WO2016197100A1 - Nozzle assembly and methods for use - Google Patents

Nozzle assembly and methods for use Download PDF

Info

Publication number
WO2016197100A1
WO2016197100A1 PCT/US2016/036012 US2016036012W WO2016197100A1 WO 2016197100 A1 WO2016197100 A1 WO 2016197100A1 US 2016036012 W US2016036012 W US 2016036012W WO 2016197100 A1 WO2016197100 A1 WO 2016197100A1
Authority
WO
WIPO (PCT)
Prior art keywords
nozzle
vessel
pressurizable chamber
particles
proximal end
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2016/036012
Other languages
English (en)
French (fr)
Inventor
Bala Subramaniam
Jahna ESPINOSA
Gregory F. Johnson
Jacob M. SITTENAUER
Joseph S. FARTHING
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
CritiTech Inc
Original Assignee
CritiTech Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by CritiTech Inc filed Critical CritiTech Inc
Priority to EP16731712.2A priority Critical patent/EP3302780B1/en
Priority to KR1020177034414A priority patent/KR102077518B1/ko
Priority to US15/573,157 priority patent/US11291646B2/en
Priority to HK18112398.3A priority patent/HK1253021B/en
Priority to CN201680032291.XA priority patent/CN107683174B/zh
Priority to AU2016270558A priority patent/AU2016270558B2/en
Priority to CA3026452A priority patent/CA3026452C/en
Priority to JP2017558020A priority patent/JP6892394B2/ja
Publication of WO2016197100A1 publication Critical patent/WO2016197100A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/02—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of powders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5192—Processes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D46/00—Filters or filtering processes specially modified for separating dispersed particles from gases or vapours
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D46/00—Filters or filtering processes specially modified for separating dispersed particles from gases or vapours
    • B01D46/24—Particle separators, e.g. dust precipitators, using rigid hollow filter bodies
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
    • B01J19/10—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing sonic or ultrasonic vibrations
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/26—Nozzle-type reactors, i.e. the distribution of the initial reactants within the reactor is effected by their introduction or injection through nozzles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
    • B01J2/04—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a gaseous medium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
    • B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
    • B01J2/06—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a liquid medium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J3/00—Processes of utilising sub-atmospheric or super-atmospheric pressure to effect chemical or physical change of matter; Apparatus therefor
    • B01J3/008—Processes carried out under supercritical conditions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J3/00—Processes of utilising sub-atmospheric or super-atmospheric pressure to effect chemical or physical change of matter; Apparatus therefor
    • B01J3/02—Feed or outlet devices therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J4/00—Feed or outlet devices; Feed or outlet control devices
    • B01J4/001—Feed or outlet devices as such, e.g. feeding tubes
    • B01J4/002—Nozzle-type elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B1/00—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means
    • B05B1/34—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl
    • B05B1/3405—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl to produce swirl
    • B05B1/341—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl to produce swirl before discharging the liquid or other fluent material, e.g. in a swirl chamber upstream the spray outlet
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B1/00—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means
    • B05B1/34—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl
    • B05B1/3405—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl to produce swirl
    • B05B1/341—Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to influence the nature of flow of the liquid or other fluent material, e.g. to produce swirl to produce swirl before discharging the liquid or other fluent material, e.g. in a swirl chamber upstream the spray outlet
    • B05B1/3489—Nozzles having concentric outlets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B13/00—Machines or plants for applying liquids or other fluent materials to surfaces of objects or other work by spraying, not covered by groups B05B1/00 - B05B11/00
    • B05B13/02—Means for supporting work; Arrangement or mounting of spray heads; Adaptation or arrangement of means for feeding work
    • B05B13/0278—Arrangement or mounting of spray heads
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2271/00—Sealings for filters specially adapted for separating dispersed particles from gases or vapours
    • B01D2271/02—Gaskets, sealings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2204/00—Aspects relating to feed or outlet devices; Regulating devices for feed or outlet devices
    • B01J2204/002—Aspects relating to feed or outlet devices; Regulating devices for feed or outlet devices the feeding side being of particular interest
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D2401/00—Form of the coating product, e.g. solution, water dispersion, powders or the like
    • B05D2401/90—Form of the coating product, e.g. solution, water dispersion, powders or the like at least one component of the composition being in supercritical state or close to supercritical state

