CN115490883A - Colon-targeting arabinoxylan hydrogel and preparation method thereof - Google Patents

Colon-targeting arabinoxylan hydrogel and preparation method thereof Download PDF

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CN115490883A
CN115490883A CN202211012431.0A CN202211012431A CN115490883A CN 115490883 A CN115490883 A CN 115490883A CN 202211012431 A CN202211012431 A CN 202211012431A CN 115490883 A CN115490883 A CN 115490883A
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arabinoxylan
colon
targeted
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water
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孙念霞
汪电雷
王重阳
韩智利
黄鹏
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Anhui University of Traditional Chinese Medicine AHUTCM
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Abstract

The invention discloses a colon-targeted arabinoxylan hydrogel and a preparation method thereof, wherein the colon-targeted arabinoxylan hydrogel comprises the following steps: dissolving water-soluble arabinoxylan in water to obtain an arabinoxylan solution, then adding pentosanase, carrying out enzymolysis reaction, carrying out enzyme deactivation in a boiling water bath after the reaction is finished, cooling, sequentially adding glucose, peroxidase and glucose oxidase, and stirring at room temperature to carry out crosslinking reaction to obtain the colon-targeted arabinoxylan hydrogel. The hydrogel disclosed by the invention has good colon targeting performance, high drug loading capacity and high drug release rate, and has good application potential as an oral colon targeting drug carrier.

Description

Colon-targeting arabinoxylan hydrogel and preparation method thereof
Technical Field
The invention relates to the technical field of functional hydrogel materials, in particular to a colon-targeted arabinoxylan hydrogel and a preparation method thereof.
Background
Oral administration of functional ingredients and drugs is the preferred route to achieve their efficacy. An Oral colon-specific drug delivery system (OCDDS) is taken as a fourth-generation pharmaceutical preparation, drugs or functional components are prevented from being inactivated by the degradation of protease in gastrointestinal tracts and the influence of pH mainly through pharmaceutical means such as drug modification, coating and the like, and the characteristics that the colon has relatively high pH (pH is more than 8), the concentration of proteolytic enzyme is low, the activity is low, the retention time of the drugs is long, the penetration resistance of colon walls to macromolecules is small, and the like, so that the colon-specific drug delivery system is favorable for full absorption, the treatment effect is enhanced, and the drug use amount and the toxic and side effects are reduced.
According to different release mechanisms, colon targeting systems mainly comprise a pH dependent type, a time dependent type, a pressure control type, a flora trigger type and the like. pH-dependent, time-dependent and pressure-controlled colon targeting systems may lead to premature or inaccurate release of nutrients due to inter-individual differences in gastrointestinal transit time, upper gastrointestinal pH and health conditions. The flora triggered OCDDS is prepared by acting enzymes generated by intestinal flora on a wrapping material to release medicines, is slightly influenced by diet, diseases, individual difference and the like, has targeting property and is a research hotspot of the OCDDS in recent years.
At present, there are more than ten kinds of target positioning materials developed and synthesized, wherein polysaccharide macromolecules are widely paid attention and are included in pharmacopoeias of various countries as flora trigger type OCDDS due to their safety and good biocompatibility. However, the existing polysaccharide still has the defects of few types, poor formability, strong water solubility and swelling property, easy medicament release in advance and the like. In order to realize the efficacy of the hydrogel as a colon-targeted drug carrier, the hydrogel is required to have low swelling rate in the stomach and small intestine and high degradation rate in the colon, and also have good drug loading rate and drug release rate. Due to the above limitations, most of the studies on colon-targeted hydrogels have been still in the theoretical stage of research, and it is rare to produce commercially available colon-targeted preparations based on polysaccharides and their derivatives. Therefore, the development and the utilization of the novel polysaccharide flora triggered colon targeting material have very important significance.
Disclosure of Invention
Based on the technical problems in the background art, the invention provides a colon-targeted arabinoxylan hydrogel and a preparation method thereof.
