WO2015168962A1

WO2015168962A1 - Method for extracting chlorogenic acid from eucommia leaves

Info

Publication number: WO2015168962A1
Application number: PCT/CN2014/077651
Authority: WO
Inventors: 张洁; 张亮; 黄望
Original assignee: 四川九章生物化工科技发展有限公司
Priority date: 2014-05-05
Filing date: 2014-05-16
Publication date: 2015-11-12
Also published as: JP2017520616A; JP6473803B2; CN103992224B; CN103992224A

Abstract

Provided is a method for extracting chlorogenic acid from Eucommia leaves, comprising the following steps: a, weighing of Eucommia leaves; b, water extraction; c, pre-treatment; d, filtration; e, loading on a macroporous adsorbent resin; f, concentrating; g, drying: spray drying, an air inlet temperature being 150^oC - 200^oC, and an air outlet temperature being 50^oC - 90^oC, thereby obtaining a chlorogenic acid crude product. The present invention uses water extraction, pre-treatment, loading on a macroporous adsorbent resin column, concentrating and drying to prepare the chlorogenic acid crude product. A water extract liquid is not concentrated, and is directly loaded on the macroporous adsorbent resin for purification treatment after being pre-treated, thereby solving the problem of decomposition caused by chlorogenic acid being concentrated in water for a long time and heated unstably, at the same time as omitting a concentrating process link to shorten the production cycle. In addition, a crude product having 20-60% of various specifications may be produced by controlling concentration parameters of different eluents.

Description

Method for extracting chlorogenic acid from Eucommia ulmoides leaves

The present invention relates to a method for extracting chlorogenic acid from Eucommia ulmoides leaves.

Background technique

Chlorogenic acid is a phenolic acid composed of caffeic acid and Quinic acid, a synonymous coffee tannin, chemical name: 3-0-caffeoyl quinic acid (3) -0-Caffeoyl quinic acid), Molecular formula: C ₁₆ H ₁₈ 0 ₉ , Molecular weight: 354.30, is a phenylpropanoid compound produced by the shikimic acid pathway in plants during aerobic respiration. Chlorogenic acid is an important biologically active substance with antibacterial, antiviral, elevated white blood cells, liver and gallbladder, anti-tumor, blood pressure lowering, blood lipid lowering, free radical scavenging and excitatory central nervous system. It is one of the active ingredients of many Chinese herbal medicines, and it is also a quality indicator for some medicines. Chlorogenic acid is widely used, mainly in the pharmaceutical, household chemicals and food industries. The presence of chlorogenic acid in a variety of plants is quite common, but plants with higher levels are rare. Recent studies have shown that the chlorogenic acid content of Eucommia ulmoides leaves is rich, ranging from 1% to 5%. China's Eucommia ulmoides forest is widely planted, producing millions of tons of Eucommia leaves every year, which provides a sufficient raw material basis for the extraction of chlorogenic acid.

