An alginate polysaccharide conductive polymer material, its preparation method and application in wound healing

Abstract

The present invention belongs to the technical field of medical supplies, and discloses an alginate polysaccharide conductive polymer material, a preparation method thereof, and an application thereof in wound healing, especially in the fields of chronic wound healing and tissue regeneration. The material of the present invention is obtained by the cross-linking reaction of sodium alginate, PEDOT:PSS and calcium carbonate, has excellent biocompatibility, and has multiple functions such as hemostasis, absorption of wound effusion, keeping the wound moist, and promoting wound healing. Moreover, it will not adhere to the wound tissue, and removing the polymer material will not cause secondary damage to the wound surface. It can be applied to the fields of chronic wound healing and tissue regeneration, especially in the preparation of skin wound healing dressings. The preparation method of the present invention has the advantages that the raw materials are cheap and easy to obtain, the synthesis conditions are mild, the production route is simple, the process flow is simple, the operability is strong, and the production quality is easier to control. Compared with existing similar products, the obtained polymer material has higher safety and clinical use value.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical supplies, and particularly relates to an alginate polysaccharide conductive polymer material, a preparation method thereof, and an application thereof in wound healing, especially in the fields of chronic wound healing and tissue regeneration. Background Art

[0002] Polysaccharides are the most abundant resources in nature, and have advantages such as significant biological activity, no obvious adverse reactions, good biocompatibility, and degradability. As a natural polysaccharide polymer, sodium alginate has good affinity. When wound exudate contacts sodium alginate, due to the interaction between biological fluids and ions, sodium alginate will slightly dissolve to produce a gel matrix, which helps to protect the wound from microorganisms and provides a moist wound environment; it also helps to promote cell proliferation and tissue granulation formation, thereby promoting wound healing. A hydrogel is a three-dimensional network formed by cross-linking hydrophilic polymer chains with good biological properties, and sodium alginate is famous for its ability to form hydrogels through ionic cross-linking. Due to the ionic interaction between calcium ions and sodium alginate, the sodium alginate ion-crosslinked hydrogel will spontaneously form an anisotropic capillary structure, and the network structure of the hydrogel and 90% water content also provide space and ionic migration ability for calcium ions and chloride ions. The free state of calcium ions can greatly reduce the resistance, and its rapid movement can enhance the conductivity.

[0003] A conductive polymer is a long-chain polymer composed of carbon atoms and a conjugated electron system. After removing an electron from the intrinsic conjugated π orbit, the dispersed π electrons move freely along the unsaturated backbone as electron carriers to conduct effective electron transfer to achieve the conductive function. Currently, conductive hydrogels are prepared by doping conductive polymers, and soft and stretchable biological tissues and conductive devices are integrated to achieve the effect of promoting wound healing. Due to its unique similarity to biological tissues and conductivity, the conductive hydrogel has become an ideal substitute for traditional metal electrodes in bioelectronic interfaces. There are various types of wound repair dressings on the market at present, but most of them have cumbersome operation steps, poor biodegradability, and insufficient conductivity, which limit their biological applications. Materials with insufficient electroactivity may not be able to provide sufficient electrical signals to promote healing. Therefore, it is very crucial to develop a material with biosafety, sufficient electroactivity, and the ability to promote wound healing. Summary of the Invention

[0004] In order to overcome the above-mentioned disadvantages and deficiencies of the prior art, the primary object of the present invention is to provide an alginate polysaccharide conductive polymer material.

[0005] The alginate polysaccharide conductive polymer material of the present invention is obtained by cross-linking sodium alginate, poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS) with calcium ions. It has excellent biocompatibility and can perform multiple functions such as hemostasis, absorbing wound effusion, keeping the wound moist, and promoting wound healing. Moreover, it will not adhere to the wound tissue, and removing this polymer material will not cause secondary damage to the wound surface.

[0006] Another object of the present invention is to provide a preparation method of the above-mentioned alginate polysaccharide conductive polymer material. The preparation method of the alginate polysaccharide conductive polymer material of the present invention is simple, the raw materials are cheap and easily available, the synthesis conditions are mild, the production route is concise, the process flow is simple, the operability is strong, and the production quality is easier to control. Compared with existing similar products, the obtained product has higher safety and clinical application value.

[0007] Another object of the present invention is to provide the application of the above-mentioned alginate polysaccharide conductive polymer material, especially its application in the fields of chronic wound healing and tissue regeneration.

[0008] The object of the present invention is achieved by the following scheme:

[0009] An alginate polysaccharide conductive polymer material is obtained by cross-linking reaction of sodium alginate, poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS) with calcium carbonate.

[0010] Preferably, the mass ratio of the sodium alginate, PEDOT:PSS to calcium carbonate can be (5 - 30):(1 - 13):(0.5 - 4).

