KR20000060614A - Extraction of Perillyl Alcohol from Orange Peel by Supercritical Carbon Dioxide - Google Patents

Abstract

PURPOSE: A method of extracting perillyl alcohol from orange peels using supercritical carbon dioxide is provided, that can produce perillyl alcohol useful as an antitumor agent in superior yield to a conventional methanol extracting method. CONSTITUTION: The method comprises the step of extracting the extract containing perillyl alcohol from orange peels by a supercritical fluid extractor which uses a carbon dioxide solvent as a supercritical fluid at higher temperature and pressure than a critical temperature and pressure of carbon dioxide. Specially, the extracting pressure is from 73 to 300 atm and the extracting temperature is from 32 to 100°C.

Description

Extraction method of peryl alcohol from tangerine peel using supercritical carbon dioxide {Extraction of Perillyl Alcohol from Orange Peel by Supercritical Carbon Dioxide}

The present invention relates to an extraction method for obtaining perillyl alcohol (perillyl alcohol), which has recently attracted attention as an anticancer agent for breast cancer, colon cancer, pancreatic cancer and the like. More specifically, the present invention relates to a method of extracting a high value anticancer agent such as peryl alcohol from a tangerine peel using a supercritical fluid extractor (SFE).

Supercritical fluid extraction is a novel separation process that allows the selective extraction of the desired components from a sample using the fluid under conditions above the critical pressure and critical temperature of the fluid. Supercritical fluids are very effective when their properties, such as their permeability, transportability, behave like gases, and their solubility is similar to liquid solvents to extract materials from porous solid samples. Moreover, the separation of the extraction solvent and the extract is easy because the change of the dissolving power due to the change of temperature and pressure is large. Carbon dioxide has excellent properties as a solvent in the supercritical state, is not toxic, inexpensive, and has low operating temperature, which is difficult to separate with conventional techniques, separation of thermodenatured mixtures, purification of polymeric materials, and natural plants. The application range of the separation of active ingredients such as medicine and fragrance is expanding.

Among the components included in citrus skin such as tangerines and oranges, limonene is an essential component of the plant. The chemical structural formula is C ₁₀ H ₁₆ and is naturally produced from monoterpine. Because of its lemon-like scent, it has been used primarily in the beverage, confectionery, pharmaceutical, and cosmetic industries, and recently, CFC 113 and 1,1,1 TCE's advanced cleaners have been designated as regulated substances that destroy the ozone layer. Is being used. The optical isomers of limonene include d and l. d body is contained in the husk oil, lemon oil, bergamot oil, fennel oil and the like, l body is contained in pine oil, peppermint oil and the like. In addition, recent studies have shown that d-limonene is effective as an anticancer agent (MA Morse and AL Toburen, Cancer Letters, 104, 211 (1996)). The components that make up a citrus fruit include limonene as well as many other ingredients. Among them, peryl alcohol has been medically proven to be effective as an anticancer agent, and in particular, its range of use is expanding because of its excellent therapeutic effects such as breast cancer, leukemia, colon cancer, pancreatic cancer, lung cancer, etc. [HC Chang et al. US Pat. No. 5,487,988] Ho (January 1996); International Application Publication No. WO95 / 24895 by MN Gould et al. (September 1995)].

The composition formula of peryl alcohol is C ₁₀ H ₁₆ O, 1-hydroxymethyl-4-isopropenyl-cyclohexene, 4-isopropenyl-1-cyclohexene-1-methanol, p-menta 1,8- It is referred to as diene-7-ol, and there is an isomer of (R)-(+)-peryl alcohol, and (S)-(-)-peryl alcohol. Methods for obtaining peryl alcohol include direct extraction from natural plants, methods of synthesis from materials with similar chemical structures [US Patent No. 5,487,988 to HC Chang et al. (January 1996)], bacteria such as bacteria Method by cell culture from HC Chang and P. Oriel, J. Food Sci., 59, 660 (1994). Foreign countries have already confirmed the efficacy of peryl alcohol and d-limonene as anticancer drugs through animal and clinical experiments for many years. However, many studies have not been conducted because the substance of peryl alcohol is not well known in Korea. to be. Recent studies have focused on the direct extraction of peryl alcohol and d-limonene from Korean tangerine peel using methanol [Korean Patent Application No. 1997-40122] and ethanol [Korean Patent Application No. 1998-27170] as extraction solvents. Patent pending.

The present invention is to use a supercritical extraction device to extract peryl alcohol from the tangerine peel which is being recycled at home or food processing factories in a higher yield than the prior art.

BRIEF DESCRIPTION OF THE DRAWINGS The chromatogram which analyzed the oil layer in the extract liquid extracted by the supercritical extraction apparatus by gas chromatography.

2 is a chromatogram obtained by analyzing a water layer in an extract extracted by a supercritical extraction device by gas chromatography.

3 is a chromatogram analyzed by gas chromatography of an extract extracted using methanol.

The present invention relates to a method of extracting a high value anticancer agent such as peryl alcohol from a tangerine peel using a supercritical fluid extractor. More specifically, the present invention is a method for obtaining an extract containing peryl alcohol from the tangerine peel using a supercritical fluid extractor using a carbon dioxide solvent as a supercritical fluid under the temperature and pressure conditions higher than the critical pressure of carbon dioxide It is about.

