CN104418852A - Extracting method and application of high-purity coptisine - Google Patents

Abstract

The present invention relates to a method for extracting high-purity coptisine and its application. The technological process is as follows: raw material (coptidis or coptis root or coptis ash)—crushing (if it is coptis root or coptis ash does not need to be crushed)—add 0.1 Soaking in ~5% sulfuric acid—heating and extracting four times—filtering—calcium oxide (or calcium hydroxide) neutralization—filtering and washing the precipitate—preconcentration—precipitation and impurity removal—precipitation of coptisine—recrystallization of coptisine—precipitation and drying— Coptisine products. The content of coptis is more than 90%. The product of the invention has good functions of lowering blood fat, losing weight and lowering blood sugar, and is an ideal raw material for treating cardiovascular diseases, obesity and diabetes.

Description

A kind of extraction method and application of high-purity coptisine

technical field

The invention belongs to biological extraction technology, in particular to a high-purity coptisine extraction technology.

Background technique

Coptis chinensis was first recorded in "Shen Nong's Materia Medica" and listed as top grade. Coptis chinensis is bitter in taste, cold in nature, and has the functions of purging fire, detoxifying, clearing away heat, and drying dampness. For dysphoria, confusion, upset and insomnia, hot and humid fullness, vomiting, abdominal pain and diarrhea, conjunctival congestion and swelling, sore tongue, eczema, burns, vomiting blood, epistaxis, etc. The results of modern pharmaceutical research show that the main active ingredients of Coptis chinensis are Coptis chinensis alkaloids, mainly including berberine (berberine), palmatine, coptisine and epiberberine ("Chinese Pharmacopoeia" 2010 edition); It has a wide range of pharmacological activities such as lowering blood fat and blood sugar; recent studies have found that, in addition to berberine, other alkaloid active components of Coptidis Rhizome (coptisine, palmatine, etc.) also have the effect of lowering blood fat and blood sugar (Hou Hong et al. .An experimental study on Coptidis alkaloids against hyperlipidemia and atherosclerosis. Shizhen Chinese Medicine, 2011, 22 (10): 2462.); also found that high-purity Coptidis alkaloids are very safe, while Coptidis Crude alkaloids will cause safety problems such as increased liver function (Jun Yi etc. Safety evaluation of main alkaloids from Rhizoma Coptidis. Journal of Ethnopharmacology, 2013.145: 303-310). Extracting high-purity coptis alkaloids has better development value.

At present, there are many extraction techniques of berberine, and industrialized production has been realized; there are some patented techniques and literature reports on the extraction techniques of berberine.

Patent literature (20091019620.7) reports a method for extracting coptisine, which mainly includes: acid extraction of raw materials - acid extraction solution neutralization and precipitation removal - precipitation removal of berberine - solution alkalinity adjustment - chromatography column separation - precipitation crystallization - Drying of crystal products—products, the purity of coptisine in the obtained products can reach more than 90%. This technology needs to adjust the acidity of the feed liquid after neutralization and removal of impurities, and then put it on a chromatographic column for separation, then put it on a macroporous resin for purification, and finally elute with ethanol; Elution with ethanol after adsorption is costly.

Patent literature (200910311352.8) reports a method for the separation and purification of coptisine monomer, which mainly includes: extraction, concentration, extraction, dissolution and filtration, high-efficiency preparative liquid chromatography separation, product recovery and other steps. This technique utilizes high-performance liquid chromatography and is difficult to apply industrially.

The patent document (200810233362.X) reported a method for extracting Coptis chinensis alkaloids co-produced from Coptidis fibrous roots, mainly including: Coptidis fibrous roots—adding an appropriate amount of 0.05-1% sulfuric acid for soaking—neutralization and precipitation to remove impurities—above Cation separation column - step-by-step elution - decolorization by grouping - solvent recovery - step-by-step precipitation and crystallization - drying - jatrorrhizine monomer, berberine monomer, and coptis compound alkaloids. This patent proposes a process technology for the simultaneous extraction of berberine and jatrorrhizine two monomers, but does not mention the extraction and separation of coptisine.

The patent document (201010519053.6) reported a method for preparing coptisine based on the mixed alkaloids of Coptidis rhizome based on common structural characteristics, which mainly includes: converting the total alkaloids of Coptidis rhizome into coptisine by chemical reaction. This technology does not involve the extraction of berberine.