At present, there are many reports on the extraction of chlorogenic acid from Eucommia ulmoides leaves. The extraction methods of chlorogenic acid mainly include organic solvent extraction method, physical strengthening extraction method, ultra-high pressure extraction method and homogenization extraction method. Such as: Qian Qi, et al, extraction and separation of chlorogenic acid from Eucommia ulmoides Oliv., Chinese wild plant resources, Vol. 20, No. 4, which is to extract Eucommia ulmoides leaf powder with 70% ethanol (pH=2.5), 3 times at 90 °C , each time for half an hour, the ratio of material to liquid is 1:12, 1:10, 1:8. The extract is concentrated to a certain volume and loaded after pretreatment. At the same time, the adsorption, elution performance and adsorption kinetics of 17 macroporous adsorption resins on Eucommia chlorogenic acid were compared. Screening experiments showed that NKA-9 was an excellent adsorbent. Wang Wei, et al. Study on extraction and separation conditions of chlorogenic acid in Eucommia ulmoides leaves, Ion exchange and adsorption, 2008, 24(1): 73-80, studied the extraction and separation of chlorogenic acid from Eucommia ulmoides Oliv. The effects of water and different concentrations of ethanol, methanol and acetone aqueous solution as extraction solvents on the yield of chlorogenic acid were investigated. The main factors affecting the extraction rate of chlorogenic acid were analyzed by orthogonal experiment and separated by macroporous resin. . The results showed that the yield of chlorogenic acid was higher at 50 °C, and the yield was 1.06%, which determined the water as the extraction solvent of chlorogenic acid. The optimum conditions for the extraction of chlorogenic acid from Eucommia ulmoides Oliv. were as follows: temperature 60° C, ratio of material to liquid 1:16, pH4, extraction time 3h, the selected GC-I resin is the best adsorbent for adsorption and separation of chlorogenic acid, the optimal pH value of adsorption is 3, and the adsorption flow rate is 3BV/h; The crude product obtained under the experimental conditions had a purity of 30.88% and a yield of 76.51%. Miao Lei, extraction and purification of chlorogenic acid from Eucommia ulmoides leaves, Beijing University of Chemical Technology, June 6, 2011, disclosed the first extraction of chlorogenic acid from Eucommia ulmoides leaves with water, and the extract was passed through NKA-9. The macroporous resin is purified, and the solvent is distilled off to obtain a chlorogenic acid product; after the residue is dried, the cell wall is decomposed by lye extraction, and then the eucommia gum is extracted by hot reflux with petroleum ether, and the extract is obtained by a jelly method. Acetone is washed to obtain a milky white gel, which is a gutta-percha product. Li Guangfeng, Extraction and purification of chlorogenic acid from Eucommia ulmoides Oliv., Hunan Agricultural University, October 2006, 2. The stability of chlorogenic acid was studied. The results showed that chlorogenic acid was within 60 °C, 4-6h. More stable. It is easy to decompose under alkaline conditions, and is most stable under acidic conditions of pH=3. Chlorogenic acid is unstable under strong light irradiation. Therefore, it should be kept as acidic and protected from light in the extraction and separation of chlorogenic acid. . The extraction solvent and extraction method of chlorogenic acid showed that the extraction solvent water and heating extraction were better. After the orthogonal test, the four factors of temperature, time, solid-liquid ratio and particle size were investigated. The heating extraction process was optimized. The results showed that the temperature was 65 ° C, the extraction time was 60 min, the solid-liquid ratio was 1:25, and the particle size was 40 mesh is better. Study on the optimization conditions of column chromatography of chlorogenic acid. By comparing the adsorbent and eluent, the results show that KLFC-150, resin as adsorbent and ethanol as eluent are the best conditions. The method of separating chlorogenic acid has higher purity and yield. High, the purity reached 56.67%, and the yield was 78.37%.

Summary of the invention

The present invention provides a method for extracting chlorogenic acid from Eucommia ulmoides leaves.

The present invention provides a method for extracting chlorogenic acid from Eucommia ulmoides leaves, which comprises the following steps: a. Weighing Eucommia ulmoides leaves;

b, water extraction: water extraction, extraction temperature 40 ° C -80 ° C, extraction time 0. 5h-4. 0h, extraction times 1-3 times, each time the water consumption is 6-14 times the mass ratio of the drug, pH Values 2-7, leaching or dynamic extraction;

The phlegm is 0. 5h-24h _{; the} amount of the medicinal material is 0.2%-1.0%, the sedimentation temperature is 40 °C-80 °C, and the sedimentation time is 0. 5h-24h _;

d. Filtration: c The pretreatment liquid is filtered through a membrane or filter element with a pore size of 50 m-200 m;

e. Upper macroporous adsorption resin: d歩 The filtrate passes through the non-polar or weakly macroporous adsorption resin, the resin column diameter ratio is 1:4-1:10; the loading flow rate is 2.0-8.0BV/H, adsorption The amount is 1:1 - 1:5 for the mass of the medicinal material and the volume ratio of the column; the amount of washing is 0.5-2.0 BV, the flow rate of washing is 2.0-8.0 BV/H; the solvent is methanol or ethanol, and the concentration is 10-80%. , the elution amount is 1.0-6.0BV, and the elution flow rate is 2.0-8.0BV/H;

f; Concentration: Concentration temperature is 40 ° C -80 ° C, the degree of vacuum is -0. 04MP 0. 09MP, the relative density is 1. 02-1. 10;

g, dry: spray drying: air inlet temperature 150 ° C -200 ° C, air outlet temperature 50 ° C -90 ° C, that is, crude chlorogenic acid.

The crude chlorogenic acid is purified and purified to obtain pure chlorogenic acid.

