CN116178592A - Preparation method of 6-O-sulfobutyl-beta-cyclodextrin - Google Patents
Preparation method of 6-O-sulfobutyl-beta-cyclodextrin Download PDFInfo
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- CN116178592A CN116178592A CN202310259829.2A CN202310259829A CN116178592A CN 116178592 A CN116178592 A CN 116178592A CN 202310259829 A CN202310259829 A CN 202310259829A CN 116178592 A CN116178592 A CN 116178592A
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- 229920000858 Cyclodextrin Polymers 0.000 title claims abstract description 68
- 239000001116 FEMA 4028 Substances 0.000 title claims abstract description 67
- 229960004853 betadex Drugs 0.000 title claims abstract description 67
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 39
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 13
- 238000006467 substitution reaction Methods 0.000 claims abstract description 11
- YEGPVWSPNYPPIK-UHFFFAOYSA-N 4-hydroxybutane-1-sulfonic acid Chemical compound OCCCCS(O)(=O)=O YEGPVWSPNYPPIK-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 230000003472 neutralizing effect Effects 0.000 claims description 5
- 238000000746 purification Methods 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 238000001694 spray drying Methods 0.000 claims description 5
- 230000002140 halogenating effect Effects 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000005658 halogenation reaction Methods 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- -1 sulfobutyl groups Chemical group 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000001728 nano-filtration Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 125000004964 sulfoalkyl group Chemical group 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- General Health & Medical Sciences (AREA)
- Materials Engineering (AREA)
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Abstract
The invention provides a preparation method of 6-O-sulfobutyl-beta-cyclodextrin, which comprises the following steps: under the action of sodium hydroxide, the hepta-6-halogeno-6-deoxy-beta-cyclodextrin and 4-hydroxy butane sulfonic acid react with N, N-dimethylformamide as a solvent to obtain the 6-O-sulfobutyl-beta-cyclodextrin. The sulfobutyl-beta-cyclodextrin with specific substitution sites is prepared by the method, is more beneficial to developing and applying the sulfobutyl-beta-cyclodextrin and meets the requirements of the sulfobutyl-beta-cyclodextrin in different fields. The method is simple to operate and high in conversion rate.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of 6-O-sulfobutyl-beta-cyclodextrin.
Background
Sulfobutyl ether- β -cyclodextrin (SBE- β -CD) is one of the more widely used derivatives of β -CD. SBE-beta-CD is a white amorphous solid powdery substance, has higher water solubility, has molecules in a truncated cone shape with thin upper part and thick lower part, has hydrophobicity in a cavity, and is externally connected with hydrophilic sulfobutyl groups. The introduced sulfobutyl group enables the SBE-beta-CD to have a plurality of anions and electronegativity, so that the inclusion capacity of the medicine with positive charges is improved. Meanwhile, the hydrophobic effect of the beta-CD cavity is further increased by the sulfobutyl group, the carbon chain in the sulfobutyl group extends outwards, the repulsive effect between charges is more obvious, hydrophobic drug molecules can be better contained in the cavity and the sulfoalkyl chain in the side chain, so that the inclusion capacity of the sulfobutyl group and the drug molecules is stronger, and the sulfobutyl group has wider application range.
The products prepared by the sulfobutyl-beta-cyclodextrin related patent are all mixtures of different substitution sites at the 2,3 and 6 positions; the patent on the specific substitution site is not reported, and the development of the sulfobutyl-beta-cyclodextrin on the specific substitution site is more beneficial to the deep discussion of the medicinal and inclusion mechanism of the sulfobutyl ether-beta-cyclodextrin in application research, and the development of the unique application of the sulfobutyl ether-beta-cyclodextrin.
Disclosure of Invention
In view of the above, the technical problem to be solved by the invention is to provide a preparation method of 6-O-sulfobutyl-beta-cyclodextrin, and 6-O-sulfobutyl-beta-cyclodextrin with single substitution site is synthesized.
The invention provides a preparation method of 6-O-sulfobutyl-beta-cyclodextrin, which comprises the following steps:
under the action of sodium hydroxide, the hepta-6-halogeno-6-deoxy-beta-cyclodextrin and 4-hydroxy butane sulfonic acid react with N, N-dimethylformamide as a solvent to obtain the 6-O-sulfobutyl-beta-cyclodextrin.
The invention synthesizes sulfobutyl-beta-cyclodextrin with single substitution site of 6-site substitution, and the structural formula is as follows:
preferably, the degree of substitution of the 6-O-sulfobutyl-beta-cyclodextrin is 1 to 7.
