CN115124739A - Injectable marine polysaccharide full-physical crosslinked hydrogel and preparation method thereof - Google Patents
Injectable marine polysaccharide full-physical crosslinked hydrogel and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title abstract description 6
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- 238000000034 method Methods 0.000 claims abstract description 12
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- 229920000447 polyanionic polymer Polymers 0.000 claims abstract description 4
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- 238000003756 stirring Methods 0.000 claims description 52
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- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
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- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Abstract
The invention discloses an injectable marine polysaccharide full-physical crosslinked hydrogel and a preparation method thereof. The invention adopts a specific two-step high-temperature and high-pressure method to prepare uniformly dispersed high-solid content marine polycation polysaccharide pre-polymerized liquid, marine polyanion polysaccharide pre-polymerized liquid and pre-prepared clay solution, and utilizes biocompatible nano clay sheets with negative electricity on the surface layer and positive electricity on the edges to form a self-assembly system with strong electrostatic interaction with the marine cationic polysaccharide and the anionic polysaccharide to prepare the injectable full-physical crosslinked marine polysaccharide hydrogel with simple and safe components, good mechanical strength and good biocompatibility, and is biodegradable, the degradable monomer has no biological toxicity, the pore size distribution of the gel is uniform and compact, and good hardness and viscosity can be realized, so that the invention is suitable for the biomedical fields of regeneration and repair of human tissues and the like.
Description
Technical Field
The invention belongs to the technical field of natural polymer hydrogel, and particularly relates to injectable marine polysaccharide full-physical crosslinked hydrogel and a preparation method thereof.
Background
The hydrogel is a three-dimensional polymer network taking water as a dispersion medium, water molecules are bound in the polymer network, and the hydrogel has formability and fluid substance transferability, and the special physical structure endows the hydrogel with the characteristics of high water retention, ion exchange, stimulus response and the like, and has great attention in the biomedical fields of tissue engineering, biosensors, slow release carriers and the like. The injectable hydrogel is a functional material which can inject a precursor or hydrogel to a target position through an injector, and has wide application prospect in the fields of tissue filling and repairing, drug delivery, bleeding plugging, biological scaffolds and the like because the injectable hydrogel can be injected into a body in a minimally invasive intervention mode.
Injectable hydrogels can be classified into chemically synthesized polymeric hydrogels and natural polymeric hydrogels according to the source of the raw material. Most synthetic hydrogels are difficult to biodegrade, and the monomers are toxic and present a safety risk when injected into the body. The natural polymer hydrogel (polysaccharide, protein and the like) has wide sources, is safe and nontoxic, and has good biocompatibility and degradability. The marine natural polysaccharide has high yield, low toxicity and low sensitization superior to protein, and is a kind of natural polymer hydrogel with excellent biomedical application foreground. Chitosan and the derivatives thereof after chitin deacetylation are only one natural polycation polysaccharide in nature, and have excellent biocompatibility, antibiosis and anti-inflammation. The algin belongs to algin, carrageenan and the like of marine sources, is polyanionic polysaccharide, and has low-sensitivity, low-toxicity biological safety and biological activity.
The marine polysaccharide hydrogel is used for injectable gel, and has certain fluidity before injection and certain mechanical strength after injection. In the prior art, on one hand, because polysaccharide contains a large amount of hydroxyl groups, a high molecular chain can absorb a large amount of water, so that the distance between the high molecular chains is increased, and only low-concentration marine polysaccharide pre-polymerization liquid can be prepared, so that the high molecular skeleton is sparse when gel is formed, and the gel strength is poor; on the other hand, the injectable marine polysaccharide hydrogel achieves mechanical enhancement in vivo through complex modification and chemical crosslinking, and a toxic chemical crosslinking agent or monomer is introduced in the crosslinking process, so that certain potential safety hazards exist during biological application. Although some two-component injectable hydrogels use physical crosslinking modes such as calcium ion chelation, the mechanical strength of the physically crosslinked hydrogels is low and the viscosity is poor, and the practical application also faces the situations of complex operation and nonuniform crosslinking, so that the large-scale application of the hydrogels is limited.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides an injectable marine polysaccharide full-physical crosslinked hydrogel.
The invention also aims to provide a preparation method of the injectable marine polysaccharide-based fully-physically-crosslinked hydrogel.
