CN117402400A

CN117402400A - Polysaccharide compound porous gel and preparation method thereof

Info

Publication number: CN117402400A
Application number: CN202210793808.4A
Authority: CN
Inventors: 石道昆; 史争争; 王凯丽; 康亚红; 黄楚波
Original assignee: Microport Aesthetics Shanghai Group Co Ltd
Current assignee: Microport Aesthetics Shanghai Group Co Ltd
Priority date: 2022-07-07
Filing date: 2022-07-07
Publication date: 2024-01-16

Abstract

The invention relates to polysaccharide compound porous gel and a preparation method thereof, wherein the preparation method comprises the following steps: mixing a polysaccharide compound, a cross-linking agent and water to obtain a mixed solution; drying the mixed solution at 20-100 ℃ to remove water to obtain a dried product with the water content lower than 10 wt%; and cross-linking the dried product at 80-160 ℃ to obtain the polysaccharide compound porous gel.

Description

Polysaccharide compound porous gel and preparation method thereof

Technical Field

The invention relates to the technical field of high polymer materials, in particular to polysaccharide compound porous gel and a preparation method thereof.

Background

The hydrogel is a substance with a three-dimensional network structure and rich in water, and the main body of the hydrogel is mainly divided into natural polymers and synthetic polymers. The three-dimensional network structure in the hydrogel generally has nano-scale meshes, and water molecules and polymer connecting sections in the meshes have strong acting force, so that the gel material forming the hydrogel generally has extremely strong hydrophilicity, and can quickly absorb a large amount of water and retain the water; gel materials with certain modulus, good biocompatibility and environmental friendliness are widely applied to the fields of agriculture, tissue engineering, drug delivery, biosensors, medical appliances and the like.

Polysaccharide (polysaccharide) is a polymeric sugar polymer carbohydrate composed of glycosidically bonded sugar chains, at least more than 10 monosaccharides. In the case of cellulose, cellulose is composed of hundreds to thousands of glucose units (C ₆ H ₁₀ O ₅ ) n is connected by glycosidic bond to form natural macromolecule, which is the main component of plant cell wall. Cellulose is most widely distributed in nature and accounts for more than 50% of the carbon content in plants. The cellulose content of cotton is close to 100%, and is the natural purest cellulose source. In general wood, cellulose accounts for 40-50%. The repeated units of the cellulose contain a plurality of hydroxyl functional groups, various polysaccharide compounds can be obtained through chemical modification and modification of the hydroxyl functional groups, and different cellulose derivatives have different chemical structures, so that the functions and the purposes of different polysaccharide compounds are different, and the cellulose has wide application in the aspects of food additives, disease diagnosis and treatment.

Polysaccharide hydrogels are bulk gel materials that use polysaccharides as hydrogels. Taking cellulose-based hydrogels as an example, cellulose-based hydrogels are a class of hydrogels prepared by cellulose or its derivatives with a physically or chemically crosslinked network structure. The raw materials of the cellulose-based hydrogel are green and nontoxic, have low cost, and simultaneously have the characteristics of high water absorption rate, strong water retention capacity, easy degradation and metabolism in the digestive system and the like of other hydrogels, so that the cellulose-based hydrogel has wide application in the industries of food health care, biological medicine and medical appliances.

However, cellulose-based hydrogels have some problems or disadvantages, such as low modulus after the hydrogel absorbs water, slow water absorption rate of the xerogel, low water absorption rate, high long-term storage requirement, and the like, and limit some applications of the cellulose-based hydrogels. Cellulose-based hydrogels have a wide range of applications including, but not limited to, wound dressing, intragastric lipid-lowering gels, and the like. Taking the application to intragastric lipid-reducing gel as an example, the cellulose-based hydrogel acts with water in the stomach after being ingested by a human body to form gel masses to induce satiety, reversibly reduce the void volume of the stomach and play a role in reducing caloric intake. Thus, such cellulose-based hydrogels are in a xerogel state before use, and the xerogel is required to have rapid water swelling while having excellent water retention capacity. Meanwhile, the cellulose-based hydrogel is required to maintain a good storage modulus after swelling by water absorption so as to maintain a good structure without being destroyed in the stomach, and a good stomach swelling effect is achieved. Therefore, the method for improving the water absorption rate and the storage modulus of the cellulose-based gel after absorption and expansion has important significance and application value.

The methods commonly used to increase the water absorption rate of gels mainly include: the addition of more hydrophilic components by copolymerization or blending methods, but generally alters the properties of the gel; the method for improving the water absorption rate of the gel by changing the physical microstructure of the dry gel and preparing the porous gel with higher porosity is simple and effective, and becomes the mainstream method.

The porous gel has the advantages of high water absorption rate, high water absorption capacity, strong environmental sensitivity and large specific surface area, so that the macroporous hydrogel has obvious advantages in the aspects of cell support, drug delivery, cell separation, enzyme immobilization and the like. In general, the porous gel can be obtained by a phase separation method, a foaming method, a pore-forming method, a freeze-drying pore-forming method, and the like.

Among them, the porous gel prepared by the phase separation method tends to have small pore size and low porosity. When the phase separation is carried out to form holes, the three-dimensional structure of the hydrogel is usually destroyed, the structure, the size and the shape of the holes are difficult to control, and the open pore property is poor.

