CN106083696B - A kind of method for crystallising of 1-DNJ - Google Patents
A kind of method for crystallising of 1-DNJ Download PDFInfo
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- CN106083696B CN106083696B CN201610395442.XA CN201610395442A CN106083696B CN 106083696 B CN106083696 B CN 106083696B CN 201610395442 A CN201610395442 A CN 201610395442A CN 106083696 B CN106083696 B CN 106083696B
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 86
- 235000019441 ethanol Nutrition 0.000 claims abstract description 60
- LRHPLDYGYMQRHN-UHFFFAOYSA-N n-butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims abstract description 56
- 240000000249 Morus alba Species 0.000 claims abstract description 46
- 235000008708 Morus alba Nutrition 0.000 claims abstract description 46
- 239000003480 eluent Substances 0.000 claims abstract description 45
- 238000000605 extraction Methods 0.000 claims abstract description 42
- 239000000047 product Substances 0.000 claims abstract description 26
- 238000001035 drying Methods 0.000 claims abstract description 22
- 239000000706 filtrate Substances 0.000 claims abstract description 21
- 239000000284 extract Substances 0.000 claims abstract description 19
- 239000012141 concentrate Substances 0.000 claims abstract description 15
- 239000003729 cation exchange resin Substances 0.000 claims abstract description 13
- 230000002378 acidificating Effects 0.000 claims abstract description 12
- 239000000287 crude extract Substances 0.000 claims abstract description 11
- 239000000843 powder Substances 0.000 claims abstract description 7
- 239000000243 solution Substances 0.000 claims description 32
- 238000010828 elution Methods 0.000 claims description 18
- 239000007788 liquid Substances 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 238000002425 crystallisation Methods 0.000 claims description 13
- 230000005712 crystallization Effects 0.000 claims description 13
- 238000001514 detection method Methods 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 238000004821 distillation Methods 0.000 claims description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 7
- 239000000908 ammonium hydroxide Substances 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 238000002514 liquid chromatography mass spectrum Methods 0.000 claims description 5
- 238000000691 measurement method Methods 0.000 claims description 5
- 239000012047 saturated solution Substances 0.000 claims description 5
- 238000009376 nuclear reprocessing Methods 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 3
- 239000002893 slag Substances 0.000 claims 1
- 238000002525 ultrasonication Methods 0.000 claims 1
- LXBIFEVIBLOUGU-FSIIMWSLSA-N 1,5-Dideoxy-1,5-Imino-D-Mannitol Chemical compound OC[C@@H]1NC[C@@H](O)[C@H](O)[C@H]1O LXBIFEVIBLOUGU-FSIIMWSLSA-N 0.000 abstract description 13
- LXBIFEVIBLOUGU-JGWLITMVSA-N 1-Deoxynojirimycin Natural products OC[C@H]1NC[C@H](O)[C@@H](O)[C@@H]1O LXBIFEVIBLOUGU-JGWLITMVSA-N 0.000 abstract description 13
- 239000002253 acid Substances 0.000 abstract description 8
- 238000011084 recovery Methods 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 6
- 238000005516 engineering process Methods 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 239000011347 resin Substances 0.000 description 15
- 229920005989 resin Polymers 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 229930003944 flavones Natural products 0.000 description 11
- 235000011949 flavones Nutrition 0.000 description 11
- 210000001217 Buttocks Anatomy 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 229930013930 alkaloids Natural products 0.000 description 8
- 150000002213 flavones Chemical class 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000005265 energy consumption Methods 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 150000003797 alkaloid derivatives Chemical class 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000003456 ion exchange resin Substances 0.000 description 5
- 229920003303 ion-exchange polymer Polymers 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 230000035695 Efflux Effects 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N al2o3 Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000005238 degreasing Methods 0.000 description 3
- -1 flavone compound Chemical class 0.000 description 3
- 238000005189 flocculation Methods 0.000 description 3
- 230000016615 flocculation Effects 0.000 description 3
- 230000002218 hypoglycaemic Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- YXOLAZRVSSWPPT-UHFFFAOYSA-N 3,5,7,2',4'-Pentahydroxyflavonol Chemical compound OC1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 YXOLAZRVSSWPPT-UHFFFAOYSA-N 0.000 description 2
- 210000004369 Blood Anatomy 0.000 description 2
- 206010012601 Diabetes mellitus Diseases 0.000 description 2
- 102100008175 MGAM Human genes 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 108010028144 alpha-Glucosidases Proteins 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229940023913 cation exchange resins Drugs 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 150000002016 disaccharides Chemical class 0.000 description 2
- 229940079593 drugs Drugs 0.000 description 2