Further preferably, it comprises the following steps: a, weighed Eucommia leaves;

b, water extraction: water extraction, extraction temperature 60 ° C -80 ° C, extraction time 0. 5h-1. 5h, extraction times 1-3 times, each time the water dosage is 10-14 times the mass ratio of the drug, pH Values of 6-7, leaching or dynamic extraction;

c, pretreatment: adding clarifying agent, the added amount is 0.4%-0.8% of the quality of the medicinal material, the sedimentation temperature is 50 °C -70 °C, the settling time is 1. Oh-2. Oh;

d. Filtration: c Pretreatment liquid is filtered through a filter or filter element with a pore size of 50 μ πΐ-100 μ πΐ;

e. Upper macroporous adsorption resin: d歩 The filtrate passes through the non-polar or weakly macroporous adsorption resin, the resin column diameter ratio is 1:4-1:8; the loading flow rate is 3.0-5.0BV/H, adsorption The amount is the ratio of the mass of the medicinal material to the column to volume ratio of 1:1 to 1:4; the amount of water to be washed is 1.0-2.0 BV, the flow rate of water washing is 3.0-5.0 BV/H; the type of eluting solvent is methanol or ethanol, and the concentration is 10-30%. , the elution amount is 4.0-6.0BV, and the elution flow rate is 2.0-4.0BV/H;

f. Concentration: Concentration temperature 50. C-70. C, the degree of vacuum is -0. 07 MP-0. 09MP, relative density is 1. 03-1. 05;

g, dry: spray drying: air inlet temperature 150 ° C -170 ° C, air outlet temperature 60 ° C -80 ° C, that is, crude chlorogenic acid.

Among them, the Eucommia ulmoides leaves described in a歩 contain 1.0-5.0% chlorogenic acid and 20% moisture content.

Wherein, the type of clarifying agent described in c is chitosan.

Wherein, the macroporous adsorption resin type described in e is a non-polar or weakly polar HPD-100, HPD-450, HPD-700, ΝΚΑ-Π, ΝΚΑ-9 or LS-46; preferably, The macroporous adsorption resin is HPD-100, HPD-450, or LS-46.

The invention adopts water extraction, pretreatment, large pore adsorption resin column, and concentrated drying to prepare crude chlorogenic acid. The water extract is pretreated and then directly subjected to macroporous adsorption resin for purification treatment to solve the problem that chlorogenic acid is decomposed due to long-term unstable heat in the water, and the concentration process is eliminated to shorten the production cycle. In addition, 20-60% of various specifications of crude products can be produced by controlling the concentration parameters of different eluents.

detailed description

Example 1 Method for extracting chlorogenic acid according to the present invention

1, extract

5, 合并倍。 Take eucommia leaves 10kg (chlorogenic acid content = 1.0%), with water, at 40 ° C for 3 times, each time 4. 0h, each time the amount of water is 60L, pH is 2.0, combined twice Extract.

2, pretreatment

0小时。 After taking the chitosan 100g, using a 1% aqueous solution of acetic acid to prepare a 2% chitosan aqueous solution, the extract was added to the mixture at 40 ° C, stirred and placed for 24. 0h. 3, filtering

The pretreated liquid was filtered through a 50 μm filter and the filtrate was collected.

4, the upper hole adsorption resin column

(1) Loading: Take macroporous adsorption resin HPD-100 wet packing to diameter ratio = 1 : 4 resin column, column volume is 50L, pretreatment liquid is loaded at 2.0BV / H flow rate;

(2) Washing: Washing with 0.5 BV of water at a flow rate of 2.0 BV/H;

(3) Elution: Elution was carried out with a 1.0 BV 80% methanol solution at a flow rate of 2.0 BV/H, and the eluate was collected;

5, concentrated

The eluate was recovered at a temperature of 40 ° C and a vacuum of -0.04 MP, and concentrated to a concentration of 1.02 (25 ° C).

6, spray drying

The concentrate was spray-dried, the inlet temperature was 200 ° C, and the outlet temperature was 90 ° C to obtain a crude chlorogenic acid.

7, product features

The crude chlorogenic acid obtained had a purity of 24.3%, a product yield of 3.2%, and a chlorogenic acid transfer rate of 77.8%. Example 2 Method for extracting chlorogenic acid according to the present invention

1, extract

Take 10kg of Eucommia ulmoides leaves (chlorogenic acid content = 3.6%), extract once with water at 80 °C, extract time 0.5h, water dosage 140L, pH 7.0, and combine two extracts.

