An absorbable bone wax and its preparation method and application
By using resorbable bone wax prepared with raw materials of specific components and proportions, the problem of traditional bone wax degradation too quickly and no bone healing is solved, and the rapid hemostasis, coagulation and continuous bone healing effect in orthopedic surgery is achieved, which is suitable for industrial applications.
Patent Information
- Application Number
- CN202210653532.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-06-10
- Publication Date
- 2025-06-20
- Estimated Expiration
- 2042-06-10
AI Technical Summary
Traditional bone waxes have problems in orthopedic surgery, such as rapid degradation, no bone healing and simple physical hemostasis function, resulting in increased risk of postoperative infection, obstructed bone wound repair and local pain.
Using an absorbable bone wax, its raw materials include hydroxyethylsilane, α-tocopherol succinate, polycarboxy-substituted chitosan and strontium salt, the bone wax is ductile, coagulation function and the ability to continuously release strontium ions by building a polymer interlocking network structure and regulating the molecular weight of polyethylene glycol, it imparts ductility, coagulation function and the ability to continuously release strontium ions.
It has achieved rapid mechanical hemostasis, coagulation properties and no hemolysis in orthopedic surgery, can continuously promote bone healing, and has dense structure and controllable degradation, which is suitable for industrialization and large-scale promotion.
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Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of the preparation of biomedical materials. More specifically, it relates to an absorbable bone wax and its preparation method and application. Background Art
[0002] Bones contain rich blood and marrow channels. When they are cut during surgical operations or suffer from traumatic fractures, a large amount of bleeding will occur, especially in the spine and sternum with high-density blood vessels. Therefore, when performing surgical repair on bones, taking hemostatic measures becomes the top priority. Currently in clinical practice, the most commonly used bone hemostatic material is sterile bone wax. This material is mainly composed of beeswax and softeners, usually existing in a waxy form, having excellent ductility and adhesiveness, and can be used for physical bone hemostasis. However, traditional bone wax is mostly non-degradable and has many clinical problems: First, as a foreign body implanted, bone wax reduces the anti-infection ability of tissues, increasing the risk of postoperative infection; second, it hinders the repair of bone wounds, causing local pain, exudation and other symptoms caused by foreign body granulomas; third, the adhesion effect between beeswax and bone is not good, it is not easy to adhere to the bone surface, and it is easy to slip off during the surgical process.
[0003] With the in-depth research of biomaterials and the application development of the bone hemostatic material market, currently, technical personnel have carried out research on bone wax substitutes from aspects such as synthetic polymer materials and biological agents, such as adding phosphates, fatty acid salts, gelatin, chitosan, poloxamer, vitamin E ester derivatives, and inorganic metal salts (strontium metal compounds, tantalum metal compounds, magnesium metal compounds, etc.) to bone wax substitutes. Although these solutions effectively solve the problem of the difficult degradation of traditional bone wax, there are still the following problems to be solved urgently:
[0004] (1) Loose structure and poor ductility, resulting in too fast degradation and unable to maintain the hemostatic function for a long time;
[0005] (2) It has no bone-healing promoting effect. Although many studies promote the bone-healing ability by loading strontium ions, due to the too fast release of strontium ions, it is impossible to ensure the promotion of bone healing;
[0006] (3) Simple physical hemostatic function and no coagulation performance.
[0007] Therefore, developing bone wax substitutes is still a challenging topic. Summary of the Invention
[0008] Based on the above background, the purpose of the present invention is to provide an absorbable bone wax, which has the advantages of high ductility, strong plasticity, moderate viscosity, etc. When used in orthopedic surgeries, this absorbable bone wax has a coagulation function, can promote rapid hemostasis of bone cross-sections, and at the same time, can continuously release strontium ions to promote the healing of bone wounds.
[0009] To achieve the above object, the present invention adopts the following technical solutions:
[0010] In a first aspect, the present invention provides an absorbable bone wax, and by mass fraction, its raw materials include: 5-10 parts of hydroxyethylsilane, 10-30 parts of polyethylene glycol α-tocopheryl succinate, 10-50 parts of multi-carboxyl substituted chitosan, and 1-5 parts of strontium salt.