The patent literature (200510044345.8) reports a technology for extracting the total alkaloids of Coptis chinensis, but does not involve the extraction technology of Coptis alkaloid monomer.

The patent document (200810069671.8) reports a process technology for extracting the total alkaloids of Coptidis Rhizoma, but does not involve the extraction of Coptis alkaloid monomer.

The patent document (201110053453.7) reported a method for the separation and purification of Coptidis rhizome alkaloids using polyamide resin, which mainly includes: mixing the crude extract of Coptis chinensis with polyamide and then putting it on a polyamide column, eluting with dichloromethane or using dichloromethane Gradient elution with a mixed solvent of methanol, check the fractions by thin-layer chromatography, combine the same fractions, and dry to obtain berberine, palmatine, coptisine, African tetrandrine, jatrorrhizine, and magnolia Alkaline, Groenlandcine and other seven alkaloids. This process technology separates Coptis chinensis alkaloid monomer, because the separation and purification process involves very toxic solvents such as dichloromethane, so the safety is difficult to guarantee.

Li Feng et al. provided a method for extracting coptisine from Coptis chinensis: Coptis chinensis was extracted with 1% hydrochloric acid, and the acid extract was concentrated under reduced pressure to adjust the acidity and precipitate to remove impurities; the supernatant was added with 5% potassium iodide to precipitate the crude product of coptisine The crude base is dissolved by heating with chloroform and methanol (1:1), cooled and crystallized to obtain the second crude product of Coptis base; the secondary crude product is subjected to alumina column chromatography, and finally the pure product of Coptis base is obtained (Li Feng, Chemical Composition and Quality Standard of Coptidis Research. Master's degree thesis of Sichuan University, 2007); this process technology requires the use of expensive reagent potassium iodide, and at the same time needs to be separated on the column, the process is cumbersome; and the safety of chloroform recrystallization is not good, it is difficult to meet the needs of large-scale preparation.

Jiang Weizhe reported the method of "preparative chromatographic system for the separation of berberine from rhizome" and reported the method of using preparative liquid chromatography to separate and purify coptisine (Jiang Weizhe et al., preparative chromatography system for the separation of berberine from rhizome. Chinese herbal medicine, 2006 , 37(7): 1017); due to the use of preparative liquid chromatography, the equipment is expensive and the investment is large, which is also not conducive to the realization of industrial production.

To sum up, although there are some reports on the technology of extracting coptisine, either the technology is complex, expensive reagents are needed, or toxic raw materials are involved.

Contents of the invention

The present invention aims at these deficiencies and aims to provide a high-purity Coptisine extraction process, which uses Coptis and its by-products (including other raw materials containing Coptis) as raw materials to extract Coptis and Coptis fibrous root and Coptis ash in Coptis ash , the process technology is simple, does not need expensive reagents and toxic raw materials, and does not need to carry out chromatographic separation, and the product has high purity. The process technology of the present invention has not been reported yet.

The present invention uses Coptidis Rhizoma and Coptidis by-products as raw materials, adopts sulfuric acid solution to soak and extract to produce Coptisine, and the method comprises:

1) Raw material preparation

Coptis chinensis or Coptidis fibrous root or Coptis chinensis ash is removed from sediment, crushed or shredded (if it is Coptis chinensis fibrous root or Coptis chinensis ash does not need to be crushed or shredded), it is used as raw material for processing.

2), soaking

Put the raw materials into the soaking pool or extraction kettle, add an appropriate amount (3 to 15 times the volume), and a concentration of 0.1 to 5% sulfuric acid aqueous solution (W/V) to soak for 1 to 48 hours.

3), extract

After soaking, heat up to 20-100°C, heat-preserve and extract for 0.1-5 hours, and extract four times; the first and second extractions are used to produce products; the third extraction is used for the soaking solution of the next batch of raw materials, The soaking solution is directly used as the first extraction solution; the fourth extraction solution is used for the second extraction solution of the next batch of raw materials.

4), feed liquid neutralization

Combine the first and second extracts, filter; the filtrate is neutralized with lime (or calcium hydroxide) to pH=2-12, and filter; the residue is then washed with an appropriate amount (0.1-3 times the amount of residue) of water 1 to 3 times to recover the alkaloids taken away by the residue;

5), pre-concentration

After neutralization, the combined filtrate and washing liquid were concentrated under reduced pressure for 0-20 times (0 times means no concentration and directly used for subsequent processing).