The technical scheme of the invention is as follows:
an injectable marine polysaccharide full-physical crosslinked hydrogel with the aperture of 5-20 μm, the hardness of 156-188Pa and the viscosity of 137-153Pa is prepared by mixing and crosslinking a preformed clay solution, a marine polycation polysaccharide pre-polymerization solution and a marine polyanion polysaccharide pre-polymerization solution according to the solid content ratio of 2-8: 5-15: 2-8,
a preformed clay solution wherein the clay is a synthetic hectorite having a concentration of 15-20% and a viscosity of 3-8 pas at 25 ℃,
the marine polycation polysaccharide pre-polymerization solution has the concentration of 7.8-8.4 percent and the viscosity of 6-9 Pa.s at 25 ℃,
the marine polyanionic polysaccharide pre-polymerization liquid has the concentration of 7.8 to 8.4 percent and the viscosity of 5 to 8 Pa.s at the temperature of 25 ℃,
in a preferred embodiment of the invention, the hectorite is model RDS or S482.
In a preferred embodiment of the present invention, the marine polyanionic polysaccharide in the marine polyanionic polysaccharide pre-polymerization solution is sodium alginate or carrageenan.
In a preferred embodiment of the invention, the marine polycationic polysaccharide in the marine polycationic polysaccharide preconcentrate is chitosan or a quaternary ammonium salt chitosan.
In a preferred embodiment of the present invention, the marine polyanionic polysaccharide in the marine polyanionic polysaccharide pre-polymerization liquid is sodium alginate or carrageenan; the marine polycation polysaccharide in the marine polycation polysaccharide pre-polymerization liquid is chitosan or quaternary ammonium salt chitosan.
The preparation method of the injectable marine polysaccharide full-physical crosslinked hydrogel comprises the following steps:
(1) preparing a high-concentration prefabricated clay solution by a two-step high-temperature high-pressure method: dissolving part of the clay powder in pure water, stirring at 1000-1200rpm for 4-6min, standing for 0.8-1.2h for curing and recovering the fluidity; then sterilizing for 8-12min at the temperature of 120-122 ℃ and under the condition of 95-110kPa for pretreatment; then adding the rest clay powder, stirring at 1000-;
(2) preparing a high-concentration marine polyanionic polysaccharide pre-polymerization solution by a two-step high-temperature high-pressure method: dissolving part of the marine polyanionic polysaccharide powder in pure water, stirring at 1000-;
(3) preparing a high-concentration marine polycation polysaccharide pre-polymerization solution by a two-step high-temperature high-pressure method: dissolving part of the marine polycation polysaccharide powder in pure water or acetic acid solution, stirring at 1000-;
(4) under the aseptic condition, uniformly mixing the marine polyanionic polysaccharide pre-polymerized liquid with the preformed clay solution, then adding the marine polycationic polysaccharide pre-polymerized liquid, and stirring to obtain the injectable marine polysaccharide full-physical crosslinked hydrogel.
In a preferred embodiment of the present invention, the step (1) is: dissolving part of clay powder in pure water, stirring at 1000rpm for 5min, standing for 1h for curing and recovering fluidity; then sterilizing for 10min at 121 ℃ under 100kPa for pretreatment; then adding the rest clay powder, stirring at 1000rpm for 5min, standing for aging for 2h and recovering fluidity, and sterilizing at 121 deg.C under 100kPa for 20min to obtain the preformed clay solution.
In a preferred embodiment of the present invention, the step (2) is: dissolving part of the marine polyanionic polysaccharide powder in pure water, stirring at 1000rpm in a water bath at 60-80 ℃ until the powder is completely dissolved, then sterilizing at 121 ℃ and 100kPa for 10min, then adding the rest of the marine polyanionic polysaccharide powder, stirring at 100 rpm until the powder is completely dispersed, and then sterilizing at 121 ℃ and 100kPa for 20min to obtain the marine polyanionic polysaccharide pre-polymerization solution.
In a preferred embodiment of the present invention, the step (3) is: dissolving part of the marine polycation polysaccharide powder in pure water or acetic acid solution, stirring at 1000rpm under water bath at 60 ℃ until the powder is completely dissolved, then sterilizing at 121 ℃ and 100kPa for 10min, then adding the rest of the marine polycation polysaccharide powder, stirring at 100 rpm and 300rpm until the marine polycation polysaccharide powder is completely dispersed, and then sterilizing at 121 ℃ and 100kPa for 20min to obtain the marine polycation polysaccharide pre-polymerization solution.
