Disclosure of Invention
The first aim of the invention is to provide a preparation method of a temperature-sensitive hydrogel wound dressing, which has simple process and good biocompatibility.
The second aim of the invention is to provide a preparation method of the temperature-sensitive hydrogel wound dressing.
The third purpose of the invention is that the carboxyl-containing bioactive molecule-based single-component temperature-sensitive hydrogel wound dressing has important application in promoting wound healing and tissue regeneration of multi-drug-resistant bacteria infection.
In order to achieve the purpose, the invention is realized by adopting the following technical scheme:
a method for preparing a temperature-sensitive hydrogel wound dressing, which comprises the following steps:
Heating and melting the block thermosensitive gel copolymer, adding bioactive molecules containing carboxyl, melting, performing melting reaction, purifying and freeze-drying to obtain a multifunctional polymer;
Dispersing the multifunctional polymer into PBS buffer solution, and forming single-component hydrogel after complete dispersion to obtain the multifunctional single-component carboxyl-containing bioactive molecule-based thermosensitive hydrogel wound auxiliary material.
As a further development of the invention, the carboxyl-containing bioactive molecules are itaconic acid, salicylic acid, ferulic acid, citric acid, chlorogenic acid, aspirin, diclofenac, folic acid, ibuprofen, indomethacin, succinic acid, maleic acid, malic acid, gamma-linolenic acid or tretinoin.
As a further improvement of the invention, the block thermosensitive gel copolymer is a thermosensitive gel triblock copolymer, a thermosensitive gel diblock copolymer and a thermosensitive gel multiblock copolymer;
The thermosensitive gel triblock copolymer can be pluronic, polylactic acid-glycolic acid copolymer-polyethylene glycol-polylactic acid-glycolic acid copolymer.
The temperature-sensitive gel diblock copolymer may be a polypropylene-poly (n-isopropyl acrylamide) block polymer.
The thermosensitive gel multiblock copolymer may be poly (N-isopropylacrylamide) -pluronic-poly (N-isopropylacrylamide).
As a further improvement of the invention, the molar ratio of the block thermosensitive gel copolymer to the carboxyl-containing bioactive molecule is 1 (0.25-4).
As a further improvement of the invention, the conditions of the melting reaction are that the temperature is 80-180 ℃, the reaction time is 4-16 hours or the microwave power is 500-1000W for 30-180 minutes.
As a further improvement of the invention, the multifunctional polymer is obtained and then is subjected to post-treatment, and the post-treatment method comprises the following steps:
After the reaction, the multifunctional polymer is dissolved in water, dialyzed, freeze-dried and refrigerated at low temperature.
As a further improvement of the present invention, the solid-to-liquid ratio of the polymer to PBS buffer is (50 mg-450 mg)/1 mL.
As a further improvement of the present invention, the gel forming temperature of the one-component hydrogel is 4-37 ℃.
The multifunctional single-component carboxyl-containing bioactive molecule-based thermosensitive hydrogel wound dressing is characterized by being prepared by the preparation method.
The multifunctional single-component carboxyl-containing bioactive molecule-based thermosensitive hydrogel wound dressing prepared by the preparation method is applied to the preparation of medicines for promoting wound healing and tissue regeneration of multi-drug-resistant bacteria infection.
Compared with the prior art, the invention has the following beneficial effects:
the method takes a carboxyl-containing bioactive molecule and a block thermosensitive gel copolymer as raw materials, and obtains the multifunctional Wen Mincheng gel poly (CCBM-BTGP) polymer through high-temperature melting reaction. And finally, dissolving the freeze-dried poly (CCBM-BTGP) polymer in PBS buffer solution to obtain the multifunctional single-component carboxyl-containing bioactive molecule-based thermosensitive hydrogel wound dressing. The preparation method is simple, no organic solvent is remained, and the used raw materials are green and environment-friendly, convenient to operate and low in cost. The dressing prepared by the method can be used for wound healing and tissue regeneration of multi-drug resistant bacterial infection. Experimental results prove that the multifunctional single-component carboxyl-containing bioactive molecule-based temperature-sensitive hydrogel wound dressing prepared by the method has good biocompatibility and good biological effect in vivo and in vitro. The prepared multifunctional single-component carboxyl-containing bioactive molecule-based thermosensitive hydrogel wound dressing (poly (itaconic acid-F127, FIA)) has the advantages of simple preparation method process, environment-friendly raw materials and low cost, can show good antibacterial and anti-inflammatory properties, can accelerate wound healing and can promote tissue regeneration, so that the hydrogel wound dressing has good application prospect in wound healing of multi-drug-resistant bacterial infection.
