A method for preparing alginate-based hydrogel

Abstract

This invention belongs to the field of seaweed chemical technology, specifically relating to a method for preparing alginate-based hydrogel. The technical solution of this invention includes the step of using a frame stirrer to stir the reaction premix to uniformly mix the reaction premix with a gel release agent to form a homogeneous reaction system; the ratio of the diameter of the stirrer paddle to the inner diameter of the reactor is 0.4–0.8, and the ratio of the stirrer paddle height to the liquid depth is 0.4–1; the rotational speed of the frame stirrer paddle is 300–600 r / min. This invention uses a frame stirrer to avoid gas intake, thus preventing air bubbles from forming inside the gel, and also to avoid dead zones, forming a uniform flow field; and by adding the gel release agent during stirring, the gel release agent is added and dispersed simultaneously, achieving uniform mixing of the sodium alginate and crosslinking agent mixture with the gel release agent.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of seaweed chemical industry, and particularly relates to a preparation method of a fucoidan-based hydrogel. BACKGROUND

[0002] Fucoidan is the general term of alginic acid and its salts, but generally refers to sodium alginate, which is a natural anionic polysaccharide and can be crosslinked with hydrogen ions or divalent metal ions except magnesium and mercury ions to form a hydrogel. The fucoidan-based hydrogel has good biocompatibility and environmental friendliness and is widely used in the fields of pharmaceutical preparations, tissue engineering, clinical treatment, cell culture and food processing.

[0003] A uniform gel structure is the key to guaranteeing the performance of the gel. Since the crosslinking reaction of alginate with multivalent metal ions is instantaneous, the reaction speed is difficult to control when using soluble salt for crosslinking, and the uniformity of the gel structure is difficult to guarantee. Researchers have proposed an in-situ release method, in which chelated, water-insoluble or slightly water-soluble multivalent metal salt is used as a crosslinking agent, and the metal ions are slowly released by adjusting the temperature or adding a release agent, so as to obtain a uniform fucoidan-based hydrogel. For example, Cuomo et al. (F. Cuomo, M. Cofflice, F. Lopez, Polymers, 2019, 11(2): 259.) used calcium disodium ethylenediaminetetraacetate (EDTA-Ca) as a crosslinking agent, Stokke et al. (B. T. Stokke, K. I. Draget, O. , Y. Yuguchi, H. Urakawa, K. Kajiwara, Macromolecules, 2000, 33: 1853-1863) used calcium ethyleneglycol diethyether diamine tetraacetate (EGTA-Ca) as a crosslinking agent, and Kuo and Ma used calcium carbonate or / and calcium sulfate (C. K. Kuo, P. X. Ma, Biomaterials, 2001, 22: 511-521) as a calcium source crosslinking agent. A freshly prepared D-gluconic acid lactone (GDL) aqueous solution was added to a mixed solution composed of sodium alginate, the calcium source crosslinking agent and water, the calcium ions were gradually released and slowly contacted with sodium alginate to form a gel, and a uniform calcium alginate gel was obtained.

[0004] The viscosity of the current algin for preparing hydrogel (the viscosity of 1% sodium alginate aqueous solution, referred to as sodium alginate viscosity) is generally less than 800 mPa·s, and the mixing of the reaction premix of sodium alginate and gelling agent with the gel releasing agent is carried out by paddle stirrer (straight-blade paddle, pitched-blade paddle or cylindrical paddle), and the rotating speed of the stirring paddle is generally between 100-500 r / min. The existing research shows that the algin-based hydrogel increases with the increase of the viscosity of sodium alginate (the viscosity of 1% sodium alginate aqueous solution, referred to as sodium alginate viscosity). Luo et al. (Luo, Zhang, Food Science and Technology, 2012, 33(06): 374-376+385.) studied the gel properties of the gel prepared from sodium alginate with a viscosity of 400-800 mPa·s (the viscosity of 1% sodium alginate aqueous solution, referred to as sodium alginate viscosity), and the results showed that, under the same conditions, for high M (mannuronic acid) type algin, the gel prepared from 800 mPa·s sodium alginate has a strength increased by 44%-166% than that prepared from 400 mPa·s sodium alginate; for high G (guluronic acid) type algin, the gel prepared from 800 mPa·s sodium alginate has a strength increased by 20%-110% than that prepared from 400 mPa·s sodium alginate.

