CN106008619B - The preparation method of neohesperidin dihydrochalcone - Google Patents
The preparation method of neohesperidin dihydrochalcone Download PDFInfo
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- 239000001329 FEMA 3811 Substances 0.000 title claims abstract description 77
- ITVGXXMINPYUHD-CUVHLRMHSA-N neohesperidin dihydrochalcone Chemical compound C1=C(O)C(OC)=CC=C1CCC(=O)C(C(=C1)O)=C(O)C=C1O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 ITVGXXMINPYUHD-CUVHLRMHSA-N 0.000 title claims abstract description 77
- 229940089953 neohesperidin dihydrochalcone Drugs 0.000 title claims abstract description 77
- 235000010434 neohesperidine DC Nutrition 0.000 title claims abstract description 77
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 238000006243 chemical reaction Methods 0.000 claims abstract description 131
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 108
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 81
- 239000013078 crystal Substances 0.000 claims abstract description 63
- 238000010828 elution Methods 0.000 claims abstract description 60
- 239000000243 solution Substances 0.000 claims abstract description 58
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 54
- 239000000706 filtrate Substances 0.000 claims abstract description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 39
- 239000001257 hydrogen Substances 0.000 claims abstract description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 38
- 239000012670 alkaline solution Substances 0.000 claims abstract description 35
- 239000003054 catalyst Substances 0.000 claims abstract description 32
- ARGKVCXINMKCAZ-UZRWAPQLSA-N neohesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@H]3[C@@H]([C@H](O)[C@@H](O)[C@H](C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UZRWAPQLSA-N 0.000 claims abstract description 30
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000003480 eluent Substances 0.000 claims abstract description 28
- 238000004108 freeze drying Methods 0.000 claims abstract description 28
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000001914 filtration Methods 0.000 claims abstract description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 238000010521 absorption reaction Methods 0.000 claims abstract description 20
- 239000011347 resin Substances 0.000 claims abstract description 20
- 229920005989 resin Polymers 0.000 claims abstract description 20
- 238000003756 stirring Methods 0.000 claims abstract description 20
- 239000007788 liquid Substances 0.000 claims abstract description 19
- 238000006073 displacement reaction Methods 0.000 claims abstract description 16
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 16
- 238000000605 extraction Methods 0.000 claims abstract description 12
- 238000001179 sorption measurement Methods 0.000 claims abstract description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 37
- 230000008569 process Effects 0.000 claims description 32
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 26
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 25
- 238000012545 processing Methods 0.000 claims description 25
- 229910001220 stainless steel Inorganic materials 0.000 claims description 22
- 239000010935 stainless steel Substances 0.000 claims description 22
- 230000005684 electric field Effects 0.000 claims description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 14
- 239000011259 mixed solution Substances 0.000 claims description 14
- 238000002347 injection Methods 0.000 claims description 13
- 239000007924 injection Substances 0.000 claims description 13
- 239000007921 spray Substances 0.000 claims description 13
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 9
- 239000004202 carbamide Substances 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 4
- 238000000859 sublimation Methods 0.000 claims description 4
- 230000008022 sublimation Effects 0.000 claims description 4
- 238000010792 warming Methods 0.000 claims description 4
- 230000005611 electricity Effects 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 abstract description 17
- 230000008025 crystallization Effects 0.000 abstract description 17
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 239000012141 concentrate Substances 0.000 description 14
- 239000007789 gas Substances 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 11
- 229910052763 palladium Inorganic materials 0.000 description 8
- 239000000126 substance Substances 0.000 description 6
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 235000019640 taste Nutrition 0.000 description 5
- 241000208340 Araliaceae Species 0.000 description 4
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 4
- 235000003140 Panax quinquefolius Nutrition 0.000 description 4
- 235000008434 ginseng Nutrition 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 125000003147 glycosyl group Chemical group 0.000 description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 238000011017 operating method Methods 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 241001529246 Platymiscium Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 235000005513 chalcones Nutrition 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- -1 crystallization Substances 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical compound C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 description 1
- PXLWOFBAEVGBOA-UHFFFAOYSA-N dihydrochalcone Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=CC(C(=O)CC(O)C=2C=CC(O)=CC=2)=C1O PXLWOFBAEVGBOA-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011265 semifinished product Substances 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/203—Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- 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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a kind of preparation methods of neohesperidin dihydrochalcone, including：(1) neohesperidin and alkaline solution are added in reaction kettle, stirring and dissolving, add catalyst palladium carbon, closed reactor, with the air in nitrogen replacement reaction kettle, then it is passed through hydrogen displacement nitrogen at normal temperatures, it is stirred to react under normal pressure, after the completion of reaction, utilizes the hydrogen in nitrogen replacement reaction kettle, then stop reaction, extraction liquid；(2) reaction solution pH is adjusted to 5-6, is crystallized under room temperature, filtered, obtain crystal A；Obtained filtrate macroporous resin adsorption after absorption, with purifying water elution, removes the salt in filtrate；Then ethanol elution is used, eluent is collected, is concentrated, crystallization is obtained by filtration crystal B, merges crystal A and B, and freeze-drying is to get to neohesperidin dihydrochalcone.It is easy to operate, production cost is low using synthesizing neohesperidin dihydrochalcone under " one kettle way " normal temperature and pressure；Obtained neohesperidin dihydrochalcone purity is high.
Description
Technical field
The invention belongs to chemosynthesis technical fields, and in particular to a kind of preparation method of neohesperidin dihydrochalcone.
