KR101090945B1 - Extraction method of 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one using supercritical fluid extraction - Google Patents

Abstract

PURPOSE: A method for extracting 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one using a supercritical fluid extracting technique is provided to improve the purity and the yield of the 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one without toxicity. CONSTITUTION: A method for extracting 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one includes the following: Tobacco leaves are primarily extracted using supercritical fluid under a temperature of 30-70 degrees Celsius and a pressure of 450-750 bar. The extracted material is secondarily extracted using the supercritical fluid under a temperature of 30-70 degrees Celsius and a pressure of 300-600 bar. 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one is separated and refined from the extract. The supercritical fluid is carbon dioxide. The flux of the supercritical fluid is between 1 and 72 g/hr.

Description

Extraction method of 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one using supercritical fluid extraction technique {extraction method of 3,5,5-trimethyl-4-butenylidene-2- cyclohexen-1-one using supercritical fluid extraction}

The present invention relates to a method for efficiently extracting 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one using a supercritical fluid extraction technique.

In recent years, interest in the environment has increased in all processes throughout the industry, and the process of extracting and purifying active ingredients of natural products, as well as the environmental and human toxicity of existing extraction and purification processes using organic solvents, Attempts have been made to introduce new processes that address selectivity, high cost, and the like.

As an alternative, supercritical fluids, which are intermediate between gas and liquid, are used as extraction fluids that are not toxic to the environment and human body, have high selectivity for target components, and are easy to control.

The extraction technology using the supercritical fluid having the above characteristics has the characteristics of a complex technology in which the principles of distillation and extraction are applied together, so that the product has high selectivity for fractionation and separation of the extract, thereby obtaining a high-purity product, without losing an extraction solvent. It can be recovered almost completely, and there is an advantage in that a purified product having no residual solvent can be obtained.

In addition, the supercritical fluid has a low viscosity, so it penetrates into the sample, so the extraction efficiency is high, the extraction speed is fast, and the extraction is performed at a relatively low temperature to avoid the damage of the extract by heat, and the viscosity of the supercritical fluid is low, so the extract and the solvent It is easy to separate.

The present invention provides a method for extracting 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one with high purity and yield from tobacco using supercritical fluid extraction technology.

The present invention also provides an electronic cigarette solution composition comprising 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one produced using a supercritical fluid extraction technique.

The present invention is a method for extracting 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one from the tobacco plant as a supercritical fluid at a temperature of 30 ~ 70 ℃ and pressure 450 ~ 750bar 1 Tea extraction step (a), secondary extraction of the material extracted in step a) into a supercritical fluid at a temperature of 30 ~ 70 ℃ and pressure 300 ~ 600bar (step b) and 3 from the extract of step b) , 5,5-trimethyl-4-butenylidene-2-cyclohexene-

Separating and purifying 1-one (3,5,5-Trimethyl-4-butenylidene-2-cyclohexen-1-one) (step c).

 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one (3,5,5-Trimethyl-4-butenylidene-2-cyclohexen-1- with high purity and high yield in tobacco) In order to obtain one), preferably, step a) is carried out at a temperature of 35 to 60 ° C and a pressure of 550 to 650 bar and b) may be performed at a temperature of 35 to 60 ° C and a pressure of 400 to 500 bar.

In the present invention, the extraction temperature is preferably 30 ~ 70 ℃ but lower than 30 ℃ if the diffusion (diffusivity), the surface tension (surface tension) associated with the substrate permeability is significantly low, the extraction is not smooth and higher than 70 ℃ The diffusion rate associated with substrate permeability is high and the surface tension is high, so the selective opportunity of extraction is increased, but the extraction amount is lowered in terms of the density related to the resolution of the liquid which is characteristic of the separation from the substrate. For this reason, 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one (3,5,5-Trimethyl-4-butenylidene-2- from the beginning of the year using the supercritical fluid of the present invention. When cyclohexen-1-one) is first extracted, a temperature of 30 to 70 ° C. and a pressure of 450 to 750 bar are preferable, and a temperature of 35 to 60 ° C. and a pressure of 550 to 650 bar are more preferable.

In order to increase the extraction yield, extraction is carried out at a temperature of 30-70 ° C. and a pressure of 450-750 bar during the first extraction, and 3,5,5-trimethyl-4-butenylidene- obtained during the first extraction during the second extraction. 3,5,5-trimethyl-4-butenylidene, which is purer than in materials containing 2-cyclohexen-1-one (3,5,5-Trimethyl-4-butenylidene-2-cyclohexen-1-one) In order to obtain -2-cyclohexen-1-one (3,5,5-Trimethyl-4-butenylidene-2-cyclohexen-1-one), extraction is preferably performed at a temperature of 30 to 70 ° C. and a pressure of 300 to 600 bar. .

