CN108947778B - Method for separating magnolia bark extract by introducing intermediate - Google Patents
Method for separating magnolia bark extract by introducing intermediate Download PDFInfo
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- C—CHEMISTRY; METALLURGY
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- C—CHEMISTRY; METALLURGY
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- C07C37/70—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment
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Abstract
The invention provides a method for separating a magnolia officinalis extract by introducing an intermediate, which comprises the following steps: adding dried 2, 2-dimethoxypropane into the crude extract of Magnolia officinalis, stirring to dissolve, adding acidic catalyst under anhydrous condition, reacting to obtain magnolol intermediate, removing catalyst after reaction, adding alkali solution, adding organic solvent, extracting to obtain oil phase and alkaline water phase, recovering water phase to obtain honokiol, and recovering oil phase for further treatment to obtain magnolol; the acid catalyst is selected from one of concentrated sulfuric acid, fuming sulfuric acid or hydrochloric acid gas. After the catalyst used in the prior art is changed, the same result can be achieved only by 1.5-2h under the condition that other conditions are not changed, and the working efficiency is greatly improved. The total yield is more than 80%, and the obtained magnolol and honokiol have high purity.
Description
Technical Field
The invention relates to the technical field of traditional Chinese medicines, in particular to a method for separating a magnolia officinalis extract by introducing an intermediate.
Background
Magnolia officinalis, which is known as Magnolia officinalis, Magnolia officinalis and Magnolia officinalis in the botanical field, is a plant of Magnoliaceae and Magnoliaceae, usually Magnolia officinalis (original subspecies) and Magnolia officinalis (subspecies), and is produced mainly in Sichuan and Hubei provinces. The Chinese medicinal materials refer to dried bark, root bark and branch bark of the plant.
Magnolia officinalis is pungent in flavor and warm in nature, and has effects of activating qi-flowing, eliminating dampness, warming middle-jiao, relieving pain, lowering adverse qi, and relieving asthma. The Magnolia officinalis decoction has strong antibacterial effect on Staphylococcus, Streptococcus, Bacillus dysenteriae, Pasteurella and Vibrio cholerae; but also has a certain relieving effect on striated muscle stiffness. Bark, root bark, flower, seed and bud can be used as the medicine, bark is the main part of the famous traditional Chinese medicine, and the medicine has the effects of resolving dampness and removing stagnancy, promoting qi circulation and relieving asthma, resolving food and eliminating phlegm, and dispelling pathogenic wind and easing pain; the seeds have the effects of improving eyesight and benefiting qi, and can be used as gynecological medicines.
The main components of cortex Magnolia officinalis are magnolol and honokiol, wherein honokiol is isomer of magnolol, and has wide pharmacological actions of resisting bacteria, resisting inflammation, resisting tumor, relaxing muscle, reducing cholesterol and resisting aging.
In the prior art, the extraction process of magnolia officinalis is multiple, but the separation of magnolol and honokiol in the extract of magnolia officinalis becomes a big difficulty, and the efficiency of obtaining the magnolol is very low. There is also literature on the isolation of two magnolols by introducing intermediates, with reaction times of 24h or 48 h. Moreover, the separation process adopts high-purity mangnolia officinalis bisphenol, the highest yield of the method is only about 60%, and the working efficiency is low.
In view of the above, the present invention is particularly proposed.
Disclosure of Invention
The invention aims to provide a method for separating magnolia officinalis extract by introducing an intermediate, wherein the separation method takes crude extract with the magnolia officinalis bisphenol content of less than 50 percent as a raw material, and adds an acid catalyst, so that the reaction time is shortened, the working efficiency is improved, the yield is improved, and the total yield is over 80 percent.
