CN104387439B - Method for preparing glycyrrhizic acid derivatives by carrying out subcritical hydrolysis reaction - Google Patents
Method for preparing glycyrrhizic acid derivatives by carrying out subcritical hydrolysis reaction Download PDFInfo
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Abstract
The invention discloses a method for preparing glycyrrhizic acid derivatives by carrying out a subcritical hydrolysis reaction and belongs to the technical field of biochemical engineering. Glycyrrhizic acid or liquorice extract is taken as a raw material, and glycyrrhetinic acid and glycyrrhetinic acid 3-O-glucuronide are prepared by carrying out the subcritical hydrolysis reaction. The method for preparing the glycyrrhizic acid derivatives by carrying out the subcritical hydrolysis reaction comprises the following steps: firstly dissolving raw materials to obtain a glycyrrhizic acid solution, then carrying out the subcritical hydrolysis reaction to prepare a reaction liquid, and centrifuging, separating, concentrating or redissolving and drying the reaction liquid, so that glycyrrhetinic acid 3-O-glucuronide and glycyrrhetinic acid are obtained. The method for preparing the glycyrrhizic acid derivatives by carrying out the subcritical hydrolysis reaction has the advantages that a preparation technology is scientific and reasonable, operation is simple and feasible, cost is low, continuous production can be realized, and the glycyrrhizic acid derivative products are easy to popularize and have a higher additional value; the amount of acid added in a preparation process is little, no destructive effect is produced to a structure of glycyrrhizic acid, product yield is high, and no pollution to the environment is produced; and the glycyrrhizic acid derivative products can be taken as a food additive and a medicine precursor substance and raw materials are provided for the food and pharmaceutical industries.
Description
Technical field
The invention belongs to technical field of biochemical industry is and in particular to glycyrrhizin derivative is prepared in a kind of subcritical hydrolysis reaction
Method.
Background technology
Radix Glycyrrhizae (glycyrrhizauralensis) another name Herba Hedyotis cantonensis root, Radix Glycyrrhizae, state are old, Herba Hedyotis cantonensis, sweet root etc., are China
One of conventional Chinese herbal medicine of tradition, is pulse family (leguminosae) Glycyrrhiza (glycyrrhizalinn) herbaceos perennial.
Radix Glycyrrhizae flat property and sweet taste, has functions that invigorating the spleen and replenishing QI, heat-clearing and toxic substances removing, expelling phlegm for arresting cough, relieving spasm to stop pain, coordinating the actions of various ingredients in a prescription, has extremely wide
Clinical value.In China, Radix Glycyrrhizae is the maximum medical herbs simply of consumption in 2000 plurality of herbal, have " ten side nine grass, no
Grass not Cheng Fang " says.Meanwhile, best a kind of natural sweetener of Radix Glycyrrhizae still discovery so far.Radix Glycyrrhizae is widely used in
The fields such as medicine, Nicotiana tabacum L., food.
Glycyrrhizic acid is the main active substances in Radix Glycyrrhizae.Glycyrrhizic acid has certain pharmacologically active, such as the liver protecting, disease-resistant
Poison and the effect of anticancer.Glycyrrhizic acid also has been widely used on food, and glycyrrhizic acid has higher sweet taste, and its sweet taste is sugarcane
170-200 times of sugar, is used as sweeting agent in food service industry.On the other hand, glycyrrhizic acid, also by as precursor compound, is used for
The synthesis of other compounds.For example, glycyrrhizic acid removes glucuronic acid and can generate enoxolone and single glucuronic acid Radix Glycyrrhizae time
Acid.Enoxolone does not have sweet taste, but its pharmacologically active is stronger than glycyrrhizic acid, has very strong liver protection, antiviral is lived
Property and anti-tumor activity.And, glycyrrhizic acid is decomposed to form Radix Glycyrrhizae through stomach acid hydrolysis or through beta-glucuronidase enzyme in liver
Subacid, the pharmacological action of glycyrrhizic acid is substantially effect of enoxolone.Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide is as glycyrrhizic acid
Derivant, both have similar biological activity, and it is even more than glycyrrhizic acid on antiinflammatory and antiallergic activity, and has aobvious
The antitumaous effect writing.And, Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide is a kind of new natural sweetener, sugariness is the 5 of glycyrrhizic acid
Times.Enoxolone and Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide have the physiology more excellent than glycyrrhizic acid and medical active, explore Radix Glycyrrhizae time
Acid and the production technology of Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide, the enoxolone of optimization high yield and Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide
Processing conditionss have good economic benefit and social meaning.
