CN103752288B - A kind of preparation method being applied to the adsorbent that rapamycin is separated - Google Patents
A kind of preparation method being applied to the adsorbent that rapamycin is separated Download PDFInfo
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- CN103752288B CN103752288B CN201410035278.2A CN201410035278A CN103752288B CN 103752288 B CN103752288 B CN 103752288B CN 201410035278 A CN201410035278 A CN 201410035278A CN 103752288 B CN103752288 B CN 103752288B
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- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 title claims abstract description 48
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 title claims abstract description 45
- 229960002930 sirolimus Drugs 0.000 title claims abstract description 45
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000003463 adsorbent Substances 0.000 title claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims abstract description 13
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims abstract description 13
- 239000011976 maleic acid Substances 0.000 claims abstract description 13
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000004088 foaming agent Substances 0.000 claims abstract description 12
- 239000002270 dispersing agent Substances 0.000 claims abstract description 6
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000011837 N,N-methylenebisacrylamide Substances 0.000 claims abstract description 4
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000012071 phase Substances 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 11
- 239000008346 aqueous phase Substances 0.000 claims description 10
- 238000007664 blowing Methods 0.000 claims description 8
- 238000010557 suspension polymerization reaction Methods 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 3
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 3
- 229920006184 cellulose methylcellulose Polymers 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- 239000003999 initiator Substances 0.000 claims description 3
- 150000002978 peroxides Chemical class 0.000 claims description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- 239000011347 resin Substances 0.000 abstract description 19
- 229920005989 resin Polymers 0.000 abstract description 19
- 230000007797 corrosion Effects 0.000 abstract description 4
- 238000005260 corrosion Methods 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 239000011159 matrix material Substances 0.000 abstract description 4
- 239000002253 acid Substances 0.000 abstract description 3
- 239000003513 alkali Substances 0.000 abstract description 3
- 125000001153 fluoro group Chemical group F* 0.000 abstract description 2
- 229920000642 polymer Polymers 0.000 abstract description 2
- 238000006116 polymerization reaction Methods 0.000 abstract description 2
- 238000010792 warming Methods 0.000 abstract description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 abstract 2
- 239000011324 bead Substances 0.000 abstract 1
- 229960003276 erythromycin Drugs 0.000 abstract 1
- 239000000047 product Substances 0.000 description 21
- 238000000034 method Methods 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000001179 sorption measurement Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 101000634900 Homo sapiens Transcriptional-regulating factor 1 Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241001506137 Rapa Species 0.000 description 3
- 102100029446 Transcriptional-regulating factor 1 Human genes 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
- 230000004151 fermentation Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 238000012710 chemistry, manufacturing and control Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- QDGONURINHVBEW-UHFFFAOYSA-N dichlorodifluoroethylene Chemical group FC(F)=C(Cl)Cl QDGONURINHVBEW-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- QFJCIRLUMZQUOT-KADBNGAOSA-N (1R,9S,12S,15R,16E,18R,19R,21R,23S,24Z,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]propan-2-yl]-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)\C(C)=C\C=C\C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-KADBNGAOSA-N 0.000 description 1
- STGNLGBPLOVYMA-TZKOHIRVSA-N (z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O STGNLGBPLOVYMA-TZKOHIRVSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical group NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 230000010190 G1 phase Effects 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003409 anti-rejection Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000011153 ceramic matrix composite Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011218 seed culture Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Landscapes
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
A kind of preparation method being applied to the adsorbent that rapamycin is separated.Invent a kind of preparation method being applied to the adsorbent that rapamycin is separated: in a kettle., squeeze into pure water, add a certain amount of dispersant, initator, methyl methacrylate/N, N-methylene-bisacrylamide/1, 1-bis-fluoro-2, 2-dichloroethylene/maleic acid, pore-foaming agent etc., be warming up to reaction temperature, question response terminates. dries, extracting pore-foaming agent, dry closing bag. the present invention introduces a small amount of 1 in polymerization, 1-bis-fluoro-2, 2-dichloroethylene, maleic acid is as comonomer, to improve the compatibility of resin and rapamycin, and resin matrix ground is high temperature resistant, the ability of acid and alkali corrosion, thus improve the intensity of polymer beads. to erythromycin good separating effect, by force selective.The introducing of fluoro-containing group, resin matrix corrosion resistance is strengthened, and spherome surface is protected, thus extends service life.
Description
Technical field
The present invention relates to a kind of preparation method of resin sorbent, particularly a kind of preparation method being applied to the adsorbent that rapamycin is separated.