In order to achieve the above purpose of the present invention, the following technical solutions are adopted:
a method for separating cortex Magnolia officinalis extract by introducing intermediate comprises the following steps:
adding dried 2, 2-dimethoxypropane into the crude extract of Magnolia officinalis, stirring to dissolve, adding acidic catalyst under anhydrous condition, reacting to obtain magnolol intermediate, removing catalyst after reaction, adding alkali solution, adding organic solvent, extracting to obtain oil phase and alkaline water phase, recovering water phase to obtain honokiol, and recovering oil phase for further treatment to obtain magnolol;
the acid catalyst is selected from one of concentrated sulfuric acid, fuming sulfuric acid or hydrochloric acid gas;
preferably, the mass ratio of the 2, 2-dimethoxypropane to the crude extract of the magnolia officinalis is (3-4): 1, more preferably (3.3-3.4): 1;
preferably, the molar ratio of the acidic catalyst to the 2, 2-dimethoxypropane is 1 (50-200), more preferably 1: 100.
Preferably, the preparation method of the crude extract of magnolia officinalis specifically comprises the following steps:
extracting cortex Magnolia officinalis powder with alkali solution, adjusting pH of the filtrate to 2-3, extracting with ethyl acetate, drying, filtering, and spin drying to obtain cortex Magnolia officinalis crude extract; more preferably, the alkali liquor is strong alkali liquor, and more preferably, the strong alkali is selected from one or two of sodium hydroxide and potassium hydroxide; more preferably, the mass concentration of the alkali liquor is 1-1.5%; more preferably, the addition amount of the alkali liquor is 8-12L per kg of mangnolia officinalis; more preferably, the number of times of extraction is 1 to 3; more preferably, the drying is carried out by adding anhydrous sodium sulfate or anhydrous magnesium sulfate.
Preferably, the concentrated sulfuric acid or the oleum is added dropwise at a rate of 2 to 3 seconds.
Preferably, the introduction speed of the hydrochloric acid gas is 20-40 mmol/min.
Preferably, the temperature of the reaction is between 15 and 40 ℃, preferably between 25 and 35 ℃; more preferably, the course of the reaction is monitored by thin layer chromatography.
Preferably, the reaction time is 1 to 4 hours, more preferably 1.5 to 2 hours.
Preferably, during the process of removing the acidic catalyst, sodium bicarbonate is added for removal.
Preferably, the organic solvent is selected from one or a combination of more of petroleum ether, n-hexane and cyclohexane; more preferred are petroleum ethers; more preferably, petroleum ether is used for extraction 3-5 times.
Preferably, the process of recovering the aqueous phase to obtain honokiol specifically comprises the following steps:
adjusting the pH value of the alkaline water phase to 2-3, extracting with petroleum ether, drying, filtering, and concentrating to obtain honokiol crystal; more preferably, the pH is adjusted by hydrochloric acid; more preferably, the temperature of the extraction is 45-55 ℃; more preferably, the added volume of petroleum ether is not less than the volume of the basic aqueous phase; more preferably, the drying is carried out using anhydrous sodium sulfate.
Preferably, the process of recovering the oil phase to obtain magnolol specifically comprises the following steps:
spin-drying the oil phase, adding an alcohol solvent and hydrochloric acid, refluxing overnight, and completely decomposing the intermediate to obtain magnolol;
more preferably, after the decomposition reaction, the method further comprises a step of purifying magnolol, and specifically comprises the following steps: adding alkaline solution to dissolve magnolol, extracting with petroleum ether, adjusting pH of the obtained water phase to 2-3, extracting with petroleum ether, drying, filtering, and concentrating to obtain magnolol crystal;
more preferably, the alcoholic solvent is selected from methanol or ethanol;
more preferably, the concentration of the hydrochloric acid is 1-1.5M;
more preferably, the mass concentration of the alkali liquor is 1-1.5%;
more preferably, the drying is performed by using anhydrous sodium sulfate or anhydrous magnesium sulfate;
more preferably, the temperature of the petroleum ether extraction after the addition of the alkali liquor is 40-45 ℃.
Preferably, the extraction temperature for the subsequent extraction with petroleum ether after adjusting the pH of the resulting aqueous phase to 2-3 is 45-55 ℃, preferably 50 ℃.
Compared with the prior art, the invention has the beneficial effects that:
(1) according to the method for separating the magnolia bark extract by introducing the intermediate, after the catalyst is changed, the same result can be achieved only by 1.5-2 hours, the reaction time is greatly shortened, and the working efficiency is improved.
