CN112745367A - Method for reducing content of heavy metal rhodium in ivermectin - Google Patents
Method for reducing content of heavy metal rhodium in ivermectin Download PDFInfo
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- CN112745367A CN112745367A CN202011632021.7A CN202011632021A CN112745367A CN 112745367 A CN112745367 A CN 112745367A CN 202011632021 A CN202011632021 A CN 202011632021A CN 112745367 A CN112745367 A CN 112745367A
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- ivermectin
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- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 title claims abstract description 70
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 title claims abstract description 70
- 229960002418 ivermectin Drugs 0.000 title claims abstract description 70
- 229910052703 rhodium Inorganic materials 0.000 title claims abstract description 28
- 239000010948 rhodium Substances 0.000 title claims abstract description 28
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000000034 method Methods 0.000 title claims abstract description 22
- 229910001385 heavy metal Inorganic materials 0.000 title claims abstract description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000000741 silica gel Substances 0.000 claims abstract description 35
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 35
- 238000003756 stirring Methods 0.000 claims abstract description 19
- 239000000706 filtrate Substances 0.000 claims abstract description 15
- 238000001914 filtration Methods 0.000 claims abstract description 14
- 239000000047 product Substances 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000012043 crude product Substances 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 abstract description 18
- 239000002904 solvent Substances 0.000 abstract description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 abstract description 12
- 239000003054 catalyst Substances 0.000 abstract description 9
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 238000000746 purification Methods 0.000 abstract description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 239000007787 solid Substances 0.000 description 31
- 230000000052 comparative effect Effects 0.000 description 8
- 239000005660 Abamectin Substances 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 244000045947 parasite Species 0.000 description 3
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 229950008167 abamectin Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- FSHNFAOXXJLGJE-UHFFFAOYSA-N [Rh].[P] Chemical compound [Rh].[P] FSHNFAOXXJLGJE-UHFFFAOYSA-N 0.000 description 1
- 239000000642 acaricide Substances 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000007830 nerve conduction Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003284 rhodium compounds Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- FEQPHYCEZKWPNE-UHFFFAOYSA-K trichlororhodium;triphenylphosphane Chemical compound Cl[Rh](Cl)Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 FEQPHYCEZKWPNE-UHFFFAOYSA-K 0.000 description 1
- 239000011995 wilkinson's catalyst Substances 0.000 description 1
Classifications
-
- 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
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for reducing the content of heavy metal rhodium in ivermectin, which comprises the following steps: dissolving the crude ivermectin in an organic solvent, adding silica gel, stirring uniformly, filtering, and concentrating the filtrate to obtain an ivermectin product. The method avoids reducing the residual heavy metal rhodium in the product by the traditional column chromatography purification method, greatly reduces the solvent dosage, shortens the operation time, reduces the production cost, and ensures that the content of the heavy metal rhodium in the finished product can reach less than 7 ppm; avoids using reagents such as thiourea, toluene and the like which are not friendly to the environment to remove the catalyst, improves the production safety, and is a reliable method suitable for industrial production and purification.
Description
Technical Field
The invention relates to a method for reducing the content of heavy metal rhodium in ivermectin.
Background
Ivermectin (Ivermectin) is prepared by hydrogenation reduction of abamectin B1 serving as a raw material at a C22-C23 position, achieves the aim of expelling parasites by inhibiting gamma-aminobutyric acid (GABA) receptors so as to block nerve conduction, and can prevent and treat parasites which have drug resistance to common medicaments. Compared with avermectin, ivermectin has less dosage and 2-3 times lower toxicity than avermectin, is more suitable for preventing and treating parasites inside and outside animals, and is a novel broad-spectrum effective anti-parasite antibiotic. The pesticide is widely used for human, animal and plant insecticides, miticides and the like, and is one of biological pesticides with great development potential.
Currently, in the pharmaceutical industry, triphenylphosphine rhodium chloride (RhCl (PPh) is mainly used as an avermectin in a hydrocarbon-soluble Wilkinson catalyst3)3) The hydrogenation under the action of (3) to prepare ivermectin generally has the problems that the catalyst in the product is difficult to separate and the heavy metal residue in the product exceeds the standard, and in order to obtain the ivermectin meeting the USP/EP standard, scientists often need to carry out complex post-treatment.