The invention provides a preparation method of colon-targeted arabinoxylan hydrogel, which comprises the following steps: dissolving water-soluble arabinoxylan in water to obtain an arabinoxylan aqueous solution with the concentration of 8-20wt%, adding pentosanase, carrying out enzymolysis reaction at 20-30 ℃ for 2-5min, carrying out enzyme deactivation in a boiling water bath after the reaction is finished, cooling, sequentially adding glucose, peroxidase and glucose oxidase, and stirring at room temperature to carry out crosslinking reaction to obtain the colon-targeted arabinoxylan hydrogel; wherein, the dosage of the pentosanase is 40-80 mug/g of the araboxylan based on the mass of the araboxylan.
Preferably, the water-soluble arabinoxylan is prepared by taking wheat flour as a raw material and adopting an enzymolysis-water extraction and alcohol precipitation method.
Preferably, the preparation method of the water-soluble arabinoxylan comprises the following steps: mixing wheat flour and water uniformly, stirring at room temperature for a period of time, centrifuging, collecting supernatant, concentrating, adding high temperature alpha-amylase for enzymolysis reaction, adding glucosidase for enzymolysis reaction, cooling, centrifuging, precipitating the obtained supernatant with ethanol to obtain precipitate, re-dissolving the precipitate in water, centrifuging, collecting supernatant, precipitating with ethanol, washing the precipitate with anhydrous ethanol, and freeze drying.
Preferably, in the preparation method of the water-soluble arabinoxylan, high-temperature alpha-amylase is added for enzymolysis reaction for 1-2h.
Preferably, in the preparation method of the water-soluble arabinoxylan, glucosidase is added for enzymolysis reaction for 1-2h.
Preferably, in the preparation method of the water-soluble arabinoxylan, the use amount of the high-temperature alpha-amylase is 0.3-0.5kg/t of wheat flour by taking the mass of the wheat flour as a reference, and the temperature of the high-temperature alpha-amylase enzymolysis reaction is 80-95 ℃. The dosage of the glucosidase is 1-2L/t of wheat flour, and the temperature of the glucosidase enzymolysis reaction is 55-70 ℃.
Preferably, in the preparation method of the water-soluble arabinoxylan, the mass ratio of the wheat flour to the water is 1: (5-10), stirring at room temperature for 40-60min, concentrating the supernatant to 1/4-1/8 of the original volume, and concentrating at 40-65 deg.C.
Preferably, in the preparation method of the water-soluble arabinoxylan, the ethanol concentration adopted by the ethanol precipitation is 60-70%, and the preparation method further comprises standing for 18-36h at 4-10 ℃ after the ethanol precipitation to obtain the precipitate.
Preferably, the dosage of glucose is 0.033-0.33mg/g of arabinoxylan, the dosage of peroxidase is 4.8-6.0U/g of arabinoxylan, and the dosage of glucose oxidase is 2000-60000 mu g/g of arabinoxylan.
Preferably, the time of the crosslinking reaction is 5 to 60min.
The invention also provides a colon-targeted arabinoxylan hydrogel prepared by the preparation method.
The invention also provides application of the arabinoxylan hydrogel as a colon-targeted drug carrier.
The invention also provides an oral colon-targeted pharmaceutical preparation, which comprises an active medicament and a medicament carrier for encapsulating the active medicament, wherein the medicament carrier is the colon-targeted arabinoxylan hydrogel prepared by the preparation method;
or the pharmaceutical preparation is prepared by replacing water in the preparation method with a buffer solution containing the active drug.
The invention also provides an oral colon targeted medicinal preparation, and the preparation method comprises the following steps:
dissolving water-soluble arabinoxylan into a buffer solution containing an active drug to obtain an arabinoxylan solution containing the active drug, then adding pentosanase, carrying out enzymolysis reaction for 2-5min at 20-30 ℃, carrying out enzyme deactivation in a boiling water bath after the reaction is finished, cooling, then sequentially adding glucose, peroxidase and glucose oxidase, and stirring at room temperature to carry out a crosslinking reaction to obtain an oral colon-targeted pharmaceutical preparation; in the arabinoxylan solution containing the active drug, the mass concentration of the arabinoxylan is 8-20wt%; the dosage of the pentosanase is 40-80 mug/g of the araboxylan based on the mass of the araboxylan.
Among them, the buffer solution is preferably Phosphate Buffered Saline (PBS).
