Patent Publication Number: US-2021187414-A1

Title: Systems and methods for extraction of compounds from botanical matter

Description:
TECHNICAL FIELD 
     This invention relates to systems and methods for extraction of compounds from botanical matter, such as  cannabis.    
     BACKGROUND 
     Variability in botanical matter raises challenges for efficiently extracting desired compounds. For example, continuing to run an extraction after a desired compound has been fully extracted wastes energy and time. Extracting undesired compounds necessitates additional separation processes to remove them. Improved systems and methods for efficient extraction of compounds from botanical matter are desirable. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying drawings illustrate non-limiting example embodiments of the invention. 
         FIG. 1  is a block diagram of an extraction system according to an embodiment of the invention. 
         FIG. 2  is a state diagram showing the major operating modes of an extraction system according to an embodiment of the invention. 
         FIG. 3  is a block diagram of an isolated section of an extraction vessel according to an embodiment of the invention. 
         FIG. 4  is a plot of FTIR data from both in-situ and ex-situ measurements according to an embodiment of the invention. 
     
    
    
     DESCRIPTION 
     Throughout the following description, specific details are set forth in order to provide a more thorough understanding of the invention. However, the invention may be practiced without these particulars. In other instances, well known elements have not been shown or described in detail to avoid unnecessarily obscuring the invention. Accordingly, the specification and drawings are to be regarded in an illustrative, rather than a restrictive, sense. 
     Some aspects of the invention relate to extraction systems operable at high throughput efficiency and reliability in a cost-effective manner. The systems are configured to increase extraction efficiency by adjusting reaction parameters such as reaction time with real time information about the extraction as it proceeds. Real time information about the extraction is obtained by in situ sensors, and based on this information the extraction is controlled in a manner that, for example, allows the run to be stopped when one or more desirable compounds are fully extracted or when one or more undesirable compounds are being extracted or reach undesirable levels. 
     As used herein, the term “ cannabis ” means a part (e.g. leaf, stem, root, flower) of and/or any product from a  Cannabis  species (e.g.,  Cannabis sativa L., Cannabis indica Lam., Cannabis ruderalis Janish .), and includes both “marijuana” and “hemp”, as well as any variety, cultivar and hybrid of such species. 
     As used herein, the term “real time” means a level of processing responsiveness sufficiently immediate for a particular process or determination (e.g. a detector obtaining signals relating to an extracted compound and communicating those signals to a controller). 
     The concentration of desirable or target compounds present in botanical matter can vary due to biological factors such as botanical matter species and strain, and environmental factors such as growing conditions (e.g. nutrients, lighting, watering) and timing of harvest. In  cannabis  extraction, for example, certain cannabinoids (e.g. tetrahydrocannabinol and/or cannabidiol), terpenes and flavonoids may be considered target compounds and the concentration of these compounds can vary between different sources and batches of  cannabis . As such, in order to fully extract the target compounds, process parameters such as extraction time, temperature and pressure, can vary. 
     In addition to the variation in the concentration of target compounds present, variation can exist in the nature and concentration of undesirable compounds that may be extracted. In  cannabis  extraction, for example, certain alkaloids and monoterpenes may be considered undesirable compounds. The concentration of undesirable compounds present in the botanical matter is also variable due to biological factors and environmental factors. As such, there is variation in the length of operation time permissible before extraction of undesirable compounds begins to occur, or occurs to an undesirable threshold level. Other variable process parameters such as temperature and pressure, may also affect the degree of extraction of undesirable compounds. 
     Signal detection and measurement of extracted compounds using a probe can also be influenced by a variety of process conditions, including: probe occlusion by fouling by extracted compounds or particulates from the botanical matter; complex flow-based movement of the compounds; state conditions of the extraction system, namely variations in temperature and pressure, influenced for example by temperature and density of the botanical matter; and variation in the physical placement of the botanical matter in relation to the probe. 
