CN106380499A - Method for separating and recovering diosmin reaction products - Google Patents
Method for separating and recovering diosmin reaction products Download PDFInfo
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- CN106380499A CN106380499A CN201610779045.2A CN201610779045A CN106380499A CN 106380499 A CN106380499 A CN 106380499A CN 201610779045 A CN201610779045 A CN 201610779045A CN 106380499 A CN106380499 A CN 106380499A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/06—Benzopyran radicals
- C07H17/065—Benzo[b]pyrans
- C07H17/07—Benzo[b]pyran-4-ones
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- C01B7/00—Halogens; Halogen acids
- C01B7/13—Iodine; Hydrogen iodide
- C01B7/14—Iodine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
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Abstract
The invention provides a method for separating and recovering diosmin reaction products. The method is characterized in that a first mixing solution after a diosmin preparation reaction is provided; the first mixing solution is subjected to underpressure distillation and separation to obtain an organic solvent and a mixture; the organic solvent is subjected to rectification and then is circularly used; the mixture is subjected to crude crystallization and primary filtering; a filtrate after primary filtering is subjected to decolouring and an oxidation reaction, then second filtering is carried out after second filtering, the precipitates are separated, and iodine is obtained. The provided method has the simple process, by separating and recovering the products in each step of the diosmin preparation processes, diosmin with high yield and purity can be obtained, and the recovery rate of the organic solvent and iodine is high.
Description
Technical field
The present invention relates to pharmaceutical field is and in particular to a kind of separation and recovery method of diosmin product.
Background technology
Diosmin, chemical name is Diosmin, that is, (7- [6-O- (6- deoxidation-
α-L- mannose)-β-D- Glucopyranose .] epoxide } -5- hydroxyl -2- (3- hydroxyl -4- methoxybenzene) -4H-L- .alpha.-5:6-benzopyran -
4- ketone).
Diosmin feeds back system and has comprehensive effect to blood vessel, and it is to Venous system, microcirculqtory system and lymph
System all plays the role of powerful.Diosmin is except significantly reducing sticking, dividing a word with a hyphen at the end of a line of leukocyte and vascular endothelial cell, suppression
Leukocyte disintegrate processed and release inflammatory mediator such as histamine, Kallidin I, complement, leukotriene, prostaglandin and removing are certainly
By base etc., it can also reduce blood viscosity, strengthen the flow velocity of erythrocyte, thus reducing microcirculatory stasis, clinically originally
Product are mainly used in treating chronic venous insufficiency.
Content in natural plants for the diosmin is very low, and the cost of extracting directly is high, and therefore it is all by oxygen
Change the chemosynthesis mode of Hesperidin to prepare.
Inevasible in the existing synthetic method preparing diosmin can be all reaction dissolvent using pyridine or morpholine,
Especially based on pyridine；Because pyridine, morpholine are difficult to eliminate as reaction dissolvent in last handling process, thus result in product
Dissolvent residual higher；Simultaneously as pyridine is two class organic solvents, Odor stimulation is larger, has larger murder by poisoning to human body
Effect, therefore the harm to environment and personnel is more apparent in process of production.
In addition, when preparing diosmin in prior art, the process of waste water and solvent process and need the plenty of time, and reclaim
Effect is bad, and is directed to the preparation method of high yield, highly purified diosmin it is necessary to carry out more post processing work, leads
Cause to separate and recovery process is complicated, and the recovery utilization rate of solvent and raw material is not high.
Content of the invention
It is an object of the invention to provide a kind of process is simple, and iodine and the high diosmin reaction of the organic solvent response rate are produced
The separation and recovery method of thing.
For solving above-mentioned technical problem, the present invention provides a kind of separation and recovery method of diosmin product, including：
Diosmin is provided to prepare reacted first mixed solution；
Described first mixed solution vacuum distillation is separated and obtains organic solvent and mixture；
Described organic solvent is used through rectification Posterior circle；
Described mixture is carried out coarse crystallization, and carries out filtering for the first time；
The first filtrate that described first time is filtrated to get carries out decolouring, oxidation reaction, carries out second after the completion of reaction
Filter, isolate precipitation, obtain iodine.
