EP4161549A1 - Process for obtaining a purified psychoactive alkaloid solution - Google Patents
Process for obtaining a purified psychoactive alkaloid solutionInfo
- Publication number
- EP4161549A1 EP4161549A1 EP21881426.7A EP21881426A EP4161549A1 EP 4161549 A1 EP4161549 A1 EP 4161549A1 EP 21881426 A EP21881426 A EP 21881426A EP 4161549 A1 EP4161549 A1 EP 4161549A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- psychoactive
- alkaloid
- purified
- psychoactive alkaloid
- solvent
- 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.)
- Pending
Links
- 229930013930 alkaloid Natural products 0.000 title claims abstract description 281
- 150000003797 alkaloid derivatives Chemical class 0.000 title claims abstract description 224
- 238000000034 method Methods 0.000 title claims abstract description 88
- 230000008569 process Effects 0.000 title claims abstract description 85
- 239000000284 extract Substances 0.000 claims abstract description 119
- 239000002904 solvent Substances 0.000 claims abstract description 110
- 239000002002 slurry Substances 0.000 claims abstract description 59
- 239000007787 solid Substances 0.000 claims abstract description 29
- 239000000463 material Substances 0.000 claims abstract description 28
- 239000003463 adsorbent Substances 0.000 claims abstract description 24
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 18
- 238000001704 evaporation Methods 0.000 claims abstract description 16
- 238000001914 filtration Methods 0.000 claims abstract description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 131
- 239000011347 resin Substances 0.000 claims description 100
- 229920005989 resin Polymers 0.000 claims description 100
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 59
- 239000000706 filtrate Substances 0.000 claims description 50
- QVDSEJDULKLHCG-UHFFFAOYSA-N Psilocybine Natural products C1=CC(OP(O)(O)=O)=C2C(CCN(C)C)=CNC2=C1 QVDSEJDULKLHCG-UHFFFAOYSA-N 0.000 claims description 47
- QKTAAWLCLHMUTJ-UHFFFAOYSA-N psilocybin Chemical compound C1C=CC(OP(O)(O)=O)=C2C(CCN(C)C)=CN=C21 QKTAAWLCLHMUTJ-UHFFFAOYSA-N 0.000 claims description 47
- 229910001868 water Inorganic materials 0.000 claims description 43
- SPCIYGNTAMCTRO-UHFFFAOYSA-N Psilocine Natural products C1=CC(O)=C2C(CCN(C)C)=CNC2=C1 SPCIYGNTAMCTRO-UHFFFAOYSA-N 0.000 claims description 37
- ZBWSBXGHYDWMAK-UHFFFAOYSA-N psilocin Chemical compound C1=CC=C(O)[C]2C(CCN(C)C)=CN=C21 ZBWSBXGHYDWMAK-UHFFFAOYSA-N 0.000 claims description 37
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 24
- WTPBXXCVZZZXKR-UHFFFAOYSA-N baeocystin Chemical compound C1=CC(OP(O)(O)=O)=C2C(CCNC)=CNC2=C1 WTPBXXCVZZZXKR-UHFFFAOYSA-N 0.000 claims description 24
- IKQGYCWFBVEAKF-UHFFFAOYSA-N norbaeocystin Chemical compound C1=CC(OP(O)(O)=O)=C2C(CCN)=CNC2=C1 IKQGYCWFBVEAKF-UHFFFAOYSA-N 0.000 claims description 24
- 239000002028 Biomass Substances 0.000 claims description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 238000005406 washing Methods 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 20
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 18
- WVVSZNPYNCNODU-CJBNDPTMSA-N Ergometrine Natural products C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@@H](CO)C)C2)=C3C2=CNC3=C1 WVVSZNPYNCNODU-CJBNDPTMSA-N 0.000 claims description 18
- WVVSZNPYNCNODU-XTQGRXLLSA-N Lysergic acid propanolamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@H](CO)C)C2)=C3C2=CNC3=C1 WVVSZNPYNCNODU-XTQGRXLLSA-N 0.000 claims description 18
- DMULVCHRPCFFGV-UHFFFAOYSA-N N,N-dimethyltryptamine Chemical compound C1=CC=C2C(CCN(C)C)=CNC2=C1 DMULVCHRPCFFGV-UHFFFAOYSA-N 0.000 claims description 17
- 150000002576 ketones Chemical class 0.000 claims description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 15
- 239000008213 purified water Substances 0.000 claims description 14
- ZSTKHSQDNIGFLM-UHFFFAOYSA-N 5-methoxy-N,N-dimethyltryptamine Chemical compound COC1=CC=C2NC=C(CCN(C)C)C2=C1 ZSTKHSQDNIGFLM-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 12
- 229960001405 ergometrine Drugs 0.000 claims description 12
- WYTJZJPVCDWOOI-KANYHAFZSA-N lysergic acid hydroxyethylamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@@H](O)C)C2)=C3C2=CNC3=C1 WYTJZJPVCDWOOI-KANYHAFZSA-N 0.000 claims description 12
- ZJQHPWUVQPJPQT-UHFFFAOYSA-N muscimol Chemical compound NCC1=CC(=O)NO1 ZJQHPWUVQPJPQT-UHFFFAOYSA-N 0.000 claims description 12
- VTTONGPRPXSUTJ-UHFFFAOYSA-N bufotenin Chemical compound C1=C(O)C=C2C(CCN(C)C)=CNC2=C1 VTTONGPRPXSUTJ-UHFFFAOYSA-N 0.000 claims description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 8
- 235000011054 acetic acid Nutrition 0.000 claims description 8
- 235000010323 ascorbic acid Nutrition 0.000 claims description 8
- 239000011668 ascorbic acid Substances 0.000 claims description 8
- 229960005070 ascorbic acid Drugs 0.000 claims description 8
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 claims description 8
- 241001343296 Anadenanthera peregrina Species 0.000 claims description 7
- HIYGARYIJIZXGW-UHFFFAOYSA-N bufotenidine Chemical compound C1=C([O-])C=C2C(CC[N+](C)(C)C)=CNC2=C1 HIYGARYIJIZXGW-UHFFFAOYSA-N 0.000 claims description 7
- 239000000377 silicon dioxide Substances 0.000 claims description 7
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 7
- IRJCBFDCFXCWGO-BYPYZUCNSA-N (2s)-2-amino-2-(3-oxo-1,2-oxazol-5-yl)acetic acid Chemical compound OC(=O)[C@@H](N)C1=CC(=O)NO1 IRJCBFDCFXCWGO-BYPYZUCNSA-N 0.000 claims description 6
- MTJOWJUQGYWRHT-UHFFFAOYSA-N 3-[2-(methylamino)ethyl]-1h-indol-4-ol Chemical compound C1=CC(O)=C2C(CCNC)=CNC2=C1 MTJOWJUQGYWRHT-UHFFFAOYSA-N 0.000 claims description 6
- GENAHGKEFJLNJB-QMTHXVAHSA-N Ergine Natural products C1=CC(C2=C[C@H](CN([C@@H]2C2)C)C(N)=O)=C3C2=CNC3=C1 GENAHGKEFJLNJB-QMTHXVAHSA-N 0.000 claims description 6
- IRJCBFDCFXCWGO-UHFFFAOYSA-N Ibotenic acid Natural products OC(=O)C(N)C1=CC(=O)NO1 IRJCBFDCFXCWGO-UHFFFAOYSA-N 0.000 claims description 6
- SAHHMCVYMGARBT-UHFFFAOYSA-N Isochanoclavine I Natural products C1=CC(C(C(NC)C2)C=C(C)CO)=C3C2=CNC3=C1 SAHHMCVYMGARBT-UHFFFAOYSA-N 0.000 claims description 6
- GENAHGKEFJLNJB-UHFFFAOYSA-N Lysergsaeure-amid Natural products C1=CC(C2=CC(CN(C2C2)C)C(N)=O)=C3C2=CNC3=C1 GENAHGKEFJLNJB-UHFFFAOYSA-N 0.000 claims description 6
- 239000005913 Maltodextrin Substances 0.000 claims description 6
- 229920002774 Maltodextrin Polymers 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- OIIPFLWAQQNCHA-UHFFFAOYSA-N aeruginascin Chemical compound C1=CC(OP(O)([O-])=O)=C2C(CC[N+](C)(C)C)=CNC2=C1 OIIPFLWAQQNCHA-UHFFFAOYSA-N 0.000 claims description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 6
- SAHHMCVYMGARBT-HEESEWQSSA-N chanoclavine-I Chemical compound C1=CC([C@H]([C@H](NC)C2)\C=C(/C)CO)=C3C2=CNC3=C1 SAHHMCVYMGARBT-HEESEWQSSA-N 0.000 claims description 6
- DAVNRFCJMIONPO-UHFFFAOYSA-N elymoclavine Natural products C1=CC(C2C=C(CO)CN(C2C2)C)=C3C2=CNC3=C1 DAVNRFCJMIONPO-UHFFFAOYSA-N 0.000 claims description 6
- IAOSEBXZNXDPEE-UKRRQHHQSA-N elymoclavine Chemical compound C1=CC=C2[C@H]3C=C(CO)CN(C)[C@@H]3CC3=CN=C1[C]32 IAOSEBXZNXDPEE-UKRRQHHQSA-N 0.000 claims description 6
- YDPHSKXTPWQXBA-QMTHXVAHSA-N ergine Chemical compound C1=CC=C2C3=C[C@@H](C(N)=O)CN(C)[C@@H]3CC3=CN=C1[C]32 YDPHSKXTPWQXBA-QMTHXVAHSA-N 0.000 claims description 6
- 235000011167 hydrochloric acid Nutrition 0.000 claims description 6
- 229940035034 maltodextrin Drugs 0.000 claims description 6
- 235000011007 phosphoric acid Nutrition 0.000 claims description 6
- 235000019832 sodium triphosphate Nutrition 0.000 claims description 6
- 241000233866 Fungi Species 0.000 claims description 5
- -1 tetrabasic Chemical compound 0.000 claims description 5
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 claims description 4
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- 240000007594 Oryza sativa Species 0.000 claims description 4
- 235000007164 Oryza sativa Nutrition 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 4
- 239000001099 ammonium carbonate Substances 0.000 claims description 4
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- BITYAPCSNKJESK-UHFFFAOYSA-N potassiosodium Chemical compound [Na].[K] BITYAPCSNKJESK-UHFFFAOYSA-N 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 235000009566 rice Nutrition 0.000 claims description 4
- 239000001509 sodium citrate Substances 0.000 claims description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 4
- 235000011083 sodium citrates Nutrition 0.000 claims description 4
- 239000001540 sodium lactate Substances 0.000 claims description 4
- 235000011088 sodium lactate Nutrition 0.000 claims description 4
- 229940005581 sodium lactate Drugs 0.000 claims description 4
- UNXRWKVEANCORM-UHFFFAOYSA-I triphosphate(5-) Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O UNXRWKVEANCORM-UHFFFAOYSA-I 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 4
- 241001237914 Psilocybe Species 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 claims description 3
- 229940078495 calcium phosphate dibasic Drugs 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- RWYRUDPAALLKPX-UHFFFAOYSA-N 2,2-difluoro-n-methylethanamine;hydrochloride Chemical compound Cl.CNCC(F)F RWYRUDPAALLKPX-UHFFFAOYSA-N 0.000 claims description 2
- AEQDJSLRWYMAQI-UHFFFAOYSA-N 2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 claims description 2
