Absorbable bone wax and preparation method thereof

Abstract

The invention discloses absorbable bone wax and a preparation method thereof, and belongs to the field of biomedical materials. The absorbable bone wax is prepared from the following components in percentage by weight: 45 to 60 weight percent of sodium carboxymethyl cellulose, 30 to 50 weight percent of binary or terpolymer containing polyethylene glycol (PEG), 5 to 10 weight percent of calcium stearate and 1.25 to 3 weight percent of citric acid, the copolymer is obtained by copolymerization of PEG and one or two of caprolactone and lactide. Sodium carboxymethyl cellulose is purified to reduce endotoxin, the molecular weight of the copolymer and the proportion of each component are controllable, and an osteogenesis active material can be added. The preparation method comprises the steps of sodium carboxymethyl cellulose purification, copolymer and citric acid vacuum dehydration thermal crosslinking, component mixing and the like. The bone wax disclosed by the invention is good in absorbability, excellent in biocompatibility and simple and controllable in preparation process, can meet clinical bone hemostasis requirements, and has a good application prospect.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to an absorbable bone wax and its preparation method. Background Technology

[0002] Bone wax is an indispensable hemostatic material in orthopedic and surgical procedures. It mainly seals the bleeding channels of cancellous or cortical bone through physical packing to achieve rapid hemostasis. Due to its ease of use and rapid onset of action, it is widely used in various surgical scenarios such as osteotomy, bone drilling, and bone defect repair.

[0003] Currently, commonly used traditional bone waxes in clinical practice are mainly composed of hydrophobic substances such as beeswax or paraffin, and their hemostatic mechanism relies solely on physical barrier effects. However, these traditional bone waxes have a core drawback—they are difficult to degrade and absorb in the body. Long-term retention in bone tissue can trigger a series of adverse reactions, including local inflammation, delayed bone healing, and increased risk of infection, seriously affecting postoperative bone repair and failing to meet the long-term safety requirements of clinical bone hemostatic materials.

[0004] To address the issue of non-absorbability of traditional bone wax, existing technologies have explored related approaches: US 7,989,000 discloses compositions containing solid particulate fatty acid salts suspended in liquid polyoxyalkylene and other excipients; US 5,356,629 discloses compositions containing polymethyl methacrylate coated particles in a cellulose ether, collagen, or hyaluronic acid matrix; US 7,553,913 discloses hydrophilic, water-soluble waxy compositions with miscible solid particles as a base of ethylene oxide and other random copolymers of ethylene oxide; US 7,914,819 discloses polymeric matrices with polysaccharide backbones; and US 7,074,425 discloses hydrophilic polyethylene glycol-based compositions composed of a mixture of high and low molecular weight polyethylene glycols with a hydrophilic-lipophilic balance value greater than 20.

[0005] Although the aforementioned existing technologies have made some progress in improving the absorbability of bone wax, there are still many shortcomings: most compositions have poor structural stability and are prone to migration and loss in the moist surgical environment or under irrigation conditions, making it impossible to maintain effective hemostasis for a sufficient duration; at the same time, it is difficult to achieve a balance between the arbitrary plasticity and shape retention required in clinical practice, and some polyethylene glycol-based compositions degrade too quickly, failing to match the bone healing cycle, and still cannot fully meet the comprehensive requirements of bone wound hemostatic materials for structural stability, controllable absorption and clinical operability.

[0006] Therefore, developing an absorbable bone wax that can be shaped to suit clinical surgical needs, is completely degradable and absorbable, and has a longer degradation time than existing polyethylene glycol-based bone waxes, can maintain long-term hemostatic effects, and does not interfere with the subsequent bone healing process has become a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0007] This invention discloses an absorbable bone wax and its preparation method, belonging to the field of biomedical materials technology. It aims to solve the technical problems of existing bone waxes, such as difficulty in being absorbed by the human body, poor biocompatibility, lack of osteogenic activity in some products, and complex preparation processes. The invention provides an absorbable bone wax with good biocompatibility, complete absorption, hemostatic and osteogenic functions, and simple preparation method.

[0008] The absorbable bone wax of the present invention comprises, by weight percentage, the following components: 45–60 wt% sodium carboxymethyl cellulose, 30–50 wt% a binary or ternary block copolymer containing polyethylene glycol (PEG), 5–10 wt% calcium stearate, and 1.25–3 wt% citric acid; the total weight percentage of each component is 100%. The binary or ternary block copolymer is obtained by copolymerizing PEG with one or two of caprolactone (PCL) and lactide (PLA). The introduction of this block copolymer effectively improves the flexibility and absorbability of the bone wax, while also enhancing its biocompatibility with human tissues.