     Regarding the complexity of flow-based movement of extracted compounds, for example, filling of the extraction vessel with solvent, such as supercritical, gaseous, or liquid carbon dioxide, causes fluidic momentum in the extraction vessel. This fluidic momentum can be represented by an in-vessel flow. In-vessel flow conditions adjacent to the probe, or the in-vessel flow conditions between the botanical matter and the probe, has variation from extraction to extraction due to the disorganized nature of the packing of botanical matter according to batch-to-batch filling process conditions. Filling of botanical matter could also be operated in a continuous filling manner with similar variations due to the disorganized packing of the botanical matter. 
     Signal measurement, if used to determine concentration of an extracted target compound alone, would be unable to predict the time required for complete extraction of the target compound due to lack of knowledge of absolute concentrations of the target compound and variability in the measurements as discussed above. Batch to batch variability in water content, particle size, and biological structure (e.g. roots, shoots, etc.) can further exacerbate these challenges. 
     The order in which the compounds are extracted from botanical matter is determined by the properties of the compounds themselves and is invariant. 
     The diffusion of extracted compounds in solution is determined by the molecular mass and polarity of the molecule. The diffusion of the extracted compounds towards and away from a probe occurs according to Fick&#39;s Laws and is invariant. 
     Aspects of the invention relate to signal measurement of a plurality of discrete compounds to provide a matrix of information relating to the extracted compounds. The inventors have determined that ratios of the measurements of extracted compounds, and changes over time thereof, can provide useful information regarding the rate at which target compounds are being extracted, and that this information in turn can be used to derive adjustments to extraction process parameters such as adjustments to pressure, temperature and extraction time to increase extraction efficiency. 
     In some embodiments, monitoring the ratio of measurements (e.g. concentrations) of two marker compounds being extracted, at a particular time point or over time depending on the embodiment, can give information regarding a target compound, or target compound for which a signal has been lost. 
     In some embodiments, monitoring one or more ratios of measurements of two or more marker compounds being extracted, at a particular time point or over time depending on the embodiment, can be used to derive the time that will be taken for complete extraction of a target compound which has yet to be fully extracted from the botanical matter. 
     In some embodiments, monitoring the ratio of measurements of a marker compound and a target compound, at a particular time point or over time depending on the embodiment, can be used to derive the time that will be taken for complete extraction of the target compound which has yet to be fully extracted from the botanical matter. 
     In some embodiments, monitoring one or more ratios of two or more marker compounds, at a particular time point or over time depending on the embodiment, can be used to determine when full extraction of a target compound will be complete and/or when an undesirable compound begins to be extracted or begins to approach undesirable concentrations. 
     Thus precise predictions of extraction times, i.e., cycle endpoints, can be derived without the need for precision in absolute measurements because reliance is on ratios and/or changes, rather than absolute values, of output signals. Stopping extraction once full extraction of the target compound(s) is complete allows for savings in energy and time in processing. Stopping extraction before undesirable compounds are extracted or reach undesirable concentrations avoids the need for additional separation processes to remove the undesirable compounds from solution. 
     In some embodiments, monitoring one or more ratios of two or more extracted compounds, at a particular time point or over time depending on the embodiment, can be used to assess the efficiency of process conditions, and based on this information adjustments to pressure and/or temperature of the extraction vessel may be made. For example, adjustments to temperature and/or pressure may be made to increase rate of extraction of more volatile target compounds. Or, for example, detection of certain components, or certain components in certain ratios, or rates of change of certain ratios of certain components, may be a signal to adjust temperature and/or pressure. For example, detection of non-decarboxylated species can be a trigger for increasing temperature and/or pressure to activate or increase rate of decarboxylation. 