The raw material seven-6-halogeno-6-deoxidized-beta-cyclodextrin selected by the invention is preferably prepared according to the following method:
DMF is taken as a solvent, triphenylphosphine is added for dissolution, and then a halogenating reagent and beta-cyclodextrin are added for halogenation reaction, thus obtaining the hepta-6-halogeno-6-deoxy-beta-cyclodextrin.
Preferably, the halogenating agent is added at a temperature of 20-40 ℃. The halogenating agent is preferably elemental iodine or N-bromosuccinimide. Then adding beta-cyclodextrin, preferably heating to 60-80 ℃ to react for 10-20h to obtain the hepta-6-halogeno-6-deoxidized-beta-cyclodextrin.
Preferably, the hepta-6-halo-6-deoxy-beta-cyclodextrin is hepta-6-iodo-6-deoxy-beta-cyclodextrin or hepta-6-bromo-6-deoxy-beta-cyclodextrin, more preferably hepta-6-iodo-6-deoxy-beta-cyclodextrin.
The preparation method provided by the invention adopts N, N-dimethylformamide as a solvent and sodium hydroxide as an acid binding agent, and experiments show that under the conventional condition, the reaction is carried out due to nucleophilic groups CD-OH, -SO in the system 3 The existence of the (C) has more byproducts, has extremely high selectivity only in a DMF and sodium hydroxide system, and can effectively avoid the nucleophilic groups CD-OH, -SO by controlling the conditions of temperature, alkalinity and the like 3 And the byproducts are generated, so that complex post-treatment is not needed, and the purity of the product is ensured.
The temperature of the reaction is preferably 70 to 90 ℃, more preferably 80 ℃.
The reaction time is preferably 10 to 30 hours, more preferably 20 to 25 hours.
The molar ratio of the hepta-6-halogeno-6-deoxy-beta-cyclodextrin to the 4-hydroxybutanesulfonic acid is preferably 1 (0.5-10).
The molar ratio of the hepta-6-halogeno-6-deoxy-beta-cyclodextrin to sodium hydroxide is preferably 1: (0.1 to 5), more preferably 1: (1-1.5).
The mass ratio of the hepta-6-halogeno-6-deoxy-beta-cyclodextrin to the N, N-dimethylformamide is preferably 1: (4-10), more preferably (5-6).
Preferably, the reaction further comprises a purification process after the completion of the reaction:
and spin-drying the feed liquid after the reaction is completed, adding sodium hydroxide aqueous solution, heating to 80-100 ℃, preserving heat, neutralizing with concentrated hydrochloric acid to adjust the pH value to be 6.0-7.0, decoloring and filtering with active carbon, nano-filtering to remove salt, and spray-drying to obtain the 6-O-sulfobutyl-beta-cyclodextrin.
The mass concentration of the sodium hydroxide aqueous solution is preferably 10% -30%.
The mass ratio of the sodium hydroxide aqueous solution to the spin-drying material is preferably 3-8: 1.
compared with the prior art, the invention provides a preparation method of 6-O-sulfobutyl-beta-cyclodextrin, which comprises the following steps: under the action of sodium hydroxide, the hepta-6-halogeno-6-deoxy-beta-cyclodextrin and 4-hydroxy butane sulfonic acid react with N, N-dimethylformamide as a solvent to obtain the 6-O-sulfobutyl-beta-cyclodextrin. The sulfobutyl-beta-cyclodextrin with specific substitution sites is prepared by the method, is more beneficial to developing and applying the sulfobutyl-beta-cyclodextrin and meets the requirements of the sulfobutyl-beta-cyclodextrin in different fields. The method is simple to operate and high in conversion rate.
Drawings
FIG. 1 is a hydrogen spectrum characterization of 6-O-sulfobutyl- β -cyclodextrin;
FIG. 2 is a carbon spectrum characterization of 6-O-sulfobutyl- β -cyclodextrin.
Detailed Description
In order to further illustrate the present invention, the following describes in detail the preparation method of 6-O-sulfobutyl-beta-cyclodextrin provided by the present invention in connection with examples.
Example 1
And (3) synthesis reaction: synthesis of 6-O-sulfobutyl-beta-cyclodextrin
Putting 12kg of N, N-dimethylformamide into a flask, opening nitrogen protection, adding 3kg of triphenylphosphine, stirring, dissolving and clarifying, controlling the temperature to be 20-40 ℃, slowly adding 2.6kg of iodine simple substance, then adding 900g of beta-cyclodextrin, heating to 80 ℃ for reacting for 20h, spinning to obtain a crude product of seven-6-iodo-6-deoxy-beta-cyclodextrin, adding the crude product into 2kg of 30% sodium methoxide methanol solution, rapidly transferring the methanol solution into 6kg of water, stirring, leaching, washing a filter cake to be neutral, and drying to obtain a pure product of seven-6-iodo-6-deoxy-beta-cyclodextrin, wherein the content is 98%, and the yield is 87%.
