CN115364273A - Preparation method of sprayable nano oxidized cellulose hemostatic gel - Google Patents
Preparation method of sprayable nano oxidized cellulose hemostatic gel Download PDFInfo
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- CN115364273A CN115364273A CN202211134178.6A CN202211134178A CN115364273A CN 115364273 A CN115364273 A CN 115364273A CN 202211134178 A CN202211134178 A CN 202211134178A CN 115364273 A CN115364273 A CN 115364273A
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- oxidized cellulose
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
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- C08L1/04—Oxycellulose; Hydrocellulose, e.g. microcrystalline cellulose
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0026—Sprayable compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0031—Hydrogels or hydrocolloids
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/08—Polysaccharides
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
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- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/202—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with halogen atoms, e.g. triclosan, povidone-iodine
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- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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- A61L2400/00—Materials characterised by their function or physical properties
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- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
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Abstract
The invention relates to the technical field of hemostatic materials, in particular to a preparation method of a sprayable nano oxidized cellulose hemostatic gel. Comprises the following steps of 1: preparing nano oxidized cellulose by a TEMPO-NaClO-NaBr oxidation system; step 2: dispersing the nano oxidized cellulose prepared in the step 1 in water; and step 3: and (3) preparing the nano oxidized cellulose dispersed in the step (2) into gel, and then adding ether and iodoform into the gel to obtain the nano oxidized cellulose spray material. The spray nano oxidized cellulose hemostatic gel disclosed by the invention quickly forms hydrogel in the presence of blood after being sprayed with nano fibers, so that the problem that the traditional gauze of a tourniquet cannot be used for packing and compressing hemostasis when bleeding occurs at the joint part of a body is solved; and the iodoform and the ether have the effects of anesthesia, disinfection and inflammation diminishing.
Description
Technical Field
The invention relates to the technical field of hemostatic materials, in particular to a preparation method of a sprayable nano oxidized cellulose hemostatic gel.
Background
At present, in the field of war wounds, the problem of timely and rapid hemostasis cannot be effectively solved, uncontrollable heavy bleeding is the primary factor of battlefield casualties, and the factor accounts for more than ninety percent of the death rate of wounds. Therefore, rapid hemostasis is of great importance to reducing battlefield casualties, the conventional gauze such as a tourniquet and the like is packed to be compressed in the conventional hemostasis mode commonly used in war wounds at present, but the conventional gauze such as the tourniquet and the like cannot be used for packing to be compressed to stop bleeding when bleeding occurs at the joint junction, the compression hemostasis effect is limited when bleeding occurs at the serious bleeding condition, and the risk of secondary bleeding is easy to occur sometimes.
Although the existing hemostatic materials make remarkable progress in terms of hemostatic effect, portability and the like, the safety and the effective hemostatic capability of the existing hemostatic materials are still a great bottleneck of the existing hemostatic problem.
Oxidized regenerated cellulose has the characteristics of low immunogenicity, healing promotion, modification of surface active sites for antibiosis and antivirus, and the like. The oxidized regenerated cellulose structure can exhibit optimal hemostatic and biodegradable properties when the carboxyl content is between 16-24%.
Oxidized regenerated cellulose is an effective hemostatic agent, and carboxyl groups in the structure of the oxidized regenerated cellulose can reduce the pH value of blood, provide an acidic environment and attract Fe in hemoglobin 3+ And meanwhile, the ion can activate platelets in blood, so that the platelets are aggregated to form thrombus, and large-area bleeding is controlled. In addition, oxidized regenerated cellulose swells after being contacted with blood, so that the tail end of a capillary vessel is pressed and closed, and the hemostasis is accelerated. The higher the carboxyl content in the oxidized regenerated cellulose is, the lower the polymerization degree is, and the better the hemostatic effect is.
Although oxidized regenerated cellulose has many excellent properties, it also has some disadvantages: the oxidized surface can enhance hemostasis, but the active surface that can be provided without nanodispersion is limited, has low pH, is prone to damage some nervous systems, and cannot be used for cerebral hemorrhage and the like.