At present, produce enoxolone using glycyrrhizic acid and Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide mainly has two methods, that is, change
Method and bioconversion method.Chinese patent (cn 101817867 a) discloses a kind of preparation method of enoxolone, should
Method is chemical method, passes through acidolysis, acetylation, alkaline hydrolysis etc. with glycyrrhizic acid for raw material and processes, obtains enoxolone, this process is easy
Control, low production cost.Chinese patent (cn 102337319 a) discloses a kind of preparing glycyrrhetinic acid by converting glycyrrhizic acid with enzymatic
Method, using microorganism produce glycyrrhizic acid hydrolytic enzyme, glycyrrhizic acid is hydrolyzed, generate enoxolone, this method conversion ratio
High.Chinese patent (cn 103788167 a) discloses and extracts glycyrrhizic acid by Radix Glycyrrhizae, the more single glucuronic acid of acidified generation
The method of enoxolone.This method is chemical method, simple to operate, low cost, cycle is short.Chinese patent (cn 103509843 a)
Disclose the method that bioconversion prepares Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide, the method is using generation specific glucose aldehydic acid glycosides
The bacterial strain of enzyme, as catalyst, with glycyrrhizic acid as substrate, prepares Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide.Chemical method conversion is to pass through
Acid, alkali effect, the glycosyl of glycyrrhizic acid is removed in hydrolysis, thus generating enoxolone and Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide, but this
Method environmental pollution is more serious, and strong acid and strong base also can produce certain destruction to glycyrrhizic acid structure, thus leading to
Products collection efficiency declines.Biotransformation method, because preparation condition and Technology are complicated, relatively costly, the cycle is long, should not realize work
Industry metaplasia is produced.
Subcritical fluid techniques are a kind of infant industry technology, can be applicable to the preparation of functional factor and food processing is discarded
Thing reclaim renewable resources it can also be used to the degradation reaction of fat, carbohydrate, protein etc..Subcritical fluids refer to certain
Under conditions of a little compounds are higher than its boiling point in temperature but are less than critical temperature, and pressure is less than its critical pressure, with fluid shape
The material that formula exists.Compared with light water, the density of subcritical water, viscosity and dielectric constant all can occur drastically to change, and have
Close to density and solvability, the viscosity of similar gas and the diffusion coefficient of liquid, its dielectric constant from normal temperature and pressure 80
Drop to the scope of similar first/ethanol, and its ionizing power increase, [h3o+] and [oh-] close to weak acid, weak base, itself
There is acid-base catalysises function.At present, there is not been reported to prepare the method for glycyrrhizin derivative using subcritical hydrolysis reaction.
Content of the invention
It is an object of the invention to, for the complicated process of preparation of above-mentioned prior art presence, high cost, cycle length, product
Rate is low and with serious pollution problem, provides a kind of method that glycyrrhizin derivative is prepared in subcritical hydrolysis reaction.
