CN117357692A - In-situ curing forming hydrogel and preparation method and application thereof - Google Patents
In-situ curing forming hydrogel and preparation method and application thereof Download PDFInfo
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- CN117357692A CN117357692A CN202311665426.4A CN202311665426A CN117357692A CN 117357692 A CN117357692 A CN 117357692A CN 202311665426 A CN202311665426 A CN 202311665426A CN 117357692 A CN117357692 A CN 117357692A
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Classifications
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- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
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- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0023—Polysaccharides
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Abstract
The invention provides in-situ curing forming hydrogel and a preparation method and application thereof, and belongs to the technical field of biomedical materials. The hydrogel precursor liquid consists of two components which are stored separately, wherein the component A consists of the following raw materials in percentage by mass: 1.0 to 2.0 percent of methacrylic chitosan, 0.1 to 1 percent of ferulic acid, 0.1 to 0.5 percent of phenyl phosphate and the balance of solvent; the component B consists of the following raw materials in percentage by mass: 1-10% of oxidized bletilla polysaccharide and the balance of solvent. The hydrogel formed by mixing the two components can be completely fit on a large-area wide and irregularly-shaped dynamic wound, and the effects of resisting bacteria, resisting inflammation and promoting wound healing are exerted. In addition, the addition of the ferulic acid can improve the toughness of the hydrogel, and can be changed along with various movement forms, so that the hydrogel is completely suitable for dynamic wounds. The two components of the hydrogel can be separated, and the hydrogel can be sprayed on wounds in sequence to exert effects when in use, is convenient to carry and low in cost, and has good application prospects in wound care.
Description
Technical Field
The invention belongs to the technical field of biomedical materials, and particularly relates to an in-situ curing molding hydrogel as well as a preparation method and application thereof.
Background
The largest organ of the human body surface in contact with the outside is the skin. It has the functions of resisting microbe, regulating body temperature and resisting external environment stimulus. Under the influence of external factors, the risk of skin injury is the greatest in the whole human tissue organ, and under the condition of facing the severe environment of the outside, the skin wound surface can be inflamed, infected and the like, and the skin healing can be slow, so that the function of the skin wound surface is lost. Thus, for better treatment of wounds, it would be desirable to provide wound dressings with antibacterial, anti-inflammatory and healing promoting properties.
The hydrogel wound dressing is a new type of wound dressing, and it uses hydrophilic high molecular gel with high water content as main component. In one aspect, the hydrogel is capable of creating a moist environment for the wound, thereby promoting wound healing. On the other hand, by incorporating functional polymers into a three-dimensional network of hydrogels, hydrogels have met biomedical needs such as adhesion and self-repair. Among the numerous hydrogels, hydrogels formed by crosslinking oxidized dextran or polysaccharides consisting of glucose/mannose (e.g., konjac, bletilla and chitosan) demonstrate certain advantages as wound dressings. For example, patent application publication No. CN112494713A discloses that a composite hydrogel can be prepared from oxidized bletilla striata polysaccharide and chitosan, and the hydrogel has a certain antibacterial activity and can promote wound healing. However, the hydrogel is only suitable for common small-area wounds, cannot be solidified and adhered around wound tissues, cannot be suitable for large-area wide and irregularly-shaped dynamic wounds, has poor mechanical properties, and is fragile and not easy to carry.
How to provide a hydrogel which has excellent antibacterial activity and wound healing promoting effect, is suitable for large-area wide dynamic wounds with irregular shapes, has good mechanical properties and is convenient to carry, and needs to be further researched.
Disclosure of Invention
The invention aims to provide an in-situ curing forming hydrogel, a preparation method and application thereof.
The invention provides an in-situ curing formed hydrogel product box, which consists of two components stored separately:
the component A consists of the following raw materials in percentage by mass: 1.0 to 2.0 percent of methacrylic chitosan, 0.1 to 1 percent of ferulic acid, 0.1 to 0.5 percent of phenyl phosphate and the balance of solvent;
the component B consists of the following raw materials in percentage by mass: 1-10% of oxidized bletilla polysaccharide and the balance of solvent.
Further, the aforementioned set-in-place shaped hydrogel product kit is composed of two components stored separately:
the component A consists of the following raw materials in percentage by mass: 2% of methacrylic chitosan, 0.8% of ferulic acid, 0.25% of phenyl phosphate and the balance of solvent;
the component B consists of the following raw materials in percentage by mass: 2% of oxidized bletilla striata polysaccharide and the balance of solvent.
Further, the method comprises the steps of,
in the component A, the phenyl phosphate is phenyl lithium phosphate;
And/or, in component a, the solvent is water;
and/or, in the component B, the solvent is water.
Further, in the component A, the preparation method of the methacrylic chitosan comprises the following steps:
dissolving chitosan in a solvent, adding methacrylic anhydride into the chitosan solution, dialyzing after the reaction, and freeze-drying to obtain the chitosan;
after the chitosan is dissolved in a solvent, the concentration is 1-5%;
and/or, the solvent is a 1% acetic acid solution;
and/or the volume ratio of the methacrylic anhydride to the chitosan solution is 1:100;
and/or the reaction temperature is 20-30 ℃; the reaction time is 24-48 hours;
and/or, the molecular weight cut-off of the dialysis bag is 4.0-8.0 kDa during dialysis;
and/or, during the dialysis, the dialysate is water;
and/or the dialysis time is 1-3 days.
Further, in the component B, the preparation method of the bletilla striata polysaccharide comprises the following steps:
1) Polysaccharide from rhizoma bletillae and NaIO 4 Respectively dissolving in solvent to obtain rhizoma bletilla polysaccharide solution and NaIO 4 A solution;
2) Mixing rhizoma bletilla polysaccharide solution and NaIO 4 After the solution is mixed and reacted, adding glycol to terminate the reaction;
3) Dialyzing the reaction solution, and freeze-drying to obtain the final product.
Further, the method comprises the steps of,
in the step 1), the bletilla polysaccharide consists of mannose and glucan, wherein the molar ratio of the mannose to the glucan is 2.946:1;
and/or, in step 1), the bletilla striata polysaccharide and the NaIO 4 The molar ratio of (2) is 0.4:1, a step of;
and/or, in step 1), the solvent is water;
and/or, in step 2), the bletilla striata polysaccharide solution and NaIO 4 Mixing the solutions and stirring for 10-20 h;
and/or, in the step 2), the temperature of the reaction is 20-30 ℃; the reaction time is 8-12 hours;
and/or, in step 3), the molecular weight cut-off of the dialysis bag is 3.5 kDa during said dialysis;
and/or, in step 3), the dialysate is water during the dialysis;
and/or, in the step 3), the dialysis time is 1-3 days.
Further, the preparation method of the bletilla striata polysaccharide comprises the following steps:
(1) Pulverizing rhizoma bletilla, and defatting;
(2) Drying defatted rhizoma bletilla, extracting with water, and filtering to obtain extract;
(3) Adding Sevage reagent into the extract to remove protein, collecting water phase, precipitating with alcohol solution, washing precipitate, and drying to obtain the final product;
in the step (1), degreasing is carried out for 2-5 hours at 70-90 ℃ by using 95% ethanol and petroleum ether with the feed liquid ratio of 1 g:5-10 mL respectively;
And/or in the step (2), the feed liquid ratio of the bletilla striata medicinal material to the water is 1 g:40-60 mL;
and/or in the step (2), the extraction temperature is 70-90 ℃ and the extraction time is 1-5 h;
and/or, in the step (3), the alcohol solution is 95% ethanol.
The invention also provides a hydrogel, which is obtained by taking the in-situ curing molding hydrogel product box and mixing the component A and the component B.
Further, the component A and the component B are respectively put into a spray bottle, one of the components is sprayed firstly, and then the other component is sprayed to obtain hydrogel;
or directly mixing the component A and the component B to obtain hydrogel;
the volume ratio of the component A to the component B is 1:1.