Definitions

  • the need is particularly pronounced in the field of pharmaceutics.
  • Conventional techniques for particle-size reduction currently practiced suffer from many disadvantages.
  • a need remains for improved equipment and processes for the preparation, harvesting and collection of small particles.
  • the invention comprises a nozzle assembly, including (a) a vessel defining a pressurizable chamber, wherein the vessel includes a distal end and a proximal end, (b) an inlet of the pressurizable chamber at the proximal end of the vessel, (c) a nozzle positioned within the pressurizable chamber, wherein the nozzle includes an inlet tube in fluid communication with the inlet of the pressurizable chamber, wherein the nozzle includes an outlet aperture, wherein the nozzle is adjustable to alter a distance between the proximal end of the vessel and the outlet aperture of the nozzle, and wherein the nozzle is adjustable to alter an angle between a longitudinal axis of the vessel and a longitudinal axis of the nozzle, and (d) an outlet of the pressurizable chamber at the distal end of the vessel.
  • the invention includes a method for isolating particles comprising (a) providing a nozzle assembly including (i) a vessel defining a pressurizable chamber, wherein the vessel includes a distal end and a proximal end, (ii) a first inlet of the pressurizable chamber at the proximal end of the vessel, (iii) a nozzle positioned within the pressurizable chamber, wherein the nozzle includes an inlet tube in fluid communication with the first inlet of the pressurizable chamber, wherein the nozzle includes an outlet aperture, wherein the nozzle is adjustable to alter a distance between the proximal end of the vessel and the outlet aperture of the nozzle, and wherein the nozzle is adjustable to alter an angle between a longitudinal axis of the vessel and a longitudinal axis of the nozzle, and (iv) an outlet of the pressurizable chamber at the distal end of the vessel, (b) positioning a sonic energy source within the pressurizable chamber adjacent to
  • FIGURE 1A illustrates a cross-section view of an example nozzle assembly, according to an example embodiment.
  • FIGURE 1B illustrates a cross-section view of another example nozzle assembly, according to an example embodiment.
  • FIGURE 2 is a block diagram of a method, according to an example embodiment. Detailed Description of the Invention
  • solvent refers to a fluid that dissolves a solute to form a solute-containing fluid (process fluid).
  • the solvent must also be soluble in or miscible with an anti-solvent such that placing a solute-containing solvent into the anti-solvent will result in precipitation of the solute to form particles.
  • the solvent is typically an organic solvent. Suitable organic solvents include ethanol, methanol, 1-propanol, isopropanol, 1-butanol, 2-butanol, tert- butanol, acetone, methylethylketone, dichloromethane, chloroform, hexafluoroisopropanol, diethyl ether, dimethylamide, and mixtures thereof.
  • anti-solvent refers to a compressed fluid that is capable of forming a supercritical fluid under the conditions used.
  • Suitable supercritical fluid-forming anti- solvents can comprise carbon dioxide, ethane, propane, butane, isobutane, nitrous oxide, xenon, sulfur hexafluoride and trifluoromethane.
  • longitudinal axis of the vessel means an axis that intersects a top and bottom surface of the vessel.
  • longitudinal axis of the nozzle means an axis that intersects a midpoint of the outlet aperture of the nozzle.
  • the“specific surface area” is the total surface area of a particle per unit of particle mass as measured by the Brunauer–Emmett–Teller (“BET”) isotherm (i.e.: the BET SSA).
  • BET Brunauer–Emmett–Teller
  • the present invention comprises a nozzle assembly, including (a) a vessel defining a pressurizable chamber, wherein the vessel includes a distal end and a proximal end, (b) an inlet of the pressurizable chamber at the proximal end of the vessel, (c) a nozzle positioned within the pressurizable chamber, wherein the nozzle includes an inlet tube in fluid communication with the inlet of the pressurizable chamber, wherein the nozzle includes an outlet aperture, wherein the nozzle is adjustable to alter a distance between the proximal end of the vessel and the outlet aperture of the nozzle, and wherein the nozzle is adjustable to alter an angle between a longitudinal axis of the vessel and a longitudinal axis of the nozzle, and (d) an outlet of the pressurizable chamber at the distal end of the vessel.
  • the systems and methods of the present invention provide a significant improvement over those disclosed in the prior art.
  • the methods of the present invention are capable of producing the particles of the invention with significantly improved specific surface area (SSA) properties, and thus significantly improved therapeutic benefits.
  • the inventors have unexpectedly been able to produce compositions comprising particles that have a mean specific surface area (SSA) of at least 18 m 2 /g an SSA using the novel nozzle assembly and methods of use as described herein.
  • SSA mean specific surface area
  • the increased specific surface area of the particles created by the nozzle assembly result in significant increases in dissolution rate compared to the raw particles and to milled products used for comparison. Dissolution takes place only at a solid/liquid interface. Therefore, increased specific surface area will increase the dissolution rate due to a larger number of molecules on the surface of the particle having contact with the dissolution media. This provides a significant improvement for use of such particles in, for example, tumor treatment.
  • the novel nozzle assembly and methods of use provide this significant improvement, at least in part, through use of the sonic energy source external to the nozzle and at a given distance from the outlet aperture of the nozzle to provide significantly enhanced sonic energy and enhanced disruption of the solvent-solute flow as it exits the nozzle.
  • the prior art describes an exemplary process for particle production using compressed anti-solvent precipitation using converging-diverging nozzle to create sonic energy.
  • the methods of the present invention incorporate use of a sonic energy source external to the nozzle and just outside the orifice of the nozzle to provide significantly increased sonic energy and enhance disruption of the solvent/compound flow as it comes out of the nozzle, resulting in the production of particles with significantly enhanced SSA characteristics.
  • the invention comprises a nozzle assembly 100 including a vessel 102 defining a pressurizable chamber 104.
  • the vessel 102 includes a distal end 106 and a proximal end 108.
  • the nozzle assembly 100 further includes an inlet 110 of the pressurizable chamber 104 at the proximal end 108 of the vessel 102.
  • the nozzle assembly 100 further includes a nozzle 112 positioned within the pressurizable chamber 104.
  • the nozzle 112 includes an inlet tube 114 in fluid communication with the inlet 110 of the pressurizable chamber 104.
  • the nozzle 112 includes an outlet aperture 116.
  • the nozzle 112 is adjustable to alter a distance 118 between the proximal end 108 of the vessel 102 and the outlet aperture 116 of the nozzle 112. As shown in Figure 1B, the nozzle 112 is further adjustable to alter an angle 120 between a longitudinal axis of the vessel 122 and a longitudinal axis of the nozzle 124.
  • the nozzle assembly 100 includes an outlet 126 of the pressurizable chamber 104 at the distal end 106 of the vessel 102.
  • the nozzle assembly 100 may further include a first reservoir 128 and a second reservoir 130.
  • the first reservoir 128 may include a supply of solvent
  • the second reservoir 130 may include a supply of anti-solvent.
  • the inlet 110 of the pressurizable chamber 104 may be in fluid communication with the first reservoir 128, and a second inlet 132 of the pressurizable chamber 104 may be in fluid communication with the second reservoir 130.
  • the first reservoir 128 is in fluid communication with the inlet tube 114 of the nozzle 112, such that the solvent enters the pressurizable chamber 104 through the nozzle 112.
  • Other examples are possible as well.
  • the outlet aperture 116 of the nozzle 112 may include a plurality of ridges to create a vortex within the nozzle 112 such that the solvent exits the nozzle 112 via turbulent flow.
  • the nozzle 112 may include a porous frit interior to the nozzle 112 such that the solvent exits the nozzle 112 via turbulent flow.
  • the outlet aperture 116 of the nozzle 112 may have a small diameter (as discussed in additional detail below) such that the solvent exits the nozzle 112 via turbulent flow. These various embodiments that cause turbulent flow may assist in mixing the solvent with the anti-solvent within the pressurizable chamber 104.
  • the inlet tube 114 of the nozzle 112 may have an inner diameter with a range from about 1.5875 mm to about 6.35 mm.
  • the outlet aperture 116 of the nozzle 112 has a diameter of between about 20 ⁇ m and about 125 ⁇ m, about 20 ⁇ m and about 115 ⁇ m, about 20 ⁇ m and about 100 ⁇ m, about 20 ⁇ m and about 90 ⁇ m, about 20 ⁇ m and about 80 ⁇ m, about 20 ⁇ m and about 70 ⁇ m, about 20 ⁇ m and about 60 ⁇ m, about 20 ⁇ m and about 50 ⁇ m, about 20 ⁇ m and about 40 ⁇ m, about 20 ⁇ m and about 30 ⁇ m, between about 30 ⁇ m and about 125 ⁇ m, about 30 ⁇ m and about 115 ⁇ m, about 30 ⁇ m and about 100 ⁇ m, about 30 ⁇ m and about 90 ⁇ m, about 30 ⁇ m and about 80 ⁇ m, about 30 ⁇ m and about 70 ⁇ m, about 30 ⁇ m and about 60 ⁇ m, about 30 ⁇ m and about 50 ⁇ m, about 30 ⁇ m and about 40 ⁇ m
  • the nozzle 112 may be adjustable to alter a distance 118 between the proximal end 108 of the vessel 102 and the outlet aperture 116 of the nozzle 112.
  • the nozzle 112 may be adjustable to alter an angle 120 between a longitudinal axis of the vessel 122 and a longitudinal axis of the nozzle 124.
  • both the angle of the nozzle 112 and the vertical position of the nozzle 112 may be adjusted manually by a user.
  • the nozzle 112 may be positioned on a vertical support that can be adjusted to alter the distance 118 between the proximal end 108 of the vessel 102 and the outlet aperture 116 of the nozzle 112.
  • the nozzle 112 may be rotated manually to adjust the angle 120 between the longitudinal axis of the vessel 122 and the longitudinal axis of the nozzle 124.
  • the nozzle assembly 100 may include a motor coupled to the nozzle 112.
  • the motor may be configured to alter the distance 118 between the proximal end 108 of the vessel 102 and the outlet aperture 116 of the nozzle 112 and/or alter the angle 120 between the longitudinal axis of the vessel 122 and the longitudinal axis of the nozzle 124.
  • Such a motor may be an electric motor powered by electrical power, or may be powered by a number of different energy sources, such as a gas-based fuel or solar power.
  • the motor may be coupled directly or indirectly to the nozzle 112, such that when the motor is turned on the distance 118 between the proximal end 108 of the vessel 102 and the outlet aperture 116 of the nozzle 112 increases or decreases depending on the direction the motor rotates.
  • the motor may be coupled to a series of gears that adjusts the distance 118 between the proximal end 108 of the vessel 102 and the outlet aperture 116 of the nozzle 112 and/or adjusts the angle 120 between the longitudinal axis of the vessel 122 and the longitudinal axis of the nozzle 124, or the motor may be coupled to a pulley system that adjusts the distance 118 between the proximal end 108 of the vessel 102 and the outlet aperture 116 of the nozzle 112 and/or adjusts the angle 120 between the longitudinal axis of the vessel 122 and the longitudinal axis of the nozzle 124.
  • Other configurations are possible as well.
  • the nozzle 112 assembly may include an actuator coupled to the nozzle 112, where the actuator alters the distance 118 between the proximal end 108 of the vessel 120 and the outlet aperture 116 of the nozzle 112 and/or alters the angle 120 between the longitudinal axis of the vessel 122 and the longitudinal axis of the nozzle 124.
  • an actuator may be an electro-mechanical actuator, including an electric motor that converts a rotary motion of the electric motor to a linear displacement via a linkage system.
  • Other potential actuators are possible as well, such as hydraulic actuators, pneumatic actuators, piezoelectric actuators, linear motors, or telescoping linear actuators, as examples.
  • the nozzle assembly 100 may include a plurality of nozzles, with each nozzle positioned at a different angle between a longitudinal axis of the vessel and a longitudinal axis of the nozzle and/or a different distance between the nozzle orifice and the sonic energy source.
  • a given nozzle of the plurality of nozzles may be chosen for a given production run to produce a certain type of particle having a given SSA. Other example embodiments are possible as well.