The method of the present invention with glycyrrhizic acid or Radix Glycyrrhizae extractum as raw material, by subcritical hydrolysis reaction prepare enoxolone and
Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide, to reduce production cost, improve production efficiency and product yield, reduces environmental pollution, and real
Existing serialization, industrialized production, provide raw material for food and medicine industry.For achieving the above object, the technology that the present invention adopts
Scheme is:
A kind of method that glycyrrhizin derivative is prepared in subcritical hydrolysis reaction, comprises the following steps:
(1) material dissolution: at 65 DEG C, glycyrrhizic acid or Radix Glycyrrhizae extractum are dissolved in 10～90% ethanol-water solution, so
Add acetic acid, sulphuric acid, nitric acid or hydrochloric acid to adjust ph to 1～3 afterwards, obtain the Radix Glycyrrhizae acid solution that concentration is 0.5～9%；
(2) subcritical hydrolysis reaction: by high pressure pump, Radix Glycyrrhizae acid solution is pumped in subcritical reaction kettle, in high temperature
It is stirred under high pressure reacting, reaction temperature is 120～200 DEG C, pressure is 5～11mpa, the time is 20～90min, stirring turns
Speed is 100～250rpm, after reaction terminates, collects reactant liquor；
(3) centrifugal treating: above-mentioned reactant liquor obtains clear liquor, centrifugal rotational speed 4200rpm, time 10min through centrifugal treating；
(4) separating treatment: using organic solvent (ethyl acetate, acetone, ether, n-butyl alcohol or chloroform) to clear liquor
Carry out extract and separate, obtain aqueous phase and organic faciess, repeat to extract 3 times, combining extraction liquid；
(5) concentration: aqueous phase is carried out concentration by vacuum evaporation, evaporating temperature is 40～60 DEG C, vacuum
For 0.05～0.08mpa, it is concentrated into soluble solid content (brix) and reaches 25～40%, obtain concentrated solution；
(6) redissolution is processed: by being evaporated in vacuo the solvent removing in organic faciess, is then redissolved with dehydrated alcohol, anhydrous second
Alcohol: wet slag=3:1 (v/w), obtain ethanol and redissolve liquid；
(7) dried: concentrated solution is adopted with spray drying method, inlet temperature is 160～200 DEG C, outlet temperature is 80
～85 DEG C, obtain Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide；To ethanol redissolve liquid using revolution boulton process, baking temperature be 40～
60 DEG C, vacuum is 0.06～0.09mpa, obtains enoxolone.
Beneficial effects of the present invention:
The preparation method of glycyrrhizin derivative of the present invention is easy and simple to handle, low cost, is capable of continuous prodution, produces effect
Rate is high；The addition of preparation process acid seldom, will not produce destruction to glycyrrhizic acid structure, product yield is high, and will not make
Become environmental pollution；The product of preparation has compared with high added value it is easy to popularization and application, serves not only as food additive, also may be used
As prodrug material, to provide raw material for food and medicine industry.
The present invention prepares glycyrrhizin derivative by subcritical hydrolysis reaction, the conversion ratio of glycyrrhizic acid can reach 45% with
On, reach as high as 94.8%, the conversion ratio of Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide can reach more than 15%, the conversion of enoxolone
Rate can reach more than 20%, and product purity can reach more than 75%.
Brief description
Fig. 1 prepares the process chart of glycyrrhizin derivative for subcritical hydrolysis reaction.
Fig. 2 prepares the reaction path of glycyrrhizin derivative for subcritical hydrolysis reaction.
Fig. 3 is the high pressure liquid chromatography figure before and after subcritical hydrolysis reaction, and wherein, upper figure is the high-pressure liquid phase color before reaction
Spectrogram, middle figure is the reacted high pressure liquid chromatography figure of embodiment 1, and figure below is the reacted high pressure liquid chromatography figure of embodiment 3.
Specific embodiment
Following non-limiting examples can make those of ordinary skill in the art that the present invention is more fully understood, but not with
Any mode limits the present invention.
In following embodiments, measure glycyrrhizic acid and product before and after reacting respectively using high pressure lipuid chromatography (HPLC) (hplc) (single
Glucuronic acid enoxolone, enoxolone) content, and as follows calculate glycyrrhizic acid, the conversion ratio of product and
Rate.