The invention also provides the application of the in-situ curing molding hydrogel product box or the hydrogel in preparing a wound repair material.
The invention provides a low-cost portable hydrogel which is antibacterial, anti-inflammatory and capable of promoting wound healing, and is used for healing various wound surfaces. The hydrogel consists of two components, when in use, one component is sprayed to a wound, then the other component is sprayed, the hydrogel can be formed, and the hydrogel can be solidified on the wound surface through illumination.
The component A of the invention is a modified methacrylic chitosan-ferulic acid mixed solution (CSMA-FA). Chitosan is a natural polysaccharide, most of which is extracted from shells of crustaceans, has good biocompatibility, degradability, antibacterial property, anti-inflammatory property and wound healing promoting property, and meanwhile, the chitosan has a plurality of active functional groups, has a simple chemical structure and is easy to combine with other functions, but has poor water solubility, so that the chitosan is subjected to structural modification of photosensitive groups, so that the chitosan has good water solubility and photocuring property. Ferulic acid is a natural small molecule, exists in a plurality of natural plants, has low toxicity, has a plurality of good physiological activities (effects of promoting healing, delaying skin aging, resisting radiation, resisting inflammation, resisting oxidation, resisting bacteria, resisting cancer, resisting diabetes and the like have been reported), is cheap and easily available, and has been widely used in pharmaceutical, food and cosmetic industries. The ferulic acid provided by the invention has pharmacological activity, can obviously improve the mechanical property of the hydrogel, improve the adhesiveness of the hydrogel, and can keep the original shape of the hydrogel in different movement modes.
The component B of the invention is oxidized bletilla polysaccharide (OBSP), is a natural soluble polymer extracted from natural Chinese herbal medicine bletilla, is composed of alpha-mannose, beta-mannose and beta-glucose, and has pharmacological activities of stopping bleeding, promoting wound healing, resisting ulcer, resisting inflammation and the like. And the bletilla striata polysaccharide is a natural nontoxic and non-irritating polymer material, has good biocompatibility and adhesiveness, and plays an important role in the preparation of adhesives, wound dressings and other medical biological materials.
Compared with the prior art, the hydrogel has the advantages that:
(1) The hydrogel has the advantages of low preparation cost, easily available materials, wide sources, natural animals and plants, good biological activity and good biological safety.
(2) The hydrogel is convenient and easy to carry, easy to store, convenient to use, applicable to various environments, and wide in application range, and is applicable to various skin wounds and wounds in sports (irregular wound surface shape, postoperative wounds, deep wounds and the like).
(3) Can reduce the use of bandage gauze, reduce the possibility of wound infection, and the hydrogel can be directly solidified on the wound for a long time, has the functions of anti-inflammation, antibiosis and healing promotion, and is solidified rapidly so as to seal the wound.
(4) The component A and the component B can be used alternatively, the component A is sprayed and covered on the wound uniformly, then the component B is sprayed immediately, the two components are used in different order (note: both components are used in a mutually matched mode and can not be used singly), the two components can be self-assembled on the wound to form hydrogel, and finally the hydrogel can be solidified on the wound surface through illumination.
In summary, the invention provides an in-situ curing forming hydrogel, a preparation method and application thereof, the hydrogel is prepared by mixing two components, the component A consists of methacrylic chitosan and ferulic acid, the component B is oxidized bletilla striata polysaccharide, and the component A and the component B can be mixed to form the hydrogel, so that the hydrogel can be completely fit on a large-area wide and irregularly-shaped dynamic wound, and meanwhile, the effects of resisting bacteria, resisting inflammation and promoting wound healing can be exerted. In addition, the addition of the ferulic acid can improve the toughness of the hydrogel, can be changed along with various movement forms, and can completely adapt to dynamic wounds. The two components of the hydrogel can be separated, and the hydrogel can be sprayed on wounds in sequence to exert effects when in use. The hydrogel disclosed by the invention is convenient to carry, low in cost and good in application prospect in wound care.
It should be apparent that, in light of the foregoing, various modifications, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
The above-described aspects of the present invention will be described in further detail below with reference to specific embodiments in the form of examples. It should not be understood that the scope of the above subject matter of the present invention is limited to the following examples only. All techniques implemented based on the above description of the invention are within the scope of the invention.
Drawings
FIG. 1 is a graph showing the results of characterization of hydrogels of the present invention and hydrogel-forming materials: a is Chitosan (CS) or methacrylated Chitosan (CSMA) 1 H-NMR nuclear magnetic resonance spectroscopy; b is bletilla polysaccharide (BSP) or oxidized bletilla polysaccharide (OBSP) 1 H-NMR nuclear magnetic resonance spectroscopy; infrared spectrum with C CS, BSP, CSMA, OBSP: d is infrared spectrogram of Ferulic Acid (FA), CSOB hydrogel (CSOB), and CSOB-FA hydrogel (CSOB-FA); e is a hydrogel vial inversion chart; f is a vial inversion chart of hydrogels prepared with different volume ratios of CSMA solution to OBSP solution at different concentrations.
Fig. 2 is a hydrogel injection and ejection shape adaptation diagram: a is a hydrogel injection diagram, wherein 1 is a diagram when hydrogel starts to be injected in water, 2 is a diagram when the hydrogel is injected for 5s, 3 is a diagram when the hydrogel is injected for 10s, and 4 is a diagram when the hydrogel is injected for 20 s; b is a plot of hydrogel injection formation "CDUTCM 2026"; c is a different shape chart formed after the hydrogel is sprayed.
Fig. 3 is a graph of hydrogel rheology, self-healing, and adhesion: a is a CSMA hydrogel rheological data diagram; b is CSOB 1st A hydrogel rheology data map; c is a CSOB hydrogel rheological data diagram; d is CSOB-FA 1st A hydrogel rheology data map; e is a CSOB-FA hydrogel rheological data diagram; f is a CSOB-FA hydrogel self-healing data graph; g is CSOB 1st Hydrogel and CSOB-FA 1st Hydrogel adhesion test chart; h is a chart for testing adhesion of CSMA, CSOB hydrogel and CSOB-FA hydrogel; i is a self-healing macroscopic view of the CSOB-FA hydrogel, 1 is an initial undivided view of the CSOB-FA hydrogel in the figure I, 2 is a separation view after shearing the CSOB-FA hydrogel, 3 is a view after shearing and healing the CSOB-FA hydrogel, 4 is a single-side stretching view after shearing and healing the CSOB-FA hydrogel, and 5 is a two-side stretching view after shearing and healing the CSOB-FA hydrogel.
FIG. 4 is a graph of mechanical properties results: a is a compression strength result graph of the CSOB hydrogel and the CSOB-FA hydrogel; b is a drawing of the CSOB-FA hydrogel, in the drawing B, 1 is an initial drawing distance drawing of the CSOB-FA hydrogel, 2 is a drawing of the CSOB-FA hydrogel for 1cm, and 3 is a drawing of the CSOB-FA hydrogel for 2 cm; c is a CSOB-FA hydrogel knuckle bending graph; d is a plot of the CSOB-FA hydrogel twisted on pigskin and twisted in water; e is a graph of the influence of different polishing times on the compressive strength of the CSOB-FA hydrogel, wherein CSOBFA-10S represents the CSOB-FA hydrogel obtained with the polishing time of 10S, CSOBFA-15S represents the CSOB-FA hydrogel obtained with the polishing time of 15S, CSOBFA-30S represents the CSOB-FA hydrogel obtained with the polishing time of 30S, and the compressive strength is expressed in KPa.
FIG. 5 is a graph of the swelling ratio and water retention results of CSMA, CSOB and CSOB-FA hydrogels: a is a water-retention result graph; b is a graph of swelling ratio results.
