阅读说明：本技术 一种大麻浸膏中去除thc多柱连续分离设备及工艺方法 (Multi-column continuous separation equipment and process method for removing THC in hemp extract ) 是由 康小虎 危凤 崔万臣 沈志刚 张树权 张晋永 杜春生 李建伟 王靖宇 于 2020-06-24 设计创作，主要内容包括：本发明公开了一种大麻浸膏中去除THC多柱连续分离设备及工艺方法,包括第一色谱柱、第二色谱柱、第三色谱柱、第四色谱柱和第五色谱柱,所述第一色谱柱的进料口与再生液储存池连接,所述第一色谱柱与第二色谱柱之间设置有高纯THC物料池,所述第三色谱柱与第四色谱柱之间与上样液储液池连接,所述第五色谱柱的出料口与分离装置连接,所述分离装置上设置有第一出料管和第二出料管,所述第一出料管与THC收集箱连接,所述第二出料管与溶剂回收装置连接,所述溶剂回收装置与所述再生液储存池连接。有益效果：能够连续上样,连续分离,去除THC,产能稳定,相对于单柱纯化,填料利用率高,溶剂用量少,产能高,成本低。(The invention discloses multi-column continuous separation equipment and a process method for removing THC in hemp extract, which comprise a first chromatographic column, a second chromatographic column, a third chromatographic column, a fourth chromatographic column and a fifth chromatographic column, wherein a feed inlet of the first chromatographic column is connected with a regenerated liquid storage pool, a high-purity THC material pool is arranged between the first chromatographic column and the second chromatographic column, a sample solution storage pool is connected between the third chromatographic column and the fourth chromatographic column, a discharge outlet of the fifth chromatographic column is connected with a separation device, a first discharge pipe and a second discharge pipe are arranged on the separation device, the first discharge pipe is connected with a THC collection box, the second discharge pipe is connected with a solvent recovery device, and the solvent recovery device is connected with the regenerated liquid storage pool. Has the advantages that: the method has the advantages of continuous sample loading, continuous separation and THC removal, stable yield, high filler utilization rate, less solvent consumption, high yield and low cost compared with single-column purification.)

1. The THC removing multi-column continuous separation equipment in the hemp extract is characterized by comprising a first chromatographic column (1), a second chromatographic column (2), a third chromatographic column (3), a fourth chromatographic column (4) and a fifth chromatographic column (5), wherein the first chromatographic column (1) is connected with the second chromatographic column (2), the second chromatographic column (2) is connected with the third chromatographic column (3), the third chromatographic column (3) is connected with the fourth chromatographic column (4), the fourth chromatographic column (4) is connected with the fifth chromatographic column (5), a feeding hole of the first chromatographic column (1) is connected with a regeneration liquid storage pool (6), a liquid inlet (7) is formed in the regeneration liquid storage pool (6), a liquid feeding pump (8) is arranged between the regeneration liquid storage pool (6) and the first chromatographic column (1), and a high-purity THC material pool (9) is arranged between the first chromatographic column (1) and the second chromatographic column (2) ) The third chromatographic column (3) and the fourth chromatographic column (4) are connected with a sample feeding liquid storage tank (10), a liquid inlet II (11) is arranged on the sample feeding liquid storage tank (10), the sample feeding liquid storage tank (10) and the third chromatographic column (3) are connected with the fourth chromatographic column (4) through a liquid feeding pump II (12), a discharge hole of the fifth chromatographic column (5) is connected with a separation device (13), the separation device (13) is provided with a first discharge pipe (14) and a second discharge pipe (15), the first discharge pipe (14) is connected with a THC collection box (16), the THC collection box (16) is connected with a liquid chromatograph (17), the second discharge pipe (15) is connected with a solvent recovery device (18), and the solvent recovery device (18) is connected with the regenerated liquid storage tank (6).