Embodiment 1
The process chart of glycyrrhizin derivative is prepared in subcritical hydrolysis reaction according to Fig. 1, by glycyrrhizic acid through Asia
Critical hydrolysis prepare Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide and enoxolone, comprise the following steps:
(1) material dissolution: at 65 DEG C, glycyrrhizic acid is dissolved in 30% ethanol-water solution, is subsequently adding acetic acid and adjusts
Ph=3, obtains the Radix Glycyrrhizae acid solution that concentration is 1.8%；
(2) subcritical hydrolysis reaction: by high pressure pump, Radix Glycyrrhizae acid solution is pumped in subcritical reaction kettle, in high temperature
It is stirred under high pressure reacting, reaction temperature is 120 DEG C, pressure is 5mpa, the time is 50min, speed of agitator is 100rpm, instead
After should terminating, collect reactant liquor；
(3) centrifugal treating: above-mentioned reactant liquor obtains clear liquor, centrifugal rotational speed 4200rpm, time 10min through centrifugal treating；
(4) separating treatment: using chloroform, extract and separate is carried out to clear liquor, obtain aqueous phase and organic faciess, repeat to extract
Take 3 times, combining extraction liquid；
(5) concentration: aqueous phase is carried out concentration by vacuum evaporation, evaporating temperature is 60 DEG C, vacuum is
0.06mpa, is concentrated into soluble solid content (brix) and reaches 25%, obtain concentrated solution；
(6) redissolution is processed: by being evaporated in vacuo the solvent removing in organic faciess, is then redissolved with dehydrated alcohol, anhydrous second
Alcohol: wet slag=3:1 (v/w), obtain ethanol and redissolve liquid；
(7) dried: concentrated solution is adopted with spray drying method, inlet temperature is 160 DEG C, outlet temperature is 80 DEG C, obtains
To Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide；Ethanol is redissolved with liquid using revolution boulton process, baking temperature is 50 DEG C, and vacuum is
0.06mpa, obtains enoxolone.
Above-mentioned reaction path is as shown in Figure 2.
The high pressure liquid chromatography figure before and after reaction shown in the upper figure of accompanying drawing 3 and middle figure, only Radix Glycyrrhizae before reaction
Acid exists, and reaction occurs in that the chromatographic peak of Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide and enoxolone after terminating, and glycyrrhizic acid content shows
Write and reduce.During made above, glycyrrhizic acid conversion ratio is 48.43%, and Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide conversion ratio is
14.58%, yield is 10.56%, content 78.5g/100g, and enoxolone conversion ratio is 15.58%, and yield is 8.56%, contains
Measure as 80.3g/100g.
Embodiment 2
Present embodiment discloses one kind by glycyrrhizic acid through subcritical hydrolysis reaction prepare Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide and
The method of enoxolone, comprises the following steps:
(1) material dissolution: at 65 DEG C, glycyrrhizic acid is dissolved in 70% ethanol-water solution, is subsequently adding acetic acid and adjusts
Ph=2, obtains the Radix Glycyrrhizae acid solution that concentration is 1.8%；
(2) subcritical hydrolysis reaction: by high pressure pump, Radix Glycyrrhizae acid solution is pumped in subcritical reaction kettle, in high temperature
It is stirred under high pressure reacting, reaction temperature is 160 DEG C, pressure is 9mpa, the time is 20min, speed of agitator is 200rpm, instead
After should terminating, collect reactant liquor；
(3) centrifugal treating: above-mentioned reactant liquor obtains clear liquor, centrifugal rotational speed 4200rpm, time 10min through centrifugal treating；
(4) separating treatment: using ethyl acetate, extract and separate is carried out to clear liquor, obtain aqueous phase and organic faciess, repeat to extract
Take 3 times, combining extraction liquid；
(5) concentration: aqueous phase is carried out concentration by vacuum evaporation, evaporating temperature is 50 DEG C, vacuum is
0.06mpa, is concentrated into soluble solid content (brix) and reaches 30%, obtain concentrated solution；
(6) redissolution is processed: by being evaporated in vacuo the solvent removing in organic faciess, is then redissolved with dehydrated alcohol, anhydrous second
Alcohol: wet slag=3:1 (v/w), obtain ethanol and redissolve liquid；
(7) dried: concentrated solution is adopted with spray drying method, inlet temperature is 160 DEG C, outlet temperature is 85 DEG C, obtains
To Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide；Ethanol is redissolved with liquid using revolution boulton process, baking temperature is 40 DEG C, and vacuum is
0.07mpa, obtains enoxolone.
During made above, glycyrrhizic acid conversion ratio is 52.67%, and Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide conversion ratio is
14.35%, yield is 9.66%, and content is 77.6g/100g, and enoxolone conversion ratio is 20.78%, and yield is 9.86%, contains
Amount 79.26g/100g.