2, pretreatment

20 g of chitosan was prepared, and 2% aqueous solution of chitosan was prepared by using 1% acetic acid aqueous solution, and the extract was added at 80 ° C, and stirred for 0.5 h.

3, filtering

The pretreated liquid was filtered through a 200 μm filter and the filtrate was collected.

(1) Loading: Take macroporous adsorption resin HPD-450 wet packing to diameter ratio = 1: 10 resin column, column volume is 10L, pretreatment liquid is loaded at 2.0BV/H flow rate;

(2) Washing: Wash with 2.0 BV of water at a flow rate of 2.0 BV/H;

(3) Elution: Elution was carried out with a 6.0 BV 10% ethanol solution at a flow rate of 2.0 BV/H, and the eluate was collected;

5, concentrated

The eluate was recovered at a temperature of 80 ° C and a vacuum of -0.09 MP, and concentrated to a concentration of 1.10 (25 ° C). 6, spray drying

The concentrate was spray-dried, the inlet temperature was 150 ° C, and the outlet temperature was 50 ° C to obtain crude chlorogenic acid.

7, product features

The obtained crude chlorogenic acid has a purity of 58.4%, a product yield of 4.8%, and a chlorogenic acid transfer rate of 77.9%. Example 3 The method for extracting chlorogenic acid of the present invention

1, extract

Take 10 kg of Eucommia ulmoides leaves (chlorogenic acid content = 5.0%), extract twice with water at 60 ° C for 1.5 h each time, use 80 L each time, pH 3.0, and combine the two extracts.

2, pretreatment

40 g of chitosan was taken and made into 2% chitosan aqueous solution with 1% acetic acid aqueous solution. The extract was added at 60 ° C, and the mixture was stirred for 12.0 h.

3, filtering

4, the upper hole adsorption resin column

(1) Loading: Take macroporous adsorption resin HPD-700 wet packing to diameter ratio = 1: 8 resin column, column volume is 20L, pretreatment liquid is loaded at 3.0BV / H flow rate;

(2) Washing: Washing with 1.0 BV of water at a flow rate of 3.0 BV/H;

(3) Elution: Elution was carried out with a 5.0 BV 20% ethanol solution at a flow rate of 3.0 BV/H, and the eluate was collected;

5, concentrated

The eluate was recovered at a temperature of 60 ° C and a vacuum of -0.08 MP, and concentrated to a concentration of 1.050 (25 ° C).

6, spray drying

The concentrate was spray-dried, the inlet temperature was 150 ° C, and the outlet temperature was 70 ° C to obtain a crude chlorogenic acid.

7, product features

The crude chlorogenic acid obtained was 52.4% pure, the product yield was 7.1%, and the chlorogenic acid transfer rate was 74.4%. Example 4 Method for extracting chlorogenic acid according to the present invention

1, extract

Take 10kg of Eucommia ulmoides leaves (chlorogenic acid content = 3.6%), extract twice with water at 60 ° C, each time

2. Oh, each time the amount of water is 100L, the pH is 4.0, and the two extracts are combined.

2, pretreatment 60 g of chitosan was taken and made into 2% chitosan aqueous solution with 1% acetic acid aqueous solution. The extract was added at 60 ° C, stirred uniformly and left for 8.0 h.

3, filtering

4, the upper hole adsorption resin column

(1) Loading: Take the macroporous adsorption resin ΝΚΑ-Π wet method to form the aspect ratio = 1: 8 resin column, the column volume is 40L, and the pretreatment liquid is loaded at the flow rate of 5.0BV/H;

(2) Washing: Washing with 2.0 BV of water at a flow rate of 5.0 BV/H;

(3) Elution: Elution was carried out with a 4.0 BV 30% ethanol solution at a flow rate of 4.0 BV/H, and the eluate was collected;

5, concentrated

The eluate was recovered at a temperature of 70 ° C and a vacuum of -0.08 MP, and concentrated to a concentration of 1.06 (25 ° C).

6, spray drying

The concentrate was spray-dried, the inlet temperature was 180 ° C, and the outlet temperature was 80 ° C to obtain crude chlorogenic acid.

