CN108176387A - A kind of silica gel chromatographic column filling material, preparation method and applications - Google Patents
A kind of silica gel chromatographic column filling material, preparation method and applications Download PDFInfo
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- CN108176387A CN108176387A CN201810191275.6A CN201810191275A CN108176387A CN 108176387 A CN108176387 A CN 108176387A CN 201810191275 A CN201810191275 A CN 201810191275A CN 108176387 A CN108176387 A CN 108176387A
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- Prior art keywords
- silica gel
- chromatographic column
- bis
- filling material
- aminopropyl
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 title claims abstract description 154
- 239000000741 silica gel Substances 0.000 title claims abstract description 103
- 229910002027 silica gel Inorganic materials 0.000 title claims abstract description 103
- 239000000463 material Substances 0.000 title claims abstract description 77
- 238000011049 filling Methods 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title abstract description 17
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 40
- 239000008101 lactose Substances 0.000 claims abstract description 40
- WWBITQUCWSFVNB-UHFFFAOYSA-N 3-silylpropan-1-amine Chemical compound NCCC[SiH3] WWBITQUCWSFVNB-UHFFFAOYSA-N 0.000 claims abstract description 24
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229910000077 silane Inorganic materials 0.000 claims abstract description 21
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims description 43
- 229920001296 polysiloxane Polymers 0.000 claims description 33
- -1 methoxyl group Chemical group 0.000 claims description 22
- 239000000758 substrate Substances 0.000 claims description 22
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 20
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 19
- 229910052710 silicon Inorganic materials 0.000 claims description 18
- 239000010703 silicon Substances 0.000 claims description 18
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 238000000926 separation method Methods 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 13
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 12
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 11
- 239000001294 propane Substances 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 8
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 7
- 239000001273 butane Substances 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims description 7
- PZJJKWKADRNWSW-UHFFFAOYSA-N trimethoxysilicon Chemical compound CO[Si](OC)OC PZJJKWKADRNWSW-UHFFFAOYSA-N 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
- CWAFVXWRGIEBPL-UHFFFAOYSA-N ethoxysilane Chemical compound CCO[SiH3] CWAFVXWRGIEBPL-UHFFFAOYSA-N 0.000 claims description 5
- 230000003213 activating effect Effects 0.000 claims description 4
- ZXPDYFSTVHQQOI-UHFFFAOYSA-N diethoxysilane Chemical compound CCO[SiH2]OCC ZXPDYFSTVHQQOI-UHFFFAOYSA-N 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- YQGOWXYZDLJBFL-UHFFFAOYSA-N dimethoxysilane Chemical compound CO[SiH2]OC YQGOWXYZDLJBFL-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- ARYZCSRUUPFYMY-UHFFFAOYSA-N methoxysilane Chemical compound CO[SiH3] ARYZCSRUUPFYMY-UHFFFAOYSA-N 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- ZPZDIFSPRVHGIF-UHFFFAOYSA-N 3-aminopropylsilicon Chemical compound NCCC[Si] ZPZDIFSPRVHGIF-UHFFFAOYSA-N 0.000 claims 2
- WLRXPHQCSYCDEP-UHFFFAOYSA-N 3-[dichloro(propan-2-yl)silyl]propan-1-amine Chemical class NCCC[Si](Cl)(Cl)C(C)C WLRXPHQCSYCDEP-UHFFFAOYSA-N 0.000 claims 1
- 239000005046 Chlorosilane Substances 0.000 claims 1
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 21
- 230000003335 steric effect Effects 0.000 abstract description 7
- 125000000217 alkyl group Chemical group 0.000 abstract description 4
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 3
- 230000002349 favourable effect Effects 0.000 abstract 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 39
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 18
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 238000012856 packing Methods 0.000 description 13
- 239000007864 aqueous solution Substances 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 239000011521 glass Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 206010013786 Dry skin Diseases 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 239000000945 filler Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 4
- 230000006837 decompression Effects 0.000 description 4
- 230000005611 electricity Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- IGSUJBNDAWQLST-UHFFFAOYSA-N chloro-di(propan-2-yl)silicon Chemical compound CC(C)[Si](Cl)C(C)C IGSUJBNDAWQLST-UHFFFAOYSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000005485 electric heating Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- XSAUEOCQIPDIQK-UHFFFAOYSA-N ethoxy(diethyl)silane Chemical compound CCO[SiH](CC)CC XSAUEOCQIPDIQK-UHFFFAOYSA-N 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229930195727 α-lactose Natural products 0.000 description 2
- FWNDRXJGQXZQOZ-UHFFFAOYSA-N 3-(ethoxy-methyl-propan-2-ylsilyl)propan-1-amine Chemical class CCO[Si](C)(C(C)C)CCCN FWNDRXJGQXZQOZ-UHFFFAOYSA-N 0.000 description 1
- BNYFUBOZYDQIDU-UHFFFAOYSA-N 3-[diethoxy(ethyl)silyl]propan-1-amine Chemical class CCO[Si](CC)(OCC)CCCN BNYFUBOZYDQIDU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- QACUPNAKIPYZAW-RMQWDSPGSA-N O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O QACUPNAKIPYZAW-RMQWDSPGSA-N 0.000 description 1