  • the nozzle assembly further includes a sonic energy source 134 positioned adjacent to the outlet aperture 116 of the nozzle 112.
  • the sonic energy source 134 may include a sonic probe extending within the pressurizable chamber 104.
  • the sonic energy source 134 may include a sonic surface positioned in the pressurizable chamber 104. The sonic waves from the sonic energy source 134 cause the liquids in the pressurizable chamber 104 to shatter, thereby enhancing mixing of the solvent and anti-solvent solutions to create particles within the pressurizable chamber 104.
  • the sonic energy source 134 is positioned at an angle of 45 degrees with respect to the longitudinal axis of the nozzle 124. Other angles are possible as well. In one example, the sonic energy source 134 may be adjustable to alter a distance between the outlet aperture 116 of the nozzle 112 and the sonic energy source 134. Further, the sonic energy source 134 may be adjustable to alter an angle between the sonic energy source 134 and the longitudinal axis of the nozzle 124.
  • the outlet aperture 116 of the nozzle 112 is located between about 2 mm and about 20 mm, about 2 mm and about 18 mm, about 2 mm and about 16 mm, about 2 mm and about 14 mm, about 2 mm and about 12 mm, about 2 mm and about 10 mm, about 2 mm and about 8 mm, about 2 mm and about 6 mm, about 2 mm and about 4 mm, about 4 mm and about 20 mm, about 4 mm and about 18 mm, about 4 mm and about 16 mm, about 4 mm and about 14 mm, about 4 mm and about 12 mm, about 4 mm and about 10 mm, about 4 mm and about 8 mm, about 4 mm and about 6 mm, about 6 mm and about 20 mm, about 6 mm and about 18 mm, about 6 mm and about 16 mm, about 6 mm and about 14 mm, about 6 mm and about 12 mm, about 6 mm and about 10 mm, about 6 mm and about 10 mm,
  • the sonic energy source 134 produces sonic energy with an amplitude between about 1% and about 100% of the total power that can be generated using the sonic energy source.
  • the sonic energy source has a total power output of between about 500 and about 900 watts; in various further embodiments, between about 600 and about 800 watts, about 650- 750 watts, or about 700 watts.
  • the sonic energy source produces sonic energy with a power output between about 5% and about 100%, about 10% and about 100%, 20% and about 100%, about 30% and about 100%, about 40% and about 100%, about 50% and about 100%, about 60% and about 100%, about 70% and about 100%, about 80% and about 100%, about 90% and about 100%, about 1% and about 90%, about 5% and about 90%, about 10% and about 90%, about 20% and about 90%, about 30% and about 90%, about 40% and about 90%, about 50% and about 90%, about 60% and about 90%, about 70% and about 90%, about 80% and about 90%, about 1% and about 80%, about 5% and about 80%, about 10% and about 80%, about 20% and about 80%, about 30% and about 80%, about 40% and about 80%, about 50% and about 80%, about 60% and about 80%, about 70% and about 80%, about 1% and about 70%, about 5% and about 70%, about 10% and about 70%, about 20% and about 70%, about 30% and about 70%, about 40% and about 70%, about 50% and about 80%, about 60% and
  • a frequency of between about 18 and about 22 kHz on the sonic energy source is utilized. In various other embodiments, a frequency of between about 19 and about 21 kHz, about 19.5 and about 20.5, or, a frequency of about 20 kHz on the sonic energy source is utilized. Any suitable source of sonic energy may be used that is compatible with the methods of the invention, including but not limited to sonic horn, a sonic probe, or a sonic plate.
  • the components of the nozzle assembly 100 may be a part of a larger particle production system.
  • a particle production system may include one or more nozzle assemblies such as those described above, a sonic energy source positioned adjacent to the orifice of each nozzle, one or more particle filtration systems in communication with one or more nozzle assemblies, and one or more particle collection devices in communication with the one or more particle filtration systems.
  • the one or more particle filtration systems comprise a tandem particle filtration system including at least one high pressure harvesting filter system and at least one low pressure collection filter system in tandem and downstream to the harvesting filter.
  • the particle production system may include at least two particle harvesting filters, two particle collection filters and two collection devices.
  • the particle collection devices in such particle production systems may include a collection vessel defining a chamber, wherein the collection vessel includes a distal end and a proximal end, an inlet port extending from the proximal end of the collection vessel, wherein the inlet port is in fluid communication with the chamber, and an outlet port extending from the proximal end of the collection vessel, and wherein the outlet port includes a porous material positioned between the chamber and the outlet port.
  • the collection device may further include a sampling tube having a distal end and a proximal end, wherein the proximal end of the sampling tube extends from the proximal end of the collection vessel, and wherein the distal end of the sampling tube extends into the chamber.
  • the sampling tube may be configured to remove a small sample of particles from the chamber during a particle production run in which additional particles are being formed.
  • the sampling tube may include a sample thief that enables an operator to remove a small sample of particles without opening the chamber or removing the sampling tube from the rest of the collection device during processing. This enables an operator to test a small sample of particles to ensure that the product is within specifications as the process continues to run. For example, particle size or residual solvent analysis may be performed on the sample. If the measured specifications do not match the desired specifications, the particle formation process may be tweaked to correct the situation before an entire batch of product is created.
  • the outlet 126 of the nozzle assembly 100 may be coupled to the inlet port of the collection device.
  • the particle production system comprises at least one of a) two particle harvesting filters, two particle collection filters and two collection devices; b) two particle harvesting filters, one particle collection filter and one or more collection devices; c) two particle harvesting filters, two particle collection filters and one or more collection devices; d) two particle harvesting filters, one particle collection filter and one or more collection devices; e) two tandem filter particle harvesting and collection devices arranged in parallel; f) two or more particle harvesting filters arranged in parallel, one particle collection filter and two or more collection devices arranged in parallel; g) two or more precipitation chambers; h) at least two tandem filter particle filtration systems; i) at least two collection devices; or j) a combination thereof.
  • the invention provides methods for isolating particles comprising (a) providing a nozzle assembly including (i) a vessel defining a pressurizable chamber, wherein the vessel includes a distal end and a proximal end, (ii) a first inlet of the pressurizable chamber at the proximal end of the vessel, (iii) a nozzle positioned within the pressurizable chamber, wherein the nozzle includes an inlet tube in fluid communication with the first inlet of the pressurizable chamber, wherein the nozzle includes an outlet aperture, wherein the nozzle is adjustable to alter a distance between the proximal end of the vessel and the outlet aperture of the nozzle, and wherein the nozzle is adjustable to alter an angle between a longitudinal axis of the vessel and a longitudinal axis of the nozzle, and (iv) an outlet of the pressurizable chamber at the distal end of the vessel, (b) positioning a sonic energy source within the pressurizable chamber adjacent to the outlet aperture of
  • the methods of the invention involve contacting a solution, including a solvent with at least one compound of interest (including but not limited to an active pharmaceutical ingredient) dispersed in the solvent, with a compressed fluid at supercritical conditions for the compressed fluid, so as to cause the compressed fluid to deplete the solvent and precipitate the compound away as extremely small particles.
  • the supercritical conditions are at or above 31.1C and 1071 psi.
  • the temperature may range from about 31.1qC to about 60qC
  • the pressure may range from about 1071 psi to about 1800psi.
  • the methods of the present invention provide a significant improvement over methods such as those disclosed in US Patent Nos. 5,833,891; 5,874,029; 6,113,795; and 8,778,181 (incorporated herein by reference in their entirety) using a compressed fluid in combination with appropriate solvents to reproducibly precipitate compounds as fine particles that have a narrow size distribution.
  • the methods of the present invention are capable of producing the particles of the invention with significantly improved SSA and dissolution properties, and thus significantly improved therapeutic benefits.
  • the methods provide this significant improvement, at least in part, through use of the sonic energy source external to the nozzle and at the recited distance from the nozzle orifice to provide significantly enhanced sonic energy and enhanced disruption of the solvent-solute flow as it exits the nozzle compared to the methods disclosed U.S. Patent Nos.5,833,891 and 5,874,029 that use a converging-diverging nozzle to create the sonic energy.
  • Figure 2 is a block diagram of a method 200, according to an example embodiment.
  • Method 200 shown in Figure 2 presents an embodiment of a method that could be used with the nozzle assembly 100, for example.
  • Method 200 may include one or more operations, functions, or actions as illustrated by one or more of blocks 202-212. Although the blocks are illustrated in a sequential order, these blocks may in some instances be performed in parallel, and/or in a different order than those described herein. Also, the various blocks may be combined into fewer blocks, divided into additional blocks, and/or removed based upon the desired implementation.
  • each block may represent a module, a segment, a portion of a manufacturing or operation process, or a portion of program code, which includes one or more instructions executable by a processor for implementing specific logical functions or steps in the process.
  • the program code may be stored on any type of computer readable medium, for example, such as a storage device including a disk or hard drive.
  • the computer readable medium may include non-transitory computer readable medium, for example, such as computer- readable media that stores data for short periods of time like register memory, processor cache and Random Access Memory (RAM).
  • the computer readable medium may also include non- transitory media, such as secondary or persistent long term storage, like read only memory (ROM), optical or magnetic disks, compact-disc read only memory (CD-ROM), for example.
  • the computer readable media may also be any other volatile or non-volatile storage systems.
  • the computer readable medium may be considered a computer readable storage medium, for example, or a tangible storage device.
  • each block in Figure 2 may represent circuitry that is wired to perform the specific logical functions in the process.
  • the method 200 includes providing a nozzle assembly including (i) a vessel defining a pressurizable chamber, wherein the vessel includes a distal end and a proximal end, (ii) an inlet of the pressurizable chamber at the proximal end of the vessel, (iii) a nozzle positioned within the pressurizable chamber, wherein the nozzle includes an inlet tube in fluid communication with the inlet of the pressurizable chamber, wherein the nozzle includes an outlet aperture, wherein the nozzle is adjustable to alter a distance between the proximal end of the vessel and the outlet aperture of the nozzle, and wherein the nozzle is adjustable to alter an angle between a longitudinal axis of the vessel and a longitudinal axis of the nozzle, and (iv) an outlet of the pressurizable chamber at the distal end of the vessel.
  • Any suitable pressurizable chamber may be used, including but not limited to those disclosed in U.S. Patent Nos. 5,833,891 and 5,874,02
  • the method 200 includes positioning a sonic energy source within the pressurizable chamber adjacent to the outlet aperture of the nozzle.
  • the method 200 includes receiving a first fluid and a second fluid into the pressurizable chamber, wherein the first fluid is transported through the outlet aperture of the nozzle and onto the sonic energy source, and wherein the second fluid is transported through a second inlet of the pressurizable chamber to thereby create a plurality of particles within the pressurizable chamber.