FIG. 6 is a graph showing the in vitro antibacterial results of each hydrogel: a is an antibacterial result graph; b is an antibacterial rate result graph.
Fig. 7 is a graph of the results of biocompatibility of each hydrogel: a is a graph of cytotoxicity results of each hydrogel; b is a cell morphology diagram of CSOB-FA hydrogel cultured for 48 hours; c is a graph of the results of blood compatibility of each hydrogel.
FIG. 8 is a graph showing the results of oxidation resistance of each hydrogel.
FIG. 9 is a graph showing hemostatic performance results for each hydrogel, wherein data is blood loss in mg.
Fig. 10 is a graph of wound healing promotion results for each hydrogel.
Detailed Description
The materials and equipment used in the embodiments of the present invention are all known products and are obtained by purchasing commercially available products.
In the invention, the room temperature is 20-30 ℃.
EXAMPLE 1 preparation of in situ cured molded hydrogel according to the invention
1. Component A:
(1) Preparation of methacrylated Chitosan (CSMA)
1g of Chitosan (CS) powder was dissolved in 100mL of 1% acetic acid solution (99 mL pure water mixed with 1 mL glacial acetic acid solution), stirred uniformly until dissolved (the concentration of chitosan was 1g/100 mL), then 1 mL methacrylic anhydride (content 98%) was added, stirred at room temperature for 24 hours, reacted and placed in a dialysis bag (MWCO: 4.0-8.0 kDa), the dialysate was pure water, and circulated and dialyzed at room temperature for 3 days, and freeze-dried, finally solid CSMA was obtained.
(2) Preparation of methacrylated chitosan-ferulic acid (CSMA-FA)
200mg of CSMA, 80mg of Ferulic Acid (FA) and 25mg of phenyl lithium phosphate (LAP for short, purity is 98%) are dissolved in 10mL of pure water, and the components A are obtained after stirring uniformly until the components A are dissolved: CSMA-FA solution (when in use, the weighed mass is variable, the concentration is not variable, CSMA concentration is 2%, FA concentration is 0.8%, and phenyl lithium phosphate concentration is 0.25%).
2. Component B:
(1) Preparation of bletilla polysaccharide (BSP)
Pulverizing dried rhizoma bletilla, sieving with 50 mesh sieve, weighing 100g of rhizoma bletilla powder, degreasing with ethanol (95%) and petroleum ether at 70deg.C for 2 times and 2 hr each time respectively according to feed-liquid ratio of 1:5 (g/mL). Naturally drying defatted medicinal material powder for 24 hr, re-weighing, adding the powder into deionized water according to a feed-liquid ratio of 1:40 (g/mL), stirring at 70deg.C for 2 hr, filtering, and concentrating the extract. Adding 1/3 of Sevage reagent to remove protein, collecting water phase, adding 95% ethanol, precipitating with ethanol, refrigerating at 4deg.C for 12 h, filtering, washing precipitate, and vacuum drying at 40-50deg.C for 72 hr to obtain BSP. The monosaccharide content and purity of BSP were determined by reverse-phase high performance liquid chromatography and high performance gel permeation chromatography.
(2) Preparation of oxidized bletilla polysaccharide (OBSP)
Sodium iodate is used as an oxidant to prepare the bletilla striata polysaccharide (OBSP). Accurately weighing the BSP of 3.00 and g, adding the BSP into 50.0 and ml deionized water, and uniformly stirring until the BSP is dissolved to obtain a BSP solution. According to BSP and NaIO 4 The molar ratio is 0.4:1, precisely 1.44 g NaIO 4 Adding into 50.0. 50.0 ml pure water to obtain NaIO 4 A solution. BSP solution and NaIO 4 The solution was mixed and stirred 12 h. 2ml of ethylene glycol was added to terminate the reaction, and the reaction system was placed in a dialysis bag (MWCO: 3.5 kDa), and the dialysate was purified water and dialyzed circularly at room temperature for 3 days. And finally obtaining the OBSP by freeze drying.
200mg of OBSP was then dissolved in 10mL of pure water to give component B: OBSP solution at a concentration of 2% (here mass%).
3. Preparation of in situ spray cured hydrogels
(1) Preparation of CSMA hydrogels
200mg of CSMA solid was dissolved in 10ml of pure water using pure water as solvent, followed by 15s of polishing (light wavelength 320-405 nm) to form CSMA gel.
(2) Preparation of CSOB hydrogels
The OBSP solution (component B) was prepared with 2% strength (mass%) of OBSP using pure water as a solvent. CSMA was formulated to give CSMA solutions (component a) at 1%, 2%, 3% concentration using pure water as solvent. The volume ratio of the component A to the component B is 1:1 to obtain CSOB with different concentrations 1st A hydrogel. Then through photo-crosslinking for 15s (the wavelength of light is 320-405 nm), the CSOB hydrogel is obtained, and the CSOB hydrogel is stored in a refrigerator at 4 ℃ in a sealing way.
(3) Preparation of CSOB-FA hydrogels
The concentration of the Ferulic Acid (FA) is 0.1-1.0% (mass percent) in the safe use, so that the concentration of the FA is 0.8%. Preparing a component A (CSMA-FA solution) according to a method of 1 (2), preparing a component B (OBSP solution) according to a method of 2 (2), respectively filling the component A and the component B into a spray bottle, respectively spraying the component A and the component B according to a volume ratio of 1:1, and mixing the component A and the component B to form CSOB-FA 1st The hydrogel was then irradiated with visible light (320-405, nm) and cured for 15s to form a CSOB-FA hydrogel.
The component A and the component B can be directly mixed or respectively put into a spray bottle for spraying.
The beneficial effects of the present invention are demonstrated by specific test examples below.
Test example 1, characterization of materials
1. Experimental method
1 H-NMR: BSP, OBSP, CS and CSMA (prepared in example 1) were weighed, dissolved in heavy water, respectively, and passed through a spectrometer (GermanyBruck corporation, AVANCE NEO 600 MHz) to ensure successful synthesis of OBSP and CSMA.
FTIR infrared spectroscopy: FTIR spectroscopy was performed using a spectroum One fourier transform infrared spectrometer (PerkinElmer, USA). OBSP, CS, FA, CSOB hydrogel lyophilized solids and CSOB-FA hydrogel lyophilized solids (prepared in example 1) were determined using KBr disc method. The wavelength scanning range of all samples is 400-4000 cm -1 Is performed in between, each sample is scanned 32 times on average, and the resolution is 4 cm -1 。
The formation of the hydrogel in example 1 was confirmed by a tube inversion test.
2. Experimental results
BSP is a heteropolysaccharide composed of mannose and glucan in a molar ratio of 2.946:1. The total carbohydrate content of the BSP was determined to be 63.46% by the phenol-sulfuric acid method. Mw and Mn of BSP were 1.16X10, respectively, as determined by High Performance Gel Permeation Chromatography (HPGPC) 5 g/mol -3.99×10 5 g/mol and 7.09X 10 4 g/mol - 1.12×10 5 g/mol; oxidizing BSP to obtain OBSP, introducing methacrylate group into CS (MW: 100000-200000) to synthesize photocrosslinkable CSMA, as shown in FIGS. 1A and 1B, by proton nuclear magnetic resonance 1 H-NMR) confirmed successful oxidation of the OBSP and successful coupling of CSMA, and the results demonstrated that the OBSP showed a low intensity peak of aldehyde groups near δ9.28ppm, demonstrating that part of the hydroxyl groups in the BSP were successfully oxidized to aldehyde groups (-CHO), while the intensity of the signal peak was able to reflect the degree of oxidation in the OBSP, since the oxidation reaction of the polysaccharide was successfully performed by the aldehyde groups obtained after the oxidation reaction, indicating that the oxidation reaction of the polysaccharide was successfully performed, resulting in the hydroformylation of bletilla polysaccharide. The methacrylate peaks are located at δ5.34 ppm and δ5.65 ppm (acrylic protons of the methacrylamide group) in CSMA, respectively.
