CN1155591C

CN1155591C - Prepn of baicalin

Info

Publication number: CN1155591C
Application number: CNB021293724A
Authority: CN
Inventors: 车庆明
Original assignee: Individual
Current assignee: Individual
Priority date: 2002-09-06
Filing date: 2002-09-06
Publication date: 2004-06-30
Anticipated expiration: 2022-09-06
Also published as: CN1398862A

Abstract

The present invention relates to a baicalin preparing method which makes one or more than two kinds of mixed acid of sulphuric acid, hydrochloric acid, phosphoric acid, or nitric acid prepared into 3 to 20% of water solution; then, the water solution is mixed with baicalin; the mixture is heated and the refluxed; after suction filtration, baicalein with certain purity is obtained; according to the requirements, the baicalein can be further extracted with organic solvent, and the baicalein with high purity can be obtained. The baicalein with the purity larger than 98% can be obtained by the extraction method of the present invention; the method is simple, and provides a new path for the industrialized production of the baicalein.

Description

A kind of method for preparing scutellarin

Technical field

The invention belongs to the extracting method of Chinese medicine, more specifically saying so prepares the method for scutellarin from baicalin.

Background technology

The root of large-flowered skullcap is the dry root of labiate root of large-flowered skullcap Scutellaria baicalensis Georgi, has the effect of heat-clearing and damp-drying drug, eliminating fire and detoxication, arresting bleeding and miscarriage prevention clinically.Be used for damp-warm syndrome, the heat temperature evil of vomitting uncomfortable in chest, cough due to lung-heat, jaundice and other inflammation (one one 1995,270 of Chinese Pharmacopoeia).The main component of the root of large-flowered skullcap is baicalin (baicalin), wogonoside (wogonin-7-0-glucronide), scutellarin (baicalein) and wogonin (wogonin) (Zhou Ruzhen, the pharmacological research of the root of large-flowered skullcap, Chinese patent medicine, 1991,13 (1): 28-29).The modern pharmacology result of study shows: baicalin and scutellarin all can suppress immunodeficiency virus reversed transcriptive enzyme (HIV-1RT) and suppress HIV-1 in cell cultures, but scutellarin suppresses the HIV-1 activity and cytotoxicity all is better than baicalin (Zhao Jing etc., synthetic and the anti human immune deficiency virus activity research of baicalin derivative, Acta Pharmaceutica Sinica, 1998,339 (1): 22-27).Baicalin is difficult to directly be absorbed (foot bridge respectful one and the Chinese in digestive tube, medical magazine, 1998,15 (1): 1), and scutellarin absorbs comparatively fast, and bioavailability is better than baicalin (Y J zhou, Q M che, S X xul.Metabolites of Baincalein in Human Urine.pharmazie, 2000,55 (8): 626).Therefore scutellarin has good pharmaceutical use.But the content of scutellarin is lower in the baikal skullcap root, be about about 0.2% (Wang Muzou, the high phase liquid-phase chromatographic analysis of herbal medicine commonly used, Beijing Science Press, 1999,319), and content of baicalin is higher, is about 9%-14% (Wang Benxiang, modern Chinese herbal medicine pharmacology, Tianjin science and technology press, 1997,301-299), how baicalin is converted into scutellarin and has certain researching value. there is the bibliographical information baicalin to be difficult to be converted into scutellarin by the method for an one-step hydrolysis, also there is document baicalin to be converted into scutellarin with chemical process, but reaction conditions comparatively complicated (Zhao Jing etc., the preparation of baicaligenin and benzyl derivative thereof and anti human immune deficiency virus experimental study, Acta Pharmaceutica Sinica, 1997,32 (2): 140-143).

Summary of the invention

The objective of the invention is to overcome the deficiency of prior art, propose a kind of industrialized method preparing baicalein that simply is easy to.

The present invention produces the method for scutellarin, comprises following process;

1. be selected from a kind of, two or more mixing acid in sulfuric acid, hydrochloric acid, phosphoric acid or the nitric acid, water is made into the aqueous solution that concentration is 3-20%, and this concentration is meant the concentration sum that all are sour for mixing acid;

2. step (1) is mixed with the aqueous solution and the baicalin that acid is made into, described baicalin concentration is 1-15%, at 100 ℃ of following backflow 1-48 hours, and cooling back suction filtration, the gained throw out is the scutellarin that purity is 25-70%.

The purity that aforesaid method obtains is that the scutellarin of 25-70% can also further be purified with organic solvent, its method is: be scutellarin organic solvent extraction 2-3 time of 25-70% with purity, the 1-3 that each quantity of solvent is a scutellarin crude product amount doubly, getting organic solvent layer is concentrated into dried, ethyl alcohol recrystallization with 90%, obtain purity and be the scutellarin more than 98%, described organic solvent is selected from a kind of, two or more the mixture in acetone, ethyl acetate, propyl carbinol, ethanol, propyl alcohol, the Virahol.

Baicalin of the present invention is the commercially available prod.

Advantage of the present invention and effect

Method of the present invention can make the scutellarin that is converted into of baicalin larger proportion, can obtain purity and be the scutellarin more than 98%, and the method for bibliographical information only is about 20%; In addition, method of the present invention is simple, is easy to suitability for industrialized production.

Embodiment

Further specify characteristics of the present invention below by specific embodiment.