[0005] However, when high-viscosity sodium alginate is used as raw material to prepare algin-based hydrogel, even if in-situ gel releasing method is used, the gel strength of the algin-based hydrogel prepared by paddle stirrer is still uneven. Luo et al. (Luo, Zhang, Food Science and Technology, 2012, 33(06): 374-376+385.) used a high-shear emulsifier with a rotating speed of 22000 r / min when preparing gel from medium-high viscosity (400-800 mPa·s) sodium alginate. The energy consumption of high-shear emulsifier is much higher than that of mechanical stirring, which is bound to be limited in industrial production. When the viscosity of sodium alginate is further increased, especially when the viscosity of sodium alginate is increased to 1000 mPa·s or more, the inventors found that, by mechanical stirring mixing with the current paddle stirrer, gel is formed in the local part of the reactor (especially the stirring paddle area) in advance (Figure 1); if the rotating speed is increased to 600 r / min, more air bubbles will be introduced (Figure 2).

[0006] In summary, when high-viscosity sodium alginate is used as raw material to prepare hydrogel, it is difficult to prepare algin-based hydrogel with uniform structure and good performance by in-situ releasing method using the current mechanical stirring of paddle stirrer. SUMMARY

[0007] The purpose of the present application is to solve the problem of uneven strength of hydrogel prepared by mechanical stirring using sodium alginate as raw material, and to provide a preparation method of algin-based hydrogel, in particular, a preparation method of algin-based hydrogel using high-viscosity algin as main raw material.

[0008] The technical scheme of the present application is as follows:

[0009] The preparation method of the alginate-based hydrogel comprises the step of stirring the reaction premix with a frame stirrer to mix the reaction premix and the gel releasing agent uniformly to form a uniform reaction system.

[0010] According to the preparation method of the present application, preferably, the ratio of the paddle diameter of the frame stirrer (frame paddle) to the inner diameter of the reactor is 0.4-0.8, and the ratio of the height of the stirring paddle of the frame stirrer (the distance between the upper end beam of the stirring paddle of the frame stirrer and the lower end beam) to the liquid depth is 0.4-1.

[0011] According to the preparation method of the present application, the frame stirrer is a known stirrer in the art comprising a stirring shaft and a frame stirrer paddle (frame paddle) fixed on the stirring shaft, which can be additionally provided with a horizontal beam (horizontal blade) and / or a vertical beam (vertical blade) inside the existing horizontal beam (horizontal blade) and vertical beam (vertical blade) of the frame stirrer paddle (for example, but not limited to, as shown in Figure 3 The frame stirrer paddle of the present application can be additionally provided with a horizontal beam (horizontal blade) and / or a vertical beam (vertical blade) inside the existing horizontal beam (horizontal blade) and vertical beam (vertical blade), or can not be additionally provided with a horizontal beam (horizontal blade) and / or a vertical beam (vertical blade) inside the existing horizontal beam (horizontal blade) and vertical beam (vertical blade). The edges of the horizontal beam and the vertical beam can be straight or arc-shaped. Further preferably, the distance between adjacent horizontal beams is not greater than 1 m, and the distance between adjacent vertical beams is not greater than 1 m. It is known in the art that the paddle diameter of the frame stirrer paddle of the frame stirrer of the present application is 2 times the distance between the outer edge of the outermost vertical beam and the axis of the stirring shaft.

[0012] According to the preparation method of the present application, preferably, the rotation speed of the frame stirrer is 300-600 r / min.

[0013] According to the preparation method of the present application, optionally, the method further comprises the following steps:

[0014] (1) uniformly mixing monovalent alginate, a crosslinking agent (a polyvalent metal salt which is difficult to dissolve in water, slightly soluble in water and / or in complex state) and water to form a reaction premix;

[0015] (2) stirring the reaction premix formed in step (1) with a frame stirrer, adding a gel releasing agent to the formed reaction system while stirring, and pouring the reaction system into a mold after stirring to form a uniform mixture to obtain an alginate-based hydrogel.

[0016] According to the method of the present application, the monovalent alginate is preferably sodium alginate and / or potassium alginate.

[0017] According to the preparation method, preferably, the mass ratio of the monovalent alginate to water in step (1) is 0.5-2:100, and the ratio of the molar amount of alginate to the molar amount of the polyvalent metal cation with a valence of n in the crosslinking agent is n:0.4-8.