- 229910003978 SiClx Inorganic materials 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- WQZGKKKJIJFFOK-DVKNGEFBSA-N alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-DVKNGEFBSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005253 cladding Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- HAKOAQCVDUCPTM-UHFFFAOYSA-N dichloro(propan-2-yl)silane Chemical compound CC(C)[SiH](Cl)Cl HAKOAQCVDUCPTM-UHFFFAOYSA-N 0.000 description 1
- MROCJMGDEKINLD-UHFFFAOYSA-N dichlorosilane Chemical compound Cl[SiH2]Cl MROCJMGDEKINLD-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- PVXAEFHZZIVEEJ-UHFFFAOYSA-N ethoxy-di(propan-2-yl)silane Chemical compound CCO[SiH](C(C)C)C(C)C PVXAEFHZZIVEEJ-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- JSWYYQXCMPNWMB-UHFFFAOYSA-N methoxy-di(propan-2-yl)silane Chemical compound CO[SiH](C(C)C)C(C)C JSWYYQXCMPNWMB-UHFFFAOYSA-N 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000012763 reinforcing filler Substances 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
- C07H3/04—Disaccharides
-
- G01N30/482—
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
- B01J2220/52—Sorbents specially adapted for preparative chromatography
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The present invention provides a kind of silica gel chromatographic column filling material, preparation method and applications, the silica gel chromatographic column filling material includes silica gel and is bonded to the organosilan of the Silica Surface, the organosilan includes γ-aminopropylsilane and other silane, wherein the γ-aminopropylsilane introduces the alkyl group with space steric effect.The silica gel chromatographic column filling material of the present invention, by introducing organic-inorganic hybrid structure and there is the alkyl group of space steric effect, the stability of the silica gel chromatographic column filling material is effectively increased, when being detached for lactose, may be such that lactose has extremely excellent peak type, higher column effect and the peak area stablized.In addition, the preparation method of the silica gel chromatographic column filling material has many advantages, such as that simple, stability is good, favorable reproducibility and is easy to large-scale production.
Description
Technical field
The present invention relates to high performance liquid chromatography packing materials, and in particular to a kind of silica gel chromatographic column filling material, preparation method and its
Using.
Background technology
Lactose (lactose) is a kind of disaccharide, by a molecule β-D- galactolipins and a molecule alpha-D-glucose β-Isosorbide-5-Nitrae-
Position forms glycosidic bond and is connected, molecular formula C12H22O11, relative molecular mass 342.3.There are two types of anomers for lactose：α-
Lactose and beta lactose, in aqueous solution can mutual inversion of phases.Alpha-lactose is easy to combine a molecular crystalline water.Lactose is as a kind of medicine
With auxiliary material, it is widely used in the form of filler or diluent in tablet, capsule, granule and freeze-drying prods.At present, market
On have the separation that method carries out the carbohydrates objects such as lactose using Hydrogen sugar column or calcium type sugar column, although Hydrogen sugar column or calcium type sugar
Column stability is better than amino chromatographic column, but the selectivity of the type chromatographic column is limited, and the separation of carbohydrate object is selected
Property not as good as amino chromatographic column, thus existing national standard, such as 2015 editions《Pharmacopoeia of People's Republic of China》Still recommend amino
Chromatographic column assay method is as standard determination method.However it finds during atual detection, use common amino linkage on the market
When conjunction silica gel chromatographic column filling material carries out the measure of the project, it is frequently encountered problems with：(1) defined is not achieved in column effect
16500 pieces/m theoretical cam curves；(2) sucrose and lactose cannot reach baseline separation；(3) the RSD values of lactose peak area cannot expire
Foot 2.0% is hereinafter, accurate quantitative analysis can not be carried out to it.
To solve the above-mentioned problems, some novel amino chromatograph packing materials are had developed in recent years.Chinese patent CN
Polyamino group silane reagent, amide groups is respectively adopted in 201310090809.3 and Chinese patent CN 200610015584.5
Silylating reagent and silica gel reaction are prepared for novel amino bonded silica gel chromatograph packing material.These novel amino chromatograph packing materials can pass through
Phase between " electrostatic screen " declines Silica Surface remnants silicone hydroxyls of the groups such as secondary amine and amide and lactose object
Interaction, and stability of the reinforcing filler in water phase mobile phase at high proportion.It is but this kind of new with " electrostatic screen " effect
Type amino chromatograph packing material there is also it is certain the shortcomings that, be mainly manifested in separate lactose process center pillar and imitate low, peak area repeatability
It is not ideal enough and big to the baseline noise of lactose chromatographic peak, so as to influence the accuracy quantitative to lactose.