[0011] Preferably, the degree of polymerization of the sodium alginate can be 80 - 750.

[0012] Preferably, the content of sodium alginate in the material is 0.5 - 3.0 wt%.

[0013] After the alginate polysaccharide conductive polymer material of the present invention is cross-linked by using sodium alginate, PEDOT:PSS and calcium carbonate to obtain a gel, a calcium ion solution can be further coated on the surface of the gel for further cross-linking to obtain a hydrogel with further cross-linked surface.

[0014] Preferably, coating can be carried out on one side or both sides of the gel according to needs; more preferably, coating is carried out on one side.

[0015] Preferably, the calcium ion solution can be obtained by dissolving a soluble calcium salt commonly used in the art in water. Such as calcium chloride, calcium sulfate, calcium gluconate, etc.

[0016] Preferably, the concentration of calcium ions in the calcium ion solution is preferably 0.05 - 0.6 mol / L.

[0017] Preferably, the coating can cover the surface of the hydrogel with a calcium ion solution by conventional methods such as spraying and smearing.

[0018] The present invention also provides a preparation method of the above alginate polysaccharide conductive polymer material, which includes mixing sodium alginate, PEDOT:PSS and calcium carbonate uniformly in an aqueous system to obtain a mixed solution, and crosslinking the mixed solution in a mold to obtain a sodium alginate-PEDOT:PSS-calcium ion hydrogel.

[0019] Preferably, sodium alginate can be first dissolved in water to obtain a solution with a sodium alginate mass concentration of 5 g / L - 30 g / L, and then PEDOT:PSS and calcium carbonate solid are added and mixed with it.

[0020] Preferably, in the mixed solution, the mass concentration of PEDOT:PSS can be 1 g / L - 13 g / L.

[0021] Preferably, in the mixed solution, the mass concentration of calcium carbonate can be 0.5 g / L - 4 g / L.

[0022] Preferably, the crosslinking temperature can be 4°C - 25°C, and the crosslinking time can be 12 h - 24 h.

[0023] Furthermore, after crosslinking in a mold to obtain a sodium alginate-PEDOT:PSS-calcium ion hydrogel, before demolding, a calcium ion solution with a calcium ion concentration of 0.05 - 0.6 mol / L can be coated on the surface of the hydrogel, and after static crosslinking, a surface further crosslinked alginate polysaccharide conductive polymer material is obtained.

[0024] Preferably, the coating can be performed on one side or both sides of the gel according to needs; more preferably, it is performed on one side.

[0025] Preferably, the amount of the calcium ion solution used is 0.01 - 0.03 times the volume of the sodium alginate-PEDOT:PSS-calcium ion hydrogel.

[0026] Preferably, the static crosslinking can be carried out at 20°C - 25°C, and the crosslinking time can be 1 s - 10 s.

[0027] Preferably, after static crosslinking, the surface of the gel can be rinsed and the surface moisture can be blotted to further obtain the target gel.

[0028] The preparation method of the present invention has the advantages that the raw materials are cheap and easy to obtain, the synthesis conditions are mild, the production route is simple, the process flow is simple, the operability is strong, and the production quality is easier to control. Compared with existing similar products, the obtained polymer material has higher safety and clinical use value.

[0029] The alginate polysaccharide conductive polymer material of the present invention is obtained by cross-linking sodium alginate, PEDOT:PSS and calcium ions, and has excellent biocompatibility. It has multiple functions such as hemostasis, absorbing wound effusion, keeping the wound moist, and promoting wound healing. Moreover, it will not adhere to the wound tissue, and removing this polymer material will not cause secondary damage to the wound surface. It can be applied to the fields of chronic wound healing and tissue regeneration, especially in the preparation of skin wound healing dressings. Description of the Drawings

[0030] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention, and therefore should not be regarded as a limitation of the scope. For those of ordinary skill in the art, without creative efforts, other related drawings can also be obtained based on these drawings.

[0031] Figures 1 - 2 Scanning electron micrograph of the alginate polysaccharide conductive polymer material prepared in Example 1.

[0032] Figure 3 Energy dispersive X-ray spectrum of the alginate polysaccharide conductive polymer material prepared in Example 1.

[0033] Figure 4 Swelling curve of the alginate polysaccharide conductive polymer material prepared in Example 1.

[0034] Figure 5 Cyclic compression curve of the alginate polysaccharide conductive polymer material prepared in Example 1. Among them, cycle1 represents one compression, and cycle5 represents five cyclic compressions.

[0035] Figure 6 Strain sweep curve of the alginate polysaccharide conductive polymer material prepared in Example 1. Among them, SA-Ca-PEDOT:PSS / Ca G' represents the storage modulus of the alginate polysaccharide conductive polymer material, and SA-Ca-PEDOT:PSS / Ca G” represents the loss modulus of the alginate polysaccharide conductive polymer material.

