/08 the carrier being a synthetic polymer
• CPC Class Codes: Y10S 530/812 Peptides or proteins is immobilized on, or in, an organic carrier

Abstract

Methods, products and kits are provided for attaching agents to a body tissue surface via microparticles using endogenous or exogenous transglutaminase. The microparticles have surface available transglutaminase substrate reactive groups. In an embodiment, the groups are part of a polymer containing at least two contiguous linked lysines or at least three contiguous linked glutamines.

Claims

1. A composition comprising

a microparticle comprising an active agent and a polymer having transglutaminase substrate reactive groups, wherein the transglutaminase substrate reactive groups are surface available, and the polymer comprises a polymer of amino acids having at least three contiguous linked glutamines.

2. The composition of claim 1, wherein the transglutaminase substrate reactive groups are surface available in an amount sufficient to attach the microparticle to a body tissue in the presence of endogenous transglutaminase.

3. The composition of claim 1, wherein the transglutaminase substrate reactive groups are surface available in an amount sufficient to attach the microparticle to a body tissue in the presence of exogenous transglutaminase.

4. The composition of claim 1, wherein the polymer is covalently linked to a synthetic polymer.

5. The composition of claim 1, wherein the polymer comprises a polymer of amino acids and wherein at least 20% of the amino acids are glutamines.

6. The composition of claim 1, wherein the active agent is selected from the group consisting of a cosmetic agent, a bulking agent, a hair conditioning agent, a hair fixative, a sunscreen agent, a moisturizing agent, a depilatory agent, an anti-nerve gas agent, a film forming agent, a vitamin, an insect repellant, a coloring agent, a pharmaceutical agent, a ligand-receptor complex and a receptor of a ligand-receptor complex.

7. A kit comprising

a package including a container containing the composition of claim 1 and instructions for topically administering the composition to a skin surface.

8. A composition comprising

a microparticle comprising an active agent and a polymer having transglutaminase substrate reactive groups, wherein the microparticle is non-biodegradable, and the transglutaminase substrate reactive groups are surface available, and the polymer comprises a polymer of amino acids having at least three contiguous linked lysines.

9. The composition of claim 8, wherein the transglutaminase substrate reactive groups are surface available in an amount sufficient to attach the microparticle to a body tissue in the presence of endogenous transglutaminase.

10. The composition of claim 8, wherein the transglutaminase substrate reactive groups are surface available in an amount sufficient to attach the microparticle to a body tissue in the presence of exogenous transglutaminase.

11. The composition of claim 8, wherein the polymer comprises a polymer of amino acids and wherein at least 50% of the amino acids are lysine.

12. The composition of claim 8, wherein the active agent is selected from the group consisting of a cosmetic agent, a bulking agent, a hair conditioning agent, a hair fixative, a sunscreen agent, a moisturizing agent, a depilatory agent, an anti-nerve gas agent, a film forming agent, a vitamin, an insect repellant, a coloring agent, a pharmaceutical agent, a ligand-receptor complex and a receptor of a ligand-receptor complex.

13. A kit comprising

a package including a container containing the composition of claim 8 and instructions for topically administering the composition to a skin surface.

14. A method of treating a subject to attach microparticles to a body tissue of the subject comprising

contacting the body tissue in the presence of endogenous or exogenous transglutaminase with microparticles having surface available transglutaminase substrate reactive groups in an amount sufficient to attach the microparticles to the body tissue in the presence of the transglutaminase,

allowing the microparticles to remain in contact with the body tissue for a time sufficient to permit a layer of microparticles to covalently attach to the body tissue,

wherein the transglutaminase substrate reactive groups are part of a polymer, and

wherein the polymer comprises a polymer selected from the group consisting of polymers containing:

(a) at least two contiguous linked lysines,

(b) at least three contiguous linked lysines,

(c) at least four contiguous linked lysines, and

(d) at least five contiguous linked lysines.

15. The method of claim 14, wherein the polymer is a polymer containing at least two contiguous linked lysines.

16. The method of claim 14, wherein the polymer is a polymer containing at least three contiguous linked lysines.

17. The method of claim 14, wherein the polymer is a polymer containing at least four contiguous linked lysines.

18. The method of claim 14, wherein the polymer is a polymer containing at least five contiguous linked lysines.

19. The method of claim 14, wherein the endogenous or exogenous transglutaminase is endogenous transglutaminase.

20. The method of claim 14, wherein the endogenous or exogenous transglutaminase is exogenous transglutaminase.

21. The method of claim 14, wherein the body tissue is integument.

22. The method of claim 21, wherein the integument is skin.

23. The method of claim 21, wherein the integument is the surface of the eye.

24. The method of claim 21, wherein the integument is a mucous membrane.

25. The method of claim 14, wherein the body tissue is an internal tissue.

26. The method of claim 14, wherein the microparticles further comprise an active agent.

34. The method of claim 24, wherein the body tissue is integument.

35. The method of claim 34, wherein the integument is skin.

36. The method of claim 34, wherein the integument is the surface of the eye.

37. The method of claim 34, wherein the integument is a mucous membrane.

27. A method of treating a subject to attach microparticles to a body tissue of the subject comprising

contacting the body tissue in the presence of endogenous or exogenous transglutaminase with microparticles having surface available transglutaminase substrate reactive groups in an amount sufficient to attach the microparticles to the body tissue in the presence of the transglutaminase,

allowing the microparticles to remain in contact with the body tissue for a time sufficient to permit a layer of microparticles to covalently attach to the body tissue,

wherein the transglutaminase substrate reactive groups are part of a polymer, and

wherein the polymer comprises a polymer selected from the group consisting of polymers containing:

(a) at least five contiguous linked glutamines,

(b) at least ten contiguous linked glutamines,

(c) at least fifteen contiguous linked glutamines, and

(d) at least twenty contiguous linked glutamines.

28. The method of claim 27, wherein the polymer is a polymer containing at least five contiguous linked glutamines.

29. The method of claim 27, wherein the polymer is a polymer containing at least ten contiguous linked glutamines.

30. The method of claim 27, wherein the polymer is a polymer containing at least fifteen contiguous linked glutamines.

31. The method of claim 27, wherein the polymer is a polymer containing at least twenty contiguous linked glutamines.

32. The method of claim 27, wherein the endogenous or exogenous transglutaminase is endogenous transglutaminase.

33. The method of claim 27, wherein the endogenous or exogenous transglutaminase is exogenous transglutaminase.

38. The method of claim 27, wherein the body tissue is an internal tissue.

39. The method of claim 27, wherein the microparticles further comprise an active agent.