SHORT PATH DISTILLATION IN VACUUM FOR ENRICHING NATURAL SUBSTANCES

Abstract

The present invention relates to a method for producing, obtaining and enriching dronabinol (9-THC) as well as natural substances from plant extracts.

Claims

1. A method for extracting tetrahydrocannabinol from cannabis plant material, characterized in that a short-path vacuum distillation is carried out.

2. The method for extracting tetrahydrocannabinol from cannabis plant material according to claim 1, characterized in that the short-path vacuum distillation is carried out using a short-path evaporator.

3. The method for extracting tetrahydrocannabinol from cannabis plant material according to claim 1, characterized in that the length of the short path is 10 cm, in particular 5 cm, in particular 2 cm, in particular 0.5 cm between the evaporator wall and the condenser.

4. The method for extracting tetrahydrocannabinol from cannabis plant material according to claim 1, characterized in that the short-path vacuum distillation is carried out using an additional column or a separating column.

5. The method for extracting tetrahydrocannabinol from cannabis plant material according to claim 4, characterized in that the length of the separating column is at least 2.50 m.

6. The method for extracting tetrahydrocannabinol from cannabis plant material according to claim 1, wherein the vacuum distillation is carried out on a first primary extract having at least 15 wt % tetrahydrocannabinol.

7. The method for extracting tetrahydrocannabinol from cannabis plant material according to claim 1, wherein the pressure is 0.001 to 50 mbar and the temperature is 120 to 240 degrees Celsius.

8. A method for extracting tetrahydrocannabinol from cannabis plant material, characterized in that one or more short-path distillations in a vacuum take place before or after at least one liquid-liquid partition chromatography step.

9. A method for extracting tetrahydrocannabinol from cannabis plant material according to claim 8, characterized in that one or more short-path distillations in a vacuum take place before or after at least one liquid-liquid partition chromatography step, wherein at least i.) a continuous change of the stationary phase to the mobile phase and vice versa takes place and/or ii.) a solvent is held stationary by centrifugal force with a second immiscible liquid phase in the mobile phase.

10. A Tetrahydrocannabinol-containing extract according to claim 1, characterized in that the extract has a residue-free evaporability.

11. A medicinal product, nutritional supplement containing a tetrahydrocannabinol-containing extract which can be obtained using the method according to claim 1, in particular for inhalation.

12. A method for separating and/or purifying natural substances from plant extracts, in particular cannabinoids from a cannabis extract, comprising at least one liquid-liquid partition chromatography step, wherein a solvent is held stationary by centrifugal force with a second immiscible liquid phase in the mobile phase and one or more short-path distillations in a vacuum take place before or after, wherein one or more fractions or one or more pure substances are removed.

13. A method for separating and/or purifying natural substances from plant extracts, in particular cannabinoids from a cannabis extract, comprising at least one liquid-liquid partition chromatography step, wherein a continuous change of the stationary phase to the mobile phase and vice versa takes place and one or more short-path distillations in a vacuum take place before or after, wherein one or more fractions or one or more pure substances are removed.

14. The method for separating and/or purifying natural substances from plant extracts according to claim 12, characterized in that the fraction(s) contain such substance classes of plant extracts selected from the group alkaloids, bitter compounds, anthocyanins, anthraquinones, coumarins, flavonoids, glucosinolates, lactones, lignans, lipids, cannabinoids, phenols, polyphenols, saponins, terpenes, xanthones.

15. The method for separating and/or purifying natural substances from plant extracts according to claim 12, characterized in that at least one plant extract is selected from the group including the genera Equiseti, Juglandis, Millefolii, Quercus, Taraxaci, Althaeae, Matricariae, Centaurium, Levisticum, Rosmarinus, Angelica, Artemisia, Astragalus, Leonurus, Salvia, Saposhnikovia, Scutellaria, Siegesbeckia, Armoracia, Capsicum, Cistus, Echinacea, Galphimia, Hedera, Melia, Olea, Pelargonium, Phytolacca, Primula, Salix, Thymus, Vitex, Vitis, Rumicis, Verbena, Sambucus, Gentiana, Cannabis, Silybum.