6), impurity removal

Add 0.1-10% concentrated hydrochloric acid (V/V) and 0-10% sodium chloride (W/V) to the concentrated solution, and place it at a low temperature (0-30°C) for 1-100 hours; filter and add a small amount of water (precipitation amount 0.1 to 1 volume) wash the precipitate.

7) Production of crude Coptis chinensis

Combine the filtrate and washing liquid after removing impurities, add 0.1-10% concentrated sulfuric acid (V/V) and 1-20% sulfate (W/V), stir well, and place it at low temperature (0-30°C) for 1 ~100 hours; filter, wash the precipitate (coptisine) with 0.1 to 1 times the amount of precipitation, and obtain the crude product of coptisine. This step is the key of the present invention, and only by adopting this mixed precipitant system, can the coptisine be selectively extracted.

8) Coptisine recrystallization

The crude Coptis base is dissolved in 1 to 10 times the volume of solvent (water or methanol or ethanol), heated to dissolve, placed at a low temperature (0 to 30°C) for 1 to 100 hours to crystallize; filtered, 0.1 to 1 times the amount of precipitated solvent to wash the precipitate (Coptis chinensis Alkaline) to obtain the finished product of Coptis base.

9), drying

Coptisine is dried at 60°C, which is a high-purity Coptisine product.

The content of coptisine obtained by the above method is more than 50%, preferably more than 90%, and can be used in drugs for lowering blood fat or treating obesity.

The following is a comparative experiment about coptisine in terms of safety and treatment of related diseases:

①. Subchronic toxicity test

The test materials are Coptisine 1 (content 90%), Coptisine 2 (content 50%) and crude Coptisine (content 40%) prepared according to the method of the present invention.

The subchronic toxicity test method was carried out in accordance with the "Guiding Principles for New Drug Research of Natural Medicines (Traditional Chinese Medicine)": SD rats were divided into four groups, namely the normal control group, Coptisine 1 (content 90%), Coptisine 2 (content 50%) ), Coptisine crude product (content 40%), 10 rats in each group, the dosage was 1g/Kg; fed continuously for 3 months, and then collected fasting blood to monitor biochemical indicators such as liver function.

Table 1. The influence of the purity of coptisine on the liver function of rats

As can be seen from the table, compared with the normal control group, Coptisine 1 and Coptisine 2 have no effect on liver function; the liver function of rats in the Coptisine crude product group is significantly increased, indicating that low-purity Coptisine has no effect on the liver function of animals. have adverse effects. This result is similar to that reported in the literature (Jun Yi etc. Safety evaluation of main alkaloids from Rhizoma Coptidis. Journal of Ethnopharmacology, 2013.145: 303-310).

②, blood lipid-lowering activity experiment

The test materials are Coptisine 1 (content 90%), Coptisine 2 (content 50%) and crude Coptisine (content 40%) prepared by the method of the present invention.

The blood lipid-lowering experiment method was carried out in accordance with the "Guiding Principles for New Drug Research of Natural Medicines (Traditional Chinese Medicine)": the golden hamsters were divided into 5 groups, one group (10) was given normal feed, and the other group (40) was given high-fat feed; 4 weeks Finally, the blood lipid index was detected, and the golden hamsters successfully modeled were divided into 3 groups (8 to 10 in each group): high-fat control group, coptisine 1 (content 90%), coptisine 2 (content 50%) , Coptisine crude product (content 40%). The drug group was given 500mg/Kg drug; continuous gavage for 4 weeks, and then fasting blood was collected to detect blood lipid indicators.

Table 2. Comparison of blood lipid-lowering effects of total alkaloids of Coptis chinensis

It can be seen from the table that compared with the normal control group, blood lipids in each test group increased, indicating that the modeling was successful; compared with the high-fat group, cholesterol (TC) in each drug group decreased, indicating that there was Blood lipid-lowering activity; Among them, Coptisine 1 has the best hypolipidemic activity, which is better than Coptisine 2 and Coptisine crude product; Coptisine 2 has a blood lipid-lowering activity better than Coptisine crude product.

③ Weight loss experiment

The test materials are Coptisine 1 (content 90%), Coptisine 2 (content 50%) and crude Coptisine (content 40%) prepared by the method of the present invention.