[0036] Figure 7 Alternating strain sweep curve of the alginate polysaccharide conductive polymer material prepared in Example 1. Among them, SA-Ca-PEDOT:PSS / Ca G' represents the storage modulus of the alginate polysaccharide conductive polymer material, and SA-Ca-PEDOT:PSS / CaG” represents the loss modulus of the alginate polysaccharide conductive polymer material.

[0037] Figure 8 Conductivity of the alginate polysaccharide conductive polymer materials prepared in Example 1, Example 2 and Example 3.

[0038] Figure 9 These are the results of the wound healing test. Among them, SA-Ca-PEDOT:PSS / Ca represents the alginate polysaccharide conductive polymer material. Specific embodiments

[0039] The present invention will be further described in detail below in conjunction with embodiments, but the implementation manners of the present invention are not limited thereto. The materials involved in the following embodiments can be obtained from commercial channels without special instructions. The methods are conventional methods without special instructions.

[0040] The present invention provides an alginate polysaccharide conductive polymer material, which is obtained by cross-linking reaction of sodium alginate, poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS) and calcium carbonate.

[0041] In the present invention, the mass ratio of the sodium alginate, PEDOT:PSS and calcium carbonate can be (5-30):(1-13):(0.5-4). In one embodiment, the dosage ratio of the sodium alginate, PEDOT:PSS and calcium carbonate is a mass ratio of 5:1:0.5; in another embodiment, the dosage ratio of the sodium alginate, PEDOT:PSS and calcium carbonate is a mass ratio of 15:6:2; in still another embodiment, the dosage ratio of the sodium alginate, PEDOT:PSS and calcium carbonate is a mass ratio of 30:13:4.

[0042] In the present invention, the degree of polymerization of the sodium alginate can be 80-750. In one embodiment, the degree of polymerization of the sodium alginate is 100-700.

[0043] In the present invention, the content of sodium alginate in the material can be the dosage of conventional hydrogel, such as 0.5-3.0 wt%. In one embodiment, the content of sodium alginate in the material is 0.5 wt%; in another embodiment, the content of sodium alginate in the material is 1.5 wt%; in still another embodiment, the content of sodium alginate in the material is 3 wt%.

[0044] In the present invention, the PEDOT:PSS is a conductive polymer, which mainly provides a conductive path for the bioelectricity of cells themselves and promotes signal transmission in the form of assisting endogenous bioelectric conduction. Conductive polymers essentially act by changing the bioelectric field of cells. Electrical stimulation promotes nerve regeneration by promoting the polarization of macrophages from the M1 phenotype to the M2 phenotype, and promotes cell proliferation and migration, thereby promoting epithelialization and nerve regeneration. In the present invention, PEDOT:PSS is cross-linked with calcium ions and sodium alginate, and can be concentrated locally at the wound during wound treatment, effectively exerting the electroactivity of PEDOT:PSS and its functions in wound healing, skin tissue regeneration, etc.

[0045] In the present invention, the calcium carbonate used is basically insoluble in water. Compared with the traditional method of forming a gel by using a metal ion solution such as calcium chloride solution and sodium alginate, the present invention uses calcium carbonate to form a gel with PEDOT:PSS and sodium alginate. Under the acidic condition of PEDOT:PSS, the calcium ions gradually released and dissociated from calcium carbonate crosslink with PEDOT:PSS and sodium alginate. The obtained crosslinked network structure is more uniform and flexible, and the combination is more firm, greatly improving the mechanical properties and structural stability of the obtained gel material.

[0046] After the alginate polysaccharide conductive polymer material of the present invention forms a gel by the crosslinking reaction of sodium alginate, PEDOT:PSS and calcium carbonate, a calcium ion solution can be further coated on the surface of the gel for further crosslinking to obtain a hydrogel with further surface crosslinking.

[0047] In the present invention, coating can be carried out on one or both sides of the gel as needed; more preferably, coating is carried out on one side.

[0048] In the present invention, the calcium ion solution can be obtained by dissolving a soluble calcium salt commonly used in the art in water. Such as calcium chloride, calcium sulfate, calcium gluconate, etc. In one embodiment, the calcium ion solution is an aqueous solution of calcium chloride; in another embodiment, the calcium ion solution is an aqueous solution of calcium sulfate; in still another embodiment, the calcium ion solution is an aqueous solution of calcium gluconate.

[0049] In the present invention, the concentration of calcium ions in the calcium ion solution is preferably 0.05 - 0.6 mol / L. In one embodiment, the concentration of calcium ions in the calcium ion solution is 0.05 M; in another embodiment, the concentration of calcium ions in the calcium ion solution is 0.2 M; in still another embodiment, the concentration of calcium ions in the calcium ion solution is 0.5 M.

