KR101343820B1 - The technology of layer crystallization for controlling total ginsenoside content in red ginseng extract and the manufactur of quatified red ginseng extract using it - Google Patents

Abstract

The present invention relates to a method for isolating and purifying high purity red ginseng concentrate by a first and a second layer crystallization and a manufacturing method for quantifying the contents of 11 kinds of ginsenosides. The present invention comprises: a first layer crystallization step for mixing the red ginseng concentrate and ethanol, then layer crystallizing primarily; and a second layer crystallization step for mixing a first acquisition and ethanol again, then layer crystallizing secondarily. The present invention provides a technique for isolating and purifying total ginsenosides from the red ginseng concentrate effectively which has an effect in cutting the unit cost of production and which upgrades the specifications of red ginseng concentrate products using high purity total ginsenosides, thereby leading the world in various high value red ginseng products market. Especially, development of the high purity total ginsenosides ensures production of the red ginseng concentrate products containing quantified total ginsenosides, thereby providing high quality products in the future market of raw material for the medicine. [Reference numerals] (AA) Red ginseng concentrate;(BB,EE) 95% Ethanol;(CC) First layer crystallization;(DD) Purity of total ginsenosides: 8.5 to 92 weight%;(FF) Mixing;(GG) First crystallized mixture;(HH) Second crystallized mixture;(II) Quantitative standard red ginseng concentrate;(JJ) Second layer crystallization;(KK) Purity of total ginsenosides: 72 to 98 weight%;(LL) High purity total ginsenosides

Description

Separation method of high purity of red ginseng concentrate using dural crystallization and preparation method of red ginseng concentrate to quantify high purity ginsenoside content using the same {The Technology of Layer Crystallization for Controlling Total Ginsenoside Content in Red Ginseng Extract and The Manufactur of Quatified Red Ginseng Extract Using It}

The present invention relates to a method for separating and purifying red ginseng concentrate with high purity and a method for preparing red ginseng concentrate for quantifying high ginsenoside content.

Red ginseng has central nervous system disease, anti-anxiety, nervous system, drug addiction, blood vessel function, alcohol detoxification, lipid metabolism and fatigue recovery, antidiabetic, hyperlipidemia, antiviral, immune enhancement, sexual function improvement, anticancer and cancer prevention effect. In particular, panaxadiol (PD) -based saponins, represented by ginsenoside Rb ₁ , have inhibitory effects on the central nervous system, and exhibit mental stability, nerve relaxation, analgesia, anticancer, anticonvulsion, blood pressure lowering action, and ginsenoside Rg. Panaxatriol (PT) -based saponins represented by ₁ are known to exhibit anti-fatigue effects on the central nervous system [Latest Ginseng Research, Korea Ginseng Society, 2007].

In general, ginseng and red ginseng are marketed as herbal medicines or teas in the form of circular form itself, powders and concentrates. Currently, the use of red ginseng concentrates is widely used in nutritional supplements, cosmetics, pharmaceutical raw materials and health functional foods. As the demand is rapidly increasing, the efficient manufacturing process technology of high value-added differentiated red ginseng concentrate has a great influence on the competitiveness in the global market according to product quality and production cost.

In particular, research on the efficacy of ginsenoside, a bioactive ingredient of red ginseng as a pharmaceutical ingredient or a health functional food ingredient [see Table 1] below, and high-purity separation and purification has been conducted for a long time. The isolated individual ginsenosides are highly purified and developed as anti-cancer, immune, stress, arthritis, and metabolic diseases treatments, and some of them have been approved by the US FDA.

Recently, red ginseng concentrate containing 4 to 95 wt% total ginsenoside content was developed to develop high value-added products. Therefore, in order to quantify and control the total ginsenoside content of the red ginseng concentrate, it is necessary to develop a technology capable of separating and purifying the ginsenosides with high purity, but since the total ginsenoside content of the conventional red ginseng concentrate is about 4% by weight, the red ginseng concentrate It was difficult to control or quantify the total ginsenoside content without adding a new separation and purification process.

