• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The invention relates to a method for preparing a co-crystal of at least two compounds by flash evaporation or flash evaporation, for example for the preparation of co-crystals in the fields of energetic materials, pharmaceutical compounds, phytopharmaceutical compounds , ferroelectric materials, non-linear response materials.
    公开号:FR3023177A1
    申请号:FR1456461
    申请日:2014-07-04
    公开日:2016-01-08
    发明作者:Benedikt Risse；Denis Spitzer
    申请人:Centre National de la Recherche Scientifique CNRS；Universite de Strasbourg；Institut Franco Allemand de Recherches de Saint Louis ISL；
    IPC主号:
    专利说明:

    [0001] The invention relates to a process for preparing a co-crystal of at least two compounds by flash evaporation or flash evaporation, for example for the preparation of co-crystals in the fields. energetic materials, pharmaceutical compounds, phytopharmaceutical compounds, ferroelectric materials, non-linear response materials or bio-electronic materials.
    [0002] Co-crystals are solids assembled at the molecular level. Several types of intermolecular interaction may allow the preparation of co-crystals. These interactions may be hydrogen bonds, ionic bonds, stacking bonds (Tr stacking) or Van der Waals bonds. The co-crystals are generally more thermodynamically stable than the starting compounds. The co-crystals generally have improved properties over the corresponding compounds used individually. Thus, the co-crystals of pharmaceutical or phytopharmaceutical substances, energetic materials or ferroelectric materials have improved properties. For example, the co-crystals of pharmaceutical or phytopharmaceutical substances generally have a better solubility and therefore a better bioavailability. They also have improved stability, especially in wet conditions. In the same way, the co-crystals of energetic materials have improved properties, in particular a better reactivity combined with a reduced sensitivity, an essential property during their handling. However, the processes for the preparation of co-crystals of the prior art have drawbacks which greatly limit the development of the use of co-crystals.
    [0003] Thus, the processes of the state of the art are not continuous or semi-continuous processes but batch preparation methods or batch processes. These methods of the state of the art therefore do not allow high yields. Four types of processes of the state of the art make it possible to prepare cocrysts. The crystallization was carried out by slow evaporation of a concentrated solution of several compounds, the grinding of the reactants in the solid state optionally in the presence of a solvent, the electrochemically induced reactions and the kinetic crystallization controlled by rapid evaporation of the solvent. a solution of the pure compounds. However, these methods do not allow the continuous or semi-continuous preparation of co-crystals.
    [0004] In addition, the co-crystals prepared by the known methods are not always of sufficient quality. The average size of the co-crystals prepared according to the known methods is not always regular and is not systematically micrometric, submicron or nanometric. In addition, the known processes do not allow to achieve high crystallization rates. Moreover, Rapid Expansion of Supercritical Solutions (RESS) technology is known for the preparation of nanoparticles in a supercritical fluid. This technology is only effective on a small scale and can not be transferred to the industrial level. Moreover, the preparation in a supercritical fluid does not make it possible to control the stoichiometry.
    [0005] There is therefore a need for a method for preparing co-crystals providing a solution to the problems of the prior art co-crystal preparation processes.
    [0006] Thus, the invention provides a process for preparing a co-crystal of at least two compounds by flash evaporation or flash evaporation which provides a solution to all or part of the problems of the processes of the state of the art. . The invention provides a process for preparing a co-crystal of at least two compounds bonded by hydrogen bonds, ionic bonds, n-stacking bonds or Van der Waals bonds, comprising the successive steps: preparing a solution comprising at least one solvent and at least two organic, inorganic or organometallic compounds capable of bonding by hydrogen bonding, by ionic bonds, by n-stacking bonds or by Van der Waals connections; heating the solution, under a pressure ranging from 3 to 300 bar, at a temperature above the boiling point of the solvent or at a temperature above the boiling point of the solvent mixture; atomizing the solution in an atomization chamber by means of at least one dispersing device and at an angle ranging from 30 to 150 ° at a pressure ranging from 0.0001 to 2 bar; separation of the solvent in gaseous form. The process according to the invention is advantageously carried out continuously or semi-continuously. Preferably, it is carried out continuously.
    [0007] Advantageously, the process according to the invention comprises the preparation of a solution comprising two to ten compounds; or two compounds; or two compounds in a molar ratio selected from 1/4, 1/3, 1/2, 1/1, 2/1, 3/1, 4/1; or three compounds; or ^ three compounds in a molar ratio X / Y / Z wherein X, Y and Z, identical or different, are 1, 2, 3 or 4; four compounds; or four compounds in a molar ratio W / X / Y / Z wherein W, X, Y and Z, the same or different, are 1, 2, 3 or 4; five compounds; or ^ five compounds in a molar ratio V / W / X / Y / Z in which V, W, X, Y and Z, identical or different, represent 1, 2, 3 or 4.