Preferably, described offer diosmin is prepared reacted first mixed solution and is specially：
The first mixed solution is obtained after amide solvent, Hesperidin are reacted with alkaline reagent Hybrid Heating.
Preferably, control during described vacuum distillation described first mixed solution temperature be 90～110 DEG C, pressure be 0.07～
0.09MPa.
Preferably, diosmin crude product, sodium iodide, unreacted alkali liquor are at least included in described mixture.
Preferably, the first filtrate that described first time is filtrated to get is carried out decolouring, oxidation reaction, specially：
Described first filtrate is concentrated, and adds the activated carbon of the first filtrate volume 1～1.5% to carry out at decolouring
Reason；
The first filtrate after desolventing technology is mixed with oxidant, carries out oxidation reaction.
Preferably, described oxidant is peroxide and the mixture of acid.
Preferably, described peroxide is hydrogen peroxide or hydrogen persulfide, and described acid is concentrated sulphuric acid, concentrated hydrochloric acid, concentrated nitric acid
One or more of.
Preferably, the mass ratio of described hydrogen peroxide and described concentrated hydrochloric acid is (2～4): (12～15).
Preferably, also include
The filter cake that described first time is filtrated to get carries out re-dissolved successively, third time filters, recrystallization, the 4th mistake
Filter；
The filtration cakes torrefaction being filtrated to get for described 4th time is pulverized, obtains diosmin.
The invention provides a kind of separation and recovery method of diosmin product, a kind of diosmin product
Separation and recovery method, including：Diosmin is provided to prepare reacted first mixed solution；By described first mixed solution decompression
Separated obtains organic solvent and mixture；Described organic solvent is used through rectification Posterior circle；Described mixture is entered
Row coarse crystallization, and carry out filtering for the first time；The first filtrate that described first time is filtrated to get carries out decolouring, oxidation reaction, instead
Carry out second filtration after the completion of answering, isolate precipitation, obtain iodine.The separation and recovery method that the present invention provides is after adjustment
The processing step of diosmin and type of organic solvent, mate different solvent recovery and iodine recovery process, because the present invention makes
It is amide solvent, amide solvent is good to dissolubilities such as inorganic base or salt, its fusing point is larger with the gap of water, Neng Goutong
Cross relatively mild condition to be reclaimed and separated.Further, since iodine first can be anti-with Hesperidin in diosmin preparation process
Answer, then form the inorganic salt of iodine after hydrolysis, and the filtrate after all coarse crystallization is carried out oxidation reaction, reclaim elemental iodine,
Efficiently iodine can be reclaimed, and be recycled.And multiple times of filtration inherently improves one of method of diosmin yield, institute
High yield and purity diosmin can be accessed with the separation and recovery method that the present invention provides, the returning of organic solvent and iodine
Yield is again high.The present invention can pass through a response path during separation and recovery, reclaim iodine and organic solvent simultaneously, can
The water content of organic solvent is made to reach less than 2%.Purity >=95% of iodine, yield is 83～86%.
Be shown experimentally that, the present invention provide method can efficient recovery iodine and organic solvent, and obtain high yield and
Highly purified diosmin.
Specific embodiment
Below in conjunction with the embodiment of the present invention, the technical scheme in the embodiment of the present invention is clearly and completely described,
Obviously, described embodiment is only a part of embodiment of the present invention, rather than whole embodiments.Based on the reality in the present invention
Apply example, those of ordinary skill in the art under the premise of not making creative work, the every other embodiment that obtained, all belong to
In the scope of the present invention.It should be noted that the equipment of all filtration steps of the present invention all preferably uses plate filter.
A kind of separation and recovery method of diosmin product, including：
Diosmin is provided to prepare reacted first mixed solution；
Described first mixed solution vacuum distillation is separated and obtains organic solvent and mixture；
Described organic solvent is used through rectification Posterior circle；
Described mixture is carried out coarse crystallization, and carries out filtering for the first time；
The first filtrate that described first time is filtrated to get carries out decolouring, oxidation reaction, carries out second after the completion of reaction
Filter, isolate precipitation, obtain iodine.