  • the first fluid comprises a solution comprising at least one solvent and at least one solute comprising a compound of interest
  • the second fluid comprises a compressed fluid under supercritical temperature and pressure.
  • any suitable solvent and solute may be used; exemplary such solutes and solvents are disclosed in U.S. Patent Nos. 5,833,891 and 5,874,029.
  • the solvent may comprise acetone, ethanol, methanol, dichloromethane, ethyl acetate, chloroform, acetonitrile, and suitable combinations thereof.
  • the solute/compound is paclitaxel and the solvent is acetone.
  • the solute/compound is docetaxel and the solvent is acetone.
  • the solvents should comprise at least about 80%, 85%, or 90% by weight of the overall solution.
  • the compressed fluid is capable of forming a supercritical fluid under the conditions used, and the solute that forms the particles is poorly soluble or insoluble in the compressed fluid.
  • a supercritical fluid is any substance at a temperature and pressure above its critical point, where distinct liquid and gas phases do not exist. Steps (c), (d), and (e), of the methods of the invention are carried out under supercritical temperature and pressure for the compressed fluid, such that the compressed fluid is present as a supercritical fluid during these processing steps.
  • the compressed fluid can serve as an anti-solvent and can be used to remove unwanted components in the particles.
  • Any suitable compressed fluid may be used in the methods of the invention; exemplary such compressed fluids are disclosed in U.S. Patent Nos. 5,833,891 and 5,874,029.
  • suitable supercritical fluid-forming compressed fluids can comprise carbon dioxide, ethane, propane, butane, isobutane, nitrous oxide, xenon, sulfur hexafluoride and trifluoromethane.
  • the compressed fluid is super critical carbon dioxide.
  • the compressed fluid should be substantially miscible with the solvent while the compound to be precipitated should be substantially insoluble in the compressed fluid, i.e., the compound, at the selected solvent/compressed fluid contacting conditions, should be no more than about 5% by weight soluble in the compressed fluid, and preferably is essentially completely insoluble.
  • the compressed fluid is super critical carbon dioxide, and the critical temperature is at least 31.1°C and up to about 60°C, and the critical pressure is at least 1071 psi and up to about 1800 psi.
  • the compressed fluid is super critical carbon dioxide, and the critical temperature is at least 31.1°C and up to about 55°C, and the critical pressure is at least 1070 psi and up to about 1500 psi. It will be understood by those of skill in the art that the specific critical temperature and pressure may be different at different steps during the processing.
  • the method 200 includes receiving the plurality of particles through the outlet of the pressurizable chamber.
  • the method 200 includes collecting the plurality of particles in a collection device.
  • the method 200 includes determining a size of one or more of the plurality of particles.
  • a flow rate of the solution through the nozzle has a range from about 0.5 mL/min to about 30 mL/min.
  • the flow rate is between about 0.5 mL/min to about 25 mL/min, 0.5 mL/min to about 20 mL/min, 0.5 mL/min to about 15 mL/min, 0.5 mL/min to about 10 mL/min, about 1 mL/min to about 30 mL/min, about 1 mL/min to about 25 mL/min, about 1 mL/min to about 20 mL/min, 1 mL/min to about 15 mL/min, about 1 mL/min to about 10 mL/min, about 2 mL/min to about 30 mL/min, about 2 mL/min to about 25 mL/min, about 2 mL/min to about 20 mL/min, about 2 mL/min to about 15 mL/min, or about 2 mL/min to about 10 mL/min.
  • the system may further include a particle size analyzer to determine a size and/or a size distribution (e.g., a mean, mode, or percentage of a size class) of particles created within the pressurizable chamber.
  • the particle size analyzer may be an instrument configured to measure a size and/or a size distribution of particles created within the pressurizable chamber. Such a configuration may use dynamic light diffraction as the measuring technique.
  • particle size and/or size distribution may be measured by particle counting. This technique tracks particles by the scattering of light off the particles. Such scattering may be tracked over a period of time and the path traveled and time is used to calculate the diffusion coefficient, which is then used to calculate the particle size and/or size distribution.
  • Other particle size analyzers are possible as well.
  • the method further includes the steps of determining a difference between a desired size of the one or more particles and the determined size of the one or more particles, and in response to the determined difference, adjusting at least one of the distance between the proximal end of the vessel and the outlet aperture of the nozzle and the angle between a longitudinal axis of the vessel and a longitudinal axis of the nozzle.
  • the system described above may be a component of a larger particle production system.
  • a particle production system may include one or more nozzle assemblies such as those described above, a sonic energy source positioned adjacent to the orifice of each nozzle, one or more particle filtration systems in communication with one or more nozzle assemblies, and one or more particle collection devices in communication with the one or more particle filtration systems.
  • the one or more particle filtration systems comprise a tandem particle filtration system including at least one high pressure harvesting filter system and at least one low pressure collection filter system in tandem and downstream to the harvesting filter.
  • the particle production system may include at least two particle harvesting filters, two particle collection filters and two collection devices.
  • the invention provides compound particles prepared by the method of any embodiment or combination of embodiments of the invention. Examples Materials and Methods
  • Raw paclitaxel and docetaxel were purchased from Phyton Biotech (British Columbia, Canada), lot number FP2-15004 and DT7-14025, respectively. Both were characterized in their raw form.
  • the milling of both drugs was accomplished using a Deco-PBM-V-0.41 mill (Deco). The milling conditions for both compounds were as follows:
  • a solution of 65 mg/ml of paclitaxel was prepared in acetone.
  • a BETE MicroWhirl ® fog nozzle (BETE Fog Nozzle, Inc) and a sonic probe (Qsonica, model number Q700) were positioned in the crystallization chamber approximately 8 mm apart.
  • a stainless steel mesh filter with approximately 100 nm holes was attached to the crystallization chamber to collect the precipitated paclitaxel nanoparticles.
  • the supercritical carbon dioxide was placed in the crystallization chamber of the manufacturing equipment and brought to approximately 1200 psi at about 38 °C and a flow rate of 24 kg/hour.
  • the sonic probe was adjusted to 60% of total output power at a frequency of 20 kHz.
  • Paclitaxel nanoparticles produced had an average number-weighted mean size of 0.81 ⁇ m with an average standard deviation of 0.74 ⁇ m over three separate runs.
  • a solution of 79.32 mg/ml of docetaxel was prepared in ethanol.
  • the nozzle and a sonic probe were positioned in the pressurizable chamber approximately 9 mm (apart.
  • a stainless steel mesh filter with approximately 100 nm holes was attached to the pressurizable chamber to collect the precipitated docetaxel nanoparticles.
  • the supercritical carbon dioxide was placed in the pressurizable chamber of the manufacturing equipment and brought to approximately 1200 psi at about 38 °C and a flow rate of 68 slpm.
  • the sonic probe was adjusted to 60% of total output power at a frequency of 20 kHz.
  • the ethanol solution containing the docetaxel was pumped through the nozzle at a flow rate of 2 mL/minute for approximately 95 minutes).
  • the precipitated docetaxel agglomerates and particles were then collected from the supercritical carbon dioxide as the mixture is pumped through the stainless steel mesh filter.
  • the filter containing the nanoparticles of docetaxel
  • Docetaxel nanoparticles produced had an average number-weighted mean size of 0.82 ⁇ m with an average standard deviation of 0.66 ⁇ m over three separate ethanol runs. Particle Size Analysis
  • Particle size was analyzed by both light obscuration and laser diffraction methods.
  • An Particle Sizing Systems AccuSizer 780 SIS system was used for the light obscuration method and Shimadzu SALD-7101 was used for the laser diffraction method.
  • Paclitaxel nanoparticles were analyzed using 0.10% (w/v) sodium dodecyl sulfate (SDS) in water as the dispersant.
  • Docetaxel nanoparticles were analyzed using isopar G as the dispersant.
  • Paclitaxel suspensions were prepared by adding approximately 7 mL of filtered dispersant to a glass vial containing approximately 4 mg of paclitaxel particles. The vials were vortexed for approximately 10 seconds and then sonicated in a sonic bath approximately 1 minute. If the sample was already suspended, 1:1 solution of paclitaxel suspension to 0.1% SDS solution was made, vortexed for 10 seconds, and sonicated in the sonic bath for 1 minute.
  • Docetaxel suspensions were prepared by adding approximately 7 mL of filtered dispersant to a plastic vial containing approximately 4 mg of docetaxel particles. The vial was vortexed for approximately 10 seconds and then sonicated in a sonic bath for approximately 2 minutes. This suspension was used for laser diffraction analysis. Unused suspension was poured into a 125mL particle-free plastic bottle, which was then filled to approximately 100 mL with filtered dispersant. The suspension was vortex for approximately 10 seconds and then sonicated in the sonic bath for approximately 2 minutes. This diluted suspension was used for light obscuration analysis.
  • a background test was first performed prior to analyzing particles on the AccuSizer 780 SIS,.
  • a new particle-free plastic bottle was filled with blank suspension solution by pumping from a reservoir, using a peristaltic pump, through a 0.22 ⁇ m Millipore filter and into the bottle.
  • a background analysis was run to ensure the particle/mL count was below 100 particles/mL.
  • Paclitaxel or docetaxel particle preparations were added to a 10 mL tared graduated cylinder through a plastic weigh funnel at room temperature. The mass of the drug was measured to a nearest 0.1 mg, the volume was determined to the nearest 0.1 mL and the density calculated. Dissolution studies
  • Paclitaxel Approximately 50 mg of material (i.e.: raw paclitaxel, milled paclitaxel, or paclitaxel particles) were coated on approximately 1.5 grams of 1 mm glass beads by tumbling the material and beads in a vial for approximately 1 hour. Beads were transferred to a stainless steel mesh container and placed in the dissolution bath containing methanol/water 50/50 (v/v) media at 37°C, pH 7, and a USP Apparatus II (Paddle), operating at 75 rpm.
  • material i.e.: raw paclitaxel, milled paclitaxel, or paclitaxel particles
  • the BET surface area of particles produced using the above protocol and variations thereof ranged between 22 and 39 m 2 /g.
  • Figure 1 shows exemplary particles produced using the methods of the invention.
  • the BET surface area of raw paclitaxel was measured at 7.25 m 2 /g( Figure 2), while paclitaxel particles made according to the methods of US patents 5833891 and 5874029 ranged from 11.3 to 15.58 m 2 /g .
  • Exemplary particle sizes produced using the methods of the invention are shown in Table 1.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Toxicology (AREA)
  • Dispersion Chemistry (AREA)
  • Dermatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • Nanotechnology (AREA)
  • Optics & Photonics (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Medicinal Preparation (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Glanulating (AREA)
  • Filtering Of Dispersed Particles In Gases (AREA)
  • Nozzles (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Processes Of Treating Macromolecular Substances (AREA)
PCT/US2016/036012 2015-06-04 2016-06-06 Nozzle assembly and methods for use Ceased WO2016197100A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
EP16731712.2A EP3302780B1 (en) 2015-06-04 2016-06-06 Nozzle assembly, method and computer readable medium for use
KR1020177034414A KR102077518B1 (ko) 2015-06-04 2016-06-06 노즐 어셈블리 및 사용 방법
US15/573,157 US11291646B2 (en) 2015-06-04 2016-06-06 Nozzle assembly and methods for use
HK18112398.3A HK1253021B (en) 2015-06-04 2016-06-06 Nozzle assembly, method and computer readable medium for use
CN201680032291.XA CN107683174B (zh) 2015-06-04 2016-06-06 喷嘴组件及其使用方法
AU2016270558A AU2016270558B2 (en) 2015-06-04 2016-06-06 Nozzle assembly and methods for use
CA3026452A CA3026452C (en) 2015-06-04 2016-06-06 Nozzle assembly and methods for use
JP2017558020A JP6892394B2 (ja) 2015-06-04 2016-06-06 ノズルアセンブリおよび使用法