The foaming method utilizes the volatilization of gas generated by the reaction of a foaming agent or organic solvent gas to form cells inside the material. Some techniques use air as a foaming agent to prepare a porous bubble gel as a component of a wound dressing; some technologies adopt carbonate or bicarbonate as a foaming agent, react under acidic conditions to generate gaseous carbon dioxide, and volatilize to form a porous structure. However, the foaming method has the problems of high gas volatilization rate, difficult control of solvent volatilization, reaction degree and pore structure, difficult control of process and poor mechanical strength of the prepared porous gel.

The pore-forming method includes a pore-forming agent pore-forming method and a template pore-forming method. The pore-forming agent pore-forming method is to dope the pore-forming agent in the polymer body, place the polymer in water, the pore-forming agent is dissolved in the water and the polymer is not dissolved, so that holes are left in the polymer, for example, some technologies adopt ethanol as the pore-forming agent, but the process of the method is complex, and some pore-forming agents are difficult to remove. The template pore-forming method has more steps, and the inert template is not easy to completely remove.

The freeze-drying pore-forming method is characterized in that the solvent in the polymer is volatilized under the low-temperature vacuum condition, holes are left in the polymer by adopting a freeze-drying mode to prepare porous hydrogel, the process period of the freeze-drying pore-forming method is longer, the energy consumption is larger, and the method is not suitable for industrial mass production.

Disclosure of Invention

Based on the above, it is necessary to provide a polysaccharide compound porous gel which has a high water absorption rate and a high modulus after absorption, is simple in process, controllable in pore size and suitable for industrial production, and a preparation method thereof.

In one aspect of the present invention, there is provided a method for preparing a porous gel of a polysaccharide compound, comprising the steps of:

mixing a polysaccharide compound, a cross-linking agent and water to obtain a mixed solution;

drying the mixed solution at 20-100 ℃ to remove water to obtain a dried product with the water content lower than 10 wt%; and

And (3) carrying out a crosslinking reaction on the dried product at the temperature of 80-160 ℃ to obtain the polysaccharide compound porous gel.

In some of these embodiments, the polysaccharide compound comprises a first polysaccharide compound selected from one or more of methylcellulose, carboxymethylcellulose, and salts thereof;

wherein the weight average molecular weight of the first polysaccharide compound is between 5 ten thousand and 130 ten thousand;

and/or, in the polysaccharide compound, the mass content of the first polysaccharide compound is 50% -100%;

and/or the viscosity of the first polysaccharide compound in a 1wt% aqueous solution at 25 ℃ is 10 to 6000cps;

and/or the degree of substitution of the first polysaccharide compound is 0.5 to 1.2.

The viscosity of the first polysaccharide compound in a 1wt% aqueous solution at 25 ℃ is 3500-6000 cps.

In some of these embodiments, the polysaccharide compound further comprises a second polysaccharide compound comprising one or more of ethylcellulose, hydroxyethylcellulose, propylcellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose, butylcellulose, hydroxybutyl cellulose, ethylhydroxyethyl cellulose, glycosaminoglycans, polyuronic acid, polymannuronate, polygalacturonic acid, heparin, dextran sulfate, dextran phosphate, diethylaminodextran, chondroitin, and carboxymethyl starch;

wherein the weight average molecular weight of the second polysaccharide compound is between 9 ten thousand and 130 ten thousand;

and/or, in the polysaccharide compound, the mass content of the second polysaccharide compound is 0-50%;

and/or the second polysaccharide compound has a viscosity of 10 to 2500cps in a 1wt% aqueous solution at 25 ℃;

and/or the degree of substitution of the second polysaccharide compound is 0.5 to 1.2.

In some of these embodiments, the second polysaccharide compound has a viscosity of 50 to 200cps in a 1wt% aqueous solution at 25 ℃.

In some of these embodiments, the crosslinking agent comprises one or more of oxalic acid, malonic acid, maleic acid, succinic acid, citric acid, phthalic acid, pyromellitic acid, ethylenediamine tetraacetic acid, and carboxyl-terminated multi-arm polyethylene glycol;

and/or the mass content of the crosslinking agent relative to the total mass of the polysaccharide compound is 0.1-5%;

and/or, in the mixed solution, the total mass content of the polysaccharide compound is 0.5-5%.

In some of these embodiments, the cross-linking agent is present in an amount of 0.1% to 2% by mass relative to the total mass of the polysaccharide compound;

and/or, in the mixed solution, the total mass content of the polysaccharide compound is 1-4%.

In some of these embodiments, the time of the crosslinking reaction is from 0.5 to 12 hours.

In some of these embodiments, the time of the crosslinking reaction is 1 to 5 hours;

and/or the temperature of the crosslinking reaction is 100-160 ℃.

In some of these embodiments, controlling the moisture content of the dried product to be less than or equal to 5wt%;

and/or the drying and dewatering time is 6-100 h.

In some embodiments, the temperature of the drying water removal is 20-80 ℃; and/or the number of the groups of groups,

the drying and dewatering time is 12-72 h.

In some of these embodiments, the temperature of the dry water removal is 40-60 ℃.

In some of these embodiments, before subjecting the dried product to the crosslinking reaction, further comprising the steps of:

and crushing and screening the dried product to obtain dried particles with the particle size range of 10-2000 mu m.

In another aspect of the present invention, there is provided a polysaccharide compound porous gel prepared by the method of any one of the above.