    [0008] Preferably, the process according to the invention comprises the preparation of a solution comprising two, three or four compounds. The process according to the invention is particularly advantageous for the preparation of co-crystals of compounds chosen from energetic compounds, pharmaceutical compounds, phytopharmaceutical compounds, coloring compounds, pigments, inks, paints, metal oxides. Preferably, the process according to the invention is carried out for the preparation of co-crystals of compounds chosen from energetic compounds, pharmaceutical compounds and phytopharmaceutical compounds.
    [0009] Also advantageously, the process according to the invention makes it possible to prepare co-crystals whose size is micrometric or which have at least one dimension less than 500 μm, preferably which have at least one dimension less than 100 μm. ..tm.35 Also advantageously, the method according to the invention makes it possible to prepare co-crystals whose size is submicrometer or which have at least one dimension between 100 and 1000 nm.
    [0010] Preferably, the process according to the invention makes it possible to prepare co-crystals whose size is nanometric or which have at least one dimension less than 100 nm. More preferably, the co-crystals prepared according to the invention have a size ranging from 2 to 100 nm; or ranging from 5 to 90 nm; or ranging from 10 to 80 nm; or from 50 to 300 nm; or from 50 to 200 nm; or from 50 to 120 nm; or ranging from 10 to 100 nm; or from 60 to 100 nm. Advantageously, the process according to the invention comprises the preparation of a solution comprising at least two organic, inorganic or organometallic compounds and at least two solvents.
    [0011] Also advantageously, the process according to the invention comprises the preparation of a solution comprising at least one solvent of one of the compounds and at least one co-solvent of one of the compounds. Also advantageously, the process according to the invention comprises the preparation of a solution comprising at least one solvent of one of the compounds and at least one anti-solvent of one of the compounds. Preferably, the solvent or solvents used have a boiling point of less than 80 ° C. or less than 60 ° C. As the solvent, alkanes, for example pentane (PE = 36 ° C.) or hexane (PE = 68 ° C.), may be used; the alcohols, for example methanol (PE = 65 ° C.) or ethanol (MW = 78 ° -79 ° C.); thiols, for example ethane-thiol (MW = 35 ° C); aldehydes, for example ethanal (PE = 20 ° C) or propionaldehyde (PE = 48 ° C); ketones, for example acetone (MW = 56 ° C); for example, methyl-tert-butyl ether (PE = 55 ° C.) or tetrahydrofuran (PE = 66 ° C.), acid esters, in particular formic acid esters, for example methyl formate ( PE = 32 ° C.), the acetic acid esters, for example methyl acetate (PE = 57-58 ° C.), the amines, for example trimethylamine (PE = 2-3 ° C.). Preferably, the method according to the invention comprises a final step of recovering the co-crystals of compounds, more preferably the recovery of the co-crystals of compounds is carried out by means of one or more devices chosen from an electrostatic separator, a cyclone, a cyclone comprising an electrostatic device.
    [0012] The conditions for carrying out the process according to the invention can vary quite widely, in particular as a function of the compounds to be co-crystallized or depending on the solvents used.
    [0013] Advantageously, the heating of the solution is carried out under a pressure ranging from 5 to 150 bar or from 10 to 60 bar. Also advantageously, the heating of the solution is carried out under pressure of an inert gas selected from nitrogen, argon, helium, neon, xenon. When atomizing the solution, the pressure is advantageously between 0.001 and 2 bar. The dispersion device used during the atomization of the solution is advantageously chosen from a hollow cone nozzle, a solid cone nozzle, a flat jet nozzle, a straight jet nozzle, a pneumatic atomizer and their combinations. A hollow cone nozzle is particularly advantageous.
    [0014] In general, the atomization can be performed at an angle that can vary widely. The atomization angle can thus be close to 180 °, for example 170 ° or else 150 ° or 120 °. There can also be mentioned a range of atomization angle ranging from 60 to 80 °.