For this reason, the present invention controls the temperature and the pressure of carbon dioxide to obtain 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one having high purity and high yield in tobacco. First extraction with supercritical fluid at a temperature of 30-70 ° C. and a pressure of 450-750 bar (step a) and second extraction of the material extracted in step a) with a supercritical fluid at a temperature of 30-70 ° C. and a pressure of 300-600 bar. (b), and further comprising separating and purifying the extract of step b) (step c).

The supercritical fluid is not particularly limited but carbon dioxide is more preferred. Carbon dioxide is a solvent mainly used in supercritical fluid extraction. It is vaporized under atmospheric pressure and extracted into the atmosphere after extraction. It is non-toxic and non-hazardous because there is no residual solvent.It can be used to make products without contamination in the food and pharmaceutical manufacturing industries. have. Liquid extraction leaves residual toxic organic solvents after distillation or vacuum separation steps. Compared to the density and solvent capacity of organic solvents, the density and solvent capacity of supercritical fluids have higher transfer efficiency, such as lower viscosity and higher diffusivity. Therefore, even if the various components as oligomers have a similar volatility, the extract has a variety of advantages that can be separated into each component, so the 3,5,5-trimethyl-4-butenylidene-2-cyclo according to the present invention Selective extraction of hexen-1-one is also preferred to use carbon dioxide as the extraction solvent.

In addition, the flow rate of the supercritical fluid according to the present invention is preferably 1 ~ 72g / hr, but lower than 1g / hr, the yield is good, but the efficiency is lowered over time and higher than 72g / hr, the proper extraction is not made, the yield can be reduced .

The 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one extracted in the present invention is not particularly limited, but is of higher purity 3,5,5-trimethyl-4-butenylidene Further purification can be performed using HPLC, distillation under reduced pressure and recrystallization to obtain -2-cyclohexen-1-one.

The present invention also provides an electronic cigarette solution composition comprising 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one extracted by supercritical fluid extraction.

The electronic cigarette solution composition comprising 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one was added to 3,5,5-trimethyl-4-butenylidene-2-cyclo in the total solution. It is preferable that hexen-1-one is contained in 1 to 25weight%.

E-cigarette solution composition comprising 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one obtained according to the present invention is 50 to 80% by weight of glycerin, 1 to 20% glycerol based on the total solution It may further comprise 1% to 10% by weight, nicotine 1 to 10% by weight, propylene glycol 1 to 20% by weight and flavoring. The fragrance may be one or a mixture of two or more selected from peach, coffee, apple, chocolate, cinnamon and menthol.

It may also further comprise one or more mixtures selected from monosaccharides, disaccharides and polysaccharides to further enhance the flavor.

The monosaccharide may be selected from glucose, galactose and fructose, the disaccharide may be selected from sugar, maltose, lactose and oligosaccharide, and the polysaccharide may be selected from starch, glucose and cellulose, but is not particularly limited.

3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one production process using the supercritical fluid extraction technology according to the present invention is simple, 3,5,5-trimethyl-4-bute Nilidene-2-cyclohexen-1-one can be selectively extracted, and using carbon dioxide as a supercritical fluid, the extract can be extracted with high purity and high yield without remaining toxic in the extract.

In addition, the solution component of the e-cigarette containing 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one extracted according to the present invention has the advantage that can serve as a high smoking cessation aid have.

Hereinafter, the present invention will be described in detail with reference to the following Examples, but the present invention is not limited by the Examples.

The supercritical fluid extraction device used in the present invention is generally divided into four parts. First, the fluid reservoir, the source of high purity supercritical carbon dioxide, is primarily a high purity liquefied carbon dioxide cylinder on a laboratory scale. Secondly, there is a high pressure pump that can adjust the pressure and flow rate constantly or easily, and the high pressure pump is called a check valve and is equipped with a device to prevent backflow of the pressure pushed into the reactor. Third, the sample is contained in the extraction tank, which is installed in the thermostat because the constant temperature must be maintained. Fourth, a restrictor keeps the required pressure in the extraction tank constant. Fluid reservoirs are mainly cylinders of steel, aluminum or stainless steel. The pressure in the cylinder is high enough for the contents to be liquid. The high pressure pumps used in supercritical fluid extraction are similar to those used in HCP or supercritical fluid chromatography. For optimal performance, a pressure of 70 to 700 bar should be obtained, and the operating pressure should be kept constant and measured immediately. It should be reproducible at 1.0 ~ 100ml / min and no pulse at the flow rate. Extraction tanks are places where supercritical fluids can come into contact, where unknown samples are placed.