Embodiment 3
Present embodiment discloses one kind by glycyrrhizic acid through subcritical hydrolysis reaction prepare Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide and
The method of enoxolone, comprises the following steps:
(1) material dissolution: at 65 DEG C, glycyrrhizic acid is dissolved in 30% ethanol-water solution, is subsequently adding acetic acid and adjusts
Ph=2, obtains the Radix Glycyrrhizae acid solution that concentration is 3.6%；
(2) subcritical hydrolysis reaction: by high pressure pump, Radix Glycyrrhizae acid solution is pumped in subcritical reaction kettle, in high temperature
It is stirred under high pressure reacting, reaction temperature is 140 DEG C, pressure is 7mpa, the time is 70min, speed of agitator is 150rpm, instead
After should terminating, collect reactant liquor；
(3) centrifugal treating: above-mentioned reactant liquor obtains clear liquor, centrifugal rotational speed 4200rpm, time 10min through centrifugal treating；
(4) separating treatment: using chloroform, extract and separate is carried out to clear liquor, obtain aqueous phase and organic faciess, repeat to extract
Take 3 times, combining extraction liquid；
(5) concentration: aqueous phase is carried out concentration by vacuum evaporation, evaporating temperature is 50 DEG C, vacuum is
0.08mpa, is concentrated into soluble solid content (brix) and reaches 35%, obtain concentrated solution；
(6) redissolution is processed: by being evaporated in vacuo the solvent removing in organic faciess, is then redissolved with dehydrated alcohol, anhydrous second
Alcohol: wet slag=3:1 (v/w), obtain ethanol and redissolve liquid；
(7) dried: concentrated solution is adopted with spray drying method, inlet temperature is 180 DEG C, outlet temperature is 80 DEG C, obtains
To Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide；Ethanol is redissolved with liquid using revolution boulton process, baking temperature is 50 DEG C, and vacuum is
0.08mpa, obtains enoxolone.
The high pressure liquid chromatography figure before and after reaction shown in the upper figure of accompanying drawing 3 and figure below, only Radix Glycyrrhizae before reaction
Acid exists, and reaction occurs in that the chromatographic peak of Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide and enoxolone, enoxolone chromatographic peak after terminating
Response value dramatically increases, and glycyrrhizic acid content significantly reduces.During made above, glycyrrhizic acid conversion ratio is 72.64%, single Portugal
Grape alduronic acid enoxolone conversion ratio is 26.29%, and yield is 18.69%, content 78.62g/100g, enoxolone conversion ratio
For 32.67%, yield is 16.98%, and content is 81.23g/100g.
Embodiment 4
Present embodiment discloses one kind by glycyrrhizic acid through subcritical hydrolysis reaction prepare Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide and
The method of enoxolone, comprises the following steps:
(1) material dissolution: at 65 DEG C, glycyrrhizic acid is dissolved in 50% ethanol-water solution, is subsequently adding acetic acid and adjusts
Ph=2, obtains the Radix Glycyrrhizae acid solution that concentration is 9%；
(2) subcritical hydrolysis reaction: by high pressure pump, Radix Glycyrrhizae acid solution is pumped in subcritical reaction kettle, in high temperature
It is stirred under high pressure reacting, reaction temperature is 200 DEG C, pressure is 5mpa, the time is 50min, speed of agitator is 250rpm, instead
After should terminating, collect reactant liquor；
(3) centrifugal treating: above-mentioned reactant liquor obtains clear liquor, centrifugal rotational speed 4200rpm, time 10min through centrifugal treating；
(4) separating treatment: using ether, extract and separate is carried out to clear liquor, obtain aqueous phase and organic faciess, repeat to extract 3
Secondary, combining extraction liquid；
(5) concentration: aqueous phase is carried out concentration by vacuum evaporation, evaporating temperature is 40 DEG C, vacuum is
0.05mpa, is concentrated into soluble solid content (brix) and reaches 40%, obtain concentrated solution；
(6) redissolution is processed: by being evaporated in vacuo the solvent removing in organic faciess, is then redissolved with dehydrated alcohol, anhydrous second
Alcohol: wet slag=3:1 (v/w), obtain ethanol and redissolve liquid；
(7) dried: concentrated solution is adopted with spray drying method, inlet temperature is 180 DEG C, outlet temperature is 80 DEG C, obtains
To Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide；Ethanol is redissolved with liquid using revolution boulton process, baking temperature is 50 DEG C, and vacuum is
0.09mpa, obtains enoxolone.
