Protonated carboxymethylcellulose human absorbable hemostatic material and method of making same
Protonated carboxymethyl cellulose (CMC) hemostatic material was prepared by coagulation regeneration and acidification treatment, which solved the problems of high cost and non-absorption of ORC hemostatic gauze. This resulted in a low-cost, high-efficiency hemostatic, antibacterial and biocompatible hemostatic material suitable for various hemostatic applications.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- FUJIAN NORMAL UNIV
- Filing Date
- 2026-04-20
- Publication Date
- 2026-06-05
Smart Images
Figure CN122140992A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a protonated carboxymethyl cellulose absorbable hemostatic material and its preparation method. Background Technology
[0002] Acute traumatic hemorrhage is one of the leading causes of death and disability worldwide. The development of highly effective hemostatic materials is of great significance for trauma treatment and public health emergency response.
[0003] Absorbable gauze is widely used in surgical procedures because it eliminates the need for secondary surgical debridement. Oxidized regenerated cellulose (ORC) gauze is a commonly used absorbable hemostatic gauze in clinical practice, with a representative product being Surgicel from Johnson & Johnson. ® ORC has already achieved clinical application. ORC physically adsorbs blood components through its porous structure, while its surface carboxyl groups ionize to create a localized acidic microenvironment, activating platelets and coagulation factors to achieve chemical coagulation, thus exhibiting a synergistic hemostatic effect combining physical and chemical methods. However, the industrial production of ORC mainly relies on the N2O4 oxidation process. This process uses highly toxic and corrosive reagents, requires high-pressure reaction conditions, places stringent requirements on equipment, and has high production costs, resulting in expensive end products. This severely limits its widespread application in resource-constrained scenarios.
[0004] Sodium carboxymethyl cellulose (CMC-Na) is a low-cost, commercially available cellulose derivative with good biocompatibility and human absorption. However, its high water solubility means it is easily dispersed by blood when used alone as a hemostatic material, limiting its hemostatic effect. To reduce its water solubility, Japanese researchers used CMC-Na as a raw material, casting its acidic solution into molds and then subjecting them to freeze-thaw cycles or direct drying to prepare water-insoluble acidic carboxymethyl cellulose sponges or films for medical use (JP2004107503A, JP2008013510A). Johnson & Johnson in the United States coated ordinary gauze with CMC-Na, dried it, and then immersed it in an acidic aqueous solution to convert the CMC-Na on the gauze surface into acidic carboxymethyl cellulose, resulting in a significantly improved hemostatic performance of the modified gauze (GB725887A). This gauze has a core-sheath structure, with the sheath being acidic carboxymethyl cellulose and the core being cellulose fibers. Since cellulose cannot be degraded in the human body, this modified gauze cannot be absorbed by the body. To date, the strategy of converting water-soluble CMC-Na into water-insoluble protonated carboxymethyl cellulose has not been applied to the preparation of fibers, hemostatic gauze, granules, and sponges that are fully absorbable by the human body. Summary of the Invention
[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a protonated carboxymethyl cellulose absorbable hemostatic material and its preparation method. This material has low raw material cost, good hemostatic effect, and the characteristics of antibacterial, human absorption, and biosafety.
[0006] To achieve the above objectives, the present invention adopts the following technical solution:
[0007] A method for preparing a protonated carboxymethyl cellulose (ORC) absorbable hemostatic material involves: obtaining protonated carboxymethyl cellulose fibers by coagulation, regeneration, and acidification of a water-soluble sodium carboxymethyl cellulose solution; and then processing the protonated carboxymethyl cellulose fibers to obtain the hemostatic material. This hemostatic material combines highly efficient hemostasis, excellent antibacterial properties, biocompatibility, and human absorbability, making it an effective way to address the shortcomings of existing ORC hemostatic gauze.
[0008] The protonated carboxymethyl cellulose absorbable hemostatic material of this invention can be processed into various forms according to clinical needs, including but not limited to hemostatic gauze, hemostatic granules, and hemostatic sponges. The gauze form is suitable for covering and compressing hemostasis of superficial wounds, surgical incisions, and visceral wounds; the granule form is suitable for filling and hemostasis in irregular cavities, deep wounds, or minimally invasive surgeries; and the sponge form is suitable for large-area bleeding wounds or as a drug carrier. All of the above-mentioned hemostatic materials in different forms maintain the synergistic hemostatic mechanism of physical absorption and chemical coagulation, and possess excellent antibacterial properties, biocompatibility, and human absorbability.