The experimental results were then verified by Fourier IR spectroscopy (FIGS. 1C and 1D), at BSP and OBSP wavenumbers of 4000-400 cm -1 Is typically a polysaccharide dominant signal, wave number 3399 cm -1 The absorption peak with long and wide part is multipleHydroxyl O-H stretching vibration peak of sugar and wave number 2927 cm -1 The weak absorption peak of (2) is C-H stretching vibration peak, wave number 1151 cm -1 、1062 cm -1 And 1031 cm -1 Showing the presence of pyranose. OBSP at 1735 cm -1 There appears a strong carbonyl (c=o) stretching vibration absorption peak indicating that the BSP changes from a partial hydroxyl group on its molecule to an aldehyde group after oxidation. On the infrared spectrum of CSMA, 838 cm -1 Out-of-plane bending vibration peak at C=C, C-H, and in 1598 cm compared to CS -1 The telescopic vibration absorption peak of-NH 2 at 1550 cm is vanished -1 、1234 cm -1 Characteristic absorption peaks of amide II and III bands appear respectively, the appearance of C=C absorption peak, and the disappearance of amino absorption peak and the formation of amide bond absorption peak also show that the amino groups on MA and CS undergo acylation reaction. As can be seen by comparing the infrared spectra of OBSP, CSMA, FA, CSOB, CSOB-FA hydrogels: 1735 cm -1 The symmetrical vibration peak at c=o belonging to OBSP is significantly reduced, 1643 cm -1 An absorption peak belonging to c=n appears, indicating that Schiff bond is formed by Schiff base reaction between-CHO group of oxidized bletilla polysaccharide and-NH 2 group of chitosan. For FA, 1695 and cm in CSOB-FA -1 the-COOH characteristic peaks at the sites are obviously weakened, which indicates that the-COOH-of FA and the-NH 2 of CSMA have electrostatic action, so that the vibration peak of the CSOB protonated amino group is blue-shifted, and the success of the hydrogel crosslinking reaction is indicated. The vial inversion experiment is shown in fig. 1E, illustrating the successful formation of hydrogels.
As shown in FIG. 1F, when CSMA and OBSP are mixed and crosslinked, the CSMA solution can meet the injection condition when the concentration of the fixed OBSP is 2% (w/v) and the concentration of the CSMA is 1% (w/v), but the prepared hydrogel has poor mechanical strength and poor transparency, part of the solution cannot participate in the reaction, the CSMA solution has high viscosity and is difficult to inject when the concentration of the CSMA is 3% (w/v), the CSMA solution is inconvenient to use, the CSMA solution can meet the injection condition when the concentration of the CSMA is 2% (w/v), and the prepared hydrogel has jelly-like shape and good mechanical strength. Thus, when the volume ratio of 2% (w/v) OBSP solution to 2% (w/v) CSMA solution is 1:1, it is the optimal formulation for preparing CSOB hydrogel. The OBSP solution and CSMA solution can be used as the precursor solution of hydrogel, and can be stored in a refrigerator at 4 ℃ for standby. As can be seen from FIG. 1F, the present invention successfully produced a CSOB-FA hydrogel.
Test example 2 injectability, ejection and shape adaptability of the hydrogels of the present invention
1. Experimental method
A CSOB-FA hydrogel was obtained by mixing a 2% (w/v) CSMA-FA solution and a 2% (w/v) OBSP solution in a volume ratio of 1:1 and photo-curing for 15s (320-405, nm) according to the method of example 1. After the CSOB-FA hydrogel was formed, methylene blue dye was added, immediately after stirring, the mixture was transferred to a syringe using a 16 gauge needle, and the injectability of the hydrogel was evaluated by injecting the term "CDUTCM 2026". Furthermore, the jettability and shape adaptability of the two hydrogel precursor solutions were evaluated by spraying 2% (w/v) CSMA-FA solution (component A) and 2% (w/v) OBSP solution (component B) in molds of different shapes.
2. Experimental results
The hydrogel can be injected using a single channel syringe to draw the "CDUTCM2026" as shown in FIGS. 2A and 2B, and the component A and component B hydrogel precursor liquids are mixed first to form a gel and then immediately transferred to a conventional syringe, which indicates that the hydrogel has certain injectability properties. The hydrogel CSOB-FA and OBSP solutions are respectively filled into spray bottles, and then sprayed into films with different shapes together (figure 2C), after gel is formed, the films are polished for 15 seconds and then taken out, so that the injectability, the sprayability and the adaptability of different shapes of the hydrogel are described, and the hydrogel spray can be adapted to wounds with irregular shapes.
Test example 3 rheological Properties and self-healing Properties of hydrogels of the invention
1. Experimental method
(1) Rheological Performance test
The rheological properties of the hydrogels were characterized by rheometer (MCR 102E, anton Paar). The hydrogel was prepared as a disk with a diameter of 1.2 cm and a height of 3 mm. At 37 ℃ the oscillation frequency is 10 -1 ~ 10 2 The storage modulus (G ') and loss modulus (G') of the hydrogels were measured under rad/s. The hydrogel sample comprises CSMA hydrogel and CSOB 1st Hydraulic condenserGel, CSOB hydrogel, CSOB-FA 1st Hydrogels and CSOB-FA hydrogels were prepared as described in example 1.
(2) Self-healing Performance test
A disk-shaped CSOB-FA hydrogel (diameter 14mm, height 3 mm) was cut into two halves from the middle and separated by a distance at room temperature, and then the halves were placed in place and waited for a certain time until the halves agglomerated again. Thereafter, the ends of the hydrogel are removed and lifted for stretching, and the healed hydrogel is kept in suspension. All photographs of the hydrogels were taken.
2. Experimental results
CSMA hydrogel, CSOB was evaluated by rheology experiments 1st Hydrogels, CSOB-FA 1st Storage modulus G' and loss modulus G″ of hydrogels and CSOB-FA hydrogels. Figures 3 a-3 e show that all samples have a storage modulus (G ') higher than the loss modulus (G ") indicating hydrogel formation, wherein the G' value is generally above G" at frequencies of 0.1 to 100 rad/s. In addition, the storage modulus of CSOB, CSOB-FA hydrogel is higher than CSMA single network hydrogel, CSOB 1st Hydrogels are more stable after photocrosslinking than the photocrosslinked hydrogels CSOB, probably because dynamically changing Schiff bonds are formed between CSMA and OBSP, whereas CSOB is more stable after photocrosslinking, CSMA and CSOB 1st CSOB-FA 1st The medium G ' value is higher than G ' at high oscillation frequency, the CSOB-FA hydrogel shows better stability after photo-crosslinking, and the formed gel characteristic G ' reaches more than 540.00, while CSOB is only about 118.89.
Then, a continuous alternative strain sweep was performed to determine the self-healing behavior of the CSOB-FA hydrogel, and after 4 consecutive alternating repeated cycles, the value of G' could still be greater than G ", indicating that the hydrogel had an autonomous healing behavior (FIG. 3F), while the complex viscosities of the different hydrogels were measured by rheometers, CSOB-FA 1st Is much higher than CSOB at 852.24 1st Hydrogel 290.73, which may be due to its increased adhesion caused by the presence of phenolic hydroxyl groups in FA, and complex viscosity of the hydrogel after polishingMore strongly, the viscosity of the CSOB-FA reached 4210.3, while the adhesion change after photocrosslinking of CSOB was not great, only 403.7, which is probably because CSOB-FA hydrogels were more densely crosslinked after photocrosslinking, resulting in more intermolecular hydrogen bonds, thus improving their viscosity (FIGS. 3G and 3H). And macroscopic self-healing experiments were used to demonstrate that hydrogels have self-healing capabilities (fig. 3I).
