US20210251948A1 - Nanoemulsion hydrophobic substances - Google Patents
Nanoemulsion hydrophobic substances Download PDFInfo
- Publication number
- US20210251948A1 US20210251948A1 US17/239,262 US202117239262A US2021251948A1 US 20210251948 A1 US20210251948 A1 US 20210251948A1 US 202117239262 A US202117239262 A US 202117239262A US 2021251948 A1 US2021251948 A1 US 2021251948A1
- Authority
- US
- United States
- Prior art keywords
- polyglyceryl
- oil
- surfactant
- acid
- emulsion
- 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.)
- Abandoned
Links
- 239000007908 nanoemulsion Substances 0.000 title claims description 82
- 230000002209 hydrophobic effect Effects 0.000 title description 16
- 239000000126 substance Substances 0.000 title description 9
- 239000004094 surface-active agent Substances 0.000 claims abstract description 239
- 239000000203 mixture Substances 0.000 claims abstract description 130
- 239000003557 cannabinoid Substances 0.000 claims abstract description 112
- 229930003827 cannabinoid Natural products 0.000 claims abstract description 111
- 239000003921 oil Substances 0.000 claims abstract description 88
- 239000002199 base oil Substances 0.000 claims abstract description 84
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 55
- 235000019198 oils Nutrition 0.000 claims description 87
- 239000000839 emulsion Substances 0.000 claims description 55
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 51
- 239000000787 lecithin Substances 0.000 claims description 51
- 235000010445 lecithin Nutrition 0.000 claims description 51
- 229940067606 lecithin Drugs 0.000 claims description 51
- 229920000136 polysorbate Polymers 0.000 claims description 42
- 229960004242 dronabinol Drugs 0.000 claims description 27
- -1 Isoceteth-20 Chemical compound 0.000 claims description 25
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 24
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 23
- 229920000053 polysorbate 80 Polymers 0.000 claims description 23
- 241000218236 Cannabis Species 0.000 claims description 22
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 22
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 22
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 22
- QHMBSVQNZZTUGM-UHFFFAOYSA-N Trans-Cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-UHFFFAOYSA-N 0.000 claims description 17
- QHMBSVQNZZTUGM-ZWKOTPCHSA-N cannabidiol Chemical compound OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-ZWKOTPCHSA-N 0.000 claims description 17
- ZTGXAWYVTLUPDT-UHFFFAOYSA-N cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CC=C(C)C1 ZTGXAWYVTLUPDT-UHFFFAOYSA-N 0.000 claims description 17
- 229950011318 cannabidiol Drugs 0.000 claims description 17
- PCXRACLQFPRCBB-ZWKOTPCHSA-N dihydrocannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)C)CCC(C)=C1 PCXRACLQFPRCBB-ZWKOTPCHSA-N 0.000 claims description 17
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 16
- 235000013305 food Nutrition 0.000 claims description 16
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 claims description 15
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 claims description 15
- 235000008390 olive oil Nutrition 0.000 claims description 14
- 239000004006 olive oil Substances 0.000 claims description 14
- 235000019864 coconut oil Nutrition 0.000 claims description 13
- 239000003240 coconut oil Substances 0.000 claims description 13
- ZLYNXDIDWUWASO-UHFFFAOYSA-N 6,6,9-trimethyl-3-pentyl-8,10-dihydro-7h-benzo[c]chromene-1,9,10-triol Chemical compound CC1(C)OC2=CC(CCCCC)=CC(O)=C2C2=C1CCC(C)(O)C2O ZLYNXDIDWUWASO-UHFFFAOYSA-N 0.000 claims description 12
- 235000019486 Sunflower oil Nutrition 0.000 claims description 12
- 150000003384 small molecules Chemical group 0.000 claims description 12
- 239000002600 sunflower oil Substances 0.000 claims description 12
- 241000196324 Embryophyta Species 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 10
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 claims description 9
- AAXZFUQLLRMVOG-UHFFFAOYSA-N 2-methyl-2-(4-methylpent-3-enyl)-7-propylchromen-5-ol Chemical compound C1=CC(C)(CCC=C(C)C)OC2=CC(CCC)=CC(O)=C21 AAXZFUQLLRMVOG-UHFFFAOYSA-N 0.000 claims description 8
- OIVPAQDCMDYIIL-UHFFFAOYSA-N 5-hydroxy-2-methyl-2-(4-methylpent-3-enyl)-7-propylchromene-6-carboxylic acid Chemical compound O1C(C)(CCC=C(C)C)C=CC2=C1C=C(CCC)C(C(O)=O)=C2O OIVPAQDCMDYIIL-UHFFFAOYSA-N 0.000 claims description 8
- NAGBBYZBIQVPIQ-UHFFFAOYSA-N 6-methyl-3-pentyl-9-prop-1-en-2-yldibenzofuran-1-ol Chemical compound C1=CC(C(C)=C)=C2C3=C(O)C=C(CCCCC)C=C3OC2=C1C NAGBBYZBIQVPIQ-UHFFFAOYSA-N 0.000 claims description 8
- 239000005711 Benzoic acid Substances 0.000 claims description 8
- UCONUSSAWGCZMV-HZPDHXFCSA-N Delta(9)-tetrahydrocannabinolic acid Chemical compound C([C@H]1C(C)(C)O2)CC(C)=C[C@H]1C1=C2C=C(CCCCC)C(C(O)=O)=C1O UCONUSSAWGCZMV-HZPDHXFCSA-N 0.000 claims description 8
- 235000010233 benzoic acid Nutrition 0.000 claims description 8
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 claims description 8
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 8
- 229940049964 oleate Drugs 0.000 claims description 8
- 239000003755 preservative agent Substances 0.000 claims description 8
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 7
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 7
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 claims description 7
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 claims description 7
- 229940070765 laurate Drugs 0.000 claims description 7
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 7
- 235000011067 sorbitan monolaureate Nutrition 0.000 claims description 7
- WIDIPARNVYRVNW-CHWSQXEVSA-N (6ar,10ar)-3,6,6,9-tetramethyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol Chemical compound CC1=CC(O)=C2[C@@H]3C=C(C)CC[C@H]3C(C)(C)OC2=C1 WIDIPARNVYRVNW-CHWSQXEVSA-N 0.000 claims description 6
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 claims description 6
- ICIDSZQHPUZUHC-UHFFFAOYSA-N 2-octadecoxyethanol Chemical compound CCCCCCCCCCCCCCCCCCOCCO ICIDSZQHPUZUHC-UHFFFAOYSA-N 0.000 claims description 6
- GKVOVXWEBSQJPA-UONOGXRCSA-N 5-methyl-2-[(1r,6r)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]benzene-1,3-diol Chemical compound CC(=C)[C@@H]1CCC(C)=C[C@H]1C1=C(O)C=C(C)C=C1O GKVOVXWEBSQJPA-UONOGXRCSA-N 0.000 claims description 6
- 230000002335 preservative effect Effects 0.000 claims description 6
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 claims description 5
- KWVPFECTOKLOBL-KTKRTIGZSA-N 2-[(z)-octadec-9-enoxy]ethanol Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCO KWVPFECTOKLOBL-KTKRTIGZSA-N 0.000 claims description 5
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 claims description 5
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims description 5
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 claims description 5
- 235000005687 corn oil Nutrition 0.000 claims description 5
- 239000002285 corn oil Substances 0.000 claims description 5
- SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 claims description 5
- 235000011803 sesame oil Nutrition 0.000 claims description 5
- 239000008159 sesame oil Substances 0.000 claims description 5
- OQCOBNKTUMOOHJ-RSGMMRJUSA-N (5as,6s,9r,9ar)-1,6-dihydroxy-6-methyl-3-pentyl-9-prop-1-en-2-yl-7,8,9,9a-tetrahydro-5ah-dibenzofuran-2-carboxylic acid Chemical compound C1=2C(O)=C(C(O)=O)C(CCCCC)=CC=2O[C@H]2[C@@H]1[C@H](C(C)=C)CC[C@]2(C)O OQCOBNKTUMOOHJ-RSGMMRJUSA-N 0.000 claims description 4
- HJMCQDCJBFTRPX-RSGMMRJUSA-N (5as,6s,9r,9ar)-1,6-dihydroxy-6-methyl-3-pentyl-9-prop-1-en-2-yl-7,8,9,9a-tetrahydro-5ah-dibenzofuran-4-carboxylic acid Chemical compound [C@H]1([C@@H](CC[C@@]2(O)C)C(C)=C)[C@@H]2Oc2c(C(O)=O)c(CCCCC)cc(O)c21 HJMCQDCJBFTRPX-RSGMMRJUSA-N 0.000 claims description 4
- RBEAVAMWZAJWOI-MTOHEIAKSA-N (5as,6s,9r,9ar)-6-methyl-3-pentyl-9-prop-1-en-2-yl-7,8,9,9a-tetrahydro-5ah-dibenzofuran-1,6-diol Chemical compound C1=2C(O)=CC(CCCCC)=CC=2O[C@H]2[C@@H]1[C@H](C(C)=C)CC[C@]2(C)O RBEAVAMWZAJWOI-MTOHEIAKSA-N 0.000 claims description 4
- IQSYWEWTWDEVNO-ZIAGYGMSSA-N (6ar,10ar)-1-hydroxy-6,6,9-trimethyl-3-propyl-6a,7,8,10a-tetrahydrobenzo[c]chromene-2-carboxylic acid Chemical compound C([C@H]1C(C)(C)O2)CC(C)=C[C@H]1C1=C2C=C(CCC)C(C(O)=O)=C1O IQSYWEWTWDEVNO-ZIAGYGMSSA-N 0.000 claims description 4
- ZROLHBHDLIHEMS-HUUCEWRRSA-N (6ar,10ar)-6,6,9-trimethyl-3-propyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCC)=CC(O)=C3[C@@H]21 ZROLHBHDLIHEMS-HUUCEWRRSA-N 0.000 claims description 4
- TZGCTXUTNDNTTE-DYZHCLJRSA-N (6ar,9s,10s,10ar)-6,6,9-trimethyl-3-pentyl-7,8,10,10a-tetrahydro-6ah-benzo[c]chromene-1,9,10-triol Chemical compound O[C@@H]1[C@@](C)(O)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 TZGCTXUTNDNTTE-DYZHCLJRSA-N 0.000 claims description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- YEDIZIGYIMTZKP-UHFFFAOYSA-N 1-methoxy-6,6,9-trimethyl-3-pentylbenzo[c]chromene Chemical compound C1=C(C)C=C2C3=C(OC)C=C(CCCCC)C=C3OC(C)(C)C2=C1 YEDIZIGYIMTZKP-UHFFFAOYSA-N 0.000 claims description 4
- CZXWOKHVLNYAHI-LSDHHAIUSA-N 2,4-dihydroxy-3-[(1r,6r)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-6-propylbenzoic acid Chemical compound OC1=C(C(O)=O)C(CCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 CZXWOKHVLNYAHI-LSDHHAIUSA-N 0.000 claims description 4
- TWKHUZXSTKISQC-UHFFFAOYSA-N 2-(5-methyl-2-prop-1-en-2-ylphenyl)-5-pentylbenzene-1,3-diol Chemical compound OC1=CC(CCCCC)=CC(O)=C1C1=CC(C)=CC=C1C(C)=C TWKHUZXSTKISQC-UHFFFAOYSA-N 0.000 claims description 4
- YJYIDZLGVYOPGU-XNTDXEJSSA-N 2-[(2e)-3,7-dimethylocta-2,6-dienyl]-5-propylbenzene-1,3-diol Chemical compound CCCC1=CC(O)=C(C\C=C(/C)CCC=C(C)C)C(O)=C1 YJYIDZLGVYOPGU-XNTDXEJSSA-N 0.000 claims description 4
- FAVCTJGKHFHFHJ-GXDHUFHOSA-N 3-[(2e)-3,7-dimethylocta-2,6-dienyl]-2,4-dihydroxy-6-propylbenzoic acid Chemical compound CCCC1=CC(O)=C(C\C=C(/C)CCC=C(C)C)C(O)=C1C(O)=O FAVCTJGKHFHFHJ-GXDHUFHOSA-N 0.000 claims description 4
- VAFRUJRAAHLCFZ-GHRIWEEISA-N 3-[(2e)-3,7-dimethylocta-2,6-dienyl]-2-hydroxy-4-methoxy-6-pentylbenzoic acid Chemical compound CCCCCC1=CC(OC)=C(C\C=C(/C)CCC=C(C)C)C(O)=C1C(O)=O VAFRUJRAAHLCFZ-GHRIWEEISA-N 0.000 claims description 4
- IPGGELGANIXRSX-RBUKOAKNSA-N 3-methoxy-2-[(1r,6r)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylphenol Chemical compound COC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 IPGGELGANIXRSX-RBUKOAKNSA-N 0.000 claims description 4
- IPGGELGANIXRSX-UHFFFAOYSA-N Cannabidiol monomethyl ether Natural products COC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CCC(C)=C1 IPGGELGANIXRSX-UHFFFAOYSA-N 0.000 claims description 4
- REOZWEGFPHTFEI-JKSUJKDBSA-N Cannabidivarin Chemical compound OC1=CC(CCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 REOZWEGFPHTFEI-JKSUJKDBSA-N 0.000 claims description 4
- KASVLYINZPAMNS-UHFFFAOYSA-N Cannabigerol monomethylether Natural products CCCCCC1=CC(O)=C(CC=C(C)CCC=C(C)C)C(OC)=C1 KASVLYINZPAMNS-UHFFFAOYSA-N 0.000 claims description 4
- ZROLHBHDLIHEMS-UHFFFAOYSA-N Delta9 tetrahydrocannabivarin Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCC)=CC(O)=C3C21 ZROLHBHDLIHEMS-UHFFFAOYSA-N 0.000 claims description 4
- 239000001534 FEMA 4201 Substances 0.000 claims description 4
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 4
- 235000014121 butter Nutrition 0.000 claims description 4
- NHZMSIOYBVIOAF-UHFFFAOYSA-N cannabichromanone A Natural products O=C1C(CCC(C)=O)C(C)(C)OC2=CC(CCCCC)=CC(O)=C21 NHZMSIOYBVIOAF-UHFFFAOYSA-N 0.000 claims description 4
- YJYIDZLGVYOPGU-UHFFFAOYSA-N cannabigeroldivarin Natural products CCCC1=CC(O)=C(CC=C(C)CCC=C(C)C)C(O)=C1 YJYIDZLGVYOPGU-UHFFFAOYSA-N 0.000 claims description 4
- VAFRUJRAAHLCFZ-UHFFFAOYSA-N cannabigerolic acid monomethyl ether Natural products CCCCCC1=CC(OC)=C(CC=C(C)CCC=C(C)C)C(O)=C1C(O)=O VAFRUJRAAHLCFZ-UHFFFAOYSA-N 0.000 claims description 4
- JVOHLEIRDMVLHS-UHFFFAOYSA-N ctk8i6127 Chemical compound C1=2C(O)=C(C(O)=O)C(CCCCC)=CC=2OC2(C)CCC3C(C)(C)C1C23 JVOHLEIRDMVLHS-UHFFFAOYSA-N 0.000 claims description 4
- 229940105132 myristate Drugs 0.000 claims description 4
- 229940097941 polyglyceryl-10 laurate Drugs 0.000 claims description 4
- 229940100518 polyglyceryl-4 isostearate Drugs 0.000 claims description 4
- 229940056099 polyglyceryl-4 oleate Drugs 0.000 claims description 4
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 claims description 4
- NLMKTBGFQGKQEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hexadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO NLMKTBGFQGKQEV-UHFFFAOYSA-N 0.000 claims description 3
- NKEQOUMMGPBKMM-UHFFFAOYSA-N 2-hydroxy-2-[2-(2-hydroxy-3-octadecanoyloxypropoxy)-2-oxoethyl]butanedioic acid Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CC(O)(C(O)=O)CC(O)=O NKEQOUMMGPBKMM-UHFFFAOYSA-N 0.000 claims description 3
- 235000019482 Palm oil Nutrition 0.000 claims description 3
- 235000000370 Passiflora edulis Nutrition 0.000 claims description 3
- 244000288157 Passiflora edulis Species 0.000 claims description 3
- 235000019483 Peanut oil Nutrition 0.000 claims description 3
- 235000021302 avocado oil Nutrition 0.000 claims description 3
- 239000008163 avocado oil Substances 0.000 claims description 3
- 235000019519 canola oil Nutrition 0.000 claims description 3
- 239000000828 canola oil Substances 0.000 claims description 3
- 229940056318 ceteth-20 Drugs 0.000 claims description 3
- 230000001815 facial effect Effects 0.000 claims description 3
- 229940074046 glyceryl laurate Drugs 0.000 claims description 3
- 229940100556 laureth-23 Drugs 0.000 claims description 3
- 229940095127 oleth-20 Drugs 0.000 claims description 3
- 239000002540 palm oil Substances 0.000 claims description 3
- 239000000312 peanut oil Substances 0.000 claims description 3
- ARIWANIATODDMH-UHFFFAOYSA-N rac-1-monolauroylglycerol Chemical compound CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 claims description 3
- 235000012424 soybean oil Nutrition 0.000 claims description 3
- 239000003549 soybean oil Substances 0.000 claims description 3
- 229940100459 steareth-20 Drugs 0.000 claims description 3
- 229940100458 steareth-21 Drugs 0.000 claims description 3
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 claims description 2
- IXJXRDCCQRZSDV-GCKMJXCFSA-N (6ar,9r,10as)-6,6,9-trimethyl-3-pentyl-6a,7,8,9,10,10a-hexahydro-6h-1,9-epoxybenzo[c]chromene Chemical compound C1C[C@@H](C(O2)(C)C)[C@@H]3C[C@]1(C)OC1=C3C2=CC(CCCCC)=C1 IXJXRDCCQRZSDV-GCKMJXCFSA-N 0.000 claims description 2
- KXKOBIRSQLNUPS-UHFFFAOYSA-N 1-hydroxy-6,6,9-trimethyl-3-pentylbenzo[c]chromene-2-carboxylic acid Chemical compound O1C(C)(C)C2=CC=C(C)C=C2C2=C1C=C(CCCCC)C(C(O)=O)=C2O KXKOBIRSQLNUPS-UHFFFAOYSA-N 0.000 claims description 2
- YUSLYKMVQSVFDX-UHFFFAOYSA-N 2,2,3,3,4-pentahydroxyoctadecanoic acid Chemical compound CCCCCCCCCCCCCCC(O)C(O)(O)C(O)(O)C(O)=O YUSLYKMVQSVFDX-UHFFFAOYSA-N 0.000 claims description 2
- COURSARJQZMTEZ-UHFFFAOYSA-N 2-(5-methyl-2-prop-1-en-2-ylphenyl)-5-propylbenzene-1,3-diol Chemical compound OC1=CC(CCC)=CC(O)=C1C1=CC(C)=CC=C1C(C)=C COURSARJQZMTEZ-UHFFFAOYSA-N 0.000 claims description 2
- JKXYOQDLERSFPT-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-octadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO JKXYOQDLERSFPT-UHFFFAOYSA-N 0.000 claims description 2
- XWIWWMIPMYDFOV-UHFFFAOYSA-N 3,6,6,9-tetramethylbenzo[c]chromen-1-ol Chemical compound C1=C(C)C=C2OC(C)(C)C3=CC=C(C)C=C3C2=C1O XWIWWMIPMYDFOV-UHFFFAOYSA-N 0.000 claims description 2
- OYHQOLUKZRVURQ-HZJYTTRNSA-M 9-cis,12-cis-Octadecadienoate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC([O-])=O OYHQOLUKZRVURQ-HZJYTTRNSA-M 0.000 claims description 2
- UVOLYTDXHDXWJU-UHFFFAOYSA-N Cannabichromene Chemical compound C1=CC(C)(CCC=C(C)C)OC2=CC(CCCCC)=CC(O)=C21 UVOLYTDXHDXWJU-UHFFFAOYSA-N 0.000 claims description 2
- VBGLYOIFKLUMQG-UHFFFAOYSA-N Cannabinol Chemical compound C1=C(C)C=C2C3=C(O)C=C(CCCCC)C=C3OC(C)(C)C2=C1 VBGLYOIFKLUMQG-UHFFFAOYSA-N 0.000 claims description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 2
- SBPMGFIOIRMBJJ-UHFFFAOYSA-N Delta7-cis-iso-tetrahydrocannabivarin Natural products C1C2(C)CCC(C(C)=C)C1C1=C(O)C=C(CCC)C=C1O2 SBPMGFIOIRMBJJ-UHFFFAOYSA-N 0.000 claims description 2
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 claims description 2
- 235000019487 Hazelnut oil Nutrition 0.000 claims description 2
- 229920002884 Laureth 4 Polymers 0.000 claims description 2
- IGHTZQUIFGUJTG-QSMXQIJUSA-N O1C2=CC(CCCCC)=CC(O)=C2[C@H]2C(C)(C)[C@@H]3[C@H]2[C@@]1(C)CC3 Chemical compound O1C2=CC(CCCCC)=CC(O)=C2[C@H]2C(C)(C)[C@@H]3[C@H]2[C@@]1(C)CC3 IGHTZQUIFGUJTG-QSMXQIJUSA-N 0.000 claims description 2
- NPEWUNHSWNKPTP-UHFFFAOYSA-N OC(C(C(C(C(=O)O)(O)O)(O)O)(O)O)CCCCCCCCCCCCC Chemical compound OC(C(C(C(C(=O)O)(O)O)(O)O)(O)O)CCCCCCCCCCCCC NPEWUNHSWNKPTP-UHFFFAOYSA-N 0.000 claims description 2
- 235000019485 Safflower oil Nutrition 0.000 claims description 2
- 229930003268 Vitamin C Natural products 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- RRQVSLLVCGRJNI-UHFFFAOYSA-N ac1l4h72 Chemical compound C1C2(C)CCC(C(C)(C)O)C1C1=C(O)C=C(CCC)C=C1O2 RRQVSLLVCGRJNI-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 229940116224 behenate Drugs 0.000 claims description 2
- UKMSUNONTOPOIO-UHFFFAOYSA-M behenate Chemical compound CCCCCCCCCCCCCCCCCCCCCC([O-])=O UKMSUNONTOPOIO-UHFFFAOYSA-M 0.000 claims description 2
- HRHJHXJQMNWQTF-UHFFFAOYSA-N cannabichromenic acid Chemical compound O1C(C)(CCC=C(C)C)C=CC2=C1C=C(CCCCC)C(C(O)=O)=C2O HRHJHXJQMNWQTF-UHFFFAOYSA-N 0.000 claims description 2
- WVOLTBSCXRRQFR-DLBZAZTESA-N cannabidiolic acid Chemical compound OC1=C(C(O)=O)C(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 WVOLTBSCXRRQFR-DLBZAZTESA-N 0.000 claims description 2
- REOZWEGFPHTFEI-UHFFFAOYSA-N cannabidivarine Natural products OC1=CC(CCC)=CC(O)=C1C1C(C(C)=C)CCC(C)=C1 REOZWEGFPHTFEI-UHFFFAOYSA-N 0.000 claims description 2