[0009] Furthermore, the method for preparing the hemostatic gauze includes the following steps:
[0010] (1) Wet spinning and coagulation regeneration: Sodium carboxymethyl cellulose solution is sprayed into a coagulation bath through a spinneret. The coagulation bath is an ethanol-water solution with a volume concentration of 70-95%, which can quickly regenerate sodium carboxymethyl cellulose in the solution to form shaped nascent fibers.
[0011] (2) Acidification treatment: The nascent fibers are placed in an acidification bath for acidification treatment, and the -COO in the fibers is removed through a protonation reaction. - The acidification process is converted to -COOH to obtain protonated carboxymethyl cellulose fibers; the acidification bath is an aqueous solution of 90% ethanol with a volume concentration of 0.5 wt.% to 8.0 wt.% hydrochloric acid; this system can achieve mild and uniform acidification and avoid fiber structure collapse.
[0012] Furthermore, the acidification time can be adjusted according to the actual hemostatic application requirements to obtain protonated carboxymethyl cellulose fibers with a carboxyl content of 2.0 ~ 4.3 mmol / g. The acidification time can be controlled between 6 and 24 h, preferably 24 h. The acidification time is positively correlated with the carboxyl content. By controlling the acidification time, protonated carboxymethyl cellulose hemostatic materials with a gradient change in carboxyl content can be prepared. The carboxyl content of the hemostatic material is a key variable in the material's hemostatic ability.
[0013] (3) Post-processing and molding: The protonated carboxymethyl cellulose fiber is repeatedly washed with deionized water to remove residual hydrochloric acid and ethanol, and then naturally dried or vacuum dried to constant weight, and then processed into hemostatic gauze.
[0014] When the hemostatic gauze comes into contact with the bleeding wound, it can quickly absorb blood and concentrate blood cells to form a physical barrier, while the carboxyl groups ionize to release H+. + It creates a local acidic microenvironment to activate platelets and intrinsic coagulation pathways, achieving synergistic hemostasis through physical aspiration and chemical coagulation. After hemostasis, it can be gradually degraded and absorbed in the body, with no risk of foreign body residue. At the same time, its acidic microenvironment can effectively inhibit bacterial proliferation and reduce the probability of wound infection.
[0015] Furthermore, the preparation method of the hemostatic granules includes the following steps:
[0016] 1) Using sodium carboxymethyl cellulose solution as the aqueous phase, slowly add it to the oil phase composed of isooctane, Span 80 and Tween 60, and stir at high speed at 1000~1500 rpm for 2~2.5 h to form a stable water-in-oil emulsion;
[0017] 2) Add a calcium chloride aqueous solution with a mass concentration of 2-10% to the above emulsion and continue stirring for 1-1.5 h. The CMC will be cross-linked by calcium ions. After the reaction is completed, pour all the emulsion into excess anhydrous ethanol to demulsify. After washing, remove the oil phase and surfactant to obtain particles.
[0018] The volume ratio of the sodium carboxymethyl cellulose solution, isooctane, Span 80, Tween 60, and calcium chloride aqueous solution is 18~25: 110~130: 4.5~5.5: 1.0~1.5: 10~15.
[0019] 3) The obtained particles were placed in an acidification solution for 20-24 h for acidification treatment. The acidification solution was an aqueous solution of 90% ethanol with a volume concentration of 0.5 wt.% to 8.0 wt.% hydrochloric acid, which converted the particles into a protonated form that is insoluble in water. Finally, after washing, drying and sieving, protonated carboxymethyl cellulose hemostatic particles with a particle size range of 50-100 μm were obtained.
[0020] Further, the preparation method of the hemostatic sponge is as follows: sodium carboxymethyl cellulose solution is injected into a mold and freeze-dried to obtain a CMC-Na sponge with three-dimensional interconnected channels. Then, the sponge is immersed in an acidification solution for 20-24 h. The acidification solution is a 90% ethanol aqueous solution containing 0.5 wt.% to 8.0 wt.% hydrochloric acid, which is converted into a water-insoluble HCMC sponge. After being thoroughly washed with deionized water, it is freeze-dried again to obtain the hemostatic sponge.