Background technology
Neohesperidin dihydrochalcone be from extracted in natural citrus platymiscium it is hydrogenated made of flavone derivative,
Have the characteristics that sugariness is big, clean taste, pleasant impression is lasting, low in calories, nontoxic, stability is good, sugariness about sucrose 1400~1800
Times, have the characteristics that splendid taste improvement, its sweet taste duration are longer, sweetener and screen taste agent is mainly used as, for eating
Improvement, enhancing and the overall improvement of product and drinks taste, have effects that splendid shielding bitter taste, when separately as a kind of artificial sweet tea
If taste agent use, a concentration of 15-20mg/L is added；It plays the role of unique enhancing mouthfeel, as synergist, it is only necessary to
The neohesperidin dihydrochalcone of addition 4-5mg/L just shows good flavor synergistic effect；As auxiliary pharmaceutical adjuvant, new orange
Skin glycosides dihydrochalcone can significantly inhibit the growth of Human Gastric carcinoma's cell strain, for gramnegative bacterium, Gram-positive
Bacterium and S. cervisiae have certain inhibiting effect；As feed addictive, can play the role of covering metallic aftertaste.More
Estimable is that the glycosyl of neohesperidin dihydrochalcone hydrolyzes in vivo, and glycosyl is almost not involved in metabolism,
So neohesperidin dihydrochalcone thermal energy value is relatively low, it is less than 8.36J/g, low-energy food sweetener can be used as.Its is right
Human-body safety is now widely used in food, health products, medicine and other fields.The traditional handicraft of neohesperidin dihydrochalcone
Middle hydrogen pressure is larger, safety is also reduced in addition to increasing technology difficulty, and high temperature is generally used during adding hydrogen
High pressure, it is more demanding to equipment and technology, it is unfavorable for operating, and dangerous larger, as patent document CN103804439A is disclosed
A kind of synthetic method of neohesperidin dihydrochalcone；Neohesperidin dihydrochalcone is being purified using traditional handicraft simultaneously
When, activated carbon decolorizing is added, increases operating procedure, the risk for introducing impurity in operation is also brought, in addition, using traditional handicraft
Obtained neohesperidin dihydrochalcone purity and yield is relatively low.
Invention content
It is excellent it is an object of the invention to solve at least the above and/or defect, and provide at least to will be described later
Point.
In order to realize these purposes and other advantages according to the present invention, a kind of neohesperidin dihydrochalcone is provided
Preparation method includes the following steps：
Step 1: being 1 by mass volume ratio:15~20 neohesperidin and alkaline solution is added in reaction kettle, and stirring is molten
Solution, adds catalyst palladium carbon, then closed reactor is passed through hydrogen at normal temperatures with the air in nitrogen replacement reaction kettle
Nitrogen is replaced, is stirred to react 10~15 hours, after the completion of reaction under normal pressure, using the hydrogen in nitrogen replacement reaction kettle, then
Stop reaction, extraction liquid；The mass ratio of the catalyst palladium carbon and neohesperidin is 1:15~20；
Step 2: reaction solution pH is adjusted to 5-6,10~15h is crystallized under room temperature, filtering obtains crystal A；Obtained filter
Liquid macroporous resin adsorption after absorption, with purifying water elution, removes the salt in filtrate；Then with the body of 15~20 times of column volumes
Fraction is 10~25% ethanol elutions, then the ethanol elution for being 30~60% with volume fraction, collects eluent, concentrates, knot
Crystalline substance, is obtained by filtration crystal B, merges crystal A and B, and freeze-drying is to get to neohesperidin dihydrochalcone.
Preferably, the mass fraction of the alkaline solution is 6~15%；The alkaline solution be sodium hydroxide solution,
Urea liquid, potassium hydroxide solution, weight ratio 1:2:Any one in 1 potassium hydroxide, urea and sodium bicarbonate solution.
Preferably, it is 40%~60% ethanol water that volume fraction is added in the alkaline solution；The ethanol water
The volume ratio of solution and alkaline solution is 1:10~30.
Preferably, the freeze-drying includes the following steps：
Step I, precooling：Cryogenic temperature -30~-50 DEG C, cooling time 1~3 hour keep crystal A and B contained humidity complete
Portion condenses into solid-state；
Step II will be warming up to 25 DEG C after precooling, be kept for 2~4 hours；
Step III, freeze-drying：The crystal that step II is obtained is added in vacuum freeze drier, and condenser temperature is arranged
It it is -50~-85 DEG C, vacuum degree is 500mpa~1000mpa, sublimation drying 12-24h, obtains neohesperidin dihydro Cha Er
Ketone.
Preferably, the step 1 replaces with following procedure：It is 1 by mass volume ratio:15~20 neohesperidin and
Alkaline solution stirring and dissolving, obtains mixed solution；It is 40%~60% ethanol water that volume fraction is added in a kettle, so
The air in nitrogen replacement reaction kettle, closed reactor are used afterwards；Mixed solution is ejected into closed reactor using electroblowing process
Ethanol water in, and ethanol water is stirred in course of injection；Reaction kettle is added in catalyst palladium carbon after the completion of injection
In, then it is passed through hydrogen displacement nitrogen at normal temperatures, closed reactor is stirred to react 10~15 hours, after the completion of reaction under normal pressure,
Using the hydrogen in nitrogen replacement reaction kettle, then stop reaction, extraction liquid；The catalyst palladium carbon and neohesperidin
Mass ratio is 1:15~20；The volume ratio of the ethanol water and alkaline solution is 1:10~30.
Preferably, the electroblowing process is：By mixed solution inject the spray containers with stainless steel nozzle in, it is described not
Rust steel nozzle stretches into closed reactor, and with the contact position of closed reactor using sealed connection；Then high-voltage electricity is used
Source applies the voltage on stainless steel nozzle, and is pumped the mixed solution in spray containers using the propulsion being connect with spray containers
It is sprayed into closed reactor by stainless steel nozzle；The injection conditions that electroblowing process uses for：The output voltage of high voltage power supply
For distance is 8~12cm, flow velocity is 10~15mL/ between ethanol water and stainless steel nozzle in 3~8kv, closed reactor
h；The internal diameter of the stainless steel nozzle is 1~2mm.