[0018] In step (2), the ratio of the molar amount of the anion with a valence of m in the gel releasing agent to the molar amount of the polyvalent metal cation with a valence of n in the crosslinking agent is (0.5-2.5)n:m.

[0019] Further preferably, the crosslinking agent comprises one or more of CaCO3, CaSO4, EDTA-Ca and EGTA-Ca, wherein the EDTA-Ca can be prepared by mixing ethylenediaminetetraacetic acid disodium salt (EDTA-2Na, Na2EDTA) and a calcium chloride solution; the gel releasing agent can be one or more of glucono-delta-lactone (GDL), sodium hexametaphosphate, sodium pyrophosphate and sodium tripolyphosphate, and the gel releasing agent is preferably glucono-delta-lactone (GDL), which can be added in the form of a solid powder or in the form of a prepared aqueous solution. Further preferably, the ratio of the molar amount (mole amount) of glucono-delta-lactone to the molar amount (mole amount) of Ca 2+ in the crosslinking agent is 1-4.5:1, the glucono-delta-lactone is added in the form of an aqueous solution, and the time for mixing the glucono-delta-lactone with water until it is completely added to the reaction system is not longer than 20 minutes.

[0020] Preferably, step (1) preferably uses a frame stirrer to stir the monovalent alginate, the crosslinking agent and water to form a reaction premix, and further preferably, the diameter of the frame stirrer blade is 0.3-0.9 times the inner diameter of the premix container, the rotation speed is 100-400 r / min, and the stirring time is 0.25-1.5 h.

[0021] Further, the mixing uniformity described in the present application is a concept known in the art, i.e., the gel strength and other gel characteristic parameters of the gel at different positions in the container are uniformly distributed, and there are no obvious air bubbles.

[0022] The present inventors have found that the use of a paddle stirrer (straight-blade, pitched-blade or cylindrical-blade paddle stirrer) to prepare a high-viscosity alginate-based hydrogel tends to create vortexes, resulting in dead zones, particularly in the region of the stirring paddle, or to cause the gel release agent to aggregate at the vortex, forming a gel prematurely (Figure 1), or to suck in gas, which is trapped by the viscous liquid or the prematurely formed gel and is difficult to escape (Figure 2). The present inventors have proposed using a frame stirrer, which creates a local vortex that is weak and does not tend to create dead zones, to stir the reaction premix of sodium alginate and crosslinking agent with the gel release agent. This avoids gas being sucked in, thereby avoiding the formation of gas bubbles in the gel, and, by avoiding dead zones, creates a uniform flow field. By adding the gel release agent during stirring, the gel release agent is dispersed as it is added, and uniform mixing of the reaction premix of sodium alginate and crosslinking agent with the gel release agent is achieved. The present inventors have found that, when mixing the reaction premix with the gel release agent, uniform dispersion of the gel release agent is achieved, and a gel having a uniform structure (Figure 4) is prepared, when the ratio of the frame stirrer blade diameter to the reactor diameter is in the range 0.4 to 0.8, the ratio of the frame stirrer blade height (the distance between the upper and lower edges of the blade) to the liquid depth is in the range 0.4 to 1, and the frame stirrer rotational speed is in the range 300 to 600 r / min. The gel thus prepared has a uniform gel strength distribution and a high gel strength. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 shows the formation of a gel from a sodium alginate having a viscosity of 1000 mPa s using a straight-blade paddle stirrer at a rotational speed of 400 r / min according to the prior art; Figure 1(a) shows the formation of a gel prematurely in the region of the local vortex and the stirring paddle, and Figure 1(b) shows the resulting gel having a non-uniform structure;

[0024] Figure 2 shows the formation of a gel from a sodium alginate having a viscosity of 1000 mPa s using a straight-blade paddle stirrer at a rotational speed of 600 r / min according to the prior art; Figure 2(a) shows the formation of a gel with a large number of gas bubbles trapped in the gel, and Figure 2(b) shows the resulting gel containing gas bubbles;

[0025] Figure 3 Figure 3 shows a frame stirrer according to the present application;

[0026] Figure 4 shows the formation of a gel from a sodium alginate having a viscosity of 1000 mPa s using a frame stirrer according to the present application at a rotational speed of 400 r / min; Figure 4(a) shows the gel, and Figure 4(b) shows the gel cut along the central axis. DETAILED DESCRIPTION

[0027] The application will be further described in connection with the following examples.

