• 专利标题:   Composite protein micro-nanoparticles in preparing postoperative wound sealing and skin repair materials or drugs, comprises e.g. structural proteins and hyaluronic acid; or modified structural protein and hyaluronic acid; or structural protein and modified hyaluronic acid.
  • 专利号:   CN115521627-A
  • 发明人:   CHEN K, WANG L, WANG H
  • 专利权人:   UNIV DALIAN TECHNOLOGY
  • 国际专利分类:   A61L027/20, A61L027/22, A61L027/50, A61L027/58, C08J003/12, C08L005/08, C08L089/00
  • 专利详细信息:   CN115521627-A 27 Dec 2022 C08L-089/00 202318 Chinese
  • 申请详细信息:   CN115521627-A CN11112181 13 Sep 2022
  • 优先权号:   CN11112181

▎ 摘  要

NOVELTY - Composite protein micro-nanoparticles, comprises structural proteins and hyaluronic acid; or modified structural protein and hyaluronic acid; or structural protein and modified hyaluronic acid; or modified structural protein and modified hyaluronic acid. USE - The composite protein micro-nanoparticles or hydrogel material: are useful in carrier or support that contains medicinal ingredients for repairing and filling of wounds or defects in bone tissue, cartilage tissue, muscle, and blood vessels; in preparing superficial skin and subcutaneous fillers, preferably plastic and cosmetic surgery; in bioprinting ink for preparing cell-loaded printing; as scaffold material for bone repair and regeneration; in preparing postoperative wound sealing and skin repair materials and drugs; in preparing postoperative wound sealing, oral ulcer material or drug application; or in preparing interstitial fluid leakage sealing, intestinal leakage sealing material or medicine; in preparing interstitial fluid leakage plugging, surgical suture materials or drugs; in preparing hemostatic materials or medicines, preferably liver hemostatic materials, bone section hemostatic materials, arterial hemostatic materials, heart hemostatic materials and medicines; and in preparing post-operative anti-adhesion gels (claimed). ADVANTAGE - The structural protein/hyaluronic acid composite micro-nano particle has excellent mechanical strength and self-repairing performance. DETAILED DESCRIPTION - Composite protein micro-nanoparticles, comprises structural proteins and hyaluronic acid; or modified structural protein and hyaluronic acid; or structural protein and modified hyaluronic acid; or modified structural protein and modified hyaluronic acid. INDEPENDENT CLAIMS are included for: preparing micro-nanoparticles comprising (1) dissolving structural protein and hyaluronic acid directly in aqueous solution at 20-80 ℃, where the concentration of structural protein is 0.1-20 w/v%, the concentration of hyaluronic acid is 0.1-20 w/v%, the mixing mass ratio between structural protein and hyaluronic acid is 0.1-10, adjusting the pH of the solution to 6-14 with acid or alkali after complete dissolution to obtain mixed aqueous solution of structural protein/hyaluronic acid when the structural protein and hyaluronic acid are not modified, dissolving the covalently cross-linkable modified structural protein and hyaluronic acid, or structural proteins and covalently cross-linkable modified hyaluronic acid, or covalently cross-linkable modified structural protein and covalently cross-linkable modified hyaluronic acid in aqueous solution, (2) maintaining the temperature of the above solution at 20-80 ℃ and a stirring at a speed of 100-1000 revolutions per minute, adding polar organic solvent dropwise into the above-mentioned structural protein/hyaluronic acid aqueous solution to obtain suspension of structural protein/hyaluronic acid composite particles, and then continue stirring for 1-3 hours, and (iii) adding cross-linking agent of structural protein/hyaluronic acid macromolecules into the suspension, and continue reacting for 1-12 hours, centrifuging, and washing to obtain structural protein/hyaluronic acid composite micro-nano particle dispersion, and freeze-drying the composite particle dispersion to obtain composite particle powder; and composite protein hydrogel material, comprising the composite microsphere particle as the basic structural unit, where the reversible self-assembly of composite microsphere particles through electrostatic interaction, hydrogen bond interaction, and hydrophobic interaction forms a continuous, porous particle network to achieve injectable, printable, and self-healing properties; core-shell structure composite protein micro-nano particle, where the nano-particle is used as the core, and the composite protein microsphere particle is used as the shell, the mass ratio between two phases of structural protein and hyaluronic acid in the composite particles is 0.2-4; and use of hydrogel material: in carrier or support that contains medicinal ingredients for repairing and filling of wounds or defects in bone tissue, cartilage tissue, muscle, and blood vessels, where the medicinal ingredients are vitamins, amino acids, mineral elements, microecological regulators, growth factors, small molecule drugs, protein macromolecular drugs, nucleic acid drugs (mRNA), antibiotics, hormones, narcotics, antiviral, antibacterial drugs, anticancer drugs, immunomodulatory drugs and/or live cells; in preparing superficial skin and subcutaneous fillers, preferably in plastic and cosmetic surgery, when applied, the structural protein/hyaluronic acid colloidal particles are blended with an aqueous solution to obtain a colloidal gel, inject the above gel directly into the superficial skin or subcutaneous area , structural protein/hyaluronic acid composite particles reversibly self-assemble under the action of non-covalent bonds to form a continuous porous particle network; in bioprinting ink for preparing cell-loaded printing, preferably the colloidal particles are blended with the aqueous solution to obtain colloidal gel, then mixed with the cell suspension to obtain the cell-loaded colloidal gel, extrude the above ink or inkjet 3D printing to obtain a stent with a 3D structure to obtain cell-loaded printing scaffolds, or in preparing bone/cartilage repair filling materials or drugs, the structural protein/hyaluronic acid colloidal particles are blended with an aqueous solution to obtain a colloidal gel, and the above-mentioned gel is directly injected into the bone/cartilage defect area, structural protein/hyaluronic acid composite particles reversibly self-assemble under the action of non-covalent bonds to form a continuous porous particle network, stably stay in the bone defect site; as scaffold material for bone repair and regeneration; or in preparing postoperative wound sealing and skin repair materials or drug application; in preparing postoperative wound sealing, oral ulcer material or drug application; or in preparing interstitial fluid leakage sealing, intestinal leakage sealing material or application of medicine; in preparing interstitial fluid leakage plugging, surgical suture materials or application of drugs; in preparing hemostatic materials or medicines, preferably the application of liver hemostatic materials, bone section hemostatic materials, arterial hemostatic materials or heart hemostatic materials or medicines; and in preparing post-operative anti-adhesion gels.