     In some embodiments, programming of computer algorithms used to examine the ratios of measured extracted compounds used as markers for determination of full extraction of target compounds can be facilitated by development of databases of results of prior testing of similar botanical matter. In example embodiments, tetrahydrocannabinol (THC) may be the last cannabinoid to be extracted, so if other cannabinoids are required preferentially, the THC signal will be the marker compound for full extraction of the more mobile cannabinoids. In some embodiments, development of such databases may be assisted by computational machine learning. Algorithm development facilitated by the use of machine learning allows for rapid automation optimization of extraction processes, independent of botanical strain or local processing conditions or known relative extraction ratios of known compounds. 
     In some embodiments, the concentration (and thus the measured signal) of the extracted compound in the extraction vessel is too low to be accurately measured and so isolation of a small portion of the extraction vessel and alteration of the environmental conditions therein to enhance the signal can be performed. For example, adjustments in the local pressure and temperature of the isolated section of the extraction vessel can cause phase separation of extracted compounds, increasing the strength of the measured signal. The term “phase separation” as used herein includes processes such as condensation, precipitation, sublimation, distillation and the like. The resulting separated material includes materials such as condensate, precipitate, sublimate, distillate and the like. 
       FIG. 1  is a block diagram of an extraction system according to one embodiment of the invention. The system  100  includes an extraction vessel  110  in fluid communication with a separation vessel  120 . 
     A solvent source  148  is in fluid communication with extraction vessel  110  via a closed conduit  170 . A valve  150  regulates flow of solvent  112  from solvent source  148  to extraction vessel  110 . A pump  149  may be provided to deliver a pressurized flow of solvent  112  to extraction vessel  110 . Pressure of solvent  112  may range for example from 1 atm to 700 atm, or from 74 atm to 340 atm. Solvent  112  may for example be fluidic carbon dioxide. 
     Extraction vessel  110  is configured to receive solvent  112  and botanical matter  111 . Botanical matter  111  may for example be  cannabis . In some embodiments, solvent  112  may be a mix of solvents. In particular embodiments, the solvent mix may include hydrocarbons, such as alcohols, in combination with carbon dioxide. The  cannabis  may be mechanically processed  cannabis  with a size distribution in the range of 10 to 5000 microns. Once compounds begin to be extracted from botanical matter  111  and dissolve in solvent  112 , solvent  112  is referred to herein as solution  112 ′. Extracted compounds in the case of  cannabis  as botanical matter may include cannabinoids (including tetrahydrocannabinol and/or cannabidiol), terpenes and flavonoids. The concentration of extracted compounds in solution  112 ′ may vary in operation of the system from 0.01% w/w to 50% w/w or more. 
     In other embodiments, alternative solvents, alternative botanical matter, and/or alternative compounds may be extracted in the invention. 
     Extraction vessel  110  may be a pressure vessel of a fixed volume. In some embodiments extraction vessel  110  may be a steel capped container or a plurality of steel capped containers connected in parallel or series. 
     A detector  129  is associated with extraction vessel  110 . Detector  129  includes a probe  131  and a measurement unit  130 . In some embodiments, detector  129  may be provided may be FTIR, LC, GC, MS, UV absorbance, UV fluorescence, IR-spectral analysis, or any other combination thereof. Probe  131  is inserted into an interior of extraction vessel  110 . The location of probe  131  within extraction vessel  110  needs to be in an area where the flow of solvent  112 /solution  112 ′ passes by, and preferably not a dead zone in extraction vessel  110  such as adjacent to the inlet for solvent  112 . In some embodiments probe  131  is placed for example from 1 nm to 50 cm, or from 100 nm to 100 um, away from botanical matter  111 . 
     In some embodiments probe  131  may be positioned in the interior of extraction vessel  110  (as illustrated in  FIG. 1 ). In some embodiments probe  131  may be positioned in closed conduit  180  anywhere upstream of throttle  151 . In some embodiments there may be one or more additional throttle elements (not shown) positioned in closed conduit  180  between extraction vessel  110  and throttle  151  downstream of extraction vessel  110  and upstream of throttle  151 . Any section of the closed conduit  180  downstream of extraction vessel  110  but upstream of throttle  151  forms part of the extraction vessel volume and as such probe  131  may be integrated into closed conduit  180  without divergence from the invention. 