Test example 4 mechanical Properties of hydrogels of the invention
1. Experimental method
The mechanical properties of the CSOB-FA hydrogel (CSOB-FA hydrogel prepared in example 1) were evaluated by compressibility of the hydrogel. The hydrogels were prepared in cylindrical shapes with a diameter of 14. 14 mm and a height of 1.2 cm. The CSOB-FA hydrogel was then tested using a texture Meter (Rapid TA+, shanghai Techno Co., ltd.) at a speed of 1 mm/min. And secondly, adhering the hydrogel to pigskin and finger joints for stretching and twisting experiments, and soaking the hydrogel in water for stretching and twisting. CSOB hydrogel (prepared in example 1) was used as a control.
2. Experimental results
The invention discovers that the toughness of the hydrogel after the FA is added is greatly improved, and compared with the CSOB hydrogel without the FA, the compressive strength of the CSOB-FA hydrogel is obviously reduced (figure 4A), the CSOB-FA hydrogel is softer, and the hydrogel can be prevented from being broken on a wound and not being retained on a dynamic wound for a long time under different movement modes due to the fact that the strength of the hydrogel after photo-curing is too strong. The addition of FA reduces the stiffness of the hydrogel, aiding in the increased flexibility of the hydrogel, and figure 4B shows that CSOB-FA hydrogels can be stretched, whereas CSMA hydrogels and CSOB hydrogels cannot. Therefore, the gel can be fitted on the wound surface for a long time without deformation and crushing, so that the gel can be better suitable for dynamic part wounds such as joint parts and the like, and the healing of the wounds is promoted (figures 4C and 4D).
In addition, the mechanical properties of the hydrogel can be easily changed by changing the polishing time so as to meet the requirements of the hydrogel on different tissues. To characterize the mechanical properties of CSOB-FA hydrogels at different crosslinking times, compression tests were performed on the samples under different crosslinking conditions of 10, 15 and 30s, respectively. As shown in fig. 4E, the compressive strength of the hydrogel increases with increasing crosslinking time. With a delay in the light time, the ultimate stress of the CSOB-FA hydrogel increases significantly (FIG. 4E). Higher cross-linking favors the formation of a strong hydrogel. In order to obtain hydrogels of suitable strength and elasticity, the present invention selects a crosslinking time of 15s as the optimal condition. The bearing capacity of physiological soft tissue is in the range of (10-200 kPa), so the compressive modulus of CSOB-FA hydrogel is suitable as a scaffold for cell proliferation, migration and differentiation in physiological soft tissue.
Test example 5 swelling Properties and Water-retaining Properties of hydrogels of the invention
1. Experimental method
CSMA hydrogel, CSOB hydrogel and CSOB-FA hydrogel were prepared separately as described in example 1, and after initial weights of the formed hydrogels were weighed, experiments were performed separately as described above.
(1) Expansion properties
The swelling ratio of each hydrogel sample was determined by the following method: briefly, once formed, the hydrogel is lyophilized and weighed (Wd). Subsequently, the hydrogel samples were placed in 10 ml PBS at room temperature. From time to time, the water on the surface of the hydrogel was filtered and weighed (Wt). Finally, the weight of the hydrogel is not changed any more, and an equilibrium swelling state is achieved. The swelling ratio of the hydrogels at various times was calculated from the following formula.
Swelling ratio= (Wt-Wd)/wd×100%
Wd and Wt represent the weight of the dried gel and the swollen gel, respectively, at different time points.
(2) Water retention properties
Each sample was placed at 37 ℃ and the relative humidity in the environment was kept at 72.06 ±0.32 RH with saturated sodium chloride, samples were taken at defined experimental points, then weighed and finally lyophilized. The water retention rate is defined as follows:
water retention (%) =W0-Wt/W0×100%
W0 and Wt represent gel weight at various time points and initial water weight after lyophilization to remove dry weight of the gel, respectively.
2. Experimental results
The swelling ratio allows an assessment of whether the hydrogel is capable of providing moist conditions to the wound and protecting the site of use from physical compression by the outside world. Thus when the hydrogel is used for wound healing, a low swelling hydrogel may be more beneficial for wound healing. They avoid reduced flexibility due to high swelling ratios, which may lead to breakage and dissolution of the hydrogel prior to wound healing, resulting in secondary trauma to the wound. The expansion ratio of CSMA hydrogels in the present invention is much higher than that of CSOB and CSOB-FA, probably because CSMA pore size after photocrosslinking is higher than that of CSOB and CSOB-FA after photocrosslinking, and thus the swelling ratio becomes higher (FIG. 5B).
The water retention properties of hydrogels are such that water remains in the hydrogel network for a long period of time, maintaining relative humidity in the wound, and the epithelial layer forms faster in moist wounds, because the epithelial cells in this case multiply more easily in moist wounds. Thereby protecting and promoting wound healing. Therefore, a water evaporation experiment was performed to evaluate the water retention capacity of the hydrogels. The experimental results are shown in fig. 5A, where the water content in all the hydrogels tested decreased with increasing time. Throughout the experiment, the water loss rate of CSMA hydrogels was the fastest and greatest, followed by CSOB hydrogels, while that of CSOB-FA hydrogels was the slowest and smallest. All hydrogels maintained a water content above 85% after 48, 48 h, however, the rate and amount of water evaporation varied between groups depending on the compactness of the network in the hydrogel. These results indicate that the CSOB-FA hydrogels have the best water retention and have a tighter hydrogel network.
Test example 6 in vitro antibacterial test of hydrogels of the invention
CSMA hydrogel, CSOB hydrogel and CSOB-FA hydrogel were prepared separately as described in example 1, and then experiments were performed.
1. Experimental method
Detection of hydrogels against gram negative E.coli (E.coli, CMCC (B) 44102) and gram positive Staphylococcus aureus (S.aureus, ATCC 25) using the plate colony counting method923 Is used for inhibiting activity. Bacteria were inoculated in a liquid medium (tryptophan soybean broth, TSB) and maintained at 37 ℃ for 48 hours to prepare a bacterial solution (10 7 CFU/ml). Hydrogels (50 mg) were placed in four groups of 3 parallel wells in each 48-well plate prior to bacterial addition. The first group was placed without hydrogel as a control group and the remaining three groups were placed with 50mg of CSMA hydrogel, CSOB hydrogel and CSOB-FA hydrogel in sequence. 200. Mu.l of the above bacterial solution and 800. Mu.l of liquid medium were added to the respective wells and kept at 37℃for 24 hours. Bacterial broth from the same set of 3 parallel wells was then removed and mixed, serially diluted with sterile saline, and spread on Plate Count Agar (PCA). Finally, all plates were incubated at 37 ℃ for 24 hours and photographed using a camera and colonies were counted using Image J software. Antibacterial ratio (%) =sample colony count/blank colony count×100%.
2. Experimental results
The antibacterial activity of chitosan is derived from the positive charge carried by its protonated amino groups, while the bacterial biofilm carries a negative charge, so that the positive charge carried by chitosan reacts with the negative charge carried by the bacterial biofilm, resulting in bacterial death. FIG. 6 shows the in vitro antibacterial effect of CSMA, CSOB and CSOB-FA hydrogels against E.coli and Staphylococcus aureus. The CSOB group had more colonies, indicating poor antibacterial activity, probably due to the reduced presence of amino groups after the reaction of CSMA with OBSP, and thus showed poor antibacterial effect, whereas both CSMA and CSOB-FA groups showed significantly less bacteria, and they showed excellent antibacterial effect against both Staphylococcus aureus and Escherichia coli (FIG. 6A). As shown in FIG. 6B, after 24 h of the CSMA hydrogel and the escherichia coli were co-cultured, the antibacterial rate of the CSOB-FA hydrogel was 99% or more.
