Compositions and methods for delivery of frozen particle adhesives

• US 9,050,251 B2
• Filed: 03/20/2009
• Issued: 06/09/2015
• 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:
  US12/383,263
• Publication Number:
  US 20100111846A1
• Time in Patent Office: 2,272 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 31/10 Sulfides; Sulfoxides; Sulfones
• 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 49/1818 particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
• CPC Class Codes: A61K 51/12 characterised by a special physical form, e.g. emulsion, microcapsules, liposomes , characterized by a special physical form, e.g. emulsions, dispersions, microcapsules liposomes A61K51/1234
• 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 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• 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 9/167 : 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: 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 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: B33Y 80/00 : Products made by additive manufacturing
• CPC Class Codes: Y10T 428/2982 : Particulate matter [e.g., sphere, flake, etc.]

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 saline solution particles including at least one adhesive agent substantially in the form of a vesicle and including an acrylic polymer;

and wherein the frozen particle composition is externally coated with at least one anesthetic, analgesic, or antimicrobial agent, wherein the analgesic or anesthetic includes at least one of an aminoamid or aminoester local anesthetic, ibuprofen, morphine, codeine, lidocaine/lignocaine, ropivacaine, mepivacaine, benzocaine, chloroprocaine, cyclomethycaine, dimethocaine/larocaine, propoxycaine, procaine/novocaine, proparacaine, tetracaine/amethocaine, articaine, bupivacaine, carticaine, cinchocaine/dibucaine, etidocaine, levobupivacaine, piperocaine, prilocaine, trimecaine, saxitoxin, tetrodotoxin, acetaminophen, a non-steroidal anti-inflammatory drug, salicylate, narcotic, or tramadol; and

wherein the antimicrobial agent includes at least one of an anti-fungal agent, antibiotic agent, anti-bacterial agent, anti-parasitic agent, or anti-worm agent.

2. The frozen particle composition of claim 1, wherein the at least one major dimension includes at least one of the radius, diameter, length, width, height, or perimeter.

3. The frozen particle composition of claim 1, wherein the at least one adhesive agent includes at least one of a monomer, prepolymer, polymer, or copolymer.

4. The frozen particle composition of claim 1, further including at least one material that solidifies in situ at physiological temperature and pH.

5. The frozen particle composition of claim 1, wherein one or more bone morphogenic proteins are encapsulated by the vesicle.

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

7. The frozen particle composition of claim 1, wherein one or more integrin peptides are encapsulated by the vesicle.

8. The frozen particle composition of claim 7, wherein one or more silica beads are encapsulated by the vesicle.

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

10. The frozen particle composition of claim 8, 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).

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

12. The frozen particle composition of claim 11, wherein the detection material includes at least one electronic identification device.

13. The frozen particle composition of claim 12, wherein the at least one electronic identification device includes at least one radio frequency identification device.

14. The frozen particle composition of claim 11, wherein the detection material includes at least one radioactive element.

15. The frozen particle composition of claim 14, wherein the at least one radioactive element includes one or more of ³²P, ³⁵S, ¹³C, ¹³¹I, ¹⁹¹Ir, ¹⁹²Ir, ¹⁹³Ir, ²⁰¹Tl, or ³H.

16. The frozen particle composition of claim 11, wherein the detection material includes at least one luminescent, colorimetric, or odorous substance.

17. The frozen particle composition of claim 11, wherein the detection material includes at least one of a diamagnetic particle, ferromagnetic particle, paramagnetic particle, super paramagnetic contrast agent, or other magnetic particle.

18. The frozen particle composition of claim 1, further including one or more explosive materials.

19. The frozen particle composition of claim 18, wherein the one or more explosive materials include at least one of a carbonate, carbon dioxide, nitroglycerine, acid, base, epoxy, acrylic polymer or copolymer, 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 is frozen.

21. The frozen particle composition of claim 1, wherein the at least one adhesive agent includes at least one a-cyanoacrylate and a fluorescent compound including at least one of a bis-benzoxazolyl compound, pyrylium salt, quantum dot, or coumarin compound.

22. 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.

23. 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.