- 244000215068 Acacia senegal Species 0.000 claims description 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 claims description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- 239000001749 Calcium fumarate Substances 0.000 claims description 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- 229920000084 Gum arabic Polymers 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 239000001747 Potassium fumarate Substances 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 239000001744 Sodium fumarate Substances 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 239000000205 acacia gum Substances 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000001361 adipic acid Substances 0.000 claims description 2
- 235000011037 adipic acid Nutrition 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- ZQKXOSJYJMDROL-UHFFFAOYSA-H aluminum;trisodium;diphosphate Chemical compound [Na+].[Na+].[Na+].[Al+3].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O ZQKXOSJYJMDROL-UHFFFAOYSA-H 0.000 claims description 2
- LCQXXBOSCBRNNT-UHFFFAOYSA-K ammonium aluminium sulfate Chemical compound [NH4+].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O LCQXXBOSCBRNNT-UHFFFAOYSA-K 0.000 claims description 2
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims description 2
- 235000012501 ammonium carbonate Nutrition 0.000 claims description 2
- 239000000908 ammonium hydroxide Substances 0.000 claims description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 2
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 2
- 235000011092 calcium acetate Nutrition 0.000 claims description 2
- 239000001639 calcium acetate Substances 0.000 claims description 2
- 229960005147 calcium acetate Drugs 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 235000010216 calcium carbonate Nutrition 0.000 claims description 2
- 239000001110 calcium chloride Substances 0.000 claims description 2
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 2
- 235000011148 calcium chloride Nutrition 0.000 claims description 2
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 claims description 2
- 239000001354 calcium citrate Substances 0.000 claims description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 2
- 235000019296 calcium fumarate Nutrition 0.000 claims description 2
- 239000004227 calcium gluconate Substances 0.000 claims description 2
- 235000013927 calcium gluconate Nutrition 0.000 claims description 2
- 229960004494 calcium gluconate Drugs 0.000 claims description 2
- 239000000920 calcium hydroxide Substances 0.000 claims description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 2
- 235000011116 calcium hydroxide Nutrition 0.000 claims description 2
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 claims description 2
- 239000001527 calcium lactate Substances 0.000 claims description 2
- 235000011086 calcium lactate Nutrition 0.000 claims description 2
- 229960002401 calcium lactate Drugs 0.000 claims description 2
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000292 calcium oxide Substances 0.000 claims description 2
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 2
- 235000012255 calcium oxide Nutrition 0.000 claims description 2
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 claims description 2
- YXVFQADLFFNVDS-UHFFFAOYSA-N diammonium citrate Chemical compound [NH4+].[NH4+].[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O YXVFQADLFFNVDS-UHFFFAOYSA-N 0.000 claims description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 2
- 235000019820 disodium diphosphate Nutrition 0.000 claims description 2
- MSJMDZAOKORVFC-SEPHDYHBSA-L disodium fumarate Chemical compound [Na+].[Na+].[O-]C(=O)\C=C\C([O-])=O MSJMDZAOKORVFC-SEPHDYHBSA-L 0.000 claims description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- 235000019800 disodium phosphate Nutrition 0.000 claims description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 2
- GYQBBRRVRKFJRG-UHFFFAOYSA-L disodium pyrophosphate Chemical compound [Na+].[Na+].OP([O-])(=O)OP(O)([O-])=O GYQBBRRVRKFJRG-UHFFFAOYSA-L 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 239000000174 gluconic acid Substances 0.000 claims description 2
- 235000012208 gluconic acid Nutrition 0.000 claims description 2
- 229940005740 hexametaphosphate Drugs 0.000 claims description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 2
- 239000001095 magnesium carbonate Substances 0.000 claims description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 2
- QUIOHQITLKCGNW-TYYBGVCCSA-L magnesium;(e)-but-2-enedioate Chemical compound [Mg+2].[O-]C(=O)\C=C\C([O-])=O QUIOHQITLKCGNW-TYYBGVCCSA-L 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 229940099690 malic acid Drugs 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 235000016337 monopotassium tartrate Nutrition 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 229960004838 phosphoric acid Drugs 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229960003975 potassium Drugs 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- KYKNRZGSIGMXFH-ZVGUSBNCSA-M potassium bitartrate Chemical compound [K+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O KYKNRZGSIGMXFH-ZVGUSBNCSA-M 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- 239000001508 potassium citrate Substances 0.000 claims description 2
- 229960002635 potassium citrate Drugs 0.000 claims description 2
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims description 2
- 235000011082 potassium citrates Nutrition 0.000 claims description 2
- SHPKCSFVQGSAJU-SEPHDYHBSA-L potassium fumarate Chemical compound [K+].[K+].[O-]C(=O)\C=C\C([O-])=O SHPKCSFVQGSAJU-SEPHDYHBSA-L 0.000 claims description 2
- 235000019295 potassium fumarate Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- PHZLMBHDXVLRIX-UHFFFAOYSA-M potassium lactate Chemical compound [K+].CC(O)C([O-])=O PHZLMBHDXVLRIX-UHFFFAOYSA-M 0.000 claims description 2
- 235000011085 potassium lactate Nutrition 0.000 claims description 2
- 239000001521 potassium lactate Substances 0.000 claims description 2
- 229960001304 potassium lactate Drugs 0.000 claims description 2
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 claims description 2
- 235000012239 silicon dioxide Nutrition 0.000 claims description 2
- 229960001866 silicon dioxide Drugs 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- GJPYYNMJTJNYTO-UHFFFAOYSA-J sodium aluminium sulfate Chemical compound [Na+].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GJPYYNMJTJNYTO-UHFFFAOYSA-J 0.000 claims description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
- 235000010234 sodium benzoate Nutrition 0.000 claims description 2
- 239000004299 sodium benzoate Substances 0.000 claims description 2
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 229960001790 sodium citrate Drugs 0.000 claims description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 2
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 claims description 2
- 235000019294 sodium fumarate Nutrition 0.000 claims description 2
- 229940005573 sodium fumarate Drugs 0.000 claims description 2
- 239000000176 sodium gluconate Substances 0.000 claims description 2
- 235000012207 sodium gluconate Nutrition 0.000 claims description 2
- 229940005574 sodium gluconate Drugs 0.000 claims description 2
- 235000019982 sodium hexametaphosphate Nutrition 0.000 claims description 2
- GCLGEJMYGQKIIW-UHFFFAOYSA-H sodium hexametaphosphate Chemical compound [Na]OP1(=O)OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])O1 GCLGEJMYGQKIIW-UHFFFAOYSA-H 0.000 claims description 2
- 229940083608 sodium hydroxide Drugs 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- 235000011008 sodium phosphates Nutrition 0.000 claims description 2
- 239000001476 sodium potassium tartrate Substances 0.000 claims description 2
- 235000011006 sodium potassium tartrate Nutrition 0.000 claims description 2
- 239000001117 sulphuric acid Substances 0.000 claims description 2
- 235000011149 sulphuric acid Nutrition 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- RYCLIXPGLDDLTM-UHFFFAOYSA-J tetrapotassium;phosphonato phosphate Chemical compound [K+].[K+].[K+].[K+].[O-]P([O-])(=O)OP([O-])([O-])=O RYCLIXPGLDDLTM-UHFFFAOYSA-J 0.000 claims description 2
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- YWYZEGXAUVWDED-UHFFFAOYSA-N triammonium citrate Chemical compound [NH4+].[NH4+].[NH4+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O YWYZEGXAUVWDED-UHFFFAOYSA-N 0.000 claims description 2
- 235000013337 tricalcium citrate Nutrition 0.000 claims description 2
- 229910000404 tripotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019798 tripotassium phosphate Nutrition 0.000 claims description 2
- 229910000406 trisodium phosphate Inorganic materials 0.000 claims description 2
- 235000019801 trisodium phosphate Nutrition 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 4
- 239000003513 alkali Substances 0.000 claims 1
- 239000001506 calcium phosphate Substances 0.000 claims 1
- 229910000389 calcium phosphate Inorganic materials 0.000 claims 1
- 229960001714 calcium phosphate Drugs 0.000 claims 1
- 235000011010 calcium phosphates Nutrition 0.000 claims 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 claims 1