In conclusion there is an urgent need for developing a kind of new silica gel chromatographic column filling material, to solve lactose separation and content in the prior art
Problems existing for measure.
Invention content
The object of the present invention is to provide a kind of for silica gel chromatographic column filling material of the lactose separation with assay and its preparation side
Method, using the silica gel chromatographic column filling material can solve existing column effect when traditional amino chromatographic column carries out lactose assay it is low,
Peak area is unstable and the problems such as baseline noise is big, has good reproducibility and stability.
To achieve these goals, the present invention adopts the following technical scheme that：
A kind of silica gel chromatographic column filling material, including：Silica gel and the organosilan for being bonded to the Silica Surface, the organosilan
Including γ-aminopropylsilane and other silane, wherein：
The chemical structure of general formula of the γ-aminopropylsilane is：
Wherein, R1For C2~4Alkyl, R2For C2~4Alkyl or C1~2Alkoxy, X1For reaction active groups, preferably
Chlorine, methoxy or ethoxy.
According to embodiment of the present invention, the chemical structure of general formula of other silane is：
Wherein, R3、R4Selected from C1~4Alkyl, X2For reaction active groups, preferably chlorine, methoxy or ethoxy；N is 2
~8 integer.
According to embodiment of the present invention, other silane are selected from 1,2- bis- (methoxyl group silicon substrate) hexane, 1,2-
Two (ethyl-silicone) hexanes, 1,2- bis- (ethyl-silicone) pentane, 1,2- bis- (ethyl-silicone) pentane, bis- (methoxies of 1,2-
Base silicon substrate) butane, 1,2- bis- (ethyl-silicone) butane, 1,2- bis- (methoxyl group silicon substrate) propane, 1,2- bis- (ethyl-silicone)
Propane, 1,2- bis- (ethyl-silicone) ethane, 1,2- bis- (ethyl-silicone) ethane, 1,2- bis- (trimethoxy silicon substrate) propane,
It is one or more in (methoxyl group silicon substrate) methane of 1,2- bis- and 1,2- bis- (trimethoxy silicon substrate) methane.
According to embodiment of the present invention, the γ-aminopropylsilane is selected from 3- aminopropyl diisopropyl ethyoxyl silicon
Alkane, 3- aminopropyl isopropyls diethoxy silane, 3- aminopropyls diethylethoxysilane, 3- aminopropyl ethyl diethoxy silicon
Alkane, 3- aminopropyl isopropyl methyls Ethoxysilane, 3- aminopropyl isopropoxyethyl radicals Ethoxysilane, 3- aminopropyl diisopropyls
Methoxy silane, 3- aminopropyl isopropyls dimethoxysilane, 3- aminopropyls diisopropyl chlorosilane and 3- aminopropyl isopropyls
It is one or more in dichlorosilane.
The present invention also provides a kind of methods for preparing above-mentioned silica gel chromatographic column filling material, include the following steps：
Silica gel activating is pre-processed, obtaining surface has the activated silica gel of silicone hydroxyl；
The activated silica gel is stirred back flow reaction in organic solvent with other silane, by other silane
The surface of the activated silica gel is bonded in, obtains the solution of the silica gel containing hybrid inorganic-organic；And
The γ-aminopropylsilane is added in the solution and is stirred back flow reaction, and the γ-aminopropylsilane is bonded in institute
The surface of hybrid inorganic-organic silica gel is stated, obtains the silica gel chromatographic column filling material.
According to embodiment of the present invention, the silicone hydroxyl on the surface of the activated silica gel and other silane rub
You are than being 1:(0.3~1.2).
According to embodiment of the present invention, the silicone hydroxyl on the surface of the activated silica gel and the γ-aminopropylsilane
Molar ratio is 1:(0.3~1.2).
According to embodiment of the present invention, the quality of the silica gel and the volume ratio of organic solvent are 1:(4~10)
g/ml。
According to embodiment of the present invention, the grain size of the silica gel is 3~10 μm, and aperture isThan
Surface area is 180~400m2/g。
The present invention also provides application of the above-mentioned silica gel chromatographic column filling material in lactose separation.