The invention has the beneficial effects that:
1. the invention adopts a specific two-step high-temperature high-pressure method to prepare uniformly dispersed high-solid-content marine polycation polysaccharide pre-polymerized liquid, marine polyanion polysaccharide pre-polymerized liquid and pre-prepared clay solution, and utilizes biocompatible nano clay sheets with negative electricity on the surface layer and positive electricity on the edges to form a self-assembly system with strong electrostatic interaction with the marine cationic polysaccharide and the anionic polysaccharide to prepare the injectable fully-physically crosslinked marine polysaccharide hydrogel with simple and safe components and good mechanical strength.
2. Compared with the traditional marine polysaccharide injectable hydrogel, the invention has good biocompatibility, is biodegradable, has no biological toxicity of degraded monomers, has uniform and compact distribution of gel pore diameter (5-20 mu m), can realize the gel strength of 156-188Pa hardness and 137-153Pa viscosity, and is suitable for the biomedical fields of regeneration and repair of human tissues and the like.
Drawings
FIG. 1 is a schematic diagram of the injectable marine polysaccharide fully physically crosslinked hydrogel with high solid content prepared in example 1 of the present invention, and it can be seen that the hydrogel has injectable properties.
Fig. 2 is a physical representation of the final product prepared in comparative example 1 of the present invention.
FIG. 3 is a scanning electron micrograph of the injectable marine polysaccharide fully physically crosslinked hydrogel with high solid content prepared in example 1 of the present invention, which shows that the pore size distribution is uniform and compact, and the size is between 5 μm and 20 μm.
FIG. 4 is a graph showing the results of the biocompatibility test of the injectable marine polysaccharide fully physically crosslinked hydrogel with high solid content prepared in examples 1 to 4 of the present invention, and control is a cell that grows normally, and thus it can be seen that the culture with the cell does not affect the normal growth of the cell, and has low toxicity and good biocompatibility.
FIG. 5 is a graph showing the mechanical properties of injectable marine polysaccharide fully physically crosslinked hydrogels with high solid content prepared in examples 1 and 2 of the present invention, wherein the left graph shows that the hydrogels achieve 188Pa and 156Pa hardness at different clay ratios, and the right graph shows that the hydrogels can achieve 153Pa and 137Pa viscosity at different clay ratios.
Fig. 6 is a rheological property diagram of the injectable marine polysaccharide fully-physically crosslinked hydrogel with high solid content prepared in examples 1 and 2 of the present invention, and it can be seen that the loss modulus and the storage modulus of the hydrogel are improved again with time, and the higher the clay content is, the higher the mechanical properties are.
Fig. 7 is a graph of the mechanical stability result of the high solid content injectable marine polysaccharide fully-physically crosslinked hydrogel prepared in example 1 of the present invention, wherein the dark color represents the storage modulus, and the light color represents the loss modulus, so that the hydrogel can be seen to deviate from balance and still return to the original state under the action of external force, and has good mechanical stability.
Detailed Description
The technical solution of the present invention will be further illustrated and described below with reference to the accompanying drawings by means of specific embodiments.
Both S482 and RDS in the following examples were obtained from Guangzhou Qingfeng New materials, Inc.
Example 1
20g of clay S482 powder was weighed, 10g was dissolved in 100mL of pure water, stirred at 1000rpm for 5 minutes at a high speed, and then allowed to stand for 1 hour to cure and recover fluidity. Sterilizing at 121 deg.C under 100kPa for 10min to obtain pre-processed clay solution with viscosity of 0.03 pas (25 deg.C). Pouring the remaining 10g of clay powder into the reactor, stirring at 1000rpm for 3min, increasing the solution viscosity, aging for 2 hr, recovering fluidity, sterilizing at 121 deg.C under 100kPa for 20min to obtain 20% clay S482 pre-polymerized solution with viscosity of 8 Pa.s (25 deg.C).