- 229960000443 hydrochloric acid Drugs 0.000 claims 1
- 238000005342 ion exchange Methods 0.000 claims 1
- 238000010298 pulverizing process Methods 0.000 claims 1
- 239000012609 strong anion exchange resin Substances 0.000 claims 1
- 239000012607 strong cation exchange resin Substances 0.000 claims 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 abstract description 12
- 230000001337 psychedelic effect Effects 0.000 abstract description 6
- 241001465754 Metazoa Species 0.000 abstract description 4
- 239000012156 elution solvent Substances 0.000 abstract description 3
- 238000000605 extraction Methods 0.000 description 66
- 239000000243 solution Substances 0.000 description 60
- 238000000746 purification Methods 0.000 description 25
- 239000000203 mixture Substances 0.000 description 24
- 238000010828 elution Methods 0.000 description 21
- 238000001223 reverse osmosis Methods 0.000 description 16
- 238000011084 recovery Methods 0.000 description 15
- 239000012535 impurity Substances 0.000 description 13
- 239000003456 ion exchange resin Substances 0.000 description 11
- 229920003303 ion-exchange polymer Polymers 0.000 description 11
- 239000006228 supernatant Substances 0.000 description 11
- 150000002500 ions Chemical class 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 229920001429 chelating resin Polymers 0.000 description 8
- 239000002031 ethanolic fraction Substances 0.000 description 8
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 7
- 241001062357 Psilocybe cubensis Species 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 238000005457 optimization Methods 0.000 description 6
- 238000001179 sorption measurement Methods 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 150000001450 anions Chemical class 0.000 description 5
- NYPXMHGZLMAMNK-UHFFFAOYSA-N bufotenin Chemical compound C1=CC(O)=C[C]2C(CCN(C)C)=CN=C21 NYPXMHGZLMAMNK-UHFFFAOYSA-N 0.000 description 5
- 239000003729 cation exchange resin Substances 0.000 description 5
- 229910052681 coesite Inorganic materials 0.000 description 5
- 229910052906 cristobalite Inorganic materials 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 229910052682 stishovite Inorganic materials 0.000 description 5
- 229910052905 tridymite Inorganic materials 0.000 description 5
- 125000000129 anionic group Chemical group 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
- 239000011707 mineral Substances 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 239000003957 anion exchange resin Substances 0.000 description 3
- 239000006286 aqueous extract Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 125000002091 cationic group Chemical group 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000003795 desorption Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003925 fat Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000001694 spray drying Methods 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229920002101 Chitin Polymers 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000003925 brain function Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical group O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- RHCSKNNOAZULRK-UHFFFAOYSA-N mescaline Chemical compound COC1=CC(CCN)=CC(OC)=C1OC RHCSKNNOAZULRK-UHFFFAOYSA-N 0.000 description 2
- 230000036651 mood Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 239000002417 nutraceutical Substances 0.000 description 2
- 235000021436 nutraceutical agent Nutrition 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000008447 perception Effects 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- MIANLSMIRRRMJS-UHFFFAOYSA-N 5-meo-dmt Chemical compound [CH]1C(OC)=CC=C2N=CC(CCN(C)C)=C21 MIANLSMIRRRMJS-UHFFFAOYSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 241000134914 Amanita muscaria Species 0.000 description 1
- 208000006561 Cluster Headache Diseases 0.000 description 1
- 241001528213 Colubrina Species 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 1
- 206010015535 Euphoric mood Diseases 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241001415382 Incilius alvarius Species 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- SSISHJJTAXXQAX-ZETCQYMHSA-N L-ergothioneine Chemical compound C[N+](C)(C)[C@H](C([O-])=O)CC1=CNC(=S)N1 SSISHJJTAXXQAX-ZETCQYMHSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 208000026251 Opioid-Related disease Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000000718 cholinopositive effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 239000002577 cryoprotective agent Substances 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 150000002137 ergosterols Chemical class 0.000 description 1
- 229940093497 ergothioneine Drugs 0.000 description 1
- 230000002743 euphoric effect Effects 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 210000002816 gill Anatomy 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000003400 hallucinatory effect Effects 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 239000011346 highly viscous material Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 208000028173 post-traumatic stress disease Diseases 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D11/00—Solvent extraction
- B01D11/02—Solvent extraction of solids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
- B01D15/361—Ion-exchange
- B01D15/362—Cation-exchange
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
- B01D15/361—Ion-exchange
- B01D15/363—Anion-exchange
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/42—Selective adsorption, e.g. chromatography characterised by the development mode, e.g. by displacement or by elution
- B01D15/424—Elution mode
- B01D15/426—Specific type of solvent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
Definitions
- This application relates to a process of purification. More specifically, the present invention relates to a purification process for obtaining a purified psychoactive alkaloid solution from an extract. Further, the present invention also relates to a process of forming a standardized extract from the purified psychoactive alkaloid solution, wherein the extract has a desired, specific concentration of psychoactive alkaloids.
- a psychoactive substance is a chemical substance that changes brain function and may result in alterations in perception, mood, consciousness, cognition, or behavior.
- Psychoactivity of these substances may include sedative, stimulant, euphoric, deliriant, and hallucinogenic effects. These substances have been used recreationally, to purposefully improve performance or alter one's consciousness, and as entheogens for ritual, spiritual, or shamanic purposes.
- Some categories of psychoactive compounds have also shown therapeutic value and are prescribed by physicians and other healthcare practitioners.
- alkaloids e.g., nicotine, morphine, cocaine, mescaline, caffeine, ephedrine, psilocin.
- Alkaloids may provide a wide range of pharmacological activities including antimalarial, antiasthma, anticancer, cholinomimetic, vasodilatory, antiarrhythmic, analgesic, antibacterial, and antihyperglycemic activities. Many alkaloids have found use in traditional or modern medicine, or as starting points for drug discovery.
- psychoactive alkaloids When psychoactive alkaloids are obtained from natural sources, there may be difficulty in obtaining psychoactive alkaloid extracts with a specific, desired alkaloid content.
- the content of psychoactive alkaloids in some plants and fungi varies from species to species, and with growing conditions, seasonality, as well as with regular crop-to-crop variations that all natural products suffer from.
- the concentration of psychoactive alkaloids varies not only from species to species, but also from organism to organism within a given species, subspecies or variety. The same holds true even for different parts of the organism.
- one of the biggest challenges in the production of finished products from such naturally produced starting materials is the inconsistency in feedstock material leading to inconsistency in the final product.
- the present invention relates to a process for obtaining a purified psychoactive alkaloid solution from a psychoactive alkaloid source.
- the purification process of the present invention allows for producing standardized preparations of psychoactive alkaloids, all while using acceptable solvent and processing systems.
- Standardization is a method that can be used to solve the problem of inconsistency in the finished product.
- a psychoactive alkaloid source is used to provide a psychoactive alkaloid extract.
- the source may be a species containing psychedelic alkaloids or a prior extract therefrom.
- Psychoactive alkaloids in the extract are adsorbed onto a resin or other adsorbent material, from which they are then eluted to provide a purified psychoactive alkaloid solution.
- the process may be repeated with different resins, different pH values and different elution solvents. Solids present in the extract may be removed at various stages by filtering or centrifuging.
- the purification process of the present invention allows for purifying relatively low-potency feedstocks to result in a purified psychoactive alkaloid solution that may have a relatively high concentration of psychoactive alkaloid.