According to the description of above-mentioned technical proposal it is found that the beneficial effects of the present invention are：
" other silane " 1. of the present invention refers to the organosilan of other types in addition to γ-aminopropylsilane.Pass through
This kind of organosilan is first bonded in Silica Surface, silica matrix can be easy to be modified to the silica gel of hybrid inorganic-organic structure,
So as to weaken the hydrolysis of amino group so that the silica gel chromatographic column filling material of amino bonded has preferable stability；
2. the alkyl functional group with space steric effect is introduced by the γ-aminopropylsilane being bonded to Silica Surface, it can be true
The remaining silicone hydroxyl of Silica Surface is protected by the shielding of high degree, is overcome " non-specificity retains " between silicone hydroxyl and lactose
Effect, so as to when being detached for lactose, may be such that lactose has extremely excellent peak type, higher column effect and the peak stablized
Area；
3. the chromatographic column that silica gel chromatographic column filling material provided by the invention is loaded, according to《2015 editions People's Republic of China's medicines
Allusion quotation》Requirement lactose is measured, can be fully solved existing for traditional amino chromatographic column that column effect is not high, peak area is unstable
The problems such as fixed and baseline noise is big.And the preparation method of the silica gel chromatographic column filling material is with preparation method is simple, stability is good, again
The advantages that existing property is good and is easy to large-scale production.
Description of the drawings
Fig. 1 is the method schematic diagram that embodiment 1 prepares silica gel chromatographic column filling material；
Fig. 2 is silica gel chromatographic column filling material prepared by embodiment 1 and No. 1 amino chromatograph packing material separation analysis lactose chromatogram；
Fig. 3 is silica gel chromatographic column filling material prepared by embodiment 1 and No. 2 amino chromatograph packing material separation analysis lactose chromatograms；
Fig. 4 is that the silica gel chromatographic column filling material prepared by embodiment 1 divides analysis of variance lactose repeatability chromatogram.
Specific embodiment
Illustrate embodiments of the present invention below by way of particular specific embodiment, those of ordinary skill in the art can be by this
Specification disclosure of that understands advantages of the present invention and effect easily.The present invention can also pass through other different embodiment party
Formula is implemented or is applied, and the various details in this specification may be based on different viewpoints and application, not depart from institute of the present invention
Different modification and change are assigned under disclosed design.In addition, all ranges of the present invention and value all include and annexable.It falls
Any numerical value or point in heretofore described range, such as any integer can serve as minimum value or maximum value to export
The next range etc..
The present invention provides a kind of silica gel chromatographic column filling material, including：Silica gel and the organosilan for being bonded to the Silica Surface, institute
It states organosilan and includes γ-aminopropylsilane and other silane, wherein：The chemical structure of general formula of the γ-aminopropylsilane is：
Wherein, R1For C2~4Alkyl, R2For C2~4Alkyl or C1~2Alkoxy, X1It (leaves away for reaction active groups
Group), preferably chlorine, methoxy or ethoxy.
" other silane " of the present invention refers to the organosilan of other types in addition to γ-aminopropylsilane.By
Silica Surface is first bonded this kind of organosilan, and silica matrix can be easy to be modified to the silica gel of hybrid inorganic-organic structure, from
And weaken the hydrolysis of amino group so that the silica gel chromatographic column filling material of amino bonded has preferable stability；Meanwhile by right
γ-aminopropylsilane introduces the alkyl functional group with space steric effect, can shield silica matrix surface largely unreacted silicon
Hydroxyl, high degree overcomes " non-specificity retains " effect between silicone hydroxyl and lactose, so that lactose has extremely
Excellent peak type, higher column effect and the peak area stablized；The hydrolysis of amino group can also be weakened by steric effect so that
Amino bonded silica gel chromatographic column filling material further has preferable stability.The chemical modification on the silica matrix surface is in addition to being had
Other than machine-inorganic hybridization modification and γ-aminopropylsilane bonding modification, do not need to fill out as the silica gel chromatograph of traditional amino bonded
Material equally needs to carry out end-group termination processing to it.
In an embodiment of the invention, the chemical structure of general formula of other silane is：
Wherein, R3、R4Selected from C1~4Alkyl, X2For reaction active groups (i.e. leaving group), preferably chlorine, methoxyl group or
Ethyoxyl；N is 2~8 integer.Further, which includes but not limited to 1,2- bis- (methoxyl group silicon substrate) hexane, 1,
2- bis- (ethyl-silicone) hexane, 1,2- bis- (ethyl-silicone) pentane, 1,2- bis- (ethyl-silicone) pentane, bis- (first of 1,2-
Oxygroup silicon substrate) butane, 1,2- bis- (ethyl-silicone) butane, 1,2- bis- (methoxyl group silicon substrate) propane, (the ethyoxyl silicon of 1,2- bis-
Base) propane, 1,2- bis- (ethyl-silicone) ethane, 1,2- bis- (ethyl-silicone) ethane, 1,2- bis- (trimethoxy silicon substrate) third
It is one or more in alkane, (methoxyl group silicon substrate) methane of 1,2- bis- and 1,2- bis- (trimethoxy silicon substrate) methane.