2. The method as claimed in claim 1, wherein the method comprises the steps of:

pulverizing and drying hemp flower and leaf to obtain powder, performing hot reflux extraction by adopting an ethanol solution with the mass concentration of 60-100%, and concentrating the obtained extracting solution under reduced pressure to obtain hemp extract;

dissolving the hemp extract with 75% ethanol water, dissolving in acetone mobile phase to obtain a sample loading solution, and storing the sample loading solution in a sample loading solution storage pool;

introducing the regeneration liquid in the regeneration liquid storage tank into a first chromatographic column, and carrying out solution balance through the first chromatographic column and a second chromatographic column;

introducing the sample solution obtained in the second step into a fourth chromatographic column, and carrying out chromatographic separation through the fourth chromatographic column and a fifth chromatographic column;

respectively introducing the solution and the THC obtained after separation into a solvent recovery device and a THC collection box through a separation device;

the mixed liquid is recovered by a solvent recovery device, and then the recovered regeneration liquid is introduced into a regeneration liquid storage tank for reuse.

3. A multi-column continuous separation apparatus for removing THC from cannabis extract according to claim 1, wherein valves are respectively disposed between the first chromatography column (1) and the second chromatography column (2), between the second chromatography column (2) and the third chromatography column (3), between the third chromatography column (3) and the fourth chromatography column (4), and between the fourth chromatography column (4) and the fifth chromatography column (5).

4. The process method for multi-column continuous separation for removing THC from cannabis extract as claimed in claim 2, wherein in step two, the cannabis extract is dissolved in 75% ethanol to obtain a sample solution, and the concentration of the sample solution is 55 g/L.

5. A cannabis extract THC removal multi-column continuous separation device according to claim 1, characterized in that the first (1), second (2), third (3), fourth (4) and fifth (5) chromatography columns have a size ID10 x 300mm, the first (1), second (2), third (3), fourth (4) and fifth (5) chromatography columns use C18 packing, the C18 packing has a particle size of 20-40 μm, and the first (1), second (2), third (3), fourth (4) and fifth (5) chromatography columns have an internal temperature of 25 ℃.

6. The multi-column continuous separation equipment for removing THC from cannabis extract as claimed in claim 1, wherein the regeneration liquid is 95% ethanol water or pure ethanol.

7. A multi-column continuous separation apparatus for removing THC from cannabis extract according to claim 1, wherein the number of the first (1), second (2), third (3), fourth (4) and fifth (5) chromatographic columns is 5 respectively.

8. The process of claim 2, wherein the ratio of the mobile phase of the regeneration liquid is 95-100% ethanol water.

9. The process for multi-column continuous separation of THC removed from cannabis extract as claimed in claim 2, wherein the thermal reflux extraction method in step one comprises: extracting with 60-100% ethanol under reflux for 2-4 times, each time for 1-3 hr, mixing extractive solutions, and concentrating under reduced pressure to obtain concentrated fluid extract.

10. The multi-column continuous separation process for removing THC from cannabis sativa extract as claimed in claim 2, wherein the mobile phase in step two is 40-90% by weight of methanol, ethanol, isopropanol, n-butanol, acetone, butanone, acetonitrile or a mixed aqueous solution of any two or more of the above.

Technical Field

The invention relates to the technical field of chemical separation, in particular to multi-column continuous separation equipment and a process method for removing THC in hemp extract.

Background

Cannabinoids or phenols are the major active ingredients of Cannabis plants. Among them, Cannabidiol for short CBD, is the main chemical component in cannabinol. The research shows that CBD has no addiction, and has the pharmacological effects of resisting spasm, epilepsy, anxiety, depression, psychosis, inflammation and pain, relieving nausea of cancer patients caused by chemotherapy, treating asthma and the like. In recent years, scientists also find that CBD is a powerful antioxidant and has a series of physiological functions of blocking breast cancer metastasis, resisting rheumatoid arthritis, resisting insomnia, resisting hallucinography and the like. Due to the medicinal value and the economic value, the heat of the big sesame is raised all over the world. However, Tetrahydrocannabinol (THC), which is also a type of cannabinol, has hallucinogenic addiction and other characteristics.