7, product features

The crude chlorogenic acid obtained had a purity of 47.4%, a product yield of 5.6%, and a chlorogenic acid transfer rate of 73.7%. Example 5 Method for extracting chlorogenic acid according to the present invention

1, extract

Take 10 kg of Eucommia ulmoides leaves (chlorogenic acid content = 3.6%), extract 3 times with water at 40 ° C, each time 4. Oh, each time the water is 80L, the pH value is 3.0, and the two extracts are combined.

2, pretreatment

100 g of chitosan was taken and made into 2% chitosan aqueous solution with 1% acetic acid aqueous solution, and the extract was added at 40 ° C, and the mixture was stirred for 24.0 h.

3, filtering

The stock solution obtained by the pretreatment was filtered through a ΙΟΟμηη filter, and the filtrate was collected.

4, the upper hole adsorption resin column

(1) Loading: Take macroporous adsorption resin ΝΚΑ-9 wet packing into diameter ratio = 1: 10 resin column, column volume is 50L, pretreatment liquid is loaded at 8.0BV/H;

(2) Washing: Wash with 2.0 BV of water at a flow rate of 8.0 BV/H;

(3) Elution: Elution was carried out with a 6.0 BV 40% ethanol solution at a flow rate of 8.0 BV/H, and the eluate was collected;

5, concentrated The eluate was recovered at a temperature of 50 ° C and a vacuum of -0.06 MP, and concentrated to a concentration of 1.08 (25 ° C).

6, spray drying

The concentrate was spray-dried, the inlet temperature was 160 ° C, and the outlet temperature was 60 ° C to obtain crude chlorogenic acid.

7. Product characteristics The crude chlorogenic acid obtained was 45.8% pure, the product yield was 5.9%, and the chlorogenic acid transfer rate was 75.1%. Example 6 Method for extracting chlorogenic acid according to the present invention

1, extract

Take 10 kg of Eucommia ulmoides leaves (chlorogenic acid content = 3.6%), and extract twice with water at 60 ° C for 1.5 h each time. The amount of water used is 120 L and the value of 11 is 6.5. Two extracts are combined.

2, pretreatment

Take chitosan 80g, prepare 2% chitosan aqueous solution with 1% acetic acid water solution, add the extract at 60 °C, stir evenly and let it sit for 2.0h.

3, filtering

4, the upper hole adsorption resin column

(1) Loading: Take the macroporous adsorption resin NKA-9 wet packing to form the aspect ratio = 1: 10 resin column, the column volume is 40L, and the pretreatment liquid is loaded at the flow rate of 6.0BV/H;

(2) Washing: Washing with 1.0 BV of water at a flow rate of 6.0 BV/H;

(3) Elution: Elution was carried out with a 3.0 BV 50% ethanol solution at a flow rate of 3.0 BV/H, and the eluate was collected;

5, concentrated

The eluate was recovered at a temperature of 60 ° C and a vacuum of -0.08 MP, and concentrated to a concentration of 1.045 (25 ° C).

6, spray drying

The concentrate was spray-dried, the inlet temperature was 160 ° C, and the outlet temperature was 70 ° C to obtain a crude chlorogenic acid.

7, product features

The crude chlorogenic acid obtained had a purity of 41.6%, a product yield of 6.2%, and a chlorogenic acid transfer rate of 71.6%. Example 7 Method for extracting chlorogenic acid according to the present invention

1, extract Take 10 kg of Eucommia ulmoides leaves (chlorogenic acid content = 3.6%), extract twice with water at 70 ° C for 1.0 h each time, use 100 L of water each time, pH 7.0, and combine the two extracts.

2, pretreatment

60 g of chitosan was prepared, and 2% aqueous solution of chitosan was prepared by using 1% acetic acid aqueous solution, and the extract was added at 70 ° C, and the mixture was stirred for 2.0 h.

3, filtering

(1) Loading: Take the macroporous adsorption resin LS-46 wet packing to the aspect ratio = 1: 8 resin column, the column volume is 20L, and the pretreatment liquid is loaded at the flow rate of 5.0BV/H;

(2) Washing: Washing with 1.0 BV of water at a flow rate of 5.0 BV/H;

5, concentrated

6, spray drying

7, product features

The crude chlorogenic acid obtained had a purity of 55.8%, a product yield of 5.5%, and a chlorogenic acid transfer rate of 85.3%. Comparative Example 1 Method for extracting chlorogenic acid

1, extract

Take 10 kg of Eucommia ulmoides leaves (chlorogenic acid content = 3.6%), extract twice with water at 70 ° C for 1.0 h each time, use 100 L of water each time, pH 7.0, and combine the two extracts.