[0011] Among them, the present invention uses specific components as raw materials and strictly limits the mass of each component, so that the absorbable bone wax has a dense structure, excellent mechanical properties and coagulation function. Specifically, the present invention first constructs a polymer interlocking network structure through polyethylene glycol α-tocopheryl succinate and multi-carboxyl substituted chitosan, so that the absorbable bone wax has a dense structure, excellent ductility and stability; secondly, by regulating the molecular weight of polyethylene glycol and its total content in the amphiphilic polyethylene glycol α-tocopheryl succinate, the absorbable bone wax is given the characteristics of controllable degradation and excellent viscosity; finally, through the chelation of strontium ions by multi-carboxyl substituted chitosan, strontium ions are effectively stabilized, achieving the effect of continuous release of strontium ions, thereby giving the absorbable bone wax an excellent bone healing promotion effect.
[0012] Further, in the polyethylene glycol α-tocopheryl succinate, the molecular weight of polyethylene glycol is 2000-10000; preferably one or more of 2000, 4000, 6000 and 10000.
[0013] Further, the hydroxyethylsilane is tetra(hydroxyethyl)silane or tris(hydroxyethyl)methylsilane.
[0014] Further, the strontium salt is one or more of strontium chloride, strontium iodide, strontium acetate, and strontium hydrogen phosphate.
[0015] Further, the preparation method of the multi-carboxyl substituted chitosan includes the following steps:
[0016] Step 1: Perform alkynyl functionalization modification on chitosan to obtain alkynylated chitosan;
[0017] Step 2: Disperse the alkynylated chitosan in an organic solvent, add an initiator and a mercapto organic acid, and react under ultraviolet light to obtain multi-carboxyl substituted chitosan.
[0018] Exemplarily, the preparation of the alkynylated chitosan includes the following steps:
[0019] Add chitosan to an isopropyl alcohol aqueous solution, stir at room temperature, add sodium hydroxide, continue stirring at room temperature, then add propargyl bromide, heat and react. After the reaction is completed, neutralize with acid, precipitate with a precipitant, wash, and dry.
[0020] Exemplarily, the preparation of the alkynylated chitosan specifically includes the following steps:
[0021] Add 1 - 10 parts of chitosan to 40 - 100 parts of isopropyl alcohol aqueous solution, stir at room temperature for 30 min, then add 5 - 10 parts of 4 mol / L sodium hydroxide solution, stir at room temperature for 30 min, and then add 0.1 - 1 part of propargyl bromide thereto, and react at 80 °C for 4 h. After the reaction is completed, neutralize with 0.5 - 1% hydrochloric acid solution, then precipitate with ether, and finally wash with ethanol 3 times and dry in vacuum.
[0022] Further, the mass ratio of the alkynylated chitosan, mercapto organic acid and initiator is 5 - 10:1 - 5:0.1 - 1.
[0023] Further, in the ultraviolet light irradiation, the wavelength of the ultraviolet light is 365 nm - 400 nm; preferably 365 nm.
[0024] Further, the molecular weight of the chitosan is in the range of 100,000 - 300,000, and the degree of deacetylation is ≥ 95%.
[0025] Further, the initiator is one or more of azobisisobutyronitrile, benzoin dimethyl ether and BASF 819.
[0026] Further, the mercapto organic acid is one or more of mercaptosuccinic acid, mercaptoacetic acid, mercaptobutyric acid and mercapto poly(ethylene glycol) carboxylic acid.
[0027] Further, in the mercapto poly(ethylene glycol) carboxylic acid, the molecular weight of the polyethylene glycol is 2000 - 20000; preferably one or more of 2000, 5000 and 20000.
[0028] In a second aspect, the present invention provides a method for preparing the above - mentioned absorbable bone wax, including the following steps:
[0029] S1. Add hydroxyethyl silane, polyethylene glycol α - tocopherol succinate and polycarboxyl - substituted chitosan in proportion in water, mix and stir, and freeze - dry to obtain a carboxyl chitosan - polyethylene glycol α - tocopherol succinate polymer.
[0030] S2. Add the carboxyl chitosan - polyethylene glycol α - tocopherol succinate polymer and strontium salt in water, mix and stir, freeze - dry, and perform sterilization after extrusion and injection molding.
[0031] Further, in step S1, the mixing and stirring is carried out at room temperature for 1 h - 3 h;
[0032] In step S2, the mixing and stirring is carried out at room temperature for 12 h - 36 h.
[0033] It can be understood that in step S2, the carboxymethyl chitosan-α-tocopherol succinate polyethylene glycol ester polymer is the total amount of the carboxymethyl chitosan-α-tocopherol succinate polyethylene glycol ester polymer generated in step S1.
[0034] Exemplarily, the sterilization method includes but is not limited to electron beam irradiation sterilization or Co-60 irradiation sterilization, etc.