According to the present invention, described separation and recovery method is the waste liquid and by-product by obtaining in the preparation process of diosmin
Thing is carried out, and mates optimum diosmin preparation technology, so also including while reclaiming：Described first time is filtered
The filter cake obtaining carries out re-dissolved successively, third time filters, recrystallization, the 4th filtration；
The filtration cakes torrefaction being filtrated to get for described 4th time is pulverized, obtains diosmin.
According to the present invention, described offer diosmin is prepared reacted first mixed solution and is specially：Amide-type is molten
Agent, Hesperidin obtain the first mixed solution with alkaline reagent Hybrid Heating after reacting.Control described first during described vacuum distillation
Mixed solution temperature is 90～110 DEG C, and pressure is 0.07～0.09MPa.
According to the present invention, described use described organic solvent through rectification Posterior circle is specially：
Described organic solvent entrance Multistage rectifying tower is carried out distillation operation, and diosmin is entered by blood circulation
Prepare in reaction vessel, recycle.Described organic solvent carries out rectification in following condition：
Table 1：Three-level rectification parameters
| Rectification series | Bottom temperature DEG C | Reflux ratio | Recovery ratio |
| One-level rectification | 98～100 | 2.5 | 88%～90% |
| Two-stage rectification | 94～96 | 2.7 | 91%～93% |
| Three-level rectification | 90～92 | 2.9 | 94%～96% |
The water content finally giving the organic solvent of recovery is less than 2%.
According to the present invention, after separation obtains mixture, carry out reclaiming the operation of iodine, in described mixture, at least include ground
Ao Siming crude product, sodium iodide, unreacted alkali liquor.
The purpose of high-purity iodine to be reclaimed to meet the present invention, the first filtrate that described first time is filtrated to get is carried out
Decolouring, oxidation reaction, specially：Described first filtrate is concentrated, and is added the activity of the first filtrate volume 1～1.5%
Charcoal carries out desolventing technology；The first filtrate after desolventing technology is preferably adjusted pH value mix with oxidant again for 1.5～2, carry out
Oxidation reaction.
According to the present invention, described oxidant is preferably peroxide and the mixture of acid.It is further preferred that described peroxide is
Hydrogen peroxide or hydrogen persulfide, described acid is one or more of concentrated sulphuric acid, concentrated hydrochloric acid, concentrated nitric acid.
Most preferably, described oxidant carries out oxidation reaction by hydrogen peroxide and concentrated hydrochloric acid compatibility, obtains iodine, described peroxide
Changing hydrogen and the mass ratio of described concentrated hydrochloric acid is (2～4): (12～15).According to the present invention, the concentration of described hydrogen peroxide is preferably
30%～40%, the concentration of described concentrated hydrochloric acid is preferably 30%～40%.
According to the present invention, in order to obtain highly purified iodine and organic solvent it is necessary to carry out multiple concentration and filtration, but
It is with by controlling cost and time-consuming raising efficiency, the scheme of being preferably as follows is operated, described first time mistake in the present invention
Filter is specially：
Crystal solution after coarse crystallization is passed through to be filtrated to get the first filtrate and the first filter cake for the first time；By described first filter cake
Carry out washing and obtain cleaning mixture；Described first filtrate is carried out reclaiming iodine operation, described cleaning mixture carries out waste water reclamation.Will be described
The first filter cake after washing carries out re-dissolved, and the lysate after re-dissolved passes through third time and filters, and obtains the 3rd filtrate and the 3rd
Filter cake；Described 3rd filtrate is carried out fine straining, obtains fine straining liquid. and described fine straining liquid is carried out recrystallization, by described recrystallization
Reactant liquor after end carries out the 4th filtration, obtains the 4th filtrate and the 4th filter cake；
Described 4th filter cake is washed, is obtained the 5th filtrate and the 5th filter cake；Described 5th filtrate carries out waste water and returns
Receive, after the 5th filtration cakes torrefaction, pulverize the highly purified diosmin being present invention preparation.
Below for the specific preparation technology of diosmin of present invention coupling.The present invention does not have to the source of all raw materials
Special restriction, is commercially available.In the present invention, the specific preparation technology of described diosmin is by amide solvent, orange
Skin glycosides is mixed with alkaline reagent, obtains material liquid；Material liquid is mixed with iodine, reacting by heating, obtain diosmin.