Weighing 8g of sodium alginate powder, dissolving 5g of sodium alginate powder in 100mL of pure water, stirring at a high speed of 1000rpm in a water bath at 60 ℃ until the powder is completely dissolved, sterilizing at 121 ℃ and 100kPa for 10min for pretreatment to obtain a preformed sodium alginate solution with the viscosity of 1.5Pa & s (25 ℃). Slowly pouring the remaining 3g of sodium alginate powder into the mixture, stirring the mixture at 100-200rpm until the mixture is completely dispersed, and then sterilizing the mixture for 20min at the temperature of 121 ℃ and the pressure of 100kPa to obtain 8% sodium alginate solution with the viscosity of 6Pa s (25 ℃).
Weighing 8g of quaternary ammonium salt chitosan, dissolving 6g of quaternary ammonium salt chitosan in 100mL of pure water, stirring at a high speed of 1000rpm in a water bath at 60 ℃ until the powder is completely dissolved, sterilizing for 10min at 121 ℃ under 100kPa for pretreatment to obtain a preformed quaternary ammonium salt chitosan solution with the viscosity of 1Pa & s (25 ℃). Slowly pouring the remaining 2g of quaternary ammonium salt chitosan powder into the solution, stirring the solution at 100-200rpm until the quaternary ammonium salt chitosan powder is completely dissolved, and then sterilizing the solution for 20min at the temperature of 121 ℃ and the pressure of 100kPa to obtain 8 percent quaternary ammonium salt chitosan prepolymer solution with the viscosity of 8Pa s (25 ℃).
After 8% sodium alginate solution and 20% clay S482 solution are mixed and dispersed evenly according to the solid content mass ratio of 2: 5 under the aseptic operation, 8% quaternary ammonium salt chitosan pre-polymerization solution (the volume ratio of the three liquids is 1: 1) is added according to the solid content ratio of 2: 5: 2, the mixture is stirred at a constant speed for 30 seconds to form a self-assembly system with strong electrostatic interaction, and the self-assembly system is crosslinked to form the injectable marine polysaccharide full-physical crosslinked hydrogel with high solid content as shown in figure 1, figure 3 to figure 7. The hydrogel is injectable and has good biocompatibility, the pore diameters of the hydrogel are respectively uniform and compact (5-20 μm), the gel strength of 188Pa hardness and 153Pa viscosity is achieved, and the hydrogel has good mechanical stability.
Example 2
15g of clay S482 powder was weighed, 10g of the powder was dissolved in 100mL of pure water, stirred at 1000rpm for 5 minutes at a high speed, and then allowed to stand for 1 hour to cure and recover fluidity. Sterilizing at 121 deg.C under 100kPa for 10min to obtain pre-processed clay solution with viscosity of 0.02 pas (25 deg.C). Pouring the remaining 5g of clay powder into the reactor, stirring at 1000rpm for 3min, increasing the solution viscosity, aging for 2h, recovering fluidity, sterilizing at 121 deg.C and 100kPa for 20min to obtain 15% clay pre-polymerization solution with viscosity of 5 pas (25 deg.C).
Weighing 8g of sodium alginate powder, dissolving 5g of sodium alginate powder in 100mL of pure water, stirring at a high speed of 1000rpm in a water bath at 60 ℃ until the powder is completely dissolved, sterilizing at 121 ℃ and 100kPa for 10min for pretreatment to obtain a preformed sodium alginate solution with the viscosity of 1.5Pa & s (25 ℃). Slowly pouring the remaining 3g of sodium alginate powder into the mixture, stirring the mixture at 100-200rpm until the mixture is completely dispersed, and sterilizing the mixture for 20min at the temperature of 121 ℃ and under the condition of 100kPa to obtain an 8% sodium alginate solution with the viscosity of 6Pa & s (25 ℃).
Weighing 8g of quaternary ammonium salt chitosan, dissolving 6g of quaternary ammonium salt chitosan in 100mL of pure water, stirring at a high speed of 1000rpm in a water bath at 60 ℃ until the powder is completely dissolved, sterilizing for 10min at 121 ℃ under 100kPa for pretreatment to obtain a preformed quaternary ammonium salt chitosan solution with the viscosity of 1Pa & s (25 ℃). Slowly pouring the remaining 2g of quaternary ammonium salt chitosan powder into the reactor, stirring the mixture at 100-200rpm until the chitosan powder is completely dissolved, and then sterilizing the mixture for 20min at the temperature of 121 ℃ and under the condition of 100kPa to obtain 8% quaternary ammonium salt chitosan prepolymer solution with the viscosity of 8Pa & s (25 ℃).