In another aspect of the invention, a polysaccharide compound porous gel is provided, wherein the water content of the polysaccharide compound porous gel is less than or equal to 2%; the expansion multiple of the polysaccharide compound porous gel is more than or equal to 50 when the polysaccharide compound porous gel absorbs water for 30min, and the storage modulus is more than or equal to 700Pa;

in some of these embodiments, the porous polysaccharide compound gel has an expansion factor of 50 to 90 and a storage modulus of 700 to 1600Pa when absorbing water for 30 minutes;

and/or the porous gel of the polysaccharide compound has a pore size of 0.5-50 μm and a porosity of 1-90%.

The preparation method of the cellulose-based porous gel comprises the steps of mixing aqueous solutions, drying at a specific temperature to remove water to obtain a dried product with a specific moisture content, and then carrying out a crosslinking reaction on the dried product at the specific temperature. Meanwhile, the porosity and the pore size of the prepared cellulose-based porous gel can be effectively regulated and controlled by controlling the drying process and the crosslinking reaction process of the mixed solution.

The preparation method has the advantages of simple process, green raw materials, no need of adding foaming agent, pore-forming agent or pore-forming template, and no problems of difficult control of the process of the traditional foaming method and difficult removal of the pore-forming agent or pore-forming template of the pore-forming method, and in addition, the preparation method adopts the temperature of 20-100 ℃ for drying and dewatering, and also avoids the problem of unsuitable process production caused by low-temperature freezing.

The polysaccharide compound porous gel prepared by the preparation method of the polysaccharide compound porous gel has a three-dimensional crosslinked network structure and a microscopic porous structure, and has larger porosity and pore diameter. The prepared polysaccharide compound porous gel is xerogel, the porous structure is easy for moisture to quickly penetrate in, the polysaccharide compound porous gel can quickly absorb water and expand in a xerogel state, has larger water absorption rate and water absorption rate, and has better storage modulus after water absorption. In addition, the porous gel of polysaccharide compound has adjustable porosity and pore size, the adjustable range of pore size is between 0.5 μm and 50 μm, and the adjustable range of the pore size is between 1% and 90%, preferably between 10% and 50%. The preparation method has the advantages of simple and convenient technical process, short preparation period, environmental protection and easy mass production, and can regulate and control the porosity and the pore diameter of the polysaccharide compound porous gel according to the application field and the requirements, and change the water absorption rate, the water absorption rate and the hydrogel modulus after water absorption. The prepared polysaccharide compound porous gel not only has good water absorption performance, but also can keep good storage modulus after water absorption expansion, and can be used for preparing intragastric lipid-reducing gel, and has rapid water absorption expansion in the stomach and excellent water retention capacity, so that the polysaccharide compound porous gel has good satiety and the effect of reducing heat intake; meanwhile, the water-absorbing and swelling composite material keeps good storage modulus after absorbing water and swelling, can keep good structure in the stomach without being damaged, and has good stomach swelling effect.

Further, the polysaccharide compound porous gel can be degraded under the action of enzymes in the small intestine and the large intestine by adopting the polysaccharide compound as a raw material, so that the polysaccharide compound porous gel is convenient to discharge outside the body, and the degradation product can also play a role in intestinal tract ventilation.

Furthermore, the first polysaccharide compound, the second polysaccharide compound and the cross-linking agent are simultaneously added to form polysaccharide compound porous gel with a three-dimensional network structure, and the polysaccharide compound porous gel can only swell in a solvent but not be completely dissolved, so that the storage modulus after water absorption can be ensured while the good water absorption performance is maintained.

Drawings

FIG. 1 is a scanning electron microscope image of the polysaccharide compound porous gel particles prepared in example 1;

FIG. 2 is a scanning electron microscope image of the polysaccharide compound porous gel particles prepared in example 2.

Detailed Description

In order that the invention may be readily understood, a more complete description of the invention will be rendered by reference to the appended drawings. Preferred embodiments of the present invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. It should be understood that these embodiments are provided so that this disclosure will be thorough and complete.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.

In the description of the present invention, the meaning of "a plurality" is two or more, unless explicitly defined otherwise.

An embodiment of the invention provides a polysaccharide compound porous gel and a preparation method thereof. The porous gel of polysaccharide compound obtained will be described in detail with reference to the preparation method.

The preparation method of the polysaccharide compound porous gel provided by the embodiment of the invention comprises the following steps S10-S30.

Step S10: mixing polysaccharide compound, cross-linking agent and water to obtain mixed solution.

In some of these embodiments, the polysaccharide compound comprises a first polysaccharide compound, the first polysaccharide compound being one or more of methylcellulose, carboxymethylcellulose, and salts thereof. For example, the first polysaccharide compound may be sodium carboxymethyl cellulose.

Further, the weight average molecular weight of the cellulose with the branched chain not containing hydroxyl is between 5 ten thousand and 130 ten thousand; further preferably, the weight average molecular weight is preferably between 30 to 100 tens of thousands.

Further, in the polysaccharide compound, the mass content of the first polysaccharide compound is 50% -100%. It will be appreciated that the polysaccharide compound porous gel described above may be made of only the first polysaccharide compound, and may also contain other polysaccharide compounds. Controlling the mass content of the first polysaccharide compound within the given range is beneficial to ensuring the water absorption performance of the polysaccharide compound porous gel.

It is understood that the mass content of the first polysaccharide compound in the polysaccharide compound may be 50%, 60%, 70%, 80%, 90%, 95%, 100%; preferably, the mass content of the first polysaccharide compound is 70% -100%.