Preferably, the dosage of glucose is 0.033-0.33mg/g arabinoxylan, the dosage of peroxidase is 4.8-6.0PU/g arabinoxylan, and the dosage of glucose oxidase is 2000-60000. Mu.g/g arabinoxylan.
Preferably, the time of the crosslinking reaction is 5 to 60min.
Preferably, the mass ratio of the active drug to the arabinoxylan is 1: (4-10).
Preferably, the active agent is a polyphenol, polypeptide or protein agent.
Arabinoxylan (called AX for short) is a non-starch polysaccharide existing in grains, accounts for about 80-90% of the total amount of bran of grains, and is cheap and easily available. Its basic structure is 1,4-beta-D-xylopyranose main chain and alpha-L-arabinofuranose side chain which are connected by glycosidic bond. Ferulic Acid (FA) is present in the C5 position of some arabinose linked by an ester bond, which is usually linked to the C3 position of xylose. Studies have shown that AX is not a simple "inert" fibrous matrix. The AX can not be utilized by the gastrointestinal tract of a human body, can be specifically degraded by colonic bacteria, and has good intestinal probiotic effect. Meanwhile, when the AX solution coexists with some oxidants, FA forms intermolecular cross-linking to generate ferulic acid diploid or triploid, thereby forming high-viscosity solution, even cross-linking to form gel.
Glucose oxidase is an important industrial enzyme in the food industry, and is widely used in deoxidation of foods such as wine, beer, fruit juice, milk powder and the like, flour improvement, browning prevention of foods and the like. The AX gel covalently crosslinked by Glucose oxidase (GOX for short) has mild forming conditions, no toxicity, good biocompatibility, insensitivity to pH and electrolyte concentration change, no digestion by gastric juice and capability of being decomposed by microorganisms in intestinal tracts to exert the intestinal tract probiotic effect.
The invention has the beneficial effects that:
according to the invention, water-soluble arabinoxylan is used as a raw material, a proper amount of pentosanase is added into an aqueous solution of the arabinoxylan with a proper concentration for enzymolysis, so that chain segments of the arabinoxylan are partially degraded, and ferulic acid on the chain segments is properly crosslinked under the action of peroxidase and glucose oxidase to form hydrogel with higher crosslinking strength, wherein the partially degraded arabinoxylan chain segments treated by the proper amount of pentosanase can form a more uniform and highly porous honeycomb structure on a microscopic scale after being properly crosslinked, so that the entrapment rate of the hydrogel formed by crosslinking on a medicament can be obviously improved, the more compact grid structure can also reduce the release of the medicament in the stomach and small intestine environments, and the proper degradation of the arabinoxylan chain segments is favorable for improving the medicament release rate in a colon; meanwhile, the hydrogel can maintain a cross-linked structure in the stomach and small intestine environments, has an extremely low swelling ratio, is degraded by enzymes generated by microorganisms in the colon, breaks the spatial network structure of the hydrogel, releases the drug, and has good colon targeting performance. The hydrogel disclosed by the invention has good colon targeting performance, high drug loading capacity and high drug release rate, and has good application potential as an oral colon targeting drug carrier.
Detailed Description
The technical solution of the present invention will be described in detail below with reference to specific examples.
In the following examples and comparative examples, water-soluble arabinoxylan was prepared by the following method:
uniformly mixing wheat flour and water according to a mass ratio of 1:5, stirring for 40min at room temperature, centrifuging for 10min at 4000rpm, taking supernatant, carrying out rotary evaporation and concentration at 60 ℃ to 1/4 of the original volume, then adding high-temperature alpha-amylase, carrying out enzymolysis reaction for 2h at 85 ℃, then adding glucosidase, carrying out enzymolysis reaction for 2h at 60 ℃, then cooling, centrifuging for 20min at 4000rpm, carrying out alcohol precipitation on the obtained supernatant by using 65% ethanol, standing for 20h at 4 ℃ to obtain precipitate, re-dissolving the precipitate in water, centrifuging for 10min at 2000rpm, taking supernatant, carrying out alcohol precipitation by using 65% ethanol, standing for 20h at 4 ℃, washing the obtained precipitate by using absolute ethanol, and then carrying out freeze drying to obtain the wheat flour, wherein the mass ratio of the high-temperature alpha-amylase is 0.4kg/t of wheat flour, the dosage of the glucosidase is 1.2L/t of wheat flour: BAN 480L,480KNU/g, novowesson Biotechnology Co., ltd., glucosidase: AMG 300L,300AGU/g, novoxil Biotechnology Ltd.