In an embodiment of the invention, the γ-aminopropylsilane includes but not limited to 3- aminopropyl diisopropyl second
Oxysilane, 3- aminopropyl isopropyls diethoxy silane, 3- aminopropyls diethylethoxysilane, 3- aminopropyl ethyl diethyls
Oxysilane, 3- aminopropyl isopropyl methyl Ethoxysilanes or 3- aminopropyl isopropoxyethyl radicals Ethoxysilane, 3- aminopropyls
Diisopropyl methoxy silane, 3- aminopropyl isopropyls dimethoxysilane, 3- aminopropyls diisopropyl chlorosilane and 3- ammonia third
It is one or more in base isopropyl dichlorosilane.
The present invention also provides the preparation methods of above-mentioned silica gel chromatographic column filling material, include the following steps：
Silica gel activating is pre-processed, obtaining surface has the activated silica gel of silicone hydroxyl；
The activated silica gel is stirred back flow reaction in organic solvent with other silane, by other silane
The surface of the activated silica gel is bonded to, obtains the solution of the silica gel containing hybrid inorganic-organic；And
γ-aminopropylsilane is added in into the solution and is stirred back flow reaction, the γ-aminopropylsilane is bonded to described
The surface of hybrid inorganic-organic silica gel obtains the silica gel chromatographic column filling material.
Specifically, the silica gel is preferably full porous spherical silica gel, further preferably the full porous ball shape and color of ultra-high purity
Spectrum silica gel.Grain size for the raw material silica gel of activation is preferably 3~10 μm, and aperture is preferablySpecific surface area
Preferably 180~400m2/g。
In an embodiment of the invention, the process of the silica gel activating pretreatment includes：Into the silica gel
The hydrofluoric acid aqueous solution that mass concentration is 0.04~0.08% is added in, the activated silica gel is made in back flow reaction；The silica gel
Quality and hydrofluoric acid aqueous solution the ratio between volume preferably 1：(8~10).It is further preferred that silica gel and hydrofluoric acid aqueous solution
React 22~24 hours under the mode of agitating and heating reflux, is filtered under the mode filtered later in decompression, by silica gel and
Hydrofluoric acid aqueous solution detaches, and cleans silica gel with ultra-pure water (redistilled water), to remove the hydrofluoric acid of its remained on surface, until
It is in neutrality for the aqueous solution of cleaning, constant weight is dried under vacuum in 90~110 DEG C, activated silica gel is made.
In an embodiment of the invention, in the preparation method of the silica gel chromatographic column filling material, to miscellaneous containing organic and inorganic
After addition γ-aminopropylsilane is stirred back flow reaction in the solution of SiClx glue, further include the product mistake after the completion of back flow reaction
Filter, and washed successively with toluene, tetrahydrofuran/water, methanol and acetonitrile, the silica gel chromatographic column filling material is made.Specifically, it will return
The solution of container is cooled to the reflux temperature of organic solvent hereinafter, being filtered under reduced pressure after the completion of stream reaction, successively with toluene,
Tetrahydrofuran/water, methanol and acetonitrile washing.Preferably, the solid product of gained is dried in vacuo 12 at a temperature of 90~200 DEG C
Hour or more, obtain filler.Further preferably, the volume ratio of above-mentioned tetrahydrofuran/water can be 8：2.Used first
Benzene, tetrahydrofuran/water, methanol and acetonitrile temperature be 40~80 DEG C.
In an embodiment of the invention, the molar ratio of the silicone hydroxyl on activated silica gel surface and organosilan is 1:
(0.3~1.2).
In an embodiment of the invention, the molar ratio of the silicone hydroxyl on activated silica gel surface and γ-aminopropylsilane is 1:
(0.3~1.2).
In an embodiment of the invention, the ratio between the quality of the raw material silica gel and the volume of organic solvent are preferred
It is 1:(4~10) g/ml.
In an embodiment of the invention, the organic solvent is preferably nonpolar solvent, such as toluene, diformazan
Benzene, n-hexane or normal heptane.
In an embodiment of the invention, the back flow reaction is preferably stirred at reflux reaction at 80~150 DEG C
22~48 hours.
In an embodiment of the invention, the silica gel chromatographic column filling material prepared by the above method, can be used as novel
The silica gel chromatographic column filling material of amino bonded is used for separate lactose.