After 8% sodium alginate solution and 15% clay S482 solution are mixed and dispersed evenly according to the solid content mass ratio of 8: 15 under the aseptic operation, 8% quaternary ammonium salt chitosan pre-polymerization solution (the volume ratio of the three liquids is 1: 1) is added according to the solid content ratio of 8: 15: 8, and is stirred at a constant speed for 30 seconds to form a self-assembly system with strong electrostatic interaction, and the injectable marine polysaccharide full-physical crosslinked hydrogel with high solid content as shown in figures 4 to 6 is formed through crosslinking. The hydrogel is injectable and has good biocompatibility, the pore diameters of the hydrogel are respectively uniform and compact (5-10 μm), the gel strength of 156Pa hardness and 137Pa viscosity is achieved, and the hydrogel has good mechanical stability.
Example 3
20g of clay RDS powder is weighed, 20g of the clay RDS powder is dissolved in 100mL of pure water, stirred at a high speed of 1000rpm for 5min and then kept stand for 1h for curing to recover the fluidity. Sterilizing at 121 deg.C under 100kPa for 10min to obtain pre-processed clay solution with viscosity of 0.02 pas (25 deg.C). Pouring the rest 10g of clay powder into the reactor, stirring at 1000rpm for 3min, increasing the solution viscosity, aging for 2 hr, recovering fluidity, sterilizing at 121 deg.C under 100kPa for 20min to obtain 20% clay RDS pre-polymerization solution with viscosity of 5 Pa.s (25 deg.C).
Weighing 8g of carrageenan powder, dissolving 5g of carrageenan powder in 100mL of pure water, stirring at a high speed of 1000rpm in a water bath at 60 ℃ until the powder is completely dissolved, sterilizing at 121 ℃ and 100kPa for 10min for pretreatment to obtain a preformed carrageenan solution with the viscosity of 2.5 Pa.s (25 ℃). Slowly pouring the remaining 3g of carrageenan powder into the reactor, stirring the mixture at 100-200rpm until the carrageenan powder is completely dispersed, and then sterilizing the mixture for 20min at the temperature of 121 ℃ and under the condition of 100kPa to obtain 8% carrageenan solution with the viscosity of 8 Pa.s (25 ℃).
Weighing 8g of quaternary ammonium salt chitosan, dissolving 6g of quaternary ammonium salt chitosan in 100mL of pure water, stirring at a high speed of 1000rpm in a water bath at 60 ℃ until the powder is completely dissolved, sterilizing for 10min at 121 ℃ under 100kPa for pretreatment to obtain a preformed quaternary ammonium salt chitosan solution with the viscosity of 1Pa & s (25 ℃). Slowly pouring the remaining 2g of quaternary ammonium salt chitosan powder into the reactor, stirring the mixture at 100-200rpm until the chitosan powder is completely dissolved, and then sterilizing the mixture for 20min at the temperature of 121 ℃ and under the condition of 100kPa to obtain 8% quaternary ammonium salt chitosan prepolymer solution with the viscosity of 8Pa & s (25 ℃).
After 8% carrageenan solution and 20% clay RDS solution are mixed and dispersed evenly according to the solid content mass ratio of 2: 5 under the aseptic operation, 8% quaternary ammonium salt chitosan prepolymer solution (the volume ratio of the three liquids is 1: 1) is added according to the solid content ratio of 2: 5: 2, and is stirred for 30 seconds at a constant speed to form a self-assembly system with strong electrostatic interaction, and the injectable marine polysaccharide full-physical crosslinked hydrogel with high solid content shown in figure 4 is formed through crosslinking. The hydrogel is injectable and has good biocompatibility, the pore diameters of the hydrogel are respectively uniform and compact (5-20 μm), the gel strength of 180Pa hardness and 150Pa viscosity is achieved, and the hydrogel has good mechanical stability.
Example 4
15g of clay RDS powder is weighed, 10g of the clay RDS powder is dissolved in 100mL of pure water, stirred at 1000rpm for 5min at a high speed, kept stand for 1h and cured to recover the fluidity. Sterilizing at 121 deg.C under 100kPa for 10min to obtain preformed clay RDS solution with viscosity of 0.01 Pa.s (25 deg.C). Pouring the rest 5g of clay RDS powder into the reactor, stirring at 1000rpm for 5min, increasing the solution viscosity, aging for 2h, recovering fluidity, sterilizing at 121 deg.C under 100kPa for 20min to obtain 15% clay RDS prepolymer with viscosity of 3 pas (25 deg.C).
