Compositions and methods for delivery of frozen particle adhesives

• US 9,060,931 B2
• Filed: 03/20/2009
• Issued: 06/23/2015
• Est. Priority Date: 10/31/2008
• Status: Active Grant

• Current Assignee: Gearbox LLC (Intellectual Ventures LLC)
• Original Assignee: The Invention Science Fund I, L.L.C. (Intellectual Ventures LLC)
• Inventors: Boyden, Edward S., Cook, Daniel B., Hyde, Roderick A., Leuthardt, Eric C., Myhrvold, Nathan P., Sweeney, Elizabeth A., Wood, Lowell L. Jr.
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): Rider, Lance W
• Application Number:
  US12/383,265
• Publication Number:
  US 20100113615A1
• Time in Patent Office: 2,286 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 41/0004 Homeopathy; Vitalisation; Resonance; Dynamisation, e.g. esoteric applications; Oxygenation of blood
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 51/1244 microparticles or nanoparticles, e.g. polymeric nanoparticles
• CPC Class Codes: A61K 9/0019 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 Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1664 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/1617
• CPC Class Codes: A61K 9/1688 resulting in pure drug agglomerate optionally containing up to 5% of excipient
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like

Abstract

Certain embodiments disclosed herein relate to compositions, methods, devices, systems, and products regarding frozen particles. In certain embodiments, the frozen particles include materials at low temperatures. In certain embodiments, the frozen particles provide vehicles for delivery of particular agents. In certain embodiments, the frozen particles are administered to at least one biological tissue.

Claims

1. A frozen particle composition, comprising:

one or more frozen particles approximately 500 microns or smaller in size;

the one or more frozen particles including at least one of a pluripotent stem cell, a mesenchymal stem cell, a fibroblast, a keratinocyte, or a dermal progenitor cell;

at least one adhesive agent of one or more of fibrinogen, thrombin, bispecific protein, adhesion molecule, or an acrylic polymer or copolymer;

and at least one encapsulated therapeutic agent including at least one growth factor, antibiotic, or anesthetic.

2. The frozen particle composition of claim 1, further including one or more of nitrogen, helium, neon, xenon, oxygen, air, krypton, chlorine, bromine, or argon.

3. The frozen particle composition of claim 1, wherein the at least one adhesive agent is located in a compartment within the frozen particle.

4. The frozen particle composition of claim 1, wherein the at least one adhesive agent is substantially in the form of a vesicle, caged compound, or other material that modulates the rate of diffusion or degradation of the at least one adhesive agent.

5. The frozen particle composition of claim 4, wherein the at least one material reduces the rate of diffusion or degradation of the at least one adhesive agent.

6. The frozen particle composition of claim 1, wherein the at least one adhesive agent includes at least one nontoxic, biocompatible, bioresorbable, or biodegradable agent.

7. The frozen particle composition of claim 1, wherein the at least one adhesive agent is configured to form one or more of a hydrogen bond, ionic bond, covalent bond, or non-covalent bond with at least one substrate.

8. The frozen particle composition of claim 1, wherein the at least one adhesive agent includes at least one crosslinking or derivatized agent.

9. The frozen particle composition of claim 8, wherein the at least one adhesive agent is configured to form a crosslink bond with at least one component of at least one substrate.

10. The frozen particle composition of claim 9, wherein the crosslink bond of the at least one adhesive agent is configured for modulation by one or more of a chemical agent, change in pH, change in exposure to air, vacuum, change in moisture content, change in pressure, or change in temperature.

11. The frozen particle composition of claim 9, wherein the formation of a crosslink bond of the at least one adhesive agent is configured for modulation by exposure of the at least one adhesive agent to one or more of electromagnetic energy, optical energy, thermal energy, laser energy, ionizing radiation, non-ionizing radiation, or sonic energy.

12. The frozen particle composition of claim 1, further including at least one therapeutic agent including at least one cytokine, hormone, vitamin, enzyme, epinephrine, or angiogenic factor.