     Detector  129  is in communication (e.g. wired or wireless) with a controller  140 , and controller  140  is in turn in communication (e.g. wired by cable  160  or wireless) with a throttle  151  provided on a closed conduit  180  that connects extraction vessel  110  to separation vessel  120 . Controller  140  includes a processor (not shown). Throttle  151  may for example be a valve. Based on analysis of results from monitoring by measurement unit  130  of detector  129 , as discussed above, controller  140  mediates actuation of throttle  151  (as well as any additional throttle elements in closed conduit  180  as discussed above) to control flow of solution  112 ′ from extraction vessel  110  to separation vessel  120 . In some embodiments, controller  140  may additionally or alternatively be in communication with valve  150  and/or pump  149  to control pressure in extraction vessel  110 , and closed circuits  170  and  180 . In some embodiments, controller  140  may additionally or alternatively be in communication with a heater and/or cooler (not shown) to control temperature in extraction vessel  110 , and closed circuits  170  and  180 . 
     Separation vessel  120  may have a fixed volume, and in some embodiments may be a steel capped container, or a plurality of steel capped containers connected in parallel or series. Solution  112 ′ laden with extracted compounds is phase separated in separation vessel  120 , for example due to decrease in pressure. Separation vessel  120  may for example maintain a pressure in the range of 1 atm to 70 atm, or 20 atm to 60 atm. Separation vessel  120  has two outlets: one leading to a closed conduit  172  with a valve  153  for discharging solvent  112 ; and another leading to closed conduit  171  with a valve  152  for recovering separated extracted compounds  190  separated from solvent  112 . 
     In some embodiments one extraction vessel is connected via closed conduit to the separation means. It will be apparent to those skilled in the art that the arrangement of extraction vessels and separation vessels could contain one or multiple extraction vessels in series or parallel connection with one or multiple separation vessel interconnected by closed conduit without divergence from the invention. 
       FIG. 2  is a state diagram describing the major operating modes of systems, and thus a method, according to one embodiment of the invention. The following description will refer to system  100  for convenience but can refer to systems according to any embodiment of the invention. 
     The six states of Filling  210 , Standby  220 , Measuring  230 , Computing  240 , Discharging  250 , and Collecting  260  represent the normal or ‘successful’ flow of events. 
     The Filling state  210  is the system state where extraction vessel  110  is being filled or emptied with botanical matter  111 . The Filling state is the state in which extraction vessel  110  will become pressurized with solvent  112  from solvent source  148  by opening valve  150 , after botanical matter  111  is received within and extraction vessel  110  is sealed. Throttle  151  is closed during Standby state  220 . 
     The Standby state  220  is the state in which extraction vessel  110  is filled with botanical matter  111  and solvent  112 , and chemical absorption is occurring and solvent  112  becomes a solution  112 ′ comprising compounds extracted from botanical matter  111 . Standby state  220  is the default state for the system and begins once the pressure in extraction vessel  110  reaches a predetermined system operating value. Throttle  151  remains closed during Standby state  220 . The duration of Standby state  220  may for example range from 1 minute to 1440 minutes, or 5 minutes to 60 minutes. The duration will depend on factors including the size of botanical matter  111 , the volume of extraction vessel  110 , and the targeted components. 
     The Measuring state  230  is the state in which detector  129  is actively taking measurements of extracted compounds. The measurements from detector  129  are sent to controller  140  in real time. Throttle  151  may remain open or closed during Measuring state  230 . 
     The Computing state  240  is the state in which the signals from Measuring state  230  are analyzed by the processor of controller  140  and determination of the next processing step occurs. 
     If the algorithmic determination of set points concludes the process requires further extraction, the operation reverts to the Standby state  220 . 
     If the algorithmic determination of set points determines the extraction is complete, the operation proceeds to the Discharging state  250 . Throttle  151  may remain open or closed during Computing state  240 . 