Detailed Description
In order to make the technical problems, technical schemes and beneficial effects to be solved more clear, the application is further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the application.
In the present application, the term "and/or" describes an association relationship of an association object, which means that three relationships may exist, for example, a and/or B may mean that a exists alone, a and B exist together, and B exists alone. Wherein A, B may be singular or plural. The character "/" generally indicates that the context-dependent object is an "or" relationship.
In the present application, "at least one" means one or more, and "a plurality" means two or more. "at least one of" or the like means any combination of these items, including any combination of single item(s) or plural items(s). For example, "at least one (a), b, or c)", or "at least one (a, b, and c)", may each represent a, b, c, a-b (i.e., a and b), a-c, b-c, or a-b-c, wherein a, b, c may be single or multiple, respectively.
It should be understood that, in various embodiments of the present application, the sequence number of each process described above does not mean that the execution sequence of some or all of the steps may be executed in parallel or executed sequentially, and the execution sequence of each process should be determined by its functions and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.
The terminology used in the embodiments of the application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in this application and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.
The weights of the relevant components mentioned in the description of the embodiments of the present application may refer not only to the specific contents of the components, but also to the proportional relationship between the weights of the components, so long as the contents of the relevant components in the description of the embodiments of the present application are scaled up or down within the scope of the disclosure of the embodiments of the present application. Specifically, the mass described in the specification of the embodiment of the application can be a mass unit which is known in the chemical industry field such as mu g, mg, g, kg.
The temperature-sensitive hydrogel (called temperature-sensitive hydrogel for short) is an in-situ gel with a temperature-responsive state closely related to temperature, is in a liquid state with good fluidity under a low-temperature condition, becomes a semisolid state under the temperature of a human body, has good adhesiveness, and can be well applied to a tissue injury part. These advantages make temperature-sensitive hydrogels one of the hot spots of biotechnology research. It is very promising to develop a single-component multifunctional thermosensitive hydrogel based on carboxyl-containing bioactive molecules for promoting healing of multi-drug resistant bacterial infection wounds. So far, research on single-component carboxyl-containing bioactive molecule-based multifunctional temperature-sensitive hydrogel dressing for wound healing and tissue regeneration of multi-drug-resistant bacteria infection has not been reported.
The invention provides a preparation method of a multifunctional single-component temperature-sensitive hydrogel wound dressing, which comprises the following steps:
Melting the block thermosensitive gel copolymer (BTGP) at high temperature, adding a carboxyl-containing bioactive molecule (CCBM) to melt under the protection of inert gas, and carrying out a melting reaction under a vacuum condition to obtain a multifunctional poly (CCBM-BTGP) polymer;
Purifying, freeze-drying and collecting the poly (CCBM-BTGP) polymer;
dispersing a multifunctional poly (CCBM-BTGP) polymer into PBS buffer solution, and after the poly (CCBM-BTGP) polymer is completely dispersed, regulating the temperature to form single-component hydrogel, thus obtaining the multifunctional single-component carboxyl-containing bioactive molecule-based thermosensitive hydrogel wound auxiliary material.
The carboxyl-containing bioactive molecules have safe, nontoxic and high permeability characteristics, and have anti-inflammatory and antioxidant activities, and are widely used in various biomedicines. The block thermosensitive gel copolymer has temperature responsive gel behavior, good biocompatibility, environment friendliness, low cost and easy obtainment.
Therefore, in the invention, the carboxyl-containing bioactive molecules are grafted onto the block thermosensitive gel copolymer to obtain the multifunctional single-component carboxyl-containing bioactive molecule-based thermosensitive hydrogel wound dressing, which has good biocompatibility and good antibacterial and anti-inflammatory properties, and is a multifunctional single-component hydrogel wound dressing for accelerating wound healing of multi-drug-resistant bacterial infection and promoting tissue repair.
The invention is described in further detail below with reference to the attached drawing figures:
The invention discloses a preparation method of a multifunctional single-component temperature-sensitive hydrogel wound dressing, which comprises the following steps:
1) First, melt esterification is carried out to obtain a polymer. Firstly, 1mM of block thermosensitive gel copolymer (such as F127) is dissolved at high temperature, then 0.25-4 mM of carboxyl-containing bioactive molecule is added, the carboxyl-containing bioactive molecule is dissolved at 80-180 ℃ under the inert gas atmosphere, and then the temperature is kept at 80-180 ℃ for 4-16 hours under the vacuum condition to obtain the multifunctional polymer, or microwave heating reaction is adopted, and the power of the microwave heating reaction is 500-1000W for 30-180 minutes.