Wherein, described amide solvent is amide solvent well known to those skilled in the art, has no special limit
System, is preferably methylacetamide, ethyl acetamide, diformazan oxalamide, dimethyl acetylamide or dimethyl formyl in the present invention
Amine, more preferably dimethylformamide；The ratio of described amide solvent and Hesperidin is preferably (4～6) L: 1kg, more preferably
For (5～6) L: 1kg；Described alkaline reagent is alkaline reagent well known to those skilled in the art, has no special restriction,
It is preferably alkali metal hydroxide, more preferably sodium hydroxide in the present invention；Described alkaline reagent is preferably content and is more than 99%
Industrial primes；Described alkaline reagent is preferably (0.03～0.07) with the mass ratio of Hesperidin: 1, more preferably (0.04～
0.06)∶1；Described iodine is preferably the iodine that content is more than 99.5%；Described iodine is preferably (0.4～0.6) with the mass ratio of Hesperidin
: 1, more preferably 0.5: 1.
Amide solvent, Hesperidin are mixed with alkaline reagent, preferably first amide solvent is mixed with alkaline reagent, so
Add Hesperidin afterwards, more preferably first adjusted the pH value of amide solvent to 6～7 with alkaline reagent, then add Hesperidin,
Obtain material liquid.In the present invention, it is preferred to stir when adding Hesperidin, so that material is fully contacted with solvent.
Material liquid obtained above is mixed with iodine, carries out reacting by heating；The temperature of described reacting by heating is preferably 70 DEG C
～100 DEG C, more preferably 80 DEG C～100 DEG C, further preferably for 90 DEG C～100 DEG C；The time of described reacting by heating be preferably 13～
15h, more preferably 14h.
After reacting by heating terminates, preferably decompression and solvent recovery；Preferably control the temperature of reactant liquor during described decompression and solvent recovery
Spend for 90 DEG C～110 DEG C, more preferably 90 DEG C～100 DEG C decompression and solvent recoveries；Recovered temperature is observed at any time in removal process
With recovering state, preferably when reactant liquor is in thin viscous, stop solvent recovery；The yield of described solvent is preferably Hesperidin weight
3.4～3.8 times of amount, more preferably 3.6～3.8 times, further preferably for 3.7 times.
The present invention using amide solvent as the solvent of oxidation reaction, its easy recycling, environmental pollution is less, and
Compare and traditional pyridine or morpholine solvent, toxicity is lower, and in the product obtaining, solvent residues amount is low, soluble in water, be easy to locate
Reason, in the product solvent residues controlled within 10ppm；Meanwhile, in this course of reaction from Hesperidin to diosmin, degraded
Thing is few so that impurity content is less in product, and pyridine or morpholine solvent boiling point are all high, in equivalent responses bar on year-on-year basis for amide solvent
Under part, more difficult volatilization.
After solvent recovery terminates, water is added to be crystallized；This process is preferably and adds water to enter in thin viscous reactant liquor
Row stirring, adds water to stir 10～20min more preferably in thin viscous reactant liquor, adds water and stir 30～90min.
Add water crystallization, preferably crystallization liquid temp is down to 30 DEG C～40 DEG C, is more preferably down to 33 DEG C～37 DEG C, further preferably drops
To after 35 DEG C, filter.
After filtration, preferably wash filter cake with water, after the liquid pH value more preferably flowing out to washing filter cake is 6～7, washing knot
Bundle.
After washing terminates, preferred pair filter cake carries out pneumatics；The pressure of described pneumatics is preferably 0.07～0.09MPa；Described
The time of pneumatics is preferably 2～4h, more preferably 2.5～3.5h, further preferably for 3h.
For obtaining impure less diosmin, preferably carry out secondary dissolution filter.First-selection pneumatics is processed after filter
Cake and alkaline solution mixed dissolution；Described alkaline solution is the aqueous solution of alkaline reagent；Alkaline reagent in described alkaline solution
For alkaline reagent well known to those skilled in the art, have no special restriction, in the present invention, be preferably alkali metal hydroxide
Thing, more preferably sodium hydroxide；Alkaline reagent in described alkaline solution is preferably (0.1～0.5) with the mass ratio of Hesperidin:
1, more preferably (0.2～0.4): 1, further preferably for 0.3: 1；The time of described mixing preferably 0.5～2h, more preferably 1～
1.5h, further preferably for 1h.