Background technology
Rapamycin (Rapamycin, RAPA), has another name called sirolimus (Sirolimus), is a kind of Novel macrocyclic lactone immunodepressant.The molecular formula of RAPA is C51H79NO13, and molecular weight 991 is white crystalline solid, and fusing point is 183-185 DEG C, and lipophilicity is dissolved in the organic solvents such as methyl alcohol, ethanol, acetone, chloroform, atomic water-soluble, is dissolved in ether hardly.RAPA, by different cytokine receptor disabling signal conduction, blocks T lymphocyte and other cells process by G1 phase to the S phase, thus plays immunosuppressive effect.Along with the increase of organ transplant quantity, immunodepressant class medicine for reducing rejection after organ transplant also presents quick growth trend, the product that particularly rapamycin etc. are new is becoming organ transplant immunodepressant main product gradually, and as a kind of novel anti-rejection medicine, be that the preparation of raw material just goes on the market at home with rapamycin.Domesticly to start late due to drug level, this type of product technology construction cycle is longer, particularly the factor such as perfect not to the utmost of existing production technology, and the technology and the level of production that have had a strong impact on rapamycin improve, because production capacity is less, existing output still can not meet domestic demand.Current China rapamycin formulation relies on import to be main, and import volume presents the trend increased year by year.The preparation made for raw material with this product is after Chinese market listing, and produce market capacity is huge, and market prospects are noticeable.
CN102433364 provides a kind of technique of preparing rapamycin by using microbial fermentation method, wherein, comprises the following steps: first in slant medium, cultivate water suction strepto-, then transfers to cultivate in fresh seeds culture medium; By the bacterial strain cultivated through described seed culture medium according to 2% inoculum concentration be seeded in fresh fermentation medium and carry out fermented and cultured, obtain the zymotic fluid containing rapamycin, utilize the dissolubility difference of rapamycin in water and organic solvent, abstraction and purification is carried out to the zymotic fluid containing rapamycin.After rapamycin dissolving crude product, upper silicagel column carries out chromatographic purifying, wash-out is carried out with the hexane solution (acetone 30%) of acetone, collect the eluent containing rapamycin, rapamycin crystal is added as seed after concentrate eluant, concentrate is cooled to 0-5 DEG C, stir after 1 hour and leave standstill crystallization, the rapamycin product obtained that is recrystallized filters rear dry acquisition rapamycin finished product.
CN101133065 describes the rapamycin of purifying and the method for obtaining purified rapamycin, it comprises: (a) is having under suitable alkali existent condition, with trim,ethylchlorosilane process rapamycin in atent solvent, thus provide rapamycin 31,42-two-0-trimethyl silyl ether; B () filters the two-0-trimethyl silyl ether of rapamycin 31,42-; C () extracts the two-0-trimethyl silyl ether of rapamycin 31,42-in heptane; D () washs the two-0-trimethyl silyl ether of stripped rapamycin 31,42-; And (e) makes the two-0-trimethyl silyl ether deprotection of stripped thunder handkerchief mould 31,42-with acid, thus produce rapamycin.
The fermentation yield of rapamycin is low, and from zymotic fluid, the difficulty of separation and Extraction rapamycin is larger.The greatest drawback of existing technique is exactly that separative efficiency is lower, energy consumption is higher, contaminated wastewater is serious.Adopt resin absorption technique to be then expected to overcome these defects, but require the adsorption capacity of resin and relatively high to the selection removal ability of pigment, common polymeric adsorbent is difficult to reach this requirement.Usually, the polarity etc. of the specific area of resin, resin pore structure and resin is larger to organic Adsorption Effect.Rapamycin is low pole material, according to the principle of " analog absorption analog ", and should be better with macroporous resin adsorption effect that is nonpolar or low pole.Meanwhile, when polymeric adsorbent has under suitable aperture can guarantee the condition of solute molecule good diffusion, resin specific area is larger, and adsorbance is also larger.Have higher compared with the adsorbance of low pole macroporous absorbent resin to rapamycin of bigger serface.
Summary of the invention
Object be for from rapamycin separation of fermentative broth rapamycin to the basic demand of adsorption and separation material, provide a kind of preparation method of adsorbent being applied to rapamycin and being separated, simultaneously openly its preparation method.
In a kettle., squeeze into pure water, add a certain amount of dispersant, initator, methyl methacrylate/N, N-methylene-bisacrylamide/1, the monomers such as 1-bis-fluoro-2,2-dichloroethylene/maleic acid, pore-foaming agent etc., be warming up to reaction temperature, question response terminates. and to dry, extracting pore-foaming agent, dry closing bag. the present invention introduces a small amount of 1 in polymerization, 1-bis-fluoro-2,2-dichloroethylene, maleic acid as comonomer, to improve the compatibility of resin and rapamycin, and resin matrix ground is high temperature resistant, the ability of acid and alkali corrosion.