- QXACEHWTBCFNSA-SFQUDFHCSA-N cannabigerol Chemical compound CCCCCC1=CC(O)=C(C\C=C(/C)CCC=C(C)C)C(O)=C1 QXACEHWTBCFNSA-SFQUDFHCSA-N 0.000 claims description 2
- SEEZIOZEUUMJME-FOWTUZBSSA-N cannabigerolic acid Chemical compound CCCCCC1=CC(O)=C(C\C=C(/C)CCC=C(C)C)C(O)=C1C(O)=O SEEZIOZEUUMJME-FOWTUZBSSA-N 0.000 claims description 2
- SVTKBAIRFMXQQF-UHFFFAOYSA-N cannabivarin Chemical compound C1=C(C)C=C2C3=C(O)C=C(CCC)C=C3OC(C)(C)C2=C1 SVTKBAIRFMXQQF-UHFFFAOYSA-N 0.000 claims description 2
- 229940073669 ceteareth 20 Drugs 0.000 claims description 2
- 229940030275 epigallocatechin gallate Drugs 0.000 claims description 2
- 150000002194 fatty esters Chemical class 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 239000008169 grapeseed oil Substances 0.000 claims description 2
- 239000010468 hazelnut oil Substances 0.000 claims description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 claims description 2
- 229940113096 isoceteth 20 Drugs 0.000 claims description 2
- 229940061515 laureth-4 Drugs 0.000 claims description 2
- 229940049918 linoleate Drugs 0.000 claims description 2
- 235000021388 linseed oil Nutrition 0.000 claims description 2
- 239000000944 linseed oil Substances 0.000 claims description 2
- 229940043733 polyglyceryl-10 decaoleate Drugs 0.000 claims description 2
- 229940061570 polyglyceryl-10 stearate Drugs 0.000 claims description 2
- 229940043707 polyglyceryl-6 distearate Drugs 0.000 claims description 2
- 229940104257 polyglyceryl-6-dioleate Drugs 0.000 claims description 2
- 235000005713 safflower oil Nutrition 0.000 claims description 2
- 239000003813 safflower oil Substances 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 235000019154 vitamin C Nutrition 0.000 claims description 2
- 239000011718 vitamin C Substances 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 229940046009 vitamin E Drugs 0.000 claims description 2
- SBPMGFIOIRMBJJ-CTHAPGQVSA-N δ-7-cis-isotetrahydrocannabivarin Chemical compound C1[C@@]2(C)CC[C@@H](C(C)=C)C1C1=C(O)C=C(CCC)C=C1O2 SBPMGFIOIRMBJJ-CTHAPGQVSA-N 0.000 claims description 2
- 229940025703 topical product Drugs 0.000 claims 5
- 210000003491 skin Anatomy 0.000 claims 4
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims 1
- 208000002874 Acne Vulgaris Diseases 0.000 claims 1
- 235000019737 Animal fat Nutrition 0.000 claims 1
- CIWBSHSKHKDKBQ-DUZGATOHSA-N D-araboascorbic acid Natural products OC[C@@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-DUZGATOHSA-N 0.000 claims 1
- 201000004624 Dermatitis Diseases 0.000 claims 1
- 239000004398 Ethyl lauroyl arginate Substances 0.000 claims 1
- 208000004898 Herpes Labialis Diseases 0.000 claims 1
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- 206010067152 Oral herpes Diseases 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
- 235000019774 Rice Bran oil Nutrition 0.000 claims 1
- 241001303601 Rosacea Species 0.000 claims 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims 1
- 206010000496 acne Diseases 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 claims 1
- 235000010323 ascorbic acid Nutrition 0.000 claims 1
- 239000011668 ascorbic acid Substances 0.000 claims 1
- 229960005070 ascorbic acid Drugs 0.000 claims 1
- 208000010668 atopic eczema Diseases 0.000 claims 1
- 229960004365 benzoic acid Drugs 0.000 claims 1
- 235000010376 calcium ascorbate Nutrition 0.000 claims 1
- 239000011692 calcium ascorbate Substances 0.000 claims 1
- 229940047036 calcium ascorbate Drugs 0.000 claims 1
- MCFVRESNTICQSJ-RJNTXXOISA-L calcium sorbate Chemical compound [Ca+2].C\C=C\C=C\C([O-])=O.C\C=C\C=C\C([O-])=O MCFVRESNTICQSJ-RJNTXXOISA-L 0.000 claims 1
- 235000010244 calcium sorbate Nutrition 0.000 claims 1
- 239000004303 calcium sorbate Substances 0.000 claims 1
- BLORRZQTHNGFTI-ZZMNMWMASA-L calcium-L-ascorbate Chemical compound [Ca+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] BLORRZQTHNGFTI-ZZMNMWMASA-L 0.000 claims 1
- 235000013351 cheese Nutrition 0.000 claims 1
- 229960004106 citric acid Drugs 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- 210000002615 epidermis Anatomy 0.000 claims 1
- 235000010350 erythorbic acid Nutrition 0.000 claims 1
- 239000004318 erythorbic acid Substances 0.000 claims 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims 1
- XJTMYVOVQZMMKX-KRWDZBQOSA-N ethyl (2s)-5-(diaminomethylideneamino)-2-(dodecanoylamino)pentanoate Chemical compound CCCCCCCCCCCC(=O)N[C@H](C(=O)OCC)CCCN=C(N)N XJTMYVOVQZMMKX-KRWDZBQOSA-N 0.000 claims 1
- 235000019455 ethyl lauroyl arginate Nutrition 0.000 claims 1
- 230000007794 irritation Effects 0.000 claims 1
- 229940026239 isoascorbic acid Drugs 0.000 claims 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
- 235000010235 potassium benzoate Nutrition 0.000 claims 1
- 239000004300 potassium benzoate Substances 0.000 claims 1
- 229940103091 potassium benzoate Drugs 0.000 claims 1
- 235000010241 potassium sorbate Nutrition 0.000 claims 1
- 239000004302 potassium sorbate Substances 0.000 claims 1
- 229940069338 potassium sorbate Drugs 0.000 claims 1
- 239000008165 rice bran oil Substances 0.000 claims 1
- 201000004700 rosacea Diseases 0.000 claims 1
- 235000010378 sodium ascorbate Nutrition 0.000 claims 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims 1
- 229960005055 sodium ascorbate Drugs 0.000 claims 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims 1
- 235000010234 sodium benzoate Nutrition 0.000 claims 1
- 239000004299 sodium benzoate Substances 0.000 claims 1
- 229960003885 sodium benzoate Drugs 0.000 claims 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 claims 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims 1
- 235000010199 sorbic acid Nutrition 0.000 claims 1
- 239000004334 sorbic acid Substances 0.000 claims 1
- 229940075582 sorbic acid Drugs 0.000 claims 1
- 229940100615 topical ointment Drugs 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 32
- 229940005741 sunflower lecithin Drugs 0.000 description 19
- 238000000527 sonication Methods 0.000 description 18
- 239000000341 volatile oil Substances 0.000 description 18
- 235000019658 bitter taste Nutrition 0.000 description 17
- 239000007788 liquid Substances 0.000 description 16
- 239000000796 flavoring agent Substances 0.000 description 14
- 235000007586 terpenes Nutrition 0.000 description 12
- 239000004615 ingredient Substances 0.000 description 11
- 150000003505 terpenes Chemical class 0.000 description 11
- 238000010790 dilution Methods 0.000 description 10
- 239000012895 dilution Substances 0.000 description 10
- 238000002156 mixing Methods 0.000 description 10
- 239000003925 fat Substances 0.000 description 9
- 235000019197 fats Nutrition 0.000 description 9
- 229920001223 polyethylene glycol Polymers 0.000 description 9
- 235000019640 taste Nutrition 0.000 description 9
- 230000008859 change Effects 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 235000019634 flavors Nutrition 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 235000013361 beverage Nutrition 0.000 description 7
- 229940065144 cannabinoids Drugs 0.000 description 7
- 235000003084 food emulsifier Nutrition 0.000 description 7
- 239000000419 plant extract Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000000699 topical effect Effects 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- 235000013355 food flavoring agent Nutrition 0.000 description 6
- 239000002105 nanoparticle Substances 0.000 description 6
- 150000008442 polyphenolic compounds Chemical class 0.000 description 6
- 235000013824 polyphenols Nutrition 0.000 description 6
- 235000010469 Glycine max Nutrition 0.000 description 5
- 235000019501 Lemon oil Nutrition 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000010501 lemon oil Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000002537 cosmetic Substances 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 4
- CDOSHBSSFJOMGT-UHFFFAOYSA-N linalool Chemical compound CC(C)=CCCC(C)(O)C=C CDOSHBSSFJOMGT-UHFFFAOYSA-N 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- HBXWUCXDUUJDRB-UHFFFAOYSA-N 1-octadecoxyoctadecane Chemical compound CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCC HBXWUCXDUUJDRB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000208818 Helianthus Species 0.000 description 3
- 235000003222 Helianthus annuus Nutrition 0.000 description 3
- 235000006679 Mentha X verticillata Nutrition 0.000 description 3
- 235000002899 Mentha suaveolens Nutrition 0.000 description 3
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- DTPCFIHYWYONMD-UHFFFAOYSA-N decaethylene glycol Polymers OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO DTPCFIHYWYONMD-UHFFFAOYSA-N 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000002296 dynamic light scattering Methods 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 239000010649 ginger oil Substances 0.000 description 3
- 238000007913 intrathecal administration Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 150000002632 lipids Chemical group 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000003904 phospholipids Chemical group 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 239000001490 (3R)-3,7-dimethylocta-1,6-dien-3-ol Substances 0.000 description 2
- CDOSHBSSFJOMGT-JTQLQIEISA-N (R)-linalool Natural products CC(C)=CCC[C@@](C)(O)C=C CDOSHBSSFJOMGT-JTQLQIEISA-N 0.000 description 2
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 2
- CMCBDXRRFKYBDG-UHFFFAOYSA-N 1-dodecoxydodecane Chemical compound CCCCCCCCCCCCOCCCCCCCCCCCC CMCBDXRRFKYBDG-UHFFFAOYSA-N 0.000 description 2
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 2
- 240000002791 Brassica napus Species 0.000 description 2
- 235000004977 Brassica sinapistrum Nutrition 0.000 description 2
- 240000007436 Cananga odorata Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 235000005979 Citrus limon Nutrition 0.000 description 2
- 244000131522 Citrus pyriformis Species 0.000 description 2
- 206010013911 Dysgeusia Diseases 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- 239000004907 Macro-emulsion Substances 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 2
- UAHWPYUMFXYFJY-UHFFFAOYSA-N beta-myrcene Natural products CC(C)=CCCC(=C)C=C UAHWPYUMFXYFJY-UHFFFAOYSA-N 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940112822 chewing gum Drugs 0.000 description 2
- 235000015218 chewing gum Nutrition 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000008157 edible vegetable oil Substances 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 2
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 2
- 229960005135 eicosapentaenoic acid Drugs 0.000 description 2
- 150000002191 fatty alcohols Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000001510 limonene Nutrition 0.000 description 2
- 229940087305 limonene Drugs 0.000 description 2
- 229930007744 linalool Natural products 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 235000019477 peppermint oil Nutrition 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 229920000223 polyglycerol Polymers 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 235000020238 sunflower seed Nutrition 0.000 description 2
- NPNUFJAVOOONJE-ZIAGYGMSSA-N β-(E)-Caryophyllene Chemical compound C1CC(C)=CCCC(=C)[C@H]2CC(C)(C)[C@@H]21 NPNUFJAVOOONJE-ZIAGYGMSSA-N 0.000 description 2
- DVSZKTAMJJTWFG-SKCDLICFSA-N (2e,4e,6e,8e,10e,12e)-docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCC\C=C\C=C\C=C\C=C\C=C\C=C\C(O)=O DVSZKTAMJJTWFG-SKCDLICFSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- OUUCZGCOAXRCHN-UHFFFAOYSA-N 1-hexadecoxyoctadecane Chemical compound CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC OUUCZGCOAXRCHN-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- LLJBKECMPVCSDS-UHFFFAOYSA-N 3-[1-[(3,5-dimethylisoxazol-4-yl)methyl]pyrazol-4-yl]-1-[(3-hydroxyphenyl)methyl]imidazolidine-2,4-dione Chemical compound CC1=NOC(C)=C1CN1N=CC(N2C(N(CC=3C=C(O)C=CC=3)CC2=O)=O)=C1 LLJBKECMPVCSDS-UHFFFAOYSA-N 0.000 description 1
- GZJLLYHBALOKEX-UHFFFAOYSA-N 6-Ketone, O18-Me-Ussuriedine Natural products CC=CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O GZJLLYHBALOKEX-UHFFFAOYSA-N 0.000 description 1
- 235000008499 Canella winterana Nutrition 0.000 description 1
- 244000080208 Canella winterana Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 244000089742 Citrus aurantifolia Species 0.000 description 1
- 241001539473 Euphoria Species 0.000 description 1
- 206010015535 Euphoric mood Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 240000007651 Rubus glaucus Species 0.000 description 1
- 235000011034 Rubus glaucus Nutrition 0.000 description 1
- 235000009122 Rubus idaeus Nutrition 0.000 description 1
- 235000000944 Santalum spicatum Nutrition 0.000 description 1
- 244000174883 Santalum spicatum Species 0.000 description 1
- AOBORMOPSGHCAX-UHFFFAOYSA-N Tocophersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-UHFFFAOYSA-N 0.000 description 1
- 235000009499 Vanilla fragrans Nutrition 0.000 description 1
- 244000263375 Vanilla tahitensis Species 0.000 description 1
- 235000012036 Vanilla tahitensis Nutrition 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 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
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- NPNUFJAVOOONJE-UHFFFAOYSA-N beta-cariophyllene Natural products C1CC(C)=CCCC(=C)C2CC(C)(C)C21 NPNUFJAVOOONJE-UHFFFAOYSA-N 0.000 description 1
- 239000001342 boswellia carteri birdw. oil Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- NPNUFJAVOOONJE-UONOGXRCSA-N caryophyllene Natural products C1CC(C)=CCCC(=C)[C@@H]2CC(C)(C)[C@@H]21 NPNUFJAVOOONJE-UONOGXRCSA-N 0.000 description 1
- 239000010627 cedar oil Substances 0.000 description 1
- 235000019480 chamomile oil Nutrition 0.000 description 1
- 239000010628 chamomile oil Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229940017545 cinnamon bark Drugs 0.000 description 1
- 239000001279 citrus aurantifolia swingle expressed oil Substances 0.000 description 1
- 239000001926 citrus aurantium l. subsp. bergamia wright et arn. oil Substances 0.000 description 1
- 239000010634 clove oil Substances 0.000 description 1
- 239000010635 coffee oil Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012611 container material Substances 0.000 description 1
- 229910052593 corundum Inorganic materials 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000001941 cymbopogon citratus dc and cymbopogon flexuosus oil Substances 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 235000020669 docosahexaenoic acid Nutrition 0.000 description 1
- KAUVQQXNCKESLC-UHFFFAOYSA-N docosahexaenoic acid (DHA) Natural products COC(=O)C(C)NOCC1=CC=CC=C1 KAUVQQXNCKESLC-UHFFFAOYSA-N 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000010642 eucalyptus oil Substances 0.000 description 1
- 229940044949 eucalyptus oil Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000002864 food coloring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- 239000010651 grapefruit oil Substances 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000001683 mentha spicata herb oil Substances 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000001738 pogostemon cablin oil Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000003134 recirculating effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000010668 rosemary oil Substances 0.000 description 1
- 229940058206 rosemary oil Drugs 0.000 description 1
- 239000010671 sandalwood oil Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 235000019721 spearmint oil Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 210000001779 taste bud Anatomy 0.000 description 1
- 239000010677 tea tree oil Substances 0.000 description 1
- 229940111630 tea tree oil Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910001845 yogo sapphire Inorganic materials 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/06—Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/39—Derivatives containing from 2 to 10 oxyalkylene groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
- A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B9/00—Essential oils; Perfumes
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/21—Emulsions characterized by droplet sizes below 1 micron
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/92—Oral administration
Definitions
- the field of the invention is cannabinoid emulsions.
- cannabinoids are not water soluble and therefore only a small percentage of the consumed cannabinoid content is absorbed by the human body. Moreover, because cannabinoids are not water soluble, it is difficult to put it in common foods and drinks. Finally, the low aqueous solubility also contributes to lower potency and slower onset of action in lower doses.
- Nanoparticles comprising cannabis are one way to improve solubility.
- US20180296493A1 to Richard Clark Kaufman teaches a nanosphere compositional structure comprising encapsulated cannabinoid.
- PCT/US2017/049219 discloses a cannabinoid nanoemulsion made from surfactant Vitamin E TPGS.
- US20120202891A1 discloses a gel comprising cannabis nanoparticles
- US20170265494 discloses a chewing gum having a liquid center and the liquid center comprises “nanozome” encapsulated cannabinoid.
- the stability of such nanoparticles disclosed is less than desirable, especially upon dilution in an aqueous carrier.
- at least some nanoparticle formulations tend to suffer from particle aggregation.
- the taste of the cannabinoid nanoparticles also remains unknown.
- cannabinoid nano-emulsion compositions, methods, and kits comprising: a cannabinoid oil, a dietically acceptable carrier oil, at least one surfactant, and water.
- the amount of water is at least 1.15 times the amount of the combination of the cannabinoid oil, the dietically acceptable carrier oil, and the surfactant.
- the amount of the dietically acceptable carrier oil is contemplated to be at least 0.3 times the amount of the cannabinoid oil.