[0021] In this invention, the sodium carboxymethyl cellulose solution is prepared by dissolving sodium carboxymethyl cellulose in deionized water, stirring until completely dissolved, filtering to remove insoluble matter, and obtaining a sodium carboxymethyl cellulose solution with a mass concentration of 2% to 20%. Further, the sodium carboxymethyl cellulose has a viscosity of 300 to 4500 mPa·s and a degree of carboxymethyl substitution of 0.3 to 1.8.
[0022] Furthermore, the hemostatic material described herein can be applied to wound hemostasis, intraoperative hemostasis during surgery, and postoperative hemostasis, with a wide range of applications. The wound hemostasis includes acute traumatic bleeding such as arterial bleeding and liver injury bleeding; the surgical procedures include clinical surgeries such as general surgery, cardiothoracic surgery, and orthopedics.
[0023] This invention employs the above technical solution, using CMC-Na solution as the mother liquor, and prepares protonated carboxymethyl cellulose hemostatic material through a green and mild solvent coagulation regeneration and acidification treatment process. This hemostatic material combines highly efficient hemostasis, excellent antibacterial properties, biocompatibility, and human absorbability, becoming an effective way to solve the shortcomings of existing ORC hemostatic gauze.
[0024] The present invention has the following beneficial effects:
[0025] 1. The hemostatic gauze of the present invention uses low-cost, commercially available sodium carboxymethyl cellulose as the sole raw material, without the need for other modifiers. It is prepared through simple wet spinning and acidification treatment. The preparation process is green and mild, avoiding the use of highly toxic reagents such as N2O4 in the preparation of traditional ORC gauze, and also eliminating the need for high-pressure reaction equipment. The production process is safe, low-cost, and easy to promote industrially. By controlling the acidification time, the carboxyl content of protonated carboxymethyl cellulose material can be precisely gradient controlled, thereby achieving customization of hemostatic, antibacterial, and human absorption properties to meet the needs of different bleeding scenarios.
[0026] 2. The hemostatic gauze of the present invention has a synergistic hemostatic mechanism of physical liquid absorption and chemical coagulation. On the one hand, the material can quickly absorb blood and concentrate blood cells to form a physical embolic barrier; on the other hand, the carboxyl groups on the surface of the material can construct a local acidic microenvironment, activate platelets and coagulation factors, and promote thrombus formation.
[0027] 3. The hemostatic gauze of this invention has excellent antibacterial properties; the higher the carboxyl content, the better the antibacterial effect against Staphylococcus aureus and Escherichia coli. Its antibacterial mechanism is the release of H+ from the ionization of carboxyl groups. + It disrupts the proton gradient of bacterial membranes and inactivates key enzymes, achieving contact antibacterial action without the need for added antibacterial agents, thus avoiding the toxic side effects and drug resistance problems associated with antibacterial agents.
[0028] 4. The hemostatic gauze of this invention has excellent biocompatibility, is non-cytotoxic to L929 fibroblasts, maintains cell viability of over 95%, and has a hemolysis rate of less than 5%, meeting international standards for blood compatibility safety of biomedical materials. It also has controllable human absorbability, with no residue after 28 days of subcutaneous implantation, no chronic inflammatory reaction during human absorption, and the degradation products are non-toxic to major organs such as the heart, liver, spleen, lungs, and kidneys, eliminating the need for secondary surgery and reducing the risk of postoperative complications.
[0029] 5. The hemostatic material of the present invention has a carboxyl content of 2.0–4.3 mmol / g and a hemolysis rate of <5%, which meets the blood compatibility safety requirements for biomedical materials; the hemostatic material has an antibacterial rate of up to 99% against Staphylococcus aureus and Escherichia coli, and can be completely absorbed by the human body after 28 days of implantation, without chronic inflammation or organ toxicity. Detailed Implementation
[0030] The present invention will be further described in detail below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto. Attached Figure Description
[0031] Figure 1 This describes the preparation process of protonated carboxymethyl cellulose (HCMCel) fibers and gauze.
[0032] Figure 2 The images show the scanning electron microscope (SEM) morphology of protonated carboxymethyl cellulose (24HCMCel) fibers and gauze. The fibers have smooth surfaces, an average diameter of about 25 μm, and can be processed into nonwoven gauze with a three-dimensional network structure.