Example 1-9

The scutellarin that example 1-9 adopts method of the present invention to make.

Preparation process: it is 8-10% solution that the sulfuric acid water is made into concentration, then it is mixed with baicalin,, cool off the back suction filtration at last at 100 ℃ of following backflow 16-20 hours, the throw out of gained is the scutellarin product of required different purity, operational condition and the results are shown in Table 1.

Example 10

The process of this examples preparation scutellarin:

Get baicalin 3 grams, 100 ℃ of the hydrochloric acid soln 300ml heating with 7% refluxed 4 hours, filtered, and got filter residue and got product A, and scutellarin content is 33.15% in the product A.

Example 11

This example is that the scutellarin product is carried out structural analysis.

Get baicalin 3 gram, refluxed 18 hours with 9% sulphuric acid soln 300ml heating (100 ℃), put cold back suction filtration, acetone extraction 2-3 time of gained precipitation got the acetone layer and is concentrated into driedly, and the ethyl alcohol recrystallization with 90% gets product B.Product B is detected with mass spectrum, proton nmr spectra, carbon-13 nmr spectra: mass spectrum (EI-MS): m/z 271[M] ⁺Proton nmr spectra [' H-NMR (dmso-d ₆)]: 12.64 (1H, S, 5-OH), 10.55 (1H, 7-OH, S), 8.80 (1H, S, 6-OH), 8.04 (2H, d, J-6,0HZ, H-2 ', 6 '), 7.56 (3H, m, H-3 ', 4 ', 5 '), 6.92 (1H, d, J=2,0HZ, H-8), 6.61 (1H, d, J=2.OHZ, H-3); Carbon-13 nmr spectra ( ¹³C-NMR): (dmso-d ₆): 182.1 (C-4), 162.8 (C-7), 153.6 (C-2), 149.8 (C-9), 147.0 (C-5), 131.7 (C-1 '), 131.0 (C-6), 129.3 (C-4 '), 129.0 (C-2 ', 6 '), 126.2 (C-3 ', 5 '), 104.4 (C-10), 104.2 (C-3), 94.0 (C-8).These data and scutellarin standard substance data (Acta Pharmaceutica Sinica, 1997,32 (2): 140-143) unanimity, prove that product A is that scutellarin proves that promptly baicalin can obtain scutellarin by sulphuric acid hydrolysis, scutellarin content is 96.518%.

Example 12

The process of this examples preparation scutellarin:

Get baicalin 3 grams, refluxed 18 hours with 9% sulphuric acid soln 300ml heating (100 ℃), put cold back suction filtration, ethyl acetate extraction 2-3 time of gained precipitation, getting ethyl acetate layer is concentrated into dried, ethyl alcohol recrystallization with 90% gets product C, and its structure is identified identical with above-mentioned product product B, and the content of scutellarin reaches 98%.

Example 13

Sulfuric acid is made into the aqueous solution that concentration 5% and hydrochloric acid is made into concentration 5% to be mixed with 1: 1 volume ratio, get its 300ml and baicalin 3g mixing, 100 ℃ were refluxed 18 hours down, put cold back suction filtration, the gained precipitation is used ethyl acetate extraction 2-3 time, getting ethyl acetate layer is concentrated into dried, ethyl alcohol recrystallization with 90% gets product D, and its structure is identified identical with above-mentioned product B, and scutellarin content reaches 98%.

Table 1

Example	Baicalin concentration (%)	Heat-up time (hour)	Sulfuric acid concentration (%)	Scutellarin relative content (%)
Example	Baicalin concentration (%)	Heat-up time (hour)	Sulfuric acid concentration (%)	Scutellarin relative content (%)	1	1	16	8	45.8333
2	1	18	9	67.9682	1	1	16	8	45.8333
2	1	18	9	67.9682	3	1	20	10	66.1834
4	1.5	16	9	42.9022	3	1	20	10	66.1834
4	1.5	16	9	42.9022	5	1.5	18	10	40.2255
6	1.5	20	8	42.2451	5	1.5	18	10	40.2255
6	1.5	20	8	42.2451	7	2	16	10	28.2139
8	2	18	8	28.9932	7	2	16	10	28.2139
8	2	18	8	28.9932	9	2	20	9	25.0276

Annotate: on to show the result be three revision test mean values.

Claims

1. method of producing scutellarin is characterized in that preparation process is as follows:

(1) be selected from a kind of, two or more mixing acid in sulfuric acid, hydrochloric acid, phosphoric acid or the nitric acid, water is made into the aqueous solution that concentration is 3-20%, and this concentration is meant the concentration sum that all are sour for mixing acid;

(2) step (1) is mixed with the aqueous solution and the baicalin that acid is made into, described baicalin concentration is 1-15%, at 100 ℃ of following backflow 1-48 hours, and cooling back suction filtration, the gained throw out is the scutellarin that purity is 25-70%.

2. according to the method for claim 1, it is characterized in that with the purity that step (2) obtains be the scutellarin of 25-70%, with organic solvent extraction 2-3 time, getting solvent layer is concentrated into dried, ethyl alcohol recrystallization with 90%, obtain the scutellarin of purity more than 98%, described organic solvent is selected from a kind of, two or more the mixture in acetone, ethyl acetate, propyl carbinol, methyl alcohol, ethanol, the Virahol.