[0050] In the present invention, the coating can cover the surface of the hydrogel with the calcium ion solution by conventional methods such as spraying and smearing. In one embodiment, the coating can cover the surface of the hydrogel with the calcium ion solution by spraying; in another embodiment, the coating can cover the surface of the hydrogel with the calcium ion solution by smearing.

[0051] The present invention also provides a preparation method of the above-mentioned alginate polysaccharide conductive polymer material, which includes mixing sodium alginate, PEDOT:PSS and calcium carbonate evenly in an aqueous system to obtain a mixed solution, and crosslinking in a mold to obtain a sodium alginate - PEDOT:PSS - calcium ion hydrogel.

[0052] In the present invention, sodium alginate can be first dissolved in water to obtain a solution with a sodium alginate mass concentration of 5 g / L - 30 g / L, and then mixed with PEDOT:PSS and calcium carbonate. In one embodiment, the mass concentration of sodium alginate in the solution is 5 g / L; in another embodiment, the mass concentration of sodium alginate in the solution is 15 g / L; in yet another embodiment, the mass concentration of sodium alginate in the solution is 30 g / L.

[0053] In the present invention, sodium alginate can be first dissolved in water to obtain a sodium alginate solution, then mixed and stirred evenly with PEDOT:PSS, and finally calcium carbonate is added and stirred evenly to obtain the mixed solution.

[0054] In the present invention, in the mixed solution, the mass concentration of PEDOT:PSS can be 1 g / L - 13 g / L. In one embodiment, the mass concentration of PEDOT:PSS is 1 g / L; in another embodiment, the mass concentration of PEDOT:PSS is 6 g / L; in yet another embodiment, the mass concentration of PEDOT:PSS is 13 g / L.

[0055] In the present invention, in the mixed solution, the mass concentration of calcium carbonate can be 0.5 g / L - 4 g / L. In one embodiment, the mass concentration of calcium carbonate is 0.5 g / L; in another embodiment, the mass concentration of calcium carbonate is 2 g / L; in yet another embodiment, the mass concentration of calcium carbonate is 4 g / L.

[0056] In the present invention, the cross-linking temperature can be 4°C - 25°C, and the cross-linking time can be 12 h - 24 h.

[0057] In the present invention, after cross-linking in a mold to obtain a sodium alginate - PEDOT:PSS - calcium ion hydrogel, before demolding, a calcium ion solution with a calcium ion concentration of 0.05 - 0.6 mol / L can be coated on the surface of the hydrogel, and after static cross-linking, a surface further cross-linked alginate polysaccharide conductive polymer material is obtained.

[0058] In the present invention, the amount of the calcium ion solution used is 0.01 - 0.03 times the volume of the sodium alginate - PEDOT:PSS - calcium ion hydrogel. In one embodiment, it is 0.01 times; in another embodiment, it is 0.02 times; in yet another embodiment, it is 0.03 times.

[0059] In the present invention, the static cross-linking can be carried out at 20°C - 25°C, and the cross-linking time can be 1 s - 10 s.

[0060] In the present invention, after static cross-linking, the surface of the gel can be rinsed and the surface moisture can be blotted dry to further obtain the target gel.

[0061] In the present invention, coating can be carried out on one side or both sides of the gel as required; more preferably, coating is carried out on one side.

[0062] In the present invention, stirring is preferably magnetic stirring at room temperature. The rotation speed of the magnetic stirring is preferably 600 rpm, and the stirring time is preferably 10 h - 14 h for the same or different times.

[0063] The preparation method of the present invention has raw materials that are cheap and easily available, mild synthesis conditions, a simple production route, a simple process flow, strong operability, and the production quality is easier to control. Compared with existing similar products, the obtained polymer material has higher safety and clinical application value.

[0064] The alginate polysaccharide conductive polymer material of the present invention is obtained by cross-linking sodium alginate, PEDOT:PSS with calcium ions. It has excellent biocompatibility and can have multiple functions such as hemostasis, absorbing wound effusion, keeping the wound moist, and promoting wound healing. Moreover, it will not adhere to the wound tissue, and removing this polymer material will not cause secondary damage to the wound surface. It can be applied to the fields of chronic wound healing and tissue regeneration, especially in the preparation of skin wound healing dressings.

[0065] The present invention has no special limitation on the preparation method of the skin wound healing dressing, and the corresponding dressing preparation method can be adopted. The present invention has no special limitation on the existence form and dosage of the alginate polysaccharide conductive polymer material in the skin wound dressing, and the conventional existence form and dosage in the dressing can be adopted.