- the amount of the surfactant is at least 1.45 times the amount of cannabinoid oil, and/or the amount of surfactant is at least 1.35 times the amount of carrier oil, and/or the amount of surfactant is at least 1.15 times the amount of combination of cannabinoid oil and carrier oil.
- the at least one surfactant contemplated herein may comprise a tween surfactant, a polyglyceryl surfactant, a long chain PEG surfactant, or combinations thereof.
- the amount of the surfactant in the composition depends on the hydrophilic-lipophilic balance (HLB).
- the amount of the surfactant is at least 0.65 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil; if the HLB of the surfactant is between 11 and 13, then the amount of the surfactant is at least 0.8 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil; and if the HLB of the surfactant is between 8.5 and 11, then the amount of the surfactant is at least 0.95 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil;
- the composition may have one or more surfactants.
- a main surfactant and a co-surfactant When there are two surfactants, say a main surfactant and a co-surfactant, and the amount of the main surfactant is at least 1.05 times the amount of combination of cannabinoid oil and carrier oil.
- the co-surfactant is contemplated to be a small molecule food surfactant, a natural lecithin, a purified lecithin, or combinations thereof.
- the amount of the co-surfactant is at least 0.75 times the amount of the dietically acceptable carrier oil; if the co-surfactant is a purified lecithin, then the amount of the co-surfactant is at least 0.50 times the amount of the dietically acceptable carrier oil; and if the co-surfactant is a small molecule food emulsifier, then the amount of the co-surfactant is at least 0.80 times the amount of the dietically acceptable carrier oil.
- the cannabinoid oil in the composition may comprise a phyto-cannabinoid or a synthetic cannabinoid.
- the composition may further comprise one or more preservatives, a flavoring agent, a bitter blocker, an essential oil and/or a terpene.
- the average diameter or Z-average of the nano-emulsions in the composition is preferably smaller than 100 nm, when tested by Dynamic Light Scattering, and in some cases, about 80% of the nano-droplets in the composition are contemplated to have a droplet size between 30-50 nm.
- the composition disclosed herein may be a liquid composition.
- the composition remains in dispersed form upon dilution in aqueous solution.
- the droplet size remains unaffected upon dilution in aqueous solution.
- the composition can be stored at room temperature for at least 6 months, or in a 55° C. oven for up to 12 weeks, without change in droplet size.
- a method of making a nano-emulsion composition comprising: mixing a cannabinoid oil, a dietically acceptable carrier oil, a main surfactant, a co-surfactant; adding water to the composition and mixing to form a coarse emulsion; and inputting energy by sonication, high shearing or microfluidic droplet generating into the mixture under temperature control until the nano-emulsions are formed.
- the temperature of the mixture is kept below 75° C. during the mixing process.
- a method of using a nano-emulsion composition comprising: administering the composition by inhalation, targeting systemic, parenteral, oral, intrathecal, intraarticular, nasal, ophthalmic and/or topical means, wherein the nano-emulsion composition comprises a cannabinoid oil, a dietically acceptable carrier oil, a main surfactant, a co-surfactant and water.
- the composition is contemplated to be added to a beverage or food prior to oral administration.
- FIG. 1 illustrates, in accordance with the embodiments herein, (A) a currently available macroemulsion cannabinoid product dispersed in water and its droplet size distribution, compared with (B) the newly disclosed nanodroplet cannabinoid composition dispersed in water and its droplet size distribution.
- FIG. 2 illustrates, in accordance with the embodiments herein, initial emulsion droplet size of the composition disclosed herein.
- the initial emulsion concentration was kept at 25 mg/mL.
- FIG. 3 illustrates, in accordance with the embodiments herein, that no precipitation was observed upon dilution of concentrated composition.
- the concentrated composition can be diluted by any fold to make the final product.
- FIG. 4 illustrates, in accordance with the embodiments herein, nanosized emulsion droplets does not change its size upon dilution.
- FIG. 7 illustrates, in accordance with the embodiments herein, emulsion stability under refrigerated conditions over four weeks, no reversed phase transformation or precipitates observed. And it also showed the emulsion is compatible with polypropylene plastic material.
- FIG. 8 illustrates, in accordance with the embodiments herein, the high repeatability and reliability of nano-emulsion potency result tested at different concentrations, detected by HPLC-DAD.
- FIG. 9 illustrates, in accordance with the embodiments herein, linearity of potency control uses the nano-emulsion.
- FIG. 10 illustrates, in accordance with the embodiments herein, droplet size change over sonication time. Smaller size can be obtained by higher energy input.
- FIG. 11 illustrates, in accordance with the embodiments herein, the appearance of the concentrated nano-emulsion at different droplet size distributions, which can be controlled and obtained by altering the sonication amplitude and time.
- compositions, kits, and methods comprising nanosized droplets, wherein the nanosized droplets comprise a hydrophobic substance, a dietically acceptable carrier oil, a surfactant or surfactant system, and a phospholipid form.
- Contemplated compositions and methods overcome the current problems with cannabinoids—most current products available are macro emulsions which have drawbacks such as long-term instability, short shelf life, slow on-set time, unappealing taste and appearance, and due to its un-even distribution in water over time and often times tend to stick to the inner surface of container, the potency and homogeneity test often fail.
- the compositions disclosed herein overcome these problems, and as discussed herein, have fast onset time, long term stability, long shelf life, compatible with various container materials and a more controlled result on potency test. The droplet size remains stable over time and upon dilution.
- compositions provided herein have several advantages over the currently available cannabinoid compositions.
- onset time or bioavailability upon smoking cannabis, only 2-45% of THC can be absorbed by lung; upon eating cannabis, only 8-15% of THC can be absorbed and it is also slow to react.
- One advantage of the nanosized droplet composition provided herein is the high bioavailability and fast onset, which occurs because the large surface area of these nanosized droplets easily attach to mucus surface and works on the body instantly.
- an adult human subject upon consuming 10 mg of the composition comprising THC as disclosed herein, an adult human subject felt lightheaded in about 10 minutes, euphoria in about 20 minutes, hunger in about 37 minutes, and happy (laughing and dancing) in about 40 minutes.
- the lecithin in the composition may form a bilayer structure, called liposome, which traps the THC inside.
- the lecithin sits on the edge of the oil droplets. Lecithin can help quicker absorption of the cannabinoid into the body.
- onset time may depend on body size and whether the stomach is empty or full. Empty stomach often gives a much faster onset time.
- the inventive subject matter provides new nano-emulsion compositions comprising: a cannabinoid oil, a dietically acceptable carrier oil, a surfactant, and water, wherein the amount of water is at least 1.15 times the amount of the combination of the cannabinoid oil, the dietically acceptable carrier oil, and the surfactant; and wherein the amount of the dietically acceptable carrier oil is at least 0.3 times the amount of the cannabinoid oil.
- the composition may comprise more than one surfactant, such as a main surfactant and a co-surfactant.
- nano-droplet and “nano-emulsion” are used interchangeably in this disclosure, and refers to dispersions or droplets comprising water, oil, and surfactant(s), as well as other lipid structures that can form as a result of hydrophobic forces that drive apolar residues (example, long hydrocarbon chains) away from water and drive polar head groups toward water, when a water immiscible oily phase is mixed with an aqueous phase.
- lipid structures include, but are not limited to, unilamellar, paucilamellar, and multilamellar lipid vesicles, micelles, and lamellar phases.
- the hydrophilic-lipophilic balance (HLB) of the surfactant plays an important role in determining its amount in the composition. If the HLB is >13, then the amount of the surfactant, or the main surfactant if there are more than one surfactant in the composition, is at least 0.65 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil. In one embodiment, if the HLB of the surfactant, or the main surfactant if there are more than one surfactant in the composition, is between 11 and 13, then the amount of the main surfactant is at least 0.8 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil.
- the amount of the main surfactant is at least 0.95 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil.
- the average droplet size in the composition is less than 100 nm, either at raw emulsion level and/or at the diluted level, for example, 0.1 mg/g. In some cases, 80% of the droplets have a droplet size between 10-70 nm, or more preferably a droplet size of 30-50 nm.
- the size and stability of the droplet does not vary with dilution or time, and the composition can be stored at room temperature for at least 12 months, or preferably at least 18 months, or more preferably at least 24 months, or more preferably at least 30 months, or most preferably at least 36 months without change in droplet size.
- the cannabinoid may be a naturally occurring phytocannabinoid or a synthetic cannabinoid.
- the cannabinoid may be Tetrahydrocannabinol (THC) or Cannabidiol (CBD), any other single cannabinoids or combinations thereof.
- THC Tetrahydrocannabinol
- CBD Cannabidiol
- the purity of the cannabinoid can be low pure (full plant distillate) or high pure (distillate).
- the cannabinoid is selected from Tetrahydrocannabinolic acid A (THCA-A), Tetrahydrocannabinolic acid B (THCA-B), Tetrahydrocannabinol (THC), Tetrahydrocannabinolic acid C (THCA-C), Tetrahydrocannbinol C (THC-C), Tetrahydrocannabi varinic acid (THCVA), Tetrahydrocannabivarin (THCV), Tetrahydrocannabiorcolic acid (THCA-C), Tetrahydrocannabiorcol (THC-C), Delta-7-cis-iso-tetrahydrocannabi varin, A-tetrahydrocannabinolic acid (A8-THCA), A-tetrahydrocannabinol (A-THC), Cannabidiolic Acid (CBDA), Cannabidiol (CBD), Cannabidiol monomethyl ether (CBDM), Cannabidiol-
- the dietically acceptable carrier oil may comprise plant derived oils or animal derived oils.
- Plant derived oils contemplated in the composition include sunflower oil, olive oil, coconut oil, sesame oil, avocado oil, palm oil, soybean oil, corn oil, peanut oil, canola oil, grape seed oil, corn oil, hazelnut oil, rice bran oi, linseed oil, safflower oil, sesame oil, passion fruit oil or combinations thereof.
- the dietically acceptable carrier oil may also comprise animal derived oils, including lard, butter, animal fats or combinations thereof.
- the surfactant may comprise one surfactant or a mixture of surfactants.
- the surfactant may be a high molecular weight main surfactant and a co-surfactant of lower molecular weight.
- the main surfactant may be a tween surfactant, a polyglyceryl surfactant, and/or a long chain PEG surfactant.
- the tween surfactant may be selected from the group consisting of Tween 20, Tween 40, Tween 45, Tween 60, Tween 65, Tween 80, Tween 81 and Tween 85.
- the polyglyceryl surfactant is selected either from polyglyceryl monoesters or polyglyceryl multi-esters.
- polyglyceryl monoesters contemplated herein include Polyglyceryl-4 Caprate, Polyglyceryl-4 Caprylate, Polyglyceryl-4 Laurate, Polyglyceryl-4 Isostearate, Polyglyceryl-4 Oleate, Polyglyceryl-5 Laurate, Polyglyceryl-5 Myristate, Polyglyceryl-5 Isostearate, Polyglyceryl-5 Oleate, Polyglyceryl-5 Stearate, Polyglyceryl-6 Isostearate, Polyglyceryl-6 Oleate, Polyglyceryl-6 Stearate, Polyglyceryl-8 Oleate Polyglyceryl-8 Stearate, Polyglyceryl-10 Laurate, Polyglyceryl-10 Myristate, Polyglyceryl-10 Palmitate, Polyglyceryl-10 Isostearate, Polyglyceryl-10 Linoleate, Polyglyceryl-10 Oleate, Polyglyceryl-10 Stearate, Polyglyceryl-10 Behenate/E
- Polyglyceryl multi-esters contemplated in the composition disclosed herein include Polyglyceryl-5 Triisostearate, Polyglyceryl-5 Dioleate, Polyglyceryl-5 Trioleate, Polyglyceryl-6 Tricaprylate, Polyglyceryl-6 Dioleate, Polyglyceryl-6 Distearate, Polyglyceryl-6 Pentastearate, Polyglyceryl-6 Octastearate, Polyglyceryl-8 Decaerucate/Decaisostearate/Decaricinoleate, Polyglyceryl-10 Caprylate/Caprate, Polyglyceryl-10 Dipalmitate, Polyglyceryl-10 Diisostearate, Polyglyceryl-10 Pentaisostearate, Polyglyceryl-10 Nonaisostearate, Polyglyceryl-10 Decaisostearate, Polyglyceryl-10 Dioleate, Polyglyceryl-10 Pentaoleate, Polyglyceryl-10 Decaoleate, Polyglyceryl-10 Di
- the long chain PEG surfactant is preferably a non-ionic surfactant sold under the trademark BRIJ®.
- BRIJ® CS20 (Ceteareth-20, Polyoxyethylene (20) Cetyl Stearyl Ether), BRIJ® C10 (Ceteth-10, Polyoxyethylene (10) cetyl ether), BRIJ® C20 (Ceteth-20, Polyoxyethylene (20) cetyl ether), BRIJ® IC20 (Isoceteth-20, Alkoxylated ether), BRIJ® IC20-70 (Isocetech-20 (Alkoxylated ether) and Aqua), BRIJ® L4 (Laureth-4, Ethoxylated Fatty Alcohol), BRIJ® L23 (Laureth-23, Polyoxyethylene (23) lauryl ether), BRIJ® L23-69 (Laureth-23 (Polyoxyethylene (23) lauryl ether) and Aqua), BRIJ® O10 (Oleth-10, Polyoxyethylene (20) Cet
- the co-surfactant is preferably a small molecule food surfactant, a natural lecithin, a purified lecithin, or combinations thereof.
- the small molecule food surfactant may comprise Span 20, Span 40, Span 60, Span 80, Span 83, Span 85, Span 120, Glyceryl Laurate, and/or Glyceryl Stearate Citrate.
- the natural lecithin if present, may be extracted from soybean, eggs, milk, marine sources, rapeseed, cottonseed, and/or sunflower seed.
- Purified lecithin when present may comprise Lipoid S 40, Lipoid H 50, Lipoid PHOSAL® 50 SA, Lipoid PHOSAL® 53 MCT, Lipoid P 75, Lipoid S 75, Lipoid S 80, Lipoid E 80, PHOSPHOLIPON® 85 G, Lipoid PHOSPHOLIPON® 90 G, Lipoid PHOSPHOLIPON® 90 H, and/or Lipoid H 100.
- the inventor was surprised to find that while Span 20 generated a nano-emulsion composition where the droplet size was less than 100 nm, Span 40, Span 60, Span 80, Span 83, Span 85, and Span 120 generated emulsions with droplet size larger than 100 nm.
- co-surfactant is a raw lecithin
- the amount of the co-surfactant is at least 0.75 times the amount of the dietically acceptable carrier oil
- co-surfactant is a purified lecithin
- the amount of the co-surfactant is at least 0.50 times the amount of the dietically acceptable carrier oil
- co-surfactant is a small molecule food emulsifier
- the amount of the co-surfactant is at least 0.80 times the amount of the dietically acceptable carrier oil.
- Phospholipids may also be present in the composition, for example lecithin such as those extracted from soybean, eggs, milk, marine sources, rapeseed, cottonseed, and/or sunflower seed.
- the composition may further comprise a preservative and/or an essential oil, or a terpene or a flavoring agent or a food color or a bitter blocker or an artificial flavor agent.
- a preservative and/or an essential oil or a terpene or a flavoring agent or a food color or a bitter blocker or an artificial flavor agent.
- the purpose is to improve taste and appearance of the composition.
- the present disclosure provides a method of making the compositions disclosed herein, comprising: mixing the hydrophobic substance, the dietically acceptable carrier oil, surfactants or co-surfactants, and phosphorus lipid form; adding water to the composition and mixing to form a coarse emulsion; and sonicating the mixture under temperature control until the nanosized droplets are formed.
- the temperature of the mixture is usually kept below 75° C. during the mixing process.
- the method may further include sterilizing the composition, for example, by filtering it.
- the instant disclosure also describes a method of using a nano-emulsion composition
- a method of using a nano-emulsion composition comprising administering the composition by inhalation, targeting systemic, parenteral, oral, intrathecal, intraarticular, nasal, ophthalmic and/or topical means, wherein the nano-emulsion composition comprises a cannabinoid oil, a dietically acceptable carrier oil, a main surfactant, a co-surfactant and water.
- the various compositions disclosed herein may be used by adding it to a food or beverage, or may be used to consume directly. All compositions can be applied in topicals, cosmetics or personal lubricant products.
- a nano-emulsion composition comprising: a cannabinoid oil, a dietically acceptable carrier oil, a main surfactant, a co-surfactant, and water, wherein the amount of water is at least 1.15 times the amount of the combination of the cannabinoid oil, the dietically acceptable carrier oil, the main surfactant, and the co-surfactant, and wherein the amount of the dietically acceptable carrier oil is at least 0.3 times the amount of the cannabinoid oil.
- hydrophilic-lipophilic balance HLB
- the amount of the main surfactant is at least 0.65 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil; if the HLB of the main surfactant is between 11 and 13, then the amount of the main surfactant is at least 0.8 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil; and if the HLB of the main surfactant is between 9 and 11, then the amount of the main surfactant is at least 0.95 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil.
- the hydrophilic-lipophilic balance (HLB) of a surfactant is a measure of the degree to which it is hydrophilic or lipophilic.
- the HLB value can be used to predict the surfactant properties of a molecule. For example, HLB of less than 10 indicates lipid-soluble (water-insoluble), while an HLB of more than 10 indicates water-soluble (lipid-insoluble).
- HLB hydrophilic-lipophilic balance
- an oil in water emulsifier has HLB of 8 to 16
- a solubilizer or hydrotope has a HLB of 16 to 18.
- HLB's of some commonly known compounds are illustrated below in Table 1.
- HLB HLB of a compound
- the list below is illustrative purposes only, and it is not meant to be an exclusive list of compounds that many be used as a surfactant for the compositions and methods disclosed herein.
- HLB is best applied to compare within the same surfactant family, and comparing HLB values between two different surfactant families often will not generate expected results.
- Table 1 shows HLB of some surfactant used in this patent.
- the inventor was surprised to find that the droplet size of the composition disclosed herein is higher than 100 nm when the main surfactant is from Polyglyceryl-4 Series, including Polyglyceryl-4 Caprate, Polyglyceryl-4 Caprylate, Polyglyceryl-4 Laurate, Polyglyceryl -4 Isostearate, and Polyglyceryl-4 Oleate. It may be due to their relatively lower HLBs compared to Polyglyceryl-6 or Polyglyceryl-10 Series.
- the final emulsion droplet average size obtained with Polyglyceryl-4 Caprate, Polyglyceryl-4 Caprylate, Polyglyceryl-4 Laurate, Polyglyceryl-4 Isostearate, and Polyglyceryl-4 Oleate were 365 nm, 427 nm, 488 nm, 371 nm, and 506 nm respectively.
- the Polyglyceryl-4 series of surfactants failed to make a nano-emulsion, they may be utilized when a larger droplet size is desired.
- cannabinoid compounds or cannabinoid derivatives. It should be noted that while the general discussion is towards cannabinoids, the instant composition can also be used for any other hydrophobic compounds that would benefit from dispersing in an aqueous solution, including terpenes, other essential oils, extract from herbs, eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) or many other hydrophobic drug molecules.
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- the average nanosized droplet size is less than 500 nm. In some cases, the average droplet size is 400 nm, or less than 200 nm, or less than 100 nm, or less than 90 nm, or less than 80 nm, or less than 70 nm. In one preferred embodiment, at least 80% of the nanosized droplets in the composition have a droplet size between 10-70 nm, or between 30-50 nm, as illustrated in FIGS. 2 and 4 . In some cases, the average nanosized droplet is 35 nm with a standard deviation of 10 nm, as illustrated in FIG. 2 .
- the composition disclosed herein is preferably a liquid composition.
- the composition remains in dispersed form upon dilution in aqueous solution, as illustrated in FIG. 3 .
- the droplet size remains unaffected upon dilution in aqueous solution.
- the composition after dilution into pH 8 solution, can be stored at room temperature (calculated from 55° C. acceleration study) for up to three years without change in droplet size.
- FIG. 6 demonstrated the composition, after diluted into pH 3.5 solution, also have up to equivalent to three years of stability at room temperature (calculated from 55° C. acceleration study). Table 2 shows the stability correlation relation between 55° C. and room temperature.
- the nano-emulsion can be diluted to any concentration and remain the integrity of nano-sized droplets, it can be applied in various different applications where different concentration of active ingredient is needed.
- Table 3 shows possible end applications the nano-emulsion can apply to:
- the hydrophobic substance of the composition disclosed herein preferably comprises a plant extract.