Wherein the molar ratio of the block thermosensitive gel copolymer to the carboxyl-containing bioactive molecule is 1 (0.25-4). 1 (0.25-2), 1 (0.4-3), 1 (2-4), 1:0.25,1:0.3,1:0.5,1:1,1:2,1:4, etc. can also be selected.
The microwave heating reaction condition is that the power is 500-1000W for 30-180 min, and the power can be selected from 500-800W for 50-100 min, 600-900W for 80-150 min, 500W for 180 min, 1000W for 30min, 560W for 150 min, 700W for 120 min, 900W for 170 min, etc. The microwave heating efficiency is higher, the reaction is quicker and more sufficient, and the microwave can promote the rapid linking of the melted molecular chains to form the multifunctional polymer.
Wherein, the reaction at the temperature of 80-180 ℃ for 4-16 hours can also be that the reaction at the temperature of 80 ℃ for 16 hours, the reaction at the temperature of 100 ℃ for 10 hours, the reaction at the temperature of 120 ℃ for 12 hours, the reaction at the temperature of 120 ℃ for 5 hours, the reaction at the temperature of 150 ℃ for 6 hours, the reaction at the temperature of 80 ℃ for 4 hours, the reaction at the temperature of 80-130 ℃ for 4-10 hours, the reaction at the temperature of 120-180 ℃ for 8-16 hours, the reaction at the temperature of 150-170 ℃ for 5-10 hours, etc.
2) The multifunctional polymer is dissolved in water at 4 ℃, and then the multifunctional polymer obtained by the reaction is purified by a dialysis tube (10 kDa) for 2-3 days. Collected and stored after freeze-drying for further use.
The number of days of dialysis depends on the final purification effect, for example, 2 days, 3 days, 2.5 days, etc.
3) Adding 50mg-450mg of multifunctional polymer into 1mLPBS mL of PBS buffer solution as a unit, stirring and dissolving in ice bath, and regulating the temperature to 4-37 ℃ to form stable hydrogel after the multifunctional polymer is completely dissolved, thus obtaining the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing.
Wherein, the 50mg-450mg of multifunctional polymer can be added into the mixture of 50mg-150mg and 150mg 350mg,250mg-450mg,50mg,150mg,250mg,350mg,100mg,200mg,300mg,400mg, etc.
The above examples are replaced by itaconic acid, and other materials such as salicylic acid, ferulic acid, citric acid, chlorogenic acid, aspirin, diclofenac, folic acid, ibuprofen, indomethacin, succinic acid, maleic acid, malic acid, gamma-linolenic acid, or tretinoin may be used. The carboxyl group-containing bioactive molecule can also be itaconic acid, salicylic acid, ferulic acid, citric acid, chlorogenic acid, aspirin, diclofenac, folic acid, ibuprofen, indomethacin, succinic acid, maleic acid, malic acid, gamma-linolenic acid or tretinoin.
The thermosensitive gel triblock copolymer can be pluronic, polylactic acid-glycolic acid copolymer-polyethylene glycol-polylactic acid-glycolic acid copolymer.
The temperature-sensitive gel diblock copolymer may be a polypropylene-poly (n-isopropyl acrylamide) block polymer.
The thermosensitive gel multiblock copolymer may be poly (N-isopropylacrylamide) -pluronic-poly (N-isopropylacrylamide).
The invention aims to prepare the multifunctional single-component temperature-sensitive hydrogel wound dressing with good biocompatibility, which can accelerate the healing of multi-drug-resistant bacteria infected wounds and promote tissue repair.
The invention also provides a multifunctional single-component carboxyl-containing bioactive molecule-based thermosensitive hydrogel wound dressing, which is characterized by being prepared by the preparation method.
For a better understanding of the present invention, the present invention will be described in detail with reference to the following examples, but the present invention is not limited to the following examples.
Example 1
1) Poly (itaconic acid-F127) polymer is prepared by melting 1mM F127 at high temperature, then adding 2mM itaconic acid, melting itaconic acid at 130℃under inert gas atmosphere, and then reacting at 130℃for 10 hours under vacuum.
2) Poly (itaconic acid-F127) Polymer collection method Poly (itaconic acid-F127) polymer was dissolved in water at 4℃and then the poly (itaconic acid-F127) polymer obtained by the reaction was purified by dialysis tubing (10 kDa) for 3 days. After freeze drying the poly (itaconic acid-F127) polymer was collected and stored for further use.