[0009] As a preferred embodiment of the absorbable bone wax of this invention, the sodium carboxymethyl cellulose is selected from one or more of three viscosity grades, with the following viscosity values ​​for a 2% aqueous solution: 750–1400 mPa·s, 1500–2800 mPa·s, and 3000–5600 mPa·s, respectively. The three different viscosities of sodium carboxymethyl cellulose can also be used in combination to balance the moldability and adhesion of the bone wax, ensuring both good shaping ability and tight adhesion to the bone wound surface for rapid hemostasis.

[0010] Furthermore, the sodium carboxymethyl cellulose undergoes purification before use to reduce endotoxin levels, ensuring the endotoxin content is less than 20 EU / g. This purification process effectively removes impurities and endotoxins from the sodium carboxymethyl cellulose, preventing endotoxin-induced inflammatory responses in the human body, improving the biosafety of the bone wax, and meeting clinical medical requirements.

[0011] Regarding the PEG-containing binary or ternary block copolymers, the present invention makes the following specific limitations: if it is a ternary polymer (PEG-PCL-PLA), the mass ratio of PEG:PCL:PLA is 1:(0.25–2):(0.25–2); if it is a binary copolymer (PCL-PEG or PLA-PEG), the mass ratio of PEG to PCL or PEG to PLA is 1:(0.5–4). The molecular weight of PEG is 400–2000, and the molecular weight of the binary or ternary block copolymer is 600–8000. By controlling the composition ratio and molecular weight of the block copolymer, the degradation rate of bone wax can be precisely adjusted to match its degradation cycle with the bone tissue repair cycle, avoiding poor hemostasis due to excessively rapid degradation or impaired bone tissue healing due to excessively slow degradation.

[0012] To further enhance the clinical application value of bone wax, the absorbable bone wax of this invention may also contain 5–10 wt% osteogenic active material, wherein the osteogenic active material is selected from at least one of hydroxyapatite, bioactive glass, and mineralized collagen fibers. The introduction of osteogenic active material can provide support and induce bone tissue repair while achieving hemostasis, promoting the healing of bone defects and shortening the repair cycle.

[0013] The mineralized collagen fibers are collagen-hydroxyapatite complexes, prepared by mixing collagen and hydroxyapatite at a mass ratio of 0.5–1.5:1 in a 50–75% (v / v) ethanol solution at 100–500 rpm for 30–60 min, followed by filtration and freeze-drying or vacuum drying. This preparation method is simple and effectively ensures the uniform compounding of collagen and hydroxyapatite, enhancing the osteogenic activity and biocompatibility of the mineralized collagen.

[0014] This invention also discloses a method for preparing the above-mentioned absorbable bone wax, comprising the following steps: (1) The sodium carboxymethyl cellulose is purified; impurities and endotoxins are removed through purification to ensure the biosafety of bone wax; (2) Mix the PEG-containing binary or ternary block copolymer with citric acid and perform vacuum dehydration thermal crosslinking; citric acid, as a crosslinking agent, can promote the formation of a stable crosslinking structure of the block copolymer, improve the mechanical properties and stability of bone wax, and vacuum dehydration can avoid the influence of moisture on the crosslinking effect. (3) Add purified sodium carboxymethyl cellulose and calcium stearate to the mixture after vacuum thermal crosslinking, and stir and mix evenly at 50–60°C to obtain absorbable bone wax; optionally, add osteogenic active material in step (3) to achieve the combination of hemostasis and osteogenic function; wherein, the PEG-containing binary or ternary block copolymer is obtained by copolymerizing PEG with one or two of PCL and PLA.

[0015] As a preferred embodiment of the preparation method, the purification process in step (1) includes: alkali treatment of sodium carboxymethyl cellulose, followed by sequential washing with 75% ethanol, 90% ethanol, and anhydrous ethanol. Alkali treatment can effectively remove residual impurities and some endotoxins from sodium carboxymethyl cellulose, and subsequent gradient ethanol washing can further remove impurities and moisture, thereby improving the purification effect.