[0066] In the present invention, all reagents in the following examples and test examples are commercially available reagents, and the purity is chromatographic pure or analytical pure unless otherwise specified. The dosage of each component is in parts by mass or volume, in g and mL.

[0067] Example 1

[0068] (1) Take 1.5 parts by mass of sodium alginate with a polymerization degree of 100 - 700 and dissolve it in 100 parts by volume of deionized water to obtain a sodium alginate solution. Take 0.6 parts by mass of PEDOT:PSS and mix it with the sodium alginate solution and stir evenly. Stir magnetically at room temperature for 12 h to obtain a sodium alginate - PEDOT:PSS solution;

[0069] (2) Disperse 0.2 parts by mass of calcium carbonate powder in the above sodium alginate - PEDOT:PSS solution and stir evenly to obtain a sodium alginate - PEDOT:PSS - calcium carbonate mixed solution;

[0070] (3) Pour the above mixed solution into the mold, and cross-link at 4 °C for 24 h to obtain a sodium alginate - PEDOT:PSS - calcium ion hydrogel (SA - Ca - PEDOT:PSS);

[0071] (4) Dissolve calcium chloride in water to prepare a solution with a calcium ion concentration of 0.1 M;

[0072] (5) Spray a calcium chloride solution with a volume 0.02 times that of the hydrogel on the surface of the sodium alginate - PEDOT:PSS - calcium ion hydrogel. After cross - linking for 3 s, demold, rinse the surface with deionized water, and blot the water on the surface of the hydrogel with filter paper to obtain the sodium alginate polysaccharide conductive polymer material (SA - Ca - PEDOT:PSS / Ca).

[0073] Example 2

[0074] (1) Take 1 part by mass of sodium alginate with a degree of polymerization of 100 - 700, dissolve it in 100 parts by volume of deionized water to obtain a sodium alginate solution. Take 0.2 part by mass of PEDOT:PSS and mix it evenly with the sodium alginate solution, and stir magnetically at room temperature for 12 h to obtain a sodium alginate - PEDOT:PSS solution;

[0075] (2) Disperse 0.01 part by mass of calcium carbonate powder in the above - mentioned sodium alginate - PEDOT:PSS solution, and stir evenly to obtain a sodium alginate - PEDOT:PSS - calcium carbonate mixed solution;

[0076] (3) Pour the mixed solution into the mold, and cross - link at 25 °C for 24 h to obtain a sodium alginate - PEDOT:PSS - calcium ion hydrogel;

[0077] (4) Dissolve calcium chloride in water to prepare a solution with a calcium ion concentration of 0.05 M;

[0078] (5) Spray a calcium chloride solution with a volume 0.01 times that of the hydrogel on the sodium alginate - PEDOT:PSS - calcium ion hydrogel. After cross - linking for 3 s, demold, rinse the surface with deionized water, and blot the water on the surface of the hydrogel with filter paper to obtain the sodium alginate polysaccharide conductive polymer material (SA - Ca - PEDOT:PSS / Ca).

[0079] Example 3

[0080] (1) Take 3 parts by mass of sodium alginate with a degree of polymerization of 100 - 700, dissolve it in 100 parts by volume of deionized water to obtain a sodium alginate solution. Take 1.3 parts by mass of PEDOT:PSS and mix it evenly with the sodium alginate solution, and stir magnetically at room temperature for 12 h to obtain a sodium alginate - PEDOT:PSS solution;

[0081] (2) Disperse 0.4 part by mass of calcium carbonate powder in the above - mentioned sodium alginate - PEDOT:PSS solution, and stir evenly to obtain a sodium alginate - PEDOT:PSS - calcium carbonate mixed solution;

[0082] (3) Pour the mixed solution into In the mold, crosslink at 4 °C for 12 h to obtain sodium alginate-PEDOT:PSS-calcium ion hydrogel (SA-Ca-PEDOT:PSS).

[0083] (4) Dissolve calcium chloride in water to prepare a solution with a calcium ion concentration of 0.2 M.

[0084] (5) Spray a calcium chloride solution with a volume 0.03 times that of the hydrogel on the sodium alginate-PEDOT:PSS-calcium ion hydrogel, take it out after crosslinking for 5 s, rinse with deionized water, and blot the surface moisture of the hydrogel with filter paper to obtain a sodium alginate polysaccharide conductive polymer material (SA-Ca-PEDOT:PSS / Ca).

[0085] Example 4

[0086] (1) Take 1.5 parts by mass of sodium alginate with a polymerization degree of 100 - 700 and dissolve it in 100 parts by volume of deionized water to obtain a sodium alginate solution. Take 0.6 parts by mass of PEDOT:PSS and mix it evenly with the sodium alginate solution, and stir magnetically at room temperature for 12 h to obtain a sodium alginate-PEDOT:PSS solution.