Looking at the high-efficiency extraction method of 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one from the tobacco using the supercritical fluid extraction technology according to the present invention, first, supercritical fluid extraction After inserting tobacco into the extraction reactor of the device, the pressurized carbon dioxide is supplied from the lower part through a pump through a heat exchanger, and the pressure in the reactor is controlled by a back pressure regulator to heat the reactor. Maintain a constant temperature through.

The extraction solvent carbon dioxide extracts 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one in an upflow manner in which supercritical carbon dioxide is in contact with the tobacco from the lower layer.

Thereafter, the extracted 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one was passed through the back pressure valve through the upper valve and the pressure was reduced and maintained at about 100 to 150 bar. At first, carbon dioxide and 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one are first separated, and the first separated carbon dioxide is again subjected to a pressure of 50 to 65 bar and gaseous conditions of carbon dioxide. Phosphorus is decompressed to 30 ~ 60 ℃ temperature in the separator 2 to cause a phase change from the liquid phase to the gaseous phase is separated into the secondary flow through the heat exchanger flows into the fluid storage tank. The fluid storage tank supplies carbon dioxide from the outside for replenishment to compensate for a small loss generated in the entire process in addition to the carbon dioxide supplied through the circulation.

 Analysis of 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one component at the beginning of the year was measured by gas chromatography, Agilent 6890 GC system (with autosampler) A column of HP-Ultra 2 (50m length, 0.32mm id, 0.52μm of phenylmethylsiloloxane) was used, and helium (1.7 ml / min) was used as a carrier gas. The oven temperature was initially increased from 60 ° C. to 3.5 ° C./min to 170 ° C., and then maintained for 5 minutes. Thereafter, the temperature was increased to 240 ° C. at 6 ° C./min, followed by a 70 minute analysis time. Injector was maintained at 260 ℃, injection was 1µl (split ratio = 60: 1), and detector was kept at FID 280 ℃.

By applying supercritical fluid extraction method at the beginning of the year, 1000g of tobacco was added to the extraction tank, and the carbon dioxide content was adjusted to 14, and then the supercritical fluid extraction method was applied to the reactor. The yield was measured by Soxhlet method, and the content of 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one in the tobacco leaf before extraction and 3,5,5- after extraction The content of trimethyl-4-butenylidene-2-cyclohexen-1-one was measured.

Example 1

1 kg of dried tobacco was pulverized and put into a supercritical fluid extractor, and supercritical extraction was carried out for 1 hour at a temperature of 60 ° C. and pressure of 600 bar at a flow rate of 72 g / hr.

50 g of the extracted extract was quantified and introduced into the supercritical fluid extractor, and the supercritical extraction was performed for 1 hour at a flow rate of 72 g / hr at a temperature of 35 ° C. and the pressure of 450 bar. Table 1 shows the contents of, 5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one.

The 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one extracted by the supercritical fluid extraction technique was once more purified by HPLC.

[Example 2]

The extract extracted first from the tobacco was extracted in the same manner as in Example 1 except the temperature was 35 ℃, pressure 550bar and the content is shown in Table 1.

Example 3

The temperature at the time of secondary extraction was extracted in the same manner as in Example 1 except for 60 ℃, the pressure of 450bar and the content is shown in Table 1.

Example 4

The temperature at the time of secondary extraction was extracted in the same manner as in Example 1 except for 60 ℃, the pressure of 450bar and the content is shown in Table 1.

Temperature (℃) Pressure (bar) content(%) Example 1-1 35 450 75 Example 1-2 35 550 83 Example 1-3 60 450 94 Example 1-4 60 550 98

Experimental results of the extraction yield showed the highest extraction yield of 98% at the temperature of 65 ℃, pressure 550bar as shown in the table.

Comparative Example 1

The extraction method was extracted with 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one except using ethanol instead of supercritical fluid extraction technology and the extraction yield was 67%. The purity was low.

[Examples 5 to 17]

Electronic cigarette solution composition containing 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one extracted in Examples 1 to 4 was prepared as shown in Table 2 and Table 3.