13. The frozen particle composition of claim 1, wherein the at least one adhesive agent includes a methacrylate.

14. The frozen particle composition of claim 13, wherein the at least one adhesive agent includes at least one of poly(N,N-dimethyl-N-(ethoxycarbonylmethyl)-N-[2′

-(methacryloyloxy)ethyl]-ammonium bromide) or poly(sulfobetaine methacrylate).

15. The frozen particle composition of claim 1, further including one or more reinforcement agents including at least one of polyaramid, vinylester matrix, ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide, nylon, silk, rayon, acetate, modacrylic, olefin, polyester, aromatic polyester, poly-lactic acid, vinyon, saran, spandex, vinalon, aromatic nylon, vinylidene chloride, modal, polybenzimidazole, sulfur, lyocell, orlon, zylon, high-performance polyethylene, polypyridobenzimidazole, vectran, acrylonitrile rubber, glass, copper, iron, steel, aluminum, magnesium, silicon, or silica.

16. The frozen particle composition of claim 1, further including one or more abrasives including one or more of alluvium, sand, calcite, emergy, pumice, rouge, borazon, corundum, zirconia alumina, diamond, or novaculite.

17. The frozen particle composition of claim 1, further including at least one of a nanoparticle, detection material, sensor, micro-syringe, or circuit.

18. The frozen particle composition of claim 1, formulated to be administered by high velocity impact.

19. The frozen particle composition of claim 1, further including one or more explosive materials including at least one of a carbonate, carbon dioxide, nitroglycerine, acid, base, epoxy, acrylamide polymer or copolymer, urethane, hypoxyapatite, or a reactive metal.

20. The frozen particle composition of claim 1, wherein the at least one adhesive agent includes a detectable state that varies with its adhesive state.

21. The frozen particle composition of claim 1, wherein the at least one adhesive agent further includes one or more epoxy adhesive, acrylic adhesive, urethane adhesive, polyurethane adhesive, silicone adhesive, cationic adhesive, anerobic adhesive, urethane acrylate, polyester acrylate, methyacrylate, or cyanoacrylate.

22. The frozen particle composition of claim 1, wherein the at least one adhesive agent includes at least one α

-cyanoacrylate and a fluorescent compound including at least one of a bis-benzoxazolyl compound, pyrylium salt, quantum dot, or coumarin compound.

23. The frozen particle composition of claim 1, wherein the at least one adhesive agent includes an α

-cyanoacrylate and 2,5-bis-(5-tert-butyl-2-benzoxasolyl)-thiophene.

24. The frozen particle composition of claim 1, wherein the at least one adhesive agent further includes one or more of a base component, initiator component, or activator component.

25. The frozen particle composition of claim 1, wherein the at least one adhesive agent further includes at least one curing component.

26. The frozen particle composition of claim 1, wherein the at least one adhesive agent further includes at least one photopolymerizable adhesive, photocurable adhesive, thermal curable adhesive, free radical curable adhesive, or aerobic curable adhesive.

27. A method for providing at least one frozen particle composition to at least one substrate, comprising:

administering at least one frozen particle composition to at least one substrate,

wherein the at least one frozen particle composition includes one or more frozen particles approximately 500 microns or smaller in size;

the one or more frozen particles including at least one of a pluripotent stem cell, a mesenchymal stem cell, a fibroblast, a keratinocyte, or a dermal progenitor cell;

at least one adhesive agent of one or more of fibrinogen, thrombin, bispecific protein, adhesion molecule, or an acrylic polymer or copolymer;

and at least one encapsulated therapeutic agent including at least one growth factor, antibiotic, or anesthetic.

28. The method of claim 27, wherein the at least one frozen composition includes one or more of nitrogen, helium, neon, xenon, oxygen, air, krypton, chlorine, bromine, or argon.

29. The method of claim 27, wherein the at least one adhesive agent includes at least one of a monomer, prepolymer, polymer, or copolymer.

30. The method of claim 29, wherein the at least one adhesive agent includes at least one monomer of a self-polymerizing agent.