Illustrate below by specific embodiment：
The preparation of 1 silica gel chromatographic column filling material of embodiment
Fig. 1 is the method schematic diagram that embodiment 1 prepares silica gel chromatographic column filling material.Specific preparation method includes the following steps：
(1) 100g silica gel (5 μm, be purchased from Japanese DAISO companies) is added in into 2L glass material reaction vessels, and is added in
1000mL distilled water stirs 30 minutes, filtering, repeats the step twice.Then it is 0.08% hydrofluoric acid to add in 1000mL mass ratioes
Aqueous solution, stirring are cleaned with distilled water to neutrality after 24 hours, are eventually adding the washing of 1000mL acetone, filtering, 110 DEG C of dryings 12
Hour, obtain activated silica gel A；
(2) the activated silica gel A prepared in " step (1) " is added in into glass material reaction vessel, and adds in 800mL dryings
Dry toluene solvent, 50.0g1,2- bis- (trimethoxy silicon substrate) propane B are stirring evenly and then adding into 170 revs/min, use
Electric heating cover is heated to 110 DEG C, is stirred at reflux reaction 24 hours, obtains the solution of the C of silica gel containing hybrid inorganic-organic, wherein should
Hybrid inorganic-organic silica gel C still contains the unreacted activity hydroxy in part；
(3) 50.0g3- aminopropyl diisopropyl Ethoxysilane D are added in into step (2) solution after reaction, are made
Electricity consumption heating mantle heats are stirred at reflux reaction 24 hours to 110 DEG C, obtain containing the upper 3- aminopropyl diisopropyl ethyoxyls of bonding
The solution of the hybrid inorganic-organic silica gel E of silane D：
(4) after reaction, turn off electric jacket, treat that glass material reaction vessel solvent temperature is cooled to 60 DEG C or so, make
It is filtered with decompression pan, is then washed successively with toluene, tetrahydrofuran/aqueous solution (v/v=8/2), methanol, acetonitrile
It washs, product is dried in vacuo 12 hours at 110 DEG C up to silica gel chromatographic column filling material.
Wherein, double-deck micro-sphere structure represents the organic and inorganic with being obtained after the reaction of 1,2- bis- (trimethoxy silicon substrate) propane
Hybridisation silica gel.It is noted that the double-layer structure of structure C is only illustrated, for specification configuration relationship, it is complete not representing outer layer organic layer
Full cladding silica gel；Structure E is only illustrated as γ-aminopropylsilane and is bonded on the hybrid inorganic-organic silica gel rather than limits key
The quantity and position relationship of splice grafting branch.
The preparation of 2 silica gel chromatographic column filling material of embodiment
(1) 100g silica gel (5 μm, be purchased from Japanese DAISO companies) is added in into 2L glass material reaction vessels, and is added in
1000mL distilled water stirs 30 minutes, filtering, repeats the step twice.Then it is 0.08% hydrofluoric acid to add in 1000mL mass ratioes
Aqueous solution, stirring are cleaned with distilled water to neutrality after 24 hours, are eventually adding the washing of 1000mL acetone, filtering, 110 DEG C of dryings 12
Hour, obtain activated silica gel；
(2) activated silica gel prepared in " step (1) " is added in into glass material reaction vessel, and adds in 800mL dryings
Dry toluene solvent, 50.0g 1 is stirring evenly and then adding into 170 revs/min, 2- bis- (methoxyl group silicon substrate) butane uses electricity
Heating mantle heats are stirred at reflux reaction 24 hours, obtain the solution of the silica gel containing hybrid inorganic-organic, wherein this has to 110 DEG C
Machine-inorganic hybridization silica gel still contains the unreacted activity hydroxy in part；
(3) 50.0g3- aminopropyl isopropyl diethoxy silanes are added in into step (2) solution after reaction, are made
Electricity consumption heating mantle heats are stirred at reflux reaction 24 hours to 110 DEG C, obtain containing the upper 3- aminopropyl isopropyl diethoxies of bonding
The solution of the hybrid inorganic-organic silica gel of silane；
(4) after reaction, turn off electric jacket, treat that glass material reaction vessel solvent temperature is cooled to 60 DEG C or so, make
It is filtered with decompression pan, is then washed successively with toluene, tetrahydrofuran/aqueous solution (v/v=8/2), methanol, acetonitrile
It washs, product is dried in vacuo 12 hours at 110 DEG C up to silica gel chromatographic column filling material.