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N flavone Chemical compound O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 150000004676 glycans Polymers 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- BGMYHTUCJVZIRP-GASJEMHNSA-N nojirimycin Chemical compound OC[C@H]1NC(O)[C@H](O)[C@@H](O)[C@@H]1O BGMYHTUCJVZIRP-GASJEMHNSA-N 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 150000004804 polysaccharides Polymers 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XNLICIUVMPYHGG-UHFFFAOYSA-N 2-Pentanone Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 1
- UFLHIIWVXFIJGU-ARJAWSKDSA-N Cis-3-Hexen-1-ol Chemical compound CC\C=C/CCO UFLHIIWVXFIJGU-ARJAWSKDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N D-Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010020993 Hypoglycaemia Diseases 0.000 description 1
- 206010022114 Injury Diseases 0.000 description 1
- 206010027476 Metastasis Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- IKGXIBQEEMLURG-BKUODXTLSA-N Rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 1
- 229940081967 Rutin Drugs 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 230000001476 alcoholic Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910001884 aluminium oxide Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminum Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 230000000259 anti-tumor Effects 0.000 description 1
- 230000000840 anti-viral Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary Effects 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 230000002255 enzymatic Effects 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 235000020828 fasting Nutrition 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 229930003935 flavonoids Natural products 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 235000007708 morin Nutrition 0.000 description 1
- 239000005445 natural product Substances 0.000 description 1
- 229930014626 natural products Natural products 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000011020 pilot scale process Methods 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000011528 polyamide (building material) Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000000291 postprandial Effects 0.000 description 1
- 230000003389 potentiating Effects 0.000 description 1
- OXGUCUVFOIWWQJ-HQBVPOQASA-M quercitrin-7-olate Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC([O-])=CC(O)=C2C1=O OXGUCUVFOIWWQJ-HQBVPOQASA-M 0.000 description 1
- 230000003252 repetitive Effects 0.000 description 1
- 239000000837 restrainer Substances 0.000 description 1
- 229930002876 rutin Natural products 0.000 description 1
- 235000005493 rutin Nutrition 0.000 description 1
- 229960004555 rutoside Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical compound OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 230000002194 synthesizing Effects 0.000 description 1
- 238000005496 tempering Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
Abstract
The invention discloses a kind of method for crystallising of 1 1-Deoxynojirimycin, this method includes：First mulberry leaf powder with acidic ethanol is impregnated, and is handled in ultrasonic cell-break machine, is filtered, is collected filtrate and be centrifuged, crude extract is made；By cation exchange resin, eluted；Collection eluent, which is placed in Rotary Evaporators, to be concentrated, then concentrate is extracted with n-butanol；Extract liquor is recycled after extraction, excess is placed in low temperature drying case and is dried；Drying is placed in ethyl alcohol, and crystal is precipitated after forming supersaturated solution, is got product after collecting crystal drying.The method for crystallising of 1 1-Deoxynojirimycin provided by the invention can obtain about 0.2% 1 DNJ recovery rates of mulberry leaf, it is significantly higher than traditional ethyl alcohol recovery rate 0.00139%, and diluted acid extraction efficiency 0.00147%, illustrate that diluted acid and ethyl alcohol are acted synergistically in 1 DNJ of mulberry leaf is extracted, produce unpredictalbe effect.
Description
Technical field
The invention belongs to medicine technical field more particularly to a kind of method for crystallising of 1-DNJ.
Background technology
1-DNJ (1-deoxynojirimycin, DNJ) be a kind of polarity compound containing N, chemical name
It is 1-DNJ, molecular formula C6H13NO4, relative molecular mass 163.1- deoxidations open country buttocks
Mycin has the function of the very strong active ingredient for inhibiting alpha-glucosidase, being hypoglycemic treatment diabetes, additionally has
The pharmacological actions such as antiviral, anti-tumor metastasis.In recent years, domestic and foreign scholars to the source of 1-DNJ, in organism
Interior synthesis mechanism and chemical synthesis process have carried out a large amount of research and probe, and research finds 1- deoxidations open country buttocks in the mulberry leaf of mulberry tree
The content of mycin is comparable considerable, and extracting method, easy to operate.
Chinese patent technology (03101988.9) reports a kind of preparation containing mulberry leaf total alkali medicinal extract and preparation method thereof：
Mulberry leaf water or hydrophilic solvent extraction, flocculation, supernatant ion exchange, hydrophilic solvent refluxing extraction are concentrated to dryness to obtain
Medicinal extract.The purity of product reaches more than 50%, and said preparation has apparent hypoglycemic and improvement sugar tolerance effect.This method needs
Flocculation；It needs to be eluted with hydrophilic solvent reflux by the goods and materials of resin adsorption, some in practical operation are inconvenient.