- the process may be a purification process that enriches the psychoactive alkaloid content of the final formulation compared to the alkaloid content in the raw materials. Purification may also be the removal of some of the impurities, irrespective of the final alkaloid content.
- the process of purification in the present invention allows use of the lowest-grade raw materials to obtain a product capable of standardization to a desired specification.
- the purification process of the present invention may be, depending on the embodiment, a relatively simple and robust psychoactive alkaloid purification process, which is suitable for the production of food-grade, nutraceutical-grade, or pharmaceutical-grade standardized extracts, especially of psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO- DMT (5-methoxy-N.N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, and/or chanoclavine.
- psilocybin especially of psiloc
- the present invention also relates to a standardization process for preparation of standardized extracts of psychoactive alkaloids.
- the standardization process of the present invention allows for standardizing the purified psychoactive alkaloid solution to result in a purified psychoactive alkaloid extract with a specific concentration of psychoactive alkaloids.
- the standardization process of the present invention may also be a simple and cost-efficient process.
- the standardized psychoactive alkaloid extracts of the present invention can be used in, for example, medical research on the use of psychedelic substances as treatments for addiction, post-traumatic stress disorder, depression, cluster headaches and other illnesses. They may also be used in traditional entheogenic practices or consumed recreationally where such activity is permitted by law.
- a process for obtaining a purified psychoactive alkaloid solution comprising: extracting a psychoactive alkaloid from a psychoactive alkaloid source to obtain a psychoactive alkaloid extract; treating the psychoactive alkaloid extract with an adsorbent material to obtain an adsorbed psychoactive alkaloid; and eluting the adsorbed psychoactive alkaloid using a solvent to obtain a purified psychoactive alkaloid solution, wherein the solvent is water, an organic solvent or a combination thereof, under basic, acidic or neutral pH.
- the process includes: evaporating a portion of solvent from the purified psychoactive alkaloid solution to obtain a concentrated slurry; standardizing the concentrated slurry by adding thereto a quantity of excipient measured to provide a specific concentration of psychoactive alkaloid when the concentrated slurry is dried; and drying the slurry by evaporating the remaining portion of the solvent to obtain a standardized, purified, powdered psychoactive alkaloid extract having the specific concentration of psychoactive alkaloid.
- FIG. 1 illustrates the steps of a basic process for obtaining a purified psychoactive alkaloid solution, according to an embodiment of the present invention.
- FIG. 2 illustrates in detail the basic and optional steps of a process for purification of a psychoactive alkaloid extract, according to an embodiment of the present invention.
- FIG. 3 illustrates a process for standardizing a purified psychoactive alkaloid solution to obtain a standardized psychoactive alkaloid extract, according to an embodiment of the present invention.
- FIG. 4 illustrates detailed steps of a process for extracting psychoactive alkaloids from Psilocybe cubensis, according to an embodiment of the present invention.
- FIG. 5 is a chart demonstrating a relationship between solvent to solid ratio and the percentage recovery of alkaloids for 1 st , 2 nd and 3 rd extractions.
- FIG. 6 is a chart demonstrating a relationship between time and total alkaloid recovery percentage.
- FIG. 7 is a chart demonstrating a relationship between mass of total alkaloids applied and total alkaloid recovery.
- FIG. 8 is a table showing the psilocybin capacity of XAD4 resin at three different flow rates for a breakthrough level of 5%.
- FIG. 9 is a chart demonstrating a relationship between bed volumes of eluent and recovery of alkaloid and dry mass on XAD4 resin.
- FIG. 10 is a chart demonstrating psilocybin content in a sample over 9 months.
- FIG. 11 shows time-point data of psilocybin, psilocin and moisture content of a psychoactive alkaloid composition.
- FIG. 12 is a chart demonstrating a relationship between solventsolid ratio and percentage recovery of alkaloids for 1 st , 2 nd and 3 rd extractions.
- FIG. 13 is a chart demonstrating a relationship between mass of psilocin applied and percentage recovery of psilocin from XAD4 resin.
- FIG. 14 shows the psilocybin capacity of XAD4 resin at three different flow rates for a breakthrough level of 5%.
- FIG. 15 is a chart demonstrating a relationship between time and psilocin recovery in a long-term stability measurement of a psychoactive alkaloid composition.
- FIG. 16 is a schematic diagram of an apparatus used for obtaining a purified psychoactive alkaloid solution and standardizing the same to result in a standardized psychoactive alkaloid extract, according to an embodiment of the present invention.
- neuroactive alkaloid refers to alkaloids that upon ingestion are capable of changing brain function, resulting in alterations in perception, mood, consciousness, cognition or behavior, for example.
- Psychoactive alkaloids are abundant in nature and can be obtained from sources such as a fungus, an animal, a mycelium, a spore, a plant, a bacterium, or a yeast.
- Examples of psychoactive alkaloids include, but are not limited to, psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT (5- methoxy-N.N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, ibotenic acid, muscimol, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, and/or chanoclavine.
- the source of the psychoactive alkaloid can also be an extract or a solution of the psychoactive alkaloid.
- the term “purified psychoactive alkaloid solution” refers to a solution of one or more desired psychoactive alkaloids, where the solution is free of impurities or contains fewer impurities compared to a similar psychoactive alkaloid solution that has not undergone any purification.
- the purified solution is obtained after a psychoactive alkaloid extracted from its source has been purified by the purification process of the present invention.
- the impurities that are commonly encountered while extracting psychoactive alkaloids from a natural source include sugars, carbohydrates, chitin, chitosan, fats, minerals, waxes, and/or proteins.
- the impurities being removed from the psychoactive alkaloid extract will vary depending on the source of the psychoactive alkaloid.
- standardized psychoactive alkaloid extract is used herein to describe a formulation derived from the purified psychoactive alkaloid solution, which has been standardized using a process described herein.
- the standardized psychoactive alkaloid extract includes psychoactive alkaloids in a specific concentration.
- resin as used herein is intended to refer to a solid or highly viscous substance of plant, mineral, or synthetic origin that has been typically converted into a polymer. Resins are usually mixtures of organic compounds. They are typically used in chromatographic techniques as a stationary phase to purify and separate compounds depending on their polarity. Resins can be physically or chemically modified to provide specificity to bind or repel particular molecules within sometimes very complex mixtures. A resin is an example of an adsorbent material.
- ion exchange resin refers to an insoluble organic polymer containing charged groups that attract and hold oppositely charged ions present in a surrounding solution in exchange for counterions previously held. Suitable ion exchange resins to be used herein contain cationic groups that attract and hold anions present in a surrounding solution and are sometimes referred to as “anion ionexchange resins”. Similarly, other ion exchange resins to be used herein contain anionic groups that attract and hold cations present in a surrounding solution and are sometimes referred to as “cation ion-exchange resins”.
- Macroporous resin refers to a nonionic, cation or anion resin with very small, highly cross-linked polymer particles with tiny channels. Macroporous resins are generally used for the adsorption of organic constituents due to their hydrophobic properties and are thus used to separate and purify compounds. The adsorption capacity of macroporous resins not only correlates with the physical and chemical properties of the adsorbent, but also with the size and chemical features of the adsorbed substance.
- adsorbed psychoactive alkaloid refers to one or more alkaloids that are adsorbed onto an adsorbent material such as a resin.
- purification process may be used herein to refer to the process described herein, i.e. a process for obtaining a purified psychoactive alkaloid solution.
- the purification process is a separate process to the standardization process.
- standardization process refers to the process of forming a psychoactive alkaloid extract that has a defined percentage content of psychoactive alkaloids.
- the standardization process may be applied to an extract that has gone through a purification process, or to an extract that has not gone through a purification process.
- purified water includes deionized water, distilled water, reverse osmosis (RO) water, or otherwise purified water which is substantially without free ions.
- adsorbent material refers to materials which can be used in place of the resin(s) to adsorb the psychoactive alkaloids. Examples of such materials include, but are not limited to, zeolites, clays, bentonite, minerals, alumina, diatomaceous earth, activated carbon, charred biomass, and others.
- a basic process for obtaining a purified psychoactive alkaloid solution includes the step 10 of extracting a psychoactive alkaloid from a psychoactive alkaloid source to obtain a psychoactive alkaloid extract.
- the psychoactive alkaloid source may be a fungus, a mycelium, an animal, a spore, a plant, a bacterium, a yeast or any other psychedelic organism.
- the psychoactive alkaloid source in some embodiments may be a prior extract of one or more psychoactive alkaloids, where the prior extract is to undergo a further extraction process.
- the psychoactive alkaloid may include, but is not limited to, psilocybin, psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, bufotenin, bufotenidine, 5-MeO-DMT (5-methoxy-N.N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrine, muscimol, ibotenic acid, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, and/or chanoclavine.
- 5-MeO-DMT (5-methoxy-N.N-dimethyltryptamine), N,N-dimethyltryptamine (DMT), ergine (LSA), ergonovine, ergometrin
- the extract from the psychoactive alkaloid source may be a fluid, as either a liquid or a slurry, or is made into a fluid by the addition of a solvent.