The invention provides a kind of preparation method being applied to the adsorbent that rapamycin is separated, realized by following steps: the preparation of step 1. aqueous phase
By weight, add 100 parts of pure water 0.5-2 part organic chemistry dispersant (preferably 0.5 part) in pressure reaction still, stir;
Described chemical dispersant is selected from polyvinyl alcohol, gelatin or CMC etc.
The preparation of step 2. oil phase
By weight, by 100 parts of methyl methacrylates, 30-100 part (preferably 70 parts) N, N-methylene-bisacrylamide, 3-10 part (preferably 6 parts) 1,1-bis-fluoro-2,2-dichloroethylene, 3-10 part (preferably 5 parts) maleic acid mixes, then adds 0.5-3 part peroxide initiator (preferably 2 parts), 10-40 part pore-foaming agent, stirs;
Step 3. suspension polymerization
Being added in step 1 to be equipped with by the oil-phase solution prepared in step 2 beaker prepares in the pressure reaction still of aqueous phase, and at 60-95 DEG C of reaction 7-20h, reaction terminates rear blowing, and washing microballoon is limpid to water, after oven dry, pore-foaming agent extracting is clean, obtains product.
Fluoro-2, the 2-dichloroethylene structural formulas of described in step 21,1-bis-are shown in formula (1), are commercially available prod, as 1,1-bis-fluoro-2, the 2-dichloroethylene products that Hangzhou Bao Kai biochemicals Co., Ltd produces.
CF
2=CCl
2(1)
Maleic acid structural formula described in step 2 is shown in formula (2), is commercially available prod, as the maleic acid product that Zhengzhou Tian Yao Science and Technology Ltd. produces.
HO
2CCH=CHCO
2H(2)
The preferred benzoyl peroxide of peroxide initiator described in step 2.
Pore-foaming agent described in step 2 is good solvent or poor solvent or mixed solvent, as white oil, and solvent naphtha, toluene etc., preferred toluene.
Beneficial effect of the present invention:
1): by the inventive method obtain a kind of be applied to rapamycin be separated adsorbent good to rapamycin compatibility, to rapamycin good separating effect, by force selective.
2) introducing of fluoro-containing group, resin matrix corrosion resistance is strengthened, and spherome surface is protected, thus extends service life.
Detailed description of the invention
Following examples are only further illustrate the present invention, are not restriction the scope of protection of the invention.
Embodiment 1
The preparation of step 1. aqueous phase
By weight, add 100 parts of pure water in pressure reaction still, 0.5 part of gelatin, stirs.
The preparation of step 2. oil phase
The oil phase component of following ratio is mixed in beaker, stirs;
Step 3. suspension polymerization
Being added in step 1 to be equipped with by the oil-phase solution prepared in step 2 prepares in the pressure reaction still of aqueous phase, and at 80 DEG C of reaction 14h, reaction terminates rear blowing, reaction terminates rear blowing, washing microballoon is limpid to water, after oven dry, pore-foaming agent extracting is clean, obtains product. be numbered W-1
Embodiment 2
The preparation of step 1. aqueous phase
By weight, add 100 parts of pure water in pressure reaction still, 1.5 parts of polyvinyl alcohol, stir.
The preparation of step 2. oil phase
The oil phase component of following ratio is mixed in beaker, stirs;
Step 3. suspension polymerization
Being added in step 1 to be equipped with by the oil-phase solution prepared in step 2 prepares in the pressure reaction still of aqueous phase, and at 60 DEG C of reaction 20h, reaction terminates rear blowing, reaction terminates rear blowing, washing microballoon is limpid to water, after oven dry, pore-foaming agent extracting is clean, obtains product. be numbered W-2
Embodiment 3
The preparation of step 1. aqueous phase
By weight, add 100 parts of pure water in pressure reaction still, 2 parts of CMCs, stir.
The preparation of step 2. oil phase
The oil phase component of following ratio is mixed in beaker, stirs;
Step 3. suspension polymerization
Being added in step 1 to be equipped with by the oil-phase solution prepared in step 2 beaker prepares in the pressure reaction still of aqueous phase, and at 95 DEG C of reaction 10h, reaction terminates rear blowing, reaction terminates rear blowing, washing microballoon is limpid to water, after oven dry, pore-foaming agent extracting is clean, obtains product. be numbered W-3
Embodiment 4
In step 2,1,1-bis-fluoro-2,2-dichloroethylene weight portions are 10, the other the same as in Example 1.Products obtained therefrom is numbered W-4.
Embodiment 5
In step 2,1,1-bis-fluoro-2,2-dichloroethylene weight portions are 3, the other the same as in Example 1.Products obtained therefrom is numbered W-5.
Embodiment 6
In step 2, maleic acid weight portion is 10, the other the same as in Example 1.Products obtained therefrom is numbered W-6.
Embodiment 7
In step 2, maleic acid weight portion is 3, the other the same as in Example 2.Products obtained therefrom is numbered W-7.