In general, the total ginsenosides contained in the red ginseng concentrate are about 22 to 32 kinds of Korean red ginseng. Among these, except for 11 kinds of ginsenosides, other ginsenosides are contained in very small amounts. Since 11 types of ginsenosides account for more than 98% of the total content of each type of side, the total ginsenoside content is determined by individually quantifying the 11 types of ginsenosides, and then sums the total values. It is also defined as the content of. Ginsenosides for 11 species are Rg ₁ , Re, Rf, Rb ₁ , Rg ₂ , Rc, Rb ₂ , Rb ₃ , Rd, Rg ₃ And Rh ₂ and, in the case of Korean ginseng, have a ratio of 11 ginsenosides to total ginsenosides as shown in the following [Table 2].

In general, as the separation and purification method, various techniques such as crystallization method, purification separation method using column, technology using membrain filter, distillation, extraction, etc. are used. It is true that the production efficiency of separation purification technology is very low. However, in the separation and purification technology of natural materials such as ginseng, since the technology using a column is mainly used, high separation and purification technology is very necessary to improve productivity.

As a prior art related to the separation and purification technology of ginsenoside, a bioactive component of red ginseng concentrate, for example, j. ginseng Res., Vol. 22, no. 3, according to the column technology using a benzene ethylene resin filler is a technology for separating and purifying PD / PT system, and published in Korea Patent Publication No. 2010-0052651, Korea Patent Publication No. 10-0228510 and domestic registered patent Publication No. 10-0899837 describes a technique for separating and purifying PD / PT-based ginsenosides by column technology using silica gel filler.

The above-mentioned prior arts use a lot of solvents, such as ethanol or butanol, because all of the separation technology uses a column technology, the scale-up technology is difficult, there is a disadvantage that the process efficiency, such as long process time is inferior.

The present invention has completed the present invention by preparing a red ginseng concentrate quantified total ginsenosides by adjusting the high purity separation of total ginsenosides from the red ginseng concentrate using the improved film crystallization technology and its content.

The present invention solves the shortcomings of the conventional separation and purification technology using a column, the method of separating and purifying the red ginseng concentrate with high purity and red ginseng quantifying the content of 11 kinds of ginsenosides (hereinafter referred to as 'total ginsenoside') The purpose of the present invention is to provide a method for preparing a concentrate, and more specifically, a method of separating and purifying high purity red ginseng concentrate from red ginseng concentrate using an improved film crystallization technique, and red ginseng quantifying the content of high purity ginsenoside using the same. It is an object to provide a method for producing a concentrate.

As a solution of the method for separating and purifying the raw red ginseng concentrate with high purity, which is the object of the present invention, the first dural crystallization step of mixing the raw red ginseng concentrate with alcohol and then performing primary film crystallization at -20 ° C. temperature, and primary film crystallization It comprises a dura-crystallization step of mixing the ethanol again with the primary obtained obtained in the step and then the second dura-crystallization at -20 ℃ temperature conditions.

And as a solution of the manufacturing method of the red ginseng concentrate quantified the content of the total ginsenoside of high purity, which is another object of the present invention, after mixing the raw red ginseng concentrate and alcohol, the first film duranic crystallization at -20 ℃ temperature conditions In the second dura crystallization step and the first dura crystallization step of mixing the first alcohol obtained by the first dura crystallization step and the first drip crystallization step and the second dura crystallization at -20 ℃ temperature conditions It consists of a method of producing a red ginseng concentrate to quantify the total ginsenoside of high purity by combining a primary product obtained or the secondary product obtained in the secondary film crystallization step with a certain ratio.