The weight loss experiment method was carried out in accordance with the "Guiding Principles for New Drug Research of Natural Medicines (Traditional Chinese Medicine)": the golden hamsters were divided into 5 groups, one group (10) was given normal feed, one group was given high-fat feed (positive control), and the other three groups Give high-fat feed respectively and at the same time give coptisine 1 (content 90%), coptisine 2 (content 50%), crude product of coptisine (content 40%); after 1 month, monitor the body weight of four groups of mice, 2 Monitor the body weight of the mice one month later.

Table 3. The effect of total alkaloids of Coptis chinensis on the body weight of golden hamsters

As can be seen from the table, compared with the normal control group, the body weight of the high-fat diet group increased significantly; The body weight of the rats in the drug group 1 decreased significantly (close to the normal group), the body weight of the coptisine 2 also decreased significantly, and the body weight of the rats in the crude drug group of coptisine also decreased but not obviously. Relevant results show that coptisine can obviously control the adverse effect of high-fat feed on the weight gain of mice, and has a better weight-loss effect.

The above research results show that the development and utilization value of high-purity Coptisine is significantly better than low-purity Coptisine in terms of safety and efficacy (lowering blood fat and weight loss).

The present invention has the following advantages:

①. The process technology of the present invention uses Coptis chinensis and its by-products as raw materials, especially by-products such as Coptis chinensis fibrous root and Coptis chinensis ash as raw materials, belongs to the scope of comprehensive utilization of resources, and the product cost is low.

②. The extract solution is neutralized with sulfuric acid by lime (or calcium hydroxide), and the impurities in the extract solution are removed by calcium sulfate adsorption. Compared with other impurity removal and purification processes, this process is simple in operation and low in cost.

③. Using mixed precipitant (sulfuric acid and sulfate) to selectively precipitate coptisine, and then recrystallize to obtain pure coptisine. The process technology is simple, the cost is low, the yield of coptisine is high, and the purity can reach more than 90%, which is safe. excellent.

④, the whole process is simple and practical, the cost of industrial production is greatly reduced, and the production efficiency is significantly improved.

⑤. Coptisine obtained by the present invention has ideal effects of lowering blood fat, losing weight and lowering blood sugar. The product Coptisine of the present invention can be used to treat hyperlipidemia, obesity, cardiovascular diseases, diabetes and the like.

Detailed ways

The present invention is specifically described by the following examples. It is necessary to point out that this example is only used to further illustrate the present invention, and cannot be interpreted as limiting the protection scope of the present invention. Those skilled in the art can according to the above-mentioned present invention The content of the invention makes some non-essential improvements and adjustments.

Example 1:

1 kg of Coptidis Rhizome is crushed or sliced, added with 3 liters of 5% sulfuric acid solution, soaked for 1 hour, heated to 100°C for reflux extraction for 0.1 hour, filtered; the residue is extracted four times with 3 liters of 5% sulfuric acid solution raised to 100°C; Combine the first and second extracts (three extractions and four extractions are used for the processing of the next batch of raw materials), and separate the supernatant after cooling (or filter to obtain the supernatant); the supernatant is made of lime (oxidized Calcium) neutralized to pH=2, filtered, the precipitate was washed 3 times with 0.1 times the precipitation amount of water; combined the filtrate and washing liquid, added 10% concentrated hydrochloric acid, placed at low temperature (0°C) for 100 hours, filtered to remove impurities, and precipitated Wash with 0.1 times the volume of the precipitated water; combine the filtrate and washing liquid, add 0.1% concentrated sulfuric acid (V/V) and 20% ammonium sulfate (W/V), stir well, place at 0°C for 1 hour, and filter , the precipitate was washed with 1 times the volume of water; the precipitate was dissolved in 10 times the volume of water, heated and dissolved, placed at 30°C for 100 hours, filtered, and the precipitate was washed with 0.1 times the volume of water; the precipitate was dried at 50-70°C to obtain product. High-performance liquid chromatography (HPLC) analyzed and monitored the content of coptisine in the product to be 90%, and the yield of coptisine was 91%.