Chinese patent technology (02113004.3) reports extract of mulberry twig and its extracting method and new application：Ramulus mori extracts
Object is by 0~95% ethanol water of single medicinal material ramulus mori or chloroform, acetone, ethyl acetate, methanol equal solvent or their group
Conjunction is extracted 1 time or 1 time or more under 10-100 DEG C of temperature condition, merges extracting solution, recycling design to obtain the final product；Or with following method into
One step purifies：Extracting solution tune pH is 7.5-9.5, and centrifuged supernatant tune pH is 4-6, and precipitation is washed to neutrality, is drying to obtain；It carries
Liquid is taken to be obtained through petroleum ether or gasoline degreasing；Extracting solution is after petroleum ether or gasoline degreasing, with chloroform, ethyl acetate, acetone, first
Alcohol or water are extracted respectively or successively and are obtained；Extracting solution is after macroporous absorbent resin adsorbs, with 10-95% ethanol water desorptions
And it obtains；Extracting solution is eluted after the absorption such as diatomite, aluminium oxide with chloroform, ethyl acetate, acetone, methanol, ethyl alcohol equal solvent
Afterwards, it is concentrated and dried and obtains；Extracting solution is through column chromatography for separation such as polyamide, silica gel or ion exchange resin.More than purification process can
It is applied alone or the combination using several method.Containing a large amount of flavones ingredients in the extract of mulberry twig of gained, including rutin, quercitrin
Element, morin etc..Purity of the extract containing DNJ is not known in the patented technology, and petroleum ether degreasing, macroreticular resin are inhaled during purifying
Attached etc., operation sequence is complicated.
Chinese patent technology (200710060127.2) reports continuously extracting alkaloids, flavones and polysaccharide from mulberry leaf and lives
The method of property ingredient：Select solvent be 20%~90% ethyl alcohol or 10%~90% acetone reflux extraction, obtain filtrate and
Filter residue；Filtrate concentration, be dissolved in water after, by macroreticular resin detach content be 30%~50% flavone compound；Through
Cross the solution after macroreticular resin, then by ion exchange resin detach content be 40%~60% alkaloid compound；
Mulberry leaf filter residue, is decocted and is decolourized with water, 10%~60% alcohol precipitation, obtains the acidic polysaccharose class compound that content is 55%~85%.
The technology needs a large amount of ethyl alcohol or acetone to extract, and technology is of high cost, high energy consumption, does not obtain DNJ sterlings.
The method that Chinese patent technology (200510030333.X) reports the effective component extracting from mulberry leaf：It will be adsorbed with
The resin of mulberry-leaf extract is placed in extraction kettle, is continuously passed through CO2Extraction elution is carried out, collects the CO of outflow extraction kettle2, release
To normal pressure, CO2Reuse after emptying or pressurization, obtains the residue after release, as mulberry leaf active ingredient, CO in extraction kettle2It is super
Critical condition.The method of the present invention, purification process is not oxidizable, is convenient for scale and is extracted from mulberry leaf, purifies mulberry leaf and take off
Oxygen nojirimycin Alkaloid and flavones in mulberry leaves, high selectivity, in product, 1-Deoxynojirimycin alkaloid and flavones in mulberry leaves it is total
Content can reach 75~90%.The technology uses supercritical extraction technique, and final products do not obtain 1-Deoxynojirimycin sterling yet.
Chinese patent technology (200710067498.3) reports a kind of side that 1-DNJ is extracted from mulberry leaf
Method：By adding in mineral acid acidified processing in the extracting solution of mulberry leaf, impurity is removed through cooling, is obtained using column chromatography.It can
Make mulberry-leaf extract content not less than 10%, but do not obtain sterling.
Chinese patent technology (200810122998.7) reports one kind and 1- deoxidations open country buttocks is detached from mulberry leaf total alkaloid
The method of mycin monomer：Mulberry leaf total alkali is dissolved in water, and ion exchange resin absorption, after the completion of absorption, stepwise elution simultaneously collects deoxidation
Nojirimycin pure fractions, are concentrated under reduced pressure drying, and repeated recrystallize obtains sterling.This method requires " total alkaloid " of raw material
Containing more than 40% 1-Deoxynojirimycin, stepwise elution agent is the alcoholic solution of various concentration, is recrystallized molten for methanol and acetone mixing
Liquid；A large amount of detection work is needed during stepwise elution and collects sterling position, operation is cumbersome, and the mixed solvent of recrystallization is difficult
With processing.
Chinese patent technology (200810236144.1) reports the compound of a kind of coproduction of mulberry tea flavone, polysaccharide and alkaloid
Extraction process, but not isolated 1-Deoxynojirimycin sterling.