[0028] Example 1

[0029] (1) 4.2 g of sodium alginate (1% sodium alginate aqueous solution viscosity 1800 mPa·s), 2.45 g of Na2EDTA, 0.73 g of CaCl2 and 450 mL of water were mixed, a frame stirrer (the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.3, and the ratio of the height of the stirring paddle to the depth of the reaction liquid was 0.4) was used to stir at a speed of 100 r / min for 1.5 h, and the pH was adjusted to 7 by a 5 mol / L NaOH solution to form a reaction premix;

[0030] (2) A frame stirrer (the frame stirrer is as shown in Figure 3 , the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.4, and the ratio of the height of the stirring paddle to the depth of the reaction liquid was 0.4) was used to stir the reaction liquid at a speed of 300 r / min, 5 g of gluconolactone (GDL) was added to the formed mixture while stirring, and after uniform mixing, it was poured into three 50 mL plastic beakers to the 30 mL mark, and placed in an incubator at 20°C for 16-18 h to prepare a laminarin-based hydrogel.

[0031] A texture analyzer (Tianjin Innovation Electronic Equipment Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the laminarin gel. The parameters were set as follows: trigger value 5 g, shape deformation 5 mm, test speed 30 mm / min, and each laminarin sample was tested 3 times. The gel strength of the sample was 206 g / cm 2 , 211 g / cm 2 , and 197 g / cm 2 .

[0032] Example 2

[0033] (1) 4.2 g of sodium alginate (1% sodium alginate aqueous solution viscosity 1800 mPa·s), 2.45 g of Na2EDTA, 0.73 g of CaCl2 and 450 mL of water were mixed, a frame stirrer (the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.6, and the ratio of the height of the stirring paddle to the depth of the reaction liquid was 0.95) was used to stir at a speed of 400 r / min for 0.25 h, and the pH was adjusted to 7 by a 5 mol / L NaOH solution to form a reaction premix;

[0034] (2) A frame stirrer (the stirring paddle is as shown in Figure 3The ratio of the paddle diameter of the stirring paddle to the inner diameter of the reactor was 0.6, and the ratio of the stirring paddle height to the reaction liquid depth was 0.90) to stir the reaction liquid at a speed of 600 r / min, and 30 mL of a 200 g / L gluconic acid lactone (GDL) aqueous solution was added to the formed mixed solution while stirring, the time for adding the gluconic acid lactone aqueous solution was 1 min, and the stirring was continued for 3 min after the addition of the gluconic acid lactone aqueous solution was completed, and then the solution was poured into three 50 mL plastic beakers to the 30 mL scale line, and was placed in a incubator at 20°C for 16-18 h to prepare the alginate-based hydrogel.

[0035] A texture analyzer (Tianjin Innovation Electronic Equipment Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the alginate gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The gel strength of the sample was 210 g / cm 2 , 231 g / cm 2 , and 223 g / cm 2 .

[0036] Example 3

[0037] (1) 4.2 g of sodium alginate (1% sodium alginate aqueous solution viscosity 1750 mPa·s), 2.71 g of Na2EDTA·2H2O, 0.73 g of CaCl2, and 450 mL of water were mixed, a frame stirrer (the ratio of the paddle diameter of the stirring paddle to the inner diameter of the reactor was 0.4, and the ratio of the stirring paddle height to the reaction liquid depth was 0.4) was used to stir at a speed of 400 r / min for 1.5 h, the pH was adjusted to 7 by a 5 mol / L NaOH solution to form a reaction premix;

[0038] (2) a frame stirrer (as shown in Figure 3 , the ratio of the paddle diameter of the stirring paddle to the inner diameter of the reactor was 0.6, and the ratio of the stirring paddle height to the reaction liquid depth was 0.65) was used to stir the reaction liquid at a speed of 300 r / min, 30 mL of a 200 g / L gluconic acid lactone (GDL) aqueous solution was added to the formed mixed solution while stirring, the time for adding the gluconic acid lactone aqueous solution was 1 min, and the stirring was continued for 3 min after the addition of the gluconic acid lactone aqueous solution was completed, and then the solution was poured into three 50 mL plastic beakers to the 30 mL scale line, and was placed in a incubator at 20°C for 16-18 h to prepare the alginate-based hydrogel.