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US201562171060P 2015-06-04 2015-06-04
US201562171008P 2015-06-04 2015-06-04
US201562171001P 2015-06-04 2015-06-04
US62/171,008 2015-06-04
US62/171,060 2015-06-04
US62/171,001 2015-06-04

Publications (1)

Publication Number Publication Date
WO2016197100A1 true WO2016197100A1 (en) 2016-12-08

Family

ID=56194575

Family Applications (3)

Application Number Title Priority Date Filing Date
PCT/US2016/036012 Ceased WO2016197100A1 (en) 2015-06-04 2016-06-06 Nozzle assembly and methods for use
PCT/US2016/036013 Ceased WO2016197101A1 (en) 2015-06-04 2016-06-06 Collection device and methods for use
PCT/US2016/035993 Ceased WO2016197091A1 (en) 2015-06-04 2016-06-06 Taxane particles and their use

Family Applications After (2)

Application Number Title Priority Date Filing Date
PCT/US2016/036013 Ceased WO2016197101A1 (en) 2015-06-04 2016-06-06 Collection device and methods for use
PCT/US2016/035993 Ceased WO2016197091A1 (en) 2015-06-04 2016-06-06 Taxane particles and their use

Country Status (14)

Country Link
US (12) US10751319B2 (https=)
EP (4) EP3302423B1 (https=)
JP (5) JP6921759B2 (https=)
KR (5) KR20200134347A (https=)
CN (4) CN107683131B (https=)
AU (3) AU2016270558B2 (https=)
CA (3) CA2988132C (https=)
DK (1) DK3302431T3 (https=)
ES (1) ES2833749T3 (https=)
HK (1) HK1253021B (https=)
PT (1) PT3302431T (https=)
RU (1) RU2750163C2 (https=)
SG (2) SG10201913947RA (https=)
WO (3) WO2016197100A1 (https=)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018227037A1 (en) 2017-06-09 2018-12-13 Crititech, Inc. Treatment of epithelial cysts by intracystic injection of antineoplastic particles
WO2018231908A1 (en) 2017-06-14 2018-12-20 Crititech, Inc. Methods for treating lung disorders
WO2019067851A1 (en) 2017-09-29 2019-04-04 Crititech, Inc. CIPROFLOXACIN POLYMORPHS AND USE THEREOF
WO2019070850A1 (en) 2017-10-03 2019-04-11 Crititech, Inc. LOCAL ADMINISTRATION OF ANINEOPLASTIC PARTICLES IN COMBINATION WITH SYSTEMIC DELIVERY OF IMMUNOTHERAPEUTIC AGENTS FOR THE TREATMENT OF CANCER
WO2019136188A1 (en) 2018-01-05 2019-07-11 Crititech, Inc. Treatment of bladder cancer by intratumoral injection of taxane particles
WO2019231567A1 (en) 2018-05-31 2019-12-05 Crititech, Inc. Methods for isolating tumor-specific immune cells from a subject for adoptive cell therapy and cancer vaccines
WO2019231499A1 (en) 2018-05-31 2019-12-05 Crititech, Inc. Use of antineoplastic agents to stimulate the immune system for treatment of cancer
WO2019231498A1 (en) 2018-05-31 2019-12-05 Crititech, Inc. Treatment of kidney tumors by intratumoral injection of taxane particles
WO2020072090A1 (en) 2018-10-03 2020-04-09 Crititech, Inc. Use of antineoplastic agents to stimulate the immune system for production of tertiary lymphoid structures (tls)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3302423B1 (en) * 2015-06-04 2022-05-25 Crititech, Inc. Particle production system and particle collection device
CA2998483C (en) 2015-09-16 2022-09-06 Dfb Soria, Llc Delivery of drug nanoparticles and methods of use thereof
BR112018069628A2 (pt) 2016-04-04 2019-02-12 Crititech, Inc. métodos para tratamento de tumor sólido
WO2017194145A1 (en) * 2016-05-12 2017-11-16 Hewlett-Packard Development Company, L.P. Build material container
WO2018170210A1 (en) 2017-03-15 2018-09-20 Dfb Soria, Llc Topical therapy for the treatment of vulvar intraepithelial neoplasia (vin) and genital warts using nanoparticles of taxanes
WO2018170196A1 (en) 2017-03-15 2018-09-20 Dfb Soria, Llc Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes
WO2018170207A1 (en) * 2017-03-15 2018-09-20 Dfb Soria, Llc Topical therapy for the treatment of skin keratoses using nanoparticles of taxanes
WO2019010316A1 (en) * 2017-07-07 2019-01-10 Dfb Pharmaceuticals, Llc TREATMENT OF HYPERPLASIC TISSUE GROWTH COMPRISING BENIGN PROSTATIC HYPERPLASIA (HBP) BY DIRECT INJECTION OF ANTINOPLASTIC AGENT
WO2019067866A1 (en) 2017-09-29 2019-04-04 Crititech, Inc. GLUCOCORTICOID PARTICLES AND THEIR USE
US11497726B2 (en) 2018-03-16 2022-11-15 Dfb Soria, Ll. Topical therapy for the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer using nanoparticles of taxanes
CN108970835B (zh) * 2018-09-20 2020-11-17 马鞍山纽泽科技服务有限公司 一种耐高温喷射装置
US10732080B1 (en) * 2019-10-14 2020-08-04 Sotax Corporation Integrated dissolution processing and sample transfer system
US11911499B2 (en) 2019-11-07 2024-02-27 Resurge Therapeutics, Inc. System and method for prostate treatment
CA3166973C (en) * 2020-02-04 2025-03-18 Zhuhai Beihai Biotech Co., Ltd. Formulations of docetaxel
CN111238911A (zh) * 2020-02-10 2020-06-05 大连医科大学 一种断层塑化专用垂直包埋箱
KR20230044423A (ko) 2020-07-23 2023-04-04 크리티테크, 인크. 라파티닙 입자 및 이의 용도
KR20230044422A (ko) * 2020-07-23 2023-04-04 크리티테크, 인크. 소라페닙 입자 및 이의 용도
US20230364021A1 (en) * 2020-07-23 2023-11-16 Crititech, Inc. Sorafenib particles and uses thereof
US20230414510A1 (en) * 2020-09-08 2023-12-28 Crititech, Inc. Niclosamide particles and uses thereof
EP4329778A4 (en) * 2021-04-26 2025-02-19 Crititech, Inc. CISPLATIN PARTICLES AND THEIR USES
CN113447635B (zh) * 2021-05-11 2023-09-29 江西农业大学 一种盆栽类土壤不同深度温室气体释放速率测定装置
CN118103031A (zh) 2021-11-10 2024-05-28 克里蒂泰克公司 尼拉帕尼颗粒及其用途
WO2023086784A1 (en) 2021-11-10 2023-05-19 Crititech, Inc. Rucaparib particles and uses thereof
US11974979B2 (en) 2022-01-29 2024-05-07 Resurge Therapeutics, Inc. Treatments for benign prostatic hyperplasia
US11957654B2 (en) 2022-01-29 2024-04-16 Resurge Therapeutics, Inc. Treating benign prostatic hyperplasia

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5833891A (en) * 1996-10-09 1998-11-10 The University Of Kansas Methods for a particle precipitation and coating using near-critical and supercritical antisolvents
US8778181B1 (en) * 2013-03-14 2014-07-15 Crititech, Inc. Equipment assembly for and method of processing particles

