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CN-122005899-A - Absorbable bone wax and preparation method thereof

CN122005899ACN 122005899 ACN122005899 ACN 122005899ACN-122005899-A

Abstract

The invention discloses absorbable bone wax and a preparation method thereof, belonging to the field of biomedical materials. The absorbable bone wax comprises, by weight, 45-60% of sodium carboxymethylcellulose, 30-50 wt% of a binary or ternary copolymer containing polyethylene glycol (PEG), 5-10 wt% of calcium stearate and 1.25-3 wt% of citric acid, wherein the copolymer is obtained by copolymerizing PEG with one or two of caprolactone and lactide. The sodium carboxymethyl cellulose is purified to reduce endotoxin, the molecular weight of the copolymer and the proportion of each component are controllable, and an osteogenic active material can be added. The preparation method comprises the steps of sodium carboxymethyl cellulose purification, vacuum dehydration and thermal crosslinking of the copolymer and citric acid, mixing of the components and the like. The bone wax has good absorbability, good biocompatibility, simple and controllable preparation process, can meet clinical bone hemostasis requirements, and has good application prospect.

Inventors

  • GAN SHAOLEI
  • MA JUN
  • YE DIAN

Assignees

  • 江西博恩锐尔生物科技有限公司

Dates

Publication Date
20260512
Application Date
20260316

Claims (12)

  1. 1. The absorbable bone wax is characterized by comprising the following components in percentage by weight: 45-60 wt% of sodium carboxymethyl cellulose, 30-50 Wt% of binary or ternary segmented copolymer containing polyethylene glycol (PEG), 5-10 Wt% of calcium stearate, Citric acid 1.25-3 wt%; The sum of the weight percentages of the components is 100 percent; wherein the binary or ternary segmented copolymer is obtained by copolymerizing PEG and one or two of caprolactone and lactide.
  2. 2. The absorbable bone wax of claim 1, wherein the sodium carboxymethyl cellulose is selected from one or more of three viscosity models, each model having a 2% aqueous solution viscosity of 750-1400 mPa s, 1500-2800 mPa s, and 3000-5600 mPa s in that order.
  3. 3. The absorbable bone wax of claim 2 wherein the sodium carboxymethyl cellulose has been purified prior to use to reduce endotoxin to less than 20 EU/g.
  4. 4. The absorbable bone wax of claim 1, wherein the mass ratio of PEG to PCL to PLA is 1 (0.25-2) in the case of a terpolymer and 1 (0.5-4) in the case of a bipolymer (PCL-PEG or PLA-PEG), wherein the molecular weight of PEG is 400-2000 and the molecular weight of the bipolymer or triblock copolymer is 600-8000.
  5. 5. The resorbable bone wax of claim 1 further comprising 5-10 wt% of an osteogenic active material selected from at least one of hydroxyapatite, bioactive glass, mineralized collagen fibers.
  6. 6. The absorbable bone wax of claim 5, wherein the mineralized collagen fibers are collagen-hydroxyapatite composite, and are prepared by mixing collagen and hydroxyapatite in a mass ratio of 0.5-1.5:1, stirring and mixing the collagen and the hydroxyapatite in an ethanol solution with a volume fraction of 50-75% by weight of 100-500 rpm for 30-60 min, filtering, and freeze-drying or vacuum drying.
  7. 7. A preparation method of the absorbable bone wax according to any one of claims 1-6 is characterized by comprising the following steps of (1) purifying sodium carboxymethyl cellulose, (2) mixing a binary or ternary segmented copolymer containing PEG with citric acid, carrying out vacuum dehydration and thermal crosslinking, (3) adding purified sodium carboxymethyl cellulose and calcium stearate into the mixture after vacuum thermal crosslinking, stirring and mixing uniformly at 50-60 ℃ to obtain the absorbable bone wax, and optionally adding an osteogenic active material into the absorbable bone wax obtained in the step (3), wherein the binary or ternary segmented copolymer containing PEG is obtained by copolymerizing PEG with one or two of PCL and PLA.
  8. 8. The method according to claim 7, wherein the purification treatment in the step (1) comprises alkali treatment of sodium carboxymethyl cellulose followed by washing with 75% ethanol, 90% ethanol, and absolute ethanol in that order.
  9. 9. The preparation method of the sodium carboxymethyl cellulose is characterized by comprising the steps of adding sodium carboxymethyl cellulose into ethanol with the volume fraction of 75% according to the feed-liquid ratio of 1:10, adding sodium hydroxide with the concentration of 2 wt%, heating and stirring at the temperature of 55-65 ℃ and the rotating speed of 100-500 rpm, condensing and refluxing for 2-4 h, neutralizing with hydrochloric acid or acetic acid to the pH of 6.5-8.0, and carrying out suction filtration to obtain a sodium carboxymethyl cellulose filter cake.
  10. 10. The preparation method of the sodium carboxymethyl cellulose, according to claim 8, is characterized in that washing is carried out by stirring a filter cake subjected to alkali treatment in a feed liquid ratio of 1:10 in 75% ethanol, 90% ethanol and absolute ethanol in sequence at a stirring speed of 100-500 rpm and a stirring speed of 100-500, filtering after each stirring, and vacuum drying the final filter cake to obtain the purified sodium carboxymethyl cellulose.
  11. 11. The method according to claim 7, wherein in the step (2), the mass ratio of the PEG-containing diblock or triblock copolymer to citric acid in the step (2) is 16 to 32:1, and the mixing is performed by melt mixing or by freeze drying after dissolving and mixing in water.
  12. 12. The process according to claim 7, wherein in the step (2), the temperature of vacuum dehydration thermal crosslinking is 105 to 140℃and the crosslinking time is 1 to 3 h.