[0033] Figure 3 The study investigated the platelet adhesion morphology and adhesion rate on the surface of protonated carboxymethyl cellulose (HCMCel) gauze. The carboxyl groups on the material surface activated platelets, causing them to extend pseudopodia and aggregate. Furthermore, the platelet adhesion rate increased with increasing acidification.
[0034] Figure 4 The in vivo hemostatic effect of protonated carboxymethyl cellulose (HCMCel) gauze in a rat femoral artery blood loss model was demonstrated; the material rapidly controlled bleeding after covering the wound; its hemostatic ability was comparable to that of Surgicel. ® quite.
[0035] Figure 5 This is a photograph showing the in vivo degradation of protonated carboxymethyl cellulose (24HCMCel) gauze. As the implantation time increases, the gauze gradually decomposes and its volume decreases.
[0036] Figure 6 This study investigates the structure-activity relationship between carboxyl group content and key properties in protonated carboxymethyl cellulose (HCMCel) gauze. Carboxyl group content is a key variable that synergistically regulates the material's hemostatic, antibacterial, and degradation behaviors. Its content is positively correlated with procoagulant and antibacterial properties, and it slows down the initial degradation rate by enhancing the intramolecular hydrogen bond network, but does not affect the final complete absorption.
[0037] Example 1
[0038] Preparation and hemostatic properties of protonated carboxymethyl cellulose hemostatic gauze acidified for 6 h
[0039] (1) Preparation of spinning solution: Sodium carboxymethyl cellulose (CMC-Na) (degree of substitution: 0.7-0.85, viscosity: 800-1200 mPa·s) was dissolved in deionized water and stirred at room temperature for 12 h until completely dissolved. The insoluble matter was removed by filtration to obtain a CMC-Na spinning solution with a mass fraction of 5%.
[0040] (2) Wet spinning: The above spinning solution is spun at 6 mL·min -1 The filaments were extruded from the spinning head into a coagulation bath (ethanol-water solution with a volume ratio of 7:3) at a certain rate to obtain CMC-Na nascent fibers.
[0041] (3) Acidification treatment: The nascent fibers were placed in an acidification bath (90 vol.% ethanol aqueous solution containing 0.5 wt.% HCl) for 6 h to obtain protonated carboxymethyl cellulose (HCMCel) fibers. Figure 1 );
[0042] (4) Post-treatment and molding: The protonated carboxymethyl cellulose fiber was washed with deionized water until neutral, and then vacuum dried to constant weight. The fiber was then randomly assembled into gauze to obtain HCMCel hemostatic gauze after acidification for 6 h, which is denoted as 6HCMCel gauze.
[0043] The 6HCMCel gauze was found to have a carboxyl content of 3.65 mmol / g, a Zeta potential of -26 mV, and a saturated water absorption rate of 2300%. Its antibacterial rates against Staphylococcus aureus and Escherichia coli were 67% and 66%, respectively. The BCI value was approximately 60%, indicating procoagulant activity. Platelet adhesion rate was approximately 35%, and it effectively activated platelets, causing them to extend their pseudopodia. In a rat femoral artery hemorrhage model, the hemorrhage volume was 598 ± 39 mg, and in a liver injury model, the hemorrhage volume was 273 ± 5 mg.
[0044] Example 2
[0045] Preparation and hemostatic properties of protonated carboxymethyl cellulose hemostatic gauze acidified for 12 h
[0046] The steps are basically the same as in Example 1, except that the acidification time in step (3) is 12 h, and the hemostatic gauze prepared is called 12HCMCel gauze.
[0047] The 12HCMCel gauze was found to have a carboxyl content of 3.82 mmol / g, a Zeta potential of -21 mV, and a saturated water absorption rate of 2000%. Its antibacterial rates against Staphylococcus aureus and Escherichia coli were 78% and 79%, respectively. The BCI value decreased to approximately 45%, its procoagulant activity was significantly enhanced, and its platelet adhesion rate increased to approximately 43%. In a rat femoral artery hemorrhage model, the hemorrhage volume was 257 ± 26 mg, and in a liver injury model, the hemorrhage volume was 175 ± 17 mg.