After mixing, preferably add water stirring；Preferably stir 10～60min, more preferably stir 20～50min, further preferably
Stirring 30～40min, most preferably stirs 30min.
After stirring, preferably stand 2～6h, more preferably stand 3～5h, further preferably stand 3～4h, most preferably stand 3h.Quiet
Postpone filtration, obtain filtrate.
In the present invention, in order to reduce impurity, preferably filtrate is filtered with fine filter, obtained the filtrate of fine straining.
After fine straining, carry out secondary crystallization.Preferably by the filtrate of fine straining and mixed in hydrochloric acid in the present invention；The quality of described hydrochloric acid
It is preferably (0.64～0.92) with the mass ratio of Hesperidin: 1；The concentration of described hydrochloric acid is preferably 30%～40%, more preferably
35%～40%, further preferably for 36%；Being preferably added to hydrochloric acid in the present invention and making the pH value of filtrate is 5～6；Described mixing when
Between be preferably 1～2h, more preferably 1～1.5h.
After mixing, filter, obtain filter cake；After preferably washing filter cake with water, it is dried, obtains diosmin.Described drying
Temperature is preferably 100 DEG C～130 DEG C；The time of described drying is preferably 10～16h；After being dried to 10h, sample in good time, use
Fast tester for water content detects moisture, when the moisture in sample is less than 5%, stops drying.
The present invention using amide solvent as reaction dissolvent, its small toxicity, soluble in water, be easy to process, thus making to obtain
Product in solvent residues amount reduce.
In order to further illustrate the present invention, the preparation side to a kind of diosmin that the present invention provides with reference to embodiments
Method is described in detail.
In following examples reagent used be commercially available.
Embodiment 1
1.1 oxidation reaction：Open vacuum pump, by 1500L dimethylformamide with vacuum sucting reaction tank, and be hydrogenated with oxygen
The pH value changing sodium regulation solvent is between 6～7；Add 250.00kg Hesperidin, stir when feeding intake, make material abundant with solvent
Contact；125kg iodine is at the uniform velocity added retort to be reacted；Control retort temperature at 70 DEG C～100 DEG C, react 14h.
1.2 solvent recovery：After completion of the reaction, non-conservation tank and dehydration tank valve, closing volume valve are opened.Control material temperature
Degree starts decompression and solvent recovery between 90 DEG C～110 DEG C.Note at any time in removal process observing recovered temperature and recovering state,
When material is in thin viscous, stop solvent recovery, enter subsequent processing.Recovered solvent carries out rectification by three-level rectifying column,
Finally give the organic solvent that water content is 1.2%.The rectification parameters of rectifying column are as shown in table 1.
Table 1：Three-level rectification parameters
| Rectification series | Bottom temperature DEG C | Reflux ratio | Recovery ratio |
| One-level rectification | 98～100 | 2.5 | 88%～90% |
| Two-stage rectification | 94～96 | 2.7 | 91%～93% |
| Three-level rectification | 90～92 | 2.9 | 94%～96% |
1.3 crude crystalline, filtration, washing：Open retort vacuum valve, from retort top suction 1500L purified water, open
Dynamic blender, stirs 10～20min, adds 1500L purified water stirring 1h；After stirring accepts, when crystallization liquid temp is down to 35
After DEG C, crystal solution is pumped into filter press and is filtered, filtrate is temporary in storage tank；Rear sheet frame water nozzle no liquid stream to be filtered
After going out, 18000L purified water is pumped into filter press and is washed；Water lotion enters in anhydrous collecting pit and carries out sewage disposal,
Being washed to effluent pH detection paper pH value is 6～7, and beaker sampling is observed water lotion and answers achromaticity and clarification transparent；Washing terminates
Afterwards, close inlet valve, open pneumatics valve and carry out pneumatics, pneumatics Stress control maintains 3h in 0.07～0.09MPa, time；
Collect filter cake, load in turnover barrel, carry out mark.
1.4 2 dissolvings, filtration：Open dissolving tank stirring, in dissolving tank, 75kg alkali A is added 1300L purified water
In, until completely dissolved, add the filter cake in turnover barrel into tank；After filter cake adds continuation stirring 1h, add 1300L purification
Water enters in tank, stirs 30min, stands 3h；Filtrate is filtered once with filter press, the solution after filtration is through fine filter fine straining
Afterwards, pump in the crystallizer of clean area.