The raw material red ginseng concentrate of the present invention is a red ginseng concentrate marketed as a standard under the Ginseng Industry Act, or the applicant extracts and concentrates the raw red ginseng so that the applicant directly meets the standard under the Ginseng Industry Act. Red ginseng concentrate is selected, and the red ginseng concentrate marketed as the standard according to the ginseng industry law used as the raw red ginseng concentrate of the present invention has 11 ginsenosides content of 38.894mg / g, and has a solid content of 60wt%. The composition components are shown in the following [Table 3].

The alcohol used in the primary and secondary duranic crystallization steps according to the present invention uses a purity of 95% by weight, and in the primary duranic crystallization step, 10% by weight to 80% by weight of the raw red ginseng concentrate is mixed. In the second dural crystallization step, it consists of mixing at a ratio of 5% by weight to 25% by weight compared to the red ginseng concentrate.

The layer crystallization applied to the present invention generally uses Burton's Boundary Layer model as shown in FIG. 1 to analyze the behavior of impurities, and as shown in FIG. When crystals grow from the cold wall of the fire, the concentration of the red ginseng concentrate (melting system) controls the cooling temperature and the super saturation is exhausted.

The present invention is an improved film-forming crystallization technique that is particularly suitable for preparing red ginseng concentrates by quantifying a total amount of ginsenosides to a certain amount by controlling the high purity separation and purification of ginsenosides from raw red ginseng concentrates.

The present invention is a technology for separating and purifying total ginsenosides from red ginseng concentrates simply and efficiently, which is highly effective in lowering the production cost of products, and can enhance the specifications of red ginseng concentrate products through high purity ginsenosides. Red ginseng products can lead the world market.

In particular, it is possible to produce red ginseng concentrate products quantified to a desired amount of total ginsenosides of high purity, so that in the future pharmaceutical raw materials market, high quality and uniform products can be efficiently provided and included in red ginseng extract or concentrate Since it uses only physical properties such as melting point or solubility of ginsenosides, it does not use fillers as compared to the conventional column purification technology, and the amount of solvent used is at least 10 times less and the process time can be reduced at least 2 times. In addition, since it can be purified by a simple process using a solvent that is not toxic to the human body, it exhibits excellent efficiency and features.

FIG. 1 is a Burton Boundary Layer model diagram for analyzing the behavior of impurities in layer crystallization.
2 and 3 are schematic process diagrams and apparatus for separating and quantifying high purity ginsenosides according to the present invention.
Figure 4 is the resultant ginsenosides prepared in the present invention quantified by purity 98% by weight (A), purity 90% by weight (B), purity 50% by weight (C) and purity 5% by weight (D). HPLC data of red ginseng concentrate.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples and drawings, and the present invention is not limited by the following Examples and Test Examples.

In addition, the part and the unit of a percentage used by this invention are shown by weight unless there is particular notice.

First, referring to [FIG. 2] and [FIG. 3], the high-purity separation and purification method of red ginseng concentrate using dural crystallization according to the present invention and a manufacturing method of the red ginseng concentrate quantifying the total ginsenoside content of high purity are briefly described.

Raw red ginseng concentrates and spirits, which are commercially available red ginseng concentrates, are prepared in a double-jacket and are equipped with a stirrer (M) in the constant temperature batch mixing tank (1). The mixed mixture was introduced into the first dura-crystallizer (2) to induce the first dura-crystallization to obtain the first obtained product, and the alcohol was mixed again with the primary obtained to flow into the second d-film crystallizer (3). To induce secondary film crystallization to obtain a secondary product, which is a red ginseng concentrate containing high purity total ginsenosides.

In addition, the primary and secondary yields consisted of a double jacket and flowed into a constant temperature batch mixing tank (4) equipped with an agitator (M) while controlling the mixing at a constant rate to quantify the high purity total ginsenoside content. Prepared red ginseng concentrate.

The primary film crystallization unit and the secondary film crystallization unit are composed of multi-tube temperature control devices (2, 3), and film-crystallization is performed while controlling at a temperature of -21 ° C.

In addition, the alcohol-containing by-products separated and discharged from the primary and secondary products of the primary and secondary film crystallizers are introduced into the vacuum distillation unit 5 to recover and recycle the alcohol.