Currently, the purification technology of ivermectin mainly adopts a column chromatography method (such as US4429042), although the product purity is high, the solvent consumption is large, the time consumption is long, the production cost is increased, and the industrial production is not facilitated.
Chinese patent CN101362786B uses active carbon (the dosage is 15-18 wt% of avermectin mass) to replace thiourea removal catalyst, reduces two environment pollution raw materials of toluene and thiourea in the traditional process, but only has detection data of related substances, and does not mention the data of heavy metal residual quantity; furthermore, the use of 15 to 18 wt.% of activated carbon also means that the product loss is not negligible. The prior art also realizes simple separation of catalyst and product by two-phase reaction, and Chinese patents CN1651449A, CN101012258A and CN103387594B are all
Similar methods are disclosed, but problems exist, such as large amounts of rhodium compound or rhodium phosphorus complex catalyst, and no data are detected to prove that the catalyst is in an aqueous phase and the organic phase has no catalyst residue.
Disclosure of Invention
The invention discloses a method for reducing the content of heavy metal rhodium in ivermectin, which comprises the following steps:
dissolving the crude ivermectin in an organic solvent, adding silica gel, stirring uniformly, filtering, and concentrating the filtrate to obtain ivermectin solid.
Further, the organic solvent is selected from any one of ethyl acetate, 95% ethanol or dichloromethane, preferably ethyl acetate or 95% ethanol, and most preferably ethyl acetate.
Further, the adding amount of the organic solvent is 20-50 mL/mg based on the mass of the ivermectin crude product.
Further, the mass ratio of the ivermectin crude product to the silica gel is 1: 0.1-6.
Further, the stirring temperature is 20-40 ℃, and the stirring time is 0.5-3 hours.
The content of heavy metal rhodium in the ivermectin finished product obtained by the method is lower than 70 ppm.
Compared with the prior art, the invention has the beneficial effects that:
1. the residual heavy metal rhodium in the product is prevented from being reduced by the traditional column chromatography purification method, the solvent dosage is greatly reduced, the operation time is shortened, the production cost is reduced, and the content of the heavy metal rhodium in the finished product can reach less than 7 ppm;
2. avoids using reagents such as thiourea, toluene and the like which are not friendly to the environment to remove the catalyst, improves the production safety, and is a reliable method suitable for industrial production and purification.
Detailed Description
The present invention will be further described by the following examples, however, the scope of the present invention is not limited to the following examples. It will be understood by those skilled in the art that various changes and modifications may be made to the invention without departing from the spirit and scope of the invention. The present invention has been described generally and/or specifically with respect to materials used in testing and testing methods. Although many materials and methods of operation are known in the art for the purpose of carrying out the invention, the invention is nevertheless described herein in as detail as possible. The detection method of the heavy metal rhodium in the embodiment of the invention is based on 0412 electricity of the four-part general rule of 2020 edition in Chinese pharmacopoeia; the main instruments used are: agilent 7800 ICP-MS.
Example 1
The preparation method of the ivermectin crude product comprises the following steps: a2000 mL autoclave was charged with abamectin (100g), 95% ethanol (1000mL), and RhCl [ PPh ] catalyst3]3(1g, 1% w/w), replacing with hydrogen for 4 times, keeping the pressure at 0.3MPa when the system is not heated, starting stirring, adjusting a temperature control device to keep the temperature at 60 ℃, reacting for 24 hours to obtain an ivermectin reaction solution, directly concentrating to dryness to obtain a crude ivermectin product, and measuring the content of heavy metal rhodium to be 152 ppm.
Example 2
5g of the crude product obtained in example 1 was dissolved in ethyl acetate (100mL) (crude mass: solvent volume: 1:20), 0.5g of column chromatography silica gel (200-300 mesh) (crude mass: silica gel mass: 1:0.1) was added, the mixture was stirred at room temperature for 0.5 hour, filtered, and the filtrate was concentrated to obtain 4.26g of ivermectin solid in 85.20% yield, which was found to have a rhodium content of 40ppm and a removal rate of 73.7% in the ivermectin solid.