[0087] (2) Disperse 0.2 parts by mass of calcium carbonate powder in the above sodium alginate-PEDOT:PSS solution and stir evenly to obtain a sodium alginate-PEDOT:PSS-calcium carbonate mixed solution.

[0088] (3) Pour the above mixed solution into the mold, crosslink at 4 °C for 24 h to obtain sodium alginate-PEDOT:PSS-calcium ion hydrogel (SA-Ca-PEDOT:PSS).

[0089] (4) Dissolve calcium gluconate in water to prepare a solution with a calcium ion concentration of 0.15.

[0090] (5) Spray a calcium gluconate solution with a volume 0.02 times that of the hydrogel on the surface of the sodium alginate-PEDOT:PSS-calcium ion hydrogel. After crosslinking for 3 s, demold, rinse the surface with deionized water, and blot the surface moisture of the hydrogel with filter paper to obtain a sodium alginate polysaccharide conductive polymer material (SA-Ca-PEDOT:PSS / Ca).

[0091] The above-prepared polymer materials were detected by scanning electron microscopy and energy-dispersive X-ray spectroscopy; the properties of the polymer materials were verified by swelling ratio tests, mechanical property tests, rheological property tests, electrical conductivity tests, and wound healing tests. In the examples, calcium alginate hydrogel was used as a comparison, and its preparation method was to replace 0.2 parts by mass of calcium carbonate in the components of Example 1 with calcium chloride having the same calcium ion concentration, and the remaining operations were the same.

[0092] (1) pH detection

[0093] The pH values of the system before and after adding calcium carbonate to the alginate polysaccharide conductive polymer material were detected. The pH measurement method of pH(SA-PEDOT:PSS-Ca / Ca) was to soak the SA-PEDOT:PSS-Ca / Ca hydrogel in deionized water for 12 h and then measure the pH of the deionized water. The pH measurement method of calcium alginate hydrogel was the same as that of SA-PEDOT:PSS-Ca / Ca. The results are shown in Table 1.

[0094] Table 1

[0095] Sample pH SA - PEDOT:PSS SA - PEDOT:PSS - Ca / Ca Calcium alginate Example 1 3.06±0.02 6.96±0.02 5.74±0.02 Example 2 3.40±0.01 7.46±0.01 5.92±0.02 Example 3 3.58±0.02 6.92±0.03 5.22±0.01

[0096] As can be seen from the table, the SA-PEDOT:PSS-Ca / Ca hydrogel of the present invention effectively solves the acidic problem brought by PEDOT:PSS in the existing SA-PEDOT:PSS hydrogel by using calcium carbonate, and is more suitable for the preparation of wound healing materials.

[0097] (2) Scanning electron microscope (SEM) detection

[0098] Take the alginate polysaccharide conductive polymer material and calcium alginate hydrogel obtained in Example 1, submerge, quench, and brittlely break them. After freeze-drying, cut them into regular and appropriate sizes. Stick the brittlely broken alginate polysaccharide conductive polymer material on the copper stage with conductive glue and spray gold on it. Use SEM to observe the microscopic morphology. Taking the calcium alginate hydrogel as a comparison, the detection results are as Figures 1 - 2 shown. Figure 1 This is the scanning electron microscope image of the alginate polysaccharide conductive polymer material prepared in Example 1 of the present invention, Figure 2 and this is the scanning electron microscope image of the calcium alginate hydrogel.

[0099] As can be seen from the figure, the alginate polysaccharide conductive polymer material of the present invention has a continuous microporous structure. These uniformly distributed pores make the obtained hydrogel present a homogeneous and loose structure inside and outside, ensuring the strong water absorption and water retention capabilities of the hydrogel, and having the characteristics of a cytoplasmic matrix-like. At the same time, the pore diameter in the hydrogel promotes the migration of ions in the pores, thereby enhancing its conductivity. While the calcium alginate hydrogel has fewer and non-uniform pore structures.

[0100] (3) Energy dispersive X-ray spectrometer (EDS) elemental analysis

[0101] Take the alginate polysaccharide conductive polymer material obtained in Example 1, submerge it, quench it, and brittlely break it. After freeze-drying, cut it into a regular and appropriate size, paste the brittlely broken alginate polysaccharide conductive polymer material on a copper stage with conductive glue and spray gold to cover it, and perform EDS scanning to analyze the types and contents of chemical elements in the selected area. The test results are as Figure 3 shown. It can be seen from the figure that the elements are evenly dispersed in the alginate polysaccharide conductive polymer material. The C and O elements come from organic matter, the Na element comes from sodium alginate, the Ca element comes from calcium carbonate, and the S element is a representative element of PEDOT:PSS, indicating that the conductive material PEDOT:PSS is evenly dispersed in the alginate polysaccharide conductive polymer material.