[0016] Specifically, the alkaline treatment is as follows: sodium carboxymethyl cellulose is added to 75% ethanol at a feed-to-liquid ratio of 1:10, along with 2 wt% sodium hydroxide. The mixture is heated and stirred at 55–65°C and 100–500 rpm, then refluxed for 2–4 hours. The solution is then neutralized to pH 6.5–8.0 with hydrochloric acid or acetic acid, and filtered to obtain a sodium carboxymethyl cellulose filter cake. These alkaline treatment conditions allow for precise control of impurity removal while avoiding overtreatment that could damage the structure of the sodium carboxymethyl cellulose, thus ensuring its performance in subsequent applications.

[0017] The washing process involves sequentially mixing the alkali-treated filter cake with 75% ethanol, 90% ethanol, and anhydrous ethanol at a feed-to-liquid ratio of 1:10 for 30–60 min at a stirring speed of 100–500 rpm, filtering after each mixing. The final filter cake is then vacuum-dried to obtain purified sodium carboxymethyl cellulose. Gradient ethanol washing gradually removes moisture and residual impurities from the filter cake, while vacuum drying avoids the damage to the structure of sodium carboxymethyl cellulose caused by high-temperature drying, ensuring that its viscosity and biocompatibility remain unaffected.

[0018] For step (2), the following further limits are specified: the mass ratio of the PEG-containing binary or ternary block copolymer to citric acid is 16–32:1; the mixing method is melt mixing or dissolving and mixing with water followed by freeze drying. This mass ratio ensures that citric acid can fully exert its cross-linking effect, while avoiding excessive citric acid that could reduce the biocompatibility of bone wax; both mixing methods can achieve uniform mixing of the block copolymer and citric acid, adapting to the needs of different production scenarios.

[0019] Furthermore, in step (2), the temperature for vacuum dehydration thermal crosslinking is 105–140°C, and the crosslinking time is 1–3 h. These crosslinking conditions allow the block copolymer to form a stable crosslinking network while avoiding polymer degradation caused by high-temperature and long-term crosslinking, thus ensuring the absorbability and mechanical properties of bone wax.

[0020] The absorbable bone wax of this invention has synergistic effects among its components, possessing excellent hemostatic properties, biocompatibility, and absorbability. It can be further enhanced with osteogenic active materials to improve bone repair. Its preparation method is simple, mild, and highly reproducible, making it suitable for large-scale production. It can be widely used in bone wound hemostasis and bone tissue repair during orthopedic surgery, and has extremely high clinical application value and market prospects.

[0021] Compared with the prior art, the present invention has the following beneficial effects: 1. Excellent hemostatic effect and strong stability: With sodium carboxymethyl cellulose as the main matrix, it has good adhesion and plasticity, and can closely adhere to irregular bone wounds to achieve rapid hemostasis; through the thermal cross-linking of PEG-containing binary or ternary copolymers with citric acid, the morphological stability of the material under moist and intraoperative irrigation conditions is significantly improved, avoiding migration and loss, and prolonging the effective hemostasis time.

[0022] 2. Convenient to operate and adapted to clinical needs: Bone wax has suitable thixotropy at room temperature and body temperature, has a moderate feel, and is not easy to flow, break or stick to surgical gloves, making it easy to handle, shape and accurately pack, greatly improving the convenience of clinical operation.

[0023] 3. Controllable degradation and high biosafety: The whole body is composed of biocompatible biodegradable materials with a slow degradation rate, which can match the bone healing cycle and avoid inflammatory reactions caused by foreign body residue; at the same time, sodium carboxymethyl cellulose is purified to reduce endotoxins, further reducing the risk of postoperative infection and ensuring greater safety.

[0024] 4. Expandable functionality and broad application prospects: Osteogenic active materials such as hydroxyapatite and bioactive glass can be added as needed, achieving hemostasis while also promoting bone repair, thus expanding clinical application scenarios. Detailed Implementation

[0025] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments, further clarifies the invention. Those skilled in the art should understand that the specific descriptions below are illustrative rather than restrictive and should not be construed as limiting the scope of protection of the present invention.