Description

Absorbable bone wax and preparation method thereof Technical Field The invention belongs to the technical field of biomedical materials, and particularly relates to absorbable bone wax and a preparation method thereof. Background Bone wax is an indispensable hemostatic material in orthopaedics and surgery, and is mainly used for blocking a bleeding channel of cancellous bone or cortical bone in a physical filling way, so that quick hemostasis is realized, and the bone wax is convenient to use and quick in effect, and is widely applied to various surgical scenes such as osteotomy, bone drilling, bone defect repair and the like. At present, the conventional bone wax commonly used in clinic takes beeswax or paraffin hydrophobic substances as main components, and the hemostatic mechanism only depends on physical barrier effect. However, the traditional bone wax has core defects that the traditional bone wax is difficult to degrade and absorb in vivo, and a series of adverse reactions can be caused after long-term retention in bone tissues, including local inflammatory reaction, delayed bone healing, increased infection risk and the like, so that the postoperative bone repair effect is seriously affected, and the long-term safety requirement of clinical bone hemostatic materials cannot be met. To solve the problem of unabsorbable conventional bone waxes, related studies have been made in the prior art, US 7,989,000 discloses compositions comprising solid particulate fatty acid salts suspended in liquid polyoxyalkylenes and other excipients, US 5,356,629 discloses compositions comprising polymethyl methacrylate coated particles in a cellulose ether, collagen or hyaluronic acid matrix, US 7,553,913 discloses hydrophilic water-soluble waxy compositions based on random copolymers of ethylene oxide and other alkylene oxides, which can mix the solid particles, US 7,914,819 discloses polymeric matrices having a polysaccharide backbone, US 7,074,425 discloses hydrophilic polyethylene glycol based compositions consisting of a mixture of high and low molecular weight polyethylene glycols having a hydrophilic lipophilic balance of greater than 20. Although the prior art has a certain progress in improving the absorbability of bone wax, the prior art still has a plurality of defects that most compositions are poor in structural stability, easy to migrate and run off under a wet operation environment or a flushing condition, can not maintain effective hemostasis for a long enough time, meanwhile, the balance between any shaping property and shaping maintainability required clinically is difficult to achieve, the degradation speed of part of polyethylene glycol-based compositions is too high, the bone healing period can not be matched, and the comprehensive requirements of the structural stability, the controllable absorbability and the clinical operability of the bone wound hemostatic material can not be completely met. Therefore, research and development of the absorbable bone wax can realize arbitrary shaping to adapt to clinical operation demands, can completely degrade and absorb the bone wax, has longer degradation time compared with the prior polyethylene glycol-based bone wax, can maintain long-acting hemostatic effect, does not interfere with the subsequent bone healing process, and becomes the technical problem to be solved in the prior art. Disclosure of Invention The invention discloses absorbable bone wax and a preparation method thereof, belongs to the technical field of biomedical materials, and aims to solve the technical problems that the conventional bone wax is difficult to absorb by a human body, has poor biocompatibility, lacks of an osteogenesis activity in part of products, has complex preparation process and the like, and provides the absorbable bone wax which has good biocompatibility, can be completely absorbed, has hemostatic and osteogenesis functions, and is simple and convenient to prepare, and the preparation method thereof. The absorbable bone wax comprises, by weight, 45-60 wt% of sodium carboxymethylcellulose, 30-50-wt% of a binary or ternary block copolymer containing polyethylene glycol (PEG), 5-10-wt% of calcium stearate, 1.25-3-wt% of citric acid, and the total weight of all the components is 100%. The binary or ternary segmented copolymer is obtained by copolymerizing PEG with one or two of caprolactone (PCL) and lactide (PLA), and by introducing the segmented copolymer, the flexibility and absorbability of bone wax can be effectively improved, and the compatibility of the bone wax with human tissues can be improved. As a preferred technical scheme of the absorbable bone wax, the sodium carboxymethyl cellulose is selected from one or more of three viscosity types, and the viscosity of a 2% aqueous solution of each type is 750-1400 mPa.s, 1500-2800 mPa.s and 3000-5600 mPa.s in sequence. The three kinds of sodium carboxymethyl cellulose with different viscosities can be used in a compoundi