(2) The method for separating the magnolia officinalis extract by introducing the intermediate provided by the application has the advantages that the total yield reaches more than 80%, and the obtained magnolol and honokiol have high purity.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
Fig. 1 is a schematic diagram of a test result of monitoring a reaction process in the method provided in embodiment 1 of the present invention.
Fig. 2 shows the purity detection result of honokiol.
Fig. 3 shows the detection result of magnolol purity.
FIG. 4 is a schematic diagram of the reaction process.
Detailed Description
The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings and the detailed description, but those skilled in the art will understand that the following described embodiments are some, not all, of the embodiments of the present invention, and are only used for illustrating the present invention, and should not be construed as limiting the scope of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
A method for separating cortex Magnolia officinalis extract by introducing intermediate comprises the following steps:
adding dried 2, 2-dimethoxypropane into the crude extract of Magnolia officinalis, stirring to dissolve, adding acidic catalyst under anhydrous condition, reacting to obtain magnolol intermediate, removing catalyst after reaction, adding alkali solution, adding organic solvent, extracting to obtain oil phase and alkaline water phase, recovering water phase to obtain honokiol, and recovering oil phase for further treatment to obtain magnolol;
the acid catalyst is selected from one of concentrated sulfuric acid, fuming sulfuric acid or hydrochloric acid gas.
In some preferred embodiments of the present application, the mass ratio of the 2, 2-dimethoxypropane to the crude extract of magnolia bark is (3-4): 1, more preferably (3.3-3.4): 1.
According to the method for separating the magnolia bark extract by introducing the intermediate, after a catalyst is changed, dried 2, 2-dimethoxypropane is used as a solvent and is used as a reactant to react with honokiol to obtain the intermediate, the magnolol and the honokiol are separated by forming the intermediate, a water phase and an oil phase are separated after extraction, and then honokiol and magnolol monomers are obtained by extraction respectively. The reaction time is only 1.5-2h, the separation of honokiol and magnolol can be realized, the purity of the separated bisphenol is high, the reaction time is greatly shortened, and the working efficiency is improved. The reaction process equation is shown in FIG. 4.
Preferably, the mass ratio of the 2, 2-dimethoxypropane to the crude extract of the magnolia officinalis is (3-4): 1, more preferably (3.3-3.4): 1;
preferably, the molar ratio of the acidic catalyst to the 2, 2-dimethoxypropane is 1 (50-200), more preferably 1: 100.
In some preferred embodiments of the present application, the preparation method of the crude extract of magnolia officinalis comprises the following steps:
extracting cortex Magnolia officinalis powder with alkali solution, adjusting pH of the filtrate to 2-3, extracting with ethyl acetate, drying, filtering, and spin drying to obtain cortex Magnolia officinalis crude extract; more preferably, the alkali liquor is strong alkali liquor, and more preferably, the strong alkali is selected from one or two of sodium hydroxide and potassium hydroxide; more preferably, the mass concentration of the alkali liquor is 1-1.5%; more preferably, the addition amount of the alkali liquor is 8-12L per kg of mangnolia officinalis; more preferably, the number of times of extraction is 1-3, 1, 2 or 3; more preferably, the drying is performed by adding anhydrous sodium sulfate or anhydrous magnesium sulfate, and the addition amount of the anhydrous sodium sulfate or anhydrous magnesium sulfate is a conventional addition amount.
The condition for extracting magnolol is optimized.
In some preferred embodiments of the present application, the concentrated or fuming sulfuric acid is added at a rate of one drop per 2 to 3 seconds.
Preferably, the introduction speed of the hydrochloric acid gas is 20-40 mmol/min.
One drop in 2-3 seconds, and the main slow effect is to control the temperature in the reaction system not to be too high; the temperature of the system can be reduced by using an ice-water bath, and the ice is removed after the concentrated sulfuric acid is added, so that the reaction temperature is raised to the room temperature. In actual operation, the whole reaction process is a normal-temperature water bath. The flow rate of the hydrochloric acid gas needs to be controlled to reduce the reaction speed, and the total addition amount of the hydrochloric acid gas is controlled by the introduction time.