- the solvent in which the extract is carried or dissolved may be a primary aliphatic alcohol, a ketone, water, and any combination therefrom.
- the primary aliphatic alcohol is a C1-4 alcohol.
- the primary aliphatic alcohol is 5% ethanol.
- the primary aliphatic alcohol is ethanol.
- the ketone is a C3-4 ketone.
- the water is selected from deionized, distilled, reverse osmosis, or otherwise purified water, which is substantially without free ions. In other embodiments, the water is not purified.
- the process then involves adsorbing, in step 12, the psychoactive alkaloid(s) in the extract obtained in step 10 onto a resin to obtain an adsorbed psychoactive alkaloid, which may include one or more adsorbed psychoactive alkaloids.
- This step may be performed by treating the extract with the resin, e.g. by passing the extract through the resin, by mixing the extract with the resin, or by otherwise contacting the extract with the resin.
- the resin is an adsorbent resin of the macroporous type, such as, a cation or anion ion-exchange resin, a non-ionic resin, or any combination therefrom.
- adsorbent resin of the macroporous type such as, a cation or anion ion-exchange resin, a non-ionic resin, or any combination therefrom.
- Representative pharmaceutical, nutraceutical or food-grade grade resins for use in accordance with the present invention are known to those skilled in the art.
- pharmaceutical grade non-ionic macroporous resins are commercially available, e.g. Amberlite® XAD4.
- the resin is a cationic ionexchange resin or an anionic-exchange resin.
- the cationic ion-exchange resin may be selected from commercially available cationic ion-exchange resins known in the art, including but not limited to Amberlite® MAC-3 H.
- the cationic ion-exchange resin may be in an IT form or an Na + form.
- the anionic ion-exchange resin may be selected from commercially available anion exchange resins known in the art, including but not limited to Amberchrom® 50WX8.
- the anionic ion-exchange resin may be in an OH' form or a Cl' form.
- the resins used may be of any particle size. In some embodiments, the resins may be gel type resins, with any size of gel bead.
- the process involves eluting, in step 14, the adsorbed psychoactive alkaloid using a solvent to obtain a purified psychoactive alkaloid solution.
- the solvent may be, for example, an organic solvent, an acid, a base, a combination of an organic solvent and a base, a combination an organic solvent and an acid, water, a combination of water and acid, a combination of water and base, or a combination of water and an organic solvent.
- the solvent is different from the solvent in which the extract is initially provided, and is either a different type of solvent or a different composition of solvent. It may be at a different temperature than the initial solvent.
- the solvent used in the elution step 14 may be a primary aliphatic alcohol, a ketone, water, and any combination therefrom.
- the primary aliphatic alcohol is a C1-4 alcohol.
- the primary aliphatic alcohol is 5% ethanol.
- the primary aliphatic alcohol is ethanol.
- the ketone is a C3-4 ketone.
- the water is deionized, distilled, reverse osmosis, or otherwise purified water, which is substantially without free ions. In other embodiments, the water is not purified.
- the solvent used in the elution step 14 is a combination of an organic solvent and an acid.
- the combination of an acid and an organic solvent is 2% hydrochloric acid and 80% ethanol, for example.
- any acidic environment will displace some of the ions from the resin, but the rate and optimization of the desorption will be affected by the acid concentration.
- the solvent used in the elution step 14 is a combination of an organic solvent and a base.
- the combination of an organic solvent and a base is of 2% sodium chloride and 80% ethanol, for example.
- any basic environment will displace some of the ions from the resin, but the rate and optimization of the desorption will be affected by the concentration of the base.
- the elution step is carried out at a temperature in the range of 4-75°C. These temperatures are limited by the boiling point of the solvent used, as well as the specifications of allowable food-grade resins, as determined by the manufacturers of the resins and governmental food and drug administrations. In another embodiment, the elution step is carried out at room temperature for convenience, i.e. at 21-25°C. [0055] In other embodiments, the process for obtaining the purified psychoactive alkaloid solution further includes repeating the steps 12 and 14 with the obtained purified psychoactive alkaloid solution to obtain a further or twice purified psychoactive alkaloid solution.
- the resin may be the same or a different resin, and the solvent may be the same or a different solvent. While the purified psychoactive alkaloid solution may have a low psychoactive alkaloid content, this may be increased by evaporation of some or all of the solvent.
- the extraction step 10 is followed by completely or partially concentrating the obtained psychoactive alkaloid extract (or solution) by evaporation of the solvent from the extract in step 22.
- step 22 of partially or completely evaporating the solvent may be considered to be part of the extraction step 10. If the solvent from the extract has been completely evaporated in step 22, then reverse osmosis water, more solvent or another solvent is added back.
- the process includes adding, in step 24, an acid or a base to the psychoactive alkaloid extract obtained in step 10 to obtain a psychoactive alkaloid solution with a specific pH.
- the acid may be acetic acid, adipic acid, ascorbic acid, phosphoric acid, ammonium aluminum sulphate, ammonium citrate dibasic, ammonium citrate monobasic, calcium citrate, calcium fumarate, calcium gluconate, calcium phosphate dibasic, calcium phosphate monobasic, hydrochloric acid, sulphuric acid monobasic, calcium phosphate tribasic, citric acid, fumaric acid, gluconic acid, magnesium fumarate, malic acid, phosphoric acid, potassium acid tartrate, potassium citrate, potassium fumarate, sodium citrate, sodium fumarate, sodium gluconate, sodium lactate, sodium potassium hexametaphosphate, sodium potassium tartrate, sodium potassium tripolyphosphate, sodium pyrophosphate tetrabasic, sodium tripolyphosphate, tartaric acid, and any combination of two or more of these.
- the acid is either only hydrochloric acid or only phosphoric acid, for example. It is also envisaged that other acids may be used.
- the base may be ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, calcium acetate, calcium carbonate, calcium chloride, calcium hydroxide, calcium lactate, calcium oxide, calcium phosphate dibasic, calcium phosphate monobasic, magnesium carbonate, potassium aluminum sulphate, potassium bicarbonate, potassium carbonate, potassium hydroxide, potassium lactate, potassium phosphate dibasic, potassium pyrophosphate tetrabasic, potassium phosphate tribasic, potassium tripolyphosphate, sodium acetate, sodium acid pyrophosphate, sodium aluminum phosphate, sodium aluminum sulphate, sodium bicarbonate, sodium bisulphate, sodium carbonate, sodium hexametaphosphate, sodium hydroxide, sodium lactate, sodium phosphate dibasic, sodium phosphate monobasic, sodium phosphate tribas
- the specific pH psychoactive alkaloid solution has a pH ranging from 2.5-4.5, or from 9-10. In other embodiments, the specific pH psychoactive alkaloid solution has a pH of 3, 4, or 9.5. The selection of the pH is chosen in a manner to allow for the efficient adsorption of the psychoactive alkaloids onto the resin(s).
- the process includes adding phosphoric acid to the psychoactive alkaloid extract to achieve a pH of 4.
- the process includes adding hydrochloric acid to the psychoactive alkaloid extract to achieve a pH of 3.
- the process includes adding sodium hydroxide to the psychoactive alkaloid extract to achieve a pH of 9.5.
- the process includes, in step 26, optionally filtering, centrifuging, or clarifying the psychoactive alkaloid solution or specific pH psychoactive alkaloid solution, as the case may be, and utilizing the obtained filtrate for the next step 12 of adsorption. Clarifying may be performed, for example, by adding an agglomeration agent.
- step 12 the process involves adsorbing the psychoactive alkaloid(s) in the solution onto the resin to obtain an adsorbed psychoactive alkaloid.
- step 32 the process involves washing the resin to remove adsorbed impurities from the resin. While not all the impurities are adsorbed onto the resin, some of them may be.
- the washing step substantially, does not remove the adsorbed psychoactive alkaloids.
- the washing solvent may be 100% ethanol, 100% reverse osmosis water, or any other washing solvent used in ion-exchange resin chromatography, provided that the washing removes impurities or by-products that are adsorbed on the resin.
- Impurities or by-products may include, for example, sugars, carbohydrates, chitin, chitosan, fats, minerals, waxes, or proteins.
- the solvent(s) for washing may include a primary aliphatic alcohol, a ketone, water, and any combination selected therefrom.
- the primary aliphatic alcohol is a C1-4 alcohol.
- the primary aliphatic alcohol is 5% ethanol.
- the primary aliphatic alcohol is ethanol.
- the ketone is a C3-4 ketone.
- the water is selected from deionized, distilled, reverse osmosis, or otherwise purified water that is substantially without free ions.
- the process involves eluting, in step 14, the adsorbed psychoactive alkaloid from the resin using a solvent to obtain a purified psychoactive alkaloid solution.
- the solvent may be an organic solvent, an acid, a base, or water, a combination of an organic solvent and a base, or a combination of an organic solvent and an acid, a combination of an organic solvent and water, a combination of water and a base, or combination of water and an acid.
- the result of the elution step is a purified psychoactive alkaloid solution.