 Next, the high purity separation and purification method of the red ginseng concentrate using the dural crystallization according to the present invention and the preparation method of the red ginseng concentrate to quantify the high purity total ginsenoside content will be described in detail by Examples and Comparative Examples.

In the Examples and Comparative Examples of the present invention, the content analysis of ginsenosides Rg ₁ , Re, Rf, Rb ₁ , Rg ₂ , Rc, Rb ₂ , Rb ₃ , Rd, Rg ₃ and Rh ₂ is carried out in the pretreatment method of food processing. After the analysis samples were prepared according to the following, HPLC (High Performance Liquid Chromatography) equipped with UVD (Ultra Visible Detector) was analyzed by HPLC analysis conditions and content formulas as shown in [Table 4] and [Table 5].

In addition, the purity and yield of the obtained ginsenosides were calculated by the following [formula 1] and [formula 2].

[Equation 1]

[Calculation 2]

For reference to the raw red ginseng concentrate according to the present invention, Korean red ginseng concentrate produced in Korea is manufactured by batch extractor and concentrator using the raw material of red ginseng: 7: 3 ratio of ginseng as a raw material. When ginseng concentrate prepared by this method is based on 60% by weight of solids, the total ginsenoside content is present in the range of 4 ± 0.5% by weight, and the red ginseng concentrate of Daedong Korea Ginseng Co., Ltd. of the present invention also meets the above criteria. Raw materials are red ginseng concentrate, and the examples and comparative examples were carried out using the raw materials.

That is, the raw material red ginseng concentrate used in the examples and comparative examples of the present invention is suitable to meet the standards of the ginseng industry law from the raw material red ginseng (6 years old domestic) for manufacturing red ginseng concentrate prepared by Daedong Goryeo Co., Ltd. (applicant of the present invention). It is extracted and concentrated, and the composition ratio of ginsenoside is as shown in [Table 3] above. When the content of individual ginsenosides is expressed in weight%, Rg ₁ 0.496%, Re 0.664%, Rf 0.125%, Rb ₁ 1.31%, Rg ₂ 0.052%, Rc 0.4%, Rb ₂ 0.54%, Rb ₃ 0.1296%, Rd 0.24%, Rg ₃ 0.032% and Rh ₂ 0.0008%, the sum of the contents is 3.8894%, the solid content is Produced to meet the 60% by weight standard.

And, for the embodiment of the present invention is composed of a double jacket type glass material consisting of an inner diameter of 15cm, an outer diameter of 17cm, a height of 20cm, through the double jacket tube, a dura mater that can control the crystallization temperature of the refrigerant at a constant flow rate The crystallizer was used, and the temperature control device used was RW-1025G constant temperature freezing circulation device manufactured by JIOTECH Co., Ltd., which can be cooled down to -25 ℃. As a by-product recovery device, EYELA's SB-1200 model Rotary concentrator was used.

Example 1 Primary Film Crystallization Step

A purity of 95% by weight spirit (product of the company) was prepared by mixing 10% by weight with respect to 1 kg of the raw red ginseng concentrate, and then, it was put into a film-forming crystallizer. Next, the temperature of the film crystallizer was kept constant at -20 ° C. for 1 hour to obtain a crystal stuck to the wall surface of the film crystallizer. Under the same conditions as above, according to 20% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, 70% by weight and 80% by weight of the red ginseng concentrate in the raw material, it was carried out as experimental variables of dural crystallization. The results are shown in [Table 6] below.

As shown in [Table 6], in the mixing ratio of the raw red ginseng concentrate to 10% by weight to 80% by weight of the first dural crystallization experiments obtained, the total ginsenoside (11 species) purity of 8.5 weight It was found that the range and yield of% ~ 92% by weight can be obtained up to 1.5% by weight to 47% by weight. These results indicate that the phase behavior of the ginsenosides in the raw red ginseng concentrate easily forms a phase transition from the crystallizer wall to the solid phase, and also when the alcohol content is less than 10% by weight and more than 80% by weight. The purity was too low or the yield was too low to obtain the desired result.