In some preferred embodiments herein, the temperature of the reaction is between 15 ℃ and 40 ℃, preferably between 25 ℃ and 35 ℃; more preferably, the course of the reaction is monitored by thin layer chromatography.
In some preferred embodiments herein, the reaction time is 1 to 4 hours, more preferably 1.5 to 2 hours.
In some preferred embodiments of the present application, during the process of removing sulfuric acid, sodium bicarbonate is added for removal.
In some preferred embodiments of the present application, the organic solvent is selected from one or a combination of petroleum ether, n-hexane and cyclohexane; more preferred are petroleum ethers; more preferably, petroleum ether is used for extraction 3-5 times.
In some preferred embodiments of the present application, the process for recovering honokiol from the aqueous phase specifically includes the following steps:
adjusting the pH value of the alkaline water phase to 2-3, extracting with petroleum ether, drying, filtering, and concentrating to obtain honokiol crystal; more preferably, the pH is adjusted by hydrochloric acid; more preferably, the temperature of the extraction is 45-55 ℃; more preferably, the added volume of petroleum ether is not less than the volume of the basic aqueous phase; more preferably, the drying is carried out using anhydrous sodium sulfate.
In some preferred embodiments of the present application, the process of recovering magnolol from the oil phase specifically includes the following steps:
and (3) spin-drying the oil phase, adding an alcohol solvent and hydrochloric acid, refluxing overnight, and completely decomposing the intermediate to obtain magnolol.
More preferably, after the decomposition reaction, the method further comprises a step of purifying magnolol, and specifically comprises the following steps: adding alkaline solution to dissolve magnolol, extracting with petroleum ether, adjusting pH of the obtained water phase to 2-3, extracting with petroleum ether, drying, filtering, and concentrating to obtain magnolol crystal.
More preferably, the alcoholic solvent is selected from methanol or ethanol.
More preferably, the hydrochloric acid has a concentration of 1 to 1.5M, and further has a concentration of 1M, 1.1M, 1.2M, 1.3M, 1.4M, or 1.5M.
More preferably, the mass concentration of the alkali liquor is 1-1.5%; further, the concentration was 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%.
More preferably, the drying is performed using anhydrous sodium sulfate or anhydrous magnesium sulfate.
More preferably, the temperature of the petroleum ether extraction after the addition of the alkali liquor is 40-45 ℃.
Wherein, the organic solvent and the alcohol can be recovered after the reaction, and the method is safe and environment-friendly.
In some preferred embodiments of the present application, the extraction temperature for the re-extraction with petroleum ether after adjusting the pH of the resulting aqueous phase to 2-3 is 45-55 ℃, preferably 50 ℃.
Example 1
(1) Pulverizing cortex Magnolia officinalis, sieving with No. 2 sieve, sampling, and detecting cortex Magnolia officinalis bisphenol content to be 3.85%, wherein magnolol is 2.40%, and honokiol is 1.45%.
(2) Extracting 1000g of cortex Magnolia officinalis powder with 10L of 1.5% alkali solution for 1 time, and filtering; adding 1.0% alkali solution 10L into the filter cake, extracting for 1 time, filtering, mixing filtrates, and adjusting pH to 2. Extracting with ethyl acetate 1L for 3 times, drying with anhydrous sodium sulfate 80g, filtering, and spin drying to obtain cortex Magnolia officinalis crude extract 75 g.
(3) Adding 300ml of dried 2, 2-dimethoxypropane into the crude extract of cortex Magnolia officinalis, stirring thoroughly to dissolve, slowly dropping 2.0ml of concentrated sulfuric acid (fuming sulfuric acid), and monitoring by TLC on-line for 2.0 h;
as shown in FIG. 1, in the monitoring process, there are 5 plates in FIG. 1, 3 lines are provided on each plate, the 3 rd line (the rightmost line) is the reaction monitoring process of example 1, the time of each test is 15:30, 15:45, 16:10, 16:40, 17:10, the 1 st and 2 nd lines are control groups, and when only one of the two dots on the third line is the same as the control group, the reaction is terminated, and the separation can be performed.