[0026] Example 1

[0027] This embodiment provides an absorbable bone wax and its preparation method, specifically: (1) Purification of sodium carboxymethyl cellulose: In a dry heat sterilized glass flask, add 200 ml of 75% ethanol aqueous solution, then add 20 g of sodium carboxymethyl cellulose (2% aqueous solution viscosity is 750-1400 mPa·s) and 4 g of sodium hydroxide; connect a condenser to the mouth of the flask, stir with a mechanical stirrer (speed 200 rpm), turn on the heating mantle to maintain the temperature of the liquid in the flask at 60℃, and continue stirring for 3 hours before turning off the heating mantle. Add 36.5 g of 10% hydrochloric acid solution to neutralize, and then finely adjust with 0.1% hydrochloric acid solution or 0.1% sodium hydroxide solution to control the pH value of the sodium carboxymethyl cellulose slurry at 6.5-8.0, and filter to obtain filter cake.

[0028] The filter cakes were placed sequentially into sterilized glass beakers, and 200 ml of 75% ethanol, 90% ethanol and anhydrous ethanol were added at a ratio of 1:10. Each time, the mixture was stirred at 200 rpm for 30 min and then filtered. The filter cakes were collected and spread evenly on sterilized stainless steel trays and placed in a vacuum drying oven for thorough drying to obtain purified sodium carboxymethyl cellulose.

[0029] The endotoxin test result of the treated sodium carboxymethyl cellulose was 6 EU / g.

[0030] (2) Vacuum dehydration thermal crosslinking: Weigh 8g of PEG-containing terpolymer (P2K, PEG:PCL:PLA mass ratio 1:0.5:0.5, PEG molecular weight 1000, copolymer molecular weight 2000) and 0.5g of anhydrous citric acid, put them into a 50℃ forced-air drying oven to fully melt the copolymer, and continue stirring until the two are mixed evenly; then put the mixture into a vacuum drying oven, set the heating temperature to 105℃, and perform vacuum dehydration thermal crosslinking for 2h to obtain the crosslinked mixture.

[0031] (3) Preparation of bone wax: 10g of purified sodium carboxymethyl cellulose and 1.5g of calcium stearate were added to the cross-linked mixture above, and the mixture was stirred continuously at 50-60℃ until it was evenly mixed to obtain the absorbable bone wax of this embodiment.

[0032] Example 2 This embodiment provides an absorbable bone wax and its preparation method, which is basically the same as that in Example 1, except that the viscosity of the sodium carboxymethyl cellulose used in step (1) is different. The sodium carboxymethyl cellulose is a 2% aqueous solution with a viscosity of 1500-2800 mPa·s.

[0033] Example 3 This embodiment provides an absorbable bone wax and its preparation method, which is basically the same as that in Example 1, except that the viscosity of the sodium carboxymethyl cellulose used in step (1) is different. The sodium carboxymethyl cellulose is a 2% aqueous solution with a viscosity of 3000-5600 mPa·s.

[0034] Example 4 This embodiment provides an absorbable bone wax and its preparation method, which is basically the same as that in Example 1, except that the amount of anhydrous citric acid used in step (2) is reduced to 0.25g.

[0035] Example 5 This embodiment provides an absorbable bone wax and its preparation method, which is basically the same as that in Example 1, except that the crosslinking temperature of vacuum dehydration thermal crosslinking is increased to 120°C in step (2).

[0036] Example 6 This embodiment provides an absorbable bone wax and its preparation method, which is basically the same as that in Example 1. The only difference is that in step (2), the mixing method of ternary polymer (P2K) and anhydrous citric acid is changed to dissolving and mixing in 20ml of water, pre-freezing in a refrigerator with the temperature set to -50℃, and then freeze-drying in a freeze dryer to obtain a mixture of ternary polymer (P2K) and anhydrous citric acid.

[0037] Example 7

[0038] This embodiment provides an absorbable bone wax and its preparation method, which is basically the same as that in Example 1. The difference is that after repeating steps (1) to (3) in Example 1 to prepare the absorbable bone wax, the following further processing is performed: Add 1.5g of hydroxyapatite (needle-shaped, 96% purity) to absorbable bone wax and stir to obtain absorbable bone wax with added hydroxyapatite.

[0039] Example 8

[0040] This embodiment provides an absorbable bone wax and its preparation method, which is basically the same as that in Example 1. The difference is that after repeating steps (1) to (3) in Example 1 to prepare the absorbable bone wax, the following further processing is performed: 10g of collagen (type I) was dispersed in 40ml of 60% ethanol aqueous solution, followed by the addition of 10g of hydroxyapatite (needle-shaped, 96% purity), and stirred at 300 rpm for 60 min. The mixture was filtered through a 20-mesh sieve to obtain a filter cake, which was then vacuum dried to obtain mineralized collagen fibers. The mineralized collagen fibers were pulverized to obtain mineralized collagen fiber powder. Subsequently, 1.5g of mineralized collagen fiber powder was added to the absorbable bone wax prepared according to steps (1) to (3) of Example 1 and stirred thoroughly to obtain absorbable bone wax with added mineralized collagen fibers.