The most globally demanded product is currently the full spectrum of oils from which THC is removed (i.e. CBD-rich industrial hemp essential oils), and the CBD monomer. The extraction method of full spectrum oil mainly comprises the steps of flower and leaf drying or airing, crushing, leaching, chromatography, evaporative concentration and packaging. The extraction method of the CBD monomer mainly comprises the steps of flower and leaf drying or airing, crushing, leaching, chromatography, evaporative concentration, crystallization, drying, crushing homogenization and packaging. Wherein, both products need to separate CBD and THC, namely remove THC. However, because the chemical formula and molecular weight of CBD are completely consistent with THC, the physicochemical properties of CBD and THC are very close to each other, which causes a certain difficulty in separation of CBD and THC, constituting a technical barrier in the industry, and the industrial solutions are almost chromatographic purification separation.

CN106831353A discloses a method for extracting cannabidiol from cannabis sativa, which adopts a chromatographic separation mode of reverse phase resin packing of polystyrene, mainly comprising a normal phase silica gel column, an adsorption resin column and a neutral alumina column. The adsorbent resin column is a filler medium column reported to be macroporous adsorbent resin, polyamide adsorbent resin, polystyrene-based reverse phase resin and the like. Wherein, the normal phase silica gel filler has lower price and larger treatment capacity, and occupies certain application market. However, the use of normal phase silica gel has two problems, one is that the normal phase silica gel has serious dead adsorption, and some useful product components, such as CBD, are lost in the chromatographic process; secondly, the service life of the normal phase silica gel is short, and the solid waste pollution is serious. The column is frequently disassembled and assembled, so that the production efficiency is influenced, the production cost is increased, and the normal phase reagent in the waste filler volatilizes to damage the body health of staff and increase the operation risk. In addition, the resin filler has larger adsorption capacity and relatively acceptable price, can be regenerated by acid washing and alkali washing, prolongs the service life and occupies certain application market. However, not only is the dead adsorption of the resin severe, but also waste water pollution is a very important problem in regenerating the resin by acid washing or alkali washing, and evaluation of the filler is a troublesome problem in GMP and FDA certification. In addition, the price of the resin with good effect per liter is required to be thousands of yuan, even thousands of yuan. As for neutral alumina fillers, the market for applications is relatively small.

For the above reasons, my company developed a reverse phase silica gel process and was a large particle reverse phase silica gel super chromatography process.

An effective solution to the problems in the related art has not been proposed yet.

Disclosure of Invention

The invention provides multi-column continuous separation equipment and a process method for removing THC in hemp extract, aiming at the problems in the related art, so as to overcome the technical problems in the prior related art.

Therefore, the invention adopts the following specific technical scheme:

a multi-column continuous separation device and a process method for removing THC in hemp extract comprise a first chromatographic column, a second chromatographic column, a third chromatographic column, a fourth chromatographic column and a fifth chromatographic column, wherein the first chromatographic column is connected with the second chromatographic column, the second chromatographic column is connected with the third chromatographic column, the third chromatographic column is connected with the fourth chromatographic column, the fourth chromatographic column is connected with the fifth chromatographic column, a feed inlet of the first chromatographic column is connected with a regeneration liquid storage tank, a first liquid inlet is arranged on the regeneration liquid storage tank, a first liquid feeding pump is arranged between the regeneration liquid storage tank and the first chromatographic column, a high-purity THC material tank is arranged between the first chromatographic column and the second chromatographic column, a second liquid inlet is arranged on the upper sample liquid storage tank, the sample loading liquid storage pool and the third chromatographic column are connected with the fourth chromatographic column through a second liquid feeding pump, a discharge port of the fifth chromatographic column is connected with a separation device, a first discharge pipe and a second discharge pipe are arranged on the separation device, the first discharge pipe is connected with a THC collection box, the THC collection box is connected with a liquid chromatograph, the second discharge pipe is connected with a solvent recovery device, and the solvent recovery device is connected with a regenerated liquid storage pool.

