CN106749770A - The method that a kind of microwave/alkali coupling prepares different degree of substitution sulfobutyl ether-beta-cyclodextrin - Google Patents
The method that a kind of microwave/alkali coupling prepares different degree of substitution sulfobutyl ether-beta-cyclodextrin Download PDFInfo
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Abstract
The present invention is to provide the method that a kind of microwave/alkali coupling prepares different degree of substitution sulfobutyl ether-beta-cyclodextrin.The method is with beta-schardinger dextrin and 1,4- fourths sultone is raw material, by controlling NaOH solution initial concentration and addition and using microwave reactor technology, make hydroxyl on beta-schardinger dextrin glucose ring that alkoxide to occur, become alkoxy anion, and the alkalescence of alkoxy anion is better than hydroxyl, it is easier to and there is nucleophilic ring opening reaction generation sulfobutyl ether-beta-cyclodextrin in Isosorbide-5-Nitrae-fourth sultone；By control 1,4- fourth sultone additions, keep reaction system pH=8.80-9.70, obtain the sulfobutyl ether-beta-cyclodextrin in substitution value range set, have respectively monosubstituted, the sulfobutyl ether-beta-cyclodextrin of 3.4-4.2,6.2-6.9 substitution value scope, molecular recognition, chiral resolution, excipient substance field are used for this；4th, the average substitution degree of product is detected using HPCE, as can be seen that substitution value is in normal distribution from spectrogram.
Description
Technical field
The present invention relates to the method that a kind of microwave/alkali coupling prepares different degree of substitution sulfobutyl ether-beta-cyclodextrin, belong to material science and technology, molecular recognition, chiral resolution, excipient substance field, be especially widely used in environment, the field of Chinese medicines.
Background technology
Cyclodextrin (cyclodextrin, abbreviation CD) it is the oligosacharides cyclic formed after being acted on through cyclodextrin glycosyl transferases by starch, it is made up of hydrophilic appearance and hydrophobic inner chamber with one, the circular hollow for being shaped as wide at the top and narrow at the bottom and both ends open bores the space structure of barrel shape spatial configuration.This unique molecular structure, cyclodextrin is set to form Supramolecular inclusion complex with guest molecule, change the physicochemical property of guest molecule, therefore cyclodextrin is as a kind of good significant subject molecule of cheap and easily-available, biocompatibility in supramolecular chemistry, and is widely used in fields such as catalysis, self assembly, molecular recognition, medicament transports.
The chemical composition of cyclodextrin is that D- glucopyranoses pass through α -1, the cyclic oligomer sugar compounds that 4- glycosidic bonds are formed by connecting, it is different according to the D- glucopyranose units quantity for forming molecule, cyclodextrin can be further subdivided into α-CD again, β-CD, γ-CD etc. (respectively containing 6,7,8 glucose units).Wherein β-CD are the most commonly used due to the advantage of the several respects such as the space geometry configuration and size in molecule, validity and price, occupy more than the 95% of current cyclodextrin consumption.
But, natural β-CD seriously limit its range of application in fields such as pharmacy, chiral resolution, molecular recognitions due to its own poorly water-soluble (solubility is only 18.5 g/L at 25 DEG C), the reason such as renal toxicity is big, haemocylolysis is strong.In order to overcome the shortcoming of natural β-CD, a series of derivative of β-CD is synthesized, has been broadly divided into and methylates or several major classes such as alkyl derivative, hydroxyalkylation derivant, branching derivative, sulfoalkyl etherification derivative.Wherein sulfoalkyl ether-beta-cyclic dextrine has water-soluble and relatively low toxicity higher due to introducing anionic group, is a kind of very promising biomaterial.