[0035] In a third aspect, the present invention provides an application of the above-mentioned absorbable bone wax for preparing or directly as a bone hemostatic, bone defect or bone graft repair material.
[0036] In addition, unless otherwise specified, any range described in the present invention includes the end values and any numerical values between the end values, as well as any sub-ranges constituted by any numerical values between the end values or the end values. The preparation methods in the present invention are all conventional methods unless otherwise specified, and the raw materials used can be obtained from public commercial channels or prepared according to the existing technology unless otherwise specified, and the solutions are aqueous solutions unless otherwise specified.
[0037] The beneficial effects of the present invention are as follows:
[0038] (1) The absorbable bone wax provided by the present invention has a dense structure, excellent viscosity, good ductility and stability, and at the same time, the degradation is controllable, which can meet the needs of different clinical scenarios.
[0039] (2) The absorbable bone wax provided by the present invention is used for preparing or directly as a bone hemostatic, bone defect or bone graft repair material, and can quickly mechanically stop bleeding. In addition to mechanical hemostasis, the absorbable bone wax also has good coagulation performance and no hemolysis phenomenon.
[0040] (3) The absorbable bone wax provided by the present invention utilizes the chelation effect of multi-carboxyl substituted chitosan on strontium ions, and can continuously release strontium ions, thereby promoting bone repair and regeneration.
[0041] (4) The preparation process of the absorbable bone wax provided by the present invention is simple, the raw materials are widely available, the application prospect is broad, and it is suitable for industrialization and large-scale promotion. Description of the Drawings
[0042] The following further details the specific embodiments of the present invention with reference to the drawings.
[0043] Figure 1 Shows a physical photo of the absorbable bone wax prepared in Example 1.
[0044] Figure 2 Shows the results of the cytotoxicity test of the absorbable bone wax prepared in Example 1, Comparative Example 1 and the blank control group.
[0045] Figure 3The figure shows the strontium ion sustained release test results of the absorbable bone wax prepared in Example 1 and Comparative Example 1.
[0046] Figure 4 The figure shows the degradation test results of the absorbable bone wax prepared in Examples 1-4 and Comparative Examples 1-4.
[0047] Figure 5 The figure shows the blood coagulation test results of the absorbable bone wax prepared in Example 1 and Comparative Example 1 and the traditional bone wax.
[0048] Figure 6 The figure shows the hemolysis test results of the absorbable bone wax prepared in Example 1 and Comparative Example 1 and the traditional bone wax. Detailed implementation mode
[0049] To illustrate the present invention more clearly, the present invention will be further described below in conjunction with preferred embodiments and the accompanying drawings. Similar components in the drawings are denoted by the same reference numerals. Those skilled in the art should understand that the content specifically described below is illustrative rather than restrictive, and should not be used to limit the protection scope of the present invention.
[0050] The preparation of the multi-carboxyl substituted chitosan used in the following examples or comparative examples includes the following steps:
[0051] (1) Add 5 parts of chitosan with a molecular weight of 100,000 and a degree of deacetylation of 95% to 40 parts of an isopropanol aqueous solution (isopropanol: water = 3:1), stir at room temperature for 30 min, then add 5 parts of a 4 mol / L sodium hydroxide solution, stir at room temperature for 30 min, and then add 0.5 part of propargyl bromide thereto, and react at 80 °C for 4 h. After the reaction is completed, neutralize with a 1% hydrochloric acid solution, then precipitate with ether, wash with ethanol 3 times, and dry in vacuo to obtain alkynylated chitosan.
[0052] (2) Disperse 5 parts of alkynylated chitosan in N,N-dimethylformamide, then add 0.1 part of azobisisobutyronitrile and 3 parts of mercaptosuccinic acid thereto, and stir at room temperature under ultraviolet light irradiation at 365 nm for 4 h. Then centrifuge, wash with ethanol 3 times, and dry to obtain multi-carboxyl substituted chitosan.
[0053] The model of the traditional bone wax used in the following test examples is: W810T; its main components are: beeswax, paraffin wax, and isopropyl palmitate.
[0054] Example 1
[0055] This example provides an absorbable bone wax, and by weight, its raw materials include: 5 parts of tetra(hydroxyethyl)silane, 30 parts of α-tocopherol succinate polyethylene glycol ester (polyethylene glycol molecular weight 2000), 10 parts of multi-carboxyl substituted chitosan, and 1 part of strontium chloride.
