Compositions and methods for therapeutic delivery with frozen particles

• US 20100111844A1
• Filed: 10/31/2008
• Published: 05/06/2010
• Est. Priority Date: 10/31/2008
• Status: Active Grant

• Current Assignee: Gearbox LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC (Intellectual Ventures LLC)
• Inventors: Myhrvold, Nathan P., Boyden, Edward S., Wood, Lowell L. JR., Hyde, Roderick A., Sweeney, Elizabeth A., Leuthardt, Eric C.
• Granted Patent: US 9,060,926 B2
• Time in Patent Office: Days
• US Class Current: 424/1.290
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• 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 51/1244 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 9/127 Liposomes
• 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 9/19 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: C07K 16/2863 against receptors for growth factors, growth regulators

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 therapeutic composition, comprising:

one or more frozen particles including at least one therapeutic agent and at least one of polyethylene glycol, acetone, ethyl acetate, dimethyl sulfoxide, dimethyl formamide, dioxane, hexamethylphosphorotriamide, perfluorohydrocarbon, methanol, ethanol, tert-butyl alcohol, formic acid, hydrogen fluoride, ammonia, acetic acid, benzene, carbon tetrachloride, acetonitrile, hexane, methylene chloride, carboxylic acid, saline, Ringer'"'"'s solution, lactated Ringer'"'"'s solution, Hartmann'"'"'s solution, acetated Ringer'"'"'s solution, phosphate buffered solution, TRIS-buffered saline solution, Hank'"'"'s balanced salt solution, Earle'"'"'s balanced salt solution, standard saline citrate, HEPES-buffered saline, dextrose, glucose, or diethyl ether.

2. The therapeutic composition of claim 1, wherein the therapeutic composition exists at about 30°

C., about 20°

C., about 10°

C., about 5°

C., about 0°

C., about −

10°

C. about −

20°

C., about −

30°

C., about −

40°

C., about −

50°

C., about −

60°

C., about −

70°

C., about −

75°

C., about −

80°

C., about −

85°

C., about −

90°

C., about −

95°

C., about −

100°

C., about −

120°

C., about −

150°

C., about −

180°

C., about −

200°

C., about −

220°

C., about −

250°

C., or any value less than or therebetween.

3. The therapeutic composition of claim 1, wherein the one or more frozen particles have at least one major dimension of approximately one centimeter or less, approximately one millimeter or less, approximately one micrometer or less, approximately one nanometer or less, or any value therebetween.

4. The therapeutic composition of claim 3, wherein the at least one major dimension includes at least one of the radius, diameter, length, width, height, or perimeter.

5. The therapeutic composition of claim 1, wherein the at least one therapeutic agent includes at least one of an organic or inorganic small molecule, clathrate or caged compound, protocell, coacervate, microsphere, proteinoid, laminate, helical rod, liposome, macroscopic tube, niosome, sphingosome, toroid, vesicular tube, vesicle, small unilamellar vesicle, large unilamellar vesicle, large multilamellar vesicle, multivesicular vesicle, lipid layer, lipid bilayer, micelle, organelle, cell, membrane, nucleic acid, peptide, polypeptide, protein, glycopeptide, glycolipid, sphingolipid, glycosphingolipid, glycoprotein, peptidoglycan, lipid, carbohydrate, metalloprotein, proteoglycan, chromosome, nucleus, acid, base, buffer, protic solvent, aprotic solvent, nitric oxide, nitric oxide synthase, amino acid, micelle, polymer, co-polymer, or piloxymer.

6. The therapeutic composition of claim 1, wherein the at least one therapeutic agent includes at least one of an anti-tumor agent, antimicrobial agent, anti-viral agent, analgesic, antiseptic, anesthetic, diagnostic agent, anti-inflammatory agent, vaccine, cell growth inhibitor, cell growth promoter, immunogen, antigen, radioactive agent, apoptotic promoting factor, angiogenic factor, anti-angiogenic factor, hormone, vitamin, mineral, nutraceutical, cytokine, chemokine, probiotic, coagulant, anti-coagulant, phage, prodrug, prebiotic, blood sugar stabilizer, smooth muscle cell activator, epinephrine, adrenaline, neurotoxin, neuro-muscular toxin, Botulinum toxin type A, microbial cell or component thereof, or virus orrotoxin, neuro-muscular toxin, microbial cell or component thereof, or virus or component thereof.

7. The therapeutic composition of claim 6, wherein the antimicrobial agent includes at least one of an anti-fungal agent, antibiotic agent, anti-parasitic agent, or anti-worm agent.

8. The therapeutic composition of claim 6, wherein the at least one anti-tumor agent includes one or more of an alkylating agent, antimetabolite, anthracycline, plant alkaloid, topoisomerase inhibitor, monoclonal antibody, or tyrosine kinase inhibitor.

9. The therapeutic composition of claim 8, wherein the at least one plant alkaloid includes paclitaxel.

10. The therapeutic composition of claim 1, wherein the at least one therapeutic agent includes one or more of a prodrug or precursor compound.

11. The therapeutic composition of claim 10, wherein the at least one therapeutic agent is activated by delivery of the therapeutic composition to at least one biological tissue.