Weighing 8g of sodium alginate powder, dissolving 5g of sodium alginate powder in 100mL of pure water, stirring at high speed of 1000rpm in a water bath at 60 ℃ until the powder is completely dissolved, sterilizing at 121 ℃ and 100kPa for 10min for pretreatment to obtain a preformed sodium alginate solution with the viscosity of 1.5Pa & s (25 ℃). Slowly pouring the remaining 3g of sodium alginate powder into the mixture, stirring the mixture at 100-200rpm until the mixture is completely dispersed, and sterilizing the mixture for 20min at the temperature of 121 ℃ and under the condition of 100kPa to obtain an 8% sodium alginate solution with the viscosity of 6Pa & s (25 ℃).
8g of chitosan was weighed, 6g was dissolved in 100mL of 1% acetic acid solution, stirred at a high speed of 1000rpm in a water bath at 60 ℃ until the powder was completely dissolved, and sterilized at 121 ℃ under 100kPa for 10min for pretreatment to obtain a pre-prepared chitosan solution having a viscosity of 1.0 pas (25 ℃). Slowly pouring the rest 2g of chitosan powder into the reactor, stirring at 100-200rpm until the chitosan powder is completely dissolved, and then sterilizing at 121 ℃ and 100kPa for 20min to obtain 8% chitosan prepolymer solution with the viscosity of 9 Pa.s (25 ℃).
After 8% sodium alginate solution and 15% clay S482 solution are mixed and dispersed evenly according to the solid content mass ratio of 8: 15 under the aseptic operation, 8% chitosan prepolymer solution (the volume ratio of the three liquids is 1: 1) is added according to the solid content ratio of 8: 15: 8, the mixture is stirred at a constant speed for 30S to form a self-assembly system with strong electrostatic interaction, and the injectable marine polysaccharide full-physical crosslinked hydrogel with high solid content shown in figure 4 is formed through crosslinking. The hydrogel is injectable and has good biocompatibility, the pore diameters of the gel are respectively uniform and compact (5-10 mu m), the gel strength of 185Pa hardness and 145Pa viscosity is achieved, and the hydrogel has good mechanical stability.
Comparative example 1
5g of clay S482 powder was weighed, 3g of the powder was dissolved in 100mL of pure water, stirred at 1000rpm for 5 minutes at a high speed, and then allowed to stand for 1 hour to cure and recover fluidity. Sterilizing at 121 deg.C under 100kPa for 10min to obtain pre-processed clay solution with viscosity of 0.003 pas at 25 deg.C. Pouring the rest 2g of clay powder into the reactor, stirring at 1000rpm for 3min, increasing the solution viscosity, aging for 2 hr, recovering fluidity, and sterilizing at 121 deg.C and 100kPa for 20min to obtain 5% clay S482 pre-polymerized solution with viscosity of 25 deg.C and 0.5 Pa.s.
Weighing 8g of sodium alginate powder, dissolving 5g of sodium alginate powder in 100mL of pure water, stirring at a high speed of 1000rpm in a water bath at 60 ℃ until the powder is completely dissolved, sterilizing at 121 ℃ and 100kPa for 10min for pretreatment to obtain a preformed sodium alginate solution with the viscosity of 1.5 Pa.s at 25 ℃. Slowly pouring the rest 3g of sodium alginate powder into the mixture, stirring the mixture at 100-200rpm until the mixture is completely dispersed, and then sterilizing the mixture for 20min at the temperature of 121 ℃ and the pressure of 100kPa to obtain 8% sodium alginate solution with the viscosity of 25 ℃ of 6 Pa.s.
Weighing 8g of quaternary ammonium salt chitosan, dissolving 6g of quaternary ammonium salt chitosan in 100mL of pure water, stirring at a high speed of 1000rpm in a water bath at 60 ℃ until the powder is completely dissolved, sterilizing for 10min at 121 ℃ under 100kPa for pretreatment to obtain a prefabricated quaternary ammonium salt chitosan solution with the viscosity of 1 Pa.s at 25 ℃. Slowly pouring the remaining 2g of quaternary ammonium salt chitosan powder into the solution, stirring the solution at 100-200rpm until the quaternary ammonium salt chitosan powder is completely dissolved, and then sterilizing the solution for 20min at the temperature of 121 ℃ and the pressure of 100kPa to obtain 8% quaternary ammonium salt chitosan pre-polymerized solution with the viscosity of 25 ℃ and 8 Pa.s.