Further, the cellulose of the first polysaccharide compound has a viscosity of 10 to 6000cps in a 1wt% aqueous solution at 25 ℃. Still further, the cellulose of the first polysaccharide compound has a viscosity of 3500 to 6000cps, more preferably 4000 to 5500cps in a 1wt% aqueous solution at 25 ℃.

Further, the degree of substitution of the cellulose of the first polysaccharide compound is 0.5 to 1.2, for example 0.5, 0.7, 0.9 or 1.2.

In some of these embodiments, the polysaccharide compound further comprises a second polysaccharide compound. The second polysaccharide compound comprises one or more of ethylcellulose, hydroxyethyl cellulose, propylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, butylcellulose, hydroxybutyl cellulose, ethylhydroxyethyl cellulose, glycosaminoglycans, polyuronic acid, polymannuronate, polygalacturonic acid, heparin, dextran sulfate, dextran phosphate, diethylaminodextran, chondroitin, and carboxymethyl starch.

Further, the weight average molecular weight of the second polysaccharide compound is between 9 ten thousand and 130 ten thousand; preferably, the weight average molecular weight is between 10 ten thousand and 50 ten thousand.

Further, in the polysaccharide compound, the mass content of the second polysaccharide compound is 0 to 50%. It is understood that the mass content of the second polysaccharide compound may be 0.

It is understood that the mass content of the second polysaccharide compound in the polysaccharide compound may be 0%, 1%, 5%, 10%, 20%, 30%, 40%, 45%, 50%; further, in the polysaccharide compound, the mass content of the second polysaccharide compound is 0% to 30%.

Further, the second polysaccharide compound has a viscosity of 10 to 2500cps in a 1wt% aqueous solution at 25 ℃; further, the viscosity is preferably 50 to 200cps.

Further, the degree of substitution of the second polysaccharide compound is 0.5 to 1.2, for example 0.5, 0.7, 0.9 or 1.2.

Generally, sodium carboxymethyl cellulose has better hygroscopicity, but the mechanical strength after moisture absorption needs to be improved; therefore, the second polysaccharide compounds such as hydroxyethyl cellulose, hydroxypropyl methyl cellulose and the like are added simultaneously, so that the first polysaccharide compound and the first polysaccharide compound can react with the cross-linking agent simultaneously, and simultaneously, the cross-linking reaction can also occur between the two polysaccharide compounds, so that the formed polysaccharide compound porous gel has a three-dimensional network cross-linking structure on a molecular structure, the cross-linking degree of the polysaccharide compound porous gel is improved, and the storage modulus after water absorption can be further improved while the better water absorption performance is maintained.

In other embodiments, the polysaccharide compound may contain other polysaccharide compounds than the first polysaccharide compound described above, and optionally include a second polysaccharide compound. Further, the sum of the mass contents of the first polysaccharide compound and the second polysaccharide compound is controlled to be more than or equal to 80 percent.

In some of these embodiments, the total mass content of polysaccharide compounds in the mixed solution is 0.5% to 5%.

It is understood that the total mass content of polysaccharide compounds in the mixed solution may be 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 5%. Further, in the mixed solution, the total mass content of the polysaccharide compound is 1% -4%, and further 2% -3.5%.

It is understood that the cross-linking agent is a reagent having multiple functionalities, for example having multiple carboxyl groups. In some of these embodiments, the crosslinking agent comprises one or more of oxalic acid, malonic acid, maleic acid, succinic acid, citric acid, phthalic acid, pyromellitic acid, ethylenediamine tetraacetic acid, and carboxyl-terminated multi-arm polyethylene glycol.

Further, the mass content of the crosslinking agent relative to the total mass of the various celluloses is 0.1% to 5%, for example, 0.1%, 0.2%, 0.5%, 0.8%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%. Still further, the mass content of the crosslinking agent with respect to the total mass of the plurality of celluloses is 0.1% to 2%, and preferably, the mass content of the crosslinking agent with respect to the total mass of the plurality of celluloses is 0.25% to 2%.

It will be appreciated that the order of adding the polysaccharide compound and the crosslinking agent in step S10 is not limited, and the polysaccharide compound and water may be mixed first and then the crosslinking agent may be added; the crosslinking agent may also be added to the water first and then the polysaccharide compound.

It can be understood that the mixing step of step S10 can be performed by measuring the viscosity of the system at fixed intervals or evaluating the uniformity of the mixed solution by light transmittance, so as to obtain a uniform mixed solution.

Step S20: drying the mixed solution at 20-100 ℃ to remove water, and obtaining a dried product with the water content lower than 10 wt%.

It is understood that the temperature of drying and water removal may be 20 ℃, 30 ℃, 40 ℃, 50 ℃, 60 ℃, 70 ℃, 80 ℃, 90 ℃, 100 ℃.

It should be noted that in step S20, the moisture content is controlled mainly by drying and dewatering, and the preliminary pore size structure is realized. The temperature controlled in step S20 is greater than 60 ℃ and is accompanied by a degree of crosslinking reaction between the polysaccharide compound and the crosslinking agent during drying and water removal. However, the drying and dewatering temperature is not easy to be too high, otherwise, the cross-linking is easy to occur, and the cross-linking degree of the final material is uncontrollable. Thus, for example, the temperature of the drying water is 20 to 80℃and more preferably 40 to 80 ℃.