Example 3
The crude ivermectin (5g) obtained in example 1 was dissolved in ethyl acetate (100mL) (crude mass: solvent volume 1:20), 5g of column chromatography silica gel (200 mesh and 300 mesh) (crude mass: silica gel mass 1:1) was added, stirring was carried out at room temperature for 0.5 hour, filtration was carried out, and the filtrate was concentrated to obtain 4.12g of ivermectin solid with a yield of 82.30%, i.e., the content of rhodium in the ivermectin solid was 19ppm, and the removal rate was 87.5%.
Example 4
The crude ivermectin (5g) obtained in example 1 was dissolved in ethyl acetate (200mL) (crude mass: solvent volume 1:40), 25g of column chromatography silica gel (200 mesh and 300 mesh) (crude mass: silica gel mass 1:5) was added, stirring was carried out at room temperature for 0.5 hour, filtration was carried out, and the filtrate was concentrated to obtain 3.93g of ivermectin solid with a yield of 78.60%, i.e., the content of rhodium in the ivermectin solid was 7ppm, and the removal rate was 95.4%.
Example 5
The crude ivermectin (5g) is dissolved in dichloromethane (100mL) (crude mass: solvent volume 1:20), 30g of column chromatography silica gel (200 meshes 300 meshes) (crude mass: silica gel mass 1:6) is added, stirring is carried out at the reflux temperature (40 ℃) for 3 hours, filtering is carried out, and the filtrate is concentrated to obtain 3.82g of ivermectin solid, wherein the yield is 76.40%, namely the content of rhodium in the ivermectin solid is 66ppm, and the removal rate is 56.6%.
Example 6
The crude ivermectin (5g) is dissolved in dichloromethane (150mL) (crude mass: solvent volume 1:20), 30g of column chromatography silica gel (200 meshes 300 meshes) (crude mass: silica gel mass 1:6) is added, stirring is carried out at the reflux temperature (40 ℃) for 0.5 hour, filtering is carried out, and the filtrate is concentrated to obtain 3.52g of ivermectin solid, wherein the yield is 70.30%, namely the content of rhodium in the ivermectin solid is 52ppm, and the removal rate is 65.8%.
Example 7
Dissolving crude ivermectin (5g) in 95% ethanol (100mL) (crude mass: solvent volume is 1:20), adding common column chromatography silica gel (200 meshes and 300 meshes) (crude mass: silica gel mass is 1:5), stirring at room temperature for 0.5 h, filtering, and concentrating the filtrate to obtain 4.00g of ivermectin solid, wherein the yield is 80.00%, namely the content of rhodium in the ivermectin solid is 70ppm, and the removal rate is 54.0%.
Example 8
The crude ivermectin (5g) is dissolved in 95% ethanol (250mL) (crude mass: solvent volume is 1:50), column chromatography silica gel (200 meshes and 300 meshes) is added (crude mass: silica gel mass is 1:5), stirring is carried out at room temperature for 0.5 hour, filtering is carried out, and the filtrate is concentrated to obtain 3.56g of ivermectin solid, wherein the yield is 71.20%, namely the content of rhodium in the ivermectin solid is 36ppm, and the removal rate is 76.3%.
Comparative example 1
The crude ivermectin (5g) is dissolved in dichloromethane (100mL) (crude mass: solvent volume 1:20), 1g of column chromatography silica gel (200 meshes 300 meshes) (crude mass: silica gel mass 1:0.2) is added, stirring is carried out at room temperature for 0.5 hour, filtering is carried out, and the filtrate is concentrated to obtain 4.54g of ivermectin solid, wherein the yield is 90.80 percent, namely the content of rhodium in the ivermectin solid is 106ppm, and the removal rate is 30.3 percent.
Comparative example 2
The crude ivermectin (5g) prepared in example was dissolved in methanol (100mL) (crude mass: solvent volume 1:20), 1g of column chromatography silica gel (200 mesh and 300 mesh) was added (crude mass: silica gel mass 1:0.2), stirring was carried out at room temperature for 0.5 hour, filtration was carried out, and the filtrate was concentrated to obtain 4.34g of ivermectin solid with a yield of 86.80%, i.e., the content of rhodium in the ivermectin solid was 108ppm, and the removal rate was 28.9%.