    [0015] The various aspects of the invention are illustrated by the following examples. Examples Co-crystals according to the invention were prepared from caffeine and oxalic acid or glutaric acid. Other co-crystals according to the invention were prepared from 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaiso-wurtzitane (CL-20 ) and 2,4,6-trinitrotoluene (TNT) or 1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX). Comparative examples were prepared from 2,4,6-trinitrotoluene (TNT) and 1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX). The co-crystals were continuously prepared by means of the device described in International Patent Application WO-2013/114671 by a method of instantaneous evaporation of a solution of the co-crystallizing compounds which is superheated and compressed. During the process, the solution experiences a very large drop in pressure when atomized by means of a hollow cone nozzle. The compounds to be co-crystallized are dissolved in a solvent whose boiling point is generally below 60 ° C. The compounds and the solvents as well as the reaction parameters used are shown in Table 1.
    [0016] The solution is compressed (40 to 60 bar) and then atomized in an atomization chamber by means of a heated hollow cone nozzle. The pressure in the atomization chamber (5 mbar) is obtained by means of a vacuum pump (35 m3 / h).
    [0017] The sudden pressure drop causes a shift of the thermodynamic equilibrium making the overheated solution unstable. The solvent is evaporated instantly and the crystals are formed. The strong drop in pressure is accompanied by a sharp drop in temperature which decreases by around 200 ° C to protect crystals formed.
    [0018] The continuous separation of the formed co-crystals is carried out by means of axial cyclones connected in parallel. examples according to the invention comparative 1 2 3 4 1 2 compounds caffeine / oxalic acid caffeine / glutaric acid TNT / CL20 HMX / CL20 TNT / HMX TNT / HMX molar ratio 2/1 1/1 1/1 1/2 1/1 1/2 Solvent acetone acetone acetone acetone acetone acetone amount (g) 3.5 / 0.8 4.8 / 3.2 2.4 / 1.2 2.7 / 8.0 3.4 / 4.5 2 , 2 / 5.7 concentration of solution (mass%) 1.0 2.0 1.0 2.7 2.0 2.0 volume of solution (mL) 500 500 460 500 500 500 nozzle temperature (° C) 160 160 170 170 160 160 temperature of cyclones (° C) 80 80 50 80 80 80 diameter of cyclones (1-1m) 60 60 60 60 60 60 pressure (bar) 40 40 40 50 50 40 duration (min ) 68 56 60 44 41 62 quantity of crystals (g) 2,77 5,13 1,59 4,93 0 0 quantity of ND ND ND ND 5,35 4,85 composites (g) yield (%) 64,7 64.1 43.8 46.1 67.8 60.6 ND: not available Table 1 The products were characterized by AFM (Atomic Force Microscopy) microscopy at room temperature and at atmospheric pressure in order not to alter the co- crystals formed s. The average particle size distribution was evaluated. The average size of the caffeine / glutaric acid cocrysts (1/1) is 111 nm. The average size of HMX / CL20 (1/2) co-crystals is 59 nm. X-ray diffraction spectra were made to characterize the co-crystals.
    [0019] The spectra obtained were compared with the spectra of the starting materials used. The spectra of the co-crystals are different from the spectra of the starting products for the crystals formed. They correspond to the spectra of the Cambridge structural databank or the spectra available in the literature.
    [0020] For TNT / HMX composites (1/1 and 1/2), the X-ray diffraction spectra always show the characteristic lines of TNT alone as well as certain lines of HMX. The absence of some HMX lines indicates that HMX is present in amorphous form. The composites TNT / HMX (1/1 and 1/2) are thus mixtures of crystals of TNT and amorphous HMX.
    [0021] The thermal properties of co-crystals have been studied by DSC (Differential Scanning Calorimetry). Heating (5 ° C / min) of TNT / CL20 co-crystals (1/1) shows the absence of the characteristic signal of pure TNT at 80 ° C, the TNT being within the co-crystal mesh. with the CL20. The characteristic melting temperature measured for the co-crystal TNT / CL20 (1/1) is 135 ° C. After the first phase of the DSC analysis, the temperature is reduced and then increased again. During the second heating, the thermal signal of the TNT is again present at 80 ° C confirming the dissociation of the co-crystal under the action of heat during the first heating followed by the crystallization of pure TNT. The heating of the caffeine / oxalic acid co-crystals (2/1) shows the presence of a thermal signal at 199 ° C. which is intermediate between the melting points of the two pure caffeine and oxalic acid compounds.
    [0022] Continued heating leads to dissociation of the co-crystal. Then the cooling followed by the second heating shows the presence of the thermal signal of pure caffeine. For the TNT / HMX composites (1/1 and 1/2) of the comparative examples, the thermal signal of the TNT is present at the first heating. Then this signal is not changed during the second heating. The composites TNT / HMX (1/1 and 1/2) are therefore simple physical mixtures of particles of TNT and HMX. The TNT and HMX molecules can not form intermolecular bonds to give a co-crystal.