Example 2

Grind or slice 1 kg of Coptis chinensis, add 15 liters of 0.1% sulfuric acid solution, soak for 48 hours, heat up to 20°C and extract for 5 hours, filter; then use 15 liters of 0.1% sulfuric acid solution for heat preservation and extraction four times; combine the first The first and second extractions (three extractions and four extractions are used for the processing of the next batch of raw materials), and the supernatant is separated after cooling (or filtered to obtain the supernatant); the supernatant is used in lime (calcium oxide) and to pH=12, filter, and wash the precipitate once with 3 times the precipitation amount of water; combine the filtrate and washing liquid, and concentrate 20 times under reduced pressure; add 0.1% concentrated hydrochloric acid and 10% sodium chloride, ) to stand for 1 hour, filter to remove impurities, and wash the precipitate with 1 times the volume of the precipitate; combine the filtrate and washing liquid, add 10% concentrated sulfuric acid (V/V) and 1% sodium sulfate (W/V), and stir well Afterwards, place at 30°C for 100 hours, filter, and wash the precipitate with 0.1 times the volume of water; Dry at 50-70°C to get the product. High performance liquid chromatography (HPLC) analyzed and monitored the content of coptisine in the product to be 91%, and the yield of coptisine was 90%.

Example 3

Grind or slice 1 kg of Coptis chinensis, add 8 liters of 3% sulfuric acid solution, soak for 12 hours, heat up to 70°C and extract for 2 hours, and filter; the residue is extracted four times with 8 liters of 3% sulfuric acid solution; combine the first The first and second extractions (three extractions and four extractions are used for the processing of the next batch of raw materials), and the supernatant is separated after cooling (or filtered to obtain the supernatant); the supernatant is used in lime (calcium oxide) and to pH=6, filter, and wash the precipitate twice with water of 1 times the amount of precipitation; combine the filtrate and washing liquid, concentrate under reduced pressure 6 times; add 5% concentrated hydrochloric acid and 5% sodium chloride, ) for 24 hours, filtered to remove impurities, and the precipitate was washed with 0.5 times the volume of the precipitated water; the filtrate and washing liquid were combined, 2% concentrated sulfuric acid (V/V) and 16% potassium sulfate (W/V) were added, and fully stirred Afterwards, place at 10°C for 24 hours, filter, and wash the precipitate with 0.5 times the volume of water; Dry at 50-70°C to get the product. High performance liquid chromatography (HPLC) analyzed and monitored the content of coptisine in the product to be 96%, and the yield of coptisine was 95%.

Example 4

Grind or slice 1 kg of Coptis chinensis, add 8 liters of 3% sulfuric acid solution, soak for 12 hours, heat up to 70°C and extract for 2 hours, and filter; the residue is extracted four times with 8 liters of 3% sulfuric acid solution; combine the first The first and second extractions (three extractions and four extractions are used for the processing of the next batch of raw materials), and the supernatant is separated after cooling (or filtered to obtain the supernatant); the supernatant is used in lime (calcium oxide) and to pH=6, filter, and wash the precipitate twice with water of 1 times the amount of precipitation; combine the filtrate and washing liquid, concentrate under reduced pressure 6 times; add 5% concentrated hydrochloric acid and 5% sodium chloride, ) for 24 hours, filtered to remove impurities, and the precipitate was washed with 0.5 times the volume of the precipitated water; the filtrate and washing liquid were combined, 5% concentrated sulfuric acid (V/V) and 4% zinc sulfate (W/V) were added, and fully stirred Afterwards, place at 10°C for 24 hours, filter, and wash the precipitate with 0.5 times the volume of water; Dry at 50-70°C to get the product. High-performance liquid chromatography (HPLC) analyzed and monitored the content of coptisine in the product to be 96%, and the yield of coptisine was 96%.

Example 5

Grind or slice 1 kg of Coptis chinensis, add 8 liters of 3% sulfuric acid solution, soak for 12 hours, heat up to 70°C and extract for 2 hours, and filter; the residue is extracted four times with 8 liters of 3% sulfuric acid solution; combine the first The first and second extractions (three extractions and four extractions are used for the processing of the next batch of raw materials), and the supernatant is separated after cooling (or filtered to obtain the supernatant); the supernatant is used in lime (calcium oxide) and to pH=6, filter, and wash the precipitate twice with water of 1 times the amount of precipitation; combine the filtrate and washing liquid, concentrate under reduced pressure 6 times; add 5% concentrated hydrochloric acid and 5% sodium chloride, ) for 24 hours, filtered to remove impurities, and the precipitate was washed with 0.5 times the volume of the precipitated water; the filtrate and washing liquid were combined, 3% concentrated sulfuric acid (V/V) and 12% ammonium sulfate (W/V) were added, and fully stirred Afterwards, place at 10°C for 24 hours, filter, and wash the precipitate with 0.5 times the volume of water; Dry at 50-70°C to get the product. High-performance liquid chromatography (HPLC) analyzed and monitored the content of coptisine in the product to be 98%, and the yield of coptisine was 96%.