1.5 secondary crystallization：Open agitator, 160～230kg 36% hydrochloric acid is slowly put in the crystallizer of clean area, survey
The pH value of amount solution is between 5.0～6.0, and the pH value surveying solution after stirring 20min should be stablized and qualified, stir 1h, carry out this
The protocol of operation.
1.6 fine work filter, washing：Crystal solution is sucked in chamber filter press with vacuum, is filtered；After filtration finishes,
Washed with 18000～20000L purified water, after washing finishes, check that water lotion answers achromaticity and clarification transparent, filtrate is entered
Sewage disposal system.
1.7 fine work are dried：Open heated-air circulation oven, control temperature at 100 DEG C～130 DEG C, drying time is maintained at 10
～16h；After 10h is dried, samples in good time, measure moisture with fast tester for water content, when sample moisture is less than 5%, stop
It is dried；Close baking oven after drying is qualified, material bagging is transported to lower operation.
1.8 fine work are pulverized：With pulverizer, dried product is pulverized, smash and watt sieve as 80 mesh, obtain buchu department
Bright.
In embodiment 1, the quality standard of all raw materials is shown in Table 2.
Table 2 supplementary material quality standard
Diosmin yield computational methods：
Diosmin product yield=(diosmin fine work weight)/(Hesperidin weight) × 100%
Embodiment 2
According to the step in embodiment 1, orthogonal experiment is set, selects with reaction temperature (A), the response time (B) is as 2
Factor, factor A arranges four levels, and factor B arranges three levels, and factor level table is shown in Table 3.With diosmin content, always miscellaneous
Matter, yield, as 3 investigation projects, using orthogonal, screen to the oxidation reaction condition of diosmin, orthogonal
Experimental result is shown in Table 4, Orthogonal experiment results analysis in table 5.
Table 3 orthogonal test factor level table
| Level | A/℃ | B/h |
| 1 | 70 | 13 |
| 2 | 80 | 14 |
| 3 | 90 | 15 |
| 4 | 100 |
Table 4 orthogonal experiments table
Table 5 orthogonal experiments analytical table
Comprehensive analysis, optimum combination is A3B2, A3B3, A4B2, in this 3 best of breeds, based on content investigation, so
Select A3B2Combination, now the content of diosmin reaches peak, and total impurities reaches minimum, i.e. diosmin optimum oxidation
Reaction condition is：90 DEG C of reaction temperature, 14 hours response time.
Embodiment 3
According to the step in embodiment 1, orthogonal experiment is set, selects solvent recovery temperature, recycling design amount ratio respectively
As single factor test, respectively it is separately provided five levels, each level makees three tests, made with diosmin content, total impurities, yield
For 3 investigation projects, experimental result is shown in Table 6 and table 7, is counted according to experimental examination result, and the solvent of diosmin synthesis is returned
Receipt part is screened.
The multilevel 3 result of the test tables of table 6 single factor test (recovered temperature)
The multilevel 3 result of the test tables of table 7 single factor test (recycling design amount ratio)
By upper table comprehensive analysis, the content of diosmin, yield reach peak, when total impurities reaches minimum, solvent
Recovered temperature is 100 DEG C, 100 DEG C, 95 DEG C respectively, and recycling design amount ratio is 3.7 times, 3.6 times, 3.4 times respectively, and result all accords with
Close quality standard, wherein project is investigated for main with content, so diosmin solvent optimum recovery condition is：Recovered temperature
100 DEG C, 3.7 times of recycling design amount ratio.
Embodiment 4
According to the step in embodiment 1, orthogonal experiment is set, selects with dimethylformamide：Hesperidin, alkali A：Pericarpium Citri junoriss
Glycosides, iodine：Hesperidin (being weight ratio) arranges three levels, factor level table respectively as 3 factors A, B, C, each factor
It is shown in Table 8.Using diosmin content, total impurities, yield as 3 investigation projects, using L9(33) orthogonal, to buchu
Take charge of bright supplementary material use ratio to be screened.Data statistic analysis are shown in Table 9 and table 10.