(4) Adding sodium bicarbonate to neutralize sulfuric acid in the reaction system, filtering and spin-drying. And (5) recovering the solvent. Adding 1000ml of 1% alkali liquor, fully dissolving, and extracting with 1000ml of petroleum ether respectively at 40 ℃ for 3 times.
(5) The aqueous phase is adjusted to pH 2 by addition of dilute hydrochloric acid and extracted 3 times with 1000ml of petroleum ether at 50 ℃. Drying with anhydrous sodium sulfate, filtering, and concentrating to about 200ml to obtain white honokiol crystal 11.75g, with purity 97%, and total honokiol yield 81%.
(6) The organic phase was spin dried, 300ml of absolute ethanol was added, 20ml of 1M hydrochloric acid was added, and the mixture was refluxed overnight. Adding sodium bicarbonate to neutralize hydrochloric acid in the reaction system, spin-drying to recover ethanol, adding 1000ml of 1% alkali liquor, dissolving completely, extracting with 500ml of petroleum ether respectively at 40 deg.C for 3 times, and recovering solvent from the organic phase. The aqueous phase is adjusted to pH 2 by addition of dilute hydrochloric acid and extracted 3 times with 1000ml of petroleum ether at 50 ℃. Drying with anhydrous sodium sulfate, filtering, and concentrating to about 200ml to obtain white magnolol crystal 19.80g with purity of 99% and total yield of magnolol of 82%.
Example 2
(1) Pulverizing cortex Magnolia officinalis, sieving with No. 2 sieve, sampling, and detecting cortex Magnolia officinalis bisphenol content to be 3.85%, wherein magnolol is 2.40%, and honokiol is 1.45%.
(2) Extracting 1000g of cortex Magnolia officinalis powder with 15L of 1.0% alkali solution for 1 time, and filtering; adding 1.5% alkali solution 6.67L into the filter cake, extracting for 1 time, filtering, adding 1.0% alkali solution 10L into the filter cake, extracting for 1 time, filtering, mixing filtrates, and adjusting pH to 3. Extracting with ethyl acetate 1L for 2 times, drying with anhydrous sodium sulfate 80g, filtering, and spin drying to obtain cortex Magnolia officinalis crude extract 72 g.
(3) Adding dried 2, 2-dimethoxypropane 300ml into cortex Magnolia officinalis crude extract, stirring thoroughly to dissolve, slowly dropping concentrated sulfuric acid (oleum) 2.0ml, and monitoring by TLC on-line for 1.5h.
(4) Adding sodium bicarbonate to neutralize sulfuric acid in the reaction system, filtering and spin-drying. And (5) recovering the solvent. Adding 1000ml of 1% alkali liquor, fully dissolving, and extracting with 1000ml of petroleum ether respectively at 45 ℃ for 3 times.
(5) The aqueous phase is adjusted to pH 3 by addition of dilute hydrochloric acid and extracted 3 times with 1000ml of petroleum ether at 45 ℃. Drying with anhydrous sodium sulfate, filtering, and concentrating to about 200ml to obtain white honokiol crystal 11.86g, with purity of 98% and total honokiol yield of 80.21%.
(6) The organic phase was spin dried, 300ml of absolute ethanol was added, 20ml of 1M hydrochloric acid was added, and the mixture was refluxed overnight. Adding sodium bicarbonate to neutralize hydrochloric acid in the reaction system, spin-drying to recover ethanol, adding 1.5% alkali solution 667ml, dissolving completely, extracting with 500ml petroleum ether at 45 deg.C for 2 times, and recovering solvent from the organic phase. The aqueous phase is adjusted to pH 3 by addition of dilute hydrochloric acid and extracted 2 times with 1000ml of petroleum ether at 45 ℃. Drying with anhydrous sodium sulfate, filtering, and concentrating to about 200ml to obtain white magnolol crystal 19.73g with purity of 98% and total magnolol yield of 80.58%.