Comparative example 3
The crude ivermectin (5g) is dissolved in toluene (100mL) (crude mass: solvent volume 1:20), 1g of column chromatography silica gel (200 meshes 300 meshes) (crude mass: silica gel mass 1:0.2) is added, stirring is carried out at room temperature for 0.5 hour, filtering is carried out, and the filtrate is concentrated to obtain 4.37g of ivermectin solid, wherein the yield is 87.40%, namely the content of rhodium in the ivermectin solid is 108ppm, and the removal rate is 28.9%.
Comparative example 4
The crude ivermectin (5g) is dissolved in isopropanol (100mL) (crude mass: solvent volume 1:20), 1g of column chromatography silica gel (200 meshes 300 meshes) (crude mass: silica gel mass 1:0.2) is added, stirring is carried out at room temperature for 0.5 hour, filtering is carried out, and the filtrate is concentrated to obtain 4.56g of ivermectin solid, wherein the yield is 91.20%, namely the content of rhodium in the ivermectin solid is 98ppm, and the removal rate is 35.5%.
Comparative example 5
The crude ivermectin (5g) was dissolved in tetrahydrofuran (100mL) (crude mass: solvent volume 1:20), 1g of column chromatography silica gel (200 mesh 300 mesh) (crude mass: silica gel mass 1:0.2) was added, stirring was carried out at room temperature for 0.5 hour, filtration was carried out, and the filtrate was concentrated to give 4.16g of ivermectin solid in 83.20% yield, i.e., the rhodium content in the ivermectin solid was 87ppm, which was reduced by 42.8%.
Comparative example 6
The crude product (5g) obtained in example 1 was subjected to column chromatography, silica gel (200-300 mesh) was used in an amount of 80g (crude product mass: silica gel mass: 1:16), the column was washed with ethyl acetate (500mL) as an eluent at room temperature, and the eluent was concentrated to obtain 3.81g of ivermectin solid in a yield of 76.20%, i.e., the content of rhodium in the ivermectin solid was 42ppm, which was decreased by 72.4%.
Comparative example 7
The crude ivermectin (10g) obtained in example 1 was subjected to column chromatography, silica gel (200-300 mesh) was used in an amount of 80g (crude mass: silica gel mass: 1:8), the column was washed with ethyl acetate (1000mL) as an eluent at room temperature, and the eluent was concentrated to obtain 8.53g of an ivermectin solid in a yield of 85.30%, i.e., the rhodium content in the ivermectin solid was 17ppm, which was decreased by 88.8%.
Comparative example 8
The crude ivermectin (15g) obtained in example 1 was subjected to column chromatography, silica gel (200-300 mesh) was used in an amount of 80g (crude mass: silica gel mass: 1:5.3), the column was washed with ethyl acetate (1500mL) as an eluent at room temperature, and the eluent was concentrated to obtain an ivermectin solid 12.66g in a yield of 84.40%, i.e., the rhodium content in the ivermectin solid was 38ppm, which was reduced by 75%.
Claims (6)
1. A method for reducing the content of heavy metal rhodium in ivermectin is characterized by comprising the following steps: the method comprises the following steps:
dissolving the crude ivermectin in an organic solvent, adding silica gel, stirring uniformly, filtering, and concentrating the filtrate to obtain an ivermectin product.
2. The method of claim 1, wherein: the organic solvent is selected from any one of ethyl acetate, 95% ethanol or dichloromethane, preferably ethyl acetate or 95% ethanol, and most preferably ethyl acetate.
3. The method of claim 1, wherein: the adding amount of the organic solvent is 20-50 mL/mg based on the mass of the ivermectin crude product.
4. The method of claim 1, wherein: the mass ratio of the ivermectin crude product to the silica gel is 1: 0.1-6.
5. The method of claim 1, wherein: the stirring temperature is 20-40 ℃, and the stirring time is 0.5-3 hours.
6. The method of claim 1, wherein: the heavy metal content in the ivermectin finished product is lower than 70 ppm.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1651449A (en) * | 2004-12-06 | 2005-08-10 | 四川大学 | Preparation method of ivermectin |
| CN104784969A (en) * | 2015-03-25 | 2015-07-22 | 苏州鼎驰金属材料有限公司 | Method for removing metal ions in solution by sulfydryl-containing quinoline functionalized mesoporous silica |
| CN108160055A (en) * | 2017-12-29 | 2018-06-15 | 阜阳欣奕华材料科技有限公司 | A kind of modified silica-gel and preparation method thereof and adsorption applications method |
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