Family Cites Families (154)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3648698A (en) * 1969-05-23 1972-03-14 George O Doherty Surgical collection unit
DE3120047C2 (de) * 1981-05-20 1984-03-29 Sterimed Gesellschaft für medizinischen Bedarf mbH, 6600 Saarbrücken Sauggerät zum Ansaugen von Körpersekreten
JPS5958019U (ja) * 1982-10-08 1984-04-16 松下電器産業株式会社 電気集塵機
US4780138A (en) * 1986-10-27 1988-10-25 Bodine Albert G Sonic apparatus and method for facilitating the extraction of minerals from ore in a leachant
US5143528A (en) * 1990-02-14 1992-09-01 Challenge Industries Lint collector
US5399363A (en) 1991-01-25 1995-03-21 Eastman Kodak Company Surface modified anticancer nanoparticles
US6749868B1 (en) 1993-02-22 2004-06-15 American Bioscience, Inc. Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof
US5409833A (en) * 1993-07-01 1995-04-25 Baxter International Inc. Microvessel cell isolation apparatus
GB9313642D0 (en) 1993-07-01 1993-08-18 Glaxo Group Ltd Method and apparatus for the formation of particles
US5886026A (en) 1993-07-19 1999-03-23 Angiotech Pharmaceuticals Inc. Anti-angiogenic compositions and methods of use
GB9413202D0 (en) 1994-06-30 1994-08-24 Univ Bradford Method and apparatus for the formation of particles
US5626862A (en) 1994-08-02 1997-05-06 Massachusetts Institute Of Technology Controlled local delivery of chemotherapeutic agents for treating solid tumors
US5480540A (en) 1994-10-17 1996-01-02 General Electric Company Spray apparatus for separating solids from fluids
US5874481A (en) 1995-06-07 1999-02-23 Alliance Pharmaceutical Corp. Fluorochemical solutions for the delivery of lipophilic pharmaceutical agents
US5874029A (en) 1996-10-09 1999-02-23 The University Of Kansas Methods for particle micronization and nanonization by recrystallization from organic solutions sprayed into a compressed antisolvent
EP0885038B1 (en) * 1996-03-01 2011-06-15 The University Of Kansas Methods and apparatus for particle precipitation and coating using near-critical and supercritical antisolvents
US6495579B1 (en) 1996-12-02 2002-12-17 Angiotech Pharmaceuticals, Inc. Method for treating multiple sclerosis
EP0954283B1 (en) 1996-12-30 2007-03-21 Battelle Memorial Institute Use of a non-encapsulated anticancer drug for the preparation of a formulation for treating neoplasms by inhalation
BRPI9810945B8 (pt) 1997-06-27 2021-05-25 Abraxis Bioscience Inc formulações de agentes farmacológicos, métodos para sua preparação e métodos para uso das mesmas
US6117949A (en) 1998-10-01 2000-09-12 Macromed, Inc. Biodegradable low molecular weight triblock poly (lactide-co-glycolide) polyethylene glycol copolymers having reverse thermal gelation properties
JPH11189403A (ja) * 1997-12-25 1999-07-13 Tic:Kk 層構造型複合粒子製造装置
JP3418751B2 (ja) 1998-01-22 2003-06-23 参天製薬株式会社 フルオロメトロン懸濁型点眼剤
IL131217A0 (en) 1998-03-10 2001-01-28 Napro Biotherapeutics Inc Novel methods and compositions for delivery of taxanes
US6221153B1 (en) 1998-06-09 2001-04-24 Trevor Percival Castor Method for producing large crystals of complex molecules
US7521068B2 (en) 1998-11-12 2009-04-21 Elan Pharma International Ltd. Dry powder aerosols of nanoparticulate drugs
US6113795A (en) 1998-11-17 2000-09-05 The University Of Kansas Process and apparatus for size selective separation of micro- and nano-particles
PT1131063E (pt) 1998-11-25 2003-08-29 Universitaetsklinikum Freiburg Pomada ou creme de hiperforina
US6537585B1 (en) 1999-03-26 2003-03-25 Guilford Pharmaceuticals, Inc. Methods and compositions for treating solid tumors
US7217735B1 (en) 1999-04-09 2007-05-15 Au Jessie L-S Methods and compositions for enhancing delivery of therapeutic agents to tissues
US6610317B2 (en) 1999-05-27 2003-08-26 Acusphere, Inc. Porous paclitaxel matrices and methods of manufacture thereof
CA2371836C (en) * 1999-05-27 2006-01-31 Acusphere, Inc. Porous drug matrices and methods of manufacture thereof
US6858199B1 (en) 2000-06-09 2005-02-22 Advanced Inhalation Research, Inc. High efficient delivery of a large therapeutic mass aerosol
US6616849B1 (en) 1999-08-25 2003-09-09 Shimadzu Corporation Method of and system for continuously processing liquid materials, and the product processed thereby
JP2003513756A (ja) 1999-11-12 2003-04-15 アンジオテック ファーマシューティカルズ，インコーポレイテッド 放射性治療と細胞周期インヒビターとの組合せの組成物
SE515604C2 (sv) * 2000-04-28 2001-09-10 Bst Ab Förfarande och anordning för uppsugning och transport av vätskor, företrädesvis blod
US6620351B2 (en) 2000-05-24 2003-09-16 Auburn University Method of forming nanoparticles and microparticles of controllable size using supercritical fluids with enhanced mass transfer
US6562952B1 (en) 2000-10-31 2003-05-13 The University Of Kansas Precipitation of proteins from organic solutions
US20020081339A1 (en) 2000-12-22 2002-06-27 Philippe Menei Treatment of inoperable tumors by stereotactic injection of microspheres
US20020192280A1 (en) 2001-05-01 2002-12-19 Angiotech Pharmaceuticals, Inc. Compositions and methods for treating inflammatory conditions utilizing protein or polysaccharide containing anti-microtubule agents
ES2261469T5 (es) 2001-07-02 2015-12-22 Micro & Nano Materials Sagl Proceso para producir micro y/o nanopartículas
TW586963B (en) * 2001-07-20 2004-05-11 Nektar Therapeutics Uk Ltd Method and apparatus for preparing target substance in particulate form and fluid inlet assembly for said apparatus
US20030054042A1 (en) 2001-09-14 2003-03-20 Elaine Liversidge Stabilization of chemical compounds using nanoparticulate formulations
US20030134810A1 (en) 2001-10-09 2003-07-17 Chris Springate Methods and compositions comprising biocompatible materials useful for the administration of therapeutic agents
WO2003032906A2 (en) * 2001-10-15 2003-04-24 Crititech, Inc. Delivery of poorly soluble drugs
EP1458361A4 (en) 2001-11-20 2007-04-25 Advanced Inhalation Res Inc COMPOSITIONS FOR DISTRIBUTING PRODUCTS WITH LASTING EFFECT
EP1480691A4 (en) 2002-03-05 2007-11-28 Univ State Cleveland AGGLOMERATED PARTICLES FOR THE DISPOSAL OF A MEDICINAL PRODUCT IN AEROSOL FORM
JP2003251127A (ja) * 2002-03-06 2003-09-09 Kazuo Hirakawa 集塵装置
EP1490030B2 (en) 2002-03-20 2010-07-14 Elan Pharma International Limited Nanoparticulate compositions of angiogenesis inhibitors
EP1501483A2 (en) * 2002-04-25 2005-02-02 Nektar Therapeutics UK Ltd Particulate materials
IL164847A0 (en) 2002-04-26 2005-12-18 Teva Pharma Microparticle pharmaceutical compositions for intratumoral delivery
US9339459B2 (en) * 2003-04-24 2016-05-17 Nektar Therapeutics Particulate materials
CN1255394C (zh) 2002-06-24 2006-05-10 成都思摩纳米技术有限公司 紫杉醇纳米微粒的制备方法及应用
KR100573289B1 (ko) 2002-07-20 2006-04-24 대화제약 주식회사 방광내 투여를 통한 방광암치료용 파클리탁셀 조성물 및그의 제조 방법
US6916389B2 (en) * 2002-08-13 2005-07-12 Nanotechnologies, Inc. Process for mixing particulates
CN2578811Y (zh) * 2002-10-24 2003-10-08 陆纪清 全闭式煤粉取样装置
EP1569620A4 (en) * 2002-10-30 2006-03-22 Spherics Inc NANOPARTICULAR BIOACTIVE AGENTS
KR100508518B1 (ko) * 2002-11-13 2005-08-17 한미약품 주식회사 초임계유체 공정을 이용한 파클리탁셀 고체분산체의 제조방법 및 이 방법으로 제조된 파클리탁셀 고체분산체
CN103405405A (zh) 2002-12-09 2013-11-27 阿布拉西斯生物科学有限责任公司 组合物和传递药剂的方法
US7455797B2 (en) 2003-02-28 2008-11-25 Ferro Corporation Method and apparatus for producing particles using supercritical fluid
EP1608359A4 (en) 2003-04-03 2011-08-17 Jessie L-S Au DRUG-LOADING PARTICLES TARGETING TUMORS
US20060147535A1 (en) 2003-04-16 2006-07-06 Poongunran Muthukumaran Methods for and compositions of anticancer medicaments
US20050059613A1 (en) 2003-07-08 2005-03-17 Bahram Memarzadeh Compositions and methods for the enhanced uptake of therapeutic agents through the bladder epithelium
US8021831B2 (en) 2003-08-25 2011-09-20 Board Of Regents, The University Of Texas System Taxane chemosensitivity prediction test
JP2007001865A (ja) 2003-09-16 2007-01-11 Ltt Bio-Pharma Co Ltd 脂溶性薬物封入微粒子、その製造法およびそれを含有する製剤
PL2286794T3 (pl) 2003-10-15 2016-10-31 Zastosowanie kationowych liposomów zawierających paklitaksel
TWI371274B (en) * 2003-10-23 2012-09-01 Bristol Myers Squibb Co Process for making sterile aripiprazole of desired mean particle size
WO2005042219A1 (en) 2003-10-24 2005-05-12 Ferro Corporation Method of forming particles
JP4787165B2 (ja) 2003-11-05 2011-10-05 エラン ファーマ インターナショナル，リミティド 表面安定剤としてペプチドを有するナノ粒子組成物
DE10357091A1 (de) * 2003-12-06 2005-07-07 Degussa Ag Vorrichtung und Verfahren zur Abscheidung feinster Partikel aus der Gasphase
GB0402963D0 (en) 2004-02-11 2004-03-17 Univ Nottingham Counter current mixing device for two different fluids
US8043631B2 (en) 2004-04-02 2011-10-25 Au Jessie L S Tumor targeting drug-loaded particles
US7833444B2 (en) 2004-10-29 2010-11-16 Nara Machinery Co., Ltd. Fine particle granulation method
EP1830813A2 (en) 2004-12-14 2007-09-12 Transave, Inc. Lipid particles comprising bioactive agents, methods of preparing and uses thereof
ES2265262B1 (es) 2005-01-31 2008-03-01 Activery Biotech, S.L.(Titular Al 50%) Procedimiento para la obtencion de sistemas micro- y nanodispersos.
US8735394B2 (en) 2005-02-18 2014-05-27 Abraxis Bioscience, Llc Combinations and modes of administration of therapeutic agents and combination therapy