Pentosanase: 2500FXU (W)/g, novoxil Biotechnology Ltd.
Peroxidase: 240U/g, sigma corporation, USA.
Glucose oxidase: 10000GODU/g, novixin Biotechnology Ltd.
Example 1
A preparation method of colon-targeted arabinoxylan hydrogel comprises the following steps: dissolving water-soluble arabinoxylan in water to obtain an arabinoxylan aqueous solution with the concentration of 8wt%, adding pentosanase, carrying out enzymolysis reaction for 5min at 20 ℃, carrying out enzyme deactivation in a boiling water bath after the reaction is finished, cooling, sequentially adding glucose, peroxidase and glucose oxidase, stirring at room temperature, and carrying out crosslinking reaction for 60min to obtain the colon-targeted arabinoxylan hydrogel; wherein the dosage of the pentosanase is 40 mu g/g of araboxylan, the dosage of the glucose is 0.033mg/g of araboxylan, the dosage of the peroxidase is 4.8PU/g of araboxylan and the dosage of the glucose oxidase is 2000 mu g/g of araboxylan based on the mass of the araboxylan.
Example 2
A preparation method of colon-targeted arabinoxylan hydrogel comprises the following steps: dissolving water-soluble arabinoxylan in water to obtain an arabinoxylan aqueous solution with the concentration of 20wt%, adding pentosanase, carrying out enzymolysis reaction for 2min at 30 ℃, carrying out enzyme deactivation in a boiling water bath after the reaction is finished, cooling, sequentially adding glucose, peroxidase and glucose oxidase, and stirring at room temperature to carry out crosslinking reaction for 5min to obtain the colon-targeted arabinoxylan hydrogel; wherein, based on the mass of the arabinoxylan, the dosage of the pentosanase is 80 mu g/g of the arabinoxylan, the dosage of the glucose is 0.33mg/g of the arabinoxylan, the dosage of the peroxidase is 6.0PU/g of the arabinoxylan, and the dosage of the glucose oxidase is 60000 mu g/g of the arabinoxylan.
Example 3
A preparation method of colon-targeted arabinoxylan hydrogel comprises the following steps: dissolving water-soluble arabinoxylan in water to obtain an arabinoxylan aqueous solution with the concentration of 10wt%, adding pentosanase, carrying out enzymolysis reaction at 25 ℃ for 3min, carrying out enzyme deactivation in a boiling water bath after the reaction is finished, cooling, sequentially adding glucose, peroxidase and glucose oxidase, and stirring at room temperature to carry out crosslinking reaction for 20min to obtain the colon-targeted arabinoxylan hydrogel; wherein the dosage of the pentosanase is 50 mu g/g of the arabinoxylan, the dosage of the glucose is 0.2mg/g of the arabinoxylan, the dosage of the peroxidase is 5.5PU/g of the arabinoxylan, and the dosage of the glucose oxidase is 5000 mu g/g of the arabinoxylan.
Example 4
A method for preparing an oral colon targeted pharmaceutical formulation, comprising the steps of: dissolving water-soluble arabinoxylan in a phosphate buffer solution (0.01M, pH = 6.0) containing ferulic acid to obtain an arabinoxylan solution containing ferulic acid (wherein the concentration of the arabinoxylan is 10 wt%), adding pentosanase, carrying out enzymolysis reaction at 25 ℃ for 3min, inactivating enzyme in a boiling water bath after the reaction is finished, sequentially adding glucose, peroxidase and glucose oxidase after cooling, and carrying out crosslinking reaction for 20min by stirring at room temperature to obtain an oral colon-targeted pharmaceutical preparation; wherein the mass ratio of the ferulic acid to the arabinoxylan is 1:10; wherein the dosage of the pentosanase is 50 mu g/g of araboxylan, the dosage of the glucose is 0.2mg/g of araboxylan, the dosage of the peroxidase is 5.5PU/g of araboxylan and the dosage of the glucose oxidase is 5000 mu g/g of araboxylan based on the mass of the araboxylan.