[0048] Example 3
[0049] Preparation and hemostatic properties of protonated carboxymethyl cellulose hemostatic gauze acidified for 18 h
[0050] The steps are basically the same as in Example 1, except that the acidification time in step (3) is 18 h, and the hemostatic gauze prepared is called 18HCMCel gauze.
[0051] The 18HCMCel gauze was found to have a carboxyl content of 4.05 mmol / g, a Zeta potential of -17 mV, and a saturated water absorption rate of 1800%. It exhibited 90% antibacterial activity against both Staphylococcus aureus and Escherichia coli. BCI decreased sharply to approximately 24%, demonstrating extremely strong procoagulant activity. Platelet adhesion rate was significantly increased, and platelet activation morphology (pseudopodia extension) was more prevalent and typical. In a rat femoral artery hemorrhage model, the hemorrhage volume was 66 ± 15 mg, and in a liver injury model, it was 70 ± 14 mg.
[0052] Example 4
[0053] Preparation and hemostatic properties of protonated carboxymethyl cellulose hemostatic gauze acidified for 24 h
[0054] The steps are basically the same as in Example 1, except that the acidification time in step (3) is 24 h, and the hemostatic gauze prepared is called 24HCMCel gauze.
[0055] The 24HCMCel gauze was found to have a carboxyl content of 4.22 mmol / g, a Zeta potential of -13 mV, and a saturated water absorption rate of 1600%. After protonation, the Coulomb repulsion between molecular chains decreased, thus the absorption rate decreased with increasing carboxyl content. It exhibited an antibacterial rate of 99% against Staphylococcus aureus and Escherichia coli, L929 cell viability >95%, and a hemolysis rate of 4.4%, below the international medical material safety standard of 5%. BCI decreased to an extremely low 4%, demonstrating excellent procoagulant activity. Platelet adhesion and activation effects were extremely significant, with a platelet adhesion rate of 74%, and most platelets exhibiting a fully extended activated morphology. In a rat femoral artery hemorrhage model, the hemorrhage volume was 12 ± 4 mg, and in a liver injury model, it was 12 ± 5 mg, comparable to commercially available Surgicel. ® (Femoral artery bleeding volume 13 ± 4 mg, liver injury bleeding volume 12 ± 5 mg) There was no significant difference in hemostatic performance. The gauze completely degraded in a lysozyme-PBS system within 14 days. In a mouse subcutaneous implantation model, the material was completely absorbed after 28 days with no residue. Histological (H&E staining) analysis showed only mild, transient acute inflammatory reactions at the implantation site, with no chronic inflammation, granulomas, or fibrous encapsulation. Furthermore, no pathological damage related to the material was observed in major organs such as the heart, liver, spleen, lungs, and kidneys. This confirms that the material can be safely and completely absorbed after effective hemostasis, avoiding the risks of long-term foreign body reactions and secondary surgical removal.
[0056] Example 5
[0057] The steps are basically the same as in Example 4, except that the mass fraction of the CMC-Na spinning solution is 10%, and the hemostatic gauze prepared is denoted as 24HCMCel-10% gauze.
[0058] At the same acidification time, increasing the concentration of the spinning solution did not significantly alter the chemical structure of the gauze; for example, the carboxyl content, zeta potential, antibacterial properties, and hemostatic properties were comparable to those of 24HCMCel in Example 4. However, its saturated water absorption decreased to approximately 1300%, requiring 16 days for complete degradation in an in vitro lysozyme-PBS system, and extending the time to complete absorption to 30 days in a mouse subcutaneous implantation model.
[0059] Example 6
[0060] The steps are basically the same as in Example 4, except that the mass fraction of the CMC-Na spinning solution is 15%, and the hemostatic gauze prepared is denoted as 24HCMCel-15% gauze.
[0061] Under the same acidification time, the carboxyl content, zeta potential, antibacterial properties and hemostatic properties of the gauze were still similar to those of the gauze in Example 4, which once again confirms that the acidification time dominates the structure and properties of the gauze.