In some published or issued patents, natural or synthetic polymeric materials, such as chitosan (CN 102198288A), alginate (CN 104013991A) graphene oxide (CN 104383578A), and the like, have been used to improve the hemostatic properties of oxidized regenerated cellulose. Although the composite hemostatic material has great significance for relevant research on oxidized regenerated cellulose, the hemostatic performance of the material is improved to a certain degree, but the improvement degree is small, namely the improvement effect is poor. Moreover, the improvement methods in the previous researches also have negative effects on the mechanical strength and the bio-absorbable performance of the oxidized regenerated cellulose hemostatic material, and the modification effect is irretrievable relative to the slightly improved hemostatic performance. In addition, the existing nano oxidized cellulose has low cross-linking strength based on hydrogen bond action among molecules, so that the hydrogel has poor strength and is easy to crush under pressure.
Disclosure of Invention
Aiming at the technical problems of slow hemostasis speed and small promotion range of hemostasis performance of the existing modified material of the nano oxidized cellulose, the invention provides a preparation method of a sprayable nano oxidized cellulose hemostasis gel. The oxidized nano-fiber can wrap small molecular substances such as drugs, protein and the like in the aspect of exerting the drug effect, so that the wound can be quickly healed after bleeding, meanwhile, the drugs such as ethyl ether, iodoform and the like are added into the nano-cellulose, so that the pain of the wound can be relieved, the antibacterial property of the hemostatic material can be ensured, the antibacterial property of the material is improved, and the material has good air permeability, water permeability and water retention characteristics.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a preparation method of sprayable nano oxidized cellulose hemostatic gel comprises the following steps:
step 1: preparing nano oxidized cellulose by a TEMPO-NaClO-NaBr oxidation system;
step 2: dispersing the nano oxidized cellulose prepared in the step 1 in water;
and step 3: and (3) preparing the nano oxidized cellulose dispersed in the step (2) into gel, and then adding ether and iodoform into the gel to obtain the nano oxidized cellulose spray material.
Preferably, the step 1 comprises:
step 1.1: firstly, placing a pulp board in distilled water, processing the pulp board into wet pulp by a processor, adjusting the pH value of the pulp to be 2 by HCI, removing mineral substances in the pulp, then filtering and washing the pulp by water, adjusting the pH value to be 7 by NaOH, finally drying the pulp for 3 hours at the temperature of 120 ℃, and measuring the content of cellulose in the pulp;
step 1.2: mixing TEMPO, naBr and deionized water according to the proportion of 0.016g of TEMPO, 0.1g of NaBr and 100ml of deionized water per gram of cellulose to prepare a solution; then adding a corresponding amount of the final product of the step 1; then adding NaClO into the solution according to the proportion of 10 mmol/g;
step 1.3: starting the reaction, adding 0.5M NaOH into the reaction solution to maintain the pH of the reaction to be 10, and finishing the reaction;
step 1.4: adding sodium borohydride and ethanol into the solution reacted in the step 1.3 according to the proportion that each gram of cellulose corresponds to 01g of sodium borohydride and 1ml of ethanol, and reacting for 3 hours;
step 1.5: and (3) washing and filtering the solution reacted in the step (1.4), and adjusting the PH value to be neutral to obtain the transparent gelatinous nano oxidized cellulose.
Preferably, the step 2 comprises:
step 2.1: dissolving the nano oxidized cellulose prepared in the step 1 in water, and treating the solution by a homogenizer to uniformly disperse the solution;
step 2.2: treating the solution dispersed in the step 2.1 for 50min by adopting an ultrasonic disperser;
step 2.3: and (3) centrifuging the solution subjected to ultrasonic treatment in the step 2.2 by using a centrifuge, and taking the centrifuged supernatant to obtain the aqueous dispersion of the nano oxidized cellulose.
Compared with the prior art, the invention has the beneficial effects that:
1. according to the sprayable nano oxidized cellulose hemostatic gel, the prepared nano cellulose is selectively oxidized by a TEMPO-NaClO-NaBr oxidation system, and a sodium carboxylate structure is introduced to the C6 position of a nano cellulose molecule, so that the specific surface area of oxidized regenerated cellulose is increased, the hemostatic performance of the obtained sprayable nano oxidized cellulose hemostatic gel is improved, and the defect that the hemostatic performance of a common hemostatic material is improved to a small extent is overcome.