The preparation of 3 silica gel chromatographic column filling material of embodiment
(1) 100g silica gel (5 μm, be purchased from Japanese DAISO companies) is added in into 2L glass material reaction vessels, and is added in
1000mL distilled water stirs 30 minutes, filtering, repeats the step twice.Then it is 0.08% hydrofluoric acid to add in 1000mL mass ratioes
Aqueous solution, stirring are cleaned with distilled water to neutrality after 24 hours, are eventually adding the washing of 1000mL acetone, filtering, 110 DEG C of dryings 12
Hour, obtain activated silica gel；
(2) activated silica gel prepared in " step (1) " is added in into glass material reaction vessel, and adds in 800mL dryings
Dry toluene solvent, be stirring evenly and then adding into 50.0g1 in 170 revs/min, 2- bis- (methoxyl group silicon substrate) ethane, using electricity plus
Hot jacket is heated to 110 DEG C, is stirred at reflux reaction 24 hours, obtains the solution of the silica gel containing hybrid inorganic-organic, and wherein this is organic-
Inorganic hybridization silica gel still contains the unreacted activity hydroxy in part；
(3) 50.0g3- aminopropyl ethyl diethoxy silanes are added in into step (2) solution after reaction, are used
Electric heating cover is heated to 110 DEG C, is stirred at reflux reaction 24 hours, obtains containing the upper 3- aminopropyl ethyl diethoxy silanes of bonding
Hybrid inorganic-organic silica gel solution；
(4) after reaction, turn off electric jacket, treat that glass material reaction vessel solvent temperature is cooled to 60 DEG C or so, make
It is filtered with decompression pan, is then washed successively with toluene, tetrahydrofuran/aqueous solution (v/v=8/2), methanol, acetonitrile
It washs, product is dried in vacuo 12 hours at 110 DEG C up to silica gel chromatographic column filling material.
The separation and analysis of 4 lactose of embodiment
By silica gel chromatographic column filling material prepared by embodiment 1 into luggage column, column length 300mm, column internal diameter 4.6mm.Fill column condition such as
Under：Column pressure 3000-7000psi is filled, is homogenized agent：Acetonitrile and isopropanol, solid-liquid ratio 1:10, finally 30min is replaced with methanol.
With acetonitrile：Water (70:30, v/v) mobile phase of the solution as separation, the flow velocity of mobile phase is 1.0mL/min, and chromatogram column temperature is
45 DEG C, differential refraction detector temperature is 40 DEG C, and the object of separation is common pharmaceutic adjuvant lactose.Separating effect such as Fig. 2 institutes
Show.
Fig. 2 is silica gel chromatographic column filling material separation analysis lactose prepared by embodiment 1 and No. 1 amino chromatograph packing material separation analysis breast
The chromatogram of sugar.The filler that wherein described " No. 1 amino chromatographic column " loads is using the 3- ammonia third without steric effect
Ethyl triethoxy silicane alkane silylating reagent and without hybrid inorganic-organic silicon structure common silica gel reaction obtain it is traditional
Amino chromatograph packing material.Abscissa is retention time, unit min, and ordinate is the response for detecting signal, unit nRIU
(the part per billion of differential refraction unit).
As shown in Fig. 2, 1a~1c, which represents No. 1 amino chromatographic column, repeats 3 needle chromatography effect of sample introduction.1d~1f is respectively to implement
Silica gel chromatographic column filling material prepared by example 1 repeats 3 needle chromatography effect of sample introduction.By the measurement result of Fig. 1 it is found that using No. 1 amino color
When composing the measure of lactose and sucrose in column progress sample, continuous 3 sample introductions, hair are carried out to lactose and sucrose mixed reference substance solution
The relative standard deviation (RSD) of existing lactose peak area is 2.72%, more than 2015 editions《Pharmacopoeia of People's Republic of China》It is defined
2.0%；And when being measured using 1 separate lactose of embodiment with silica filler, 3 needle of continuous sample introduction finds that the RSD of lactose peak area is
0.86%, less than 2015 editions《Pharmacopoeia of People's Republic of China》Defined 2.0%, meet 2015 editions《People's Republic of China's medicine
Allusion quotation》It is required that.
Fig. 3 is silica gel chromatographic column filling material separation analysis lactose prepared by embodiment 1 and No. 2 amino chromatograph packing material separation analysis breasts
The chromatogram of sugar.The filler that wherein described " No. 2 amino chromatographic columns " loads is using the 3- aminopropyls with steric effect
Diisopropyl Ethoxysilane and without hybrid inorganic-organic structure silica gel reaction obtained amino chromatograph packing material.It is horizontal
Coordinate is retention time, and unit min, ordinate is the response for detecting signal, and unit is nRIU (the ten of differential refraction unit
1/100000000th).
As shown in figure 3,1a~1c, which represents No. 2 amino chromatographic columns, repeats 3 needle chromatography effect of sample introduction.1d~1f is respectively to implement
Silica gel chromatographic column filling material prepared by example 1 repeats 3 needle chromatography effect of sample introduction.By the measurement result of Fig. 3 it is found that using No. 2 amino colors
When composing the measure of lactose and sucrose in column progress sample, continuous 3 sample introductions, hair are carried out to lactose and sucrose mixed reference substance solution
The relative standard deviation (RSD) of existing lactose peak area is 1.14%, not as good as the measure of amino chromatograph packing material prepared in embodiment 1
Effect.
Fig. 4 is the later lactose design sketch of 200 needle of silica gel chromatographic column filling material sample introduction of the preparation of embodiment 1, as shown in Figure 4, should
For chromatograph packing material after 200 needles measure, peak type is good, and column effect does not significantly decrease.