[0102] (4) Swelling ratio test

[0103] Take the alginate polysaccharide conductive polymer material prepared in Example 1 and weigh the initial mass M0. Put it into a 50 mL centrifuge tube. Each group of samples has three parallel samples. Add 10 mL of PBS buffer solution with pH = 7.4 to each centrifuge tube, and place the centrifuge tube in a constant temperature shaker at 37 °C and shake (150 rpm). Take it out at different time points, absorb the surface moisture and then weigh it. When the mass change of the hydrogel is not significant, record it as M s . The calculation formula for the swelling ratio (S) of the sample: S% = (M s - M0) / M0 × 100%. The results of the swelling ratio test are shown in Figure 4 . Among them, a is the swelling curve of the alginate polysaccharide conductive polymer material prepared in Example 1, and b is the swelling curve of the calcium alginate hydrogel. It can be seen from the figure that the alginate polysaccharide conductive polymer material of the present invention reaches the swelling equilibrium at 12 h, and the swelling ratio is 120%, which means that the hydrogel can effectively absorb exudates and maintain its shape without being rapidly released, ensuring that the moisture content of the wound bed is appropriate to promote wound healing. While the calcium alginate hydrogel reaches the swelling equilibrium at 8 h, and the swelling ratio is 58%.

[0104] (5) Cyclic compression curve

[0105] Take the alginate polysaccharide conductive polymer material prepared in Example 1. Each group of samples has at least three parallel samples. Place the samples on a testing machine and compress the samples at a rate of 3 mm / min, with a maximum compression deformation of 60%. The cyclic compression is the same as the ordinary compression experiment operation, and it is compressed 5 times. The values of stress and strain are recorded starting from the compression displacement of zero, and the compression stroke is 60%. Calculate the strain and stress by testing the displacement and load to obtain the stress-strain curve. Calculation formula: σ = 4F / D 2 ; ε = ΔL / L; where σ is the stress, ε is the strain, F is the load, D is the sample diameter, ΔL is the displacement, and L is the sample thickness. Three samples are tested for each group. The results of the cyclic compression curve are shown inFigure 5 As can be seen from the figure, the alginate polysaccharide conductive polymer material of the present invention still has good resilience after being cyclically compressed five times, indicating that it can provide auxiliary pressure to the wound surface, help stop bleeding, and avoid squeezing the wound surface.

[0106] (6) Strain sweep curve

[0107] The alginate polysaccharide conductive polymer material prepared in Example 1 was placed on the rheometer platform for strain sweep testing at a frequency of 1 Hz, a temperature of 25 °C, and the results of the strain sweep curve are as Figure 6 shown. As can be seen from the figure, in the strain sweep mode, for the alginate polysaccharide conductive polymer material of the present invention, as the strain increases, G' is always greater than G". Continuously applying a greater strain to the gel, the hydrogel will reach the critical point of G' = G". When the strain is greater than 28.39%, G' and G" begin to decrease, and the decreasing speed of G' is greater than G', indicating that the alginate polysaccharide conductive polymer material has appropriate mechanical properties and viscoelasticity, and its flexibility is beneficial to covering irregular wound surfaces.

[0108] (7) Alternating strain sweep curve

[0109] The alginate polysaccharide conductive polymer material prepared in Example 1 was placed on the rheometer platform for alternating strain sweep testing with a small strain of 1% and a large strain of 200%, a frequency of 1 Hz, and a temperature of 25 °C. The results of the alternating strain sweep curve are as Figure 7 shown. As can be seen from the figure, for the alginate polysaccharide conductive polymer material, at low strains, G' is always higher than G", and at higher strains, G" is always higher than G'. Moreover, after three cycles, G' and G" can still quickly recover, indicating that the alginate polysaccharide conductive polymer material has good self-healing properties.

[0110] (8) Electrical property testing

[0111] The alginate polysaccharide conductive polymer materials prepared in Example 1, Example 2, and Example 3 were taken, with at least three parallel samples in each group. The two sides of the hydrogel were connected to a universal source meter to measure the I-V curve, and the resistance of the hydrogel was calculated through Ohm's law, and then the conductivity was obtained. Formula: R = U / I; ρ = R×A / L; σ = 1 / ρ = L / RA; where R is the resistance, U is the voltage, I is the current, ρ is the resistivity, A is the cross-sectional area of the hydrogel, L is the length of the hydrogel, and σ is the conductivity of the hydrogel. The results of the electrical properties are as Figure 8 shown. As can be seen from the figure, the conductivities of the alginate polysaccharide conductive polymer materials of the present invention are 1.46×10 -3 , 5.35×10 -4 and 1.99×10 -3 S / cm, and the conductivity of human skin is 2.6×10-3 from 1×10 -7 Between S / cm, the matching of the conductivity with the conductivity of normal skin helps to maximize the application of current to damaged tissues, thereby increasing the wound healing effect. The results show that the alginate polysaccharide conductive polymer material of the present invention has suitable electrical properties for promoting wound healing.