[0041] Comparative Example 1 To further illustrate the beneficial effects of the present invention, Comparative Example 1 is provided. Compared with Example 1, the only difference of this comparative example is that anhydrous citric acid will not be added in step (2).

[0042] Comparative Example 2 To further illustrate the beneficial effects of the present invention, Comparative Example 2 is provided. Comparative Example 2 is mainly prepared based on polyethylene glycol as a raw material, and its specific preparation process is as follows: Weigh out 12g of polyethylene glycol (molecular weight 1500), 3g of polyethylene glycol (number average molecular weight 400), 3g of purified sodium carboxymethyl cellulose (2% aqueous solution, viscosity 750-1400 mPa·s), and 3g of hydroxyapatite (needle-shaped, purity 96%). Add the above substances to a forced-air drying oven set at 60℃ to melt the polyethylene glycol (molecular weight 1500). Then remove the oven and continuously stir to ensure uniform mixing. An absorbable bone wax sample based on polyethylene glycol is obtained.

[0043] Performance testing: (1) In vitro degradation time test The test samples from different groups were prepared into uniform small discs with a diameter of 6 mm and a thickness of 3 mm. They were then placed in sample bottles containing 50 ml of PBS solution, sealed, and placed in a constant temperature shaker. The degradation test was carried out at a shaking frequency of 80 rpm and a water temperature of 37 °C. The samples were observed every 30 minutes, and the time required for complete degradation was recorded. The experimental results are shown in Table 1.

[0044] (2) Compression performance test Test samples from different groups were prepared into uniform small cylinders with a diameter of 10 mm and a thickness of 6 mm. The compressive strength of the samples was tested using a universal testing machine under the following conditions: compression speed 2 mm / min, compression deformation 20%. The compressive modulus of bone wax was calculated based on the test results, and the experimental results are shown in Table 1.

[0045] (3) Adhesion performance test 0.5g of different test samples were evenly coated onto the surface of a bovine bone. Another bovine bone was placed in contact with the surface of the bovine bone coated with absorbable bone wax. The pressure plate of a universal testing machine was used to continuously compress the sample with a force of 50N for 1 minute. Then, a tensile testing fixture was used and the bovine bone was connected. The two bovine bones were gradually separated by pulling upwards at a speed of 1mm / min. The maximum tensile force at the point of separation was recorded as the maximum adhesive load of the bone wax. The experimental results are shown in Table 1.

[0046] Table 1

[0047] A comparison of the results from Examples 1, 2, and 3 shows that the absorbable bone wax prepared using sodium carboxymethyl cellulose with higher viscosity has improved degradation time, compressive modulus, and adhesion properties.

[0048] The results of Examples 1 and 4 and Comparative Example 1 show that adding citric acid and crosslinking it with the ternary polymer (P2K) can improve the degradation time, compressive modulus and adhesion properties, and increasing the amount of citric acid added can further improve the degradation time, compressive modulus and adhesion properties.

[0049] The comparison of the results of Examples 1 and 5 shows that the degradation time, compressive modulus and adhesion properties decreased after increasing the crosslinking temperature, which may be due to the partial degradation of the ternary polymer caused by the excessively high crosslinking temperature.

[0050] The results of Examples 1 and 6 show that the bone wax prepared by lyophilizing the mixture obtained by dissolving the ternary polymer (P2K) and citric acid in water has improved degradation time, compression modulus and adhesion properties. This may be because this mixing method is more uniform than melting and stirring, resulting in a higher degree of crosslinking.

[0051] A comparison of the results from Examples 1, 7, and 8 shows that the addition of osteogenic active ingredients such as hydroxyapatite and mineralized collagen increases the compressive modulus of bone wax but decreases its adhesive properties. When hydroxyapatite is added as the osteogenic active ingredient, the degradation time of the bone wax is shorter; when mineralized collagen is added as the osteogenic active ingredient, the degradation time is prolonged to some extent.