An electronic cigarette comprising the prepared electronic cigarette solution composition of Examples 5 to 17 was prepared, and smoking satisfaction was evaluated by a five-point measurement method for 50 smokers, and the values thereof were averaged in Tables 2 and 3 below. (Very satisfied: 5, somewhat satisfied: 4, moderately satisfied: 3, somewhat dissatisfied: 2 very dissatisfied: 1)

                                                           (content : %) ingredient Example 5 Example 6 Example 7 Example 8 Example 9 Example 10 Example 11 glycerin 77 72 69 64 61 57 55 ethanol 4 6 7 9 13 15 7 nicotine 7 4 6 6 3 3 7 Extract of Preparation Example 10 15 14 17 19 23 15 Propylene glycol 14 Peach flavor 2 2 2 2 2 Coffee flavor 3 2 Apple flavor Chocolate flavor Cinnamon 2 Menthol 2 2 Tobacco flavor
The presence or absence U U U U U U U smoking
satisfaction 4.23 4.44 4.52 4.37 4.27 4.52 4.26

                                                           (content : %) ingredient Example 12 Example 13 Example 14 Example 15 Example 16 Example 17 glycerin 75 71 69 61 58 52 ethanol 4 6 7 9 13 15 nicotine 7 4 6 6 3 3 Extract of Preparation Example 10 15 14 17 19 23 Xylitol 2 3 Sugar 2 3 oligosaccharide 2 3 Peach flavor 2 2 2 2 Coffee flavor 2 Cinnamon 2 Menthol 2 2 2 Tobacco flavor
The presence or absence U U U U U U smoking
satisfaction 4.3 4.2 4.45 4.78 4.63 4.54

[Comparative Examples 2 to 10]

An electronic cigarette solution composition not containing 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one was prepared in Comparative Examples 2 to 10 with the composition shown in Table 4 below.

An electronic cigarette including the electronic cigarette solution composition prepared in Comparative Examples 2 to 10 was prepared, and smoking satisfaction was evaluated by a five-point measurement method for 50 smokers. The results are shown in Table 4 below. (Very satisfied: 5, somewhat satisfied: 4, moderately satisfied: 3, somewhat dissatisfied: 2 very dissatisfied: 1)

ingredient Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 Comparative Example 9 Comparative Example 10 glycerin 85 86 89 84 80 80 81 90 84 ethanol 5 4 2 4 8 8 7 2 4 nicotine 8 5 5 8 8 8 8 5 8 Peach flavor 2 2 2 2 Coffee flavor 5 2 Apple flavor 4 Chocolate flavor 4 Cinnamon 4 2 Menthol 2 3 Tobacco flavor radish radish radish radish radish radish radish radish radish Smoking satisfaction 3.12 3.47 2.68 2.43 2.82 3.27 2.12 2.14 2.53

As shown in this example, an electronic cigarette prepared from an electronic cigarette solution containing 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one extracted in Preparation Examples 1 to 4 was used. Smoking satisfaction was higher than e-cigarettes that did not contain and the flavor was better when 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one was added and sugar, oligosaccharides and xylitol were added. Smoking satisfaction was also high.

Claims (9)

a) first extracting tobacco as a supercritical fluid at a temperature of 30-70 ° C. and a pressure of 450-750 bar;
b) secondary extraction of the material extracted in step a) into a supercritical fluid at a temperature of 30 to 70 ° C. and a pressure of 300 to 600 bar;
c) 3,5,5-trimethyl-4-bute comprising separating and purifying 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one from the extract of step b) Extraction method of nilidene-2-cyclohexen-1-one. The method of claim 1,
Step a) is a temperature of 35 to 60 ° C. and pressure 550 to 650 bar and b) is a 3,5,5-trimethyl-4-butenylidene-2-cyclohexene carried out at a temperature of 35 to 60 ° C. and a pressure of 400 to 500 bar. Extraction method of -1-one. The method of claim 1,
The supercritical fluid is carbon dioxide extraction method of 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one. The method of claim 1,
Supercritical fluid extraction method of 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one having a flow rate of 1 ~ 72g / hr. The method of claim 1,
Separation and purification of step c) is extraction method of 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one which is HPLC, distillation under reduced pressure and recrystallization. An electronic cigarette solution composition comprising 3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one produced by the method according to any one of claims 1 to 5. The method of claim 6,
3,5,5-trimethyl-4-butenylidene-2-cyclohexen-1-one is contained in 1 to 25% by weight electronic cigarette solution composition. The method of claim 7, wherein
E-cigarette solution composition further comprises 50 to 80% by weight glycerin, 1 to 20% by weight ethanol, 1 to 10% by weight nicotine, 1 to 20% by weight propylene glycol and 1 to 10% by weight. The method of claim 7, wherein
Electronic cigarette solution composition further comprises one or more substances selected from monosaccharides, disaccharides and polysaccharides.