Method of preparing soy isoflavone nanoparticles by precipitation with compressed antisolvent (PCA) using a supercritical fluid
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Publication Number
US-9259396-B2
Publication Date
2016-02-16
Expiration Date
Abstract
The present invention relates to a method of preparing a solid form of soy isoflavone (e.g. genistein). In particular, the present invention relates to a method of preparing a solid form of soy isoflavone by precipitation with compressed antisolvent using a supercritical fluid to produce nano-sized particles of soy isoflavone with an improved dissolution rate and bioavailability. An oral composition or aerosolized formulation comprising the nanoparticles of the soy isoflavone prepared by the method of the present invention is also disclosed herein. The dissolution rate and bioavailability of the nanoparticles of the soy isoflavone prepared by the method of the present invention have a 2-fold increase and a 2.6-fold increase respectively as compared to those of the raw soy isoflavone.
Core Innovation
The invention relates to a method of preparing elongated soy isoflavone nanoparticles having a length/width ratio of 8.3 to 10.8 for improving in vivo bioavailability. The method is based on precipitation with compressed antisolvent using a supercritical fluid as the compressed antisolvent to precipitate the elongated soy isoflavone nanoparticles in a precipitation chamber. The supercritical fluid is supercritical or near supercritical CO2, and precipitation reduces the size of the soy isoflavone from a dissolved raw soy isoflavone in an organic solvent.
Raw soy isoflavone is dissolved in acetone to form a solution of soy isoflavone at a concentration of 0.4 mg/mL to 4 mg/mL. The precipitation chamber is preset to conditions comprising a temperature ranging of 31°C to 60°C and a pressure ranging of 85 to 120 bar. After the chamber reaches the preset conditions, the soy isoflavone solution is introduced into the precipitation chamber through a co-axial nozzle, and the supercritical CO2 is mixed with the solution in the chamber to precipitate the elongated soy isoflavone nanoparticles, under a feed rate ratio of the supercritical fluid to the soy isoflavone solution ranging from 30 to 90 g/mL.
After precipitation, excess supercritical fluid is provided into the precipitation chamber to remove remaining organic residue from the elongated soy isoflavone nanoparticles. The nanoparticles are collected from a metal filter at the bottom of the precipitation chamber after gradual depressurization to atmospheric pressure. The documented examples indicate elongated soy isoflavone nanoparticles with markedly reduced width and retention of genistein crystal structure, while showing improved dissolution rate and oral bioavailability versus raw genistein.
Claims Coverage
The document contains one independent claim directed to a method, and the remaining claims provide dependent refinements that further specify the starting soy isoflavones, concentration relative to saturation point, particle width threshold, solvent recovery, and related processing details. Across the claim set, the core coverage focuses on forming elongated soy isoflavone nanoparticles via compressed antisolvent precipitation using supercritical or near-supercritical CO2, with defined chamber conditions, nozzle mixing, feed rate ratio, and post-precipitation residue removal and collection steps.
Elongated soy isoflavone nanoparticles for improved in vivo bioavailability via compressed antisolvent precipitation
Preparing elongated soy isoflavone nanoparticles having a length/width ratio of 8.3 to 10.8 for improving in vivo bioavailability based on precipitation with compressed antisolvent.
Supercritical or near-supercritical CO2 as compressed antisolvent in a precipitation chamber
Providing a supercritical fluid as the compressed antisolvent to a precipitation chamber where precipitation takes place, wherein the supercritical fluid is supercritical or near supercritical CO2.
Acetone solution of raw soy isoflavone at specified concentration
Dissolving raw soy isoflavone in an organic solvent to form a solution of soy isoflavone at a concentration of 0.4 mg/mL to 4 mg/mL, wherein the organic solvent is acetone.
Preset precipitation chamber temperature and pressure range
Presetting the precipitation chamber to reach conditions comprising a temperature ranging of 31°C to 60°C and a pressure ranging of 85 to 120 bar.
Co-axial nozzle introduction and supercritical mixing under feed rate ratio
Introducing the solution of soy isoflavone into the precipitation chamber through a co-axial nozzle after the conditions are reached in the precipitation chamber; mixing the supercritical fluid and the solution to precipitate the elongated soy isoflavone nanoparticles, wherein a feed rate ratio of the supercritical fluid to the solution ranges from 30 to 90 g/mL.
Excess supercritical fluid to remove remaining organic residue and metal filter collection
Providing excess supercritical fluid into the precipitation chamber to remove remaining organic residue from the elongated soy isoflavone nanoparticles; collecting the elongated soy isoflavone nanoparticles from a metal filter at the bottom of the precipitation chamber after gradual depressurization to atmospheric pressure.
Specific elongated nanoparticle width limitation
Elongated soy isoflavone nanoparticles having an average width of less than 1 μm.
Optional specific raw soy isoflavone selection (aglycone or glucoside lists)
Selecting the raw soy isoflavone as either a soy aglycone isoflavone or a soy glucoside isoflavone via explicit lists of named isoflavones.
Concentration more than tenfold lower than saturation point at room temperature and atmospheric pressure
Using a soy isoflavone solution in acetone wherein the raw soy isoflavone concentration is more than tenfold lower than its saturation point at room temperature and atmospheric pressure.
Recollecting organic solvent via low-pressure cyclone separator and venting
Further recollecting an organic solvent from a low-pressure cyclone separator while excess supercritical fluid vaporizes in the separator and is vented through a connected vent.
Overall claim coverage is directed to a compressed antisolvent precipitation process that forms elongated soy isoflavone nanoparticles using supercritical or near-supercritical CO2, with specified chamber temperature/pressure, co-axial nozzle introduction, defined feed rate ratio, and steps to remove residual organic solvent and collect the nanoparticles via a metal filter after depressurization. Dependent claims narrow the product width, specify allowable soy isoflavone species, impose a concentration-versus-saturation-point condition, and further define an organic solvent recollection approach using a low-pressure cyclone separator and venting.
Stated Advantages
Improving in vivo bioavailability of soy isoflavone nanoparticles with length/width ratio of 8.3 to 10.8.
Improved dissolution rate versus raw genistein (reported approximately 2-fold higher dissolution rate).
Improved oral bioavailability versus raw genistein (reported approximately 2.6-fold higher oral bioavailability in rats).
Reduced organic residue remaining after precipitation via providing excess supercritical fluid.
Documented Applications
Oral administration compositions containing the soy isoflavone nanoparticles.
Aerosol inhalation formulation containing the soy isoflavone nanoparticles.
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