Chinese patent technology (200910192542.2) reports one kind successive extract 1- deoxidations open country buttocks from mulberry leaf
The method of mycin (DNJ), flavones：It is extracted after mulberry leaf and ethyl alcohol are mixed, centrifugal filtration, it is heavy that flocculant flocculation is added in after concentration
It forms sediment；Filtrate is added in multiple cation exchange resin columns of connection after removing precipitation, and flows through and is chained together with the resin column
Large pore resin absorption column；Filtrate add in after with it is pure be washed to macroporous resin column efflux it is colourless when disconnected, then
With ammonium hydroxide or the ethanol solution containing ammonia elutes 1-DNJ (DNJ) from cationic resin column；Eluent again Shangyang from
Sub- resin column collects eluent after repetitive operation, with being spray-dried after 80D NF membrane thickening filtrations, obtains brownish-yellow powder shape 1-
1-Deoxynojirimycin (DNJ).Macroporous resin column is washed with 3%~10% ethyl alcohol to remove colloidality impurity, then with 50%~
70% ethanol elution flavones collects brownish red eluent, is spray-dried after recycling ethyl alcohol is concentrated under reduced pressure, obtains the powdered mulberry of yellowish-brown
Leaf flavonoids.The technology raw material needs to be extracted repeatedly with ethyl alcohol, and production cost is higher, and energy consumption is also higher.
Chinese patent technology (200710099911.4) reports a kind of spent ion exchange resin separating folium mori total
Method.The technology does not obtain 1-Deoxynojirimycin monomer.
Chinese patent technology (201010130263.6) reports a kind of method that flavones, alkaloid are prepared from mulberry leaf：
Buck heating extraction flavones, 90-95% ethyl alcohol and activated carbon extract alkaloid again, and flavone extractive tune acid crosses macroporous resin column,
Acidizing crystal and 70-80% ethyl alcohol dissolving-recrystallizations, alkaloids extract concentration, acetone are redissolved, peroxidating aluminium short wide column, ammonia
Change crystallization and 85-90% ethyl alcohol dissolving-recrystallizations.This technology needs a large amount of organic solvent, and does not obtain 1-Deoxynojirimycin
Monomer.
Chinese patent technology (201110021131.4) reports the preparation method of 1-Deoxynojirimycin in Mulberry Leaves：Using
The method that high-voltage pulse electric field technology produces 1-DNJ due to being room temperature extraction, while improves product quality
And production efficiency, reduce production cost.The technology does not obtain 1-Deoxynojirimycin sterling.
It is mould that Chinese patent technology (200910167602.5) reports the high-purity 1- deoxidations open country buttocks of extraction separation in natural products
The method of element：Raw material dry powder is extracted with hydrophilic solvent, is impregnated after extracting solution acidification, concentration with anion exchange resin, efflux
It is extracted after being concentrated with water lotion with cation exchange column chromatography, organic solvent, recrystallization, gel filtration chromatography are purified, products therefrom
Middle 1-DNJ content is no less than 98%, and specific implementation has been enter into pilot scale.The technology need anion exchange resin and
Cation exchange resin, while need a variety of organic solvents such as alcohol, acetone, chloroform, butanol, more particularly, to chloroform, toxicity compared with
Greatly；It needs repeatedly to concentrate in extraction process, energy consumption is higher.
Chinese patent technology (201110038204.0) reports mould by extracting separating high-purity 1- deoxidations open country buttocks in mulberry leaf
The method of element：Raw material powder with aqueous solvent is extracted, filters the dregs of a decoction, material centrifugation obtains extracting solution；Extracting solution is concentrated into no second
Alcohol, ultrafiltration membrance filter；Again with inorganic acid tune pH to 3.0-4.0, precipitation, centrifugation removal of impurities；It is acidified highly acidic cation tree in feed liquid
Fat column, washing, then carry out ammonium hydroxide elution；Macroporous resin column in feed liquid, washing, then the ethanol gradient elution with various concentration, are received
Collect target eluent；Target eluent is concentrated under reduced pressure, is dry, obtains crude product；Crude product is dissolved with absolute ethyl alcohol, parlkaline adsorption column
Efflux is collected in removal of impurities；Efflux is concentrated under reduced pressure, and carries out room temperature crystallization and recrystallization, obtains 1-DNJ highly finished product.The present invention is whole
In a technical process, other organic solvents are not used in addition to ethyl alcohol, safe operation, 1-DNJ contents are up to 98.3%.The technique needs
Hyperfiltration technique is used, ethyl alcohol stepwise elution, collecting target eluent needs constantly detection outflow component etc., complicated for operation；Energy
Consumption is higher.
Up to the present, from existing literature and patented technology, 1-Deoxynojirimycin sterling is extracted or using excessive
Organic solvent, especially with chloroform, cause safety not high；Or need repeatedly concentration, energy consumption higher；Or it needs to make
It is detected with excessive step or needs substep and collects target component, since 1-Deoxynojirimycin does not have UV absorption, detection
Cumbersome, complicated for operation, industrial production is difficult to control；Or sterling etc. can not be obtained.
The shortcomings that prior art one
The price of 1-DNJ standard items is excessively high.
The 1-DNJ and experiment that high-purity can not be obtained are used as reference.
Experimental raw exists only in two season of spring and summer, the easy moldy metamorphism of raw material of long-time storage.The concentration of product
It is not high.