800g of N, N-dimethylformamide is put into a flask, 5g of sodium hydroxide and 200g of seven-6-iodo-6-deoxy-beta-cyclodextrin are added, the mixture is stirred and heated to 80 ℃, 80g of 4-hydroxybutanesulfonic acid is added dropwise, and the reaction is carried out for 20 hours;
purification reaction: and (3) spin-drying the feed liquid after the reaction is finished, adding 80g of 30% sodium hydroxide aqueous solution, heating to 80 ℃, preserving heat for 2 hours, neutralizing with concentrated hydrochloric acid to adjust the pH value to be 6.0-7.0, decoloring and filtering with active carbon, then removing salt by nanofiltration, and spray-drying to obtain the 6-O-sulfobutyl-beta-cyclodextrin. The yield thereof was found to be 86% and the content thereof was found to be 99%.
FIG. 1 is a hydrogen spectrum characterization of 6-O-sulfobutyl- β -cyclodextrin; FIG. 2 is a carbon spectrum characterization of 6-O-sulfobutyl- β -cyclodextrin.
In the hydrogen spectrum, the positions delta 2.9 and 1.8 are respectively assigned to substituent groups-CH 2 -CH 2 -CH 2 -CH 2 -SO 3 -upper near SO 3 -CH of 2 -2 hydrogens on the substituent centre-CH 2 -CH 2 -4 hydrogens on, and the integration ratio is 1:2; the theoretical calculation value is met, which indicates that the sulfobutyl group is substituted on the cyclodextrin.
In the carbon spectrum, the carbon spectrum data is δ (ppm): the substituted 6 position is shifted from 60.5 (C-6) to 70.5 (CS-6) toward the low field; the substituted 2-position was shifted from 102 (C-1) to the high field by 2ppm, and no peak was found; the substituted 3-position was shifted from 81 (C-4) to the high field, and no peak was found. The position of the sulfobutyl group substitution was thus confirmed to be the 6-position.
Example 2
And (3) synthesis reaction: synthesis of 6-O-sulfobutyl-beta-cyclodextrin
800g of N, N-dimethylformamide is put into a flask, 6g of sodium hydroxide and 200g of seven-6-bromo-6-deoxy-beta-cyclodextrin are added, stirring is carried out, the temperature is raised to 80 ℃, 100g of 4-hydroxybutanesulfonic acid is added dropwise, and the reaction is carried out for 20 hours;
purification reaction: and (3) spin-drying the feed liquid after the reaction is finished, adding 80g of 30% sodium hydroxide aqueous solution, heating to 80 ℃, preserving heat for 2 hours, neutralizing with concentrated hydrochloric acid to adjust the pH value to be 6.0-7.0, decoloring and filtering with active carbon, then removing salt by nanofiltration, and spray-drying to obtain the 6-O-sulfobutyl-beta-cyclodextrin. Yield 67%, content 99%
Comparative example 1:
800g of N, N-dimethylformamide is put into a flask, 5g of potassium hydroxide and 200g of seven-6-iodo-6-deoxy-beta-cyclodextrin are added, the mixture is stirred and heated to 80 ℃, 80g of 4-hydroxybutanesulfonic acid is added dropwise, and the reaction is carried out for 20 hours;
purification reaction: and (3) spin-drying the feed liquid after the reaction is finished, adding 80g of 30% sodium hydroxide aqueous solution, heating to 80 ℃, preserving heat for 2 hours, neutralizing with concentrated hydrochloric acid to adjust the pH value to be 6.0-7.0, decoloring and filtering with active carbon, then removing salt by nanofiltration, and spray-drying to obtain the 6-O-sulfobutyl-beta-cyclodextrin. The product contains more 2-bit or 2, 6-bit mixed products, and is difficult to separate.
The above description of the embodiments is only for aiding in the understanding of the method of the present invention and its core ideas. It should be noted that it will be apparent to those skilled in the art that various modifications and adaptations of the invention can be made without departing from the principles of the invention and these modifications and adaptations are intended to be within the scope of the invention as defined in the following claims.
Claims (10)
1. A preparation method of 6-O-sulfobutyl-beta-cyclodextrin, which comprises the following steps:
under the action of sodium hydroxide, the hepta-6-halogeno-6-deoxy-beta-cyclodextrin and 4-hydroxy butane sulfonic acid react with N, N-dimethylformamide as a solvent to obtain the 6-O-sulfobutyl-beta-cyclodextrin.
2. The method of claim 1, wherein the hepta-6-halo-6-deoxy- β -cyclodextrin is prepared according to the following method:
DMF is taken as a solvent, triphenylphosphine is added for dissolution, and then a halogenating reagent and beta-cyclodextrin are added for halogenation reaction, thus obtaining the hepta-6-halogeno-6-deoxy-beta-cyclodextrin.