Silica gel chromatographic column filling material prepared by the various embodiments described above loads chromatographic column, according to《2015 editions People's Republic of China (PRC)
Pharmacopeia》Requirement lactose is measured respectively, can solve existing for traditional amino chromatographic column column and imitate not high, peak area
Unstable, the problems such as baseline noise is big.Preparation method provided by the invention is with preparation method is simple, stability is good, reproducibility
The advantages that well and being easy to large-scale production.
Above-described embodiment is only to be illustrated, and is not intended to limit the present invention.Any those of ordinary skill in the art are equal
Can without prejudice to the present invention design and under the scope of, above-described embodiment is modified and is changed.Therefore, right of the invention is protected
Protecting range is defined by claims appended hereto, as long as not influencing the effect of the present invention and implementing purpose, Ying Han
It is placed in the displosure technology contents.
Claims (10)
1. a kind of silica gel chromatographic column filling material, including：Silica gel and the organosilan for being bonded to the Silica Surface, the organosilan packet
γ-aminopropylsilane and other silane are included, wherein：
The chemical structure of general formula of the γ-aminopropylsilane is：
Wherein, R1For C2~4Alkyl, R2For C2~4Alkyl or C1~2Alkoxy, X1For reaction active groups, preferably chlorine,
Methoxy or ethoxy.
2. silica gel chromatographic column filling material according to claim 1, which is characterized in that the chemical structure of general formula of other silane
For：
Wherein, R3、R4Selected from C1~4Alkyl, X2For reaction active groups, preferably chlorine, methoxy or ethoxy；N is 2~8
Integer.
3. silica gel chromatographic column filling material according to claim 2, which is characterized in that other silane are selected from 1,2-, bis- (methoxies
Base silicon substrate) hexane, 1,2- bis- (ethyl-silicone) hexane, 1,2- bis- (ethyl-silicone) pentane, 1,2- bis- (ethyl-silicone)
Pentane, 1,2- bis- (methoxyl group silicon substrate) butane, 1,2- bis- (ethyl-silicone) butane, 1,2- bis- (methoxyl group silicon substrate) propane, 1,
2- bis- (ethyl-silicone) propane, 1,2- bis- (ethyl-silicone) ethane, 1,2- bis- (ethyl-silicone) ethane, 1,2- bis- (three
Methoxyl group silicon substrate) one kind or more in propane, (methoxyl group silicon substrate) methane of 1,2- bis- and 1,2- bis- (trimethoxy silicon substrate) methane
Kind.
4. silica gel chromatographic column filling material according to any one of claim 1-3, which is characterized in that the γ-aminopropylsilane is selected from
3- aminopropyl diisopropyls Ethoxysilane, 3- aminopropyl isopropyls diethoxy silane, 3- aminopropyl diethyl ethoxy silicon
Alkane, 3- aminopropyl ethyls diethoxy silane, 3- aminopropyl isopropyl methyls Ethoxysilane, 3- aminopropyl isopropoxyethyl radicals second
Oxysilane, 3- aminopropyl diisopropyls methoxy silane, 3- aminopropyl isopropyls dimethoxysilane, 3- aminopropyl diisopropyls
It is one or more in base chlorosilane and 3- aminopropyl isopropyl dichlorosilanes.
5. a kind of method for the silica gel chromatographic column filling material for preparing any one of claim 1-4, includes the following steps：
Silica gel activating is pre-processed, obtaining surface has the activated silica gel of silicone hydroxyl；
The activated silica gel is stirred back flow reaction in organic solvent with other silane, by other silane groups
In the surface of the activated silica gel, the solution of the silica gel containing hybrid inorganic-organic is obtained；And aminopropyl silicon is added in into the solution
Alkane is stirred back flow reaction, and the γ-aminopropylsilane is bonded to the surface of the hybrid inorganic-organic silica gel, obtains described
Silica gel chromatographic column filling material.
6. method according to claim 5, which is characterized in that the silicone hydroxyl on the surface of the activated silica gel and other silane
Molar ratio be 1:(0.3~1.2).
7. method according to claim 5, which is characterized in that the silicone hydroxyl on the surface of the activated silica gel and the aminopropyl silicon
The molar ratio of alkane is 1:(0.3~1.2).
8. according to the method described in claim 5, it is characterized in that, the quality of the silica gel and the volume ratio of organic solvent are 1:
(4~10) g/ml.
9. according to claim 5-8 any one of them methods, which is characterized in that the grain size of the silica gel is 3~10 μm, aperture
ForSpecific surface area is 180~400m2/g。
10. according to application of the claim 1-4 any one of them silica gel chromatographic column filling material in lactose separation.
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| CN111250069A (en) * | 2020-01-20 | 2020-06-09 | 浙江月旭材料科技有限公司 | Silica gel chromatographic packing and preparation method and application thereof |
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