[0062] Example 7
[0063] Preparation of protonated carboxymethyl cellulose particles
[0064] First, 20 mL of a 2 wt.% CMC-Na aqueous solution was prepared as the aqueous phase. Then, it was slowly added to the oil phase, which consisted of 120 mL isooctane, 5.0 mL Span 80, and 1 mL Tween 60. The mixture was stirred at 1300 rpm for 2 h to form a stable water-in-oil emulsion. Next, 10 mL of a 2 wt.% calcium chloride aqueous solution was added to the emulsion, and stirring continued for 1 h to allow CMC crosslinking via calcium ions. After the reaction, the entire emulsion was poured into excess anhydrous ethanol to demulsify, and the oil phase and surfactant were removed by washing. The resulting particles were then placed in an acidification solution (a 90% ethanol aqueous solution containing 1 wt.% hydrochloric acid) for 24 h to convert them into a water-insoluble protonated form. Finally, after washing, drying, and sieving, HCMC particles with a particle size range of 50-100 μm were obtained.
[0065] The prepared HCMC particles exhibited chemical properties consistent with their gauze form, possessing similar carboxyl content, zeta potential, antibacterial activity, and procoagulant activity. These HCMC particles maintained structural integrity for over 24 hours in simulated body fluids, making them suitable for irregular wounds where traditional dressings are difficult to apply. In a rat femoral artery hemorrhage model, their hemostatic speed was comparable to that of sheet gauze. Furthermore, the particles demonstrated good bioabsorbability, completely degrading in approximately 14 days in an in vitro lysozyme-PBS system, and were safely absorbed without residue 28 days after subcutaneous implantation in mice.
[0066] Example 8
[0067] Preparation of protonated carboxymethyl cellulose granular sponge
[0068] A 3 wt.% CMC-Na aqueous solution was injected into a mold and freeze-dried (-40°C, 0.1 mbar, 24 h) to obtain a CMC-Na sponge with three-dimensional interconnected channels. The sponge was then immersed in an acidification solution (a 90% ethanol aqueous solution containing 1.0 wt.% hydrochloric acid) for 24 h to convert it into a water-insoluble HCMC sponge. After thorough washing with deionized water, it was freeze-dried again to obtain the final product.
[0069] This sponge has a porosity of 75-85% and a saturated water absorption rate of 2000-2500%. Based on the acidic microenvironment formed by abundant surface carboxyl groups, it exhibits an antibacterial rate of ≥99% against both Staphylococcus aureus and Escherichia coli. In a rat liver hemorrhage model, its hemostatic effect is comparable to that of the commercial product Surgicel. ®The material is highly bioabsorbable and completely degrades in the body within approximately 28 days, leaving no residue. This product can be used to stop bleeding in irregular or deep wounds where pressure-based hemostasis is not possible.
[0070] The above results indicate that protonated carboxymethyl cellulose materials can be processed into various forms such as gauze, granules, and sponges to meet the needs of different clinical hemostasis scenarios.
[0071] Comparative Example 1
[0072] Traditional cotton gauze
[0073] Using commercially available medical cotton gauze (denoted as Cotton Gauze) as a control, its BCI value was found to be 84%, and its platelet adhesion rate was 15%. In a rat femoral artery hemorrhage model, the hemorrhage volume was 1553 ± 117 mg, and in a liver injury model, the hemorrhage volume was 772 ± 104 mg. This material has a single hemostatic mechanism, relying solely on physical packing and fluid absorption, lacking active chemical coagulation and antibacterial functions, and cannot be absorbed by the human body, requiring a secondary surgical removal.
[0074] Comparative Example 2
[0075] Unacidified CMC-Na fiber gauze
[0076] Gauze directly assembled from untreated CMC-Na fibers was used as a control. Due to the lack of protonation, this material dissolved rapidly in water, causing structural disintegration. When used for hemostasis, the dressing dissolved upon contact with blood, failing to maintain its physical form and resulting in continuous blood seepage, thus failing to achieve effective hemostasis. This demonstrates that converting water-soluble CMC-Na into water-insoluble HCMCel through acidification is a crucial prerequisite for obtaining stable and usable hemostatic materials.
[0077] Based on the above embodiments and comparative examples, it can be seen that the present invention achieves the green and simple preparation of protonated carboxymethyl cellulose hemostatic gauze, granules, and sponges with precisely adjustable carboxyl content through controllable acidification treatment. The prepared hemostatic materials exhibit a clear quantitative structure-activity relationship, showing a significant positive correlation between carboxyl content and hemostatic and antibacterial properties, thereby allowing for on-demand control of their degradation rate. The prepared hemostatic materials possess a synergistic hemostatic mechanism combining physical absorption and chemical coagulation, and their in vivo hemostatic efficacy is comparable to that of the clinical gold standard product Surgicel. ® This invention provides a novel absorbable hemostatic material that integrates hemostasis, antibacterial properties, human absorption, and biocompatibility into a single material.