Test example 7 biocompatibility and blood compatibility of hydrogels of the present invention
CSMA hydrogel, CSOB hydrogel and CSOB-FA hydrogel were prepared separately as described in example 1, and then experiments were performed.
1. Experimental method
(1) Biocompatibility of
To investigate the cytotoxicity of the hydrogels, 200 mg sterile hydrogels were immersed in 50 mL complete medium, incubated at 37 ℃ for 24 h, hydrogel extracts were obtained and used for cell culture, the hydrogel extract concentrations were (4 mg/ml, 2 mg/ml, 1 mg/ml, 0.5 mg/ml, respectively). L929 cells were seeded at a density of 5000 cells/well in 96-well plates and in CO 2 Culture 24 h in incubator. The hydrogel extracts were then co-cultured with cells 24 h and 48h, 10 μl of CCK-8 reagent was added to each well, and the plates were incubated for an additional 30 minutes. Absorbance (OD) was read by a microplate reader. Relative cell viability was calculated by the equation:
relative cell viability (%) = ((OD) s −OD b ）/（OD c –OD b ））×100%，
OD s Is the average absorbance of the sample (hydrogel) group; OD (optical density) c Mean absorbance for control group; OD (optical density) b Is the average absorbance of the blank group.
(2) Blood compatibility
The blood compatibility of the hydrogels was evaluated using an in vitro hemolysis test. 1.0g of the hydrogel sample was weighed, added to 10ml of physiological saline, and immersed in a biochemical incubator at 37℃for 48 hours. New Zealand white rabbit ear venous blood was centrifuged at 2000 rpm for 10 minutes to separate red blood cells, which were then washed three times with physiological saline. The purified erythrocytes were diluted with physiological saline to obtain an erythrocyte suspension (5%, v/v). The invention selects a physiological saline negative control group and a 0.1% Triton X-100 positive control group. 200 μl of RBC suspension is prepared and mixed with 100 μl of hydrogel suspension and 700 μl of 0.9% NaCl solution to serve as an experimental group. Incubate for 1h at 37℃and centrifuge the tube at 1500 rpm for 5 minutes to absorb the supernatant and measure absorbance at 540 nm.
2. Experimental results
Safety was the first criterion applied in medicine, so whether hydrogel had good cell compatibility was critical to biomedical application of the hydrogel, CCK-8 and direct contact experiments were used to evaluate cytotoxicity of CSMA, CSOB, CSOB-FA hydrogel, as shown in fig. 7A, different concentrations of hydrogels showed good cell compatibility (both exceeding 80%) at 24 h and all produced cell proliferation cases, indicating that the series of hydrogels were not cytotoxic and produced satisfactory cell compatibility, and then CSOB-FA hydrogel cultures were co-cultured with cells for 48h to verify the experimental results, as shown in fig. 7B, a large number of viable cells in spindle form were observed under confocal fluorescence microscopy, and cell morphology after 48h was normal, almost dead cells, and furthermore, from day 0, all continued to show cell proliferation states, although CSMA, CSOB, CSOB-FA hydrogels were shown to have good cell compatibility, but overall CSOB-FA hydrogels had more excellent cell compatibility than the other two groups. Furthermore, since the wound dressing inevitably comes into contact with blood, haemolysis is considered an important indicator for evaluating the compatibility of biological materials, and thus the haemocompatibility of hydrogels is evaluated by a haemolysis test. All hydrogels did not result in any significant hemolysis after incubation, indicating that these hydrogels had good hemocompatibility (fig. 7C). Taken together, these results demonstrate that CSOB-FA hydrogels have good biocompatibility, non-hemolytic, and support cell adhesion, growth, and proliferation.
Test example 8 antioxidant Activity of hydrogels of the present invention
CSMA hydrogel, CSOB hydrogel and CSOB-FA hydrogel were prepared separately as described in example 1, and then experiments were performed.
1. Experimental method
The antioxidant activity of the hydrogels was evaluated by DPPH radical scavenging assay. Briefly, 40.0. 40.0 mg hydrogel solutions were dispersed in 10.0. 10.0 ml pure water. The above dispersion was diluted to 4mg/ml, 2 mg/ml, 1 mg/ml, and 0.5 mg/ml, respectively, and added to DPPH solution (0.08 mg/ml), pure water was added, and the final volume was 1 ml. After 2 hours of reaction at 37 ℃, the absorbance at 517 nm was measured by uv-vis spectrometry. The degradation calculation formula of DPPH is:
DPPH clearance (%) = (a) 0 -A n )/A0×100%
A 0 Absorbance of the final solution was dispersed to 0. Mu.l of sample, A n Absorbance of the final solution was dispersed for different volumes of sample.
2. Experimental results
In the diabetic wound environment, a large amount of ROS is generated, and as ROS is accumulated in a large amount, the wound may exhibit a chronic oxidative stress state. The wound dressing containing the antioxidant can effectively remove ROS and is beneficial to chronic wound healing. FA is reported to be a good antioxidant, which is usually encapsulated in various carriers to prevent it from being oxidized and to achieve a slow release effect when used for wound repair. Therefore, in order to evaluate that the CSOB-FA hydrogel has good antioxidant effect on diabetic wounds. The in vitro oxidation resistance of the CSOB-FA hydrogel is researched through a DPPH free radical scavenging experiment, the DPPH scavenging efficiency is continuously improved along with the increase of the hydrogel concentration, when the hydrogel concentration is increased to 4mg/ml, the DPPH free radical scavenging rate is greatly improved (figure 8), and the DPPH free radical scavenging efficiency of the CSMA hydrogel and the CSOB hydrogel is obviously poorer than that of the CSOB-FA hydrogel.
Test example 9 hemostasis test of the hydrogels of the present invention
CSMA hydrogel, CSOB hydrogel and CSOB-FA hydrogel were prepared separately as described in example 1, and then experiments were performed.
1. Experimental method
The CSOB-FA spray hydrogel has the advantages of good mechanical strength and stability, self-healing capacity, biocompatibility, high antibacterial efficiency, good adhesion and the like, and is therefore selected for subsequent in vivo study. The hemostatic properties of the prepared hydrogels were evaluated by hemorrhagic liver mouse model. The amount of blood loss during hemostasis after hydrogel application or untreated was recorded and acute liver bleeding mice (Kunming mice, 30-35 g, males) were used to assess the hemostatic potential of CSOB-FA hydrogels in vivo. The liver was carefully exposed with surgical scissors after sterilizing the abdominal skin with alcohol, divided into 4 groups of 5. Pre-weighed filter papers were placed under the liver. Acute bleeding wound of liver was induced by needle, then covered with hydrogel rapidly, untreated acute wound was used as control group. Digital images were taken at 10, 20 and 30 seconds, and finally the filters were weighed to quantify the blood loss of each group.
2. Experimental results
Vascular disease is a complication of diabetics, and thus anticoagulant therapy is one of the conventional treatments to prevent the remaining complications, and thus, continuous bleeding after debridement is not negligible, and effective hemostasis is one of the prerequisites for effective wound healing. CSMA also showed some hemostatic capacity by the mouse liver hemorrhage model for evaluation of the hemostatic capacity of CSOB-FA hydrogel, with significantly reduced blood loss of CSOB and CSOB-FA compared to the blank (fig. 9).
Test example 10 hydrogel wound healing experiments according to the invention
CSMA hydrogel, CSOB hydrogel and CSOB-FA hydrogel were prepared separately as described in example 1, and then experiments were performed.