3. The method of claim 1, wherein the hepta-6-halo-6-deoxy- β -cyclodextrin is hepta-6-iodo-6-deoxy- β -cyclodextrin or hepta-6-bromo-6-deoxy- β -cyclodextrin.
4. The preparation method according to claim 1, wherein the reaction temperature is 70-90 ℃ and the reaction time is 10-30 h.
5. The method according to claim 1, wherein the molar ratio of the hepta-6-halo-6-deoxy- β -cyclodextrin to the 4-hydroxybutanesulfonic acid is 1: (0.5-10).
6. The method according to claim 1, wherein the molar ratio of the hepta-6-halo-6-deoxy- β -cyclodextrin to sodium hydroxide is 1: (0.1-5).
7. The preparation method according to claim 1, wherein the mass ratio of the hepta-6-halo-6-deoxy-beta-cyclodextrin to the N, N-dimethylformamide is 1: (4-10).
8. The method according to claim 1, wherein the reaction further comprises a purification process after completion of the reaction:
and spin-drying the feed liquid after the reaction is completed, adding sodium hydroxide aqueous solution, heating to 80-100 ℃, preserving heat, neutralizing with concentrated hydrochloric acid to adjust the pH value to be 6.0-7.0, decoloring and filtering with active carbon, nano-filtering to remove salt, and spray-drying to obtain the 6-O-sulfobutyl-beta-cyclodextrin.
9. The preparation method according to claim 8, wherein the mass concentration of the aqueous sodium hydroxide solution is 10% -30%;
the mass ratio of the sodium hydroxide aqueous solution to the spin-drying material is 3-8: 1.
10. the method according to claim 1, wherein the degree of substitution of the 6-O-sulfobutyl- β -cyclodextrin is 1 to 7.
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1800221A (en) * | 2005-11-02 | 2006-07-12 | 南京师范大学 | Hydroxypropyl- sulfobutyl-beta- cyclodextrin and its preparation method, analytical method and pharmaceutical uses |
CN104628891A (en) * | 2015-01-20 | 2015-05-20 | 中国大冢制药有限公司 | Method for preparing 6-deoxy-6-haloalkyl cyclodextrin |
CN105924545A (en) * | 2016-05-20 | 2016-09-07 | 山东滨州智源生物科技有限公司 | Production process of novel high-safety sulfobutyl ether-beta-cyclodextrin sodium salt |
CN111171188A (en) * | 2020-03-20 | 2020-05-19 | 淄博千汇生物科技有限公司 | Green preparation process of sulfobutyl betacyclodextrin sodium |
CN113929794A (en) * | 2021-11-10 | 2022-01-14 | 山东滨州智源生物科技有限公司 | Cyclodextrin derivatives and process for producing the same |
WO2022170081A1 (en) * | 2021-02-05 | 2022-08-11 | Incarda Therapeutics, Inc. | Antiarrhythmic formulation |
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1800221A (en) * | 2005-11-02 | 2006-07-12 | 南京师范大学 | Hydroxypropyl- sulfobutyl-beta- cyclodextrin and its preparation method, analytical method and pharmaceutical uses |
CN104628891A (en) * | 2015-01-20 | 2015-05-20 | 中国大冢制药有限公司 | Method for preparing 6-deoxy-6-haloalkyl cyclodextrin |
CN105924545A (en) * | 2016-05-20 | 2016-09-07 | 山东滨州智源生物科技有限公司 | Production process of novel high-safety sulfobutyl ether-beta-cyclodextrin sodium salt |
CN111171188A (en) * | 2020-03-20 | 2020-05-19 | 淄博千汇生物科技有限公司 | Green preparation process of sulfobutyl betacyclodextrin sodium |
WO2022170081A1 (en) * | 2021-02-05 | 2022-08-11 | Incarda Therapeutics, Inc. | Antiarrhythmic formulation |
CN113929794A (en) * | 2021-11-10 | 2022-01-14 | 山东滨州智源生物科技有限公司 | Cyclodextrin derivatives and process for producing the same |
Non-Patent Citations (2)
Title |
---|
KAI GONG 等: ""β-Cyclodextrin-butane sulfonic acid: an efficient and reusable catalyst for the multicomponent synthesis of 1-amidoalkyl-2-naphthols under solvent-free conditions"", 《GREEN CHEMISTRY》, vol. 17, no. 5, 25 June 2015 (2015-06-25), pages 3141 - 3147 * |
沈海民;方红果;武宏科;纪红兵;史鸿鑫;: "环糊精衍生物的分子形态及其构筑策略研究进展", 化工进展, no. 02, pages 430 - 446 * |
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