[0078] The above description is only a preferred embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.
Claims
1. A method for preparing a protonated carboxymethyl cellulose absorbable hemostatic material, characterized in that, Protonated carboxymethyl cellulose fibers are obtained by coagulating and regenerating sodium carboxymethyl cellulose solution and then acidifying it. The protonated carboxymethyl cellulose fibers are then processed to obtain hemostatic materials.
2. The method for preparing a protonated carboxymethyl cellulose absorbable hemostatic material according to claim 1, characterized in that, The hemostatic materials mentioned above are hemostatic gauze, hemostatic granules, or hemostatic sponges.
3. The method for preparing a protonated carboxymethyl cellulose absorbable hemostatic material according to claim 2, characterized in that, The method for preparing the hemostatic gauze includes the following steps: (1) Wet spinning and coagulation regeneration: Sodium carboxymethyl cellulose solution is sprayed into a coagulation bath through a spinneret to obtain nascent fibers. The coagulation bath is an ethanol-water solution with a volume concentration of 70-95%. (2) Acidification treatment: The nascent fibers are placed in an acidification bath for acidification treatment to obtain protonated carboxymethyl cellulose fibers; the acidification bath is an aqueous solution of 90% ethanol containing 0.5 wt.% ~ 8.0 wt.% hydrochloric acid. (3) Post-processing and molding: The protonated carboxymethyl cellulose fiber is washed, dried, and then processed into hemostatic gauze.
4. The method for preparing a protonated carboxymethyl cellulose absorbable hemostatic material according to claim 3, characterized in that, The acidification time is 6~24h.
5. The method for preparing a protonated carboxymethyl cellulose absorbable hemostatic material according to claim 2, characterized in that, The preparation method of the hemostatic granules includes the following steps: 1) Using sodium carboxymethyl cellulose solution as the aqueous phase, add it to the oil phase composed of isooctane, Span 80 and Tween 60, and stir at high speed at 1000~1500 rpm for 2~2.5 h to form a stable water-in-oil emulsion; 2) Add calcium chloride aqueous solution to the above emulsion and continue stirring for 1 to 1.5 h. After the reaction is complete, pour all the emulsion into excess anhydrous ethanol to break the emulsion, wash, and obtain granules. 3) The obtained particles were placed in an acidification solution for 20-24 h for acidification treatment. The acidification solution was an aqueous solution of 90% ethanol with a volume concentration of 0.5 wt.% to 8.0 wt.% hydrochloric acid. Finally, after washing, drying and sieving, protonated carboxymethyl cellulose hemostatic particles were obtained.
6. The method for preparing a protonated carboxymethyl cellulose absorbable hemostatic material according to claim 2, characterized in that, The method for preparing the hemostatic sponge is as follows: sodium carboxymethyl cellulose solution is injected into a mold, freeze-dried to obtain CMC-Na sponge, and then the sponge is immersed in an acidification solution for 20-24 h. The acidification solution is an aqueous solution of 90% ethanol with a volume concentration of 0.5 wt.% to 8.0 wt.% hydrochloric acid. After washing, the sponge is freeze-dried again to obtain the hemostatic sponge.
7. The method for preparing a protonated carboxymethyl cellulose absorbable hemostatic material according to claim 1, characterized in that, The sodium carboxymethyl cellulose solution has a mass concentration of 2% to 20%, a viscosity of 300 to 4500 mPa·s, and a degree of carboxymethyl substitution of 0.3 to 1.
8.
8. A protonated carboxymethyl cellulose absorbable hemostatic material obtained by the preparation method according to any one of claims 1 to 7.
9. The protonated carboxymethyl cellulose absorbable hemostatic material according to claim 8, characterized in that, The hemostatic material has a carboxyl content of 2.0 ~ 4.3 mmol / g and a hemolysis rate of <5%.
10. The application of the protonated carboxymethyl cellulose human absorbable hemostatic material as described in claim 8 in wound hemostasis, intraoperative hemostasis during surgery, and postoperative hemostasis after surgery.