     The Discharging state  250  is the state in which throttle  151  and any other additional throttle elements of closed conduit  180  controlling flow between extraction vessel  110  and separation vessel  120  are opened to allow for solution  112 ′ (laden with extracted compounds) to flow into separation vessel  120 . The Discharging state includes phase separation of the extracted compounds  190  from solution  112 ′ (due to the pressure drop from extraction vessel  110  to separation vessel  120 ). Solution  112 ′ thus reverts to solvent  112  and is discharged through conduit  172  by operation of valve  153 . In some cases, while the system is being discharged, throttle  150  may be controlled to maintain constant system pressure in extraction vessel  110 . 
     The Collecting state  260  is the state in which system  100  is substantially discharged, and extracted compounds  190  may be recovered from (for example a bottom ⅓ of) separation vessel  120  through conduit  171  by operation of valve  152 . 
       FIG. 3  is a block diagram of an isolated section  180 ( i ) of an extraction system according to one embodiment of the invention. In some embodiments probe  131  may be positioned in closed conduit  180  anywhere upstream of throttle  151 ( b ). In some embodiments there may be one or more additional throttle elements such as throttle  151 ( a ) positioned in closed conduit  180  between extraction vessel  110  (not shown) and throttle  151 ( b ). An isolated section of the extraction vessel  180 ( i ) is then formed in which the temperature and/or pressure of isolated section  180 ( i ) can be changed independently of the environmental conditions of the rest of closed conduit  180  and extraction vessel  110  (not shown). In some embodiments, the temperature and/or pressure of the isolated section is reduced in order to phase separate extracted compounds near and/or on the probe to facilitate detection of a more intense probe signal. Isolated section of extraction vessel  180 ( i ) may be caused to have a reduced pressure for example in the range of 1 atm to 72 atm, or 20 atm to 60 atm, and/or a reduced temperature in the range of 31° C. to −56° C., or 31° C. to 0° C. 
       FIG. 4  shows an example of results of in-situ FTIR probe measurements of system operation in comparison with an ex-situ measurement of extracted compounds  190 . In each plot the y-axis represents measured absorption (A.U.) and the x-axis represents wave number (cm −1 ). Plot A shows the measurement when the system is initially loaded with botanical matter  111 . Plot B shows the measurement when the system is initially pressurized with solvent  112 , in this case fluidic CO 2 . Plot C shows measurement of the CO 2  pressurized system after 8 hours when solvent  112  has been allowed to absorb extracted compounds  190 , to become solution  112 ′. Plots D and E are essentially at the same time point as Plot C, but Plot D shows in-situ measurement of compounds  190  phase separated from solution  112 ′ through reduction in system pressure, and Plot E is the corresponding ex-situ measurement of the extracted compounds  190  recovered from separator vessel  120 . The large peak at around 2300 cm −1  in Plots B and C indicate the presence of supercritical CO 2  and the disappearance of this peak in Plots D and E is consistent with pressure reduction causing supercritical CO 2  to become non-detected gaseous CO 2 . Importantly, Plot D, compared to Plot C, shows a distinct enhancement in in-situ measured signal of extracted compounds  190  (e.g. the peaks at around 2800 cm −1  to around 3000 cm −1  and at around 1700 cm −1  and below), and these more intense probe signals are congruent with the corresponding ex-situ measured signals in Plot E. 
     Where a component is referred to above, unless otherwise indicated, reference to that component (including a reference to a “means”) should be interpreted as including as equivalents of that component any component which performs the function of the described component (i.e., that is functionally equivalent), including components which are not structurally equivalent to the disclosed structure which performs the function in the illustrated exemplary embodiments of the invention. 
     This application is intended to cover any variations, uses, or adaptations of the invention using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the limits of the appended claims. Accordingly, the scope of the claims should not be limited by the preferred embodiments set forth in the description, but should be given the broadest interpretation consistent with the description as a whole.