    权利要求:
    Claims (14)
    [0001]
    REVENDICATIONS1. Process for the preparation of a co-crystal of at least two compounds linked by hydrogen bonds, ionic bonds, stacking bonds or van der Waals bonds, comprising the following steps: preparing a solution comprising at least one solvent and at least two organic, inorganic or organometallic compounds capable of bonding by hydrogen bonding, ionic bonding, stacking bonds or van der bonds Waals; heating the solution at a pressure of from 3 to 300 bar at a temperature above the boiling point of the solvent or at a temperature above the boiling point of the solvent mixture; atomizing the solution in an atomization chamber by means of at least one dispersing device and at an angle ranging from 30 to 150 ° at a pressure ranging from 0.0001 to 2 bar; separation of the solvent in gaseous form.
    [0002]
    2. A process according to claim 1 comprising preparing a solution comprising two to ten compounds; or two compounds; or two compounds in a molar ratio selected from 1/4, 1/3, 1/2, 1/1, 2/1, 3/1, 4/1; or three compounds; or ^ three compounds in a molar ratio X / Y / Z wherein X, Y and Z, identical or different, are 1, 2, 3 or 4; four compounds; or four compounds in a molar ratio W / X / WZ wherein W, X, Y and Z, which may be identical or different, are 1, 2, 3 or 4; five compounds; or five compounds in a VNV / X / Y / Z molar ratio in which V, W, X, Y and Z, identical or different, are 1, 2, 3 or 4.
    [0003]
    3. Method according to one of claims 1 or 2 wherein the co-crystal ^ is micron size; or has at least one dimension less than 500 μm; or has at least one dimension less than 100 μm; or ^ is of submicron size; or has at least one dimension between 100 nm and 1000 nm; or ^ is of nanometric size; or has at least one dimension less than 100 nm; or ^ is of size ranging from 2 to 100 nm; or is of size ranging from 5 to 90 nm; or is of size ranging from 10 to 80 nm; or is of size ranging from 50 to 300 nm; or is of size ranging from 50 to 200 nm; or ^ is of size ranging from 50 to 120 nm; or is of size ranging from 10 to 100 nm; or ^ is of size ranging from 60 to 100 nm.
    [0004]
    4. Method according to one of claims 1 to 3 comprising preparing a solution comprising at least two organic compounds, inorganic or organometallic and at least two solvents or at least one solvent and at least one co-solvent or at least one solvent and at least one anti-solvent of one of the compounds.
    [0005]
    5. Method according to one of claims 1 to 4 comprising a final step of recovering the co-crystals of compounds by means of one or more devices selected from an electrostatic separator, a cyclone, a cyclone comprising an electrostatic device.
    [0006]
    6. Method according to one of claims 1 to 5 which is continuous or semi-continuous.
    [0007]
    7. Method according to one of claims 1 to 6 wherein the boiling point of the solvent or solvent mixture is less than 80 ° C west below 60 ° C.
    [0008]
    8. Method according to one of claims 1 to 7 wherein the heating of the solution is carried out under a pressure ranging from 5 to 150 bar or from 10 to 60 bar.
    [0009]
    9. Method according to one of claims 1 to 8 wherein the heating of the solution is carried out under pressure of an inert gas selected from nitrogen, argon, helium, neon, xenon.
    [0010]
    10. Method according to one of claims 1 to 9 wherein the atomization of the solution is carried out at a pressure ranging from 0.001 to 2 bar.
    [0011]
    11. Method according to one of claims 1 to 10 wherein the dispersing device is selected from a hollow cone nozzle, a solid cone nozzle, a jet nozzle, a jet nozzle, a pneumatic atomizer and their associations.
    [0012]
    12. Method according to one of claims 1 to 11 for which the dispersion device is a hollow cone nozzle.
    [0013]
    13. Method according to one of claims 1 to 12 wherein the compound is selected from energetic compounds, pharmaceutical compounds, phytopharmaceutical compounds, coloring compounds, pigments, inks, paints, metal oxides.