16. The method for separating and/or purifying natural substances from plant extracts according to claim 15, characterized in that at least one plant extract is selected from the group including the species Equiseti herba (horsetail), Juglandis folium (walnut leaf), Millefolii herba (yarrow), Quercus cortex (oak bark), Taraxaci herba (dandelion), Althaeae radix (marshmallow root) and Matricariae flos (or Flos chamomillae (chamomile)) Centaurium erythraea (centaury), Levisticum officinale (lovage), Rosmarinus officinalis (rosemary), Angelica dahurica (Dahurian angelica, Pinyin name: Bai Zhi), Angelica sinensis (Chinese angelika, Pinyin name: Dang Gui), Artemisia scoparia (capillary wormwood, Pinyin name: Yin Chen), Astragalus membranaceus (var. Mongolicus) (Mongolian milkvetch, Chin.: Huang-Qi), Leonurus japonicus (Oriental motherwort, Chin.: T'uei), Salvia miltiorrhiza (red sagei, Chin.: Danshen), Saposhnikovia divaricata (siler, Pinyin name: Fang Feng), Scutellaria baicalensis (Baikal skullcap), Siegesbeckia pubescens (Pinyin name: Xi Xian Cao), Armoracia rusticana (horseradish), Capsicum sp. (pepper), Cistus incanus (hoary rock-rose), Echinacea angustifolia (narrow-leaved purple coneflower), Echinacea purpurea (purple coneflower), Galphimia glauca, Hedera helix (ivy), Melia toosendan (Chinese elderberries, Chin.: Chuan Lian Zi), Olea europaea (olive), Pelargonium sp. (pelargonia), Phytolacca americana (pokeweed), Primula veris (cowslip), Salix sp. (willow), Thymus L. (thyme) Vitex agnus castus (chasteberry), Vitis vinifera (common grape vine), Rumicis herba (sorrel herb), Verbena officinalis (verbena), Sambucus nigra (black elder), Gentiana lutea (yellow gentian), Cannabis sativa (hemp), Silybum marianum (milk thistle).

17. The method for extracting tetrahydrocannabinol from cannabis plant material according to claim 2, characterized in that the length of the short path is 10 cm, in particular 5 cm, in particular 2 cm, in particular 0.5 cm between the evaporator wall and the condenser.

18. The method for separating and/or purifying natural substances from plant extracts according to claim 13, characterized in that the fraction(s) contain such substance classes of plant extracts selected from the group alkaloids, bitter compounds, anthocyanins, anthraquinones, coumarins, flavonoids, glucosinolates, lactones, lignans, lipids, cannabinoids, phenols, polyphenols, saponins, terpenes, xanthones.

19. The method for separating and/or purifying natural substances from plant extracts according to claim 13, characterized in that at least one plant extract is selected from the group including the genera Equiseti, Juglandis, Millefolii, Quercus, Taraxaci, Althaeae, Matricariae, Centaurium, Levisticum, Rosmarinus, Angelica, Artemisia, Astragalus, Leonurus, Salvia, Saposhnikovia, Scutellaria, Siegesbeckia, Armoracia, Capsicum, Cistus, Echinacea, Galphimia, Hedera, Melia, Olea, Pelargonium, Phytolacca, Primula, Salix, Thymus, Vitex, Vitis, Rumicis, Verbena, Sambucus, Gentiana, Cannabis, Silybum.

20. The method for separating and/or purifying natural substances from plant extracts according to claim 18, characterized in that at least one plant extract is selected from the group including the species Equiseti herba (horsetail), Juglandis folium (walnut leaf), Millefolii herba (yarrow), Quercus cortex (oak bark), Taraxaci herba (dandelion), Althaeae radix (marshmallow root) and Matricariae flos (or Flos chamomillae (chamomile)) Centaurium erythraea (centaury), Levisticum officinale (lovage), Rosmarinus officinalis (rosemary), Angelica dahurica (Dahurian angelica, Pinyin name: Bai Zhi), Angelica sinensis (Chinese angelika, Pinyin name: Dang Gui), Artemisia scoparia (capillary wormwood, Pinyin name: Yin Chen), Astragalus membranaceus (var. Mongolicus) (Mongolian milkvetch, Chin.: Huang-Qi), Leonurus japonicus (Oriental motherwort, Chin.: Tuei), Salvia miltiorrhiza (red sagei, Chin.: Danshen), Saposhnikovia divaricata (siler, Pinyin name: Fang Feng), Scutellaria baicalensis (Baikal skullcap), Siegesbeckia pubescens (Pinyin name: Xi Xian Cao), Armoracia rusticana (horseradish), Capsicum sp. (pepper), Cistus incanus (hoary rock-rose), Echinacea angustifolia (narrow-leaved purple coneflower), Echinacea purpurea (purple coneflower), Galphimia glauca, Hedera helix (ivy), Melia toosendan (Chinese elderberries, Chin.: Chuan Lian Zi), Olea europaea (olive), Pelargonium sp. (pelargonia), Phytolacca americana (pokeweed), Primula veris (cowslip), Salix sp. (willow), Thymus L. (thyme) Vitex agnus castus (chasteberry), Vitis vinifera (common grape vine), Rumicis herba (sorrel herb), Verbena officinalis (verbena), Sambucus nigra (black elder), Gentiana lutea (yellow gentian), Cannabis sativa (hemp), Silybum marianum (milk thistle).