31. The method of claim 27, wherein administering at least one frozen particle composition to at least one substrate includes accelerating, propelling, or ejecting the frozen particle composition toward the at least one substrate.

32. The method of claim 27, wherein administering the at least one frozen particle composition to at least one substrate includes propelling, ejecting, or accelerating the at least one frozen particle composition toward the at least one substrate at a predetermined angle, predetermined velocity, or predetermined rate of administration.

33. The method of claim 27, further including varying the rate, velocity, or angle at which the at least one frozen particle composition is administered to at least one substrate.

34. The method of claim 27, further including administering to the at least one substrate at least one of a nanoparticle, detection material, sensor, micro-syringe, or circuit.

35. The method of claim 27, wherein the at least one adhesive agent includes a detectable state that varies with its adhesive state.

36. The method of claim 35, wherein the at least one adhesive agent includes one or more epoxy adhesive, acrylic adhesive, urethane adhesive, polyurethane adhesive, silicone adhesive, cationic adhesive, anerobic adhesive, urethane acrylate, polyester acrylate, methyacrylate, or cyanoacrylate.

37. The method of claim 35, wherein the at least one adhesive agent includes at least one α

-cyanoacrylate and a fluorescent compound including at least one of a bis-benzoxazolyl compound, pyrylium salt, quantum dot, or coumarin compound.

38. The method of claim 35, wherein the at least one adhesive agent includes an α

-cyanoacrylate and 2,5-bis-(5-tert-butyl-2-benzoxasolyl)-thiophene.

39. The method of claim 27, wherein the at least one adhesive agent further includes one or more of a base component, initiator component, or activator component.

40. The method of claim 27, wherein the at least one adhesive agent further includes at least one curing component.

41. The method of claim 27, wherein the at least one adhesive agent includes at least one photopolymerizable adhesive, photocurable adhesive, thermal curable adhesive, free radical curable adhesive, or aerobic curable adhesive.

42. The method of claim 27, wherein the adhesive agent includes at least one dye coinitiator.

43. The method of claim 27, wherein the at least one adhesive agent includes one or more components that are inactive.

44. The method of claim 43, wherein the one or more components are configured to be activated by administration.

45. The method of claim 27, wherein the at least one adhesive agent includes two or more components configured to combine upon administration to at least one substrate.

46. A method of maintaining the approximation of tissue of at least one wound of a subject, comprising:

administering at least one frozen particle composition to at least one wound of a subject for a time sufficient to maintain the approximation of tissue of the at least one wound;

wherein the at least one frozen particle composition includes one or more frozen particles approximately 500 microns or smaller in size;

the one or more frozen particles including at least one of a pluripotent stem cell, a mesenchymal stem cell, a fibroblast, a keratinocyte, or a dermal progenitor cell;

at least one adhesive agent of one or more of fibrinogen, thrombin, bispecific protein, adhesion molecule, or an acrylic polymer or copolymer;

and at least one encapsulated therapeutic agent including at least one growth factor, antibiotic, or anesthetic.

47. A frozen particle composition, comprising:

one or more frozen particles approximately 250 microns or smaller in size;

the one or more frozen particles including at least one of a pluripotent stem cell, a mesenchymal stem cell, a fibroblast, a keratinocyte, or a dermal progenitor cell;

wherein the one or more frozen particles are coated by at least one adhesive agent of one or more of fibrinogen, thrombin, bispecific protein, adhesion molecule, or an acrylic polymer or copolymer.

48. A method for providing at least one frozen particle composition to at least one substrate, comprising:

administering at least one frozen particle composition to at least one substrate,

wherein the at least one frozen particle composition includes one or more frozen particles approximately 250 microns or smaller in size;

the one or more frozen particles including at least one of a pluripotent stem cell, a mesenchymal stem cell, a fibroblast, a keratinocyte, or a dermal progenitor cell;

wherein the one or more frozen particles are coated by at least one adhesive agent of one or more of fibrinogen, thrombin, bispecific protein, adhesion molecule, or an acrylic polymer or copolymer.