2. The surface of the sprayable nano oxidized cellulose hemostatic gel is provided with carboxyl, so that the sprayable nano oxidized cellulose hemostatic gel has double hemostatic effects, the hemostatic time is greatly shortened, the quick hemostatic effect is achieved, and medicines such as diethyl ether, iodoform and the like are added, so that the pain of wounds can be relieved, and the antibacterial property of a hemostatic material can be ensured.
3. The preparation process of the sprayable nano oxidized cellulose hemostatic gel does not need special equipment, has mild reaction conditions, and can realize industrial production.
4. The raw materials in the preparation process of the sprayable nano oxidized cellulose hemostatic gel are renewable resources and have low cost, and the cost reduction of the nano cellulose/oxidized regenerated cellulose composite hemostatic material can be realized.
5. The spraying nano oxidized cellulose hemostatic gel prepared by the invention can reduce the bleeding amount by 10-20% when the liver and artery bleed.
6. The nanometer oxidized cellulose hemostatic gel capable of being sprayed out quickly forms hydrogel when meeting blood after spraying nanometer fiber, and the problem that the traditional gauze of a tourniquet can not be used for packing and compressing hemostasis when bleeding occurs at the joint interface of a body is solved.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention and not to limit the invention.
In the drawings:
FIG. 1 is a flow chart of a method of the present invention;
FIG. 2 is a graph of the results of a rat hemostasis test using nano oxidized cellulose;
FIG. 2 is a graph of the results of a leg artery hemostasis experiment of a nano oxidized cellulose SD rat;
FIG. 3 is a diagram showing the result of an animal liver hemostasis test, (a) the observation of the hemostasis effect of nano oxidized cellulose, and (b) the result of liver hemorrhage amount detection;
FIG. 4 is a safety test of nano-oxidized cellulose prepared by the present invention;
FIG. 5 shows the result of ELSA detection of blood inflammatory factors after the nano oxidized cellulose prepared by the present invention is treated;
FIG. 6 shows the water contact angle test results of the oxidized nanofiber material;
FIG. 7 macroscopic topography observations of oxidized nanocellulose materials;
FIG. 8 shows the surface micro-topography of oxidized nano-cellulose material before and after drying;
FIG. 9 stress-strain results for oxidized nanocellulose material and other hemostatic materials;
FIG. 10 structural comparison analysis of oxidized nanocellulose material with other hemostatic materials;
fig. 11 viscosity observation of oxidized nanocellulose material.
Detailed Description
The preferred embodiments of the present invention will be described in conjunction with the accompanying drawings, and it will be understood that they are described herein for the purpose of illustration and explanation and not limitation.
Example (b):
referring to fig. 1-11, a method for preparing a sprayable nano oxidized cellulose hemostatic gel comprises:
step 1: preparing nano oxidized cellulose by a TEMPO-NaClO-NaBr oxidation system;
step 1.1: firstly, placing a pulp board in distilled water, processing the pulp board into wet pulp by a processor, adjusting the pH of the pulp board to be 2 by HCI, removing mineral substances in the pulp board, then filtering and washing the pulp board, adjusting the pH of the pulp board to be 7 by NaOH, finally drying the pulp board for 3 hours at the temperature of 120 ℃, and measuring the content of cellulose in the pulp board;
step 1.2: mixing TEMPO, naBr and deionized water according to the proportion of 0.016g of TEMPO, 0.1g of NaBr and 100ml of deionized water per gram of cellulose to prepare a solution; then adding a corresponding amount of the final product of the step 1; then adding NaClO into the solution according to the proportion of 10 mmol/g;
step 1.3: starting the reaction, adding 0.5M NaOH into the reaction solution to maintain the pH of the reaction to be 10, and finishing the reaction;
step 1.4: adding sodium borohydride and ethanol into the solution reacted in the step 1.3 according to the proportion that each gram of cellulose corresponds to 01g of sodium borohydride and 1ml of ethanol, and reacting for 3 hours;
step 1.5: and (3) washing and filtering the solution reacted in the step (1.4), and adjusting the PH value to be neutral to obtain the transparent gelatinous nano oxidized cellulose.