    [0014]
    14. Method according to one of claims 1 to 13 wherein the solvent is selected from alkanes, for example pentane (PE = 36 ° C) or hexane (PE = 68 ° C); alcohols, for example methanol (PE = 65 ° C) or ethanol (FE = 78-79 ° C); thiols, for example ethane-thiol (MW = 35 ° C); aldehydes, for example ethanal (PE = 20 ° C) or propionaldehyde (PE = 48 ° C); ketones, for example acetone (MW = 56 ° C); ethers, for example methyl tert-butyl ether (PE = 55 ° C.) or tetrahydrofuran (MW = 66 ° C.); acid esters, especially formic aid esters, for example methyl formate (PE = 32 ° C.), acetic acid esters, for example methyl acetate (MW = 57-58 ° C.) ; amines, for example trimethylamine (PE = 2-3 ° C).
    类似技术:
    公开号 | 公开日 | 专利标题
    JP2020108890A|2020-07-16|Method for producing cocrystals by means of flash evaporation
    Pando et al.2016|Preparation of pharmaceutical co-crystals through sustainable processes using supercritical carbon dioxide: A review
    EP2812104B1|2019-08-14|Process and device for the preparation of nanoparticles by flash evaporation
    FR2815540A1|2002-04-26|A method and apparatus for making very fine particles containing a complex of an active principle and a cyclodextrin for e.g. pharmaceutical use by placing them in a solvent or solvents and contacting with a supercritical liquid
    Kröber et al.2002|Materials processing with supercritical antisolvent precipitation: process parameters and morphology of tartaric acid
    WO2011083281A1|2011-07-14|Method for preparing aminoethyl imidazolidinone or the thiocarbonyl thereof
    EP2819776B1|2020-05-13|Method for manufacturing nanoparticles by detonation
    EP1239938B1|2009-03-11|Method for capturing fine particles by percolation in a bed of granules
    JP4635154B2|2011-02-23|Particulate generating device for particulate compound explosives, apparatus for producing particulate compound explosives, and method for producing particulate compound explosives
    JP3964214B2|2007-08-22|Method and apparatus for producing powdered explosive composition
    EP2323962A1|2011-05-25|Method for obtaining adn crystals through crystallization in a viscous medium
    Zuev et al.2021|Preparation of Polyurethane–Carbon Nanotube Composites via Suspension Supercritical Antisolvent Precipitation
    FR3087351A1|2020-04-24|HIGH AND LOW TEMPERATURE OUT OF BALANCE SYNTHESIS BY SPRAY FLASH SYNTHESIS
    FR3061439A1|2018-07-06|PARTICLES OF THE HEART-ECORCE TYPE
    EP2419088B1|2015-08-05|Method for preparing pharmaceutical compositions comprising fine particles of active substance
    WO2019179598A1|2019-09-26|Core-shell particles
    WO2003090668A2|2003-11-06|Method of obtaining amorphous solid particles
    FR3021317A1|2015-11-27|PROCESS FOR OBTAINING BORAZANE
    JP2002179490A|2002-06-26|Producing method of powdery gunpowder composition and producing equipment thereof
    RU2481362C2|2013-05-10|Method of producing porous microparticles of especially pure polystyrene as carriers of biologically active forms of prolonged action
    FR2774983A1|1999-08-20|A new process for obtaining small spherical particles of 5-oxo-3-nitro 1,2,4-triazole |, used in pyrotechnic and explosive compositions
    CH260572A|1949-03-31|Method of manufacturing melamine.