[0039] A texture analyzer (Tianjin Innovation Electronic Equipment Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the alginate gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The gel strength of the sample was 225 g / cm 2, 232 g / cm 2 , 241 g / cm 2 .

[0040] Example 4

[0041] (1) 4.2 g of sodium alginate (1% sodium alginate aqueous solution viscosity 1750 mPa s), 2.71 g of Na2EDTA 2H2O, 0.73 g of CaCl2 and 450 mL of water were mixed, a frame stirrer (the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.4, and the ratio of the height of the stirring paddle to the depth of the reaction liquid was 0.4) was used to stir at a speed of 400 r / min for 1.5 h, and the pH was adjusted to 7 by a 5 mol / L NaOH solution to form a reaction premix;

[0042] (2) A frame stirrer (the frame stirrer is as shown in Figure 3 , the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.6, and the ratio of the height of the stirring paddle to the depth of the reaction liquid was 0.65) was used to stir the reaction liquid at a speed of 350 r / min, 30 mL of 200 g / L gluconolactone (GDL) aqueous solution was added to the formed mixture while stirring, the time for adding the gluconolactone aqueous solution was 1 min, and after the addition of the gluconolactone aqueous solution was completed, stirring was continued for 3 min, and then the mixture was poured into three 50 mL plastic beakers to the 50 mL mark. It was placed in an incubator at 20°C for 16-18 h to prepare a alginate-based hydrogel.

[0043] A texture analyzer (Tianjin Innovation Electronic Equipment Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the alginate gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The gel strength of the sample was 248 g / cm 2 , 243 g / cm 2 , 236 g / cm 2 .

[0044] Example 5

[0045] (1) 4.2 g of sodium alginate (1% sodium alginate aqueous solution viscosity 1750 mPa s), 2.71 g of Na2EDTA 2H2O, 0.73 g of CaCl2 and 450 mL of water were mixed, a frame stirrer (the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.4, and the ratio of the height of the stirring paddle to the depth of the reaction liquid was 0.4) was used to stir at a speed of 400 r / min for 1.5 h, and the pH was adjusted to 7 by a 5 mol / L NaOH solution to form a reaction premix;

[0046] (2) A frame stirrer (the frame stirrer is as shown in Figure 3The ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.6, and the ratio of the stirrer height to the reaction liquid depth was 0.65) to stir the reaction liquid at a speed of 400 r / min. While stirring, 30 mL of a 200 g / L gluconic acid lactone (GDL) aqueous solution was added to the formed mixture. The time for adding the gluconic acid lactone aqueous solution was 1 min. After the addition of the gluconic acid lactone aqueous solution was completed, the mixture was stirred for 3 min. The mixture was poured into three 50 mL plastic beakers to the 30 mL scale. The mixture was placed in an incubator at 20°C for 16-18 h to prepare a laminarin-based hydrogel.

[0047] A texture analyzer (Tianjin Inno Instruments Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the laminarin gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The gel strength of the sample was 225 g / cm 2 , 230 g / cm 2 , and 222 g / cm 2 .

[0048] Example 6

[0049] (1) 4.2 g of sodium alginate (1% sodium alginate aqueous solution viscosity 1750 mPa·s), 2.71 g of Na2EDTA·2H2O, 0.73 g of CaCl2, and 450 mL of water were mixed. A frame stirrer (the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.4, and the ratio of the stirrer height to the reaction liquid depth was 0.4) was used to stir the mixture at a speed of 400 r / min for 1.5 h. The pH was adjusted to 7 by using a 5 mol / L NaOH solution to form a reaction premix.

[0050] (2) A frame stirrer (as shown in Figure 3 , the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.6, and the ratio of the stirrer height to the reaction liquid depth was 0.65) was used to stir the reaction liquid at a speed of 400 r / min. While stirring, 30 mL of a 200 g / L gluconic acid lactone (GDL) aqueous solution was added to the formed mixture. The time for adding the gluconic acid lactone aqueous solution was 1 min. After the addition of the gluconic acid lactone aqueous solution was completed, the mixture was stirred for 3 min. The mixture was poured into three 50 mL plastic beakers to the 30 mL scale. The mixture was placed in an incubator at 20°C for 16-18 h to prepare a laminarin-based hydrogel.

[0051] A texture analyzer (Tianjin Inno Instruments Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the laminarin gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The gel strength of the sample was 239 g / cm2 , 231 g / cm 2 , 232 g / cm 2 .