3) The preparation method of the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel comprises the steps of adding 300mg of poly (itaconic acid-F127) polymer into 1mLPBS buffer solution, stirring and dissolving in an ice bath, and adjusting the temperature to 37 ℃ after the poly (itaconic acid-F127) polymer is completely dissolved to form stable hydrogel, thus obtaining the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing.
The multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing prepared by the method provided by the invention has good biocompatibility and good anti-inflammatory performance, and is a hydrogel wound dressing for accelerating wound healing of multi-drug-resistant bacterial infection and promoting tissue repair, and the hydrogel wound dressing is analyzed in detail by combining experimental data.
FIG. 1 shows the structural formulas of monomers and polymers in a multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing synthesized by the invention, wherein A is the structural formula of Itaconic Acid (IA), B is the structural formula of F127, and C is the structural formula of poly (itaconic acid-F127) polymer.
FIG. 2 is a FT-IR spectrum of each monomer and the resulting poly (itaconic acid-F127) polymer, showing that the peak at 1730cm-1 is attributed to-C=O in the poly (itaconic acid-F127) polymer, indicating the formation of the poly (itaconic acid-F127) polymer
FIG. 3 is an SEM image of a multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel (FIA) prepared by the invention, and the FIA hydrogel can be seen to have a three-dimensional porous structure.
FIG. 4 shows cytotoxicity measurement of the multifunctional single-component poly (itaconic acid-F127) polymer prepared by the invention on fibroblasts (L929), and the cytotoxicity of FIA with different concentrations is not shown in the figure, and the multifunctional single-component poly (itaconic acid-F127) polymer has good biocompatibility.
Fig. 5 shows the inhibition results of the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing (FIA) prepared by the invention on escherichia coli (e.coli), staphylococcus aureus (s.aureus) and methicillin-resistant staphylococcus aureus (MRSA), and the fig. shows that the FIA hydrogel shows good broad-spectrum antibacterial capability.
FIG. 6 shows the in vitro anti-inflammatory results of the multifunctional single-component poly (itaconic acid-F127) polymer prepared according to the present invention, which shows good anti-inflammatory ability when the concentration of poly (itaconic acid-F127) polymer is 25. Mu.g/mL.
FIG. 7 shows the result of in vivo MRSA infection wound healing of the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing (FIA) prepared by the invention, and it can be seen from the figure that the wound area of each group is reduced from that of the 0 th day after the operation. After 7 days of treatment, the FIA group exhibited the largest wound shrinkage area (59.16%) while the 3M group (commercial dressing) had a smaller wound shrinkage area (29.61%), indicating that the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel had a significant promoting effect on wound healing of drug-resistant bacterial infections.
Example 2
1) Poly (itaconic acid-F127) polymer is prepared by melting 1mM F127 at high temperature, then adding 2mM itaconic acid, melting itaconic acid at 140℃under inert gas atmosphere, and then reacting at 140℃for 8 hours under vacuum.
2) Poly (itaconic acid-F127) Polymer collection method Poly (itaconic acid-F127) polymer was dissolved in water at 4℃and then the poly (itaconic acid-F127) polymer obtained by the reaction was purified by dialysis tubing (10 kDa) for 3 days. After freeze drying the poly (itaconic acid-F127) polymer was collected and stored for further use.
3) The preparation method of the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel comprises the steps of adding 300mg of poly (itaconic acid-F127) polymer into 1mLPBS buffer solution, stirring and dissolving in an ice bath, and adjusting the temperature to 37 ℃ after the poly (itaconic acid-F127) polymer is completely dissolved to form stable hydrogel, thus obtaining the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing.
Example 3
1) Poly (itaconic acid-F127) polymer is prepared by melting 1mM F127 at high temperature, then adding 2mM itaconic acid, melting itaconic acid at 120℃under inert gas atmosphere, and then reacting at 120℃for 12 hours under vacuum.
2) Poly (itaconic acid-F127) Polymer collection method Poly (itaconic acid-F127) polymer was dissolved in water at 4℃and then the poly (itaconic acid-F127) polymer obtained by the reaction was purified by dialysis tubing (10 kDa) for 3 days. After freeze drying the poly (itaconic acid-F127) polymer was collected and stored for further use.
3) The preparation method of the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel comprises the steps of adding 300mg of poly (itaconic acid-F127) polymer into 1mLPBS buffer solution, stirring and dissolving in an ice bath, and adjusting the temperature to 37 ℃ after the poly (itaconic acid-F127) polymer is completely dissolved to form stable hydrogel, thus obtaining the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing.