Further, the temperature of the drying water removal is 40 ℃ to 60 ℃, and the drying water removal is performed within the given temperature range, and the crosslinking reaction occurs substantially or to a small extent in the step S20.

In some of these embodiments, the drying water removal time is 6 to 100 hours, such as 6 hours, 8 hours, 10 hours, 12 hours, 15 hours, 20 hours, 25 hours, 30 hours, 35 hours, 40 hours, 50 hours, 60 hours, 65 hours, 72 hours, 75 hours, 80 hours, 90 hours, 95 hours, 100 hours. Further, the drying and dewatering time is 12-72 h. It will be appreciated that the time of the dewatering and drying may be controlled depending on the dewatering temperature selected and the moisture content of the dried product to be controlled.

It is understood that the moisture content of the dried product can be measured by a moisture tester. In some preferred embodiments, the moisture content of the dried product is controlled to be less than or equal to 9wt%; further controlling the weight percent to be less than or equal to 5 percent.

Step S30: and (3) carrying out a crosslinking reaction on the dried product at the temperature of 80-160 ℃ to obtain the polysaccharide compound porous gel.

It is worth noting that in step S30, a crosslinking reaction between the polysaccharide compound and the crosslinking agent occurs, and the mechanism of the crosslinking reaction is that the crosslinking agent is dehydrated under heating to form a cyclic anhydride, and the cyclic anhydride reacts with hydroxyl groups of the polysaccharide compound to crosslink molecules of the polysaccharide compound. Meanwhile, in the step S30, the regulation and control of the porosity and the pore size of the polysaccharide compound porous gel are further realized.

In some of these embodiments, the temperature of the crosslinking reaction may be 80 ℃, 90 ℃, 100 ℃, 110 ℃, 120 ℃, 130 ℃, 140 ℃, 150 ℃, 160 ℃. Further, the temperature of the crosslinking reaction is 100-160 ℃.

In some of these embodiments, the time of the crosslinking reaction is 0.5 to 12 hours, for example 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours; further, the time of the crosslinking reaction is 1 to 5 hours.

In some of these embodiments, after step S20 and before step S30, the method further includes the following step S40: granulating the dried product to obtain dried granules; correspondingly, step S30 carries out a crosslinking reaction on the dried particles, and the prepared polysaccharide compound gel is polysaccharide compound porous gel particles.

Further, the step S40 specifically includes: crushing and screening the dried product to obtain the dried particles. Further, the particle diameter of the dry particles is controlled to be in the range of 10 to 2000. Mu.m, preferably 50 to 1000. Mu.m.

The polysaccharide compound porous gel is prepared by mixing aqueous solutions, drying at a specific temperature to remove water to obtain a dried product with a specific moisture content, and then carrying out a crosslinking reaction on the dried product at the specific temperature. Meanwhile, the total mass content of various celluloses in the mixed solution, the drying process of the mixed solution and the crosslinking reaction process are controlled, so that the porosity and the pore size of the prepared polysaccharide compound porous gel can be effectively regulated.

The polysaccharide compound porous gel prepared by the preparation method of the polysaccharide compound porous gel has a three-dimensional crosslinked network structure and a microscopic porous structure, and has larger porosity and pore diameter. The prepared polysaccharide compound porous gel is xerogel, the porous structure is easy for moisture to quickly penetrate in, the polysaccharide compound porous gel can quickly absorb water and expand in a xerogel state, has larger water absorption rate and water absorption rate, and has better storage modulus after water absorption.

The mass content of water in the polysaccharide compound porous gel is less than or equal to 2%; the expansion multiple of the polysaccharide compound porous gel is more than or equal to 65 when the polysaccharide compound porous gel absorbs water for 30min, and the storage modulus is more than or equal to 700Pa.

In some embodiments, the porous polysaccharide compound gel has an expansion factor of 50 to 90 and a storage modulus of 700 to 1600Pa when absorbing water for 30min.

In addition, the porous gel of polysaccharide compound has adjustable porosity and pore size, the adjustable range of pore size is between 0.5 μm and 50 μm, and the adjustable range of the pore size is between 1% and 90%, preferably between 10% and 50%.

The preparation method has the advantages of simple and convenient technical process, short preparation period, environmental protection and easy mass production, and can regulate and control the porosity and the pore diameter of the polysaccharide compound porous gel according to the application field and the requirements, and change the water absorption rate, the water absorption rate and the hydrogel modulus after water absorption. The prepared polysaccharide compound porous gel not only has good absorption performance, but also can keep good storage modulus after water swelling, and can be used for preparing intragastric lipid-reducing gel, and has rapid water swelling in the stomach and excellent water-retaining capacity, so that the polysaccharide compound porous gel has good satiety and the effect of reducing heat intake; meanwhile, the water-absorbing and swelling composite material keeps good storage modulus after absorbing water and swelling, can keep good structure in the stomach without being damaged, and has good stomach swelling effect.

The polysaccharide compound porous gel has important application value in the fields of agriculture, tissue engineering, drug delivery, biosensors, medical instruments and the like.

Wherein the water absorption rate refers to the rate at which water is absorbed per unit time per unit mass of the water absorbing agent; the water absorption capacity means water that can be absorbed by the water absorbing agent per unit mass or volume, and is the ratio of the water that can be absorbed by the water absorbing agent to the volume or mass of the water absorbing agent itself.