Example 3
(1) Pulverizing cortex Magnolia officinalis, sieving with No. 2 sieve, sampling, and detecting cortex Magnolia officinalis bisphenol content to be 3.85%, wherein magnolol is 2.40%, and honokiol is 1.45%.
(2) Extracting 1000g of cortex Magnolia officinalis powder with 10% alkali solution 15L for 1 time, and filtering; adding 1.0% alkali solution 10L into the filter cake, extracting for 1 time, filtering, adding 1.2% alkali solution 8.33L into the filter cake, extracting for 1 time, filtering, mixing filtrates, and adjusting pH to 2.5. Extracting with ethyl acetate 1L for 3 times, drying with anhydrous sodium sulfate 80g, filtering, and spin drying to obtain crude extract 74.57g of cortex Magnolia officinalis.
(3) Adding dried 2, 2-dimethoxypropane 300ml into cortex Magnolia officinalis crude extract, stirring thoroughly to dissolve, slowly dropping concentrated sulfuric acid (oleum) 2.0ml, and TLC on-line monitoring for 2.0h.
(4) Adding sodium bicarbonate to neutralize sulfuric acid in the reaction system, filtering and spin-drying. And (5) recovering the solvent. Adding 1000ml of 1% alkali liquor, fully dissolving, and extracting with 1000ml of petroleum ether respectively at 40 ℃ for 3 times.
(5) The aqueous phase is adjusted to pH 2-3 by adding dilute hydrochloric acid and extracted 3 times with 1000ml of petroleum ether at 50 ℃. Drying with anhydrous sodium sulfate, filtering, and concentrating to about 200ml to obtain white honokiol crystal 11.55g, with purity of 98% and total honokiol yield of 79.97%.
(6) The organic phase was spin dried, 300ml of absolute ethanol was added, 20ml of 1.5M hydrochloric acid was added, and the mixture was refluxed overnight. Adding sodium bicarbonate to neutralize hydrochloric acid in the reaction system, spin-drying to recover ethanol, adding 1000ml of 1% alkali liquor, dissolving completely, extracting with 500ml of petroleum ether respectively at 45 deg.C for 3 times, and recovering solvent from the organic phase. The aqueous phase is adjusted to pH 3 by addition of dilute hydrochloric acid and extracted 3 times with 1000ml of petroleum ether at 50 ℃. Drying with anhydrous sodium sulfate, filtering, and concentrating to about 200ml to obtain white magnolol crystal 19.62g with purity of 98% and total magnolol yield of 81.75%.
Compared with the prior art, the method can greatly shorten the reaction time, improve the extraction efficiency, and obtain the magnolol and honokiol with high purity and yield.
While particular embodiments of the present invention have been illustrated and described, it will be appreciated that the above embodiments are merely illustrative of the technical solution of the present invention and are not restrictive; those of ordinary skill in the art will understand that: modifications may be made to the above-described embodiments, or equivalents may be substituted for some or all of the features thereof without departing from the spirit and scope of the present invention; the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention; it is therefore intended to cover in the appended claims all such alternatives and modifications that are within the scope of the invention.
Claims (33)
1. A method for introducing an intermediate to separate a magnolia bark extract is characterized by comprising the following steps:
adding dried 2, 2-dimethoxypropane into the crude extract of Magnolia officinalis, stirring to dissolve, adding acidic catalyst under anhydrous condition, reacting to obtain magnolol intermediate, removing catalyst after reaction, adding alkali solution, adding organic solvent, extracting to obtain oil phase and alkaline water phase, recovering water phase to obtain honokiol, and recovering oil phase for further treatment to obtain magnolol;
the acid catalyst is selected from one of concentrated sulfuric acid, fuming sulfuric acid or hydrochloric acid gas;
the mass ratio of the 2, 2-dimethoxypropane to the crude extract of the magnolia officinalis is (3-4): 1;
the molar ratio of the acidic catalyst to the 2, 2-dimethoxypropane is 1 (50-200);
the reaction time is 1-4 hours.
