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CN-122005916-A - Drug-loaded bone cement and preparation method thereof

CN122005916ACN 122005916 ACN122005916 ACN 122005916ACN-122005916-A

Abstract

The invention relates to the technical field of biomedical materials, in particular to a drug-loaded bone cement and a preparation method thereof, which are used for solving the problems of nonuniform dosage, blockage of a needle head, obvious drug burst and the like caused by separation of drug-loaded particles and matrix particles in the injection process in the prior art. The composite microsphere comprises 100 parts by mass of bone cement powder, 20-30 parts by mass of composite microsphere and 40-60 parts by mass of curing liquid. Effectively avoiding the problems of particle separation, needle blockage, abrupt drug release and the like in the injection process.

Inventors

  • REN ZHISHUAI
  • YANG RUITONG
  • LI GUANG
  • HAO CHUNHUA
  • WANG SHIYUAN
  • YUAN JIANJUN

Assignees

  • 天津市人民医院

Dates

Publication Date
20260512
Application Date
20260326

Claims (10)

  1. 1. The drug loaded bone cement is characterized by comprising bone cement powder, drug loaded composite microspheres and curing liquid, wherein the components are as follows in parts by mass: 100 parts by mass of bone cement powder; 20-30 parts by mass of drug-loaded composite microspheres; 40-60 parts by mass of a curing liquid; wherein, the bone cement powder comprises the following components in parts by mass: 15-25 parts by mass of glass composite particles; 15-25 parts by mass of strontium-doped hydroxyapatite; 40-60 parts by mass of calcium hydrophosphate; 15-25 parts by mass of sodium dihydrogen phosphate; wherein the mass ratio of the magnesium oxide to the mesoporous bioactive glass in the glass composite particles is 7:3-6:4.
  2. 2. The drug-loaded bone cement according to claim 1, wherein the glass composite particles have a particle diameter of 50 to 80 μm and an apparent density of 1.8 to 2.2 g/cm3.
  3. 3. The drug-loaded bone cement of claim 2, wherein the bone cement is selected from the group consisting of, The surface of the glass composite particle is grafted with a zwitterionic polymer, the zwitterionic polymer is polysulphonazine, and the grafting thickness is 10-50nm.
  4. 4. A drug-loaded bone cement according to claim 3, wherein the strontium-doped hydroxyapatite has a molar ratio of Sr/(ca+sr) of 0.05 to 0.1 and a particle size of 1 to 10 μm.
  5. 5. The drug-loaded bone cement according to claim 4, wherein the drug-loaded composite microsphere is composed of a core and a coating layer, the core is a lipoic acid-loaded porous inorganic nanoparticle, and the coating layer is gelatin or chitosan.
  6. 6. The drug-loaded bone cement according to claim 5, wherein the core is mesoporous silica nanoparticles or nano-hydroxyapatite, the particle size is 200-500nm, and the lipoic acid loading amount is 100-200 μmol per gram of porous inorganic nanoparticles.
  7. 7. The drug-loaded bone cement of claim 6, wherein the bone cement is selected from the group consisting of, The overall particle size of the drug-loaded composite microsphere is 50-100 mu m, the apparent density is 1.2-1.5 g/cm < 3 >, and the mass ratio of the core to the coating layer is 100:10-30.
  8. 8. The drug-loaded bone cement according to claim 7, wherein the curing liquid consists of the following components in parts by mass: 5-10 parts by mass of sodium phytate; 0.5 to 1.5 parts by mass of sodium carboxymethylcellulose; 0.2-1.0 parts by mass of magnesium chloride hexahydrate; 90-95 parts of water.
  9. 9. A method of preparing the anti-separation drug-loaded bone repair material of claim 8, comprising the steps of: (1) Dispersing magnesium oxide micropowder in a mesoporous bioactive glass precursor solution, and granulating by spraying to form composite particles, dispersing the prepared composite particles in a silane coupling agent solution, washing and drying, adding a sulfobetaine monomer and an initiator azodiisobutyronitrile, washing and drying to obtain glass composite particles with the surfaces grafted with the polysulfobetaine; (2) Dissolving calcium salt, strontium salt and phosphate in deionized water according to a certain proportion, regulating the pH value to 9-11 by ammonia water, transferring into a hydrothermal reaction kettle for reaction, cooling, centrifuging, washing and drying to obtain strontium-doped hydroxyapatite; (3) Immersing porous inorganic nano particles in lipoic acid solution, stirring, centrifuging, separating and drying to obtain lipoic acid-loaded core particles, dispersing the lipoic acid-loaded core particles in gelatin or chitosan solution, and coating by spray drying to obtain the drug-loaded composite microspheres; (4) Uniformly mixing the glass composite particles, the strontium-doped hydroxyapatite, the calcium hydrophosphate and the sodium dihydrogen phosphate to obtain bone cement powder; (5) Dissolving sodium phytate, sodium carboxymethyl cellulose and magnesium chloride hexahydrate in deionized water, and uniformly stirring to form a curing liquid; (6) Preparing mixed powder, namely uniformly mixing the bone cement powder and the drug-loaded composite microspheres to obtain mixed powder; (7) Slurry blending, namely operating the mixed powder and the curing liquid through a dual-injector system.
  10. 10. The method of claim 9, wherein the composition of the mesoporous bioactive glass precursor solution is ethyl orthosilicate, triethyl phosphate, and calcium nitrate in a molar ratio of SIO 2 :P 2 O 5 :cao = 60:4:36.