Example 5
A method for preparing an oral colon targeted pharmaceutical formulation, comprising the steps of: dissolving water-soluble arabinoxylan in phosphate buffer solution (0.01M, pH = 6.0) containing bovine serum albumin to obtain arabinoxylan solution containing bovine serum albumin (wherein the concentration of the arabinoxylan is 8 wt%), adding pentosanase, carrying out enzymolysis reaction at 20 ℃ for 5min, inactivating enzyme in boiling water bath after the reaction is finished, cooling, sequentially adding glucose, peroxidase and glucose oxidase, and carrying out crosslinking reaction for 60min under stirring at room temperature to obtain the arabinoxylan solution; wherein the mass ratio of the bovine serum albumin to the arabinoxylan is 1:6; based on the mass of the arabinoxylan, the dosage of the pentosanase is 40 mu g/g of the arabinoxylan, the dosage of the glucose is 0.033mg/g of the arabinoxylan, the dosage of the peroxidase is 4.8PU/g of the arabinoxylan, and the dosage of the glucose oxidase is 2000 mu g/g of the arabinoxylan.
Example 6
A method for preparing an oral colon-targeted pharmaceutical formulation, comprising the steps of: dissolving water-soluble arabinoxylan in phosphate buffer solution (0.01M, pH = 6.0) containing bovine serum albumin to obtain arabinoxylan solution containing bovine serum albumin (wherein the concentration of the arabinoxylan is 20 wt%), adding pentosanase, carrying out enzymolysis reaction at 30 ℃ for 2min, inactivating enzyme in boiling water bath after the reaction is finished, cooling, sequentially adding glucose, peroxidase and glucose oxidase, and carrying out crosslinking reaction for 5min under stirring at room temperature to obtain the arabinoxylan solution; wherein the mass ratio of the bovine serum albumin to the arabinoxylan is 1:6; based on the mass of the arabinoxylan, the dosage of the pentosanase is 80 mu g/g of the arabinoxylan, the dosage of the glucose is 0.33mg/g of the arabinoxylan, the dosage of the peroxidase is 6.0PU/g of the arabinoxylan, and the dosage of the glucose oxidase is 60000 mu g/g of the arabinoxylan.
Example 7
A method for preparing an oral colon targeted pharmaceutical formulation, comprising the steps of: dissolving water-soluble arabinoxylan in phosphate buffer solution (0.01M, pH = 6.0) containing bovine serum albumin to obtain arabinoxylan solution containing bovine serum albumin (wherein the concentration of the arabinoxylan is 10 wt%), adding pentosanase, carrying out enzymolysis reaction at 25 ℃ for 3min, inactivating enzyme in boiling water bath after the reaction is finished, cooling, sequentially adding glucose, peroxidase and glucose oxidase, and carrying out crosslinking reaction for 20min under stirring at room temperature to obtain the arabinoxylan solution; wherein the mass ratio of the bovine serum albumin to the arabinoxylan is 1:6; based on the mass of the arabinoxylan, the dosage of the pentosanase is 50 mu g/g of the arabinoxylan, the dosage of the glucose is 0.2mg/g of the arabinoxylan, the dosage of the peroxidase is 5.5PU/g of the arabinoxylan, and the dosage of the glucose oxidase is 5000 mu g/g of the arabinoxylan.
Comparative example 1
Comparative example 1 differs from example 7 only in that: the arabinoxylan solution containing bovine serum albumin had an arabinoxylan concentration of 5wt%.
Comparative example 2
Comparative example 2 differs from example 7 only in that: the arabinoxylan solution containing bovine serum albumin had an arabinoxylan concentration of 25wt%.
Comparative example 3
Comparative example 3 differs from example 7 only in that: the pentosanase is used in an amount of 25. Mu.g/g arabinoxylan.
Comparative example 4
Comparative example 4 differs from example 7 only in that: the pentosanase is used in an amount of 100. Mu.g/g arabinoxylan.