Sulfobutyl ether-beta-cyclodextrin has water-soluble good as a kind of new cyclodextrine derivatives compared with cyclodextrin and other derivatives, and toxic and side effect is few, the features such as stability is high, in the field extensive use such as excipient substance, chiral resolution, molecular recognition.The synthetic method of current sulfobutyl ether-beta-cyclodextrin mainly has three kinds：1st, United States Patent (USP) US5134127 and US6153746 is using the 2 of beta-schardinger dextrin glucose unit, there is substitution reaction in alkaline solution with Isosorbide-5-Nitrae fourth sultone in the hydroxyl on 3,6 carbon, monosubstituted and polysubstituted sulfobutyl ether-beta-cyclodextrin is synthesized, yield is between 60-70%；2nd, Chinese patent CN1858071A uses metallic sodium in organic solvent 1, capture the hydrogen on beta-schardinger dextrin hydroxyl in 4- dioxane, the sodium alkoxide for producing alkalescence stronger, with 1, there is nucleophilic displacement of fluorine in 4- fourths sultone, the product substitution value wider range and yield for obtaining are between 40-60%；3rd, Chinese patent CN103694376A improves above two method, organic solvent tetrahydrofuran is introduced in alkaline aqueous solution, 1, one kind in 4- dioxane or 2- methyltetrahydrofurans, improve 1, the solubility of 4- fourth sultone, obtains the sulfobutyl ether-beta-cyclodextrin that average substitution degree is 6.7, and yield is between 75-80%.
Zhang Yimin etc., with beta-schardinger dextrin and dimethyl carbonate as raw material, successfully synthesizes beta-schardinger dextrin-methyl carbonate once using the method for microwave, and the reaction time is only 21min, and the high conversion rate of beta-schardinger dextrin is up to 95.01%.This method shortens reaction time decades of times, energy-conservation decades of times than prior synthesizing method.
The content of the invention
The present invention is to provide the method that a kind of microwave/alkali coupling prepares different degree of substitution sulfobutyl ether-beta-cyclodextrin.The method is with beta-schardinger dextrin and 1,4- fourths sultone is raw material, by controlling NaOH solution initial concentration and addition and using microwave reactor technology, make hydroxyl on beta-schardinger dextrin glucose ring that alkoxide to occur, become alkoxy anion, and the alkalescence of alkoxy anion is better than hydroxyl, it is easier to and there is nucleophilic ring opening reaction generation sulfobutyl ether-beta-cyclodextrin in Isosorbide-5-Nitrae-fourth sultone；By controlling the addition and pH value of solution scope of Isosorbide-5-Nitrae-fourth sultone, the preparation of the sulfobutyl ether-beta-cyclodextrin of different degree of substitution scope is realized, in obtaining substitution value range set, product yield target product high；Alkali lye is added by the introducing and substep of microwave reactor, reaction rate is accelerated, energy consumption is reduced, the yield of product is improve, generation and the raw material residual quantity of accessory substance 4- hydroxyl fourth sodium sulfonates and two sulphur butyl ether sodium is reduced.
The present invention is proposed in alkaline aqueous solution, with beta-schardinger dextrin and Isosorbide-5-Nitrae-fourth sultone as raw material, control concentration of lye, addition and reaction time, pH value of solution=8.80-9.70 is kept using pH automatic balance instruments, obtains that yield is high and the sulfobutyl ether-beta-cyclodextrin in substitution value range set.
The technical scheme of this technique is as follows：
1st, 65-75 DEG C is warming up to, beta-schardinger dextrin is dissolved in 12.5-15%（w/w）NaOH solution in（The molar equivalent of NaOH is 6.5）Beta-schardinger dextrin solution is become colorless clear solution by muddiness, after stirring 30min, to a certain amount of Isosorbide-5-Nitrae-fourth sultone is slowly added dropwise in reaction bulb, row etherification reaction is flowed back at 65-75 DEG C, changed using pH automatic balance instrument detection architectures pH, after reaction a period of time, pH value of solution changes, by 12.5-15%（w/w）NaOH solution（The molar equivalent of NaOH is 2.5）It is put into beaker, it is connected with pH automatic balance instruments, it is 8.80-9.70 to keep pH value of reaction system scope, after reaction carries out 30min-6h, by in remaining NaOH solution in beaker all addition reaction bulb, continue to react 5h, when surplus is no more than 1% to beta-schardinger dextrin in the reactive mixture, additionally add 25-30%（w/w）NaOH solution（The molar equivalent of NaOH is 1.5）, continue to react 1-3h, hydrolyze unreacted Isosorbide-5-Nitrae-fourth sultone.The percentage of beta-schardinger dextrin raw material total amount is accounted for less than 5%wt with HPLC tracing detections to beta-schardinger dextrin surplus, and 25ppm is less than with GC tracing detections to Isosorbide-5-Nitrae-fourth sultone residual volume.After the completion of reaction, with sour neutralization reaction solution to 6.8-7.2, natural filtration obtains glassy yellow clear solution, using sephadex or ultrafiltration apparatus, except desalting and accessory substance, then product is rinsed with absolute ethyl alcohol, the fourth sultone of residual is removed, pure product is obtained.The average substitution degree of sulfobutyl ether-beta-cyclodextrin is detected with HPCE, superconduction nuclear magnetic resonance spectrometer, mass spectrograph.（On the basis of the amount of the material of beta-schardinger dextrin, the consumption of Isosorbide-5-Nitrae-fourth sultone is 2-8 times of beta-schardinger dextrin amount for the reaction）.
The method that a kind of microwave involved in the present invention/alkali coupling prepares different degree of substitution sulfobutyl ether-beta-cyclodextrin, synthesis process is as follows：
Beneficial effects of the present invention are：1st, beta-schardinger dextrin and Isosorbide-5-Nitrae-fourth sultone are raw material, by controlling concentration of lye and addition, substantially increase beta-schardinger dextrin alcoxyl negative ionization, and promoting reaction is carried out, and substantially increases reaction yield；2nd, alkali lye addition is controlled using pH automatic balance instruments, keeps reaction system pH=8.80-9.70；3rd, by control 1,4- fourth sultone additions, keep reaction system pH=8.80-9.70, obtain the sulfobutyl ether-beta-cyclodextrin in substitution value range set, have respectively monosubstituted, the sulfobutyl ether-beta-cyclodextrin of 3.4-4.2,6.2-6.9 substitution value scope, molecular recognition, chiral resolution, excipient substance field are used for this；4th, the average substitution degree of product is detected using HPCE, as can be seen that substitution value is in normal distribution from spectrogram.
This technological reaction mild condition, post processing is simple, and alkali lye addition is controlled using pH automatic balance instruments, keeps reaction system pH=8.80-9.70, obtains the product in substitution value range set and yield is higher, and yield is 80-90%, is adapted to large-scale production.
It is above-mentioned only to the present invention in several specific implementation cases be illustrated; but can not be used as protection scope of the present invention; the equivalent change or modification or equal proportion that every design spirit according in the present invention is made are zoomed in or out, and are deemed to fall protection scope of the present invention.
Brief description of the drawings
Fig. 1 is sulfobutyl ether-beta-cyclodextrin Capillary Electrophoresis figure prepared by embodiment 2.
Fig. 2 is sulfobutyl ether-beta-cyclodextrin Capillary Electrophoresis figure prepared by embodiment 3.
Fig. 3 is sulfobutyl ether-beta-cyclodextrin Capillary Electrophoresis figure prepared by embodiment 4.
Fig. 4 is sulfobutyl ether-beta-cyclodextrin Capillary Electrophoresis figure prepared by embodiment 5.
Specific embodiment
In order to absolutely prove the essence of patent of the present invention, prepare thinking and design, preparation method of the present invention is verified in the following embodiments, these embodiments are only represented for illustration and special case, should not be construed or be interpreted as the limitation to present invention protection.Example below is carried out in microwave reactor.
Embodiment 1：
In 100mL three-neck flasks, 15.3mL 15% is added（w/w）NaOH solution, temperature control is added thereto to 10g at 75 DEG C（8.81*10-3mol）Beta-schardinger dextrin, initial NaOH is 6.5 with the amount ratio of the material of beta-schardinger dextrin:1；It is stirred vigorously, is then slowly added dropwise 1.8mL（1.76*10-2mol）Isosorbide-5-Nitrae-fourth sultone, 20-30min completion of dropping, Isosorbide-5-Nitrae-fourth sultone is 2 with the amount ratio of the material of β-CD:1；After adding Isosorbide-5-Nitrae-fourth sultone, reaction temperature is increased to 90 DEG C, and pH value of solution takes place decline after a period of time, by 7mL 12.5%（w/w）NaOH solution（It is 2.5 with the amount ratio of the material of beta-schardinger dextrin:1）Add in beaker, be connected with pH automatic balance instruments, automatic dripping NaOH solution keeps pH value of solution=8.80-9.70, react after carrying out 2h, remaining NaOH solution in beaker is all then added into reaction bulb, continue to react 3h or so.It is extra to add 2.1mL 25% (w/w) NaOH solution when surplus is no more than 1%wt to beta-schardinger dextrin in the reactive mixture（It is 1.5 with the amount ratio of the material of beta-schardinger dextrin:1）, continue to react 10-15h, hydrolyze unreacted Isosorbide-5-Nitrae-fourth sultone.It was observed that solution is homogeneous phase solution, i.e. reaction terminates.Reaction solution is cooled to room temperature, is diluted with 20mL deionized waters, is then neutralized with hydrochloric acid to neutrality.Eluted using sephadex A-25 chromatographic columns, remove unreacted beta-schardinger dextrin and accessory substance, the chromatographic column of sephadex G -25 wash-out, go out sodium chloride, then rinse product with absolute ethyl alcohol, the fourth sultone of residual is removed, pure product 9.8g, yield 84% is obtained.Average substitution degree by capillary electrophoresis detection sulfobutyl ether-beta-cyclodextrin is that each substitution value is in normal distribution in 1.23, and spectrogram.
Embodiment 2：
In 100mL three-neck flasks, 18.3mL 12.5% is added（w/w）NaOH solution, temperature control is added thereto to 10g at 70 DEG C（8.81*10-3mol）Beta-schardinger dextrin, initial NaOH is 6.5 with the amount ratio of the material of beta-schardinger dextrin:1；It is stirred vigorously, is then slowly added dropwise 4.5mL（4.40*10-2mol）Isosorbide-5-Nitrae-fourth sultone, 20-30min completion of dropping, Isosorbide-5-Nitrae-fourth sultone is 5 with the amount ratio of the material of β-CD:1；After adding Isosorbide-5-Nitrae-fourth sultone, reaction temperature is increased to 90 DEG C, and pH value of solution takes place decline after a period of time, by 7mL 12.5%（w/w）NaOH solution（It is 2.5 with the amount ratio of the material of beta-schardinger dextrin:1）Add in beaker, be connected with pH automatic balance instruments, automatic dripping NaOH solution keeps pH value of solution=8.80-9.70, react after carrying out 1h, remaining NaOH solution in beaker is all then added into reaction bulb, continue to react 5h or so.It is extra to add 2.1mL 25% (w/w) NaOH solution when surplus is no more than 1%wt to beta-schardinger dextrin in the reactive mixture（It is 1.5 with the amount ratio of the material of beta-schardinger dextrin:1）, continue to react 10-15h, hydrolyze unreacted Isosorbide-5-Nitrae-fourth sultone.It was observed that solution is homogeneous phase solution, i.e. reaction terminates.Reaction solution is cooled to room temperature, is diluted with 20mL deionized waters, is then neutralized with hydrochloric acid to neutrality.Sodium chloride and accessory substance are removed using ultrafiltration apparatus, then product is rinsed with absolute ethyl alcohol, remove the fourth sultone of residual, obtain pure product 12.6g, yield 81%.Average substitution degree by capillary electrophoresis detection sulfobutyl ether-beta-cyclodextrin is that each substitution value is in normal distribution in 3.91, and spectrogram.
Embodiment 3：
In 100mL three-neck flasks, 18.3mL 12.5% is added（w/w）NaOH solution, temperature control is added thereto to 10g at 70 DEG C（8.81*10-3mol）Beta-schardinger dextrin, initial NaOH is 6.5 with the amount ratio of the material of beta-schardinger dextrin:1；It is stirred vigorously, is then slowly added dropwise 7.2mL（7.05*10-2mol）Isosorbide-5-Nitrae-fourth sultone, 20-30min completion of dropping, Isosorbide-5-Nitrae-fourth sultone is 8 with the amount ratio of the material of β-CD:1；After adding Isosorbide-5-Nitrae-fourth sultone, reaction temperature is increased to 90 DEG C, and pH value of solution takes place decline after a period of time, by 7mL 12.5%（w/w）NaOH solution（It is 2.5 with the amount ratio of the material of beta-schardinger dextrin:1）Add in beaker, be connected with pH automatic balance instruments, automatic dripping NaOH solution keeps pH value of solution=8.80-9.70, react after carrying out 30min, remaining NaOH solution in beaker is all then added into reaction bulb, continue to react 5h or so.It is extra to add 2.1mL 25% (w/w) NaOH solution when surplus is no more than 1%wt to beta-schardinger dextrin in the reactive mixture（It is 1.5 with the amount ratio of the material of beta-schardinger dextrin:1）, continue to react 10-15h, hydrolyze unreacted Isosorbide-5-Nitrae-fourth sultone.It was observed that solution is homogeneous phase solution, i.e. reaction terminates.Reaction solution is cooled to room temperature, is diluted with 20mL deionized waters, is then neutralized with hydrochloric acid to neutrality.Eluted using sephadex A-25 chromatographic columns, remove unreacted beta-schardinger dextrin and accessory substance, the chromatographic column of sephadex G -25 wash-out, go out sodium chloride, then product is rinsed with absolute ethyl alcohol, remove the fourth sultone of residual, obtain pure product 16.25g, yield 86%.Average substitution degree by capillary electrophoresis detection sulfobutyl ether-beta-cyclodextrin is that each substitution value is in normal distribution in 6.46, and spectrogram.
Embodiment 4：
In 500mL three-neck flasks, 183mL 12.5% is added（w/w）NaOH solution, temperature control is added thereto to 100g beta-schardinger dextrins at 70 DEG C, and initial NaOH is 6.5 with the amount ratio of the material of beta-schardinger dextrin:1；It is stirred vigorously, is then slowly added dropwise 72mL1,4- fourth sultone, 20-30min completion of dropping, Isosorbide-5-Nitrae-fourth sultone is 8 with the amount ratio of the material of β-CD:1；After adding Isosorbide-5-Nitrae-fourth sultone, reaction temperature is increased to 90 DEG C, and pH value of solution takes place decline after a period of time, by 70mL 12.5%（w/w）NaOH solution（It is 2.5 with the amount ratio of the material of beta-schardinger dextrin:1）Add in beaker, be connected with pH automatic balance instruments, automatic dripping NaOH solution keeps pH value of solution=8.80-9.70, react after carrying out 40min, remaining NaOH solution in beaker is all then added into reaction bulb, continue to react 1h or so.It is extra to add 21mL 25% (w/w) NaOH solution when surplus is no more than 1%wt to beta-schardinger dextrin in the reactive mixture（It is 1.5 with the amount ratio of the material of beta-schardinger dextrin:1）, continue to react 10-15h, hydrolyze unreacted Isosorbide-5-Nitrae-fourth sultone.It was observed that solution is homogeneous phase solution, i.e. reaction terminates.Reaction solution is cooled to room temperature, is diluted with 50mL deionized waters, is then neutralized with hydrochloric acid to neutrality.Sodium chloride and accessory substance are removed using ultrafiltration apparatus, then product is rinsed with absolute ethyl alcohol, remove the fourth sultone of residual, obtain pure product 153.7g, yield 90%.Average substitution degree by capillary electrophoresis detection sulfobutyl ether-beta-cyclodextrin is that each substitution value is in normal distribution in 6.69, and spectrogram.
The above is only the preferred embodiment of the present invention, it is noted that for those skilled in the art, under the premise without departing from the principles of the invention, can also make some improvement, and these improvement also should be regarded as protection scope of the present invention.
Claims (10)
1. the method that a kind of microwave/alkali coupling prepares different degree of substitution sulfobutyl ether-beta-cyclodextrin, it is characterised in that：The method coupled using microwave/alkali, different degree of substitution sulfobutyl ether-beta-cyclodextrin is prepared with beta-schardinger dextrin and Isosorbide-5-Nitrae-fourth sultone as raw material.
2. according to claim 1, it is characterised in that：In microwave reactor, control temperature for 65-75 DEG C, beta-schardinger dextrin is dissolved in 12.5-15%（w/w）NaOH solution in, beta-schardinger dextrin solution is become colorless clear solution by muddiness, after stirring 30min, to a certain amount of Isosorbide-5-Nitrae-fourth sultone is slowly added dropwise in reaction bulb, row etherification reaction is flowed back at 65-75 DEG C, changed using pH automatic balance instrument detection architectures pH, after reaction a period of time, pH value of solution changes, by 12.5-15%（w/w）NaOH solution（The molar equivalent of NaOH is 2.5）It is put into beaker, it is connected with pH automatic balance instruments, it is 8.80-9.70 to keep pH value of reaction system scope, after reaction carries out 30min-6h, by in remaining NaOH solution in beaker all addition reaction bulb, continue to react 2-5h, when surplus is no more than 1% to beta-schardinger dextrin in the reactive mixture, additionally add 25-30%（w/w）NaOH solution（The molar equivalent of NaOH is 1.5）, continue to react 1-3h, hydrolyze unreacted Isosorbide-5-Nitrae-fourth sultone；The percentage of beta-schardinger dextrin raw material total amount is accounted for less than 5%wt with HPLC tracing detections to beta-schardinger dextrin surplus, and 25ppm is less than with GC tracing detections to Isosorbide-5-Nitrae-fourth sultone residual volume；After the completion of reaction, with sour neutralization reaction solution to 6.8-7.2, natural filtration obtains glassy yellow clear solution, using sephadex or nano filter membrance device, except desalting and accessory substance, then product is rinsed with absolute ethyl alcohol, the fourth sultone of residual is removed, pure product is obtained；The average substitution degree of sulfobutyl ether-beta-cyclodextrin is detected with HPCE, nuclear magnetic resonance spectrometer, mass spectrograph（On the basis of the amount of the material of beta-schardinger dextrin, the consumption of Isosorbide-5-Nitrae-fourth sultone is 2-8 times of beta-schardinger dextrin amount for the reaction）.
3. synthetic method according to claim 1, it is characterised in that etherification reaction system temperature is controlled at 65-75 DEG C；NaOH solution is that substep adds reaction system during etherification reaction.
4. synthetic method according to claim 1, it is characterised in that the concentration that alkali is initially added during etherification reaction and the concentration range for adding alkali for second are 12.5-15%（w/w）, it is 25-30% that third time adds the concentration range of alkali（w/w）.
5. synthetic method according to claim 1, it is characterised in that the NaOH molar equivalents of three additions are fixed during etherification reaction, are respectively 6.5,2.5,1.5（On the basis of the amount of the material of beta-schardinger dextrin）.
6. synthetic method according to claim 1, it is characterised in that it is between 8.80-9.70, to realize that alkali lye automatically controls sample introduction to keep system pH scopes using pH automatic balance instruments during etherification reaction.
7. synthesis technique according to claim 1, it is characterised in that after etherification reaction terminates, solution is neutralized between pH=6.8-7.2 with acid, and a small amount of flocculent deposit occurs, and natural filtration removes precipitation.
8. synthetic method according to claim 1, it is characterised in that after etherification reaction terminates, using sephadex A-25, G-25 removes the accessory substance and salt in reaction solution successively, or removes accessory substance and salt using nano filter membrance device.
9. synthetic method according to claim 1, it is characterised in that the sulfobutyl ether-beta-cyclodextrin of different degree of substitution is respectively monosubstituted, 3.4-4.2, the sulfobutyl ether-beta-cyclodextrin in the range of 6.2-6.9.
10. method according to claim 1, the high conversion rate of beta-schardinger dextrin reaches 60-90%；Reaction time is 30min-6h.
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| CN108484799A (en) * | 2018-03-15 | 2018-09-04 | 山东滨州智源生物科技有限公司 | The method that microwave removes 1,4- butane sultones in sulfobutyl ether betadex sodium salt crude product liquid |
| CN111138566A (en) * | 2020-01-10 | 2020-05-12 | 山西和佳通生物科技有限公司 | Method for preparing low-substitution sulfobutyl ether- β -CD through alkaline electrolysis water method-microwave radiation cooperation |
| CN115505052A (en) * | 2022-08-23 | 2022-12-23 | 安徽普利药业有限公司 | Preparation method of beta-cyclodextrin derivative |
| CN116655831A (en) * | 2023-07-24 | 2023-08-29 | 淄博千汇生物科技有限公司 | Preparation method of sulfobutyl-beta-cyclodextrin |
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Cited By (5)
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| CN108484799A (en) * | 2018-03-15 | 2018-09-04 | 山东滨州智源生物科技有限公司 | The method that microwave removes 1,4- butane sultones in sulfobutyl ether betadex sodium salt crude product liquid |
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| CN115505052A (en) * | 2022-08-23 | 2022-12-23 | 安徽普利药业有限公司 | Preparation method of beta-cyclodextrin derivative |
| CN116655831A (en) * | 2023-07-24 | 2023-08-29 | 淄博千汇生物科技有限公司 | Preparation method of sulfobutyl-beta-cyclodextrin |
| CN116655831B (en) * | 2023-07-24 | 2023-10-03 | 淄博千汇生物科技有限公司 | Preparation method of sulfobutyl-beta-cyclodextrin |
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Application publication date: 20170531 |