MX2007010394A (es) * 2005-02-24 2008-02-19 Elan Pharma Int Ltd Formulaciones nanoparticuladas de docetaxel y analogos del mismo.
US7872050B2 (en) 2005-03-14 2011-01-18 Yaupon Therapeutics Inc. Stabilized compositions of volatile alkylating agents and methods of using thereof
US8118795B2 (en) * 2005-03-22 2012-02-21 Medindica-Pak, Inc Disposal chain supply systems method and apparatus
ES2557988T3 (es) 2005-03-31 2016-02-01 Lidds Ab Método para tratar enfermedades de próstata basado en el suministro local de principios activos
CN1923189A (zh) 2005-08-30 2007-03-07 孔庆忠 一种紫杉碱类抗癌药物的缓释注射剂
AU2006284657B2 (en) 2005-08-31 2012-07-19 Abraxis Bioscience, Llc Compositions and methods for preparation of poorly water soluble drugs with increased stability
WO2007065446A2 (en) 2005-12-11 2007-06-14 Scf Technologies A/S Production of nanosized materials
US8906392B2 (en) * 2005-12-16 2014-12-09 University Of Kansas Nanocluster compositions and methods
AR054215A1 (es) 2006-01-20 2007-06-13 Eriochem Sa Una formulacion farmaceutica de un taxano, una composicion solida de un taxano liofilizado a partir de una solucion de acido acetico, un procedimiento para la preparacion de dicha composicion solida de un taxano, una composicion solubilizante de un taxano liofilizado, y un conjunto de elementos (kit
CN101336899A (zh) 2006-01-25 2009-01-07 济南帅华医药科技有限公司 含紫杉烷的抗癌缓释注射剂
DK1996160T3 (da) 2006-03-14 2010-07-05 Lidds Ab Bioresorberbar sammensætning med kontrolleret frigivelse
US7964029B2 (en) * 2006-07-17 2011-06-21 Thar Instrument, Inc. Process flowstream collection system
EP2077823B1 (en) 2006-10-11 2012-06-27 Crititech, Inc. Method for precipitation of small medicament particles into use containers
WO2008044092A1 (en) 2006-10-11 2008-04-17 Renault Trucks Truck provided with a passive keyless access system
TWI405590B (zh) * 2007-04-06 2013-08-21 活效製藥股份有限公司 微粉碎化有機化合物粒子之製法
US20100166869A1 (en) 2007-05-03 2010-07-01 Desai Neil P Methods and compositions for treating pulmonary hypertension
WO2009006590A2 (en) 2007-07-04 2009-01-08 Dr. Reddy's Laboratories Ltd. Docetaxel process and polymorphs
CN101129338A (zh) * 2007-08-27 2008-02-27 四川大学 超临界流体新技术微细化抗癌药物紫杉醇
WO2009111271A1 (en) 2008-03-06 2009-09-11 Nitto Denko Corporation Polymer paclitaxel conjugates and methods for treating cancer
WO2009119055A1 (ja) * 2008-03-24 2009-10-01 三洋化成工業株式会社 樹脂粒子及びその製造方法
KR101455446B1 (ko) 2008-09-19 2014-10-27 액티버스 파마 컴퍼니 리미티드 의료용 복합 유기 화합물 분체, 그 제조 방법 및 현탁액
CA2745238A1 (en) 2008-12-02 2010-06-10 Biocompatibles Uk Limited Pancreatic tumour treatment
PT104693B (pt) 2009-07-27 2011-11-24 Univ Lisboa Nanopartículas lipídicas semi-sólidas contendo um agente antineoplásico e seu processo de preparação
EP3101122B1 (en) 2009-08-24 2023-06-14 Baylor College of Medicine Generation of ctl lines with specificity against multiple tumor antigens or multiple viruses
US20110209578A1 (en) * 2010-02-26 2011-09-01 Kuniaki Ara Nanoparticle manufacturing device and nanoparticle manufacturing method and method of manufacturing nanoparticle-dispersed liquid alkali metal
CN101829061A (zh) * 2010-05-14 2010-09-15 无锡纳生生物科技有限公司 一种紫杉醇纳米颗粒组合物及其制备方法
WO2011153009A1 (en) 2010-06-02 2011-12-08 Abraxis Bioscience, Llc Methods of treating bladder cancer
CA2811869A1 (en) 2010-09-21 2012-03-29 Cristal Delivery B.V. Tunable, biodegradable linker molecules for transient conjugation of components in drug delivery systems, and drug delivery systems prepared therewith
EP2627317A4 (en) 2010-10-15 2014-08-20 Glaxo Group Ltd MEDICINAL FORMULATIONS FROM AGGREGATED NANOPARTICLES AND THEIR PREPARATION AND USE
EP2632580A2 (en) * 2010-10-29 2013-09-04 Velico Medical, Inc. System and method for spray drying a liquid
WO2012096995A2 (en) * 2011-01-11 2012-07-19 Boston Scientific Scimed, Inc. Coated medical devices
JP6038881B2 (ja) 2011-04-20 2016-12-07 ザ・ユニバーシティ・オブ・シドニー 治療の方法及びそのために有用な剤
US20140154269A1 (en) 2011-04-26 2014-06-05 The Methodist Hospital Research Institute Targeted nanovectors and their use for treatment of brain tumors
US10973763B2 (en) 2011-06-17 2021-04-13 Berg Llc Inhalable pharmaceutical compositions
BR112013033466A8 (pt) 2011-06-27 2018-03-06 Cristal Delivery B V uso de um sistema de liberação controlada e sistema de liberação controlada
US11766459B2 (en) * 2011-07-08 2023-09-26 Jointechlabs, Inc. System and methods for preparation of adipose-derived stem cells
US9586923B2 (en) * 2011-08-31 2017-03-07 University Of Kansas Spray oxidation process for producing 2,5-furandicarboxylic acid from hydroxymethylfurfural
FR2980683B1 (fr) 2011-09-30 2014-11-21 Univ Paris Curie Dispositif de guidage d'un instrument medical insere dans une voie naturelle ou une voie artificielle d'un patient
CN102319898B (zh) 2011-10-13 2013-05-08 西北工业大学 一种制备合金及金属基复合材料零部件的喷射成形系统
CN102488682A (zh) 2011-11-22 2012-06-13 四川九章生物化工科技发展有限公司 绿原酸的抗癌新用途
JP2013212494A (ja) * 2012-03-05 2013-10-17 Ricoh Co Ltd 樹脂微粒子の製造方法
US10555911B2 (en) 2012-05-04 2020-02-11 Yale University Highly penetrative nanocarriers for treatment of CNS disease
CN102728414A (zh) 2012-07-07 2012-10-17 中山大学 用于制备单壁碳纳米管的催化剂的制备方法及其运用
TW201408304A (zh) 2012-08-31 2014-03-01 Cathay General Hospital 一種合併抗癌藥物及荷爾蒙之抗腎細胞癌藥物及其製造方法
CN104884065B (zh) 2012-09-21 2019-01-01 强烈治疗剂公司 治疗癌症的方法
WO2014081881A2 (en) * 2012-11-20 2014-05-30 Andrew Paul Joseph Fluid-based extractor
US9511046B2 (en) 2013-01-11 2016-12-06 Abraxis Bioscience, Llc Methods of treating pancreatic cancer
ES2792082T3 (es) 2013-02-28 2020-11-10 Pf Consumer Healthcare 1 Llc Estabilidad mejorada de composiciones líquidas novedosas
US9925512B2 (en) 2013-03-14 2018-03-27 Crititech, Inc. Equipment assembly for and method of processing particles
US20140294967A1 (en) 2013-03-28 2014-10-02 Bbs Nanotechnology Llc. Stable nanocomposition comprising paclitaxel, process for the preparation thereof, its use and pharmaceutical compositions containing it
CA2944480C (en) 2013-04-10 2021-05-18 Massachusetts Institute Of Technology Local drug delivery devices and methods for treating cancer
CN203699094U (zh) * 2013-10-15 2014-07-09 雷海平 新式垃圾桶及配套内桶
US10188738B2 (en) 2013-10-16 2019-01-29 Université Libre de Bruxelles Formulations useful in the treatment of proliferative diseases affecting the respiratory tract
WO2015095404A2 (en) 2013-12-17 2015-06-25 Genentech, Inc. Methods of treating cancers using pd-1 axis binding antagonists and taxanes
EP3082853A2 (en) 2013-12-20 2016-10-26 The Broad Institute, Inc. Combination therapy with neoantigen vaccine
WO2015103005A1 (en) 2014-01-03 2015-07-09 Research Institute At Nationwide Children's Hospital Amphiphilic amine compounds and their use as therapeutic agents and nanocarriers
CN203737192U (zh) * 2014-01-20 2014-07-30 四川西汉电子科技有限责任公司 一种造粒机
TWI601542B (zh) 2014-04-18 2017-10-11 林信湧 一種用於治療肺癌之吸入式醫藥組成物及其備製方法
WO2015187194A1 (en) 2014-06-01 2015-12-10 Crititech, Inc. Use of paclitaxel particles
CN203847940U (zh) 2014-06-04 2014-09-24 刘希 一种加料喷嘴调节支架
WO2015191590A2 (en) 2014-06-09 2015-12-17 Biomed Valley Discoveries, Inc. Combination therapies targeting tumor-associated stroma or tumor cells and microtubules
US9533449B2 (en) * 2014-06-19 2017-01-03 Autodesk, Inc. Material deposition systems with four or more axes
US10975442B2 (en) 2014-12-19 2021-04-13 Massachusetts Institute Of Technology Molecular biomarkers for cancer immunotherapy
EP3302423B1 (en) 2015-06-04 2022-05-25 Crititech, Inc. Particle production system and particle collection device
CA2998483C (en) 2015-09-16 2022-09-06 Dfb Soria, Llc Delivery of drug nanoparticles and methods of use thereof
US10517961B2 (en) 2015-09-25 2019-12-31 ZY Therapeutics, Inc. Drug formulation based on particulates comprising polysaccharide-vitamin conjugate
DE202016006620U1 (de) 2015-10-28 2017-04-12 Qass Gmbh Vorrichtungen zum Beobachten eines Magnetfelds eines Materialvolumens
CA3010236A1 (en) 2016-01-20 2017-07-27 Fate Therapeutics, Inc. Compositions and methods for immune cell modulation in adoptive immunotherapies
BR112018069628A2 (pt) * 2016-04-04 2019-02-12 Crititech, Inc. métodos para tratamento de tumor sólido
CN107281502B (zh) 2016-04-05 2021-05-04 上海市肿瘤研究所 一种复合显影温敏凝胶栓塞剂、制备方法及其应用
US10894093B2 (en) 2016-04-15 2021-01-19 Cellectis Method of engineering drug-specific hypersensitive t-cells for immunotherapy by gene inactivation
CN108883579B (zh) * 2016-05-12 2023-09-29 惠普发展公司，有限责任合伙企业 构建材料容器
US9567399B1 (en) 2016-06-20 2017-02-14 Kymab Limited Antibodies and immunocytokines
CN109890419A (zh) 2016-09-01 2019-06-14 梅约医学教育与研究基金会 用于治疗癌症的载体-pd-l1结合剂组合物
WO2018170207A1 (en) 2017-03-15 2018-09-20 Dfb Soria, Llc Topical therapy for the treatment of skin keratoses using nanoparticles of taxanes
WO2018170196A1 (en) 2017-03-15 2018-09-20 Dfb Soria, Llc Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes
WO2018170210A1 (en) 2017-03-15 2018-09-20 Dfb Soria, Llc Topical therapy for the treatment of vulvar intraepithelial neoplasia (vin) and genital warts using nanoparticles of taxanes
EP3615145B1 (en) 2017-06-09 2024-05-15 Crititech, Inc. Compositions for use in the treatment of epithelial cysts by intracystic injection of antineoplastic particles
WO2018231908A1 (en) 2017-06-14 2018-12-20 Crititech, Inc. Methods for treating lung disorders