During made above, glycyrrhizic acid conversion ratio is 94.80%, and Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide conversion ratio is
1.24%, yield is 0.66%, content 79.26g/100g, and enoxolone conversion ratio is 24.29%, and yield is 10.98%, contains
Measure as 78.89g/100g.
Embodiment 5
Present embodiment discloses one kind by glycyrrhizic acid through subcritical hydrolysis reaction prepare Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide and
The method of enoxolone, comprises the following steps:
(1) material dissolution: at 65 DEG C, glycyrrhizic acid is dissolved in 90% ethanol-water solution, is subsequently adding acetic acid and adjusts
Ph=2, obtains the Radix Glycyrrhizae acid solution that concentration is 1.2%；
(2) subcritical hydrolysis reaction: by high pressure pump, Radix Glycyrrhizae acid solution is pumped in subcritical reaction kettle, in high temperature
It is stirred under high pressure reacting, reaction temperature is 180 DEG C, pressure is 7mpa, the time is 90min, speed of agitator is 250rpm, instead
After should terminating, collect reactant liquor；
(3) centrifugal treating: above-mentioned reactant liquor obtains clear liquor, centrifugal rotational speed 4200rpm, time 10min through centrifugal treating；
(4) separating treatment: using acetone, extract and separate is carried out to clear liquor, obtain aqueous phase and organic faciess, repeat to extract 3
Secondary, combining extraction liquid；
(5) concentration: aqueous phase is carried out concentration by vacuum evaporation, evaporating temperature is 40 DEG C, vacuum is
0.07mpa, is concentrated into soluble solid content (brix) and reaches 30%, obtain concentrated solution；
(6) redissolution is processed: is removed the solvent in machine phase by being evaporated in vacuo, is then redissolved with dehydrated alcohol, anhydrous second
Alcohol: wet slag=3:1 (v/w), obtain ethanol and redissolve liquid；
(7) dried: concentrated solution is adopted with spray drying method, inlet temperature is 180 DEG C, outlet temperature is 80 DEG C, obtains
To Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide；Ethanol is redissolved with liquid using revolution boulton process, baking temperature is 40 DEG C, and vacuum is
0.08mpa, obtains enoxolone.
During made above, glycyrrhizic acid conversion ratio is 89.31%, and Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide conversion ratio is
3.48%, yield is 1.66%, content 75.23g/100g, and enoxolone conversion ratio is 34.61%, and yield is 16.26%, contains
Measure as 76.62g/100g.
Embodiment 6
Present embodiment discloses one kind prepares Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide by Radix Glycyrrhizae extractum through subcritical hydrolysis reaction
With the method for enoxolone, comprise the following steps:
(1) material dissolution: at 65 DEG C, Radix Glycyrrhizae extractum is dissolved in 30% ethanol-water solution, is subsequently adding acetic acid and adjusts
Section ph=3, obtains the Radix Glycyrrhizae acid solution that concentration is 0.8%；
(2) subcritical hydrolysis reaction: by high pressure pump, Radix Glycyrrhizae acid solution is pumped in subcritical reaction kettle, in high temperature
It is stirred under high pressure reacting, reaction temperature is 140 DEG C, pressure is 11mpa, the time is 70min, speed of agitator is 250rpm,
After reaction terminates, collect reactant liquor；
(3) centrifugal treating: above-mentioned reactant liquor obtains clear liquor, centrifugal rotational speed 4200rpm, time 10min through centrifugal treating；
(4) separating treatment: using n-butyl alcohol, extract and separate is carried out to clear liquor, obtain aqueous phase and organic faciess, repeat to extract 3
Secondary, combining extraction liquid；
(5) concentration: aqueous phase is carried out concentration by vacuum evaporation, evaporating temperature is 60 DEG C, vacuum is
0.08mpa, is concentrated into soluble solid content (brix) and reaches 25%, obtain concentrated solution；
(6) redissolution is processed: by being evaporated in vacuo the solvent removing in organic faciess, after solvent removes, multiple with dehydrated alcohol
Molten, dehydrated alcohol: wet slag=3:1 (v/w), obtain ethanol and redissolve liquid；
(7) dried: concentrated solution is adopted with spray drying method, inlet temperature is 200 DEG C, outlet temperature is 85 DEG C, obtains
To Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide；Ethanol is redissolved with liquid using revolution boulton process, baking temperature is 60 DEG C, and vacuum is
0.09mpa, obtains enoxolone.