Preferably, in the step 2, reaction solution pH is adjusted under 5-6 and room temperature between crystallizing 10~15h and is also wrapped
Include following procedure：Reaction solution after adjusting pH is inputted in high-voltage pulse electric field processing chamber, at high-pressure pulse electric
Reason；The parameter of high-pressure pulse electric processing is：Impulse amplitude is 10~20KV, and pulse frequency is 800~1200Hz, pulse
Width is 8~15us, processing time 60-90min.
Preferably, the high-voltage pulse electric field processing chamber periphery is provided with cold water circulating system, wherein circulating water temperature
Degree is 1~5 DEG C, and water circulating speed is 2~5m/s；The spacing of two-plate is 1~3cm in the high-voltage pulse electric field processing chamber.
Preferably, after the collection eluent by eluent frequency is 20~30KHz, output power is 30~60W
Sound field under, be cooled to -5~0 DEG C with 5~10 DEG C/h of speed, crystal B is obtained by filtration in growing the grain 2~5 hours.
Preferably, the macroreticular resin is any one in macroreticular resin D101, D201, DM301, AB-8.
The present invention includes at least following advantageous effect：
(1) neohesperidin dihydrochalcone is synthesized at normal temperatures and pressures, by macroreticular resin to novel orange peel dihydro Cha Er
Ketone sample liquid is post-processed, and a large amount of salt in solution is eliminated with pure water, can be solved removing not increasing apparatus separately
Salt in solution reduces the operating procedure of post-processing.Using ethanol elution, the impurity in sample liquid, eluent second are removed
Alcohol is easily recycled and utilizes again, reduces production cost.To treated, semi-finished product liquid carries out recrystallization processing, and direct
Concentrated mother liquor crystalline phase ratio again, the method sample yield higher after crystallizing for the first time.With directly passing through the mother after condensing crystallizing
The method of liquid carries out secondary crystallization, reduces the impurity component in mother liquor relative to the content in solution so that crystallization is more held
Easily and person reduces crystallization time.
(2) using neohesperidin dihydrochalcone is synthesized under " one kettle way " normal temperature and pressure, neohesperidin is cyclic compound,
When open loop obtains neohesperidin chalcone under room temperature alkaline condition for it, then palladium carbon catalytic hydrogenation is used to synthesize neohesperidin dihydro
Chalcone.The Elements research such as the type of catalyst, reaction temperature, pressure and time, post processing mode are grasped by control
Work is simple, production cost is low, is suitable for the technological parameter that the neohesperidin dihydrochalcone of industrialized production synthesizes, and obtains high-quality
The neohesperidin dihydrochalcone of amount.
Part is illustrated to embody by further advantage, target and the feature of the present invention by following, and part will also be by this
The research and practice of invention and be understood by the person skilled in the art.
Description of the drawings：
Fig. 1 is the process flow chart of the preparation method of neohesperidin dihydrochalcone of the present invention；
Fig. 2 is the reaction unit figure of the preparation method of neohesperidin dihydrochalcone of the present invention.
Specific implementation mode：
Present invention will be described in further detail below with reference to the accompanying drawings, to enable those skilled in the art with reference to specification text
Word can be implemented according to this.
It should be appreciated that such as " having ", "comprising" and " comprising " term used herein do not allot one or more
The presence or addition of a other elements or combinations thereof.
Embodiment 1：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: the sodium hydroxide solution that 1kg neohesperidins and 15kg mass fractions are 6% is added in reaction kettle, stir
Dissolving is mixed, adds 0.05kg catalyst palladium carbons, closed reactor, with the air in nitrogen replacement reaction kettle, then in room temperature
Under be passed through hydrogen displacement nitrogen, be stirred to react 10 hours, after the completion of reaction under normal pressure, utilize the hydrogen in nitrogen replacement reaction kettle
Then gas stops reaction, extraction liquid；
Step 2: reaction solution pH is adjusted to 5,10h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole resin D101 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 15 times of column volumes
For 10% ethanol elution, then be 30% with volume fraction ethanol elution, collect eluent, concentrate, crystalline substance is obtained by filtration in crystallization
Body B merges crystal A and B, and freeze-drying is to get to neohesperidin dihydrochalcone；Yield is 88%, purity 98.5%.
Embodiment 2：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: the sodium hydroxide solution that 1kg neohesperidins and 20kg mass fractions are 15% is added in reaction kettle, stir
Dissolving is mixed, adds 0.06kg catalyst palladium carbons, closed reactor, with the air in nitrogen replacement reaction kettle, then in room temperature
Under be passed through hydrogen displacement nitrogen, be stirred to react 15 hours, after the completion of reaction under normal pressure, utilize the hydrogen in nitrogen replacement reaction kettle
Then gas stops reaction, extraction liquid；
Step 2: reaction solution pH is adjusted to 6,15h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole resin D101 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 20 times of column volumes
For 25% ethanol elution, then be 60% with volume fraction ethanol elution, collect eluent, concentrate, crystalline substance is obtained by filtration in crystallization
Body B merges crystal A and B, and freeze-drying is to get to neohesperidin dihydrochalcone；Yield is 89%, purity 98.8%.