1-DNJ belongs to potent alpha-glucosidase restrainer, and 1-DNJ passes through to disaccharides point
It solves enzymatic activity and generates inhibiting effect, so as to inhibit absorption of the small intestine to disaccharide, reduce the peak value of blood glucose after food.And then inhibit people
The conversion of body sugar reduces the raising of fasting blood-glucose and postprandial blood sugar better than sulfonylurea drugs, and hypoglycemia and other pairs occurs
The possibility of effect is significantly less than other hypoglycemic drugs, and safety is good；It can not be changed normally using 1-DNJ
Dietary structure.1-DNJ is current treating diabetes unique internationally recognized zero injury biology system in the market
Agent.At present, the source of domestic 1-DNJ belongs to greatly import, and expensive, and every kilogram of 1- deoxidation of high-purity is wild
The price of buttocks mycin can reach 2 to 3,000 yuan.The purity of domestic medicinal 1-DNJ all compares low, and net content is low
In 5%, and it is comparable plain for the research of 1-DNJ, also the purifying of 1-DNJ can not be reached knot
Into crystal, do not have the flow process technology that pure 1-DNJ really can be accurately extracted from mulberry leaf.
Invention content
The purpose of the present invention is to provide a kind of method for crystallising of 1-DNJ, it is intended to solve extraction deoxidation at present
Nojirimycin sterling safety is not high；Energy consumption is higher；Cumbersome, detection is cumbersome, and industrial production is difficult to control, and can not be obtained
To sterling, and it is at high price the problem of.
The invention is realized in this way a kind of method for crystallising of 1-DNJ, this method include the following steps：
First mulberry leaf powder with acidic ethanol is impregnated, and is handled in ultrasonic cell-break machine, is filtered, collects filtrate progress
It centrifuges, crude extract is made；
The crude extract prepared is eluted by 732H feminine gender cation exchange resins again；
Collection eluent, which is placed in Rotary Evaporators, to be concentrated, then concentrate is extracted with n-butanol；
Extract liquor is recycled after extraction, the extract liquor containing 1-DNJ is placed in low temperature drying case and is done
It is dry；
Drying is placed in ethyl alcohol, and crystal is precipitated after forming supersaturated solution, is got product after collecting crystal drying.
Further, the method for crystallising of 1-DNJ is specially：
Extraction：
Mulberry leaf be crushed into 40 mesh sieve, 300g is weighed in 1000mL beakers, add in and be mixed to get pH with ethyl alcohol by HCL and be
6.5 65% acidic ethanol 800mL impregnates 30min, is put into ultrasonic cell-break machine and handles 20min, filters, and collects filter
Liquid, residue add in the reprocessing of 65% acidic ethanols of 400mL once, and filtering discards residue, merges filtrate twice, will merge two
Filtrate after secondary recycles ethyl alcohol with Rotary Evaporators and is concentrated into small size, and extracting solution is centrifuged, crude extract is made,
The power of ultrasonic wave is 300W；
Purifying：The 1-DNJ coarse extraction solution collected after preparation is loaded to the exchange of cation exchange resin
Column, and with water elution is distilled, flow velocity is 1.0~2.0ml/min；When eluent from it is colourless become faint yellow when start to collect, directly
The first eluent is obtained until eluent is substantially colorless, then elutes the first eluent, elution with the ammonium hydroxide of 0.25mol/L again
Speed is 1 one 2ml/min, collects eluent, obtains the second eluent；
Concentration：Second eluent is placed in Rotary Evaporators, 1-DNJ is concentrated, in 600mmHg
Under the conditions of concentrate 30min；
Extraction：With the extracting n-butyl alcohol 3 times of concentrate same volume, the extracting n-butyl alcohol of 1-DNJ is obtained
Liquid；
It is dry：The n-butanol in the butanol extraction liquid of 1-DNJ is recycled, then will remove with the way of distillation
The substance obtained after n-butanol is gone to be placed in 300mmHg, 1-DNJ finished product is drying to obtain in the vacuum under the conditions of 10 DEG C；
Crystallization：
The heating of a part of 1-DNJ finished product is dissolved in water, forms saturated solution, opening is positioned over dry environment,
Supersaturated solution is obtained, monocrystalline crystal is precipitated；Remaining another part distillation adds in 96% ethyl alcohol stirred crystallization to 0.8g/ml
Obtain powdered crystal；
The detection method of 1-DNJ crystal：Utilize high performance liquid chromatography-mass spectrum On-line measurement method.
Further,
Opening described in crystallization is positioned over dry environment, specially：Opening is placed for 24 hours, is positioned over relative humidity 20%
Dry environment.
Further, 1-DNJ crystal is placed under the conditions of 40 DEG C and be dried.
Further, the second eluent is stood 12 hours in the concentration to be placed in Rotary Evaporators, to 1- deoxidations open country
Buttocks mycin is concentrated.