Example 2 Secondary Film Crystallization Step

Each ginsenoside Rg ₁ 7.75%, Re 10.38%, Rf 1.96%, Rb ₁ 20.5%, Rg ₂ 0.88%, respectively, which is a result obtained when the alcohol content is 50% by weight based on the raw red ginseng concentrate in <Example 1> Rc 6.25%, Rb ₂ 8.5%, Rb ₃ 2.03%, Rd 3.75%, Rg ₃ 500 g of red ginseng concentrate having 0.5% and Rh ₂ 0.01% and the sum of the contents thereof were 62.51% was used as a raw material.

100 g of the red ginseng concentrate was prepared by mixing 95 wt. Thereafter, the temperature of the film crystallizer was kept constant at -20 ° C. for 1 hour to obtain a crystal that adhered to the wall surface of the film crystallizer.

 Under the same conditions as above, according to the mixing ratio of 10% by weight, 15% by weight, 20% by weight and 25% by weight of red ginseng concentrate as an experimental variable of dural crystallization, respectively, the results are shown in Table 7 below.

As shown in [Table 7], in the mixing ratio of alcohol to red ginseng concentrate in the range of 5% by weight to 25% by weight of the second dural crystallization experiment, the purity of the total ginsenoside (11 species) was 72% by weight ~ It was found that the yield can be obtained in a range of 98.4 wt% and a yield of 45.2 wt% to 86.8 wt%. From these results, it can be seen that by performing the second refilm crystallization of the first dura crystallized product, the total ginsenoside content can be easily obtained by a simple process up to 98%, and also when the alcohol content is less than 5% by weight. At 25 wt% or more, it was difficult to obtain the desired result because the purity was too low or the yield was too low in terms of the efficiency of refilm crystallization.

<Example 3> Preparation of red ginseng concentrate quantified high purity total ginsenoside content

On the basis of the obtained first and second film-forming crystallizations obtained from <Example 1> and <Example 2>, single or primary and secondary yields, i.e., two kinds of obtained products were blended at a constant ratio to obtain a solid content of 60. Total ginsenosides (11 species) in weight percent prepared red ginseng concentrate quantified from 5% to 95% by weight, respectively, the composition of the result is shown in [Table 8] below.

As shown in [Table 8], the red ginseng concentrate containing various ginsenosides of various contents could be prepared through primary and secondary dural crystallization. From these results, the total ginsenoside content could be easily controlled. Through this, red ginseng concentrate quantified in various forms, including the composition of total ginsenosides, could be more easily prepared.

 <Comparative Example>

In preparing high purity total ginsenoside from red ginseng concentrate, the same as the raw red ginseng concentrate used in <Example 1> was carried out in order to execute the production efficiency test by comparing the film-crystallization technique of the present invention and the separation and purification technique using a conventional column. As a raw red ginseng concentrate, dura-crystallization and column purification were performed according to the present invention.

a) dural crystallization according to the invention

100 g of red ginseng concentrate was prepared by mixing 95% by weight of ethanol at 50% by weight, and then, placed in the same film crystallizer as in <Example 1>, and kept at a constant temperature at -20 ° C for 1 hour, followed by film formation crystals. Obtain 6.4 g of the primary product adhering to the wall of the firearm, mix 95% by weight of alcohol with 15% by weight of ethanol with respect to 6.4 g of the first crystallization, and then put it into a film crystallization unit at -20 ° C. After keeping constant for a period of time, 4.1 g of a secondary product was obtained, which clinged to the wall of the dura-crystallizer.