- a further washing step 36 may be employed using 100% ethanol, for example, to wash the resin. This may be considered to be a cleaning step, to refresh the resin and make it ready to be used again in a subsequent step or in another process.
- the solvent for further washing may be a primary aliphatic alcohol, a ketone, water, and any combination therefrom.
- the primary aliphatic alcohol is a C1-4 alcohol.
- the primary aliphatic alcohol is 5% ethanol.
- the ketone is a C3-4 ketone.
- the water is selected from deionized, distilled, reverse osmosis, or otherwise purified water that is substantially without free ions.
- the result of the elution is a purified psychoactive alkaloid solution.
- the purified psychoactive alkaloid solution has a concentration of 0.07% by weight of a psychoactive alkaloid, which is the concentration before removal of some or all of the solvent. This concentration may be different in other embodiments, depending on the amount solvent used for the elution and the potency of the raw materials.
- the purified psychoactive alkaloid solution is concentrated by evaporating the solvent to form a purified psychoactive slurry that has at least of 5% by weight or more of a psychoactive alkaloid.
- the purified psychoactive alkaloid slurry has 5-68% by weight of a psychoactive alkaloid.
- the purified psychoactive alkaloid slurry has a concentration of psychoactive alkaloid outside these ranges, and, when dried, can be as low as 0.1 % or as high as 99% dry wt/wt%.
- the obtained purified psychoactive alkaloid solution is further purified by filtering the obtained purified psychoactive alkaloid solution to obtain a filtrate, and then repeating at least steps 12 and 14 with the obtained filtrate.
- Different processes may employ the steps in a different order, and some of the steps may be repeated with the same or different parameters.
- the order of the steps may be 24, 12, 26, 32, 14, 24, 26, 22, 26, 12, 32 and 14.
- the present invention also relates to a process of obtaining a standardized, purified, psychoactive alkaloid extract.
- the process includes, in step 42, concentrating the purified psychoactive alkaloid solution to obtain a purified psychoactive alkaloid slurry.
- the slurry is then standardized, in step 44, to obtain a standardized psychoactive alkaloid extract.
- the standardizing step 44 includes adding excipients to the purified psychoactive alkaloid slurry to obtain the standardized psychoactive alkaloid extract.
- concentration of alkaloids in the slurry is measured and the proportion of dry weight in the slurry is calculated. Knowing this concentration and the dry weight content, the amounts of excipients are chosen to result in a powder of known alkaloid concentration after the solvent in the slurry has been evaporated.
- excipients described herein refer to excipients to aid in the manufacturing and/or administration of the compositions described herein.
- excipients are well known in the art and include flavorants, colorants, palatants, antioxidants, viscosity modifying agents, tonicity agents, drug carriers, sustained-release agents, comfort-enhancing agents, emulsifiers, solubilizing aids, lubricants, binding agents, bioavailability-enhancing agents, stabilizing agents and other agents to aid in the manufacturing and/or administration of the compositions.
- the excipients used in the present invention are acceptable for use in pharmaceutical or nutraceutical applications or as food ingredients.
- the excipients are selected from silicon dioxide, ascorbic acid, maltodextrin from corn, potato or tapioca for example, gum arabic, microcrystalline cellulose, sodium benzoate, sodium phosphate, sodium citrate, rice hulls, and rice. A combination of any of these excipients may be used.
- the standardized psychoactive alkaloid extract may have a psychoactive alkaloid concentration ranging from 0.1-99% by weight, and the concentration may be specified to two decimal places or two significant figures. For the highest percentage concentration, only 1 % of the standardized psychoactive extract will be excipient.
- the standardized psychoactive alkaloid extracts have psychoactive alkaloid concentrations of 5.00% by weight, 54% by weight and 68% by weight.
- the extracting step 10 may include, as an example, extracting psychoactive alkaloids from raw, psychedelic mushrooms.
- the mushrooms are dried and ground to result in a dried biomass.
- the next step involves heating the dried biomass in a solvent in order for the extraction to occur.
- the obtained slurry is filtered to obtain a first filtrate and a first residue.
- the first residue undergoes a second extraction, using a second solvent to obtain a second slurry, which is then filtered to obtain a second filtrate and a second residue.
- the first filtrate and the second filtrate are mixed to obtain the psychoactive alkaloid extract. More extract can be obtained this way, i.e. by splitting the solvent into two or more batches and using each one sequentially to soak the biomass, compared to using a single volume of solvent.
- the extraction may further include completely or partially concentrating the obtained psychoactive alkaloid extract, by evaporation of the solvent from the combined filtrates.
- the first solvent and the second solvent are selected from a primary aliphatic alcohol, a ketone, water, and any combination therefrom.
- the primary aliphatic alcohol is a C1-4 alcohol.
- the ketone is a C3-4 ketone.
- the first solvent is an ethanol- water mixture with 3 parts ethanol to 1 part water by weight.
- the second solvent is an ethanol-water mixture with 3 parts ethanol to 1 part water by weight.
- the water is selected from deionized, distilled, reverse osmosis, or otherwise purified water, which has substantially no free ions. The selection of the solvent will depend on the nature of the starting material for extraction and the reaction conditions, according to which a person of skill in the art can make the appropriate solvent selection.
- the extraction is carried out at a temperature ranging from 5-95°C.
- the useful temperature range spans most of the liquid state of the solvent used, and upper and lower limits are determined by physical practicalities and limits of the available apparatus. Still, the temperature of the solvent may be outside of this range in other embodiments.
- the extraction is carried out at a temperature of 70°C. Temperature and pressure, if applied, are generally selected so that the solvent does not boil if elevated temperatures are used. In one embodiment, the extraction is carried out for a time duration ranging from 10 minutes to 12 hours. In yet another embodiment, the extraction is carried out for a time duration of 4 hours.
- Psilocybe cubensis and Anadenanthera peregrina can be readily substituted by other sources of psychoactive alkaloids to obtain a variety of purified psychoactive alkaloids having similar properties, such alkaloids being, besides those mentioned above, baeocystin, norbaeocystin, norpsilocin, aeruginascin, N,N-dimethyltryptamine (DMT), ergine (LSA), ibotenic acid, ergonovine, ergometrine, muscimol, lysergic acid hydroxyethylamide (LSH), elymoclavine, ergometrinine, and/or chanoclavine, to name a few, and to result in compositions with similar efficacy and efficiency as well.
- alkaloids being, besides those mentioned above, baeocystin, norbaeocystin, norpsilocin, a
- the venom of the toad Incilius alvarius, the Anandenanthera colubrina tree or the Amanita muscaria mushroom may be used as other sources of psychoactive alkaloids.
- the lists of sources and psychoactive alkaloids are included to provide examples, and are non-exhaustive lists.
- step 50 2.5 kilograms of fresh Psilocybe cubensis (caps, stems and gills) was taken (step 50) and dried (step 52) in a forced air oven at 25°C for 5-10 hours. A mass of 140 grams of dried biomass was obtained. The dried biomass was pulverized (step 54) to a size of 200 mesh with a hammer mill to result in a dried, powdered biomass. The dried, powdered biomass was placed in an agitated, heat- controlled extraction vessel with 5 kilograms of a hydro-ethanol mixture, with 3 parts ethanol to 1 part water by weight, as a solvent (step 56).
- step 60 The extraction (step 60) was carried out for 4 hours at a controlled temperature of 70°C to obtain an extract in the form of a slurry.
- the extraction slurry was filtered (step 62) while it was hot, and filtrate A was collected.
- the filter residue was retained (step 64) and placed back into the extraction vessel, followed by addition (step 66) of another 5 kilograms of 3:1 ethanokwater mixture by weight as a solvent.
- the extraction was repeated (step 70).
- the temperature of extraction was again carried out at 70°C for a duration of 4 hours.
- the obtained extraction slurry was filtered (step 72) while hot and filtrate B was collected. Filtrate A and filtrate B from the first and second extractions were mixed (step 74).
- the mixture was then partially concentrated by evaporation (step 76) of the solvent from the combined filtrates to provide a 2.5 litre volume of psychoactive alkaloid extract solution.
- Step 76 is similar to step 22 of FIG. 2.
- Example 1.3 Preparation of Anadenanthera peregrina seed extract
- Example 2.1 Purifying the psychoactive alkaloid extract using a non-ionic macroporous resin
- the pH of the partially concentrated extract of example 1.1 which was an aqueous extract, was adjusted to pH 4.0 (+/- 0.5) by adding 2 M phosphoric acid and centrifuged for 15 minutes at 3000g to remove any solid precipitate.
- the pH of 4 corresponds to the isoelectric point of psilocybin, and psilocin’s polarity is such that it is partitioned onto the resin, thus allowing effective binding of the psychoactive alkaloids psilocybin and psilocin to the macroporous resin.
- Norbaeocystin and baeocystin are phosphorylated and behave in the same way as psilocybin.
- the supernatant obtained was loaded onto a column of Amberlite® XAD4, a non-ionic macroporous resin (50.34 g of dry resin) at a flow rate of 2 bed volumes per hour, to allow components in the supernatant to be adsorbed onto the macroporous resin.