Comparative example 5
Comparative example 5 differs from example 7 only in that: adding pentosanase, and performing enzymolysis reaction at 15 deg.C for 1min.
Comparative example 6
Comparative example 6 differs from example 7 only in that: adding pentosanase, and performing enzymolysis reaction at 30 deg.C for 10min.
Test examples
1. Swelling property test:
1. preparing a medium:
artificial gastric fluid (SGF): taking 23.4ml of hydrochloric acid, adding water to dilute the hydrochloric acid to 100ml to obtain a dilute hydrochloric acid solution; taking 4.1mL of dilute hydrochloric acid, adding about 200mL of water and 2.5g of pepsin, shaking up, and adding water to dilute into 250mL to obtain the compound.
Artificial intestinal fluid (SIF) (containing pancreatin): 6.8g of potassium dihydrogen phosphate is removed, 500mL of water is added for dissolution, and the pH value is adjusted to 6.8 by 0.1mol/L sodium hydroxide; dissolving pancreatin 10g in water, mixing the two solutions, and diluting to 1000 mL.
Preparing simulated colon liquid: 5.59g of dipotassium hydrogen phosphate, 0.41g of monopotassium phosphate and 0.5g of pentosanase are taken, and 1000mL of water is added for dissolution, so as to obtain the xylanase.
2. The test method comprises the following steps:
precisely weighing 30mg of the freeze-dried hydrogel of the embodiment 1-3, soaking the hydrogel in each medium, taking out the hydrogel after 15min, 30min, 45min, 60min, 120min, 180min, 240min, 300min and 360min from the beginning of placing the hydrogel in a beaker, precisely weighing the weight of the gel after absorbing surface liquid by using filter paper, and calculating the Swelling Ratio (SR) of the hydrogel at each time point, wherein the SR calculation formula is as follows:
SR＝(W t -W 0 )/W 0 ×100％
W t denotes the hydrogel mass (g), W at time t 0 Represents the dry weight (g) of the hydrogel before soaking.
3. Test results
The swelling ratios of the hydrogels of examples 1-3 in each medium are shown in Table 1:
TABLE 1
Figure BDA0003811442220000111
As can be seen from Table 1, the hydrogel of the present invention can maintain its crosslinked structure in the stomach and small intestine environments, has a very low swelling ratio, can well entrap drugs, and is degraded by pentosanase in the colon, the crosslinked structure is destroyed, no swelling occurs, and the weight is lost, which indicates that the hydrogel of the present invention can maintain its crosslinked structure in the stomach and small intestine environments, the crosslinked structure is degraded and destroyed in the colon, and has a very good colon targeting performance.
2. Drug loading and in vitro release rate testing:
1. the test method comprises the following steps:
(1) And (3) measuring the drug loading rate:
20mg of the freeze-dried samples of examples 5 to 7 and comparative examples 1 to 6 were precisely weighed, placed in a 10mL measuring flask, and added with PBS to a constant volume. Carrying out warm bath at 37 ℃ for 2h, carrying out ultrasonic treatment for 10min, taking out supernatant, determining the content of bovine serum albumin in the supernatant by using a BCA method, and determining drug Loading Capacity (LC), wherein the formula is as follows:
LC＝(A-B)/C×100％
a is the amount of bovine serum albumin added, B is the amount of bovine serum albumin in the supernatant, and C is the total mass of arabinoxylan and bovine serum albumin.
(2) In vitro release rate determination:
200mg of the samples of examples 5 to 7 and comparative examples 1 to 8 were precisely weighed and placed in a dialysis bag with a cut-off of 10000Da, the dialysis bag was placed in a beaker containing 100mL of release medium, stirred at 100rpm/min in a constant temperature water bath, maintained at (37. + -. 0.5) ℃ and placed in SGF for 2h, taken out and placed in SIF for 4h, and then placed in simulated colon fluid with enzymes added for 12h. 3mL of dissolution medium was removed at 1, 2, 4, 6, 8, 10, 12, 18h and an equal amount of fresh dissolution medium was added. The sample was filtered through a 0.45 μm syringe filter and analyzed by high performance liquid chromatography to calculate the cumulative release rate.