Embodiment 3：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: the sodium hydroxide solution that 1kg neohesperidins and 18kg mass fractions are 10% is added in reaction kettle, stir
Dissolving is mixed, adds 0.0625kg catalyst palladium carbons, closed reactor, with the air in nitrogen replacement reaction kettle, then normal
It is passed through hydrogen displacement nitrogen under temperature, is stirred to react 12 hours, after the completion of reaction under normal pressure, utilizes the hydrogen in nitrogen replacement reaction kettle
Then gas stops reaction, extraction liquid；
Step 2: reaction solution pH is adjusted to 6,12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole resin D101 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 18 times of column volumes
For 20% ethanol elution, then be 40% with volume fraction ethanol elution, collect eluent, concentrate, crystalline substance is obtained by filtration in crystallization
Body B merges crystal A and B, and freeze-drying is to get to neohesperidin dihydrochalcone；Yield is 88.5%, purity 98.6%.
Embodiment 4：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: being 1 by mass volume ratio:18 neohesperidin and alkaline solution is added in reaction kettle, stirring and dissolving, then
Catalyst palladium carbon is added, then closed reactor is passed through hydrogen displacement nitrogen at normal temperatures with the air in nitrogen replacement reaction kettle
Gas is stirred to react 10 hours, after the completion of reaction under normal pressure, utilizes the hydrogen in nitrogen replacement reaction kettle, then stops reaction, is taken out
Go out reaction solution；The mass ratio of the catalyst palladium carbon and neohesperidin is 1:18；The mass fraction of the alkaline solution is 10%；
The alkaline solution is that weight ratio is 1:2:1 potassium hydroxide, urea and sodium bicarbonate solution；
Step 2: reaction solution pH is adjusted to 5,12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole Resin A B-8 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 18 times of column volumes
For 20% ethanol elution, then be 40% with volume fraction ethanol elution, collect eluent, concentrate, crystal is obtained by filtration in crystallization
B merges crystal A and B, and freeze-drying is to get to neohesperidin dihydrochalcone；Yield is 89.5%, purity 98.9%.
Embodiment 5：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: the sodium hydroxide solution that 1kg neohesperidins and 20kg mass fractions are 15% is added in reaction kettle, stir
Dissolving is mixed, adds 0.06kg catalyst palladium carbons, closed reactor, with the air in nitrogen replacement reaction kettle, then in room temperature
Under be passed through hydrogen displacement nitrogen, be stirred to react 15 hours, after the completion of reaction under normal pressure, utilize the hydrogen in nitrogen replacement reaction kettle
Then gas stops reaction, extraction liquid；It is 50% ethanol water that volume fraction is added in the sodium hydroxide solution；Institute
The volume ratio for stating ethanol water and sodium hydroxide solution is 1:20；
Step 2: reaction solution pH is adjusted to 6,15h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole resin D101 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 20 times of column volumes
For 25% ethanol elution, then be 60% with volume fraction ethanol elution, collect eluent, concentrate, crystalline substance is obtained by filtration in crystallization
Body B merges crystal A and B, and freeze-drying is to get to neohesperidin dihydrochalcone；Yield is 89%, purity 98.9%.
Embodiment 6：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: being 1 by mass volume ratio:18 neohesperidin and alkaline solution is added in reaction kettle, stirring and dissolving, then
Catalyst palladium carbon is added, then closed reactor is passed through hydrogen displacement nitrogen at normal temperatures with the air in nitrogen replacement reaction kettle
Gas is stirred to react 10 hours, after the completion of reaction under normal pressure, utilizes the hydrogen in nitrogen replacement reaction kettle, then stops reaction, is taken out
Go out reaction solution；The mass ratio of the catalyst palladium carbon and neohesperidin is 1:18；The mass fraction of the alkaline solution is 10%；
The alkaline solution is that weight ratio is 1:2:1 potassium hydroxide, urea and sodium bicarbonate solution；Body is added in the alkaline solution
Fraction is 50% ethanol water；The volume ratio of the ethanol water and alkaline solution is 1:25；
Step 2: reaction solution pH is adjusted to 5,12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole Resin A B-8 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 18 times of column volumes
For 20% ethanol elution, then be 40% with volume fraction ethanol elution, collect eluent, concentrate, crystal is obtained by filtration in crystallization
B merges crystal A and B, and freeze-drying is to get to neohesperidin dihydrochalcone；Yield is 90%, purity 99%.
Embodiment 7：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: the sodium hydroxide solution that 1kg neohesperidins and 16kg mass fractions are 10% is added in reaction kettle, stir
Dissolving is mixed, adds 0.06kg catalyst palladium carbons, closed reactor, with the air in nitrogen replacement reaction kettle, then in room temperature
Under be passed through hydrogen displacement nitrogen, be stirred to react 10 hours, after the completion of reaction under normal pressure, utilize the hydrogen in nitrogen replacement reaction kettle
Then gas stops reaction, extraction liquid；
Step 2: reaction solution pH is adjusted to 6,12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole resin D101 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 16 times of column volumes
For 25% ethanol elution, then be 60% with volume fraction ethanol elution, collect eluent, concentrate, crystalline substance is obtained by filtration in crystallization
Body B merges crystal A and B, freeze-drying；The freeze-drying includes the following steps：
Step I, precooling：- 50 DEG C of cryogenic temperature, cooling time 1 hour make crystal A and B contained humidity all condense into
Solid-state；
Step II will be warming up to 25 DEG C after precooling, be kept for 2 hours；
Step III, freeze-drying：The crystal that step II is obtained is added in vacuum freeze drier, and condenser temperature is arranged
It it is -85 DEG C, vacuum degree 1000mpa, sublimation drying for 24 hours, obtains neohesperidin dihydrochalcone；Yield is 91%, pure
Degree is 99.2%.