The individual ginsenosides of the final product were Rg ₁ 12.18%, Re 16.32%, Rf 3.08%, Rb ₁ 32.21%, Rg ₂ 1.37%, Rc 9.82%, Rb ₂ 13.36%, Rb ₃ It had a content of 3.18%, Rd 5.89%, Rg ₃ 0.8% and Rh ₂ 0.02% and the sum of the contents was 98.21%.

 b) Separation and purification using existing column

10 g of purified water was prepared by mixing 25 g of the red ginseng concentrate, and 0.5 ml / sec of the prepared liquid in a column purifier filled with 210 g of filler (HP-20) in a glass tube material (4.9 cm in diameter and 60 cm in height). The total ginsenosides in the red ginseng concentrate are adsorbed to the filler. Then, in order to obtain the total ginsenosides adsorbed on the filler, 3.5 liters of 50 wt% alcohol was passed through the column purifier at 0.5 ml / sec to obtain a liquid passed therein, and then put into a rotary evaporator to evaporate both alcohol and purified water. To give 0.875 g of the final product.

The individual ginsenosides of the final product were Rg ₁ 12.19%, Re 16.32%, Rf 3.09%, Rb ₁ It had a content of 32.22%, Rg ₂ 1.39%, Rc 9.81%, Rb ₂ 13.36%, Rb ₃ 3.18%, Rd 5.91%, Rg ₃ 0.79%, Rh ₂ 0.02% and so on, and the sum of these contents was 98.28%.

Comparison results of the production efficiency from the experimental results of the film-crystallization technology and column purification technology according to the present invention is shown in Table 9 below.

As shown in [Table 9], in separating and purifying high purity total ginsenosides of 98% by weight or more from red ginseng concentrate, the film-crystallization technology according to the present invention is somewhat inferior in process efficiency in terms of process temperature compared to conventional column purification technology. It can be seen that the use of a full filler, solvent use ratio and yield compared to the raw material, the process time has a very high efficiency, the film-crystallization method according to the present invention is not only the process efficiency compared to the column purification technology, but also generally scale-up and process maintenance In terms of management, it can be confirmed that the technology is more efficient.

1, 4: constant temperature batch mixing tank of double jacket 2, 3: primary and secondary film crystallizers
5: vacuum distillation H: heater
M: Stirrer P: Pump
V: Valve

Claims (4)

a) a first dural crystallization step of mixing the raw red ginseng concentrate with 95% by weight of alcohol and then first duranic crystallization at -20 ° C;
b) from the red ginseng concentrate, which comprises a duranic crystallization step of mixing dextrose with a purity of 95% by weight with respect to the first obtained product obtained in the first duranic crystallization step, and then performing a second dural crystallization at -20 ° C. Method for separating and purifying total ginsenosides.
In the above, the total ginsenosides are Rg ₁ , Re, Rf, Rb ₁ , Rg ₂ , Rc, Rb ₂ , Rb ₃ , Rd, Rg ₃ and Rh ₂ . The method according to claim 1, wherein the mixing of the alcohol in the primary duranic crystallization step of 10% by weight to 80% by weight based on the raw red ginseng concentrate, and the mixing of the alcohol in the second dura crystallization step is 5% by weight to the raw red ginseng concentrate A method for separating and purifying ginsenosides from red ginseng concentrate, characterized in that blending at 25% by weight. The method for separating and purifying total ginsenosides from red ginseng concentrate according to claim 1 or 2, wherein the total ginsenoside purity is 72% by weight to 98.5% by weight. The total ginsenoside content according to claim 3, wherein the primary or obtained product obtained in the primary film-forming crystallization step and the secondary product obtained in the second film-forming crystallization step are combined to obtain a total ginsenoside content of 5% by weight, 10% by weight, and 15%. % By weight, 20% by weight, 25% by weight, 30% by weight, 35% by weight, 40% by weight, 45% by weight, 50% by weight, 55% by weight, 60% by weight, 65% by weight, 70% by weight, 75% by weight , 80% by weight, 85% by weight, 90% by weight and 95% by weight of the method for separating and purifying ginsenosides from the red ginseng concentrate, characterized in that quantified.

Images