- the hydrophobic substance comprises a cannabinoid.
- the cannabinoid may be a phytocannabinoid or a synthetic cannabinoid, as disclosed above.
- the nanosized droplets may comprise more than one hydrophobic substance.
- the more than one hydrophobic substance will have synergistic effect with each other to produce a result that is better than the sum of its parts.
- each nanosized droplet in the composition may comprise THC, CBD and a terpene compound.
- the amounts of each component in the droplet may be controlled.
- each nanosized droplet may have 1 ⁇ THC, 3'CBD, and 4 ⁇ Terpene.
- THC, CBD, terpene, together with other cannabinoid compounds have synergistic effect, they often have better results compared to just consuming one compound.
- the droplet may have another flavoring agent, such as mint oil, orange oil or lemon oil.
- the cannabis oil may be infused with any other oil in the nano-emulsion form.
- different kinds of nano-emulsions may be prepared from different plant extract; and these nano-emulsions may be used in a drink to mimic the natural effect of the plant, or even create other special effect which is not available from natural plants themselves.
- composition disclosed herein also comprises an edible carrier oil.
- the edible carrier oil as contemplated herein may be from the plant material, which comprises sunflower oil, olive oil, coconut oil, sesame oil, avocado oil, palm oil, soybean oil, corn oil, peanut oil, canola oil, or combinations thereof.
- the edible oil may also be from animal parts, such as for example, lard or butter.
- the composition also typically includes one or more surfactant.
- one surfactant preferably one is a high molecular weight surfactant and the other is a low molecular weight surfactant.
- the surfactant comprises a main surfactant and a co-surfactant, wherein the main surfactant is a high molecular weight surfactant, and the co-surfactant is a lower molecular weight surfactant.
- the compositions described herein may further comprise a preservative and/or a flavoring agent.
- the preservative if present, is usually between 0-2% of the composition. In one example, the preservative is citric acid and/or benzoic acid.
- the preservative system can also be natural compounds like Vitamin E and Vitamin C.
- the flavoring agent may be an essential oil, such as for example, Lemon oil, orange oil, peppermint oil, Ylang Ylang oil, Lemon Grass oil, Tea Tree oil, Rosemary oil, Australian Sandalwood oil, Grape fruit oil, frankincense oil, cedarwood oil, patchouli oil, cinnamon bark oil, bergamot oil, chamomile oil, Lemon Eucalyptus oil, ginger oil, key lime oil, vanilla oil and/or clove oil.
- the flavoring agent if present, comprises about 1-10% of the composition.
- compositions disclosed herein may also comprise different types of bitter blockers.
- Synthetic or natural bitter blockers can be used in cannabinoid nano-emulsions to block bitterness that originated from un-pure plant extracts, wax, polyphenols or undesired flavors from surfactant systems.
- bitter blockers used in the compositions disclosed herein include BB68 (3-[1-[(3,5-dimethylisoxazol-4-yl)methyl]pyrazol-4-yl]-1-[(3-hydroxyphenyl)methyl]imidazolidi ne-2,4-dione) from Senomyx, GG-605-390-4, NP-844-232-9 and QJ-615-696-6 from Givaudan, TRUCLEARTM from Tastesnaturel and/or CLEARTASTETM from MycoTechnology.
- BB68 was introduced either by ethanol or polypropylene glycol into the final nano-emulsion system at the concentration range from 2.5-10 ppm, depending on the certain bitterness of diluted emulsion.
- GG-605-390-4, NP-844-232-9 and QJ-615-696-6 were directly added into the diluted nano-emulsion at concentration range from 0.01%-0.05%.
- TRUCLEARTM and CLEARTASTETM can be used at the concentration of 0.001-0.1%, depending on nano-emulsion's composition.
- different bitter blockers can be mixed and used together, for example, 0.015% NP-844-232-9 plus 0.015% GG-605-390-4 has a better effect on flavor compared to using 0.03% GG-605-390-4 or 0.03% NP-844-232-9 along. It should be noted that all those bitter blockers can also be added into the raw emulsion at higher concentration, so that when the raw emulsion get diluted into final drinks, the bitter blockers' concentration can reach to the level mentioned above.
- compositions disclosed herein may comprise various amounts of the hydrophobic substance, the dietically acceptable carrier oil, the surfactant, and the phospholipid form as described above.
- One non-limiting composition include: 10-20% of cannabis oil, 5-15% of sunflower oil, olive oil or coconut oil, 60-70% of Tween 80, and 5-15% of sunflower lecithin.
- Another non-limiting composition include: 10-20% of cannabis oil, 5-15% of sunflower oil, olive oil or coconut oil, 60-70% of Tween 20, and 5-15% of sunflower lecithin.
- a composition disclosed herein having a tween series main surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 2-4 parts main surfactant of the Tween series, 0.5-3.5 parts co-surfactant, and 30 parts water.
- a composition disclosed herein has a tween series main surfactant and a natural lecithin as a co-surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.75-4 parts main surfactant of the Tween series, 0.5-3.5 parts natural lecithin, and 30 parts water.
- the composition comprises a main surfactant tween series and a purified lecithin as a co-surfactant
- the composition would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.2-3 parts main surfactant of the Tween series, 0.85-3 parts purified lecithin, and 30 parts water.
- composition disclosed herein having a polyglyceryl series main surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.75-3.5 parts main surfactant of the polyglyceryl series, 1-3.5 parts co-surfactant, and 30 parts water.
- a composition disclosed herein having a polyglyceryl series main surfactant and a natural lecithin as a co-surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.9-4 parts main surfactant of the polyglyceryl series, 0.5-3.5 parts natural lecithin, and 30 parts water.
- the composition comprises a main surfactant polyglyceryl series and a purified lecithin as a co-surfactant
- the composition would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.5-4 parts main surfactant of the polyglyceryl series, 0.85-3 parts purified lecithin, and 30 parts water.
- composition disclosed herein having a long chain PEG series main surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.25-3.75 parts main surfactant of the long chain PEG series, 0.5-3 parts co-surfactant, and 30 parts water.
- a composition disclosed herein having a long chain PEG series main surfactant and a natural lecithin as a co-surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.75-4 parts main surfactant of the long chain PEG series, 0.35-3 parts natural lecithin, and 30 parts water.
- the composition comprises a main surfactant long chain PEG series and a purified lecithin as a co-surfactant
- the composition would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1-3 parts main surfactant of the long-chain PEG series, 0.85-3 parts purified lecithin, and 30 parts water.
- main surfactant is at least 1.05 times the amount of combination of cannabinoid oil and carrier oil and if the co-surfactant is a natural lecithin, then the amount of the co-surfactant is at least 0.75 times the amount of the dietically acceptable carrier oil; if the co-surfactant is a purified lecithin, then the amount of the co-surfactant is at least 0.50 times the amount of the dietically acceptable carrier oil; and if the co-surfactant is a small molecule food emulsifier, then the amount of the co-surfactant is at least 0.80 times the amount of the dietically acceptable carrier oil.
- droplet sizes and their distribution may affect the human feeling on flavor.
- nano-size can amplify or even alter the taste, something tastes plain at bulk may taste bitter or sour in nano-scale.
- taste buds on tongue tend to have different time reactions to different sizes of particles.
- the smaller droplets can quickly absorb at the gap of the tasting buds, thus blocking the touching/feeling from bigger droplets.
- the droplet size can be well controlled by how much energy is put into the liquid system, which can be controlled either by amplitude % of the sonicator or by how long the liquid is being sonicated at certain amplitude %. For example, shown in FIG.
- ultrasonic frequency of a sonicator is generally fixed at 20 kHz and does not fluctuate during sonication.
- the sonicator continuously calibrates itself to ensure consistent output.
- a commercially available sonicator may be used to make the compositions disclosed herein.
- the wattage of such a sonicator may vary from 250 W to about 800 W, and more preferably between about 350 W to about 650 W, and most preferably between 450 W to about 550 W.
- the output energy depends on the viscosity of the emulsion and also temperature.
- the total energy required to generate nano-emulsion (J/mL) will be less than a formula that contains less surfactants and less water, which is due to how easy it is for the droplet to form in the emulsion and viscosity.
- Processing amplitude are adjustable, and it is within a linear relation with intensity.
- process time can also be adjustable, which will determine total input energy under certain intensity. Since each formula may need different amount of energy to get into nanosize, we usually monitor droplet size change with Dynamic Light Scattering over production time to determine when to stop the sonication.
- batch mode There are two major methods to operate sonication: batch mode and continuous mode.
- batch mode is applied, which includes a sonication probe immersed into the target liquid.
- continuous mode is preferred, where the raw emulsion was stored in a tank, and it gets pumped into the sonication chamber and pumped back into the tank. The energy input happens at the sonication chamber.
- Heat is generated during the sonication process, overheat not only damage equipment, but also will degrade cannabinoid.
- ice/dry ice batch is applied to maintain the temperature.
- recirculating chillers were applied to cool down the reaction chamber during the process. The temperature was kept below 70° C. for both modes.
- a method of making a composition comprising: mixing the hydrophobic substance, the dietically acceptable carrier oil, surfactant, and phosphorus lipid form; adding water to the composition and mixing to form an emulsion; and sonicating the mixture under temperature control until the nanosized droplets are formed.
- the temperature of the mixture is usually kept below 75° C. during the mixing process.
- the composition is sterilized by filtering through a 0.2 um filter.
- the composition is usually stored in a light blocking vessel and stored at 4° C. If larger droplets are desired for a particular application, for example microsized droplets, the energy put in during the mixing process is lowered.
- compositions disclosed herein may be administered to a subject in a variety of ways, such as, for example, by inhalation, targeting systemic, parenteral, oral, intrathecal, intraarticular, nasal, ophthalmic and/or topical means.
- the compositions disclosed herein may be added to a beverage or food prior to oral administration.
- the compositions may be used for an application that uses aqueous infusion, say for example, water-based lube, chewing gum, topicals, facial spray, makeup remover etc.
- the technology of nanosized particles may also be used for other applications, for example, pharmaceutical drug delivery of a hydrophobic drug, or general food and agriculture material treatment.
- compositions disclosed herein may be grouped as systems; each such system is discussed in detail below.
- Each system contains target oil (cannabis oil in particular), carrier oil, one to three surfactant types, and water.
- target oil can be used in particular
- carrier oil can be used in particular
- surfactant types such as butane, butanediol, sulfate, sulfate, sulfate, sulfate, sulfate, sulfate, sulfate, sulfate, sulfate, stylene glycol, glycerin, octylene glycol, ol, ol, ol, ol, ol, ol, ol, ol, ol, ol, sulfate, sulfate, sulfate, sulfate, sulfate, sulfate, sulfate, sulfate
- Polyglyceryl surfactant series are generally regarded to be very safe to consume, there is usually no upper limit of consumption in food. Its main structure contains a polyglycerol chain as hydrophilic head and a fatty acid as hydrophobic tail.
- the co-surfactants applied here can be small molecule food emulsifiers, natural lecithin or purified lecithin.
- the total mass amount of polyglycerol surfactant plus co-surfactant should be higher than twice the total mass amount of target oil plus carrier oil. In some cases, the mass amount of co-surfactant should be higher than the mass amount of carrier oil.
- the relative ratio of polyglyceryl surfactant used in the system can be determined by its HLB, as disclosed herein.
- BRIJ® surfactants are widely used in cosmetic products due to their excellent surface activity.
- BRIJ® surfactant can be used in combination of co-surfactant to make cannabinoid nano-emulsion.
- Co-surfactant in this system can be small molecule food emulsifiers, natural lecithin and/or purified lecithin.
- the total mass amount of BRJI surfactant plus co-surfactant should be higher than twice the total mass amount of target oil plus carrier oil. In some cases, the mass amount of co-surfactant should be higher than the mass amount of carrier oil.
- the relative ratio of BRIJ® surfactant used in the system can be determined by its HLB, which is disclosed in herein.
- Tween Polysorbate (Tween) surfactants are commonly used in food and cosmetic industry due to their high surface property and relative safety to human consumption. It includes Tween 20, Tween 40, Tween 45, Tween 60, Tween 65, Tween 80 and Tween 85. They share the same hydrophilic head, the only difference lays in their hydrophobic chain in terms of chain length and saturation. The Tween family system can be used with various co-surfactants to generate nanoemulsions.
- tween surfactant's amount in mass should be higher than 0.65 times the total weight of target oil and carrier oil
- co-surfactant's amount in mass should be higher than 0.80 times the weight of carrier oil.
- the total amount of tween surfactant plus the co-surfactant should be higher than 1.85 times of weight of target oil, and/or 1.35 times the weight of carrier oil and/or 1.15 times the total weight of target oil and carrier oil.
- a combination of different types of main surfactants can also generate cannabinoid nano-emulsions.
- the main surfactant types include polyglyceryl series, tween series and/or BRIJ® series.
- the ratio of different types of main surfactants can be adjusted to any desired range as long as the amount of combination of main surfactants should be at 1.05 times the amount combination of cannabinoid oil and carrier oil.
- the main surfactants can be split into half as Tween Series and half as polyglyceryl Series, or 1 ⁇ 3 as Tween Series, 1 ⁇ 3 as polyglyceryl Series and 1 ⁇ 3 as BRIJ® series. As long as their total amount is greater than 1.05 times the amount combination of cannabinoid oil and carrier oil.
- inventive subject matter provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus, if one embodiment comprises elements sunflower oil, tween-80, sunflower lecithin, and cannabinoid, and a second embodiment comprises elements coconut oil, tween-20, sunflower lecithin, cannabinoid and lemon oil, then the inventive subject matter is also considered to include other remaining combinations of sunflower oil, coconut oil, tween-80, tween-20, sunflower lecithin, cannabinoid, and lemon oil, even if not explicitly disclosed.
- the formula 1 disclosed below is a general base formula that works with many starting materials.
- This composition has a bitter taste due to the presence of Tween-80.
- the bitter taste may be desirable in some cases. If the bitter taste is not desired, then additives such as essential oils may be added to mask the bitter taste.
- 1 g of cannabis and 5 g of the Formula 1 are added to a 100 ml beaker, and mechanically stirred under controlled heat ( ⁇ 60° C.), until it is well mixed.
- the cannabis oil may be a full plant extract or a high pure distillate.
- Water is added to the mixture, the amount of water is determined by the final targeting concentration.
- the mixture is kept stirring until a homogenous milky coarse emulsion is formed.
- the mixture is put in an ice bath and a sonicator probe is inserted into the liquid. The mixture is sonicated at 80% amplitude.
- Nanoemulsion Temperature of the liquid should be constantly monitored, when temperature is above 70° C., the sonication should be stopped, let the liquid cool down to room temperature and restart the sonication until the liquid become translucent/transparent (nanoemulsion). Sometimes, in order to further improve the taste, finished nanoemulsion will flow through a packed Al 2 O 3 or activated charcoal column. The nanoemulsion is then filtered through a nylon 0.2 um filter, collected in a light blocking vessel, and kept at 4° C.
- the concentration ranges of ingredients above represent a scenario where nano-emulsion can be generated.
- the ingredients' concentration ranges can be flexible.
- the desirable range of each ingredient can be: cannabinoids (1 g), carrier oil (0.5-2 g), Tween 80 (2.5-4.5 g) and lecithin (0.3-3 g).
- Tween 80 is the major driving force in the formula, with enough of it, the final formulation can be driven into nano-size.
- the desirable range of each ingredient can be: cannabinoids (1 g), carrier oil (0.5-6 g), Tween 80 (1-2 g) and lecithin (0.3-3 g).
- the above formula 1 is a general base formula to which different ingredients can be added to suit the needs of a particular application.
- the ingredients and the amounts may be varied to vary onset time, flavor, look, stability, compatibility, concentration, texture.
- a water lube needs to have a good taste, a good smell, and a high concentration of cannabinoid and a low droplet size distribution to allow the cannabinoid to absorb quicker, also need to keep the texture of product to be viscous and smooth.
- the concentration of cannabinoid in the nano-emulsion would be higher, since only a small volume of nano-emulsion can be added to the lube base.
- the carrier oil or essential oil in the formula will have no such effect because oil is trapped inside the tiny droplets, which is protected by the surfactants on the edge as an insulating layer. This protection effect is better when the surfactant hydrophilic heads are bigger, which offer more room for the protection layer.
- the formula 2 disclosed herein works with most high purity distillate cannabis oil. It is less bitter than Formula 1 due to the incorporation of Tween 20 instead of Tween 80. Similar to formula 1, 1 g of cannabis oil is mixed with 5 g of the formula 2 and the method disclosed above for formula 1 is used to making the composition. The desirable concentration range of Formula 2 is similar to the Formula 1 as described above.
- Formula 3 can tolerate more carrier oil and still generate nanoemulsions of cannabinoinds.
- the carrier oil can be fats from animal parts, such as lard or butter, or from plants, such as sunflower oil, liquid coconut oil or any other forms. Similar to above, 1 g of cannabis oil (either full plant extract or high pure distillate) is added to 6 g of natural fats first, stir and heat is applied to make sure the natural fats and cannabinoids are fully mixed into one continuous phase. Then, 7 g of Tween 20 and 1.2 g of Sunflower lecithin were added into the oil mixture. In one embodiment, the method disclosed above for formula 1 is used to making the instant composition.
- Each ingredient's concentration range is determined by the target needs.
- 6 g of fats are used.
- Tween 20 range can be anywhere from 6-8.5 g and sunflower lecithin range can be anywhere from 4.68-6 g.
- cannabinoid nanoemulsion can be generated: amount of the total surfactants is at least 1.45 times the amount of cannabinoid oil, and/or the amount of total surfactants is at least 1.35 times the amount of carrier oil, and/or the amount of total surfactants is at least 1.15 times the amount of combination of cannabinoid oil and carrier oil.
- THC distillates can be obtained from different purification methods, which will contribute different portion of polyphenols in the product.
- the other components' ranges can be Tween 20 as of 1.5-7 g and lecithin can be as of 0.3-4 g.
- Formula 4 provides an advantage over Formulas 1 and 2 by blocking the bitterness by adding additional essential oils. Similar to above, 1 g of cannabis oil (either full plant extract or high pure distillate) is added 5 g of formula 2, and the method disclosed above for Formula 1 is used for making the composition.
- each essential oil will have a different synergetic effect on the flavor side with the cannabinoid, which can result in less or more dosage in the final composition.
- mint oil and ginger oil are so far the best to cover the bitterness flavor from cannabinoid.
- the ratio of them to cannabinoid can be as low as 2:1.
- Other essential oils may be applied in a higher quantity to cover the bitterness, which can be over 3:1 or higher.
- Tween 20 range can be more flexible, which can be anywhere from 1.5-5 g, depending on how much quantity of essential oil has been used.
- Formula 5 is robust to mostly any kind of pure or mixed terpenes, which can be either extracted from cannabis plants or other agricultural plants. Some tested terpenes include pinene, limonene, linalool, beta-caryophyllene, myrcene and others. Formula 5 also works to generate any kind of nano-emulsion based on the essential oil. Similar to above, 0.2-1 g of terpenes (either full plant extract or high pure distillate) or 0.2-1 g of essential oil is added with 5 g of formula 2, and the method disclosed above for Formula 1 is used for making the composition.
- Tween 20 can be used in a slightly wide range from 1.5 g to 5 g.
- the fats range can be 0.35 g to 2 g and lecithin range can be 0.35 g to 3 g.
- Formula 6 is developed to not only generate nano-emulsion for 97% CBD isolate, but also block the bitterness of this nano-emulsion.
- nano-emulsion of CBD isolate can be generated.
- the bitterness taste may not be desired in food additives.
- the inventor found out that the trace amount of polyphenols present in the CBD isolate may contribute to the bitterness.
- Method 1 pre-sonication, dissolve lg CBD powder into 10 mL organic solvent such as chloroform, ether or hexane, then wash this organic layer in a separating funnel with 20 mL of 0.01N HCl Solution three times, 20 mL of 5% NaHCO 3 three times and saturated NaCl solution 3 times. Then the organic layer was collected, dried with 1-2 g of MgSO 3 , filtered and then evaporated to dryness.
- Another washing agent can be 1-3% PVP40 solution: repeat the same wash procedure like above three times with 20 mL of PVP40 solution, then wash with saturated NaCl solution, dried by MgSO 3 , filtered and then evaporated to dryness.