Comparative Example 6

Grind or slice 1 kg of Coptis chinensis, add 8 liters of 3% sulfuric acid solution, soak for 12 hours, heat up to 70°C and extract for 2 hours, and filter; the residue is extracted four times with 8 liters of 3% sulfuric acid solution; combine the first The first and second extractions (three extractions and four extractions are used for the processing of the next batch of raw materials), and the supernatant is separated after cooling (or filtered to obtain the supernatant); the supernatant is used in lime (calcium oxide) and to pH=6, filter, and wash the precipitate twice with water of 1 times the amount of precipitation; combine the filtrate and washing liquid, concentrate under reduced pressure 6 times; add 5% concentrated hydrochloric acid and 5% sodium chloride, ) for 24 hours, filtered to remove impurities, and the precipitate was washed with 0.5 times the volume of the precipitated water; the filtrate and washing liquid were combined, 3% concentrated hydrochloric acid (V/V) and 12% ammonium sulfate (W/V) were added, and fully stirred Afterwards, place at 10°C for 24 hours, filter, and wash the precipitate with 0.5 times the volume of water; Dry at 50-70°C to get the product. High-performance liquid chromatography (HPLC) analyzed and monitored the content of coptisine in the product to be 45%, and the yield of coptisine was 91%.

Comparative Example 7

Grind or slice 1 kg of Coptis chinensis, add 8 liters of 3% sulfuric acid solution, soak for 12 hours, heat up to 70°C and extract for 2 hours, and filter; the residue is extracted four times with 8 liters of 3% sulfuric acid solution; combine the first The first and second extractions (three extractions and four extractions are used for the processing of the next batch of raw materials), and the supernatant is separated after cooling (or filtered to obtain the supernatant); the supernatant is used in lime (calcium oxide) and to pH=6, filter, and wash the precipitate twice with water of 1 times the amount of precipitation; combine the filtrate and washing liquid, concentrate under reduced pressure 6 times; add 5% concentrated hydrochloric acid and 5% sodium chloride, ) for 24 hours, filtered to remove impurities, and the precipitate was washed with 0.5 times the volume of the precipitated water; the filtrate and washing liquid were combined, 3% concentrated phosphoric acid (V/V) and 12% ammonium sulfate (W/V) were added, and fully stirred Afterwards, place at 10°C for 24 hours, filter, and wash the precipitate with 0.5 times the volume of water; Dry at 50-70°C to get the product. High-performance liquid chromatography (HPLC) analyzed and monitored the content of coptisine in the product to be 43%, and the yield of coptisine was 85%.

Comparative Example 8

Grind or slice 1 kg of Coptis chinensis, add 8 liters of 3% sulfuric acid solution, soak for 12 hours, heat up to 70°C and extract for 2 hours, and filter; the residue is extracted four times with 8 liters of 3% sulfuric acid solution; combine the first The first and second extractions (three extractions and four extractions are used for the processing of the next batch of raw materials), and the supernatant is separated after cooling (or filtered to obtain the supernatant); the supernatant is used in lime (calcium oxide) and to pH=6, filter, and wash the precipitate twice with water of 1 times the amount of precipitation; combine the filtrate and washing liquid, concentrate under reduced pressure 6 times; add 5% concentrated hydrochloric acid and 5% sodium chloride, ) for 24 hours, filtered to remove impurities, and the precipitate was washed with 0.5 times the volume of the precipitated water; the filtrate and washing liquid were combined, 3% concentrated nitric acid (V/V) and 12% ammonium sulfate (W/V) were added, and fully stirred Afterwards, place at 10°C for 24 hours, filter, and wash the precipitate with 0.5 times the volume of water; Dry at 50-70°C to get the product. High-performance liquid chromatography (HPLC) analyzed and monitored the content of coptisine in the product to be 32%, and the yield of coptisine was 68%.

As can be seen from the above comparative examples, under the premise that other process conditions remain unchanged, only the mixed solution of concentrated hydrochloric acid and sulfate can carry out selective precipitation to the filtrate and washing liquid after impurity removal, so that the final product obtained The content of coptis and the yield of coptis are much higher than those of other mixed solutions.