Further, the multi-column continuous separation process method for removing THC from the hemp extract comprises the following steps:

pulverizing and drying hemp flower and leaf to obtain powder, performing hot reflux extraction by adopting an ethanol solution with the mass concentration of 60-100%, and concentrating the obtained extracting solution under reduced pressure to obtain hemp extract;

dissolving the hemp extract with 75% ethanol water, dissolving in acetone mobile phase to obtain a sample loading solution, and storing the sample loading solution in a sample loading solution storage pool;

introducing the regeneration liquid in the regeneration liquid storage tank into a first chromatographic column, and carrying out solution balance through the first chromatographic column and a second chromatographic column;

introducing the sample solution obtained in the second step into a fourth chromatographic column, and carrying out chromatographic separation through the fourth chromatographic column and a fifth chromatographic column;

respectively introducing the solution and the THC obtained after separation into a solvent recovery device and a THC collection box through a separation device;

the mixed liquid is recovered by a solvent recovery device, and then the recovered regeneration liquid is introduced into a regeneration liquid storage tank for reuse.

Further, valves are respectively arranged between the first chromatographic column and the second chromatographic column, between the second chromatographic column and the third chromatographic column, between the third chromatographic column and the fourth chromatographic column, and between the fourth chromatographic column and the fifth chromatographic column.

Further, in the second step, the cannabis extract is dissolved by 75% ethanol to obtain a sample solution, and the concentration of the sample solution is 55 g/L.

Further, the size of the first, second, third, fourth and fifth chromatographic columns is ID10 × 300mm, the packing used in the first, second, third, fourth and fifth chromatographic columns is C18 packing, the C18 packing has a particle size of 20-40 μm, and the internal temperature of the first, second, third, fourth and fifth chromatographic columns is 25 ℃.

Further, the regeneration liquid is ethanol water or pure ethanol with the concentration of 95%.

Further, the number of the first chromatographic column, the second chromatographic column, the third chromatographic column, the fourth chromatographic column and the fifth chromatographic column is the same as the number of the third chromatographic column.

Furthermore, the proportion of the mobile phase of the regeneration liquid is 95-100% of ethanol water.

Further, the hot reflux extraction method in the first step comprises: extracting with 60-100% ethanol under reflux for 2-4 times, each time for 1-3 hr, mixing extractive solutions, and concentrating under reduced pressure to obtain concentrated fluid extract.

Further, the mobile phase in the second step is methanol, ethanol, isopropanol, n-butanol, acetone, butanone, acetonitrile or a mixed aqueous solution of any two or more of the above with the mass fraction of 40-90%.

The invention has the beneficial effects that: the chromatographic process only uses an ethanol aqueous solvent, only uses one ethanol proportion for purification, only uses one ethanol proportion for regeneration, and is simple to recover and apply; the reversed phase silica gel filler used in the chromatography process has good separation effect, simple GMP/FDA certification, reusability and small environmental pollution; the filler utilization rate of the super-chromatographic purification process is high, the unit time unit filler raw material treatment capacity is large, the productivity is high, and the unit product ethanol use amount is small; the super-chromatographic purification process can obtain broad-spectrum oil with THC less than 0.1% or without detection by one-time preparation, in a word, the super-chromatographic purification process has the advantages of low production cost, good product quality, high CBD yield, environmental friendliness and contribution to industrial production.

Drawings

In order to more clearly illustrate the technical solutions of the present invention in the implementation side or the prior art, the drawings needed to be used in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings without creative efforts.

Fig. 1 is a schematic structural diagram of a multi-column continuous separation device for removing THC from cannabis extract according to an embodiment of the invention;

fig. 2 is a flow chart of a multi-column continuous separation process for removing THC from a cannabis extract according to an embodiment of the invention.

In the figure:

1. a first chromatographic column; 2. a second chromatography column; 3. a third chromatographic column; 4. a fourth chromatographic column; 5. a fifth chromatographic column; 6. a regenerated liquid storage tank; 7. a first liquid inlet; 8. a first liquid sending pump; 9. a high purity THC feed tank; 10. a sample loading liquid storage tank; 11. a liquid inlet II; 12. a liquid feeding pump II; 13. a separation device; 14. a first discharge pipe; 15. a second discharge pipe; 16. a THC collection box; 17. a liquid chromatograph; 18. a solvent recovery device.