Step 2: dispersing the nano oxidized cellulose prepared in the step 1 in water;
step 2.1: dissolving the nano oxidized cellulose prepared in the step 1 in water, and treating the solution by a homogenizer to uniformly disperse the solution;
step 2.2: treating the solution dispersed in the step 2.1 for 50min by adopting an ultrasonic disperser;
step 2.3: and (3) centrifuging the solution subjected to ultrasonic treatment in the step (2.2) by using a centrifuge, and taking the centrifuged supernatant to obtain the aqueous dispersion of the nano oxidized cellulose.
And step 3: and (3) preparing the nano oxidized cellulose dispersed in the step (2) into gel, and then adding ether and iodoform into the gel to obtain the nano oxidized cellulose spray material.
The experimental results are as follows:
1. solution viscosity measurement
Measured at the same concentration using a rotational viscometer (NDJ-79) as shown in Table 1 below:
TABLE 1 viscosity of commonly used hemostatic materials
From the above table it can be seen that: from the data in the table, the viscosity of the oxidized nanocellulose is far superior to other materials at the same concentration. Fig. 11 shows viscosity observations of oxidized nanocellulose, which can be seen to have good viscosity.
2. Solution surface tension measurement
The hemostatic mechanism of oxidized cellulose, measured with a contact angle measuring instrument (KRUSS, america), is mainly through the self-COOH structure and Fe in blood as shown in FIG. 6 3+ The brown thrombus gel block is formed by combination, the blood vessel is sealed, the hemostatic effect is achieved, the process does not need to participate in a normal physiological blood coagulation mechanism, secondly, oxidized cellulose with rough surface is easy to cause platelet aggregation and rupture to form platelet embolus, blood coagulation factors are activated, a blood coagulation system is activated, fibrinogen is promoted to be converted into fibrin, and thrombus hemostasis is formed. Furthermore, the hydroxyl groups in the oxidized cellulose can also react with Ca in the plasma 2+ Formation of crosslinksThe gel-like blood clots can block the damaged blood vessels to stop bleeding.
The control group and Fe are designed according to the hemostasis mechanism of the nano oxidized cellulose 3+ After the combination of experiments, the water contact angle test is used to characterize the hydrophilicity and hydrophobicity of the material, and as can be seen from fig. 6, the hydrophilic effect of oxidized cellulose is the best and with Fe 3+ The hydrophilicity after binding is substantially comparable.
3. Macroscopic topography observation
RCMs morphology was observed in an optical microscope (BX 41, OLYMPUS) and the shape of the liquid at the tip of the needle was photographed by a digital camera (IXUS 220HS, canon).
As shown in FIG. 7, the general state of the nano oxidized cellulose gel was observed and the sprayed state was confirmed that the nano oxidized cellulose gel could be made into a spray state, which is advantageous for the treatment of bleeding.
4 surface micro-topography
Surface microtopography was characterized using atomic force microscopy. The nanometer oxidized cellulose prepared by TEMPO oxidation is observed by an atomic force microscope, the width is 2-3 nm, the length is 500-1000 nm, as shown in the right graph of figure 8, and the surface of the oxidized cellulose membrane obtained by drying is distributed with the nanometer oxidized cellulose.
5. Stress-strain of oxidized nanocellulose materials and other hemostatic materials
The stress strain of the various materials was tested and it can be seen from figure 9 that oxidized cellulose can withstand higher maximum stresses than the other materials.
Young's modulus was obtained by calculating a stress-strain curve as shown in Table 2 below:
TABLE 2 Young's modulus of oxidized nanocellulose materials with other hemostatic materials
The larger the Young's modulus is, the more difficult the material is to deform, and it can be seen from the above table that the Young's modulus of the oxidized nano-cellulose material is greater than that of other materials, which proves that the oxidized nano-cellulose material has good performance and is not easy to deform.