- the column was washed in a single pass with 5 bed volumes of reverse osmosis water at room temperature. This was followed by elution with 5 bed volumes of 5% ethanol (by weight), again at room temperature. Finally, the column was washed in a single pass with 5 bed volumes of 100% ethanol. The elution was performed at room temperature. Each of these three fractions was collected separately.
- the particular order for the washing steps and the elution was selected to be in the order of the polarity of the solvents. If the order were different, an inferior result may have ensued, such as a lower yield.
- the first fraction using reverse osmosis water removed the most polar compounds from the resin.
- the hydroethanol fraction eluted compounds of lesser polarity, and the 100% ethanol solvent removed the least polar compounds. Less polar solvents could also be used to elute less polar compounds.
- the 5% ethanol fraction (i.e. the purified psychoactive alkaloid solution) was then concentrated in a rotary evaporator to form 3.90 g of concentrated aqueous slurry at 30% solids, containing 195.1 mg of total alkaloids, i.e. psilocybin, psilocin, norbaeocystin, and baeocystin.
- the result was a purified psychoactive alkaloid slurry having a total psychoactive alkaloid concentration of 5.00% by weight.
- Example 2.2 Purifying the psychoactive alkaloid extract using cation exchange and non-ionic macroporous resins
- the filtrate-resin mixture was agitated for 4 hours at room temperature (21 °C - 25°C) and then filtered. The filtrate was discarded, and the resin was rinsed with 2.0 L of 100% EtOH and then 2.0 L of H 2 O to remove any impurities. Finally, the psilocybin/psilocin fraction was eluted with 2.0 L of 2% HCI/80% EtOH, for 4 hours at room temperature.
- the eluted fraction was brought to a pH of 4.0 (i.e. the isoelectric point of psilocybin) by adding 2M NaOH.
- the filtrate was then centrifuged at 3000g to remove any solid precipitate.
- the resultant filtrate, in form of an aqueous solution was then placed into a rotary evaporator and the solvent was removed until the aqueous solution reached a volume of 400 mL.
- the aqueous solution was then again centrifuged for 15 minutes at 3000g to remove any solid precipitate.
- the supernatant was loaded onto a column of Amberlite® XAD4 macroporous resin (45.53 g of dry resin) at a flow rate of 2 bed volumes per hour.
- the 5% ethanol fraction i.e. the purified psychoactive alkaloid solution
- the 5% ethanol fraction was concentrated in a rotary evaporator to form 258 mg of solution containing 175 mg of total alkaloids (i.e. psilocybin, psilocin, norbaeocystin, and baeocystin).
- Example 2.3 Purifying the psychoactive alkaloid extract using anion exchange and non-ionic macroporous resins
- the combination of filtrates of example 1.2 was taken as the starting point.
- the pH of the filtrate combination was adjusted to 9.5 (+/- 0.5) by adding 1 M NaOH and then mixed with 150g of Amberchrom® 50WX8 strong anionic ion-exchange resin in its hydrogen form to result in a filtrate-resin mixture, in which components of the psychoactive alkaloid filtrate were adsorbed onto the anion exchange resin.
- the pH of 9.5 (+/- 0.5) ensured that the psilocybin, psilocin, norbaeocystin, and baeocystin were deprotonated and had a net negative charge for efficient adsorption onto the strong anion exchanger.
- the eluted fraction was brought to a pH of 4.0 with the addition 2 M HCI.
- the extract was then centrifuged at 3000g to remove any solid precipitate.
- the resultant extract, in from of a solution, was then placed into a rotary evaporator and the solvent was removed to result in a volume of 400 mL.
- the resultant 400 mL aqueous solution was centrifuged for 15 minutes at 3000g to remove any solid precipitate.
- the supernatant was loaded onto a column of Amberlite® XAD4 macroporous resin (45.53 g of dry resin) at a flow rate of 2 bed volumes per hour, to allow components of the supernatant to be adsorbed onto the macroporous resin.
- the column was initially washed with 5 bed volumes of reverse osmosis water, followed by elution with 5 bed volumes of 5% ethanol (by weight) and then a final wash with 100% ethanol was performed. Each of these fractions was collected separately.
- the 5% ethanol fraction i.e.
- the purified psychoactive alkaloid solution was concentrated in a rotary evaporator to form 325 mg of solution containing 175 mg of total alkaloids (i.e. psilocybin, psilocin, norbaeocystin, and baeocystin).
- a purified psychoactive alkaloid slurry with a concentration of 54% dry wt/wt% of total alkaloids was therefore obtained.
- Example 2.4 Purifying the Anadenanthera peregrina seed extract
- Example 3.1 Process for preparing standardized psychoactive alkaloid extract
- Example 3.2 Process for preparing standardized psychoactive alkaloid extract from Anadenanthera peregrina seeds
- the dried powdered biomass was placed into an agitated, heat-controlled vessel with 58 L of solvent, i.e. a solvent to solid ratio of 40 L/kg.
- the solvent was acidified methanol (5% acetic acid 195% anhydrous methanol v/v%). It is noteworthy that while methanol works well, acidified methanol works 10-15% better. Both, however, are acceptable extraction solvents for psilocybin.
- FIG. 5 shows a chart for the solvent to solid ratio optimization, in which the percentage alkaloid recovery was measured for different solvent to solid ratios, for 1 extraction (1 st ), 2 extractions (2 nd ), and 3 extractions (3 rd ).
- FIG. 6 shows a graph of time and temperature optimization, in which total alkaloid recovery was measured at various times for extractions at temperatures of 20°C, 50°C and 70°C. This indicates that higher temperatures increase the extraction efficiency in the short term, but also cause degradation when extended beyond 20-30 minutes. Given that, at scale, the increased complexity of elevating the temperature of the extraction vessel would introduce a significant warming and cooling time, it was decided to select the extraction temperature of 20°C, and keep the extended extraction time at 30-50 minutes to avoid degradation of the alkaloids.
- the pooled filtrate was placed into a rotary-evaporator, and the methanol was evaporated until the volume was reduced to around 5.8 L, forming a concentrated solution. 5.8 L was roughly 5% of the pooled filtrate volume, the solvent being entirely acetic acid at this point and the filtrate having a pH around 2.4. Basically, it is required to remove all of the methanol for further purification.
- the content of psilocybin in this concentrated solution was 1.18 g/L, and the yield was 94.2%.
- the dry mass yield at this stage was 44.23% (i.e. 641.3 g of the original 1.45 kg was present).
- Components that are still present in the extract at this point are small chain carbohydrates/polysaccharides, free sugars, polyphenols, alkaloids, some glycoproteins, ergothioneine, tocopherols, ergosterols and fats. Many of these components are targeted for removal with purification. Components that are present in the mushroom that are left behind in the biomass are proteins, large carbohydrates/polysaccharides and B-glucans.
- the concentrated, acetic acid solution was then diluted with RO water to 50 L (1.28 % dry mass concentration).
- the aqueous extract was then adjusted to pH 4.0 (+/- 0.5) with 2 M sodium hydroxide and filtered through a 5 pm stainless steel filter to remove any solid precipitate. It is important to have the extract be at pH 4.0 before application to the adsorbent resin, because pH 4 is the isoelectric point of psilocybin, and it is also the maximum stability pH for psilocin.
- the supernatant was loaded onto a column of Amberlite® XAD4 macroporous resin (5000 mL of hydrated resin, -1.39 mg psilocybin/mL of hydrated resin) at a flow rate of 2 bed volumes per hour. Optimization of breakthrough and determination of capacity is shown in FIG. 7, in which total alkaloid (psilocybin) recovery was measured as a function of mass of alkaloid applied, for flow rates of 2, 4 and 6 BV/h. See also FIG. 8, which is a table showing the maximum psilocybin capacity of XAD4 resin at three different flow rates and a breakthrough of 5%.
- FIG. 9 shows a graph of recovery of psilocybin and dry mass recovery from XAD4 resulting from a single pass of the supernatant through the resin. Desorption with 15% ethanol resulted in 99.2% recovery of psilocybin while retaining only 2.5% of the dry mass in the same fraction. This resulted in a ⁇ 40X increase in concentration over the extract and a 45% dry wt/wt% content of psilocybin in the first pass purified extract.
- the 15% ethanol fraction contained 6.79 g of psilocybin and a total of 16.03 g of dry mass, resulting in an extract of 42.35% psilocybin by weight (the psilocybin mass is included in the dry mass).
- the 15% ethanol fraction was then concentrated in a rotary evaporator to form 53.45 g of concentrated aqueous slurry at 30% solids.
- Ascorbic acid is an antioxidant, allowing protection from oxidation by first oxidizing itself, and citric acid is a chelating agent that may impart increased bioavailability and pH buffering once inside the stomach.
- This composition has shown 9 months of shelf stability, as shown in FIG. 10, which shows percentage of psilocybin recovery on a monthly basis, for sample PYEX-FP-200820 stored at 25°C and 65% relative humidity.