Detailed Description

For further explanation of the various embodiments, the drawings which form a part of the disclosure and which are incorporated in and constitute a part of this specification, illustrate embodiments and, together with the description, serve to explain the principles of operation of the embodiments, and to enable others of ordinary skill in the art to understand the various embodiments and advantages of the invention, and, by reference to these figures, reference is made to the accompanying drawings, which are not to scale and wherein like reference numerals generally refer to like elements.

According to the embodiment of the invention, the multi-column continuous separation equipment and the process method for removing THC in the hemp extract are provided.

The first embodiment is as follows:

as shown in fig. 1, the multi-column continuous separation apparatus for removing THC from cannabis sativa extract according to an embodiment of the present invention includes a first chromatographic column 1, a second chromatographic column 2, a third chromatographic column 3, a fourth chromatographic column 4 and a fifth chromatographic column 5, wherein the first chromatographic column 1 is connected to the second chromatographic column 2, the second chromatographic column 2 is connected to the third chromatographic column 3, the third chromatographic column 3 is connected to the fourth chromatographic column 4, the fourth chromatographic column 4 is connected to the fifth chromatographic column 5, a feed port of the first chromatographic column 1 is connected to a regeneration liquid storage tank 6, the regeneration liquid storage tank 6 is provided with a first liquid inlet 7, a first liquid feeding pump 8 is provided between the regeneration liquid storage tank 6 and the first chromatographic column 1, a high purity THC material tank 9 is provided between the first chromatographic column 1 and the second chromatographic column 2, and a sample loading liquid storage tank 10 is provided between the third chromatographic column 3 and the fourth chromatographic column 4, the sample loading liquid storage tank 10 is provided with a liquid inlet two 11, the sample loading liquid storage tank 10 is provided with a liquid feeding pump two 12 between the third chromatographic column 3 and the fourth chromatographic column 4, a discharge hole of the fifth chromatographic column 5 is connected with a separation device 13, the separation device 13 is provided with a first discharge pipe 14 and a second discharge pipe 15, the first discharge pipe 14 is connected with a THC collection box 16, the THC collection box 16 is connected with a liquid chromatograph 17, the second discharge pipe 15 is connected with a solvent recovery device 18, and the solvent recovery device 18 is connected with the regenerated liquid storage tank 6.

By means of the technical scheme, the chromatographic process only uses an ethanol aqueous solvent, only one ethanol proportion is used for purification, only one ethanol proportion is used for regeneration, and the recovery and the application are simple; the reversed phase silica gel filler used in the chromatography process has good separation effect, simple GMP/FDA certification, reusability and small environmental pollution; the filler utilization rate of the super-chromatographic purification process is high, the unit time unit filler raw material treatment capacity is large, the productivity is high, and the unit product ethanol use amount is small; the super-chromatographic purification process can obtain broad-spectrum oil with THC less than 0.1% or without detection by one-time preparation, in a word, the super-chromatographic purification process has the advantages of low production cost, good product quality, high CBD yield, environmental friendliness and contribution to industrial production.

A multi-column continuous separation device and a process method for removing THC in a hemp extract comprise the following steps:

pulverizing and drying hemp flower and leaf to obtain powder, performing hot reflux extraction by adopting an ethanol solution with the mass concentration of 60-100%, and concentrating the obtained extracting solution under reduced pressure to obtain hemp extract;

dissolving the hemp extract with 75% ethanol water, dissolving in acetone mobile phase to obtain a sample loading solution, and storing the sample loading solution in a sample loading solution storage pool;

introducing the regeneration liquid in the regeneration liquid storage tank into a first chromatographic column, and carrying out solution balance through the first chromatographic column and a second chromatographic column;

introducing the sample solution obtained in the second step into a fourth chromatographic column, and carrying out chromatographic separation through the fourth chromatographic column and a fifth chromatographic column;

respectively introducing the solution and the THC obtained after separation into a solvent recovery device and a THC collection box through a separation device;

the mixed liquid is recovered by a solvent recovery device, and then the recovered regeneration liquid is introduced into a regeneration liquid storage tank for reuse.