The method for crystallising of 1-DNJ provided by the invention can obtain about 0.2% mulberry leaf 1-DNJ recovery rates, show
It writes higher than traditional ethyl alcohol recovery rate 0.00139% and diluted acid extraction efficiency 0.00147%, illustrates that diluted acid and ethyl alcohol are extracting
Acted synergistically in mulberry leaf 1-DNJ, produce unpredictalbe effect, be mulberry leaf 1-DNJ products medicine and health care
Utilization in terms of product provide theories integration and technological guidance；
The present invention crystallizes out 1-DNJ extraction contained in mulberry leaf, maximumlly that 1- deoxidations open country buttocks is mould
Element crystallisation concentration improve, reach more than 50%, solved at present 1-DNJ purity is relatively low on the market and price is high
The problem of high.
Description of the drawings
Fig. 1 is the method for crystallising flow chart of 1-DNJ provided in an embodiment of the present invention.
Specific embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
Below in conjunction with the accompanying drawings and specific embodiment is further described the application principle of the present invention.
As shown in Figure 1：A kind of method for crystallising of 1-DNJ, this method include the following steps：
S101：First mulberry leaf powder with acidic ethanol is impregnated, and is handled in ultrasonic cell-break machine, filters, collects filter
Liquid is centrifuged, and crude extract is made；
S102：The crude extract prepared is eluted by cation exchange resin again；
S103：Collection eluent, which is placed in Rotary Evaporators, to be concentrated, then concentrate is extracted with n-butanol；
S104：Extract liquor is recycled after extraction, excess is placed in low temperature drying case and is dried；
S105：Drying is placed in ethyl alcohol, and crystal is precipitated after forming supersaturated solution, collect after crystal drying up into
Product.
The method for crystallising of 1-DNJ is specially：
Extraction：
Mulberry leaf be crushed into 40 mesh sieve, 300g is weighed in 1000mL beakers, 65% acidic ethanol 800mL is added to impregnate
30min is put into ultrasonic cell-break machine and handles 20min, filtering, collects filtrate, and residue adds in 65% ethyl alcohol weights of 400mL
Multiple processing is primary, and filtering discards residue, merges filtrate twice, and the filtrate after merging twice is recycled ethyl alcohol with Rotary Evaporators
And small size is concentrated into, extracting solution is centrifuged, crude extract is made, the power of ultrasonic wave is 300W；
Purifying：The 1-DNJ coarse extraction solution collected after preparation is loaded to the exchange of cation exchange resin
Column, and with water elution is distilled, flow velocity is 1.0~2.0ml/min；When eluent from it is colourless become faint yellow when start to collect, directly
The first eluent is obtained until eluent is substantially colorless, then elutes the first eluent, elution with the ammonium hydroxide of 0.25mol/L again
Speed is 1 one 2ml/min, collects eluent, obtains the second eluent；
Concentration：Second eluent is placed in Rotary Evaporators, 1-DNJ is concentrated, in 600mmHg
Under the conditions of concentrate 30min；
Extraction：With the extracting n-butyl alcohol 3 times of concentrate same volume, the extracting n-butyl alcohol of 1-DNJ is obtained
Liquid；
It is dry：The n-butanol in the butanol extraction liquid of 1-DNJ is recycled, then will remove with the way of distillation
The substance obtained after n-butanol is gone to be placed in 300mmHg, 1-DNJ finished product is drying to obtain in the vacuum under the conditions of 10 DEG C；
Crystallization：
The 1-DNJ heating of a part of finished product is dissolved in ethyl alcohol, forms saturated solution.Opening is positioned over drying
Environment (relative humidity 20%, about for 24 hours), obtains supersaturated solution, is crystallized under conditions of stirring and obtains 1-DNJ
Crystal；
The detection method of 1-DNJ crystal：Utilize high performance liquid chromatography-mass spectrum On-line measurement method.
Opening described in crystallization is positioned over dry environment, specially：Opening is placed for 24 hours, is positioned over relative humidity 20%
Dry environment.
1-DNJ crystal obtained is also needed to be dried.
The second eluent is stood in the concentration and is placed in Rotary Evaporators within 12 hours, to 1-DNJ into
Row concentration.
With reference to experimental program, the present invention is further described.
Experimental designs
Extraction
Mulberry leaf be crushed into 40 mesh sieve, 300g is weighed in 1000mL beakers, 65% ethyl alcohol 800mL is added to impregnate 30min, is put
Enter processing 20min in ultrasonic wave biomixer (power of ultrasonic wave is 300W), filtrate is collected in filtering.Residue adds in 400mL
The reprocessing of 65% ethyl alcohol is primary, and filtering discards residue, merges filtrate twice, and filtrate is recycled ethyl alcohol simultaneously with Rotary Evaporators
Small size is concentrated into, extracting solution is centrifuged.
Purifying ----cation exchange resin processes
The 1-DNJ coarse extraction solution collected after preparation is loaded to the exchange column of cation exchange resin, and
With distillation water elution, flow velocity is 1.0~2.0ml/min.Flow velocity is slow during upper prop, and concentrate is made to be filled with ion exchange resin
Divide and combine.When eluent from it is colourless become faint yellow when start to collect, eluent 1 is obtained until eluent is substantially colorless.