- the purified CBD then can be turned into nano-emulsion using formula 2 with much less bitterness.
- Method 2 did not treat the CBD raw material but make a nano-emulsion of it with Formula 2, then for every 50 mL of the nano-emulsion, apply 1-10 g of absorbance material to the nano-emulsion as disclosed herein.
- Formula 7 comprises a surfactant from the polyglyceryl-10 series.
- Polyglyceryl-10 series surfactants are not only very safe to consume, but they also present better surface activity in making cannabinoid nanoemulsions. Especially for Polyglyceryl-10 Oleate, Polyglyceryl-10 Laurate, Polyglyceryl-10 Caprylate/Caprate and Polyglyceryl Ester Fatty Acid (POLYALDO® 10-2-P), they can used in less amount compared to Tween series surfactants to generate cannabinoid nanoemulsion. Sometimes, due to the surfactants' own milky colors, the finished nanoemulsion appears to be milky/translucent instead of fully transparent. Polyglyceryl-10 series surfactants can be used together with sunflower lecithin or purified lecithin for nanoemulsion generation. Due to the safety nature of Polyglyceryl-10 series surfactants and lecithin, this combination may have huge potential applications as premium food/drink ingredients.
- the main building blocks within each formula comprise carrier oil, tween 20 or tween 80 and Sunflower lecithin.
- carrier oil's range should be within 0.25 g to 8 g
- Tween 20 or Tween 80 range should be within 2.5 g to 8 g
- sunflower lecithin should be within the range of 0.3 g to 4 g.
- mint oil works the best as masking the bitterness
- lemon oil takes advantage its own natural bitterness to cover the cannabinoid bitterness. So of the essential oils may be needed at least 2-3 times higher mass than cannabinoid oils' mass.
- surfactant types may not work as good as the combination of tween 20/tween 80 with Sunflower lecithin.
- soy derived lecithin is a solid wax, it does not work as well as sunflower lecithin.
- surfactants like Span 80, Span 20 works with the combination of Tween 20 or Tween 80, but not used as primary surfactant by themselves.
- Surfactants like Glyceryl Laurate, PolyGlyceryl 3-Laruate, PolyGlyceryl 3-Oleate and Glyceryl Stearate Citrate often offer a cloudy emulsion with droplet size in the range over 200 nm. They can be used in the case where nano-size is not required. Thus, they are not used directly in the formula disclosed herein.
- the power of converting hydrophobic materials into water soluble nano-emulsion also helps recombine and regenerate the desired final aqueous product, some of those can be found in natural material, some of them can be simulated in a way which has never been explored from natural compounds.
- a synthetic drink can be generated. It can quickly ease the nerve and calm people down with a very mild brain reaction. This combination can not be found in nature, and the nano-emulsion formula enabled unlimited discovery like this.
- the inventor unexpectedly and surprisingly found that while Span 20 resulted in a nano-emulsion having average particle size of less than 100 nm, Span 40, Span 60, Span 80, Span 83, Span 85, and Span 120 resulted in nano-emulsions having average particle size of more than 100 nm.
- Span 40, Span 60, Span 80, Span 83, Span 85, and Span 120 resulted in nano-emulsions having average particle size of more than 100 nm.
- Span 40, Span 60, Span 80, Span 83, Span 85, and Span 120 resulted in nano-emulsions having average particle size of more than 100 nm.
- Span 40, Span 60, Span 80, Span 83, Span 85, and Span 120 resulted in nano-emulsions having average particle size of more than 100 nm.
- the 80% amplitude of sonication was applied to 45 mL of total volume of mixed liquid with Span, Tween 80, carrier oil, cannabinoid oil and water. Droplet size change was monitored by DLS time wise. Sonication was stopped when droplet size reach plateau and does not decrease.
- Span 20 can generate emulsion that have droplet size smaller than 100 nm. With decrease HLB of Span surfactant, the droplet size increases. Even though most of Span surfactants failed to make nanoemulsion, but they may be utilized when a larger droplet sized emulsion is desired.
- lecithin may be used as a co-surfactant in the composition disclosed herein.
- the inventor found that unexpectedly and unanticipatedly, natural lecithin from Soy does not work in the composition while natural lecithin from Sunflower works!
- Natural lecithin from Sunflower is a viscous dark brown liquid; it is easier to dissolve in the cannabinoid+carrier oil+main surfactant system. In example 1, together with Tween 80, it can generate emulsion with average droplet size of 40-50 nm.
- natural lecithin from Soy it takes longer to dissolve into the cannabinoid+carrier oil+main surfactant system. And with adding water, some of it precipitated out.
- Soy lecithin together with Tween 80, cannabinoid oil, edible oil, and water could generate emulsion with average droplet size of 150-170 nm, but could not generate a nano-emulsion with average droplet size of less than 100 nm.
- the inventor unexpectedly discovered that the amount of water in the composition is important for the droplet size.
- the inventor found that when the amount of water in the composition is less than 1.15 times the combination amount of cannabinoid oil, carrier oil, main surfactant and co-surfactant, the resulting emulsion has a droplet size of more than 100 nm.
- the starting emulsion may not have a nanosized droplet.
- the inventor found that in system 4 , when there is no co-surfactant as of natural lecithin, purified lecithin, or small molecule food emulsifiers, the main surfactant can make nano-emulsion with average size of 50 nm.
- the nano-emulsion made by such a process does not have long term stability.
- the droplet size of the nano-emulsion increases from 50 nm to 150 nm in 2 weeks, and to 300 nm in 5 weeks and to 620 nm in 8 weeks. At week 8, it becomes a little bit opaque.
- system 4 can generate a nano-emulsion, but its stability dramatically decreases compared to other systems with co-surfactant.
- the composition had long term stability—12 weeks no layer separation in 55° C. Oven.
- water amount can be varied dramatically as long as it is 1.15 times higher than the amount of combination of cannabinoid oil, carrier oil and surfactant systems.
- concentration of the cannabinoid in the finished emulsion can vary from ⁇ 60-70 mg/g down to very low as of 0.01 mg/g, in which case excess amount of water is added.
- formula combinations in this disclosure can not only make concentration nanoemulsion that can be diluted later into food or cosmetic, they can also generate end product with variable targeted concentrations.
- the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
Abstract
Description
- This patent application is a continuation application of U.S. application Ser. No. 16/206,869, filed on Nov. 30, 2018, which in turn claims the benefit of provisional patent Application No. 62/700,642 filed on Jul. 19, 2018. All of the foregoing are fully incorporated by reference herein.
- The field of the invention is cannabinoid emulsions.
- The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
- All publications identified herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
- There are many ways to administer medical and recreational cannabis. One common problem with currently available cannabinoid compositions and methods of administration is that cannabinoids are not water soluble and therefore only a small percentage of the consumed cannabinoid content is absorbed by the human body. Moreover, because cannabinoids are not water soluble, it is difficult to put it in common foods and drinks. Finally, the low aqueous solubility also contributes to lower potency and slower onset of action in lower doses.
- Nanoparticles comprising cannabis are one way to improve solubility. For example, US20180296493A1 to Richard Clark Kaufman teaches a nanosphere compositional structure comprising encapsulated cannabinoid. PCT/US2017/049219 discloses a cannabinoid nanoemulsion made from surfactant Vitamin E TPGS. US20120202891A1 discloses a gel comprising cannabis nanoparticles, and US20170265494 discloses a chewing gum having a liquid center and the liquid center comprises “nanozome” encapsulated cannabinoid. However, in each of the above methods, the stability of such nanoparticles disclosed is less than desirable, especially upon dilution in an aqueous carrier. Moreover, at least some nanoparticle formulations tend to suffer from particle aggregation. Finally, the taste of the cannabinoid nanoparticles also remains unknown.
- Thus, there remains a need in the art for new compositions of cannabinoid that remain dispersed in water and thereby leads to higher potency, faster onset of action, and have a pleasant taste such that it can be easily added to common foods and drinks.
- Various embodiments disclosed herein are drawn towards cannabinoid nano-emulsion compositions, methods, and kits, comprising: a cannabinoid oil, a dietically acceptable carrier oil, at least one surfactant, and water. In preferred embodiments, the amount of water is at least 1.15 times the amount of the combination of the cannabinoid oil, the dietically acceptable carrier oil, and the surfactant. In preferred embodiments, the amount of the dietically acceptable carrier oil is contemplated to be at least 0.3 times the amount of the cannabinoid oil. Furthermore, in some embodiments, the amount of the surfactant is at least 1.45 times the amount of cannabinoid oil, and/or the amount of surfactant is at least 1.35 times the amount of carrier oil, and/or the amount of surfactant is at least 1.15 times the amount of combination of cannabinoid oil and carrier oil.
- The at least one surfactant contemplated herein may comprise a tween surfactant, a polyglyceryl surfactant, a long chain PEG surfactant, or combinations thereof. The amount of the surfactant in the composition depends on the hydrophilic-lipophilic balance (HLB). If the HLB of the surfactant is >13, then the amount of the surfactant is at least 0.65 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil; if the HLB of the surfactant is between 11 and 13, then the amount of the surfactant is at least 0.8 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil; and if the HLB of the surfactant is between 8.5 and 11, then the amount of the surfactant is at least 0.95 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil;
- The composition may have one or more surfactants. When there are two surfactants, say a main surfactant and a co-surfactant, and the amount of the main surfactant is at least 1.05 times the amount of combination of cannabinoid oil and carrier oil. The co-surfactant is contemplated to be a small molecule food surfactant, a natural lecithin, a purified lecithin, or combinations thereof. If the co-surfactant is a natural lecithin, then the amount of the co-surfactant is at least 0.75 times the amount of the dietically acceptable carrier oil; if the co-surfactant is a purified lecithin, then the amount of the co-surfactant is at least 0.50 times the amount of the dietically acceptable carrier oil; and if the co-surfactant is a small molecule food emulsifier, then the amount of the co-surfactant is at least 0.80 times the amount of the dietically acceptable carrier oil.
- The cannabinoid oil in the composition may comprise a phyto-cannabinoid or a synthetic cannabinoid. The composition may further comprise one or more preservatives, a flavoring agent, a bitter blocker, an essential oil and/or a terpene.
- The average diameter or Z-average of the nano-emulsions in the composition is preferably smaller than 100 nm, when tested by Dynamic Light Scattering, and in some cases, about 80% of the nano-droplets in the composition are contemplated to have a droplet size between 30-50 nm. Notably, the composition disclosed herein may be a liquid composition. The composition remains in dispersed form upon dilution in aqueous solution. The droplet size remains unaffected upon dilution in aqueous solution. The composition can be stored at room temperature for at least 6 months, or in a 55° C. oven for up to 12 weeks, without change in droplet size.
- In another aspect, disclosed herein is a method of making a nano-emulsion composition comprising: mixing a cannabinoid oil, a dietically acceptable carrier oil, a main surfactant, a co-surfactant; adding water to the composition and mixing to form a coarse emulsion; and inputting energy by sonication, high shearing or microfluidic droplet generating into the mixture under temperature control until the nano-emulsions are formed. The temperature of the mixture is kept below 75° C. during the mixing process.
- In another aspect, disclosed herein is a method of using a nano-emulsion composition comprising: administering the composition by inhalation, targeting systemic, parenteral, oral, intrathecal, intraarticular, nasal, ophthalmic and/or topical means, wherein the nano-emulsion composition comprises a cannabinoid oil, a dietically acceptable carrier oil, a main surfactant, a co-surfactant and water. The composition is contemplated to be added to a beverage or food prior to oral administration.
- Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments, along with the accompanying drawing figures in which like numerals represent like components.
-
FIG. 1 illustrates, in accordance with the embodiments herein, (A) a currently available macroemulsion cannabinoid product dispersed in water and its droplet size distribution, compared with (B) the newly disclosed nanodroplet cannabinoid composition dispersed in water and its droplet size distribution. -
FIG. 2 illustrates, in accordance with the embodiments herein, initial emulsion droplet size of the composition disclosed herein. The initial emulsion concentration was kept at 25 mg/mL. -
FIG. 3 illustrates, in accordance with the embodiments herein, that no precipitation was observed upon dilution of concentrated composition. The concentrated composition can be diluted by any fold to make the final product. -
FIG. 4 illustrates, in accordance with the embodiments herein, nanosized emulsion droplets does not change its size upon dilution. -
FIG. 5 illustrates, in accordance with the embodiments herein, droplet physical stability over time in pH=8 buffer solution. -
FIG. 6 illustrates, in accordance with the embodiments herein, droplet physical stability over time in pH=3.5 buffer solution. -
FIG. 7 illustrates, in accordance with the embodiments herein, emulsion stability under refrigerated conditions over four weeks, no reversed phase transformation or precipitates observed. And it also showed the emulsion is compatible with polypropylene plastic material. -
FIG. 8 illustrates, in accordance with the embodiments herein, the high repeatability and reliability of nano-emulsion potency result tested at different concentrations, detected by HPLC-DAD. -
FIG. 9 illustrates, in accordance with the embodiments herein, linearity of potency control uses the nano-emulsion. -
FIG. 10 illustrates, in accordance with the embodiments herein, droplet size change over sonication time. Smaller size can be obtained by higher energy input. -
FIG. 11 illustrates, in accordance with the embodiments herein, the appearance of the concentrated nano-emulsion at different droplet size distributions, which can be controlled and obtained by altering the sonication amplitude and time. - The instant subject matter is directed towards compositions, kits, and methods comprising nanosized droplets, wherein the nanosized droplets comprise a hydrophobic substance, a dietically acceptable carrier oil, a surfactant or surfactant system, and a phospholipid form. Contemplated compositions and methods overcome the current problems with cannabinoids—most current products available are macro emulsions which have drawbacks such as long-term instability, short shelf life, slow on-set time, unappealing taste and appearance, and due to its un-even distribution in water over time and often times tend to stick to the inner surface of container, the potency and homogeneity test often fail. The compositions disclosed herein overcome these problems, and as discussed herein, have fast onset time, long term stability, long shelf life, compatible with various container materials and a more controlled result on potency test. The droplet size remains stable over time and upon dilution.
- The compositions provided herein have several advantages over the currently available cannabinoid compositions. In terms of onset time or bioavailability, upon smoking cannabis, only 2-45% of THC can be absorbed by lung; upon eating cannabis, only 8-15% of THC can be absorbed and it is also slow to react. One advantage of the nanosized droplet composition provided herein is the high bioavailability and fast onset, which occurs because the large surface area of these nanosized droplets easily attach to mucus surface and works on the body instantly. For example, in one embodiment, upon consuming 10 mg of the composition comprising THC as disclosed herein, an adult human subject felt lightheaded in about 10 minutes, euphoria in about 20 minutes, hunger in about 37 minutes, and happy (laughing and dancing) in about 40 minutes. Furthermore, in some embodiments, the lecithin in the composition may form a bilayer structure, called liposome, which traps the THC inside. In other embodiments, the lecithin sits on the edge of the oil droplets. Lecithin can help quicker absorption of the cannabinoid into the body. In one embodiment, onset time may depend on body size and whether the stomach is empty or full. Empty stomach often gives a much faster onset time.
- The inventive subject matter provides new nano-emulsion compositions comprising: a cannabinoid oil, a dietically acceptable carrier oil, a surfactant, and water, wherein the amount of water is at least 1.15 times the amount of the combination of the cannabinoid oil, the dietically acceptable carrier oil, and the surfactant; and wherein the amount of the dietically acceptable carrier oil is at least 0.3 times the amount of the cannabinoid oil. In some embodiments, the composition may comprise more than one surfactant, such as a main surfactant and a co-surfactant. The terms “nano-droplet” and “nano-emulsion” are used interchangeably in this disclosure, and refers to dispersions or droplets comprising water, oil, and surfactant(s), as well as other lipid structures that can form as a result of hydrophobic forces that drive apolar residues (example, long hydrocarbon chains) away from water and drive polar head groups toward water, when a water immiscible oily phase is mixed with an aqueous phase. These other lipid structures include, but are not limited to, unilamellar, paucilamellar, and multilamellar lipid vesicles, micelles, and lamellar phases.
- As further described throughout this disclosure, the hydrophilic-lipophilic balance (HLB) of the surfactant plays an important role in determining its amount in the composition. If the HLB is >13, then the amount of the surfactant, or the main surfactant if there are more than one surfactant in the composition, is at least 0.65 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil. In one embodiment, if the HLB of the surfactant, or the main surfactant if there are more than one surfactant in the composition, is between 11 and 13, then the amount of the main surfactant is at least 0.8 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil. In one embodiment, if the HLB of the surfactant, or the main surfactant if there are more than one surfactant in the composition, is between 9 and 11, then the amount of the main surfactant is at least 0.95 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil. The compositions provided herein have higher potency, faster onset of action, and can be easily added to common foods and drinks.
- The average droplet size in the composition is less than 100 nm, either at raw emulsion level and/or at the diluted level, for example, 0.1 mg/g. In some cases, 80% of the droplets have a droplet size between 10-70 nm, or more preferably a droplet size of 30-50 nm. The size and stability of the droplet does not vary with dilution or time, and the composition can be stored at room temperature for at least 12 months, or preferably at least 18 months, or more preferably at least 24 months, or more preferably at least 30 months, or most preferably at least 36 months without change in droplet size.
- The cannabinoid may be a naturally occurring phytocannabinoid or a synthetic cannabinoid. The cannabinoid may be Tetrahydrocannabinol (THC) or Cannabidiol (CBD), any other single cannabinoids or combinations thereof. The purity of the cannabinoid can be low pure (full plant distillate) or high pure (distillate). In one embodiment, the cannabinoid is selected from Tetrahydrocannabinolic acid A (THCA-A), Tetrahydrocannabinolic acid B (THCA-B), Tetrahydrocannabinol (THC), Tetrahydrocannabinolic acid C (THCA-C), Tetrahydrocannbinol C (THC-C), Tetrahydrocannabi varinic acid (THCVA), Tetrahydrocannabivarin (THCV), Tetrahydrocannabiorcolic acid (THCA-C), Tetrahydrocannabiorcol (THC-C), Delta-7-cis-iso-tetrahydrocannabi varin, A-tetrahydrocannabinolic acid (A8-THCA), A-tetrahydrocannabinol (A-THC), Cannabidiolic Acid (CBDA), Cannabidiol (CBD), Cannabidiol monomethyl ether (CBDM), Cannabidiol-C (CBD-C), Cannabidivarinic Acid (CBDVA), Cannabidivarin (CBDV), Cannabidiorcol (CBD-C), Cannabigerolic Acid (CBGA), Cannabigerolic Acid monomethylether (CBGAM), Cannabigerol (CBG), Cannabigerol monomethylether (CBGM), Cannabigerovarinic Acid (CBGVA), Cannabigerovarin (CBGV), Cannabichromenic Acid (CBCA), Cannabichromene (CBC), Cannabichromevarinic Acid (CBCVA), Cannabichromevarin (CBCV), Cannabicyclolic acid (CBLA), Cannabicyclol (CBL), Cannabicyclovarin (CBLV), Cannabielsoic acid A (CBEA-A), Cannabielsoic acid B (CBEA-B), Cannabielsoin (CBE), Cannabinolic acid (CBNA), Cannabinol (CBN), Cannabinol methylether (CBNM), Cannabinol-C (CBN-C), Cannabivarin (CBV), Cannabino-C (CBN-C), Cannabiorcol (CBN-C), Cannabinodiol (CBND), Cannabinodivarin (CBDV), Cannabitriol (CBT), 10-Ethoxy-9-hydroxy-A″-tetrahydrocannabinol, 8.9-Dihydroxy-A′-tetrahydrocannabinol (8.9-Di-OH CBT-C), Cannabitriolvarin (CBTV), Ethoxy-cannabitriol varin (CBTVE), Dehydrocannabifuran (DCBF), Cannbifuran (CBF), Cannabichromanon (CBCN), Cannabicitran (CBT), 10-Oxo-A′-tetrahydrocannabinol (OTHC), A-cis-tetrahydrocannabinol (cis-THC), Cannabiripsol (CBR), 3,4,5,6-tetrahydro-7-hydroxy-alpha-alpha-2-trim ethyl-9-n-propyl-2,6-methano-2H-1-benzoxocin-5-metha nol (OH-iso-HHCV), Trihydroxy-delta-9-tetrahydrocannabinol (triCH-THC), Isocanabinoids, Epigallocatechin gallate, or combinations thereof.