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

25. The frozen particle composition of claim 1, wherein the adhesive agent includes at least one dye coinitiator.

49. The frozen particle composition of claim 1, wherein the adhesive agent further includes at least one of urethane, gum Arabic, polyester, polyhydroxyalkanoate, poly(L-lactic acid), polyglycolide, polylactic acid, polyether, polyol, polyvinylpyrrolidone, pyroxylin, polymethylacrylate-isobutene-monoisopropylmaleate, siloxane polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate, poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate, polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone), sialyl Lewis^x, heme group, hemoglobin, healon, carboxymethylcellulose, silicone, cadherin, integrin, hydroxyapatite, polyelectrolyte, maleic polyelectrolyte, cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate, butyl-2-cyanoacrylate, methyl 2-cyanoacrylate, polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen, hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon, collagen, glycosaminoglycan, selectin, polyurethane, methacrylate, polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone, albumin, glutaraldehyde, or polyethylene glycol.

50. The frozen particle composition of claim 1, wherein the frozen solution of saline in water further includes a surfactant in the frozen solution.

51. The frozen particle composition of claim 1, further including at least one anti-inflammatory agent.

52. The frozen particle composition of claim 1, further including at least one angiogenic factor.

53. The frozen particle composition of claim 1, further including at least one cytokine.

54. The frozen particle composition of claim 1, further including at least one coagulant.

55. The frozen particle composition of claim 1, further including at least one cytotoxic agent.

26. A method for providing at least one adhesive agent 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 saline solution particles including at least one adhesive agent substantially in the form of a vesicle and including an acrylic polymer;

and wherein the frozen particle composition is externally coated with at least one anesthetic, analgesic, or antimicrobial agent, wherein the analgesic or anesthetic includes at least one of an aminoamid or aminoester local anesthetic, ibuprofen, morphine, codeine, lidocaine/lignocaine, ropivacaine, mepivacaine, benzocaine, chloroprocaine, cyclomethycaine, dimethocaine/larocaine, propoxycaine, procaine/novocaine, proparacaine, tetracaine/amethocaine, articaine, bupivacaine, carticaine, cinchocaine/dibucaine, etidocaine, levobupivacaine, piperocaine, prilocaine, trimecaine, saxitoxin, tetrodotoxin, acetaminophen, a non-steroidal anti-inflammatory drug, salicylate, narcotic, or tramadol; and

wherein the antimicrobial agent includes at least one of an anti-fungal agent, antibiotic agent, anti-bacterial agent, anti-parasitic agent, or anti-worm agent.

27. The method of claim 26, wherein the at least one frozen particle composition is in at least one crystalline or amorphous phase.

28. The method of claim 26, wherein the at least one adhesive agent is configured to polymerize at or above the temperature of the at least one substrate.

29. The method of claim 26, wherein the at least one adhesive agent is configured to polymerize at or above the temperature of at least one biological tissue.

30. The method of claim 26, wherein the at least one adhesive agent is configured to polymerize at or above the temperature of at least one subject.

31. The method of claim 26, wherein the at least one substrate includes one or more of a cell, tissue, organ, structure, or device.

32. The method of claim 31, wherein the structure includes one or more of a prosthesis, cell matrix, or tissue matrix.

33. The method of claim 31, wherein the device includes at least one mechanical or electrical device.

34. The method of claim 26, wherein the at least one substrate includes at least one implantable substrate.

35. The method of claim 26, wherein the at least substrate includes at least one cell mass.

36. The method of claim 26, wherein the at least one substrate includes one or more wounds.

37. The method of claim 36, wherein the one or more wounds are located in at least one biological tissue including at least one of skin tissue, muscle tissue, eye tissue, an organ, connective tissue, fetal tissue, nervous tissue, peritoneal tissue, neoplastic tissue, or bone tissue.

38. The method of claim 26, 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.

39. The method of claim 26, further including varying the rate, velocity, or angle at which the at least one frozen particle composition is administered to at least one substrate.

40. The method of claim 26, further including a plurality of frozen particle compositions, wherein two or more of the plurality of frozen particle compositions include two or more adhesive agents are configured to physically or chemically bind upon administration.

41. The method of claim 26, further including administering to the at least one substrate at least one of a nanoparticle, detection material, sensor, micro-syringe, or circuit.

42. The method of claim 26, wherein the at least one adhesive agent includes a detectable state that varies with its adhesive state.

43. The method of claim 26, wherein the at least one adhesive agent further includes one or more of a base component, initiator component, or activator component.