In particular, the polysaccharide compound porous gel can be applied to wound dressing, intragastric lipid-reducing hydrogel and the like. For example, when the hydrogel is applied to intragastric lipid-reducing hydrogel, the hydrogel has quick water absorption capacity, can reach an absorption expansion multiple of approximately 90 times at 30 minutes, and can be seen to have larger water absorption rate and water absorption rate.

The polysaccharide compound porous gel is formed by chemical crosslinking, and optionally physical interaction exists, and the polysaccharide compound gel with a three-dimensional network structure can only be swelled in a solvent and cannot be completely dissolved. Wherein the physical interactions include entanglement between macromolecular chains of the polysaccharide compound, hydrogen bonding between macromolecules or between macromolecules and water, and ionic interactions.

In order to make the objects, technical solutions and advantages of the present invention more concise, the present invention will be described in the following specific examples, but the present invention is by no means limited to these examples. The following examples are only preferred embodiments of the present invention, which can be used to describe the present invention, and should not be construed as limiting the scope of the invention. It should be noted that any modifications, equivalent substitutions and improvements made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

In order to better illustrate the present invention, the following description of the present invention will be given with reference to examples. The following are specific examples.

Example 1

Materials: sodium carboxymethylcellulose (CMCNa, viscosity 4300cps in 1w% aqueous solution at 25 ℃, weight average molecular weight 72w, degree of substitution 0.9); hydroxyethylcellulose (HEC, viscosity 20cps in 1w% aqueous solution at 25 ℃, weight average molecular weight 9w, degree of substitution 0.9) was purchased from ashland tm, and Citric Acid (CA) was purchased from Sigma.

The preparation method comprises the following steps:

1) Adding 10L of purified water into a 20L stirring reactor, adding 2gCA to water, then adding 160g of CMCNa and 40g of HEC into the solution, and fully stirring at 100rpm for 10 hours at room temperature to uniformly mix the systems to obtain a mixed solution;

2) Adding the obtained mixed solution into a stainless steel tray, and then placing the tray in a 40 ℃ oven to dry and remove water for 72 hours to obtain a dry product with the water content of about 5wt%;

3) Pulverizing and sieving the obtained dry product, and controlling the particle size to 200 μm to obtain dry particles;

4) The sieved dry particles were dispersed on a tray, placed in an oven at 140 ℃ for 1 hour to perform a crosslinking reaction, to obtain polysaccharide compound porous gel particles, and the moisture content thereof was tested.

The following is a performance test, and each of the examples and comparative examples in tables 1 to 3 uses a similar test method.

Scanning electron microscope

The polysaccharide compound porous gel particles in example 1 were subjected to scanning electron microscope characterization, and SEM pictures obtained are shown in FIG. 1, from which it is seen that the pore size is less than 0.5. Mu.m.

And (II) water absorption test, obtaining the water absorption expansion coefficient parameters of 30min in table 1.

The porous gel particles of polysaccharide compound of 0.25g in each example or comparative example were subjected to a water absorption test using 1/8x gastric acid simulation as follows:

A. a sample of 0.250±0.005g was weighed, the actual mass was recorded as m1, and the sample was added to a beaker.

B. 40.0.+ -. 1.0mL of aqueous solution having a pH of 2.1.+ -. 0.1 is added to the beaker.

C. The beaker was placed on a magnetic stirrer and gently stirred at room temperature for a corresponding time without generating vortexes.

D. The resulting suspension was filtered through a dust-free cloth and allowed to stand for 10.+ -. 1 min to allow the solution to sufficiently filter.

E. Collecting the residual substances by using a medicine spoon, weighing the mass of the residual substances, and marking the mass as m2.

The water absorption expansion ratio (MUR) was calculated according to the following formula: mur= (m 2-m 1)/m 1. And taking an average value at least three times to obtain the water absorption multiple.

And (III) testing storage modulus performance to obtain storage modulus parameters.

1) Sample preparation

A. Samples of 0.250.+ -. 0.005g of each example or comparative example were weighed and placed in 40.0.+ -. 1.0mL of an aqueous solution having a pH of 2.1.+ -. 0.1 and stirred gently at 37 ℃ for 30min without swirling.

B. The sample was filtered using a dust-free cloth, poured onto an elevated dust-free cloth, and the liquid was filtered off.

C. The dust-free cloth was stretched and the sample was spread to allow rapid filtration of the liquid.

D. The dust-free cloth with the sample was placed on a paper towel (3 layers) and allowed to stand for 5s.

E. The dust-free cloth with the sample was taken off the paper towel and placed on a table for 5min.

F. Samples were taken for storage modulus testing.

2) Storage modulus testing stage

A. Saw tooth anti-slip parallel plates with a diameter of 20mm were selected and the parallel plate spacing was made zero.

B. The following parameters were set: the parallel plate spacing is 1.0mm, the oscillation mode and the frequency scanning (0.159-4.77 Hz/0.999-29.97 rad/s), and the number of sampling points of each order of magnitude is 10.

C. The upper plate is lifted and a proper amount of sample is placed on the lower plate, so that the sample can fill the gap after the upper plate is reset and does not overflow the lower plate as much as possible.

D. The sample was not fringing.

E. The sample stage temperature was controlled at 37℃and the sample was held for 5min.

F. The test is started.

G. After the test, the storage modulus values corresponding to 10rad/s and 3Hz are recorded. The average value obtained by at least three times of testing is the storage modulus value.