6. Rat hemostasis experiment of nano cellulose oxide membrane prepared by the invention
As shown in fig. 2 (a), the arrow points to the position of the blood vessel of the leg of the rat, after the artery blood vessel of the leg of the rat is cut short, the nano-oxidized cellulose hemostatic gel material prepared by the invention is sprayed, and after a period of observation, suturing is carried out, and as shown in fig. 2 (b), the left side is a control group, and the right side is a nano-oxidized cellulose gel group, so that the obvious bleeding can be seen in the interior of the control group, and the bleeding overflows, and the hemostatic effect of the nano-oxidized cellulose gel group is good.
7. Hemostasis test of animal internal organs
The animal was eviscerated into control and nano-oxidized cellulose gel groups, observed and the amount of bleeding was measured. The observation results are shown in fig. 3 (a), and the detection results of the amount of bleeding are shown in fig. 3 (b). Therefore, the nano oxidized cellulose of the invention has good hemostatic effect.
8. Safety test
As shown in fig. 4, the results of HE staining the heart, liver, spleen, lung, kidney and the experimental part of nano oxidized cellulose through HE showed that the safety of nano oxidized cellulose is good, and the final group is the result of bleeding tissue part, which indicates no influence on skin and good safety.
ELSA inflammatory factor detection
As shown in fig. 5, the blood of the experimental rat was used for the detection of the ELSA inflammatory factor, and it was found that the nano oxidized cellulose did not cause local and systemic inflammation.
11. Structural analysis of materials
As shown in fig. 10, the structures of oxidized cellulose, chitosan, sodium alginate and gelatin are the closest to oxidized cellulose in terms of structural similarity.
The foregoing shows and describes the general principles, principal features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (3)
1. A preparation method of a sprayable nano oxidized cellulose hemostatic gel is characterized by comprising the following steps: the method comprises the following steps:
step 1: preparing nano oxidized cellulose by a TEMPO-NaClO-NaBr oxidation system;
and 2, step: dispersing the nano oxidized cellulose prepared in the step 1 in water;
and step 3: and (3) preparing the nano oxidized cellulose dispersed in the step (2) into gel, and then adding ether and iodoform into the gel to obtain the nano oxidized cellulose spray material.
2. The method for preparing the sprayable nano oxidized cellulose hemostatic gel according to claim 1, wherein the method comprises the following steps: the step 1 comprises the following steps:
step 1.1: firstly, placing a pulp board in distilled water, processing the pulp board into wet pulp by a processor, adjusting the pH of the pulp board to be 2 by HCI, removing mineral substances in the pulp board, then filtering and washing the pulp board, adjusting the pH of the pulp board to be 7 by NaOH, finally drying the pulp board for 3 hours at the temperature of 120 ℃, and measuring the content of cellulose in the pulp board;
step 1.2: mixing TEMPO, naBr and deionized water according to the proportion of 0.016g TEMPO, 0.1g NaBr and 100ml deionized water corresponding to each gram of cellulose to obtain a solution; then adding a corresponding amount of the final product of the step 1; then adding NaClO into the solution according to the proportion of 10 mmol/g;
step 1.3: starting the reaction, adding 0.5M NaOH into the reaction solution to maintain the pH of the reaction to be 10, and finishing the reaction;
step 1.4: adding sodium borohydride and ethanol into the solution reacted in the step 1.3 according to the proportion that each gram of cellulose corresponds to 01g of sodium borohydride and 1ml of ethanol, and reacting for 3 hours;
step 1.5: and (3) washing and filtering the solution reacted in the step (1.4), and adjusting the PH to be neutral to obtain the transparent gelatinous nano oxidized cellulose.
3. The method for preparing the sprayable nano oxidized cellulose hemostatic gel according to claim 2, wherein the method comprises the following steps: the step 2 comprises the following steps:
step 2.1: dissolving the nano oxidized cellulose prepared in the step 1 in water, and treating the solution by a homogenizer to uniformly disperse the solution;
step 2.2: treating the solution dispersed in the step 2.1 for 50min by adopting an ultrasonic disperser;
step 2.3: and (3) centrifuging the solution subjected to ultrasonic treatment in the step (2.2) by using a centrifuge, and taking the centrifuged supernatant to obtain the aqueous dispersion of the nano oxidized cellulose.
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