[0056] Its preparation method comprises the following steps: (1) Dissolve the raw materials, i.e., tetra (hydroxyethyl) silane, polyethylene glycol α-tocopheryl succinate, and polycarboxyl-substituted chitosan, in 70 parts of aqueous solution, stir at room temperature for 3 h, and then perform freeze-drying to obtain a carboxylated chitosan-polyethylene glycol α-tocopheryl succinate polymer.
[0057] (2) Add the carboxylated chitosan-polyethylene glycol α-tocopheryl succinate polymer obtained in step (1) and strontium chloride into 30 parts of water, stir at room temperature for 12 h, then perform freeze-drying on the product, and obtain a waxy sample by extrusion and injection molding. Then, perform electron beam irradiation sterilization and packaging to obtain an absorbable bone wax (for the physical object of the absorbable bone wax, see Figure 1 shown).
[0058] Example 2
[0059] Same as Example 1, the only difference is that in polyethylene glycol α-tocopheryl succinate, the molecular weight of polyethylene glycol is 4000.
[0060] Example 3
[0061] Same as Example 1, the only difference is that in polyethylene glycol α-tocopheryl succinate, the molecular weight of polyethylene glycol is 6000.
[0062] Example 4
[0063] Same as Example 1, the only difference is that in polyethylene glycol α-tocopheryl succinate, the molecular weight of polyethylene glycol is 10000.
[0064] Comparative Example 1
[0065] This example provides an absorbable bone wax. By weight, its raw materials include: 30 parts of polyethylene glycol α-tocopheryl succinate (the molecular weight of polyethylene glycol is 2000), 10 parts of chitosan, and 0.1 part of strontium chloride.
[0066] Its preparation method comprises the following steps:
[0067] Dissolve the raw materials, i.e., polyethylene glycol α-tocopheryl succinate, chitosan, and strontium chloride, in 30 parts of water, perform mechanical stirring, then perform freeze-drying, and obtain a waxy sample by extrusion and injection molding. Finally, perform electron beam irradiation sterilization and packaging.
[0068] Comparative Example 2
[0069] Same as Comparative Example 1, the only difference is that in polyethylene glycol α-tocopheryl succinate, the molecular weight of polyethylene glycol is 4000.
[0070] Comparative Example 3
[0071] Same as Comparative Example 1, the only difference is that in polyethylene glycol α-tocopheryl succinate, the molecular weight of polyethylene glycol is 6000.
[0072] Comparative Example 4
[0073] Same as Comparative Example 1, except that in the polyethylene glycol α-tocopherol succinate, the molecular weight of polyethylene glycol is 10,000.
[0074] Test Example 1
[0075] Cytotoxicity test
[0076] Preparation of the leaching solution: The leaching solution was prepared according to the national standard GB / T 16886.12-2005. The absorbable bone wax prepared in Example 1 and Comparative Example 1 was added to the cell culture medium respectively, and the leaching ratio was 0.2 g / mL. Then it was cultured in an incubator at 37°C for 24 h, and the cultured leaching solution was refrigerated at 4°C for standby.
[0077] The cultured extract was added to a 96-well plate, 2000 cells were inoculated in each well, 10% FBS was added to each well, and it was cultured at 37°C in 5% CO2 for 7 days. The Incucyte TM Zoom system was used to observe the effect of the extract on human embryonic lung fibroblasts (MRC-5) in real time, and the cell culture medium without the leaching solution was used as the blank control group. The statistical results of cell survival rate are as Figure 2 shown.
[0078] From Figure 2 it can be seen that the relative cell survival rate in the extracts of the absorbable bone waxes of Comparative Example 1 and Example 1 is comparable to that of the blank control group, indicating that the absorbable bone waxes prepared in Comparative Example 1 and Example 1 have no cytotoxicity.
[0079] Test Example 2
[0080] Strontium ion sustained release test
[0081] 1 g of the absorbable bone wax prepared in Example 1 and Comparative Example 1 was selected respectively and placed in a container containing 50 mL of PBS buffer solution (pH = 7.4, 0.02 M); the container was placed in a constant temperature shaker at 37°C with a speed of 100 rpm; 5 mL of the solution was accurately measured at 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 216 h, 240 h, 264 h, 288 h, 312 h, 336 h respectively, and the supernatant was taken, and the strontium ion concentration was measured by inductively coupled plasma atomic emission spectrometry, and the curve of the strontium ion release degree versus time was drawn, as Figure 3 shown.