Embodiment 8：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: being 1 by mass volume ratio:16 neohesperidin and alkaline solution is added in reaction kettle, stirring and dissolving, then
Catalyst palladium carbon is added, then closed reactor is passed through hydrogen displacement nitrogen at normal temperatures with the air in nitrogen replacement reaction kettle
Gas is stirred to react 12 hours, after the completion of reaction under normal pressure, utilizes the hydrogen in nitrogen replacement reaction kettle, then stops reaction, is taken out
Go out reaction solution；The mass ratio of the catalyst palladium carbon and neohesperidin is 1:16；The mass fraction of the alkaline solution is 12%；
The alkaline solution is that weight ratio is 1:2:1 potassium hydroxide, urea and sodium bicarbonate solution；
Step 2: reaction solution pH is adjusted to 5,12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole Resin A B-8 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 15 times of column volumes
For 25% ethanol elution, then be 50% with volume fraction ethanol elution, collect eluent, concentrate, crystal is obtained by filtration in crystallization
B, merges crystal A and B, freeze-drying, and the freeze-drying includes the following steps：
Step I, precooling：- 40 DEG C of cryogenic temperature, cooling time 2 hours make crystal A and B contained humidity all condense into
Solid-state；
Step II will be warming up to 25 DEG C after precooling, be kept for 3 hours；
Step III, freeze-drying：The crystal that step II is obtained is added in vacuum freeze drier, and condenser temperature is arranged
It it is -60 DEG C, vacuum degree 800mpa, sublimation drying for 24 hours, obtains neohesperidin dihydrochalcone；Yield is 91.5%, pure
Degree is 99.28%.
Embodiment 9：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: by 1kg neohesperidins and 17kg potassium hydroxide solution stirring and dissolvings, mixed solution is obtained；In reaction kettle
Middle addition volume fraction is 60% ethanol water, then uses the air in nitrogen replacement reaction kettle, closed reactor；It will mixing
Solution is ejected into using electroblowing process in the ethanol water of closed reactor, and with the speed of 300r/min in course of injection
Stir ethanol water；0.0625kg catalyst palladium carbons are added in reaction kettle after the completion of injection, then are passed through hydrogen at normal temperatures
Nitrogen is replaced, closed reactor is stirred to react 10 hours, after the completion of reaction with 300r/min under normal pressure, is replaced using nitrogen anti-
The hydrogen in kettle is answered, reaction, extraction liquid are then stopped；The volume ratio of the ethanol water and potassium hydroxide solution is 1:
10；The electroblowing process is as shown in Figure 2：Mixed solution is injected in the spray containers 2 with stainless steel nozzle 4, it is described stainless
Steel nozzle 4 stretches into closed reactor 1, and with the contact position of closed reactor 1 using sealed connection；Then high-voltage electricity is used
Source 5 applies the voltage on stainless steel nozzle 4, and will be mixed in spray containers 2 using the propulsion pump 3 being connect with spray containers 2
Solution is closed to spray into closed reactor 1 by stainless steel nozzle 4；The injection conditions that electroblowing process uses for：High voltage power supply
Output voltage is 6kv, in closed reactor between ethanol water and stainless steel nozzle distance be 8cm, flow velocity 10mL/h；Institute
The internal diameter for stating stainless steel nozzle is 1.5mm；
Step 2: reaction solution pH is adjusted to 5,12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole Resin A B-8 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 15 times of column volumes
For 25% ethanol elution, then be 50% with volume fraction ethanol elution, collect eluent, concentrate, crystal is obtained by filtration in crystallization
B merges crystal A and B, and freeze-drying is to get to neohesperidin dihydrochalcone；Yield is 92.5%, purity 99.5%.
Embodiment 10：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: being 1 by mass volume ratio:15 neohesperidin and alkaline solution stirring and dissolving, obtains mixed solution；?
It is 40% ethanol water that volume fraction is added in reaction kettle, then uses the air in nitrogen replacement reaction kettle, closed reactor；
Mixed solution is ejected into using electroblowing process in the ethanol water of closed reactor, and stirs ethanol water in course of injection
Solution；Catalyst palladium carbon is added in reaction kettle after the completion of injection, then is passed through hydrogen displacement nitrogen, confined reaction at normal temperatures
Kettle is stirred to react 10 hours, after the completion of reaction under normal pressure, utilizes the hydrogen in nitrogen replacement reaction kettle, then stops reaction, is taken out
Go out reaction solution；The mass ratio of the catalyst palladium carbon and neohesperidin is 1:15；The body of the ethanol water and alkaline solution
Product is than being 1:20；The electroblowing process is：Mixed solution is injected in the spray containers with stainless steel nozzle, the stainless steel spray
Head stretches into closed reactor, and with the contact position of closed reactor using sealed connection；It then will be electric with high voltage power supply
Pressure is applied on stainless steel nozzle, and is passed through the mixed solution in spray containers not using the propulsion pump being connect with spray containers
Rust steel nozzle is sprayed into closed reactor；The injection conditions that electroblowing process uses for：The output voltage of high voltage power supply be 5kv,
In closed reactor between ethanol water and stainless steel nozzle distance be 10cm, flow velocity 12mL/h；The stainless steel nozzle
Internal diameter be 1mm；
Step 2: reaction solution pH is adjusted to 5,12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole resin adsorption after absorption, with purifying water elution, removes the salt in filtrate；Then it is with the volume fraction of 18 times of column volumes
20% ethanol elution, then with volume fraction be 50% ethanol elution, collect eluent, concentrate, crystallization, crystal B is obtained by filtration,
Merge crystal A and B, freeze-drying is to get to neohesperidin dihydrochalcone；Yield is 92.8%, purity 99.55%.