In one embodiment, valves are disposed between the first chromatography column 1 and the second chromatography column 2, between the second chromatography column 2 and the third chromatography column 3, between the third chromatography column 3 and the fourth chromatography column 4, and between the fourth chromatography column 4 and the fifth chromatography column 5, respectively.

In one embodiment, in the second step, the cannabis extract is dissolved in 75% ethanol to obtain a sample solution, and the concentration of the sample solution is 55 g/L.

In one embodiment, the first, second, third, fourth and fifth chromatography columns 1, 2, 3, 4 and 5 have a size of ID10 x 300mm, the packing used for the first, second, third, fourth and fifth chromatography columns 1, 2, 3, 4 and 5 is C18 packing, the C18 packing has a particle size of 20-40 μm, and the internal temperature of the first, second, third, fourth and fifth chromatography columns 1, 2, 3, 4 and 5 is 25 ℃.

In one embodiment, the regeneration liquid is 95% ethanol water or pure ethanol.

In one embodiment, the number of the first chromatography column 1, the second chromatography column 2, the third chromatography column 3, the fourth chromatography column 4 and the fifth chromatography column 5 is 5 each.

In one embodiment, the regeneration liquid mobile phase ratio is 95-100% ethanol water.

In one embodiment, the hot reflux extraction method in the first step is as follows: extracting with 60-100% ethanol under reflux for 2-4 times, each time for 1-3 hr, mixing extractive solutions, and concentrating under reduced pressure to obtain concentrated fluid extract.

In one embodiment, the mobile phase in the second step is 40-90% by mass of methanol, ethanol, isopropanol, n-butanol, acetone, butanone, acetonitrile or a mixed aqueous solution of any two or more of the above.

As shown in fig. 2, in the actual production process, the process method for removing THC from the cannabis extract by multi-column continuous separation comprises the following steps:

step S101, hemp flower and leaf are taken, crushed and dried to obtain powder, ethanol solution with the mass concentration of 60-100% is adopted for hot reflux extraction, and the obtained extracting solution is decompressed and concentrated to obtain hemp extract;

step S103, dissolving the hemp extract with 75% ethanol water, then dissolving the hemp extract in an acetone mobile phase to obtain a sample loading solution, and storing the sample loading solution in a sample loading solution storage pool;

step S105, introducing the regeneration liquid in the regeneration liquid storage tank into a first chromatographic column, and carrying out solution balance through the first chromatographic column and a second chromatographic column;

step S107, introducing the sample solution obtained in the step two into a fourth chromatographic column, and carrying out chromatographic separation through the fourth chromatographic column and a fifth chromatographic column;

step S109, respectively introducing the solution and the THC obtained after separation into a solvent recovery device and a THC collection box through a separation device;

step S111 is to recover the mixed solution by the solvent recovery device, and then to introduce the recovered regenerated solution into a regenerated solution storage tank for reuse.

In conclusion, by means of the technical scheme, only the ethanol water solvent is used in the chromatography process, only one ethanol proportion is used for purification, only one ethanol proportion is used for regeneration, and the recovery and the application are simple; the reversed phase silica gel filler used in the chromatography process has good separation effect, simple GMP/FDA certification, reusability and small environmental pollution; the filler utilization rate of the super-chromatographic purification process is high, the unit time unit filler raw material treatment capacity is large, the productivity is high, and the unit product ethanol use amount is small; the super-chromatographic purification process can obtain broad-spectrum oil with THC less than 0.1% or without detection by one-time preparation, in a word, the super-chromatographic purification process has the advantages of low production cost, good product quality, high CBD yield, environmental friendliness and contribution to industrial production.

In the present invention, unless otherwise expressly specified or limited, the terms "mounted," "disposed," "connected," "secured," "screwed" and the like are to be construed broadly, e.g., as meaning fixedly connected, detachably connected, or integrally formed; can be mechanically or electrically connected; the terms may be directly connected or indirectly connected through an intermediate, and may be communication between two elements or interaction relationship between two elements, unless otherwise specifically limited, and the specific meaning of the terms in the present invention will be understood by those skilled in the art according to specific situations.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.