During made above, glycyrrhizic acid conversion ratio is 65.31%, and Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide conversion ratio is
9.97%, yield is 5.96%, content 77.23g/100g, and enoxolone conversion ratio is 16.61%, and yield is 6.67%, content
For 76.86g/100g.
Claims (8)
1. a kind of method that glycyrrhizin derivative is prepared in subcritical hydrolysis reaction, described glycyrrhizin derivative is single glucuronic acid
Enoxolone and enoxolone are it is characterised in that comprise the following steps:
(1) material dissolution: glycyrrhizic acid is dissolved in organic solvent, then adjusts ph to 1～3, obtain Radix Glycyrrhizae acid solution；Described sweet
The concentration of oxalic acid solution is 0.5～9%；
(2) subcritical hydrolysis reaction: by high pressure pump, Radix Glycyrrhizae acid solution is pumped in subcritical reaction kettle, in High Temperature High Pressure
Under be stirred react, reaction terminate after, collect reactant liquor；Described reaction temperature is 120～200 DEG C, and pressure is 5～11mpa,
Time is 20～90min, and speed of agitator is 100～250rpm；
(3) centrifugal treating: above-mentioned reactant liquor obtains clear liquor through centrifugal treating；
(4) separating treatment: using organic solvent, extract and separate is carried out to clear liquor, obtain aqueous phase and organic faciess；
(5) concentration: it is 25～40% that aqueous phase is concentrated into soluble solid content, obtains concentrated solution；
(6) redissolution is processed: first removes the solvent in organic faciess, is then redissolved with dehydrated alcohol, obtains ethanol and redissolve liquid；
(7) dried: liquid is redissolved to concentrated solution and ethanol and is dried process respectively, obtain Glycyrrhetic acid 3-O-mono-BETA-D-glucuronide
And enoxolone.
2. a kind of subcritical hydrolysis reaction according to claim 1 prepare glycyrrhizin derivative method it is characterised in that:
Organic solvent described in step (1) is 10～90% ethanol-water solution.
3. a kind of subcritical hydrolysis reaction according to claim 1 prepare glycyrrhizin derivative method it is characterised in that:
Regulation ph described in step (1) is to add acetic acid, sulphuric acid, nitric acid or hydrochloric acid to be adjusted.
4. a kind of subcritical hydrolysis reaction according to claim 1 prepare glycyrrhizin derivative method it is characterised in that:
Described in step (3), the condition of centrifugal treating is: rotating speed 4200rpm, time 10min.
5. a kind of subcritical hydrolysis reaction according to claim 1 prepare glycyrrhizin derivative method it is characterised in that:
Organic solvent described in step (4) is ethyl acetate, acetone, ether, n-butyl alcohol or chloroform.
6. a kind of subcritical hydrolysis reaction according to claim 1 prepare glycyrrhizin derivative method it is characterised in that:
The method of concentration described in step (5) is to be evaporated in vacuo, and temperature is 40～60 DEG C, and vacuum is 0.05～0.08mpa.
7. a kind of subcritical hydrolysis reaction according to claim 1 prepare glycyrrhizin derivative method it is characterised in that:
Step is dried process to concentrated solution in (7), and using spray drying method, inlet temperature is 160～200 DEG C, and outlet temperature is
80～85 DEG C.
8. a kind of subcritical hydrolysis reaction according to claim 1 prepare glycyrrhizin derivative method it is characterised in that:
In step (7), liquid is redissolved to ethanol and be dried process, using revolution boulton process, baking temperature is 40～60 DEG C, vacuum
Spend for 0.06～0.09mpa.
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