1. Experimental method
Male SD rats weighing 180-250g were selected as experimental study subjects, and on day 0, rats were randomly divided into control group and experimental group, back hair was removed after anesthesia, and circular wound surface with diameter of 8 mm was made on the back of the rats with a biopsy punch. Adding 50 μl of bacterial suspension (Staphylococcus aureus, 10) 8 CFU/mL), covering the wound surface with a sterile closed PU film for 24 hours to prepare a bacterial infection wound surface model. On day 1, three hydrogels of CSMA, CSOB and CSOB-FA were spray crosslinked at the wound site, followed by UV curing for 15s. Animals were randomly divided into 4 groups, and control, CSMA, CSOB, and CSOB-FA hydrogels were applied, respectively. Digital images of the wound were collected at 4, 8, 11, 14 days post-surgery, respectively, and measured with ImageJ software.
2. Experimental results
In order to evaluate the healing effect of CSOB-FA hydrogel on in-vivo wound surfaces, an SD rat bacterial infectious skin defect model is established, a staphylococcus aureus infected rat full-layer skin defect model is adopted, the healing capacity of the hydrogel on the infected wound surfaces is evaluated, and the experimental results are shown in figure 10, and obviously, the CSOB-FA group hydrogel is almost completely healed, but is still clearly visible on blank and CSMA group wounds. While scar on the wound surface is still evident compared to the CSOB group, these results show that CSOB-FA hydrogels have better wound healing ability, probably because the hydrogel component OBSP has good ability to promote tissue repair while FA helps to provide antibacterial ability to promote wound healing acceleration.
In summary, the invention provides an in-situ curing forming hydrogel, a preparation method and application thereof, the hydrogel is prepared by mixing two components, the component A consists of methacrylic chitosan and ferulic acid, the component B is oxidized bletilla striata polysaccharide, and the component A and the component B can be mixed to form the hydrogel, so that the hydrogel can be completely fit on a large-area wide and irregularly-shaped dynamic wound, and meanwhile, the effects of resisting bacteria, resisting inflammation and promoting wound healing can be exerted. In addition, the addition of the ferulic acid can improve the toughness of the hydrogel, can be changed along with various movement forms, and can completely adapt to dynamic wounds. The two components of the hydrogel can be separated, and the hydrogel can be sprayed on wounds in sequence to exert effects when in use. The hydrogel disclosed by the invention is convenient to carry, low in cost and good in application prospect in wound care.
Claims (10)
1. An in situ cured molded hydrogel product kit, characterized in that: it is composed of two components which are stored separately:
the component A consists of the following raw materials in percentage by mass: 1.0 to 2.0 percent of methacrylic chitosan, 0.1 to 1 percent of ferulic acid, 0.1 to 0.5 percent of phenyl phosphate and the balance of solvent;
the component B consists of the following raw materials in percentage by mass: 1-10% of oxidized bletilla polysaccharide and the balance of solvent.
2. The in situ curing molded hydrogel product kit of claim 1, wherein: it is composed of two components which are stored separately:
the component A consists of the following raw materials in percentage by mass: 2% of methacrylic chitosan, 0.8% of ferulic acid, 0.25% of phenyl phosphate and the balance of solvent;
the component B consists of the following raw materials in percentage by mass: 2% of oxidized bletilla striata polysaccharide and the balance of solvent.
3. The set forth in claim 1 or 2, wherein the set molded hydrogel product cartridge is characterized by:
in the component A, the phenyl phosphate is phenyl lithium phosphate;
and/or, in component a, the solvent is water;
and/or, in the component B, the solvent is water.
4. The set forth in claim 1 or 2, wherein the set molded hydrogel product cartridge is characterized by: in the component A, the preparation method of the methacrylic chitosan comprises the following steps:
dissolving chitosan in a solvent, adding methacrylic anhydride into the chitosan solution, dialyzing after the reaction, and freeze-drying to obtain the chitosan;
after the chitosan is dissolved in a solvent, the concentration is 1-5%;
and/or, the solvent is a 1% acetic acid solution;
and/or the volume ratio of the methacrylic anhydride to the chitosan solution is 1:100;
And/or the reaction temperature is 20-30 ℃; the reaction time is 24-48 hours;
and/or, the molecular weight cut-off of the dialysis bag is 4.0-8.0 kDa during dialysis;
and/or, during the dialysis, the dialysate is water;
and/or the dialysis time is 1-3 days.
5. The set forth in claim 1 or 2, wherein the set molded hydrogel product cartridge is characterized by: in the component B, the preparation method of the rhizoma bletillae polysaccharide comprises the following steps:
1) Polysaccharide from rhizoma bletillae and NaIO 4 Respectively dissolving in solvent to obtain rhizoma bletilla polysaccharide solution and NaIO 4 A solution;
2) Mixing rhizoma bletilla polysaccharide solution and NaIO 4 SolutionAfter the mixed reaction, adding glycol to terminate the reaction;
3) Dialyzing the reaction solution, and freeze-drying to obtain the final product.
6. The set forth in claim 5, wherein the set molded hydrogel product cartridge comprises:
in the step 1), the bletilla polysaccharide consists of mannose and glucan, wherein the molar ratio of the mannose to the glucan is 2.946:1;
and/or, in step 1), the bletilla striata polysaccharide and the NaIO 4 The molar ratio of (2) is 0.4:1, a step of;
and/or, in step 1), the solvent is water;
and/or, in step 2), the bletilla striata polysaccharide solution and NaIO 4 Mixing the solutions and stirring for 10-20 h;
and/or, in the step 2), the temperature of the reaction is 20-30 ℃; the reaction time is 8-12 hours;
and/or, in step 3), the molecular weight cut-off of the dialysis bag is 3.5 kDa during said dialysis;
and/or, in step 3), the dialysate is water during the dialysis;
and/or, in the step 3), the dialysis time is 1-3 days.
7. The in situ curing molded hydrogel product kit of claim 6, wherein: the preparation method of the bletilla striata polysaccharide comprises the following steps:
(1) Pulverizing rhizoma bletilla, and defatting;
(2) Drying defatted rhizoma bletilla, extracting with water, and filtering to obtain extract;
(3) Adding Sevage reagent into the extract to remove protein, collecting water phase, precipitating with alcohol solution, washing precipitate, and drying to obtain the final product;
in the step (1), degreasing is carried out for 2-5 hours at 70-90 ℃ by using 95% ethanol and petroleum ether with the feed liquid ratio of 1 g:5-10 mL respectively;
and/or in the step (2), the feed liquid ratio of the bletilla striata medicinal material to the water is 1 g:40-60 mL;
and/or in the step (2), the extraction temperature is 70-90 ℃ and the extraction time is 1-5 h;
And/or, in the step (3), the alcohol solution is 95% ethanol.
8. A hydrogel, characterized in that: the in-situ curing molding hydrogel product box according to any one of claims 1-7 is obtained by mixing the component A and the component B.
9. The hydrogel of claim 8, wherein: the component A and the component B are respectively put in a spray bottle, one of the components is sprayed firstly, and then the other component is sprayed to obtain hydrogel;
or directly mixing the component A and the component B to obtain hydrogel;
the volume ratio of the component A to the component B is 1:1.