Then eluent is collected, is obtained eluent 2 with the ammonium hydroxide of 0.25mol/L elution (1 one 2ml/min of elution speed) again.
Concentration
Eluent 2 is placed in Rotary Evaporators, 1-DNJ is concentrated, it is dense under the conditions of 600mmHg
Contracting 30min.
Extraction
With the extracting n-butyl alcohol 3 times of concentrate same volume, the butanol extraction liquid of 1-DNJ is obtained.
It is dry
The n-butanol in the butanol extraction liquid of 1-DNJ is recycled, then positive fourth will be removed with the way of distillation
The substance obtained after alcohol is placed in 300mmHg, and finished product is drying to obtain in the vacuum under the conditions of 10 DEG C.
Crystallization
The 1-DNJ heating of a part of finished product is dissolved in ethyl alcohol, forms saturated solution.Opening is positioned over drying
Environment (relative humidity 20%, about for 24 hours), obtains supersaturated solution, is crystallized under conditions of stirring and obtains 1-DNJ
Crystal.
The detection method of finished product：High performance liquid chromatography-mass spectrum On-line measurement method.
The present invention improves the degree of purity of 1-DNJ, obtains the crystal of 1-DNJ, more convenient
It is to add in 1-DNJ in drug to provide a convenient.
The method of the present invention can obtain about 0.2% mulberry leaf 1-DNJ recovery rates, be significantly higher than traditional ethyl alcohol recovery rate
0.00139% and diluted acid extraction efficiency 0.00147%, illustrate that collaboration has occurred in mulberry leaf 1-DNJ is extracted and makees for diluted acid and ethyl alcohol
With producing unpredictalbe effect, theory provided for the utilization of mulberry leaf 1-DNJ products in terms of medicine and health products
Support and technological guidance.
1-DNJ provided by the invention optimizes key process parameter using ultrasonic wave auxiliary law.1- deoxidations are wild
The comparative comparison of cation exchange resin and macroreticular resin when buttocks mycin purifies.Rotation is used when 1-DNJ concentrates
The time and temperature for turning evaporimeter are controlled.The items of process conditions required during 1-DNJ crystallization are determined
The selection of index parameter.
The application effect of the present invention is explained in detail with reference to specific embodiment
Illustrate by taking the method for crystallising of 6000g mulberry leaf extraction 1-DNJ as an example：
(1) it extracts：
Mulberry leaf be crushed into 40 mesh sieve, 6000g is weighed in 20L tempering tanks, 65% acidic ethanol 16L is added to impregnate 30min,
It is put into ultrasonic cell-break machine and handles 20min, filter, collect filtrate, residue adds in 65% ethyl alcohol of 8L reprocessing one
Secondary, filtering discards residue, merges filtrate twice, and the filtrate after merging twice is recycled ethyl alcohol with Rotary Evaporators and is concentrated into
Extracting solution is centrifuged in small size, crude extract is made, the power of ultrasonic wave is 300W；
(2) it purifies：
The 1-DNJ coarse extraction solution collected after preparation is loaded to the friendship of 732H type cation exchange resins
Column is changed, and with water elution is distilled, flow velocity is 1.0~2.0ml/min；When eluent from it is colourless become faint yellow when start to collect,
The first eluent is obtained until eluent is substantially colorless, then the first eluent is eluted with the ammonium hydroxide of 0.25mol/L again, washes
De- speed is 1~2ml/min, collects eluent, obtains the second eluent；
(3) it concentrates：
Second eluent is placed in Rotary Evaporators, the extracting solution containing 1-DNJ is concentrated,
30min is concentrated under the conditions of 600mmHg；
(4) it extracts：
With the extracting n-butyl alcohol 3 times with concentrate same volume, the butanol extraction liquid of 1-DNJ is obtained；
(5) it is dry：
The n-butanol in the butanol extraction liquid of 1-DNJ is recycled, then positive fourth will be removed with the way of distillation
The substance obtained after alcohol is placed in 300mmHg, and 1-DNJ finished product is drying to obtain in the vacuum under the conditions of 10 DEG C；
(6) it crystallizes：
The 1-DNJ heating of a part of finished product is dissolved in ethyl alcohol, forms saturated solution.Opening is positioned over drying
Environment (relative humidity 20%, about for 24 hours), obtains supersaturated solution, is crystallized under conditions of stirring and obtains 1-DNJ
Crystal.
The detection method of 1-DNJ crystal：Utilize high performance liquid chromatography-mass spectrum On-line measurement method.
After testing：The extract of the 1-DNJ of 6000g mulberry leaf and the standard curve pair of 1-DNJ
It is 0.18% that recovery rate is obtained than after.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
All any modification, equivalent and improvement made within refreshing and principle etc., should all be included in the protection scope of the present invention.