Example 4
1) Poly (itaconic acid-F127) polymer is prepared by melting 1mM F127 at high temperature, then adding 1mM itaconic acid, melting itaconic acid at 150℃under inert gas atmosphere, and then reacting at 150℃for 10 hours under vacuum.
2) Poly (itaconic acid-F127) Polymer collection method Poly (itaconic acid-F127) polymer was dissolved in water at 4℃and then the poly (itaconic acid-F127) polymer obtained by the reaction was purified by dialysis tubing (10 kDa) for 3 days. After freeze drying the poly (itaconic acid-F127) polymer was collected and stored for further use.
3) The preparation method of the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel comprises the steps of adding 300mg of poly (itaconic acid-F127) polymer into 1mLPBS buffer solution, stirring and dissolving in an ice bath, and adjusting the temperature to 37 ℃ after the poly (itaconic acid-F127) polymer is completely dissolved to form stable hydrogel, thus obtaining the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing.
Example 5
1) Poly (itaconic acid-F127) polymer is prepared by melting 1mM F127 at high temperature, then adding 1mM itaconic acid, melting itaconic acid at 150℃under inert gas atmosphere, and then reacting at 150℃for 8 hours under vacuum.
2) Poly (itaconic acid-F127) Polymer collection method Poly (itaconic acid-F127) polymer was dissolved in water at 4℃and then the poly (itaconic acid-F127) polymer obtained by the reaction was purified by dialysis tubing (10 kDa) for 3 days. After freeze drying the poly (itaconic acid-F127) polymer was collected and stored for further use.
3) The preparation method of the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel comprises the steps of adding 300mg of poly (itaconic acid-F127) polymer into 1mLPBS buffer solution, stirring and dissolving in an ice bath, and adjusting the temperature to 37 ℃ after the poly (itaconic acid-F127) polymer is completely dissolved to form stable hydrogel, thus obtaining the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing.
Example 6
1) Poly (salicylic acid-F127) polymer was prepared by first melting 1mM F127 at high temperature, then adding 2mM salicylic acid, allowing the salicylic acid to melt at 160℃under an inert gas atmosphere, and then reacting at 160℃for 10 hours under vacuum.
2) Poly (salicylic acid-F127) Polymer collection method Poly (salicylic acid-F127) polymer was dissolved in water at 4℃and the poly (salicylic acid-F127) polymer obtained by the reaction was purified by dialysis tubing (10 kDa) for 3 days. After freeze drying the poly (salicylic acid-F127) polymer was collected and stored for further use.
3) The preparation method of the multifunctional single-component poly (salicylic acid-F127) temperature-sensitive hydrogel comprises the steps of adding 300mg of poly (salicylic acid-F127) polymer into 1mLPBS buffer solution, stirring and dissolving in an ice bath, and adjusting the temperature to 37 ℃ after the poly (salicylic acid-F127) polymer is completely dissolved to form stable hydrogel, thus obtaining the multifunctional single-component poly (salicylic acid-F127) temperature-sensitive hydrogel wound dressing.
Example 7
1) Poly (ferulic acid-F127) polymer is prepared by melting 1mM F127 at high temperature, adding 2mM ferulic acid, melting ferulic acid at 160deg.C under inert gas atmosphere, and maintaining microwave power 1000W under vacuum condition for 30 min.
2) Poly (ferulic acid-F127) polymer collection method the poly (ferulic acid-F127) polymer was dissolved in water at 4℃and then the poly (ferulic acid-F127) polymer obtained by the reaction was purified by dialysis tubing (10 kDa) for 3 days. After freeze drying the poly (ferulic acid-F127) polymer was collected and stored for further use.
3) The preparation method of the multifunctional single-component poly (ferulic acid-F127) temperature-sensitive hydrogel comprises the steps of adding 300mg of poly (ferulic acid-F127) polymer into 1mLPBS buffer solution, stirring and dissolving in an ice bath, and adjusting the temperature to 37 ℃ after the poly (ferulic acid-F127) polymer is completely dissolved to form stable hydrogel, thus obtaining the multifunctional single-component poly (ferulic acid-F127) temperature-sensitive hydrogel wound dressing.