Description

EXAMPLE 1

1.1 Short-Path Distillation V9001

[0100] Cannabis extract 50-95% Cannabis sativa was used as the educt. The educt was previously heated at 80 C. in the oil bath and transferred to the heated drip funnel of the short-path distillation. The used quantity was 103.3 g. The temperature in the dosing vessel was 70 C. The speed of the stirrer was 400 rpm and the temperature in the evaporator was 180 C. The extract was fed in with a speed of 180 ml/h-200 ml/h and the pressure in the overall apparatus was 1.2*10-1 mbar. The distillation took a total of 35 minutes. It was possible to obtain 79.53 g distillate and 58.15 g residue, which corresponds to a cut ratio of approximately 75/25. During distillation, a distillate additionally formed on the cold trap. The quantity of distillate was approximately 3 ml. A hot air dryer was needed to get the resulting residue into a flowable form. The distillate, which was subsequently used further, had a bright yellow color.

1.2 Short-Path Distillation V9002

[0101] 137.51 g cannabis extract 50-95% Batch 0000106433 was used. The temperature in the dosing vessel was 70 C., the temperature in the evaporator was 165 C. As before, the speed was set to 400 rpm. The entire distillation took about 45 minutes. It was possible to obtain 90.4 g distillate, while 61.31 g of residue formed. Approximately 3 ml of a distillate formed in the cold trap. The cut ratio was 65/35. The distillate, which was subsequently used further, had a bright yellow color.

1.3 Preparation of the Stock Solution V9001

[0102] The distillate from the short-path distillation was used as the starting material for the stock solution. The same concentration was used for both the stock solution and the FCPC system, i.e. 0.1 g/ml. The distillate from V9001 was dissolved in the water bath at 80 C., then transferred into a 1000 ml round-bottom flask. The weight was 62.26 g. The 1000 ml round-bottom flask was then again dissolved in a water bath at 80 C. and mixed with 622 ml heptane FCPC and dissolved.

[0103] The results are shown in Table 1.

EXAMPLE 2

[0104] Comparison test of a THC-containing cannabis extract, with and without short-path vacuum distillation (short path: 2-5 cm)

TABLE-US-00003 Information provided in wt % without SPD with SPD D9-THC 97.53 98.90 Impurity A 0.00 0.05 Impurity B 0.12 0.00 Impurity C 0.09 0.08 Impurity D 0.32 0.24 Impurity E 0.05 0.06 CBD 0.00 0.00 CBN 0.05 0.10 CBC 0.64 0.62 Exo-THC <0.05 <0.05 D8-THC 0.00 0.00 Other impurities 1.30 <0.05

[0105] Impurities can be significantly minimized.

[0106] FIGS. 1 and 2 show a cross section of suitable systems for short-path vacuum distillation with the following reference signs: [0107] 1 Wiper motor [0108] 2 Evaporator [0109] 3 (Internal) condenser [0110] 4 Distillate discharge [0111] 5 Residue discharge