[0052] Example 7

[0053] (1) 4.5 g of sodium alginate (1% sodium alginate aqueous solution viscosity is 1750 mPa-s), 7.00 g of Na2EDTA-2H2O, 2.50 g of CaCl2-2H2O and 450 mL of water were mixed, a frame stirrer (the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor is 0.4, and the ratio of the height of the stirring paddle to the depth of the reaction liquid is 0.7) was used to stir at a speed of 400 r / min for 1 h, the pH was adjusted to 7 by a 5 mol / L NaOH solution to form a reaction premix;

[0054] (2) a frame stirrer (as shown in Figure 3 , the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor is 0.6, and the ratio of the height of the stirring paddle to the depth of the reaction liquid is 0.65) was used to stir the reaction liquid at a speed of 350 r / min, 30 mL of 200 g / L gluconolactone (GDL) aqueous solution was added to the formed mixture while stirring, the time for adding the gluconolactone aqueous solution was 3 min, after the addition of the gluconolactone aqueous solution was completed, stirring was continued for 2 min, and then poured into three 50 mL plastic beakers to the 30 mL mark, and placed in an incubator at 20°C for 16-18 h to prepare the alginate-based hydrogel.

[0055] A texture analyzer (Tianjin Innovation Electronic Equipment Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the alginate gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The texture analyzer was used to measure the gel strength of the prepared alginate gel product. The parameters were set as follows: probe model P / 0.5, trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The gel strength of the sample was 305 g / cm 2 , 317 g / cm 2 , 314 g / cm 2 .

[0056] Example 8

[0057] (1) 2.16 g of sodium alginate (1% aqueous solution viscosity is 1800 mPa s), 1.08 g of Na2EDTA 2H2O, 0.29 g of CaCl2 and 180 mL of water were mixed, a frame stirrer (the ratio of the paddle diameter of the frame stirring paddle to the inner diameter of the reactor is 0.8, and the ratio of the stirring paddle height to the reaction liquid depth is 0.9) was used to stir at a speed of 100 r / min for 0.25 h, the pH was adjusted to 7 by 5 mol / L NaOH solution, and a reaction premix was formed;

[0058] (2) A frame stirrer (the frame stirring paddle is as shown in Figure 3 , the ratio of the paddle diameter of the frame stirring paddle to the inner diameter of the reactor is 0.6, and the ratio of the stirring paddle height to the reaction liquid depth is 0.65) was used to stir the reaction liquid at a speed of 450 r / min, 14 mL of 160 g / L gluconolactone (GDL) aqueous solution was added to the formed mixture while stirring, the time for adding the gluconolactone aqueous solution was 1 min, the stirring time after adding the gluconolactone was 2 min, 3 50 mL plastic beakers were poured to the 30 mL scale, and placed in an incubator at 20°C for 16-18 h to prepare a alginate-based hydrogel.

[0059] A texture analyzer (Tianjin Innovation Electronics Equipment Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the alginate gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The prepared alginate gel product was measured by the texture analyzer. The parameters were set as follows: probe model P / 0.5, trigger value 5 g, deformation 5 mm, pre-test speed 60 mm / min, and test speed 30 mm / min. The gel strength of the sample was 309 g / cm 2 , 308 g / cm 2 , and 323 g / cm 2 .

[0060] Example 9

[0061] (1) 4.2 g of sodium alginate (1% aqueous solution viscosity is 1750 mPa s), 2.71 g of Na2EDTA 2H2O, 0.88 g of CaCl2 and 450 mL of water were mixed, a frame stirrer (the ratio of the paddle diameter of the frame stirring paddle to the inner diameter of the reactor is 0.4, and the ratio of the stirring paddle height to the reaction liquid depth is 0.4) was used to stir at a speed of 400 r / min for 1.5 h, the pH was adjusted to 7 by 5 mol / L NaOH solution, and a reaction premix was formed;

[0062] (2) A frame stirrer (the frame stirring paddle is as shown in Figure 3The ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.6, and the ratio of the stirrer height to the reaction liquid depth was 0.65) to stir the reaction liquid at a speed of 400 r / min. While stirring, 35 mL of a 200 g / L glucose acid lactone (GDL) aqueous solution was added to the formed mixed solution, the time for adding the glucose acid lactone aqueous solution was 1 min, after adding the glucose acid lactone, stirring was performed for 3 min, and then the solution was poured into three 50 mL plastic beakers to the 30 mL scale line, and then placed in a incubator at 20°C for 16-18 h to prepare the alginate-based hydrogel.