Examples 2 to 9 and comparative examples 1 to 2 are substantially the same as example 1 except that: the parameters of step 2) and step 4) are different; the parameters of the corresponding examples and comparative examples and the performance data of the polysaccharide compound porous gel particle products produced are shown in Table 1.

TABLE 1

Comparative example 1, although the drying temperature was set at 40 ℃, the drying time was short, and the moisture content of the dried product was 50wt%, so that the subsequent crosslinking reaction was performed, the crosslinking reaction efficiency was not high and the uniformity of the crosslinking reaction was poor, resulting in a low degree of crosslinking reaction, and the moisture content of the prepared polysaccharide compound porous gel particle sample was high, thereby seriously affecting the expansion ratio of water absorption for 30min.

Comparative example 2 the drying temperature was set at a higher temperature, and although the moisture content of the dried product was controlled at a lower level, the drying water removal temperature was relatively high, crosslinking was liable to occur, and the degree of crosslinking of the finally produced porous gel particles of the polysaccharide compound was uncontrollable, and thus the 30min storage modulus of water absorption of the produced porous gel particles of the polysaccharide compound was high, but the water absorption capacity was low.

As can be seen from table 1, the porous gel particle samples of polysaccharide compound prepared in each example have a swelling ratio of 65 or more, specifically 65 to 85, when absorbing water for 30 min; the storage modulus of the water absorption for 30min is more than 700Pa, specifically between 700Pa and 1100 Pa.

As is clear from examples 1 to 8 and example 9, the water content of the dried product was preferably controlled to 5% by weight or less, and the water absorption capacity and storage modulus of 30 minutes in the obtained polysaccharide compound porous gel particle sample were high.

From examples 1 to 4, example 4 was dried to remove water at a higher temperature, which in turn resulted in a lower water absorption rate in the polysaccharide compound porous gel particle samples prepared therefrom relative to examples 2 to 3, and a relatively higher storage modulus at 30 minutes of water absorption. Wherein, the preparation schemes of example 2 and example 1 are basically the same, except that: the drying temperature set in the preparation step 2) of example 2 was 80℃to make the volatilization speed of the solvent in the mixed solution faster. And SEM characterization and determination of the water absorption rate were performed on the products obtained in examples 1 and 2, and SEM characterization results are shown in fig. 1 to 2.

It can be seen from fig. 1 and 2 that the porous gel particle sample of polysaccharide compound is net-shaped, and the pore size of the product in fig. 1 is less than 0.5 μm, while the pore size of the product in fig. 2 is between 1 and 10 μm, so that increasing the drying temperature can increase the pore size of the product.

According to the water absorption rate profile (not shown) of example 1, the sample obtained in example 1 had a water absorption expansion ratio of 45 at 5min, 65 at 10min, 73 at 15min, and 85 at 30 min; according to the water absorption rate profile of example 2 (not shown), the sample obtained in example 2 reached 80 in water absorption expansion at 30min. The sample of example 13 has a significantly higher water absorption rate than the sample obtained in example 1, thanks to its larger pore structure, making it easier for the water to diffuse in the sample.

As is clear from examples 1 and 5 to 8, the polysaccharide compound porous gel particle sample obtained preferably has a crosslinking reaction temperature of 100℃to 160℃and a high water absorption capacity and storage modulus after absorption.

Examples 10 to 14 were substantially the same as example 1, except that the CMC and HEC were added in different proportions, and the number and performance data are shown in Table 2.

TABLE 2

As can be seen from Table 2, the mass contents of CMCna in examples 1 and examples 9 to 13 in CMCna and HEC are 80%, 50%, 60%, 70%, 90% and 100%, respectively, and as the content of CMCna increases, the water expansion coefficient of the product increases, and the storage modulus decreases, because the CMCna branched chain contains a large number of carboxyl groups, which are the main groups for water absorption of the product, and therefore the water expansion coefficient of the product increases with the increase of the content of CMCna. The branched chain of HEC contains a large number of hydroxyl groups, and the branched chain is easier to crosslink due to smaller steric hindrance, so that the more HEC content in the product, the better the crosslinking effect of the product is, and the better crosslinking effect can improve the storage modulus of the product, but seriously affects the main performance of the product, namely the expansion coefficient of water absorption.

The expansion times of the polysaccharide compound porous gel prepared in the embodiment 1 and the embodiment 9 to 13 are more than or equal to 50, particularly 50 to 90 when the polysaccharide compound porous gel absorbs water for 30 min; the storage modulus is more than or equal to 700Pa, and is particularly 700-1600 Pa. Preferably, the mass content of the CMCNa in the total amount of the CMCNa and the HEC is controlled to be 70-100%. The expansion multiple of the polysaccharide compound porous gel prepared in the preferred range is more than or equal to 70, and is particularly 70-90 when the polysaccharide compound porous gel absorbs water for 30 min; the storage modulus is more than or equal to 700Pa, specifically 700-1000 Pa, and the water absorption performance and the storage modulus of the polysaccharide compound porous gel can be simultaneously and well satisfied.