Comparative example 1
In step 2,1,1-bis-fluoro-2,2-dichloroethylene weight portions are 0, the other the same as in Example 1.Products obtained therefrom is numbered W-8
Comparative example 2
In step 2, maleic acid weight portion is 0, the other the same as in Example 1.Products obtained therefrom is numbered W-9
Comparative example 3
In step 2, maleic acid weight portion is 0, and other is with embodiment 8.Products obtained therefrom is numbered W-10
With FTIS, pressing potassium bromide troche does infrared spectrum analysis to synthesized each resin.Infrared spectrum from product: W1-W10 is at 1725cm
-1near there is the carbonyl peak of ester group, at 3305cm
-1near there is N-H stretching vibration peak, illustrate and introduce acrylamide group in the skeleton of resin; At 1250cm in the collection of illustrative plates of W1-W7, W9 sample
-1near have CF
2, CF
3stretching vibration peak, 665cm
-1near have CF
2cF
3absworption peak, illustrated 1,1-bis-fluoro-2,2-dichloroethylene exist; 720cm
-1near there is cis C-H architectural feature peak, the existence of maleic acid (maleic acid) is described; So can determine that this patent product generates by methyl methacrylate cross-linking system and fluoro-2, the 2-dichloroethylene of 1,1-bis-, the polymer of maleic acid monomer copolymerization.
Embodiment 8
Accurately take each 5g of wet resin that pretreated embodiment 1-7 and comparative example 8-10 is obtained, be placed in 250mL tool plug ground triangular flask, precision adds people 100mL and extracts stoste, at room temperature vibrate triangular flask 5h, fully after absorption, filters, getting filtrate uses LC-10AD high performance liquid chromatograph to measure the concentration of rapamycin, compare with the measurement result extracting stoste, be calculated as follows adsorption capacity, in table 1:
Adsorbance (w/%)=[(extracting original liquid concentration-filter liquor concentration) x liquor capacity)/dried resin quality] x100%
Table 1: the polymeric adsorbent adsorption capacity list that this patent is obtained
Claims (1)
1. be applied to a preparation method for the adsorbent that rapamycin is separated, it is characterized in that comprising the following steps:
The preparation of step 1. aqueous phase
By weight, add 100 parts of pure water in a kettle., 0.5-2 part organic chemistry dispersant, stirs;
Described chemical dispersant is selected from polyvinyl alcohol, gelatin or CMC;
The preparation of step 2. oil phase
By weight, by 100 parts of methyl methacrylates, 30-100 part N, N-methylene-bisacrylamide, 3-10 part 1, fluoro-2, the 2-dichloroethylene of 1-bis-, 3-10 part maleic acid mixes, add 0.5-3 part peroxide initiator, 10-40 part pore-foaming agent again, stir;
Step 3. suspension polymerization
Being added to be equipped with by the oil-phase solution prepared in step 2 prepares in the reactor of aqueous phase, and at 70-100 DEG C of reaction 10-20h, reaction terminates rear blowing, and washing microballoon is limpid to water, after oven dry, pore-foaming agent extracting is clean, obtains product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410035278.2A CN103752288B (en) | 2014-01-22 | 2014-01-22 | A kind of preparation method being applied to the adsorbent that rapamycin is separated |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410035278.2A CN103752288B (en) | 2014-01-22 | 2014-01-22 | A kind of preparation method being applied to the adsorbent that rapamycin is separated |
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| Publication Number | Publication Date |
|---|---|
| CN103752288A CN103752288A (en) | 2014-04-30 |
| CN103752288B true CN103752288B (en) | 2016-03-30 |
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| CN104262358B (en) * | 2014-09-29 | 2016-02-17 | 常州兰陵制药有限公司 | Extract the method for rapamycin |
| CN105289545B (en) * | 2015-11-30 | 2017-12-01 | 王琪宇 | A kind of preparation of rapamycin separation adsorbent |
| CN105582901B (en) * | 2015-12-21 | 2018-03-02 | 王金明 | A kind of preparation of the adsorbent of long carbochain biatomic acid zymotic fluid |
| CN105597711B (en) * | 2016-03-09 | 2018-11-23 | 徐州鸿丰高分子材料有限公司 | A kind of preparation method of the adsorbent material of binary acid treating |
| CN105646801A (en) * | 2016-03-09 | 2016-06-08 | 张玲 | Preparation of octylphenol ethoxylate adsorbing material |
| CN105833854A (en) * | 2016-06-13 | 2016-08-10 | 王金明 | Preparation method of purified vanadium adsorption material |
| CN106268688A (en) * | 2016-08-21 | 2017-01-04 | 王琪宇 | A kind of preparation method of expoxy propane purification adsorbent |
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