[0052] The results of Example 1 and Comparative Example 2 show that the bone wax in this invention has a longer degradation time than polyethylene glycol-based bone wax, which can maintain a longer sealing time; its compressive modulus is lower than that of polyethylene glycol-based bone wax, which can be more easily kneaded into any shape for use; and its adhesion performance is also better than that of polyethylene glycol-based bone wax, which can achieve a better sealing effect.

[0053] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An absorbable bone wax, characterized in that, By weight percentage, it includes the following components: Sodium carboxymethyl cellulose 45–60 wt% 30–50 wt% of binary or ternary block copolymers containing polyethylene glycol (PEG) Calcium stearate 5–10 wt% Citric acid 1.25–3 wt% The total weight percentage of all components is 100%. The binary or ternary block copolymer is obtained by copolymerizing PEG with one or two of caprolactone and lactide.

2. The absorbable bone wax according to claim 1, characterized in that, The sodium carboxymethyl cellulose is selected from one or more of three viscosity grades, and the viscosity of a 2% aqueous solution of each grade is 750–1400 mPa·s, 1500–2800 mPa·s and 3000–5600 mPa·s, respectively.

3. The absorbable bone wax according to claim 2, characterized in that, The sodium carboxymethyl cellulose is purified before use to reduce endotoxin levels to less than 20 EU / g.

4. The absorbable bone wax according to claim 1, characterized in that, If it is a ternary polymer, the mass ratio of PEG:PCL:PLA is 1:(0.25–2):(0.25–2); if it is a binary copolymer (PCL-PEG or PLA-PEG), the mass ratio of PEG to PCL or PEG to PLA is 1:(0.5–4); wherein the molecular weight of PEG is 400–2000, and the molecular weight of the binary or ternary block copolymer is 600–8000.

5. The absorbable bone wax according to claim 1, characterized in that, It also contains 5–10 wt% of osteogenic active material, which is selected from at least one of hydroxyapatite, bioactive glass, and mineralized collagen fibers.

6. The absorbable bone wax according to claim 5, characterized in that, The mineralized collagen fiber is a collagen-hydroxyapatite complex, which is prepared by mixing collagen and hydroxyapatite at a mass ratio of 0.5–1.5:1 in an ethanol solution with a volume fraction of 50–75% by stirring at 100–500 rpm for 30–60 min, filtering, and then freeze-drying or vacuum drying.

7. A method for preparing the absorbable bone wax according to any one of claims 1-6, characterized in that, The steps include: (1) purifying sodium carboxymethyl cellulose; (2) mixing a PEG-containing binary or ternary block copolymer with citric acid and performing vacuum dehydration and thermal crosslinking. (3) Add purified sodium carboxymethyl cellulose and calcium stearate to the mixture after vacuum thermal crosslinking, and stir and mix evenly at 50–60°C to obtain absorbable bone wax; optionally, add osteogenic active material to the absorbable bone wax obtained in step (3); wherein the PEG-containing binary or ternary block copolymer is obtained by copolymerizing PEG with one or two of PCL and PLA.

8. The preparation method according to claim 7, characterized in that, The purification process described in step (1) includes: treating sodium carboxymethyl cellulose with alkali, and then washing it sequentially with 75% ethanol, 90% ethanol, and anhydrous ethanol.

9. The preparation method according to claim 8, characterized in that, The alkaline treatment is as follows: sodium carboxymethyl cellulose is added to 75% ethanol at a feed-to-liquid ratio of 1:10, and 2 wt% sodium hydroxide is added. The mixture is heated and stirred at 55–65°C and 100–500 rpm, and then refluxed for 2–4 h. The mixture is then neutralized to pH 6.5–8.0 with hydrochloric acid or acetic acid, and filtered to obtain sodium carboxymethyl cellulose filter cake.

10. The preparation method according to claim 8, characterized in that, The washing process involves: stirring the alkali-treated filter cake in 75% ethanol, 90% ethanol, and anhydrous ethanol at a ratio of 1:10 for 30–60 min at a stirring speed of 100–500 rpm, and filtering after each stirring; then vacuum drying the final filter cake to obtain purified sodium carboxymethyl cellulose.

11. The preparation method according to claim 7, characterized in that, In step (2), the mass ratio of the PEG-containing binary or ternary block copolymer to citric acid is 16–32:1; the mixing method is melt mixing, or dissolving and mixing with water followed by freeze drying.

12. The preparation method according to claim 7, characterized in that, In step (2), the temperature for vacuum dehydration thermal crosslinking is 105–140℃, and the crosslinking time is 1–3 h.

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