Claims (4)
1. a kind of method for crystallising of 1-DNJ, which is characterized in that the method for crystallising of the 1-DNJ includes
Following steps：
First mulberry leaf powder with acidic ethanol is impregnated, and is handled in ultrasonic cell-break machine, is filtered, is collected filtrate and centrifuged
Crude extract is made in separation；
The crude extract prepared is eluted by cation exchange resin again；
Collection eluent, which is placed in Rotary Evaporators, to be concentrated, then concentrate is extracted with n-butanol；
Extract liquor is recycled after extraction, excess is placed in low temperature drying case and is dried；
Drying is placed in ethyl alcohol, and crystal is precipitated after forming supersaturated solution, is got product after collecting crystal drying；
The method for crystallising of the 1-DNJ is specially：
Extraction：
Mulberry leaf be crushed into 40 mesh sieve, weigh 300g in 1000mL beakers, it is 6.5 to add in and be mixed to get pH by HCL and ethyl alcohol
65% acidic ethanol 800mL impregnate 30min, be put into power be 300W ultrasonication 20min, filtering, collect filtrate, it is residual
The acidic ethanol reprocessing that slag adds in 400mL 65% is primary, and filtering discards residue, merges filtrate twice, will merge twice
Filtrate afterwards recycles ethyl alcohol with Rotary Evaporators and is concentrated into small size, and extracting solution is centrifuged, and crude extract is made；
Purifying：The 1-DNJ coarse extraction solution collected after preparation is loaded to the exchange column of cation exchange resin,
And with water elution is distilled, flow velocity is 1.0~2.0ml/min；When eluent from it is colourless become faint yellow when start to collect, until wash
The first eluent is obtained until de- liquid is substantially colorless, then elutes the first eluent, elution speed with the ammonium hydroxide of 0.25mol/L again
For 1 one 2ml/min, eluent is collected, obtains the second eluent；
Concentration：Second eluent is placed in Rotary Evaporators, 1-DNJ is concentrated, in 600mmHg conditions
Lower concentration 30min；
Extraction：With the extracting n-butyl alcohol 3 times of concentrate same volume, the butanol extraction liquid of 1-DNJ is obtained；
It is dry：The n-butanol in the butanol extraction liquid of 1-DNJ is recycled with the way of distillation, then will be removed just
The substance obtained after butanol is placed in 300mmHg, and 1-DNJ finished product is drying to obtain in the vacuum under the conditions of 10 DEG C；
Crystallization：
The heating of a part of 1-DNJ finished product is dissolved in ethyl alcohol, forms saturated solution, opening is positioned over dry environment, shape
Into supersaturated solution, monocrystalline crystal is precipitated；Remaining another part distillation adds in 96% ethyl alcohol stirred crystallization and obtains to 0.8g/ml
To powdered crystal；
The detection method of monocrystalline crystal and powdered crystal：Utilize high performance liquid chromatography-mass spectrum On-line measurement method.
2. the method for crystallising of 1-DNJ as described in claim 1, which is characterized in that open described in crystallization to place
In dry environment, specially：Opening is placed for 24 hours, is positioned over the dry environment of relative humidity 20%.
3. the method for crystallising of 1-DNJ as described in claim 1, which is characterized in that monocrystalline crystal obtained and
Powdered crystal also needs to be dried.
4. the method for crystallising of 1-DNJ as described in claim 1, which is characterized in that washed in the concentration by second
De- liquid stands 12 hours and is placed in Rotary Evaporators, and 1-DNJ is concentrated.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101224240A (en) * | 2007-01-17 | 2008-07-23 | 周应军 | Antidiabetics extract, preparing method and uses thereof |
| CN101654428A (en) * | 2009-09-11 | 2010-02-24 | 成都市金医生科技健康产业有限公司 | Method for extracting and separating 1-deoxynojirimycin with high purity from natural products |
| CN102153504A (en) * | 2011-01-19 | 2011-08-17 | 长沙华康生物技术开发有限公司 | Method for preparing 1-deoxynojirimycin in mulberry leaves |
| CN102491938A (en) * | 2011-12-16 | 2012-06-13 | 北京贯虹科技集团有限公司 | Purification method of deoxynojirimycin |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101224240A (en) * | 2007-01-17 | 2008-07-23 | 周应军 | Antidiabetics extract, preparing method and uses thereof |
| CN101654428A (en) * | 2009-09-11 | 2010-02-24 | 成都市金医生科技健康产业有限公司 | Method for extracting and separating 1-deoxynojirimycin with high purity from natural products |
| CN102153504A (en) * | 2011-01-19 | 2011-08-17 | 长沙华康生物技术开发有限公司 | Method for preparing 1-deoxynojirimycin in mulberry leaves |
| CN102491938A (en) * | 2011-12-16 | 2012-06-13 | 北京贯虹科技集团有限公司 | Purification method of deoxynojirimycin |
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