10. Use of the cured in place shaped hydrogel product kit of any one of claims 1 to 7 or the hydrogel of any one of claims 8 to 9 in the preparation of a wound repair material.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1609462A1 (en) * | 2004-04-22 | 2005-12-28 | JUVENA (International) AG | Cosmetic or dermatological preparation comprising a nutrient medium phase |
| CN1944495A (en) * | 2006-09-29 | 2007-04-11 | 北京大学 | Water gel containing natural high molecule and its radiation preparing method |
| WO2008070368A2 (en) * | 2006-11-01 | 2008-06-12 | Living Proof, Inc. | Methods and compositions for skin care |
| US20130022569A1 (en) * | 2011-05-16 | 2013-01-24 | Uhrich Kathryn E | Hydrogels |
| CN103200971A (en) * | 2010-08-30 | 2013-07-10 | 哈佛大学校长及研究员协会 | A high strength chitin composite material and method of making |
| CN103554532A (en) * | 2013-10-18 | 2014-02-05 | 仲恺农业工程学院 | Ferulic acid-collagen antimicrobial film, and preparation method and application thereof |
| CN104027833A (en) * | 2014-06-04 | 2014-09-10 | 武汉纺织大学 | Preparation method of chitosan hydrogel dressing |
| CN109776819A (en) * | 2019-01-10 | 2019-05-21 | 汕头大学 | A kind of bletilla polysaccharide-carboxymethyl chitosan composite hydrogel and its preparation |
| CN112812484A (en) * | 2021-01-26 | 2021-05-18 | 侯龙辉 | Antibacterial moisturizing degradable porous gel preservative film and preparation method thereof |
| CN113512132A (en) * | 2021-04-02 | 2021-10-19 | 杭州鹿扬科技有限公司 | Quick hemostatic hydrogel and preparation method thereof |
| CN114343975A (en) * | 2022-01-12 | 2022-04-15 | 河北卫崭医疗科技有限公司 | Wet wound dressing and its prepn |
| CN114748676A (en) * | 2022-04-08 | 2022-07-15 | 四川大学 | Chitosan-based efficient hemostatic with Janus structure, and preparation method and application thereof |
| CN114767918A (en) * | 2022-03-21 | 2022-07-22 | 东莞市人民医院 | Coagulation-promoting hemostatic protein material, coagulation-promoting hemostatic antibacterial material and preparation method thereof |
| CN114920956A (en) * | 2022-05-20 | 2022-08-19 | 武汉理工大学 | Hemostatic, antibacterial and healing-promoting hydrogel with real-time monitoring function and preparation method thereof |
| CN115353646A (en) * | 2022-07-21 | 2022-11-18 | 中国热带农业科学院海口实验站 | Amyloid fiber-ferulic acid-chitosan double-network hydrogel and preparation method and application thereof |
| CN115501376A (en) * | 2022-09-16 | 2022-12-23 | 常州美杰医疗用品有限公司 | Gel type antibacterial medical band-aid and preparation method thereof |
| CN115926359A (en) * | 2022-12-02 | 2023-04-07 | 广东省科学院生物与医学工程研究所 | Double-bond bletilla striata polysaccharide-carboxymethyl chitosan gel and preparation method and application thereof |
| CN115957371A (en) * | 2022-11-24 | 2023-04-14 | 中国医学科学院放射医学研究所 | Gel application for repairing skin injury and preparation method and application thereof |
| CN116019973A (en) * | 2023-01-18 | 2023-04-28 | 东南大学 | Nanometer hybridized double-network hydrogel based on nanometer enzyme complex, and preparation method and application thereof |
| CN116426003A (en) * | 2023-04-12 | 2023-07-14 | 中国海洋大学 | 3D hydrogel for cell expansion culture and preparation method thereof |
| CN116942890A (en) * | 2023-06-09 | 2023-10-27 | 西南交通大学 | Antibacterial anti-inflammatory thermosensitive hydrogel with function of promoting wound closure and preparation method thereof |
-
2023
- 2023-12-06 CN CN202311665426.4A patent/CN117357692B/en active Active
Patent Citations (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1609462A1 (en) * | 2004-04-22 | 2005-12-28 | JUVENA (International) AG | Cosmetic or dermatological preparation comprising a nutrient medium phase |
| CN1944495A (en) * | 2006-09-29 | 2007-04-11 | 北京大学 | Water gel containing natural high molecule and its radiation preparing method |
| WO2008070368A2 (en) * | 2006-11-01 | 2008-06-12 | Living Proof, Inc. | Methods and compositions for skin care |
| CN103200971A (en) * | 2010-08-30 | 2013-07-10 | 哈佛大学校长及研究员协会 | A high strength chitin composite material and method of making |
| US20130022569A1 (en) * | 2011-05-16 | 2013-01-24 | Uhrich Kathryn E | Hydrogels |
| CN103554532A (en) * | 2013-10-18 | 2014-02-05 | 仲恺农业工程学院 | Ferulic acid-collagen antimicrobial film, and preparation method and application thereof |
| CN104027833A (en) * | 2014-06-04 | 2014-09-10 | 武汉纺织大学 | Preparation method of chitosan hydrogel dressing |
| CN109776819A (en) * | 2019-01-10 | 2019-05-21 | 汕头大学 | A kind of bletilla polysaccharide-carboxymethyl chitosan composite hydrogel and its preparation |
| CN112812484A (en) * | 2021-01-26 | 2021-05-18 | 侯龙辉 | Antibacterial moisturizing degradable porous gel preservative film and preparation method thereof |
| CN113512132A (en) * | 2021-04-02 | 2021-10-19 | 杭州鹿扬科技有限公司 | Quick hemostatic hydrogel and preparation method thereof |
| CN114343975A (en) * | 2022-01-12 | 2022-04-15 | 河北卫崭医疗科技有限公司 | Wet wound dressing and its prepn |
| CN114767918A (en) * | 2022-03-21 | 2022-07-22 | 东莞市人民医院 | Coagulation-promoting hemostatic protein material, coagulation-promoting hemostatic antibacterial material and preparation method thereof |
| CN114748676A (en) * | 2022-04-08 | 2022-07-15 | 四川大学 | Chitosan-based efficient hemostatic with Janus structure, and preparation method and application thereof |
| CN114920956A (en) * | 2022-05-20 | 2022-08-19 | 武汉理工大学 | Hemostatic, antibacterial and healing-promoting hydrogel with real-time monitoring function and preparation method thereof |
| CN115353646A (en) * | 2022-07-21 | 2022-11-18 | 中国热带农业科学院海口实验站 | Amyloid fiber-ferulic acid-chitosan double-network hydrogel and preparation method and application thereof |
| CN115501376A (en) * | 2022-09-16 | 2022-12-23 | 常州美杰医疗用品有限公司 | Gel type antibacterial medical band-aid and preparation method thereof |
| CN115957371A (en) * | 2022-11-24 | 2023-04-14 | 中国医学科学院放射医学研究所 | Gel application for repairing skin injury and preparation method and application thereof |
| CN115926359A (en) * | 2022-12-02 | 2023-04-07 | 广东省科学院生物与医学工程研究所 | Double-bond bletilla striata polysaccharide-carboxymethyl chitosan gel and preparation method and application thereof |
| CN116019973A (en) * | 2023-01-18 | 2023-04-28 | 东南大学 | Nanometer hybridized double-network hydrogel based on nanometer enzyme complex, and preparation method and application thereof |
| CN116426003A (en) * | 2023-04-12 | 2023-07-14 | 中国海洋大学 | 3D hydrogel for cell expansion culture and preparation method thereof |
| CN116942890A (en) * | 2023-06-09 | 2023-10-27 | 西南交通大学 | Antibacterial anti-inflammatory thermosensitive hydrogel with function of promoting wound closure and preparation method thereof |
Non-Patent Citations (5)
| Title |
|---|
| LIDA ZHU ET AL: "pH sensitive methacrylated chitosan hydrogels with tunable physical and chemical properties", BIOCHEMICAL ENGINEERING JOURNAL, pages 38 * |
| SUDHA ANJALI ET AL: "Ferulic acid incorporated anti-microbial self cross-linking hydrogel: A promising system for moderately exudating wounds", JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, pages 103446 * |
| 候冰娜: "光交联羧甲基壳聚糖水凝胶的制备及药物缓释性能研究", 材料工程, pages 76 - 84 * |
| 王锐: "川芎提取物接枝型鼻用温敏凝胶制备及药效学研究", 上海中医药杂志, pages 1007 - 1334 * |
| 瞿燕: "白及多糖水凝胶的制备、表征及其促染菌伤口愈合作用的研究", 中药与临床, pages 29 - 35 * |
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