TABLE-US-00004 TABLE 1 Test No. Info V9001 V9001 V9001 V9002 V9002 V9002 V9005 V9005 V9005 V9006 V9006 Description NTHC KDL 1 CW46, 2016 Start End Start End Start End Start Feed, from protocol Cannabis extract 50-95% Batch B: 0000106433 Date mm/dd/yyyy 11/16/2016 11/16/2016 11/16/2016 11/17/2016 11/17/2017 01/13/2017 01/13/2017 01/13/2017 Time hh:mm 1:50 p.m. 2:00 pm 2:45 pm 9:43 a.m. 10:30 a.m. 10:47 a.m. 11:30 a.m. 11:30 a.m. Dosing vessel C. 70 70 70 70 70 70 70 70 Evaporator C. 180 180 180 165 165 195 195 215 Vacuum mbar 0.17-0.18 0.12 0.12 0.12 0.12 0.17-0.18 0.17-0.18 Speed RPM 400 400 400 400 400 400 400 400 Feed, set ml/h 180-200 180-200 200 180-200 180-200 180 180 Feed, protocol g/h Distillation time min 35 47 43 Feed calculated g/h 177 176 136 m (educt, start) g 800.26 692.85 527.00 m (educt, after removal) g 696.96 555.34 429.27 m (educt, consumed), feed F g 103.30 137.51 215.529 97.73 m (distillate) + m (flask) g 127.39 138.56 126.93 m (distillate flask) tare g 47.86 48.14 49.28 m (distillate) Distillate D g 79.53 90.42 77.65 m (residue) + m (flask) g 58.15 61.31 54.02 m (residue flask) tare g 47.77 48.11 47.77 m (residue) Residue R g 23.77 47.09 6.25 m (cold trap) Cold trap K g m (cold trap/feed) K/F % Cut ratio D/R D/R It. Protocol % 75/25 65/35 Cut ratio D/F calculated % 77 66 79 Test Mass fraction V9001 V9001 V9001 V9002 V9002 V9002 V9005 V9005 V9005 V9006 V9006 Analysis [%] Current F D R F D R F D R F D CBG % 1.36 1.67 0.52 1.36 1.51 0.67 1.36 1.36 CBN % 0.62 0.81 0.21 0.62 0.73 0.27 0.62 0.62 D9-THC % 78.84 88.73 16.54 78.84 92.04 18.78 78.84 85.00 6.70 78.84 81.40 D8-THC % 0.08 0.13 0.04 0.08 0.02 0.04 0.08 0.08 CBC % 0.69 0.85 0.11 0.69 0.83 0.14 0.69 0.69 VU74 at RT 74 % 0.00 0.00 0.46 0.00 0.00 0.91 0.00 0.00 VU77 at RT 77 % 0.00 0.00 0.53 0.00 0.00 1.09 0.00 0.00 Vux at RT 150 % 0.20 0.00 0.20 0.20 0.00 1.33 0.20 0.20 Test Absolute mass V9001 V9001 V9001 V9002 V9002 V9002 V9005 V9005 V9005 V9006 V9006 Evaluation [g] Current F D R F D R F D R F D CBG g 1.40 1.32 0.12 1.87 1.37 0.32 1.33 0.00 0.00 1.60 0.00 CBN g 0.64 0.65 0.05 0.85 0.66 0.13 0.60 0.00 0.00 0.73 0.00 D9-THC g 81.44 70.57 3.93 108.41 83.23 8.85 77.04 66.00 0.42 92.87 81.05 D8-THC g 0.09 0.10 0.01 0.11 0.02 0.02 0.08 0.00 0.00 0.10 0.00 CBC g 0.72 0.68 0.03 0.96 0.75 0.07 0.68 0.00 0.00 0.82 0.00 VU74 at RT 74 g 0.00 0.00 0.11 0.00 0.00 0.43 0.00 0.00 0.00 0.00 0.00 VU77 at RT 77 g 0.00 0.00 0.13 0.00 0.00 0.52 0.00 0.00 0.00 0.00 0.00 Vux at RT 150 g 0.21 0.00 0.05 0.28 0.00 0.63 0.20 0.00 0.00 0.24 0.00 Test Enrichment V9001 V9002 V9005 V9006 Yield in distillate [%] Current D D D D CBG VU % 94.42 73.16 0.00 0.00 CBN VU % 100.00 78.17 0.00 0.00 D9-THC Product % 86.65 76.77 85.67 87.27 D8-THC VU % 100.00 16.75 0.00 0.00 CBC VU % 94.60 78.14 0.00 0.00 VU74 at RT 74 VU % VU77 at RT 77 VU % Vux at RT 150 VU % 0.00 0.00 0.00 0.00 Mass balance D9-THC TARGET = 0 g 6.9 16.3 10.6 11.6 Mass balance D9-THC Deviation in % % 8.5 15.1 13.8 12.5 Summary D9 THC in feed (educt) V9001 V9002 V9005 V9006 w (D9-THC) feed w(D9-THC) % 78.8 78.8 78.8 78.8 Summary D9-THC in the product V9001 V9002 V9005 V9006 Cut ratio D/F % 77.0 65.8 79.5 84.5 w (D9-THC) product w(D9-THC) % 88.7 92.0 85.0 81.4 Yield D9-THC m(D9,D)/m(D9,F) % 86.7 76.8 85.7 87.3 % = wt %