- The dietically acceptable carrier oil may comprise plant derived oils or animal derived oils. Plant derived oils contemplated in the composition include sunflower oil, olive oil, coconut oil, sesame oil, avocado oil, palm oil, soybean oil, corn oil, peanut oil, canola oil, grape seed oil, corn oil, hazelnut oil, rice bran oi, linseed oil, safflower oil, sesame oil, passion fruit oil or combinations thereof. The dietically acceptable carrier oil may also comprise animal derived oils, including lard, butter, animal fats or combinations thereof.
- The surfactant may comprise one surfactant or a mixture of surfactants. For example, the surfactant may be a high molecular weight main surfactant and a co-surfactant of lower molecular weight. The main surfactant may be a tween surfactant, a polyglyceryl surfactant, and/or a long chain PEG surfactant. In one embodiment, the tween surfactant may be selected from the group consisting of
Tween 20, Tween 40, Tween 45, Tween 60, Tween 65,Tween 80, Tween 81 and Tween 85. In one embodiment, the polyglyceryl surfactant is selected either from polyglyceryl monoesters or polyglyceryl multi-esters. Examples of polyglyceryl monoesters contemplated herein include Polyglyceryl-4 Caprate, Polyglyceryl-4 Caprylate, Polyglyceryl-4 Laurate, Polyglyceryl-4 Isostearate, Polyglyceryl-4 Oleate, Polyglyceryl-5 Laurate, Polyglyceryl-5 Myristate, Polyglyceryl-5 Isostearate, Polyglyceryl-5 Oleate, Polyglyceryl-5 Stearate, Polyglyceryl-6 Isostearate, Polyglyceryl-6 Oleate, Polyglyceryl-6 Stearate, Polyglyceryl-8 Oleate Polyglyceryl-8 Stearate, Polyglyceryl-10 Laurate, Polyglyceryl-10 Myristate, Polyglyceryl-10 Palmitate, Polyglyceryl-10 Isostearate, Polyglyceryl-10 Linoleate, Polyglyceryl-10 Oleate, Polyglyceryl-10 Stearate, Polyglyceryl-10 Behenate/Eicosadioate, Polyglyceryl-10 Hydroxystearate/Stearate/Eicosadioate and Polyglyceryl-10 fatty ester (POLYALDO® 10-2-P). Polyglyceryl multi-esters contemplated in the composition disclosed herein include Polyglyceryl-5 Triisostearate, Polyglyceryl-5 Dioleate, Polyglyceryl-5 Trioleate, Polyglyceryl-6 Tricaprylate, Polyglyceryl-6 Dioleate, Polyglyceryl-6 Distearate, Polyglyceryl-6 Pentastearate, Polyglyceryl-6 Octastearate, Polyglyceryl-8 Decaerucate/Decaisostearate/Decaricinoleate, Polyglyceryl-10 Caprylate/Caprate, Polyglyceryl-10 Dipalmitate, Polyglyceryl-10 Diisostearate, Polyglyceryl-10 Pentaisostearate, Polyglyceryl-10 Nonaisostearate, Polyglyceryl-10 Decaisostearate, Polyglyceryl-10 Dioleate, Polyglyceryl-10 Pentaoleate, Polyglyceryl-10 Decaoleate, Polyglyceryl-10 Distearate, Polyglyceryl-10 Tristearate, Polyglyceryl-10 Pentastearate, Polyglyceryl-10 Pentahydroxystearate, and/or Polyglyceryl-10 Heptahydroxystearate. - In some embodiments, the long chain PEG surfactant is preferably a non-ionic surfactant sold under the trademark BRIJ®. Examples include BRIJ® CS20 (Ceteareth-20, Polyoxyethylene (20) Cetyl Stearyl Ether), BRIJ® C10 (Ceteth-10, Polyoxyethylene (10) cetyl ether), BRIJ® C20 (Ceteth-20, Polyoxyethylene (20) cetyl ether), BRIJ® IC20 (Isoceteth-20, Alkoxylated ether), BRIJ® IC20-70 (Isocetech-20 (Alkoxylated ether) and Aqua), BRIJ® L4 (Laureth-4, Ethoxylated Fatty Alcohol), BRIJ® L23 (Laureth-23, Polyoxyethylene (23) lauryl ether), BRIJ® L23-69 (Laureth-23 (Polyoxyethylene (23) lauryl ether) and Aqua), BRIJ® O10 (Oleth-10, Polyoxyethylene (10) oleyl ether), BRIJ® O20 (Oleth-20, Polyoxyethylene (20) oleyl ether), BRIJ® S10 (Steareth-10, Polyoxyethylene (10) stearyl ether), BRIJ® S20 (Steareth-20, Polyoxyethylene (20) stearyl ether), BRIJ® S100 (Steareth-100, Polyoxyethylene (100) stearyl ether) and/or BRIJ® S721 (Steareth-21, ethoxylated fatty alcohols).
- The co-surfactant is preferably a small molecule food surfactant, a natural lecithin, a purified lecithin, or combinations thereof. The small molecule food surfactant may comprise
Span 20, Span 40, Span 60,Span 80, Span 83, Span 85, Span 120, Glyceryl Laurate, and/or Glyceryl Stearate Citrate. The natural lecithin, if present, may be extracted from soybean, eggs, milk, marine sources, rapeseed, cottonseed, and/or sunflower seed. Purified lecithin, when present may comprise Lipoid S 40, Lipoid H 50, Lipoid PHOSAL® 50 SA, Lipoid PHOSAL® 53 MCT, Lipoid P 75, Lipoid S 75,Lipoid S 80,Lipoid E 80, PHOSPHOLIPON® 85 G, Lipoid PHOSPHOLIPON® 90 G, Lipoid PHOSPHOLIPON® 90 H, and/orLipoid H 100. - In one embodiment, the inventor was surprised to find that while
Span 20 generated a nano-emulsion composition where the droplet size was less than 100 nm, Span 40, Span 60,Span 80, Span 83, Span 85, and Span 120 generated emulsions with droplet size larger than 100 nm. - In some embodiments of the composition disclosed herein, if co-surfactant is a raw lecithin, then the amount of the co-surfactant is at least 0.75 times the amount of the dietically acceptable carrier oil; wherein if co-surfactant is a purified lecithin, then the amount of the co-surfactant is at least 0.50 times the amount of the dietically acceptable carrier oil; and wherein if co-surfactant is a small molecule food emulsifier, then the amount of the co-surfactant is at least 0.80 times the amount of the dietically acceptable carrier oil.
- Phospholipids may also be present in the composition, for example lecithin such as those extracted from soybean, eggs, milk, marine sources, rapeseed, cottonseed, and/or sunflower seed.
- The composition may further comprise a preservative and/or an essential oil, or a terpene or a flavoring agent or a food color or a bitter blocker or an artificial flavor agent. The purpose is to improve taste and appearance of the composition.
- In another aspect, the present disclosure provides a method of making the compositions disclosed herein, comprising: mixing the hydrophobic substance, the dietically acceptable carrier oil, surfactants or co-surfactants, and phosphorus lipid form; adding water to the composition and mixing to form a coarse emulsion; and sonicating the mixture under temperature control until the nanosized droplets are formed. The temperature of the mixture is usually kept below 75° C. during the mixing process. The method may further include sterilizing the composition, for example, by filtering it.
- The instant disclosure also describes a method of using a nano-emulsion composition comprising administering the composition by inhalation, targeting systemic, parenteral, oral, intrathecal, intraarticular, nasal, ophthalmic and/or topical means, wherein the nano-emulsion composition comprises a cannabinoid oil, a dietically acceptable carrier oil, a main surfactant, a co-surfactant and water. Thus, the various compositions disclosed herein may be used by adding it to a food or beverage, or may be used to consume directly. All compositions can be applied in topicals, cosmetics or personal lubricant products.
- In another preferred aspect, disclosed herein is a nano-emulsion composition comprising: a cannabinoid oil, a dietically acceptable carrier oil, a main surfactant, a co-surfactant, and water, wherein the amount of water is at least 1.15 times the amount of the combination of the cannabinoid oil, the dietically acceptable carrier oil, the main surfactant, and the co-surfactant, and wherein the amount of the dietically acceptable carrier oil is at least 0.3 times the amount of the cannabinoid oil. Within the same surfactant family, when the main surfactants have similar structures, hydrophilic-lipophilic balance (HLB) can help determine the relative ratios needed to make nano-emulsions. For example, within the same surfactant category, if the HLB of the main surfactant is >13, then the amount of the main surfactant is at least 0.65 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil; if the HLB of the main surfactant is between 11 and 13, then the amount of the main surfactant is at least 0.8 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil; and if the HLB of the main surfactant is between 9 and 11, then the amount of the main surfactant is at least 0.95 times the amount of the combination of the cannabinoid oil and the dietically acceptable carrier oil.
- The hydrophilic-lipophilic balance (HLB) of a surfactant is a measure of the degree to which it is hydrophilic or lipophilic. The HLB value can be used to predict the surfactant properties of a molecule. For example, HLB of less than 10 indicates lipid-soluble (water-insoluble), while an HLB of more than 10 indicates water-soluble (lipid-insoluble). Generally, an oil in water emulsifier has HLB of 8 to 16, while a solubilizer or hydrotope has a HLB of 16 to 18. HLB's of some commonly known compounds are illustrated below in Table 1. It should be noted that the HLB of a compound would be known to a skilled artisan in the art, and the list below is illustrative purposes only, and it is not meant to be an exclusive list of compounds that many be used as a surfactant for the compositions and methods disclosed herein. Furthermore, as would be known to a skilled artisan in the art, HLB is best applied to compare within the same surfactant family, and comparing HLB values between two different surfactant families often will not generate expected results.
- HLB is calculated as HLB=20*Mh/M where Mh is the molecular mass of the hydrophilic portion of the molecule, and M is the molecular mass of the whole molecule, giving a result on a scale of 0 to 20. Table 1 shows HLB of some surfactant used in this patent.
-
TABLE 1 Compound HLB polyglyceryl-6 oleate 9 Polyglyceryl-6 Stearate 9 Polyglyceryl-6 Laurate 14.5 Polyglyceryl-6 caprylate 15 Glyceryl Stearate 3.8 Oleth-20 15.3 Steareth-20 15.3 Steareth-21 15.5 Ceteth-20 15.7 Tween 2016.7 Tween 21 13.3 Tween 40 15.6 Tween 60 14.9 Tween 61 9.6 Tween 65 10.5 Tween 8015 Tween 81 10 Tween 85 11 - In one embodiment, the inventor was surprised to find that the droplet size of the composition disclosed herein is higher than 100 nm when the main surfactant is from Polyglyceryl-4 Series, including Polyglyceryl-4 Caprate, Polyglyceryl-4 Caprylate, Polyglyceryl-4 Laurate, Polyglyceryl -4 Isostearate, and Polyglyceryl-4 Oleate. It may be due to their relatively lower HLBs compared to Polyglyceryl-6 or Polyglyceryl-10 Series. When 1 g of cannabinoid oil, 0.7 g of olive oil, 2.5 g of a Polyglyceryl-4 surfactant, 1.5 g of lecithin with sunflower, and 40 g of water, were mixed and sonicated at 80% amplitude, the Polyglyceryl-4 surfactants failed to make a nano-emulsion. Droplet size change was monitored by DLS time wise. Sonication was stopped when droplet size reach plateau and does not decrease. The final emulsion droplet average size obtained with Polyglyceryl-4 Caprate, Polyglyceryl-4 Caprylate, Polyglyceryl-4 Laurate, Polyglyceryl-4 Isostearate, and Polyglyceryl-4 Oleate were 365 nm, 427 nm, 488 nm, 371 nm, and 506 nm respectively. This unexpected result illustrated that while some surfactants result in the desired claimed nano-emulsion composition, other surfactants may not. It should be noted, however, that while the Polyglyceryl-4 series of surfactants failed to make a nano-emulsion, they may be utilized when a larger droplet size is desired.
- Throughout the following discussion, numerous references are made regarding cannabinoid compounds or cannabinoid derivatives. It should be noted that while the general discussion is towards cannabinoids, the instant composition can also be used for any other hydrophobic compounds that would benefit from dispersing in an aqueous solution, including terpenes, other essential oils, extract from herbs, eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) or many other hydrophobic drug molecules.
- In the various embodiments disclosed herein, the average nanosized droplet size is less than 500 nm. In some cases, the average droplet size is 400 nm, or less than 200 nm, or less than 100 nm, or less than 90 nm, or less than 80 nm, or less than 70 nm. In one preferred embodiment, at least 80% of the nanosized droplets in the composition have a droplet size between 10-70 nm, or between 30-50 nm, as illustrated in
FIGS. 2 and 4 . In some cases, the average nanosized droplet is 35 nm with a standard deviation of 10 nm, as illustrated inFIG. 2 . When the composition is diluted the average nanosized droplet is 46 nm with a standard deviation of 15 nm, as illustrated inFIG. 4 . Sometimes, measuring concentrated nano-emulsion (>10 mg/g) by Dynamic Light Scattering could have misleading data. Since at higher concentration, the emulsion droplets pack close to each other and may generate unreal scattering pattern. Emulsion concentration at 0.1 mg/g (of active ingredient) is usually used as the standard measuring concentration. While the nanosized droplets are a preferred embodiment of the instant application, larger sized droplets are contemplated as well. Sometimes, larger size emulsion is generated by design to achieve desirable effects. In one aspect, the composition disclosed herein is preferably a liquid composition. The composition remains in dispersed form upon dilution in aqueous solution, as illustrated inFIG. 3 . As shown inFIG. 4 , the droplet size remains unaffected upon dilution in aqueous solution. As shown inFIG. 5 , the composition, after dilution intopH 8 solution, can be stored at room temperature (calculated from 55° C. acceleration study) for up to three years without change in droplet size.FIG. 6 demonstrated the composition, after diluted into pH 3.5 solution, also have up to equivalent to three years of stability at room temperature (calculated from 55° C. acceleration study). Table 2 shows the stability correlation relation between 55° C. and room temperature. -
TABLE 2 Equivalent shelf life at Room Stability at 55° C. Temperature 1 week 3 month 3 week 9 month 6 week 18 month (1.5 years) 9 week 27 month 12 week 36 month (3 years) - Since the nano-emulsion can be diluted to any concentration and remain the integrity of nano-sized droplets, it can be applied in various different applications where different concentration of active ingredient is needed. For example, Table 3 shows possible end applications the nano-emulsion can apply to:
-
TABLE 3 Final cannabinoid Product types that is suitable at this concentration (mg/g) concentration 12.5 High concentration topicals 6.25 High concentration tinctures 3.125 Topicals or lubricants 1.6 Facial creams 0.8 Directly used cannabis shot 0.4 Flavored cannabis Shot 0.2 Beverages for medical patients 0.1 High dose beverages 0.05 Low dose beverages 0.025 Micro-dosing beverages - The hydrophobic substance of the composition disclosed herein preferably comprises a plant extract. In especially preferred embodiments, the hydrophobic substance comprises a cannabinoid. The cannabinoid may be a phytocannabinoid or a synthetic cannabinoid, as disclosed above.
- In some embodiments, the nanosized droplets may comprise more than one hydrophobic substance. In some instances, it is contemplated that the more than one hydrophobic substance will have synergistic effect with each other to produce a result that is better than the sum of its parts. For example, by way of example, each nanosized droplet in the composition may comprise THC, CBD and a terpene compound. The amounts of each component in the droplet may be controlled. For example, in some embodiment, each nanosized droplet may have 1×THC, 3'CBD, and 4×Terpene. As is generally known in the art, THC, CBD, terpene, together with other cannabinoid compounds, have synergistic effect, they often have better results compared to just consuming one compound. Furthermore, the droplet may have another flavoring agent, such as mint oil, orange oil or lemon oil. Thus, the cannabis oil may be infused with any other oil in the nano-emulsion form. Thus, in one embodiment, by using this method, different kinds of nano-emulsions may be prepared from different plant extract; and these nano-emulsions may be used in a drink to mimic the natural effect of the plant, or even create other special effect which is not available from natural plants themselves.
- The composition disclosed herein also comprises an edible carrier oil. The edible carrier oil as contemplated herein may be from the plant material, which comprises sunflower oil, olive oil, coconut oil, sesame oil, avocado oil, palm oil, soybean oil, corn oil, peanut oil, canola oil, or combinations thereof. The edible oil may also be from animal parts, such as for example, lard or butter.
- The composition also typically includes one or more surfactant. When more than one surfactant is used, preferably one is a high molecular weight surfactant and the other is a low molecular weight surfactant. Thus, in one case, the surfactant comprises a main surfactant and a co-surfactant, wherein the main surfactant is a high molecular weight surfactant, and the co-surfactant is a lower molecular weight surfactant. The compositions described herein may further comprise a preservative and/or a flavoring agent. The preservative, if present, is usually between 0-2% of the composition. In one example, the preservative is citric acid and/or benzoic acid. The preservative system can also be natural compounds like Vitamin E and Vitamin C. The flavoring agent may be an essential oil, such as for example, Lemon oil, orange oil, peppermint oil, Ylang Ylang oil, Lemon Grass oil, Tea Tree oil, Rosemary oil, Australian Sandalwood oil, Grape fruit oil, frankincense oil, cedarwood oil, patchouli oil, cinnamon bark oil, bergamot oil, chamomile oil, Lemon Eucalyptus oil, ginger oil, key lime oil, vanilla oil and/or clove oil. The flavoring agent, if present, comprises about 1-10% of the composition.
- The compositions disclosed herein may also comprise different types of bitter blockers. Synthetic or natural bitter blockers can be used in cannabinoid nano-emulsions to block bitterness that originated from un-pure plant extracts, wax, polyphenols or undesired flavors from surfactant systems. The bitter blockers used in the compositions disclosed herein include BB68 (3-[1-[(3,5-dimethylisoxazol-4-yl)methyl]pyrazol-4-yl]-1-[(3-hydroxyphenyl)methyl]imidazolidi ne-2,4-dione) from Senomyx, GG-605-390-4, NP-844-232-9 and QJ-615-696-6 from Givaudan, TRUCLEAR™ from Tastesnaturel and/or CLEARTASTE™ from MycoTechnology.BB68 was introduced either by ethanol or polypropylene glycol into the final nano-emulsion system at the concentration range from 2.5-10 ppm, depending on the certain bitterness of diluted emulsion. GG-605-390-4, NP-844-232-9 and QJ-615-696-6 were directly added into the diluted nano-emulsion at concentration range from 0.01%-0.05%. TRUCLEAR™ and CLEARTASTE™ can be used at the concentration of 0.001-0.1%, depending on nano-emulsion's composition. Sometimes, different bitter blockers can be mixed and used together, for example, 0.015% NP-844-232-9 plus 0.015% GG-605-390-4 has a better effect on flavor compared to using 0.03% GG-605-390-4 or 0.03% NP-844-232-9 along. It should be noted that all those bitter blockers can also be added into the raw emulsion at higher concentration, so that when the raw emulsion get diluted into final drinks, the bitter blockers' concentration can reach to the level mentioned above.
- The compositions disclosed herein may comprise various amounts of the hydrophobic substance, the dietically acceptable carrier oil, the surfactant, and the phospholipid form as described above. One non-limiting composition include: 10-20% of cannabis oil, 5-15% of sunflower oil, olive oil or coconut oil, 60-70% of
Tween 80, and 5-15% of sunflower lecithin. Another non-limiting composition include: 10-20% of cannabis oil, 5-15% of sunflower oil, olive oil or coconut oil, 60-70% ofTween 20, and 5-15% of sunflower lecithin. - By way of example, a composition disclosed herein having a tween series main surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 2-4 parts main surfactant of the Tween series, 0.5-3.5 parts co-surfactant, and 30 parts water. Similarly, when a composition disclosed herein has a tween series main surfactant and a natural lecithin as a co-surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.75-4 parts main surfactant of the Tween series, 0.5-3.5 parts natural lecithin, and 30 parts water. When the composition comprises a main surfactant tween series and a purified lecithin as a co-surfactant, the composition would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.2-3 parts main surfactant of the Tween series, 0.85-3 parts purified lecithin, and 30 parts water.