Table 8 embodiment 4 orthogonal test factor level table
| Level | A/ times | B/ times | C/ times |
| 1 | 4 | 0.03 | 0.4 |
| 2 | 5 | 0.05 | 0.5 |
| 3 | 6 | 0.07 | 0.6 |
Table 9 embodiment 4 orthogonal experiments table
| Sequence number | A | B | C | Content/% | Total impurities/% | Yield/% |
| 1 | 4 | 0.03 | 0.4 | 92.5 | 5.42 | 85.1 |
| 2 | 4 | 0.05 | 0.5 | 93.1 | 5.23 | 85.4 |
| 3 | 4 | 0.07 | 0.6 | 92.7 | 5.56 | 85.2 |
| 4 | 5 | 0.03 | 0.6 | 93.2 | 4.68 | 85.1 |
| 5 | 5 | 0.05 | 0.4 | 93.4 | 4.43 | 85.5 |
| 6 | 5 | 0.07 | 0.5 | 93.5 | 4.35 | 85.7 |
| 7 | 6 | 0.03 | 0.5 | 94.4 | 4.98 | 86.6 |
| 8 | 6 | 0.05 | 0.6 | 93.8 | 5.12 | 86.2 |
| 9 | 6 | 0.07 | 0.4 | 94.2 | 5.06 | 86.1 |
Table 10 embodiment 4 orthogonal experiments analytical table
Comprehensive analysis, optimum combination is A3B3C2, A2B2C2, A3B2C2, in this 3 best of breeds, to investigate content it is
Main, so selecting A3B2C2Combination, now the content of diosmin, yield all reach peak, and total impurities reaches minimum, that is,
Diosmin optimal supplementary material use ratio is：Dimethylformamide: Hesperidin=6: the sodium hydroxide adding during 1 oxidation reaction
: Hesperidin=0.05: 1, iodine: Hesperidin=0.5: 1.
Diosmin crude crystalline liquid, through filtering, obtains the first filtrate, takes the first filtrate, be concentrated into thin viscous, adds
The activated carbon of the first filtrate volume 1～1.5% carries out desolventing technology, is eventually adding the first filtrate volume 2.9～3.6% mass
Hydrogen peroxide and the concentrated hydrochloric acid of the first filtrate volume 12.9～14.3% mass, take and iodinate, finally wash, drain, must contain
Measure as >=95%, yield is that 83～86% high-quality reclaims iodine.
Embodiment 5
According to iodine recovery process, orthogonal test is set, selects with activated carbon：First filtrate volume, hydrogen peroxide：First filter
Liquid amasss, concentrated hydrochloric acid：First filtrate volume (being plastid ratio) arranges three water respectively as 3 factors A, B, C, each factor
Flat, factor level table is shown in Table 11.To reclaim content of iodine, yield as 2 investigation projects, using Orthogonal Experiment and Design, iodine is returned
The supplementary material use ratio received is screened.Data statistic analysis are shown in Table 12 and table 13.
Table 11 iodine reclaims orthogonal test factor level table
| Level | A/% | B/% | C/% |
| 1 | 1 | 2.9 | 12.9 |
| 2 | 1.25 | 3.25 | 13.6 |
| 3 | 1.5 | 3.6 | 14.3 |
Table 12 iodine reclaims orthogonal experiments table
Table 13 iodine reclaims orthogonal experiments analytical table
Comprehensive analysis, optimum combination is A1B3C2, now reclaim the content of iodine, yield all reaches peak, that is, reclaim iodine
Good supplementary material use ratio is：Activated carbon：First filtrate volume=1%, hydrogen peroxide：First filtrate volume=3.6%, dense salt
Acid：First filtrate volume=13.6%.
Above a kind of separation and recovery method of diosmin product provided by the present invention is described in detail.
Specific case used herein is set forth to the principle of the present invention and embodiment, and the explanation of above example is to use
Understand the method for the present invention and its core concept in help.It should be pointed out that for those skilled in the art,
Under the premise without departing from the principles of the invention, the present invention can also be carried out with some improvement and modify, these improve and modify
Fall in the protection domain of the claims in the present invention.