[0063] A texture analyzer (Tianjin InnoScan Electronic Equipment Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the alginate gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The gel strength of the sample was 225.5 g / cm 2 , 229.8 g / cm 2 , and 222.8 g / cm 2 .

[0064] Example 10

[0065] (1) 4.2 g of sodium alginate (1% aqueous solution viscosity 716 mPa·s), 2.71 g of Na2EDTA·2H2O, 0.73 g of CaCl2, and 450 mL of water were mixed, and a frame stirrer (the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.4, and the ratio of the stirrer height to the reaction liquid depth was 0.4) was used to stir at a speed of 400 r / min for 0.25 h, and the pH was adjusted to 7 by using a 5 mol / L NaOH solution to form a reaction premix;

[0066] (2) A frame stirrer (as shown in Figure 3 , the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.6, and the ratio of the stirrer height to the reaction liquid depth was 0.65) was used to stir the reaction liquid at a speed of 500 r / min, and while stirring, 35 mL of a 200 g / L glucose acid lactone aqueous solution was added to the formed mixed solution, the time for adding the glucose acid lactone aqueous solution was 1 min 20 s, after adding the glucose acid lactone, stirring was performed for 3 min, and then the solution was poured into three 50 mL plastic beakers to the 30 mL scale line, and then placed in a incubator at 20°C for 16-18 h to prepare the alginate-based hydrogel.

[0067] A texture analyzer (Tianjin InnoScan Electronic Equipment Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the alginate gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The gel strength of the sample was 170.7 g / cm2 , 175.2 g / cm 2 , 176.0 g / cm 2 .

[0068] Comparative Example 1

[0069] (1) 4.5 g of sodium alginate (1% sodium alginate aqueous solution viscosity 1750 mPa-s), 2.71 g of Na2EDTA-2H2O, 0.73 g of CaCl2 and 450 mL of water were mixed, a frame stirrer (the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.4, and the ratio of the height of the stirring paddle to the depth of the reaction liquid was 0.4) was used to stir at a speed of 400 r / min for 1.5 h, and the pH was adjusted to 7 by a 5 mol / L NaOH solution to form a reaction premix;

[0070] (2) A paddle stirrer with a cylindrical paddle (the ratio of the paddle diameter of the stirring paddle to the inner diameter of the reactor was 0.6) was used to stir the reaction liquid at a speed of 400 r / min, 30 mL of 200 g / L gluconolactone (GDL) aqueous solution was added to the formed mixture while stirring, the time for adding the gluconolactone aqueous solution was 1 min, and after the addition of the gluconolactone aqueous solution was completed, stirring was continued for 3 min, and then poured into three 50 mL plastic beakers to the 30 mL mark, and placed in an incubator at 20°C for 16-18 h to prepare a sodium alginate-based hydrogel.

[0071] A texture analyzer (Tianjin Innovation Electronic Equipment Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the sodium alginate gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The gel strength of the sample was 190.4 g / cm 2 , 178.1 g / cm 2 , 53.32 g / cm 2 .

[0072] Comparative Example 2

[0073] (1) 4.2 g of sodium alginate (1% sodium alginate aqueous solution viscosity 1750 mPa-s), 2.71 g of Na2EDTA-2H2O, 0.73 g of CaCl2 and 450 mL of water were mixed, a frame stirrer (the ratio of the paddle diameter of the frame stirrer to the inner diameter of the reactor was 0.4, and the ratio of the height of the stirring paddle to the depth of the reaction liquid was 0.4) was used to stir at a speed of 400 r / min for 1.5 h, and the pH was adjusted to 7 by a 5 mol / L NaOH solution to form a reaction premix;

[0074] (2) using a straight-blade paddle stirrer (the ratio of the paddle diameter of the stirring paddle to the inner diameter of the reactor was 0.6) to stir the reaction liquid at a speed of 400 r / min, while stirring, 30 mL of a 200 g / L gluconic lactone (GDL) aqueous solution was added to the formed mixture, the time for adding the gluconic lactone aqueous solution was 1 min, after the addition of the gluconic lactone aqueous solution was completed, stirring was performed for 3 min, 3 50 mL plastic beakers were filled to the 30 mL mark, and the 3 50 mL plastic beakers were placed in a 20°C incubator for 16-18 h to prepare the alginate-based hydrogel.