- By way of another example, for a composition disclosed herein having a polyglyceryl series main surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.75-3.5 parts main surfactant of the polyglyceryl series, 1-3.5 parts co-surfactant, and 30 parts water. Similarly, when a composition disclosed herein has a polyglyceryl series main surfactant and a natural lecithin as a co-surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.9-4 parts main surfactant of the polyglyceryl series, 0.5-3.5 parts natural lecithin, and 30 parts water. When the composition comprises a main surfactant polyglyceryl series and a purified lecithin as a co-surfactant, the composition would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.5-4 parts main surfactant of the polyglyceryl series, 0.85-3 parts purified lecithin, and 30 parts water.
- By way of a further example, for a composition disclosed herein having a long chain PEG series main surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.25-3.75 parts main surfactant of the long chain PEG series, 0.5-3 parts co-surfactant, and 30 parts water. Similarly, when a composition disclosed herein has a long chain PEG series main surfactant and a natural lecithin as a co-surfactant would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1.75-4 parts main surfactant of the long chain PEG series, 0.35-3 parts natural lecithin, and 30 parts water. When the composition comprises a main surfactant long chain PEG series and a purified lecithin as a co-surfactant, the composition would have about 1 part by mass of the cannabinoid oil, 0.35-3 parts carrier oil, 1-3 parts main surfactant of the long-chain PEG series, 0.85-3 parts purified lecithin, and 30 parts water.
- No matter using which main surfactant category is selected, carrier oil can sometimes exceed cannabinoid oil by many folds, as long as the following criteria is met, nano-emulsion can still be produced: main surfactant is at least 1.05 times the amount of combination of cannabinoid oil and carrier oil and if the co-surfactant is a natural lecithin, then the amount of the co-surfactant is at least 0.75 times the amount of the dietically acceptable carrier oil; if the co-surfactant is a purified lecithin, then the amount of the co-surfactant is at least 0.50 times the amount of the dietically acceptable carrier oil; and if the co-surfactant is a small molecule food emulsifier, then the amount of the co-surfactant is at least 0.80 times the amount of the dietically acceptable carrier oil.
- As is generally known in the art, droplet sizes and their distribution may affect the human feeling on flavor. On one side, nano-size can amplify or even alter the taste, something tastes plain at bulk may taste bitter or sour in nano-scale. On the other side, taste buds on tongue tend to have different time reactions to different sizes of particles. The smaller droplets can quickly absorb at the gap of the tasting buds, thus blocking the touching/feeling from bigger droplets. The droplet size can be well controlled by how much energy is put into the liquid system, which can be controlled either by amplitude % of the sonicator or by how long the liquid is being sonicated at certain amplitude %. For example, shown in
FIG. 10 , 8-10 mins of sonication at 80% amplitude can generate an average of 30 nm olive oil nano-emulsion, while 4-5 mins of sonication at 80% amplitude can generate an average of 70 nm cannabinoid nano-emulsion. - It would be generally known to a skilled artisan in the art that ultrasonic frequency of a sonicator is generally fixed at 20 kHz and does not fluctuate during sonication. The sonicator continuously calibrates itself to ensure consistent output. A commercially available sonicator may be used to make the compositions disclosed herein. The wattage of such a sonicator may vary from 250 W to about 800 W, and more preferably between about 350 W to about 650 W, and most preferably between 450 W to about 550 W. The output energy depends on the viscosity of the emulsion and also temperature. For example, when the formula contains enough amount of surfactant and enough amount of water, the total energy required to generate nano-emulsion (J/mL) will be less than a formula that contains less surfactants and less water, which is due to how easy it is for the droplet to form in the emulsion and viscosity. Processing amplitude are adjustable, and it is within a linear relation with intensity. And process time can also be adjustable, which will determine total input energy under certain intensity. Since each formula may need different amount of energy to get into nanosize, we usually monitor droplet size change with Dynamic Light Scattering over production time to determine when to stop the sonication.
- There are two major methods to operate sonication: batch mode and continuous mode. For batch size less than 200 mL, batch mode is applied, which includes a sonication probe immersed into the target liquid. For batch size larger than 1 L, continuous mode is preferred, where the raw emulsion was stored in a tank, and it gets pumped into the sonication chamber and pumped back into the tank. The energy input happens at the sonication chamber. Usually, in preferred embodiments, the whole volume of liquid would be circulated 12-20 times to achieve nanosize. For example, for a 10 L tank, under 2 L per min pumping rate, the amount to time needed to generate a nano-emulsion is calculated as follows: (12-20)×10 L/2 L/mins=60-100 mins.
- Heat is generated during the sonication process, overheat not only damage equipment, but also will degrade cannabinoid. For batch mode, ice/dry ice batch is applied to maintain the temperature. For continuous mode, recirculating chillers were applied to cool down the reaction chamber during the process. The temperature was kept below 70° C. for both modes.
- In one aspect, provided herein is a method of making a composition comprising: mixing the hydrophobic substance, the dietically acceptable carrier oil, surfactant, and phosphorus lipid form; adding water to the composition and mixing to form an emulsion; and sonicating the mixture under temperature control until the nanosized droplets are formed. The temperature of the mixture is usually kept below 75° C. during the mixing process. In some instances, the composition is sterilized by filtering through a 0.2 um filter. The composition is usually stored in a light blocking vessel and stored at 4° C. If larger droplets are desired for a particular application, for example microsized droplets, the energy put in during the mixing process is lowered.
- The compositions disclosed herein may be administered to a subject in a variety of ways, such as, for example, by inhalation, targeting systemic, parenteral, oral, intrathecal, intraarticular, nasal, ophthalmic and/or topical means. In one embodiment, the compositions disclosed herein may be added to a beverage or food prior to oral administration. The compositions may be used for an application that uses aqueous infusion, say for example, water-based lube, chewing gum, topicals, facial spray, makeup remover etc. The technology of nanosized particles may also be used for other applications, for example, pharmaceutical drug delivery of a hydrophobic drug, or general food and agriculture material treatment.
- Viewed from a different perspective, the compositions disclosed herein may be grouped as systems; each such system is discussed in detail below. Each system contains target oil (cannabis oil in particular), carrier oil, one to three surfactant types, and water. The major differences between systems are the combination of surfactant types and its relative amount to other ingredients.
- System 1: Polyglyceryl Series Surfactant+Co-Surfactant
- Polyglyceryl surfactant series are generally regarded to be very safe to consume, there is usually no upper limit of consumption in food. Its main structure contains a polyglycerol chain as hydrophilic head and a fatty acid as hydrophobic tail. The co-surfactants applied here can be small molecule food emulsifiers, natural lecithin or purified lecithin. In a typical formula, the total mass amount of polyglycerol surfactant plus co-surfactant should be higher than twice the total mass amount of target oil plus carrier oil. In some cases, the mass amount of co-surfactant should be higher than the mass amount of carrier oil. The relative ratio of polyglyceryl surfactant used in the system can be determined by its HLB, as disclosed herein.
- System 2: Long Chain PEG (BRIJ®) Series Surfactant+Co-Surfactant
- BRIJ® surfactants are widely used in cosmetic products due to their excellent surface activity. BRIJ® surfactant can be used in combination of co-surfactant to make cannabinoid nano-emulsion. Co-surfactant in this system can be small molecule food emulsifiers, natural lecithin and/or purified lecithin. In a typical formula, the total mass amount of BRJI surfactant plus co-surfactant should be higher than twice the total mass amount of target oil plus carrier oil. In some cases, the mass amount of co-surfactant should be higher than the mass amount of carrier oil. The relative ratio of BRIJ® surfactant used in the system can be determined by its HLB, which is disclosed in herein.
- System 3: Tween Surfactant with Co-Surfactant:
- Polysorbate (Tween) surfactants are commonly used in food and cosmetic industry due to their high surface property and relative safety to human consumption. It includes
Tween 20, Tween 40, Tween 45, Tween 60, Tween 65,Tween 80 and Tween 85. They share the same hydrophilic head, the only difference lays in their hydrophobic chain in terms of chain length and saturation. The Tween family system can be used with various co-surfactants to generate nanoemulsions. - In general, tween surfactant's amount in mass should be higher than 0.65 times the total weight of target oil and carrier oil, and co-surfactant's amount in mass should be higher than 0.80 times the weight of carrier oil. The total amount of tween surfactant plus the co-surfactant should be higher than 1.85 times of weight of target oil, and/or 1.35 times the weight of carrier oil and/or 1.15 times the total weight of target oil and carrier oil. Below are 7 examples from the
system 3 using Tween surfactants and co-surfactant. - System 4: Combination of Different Main Surfactants
- Sometimes, a combination of different types of main surfactants, can also generate cannabinoid nano-emulsions. The main surfactant types include polyglyceryl series, tween series and/or BRIJ® series. The ratio of different types of main surfactants can be adjusted to any desired range as long as the amount of combination of main surfactants should be at 1.05 times the amount combination of cannabinoid oil and carrier oil. For example, the main surfactants can be split into half as Tween Series and half as polyglyceryl Series, or ⅓ as Tween Series, ⅓ as polyglyceryl Series and ⅓ as BRIJ® series. As long as their total amount is greater than 1.05 times the amount combination of cannabinoid oil and carrier oil.
- The description throughout this disclosure provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus, if one embodiment comprises elements sunflower oil, tween-80, sunflower lecithin, and cannabinoid, and a second embodiment comprises elements coconut oil, tween-20, sunflower lecithin, cannabinoid and lemon oil, then the inventive subject matter is also considered to include other remaining combinations of sunflower oil, coconut oil, tween-80, tween-20, sunflower lecithin, cannabinoid, and lemon oil, even if not explicitly disclosed.
- Embodiments of the present disclosure are further described in the following examples. The examples are merely illustrative and do not in any way limit the scope of the invention as claimed.
- The
formula 1 disclosed below is a general base formula that works with many starting materials. This composition has a bitter taste due to the presence of Tween-80. The bitter taste may be desirable in some cases. If the bitter taste is not desired, then additives such as essential oils may be added to mask the bitter taste. -
Formula 1.Items Mass (g) Mass Ratio Sunflower oil or olive oil or solid coconut oil or 0.625 1 liquid coconut oil Tween 80 2.5-4.5 4-7.2 Sunflower lecithin 0.625-0.9 1-1.44 Citric acid or benzoic acid (optional, not active) 0.001 or 0 - 1 g of cannabis and 5 g of the
Formula 1 are added to a 100 ml beaker, and mechanically stirred under controlled heat (<60° C.), until it is well mixed. The cannabis oil may be a full plant extract or a high pure distillate. Water is added to the mixture, the amount of water is determined by the final targeting concentration. The mixture is kept stirring until a homogenous milky coarse emulsion is formed. The mixture is put in an ice bath and a sonicator probe is inserted into the liquid. The mixture is sonicated at 80% amplitude. Temperature of the liquid should be constantly monitored, when temperature is above 70° C., the sonication should be stopped, let the liquid cool down to room temperature and restart the sonication until the liquid become translucent/transparent (nanoemulsion). Sometimes, in order to further improve the taste, finished nanoemulsion will flow through a packed Al2O3 or activated charcoal column. The nanoemulsion is then filtered through a nylon 0.2 um filter, collected in a light blocking vessel, and kept at 4° C. - The concentration ranges of ingredients above represent a scenario where nano-emulsion can be generated. In the meanwhile, depending on final target droplet sizes, the ingredients' concentration ranges can be flexible. For example, if nano-emulsion is target (<100 nm), then the desirable range of each ingredient can be: cannabinoids (1 g), carrier oil (0.5-2 g), Tween 80 (2.5-4.5 g) and lecithin (0.3-3 g).
Tween 80 is the major driving force in the formula, with enough of it, the final formulation can be driven into nano-size. Another example, if an emulsion with droplet size in the range over 100 nm is desired, the desirable range of each ingredient can be: cannabinoids (1 g), carrier oil (0.5-6 g), Tween 80 (1-2 g) and lecithin (0.3-3 g). - The
above formula 1 is a general base formula to which different ingredients can be added to suit the needs of a particular application. For example, the ingredients and the amounts may be varied to vary onset time, flavor, look, stability, compatibility, concentration, texture. For example, a water lube needs to have a good taste, a good smell, and a high concentration of cannabinoid and a low droplet size distribution to allow the cannabinoid to absorb quicker, also need to keep the texture of product to be viscous and smooth. Thus, in this example, the concentration of cannabinoid in the nano-emulsion would be higher, since only a small volume of nano-emulsion can be added to the lube base. Furthermore, it is noted that while oil may break down a latex condom, the carrier oil or essential oil in the formula will have no such effect because oil is trapped inside the tiny droplets, which is protected by the surfactants on the edge as an insulating layer. This protection effect is better when the surfactant hydrophilic heads are bigger, which offer more room for the protection layer. - The
formula 2 disclosed herein works with most high purity distillate cannabis oil. It is less bitter thanFormula 1 due to the incorporation ofTween 20 instead ofTween 80. Similar toformula 1, 1 g of cannabis oil is mixed with 5 g of theformula 2 and the method disclosed above forformula 1 is used to making the composition. The desirable concentration range ofFormula 2 is similar to theFormula 1 as described above. -
Formula 2.Items Mass (g) Mass Ratio Sunflower oil or olive oil or solid coconut oil 0.625 1 or liquid coconut oil Tween 20 2.5-4.5 4-7.2 Sunflower lecithin 0.625-0.9 1-1.44 Citric acid or benzoic acid (optional, not 0.001 or 0 active) -
Formula 3 can tolerate more carrier oil and still generate nanoemulsions of cannabinoinds. The carrier oil can be fats from animal parts, such as lard or butter, or from plants, such as sunflower oil, liquid coconut oil or any other forms. Similar to above, 1 g of cannabis oil (either full plant extract or high pure distillate) is added to 6 g of natural fats first, stir and heat is applied to make sure the natural fats and cannabinoids are fully mixed into one continuous phase. Then, 7 g ofTween 20 and 1.2 g of Sunflower lecithin were added into the oil mixture. In one embodiment, the method disclosed above forformula 1 is used to making the instant composition. - Each ingredient's concentration range is determined by the target needs. In one embodiment, for example, for each 1 g of THC distillate, 6 g of fats are used. Under this combination,
Tween 20 range can be anywhere from 6-8.5 g and sunflower lecithin range can be anywhere from 4.68-6 g. As long as main surfactant and co-surfactant amount increase together with the carrier oil following the rule as below, cannabinoid nanoemulsion can be generated: amount of the total surfactants is at least 1.45 times the amount of cannabinoid oil, and/or the amount of total surfactants is at least 1.35 times the amount of carrier oil, and/or the amount of total surfactants is at least 1.15 times the amount of combination of cannabinoid oil and carrier oil. THC distillates can be obtained from different purification methods, which will contribute different portion of polyphenols in the product. In this case, the other components' ranges can beTween 20 as of 1.5-7 g and lecithin can be as of 0.3-4 g. -
Formula 3Items Mass (g) Mass Ratio Fats from either animal parts or 6 1 plants parts Tween 20 6-8.5 1-1.4 Sunflower lecithin 4.68-6 0.78-1 Citric acid or benzoic acid 0.001 or 0 (optional, not active) - Formula 4 provides an advantage over
Formulas formula 2, and the method disclosed above forFormula 1 is used for making the composition. - Each essential oil will have a different synergetic effect on the flavor side with the cannabinoid, which can result in less or more dosage in the final composition. For example, mint oil and ginger oil are so far the best to cover the bitterness flavor from cannabinoid. The ratio of them to cannabinoid can be as low as 2:1. Other essential oils may be applied in a higher quantity to cover the bitterness, which can be over 3:1 or higher. In this formula,
Tween 20 range can be more flexible, which can be anywhere from 1.5-5 g, depending on how much quantity of essential oil has been used. -
Formula 4 Items Mass (g) Mass Ratio Olive oil or liquid coconut oil 0.625 1 Tween 202.5-5.4 4-8.64 Sunflower lecithin 0.625-0.9 1-1.44 Citric acid or benzoic acid (optional, not active) 0.001 or 0 Spearmint oil, Peppermint oil, Ginger oil, lemon 2-4.5 3.2-7.2 oil, coffee oil, Ylang Ylang oil, raspberry oil, and/or Passion Fruit Oil, any other kinds - Formula 5 is robust to mostly any kind of pure or mixed terpenes, which can be either extracted from cannabis plants or other agricultural plants. Some tested terpenes include pinene, limonene, linalool, beta-caryophyllene, myrcene and others. Formula 5 also works to generate any kind of nano-emulsion based on the essential oil. Similar to above, 0.2-1 g of terpenes (either full plant extract or high pure distillate) or 0.2-1 g of essential oil is added with 5 g of
formula 2, and the method disclosed above forFormula 1 is used for making the composition. - Since terpenes and essential oils are easier to be made into nano-emulsion compare to cannabinoid,
Tween 20 can be used in a slightly wide range from 1.5 g to 5 g. The fats range can be 0.35 g to 2 g and lecithin range can be 0.35 g to 3 g. -
Formula 5 Items Mass (g) Mass Ratio Sunflower oil, Olive oil or other fats 0.625 1 Tween 202.5-5.4 4-8.64 Sunflower lecithin 0..625-0.9 1-1.44 Citric acid or benzoic acid (optional, 0.001 or 0 not active) Terpenes or essential oils 0.2-1 0.32-1.6 -
Formula 6 is developed to not only generate nano-emulsion for 97% CBD isolate, but also block the bitterness of this nano-emulsion. With the composition fromFormula 2, nano-emulsion of CBD isolate can be generated. However, in some instances, the bitterness taste may not be desired in food additives. In one embodiment, the inventor found out that the trace amount of polyphenols present in the CBD isolate may contribute to the bitterness. In one embodiment, it was found that the polyphenols are present in the bulk form of the crystals, and whenTween 20 is added, it dissolves the polyphenol out of the system and amplify the bitterness. - To solve this problem, the inventor developed two methods to remove the polyphenols in the system as described below.
- Method 1: pre-sonication, dissolve lg CBD powder into 10 mL organic solvent such as chloroform, ether or hexane, then wash this organic layer in a separating funnel with 20 mL of 0.01N HCl Solution three times, 20 mL of 5% NaHCO3 three times and saturated
NaCl solution 3 times. Then the organic layer was collected, dried with 1-2 g of MgSO3, filtered and then evaporated to dryness. Another washing agent can be 1-3% PVP40 solution: repeat the same wash procedure like above three times with 20 mL of PVP40 solution, then wash with saturated NaCl solution, dried by MgSO3, filtered and then evaporated to dryness. The purified CBD then can be turned into nano-emulsion using formula 2 with much less bitterness. - Method 2: did not treat the CBD raw material but make a nano-emulsion of it with
Formula 2, then for every 50 mL of the nano-emulsion, apply 1-10 g of absorbance material to the nano-emulsion as disclosed herein. - As further described below, Formula 7 comprises a surfactant from the polyglyceryl-10 series.
-
Formula 7 Items Mass (g) Mass Ratio Sunflower oil, Olive oil or other fats 0.625 1 Polyglyceryl-10 Oleate, Polyglyceryl-10 Laurate, 1.95-2.5 3.12-4 Polyglyceryl-10 Caprylate/Caprate or Polyglyceryl Ester Fatty Acid (POLYALDO ® 10-2-P) Sunflower lecithin or purified lecithin 0.625-0.9 1-1.44 Citric acid or benzoic acid (optional, not active) 0.001 or 0 - Polyglyceryl-10 series surfactants are not only very safe to consume, but they also present better surface activity in making cannabinoid nanoemulsions. Especially for Polyglyceryl-10 Oleate, Polyglyceryl-10 Laurate, Polyglyceryl-10 Caprylate/Caprate and Polyglyceryl Ester Fatty Acid (POLYALDO® 10-2-P), they can used in less amount compared to Tween series surfactants to generate cannabinoid nanoemulsion. Sometimes, due to the surfactants' own milky colors, the finished nanoemulsion appears to be milky/translucent instead of fully transparent. Polyglyceryl-10 series surfactants can be used together with sunflower lecithin or purified lecithin for nanoemulsion generation. Due to the safety nature of Polyglyceryl-10 series surfactants and lecithin, this combination may have huge potential applications as premium food/drink ingredients.
- In one embodiment, the main building blocks within each formula comprise carrier oil,
tween 20 ortween 80 and Sunflower lecithin. For every 1 g of cannabinoid oil used, carrier oil's range should be within 0.25 g to 8 g,Tween 20 orTween 80 range should be within 2.5 g to 8 g, and sunflower lecithin should be within the range of 0.3 g to 4 g. - If other essential oils are used to block the flavor, mint oil works the best as masking the bitterness, while lemon oil takes advantage its own natural bitterness to cover the cannabinoid bitterness. So of the essential oils may be needed at least 2-3 times higher mass than cannabinoid oils' mass.