12. The therapeutic composition of claim 1, wherein the one or more frozen particles further comprise at least one of nitrogen, hydrogen oxide, argon, helium, air, oxygen, neon, xenon, krypton, chlorine, bromine, or carbon dioxide.

13. The therapeutic composition of claim 1, wherein the one or more frozen particles approximate the shape of at least one of a sphere, bullet, flechette, cone, needle, arrow, spear, diamond, pyramid, cylinder, minie ball, shuttlecock, spiral, bell, pear, crystal, cube, spheroid, tetrahedron, crescent, or high aspect ratio shape.

14. The therapeutic composition of claim 1, wherein the at least one therapeutic agent resides in one or more distinct regions of the one or more frozen particles.

15. The therapeutic composition of claim 1, wherein the one or more frozen particles include a plurality of frozen particles that are approximately uniform in size, shape, weight, or density.

16. The therapeutic composition of claim 1, wherein the therapeutic composition includes at least one of a solid, liquid, or gas.

17. The therapeutic composition of claim 1, wherein the therapeutic composition includes one or more of a suspension, mixture, solution, clathrate, sol, colloid, emulsion, microemulsion, aerosol, ointment, capsule, powder, tablet, suppository, cream, device, paste, liniment, lotion, ampule, elixir, spray, suspension, syrup, tincture, detection material, polymer, biopolymer, buffer, adjuvant, diluent, lubricant, disintegration agent, suspending agent, solvent, calorimetric agent, glidant, anti-adherent, anti-static agent, surfactant, plasticizer, emulsifying agent, flavor, gum, sweetener, coating, binder, filler, compression aid, encapsulation aid, preservative, granulation agent, spheronization agent, stabilizer, adhesive, pigment, sorbent, nanoparticle, or gel.

18. The therapeutic composition of claim 1, further comprising one or more reinforcement agents.

19. The therapeutic composition of claim 18, wherein the one or more reinforcement agents include at least one of a natural, artificial, or synthetic agent.

20. The therapeutic composition of claim 18, wherein the one or more reinforcement agents include at least one of a plate, fiber, or spheroid.

21. The therapeutic composition of claim 18, wherein the at least one of polyaramid, vinylester matrix, metal, ceramic, fiberglass, cellulose, broad carbide, aromatic polyamide, nylon, silk, rayon, acetate, modacrylic, olefin, acrylic, 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, sodium, potassium, calcium, zinc, manganese, carbon, magnesium, silicon, silica, frozen hydrogen oxide ice, plant matter, animal matter, or mineral matter.

22. The therapeutic composition of claim 18, wherein the one or more reinforcement agents are located at least on the surface or beneath the surface of the particle.

23. The therapeutic composition of claim 18, wherein the one or more reinforcement agents are located within the particle.

24. The therapeutic composition of claim 1, further comprising at least one polymer, biopolymer, nanoparticle, or detection material.

25. The therapeutic composition of claim 24, wherein the detection material includes at least one electronic identification device.

26. The therapeutic composition of claim 25, wherein the at least one electronic identification device includes at least one radio frequency identification device.

27. The therapeutic composition of claim 24, wherein the detection material includes at least one radioactive element.

28. The therapeutic composition of claim 27, wherein the at least one radioactive element includes one or more of ³²P, ³⁵S, ¹³C, ¹³¹I, ¹⁹¹Ir, ¹⁹²Ir, ¹⁹³Ir, ²⁰¹Tl, or ³H.

29. The therapeutic composition of claim 24, wherein the detection material includes at least one colorimetric substance.

30. The therapeutic composition of claim 29, wherein the at least one calorimetric substance includes one or more of an inorganic, organic, biological, natural, artificial, or synthetic substance.

31. The therapeutic composition of claim 29, wherein the at least one calorimetric substance includes one or more of a dye, pigment, or light-emitting substance.

32. The therapeutic composition of claim 31, wherein the light-emitting substance includes at least one of a fluorescent substance, phosphorescent substance, or quantum dot.

33. The therapeutic composition of claim 29, wherein the at least one colorimetric substance is biocompatible.

34. The therapeutic composition of claim 24, wherein the detection material includes at least one of a diamagnetic particle, ferromagnetic particle, paramagnetic particle, super paramagnetic contrast agent, or other magnetic particle.

35. The therapeutic composition of claim 1, formulated to be administered by one or more of topical delivery, oral delivery, enteral delivery, mucosal delivery, percutaneous delivery, or parenteral delivery.

36. The therapeutic composition of claim 1, wherein parenteral delivery includes at least one of intravenous delivery, intra-arterial delivery, intracardiac delivery, subcutaneous delivery, intraperitoneal delivery, or intramuscular delivery.

37. The therapeutic composition of claim 1, formulated to be administered by high velocity impact.

38. The therapeutic composition of claim 1, formulated to be administered by one or more devices.

39. The therapeutic composition of claim 1, further comprising at least one pharmaceutically-acceptable carrier or excipient.

40. The therapeutic composition of claim 1, further comprising one or more explosive materials.

41-149. -149. (canceled)