44. The method of claim 26, wherein the at least one adhesive agent further includes at least one curing component.

45. The method of claim 26, wherein the adhesive agent includes at least one dye coinitiator.

46. A method of maintaining the approximation of tissue of the 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 saline solution particles including at least one adhesive agent substantially in the form of a vesicle and including an acrylic polymer;

and wherein the frozen particle composition is externally coated with at least one anesthetic, analgesic, or antimicrobial agent, wherein the analgesic or anesthetic includes at least one of an aminoamid or aminoester local anesthetic, ibuprofen, morphine, codeine, lidocaine/lignocaine, ropivacaine, mepivacaine, benzocaine, chloroprocaine, cyclomethycaine, dimethocaine/larocaine, propoxycaine, procaine/novocaine, proparacaine, tetracaine/amethocaine, articaine, bupivacaine, carticaine, cinchocaine/dibucaine, etidocaine, levobupivacaine, piperocaine, prilocaine, trimecaine, saxitoxin, tetrodotoxin, acetaminophen, a non-steroidal anti-inflammatory drug, salicylate, narcotic, or tramadol; and

wherein the antimicrobial agent includes at least one of an anti-fungal agent, antibiotic agent, anti-bacterial agent, anti-parasitic agent, or anti-worm agent.

47. The method of claim 46, 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.

48. The method of claim 46, further including varying the rate, velocity, or angle at which the at least one frozen particle composition is administered to at least one wound.

56. A frozen particle composition, comprising:

one or more frozen salt buffer solution particles containing at least one acrylic polymer substantially in the form of a vesicle and encapsulating at least one antibody;

wherein the one or more frozen salt buffer solution particles are a frozen solution in particle form of at least one salt buffer including TRIS-buffered saline, standard saline citrate, HEPES-buffered saline, Ringer'"'"'s solution, lactated Ringer'"'"'s solution, Hank'"'"'s balanced salt solution, Earle'"'"'s balanced salt solution, Hartmann'"'"'s solution, HEPES buffer, or phosphate buffered solution, and further include zinc oxide powder and phosphoric acid; and

wherein the frozen salt buffer solution particles have at least one major dimension of approximately one micrometer or less, approximately one nanometer or less, or any value therebetween.

57. The frozen particle composition of claim 56, further including methyl methacrylate and polymethyl methacrylate.

58. The frozen particle composition of claim 56, further including at least one cytotoxic agent.

59. A frozen particle composition, comprising:

one or more frozen dimethyl sulfoxide solution particles containing at least one adhesive agent of acrylic polymer, polylactic acid, poly (L-lactic acid), polyethylene glycol, polyol, polyether, polyol, polyvinylpyrrolidone, pyroxylin, polymethylacrylate-isobutene-monoisopropylmaleate, siloxane polymer, polylactic-co-glycolic-acid, poly-3-hydroxybutyrate, poly-4-hydroxybutyrate, polyhydroxyvalerate, polydydroxyhexanoate, polydyroxyoctanoate, polycaprolactone, poly (e-caprolactone), sialyl Lewis^x, heme group, hemoglobin, healon, carboxymethylcellulose, hydroxyapatite, silicone, cadherin, integrin, polyelectrolyte, maleic polyelectrolyte, cellulose, resilin, cyanoacrylate, isocyanate, 2-octyl cyanoacrylate, 2-butyl-n-cyanoacrylate, n-butyl-2-cyanoacrylate, butyl-2-cyanoacrylate, methyl 2-cyanoacrylate, polyisohexylcyanoacrylate, fibrin, thrombin, fibrinogen, hyaluronate, chitin, Factor XIII, Factor XII, silk, nylon, collagen, glycosaminoglycan, selectin, polyurethane, methacrylate, polysulfide, polyanhydride, polydioxanone, poly-p-dioxanone, albumin, glutaraldehyde or gelatin substantially in the form of a vesicle and encapsulating at least one stem cell;

one or more reinforcement agents of kaolin, or cellulose;

wherein the one or more frozen dimethyl sulfoxide solution particles are a frozen solution of dimethyl sulfoxide, and wherein the frozen dimethyl sulfoxide solution particles have at least one major dimension of approximately one micrometer or less, approximately one nanometer or less, or any value therebetween.

60. The frozen composition of claim 59, wherein the frozen dimethyl sulfoxide solution particles further include at least one coagulant, anti-coagulant, anesthetic, antimicrobial agent, anti-inflammatory, or analgesic.