According to the present invention, a method of extracting tangerine peel peryl alcohol using a supercritical extraction device can be summarized as the following schematic.

The method of extracting the tangerine peel rotor peryl alcohol using a supercritical extraction device is as follows. It is introduced into the device and consists of extraction using carbon dioxide as the supercritical fluid for a period of time under a temperature and pressure above the critical temperature and critical pressure of the carbon dioxide. The extracted extract is divided into an oil layer and a water layer, and peryl alcohol can be obtained in the oil layer by analyzing a sample of the divided oil layer and the water layer by gas chromatography.

In this method, the tangerine peel is ground into a powder having a diameter of 1 to 3.5 mm, and the flow rate of carbon dioxide used as a supercritical fluid is, for example, 0.3 to 11.9 kg / hr, and 10 to 500 g of carbon dioxide per 1 g of tangerine is passed. It is used in an amount to do. Extraction in a supercritical extraction device is carried out at temperatures and pressures higher than the critical temperature (31.1 ° C.) and critical pressure (72.8 atm (73.8 bar)) of carbon dioxide, for example at least 32 ° C., preferably at 32 to 100 ° C. and 73 atm. Above, preferably at least 10 hours under conditions of 73 to 300 atmospheres. The extract sample, which is divided into an oil layer and a water layer, has a sample injection volume of 1 μl, a N ₂ flow rate of 0.8 ml / minute, an injector temperature of 250 ° C., a probe temperature of 300 ° C., a split ratio of 1:50, and an oven temperature of 50 ° C. to 80 ° C. of 10 ° C. Minutes, 80 ° C. to 250 ° C., are analyzed using gas chromatography under conditions that apply an elevated temperature program at a rate of 5 ° C./min.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are only for illustrating the present description, and the present invention is not limited only to these examples.

<Example 1>

In this embodiment, in order to extract the peryl alcohol contained in the tangerine peel, a supercritical fluid extraction device was used instead of the conventional solvent extraction method using a solvent. A 10 liter iron extractor was filled with 2,000 g of dried orange peel 1 to 1.3 mm in diameter, and the working conditions at the extractor were 35 ° C. and 148 atm (150 bar) above the critical temperature and the critical pressure of the carbon dioxide. An extract of about 50 g was obtained when the flow rate of was passed through 11.9 kg / hr for 12 hours. The extract was divided into two layers, water and oil, and each of the water and oil layers was injected into HP-5 (crosslinked 5% PH ME siloxane, 30m × 0.32 mm) capillary to obtain gas chromatography (conditions: 1 μl sample injection volume); N ₂ flow rate 0.8 ml / min; injector temperature 250 ° C .; probe temperature 300 ° C .; split ratio 1:50; oven temperature 50 ° C. to 80 ° C., 10 ° C./min, 80 ° C. to 250 ° C., 5 ° C./min. An elevated temperature program). Analysis of the oil layer showed that 0.354 mg / ml of peryl alcohol was obtained. Peryl alcohol was not analyzed in the water layer. Standard reagents of peryl alcohol used for quantitative analysis in this Example were purchased from Aldrich Co. 1 is a chromatogram obtained by analyzing an oil layer in a gas extract extracted using a supercritical fluid extractor. 2 is a chromatogram analysis of the water layer.

<Example 2>

A 200 ml iron extractor was filled with 70 g of dried orange peel of 1 to 3.5 mm in diameter, the working conditions at the extractor were 60 ° C. and 197.4 atm (200 bar), and the flow rate of carbon dioxide was 0.3 kg / hr. When passed for 10 hours to obtain an extract of about 0.65 g. Analysis of the oil layer by gas chromatography under the same conditions as in Example 1 yielded 0.410 mg / ml of peryl alcohol.

<Comparative Example 1>

The yield of peryl alcohol extraction by the supercritical fluid extraction method and the conventional solvent extraction method of Example 1 was compared. Methanol having the best yield of peryl alcohol by solvent extraction was used. 3 is a chromatogram analyzed by gas chromatography of an extract extracted using methanol. When peryl alcohol was extracted from the dried tangerine peel using methanol as a solvent, it was found that the extract contained 0.002 mg / ml of peryl alcohol. Therefore, when using the supercritical carbon dioxide of Example 1, it can be seen that more than 170 times more peryl alcohol than methanol solvent extraction method can be extracted.

According to the extraction method of the present invention using supercritical carbon dioxide, peryl alcohol useful as an anticancer agent and the like can be obtained in much better yield than the conventional methanol solvent extraction method. Therefore, the present invention can greatly contribute to the provision of demand in the domestic anticancer drug market, which is rapidly growing in recent years, the advantage of international competitiveness, and the activation of industrial fields related to medicine.

Claims (3)

A method for obtaining peryl alcohol-containing extract from tangerine peel using a supercritical fluid extractor using carbon dioxide solvent as a supercritical fluid under temperature and pressure conditions higher than the critical pressure of carbon dioxide. The process of claim 1 wherein the extraction pressure is between 73 and 300 atmospheres. The method of claim 1 wherein the extraction temperature is from 32 ° C. to 100 ° C. 3.