2. The method for the isolation of magnolia bark extract introduced as an intermediate according to claim 1, wherein the mass ratio of the 2, 2-dimethoxypropane to the crude extract of magnolia bark is (3.3-3.4): 1.
3. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 1, wherein the molar ratio of the acidic catalyst to the 2, 2-dimethoxypropane is 1: 100.
4. The method for separating magnolia bark extract introduced with the intermediate as claimed in claim 1, wherein the preparation method of the crude magnolia bark extract comprises the following steps:
extracting cortex Magnolia officinalis powder with alkali solution, adjusting pH of filtrate =2-3, extracting with ethyl acetate, drying, filtering, and spin drying to obtain crude extract of cortex Magnolia officinalis.
5. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 4, wherein the lye is a strong lye.
6. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 5, wherein the strong base is selected from one or both of sodium hydroxide and potassium hydroxide.
7. The method for separating magnolia bark extract introduced as the intermediate as claimed in claim 5, wherein the concentration of the alkali solution is 1% to 1.5% by mass.
8. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 7, wherein the lye is added in an amount of 8-12L per kg of magnolia bark powder.
9. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 4, wherein the number of extractions is 1-3.
10. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 4, wherein the drying is performed with the addition of anhydrous sodium sulfate or anhydrous magnesium sulfate.
11. The method for the isolation of magnolia bark extract as claimed in claim 1, wherein the dropping rate of the concentrated sulfuric acid or the oleum is one drop per 2-3 seconds; or the introduction speed of the hydrochloric acid gas is 20-40 mmol/min.
12. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 1, wherein the temperature of the reaction is between 15-40 ℃.
13. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 1, wherein the temperature of the reaction is between 25 ℃ and 35 ℃.
14. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 13, wherein the process of the reaction is supervised by thin layer chromatography.
15. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 1, wherein the reaction time is 1.5-2 hours.
16. The method for separating magnolia bark extract as claimed in claim 1, wherein the removal of the catalyst is performed by adding sodium bicarbonate.
17. The method for separating magnolia bark extract introduced as the intermediate according to claim 1, wherein the organic solvent is selected from one or a combination of petroleum ether, n-hexane and cyclohexane.
18. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 1, wherein the organic solvent is petroleum ether.
19. The method for isolating magnolia bark extract as claimed in claim 18, wherein petroleum ether is used for 3-5 extractions.
20. The method for separating magnolia bark extract by introducing an intermediate as claimed in claim 1, wherein the process of recovering honokiol from the aqueous phase comprises the following steps:
adjusting pH of alkaline water phase =2-3, extracting with petroleum ether, drying, filtering, and concentrating to obtain honokiol crystal.
21. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 20, wherein the pH adjustment is performed using hydrochloric acid.
22. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 20, wherein the temperature of the extraction is 45-55 ℃.
23. The method for the isolation of magnolia extract incorporating an intermediate of claim 20, wherein the petroleum ether is added in a volume not less than the volume of the basic aqueous phase.
24. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 20, wherein the drying is performed using anhydrous sodium sulfate.
25. The method for separating magnolia bark extract by introducing the intermediate as claimed in claim 1, wherein the process of recovering magnolol from the oil phase comprises the following steps:
and (3) spin-drying the oil phase, adding an alcohol solvent and hydrochloric acid, refluxing overnight, and completely decomposing the intermediate to obtain magnolol.
26. The method for isolating magnolia extract with the introduction of an intermediate as claimed in claim 25, further comprising a step of purifying magnolol after the decomposition reaction, comprising in particular the steps of: adding alkaline solution to dissolve magnolol, extracting with petroleum ether, adjusting pH of the obtained water phase to =2-3, extracting with petroleum ether, drying, filtering, and concentrating to obtain magnolol crystal.
27. The method for the isolation of magnolia extract incorporating an intermediate as claimed in claim 25, wherein the alcoholic solvent is selected from methanol or ethanol.
28. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 25, wherein the concentration of hydrochloric acid is 1 to 1.5M.
29. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 26, wherein the lye is present in a concentration of 1% to 1.5% by mass.
30. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 26, wherein the drying is performed with anhydrous sodium sulfate or anhydrous magnesium sulfate.