2. And (3) testing results:
the drug loading and in vitro release rate test results for the drug formulations of examples 5-7 and comparative examples 1-6 are shown in table 2:
TABLE 2
Figure BDA0003811442220000121
As can be seen from Table 2, the hydrogel of the invention has high drug loading, low drug release rate in artificial gastric juice and artificial intestinal juice, and high drug release rate in simulated colon fluid, which fully shows that the hydrogel has excellent colon-targeted drug release performance.
Therefore, the invention obviously improves the drug-loading rate and the in vitro release rate of the hydrogel by optimizing the dosage of the pentosanase, the concentration of the arabinoxylan and the reaction conditions, and has good application prospect.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.

Claims (10)

1. A preparation method of colon-targeted arabinoxylan hydrogel is characterized by comprising the following steps: dissolving water-soluble arabinoxylan in water to obtain an arabinoxylan solution, adding pentosanase, carrying out enzymolysis reaction at 20-30 ℃ for 2-5min, carrying out enzyme deactivation in boiling water bath after the reaction is finished, cooling, sequentially adding glucose, peroxidase and glucose oxidase, and stirring at room temperature to carry out crosslinking reaction to obtain a colon-targeted arabinoxylan hydrogel; in the arabinoxylan solution, the concentration of the arabinoxylan is 8-20wt%; the dosage of pentosanase is 40-80 mug/g araboxylan based on the mass of araboxylan.
2. The method for preparing the colon-targeted arabinoxylan hydrogel according to claim 1, wherein the water-soluble arabinoxylan is prepared from wheat flour as a raw material by an enzymolysis-water extraction-alcohol precipitation method.
3. The method for preparing colon-targeted arabinoxylan hydrogel according to claim 1, wherein the method for preparing the water-soluble arabinoxylan comprises: uniformly mixing wheat flour and water, stirring for a period of time at room temperature, centrifuging, taking supernatant, concentrating, adding high-temperature alpha-amylase for enzymolysis reaction, then adding glucosidase for enzymolysis reaction, cooling, centrifuging, carrying out alcohol precipitation on obtained supernatant by using ethanol to obtain precipitate, re-dissolving the precipitate in water, centrifuging, taking supernatant, carrying out alcohol precipitation by using ethanol, washing obtained precipitate by using absolute ethanol, and freeze-drying to obtain the wheat flour-containing food additive.
4. The method for preparing colon-targeted arabinoxylan hydrogel according to claim 3, wherein the amount of the high temperature alpha-amylase used in the method for preparing water-soluble arabinoxylan is 0.3 to 0.5kg/t of wheat flour based on the mass of the wheat flour, and the temperature of the high temperature alpha-amylase is 80 to 95 ℃. The dosage of the glucosidase is 1-2L/t of wheat flour, and the temperature of the glucosidase enzymolysis reaction is 55-70 ℃.
5. The method for preparing colon-targeted arabinoxylan hydrogel according to claim 1, wherein the amount of glucose is 0.033 to 0.33mg/g of arabinoxylan, the amount of peroxidase is 4.8 to 6.0U/g of arabinoxylan, and the amount of glucose oxidase is 2000 to 60000 μ g/g of arabinoxylan, based on the mass of the arabinoxylan.
6. The method for preparing colon-targeted arabinoxylan hydrogel according to claim 1, wherein the time for the crosslinking reaction is 5 to 60min.
7. A colon-targeted arabinoxylan hydrogel produced by the method of any one of claims 1 to 6.
8. Use of an arabinoxylan hydrogel of claim 7 as a colon targeted drug carrier.
9. An oral colon-targeted drug preparation, which is characterized by comprising an active drug and a drug carrier for encapsulating the active drug, wherein the drug carrier is the colon-targeted arabinoxylan hydrogel prepared by the preparation method in any one of claims 1 to 6;
or the pharmaceutical preparation is prepared by replacing water in the preparation method according to any one of claims 1 to 6 with a buffer solution containing the active drug.
10. The drug-loaded oral colon targeted formulation of claim 9, wherein the active drug is a polyphenol, polypeptide or protein drug.
CN202211012431.0A 2022-08-23 2022-08-23 Colon-targeting arabinoxylan hydrogel and preparation method thereof Pending CN115490883A (en)

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