After 8% sodium alginate solution and 5% clay S482 solution are mixed and dispersed evenly according to the solid content mass ratio of 8: 5 under the aseptic operation, 8% quaternary ammonium salt chitosan prepolymer solution (the volume ratio of the three liquids is 1: 1) is added according to the solid content ratio of 8: 5: 8, and stirred at a constant speed for 30S, as shown in figure 2, the electrostatic effect of the prepolymer solution is not strong, and the crosslinking can not be carried out, so that the injectable marine polysaccharide full-physical crosslinked hydrogel with high solid content can not be formed.
Comparative example 2
15g of clay S482 powder was weighed, 10g of the powder was dissolved in 100mL of pure water, stirred at 1000rpm for 5 minutes at a high speed, and then allowed to stand for 1 hour to cure and recover fluidity. Sterilizing at 121 deg.C and 100kPa for 10min to obtain pre-prepared clay solution with viscosity of 0.01 Pa.s at 25 deg.C. Pouring the rest 5g of clay powder into the reactor, stirring at 1000rpm for 3min, increasing the solution viscosity, aging for 2 hr, recovering fluidity, and sterilizing at 121 deg.C and 100kPa for 20min to obtain 15% clay S482 pre-polymerized solution with viscosity of 25 deg.C and 3 Pa.s.
Weighing 2g of sodium alginate powder, dissolving 1g of sodium alginate powder in 100mL of pure water, stirring at a high speed of 1000rpm in a water bath at 60 ℃ until the powder is completely dissolved, sterilizing at 121 ℃ and 100kPa for 10min for pretreatment to obtain a preformed sodium alginate solution with the viscosity of 0.4 Pa.s at 25 ℃. Slowly pouring the remaining 1g of sodium alginate powder into the reactor, stirring at 100-200rpm until the sodium alginate powder is completely dispersed, and sterilizing at 121 ℃ and 100kPa for 20min to obtain a 2% sodium alginate solution with the viscosity of 25 ℃ 2 Pa.s.
Weighing 4g of quaternary ammonium salt chitosan, dissolving 3g of quaternary ammonium salt chitosan in 100mL of pure water, stirring at a high speed of 1000rpm under a water bath at 60 ℃ until the powder is completely dissolved, sterilizing for 10min at 121 ℃ under 100kPa for pretreatment, and obtaining a prefabricated quaternary ammonium salt chitosan solution with the viscosity of 0.4 Pa.s at 25 ℃. Slowly pouring the remaining 1g of quaternary ammonium salt chitosan powder into the solution, stirring the solution at 100-200rpm until the chitosan powder is completely dissolved, and then sterilizing the solution for 20min at the temperature of 121 ℃ and the pressure of 100kPa to obtain 4% quaternary ammonium salt chitosan prepolymer solution with the viscosity of 25 ℃ and the pressure of 3 Pa.s.
After a 2% sodium alginate solution and a 15% clay S482 solution are uniformly mixed and dispersed according to the solid content mass ratio of 2: 15 under aseptic operation, 4% quaternary ammonium salt chitosan prepolymer solution (the volume ratio of the three liquids is 1: 1) is added according to the solid content ratio of 2: 15: 4, and the mixture is stirred at a constant speed for 30S, so that the prepolymer solution has weak electrostatic action and can not be crosslinked, and the injectable marine polysaccharide full-physical crosslinked hydrogel with high solid content can not be formed.
The above description is only a preferred embodiment of the present invention, and therefore should not be taken as limiting the scope of the invention, which is defined by the appended claims.
Claims (9)
1. An injectable marine polysaccharide full-physical crosslinked hydrogel, which is characterized in that: the pore diameter is 5-20 μm, the hardness is 188Pa and the viscosity is 153Pa, the viscosity is 137-153Pa, the method is formed by mixing and crosslinking a preformed clay solution, a marine polycation polysaccharide pre-polymerization solution and a marine polyanion polysaccharide pre-polymerization solution according to the solid content ratio of 2-8: 5-15: 2-8,
a preformed clay solution wherein the clay is a synthetic hectorite having a concentration of 15-20% and a viscosity of 3-8 pas at 25 ℃,
the marine polycation polysaccharide pre-polymerization solution has the concentration of 7.8-8.4 percent and the viscosity of 6-9 Pa.s at 25 ℃,
the marine polyanionic polysaccharide pre-polymerization liquid has the concentration of 7.8-8.4% and the viscosity of 5-8 Pa.s at 25 ℃.