[0082] From Figure 3It can be seen that the absorbable bone wax prepared in Comparative Example 1 was completely released after 48 h, while the absorbable bone wax prepared in Example 1 required 288 h. This result indicates that the absorbable bone wax prepared in Example 1 has a good complexing effect on strontium ions and has the ability to slowly release strontium ions for a long time.
[0083] Test Example 3
[0084] Degradation test
[0085] 1 g of the absorbable bone waxes prepared in Examples 1-4 and Comparative Examples 1-4 were respectively placed in containers containing 50 mL of PBS buffer (pH = 7.4, 0.02 M); the containers were placed in a constant temperature shaker at 37 °C with a speed of 100 rpm; the absorbable bone waxes were taken out and dried and weighed on the 1st day, 2nd day, 3rd day, 5th day, 7th day, 9th day, 12th day, 15th day, 20th day, 25th day, and 30th day respectively. The results are as Figure 4 shown.
[0086] From Figure 4 it can be seen that the absorbable bone waxes prepared in Comparative Examples 1-4 took 3 days to complete degradation, while for the absorbable bone waxes prepared in Examples 1-4, 20% was still undegraded after 30 days. Moreover, as the molecular weight of polyethylene glycol in polyethyleneglycol-α-tocopheryl succinate increased, the degree of degradation gradually decreased.
[0087] Test Example 4
[0088] Coagulation test
[0089] First, 10 mg of the absorbable bone wax prepared in Example 1, the absorbable bone wax prepared in Comparative Example 1, and the traditional bone wax were respectively added to 50 μL of whole blood solution (containing 10 mM CaCl2). Then, they were incubated at 37 °C for 1 min, 2 min, 3 min, and 4 min respectively, 10 mL of deionized water was added, and the absorbance of the supernatant was detected at 545 nm. As a blank control, 50 μL of whole blood solution was added to 10 mL of deionized water. The blood coagulation index (BCI) of the material was calculated using the formula:
[0090] BCI = A M / A0×100%, where A M and A0 are the absorbances of the absorbable bone wax and the blank control respectively; the curve of the blood coagulation index of the material versus time was plotted, as Figure 5 shown.
[0091] From Figure 5 it can be seen that the absorbable bone wax prepared in Example 1 could achieve the blood coagulation effect after 4 min, the blood coagulation effect of the absorbable bone wax prepared in Comparative Example 1 was worse than that of Example 1, and the traditional bone wax had no blood coagulation effect.
[0092] Test Example 5
[0093] Hemolysis test
[0094] The absorbable bone waxes prepared in Example 1 and Comparative Example 1 and the traditional bone wax were respectively immersed in 3 mL of PBS to make their concentrations 10 mg / mL. Then, 60 μL of red blood cells were respectively added, and they were cultured at 37 °C for 1 h. The cultured mixture was centrifuged at 1500 rpm for 10 min, and the supernatant was collected. The absorbance of the supernatant at 545 nm was measured using an ultraviolet spectrophotometer. Distilled water was used as the positive control, and PBS was used as the negative control. The hemolysis rate (HR) of the material was calculated using the formula:
[0095] Hemolysis rate (HR) = [(A0 - A m ) / (A0 - A p )] × 100%, where A M , A p and A0 were the absorbances of the material, distilled water, and PBS, respectively; the statistical results of the hemolysis rates of each material were as shown in Figure 6 .
[0096] It can be seen from Figure 6 that there was no hemolysis phenomenon (HR < 5) in the absorbable bone waxes prepared in Example 1 and Comparative Example 1 and the traditional bone wax, but the hemolysis rates of Example 1 and Comparative Example 1 were both lower than that of the traditional bone wax.