2, concentrated

The extract is concentrated to half of the stock solution at a temperature of 60 ° C and a vacuum of -0.08 MP;

3, pretreatment

Take 40g of chitosan, prepare 2% chitosan aqueous solution with 1% acetic acid water solution, add the extract at 60 °C, stir evenly and let stand for 2.0h.

4, filtering

5, the upper hole adsorption resin column

(1) Loading: Take the macroporous adsorption resin LS-46 wet packing column to the aspect ratio = 1: 8 resin column, column The volume is 20L, and the pretreatment liquid is loaded at a flow rate of 5. OBV/H;

(2) Washing: Washing with 1.0 BV of water at a flow rate of 5.0 BV/H;

6, concentrated

The eluate was recovered at a temperature of 60 ° C and a vacuum of -0.08 MP, and concentrated to a concentration of 1.03 (25 ° C).

7, spray drying

8, product features

The crude chlorogenic acid obtained had a purity of 44.6%, a product yield of 4.5%, and a chlorogenic acid transfer rate of 55.8%.

The invention adopts water as an extraction solvent, is directly clarified by chitosan, and is directly applied to a macroporous adsorption resin column, and is concentrated and dried after elution. The process is simple and operability is strong, and the concentration process of most processes before the upper column is omitted. Shorten the production cycle. It is possible to produce 20-60% of various specifications of crude products by controlling the concentration parameters of different eluents, and the chlorogenic acid transfer rate is relatively high, at 70-90%, wherein the conditions of Example 7 are optimal.

Claims

A method for extracting chlorogenic acid from Eucommia ulmoides leaves, comprising the following steps:

a, weighed Eucommia leaves;

e. Upper macroporous adsorption resin: d歩 The filtrate passes through the non-polar or weakly macroporous adsorption resin, the resin column diameter ratio is 1:4-1:10; the loading flow rate is 2.0-8.0BV/H, adsorption The amount is 1:1 - 1:5 for the mass of the medicinal material and the volume ratio of the column; the amount of washing is 0.5-2.0 BV, the flow rate of washing is 2.0-8.0 BV/H; the solvent is methanol or ethanol, and the concentration is 10-80%. , the elution amount is 1.0-6.0BV, the elution flow rate is 2.0-8.0BV/H; g, dry: the crude chlorogenic acid is obtained.

2. The extraction method according to claim 1, wherein: the concentration condition is: a concentration temperature of 40 ° C -80 ° C, a vacuum of -0. 04 MP-0. 09MP, relative The density is 1. 02-1. 10; g drying conditions are as follows: spray drying: air inlet temperature 150 ° C -200 ° C, air outlet temperature 50 ° C -90 ° C, that is, chlorogenic acid Crude.

3. The extraction method according to claim 1, characterized in that it comprises the following steps: a. Weighing the leaves of Eucommia;

e. Upper macroporous adsorption resin: d歩 The filtrate passes through non-polar or weakly polar macroporous adsorption resin, the resin column diameter ratio is 1:4-1:8; the loading flow rate is 3.0-5.0BV/H, The adsorption amount is 1:1 to 1:4 for the mass of the medicinal material and the volume ratio of the column; the amount of water to be washed is 1.0-2.0 BV, the flow rate of water washing is 3.0-5.0 BV/H; the type of eluting solvent is methanol or ethanol, and the concentration is 10-30. %, elution amount is 4.0-6.0BV, elution flow rate

2.0-4.0BV/H;

f. Concentration: Concentration temperature 50. C-70. C, the degree of vacuum is -0. 07 MP-0. 09MP, the relative density is 1. 03-1. 05;

The extraction method according to claim 1 or 2, wherein the eucalyptus leaves in the step a) contain 1.0% to 5.0% of chlorogenic acid.

The extraction method according to claim 1 or 2, wherein the clarifying agent type is chitosan.

6. The extraction method according to claim 1 or 2, wherein: the macroporous adsorption resin type described in the step is HPD-100, HPD-450, HPD-700, NKA-II, NKA-9 or LS-46; Preferably, the macroporous adsorption resin is HPD-100, HPD-450, or LS-46.