[0112] (9) Results of wound healing test

[0113] SPF-grade male Sprague-Dawley (SD) rats at 6 to 8 weeks old were randomly divided into 6 groups, with 3 rats in each group. They were individually housed in ventilated cages at a temperature of (21±2) °C and a relative humidity of (55±10)%. Food and water were freely available. After anesthetizing the rats by intraperitoneal injection of 20 mg / mL sodium pentobarbital (dose: 2 mL / kg), their backs were completely exposed by shaving and using depilatory cream. The surgical area was disinfected with 75% ethanol. The skin of the rats was gently lifted, and then a magnet with a diameter of 2.0 cm was used to clamp the skin to create local ischemic pressure. After maintaining the compression state for 12 h, the magnet was removed to allow the skin to recover blood flow for 12 h. This was repeated continuously for 3 to 4 days to form ischemic ulcers. All animal experiments were carried out in a specific pathogen-free environment. After successful pressure ulcer modeling, medical bandages and commercial Tegaderm (3M, 1624WB) films were used as the negative and positive control groups, respectively. The experimental groups were the ES group alone, the SA-Ca-PEDOT:PSS / Ca group (gel group of Example 1), the ES+SA-Ca-HCL / Ca group, and the ES+SA-Ca-PEDOT:PSS / Ca group. For ES, two platinum electrodes connected to a DC power supply were placed on both sides of the wound every day, and an electric field of 100 mV / mm was applied for 30 minutes. After the electrical stimulation, a multimeter was used to monitor the wound resistance. The dressing and bandage were removed every day, and the wound was gently debrided with normal saline and cotton swabs. All materials were fixed on the injured area with elastic band-aids and secondarily fixed with medical bandages. The wound was photographed with a camera at 0, 3, 7, and 10 days, and the wound area was calculated using ImageJ software. The degree of wound healing was calculated by the percentage of wound area contraction (WA): WA (%) = At / A0×100%; where A0 is the initial wound area and At is the wound area on the t-th day. The results are as Figure 9 shown. As can be seen from the figure, the alginate polysaccharide conductive polymer material of the present invention can significantly promote wound healing.

[0114] In summary, the present invention provides an alginate polysaccharide conductive polymer material, which has the effect of promoting wound healing. At the same time, the main raw materials of the preparation method of the material of the present invention are widely sourced, low in cost, with mild synthesis conditions, a simple production route, a simple process flow, strong operability, and easier control of production quality. Compared with existing similar products, it has safety and clinical use value.

[0115] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. An alginate polysaccharide conductive polymer dressing, characterized in that The invention is obtained by cross-linking reaction of sodium alginate, poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate and calcium carbonate; the mass ratio of the sodium alginate, poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate and calcium carbonate is (5-30): (1-13): (0.5-4).

2. The alginate polysaccharide conductive polymer dressing according to claim 1, characterized in that The content of sodium alginate in the material is 0.5-3.0wt%.

3. The alginate polysaccharide conductive polymer material dressing according to claim 1, characterized in that: The polymerization degree of the sodium alginate is 80-750.

4. The alginate polysaccharide conductive polymer material dressing according to claim 1, characterized in that A calcium ion solution is further coated on the surface of the gel for further cross-linking, thereby obtaining a hydrogel with further cross-linked surface.

5. The alginate polysaccharide conductive polymer material dressing according to claim 4, characterized in that: The concentration of calcium ions in the calcium ion solution is 0.05-0.6 mol / L.

6. A method for preparing the alginate polysaccharide conductive polymer dressing according to any one of claims 1 to 5, characterized in that The method comprises mixing sodium alginate, poly (3, 4-ethylenedioxythiophene) -polystyrene sulfonate and calcium carbonate in a water system to obtain a mixed solution, placing the mixed solution in a mold for cross-linking to obtain a sodium alginate-PEDOT:PSS-calcium ion hydrogel.

7. The preparation method according to claim 6, characterized in that: In the mixed solution, the mass concentration of poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate is 1g / L-13g / L; the mass concentration of calcium carbonate is 0.5g / L-4g / L.

8. The preparation method according to claim 6, characterized in that After the sodium alginate-PEDOT:PSS-calcium ion hydrogel is obtained by cross-linking in the mold, a calcium ion solution with a calcium ion concentration of 0.05-0.6 mol / L is coated on the surface of the hydrogel, and after static cross-linking, an alginate polysaccharide conductive polymer material with further cross-linking on the surface is obtained.

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