- Some other surfactant types may not work as good as the combination of
tween 20/tween 80 with Sunflower lecithin. For example, soy derived lecithin is a solid wax, it does not work as well as sunflower lecithin. Also, surfactants likeSpan 80,Span 20 works with the combination ofTween 20 orTween 80, but not used as primary surfactant by themselves. Surfactants like Glyceryl Laurate, PolyGlyceryl 3-Laruate, PolyGlyceryl 3-Oleate and Glyceryl Stearate Citrate often offer a cloudy emulsion with droplet size in the range over 200 nm. They can be used in the case where nano-size is not required. Thus, they are not used directly in the formula disclosed herein. - The power of converting hydrophobic materials into water soluble nano-emulsion also helps recombine and regenerate the desired final aqueous product, some of those can be found in natural material, some of them can be simulated in a way which has never been explored from natural compounds. For example, by adding 4 parts of full plant CBD nano-emulsion with 1 part of linalool nano-emulsion and 2 parts of limonene nano-emulsion, a synthetic drink can be generated. It can quickly ease the nerve and calm people down with a very mild brain reaction. This combination can not be found in nature, and the nano-emulsion formula enabled unlimited discovery like this.
- In one embodiment, the inventor unexpectedly and surprisingly found that while
Span 20 resulted in a nano-emulsion having average particle size of less than 100 nm, Span 40, Span 60,Span 80, Span 83, Span 85, and Span 120 resulted in nano-emulsions having average particle size of more than 100 nm. In this example, lg of cannabinoid, 0.625 g of olive oil, 3.75 g ofTween 80, and different kinds of Span surfactant were used to make the composition. Thus, in each case, Span toTween 80 is at mass ratio of 1:6. The 80% amplitude of sonication was applied to 45 mL of total volume of mixed liquid with Span,Tween 80, carrier oil, cannabinoid oil and water. Droplet size change was monitored by DLS time wise. Sonication was stopped when droplet size reach plateau and does not decrease. - The table shows that only Span 20 can generate emulsion that have droplet size smaller than 100 nm. With decrease HLB of Span surfactant, the droplet size increases. Even though most of Span surfactants failed to make nanoemulsion, but they may be utilized when a larger droplet sized emulsion is desired.
-
Final Emulsion droplet Span Surfactants HLB average size (nm) Span 208.6 91 Span 40 6.7 245 Span 60 4.7 316 Span 804.3 387 Span 83 3.7 560 Span 85 1.8 876 Span 120 4.7 302 - As described throughout this application, lecithin may be used as a co-surfactant in the composition disclosed herein. In one embodiment, the inventor found that unexpectedly and unanticipatedly, natural lecithin from Soy does not work in the composition while natural lecithin from Sunflower works! Natural lecithin from Sunflower is a viscous dark brown liquid; it is easier to dissolve in the cannabinoid+carrier oil+main surfactant system. In example 1, together with
Tween 80, it can generate emulsion with average droplet size of 40-50 nm. However, natural lecithin from Soy it takes longer to dissolve into the cannabinoid+carrier oil+main surfactant system. And with adding water, some of it precipitated out. It needed longer time to get it back into a homogenous system. Soy lecithin, together withTween 80, cannabinoid oil, edible oil, and water could generate emulsion with average droplet size of 150-170 nm, but could not generate a nano-emulsion with average droplet size of less than 100 nm. - In another embodiment, the inventor unexpectedly discovered that the amount of water in the composition is important for the droplet size. The inventor found that when the amount of water in the composition is less than 1.15 times the combination amount of cannabinoid oil, carrier oil, main surfactant and co-surfactant, the resulting emulsion has a droplet size of more than 100 nm.
- For example, when 10 g of cannabinoid, 6.25 g of olive oil, 37.5 g of
Tween 80, and 6.25 g of sunflower lecithin was mixed with different amounts of water and sonicated as described, the final emulsion droplet average size varied as shown below in the chart. -
Water Cannabinoid concentration in Final Emulsion droplet average amount final emulsion (mg/g) size (nm) 70 76.92 197 90 66.67 124 120 55.56 98 170 43.48 64 250 32.26 41 - Thus, when the amount of the other ingredients is kept the same, and the amount of water was varied, the more water there is, the smaller the droplet size. In other words, if the final cannabinoid concentration in the starting emulsion is more than 65 mg/g, then the starting emulsion may not have a nanosized droplet.
- In another surprising result, the inventor found that in system 4, when there is no co-surfactant as of natural lecithin, purified lecithin, or small molecule food emulsifiers, the main surfactant can make nano-emulsion with average size of 50 nm. However, the nano-emulsion made by such a process does not have long term stability. In an elevated temperature (55° C. Oven) stability study, the droplet size of the nano-emulsion increases from 50 nm to 150 nm in 2 weeks, and to 300 nm in 5 weeks and to 620 nm in 8 weeks. At
week 8, it becomes a little bit opaque. So, without co-surfactant, system 4 can generate a nano-emulsion, but its stability dramatically decreases compared to other systems with co-surfactant. On the other hand, when a co-surfactant is present, the composition had long term stability—12 weeks no layer separation in 55° C. Oven. - For all the examples above, and for all formula combinations mentioned in this disclosure, water amount can be varied dramatically as long as it is 1.15 times higher than the amount of combination of cannabinoid oil, carrier oil and surfactant systems. This indicates the final concentration of the cannabinoid in the finished emulsion can vary from ˜60-70 mg/g down to very low as of 0.01 mg/g, in which case excess amount of water is added. It means all the formula combinations in this disclosure can not only make concentration nanoemulsion that can be diluted later into food or cosmetic, they can also generate end product with variable targeted concentrations.
- In some embodiments, the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
- Unless the context dictates the contrary, all ranges set forth herein should be interpreted as being inclusive of their endpoints and open-ended ranges should be interpreted to include only commercially practical values. Similarly, all lists of values should be considered as inclusive of intermediate values unless the context indicates the contrary.
- As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.
- The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value with a range is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
- Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.
- It should be apparent to those skilled in the art that many more modifications besides those already described are possible without departing from the inventive concepts herein. The inventive subject matter, therefore, is not to be restricted except in the spirit of the appended claims. Moreover, in interpreting both the specification and the claims, all terms should be interpreted in the broadest possible manner consistent with the context. In particular, the terms “comprises” and “comprising” should be interpreted as referring to elements, components, or steps in a non-exclusive manner, indicating that the referenced elements, components, or steps may be present, or utilized, or combined with other elements, components, or steps that are not expressly referenced.
Claims (17)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17/239,262 US20210251948A1 (en) | 2018-07-19 | 2021-05-06 | Nanoemulsion hydrophobic substances |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201862700642P | 2018-07-19 | 2018-07-19 | |
US16/206,869 US11013715B2 (en) | 2018-07-19 | 2018-11-30 | Nanoemulsion hydrophobic substances |
US17/239,262 US20210251948A1 (en) | 2018-07-19 | 2021-05-06 | Nanoemulsion hydrophobic substances |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US16/206,869 Continuation US11013715B2 (en) | 2018-07-19 | 2018-11-30 | Nanoemulsion hydrophobic substances |
Publications (1)
Publication Number | Publication Date |
---|---|
US20210251948A1 true US20210251948A1 (en) | 2021-08-19 |
Family
ID=69165096
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US16/206,869 Active US11013715B2 (en) | 2018-07-19 | 2018-11-30 | Nanoemulsion hydrophobic substances |
US17/239,262 Abandoned US20210251948A1 (en) | 2018-07-19 | 2021-05-06 | Nanoemulsion hydrophobic substances |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US16/206,869 Active US11013715B2 (en) | 2018-07-19 | 2018-11-30 | Nanoemulsion hydrophobic substances |
Country Status (5)
Country | Link |
---|---|
US (2) | US11013715B2 (en) |
EP (1) | EP3823585A4 (en) |
CA (1) | CA3106840A1 (en) |
MX (2) | MX2021000716A (en) |
WO (1) | WO2020018512A1 (en) |
Families Citing this family (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2020277341A1 (en) * | 2019-05-20 | 2021-11-11 | Poviva Corp. | Nanoemulsion compositions comprising biologically active ingredients |
WO2020234650A1 (en) * | 2019-05-21 | 2020-11-26 | Timeless Herbal Care (Canada) Ltd. | Pharmaceutical compositions comprising cbd and terpene compositions |
GB201909358D0 (en) * | 2019-06-28 | 2019-08-14 | Smoukov Stoyan K | Oil-in-water emulsion of nano-sized self-emulsified particulates |
US20210015759A1 (en) * | 2019-07-17 | 2021-01-21 | Canateq Holdings Corp. | Cannabinoid compositions and processes for making same |
CA3149768A1 (en) * | 2019-09-05 | 2021-03-11 | Stephen Goldner | Cannabinoid-containing additive and method therefor |
JP2023505357A (en) * | 2019-12-09 | 2023-02-08 | ニコベンチャーズ トレーディング リミテッド | Oral products containing cannabinoids |
EP4076487A4 (en) * | 2019-12-20 | 2024-02-07 | Organigram Inc | Emulsifying formulations of cannabinoids and/or cannabinoid extracts |
US20210299062A1 (en) * | 2020-03-29 | 2021-09-30 | Mark J. Rosenfeld | Cannabinoid compositions and methods of treatment |
US20230310465A1 (en) * | 2020-08-18 | 2023-10-05 | Leiutis Pharmaceuticals Llp | Nano lipid carrier system for improving permeation of active ingredients |
US20220087289A1 (en) * | 2020-09-23 | 2022-03-24 | Vertosa Inc. | Systems for retaining potency in an infused beverage |
GB2599660A (en) * | 2020-10-07 | 2022-04-13 | Almora Botanica Uk Ltd | A nano-emulsion composition for skin care application |
CA3135067A1 (en) * | 2020-10-21 | 2022-04-21 | Corn Products Development, Inc. | Cannabinoid emulsions |
US20220117278A1 (en) * | 2020-10-21 | 2022-04-21 | Corn Products Development, Inc. | Cannabinoid emulsions |
WO2022137215A1 (en) * | 2020-12-24 | 2022-06-30 | Czupiel Petro Pawlo | Safe-to-ingest cationic microemulsions and nanoemulsions containing lipophilic components |
WO2022133612A1 (en) * | 2020-12-24 | 2022-06-30 | Tetra Bio-Pharma Inc. | Parenteral cannabinoid formulations and uses thereof |
CN114712307B (en) * | 2021-01-05 | 2023-06-09 | 上海交通大学医学院附属第九人民医院 | Fat emulsion dialysate and preparation method and application thereof |
WO2022187123A1 (en) | 2021-03-01 | 2022-09-09 | Bidio, Llc | Cannabinoid infused coffee and methods of making same |
EP4304569A1 (en) * | 2021-03-12 | 2024-01-17 | Nicoventures Trading Limited | Oral products with self-emulsifying system |
WO2023070170A1 (en) * | 2021-10-29 | 2023-05-04 | Aquila Black Limited | Water dispersible cannabinoid compositions |
WO2023154264A1 (en) * | 2022-02-11 | 2023-08-17 | Akos Biosciences, Inc. | Compositions for topical treatment of radiation dermatitis |
PL440642A1 (en) * | 2022-03-15 | 2023-09-18 | Healthcann Spółka Z Ograniczoną Odpowiedzialnością | Composition forming a stable monodisperse emulsion in water containing a fat-soluble active substance |
CN115287115B (en) * | 2022-08-05 | 2023-03-10 | 中冶武汉冶金建筑研究院有限公司 | Water-based concrete release agent and preparation method thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6139848A (en) * | 1999-02-12 | 2000-10-31 | Mcneil-Ppc, Inc. | Personal lubricant compositions |
US20170246120A9 (en) * | 2014-10-18 | 2017-08-31 | Matthew J. Stepovich | Herbal compositions including cannabidiol to enhance the sexual experience |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5585506A (en) * | 1994-07-22 | 1996-12-17 | Lonza Inc. | One phase production of polyglycerol esters |
FR2787326B1 (en) * | 1998-12-17 | 2001-01-26 | Oreal | NANOEMULSION BASED ON FATTY ESTERS OF GLYCEROL, AND ITS USES IN THE COSMETIC, DERMATOLOGICAL AND / OR OPHTHALMOLOGICAL FIELDS |
US20030040571A1 (en) * | 2001-07-30 | 2003-02-27 | Feng Qian Jane | Clear silicone microemulsions formed spontaneously |
US7790377B2 (en) * | 2003-08-29 | 2010-09-07 | The University Of North Carolina At Greensboro | Compounds that act to modulate insect growth and methods and systems for identifying such compounds |
WO2009016064A1 (en) * | 2007-07-31 | 2009-02-05 | Basf Se | Use of nanodispersions to protect water-soluble ingredients in cosmetic end formulations |
WO2009020666A1 (en) | 2007-08-06 | 2009-02-12 | Insys Therapeutics Inc. | Oral cannabinoid liquid formulations and methods of treatment |
DE102007063134A1 (en) * | 2007-12-24 | 2009-06-25 | Sasol Germany Gmbh | Process for the preparation of oil in water Emulsions of self-emulsifying gel concentrates |
US20090196972A1 (en) * | 2008-02-04 | 2009-08-06 | Adelmo Monsalve-Gonzalez | Natural Flavor Enhancement Compositions for Food Emulsions |
AU2009345154A1 (en) | 2009-04-29 | 2011-12-22 | University Of Kentucky Research Foundation | Cannabinoid-containing compositions and methods for their use |
US8623433B1 (en) * | 2011-01-07 | 2014-01-07 | Innovitamin Organics, Llc | Safflower oil emulsion as dietary supplement and preparation thereof |
US8758826B2 (en) | 2011-07-05 | 2014-06-24 | Wet Inc. | Cannabinoid receptor binding agents, compositions, and methods |
US9925149B2 (en) | 2013-10-14 | 2018-03-27 | Nanosphere Health Sciences, Llc | Nanoparticle compositions and methods as carriers of nutraceutical factors across cell membranes and biological barriers |
US9572364B2 (en) * | 2014-08-26 | 2017-02-21 | Mycotechnology, Inc. | Methods for the production and use of mycelial liquid tissue culture |
WO2016097425A1 (en) * | 2014-12-19 | 2016-06-23 | Thc Pharm Gmbh | Cbd-containing beverage |
EP3268043A4 (en) * | 2015-03-10 | 2018-12-19 | Nanosphere Health Sciences, LLC | Lipid nanoparticle compositions and methods as carriers of cannabinoids in standardized precision-metered dosage forms |
AU2016231788A1 (en) | 2015-03-19 | 2017-10-12 | One World Cannabis Ltd | Preparations of cannabis emulsions and methods thereof |
US20170042791A1 (en) * | 2015-08-11 | 2017-02-16 | KannaInnovations LLC | Topical compositions comprising hydroxy acids and cannabinoids for skin care |
WO2017059513A2 (en) * | 2015-10-09 | 2017-04-13 | Fernando Thome Kreutz | Nanoemulsion compositions and methods |
US20160376263A1 (en) | 2016-07-26 | 2016-12-29 | Senomyx, Inc. | Bitter taste modifiers including substituted 1-benzyl-3-(1-(isoxazol-4-ylmethyl)-1h-pyrazol-4-yl)imidazolidine-2,4-diones and compositions thereof |
PE20200676A1 (en) * | 2016-08-03 | 2020-06-11 | Zelda Therapeutics Operations Pty Ltd | CANNABIS COMPOSITION |
EP3308766B1 (en) * | 2016-10-11 | 2019-12-25 | Ionia Azure AG | Cosmetic water-in-oil microemulsion |
WO2018152334A1 (en) | 2017-02-15 | 2018-08-23 | Molecular Infusions, Llc | Formulations |
US20170265494A1 (en) | 2017-06-05 | 2017-09-21 | International Consolidated Companies, Inc. | Chewing gum including nanozome encapsulated cannabidiol |
WO2018232362A1 (en) * | 2017-06-16 | 2018-12-20 | Tarukino Holdings, Inc. | Preparing stable liquid emulsion forms of plant extract |
-
2018
- 2018-11-30 US US16/206,869 patent/US11013715B2/en active Active
-
2019
- 2019-07-16 CA CA3106840A patent/CA3106840A1/en active Pending
- 2019-07-16 MX MX2021000716A patent/MX2021000716A/en unknown
- 2019-07-16 WO PCT/US2019/041965 patent/WO2020018512A1/en active Search and Examination
- 2019-07-16 EP EP19837387.0A patent/EP3823585A4/en not_active Withdrawn
-
2021
- 2021-01-18 MX MX2021010326A patent/MX2021010326A/en unknown
- 2021-05-06 US US17/239,262 patent/US20210251948A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6139848A (en) * | 1999-02-12 | 2000-10-31 | Mcneil-Ppc, Inc. | Personal lubricant compositions |
US20170246120A9 (en) * | 2014-10-18 | 2017-08-31 | Matthew J. Stepovich | Herbal compositions including cannabidiol to enhance the sexual experience |
Non-Patent Citations (4)
Title |
---|
Azeem et al.; "Microemulsions as Surrogate Carriers for Dermal Drug Delivery," 2009, Informa; Drug Development and Industrial Pharmacy, Vol. 35, No. 5, pp. 525-547. (Year: 2009) * |
Chen et al.; "Thermal and UV stability of β-carotene dissolved in peppermint oil microemulsified by sunflower lecithin and Tween 20 blend," 2015, ELSEVIER; Food Chemistry, Vol. 174, pp. 630-636. (Year: 2015) * |
Komaiko et al.; "Formation of Oil-in-Water Emulsions from Natural Emulsifiers Using Spontanous Emulsification: Sunflower Phospholipids," 2015; ACS; Journal of Agricultural and Food Chemistry, Vol. 63, pp. 10078-10088. (Year: 2015) * |
Zhong et al.; "Microemulsions Based on Sunflower Lecithin--Tween 20 Blend Have High Capacity for Dissolving Peppermint Oil and Stabilizing Coenzyme Q10," 2015; ACS; Journal of Agricultural and Food Chemistry, Vol. 63, pp. 983-989. (Year: 2015) * |
Also Published As
Publication number | Publication date |
---|---|
EP3823585A1 (en) | 2021-05-26 |
MX2021010326A (en) | 2021-10-13 |
US20210015786A1 (en) | 2021-01-21 |
EP3823585A4 (en) | 2022-06-01 |
US11013715B2 (en) | 2021-05-25 |
MX2021000716A (en) | 2021-09-28 |
CA3106840A1 (en) | 2020-01-23 |
WO2020018512A1 (en) | 2020-01-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20210251948A1 (en) | Nanoemulsion hydrophobic substances | |
Ashaolu | Nanoemulsions for health, food, and cosmetics: a review | |
Barradas et al. | Nanoemulsions of essential oils to improve solubility, stability and permeability: a review | |
US10709747B2 (en) | Encapsulated cannabinoid formulations for oral delivery | |
CA2706517C (en) | Nanoemulsion as delivery vehicles for active components | |
JP2023109849A (en) | Dilutable formulations of cannabinoids and processes for their preparation | |
AU2018377175A1 (en) | Liquid dosage forms, methods of making and use | |
CA2962900C (en) | Non-synthetic emulsion-based lipid formulations and methods of use | |
Barradas et al. | Nanoemulsions as optimized vehicles for essential oils | |
US20220241199A1 (en) | Cannabinoid emulsion composition and method of manufacture | |
US20220054414A1 (en) | Nanoemulsion Compositions Comprising Saponins for Increasing Bioavailability | |
US20220183972A1 (en) | Nanoemulsion hydrophobic substances | |
JP2007161635A (en) | Two layer separating type cosmetic | |
CA3215201A1 (en) | High potency emulsions | |
WO2023283277A1 (en) | Fermented uni-sourced nanoemulsion of nigella sativa or cannabis sativa for use in medical, cosmetic, and recreational indications with a method of its production and use | |
JPS60260511A (en) | Stable emulsion preparation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: VERTOSA INC., CALIFORNIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:HAN, CHUNXIAO;REEL/FRAME:056504/0904 Effective date: 20200814 |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: FINAL REJECTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE AFTER FINAL ACTION FORWARDED TO EXAMINER |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: ADVISORY ACTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |