Method for removing beta-cyclodextrin impurity in alpha-cyclodextrin production process

Abstract

The invention discloses a method for removing beta-cyclodextrin impurities in an alpha-cyclodextrin production process, which comprises the following steps: screening out methyl tert-butyl ether, n-caprylic alcohol, n-hexane and other assistants which have strong inclusion force with alpha-cyclodextrin, and introducing the assistants in a purification stage after conversion. The separation pertinence is improved, and the auxiliary consumption is reduced; the conversion stage and the purification stage are separately regulated and controlled, and the types and dosages of auxiliaries can be flexibly adjusted according to the composition of the cyclodextrin mixture in the purification stage, so that the product stability is ensured.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of α-cyclodextrin synthesis process, and particularly relates to a method for removing β-cyclodextrin impurities in an α-cyclodextrin production process. BACKGROUND

[0002] α-cyclodextrin is a cyclic oligosaccharide composed of 6 glucose units, which has a conical cavity structure of "internal hydrophobic and external hydrophilic", and can selectively include guest molecules with matching size and properties. This property makes it play an irreplaceable role in solubilization, stabilization, protection, controlled release, masking, separation and purification, and is widely used in pharmaceutical, food, cosmetics, analysis, environmental protection, material and other high-tech and people's livelihood fields. Compared with β-cyclodextrin, the molecular gap of α-cyclodextrin is smaller, and it is more suitable for inclusion of low molecular weight substances, and has higher water solubility and safety, and has irreplaceable advantages in the fields of food and medicine. However, due to the limitation of enzyme selectivity, a large amount of β-cyclodextrin impurities often appear in the preparation process of α-cyclodextrin, which is difficult to separate and affects the actual effect of α-cyclodextrin.

[0003] At present, there are mainly the following methods for removing β-cyclodextrin impurities in the production process of α-cyclodextrin, (1) conversion aid precipitation method, which has the advantages of inhibiting the generation of β-cyclodextrin during the conversion process, and can reduce the content of β-cyclodextrin in the product to a certain extent, but the aid is expensive, the dosage is large, the selectivity is limited, and the subsequent removal of the aid is complicated; (2) chromatographic separation method, which has obvious improvement in safety and removal rate, but needs to introduce new equipment, which is expensive and increases production cost; (3) solubility difference method, which utilizes the difference in solubility of α-cyclodextrin and β-cyclodextrin at different temperatures, and controls the temperature to make β-cyclodextrin precipitate first. This process is harsh in requirements, and α-cyclodextrin is lost in the repeated crystallization process. SUMMARY

[0004] Based on the deficiencies of the prior art, the technical problem solved by the present application is to provide a method for removing β-cyclodextrin impurities in the production process of α-cyclodextrin with good treatment effect. In the production process of α-cyclodextrin, the production process of α-cyclodextrin is improved to efficiently remove β-cyclodextrin impurities, obtain a product with high yield and high stability, and the preparation process is different from the prior art method, which has industrial controllability.

[0005] In order to solve the above technical problems, the present application provides a method for removing β-cyclodextrin impurities in the production process of α-cyclodextrin, comprising the following steps: (1) dry corn starch is stirred and pulped under heating conditions, then heated and stirred to gelatinize, then α-amylase with an enzyme activity of 10000 U / g is added, the enzyme addition amount is 1.25 U / g of dry substrate, and the mixture is placed in a boiling water bath for heating and inactivation to obtain a liquefied liquid; (2) Stir and cool the liquefied liquid, add α-CGTase and isoamylase, stir, heat and keep warm, then filter to obtain filtrate containing cyclodextrin; (3) After cooling the filtrate, add the auxiliary agent, stir, filter and separate, and rinse with purified water 2-3 times to obtain the inclusion complex filter cake; (4) After inclusion is completed, the inclusion filter cake is added to purified water and slurryed, then heated to remove the auxiliary agent. Then activated carbon is added, stirred and filtered to obtain α-cyclodextrin solution. (5) After the α-cyclodextrin solution is concentrated and crystallized, the white crystals are filtered and separated, rinsed with purified water and dried to obtain the α-cyclodextrin product.

[0006] As a preferred embodiment of the above technical solution, the method for removing β-cyclodextrin impurities during the production of α-cyclodextrin provided by the present invention further includes some or all of the following technical features: As an improvement to the above technical solution, in step (1), the mass ratio of dry corn starch to purified water is between 17.65% and 25%.

[0007] As an improvement to the above technical solution, in step (1), the heating conditions are 40°C, the temperature for heating and stirring is 85°C, the gelatinization time is 6 min, the liquefaction time is 5 min, and the heating inactivation time is 20 min.

[0008] As an improvement to the above technical solution, in step (2), the temperature of the liquefied liquid being stirred and cooled is 40-45℃, and the stirring speed is 10-15 rpm; the stirring, heating and heat preservation process specifically involves stirring for 20 hours, then heating to above 95℃ and maintaining it for 15 minutes. A heat-collecting magnetic stirrer is preferred for magnetic stirring.

[0009] As an improvement to the above technical solution, the α-CGTase enzyme activity is 100 U / mL, and the amount added is between 15-30 U / g dry substrate, with 25 U / g dry substrate preferred in this invention; the isoamylase enzyme activity is 1000 U / mL, and the amount added is between 40-100 U / g dry substrate, with 70 U / g dry substrate preferred in this invention.

[0010] As an improvement to the above technical solution, the auxiliary agent in step (3) is one of methyl tert-butyl ether, n-hexane, and n-octanol; the molar ratio of the auxiliary agent to α-CD in the conversion liquid is ≥1:1.

[0011] As an improvement to the above technical solution, in step (3), the filtrate cooling temperature is 40℃, the stirring speed is 300rpm, and the stirring time is 5h.

[0012] As an improvement to the above technical solution, in step (4), the mass ratio of purified water to corn starch used for pulping is 600:90, the heating temperature after pulping is 80℃, and the time is 3h; the mass ratio of activated carbon to corn starch is 2.7:90, and the stirring time after adding activated carbon is 30min.

[0013] As an improvement to the above technical solution, step (5) specifically involves concentrating the α-cyclodextrin solution obtained in step (4) to a mass concentration of 30%, cooling it to 4°C, and crystallizing it at a rotation speed of 250 rpm for 16 hours. After the crystallization is relatively complete, the obtained white crystals are filtered and separated, rinsed with purified water, and then placed in a 60°C oven to dry for 6 hours to obtain the α-cyclodextrin product.

[0014] As an improvement to the above technical solution, the purity of the α-cyclodextrin product is above 98.5%, and the content of β-cyclodextrin impurities is below 0.25%.

[0015] This invention screened out adjuvants such as methyl tert-butyl ether, n-octanol, and n-hexane, which have strong inclusion complexation with α-cyclodextrin. The adjuvants are introduced during the purification stage after conversion. This method improves the separation specificity and reduces adjuvant consumption without affecting the conversion efficiency. Moreover, the conversion and purification stages are controlled separately. During the purification stage, the type and amount of adjuvants can be flexibly adjusted according to the composition of the cyclodextrin mixture to ensure product stability.

[0016] Compared with the prior art, the technical solution of the present invention has the following beneficial effects: This invention relates to the field of α-cyclodextrin preparation technology, specifically to a method for removing β-cyclodextrin impurities during α-cyclodextrin production. Its specific features include the following steps: (1) after starch slurry liquefaction, enzymes are added for conversion, the starch chains are cleaved and cyclized to generate a mixture containing α-cyclodextrin, β-cyclodextrin, and small molecule sugars (where α-cyclodextrin accounts for a certain proportion); (2) after the reaction reaches the expected value, the enzyme is inactivated by heating, and the mixture is filtered to obtain a filtrate containing cyclodextrin; (3) an auxiliary agent (methyl tert-butyl ether, n-octanol, n-hexane, etc.) is added to the filtrate to form an inclusion complex with α-cyclodextrin, and then the inclusion complex is separated; (4) the α-cyclodextrin complexing agent inclusion complex is destroyed, the complexing agent is removed, and an α-cyclodextrin solution is obtained; (5) after decolorization, concentration, crystallization, and other post-treatment processes, a high-purity α-cyclodextrin product is obtained.

[0017] The α-cyclodextrin prepared by this invention has high purity, low β-cyclodextrin residue, and good stability. In addition, this process can reduce the consumption of auxiliary agents and power energy without affecting the enzyme catalytic efficiency, simplify the production process, improve the accuracy and economy of separation, and has simple equipment requirements and is easy to operate, making it more suitable for large-scale production.

[0018] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it in accordance with the contents of the specification, and to make the above and other objects, features and advantages of the present invention more apparent and understandable, the following detailed description is provided in conjunction with preferred embodiments. Attached Figure Description

[0019] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings of the embodiments will be briefly described below.

[0020] Figure 1 This is a liquid phase detection image of β-cyclodextrin impurities in α-cyclodextrin prepared according to preferred embodiment 5 of the present invention; Figure 2 This is a partial magnified liquid phase detection image of β-cyclodextrin impurities in α-cyclodextrin prepared according to preferred embodiment 5 of the present invention. Figure 3 This is a liquid phase detection image of α-cyclodextrin prepared in preferred embodiment 5 of the present invention; Figure 4 This is a partial magnified liquid phase detection image of the α-cyclodextrin prepared in preferred embodiment 5 of the present invention. Detailed Implementation

[0021] The following detailed description of specific embodiments of the present invention is part of this specification. The principles of the present invention are illustrated through examples, and other aspects, features and advantages of the present invention will become apparent from this detailed description.

[0022] Example 1: Preparation steps: (1) Add 90g of dry corn starch and 510g of purified water to a 1L beaker. Stir and beat at 40℃, then transfer to a water bath at 85℃ and stir to gelatinize for 6min. Add α-amylase with 10000U / g enzyme activity, and the enzyme addition amount is 1.25U / g. Liquefy the dry substrate for 5min, then take it out and transfer it to a boiling water bath for 20min to heat and inactivate. (2) After taking out the liquefied liquid, put it into a magnetic stirrer and transfer it to a heat-collecting magnetic stirrer to cool it down to 40-45℃. Stir it magnetically at 10-15 rpm. At the same time, add 22.5g of α-CGTase (α-CGTase enzyme activity 100U / mL) and 6.3g of isoamylase (isoamylase enzyme activity 1000U / mL). After stirring for 20h, heat it to above 95℃ and maintain it for 15min. Then filter to obtain the filtrate containing cyclodextrin. (3) After cooling the filtrate to 40°C, add 8.84 g of n-octanol (0.068 mol), stir at 300 rpm for 5 h at this temperature, filter and separate, and wash with purified water 2-3 times to obtain the inclusion filter cake; (4) Add 600g of purified water to the inclusion complex filter cake and slurry it. Then remove the n-octanol auxiliary agent by steam distillation. After 3 hours, add 2.7g of activated carbon to the de-auxiliary liquid, stir for 30 minutes, and then filter to obtain α-cyclodextrin solution. (5) The obtained α-cyclodextrin solution was concentrated to a mass concentration of 30%, then cooled to 4℃ and timed to crystallize at 250 rpm for 16 hours. After relatively complete crystallization, the obtained white crystals were filtered and separated, rinsed with purified water, and then dried in a 60℃ oven for 6 hours to obtain the α-cyclodextrin product. (α-CD purity 99.4%, β-CD content 0.21%, yield 65.3%) Example 2: Preparation steps: (1) Add 90g of dry corn starch and 510g of purified water to a 1L beaker. Stir and beat at 40℃, then transfer to a water bath at 85℃ and stir to gelatinize for 6min. Add α-amylase with 10000U / g enzyme activity, and the enzyme addition amount is 1.25U / g. Liquefy the dry substrate for 5min, then take it out and transfer it to a boiling water bath for 20min to heat and inactivate. (2) After liquefaction is completed, the liquefied liquid is taken out and transferred to a magnetic stirrer to cool down to 40-45℃. The mixture is then magnetically stirred at 10-15 rpm. At the same time, 22.5 g of α-CGTase (α-CGTase enzyme activity 100 U / mL) and 6.3 g of isoamylase (isoamylase enzyme activity 1000 U / mL) are added. After stirring for 20 h, the mixture is heated to above 95℃ and maintained for 15 min. The mixture is then filtered to obtain a filtrate containing cyclodextrin. (3) After cooling the filtrate to 40°C, add 5.99 g of methyl tert-butyl ether (0.068 mol), stir at 300 rpm for 5 h at this temperature, filter and separate, and wash with purified water 2-3 times to obtain the inclusion filter cake; (4) After inclusion is completed, the inclusion filter cake is added to 600g of purified water and stirred until it is heated to 85℃ to remove the methyl tert-butyl ether additive. After 3 hours, 2.7g of activated carbon is added to the de-additive liquid and stirred for 30 minutes before filtration to obtain α-cyclodextrin solution. (5) The obtained α-cyclodextrin solution was concentrated to a mass concentration of 30%, then cooled to 4℃ and timed to crystallize at 250 rpm for 16 hours. After relatively complete crystallization, the obtained white crystals were filtered and separated, rinsed with purified water, and then placed in a 60℃ oven for 6 hours to obtain the α-cyclodextrin product. (α-CD purity 99.3%, β-CD content 0.07%, yield 73.4%) Example 3: Preparation steps: (1) Add 90g of dry corn starch and 510g of purified water to a 1L beaker. Stir and beat at 40℃, then transfer to a water bath at 85℃ and stir to gelatinize for 6min. Add α-amylase with 10000U / g enzyme activity, and the enzyme addition amount is 1.25U / g. Liquefy the dry substrate for 5min, then take it out and transfer it to a boiling water bath for 20min to heat and inactivate. (2) After taking out the liquefied liquid, put it into a magnetic stirrer and transfer it to a heat-collecting magnetic stirrer to cool it down to 40-45℃. Stir it magnetically at 10-15 rpm. At the same time, add 22.5g of α-CGTase (α-CGTase enzyme activity 100U / mL) and 6.3g of isoamylase (isoamylase enzyme activity 1000U / mL). After stirring for 20h, heat it to above 95℃ and maintain it for 15min. Then filter to obtain the filtrate containing cyclodextrin. (3) After cooling the filtrate to 40°C, add 5.86 g of n-hexane (0.068 mol), stir at 300 rpm for 5 h at this temperature, filter and separate, and wash with purified water 2-3 times to obtain the inclusion filter cake; (4) Add 600g of purified water to the inclusion complex filter cake, stir and heat to 80℃ to remove the n-hexane auxiliary agent. After 3 hours, add 2.7g of activated carbon to the de-auxiliary liquid, stir for 30 minutes and filter to obtain α-cyclodextrin solution. (5) The obtained α-cyclodextrin solution was concentrated to a mass concentration of 30%, then cooled to 4℃ and timed to crystallize at 250 rpm for 16 hours. After relatively complete crystallization, the obtained white crystals were filtered and separated, rinsed with purified water, and then placed in a 60℃ oven for 6 hours to obtain the α-cyclodextrin product. (α-CD purity 98.5%, β-CD content 0.25%, yield 67.5%) Example 4 Preparation steps: (1) Add 90g of dry corn starch and 510g of purified water to a 1L beaker. Stir and beat at 40℃, then transfer to a water bath at 85℃ and stir to gelatinize for 6min. Add α-amylase with 10000U / g enzyme activity, and the enzyme addition amount is 1.25U / g. Liquefy the dry substrate for 5min, then take it out and transfer it to a boiling water bath for 20min to heat and inactivate. (2) After liquefaction is completed, the liquefied liquid is taken out and placed in a magnetic stirrer to cool down to 40-45℃. The mixture is then magnetically stirred at 10-15 rpm. At the same time, 22.5 g of α-CGTase (α-CGTase enzyme activity 100 U / mL) and 6.3 g of isoamylase (isoamylase enzyme activity 100 U / mL) are added. After stirring for 20 h, the mixture is heated to above 95℃ and maintained for 15 min. The mixture is then filtered to obtain a filtrate containing cyclodextrin. (3) After cooling the filtrate to 40°C, add 3.00 g of methyl tert-butyl ether (0.034 mol), stir at 300 rpm for 5 h at this temperature, filter and separate, and wash with purified water 2-3 times to obtain the inclusion filter cake; (4) After inclusion is completed, the inclusion filter cake is added to 600g of purified water and stirred until it is heated to 85℃ to remove the methyl tert-butyl ether additive. After 3 hours, 2.7g of activated carbon is added to the de-additive liquid and stirred for 30 minutes before filtration to obtain α-cyclodextrin solution. (5) The obtained α-cyclodextrin solution was concentrated to a mass concentration of 30%, then cooled to 15℃ and timed to crystallize at 250 rpm for 16 hours. After relatively complete crystallization, the obtained white crystals were filtered and separated, rinsed with purified water, and then dried in a 60℃ oven for 6 hours to obtain the α-cyclodextrin product. (α-CD purity 99.5%, β-CD content 0.01%, yield 68.3%) Example 5: Preparation steps: (1) Add 90g of dry corn starch and 510g of purified water to a 1L beaker. Stir and beat at 40℃, then transfer to a water bath at 85℃ and stir to gelatinize for 6min. Add α-amylase with 10000U / g enzyme activity, and the enzyme addition amount is 1.25U / g. Liquefy the dry substrate for 5min, then take it out and transfer it to a boiling water bath for 20min to heat and inactivate. (2) After liquefaction is completed, the liquefied liquid is taken out and transferred to a magnetic stirrer to cool down to 40-45℃. The mixture is then magnetically stirred at 10-15 rpm. At the same time, 22.5 g of α-CGTase (α-CGTase enzyme activity 100 U / mL) and 6.3 g of isoamylase (isoamylase enzyme activity 1000 U / mL) are added. After stirring for 20 h, the mixture is heated to above 95℃ and maintained for 15 min. The mixture is then filtered to obtain a filtrate containing cyclodextrin. (3) After cooling the filtrate to 40°C, add 3.00 g of methyl tert-butyl ether (0.034 mol), stir at 300 rpm for 5 h at this temperature, filter and separate, and wash with purified water 2-3 times to obtain the inclusion filter cake; (4) After inclusion is completed, the inclusion filter cake is added to 600g of purified water and stirred until it is heated to 85℃ to remove the methyl tert-butyl ether additive. After 3 hours, 2.7g of activated carbon is added to the de-additive liquid and stirred for 30 minutes before filtration to obtain α-cyclodextrin solution. (5) The obtained α-cyclodextrin solution was concentrated to a mass concentration of 30%, then cooled to 4℃ and timed to crystallize at 250 rpm for 16 hours. After relatively complete crystallization, the obtained white crystals were filtered and separated, rinsed with purified water, and then placed in a 60℃ oven for 6 hours to obtain the α-cyclodextrin product. (α-CD purity 99.2%, β-CD content 0.03%, yield 70.2%) Comparative example: (1) Add 90g of dry corn starch and 510g of purified water to a 1L beaker. Stir and beat at 40℃, then transfer to a water bath at 85℃ and stir to gelatinize for 6min. Add α-amylase with 10000U / g enzyme activity, and the enzyme addition amount is 1.25U / g. Liquefy the dry substrate for 5min, then take it out and transfer it to a boiling water bath for 20min to heat and inactivate. (2) After liquefaction is completed, the liquefied liquid is taken out and transferred to a magnetic stirrer to cool down to 40-45℃. The mixture is then magnetically stirred at 10-15 rpm. At the same time, 22.5 g of α-CGTase (α-CGTase enzyme activity 100 U / mL) and 6.3 g of isoamylase (isoamylase enzyme activity 1000 U / mL) are added. After stirring for 20 h, the mixture is heated to above 95℃ and maintained for 15 min. The mixture is then filtered to obtain a filtrate containing cyclodextrin. (3) Cool the filtrate containing dextrin to 5℃-15℃ and stir slowly for 5h to crystallize. Then filter to remove β-CD. Add 0.07% of starch dry weight of α-amylase and immobilized saccharifying enzyme to the filtrate. Heat to 55℃ and stir for 1h to remove sugar impurities. Add 2.7g of activated carbon and stir for 30min. After filtration, obtain α-cyclodextrin solution. (4) The obtained α-cyclodextrin solution was concentrated to a mass concentration of 30%, then cooled to 4℃ and timed to crystallize at 250 rpm for 16 hours. After relatively complete crystallization, the obtained white crystals were filtered and separated, rinsed with purified water, and then dried in a 60℃ oven for 6 hours to obtain the α-cyclodextrin product. (α-CD purity 97.6%, β-CD content 0.33%, yield 50.2%) The above results are summarized in Table 1: Table 1. Experimental results of each embodiment and comparative example

[0023] From the results summarized in Table 1, we can see that the α-cyclodextrin prepared by this invention has high purity (over 98.5%), low β-cyclodextrin residue, and good stability. In Example 4, the yield was low due to insufficient addition of auxiliary agents, but its purity was still very stable.

[0024] The α-cyclodextrin product from Example 5 was analyzed, such as... Figures 1-4 As shown in Table 2-4, the results were analyzed using a differential refractive index detector according to the 2020 edition of the Chinese Pharmacopoeia for the determination of related substances and their contents in alpha cyclodextrin. 10 mg / mL and 1 mg / mL aqueous solutions were prepared (sample number RLDW250620-1-07 for 10 mg / mL, detecting related substances such as β-CD and γ-CD). Figure 1For a 10 mg / mL sample, the peak eluted at 3.7 min was α-CD, and the peak eluted at 5.8 min. Based on the content, β-CD accounted for 0.03% of the total product. Figure 2 For a sample with a concentration of 1 mg / mL, numbered RLDW250620-1-08, the α-CD content was determined. Figure 2 The α-CD content in the product is calculated to be 99.19%. Instrument detection of solvent water will produce impurity peaks. The area ratio of non-cyclodextrin impurity peaks will be calculated after subtracting the solvent peaks.

[0025] Table 2. Liquid Chromatography Analysis Results of Sample RLDW250620-1-07 from Example 5

[0026] Table 3. Liquid Chromatography Analysis Results of Sample RLDW250620-1-08 from Example 5

[0027] Table 4. Sample test results of Example 5

[0028] All the raw materials listed in this invention, as well as the upper and lower limits and ranges of the raw materials and the upper and lower limits and ranges of the process parameters (such as temperature, time, etc.), can realize this invention. Examples are not listed one by one here.

[0029] The above description is merely a preferred embodiment of the present invention, and should not be construed as limiting the scope of the invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications are also considered to be within the scope of protection of the present invention.