31. The method for isolating magnolia extract incorporating an intermediate of claim 26, wherein the temperature of the petroleum ether extraction after the addition of the caustic solution is 40-45 ℃.
32. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 26, wherein the extraction temperature for the re-extraction with petroleum ether after adjusting the pH =2-3 of the resulting aqueous phase is 45-55 ℃.
33. The method for the isolation of magnolia bark extract incorporating an intermediate as claimed in claim 26, wherein the extraction temperature for the re-extraction with petroleum ether after adjusting the pH =2-3 of the resulting aqueous phase is 50 ℃.
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN85103128A (en) * | 1985-04-30 | 1987-02-04 | 上海市中药研究所 | The extracting method of magnolol and Honokiol |
| CN1583700A (en) * | 2004-06-08 | 2005-02-23 | 河北农业大学 | Preparation technology of high-purity magnolol |
| CN101445430A (en) * | 2008-12-30 | 2009-06-03 | 浙江工业大学 | Magnolol and separation method thereof |
| CN101507755A (en) * | 2009-03-25 | 2009-08-19 | 湖南省中药提取工程研究中心有限公司 | Preparation method of high-purity magnolia bark total-phenol |
| CN102408314A (en) * | 2011-12-09 | 2012-04-11 | 广西大学 | Method for preparing high-purity magnolol and magnolol |
| CN105130759A (en) * | 2015-08-12 | 2015-12-09 | 广州普星药业有限公司 | Extraction method of magnolia officinalis extract |
| CN106588580A (en) * | 2016-11-23 | 2017-04-26 | 成都金瑞基业生物科技有限公司 | Method for preparing high-purity magnolol from Mangnolia officinalis |
| CN107652166A (en) * | 2017-09-30 | 2018-02-02 | 北京国康本草物种生物科学技术研究院有限公司 | A kind of separation method of bark of official magnolia bis-phenol |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006107451A2 (en) * | 2005-02-23 | 2006-10-12 | Univ Emory | Honokiol derivatives for the treatment of proliferative disorders |
-
2018
- 2018-08-28 CN CN201810991607.9A patent/CN108947778B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN85103128A (en) * | 1985-04-30 | 1987-02-04 | 上海市中药研究所 | The extracting method of magnolol and Honokiol |
| CN1583700A (en) * | 2004-06-08 | 2005-02-23 | 河北农业大学 | Preparation technology of high-purity magnolol |
| CN1268597C (en) * | 2004-06-08 | 2006-08-09 | 河北农业大学 | Preparation technology of high-purity magnolol |
| CN101445430A (en) * | 2008-12-30 | 2009-06-03 | 浙江工业大学 | Magnolol and separation method thereof |
| CN101507755A (en) * | 2009-03-25 | 2009-08-19 | 湖南省中药提取工程研究中心有限公司 | Preparation method of high-purity magnolia bark total-phenol |
| CN102408314A (en) * | 2011-12-09 | 2012-04-11 | 广西大学 | Method for preparing high-purity magnolol and magnolol |
| CN105130759A (en) * | 2015-08-12 | 2015-12-09 | 广州普星药业有限公司 | Extraction method of magnolia officinalis extract |
| CN106588580A (en) * | 2016-11-23 | 2017-04-26 | 成都金瑞基业生物科技有限公司 | Method for preparing high-purity magnolol from Mangnolia officinalis |
| CN107652166A (en) * | 2017-09-30 | 2018-02-02 | 北京国康本草物种生物科学技术研究院有限公司 | A kind of separation method of bark of official magnolia bis-phenol |
Non-Patent Citations (2)
| Title |
|---|
| Facile Purification of Honokiol and Its Antiviral and Cytotoxic Properties;Franck Amblard等;《J.Med.Chem.》;20060601;第49卷(第11期);第3426页右栏第5段、第3427页左栏第3段 * |
| 厚朴粗提物中和厚朴酚与厚朴酚的分离纯化;谢达春等;《华西药学杂志》;20090615;第24卷(第3期);第275页第1.2.3、1.2.4部分 * |
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