Examples 15 to 17

Materials: sodium carboxymethylcellulose (CMCNa-1, viscosity 4300cps in 1w% aqueous solution at 25 ℃, weight average molecular weight 72w, degree of substitution 0.9); sodium carboxymethylcellulose-2 (CMCNa-2, viscosity in 1w% aqueous solution at 25 ℃ c. Is 1500cps, weight average molecular weight is 36w, degree of substitution is 0.9); hydroxyethylcellulose (HEC, viscosity 20cps in 1w% aqueous solution at 25 ℃, weight average molecular weight 9w, degree of substitution 0.9); hydroxypropyl cellulose (HPC, viscosity 100cps in 1w% aqueous solution at 25 ℃, weight average molecular weight 37 w) hydroxypropyl methylcellulose ((HPMC, viscosity 80cps in 1w% aqueous solution at 25 ℃, weight average molecular weight 20 w)) was purchased from ashland tm, and Citric Acid (CA) was purchased from Sigma.

The preparation schemes of examples 15 to 17 and example 1 are substantially the same, except that: the kinds of polysaccharide compound 1 and polysaccharide compound 2 added were different to replace CMCNa-1 and/or HEC in example 1. The specific parameters and performance results are shown in Table 3.

TABLE 3 Table 3

From the comparison in Table 3, the higher the viscosity of CMCNa, the higher the water swelling of the product, while HEC, HPC and HPMC are not particularly different in their major performance impact.

Examples 18 to 22

Examples 18 to 22 were substantially the same as example 1, except that the total amount of CMCNa and HEC added was different, and the ratio was the same. The parameters and performance test results are shown in table 4 below:

TABLE 4 Table 4

The dissolution time in table 4 refers to the dissolution time required for the two polysaccharide compounds to form a mixed solution. It is clear from table 4 that the properties of the product do not vary greatly with the content of the two polysaccharide compounds in the solution, but as the total mass content of the two polysaccharide compounds increases, the time required for dissolution increases rapidly, the preparation time of the two polysaccharide compounds in the solution at 4wt% and 5wt% is 2.5 and 6 times the preparation time of the 2% solution, which means that an increase in the content of the two polysaccharide compounds in the solution will result in an extended production cycle, preferably a content of the two polysaccharide compounds in the solution of 1 to 4wt%. Further preferably, the polysaccharide compound porous gel particle samples prepared in example 1 and example 18 are high in both water absorption capacity and storage modulus after absorption.

The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.

The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. The scope of the invention is therefore intended to be covered by the appended claims, and the description and drawings may be interpreted in accordance with the contents of the claims.

Claims

1. A method for preparing a polysaccharide compound porous gel, comprising the steps of:

2. The method of preparation of claim 1, wherein the polysaccharide compound comprises a first polysaccharide compound selected from one or more of methylcellulose, carboxymethylcellulose, and salts thereof;

3. The method of claim 2, wherein the first polysaccharide compound has a viscosity of 3500 to 6000cps in a 1wt% aqueous solution at 25 ℃.

4. The method of any one of claims 1 to 3, wherein the polysaccharide compound further comprises a second polysaccharide compound comprising one or more of ethylcellulose, hydroxyethylcellulose, propylcellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose, butylcellulose, hydroxybutyl cellulose, ethylhydroxyethylcellulose, glycosaminoglycan, polyuronic acid, polymannuronate, polygalacturonic acid, heparin, dextran sulfate, dextran phosphate, diethylaminodextran, chondroitin, and carboxymethyl starch;

5. The process according to claim 4, wherein the second polysaccharide compound has a viscosity of 50 to 200cps in a 1wt% aqueous solution at 25 ℃.

6. The method of any one of claims 1 to 3 or 5, wherein the cross-linking agent comprises one or more of oxalic acid, malonic acid, maleic acid, succinic acid, citric acid, phthalic acid, pyromellitic acid, ethylenediamine tetraacetic acid, and carboxyl-terminated multi-arm polyethylene glycol;

7. The method according to claim 6, wherein the mass content of the crosslinking agent relative to the total mass of the polysaccharide compound is 0.1% to 2%;

8. The method according to any one of claims 1 to 3, 5 and 7, wherein the time of the crosslinking reaction is 0.5 to 12 hours.

9. The method according to any one of claims 1 to 3, 5 and 7, wherein the time of the crosslinking reaction is 1 to 5 hours;

and/or the temperature of the crosslinking reaction is 100-160 ℃.

10. The production method according to any one of claims 1 to 3, 5 and 7, wherein the moisture content of the dried product is controlled to be 5wt% or less;

and/or the drying and dewatering time is 6-100 h.

11. The method according to any one of claims 1 to 3, 5 and 7, wherein the temperature of the drying water removal is 20 to 80 ℃; and/or the number of the groups of groups,

the drying and dewatering time is 12-72 h.

12. The method of claim 11, wherein the temperature of the drying water is 40-60 ℃.

13. The production method according to any one of claims 1 to 3, 5 and 7, characterized by further comprising the steps of, before subjecting the dried product to the crosslinking reaction:

14. A polysaccharide compound porous gel prepared by the preparation method of any one of claims 1 to 13.

15. The polysaccharide compound porous gel is characterized in that the water content of the polysaccharide compound porous gel is less than or equal to 2%; the expansion multiple of the polysaccharide compound porous gel is more than or equal to 50 when the polysaccharide compound porous gel absorbs water for 30min, and the storage modulus is more than or equal to 700Pa.

16. The polysaccharide compound porous gel of claim 14 or 15, wherein the polysaccharide compound porous gel has a swelling factor of 50 to 90 and a storage modulus of 700 to 1600Pa when absorbing water for 30 min;