    FR3012144A1|2015-04-24|CONTINUOUS PROCESS FOR THE PREPARATION OF BORONIC ACIDS AND THEIR DERIVATIVES
    BE567282A|
    同族专利:
    公开号 | 公开日
    JP2017529234A|2017-10-05|
    JP2020108890A|2020-07-16|
    EP3164201A1|2017-05-10|
    FR3023177B1|2016-08-12|
    US10946305B2|2021-03-16|
    WO2016001445A1|2016-01-07|
    US20170157528A1|2017-06-08|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    WO2010007446A1|2008-07-18|2010-01-21|Prosonix Limited|Process for improving crystallinity of fluticasone particles|
    WO2013117671A1|2012-02-07|2013-08-15|Centre National De La Recherche Scientifique |Preparation of nanoparticles by flash evaporation|
    US3361523A|1963-03-19|1968-01-02|Monsanto Co|Method for producing phosphates|
    US4518488A|1983-02-28|1985-05-21|Standard Oil Company |Metal-containing active carbon and methods for making and using same|
    US4482641A|1983-02-28|1984-11-13|Standard Oil Company |Metal-containing active carbon and method for making same|
    US4567031A|1983-12-27|1986-01-28|Combustion Engineering, Inc.|Process for preparing mixed metal oxides|
    JPS6146238A|1984-08-08|1986-03-06|Hitachi Ltd|Method and apparatus for manufacturing fine particle|
    GB8604328D0|1986-02-21|1986-03-26|Ici Plc|Producing spray of droplets of liquid|
    JP2524379B2|1988-01-29|1996-08-14|大川原化工機株式会社|Nozzle device and spray dryer device incorporating it|
    DE69022861T2|1989-01-24|1996-04-04|Spi Polyols Inc|Cryoprotective crystalline sorbitol beads.|
    JPH07332847A|1994-06-03|1995-12-22|Mitsubishi Chem Corp|Spray-drying method|
    US6236946B1|1995-12-13|2001-05-22|Thomas S. Scanlan|Nuclear receptor ligands and ligand binding domains|
    US6001262A|1997-06-16|1999-12-14|Kelada; Maher I.|Cascade ion exchange for high purity water production|
    EP1727520A2|2003-12-09|2006-12-06|Medcrystalforms, Llc|Method of preparation of mixed phase co-crystals with active agents|
    US7628893B1|2005-08-01|2009-12-08|Pure Energy Technology Co|Apparatus and method for separation|
    US20080075777A1|2006-07-31|2008-03-27|Kennedy Michael T|Apparatus and methods for preparing solid particles|
    KR101817361B1|2009-03-09|2018-01-11|에스피아이 파르마, 인크.|Highly Compactable and Durable Direct Compression Excipients and Excipient Systems|
    EP2435480A1|2009-05-27|2012-04-04|Ablynx N.V.|Biparatopic protein constructs directed against il-23|
    EP2611529B1|2010-09-03|2019-01-23|Bend Research, Inc.|Spray-drying method|
    GB201222287D0|2012-12-11|2013-01-23|Ct For Process Innovation Ltd|Methods for making active crystalline materials|
    US9513183B2|2014-06-30|2016-12-06|Rosemount Inc.|Process isolation diaphragm assembly for metal process seal|PT109445B|2016-06-08|2018-11-06|Hovione Farm Sa|CRYSTALINE PHARMACEUTICAL CO-CRYSTALS OF LACTOSE GLYCOPYRONIUM BROMETTE|
    CN106518883B|2016-10-12|2018-12-25|中国工程物理研究院化工材料研究所|Six azepine isoamyl of nanometer ε crystal form hexanitro hereby alkane explosive and its batch preparation|
    FR3087351B1|2018-10-22|2021-07-16|Centre Nat Rech Scient|HIGH AND LOW TEMPERATURE OUT OF BALANCE SYNTHESIS BY SPRAY FLASH SYNTHESIS|
    FR3112341A1|2020-07-09|2022-01-14|Davey Bickford|DETONATING COMBINATION, RELAY FOR DETONATOR COMPRISING SUCH DETONATING COMBINATION AND DETONATOR COMPRISING SUCH RELAY|
    法律状态:
    2015-06-25| PLFP| Fee payment|Year of fee payment: 2 |
    2016-01-08| PLSC| Search report ready|Effective date: 20160108 |
    2016-06-22| PLFP| Fee payment|Year of fee payment: 3 |
    2017-06-21| PLFP| Fee payment|Year of fee payment: 4 |
    2018-07-27| PLFP| Fee payment|Year of fee payment: 5 |
    2019-07-31| PLFP| Fee payment|Year of fee payment: 6 |
    2020-07-31| PLFP| Fee payment|Year of fee payment: 7 |
    2021-07-29| PLFP| Fee payment|Year of fee payment: 8 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1456461A|FR3023177B1|2014-07-04|2014-07-04|PROCESS FOR THE PREPARATION OF CO-CRYSTALS BY FLASH EVAPORATION|FR1456461A| FR3023177B1|2014-07-04|2014-07-04|PROCESS FOR THE PREPARATION OF CO-CRYSTALS BY FLASH EVAPORATION|
    PCT/EP2015/065335| WO2016001445A1|2014-07-04|2015-07-06|Method for producing cocrystals by means of flash evaporation|
    EP15734366.6A| EP3164201A1|2014-07-04|2015-07-06|Method for producing cocrystals by means of flash evaporation|
    JP2017520006A| JP2017529234A|2014-07-04|2015-07-06|Method for producing co-crystals by flash evaporation|
    US15/323,654| US10946305B2|2014-07-04|2015-07-06|Method for producing cocrystals by means of flash evaporation|
    JP2020046260A| JP2020108890A|2014-07-04|2020-03-17|Method for producing cocrystals by means of flash evaporation|
    [返回顶部]