Example 8
The multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing (FIA) prepared by the invention has the advantages of simple preparation method process, environment-friendly raw materials and low cost, can show good antibacterial and anti-inflammatory properties, can accelerate the healing of multi-drug-resistant bacterial infection wounds and can promote tissue regeneration, so that the hydrogel wound dressing has good application prospect in the healing of multi-drug-resistant bacterial infection wounds.
Example 9
1) Poly (succinic acid-F127) polymer was prepared by first melting 1mM F127 at high temperature, then adding 4mM succinic acid, melting succinic acid at 180℃under an inert gas atmosphere, and then reacting for 180 minutes under vacuum with a microwave power of 500W.
2) Poly (succinic acid-F127) Polymer collection method Poly (succinic acid-F127) polymer was dissolved in water at 3℃and then the poly (succinic acid-F127) polymer obtained by the reaction was purified by dialysis tubing (10 kDa) for 2 days. After freeze drying the poly (succinic acid-F127) polymer was collected and stored for further use.
3) The preparation method of the multifunctional single-component poly (succinic acid-F127) temperature-sensitive hydrogel comprises the steps of adding 50mg of poly (succinic acid-F127) polymer into 1mLPBS buffer solution, stirring and dissolving in an ice bath, and adjusting the temperature to 25 ℃ after the poly (succinic acid-F127) polymer is completely dissolved to form stable hydrogel, thus obtaining the multifunctional single-component poly (succinic acid-F127) temperature-sensitive hydrogel wound dressing.
Example 10
1) Poly (aspirin-F108) polymer is prepared by melting 1mM F108 at high temperature, adding 2mM aspirin, melting at 80deg.C under inert gas atmosphere, and maintaining microwave power at 800W under vacuum for 140 min.
2) Poly (aspirin-F108) Polymer collection method Poly (aspirin-F108) Polymer was dissolved in water at 4℃and then the poly (aspirin-F108) polymer obtained by the reaction was purified by a dialysis tubing (10 kDa) for 3 days. After freeze-drying the poly (aspirin-F108) polymer was collected and stored for further use.
3) The preparation method of the multifunctional single-component poly (aspirin-F108) temperature-sensitive hydrogel comprises the steps of adding 450mg of poly (aspirin-F108) polymer into a buffer solution of 1mLPBS, stirring and dissolving in an ice bath, and adjusting the temperature to 30 ℃ after the poly (aspirin-F108) polymer is completely dissolved to form stable hydrogel, thus obtaining the multifunctional single-component poly (aspirin-F108) temperature-sensitive hydrogel wound dressing.
The multifunctional single-component carboxyl-containing bioactive molecule-based thermosensitive hydrogel wound dressing prepared by the preparation method disclosed by the invention is applied to the preparation of medicines for promoting wound healing and tissue regeneration of multi-drug-resistant bacteria infection.
The invention also has the following advantages:
(1) The F127 and the like used by the invention have body temperature responsive gel behavior, and simultaneously have good biocompatibility, are environment-friendly, and are cheap and easy to obtain.
(2) Itaconic acid used in the present invention is an important metabolite produced by the mitochondrial tricarboxylic acid cycle and has safe, non-toxic, and high permeability characteristics. Itaconic acid shows excellent biological activity in terms of immunomodulation, antioxidation, antibacterial and antiviral properties, etc.
(3) The poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing (FIA) prepared by the invention has simple preparation method and process, can be obtained in one step and has simple components.
(4) The multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing (FIA) prepared in the invention has anti-inflammatory and antibacterial capabilities.
(5) The solvent used in the invention is deionized water, and the multifunctional single-component poly (itaconic acid-F127) temperature-sensitive hydrogel wound dressing (FIA) prepared by the method does not contain any organic solvent.
In summary, according to the preparation method of the thermosensitive hydrogel wound dressing, the poly (itaconic acid-F127) polymer is prepared through a melting reaction, the poly (itaconic acid-F127) polymer is dispersed into the PBS buffer solution, and after the poly (itaconic acid-F127) polymer is completely dispersed, the temperature is regulated to form the multifunctional single-component hydrogel, so that the multifunctional single-component poly (itaconic acid-F127) thermosensitive hydrogel wound dressing (FIA) is obtained.
FIA also shows good biocompatibility in vitro and in vivo, and simultaneously has good anti-inflammatory and antibacterial properties, so that the hydrogel dressing has good application prospects in wound healing and tissue regeneration caused by multi-drug-resistant bacterial infection.
The above is only for illustrating the technical idea of the present invention, and the protection scope of the present invention is not limited by this, and any modification made on the basis of the technical scheme according to the technical idea of the present invention falls within the protection scope of the claims of the present invention.