[0097] Test Example 6
[0098] Hemostasis test and wound healing test
[0099] Forty-eight adult rabbits of equal weight were selected and divided into 4 groups, namely the absorbable bone wax prepared in Example 1, the absorbable bone wax prepared in Comparative Example 1, the control group (i.e., the traditional bone wax), and the blank group, with 12 rabbits in each group. Experimental procedure: (1) The rabbits were anesthetized by intravenous injection of 1% sodium pentobarbital (3 mL / Kg) into the marginal ear vein. (2) A longitudinal incision was made on the anterior side of the tibia and fibula of the hind leg of the rabbit. The skin and subcutaneous tissue were successively incised with a scalpel to expose the anterior edge of the tibia and fibula of the hind leg of the rabbit. (4) The anterior edge of the tibia was bitten off using a pointed bone rongeur, and the fracture fragment was about 0.5 cm × 1 cm in size, and the bleeding situation was observed. (5) The absorbable bone waxes prepared in Example 1 and Comparative Example 1 and the traditional bone wax were respectively used for hemostasis, and no material was filled in the blank group. The hemostasis time was recorded. (6) After the recording was completed, the subcutaneous tissue and skin were sutured layer by layer. After disinfecting the wound with iodophor again, it was wet-compressed with alcohol gauze, and the wound was bandaged with a sterile dressing. (7) An equal dose (100,000 units) of penicillin was injected to prevent wound infection, once a day for 3 consecutive days, and the diet and drinking water of the animals were observed every day. The rabbits were sacrificed in stages at 4 weeks, 8 weeks, and 12 weeks after the operation, 4 rabbits in each group were sacrificed each time, and the healing situation of the bone defect wound was observed using a nuclear magnetic resonance (MRI) device. The results are shown in Table 1.
[0100] Table 1: Hemostasis test and wound healing test
[0101]
[0102] As can be seen from Table 1, the absorbable bone wax prepared in Example 1 has excellent hemostatic effect and can effectively promote bone healing.
[0103] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, rather than limiting the implementation manners of the present invention. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the implementation manners here. Any obvious changes or modifications derived from the technical solutions of the present invention still fall within the protection scope of the present invention.
Claims
1. An absorbable bone wax, characterized in that, By mass parts, its raw materials include: 5-10 parts of hydroxyethylsilane, 10-30 parts of polyethylene glycol α-tocopherol succinate, 10-50 parts of polycarboxyl-substituted chitosan, and 1-5 parts of strontium salt; In the polyethylene glycol α-tocopherol succinate, the molecular weight of polyethylene glycol is 2000-10000; The preparation method of the absorbable bone wax includes the following steps: S1. Add hydroxyethylsilane, polyethylene glycol α-tocopherol succinate and polycarboxyl-substituted chitosan into water in proportion, mix and stir, and freeze-dry to obtain carboxyl chitosan-polyethylene glycol α-tocopherol succinate polymer; S2. Add the carboxyl chitosan-polyethylene glycol α-tocopherol succinate polymer and strontium salt into water, mix and stir, freeze-dry, extrude and inject, and then sterilize to obtain the product; Among them, the preparation method of the polycarboxyl-substituted chitosan includes the following steps: Step 1: Modify chitosan with alkynyl functional groups to obtain alkynylated chitosan; Step 2: Disperse the alkynylated chitosan in an organic solvent, add an initiator and a mercapto organic acid, and react under ultraviolet light to obtain polycarboxyl-substituted chitosan; the mass ratio of the alkynylated chitosan, the mercapto organic acid to the initiator is 5-10:1-5:0.1-1; in the ultraviolet light, the wavelength of the ultraviolet light is 365nm-400nm; the mercapto organic acid is one or more of mercapto succinic acid, mercaptoacetic acid, mercaptobutyric acid and mercapto polyethylene glycol carboxylic acid.
2. The absorbable bone wax according to claim 1, characterized in that, In the polyethylene glycol α-tocopherol succinate, the molecular weight of polyethylene glycol is one or more of 2000, 4000, 6000 and 10000.
3. The absorbable bone wax according to claim 1, characterized in that, The hydroxyethylsilane is tetra(hydroxyethyl)silane or tri(hydroxyethyl)methylsilane.
4. The absorbable bone wax according to claim 1, characterized in that, The strontium salt is one or more of strontium chloride, strontium iodide, strontium acetate and strontium hydrogen phosphate.
5. The absorbable bone wax according to claim 1, characterized in that, The molecular weight of the chitosan is in the range of 100,000-300,000, and the degree of deacetylation is ≥95%; The initiator is one or more of azobisisobutyronitrile, benzoin dimethyl ether and BASF 819.
6. The absorbable bone wax according to claim 1, characterized in that, In the mercapto polyethylene glycol carboxylic acid, the molecular weight of polyethylene glycol is 2000-20000.
7. The absorbable bone wax according to claim 1, characterized in that, In step S1, the mixing and stirring are carried out at room temperature for 1h-3h; In step S2, the mixing and stirring are carried out at room temperature for 12h-36h.
8. Use of an absorbable bone wax as described in any one of claims 1 - 7 in the preparation of a bone hemostatic, bone defect or bone graft repair material.
Citation Information
Patent Citations
Degradable and absorbable bone hemostatic material and preparation method
CN111317858A