Embodiment 11：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: the sodium hydroxide solution that 1kg neohesperidins and 18kg mass fractions are 10% is added in reaction kettle, stir
Dissolving is mixed, adds 0.0625kg catalyst palladium carbons, closed reactor, with the air in nitrogen replacement reaction kettle, then normal
It is passed through hydrogen displacement nitrogen under temperature, is stirred to react 12 hours, after the completion of reaction under normal pressure, utilizes the hydrogen in nitrogen replacement reaction kettle
Then gas stops reaction, extraction liquid；
Step 2: reaction solution pH is adjusted to 6, then inputs in high-voltage pulse electric field processing chamber, utilize high-voltage pulse electric
Field is handled, and 12h is then crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is adsorbed with macroreticular resin D101, absorption
Afterwards, with purifying water elution, the salt in filtrate is removed；Then the ethanol elution for being 20% with the volume fraction of 18 times of column volumes, then
The ethanol elution for being 40% with volume fraction collects eluent, concentrates, and crystallization is obtained by filtration crystal B, merges crystal A and B, cold
It is lyophilized dry to get to neohesperidin dihydrochalcone；Yield is 92.5%, purity 99.6%；At the high-pressure pulse electric
The parameter of reason is：Impulse amplitude is 15KV, pulse frequency 800Hz, pulse width 10us, processing time 60min；It is described
High-voltage pulse electric field processing chamber periphery is provided with cold water circulating system, and wherein circulating water temperature is 3 DEG C, and water circulating speed is
4m/s；The spacing of two-plate is 2cm in the high-voltage pulse electric field processing chamber.
Embodiment 12：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: being 1 by mass volume ratio:18 neohesperidin and alkaline solution is added in reaction kettle, stirring and dissolving, then
Catalyst palladium carbon is added, then closed reactor is passed through hydrogen displacement nitrogen at normal temperatures with the air in nitrogen replacement reaction kettle
Gas is stirred to react 10 hours, after the completion of reaction under normal pressure, utilizes the hydrogen in nitrogen replacement reaction kettle, then stops reaction, is taken out
Go out reaction solution；The mass ratio of the catalyst palladium carbon and neohesperidin is 1:18；The mass fraction of the alkaline solution is 10%；
The alkaline solution is that weight ratio is 1:2:1 potassium hydroxide, urea and sodium bicarbonate solution；
Step 2: reaction solution pH is adjusted to 5, then inputs in high-voltage pulse electric field processing chamber, utilize high-voltage pulse electric
Field is handled；12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is adsorbed with macroreticular resin AB-8, after absorption,
With purifying water elution, the salt in filtrate is removed；Then it is 20% ethanol elution with the volume fraction of 18 times of column volumes, then uses volume
The ethanol elution that score is 40% collects eluent, concentrates, and crystal B is obtained by filtration in crystallization, merges crystal A and B, and freezing is dry
It is dry to get to neohesperidin dihydrochalcone；Yield is 92.8%, purity 99.63%；The high-pressure pulse electric processing
Parameter is：Impulse amplitude is 15KV, pulse frequency 1000Hz, pulse width 12us, processing time 80min；The height
Pressure pulse electric field process chamber periphery is provided with cold water circulating system, and wherein circulating water temperature is 3 DEG C, water circulating speed 4m/
s；The spacing of two-plate is 2cm in the high-voltage pulse electric field processing chamber.
Embodiment 13：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: the sodium hydroxide solution that 1kg neohesperidins and 18kg mass fractions are 10% is added in reaction kettle, stir
Dissolving is mixed, adds 0.0625kg catalyst palladium carbons, closed reactor, with the air in nitrogen replacement reaction kettle, then normal
It is passed through hydrogen displacement nitrogen under temperature, is stirred to react 12 hours, after the completion of reaction under normal pressure, utilizes the hydrogen in nitrogen replacement reaction kettle
Then gas stops reaction, extraction liquid；
Step 2: reaction solution pH is adjusted to 6,12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole resin D101 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 18 times of column volumes
For 20% ethanol elution, then be 40% with volume fraction ethanol elution, collect eluent, be in frequency by eluent
Under 20KHz, the sound field that output power is 60W, it is cooled to 0 DEG C with 5 DEG C/h of speed, crystal is obtained by filtration in growing the grain 2 hours
B merges crystal A and B, and freeze-drying is to get to neohesperidin dihydrochalcone；Yield is 92.5%, purity 99.6%.
Embodiment 14：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: being 1 by mass volume ratio:20 neohesperidin and alkaline solution is added in reaction kettle, stirring and dissolving, then
Catalyst palladium carbon is added, then closed reactor is passed through hydrogen displacement nitrogen at normal temperatures with the air in nitrogen replacement reaction kettle
Gas is stirred to react 12 hours, after the completion of reaction under normal pressure, utilizes the hydrogen in nitrogen replacement reaction kettle, then stops reaction, is taken out
Go out reaction solution；The mass ratio of the catalyst palladium carbon and neohesperidin is 1:16；The mass fraction of the alkaline solution is 8%；
The alkaline solution is that weight ratio is 1:2:1 potassium hydroxide, urea and sodium bicarbonate solution；
Step 2: reaction solution pH is adjusted to 6,15h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole Resin A B-8 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 20 times of column volumes
For 20% ethanol elution, then be 40% with volume fraction ethanol elution, collect eluent, by eluent frequency be 30KHz,
Output power is to be cooled to -5 DEG C under the sound field of 60W with 8 DEG C/h of speed, and crystal B is obtained by filtration in growing the grain 5 hours, merges
Crystal A and B, freeze-drying is to get to neohesperidin dihydrochalcone；Yield is 93%, purity 99.65%.