Description

Drug-loaded bone cement and preparation method thereof Technical Field The invention relates to the technical field of biomedical materials, in particular to a drug-loaded bone cement and a preparation method thereof. Background The bone repair material is an important biomedical material for treating bone diseases such as osteoporosis fracture, bone defect and the like. The injectable bone cement is one of the orthopedic biomaterials with the largest clinical requirement because of the capability of minimally invasive filling of irregular bone defects, in-situ solidification and mechanical support. Drug-loaded bone cements are a recent research focus, and by loading drugs contributing to bone, anti-osteoporosis, or anti-infective into bone cements, dual functions of topical drug treatment and bone repair can be achieved. Chinese patent CN111870738B discloses a magnesium-based bone repair material composition, which comprises bone cement powder composed of magnesium oxide, calcium hydrogen phosphate, sodium dihydrogen phosphate and hydroxyapatite, and sodium phytate solidifying solution, and realizes anti-osteoporosis and bone effect by loading lipoic acid on the hydroxyapatite. However, the following technical problems still exist in the actual clinical application of the prior art: First, drug-loaded particles separate from matrix particles during injection, resulting in non-uniform doses. Bone cement powder is a multi-component particle system, and the particle sizes and densities of different components are obviously different. During the standing and injection of the slurry, the particles with high density settle rapidly, and the particles with low density suspend in the upper layer, resulting in large difference in drug concentration between the initial stage and the later stage of injection. The physician cannot precisely control the dosage of the drug implanted in the defective area of the bone, and may cause the local drug concentration to be too high or too low. Second, agglomeration of the fine drug-loaded particles results in needle clogging. The drug-loaded hydroxyapatite has small particle size, is easy to agglomerate in the slurry, blocks the small-caliber needle head, and influences the success rate and the safety of the operation. Third, the drug burst phenomenon is remarkable. The drug-loaded hydroxyapatite is directly exposed in a bone cement matrix, the drug release lacks an effective barrier, the initial burst release is serious, the release amount reaches 56% in the previous 5 days in the embodiment of the patent effect, the local tissue irritation can be caused, the later drug concentration is insufficient, and the long-term curative effect is difficult to maintain. Disclosure of Invention The invention provides a drug-loaded bone cement, which is used for solving the problems of nonuniform dosage, blockage of a needle head, remarkable drug burst release phenomenon and the like caused by separation of drug-loaded particles and matrix particles in the injection process in the prior art. The technical scheme provided by the invention is as follows: The drug-loaded bone cement consists of bone cement powder, drug-loaded composite microspheres and curing liquid, wherein the components are as follows in parts by mass: 100 parts by mass of bone cement powder; 20-30 parts by mass of drug-loaded composite microspheres; 40-60 parts of curing liquid. Wherein, the bone cement powder comprises the following components in parts by mass: 15-25 parts by mass of glass composite particles; 15-25 parts by mass of strontium-doped hydroxyapatite; 40-60 parts by mass of calcium hydrophosphate; 15-25 parts by mass of sodium dihydrogen phosphate; wherein the mass ratio of the magnesium oxide to the mesoporous bioactive glass in the glass composite particles is 7:3-6:4. Still further, the method further comprises the steps of, The particle size of the glass composite particles is 50-80 mu m, and the apparent density is 1.8-2.2 g/cm < 3 >. Still further, the method further comprises the steps of, The surface of the glass composite particle is grafted with a zwitterionic polymer, the zwitterionic polymer is polysulphonazine, and the grafting thickness is 10-50nm. Still further, the method further comprises the steps of, The mole ratio of Sr/(Ca+Sr) of the strontium-doped hydroxyapatite is 0.05-0.1, and the grain diameter is 1-10 mu m. Still further, the method further comprises the steps of, The drug-loaded composite microsphere consists of a core and a coating layer, wherein the core is porous inorganic nano particles loaded with lipoic acid, and the coating layer is gelatin or chitosan. Still further, the method further comprises the steps of, The core is mesoporous silica nanoparticle or nano hydroxyapatite, the particle size is 200-500nm, and the load of lipoic acid is 100-200 mu mol loaded per gram of porous inorganic nanoparticle; The overall particle size of the drug-loaded composite microsphere is 50-1