Claims (10)

1. an extracting method for high purity coptisine, with the coptis and coptis plant for raw material, adopt sulphuric acid soln soak extraction production high purity coptisine, described method comprises:

1), raw material prepares

The coptis or coptis fibrous root or coptis lime-ash are removed silt, pulverizes or chopping;

2), soak

Add aqueous sulfuric acid in the feed to soak;

3), extract

After immersion, extract more than twice;

4), feed liquid neutralization

To merge with second time extracting solution first time, filter; Filtrate lime or calcium hydroxide neutralize pH=2 ~ 12 of solution, filter; Residue uses appropriate water washing again; , reclaim the alkaloid that residue is taken away, obtain washing lotion; Merge washing lotion and filtrate, for subsequent disposal;

5), removal of impurities

Add concentrated hydrochloric acid and the sodium-chlor of liquor capacity than 0 ~ 10% according to 0.1 ~ 10% of filtrate volume, place 1 ~ 100 hour at low temperature 0 ~ 30 DEG C; Filter, then use appropriate water washing; Merge washing lotion and filtrate, for subsequent disposal;

6), coptisine crude product is produced

Add the vitriol of the vitriol oil and 1 ~ 20% (W/V) of 0.1 ~ 10% according to liquor capacity, after filling stirring, low temperature 0 ~ 30 DEG C is placed 1 ~ 100 hour; Filter, wash precipitation with water, obtain coptisine crude product;

7), coptisine recrystallization

Coptisine crude product is dissolved in 1 ~ 10 times of volume of solvent, rising temperature for dissolving, and low temperature 0 ~ 30 DEG C places crystallization 1 ~ 100 hour; Filter, 0.1 ~ 1 times of precipitation capacity solvent wash precipitation, obtains coptisine finished product;

8), dry

Coptisine finished product is dried at 60 DEG C, is high purity coptisine product, the content more than 90% of coptisine.

2. according to claim 1ly extract high purity coptisine with the coptis and coptis plant for raw material, it is characterized in that the ratio of the interpolation vitriol oil that described step 6) is more optimized and vitriol is 2 ~ 5%(V/V) the vitriol of the vitriol oil and 4 ~ 16% (W/V).

3. according to claim 1 and 2ly extract high purity coptisine with the coptis and coptis plant for raw material, it is characterized in that described vitriol refers to the water soluble salts such as ammonium sulfate, sodium sulfate, potassium sulfate, magnesium sulfate, zinc sulfate.

4. according to claim 1 and 2ly extract high purity coptisine with the coptis and coptis plant for raw material, it is characterized in that described step 7) coptisine crude product recrystallization solvent is water or methyl alcohol or ethanol; Step 2) soak 3 ~ 15 times of volumes that the consumption of aqueous sulfuric acid adopted is raw material, the concentration of aqueous sulfuric acid is 0.1 ~ 5%, and soak time is 1 ~ 48 hour; The extraction of step 3) is incubated extraction 0.1 ~ 5 hour after being warmed up to 20 ~ 100 DEG C.

5. according to claim 1 and 2 with the coptis and coptis plant for raw material extracts high purity coptisine, what it is characterized in that step 3) is extracted as four times, and first time and second time extracting solution are for the production of product; Third time, extracting solution was used for the soak solution of next batch raw material, and soak solution is directly as primary extracting solution; No. the 4th extracting solution is used for the second time extracting solution of next batch raw material.

6. according to claim 1 and 2 with the coptis and coptis plant for raw material extracts high purity coptisine, it is characterized in that to merge the filtrate of step 4) and washing lotion and then carry out pre-concentration, concentrating under reduced pressure 1 ~ 20 times, concentrated solution carries out the 5th again) process of step.

7. the application of high purity coptisine in the medicine being used as reducing blood-fat or treatment obesity, described high purity coptisine refers to that coptisine content is the coptisine of more than 50%.

8. the application of high purity coptisine in the medicine being used as reducing blood-fat or treatment obesity, described high purity coptisine refers to that coptisine content is the coptisine of more than 90%.

9. the application of high purity coptisine in the medicine being used as reducing blood-fat or treatment obesity, described high purity coptisine refers to that the coptisine content adopting the method described in claim 1-6 to prepare is the coptisine of more than 50%.

10. the application of high purity coptisine in the medicine being used as reducing blood-fat or treatment obesity, described high purity coptisine refers to that the coptisine content adopting the method described in claim 1-6 to prepare is the coptisine of more than 90%.