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5833891A (en) * 1996-10-09 1998-11-10 The University Of Kansas Methods for a particle precipitation and coating using near-critical and supercritical antisolvents
US8778181B1 (en) * 2013-03-14 2014-07-15 Crititech, Inc. Equipment assembly for and method of processing particles

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018227037A1 (en) 2017-06-09 2018-12-13 Crititech, Inc. Treatment of epithelial cysts by intracystic injection of antineoplastic particles
WO2018231908A1 (en) 2017-06-14 2018-12-20 Crititech, Inc. Methods for treating lung disorders
WO2019067851A1 (en) 2017-09-29 2019-04-04 Crititech, Inc. CIPROFLOXACIN POLYMORPHS AND USE THEREOF
WO2019070850A1 (en) 2017-10-03 2019-04-11 Crititech, Inc. LOCAL ADMINISTRATION OF ANINEOPLASTIC PARTICLES IN COMBINATION WITH SYSTEMIC DELIVERY OF IMMUNOTHERAPEUTIC AGENTS FOR THE TREATMENT OF CANCER
WO2019136188A1 (en) 2018-01-05 2019-07-11 Crititech, Inc. Treatment of bladder cancer by intratumoral injection of taxane particles
WO2019136187A1 (en) 2018-01-05 2019-07-11 Crititech, Inc. Treatment of bladder cancer by local administration of taxane particles
WO2019231567A1 (en) 2018-05-31 2019-12-05 Crititech, Inc. Methods for isolating tumor-specific immune cells from a subject for adoptive cell therapy and cancer vaccines
WO2019231499A1 (en) 2018-05-31 2019-12-05 Crititech, Inc. Use of antineoplastic agents to stimulate the immune system for treatment of cancer
WO2019231498A1 (en) 2018-05-31 2019-12-05 Crititech, Inc. Treatment of kidney tumors by intratumoral injection of taxane particles
WO2020072090A1 (en) 2018-10-03 2020-04-09 Crititech, Inc. Use of antineoplastic agents to stimulate the immune system for production of tertiary lymphoid structures (tls)

Also Published As

Publication number Publication date
CA2988132C (en) 2021-04-27
JP6921759B2 (ja) 2021-08-18
EP3302780B1 (en) 2019-04-17
BR112017025815A2 (pt) 2018-08-14
CN107683131B (zh) 2021-09-28
US20200405684A1 (en) 2020-12-31
KR20200134347A (ko) 2020-12-01
US20200101039A1 (en) 2020-04-02
RU2017140678A (ru) 2019-07-09
HK1253021A1 (en) 2019-06-06
US20180116910A1 (en) 2018-05-03
US20210000786A1 (en) 2021-01-07
JP7096299B2 (ja) 2022-07-05
CN114010628A (zh) 2022-02-08
HK1253018A1 (en) 2019-06-06
US20180169058A1 (en) 2018-06-21
KR20200020995A (ko) 2020-02-26
ES2833749T3 (es) 2021-06-15
US10751319B2 (en) 2020-08-25
PT3302431T (pt) 2020-11-30
KR20180016366A (ko) 2018-02-14
US10507195B2 (en) 2019-12-17
WO2016197091A1 (en) 2016-12-08
JP2022121532A (ja) 2022-08-19
SG10201913945QA (en) 2020-03-30
AU2016270559B2 (en) 2020-12-10
JP6758325B2 (ja) 2020-09-23
CN107683174B (zh) 2021-02-19
CN107683174A (zh) 2018-02-09
US20200163928A1 (en) 2020-05-28
US20170224650A1 (en) 2017-08-10
US20160374953A1 (en) 2016-12-29
KR102317107B1 (ko) 2021-10-25
JP6892394B2 (ja) 2021-06-23
EP3302780A1 (en) 2018-04-11
AU2016270549A1 (en) 2017-11-16
US20250186390A1 (en) 2025-06-12
AU2016270558B2 (en) 2020-08-13
US9918957B2 (en) 2018-03-20
US10993927B2 (en) 2021-05-04
HK1253021B (en) 2020-01-24
CA3026454C (en) 2023-07-04
CN107683131A (zh) 2018-02-09
AU2016270559A1 (en) 2017-11-16
SG10201913947RA (en) 2020-03-30
CA2988132A1 (en) 2016-12-08
US11123322B2 (en) 2021-09-21
US11291646B2 (en) 2022-04-05
AU2016270558A1 (en) 2017-11-16
EP3302423A1 (en) 2018-04-11
US20210393569A1 (en) 2021-12-23
JP2020203913A (ja) 2020-12-24
JP2018516907A (ja) 2018-06-28
KR20180015635A (ko) 2018-02-13
DK3302431T3 (da) 2020-11-30
JP2018524145A (ja) 2018-08-30
CA3026452C (en) 2023-03-21
EP3838264A1 (en) 2021-06-23
AU2016270549B2 (en) 2019-01-17
KR20180013906A (ko) 2018-02-07
US9814685B2 (en) 2017-11-14
KR102551708B1 (ko) 2023-07-06
HK1253020A1 (en) 2019-06-06
CA3026452A1 (en) 2016-12-08
CA3026454A1 (en) 2016-12-08
EP3302423B1 (en) 2022-05-25
KR102077518B1 (ko) 2020-02-14
RU2750163C2 (ru) 2021-06-22
CN107743418A (zh) 2018-02-27
US10729673B2 (en) 2020-08-04
WO2016197101A1 (en) 2016-12-08
RU2017140678A3 (https=) 2019-07-17
JP2018526188A (ja) 2018-09-13
US20180125783A1 (en) 2018-05-10
EP3302431A1 (en) 2018-04-11
US20160354336A1 (en) 2016-12-08
KR102337080B1 (ko) 2021-12-08
EP3302431B1 (en) 2020-11-11

Similar Documents

Publication Publication Date Title
CA3026452C (en) Nozzle assembly and methods for use
HK40056120A (en) Taxane particles and their use
HK1253020B (en) Particle production system and particle collection device
HK1253018B (en) Taxane particles and their use

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16731712

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2017558020

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 15573157

Country of ref document: US

ENP Entry into the national phase

Ref document number: 2016270558

Country of ref document: AU

Date of ref document: 20160606

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 11201709270P

Country of ref document: SG

ENP Entry into the national phase

Ref document number: 20177034414

Country of ref document: KR

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2016731712

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 3026452

Country of ref document: CA