Embodiment 15：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: using the process of step 1 in embodiment 10；
Step 2: reaction solution pH is adjusted to 5, then inputs in high-voltage pulse electric field processing chamber, utilize high-voltage pulse electric
Field is handled；12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is adsorbed with macroreticular resin AB-8, after absorption,
With purifying water elution, the salt in filtrate is removed；Then it is 20% ethanol elution with the volume fraction of 18 times of column volumes, then uses volume
The ethanol elution that score is 40% collects eluent, concentrates, and crystal B is obtained by filtration in crystallization, merges crystal A and B, and freezing is dry
It is dry to get to neohesperidin dihydrochalcone；Yield is 93.5%, purity 99.68%；The high-pressure pulse electric processing
Parameter is：Impulse amplitude is 15KV, pulse frequency 1000Hz, pulse width 12us, processing time 80min；The height
Pressure pulse electric field process chamber periphery is provided with cold water circulating system, and wherein circulating water temperature is 3 DEG C, water circulating speed 4m/
s；The spacing of two-plate is 2cm in the high-voltage pulse electric field processing chamber；Wherein freeze-drying is dry using the freezing in embodiment 8
Dry process.
Embodiment 16：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: using the process of step 1 in embodiment 10；
Step 2: reaction solution pH is adjusted to 6,12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is with greatly
Hole resin D101 is adsorbed, and after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume fraction of 18 times of column volumes
For 20% ethanol elution, then be 40% with volume fraction ethanol elution, collect eluent, be in frequency by eluent
Under 20KHz, the sound field that output power is 60W, it is cooled to 0 DEG C with 5 DEG C/h of speed, crystal is obtained by filtration in growing the grain 2 hours
B merges crystal A and B, and freeze-drying is to get to neohesperidin dihydrochalcone；Yield is 94%, purity 99.72%；Its
Middle freeze-drying is using the freezing dry process in embodiment 8.
Embodiment 17：
A kind of preparation method of neohesperidin dihydrochalcone, includes the following steps：
Step 1: using the process of step 1 in embodiment 10；
Step 2: reaction solution pH is adjusted to 5, then inputs in high-voltage pulse electric field processing chamber, utilize high-voltage pulse electric
Field is handled；12h is crystallized under room temperature, is filtered, is obtained crystal A；Obtained filtrate is adsorbed with macroreticular resin AB-8, after absorption,
With purifying water elution, the salt in filtrate is removed；Then it is 20% ethanol elution with the volume fraction of 18 times of column volumes, then uses volume
The ethanol elution that score is 40% collects eluent, by eluent under the sound field that frequency is 20KHz, output power is 60W,
Be cooled to 0 DEG C with 5 DEG C/h of speed, crystal B is obtained by filtration in growing the grain 2 hours, merges crystal A and B, freeze-drying to get
To neohesperidin dihydrochalcone；Yield is 95%, purity 99.9%；The parameter of high-pressure pulse electric processing is：Arteries and veins
It is 15KV, pulse frequency 1000Hz, pulse width 12us, processing time 80min to rush amplitude；The high-pressure pulse electric
Process chamber periphery is provided with cold water circulating system, and wherein circulating water temperature is 3 DEG C, water circulating speed 4m/s；The high pressure
The spacing of two-plate is 2cm in pulse electric field process chamber；Wherein freeze-drying is using the freezing dry process in embodiment 8.
In the present invention, using high-pressure pulse electric and electroblowing process, make the yield and purity of neohesperidin dihydrochalcone
It is obviously improved, increases the utilization rate of neohesperidin dihydrochalcone.
In order to illustrate the effect of the present invention, it is as follows that inventor provides comparative experiments：
Comparative example 1：
In step 1, the amount of the sodium hydroxide solution of addition is 14kg, remaining parameter and the complete phase in embodiment 1
Together, technical process is also identical, and the yield of obtained neohesperidin dihydrochalcone is 80%, purity 95.5%.
Comparative example 2：
In step 1, the amount of the sodium hydroxide solution of addition is 21kg, remaining parameter and the complete phase in embodiment 1
Together, technical process is also identical, and the yield of obtained neohesperidin dihydrochalcone is 81%, purity 95.8%.
Comparative example 3：
It is 1 by mass volume ratio in step 1:14 neohesperidin and alkaline solution is added in reaction kettle, remaining ginseng
Number with it is identical in embodiment 4, technical process is also identical, and the yield of obtained neohesperidin dihydrochalcone is
82%, purity 96%.
Comparative example 4：
It is 1 by mass volume ratio in step 1:21 neohesperidin and alkaline solution is added in reaction kettle, remaining ginseng
Number with it is identical in embodiment 4, technical process is also identical, and the yield of obtained neohesperidin dihydrochalcone is
81%, purity 95.7%.
Comparative example 5：
In step 1, the mass ratio of the catalyst palladium carbon and neohesperidin is 1:14, in remaining parameter and embodiment 4
It is identical, technical process is also identical, and the yield of obtained neohesperidin dihydrochalcone is 78%, and purity is
94%.
Comparative example 6：
In step 1, the mass ratio of the catalyst palladium carbon and neohesperidin is 1:21, in remaining parameter and embodiment 4
It is identical, technical process is also identical, and the yield of obtained neohesperidin dihydrochalcone is 76%, and purity is
92.8%.
Comparative example 7：
It is 1 by mass volume ratio in step 1:14 neohesperidin and alkaline solution is added in reaction kettle, remaining ginseng
Number with it is identical in embodiment 10, technical process is also identical, and the yield of obtained neohesperidin dihydrochalcone is
85%, purity 96.7%.
Comparative example 8：
It is 1 by mass volume ratio in step 1:21 neohesperidin and alkaline solution is added in reaction kettle, remaining ginseng
Number with it is identical in embodiment 10, technical process is also identical, and the yield of obtained neohesperidin dihydrochalcone is
85.2%, purity 96.9%.
Comparative example 9：
In step 1, the mass ratio of the catalyst palladium carbon and neohesperidin is 1:14, remaining parameter and embodiment 10
In it is identical, technical process is also identical, and the yield of obtained neohesperidin dihydrochalcone is 82%, and purity is
95%.