2. The injectable marine polysaccharide fully physically crosslinked hydrogel of claim 1, wherein: the type of the hectorite is RDS or S482.
3. The injectable marine polysaccharide fully physically crosslinked hydrogel of claim 1, wherein: the marine polyanionic polysaccharide in the marine polyanionic polysaccharide pre-polymerization liquid is sodium alginate or carrageenan.
4. The injectable marine polysaccharide fully physically crosslinked hydrogel of claim 1, wherein: the marine polycation polysaccharide in the marine polycation polysaccharide pre-polymerization liquid is chitosan or quaternary ammonium salt chitosan.
5. The injectable marine polysaccharide fully physically crosslinked hydrogel of claim 1, wherein: the marine polyanionic polysaccharide in the marine polyanionic polysaccharide pre-polymerization liquid is sodium alginate or carrageenan; the marine polycation polysaccharide in the marine polycation polysaccharide pre-polymerization solution is chitosan or quaternary ammonium salt chitosan.
6. The method for preparing injectable marine polysaccharide fully physically crosslinked hydrogel according to any of claims 1 to 5, characterized in that: the method comprises the following steps:
(1) dissolving part of the clay powder in pure water, stirring at 1000-1200rpm for 4-6min, standing for 0.8-1.2h for curing and recovering the fluidity; then sterilizing for 8-12min at the temperature of 120-122 ℃ and under the condition of 95-110kPa for pretreatment; then adding the rest clay powder, stirring at 1000-;
(2) dissolving part of the marine polyanionic polysaccharide powder in pure water, stirring at 1000-;
(3) dissolving part of the marine polycation polysaccharide powder in pure water or acetic acid solution, stirring at 1000-1200rpm in water bath at 60-65 ℃ until the powder is completely dissolved, then sterilizing at 120-122 ℃ and 95-110kPa for 8-12min, then adding the rest of the marine polycation polysaccharide powder, stirring at 100-300rpm until the powder is completely dispersed, and then sterilizing at 120-122 ℃ and 95-110kPa for at least 20min to obtain the marine polycation polysaccharide pre-polymerization solution;
(4) under the aseptic condition, uniformly mixing the marine polyanionic polysaccharide pre-polymerized liquid with the preformed clay solution, then adding the marine polycationic polysaccharide pre-polymerized liquid, and stirring to obtain the injectable marine polysaccharide full-physical crosslinked hydrogel.
7. The method of claim 6, wherein: the step (1) is as follows: dissolving part of clay powder in pure water, stirring at 1000rpm for 5min, standing for 1h for curing and recovering fluidity; then sterilizing for 10min at 121 ℃ under 100kPa for pretreatment; then adding the rest clay powder, stirring at 1000rpm for 5min, standing for aging for 2h and recovering fluidity, and sterilizing at 121 deg.C under 100kPa for 20min to obtain the preformed clay solution.
8. The method of claim 6, wherein: the step (2) is as follows: dissolving part of the marine polyanionic polysaccharide powder in pure water, stirring at 1000rpm in a water bath at 60-80 ℃ until the powder is completely dissolved, then sterilizing at 121 ℃ and 100kPa for 10min, then adding the rest of the marine polyanionic polysaccharide powder, stirring at 100 rpm until the powder is completely dispersed, and then sterilizing at 121 ℃ and 100kPa for 20min to obtain the marine polyanionic polysaccharide pre-polymerization liquid.
9. The method of claim 6, wherein: the step (3) is as follows: dissolving part of the marine polycation polysaccharide powder in pure water or acetic acid solution, stirring at 1000rpm under water bath at 60 ℃ until the powder is completely dissolved, then sterilizing at 121 ℃ and 100kPa for 10min, then adding the rest of the marine polycation polysaccharide powder, stirring at 100 rpm and 300rpm until the marine polycation polysaccharide powder is completely dispersed, and then sterilizing at 121 ℃ and 100kPa for 20min to obtain the marine polycation polysaccharide pre-polymerization solution.
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