[0075] A texture analyzer (Tianjin InnoScan Electronic Equipment Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the alginate gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The gel strength of the sample was 242 g / cm 2 , 201 g / cm 2 , and 159 g / cm 2 .

[0076] Comparative Example 3

[0077] (1) 4.2 g of sodium alginate (1% sodium alginate aqueous solution viscosity 1750 mPa·s), 2.71 g of Na2EDTA·2H2O, 0.73 g of CaCl2, and 450 mL of water were mixed, a frame stirrer (the ratio of the paddle diameter of the stirring paddle to the inner diameter of the reactor was 0.4, and the ratio of the height of the stirring paddle to the depth of the reaction liquid was 0.4) was used to stir at a speed of 400 r / min for 1.5 h, the pH was adjusted to 7 by using a 5 mol / L NaOH solution to form a reaction premix;

[0078] (2) using a straight-blade paddle stirrer (the ratio of the paddle diameter of the stirring paddle to the inner diameter of the reactor was 0.6) to stir the reaction liquid at a speed of 400 r / min, while stirring, 30 mL of a 200 g / L gluconic lactone (GDL) aqueous solution was added to the formed mixture, the time for adding the gluconic lactone aqueous solution was 1 min, after the addition of the gluconic lactone aqueous solution was completed, stirring was performed for 3 min, 3 50 mL plastic beakers were filled to the 30 mL mark, and the 3 50 mL plastic beakers were placed in a 20°C incubator for 16-18 h to prepare the alginate-based hydrogel.

[0079] A texture analyzer (Tianjin InnoScan Electronic Equipment Co., Ltd., model CTA-20HS, probe model P / 0.5) was used to test the gel strength of the alginate gel. The parameters were set as follows: trigger value 5 g, deformation 5 mm, and test speed 30 mm / min. The gel strength of the sample was 237 g / cm 2, 203 g / cm 2 , 197 g / cm 2 .

[0080] Finally, it should be noted that the above examples are merely intended to illustrate the technical solutions of the present application but not to limit the present application. Although the present application has been described in detail with reference to the examples, those skilled in the art should understand that modifications or equivalent replacements to the technical solutions of the present application can be made without departing from the spirit and scope of the present application, and all these modifications and equivalent replacements should be included in the scope of the claims of the present application.

Claims

1. A method for preparing alginate-based hydrogel, comprising: (1) mixing monovalent alginate, crosslinking agent and water uniformly to form a reaction premix, the mass ratio of monovalent alginate to water being 0.5-1.5:100; (2) stirring the reaction premix formed in step (1) using a frame stirrer, adding gel releasing agent to the formed reaction system while stirring, and then pouring the mixed reaction system into a mold to obtain alginate-based hydrogel; The ratio of the paddle diameter of the stirring paddle of the frame stirrer to the inner diameter of the reactor is 0.4-0.8, and the ratio of the height of the stirring paddle to the liquid depth is 0.4-1; the rotation speed of the frame stirrer is 300-600 r / min.

2. The production method according to claim 1, characterized by, The ratio of the amount of substance of alginate to the amount of substance of polyvalent metal cation with valence n in the crosslinking agent is n:0.4-8.

3. The production method according to claim 1, characterized by, The ratio of the amount of substance of anion with valence m in the gel releasing agent to the amount of substance of polyvalent metal cation with valence n in the crosslinking agent is (0.5-2.5)n:m.

4. The production method according to any one of claims 1 to 3, characterized by, The monovalent alginate is sodium alginate and / or potassium alginate; the crosslinking agent comprises one or more than two of CaCO3, CaSO4, EDTA-Ca and EGTA-Ca; and the gel releasing agent comprises one or more than two of gluconolactone, sodium hexametaphosphate, sodium pyrophosphate and sodium tripolyphosphate.

5. The preparation method according to claim 4, characterized in that, The gel releasing agent is gluconolactone solid or gluconolactone aqueous solution.

6. The method of claim 1, wherein, Step (1) uses a frame stirrer to stir and mix uniformly.

7. The production method according to claim 6, characterized by, The paddle diameter of the stirring paddle of the frame stirrer is 0.3-0.9 of the inner diameter of the premix container, the rotation speed is 100-400 r / min, and the stirring time is 0.25-1.5 h.

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