Claims

1. A method for removing β-cyclodextrin impurities during the production of α-cyclodextrin, characterized in that, It includes the following steps: (1) Dry corn starch is stirred and slurried in purified water under heating conditions, then heated and stirred to gelatinize, α-amylase is added, liquefied and placed in a boiling water bath for heating and inactivation to obtain liquefied liquid; (2) Stir and cool the liquefied liquid, add α-CGTase and isoamylase, stir, heat and keep warm, then filter to obtain filtrate containing cyclodextrin; (3) After cooling the filtrate, add the auxiliary agent, stir and filter to separate. Rinse with purified water 2-3 times to obtain the inclusion complex filter cake; the auxiliary agent is one of methyl tert-butyl ether, n-hexane, and n-octanol; (4) After inclusion is completed, the inclusion filter cake is added to purified water and slurryed, then heated to remove the auxiliary agent. Then activated carbon is added, stirred and filtered to obtain α-cyclodextrin solution. (5) After the α-cyclodextrin solution is concentrated and crystallized, the white crystals are filtered and separated, rinsed with purified water and dried to obtain the α-cyclodextrin product.

2. The method for removing β-cyclodextrin impurities during the production of α-cyclodextrin as described in claim 1, characterized in that: In step (1), the enzyme activity of α-amylase is 10000 U / g, and the amount of enzyme added is 1.25 U / g of dry substrate; the mass ratio of dry corn starch to purified water is between 17.65% and 25%.

3. The method for removing β-cyclodextrin impurities during the production of α-cyclodextrin as described in claim 1, characterized in that: In step (1), the heating conditions are 40°C, the temperature for stirring is 85°C, the gelatinization time is 6 min, the liquefaction time is 5 min, and the heating inactivation time is 20 min.

4. The method for removing β-cyclodextrin impurities during the production of α-cyclodextrin as described in claim 1, characterized in that: In step (2), the temperature of the liquefied liquid is 40-45℃ and the stirring speed is 10-15 rpm. The process of stirring, heating and keeping warm is as follows: after stirring for 20 hours, heat and keep warm at 95℃ or above for 15 minutes.

5. The method for removing β-cyclodextrin impurities during the production of α-cyclodextrin as described in claim 1, characterized in that: α-CGTase activity 100 U / mL, added at 15-30 U / g dry substrate; isoamylase activity 1000 U / mL, added at 40-100 U / g dry substrate.

6. The method for removing β-cyclodextrin impurities during the production of α-cyclodextrin as described in claim 1, characterized in that: The molar ratio of the auxiliaries in step (3) to the α-CD in the conversion solution is ≥1:

1.

7. The method for removing β-cyclodextrin impurities during the production of α-cyclodextrin as described in claim 1, characterized in that: In step (3), the filtrate cooling temperature is 40℃, the stirring speed is 300rpm, and the stirring time is 5h.

8. The method for removing β-cyclodextrin impurities during the production of α-cyclodextrin as described in claim 1, characterized in that: In step (4), the mass ratio of purified water to corn starch used for pulping is 600:90, the heating temperature after pulping is 80℃, and the time is 3h; the mass ratio of activated carbon to corn starch is 2.7:90, and the stirring time after adding activated carbon is 30min.

9. The method for removing β-cyclodextrin impurities during the production of α-cyclodextrin as described in claim 1, characterized in that: The specific process of step (5) is as follows: the α-cyclodextrin solution obtained in step (4) is concentrated to a mass concentration of 30%, then cooled to 4°C and crystallized at a speed of 250 rpm for 16 hours. After the crystallization is relatively complete, the obtained white crystals are filtered and separated, rinsed with purified water, and then placed in a 60°C oven to dry for 6 hours to obtain the α-cyclodextrin product.

10. The method for removing β-cyclodextrin impurities during the production of α-cyclodextrin as described in claim 1, characterized in that: The purity of the α-cyclodextrin product is above 98.5%, and the content of β-cyclodextrin impurities is below 0.25%.

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