- FIG. 11 shows the individual time-point data of psilocybin, psilocin and moisture content of the PYEX-FP- 200820 sample.
- the dried powdered biomass was placed into an agitated, heat-controlled vessel with 78.5 L of solvent (50 L/kg).
- the solvent was acidified water (0.15 M citric acid, pH 2.0).
- FIG. 12 shows a chart of solvent to solid ratio optimization for 0.15M citric acid in water, for one (1 st ), two (2 nd ) and three (3 rd ) extractions.
- the optimal was 50 L/kg, which was the lowest solvent to solid ratio that could obtain >90% psilocin yield in two extractions.
- the extraction was controlled to a constant 25°C temperature and was under atmospheric pressure. The extraction was carried out under these conditions for 60 minutes, and the extraction slurry was filtered through a 5 pm stainless steel filter.
- the filtrate was placed into another vessel and put aside.
- the now-dry filter cake was again placed into the extraction vessel, and an additional 78.5 L of extraction solvent was added to the vessel.
- the extraction was again carried out under the same conditions for 60 minutes.
- the slurry was then filtered and the filtrate combined with the filtrate set aside in order to create the pooled filtrate.
- the pooled filtrate had a content of psilocin of 0.034 g/L, and the yield was 91.23%.
- the dry mass yield at this stage was 68.92%. The dry mass yield was this high because of the citric acid content.
- FIG. 13 shows the XAD4 adsorption breakthrough measurements for the recovery of psilocin at loading flow rates of 2, 4 and 6 BV/h.
- FIG. 14 is a table of XAD4 psilocin capacity at three different flow rates for a breakthrough level of about 5%.
- Macroporous resin adsorption/desorption is an efficient purification platform to concentrate the total alkaloid content in an extract, particularly since the concentration factor from extraction alone is underwhelming.
- TABLE 1 gives examples of solvents and/or extraction processes that may be used to obtain extracts that are psilocybin, psilocin or a combination.
- TABLE 1 provides an indication of purification methodologies depending on whether the goal is highest purity psilocybin, highest purity psilocin or a partial purification of psilocin and psilocybin.
- FIG. 16 an example of the apparatus is shown schematically.
- Raw Psilocybe cubensis mushrooms were added to a hopper 100, and were released in batches into container 102.
- the raw fungal material was then dried in a forced air oven 104 to result in dried biomass.
- the dried biomass was placed into a grinder 106 for grinding.
- the dried powdered biomass was placed into a heat-controlled vessel 110 and solvent (S) was added to the heat-controlled vessel.
- the vessel 110 was surrounded by an insulating wall 108. Alternately, an insulating jacket may have been wrapped around the vessel.
- the insulating wall 108 or jacket helps to maintain the contents 112 under a constant temperature (T) between 5 - 95°C.
- the pressure (P) inside the extraction vessel 110 may be regulated up to 100 MPa (15,000 psig).
- the bottom of the extraction vessel 110 was opened at outlet 114 and the extraction slurry was collected in a container 120.
- the extraction slurry was then fed into a filter 122 and a first filtrate was collected in container 124.
- the first filtrate residue 130 was then fed back (R) into the agitated, heat-controlled vessel 110 and more solvent (S) was added for a second extraction.
- the extraction slurry was collected in the container 120 and was then fed into a filter 132. After filtration, the obtained second filtrate was collected in container 136.
- the filtrates were mixed in container 140 to obtain a bulk filtrate. In other embodiments, if there is only a single filtration step, this mixing step is not required.
- the bulk filtrate was placed in a rotary evaporator 142 and part of the solvent was evaporated from the bulk filtrate.
- the resultant extract was transferred to a container 144, where the pH of the extract was adjusted, followed by centrifugation 146 to remove the solid precipitates.
- the resultant supernatant was loaded onto a column 150 of resin.
- An initial wash was given to the column with a solvent to remove impurities from the resin, and fraction 154 was collected.
- a second wash was given to the column with another solvent to elute the psychoactive alkaloids from the column and result in fraction 156.
- a final wash was given to the column with another solvent to wash any impurities from the column, to prepare the column for use again, and the fraction 158 was obtained.
- the elution fraction 156 with the psychoactive alkaloids was then concentrated in a rotary evaporator 160 to result in the purified psychoactive alkaloid solution.
- a container 164 the purified psychoactive alkaloid solution and desired excipients were added together and thoroughly mixed to result in a final standardized slurry having a specified concentration of alkaloids.
- the final standardized slurry was then subjected to spray-drying 168 to obtain a final powdered alkaloid extract 170 with a total psilocybin/psilocin concentration defined as a percentage to two decimal places or two significant figures by dry weight.
- parts of the apparatus may be reused or duplicated.
- the elution fraction 156 may be reloaded into the container 144 for pH adjustment and the steps from thereon can be repeated to allow for further purification of the obtained purified psychoactive alkaloid solution.
- ranges given include all subranges within the range. For example, if a range is given as m-q, then the ranges m-n, n-p and p-q are included, where n and p are any values that satisfy m ⁇ n ⁇ p ⁇ q.
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA3097246A CA3097246C (en) | 2020-10-23 | 2020-10-23 | Process for obtaining a purified psychoactive alkaloid solution |
PCT/CA2021/050813 WO2021253116A1 (en) | 2020-06-17 | 2021-06-14 | Compositions comprising psychoactive compounds from psychoactive organisms |
PCT/CA2021/051495 WO2022082320A1 (en) | 2020-10-23 | 2021-10-23 | Process for obtaining a purified psychoactive alkaloid solution |
Publications (2)
Publication Number | Publication Date |
---|---|
EP4161549A1 true EP4161549A1 (en) | 2023-04-12 |
EP4161549A4 EP4161549A4 (en) | 2023-11-29 |
Family
ID=81291112
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP21881426.7A Pending EP4161549A4 (en) | 2020-10-23 | 2021-10-23 | Process for obtaining a purified psychoactive alkaloid solution |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP4161549A4 (en) |
BR (1) | BR112022025782A2 (en) |
MX (1) | MX2023004350A (en) |
WO (1) | WO2022082320A1 (en) |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101491647A (en) * | 2007-04-18 | 2009-07-29 | 北京和润创新医药科技发展有限公司 | Method for separating ergot total alkaloids in ergot stem extract |
JP2022529662A (en) * | 2019-04-26 | 2022-06-23 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | Methods and Compositions for Double Glycan-Binding AAV2.5 Vectors |
CA3123908C (en) * | 2020-06-17 | 2022-03-22 | Psilo Scientific Ltd. | Ethanol extraction of psychoactive compounds from psilocybin fungus |
-
2021
- 2021-10-23 WO PCT/CA2021/051495 patent/WO2022082320A1/en unknown
- 2021-10-23 BR BR112022025782A patent/BR112022025782A2/en unknown
- 2021-10-23 MX MX2023004350A patent/MX2023004350A/en unknown
- 2021-10-23 EP EP21881426.7A patent/EP4161549A4/en active Pending
Also Published As
Publication number | Publication date |
---|---|
WO2022082320A1 (en) | 2022-04-28 |
BR112022025782A2 (en) | 2024-01-30 |
MX2023004350A (en) | 2023-09-12 |
EP4161549A4 (en) | 2023-11-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA3097246C (en) | Process for obtaining a purified psychoactive alkaloid solution | |
AU2021290454B2 (en) | Process for Obtaining a Purified Psychoactive Alkaloid Solution | |
CA3157550C (en) | Injectable psychoactive alkaloid composition and preparation thereof | |
US11382942B2 (en) | Extraction of psychoactive compounds from psilocybin fungus | |
WO2021253116A1 (en) | Compositions comprising psychoactive compounds from psychoactive organisms | |
CA3103707C (en) | Standardized psychoactive alkaloid extract composition | |
EP4161549A1 (en) | Process for obtaining a purified psychoactive alkaloid solution | |
CA3137016C (en) | Psychoactive alkaloid extraction and composition with inhibited dephosphorylation | |
US11510952B2 (en) | Ethanol extraction of psychoactive compounds from psilocybin fungus | |
CA3161491C (en) | Vaporizable psychoactive alkaloid composition and preparation thereof | |
CA3169140A1 (en) | Dephosphorylation-controlled extraction of phosphorylatable psychoactive alkaloids |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE |
|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE |
|
17P | Request for examination filed |
Effective date: 20230106 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
RAP3 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: PSILO SCIENTIFIC LTD |
|
A4 | Supplementary search report drawn up and despatched |
Effective date: 20231102 |
|
RIC1 | Information provided on ipc code assigned before grant |
Ipc: B01D 15/42 20060101ALI20231025BHEP Ipc: B01D 15/36 20060101ALI20231025BHEP Ipc: B01D 15/08 20060101ALI20231025BHEP Ipc: B01D 11/02 20060101ALI20231025BHEP Ipc: A61K 36/07 20060101ALI20231025BHEP Ipc: A61K 36/48 20060101AFI20231025BHEP |
|
DAV | Request for validation of the european patent (deleted) | ||
DAX | Request for extension of the european patent (deleted) |