Comparative example 10：
In step 1, the mass ratio of the catalyst palladium carbon and neohesperidin is 1:21, remaining parameter and embodiment 10
In it is identical, technical process is also identical, and the yield of obtained neohesperidin dihydrochalcone is 82.5%, and purity is
95.8%.
Although the embodiments of the present invention have been disclosed as above, but its is not only in the description and the implementation listed
With it can be fully applied to various fields suitable for the present invention, for those skilled in the art, can be easily
Realize other modification, therefore without departing from the general concept defined in the claims and the equivalent scope, the present invention is simultaneously unlimited
In specific details and legend shown and described herein.
Claims (5)
1. a kind of preparation method of neohesperidin dihydrochalcone, which is characterized in that include the following steps：
Step 1: being 1 by mass volume ratio:15~20 neohesperidin and alkaline solution stirring and dissolving, obtains mixed solution；?
It is 40%~60% ethanol water that volume fraction is added in reaction kettle, then uses the air in nitrogen replacement reaction kettle, closed
Reaction kettle；Mixed solution is ejected into using electroblowing process in the ethanol water of closed reactor, and is stirred in course of injection
Mix ethanol water；Catalyst palladium carbon is added in reaction kettle after the completion of injection, then is passed through hydrogen displacement nitrogen at normal temperatures, it is close
Reaction kettle is closed, is stirred to react 10~15 hours, after the completion of reaction under normal pressure, using the hydrogen in nitrogen replacement reaction kettle, then
Stop reaction, extraction liquid；The mass ratio of the catalyst palladium carbon and neohesperidin is 1:15~20；The ethanol water
Volume ratio with alkaline solution is 1:10~30；The electroblowing process is：Mixed solution is injected into the injection with stainless steel nozzle
In container, the stainless steel nozzle stretches into closed reactor, and with the contact position of closed reactor using sealed connection；
Then it is applied the voltage on stainless steel nozzle with high voltage power supply, and is pumped spray containers using the propulsion being connect with spray containers
Interior mixed solution is sprayed by stainless steel nozzle into closed reactor；The injection conditions that electroblowing process uses for：High-voltage electricity
The output voltage in source is 3~8kv, in closed reactor between ethanol water and stainless steel nozzle distance be 8~12cm, flow velocity
For 10~15mL/h；The internal diameter of the stainless steel nozzle is 1~2mm；
Step 2: reaction solution pH is adjusted to 5-6,10~15h is crystallized under room temperature, filtering obtains crystal A；Obtained filtrate is used
Macroporous resin adsorption after absorption, with purifying water elution, removes the salt in filtrate；Then with the volume of 15~20 times of column volumes point
Number is 10~25% ethanol elutions, then the ethanol elution for being 30~60% with volume fraction, eluent is collected, by eluent in frequency
Under the sound field that rate is 20~30KHz, output power is 30~60W, it is cooled to -5~0 DEG C with 5~10 DEG C/h of speed, is supported
Brilliant 2~5 hours, crystal B is obtained by filtration, merges crystal A and B, freeze-drying is to get to neohesperidin dihydrochalcone；
The freeze-drying includes the following steps：
Step I, precooling：Cryogenic temperature -30~-50 DEG C, cooling time 1~3 hour keep crystal A and B contained humidity all solidifying
Form solid-state；
Step II will be warming up to 25 DEG C after precooling, be kept for 2~4 hours；
Step III, freeze-drying：The crystal that step II is obtained is added in vacuum freeze drier, and setting condenser temperature is -50
~-85 DEG C, vacuum degree is 500mpa~1000mpa, and sublimation drying 12-24h obtains neohesperidin dihydrochalcone.
2. the preparation method of neohesperidin dihydrochalcone as described in claim 1, which is characterized in that the alkaline solution
Mass fraction is 6~15%；The alkaline solution is sodium hydroxide solution, urea liquid, potassium hydroxide solution, weight ratio 1:
2:Any one in 1 potassium hydroxide, urea and sodium bicarbonate solution.
3. the preparation method of neohesperidin dihydrochalcone as described in claim 1, which is characterized in that in the step 2,
It further includes following procedure reaction solution pH to be adjusted under 5-6 and room temperature between crystallizing 10~15h：Reaction solution after adjusting pH is defeated
Enter in high-voltage pulse electric field processing chamber, is handled using high-pressure pulse electric；The parameter of high-pressure pulse electric processing is：
Impulse amplitude is 10~20KV, and pulse frequency is 800~1200Hz, and pulse width is 8~15us, processing time 60-
90min。
4. the preparation method of neohesperidin dihydrochalcone as claimed in claim 3, which is characterized in that the high-voltage pulse electric
Field process chamber periphery is provided with cold water circulating system, and wherein circulating water temperature is 1~5 DEG C, and water circulating speed is 2~5m/s；
The spacing of two-plate is 1~3cm in the high-voltage pulse electric field processing chamber.
5. the preparation method of neohesperidin dihydrochalcone as described in claim 1, which is characterized in that the macroreticular resin is
Any one in macroreticular resin D101, D201, DM301, AB-8.
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| CN114621991A (en) * | 2020-12-14 | 2022-06-14 | 桂林莱茵生物科技股份有限公司 | Method for preparing neohesperidin dihydrochalcone by biological enzyme method |
| CN114621301A (en) * | 2020-12-14 | 2022-06-14 | 桂林莱茵生物科技股份有限公司 | Preparation method of neohesperidin dihydrochalcone |
| CN114280205A (en) * | 2021-12-29 | 2022-04-05 | 广州健顺生物医药研究院有限公司 | Method for efficiently preparing neohesperidin dihydrochalcone |
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