Claims (9)
1. a kind of separation and recovery method of diosmin product is it is characterised in that include：
Diosmin is provided to prepare reacted first mixed solution；
Described first mixed solution vacuum distillation is separated and obtains organic solvent and mixture；
Described organic solvent is used through rectification Posterior circle；
Described mixture is carried out coarse crystallization, and carries out filtering for the first time；
The first filtrate that described first time is filtrated to get carries out decolouring, oxidation reaction, carries out second filtration after the completion of reaction,
Isolate precipitation, obtain iodine.
2. separation and recovery method according to claim 1 it is characterised in that described offer diosmin prepare reacted
First mixed solution is specially：
The first mixed solution is obtained after amide solvent, Hesperidin are reacted with alkaline reagent Hybrid Heating.
3. separation and recovery method according to claim 1 is it is characterised in that control during described vacuum distillation described first to mix
Close solution temperature and be 90～110 DEG C, pressure is 0.07～0.09MPa.
4. separation and recovery method according to claim 1 is it is characterised in that at least include diosmin in described mixture
Crude product, sodium iodide, unreacted alkali liquor.
5. separation and recovery method according to claim 1 it is characterised in that described first time be filtrated to get first filter
Liquid carries out decolouring, oxidation reaction, specially：
Described first filtrate is concentrated, and adds the activated carbon of the first filtrate volume 1～1.5% to carry out desolventing technology；
The first filtrate after desolventing technology is adjusted pH to 1.5～2 with acid, then mixes with oxidant, carry out oxidation reaction.
6. separation and recovery method according to claim 5 is it is characterised in that described oxidant is peroxide and sour mixing
Compound.
7. separation and recovery method according to claim 6 is it is characterised in that described peroxide is hydrogen peroxide or over cure
Change hydrogen, described acid is one or more of concentrated sulphuric acid, concentrated hydrochloric acid, concentrated nitric acid.
8. separation and recovery method according to claim 7 is it is characterised in that the matter of described hydrogen peroxide and described concentrated hydrochloric acid
Amount ratio is (2～4): (12～15).
9. separation and recovery method according to claim 1 is it is characterised in that also include
The filter cake that described first time is filtrated to get carries out re-dissolved successively, third time filters, recrystallization, the 4th filtration；
The filtration cakes torrefaction being filtrated to get for described 4th time is pulverized, obtains diosmin.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108558972A (en) * | 2018-03-28 | 2018-09-21 | 四川青益纯医药科技有限公司 | A kind of preparation method of high-purity diosmin |
| CN108862199A (en) * | 2018-06-28 | 2018-11-23 | 广东先导稀材股份有限公司 | The method of iodine is recycled in the waste liquid of trimethyl gallium containing iodine |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101089009A (en) * | 2006-06-16 | 2007-12-19 | 四川协力制药有限公司 | Diosmin producing process |
| WO2010092592A2 (en) * | 2009-02-11 | 2010-08-19 | Elder Pharmaceuticals Ltd. | Process for the preparation of diosmin |
| CN102070689A (en) * | 2011-01-25 | 2011-05-25 | 湖南圆通药业有限公司 | Method for producing diosmin |
| CN102875621A (en) * | 2012-10-26 | 2013-01-16 | 成都澜绮制药有限公司 | Synthesis method of diosmin |
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- 2016-08-30 CN CN201610779045.2A patent/CN106380499A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101089009A (en) * | 2006-06-16 | 2007-12-19 | 四川协力制药有限公司 | Diosmin producing process |
| WO2010092592A2 (en) * | 2009-02-11 | 2010-08-19 | Elder Pharmaceuticals Ltd. | Process for the preparation of diosmin |
| CN102070689A (en) * | 2011-01-25 | 2011-05-25 | 湖南圆通药业有限公司 | Method for producing diosmin |
| CN102875621A (en) * | 2012-10-26 | 2013-01-16 | 成都澜绮制药有限公司 | Synthesis method of diosmin |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108558972A (en) * | 2018-03-28 | 2018-09-21 | 四川青益纯医药科技有限公司 | A kind of preparation method of high-purity diosmin |
| CN108862199A (en) * | 2018-06-28 | 2018-11-23 | 广东先导稀材股份有限公司 | The method of iodine is recycled in the waste liquid of trimethyl gallium containing iodine |
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