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CN-122005934-A - Endophytic material capable of slowly releasing antibiotics and preparation method and application thereof

CN122005934ACN 122005934 ACN122005934 ACN 122005934ACN-122005934-A

Abstract

The invention belongs to the application fields of atomic layer deposition and medical antibacterial, and particularly relates to an endophyte material capable of slowly releasing antibiotics, and a preparation method and application thereof. According to the invention, an atomic layer deposition technology is combined with an antibiotic clinical medicine technology, the surface of the endophyte material is a porous medium layer, the porous medium layer can absorb and/or contain antibiotics, the porous medium layer absorbing and/or containing the antibiotics is covered and/or encapsulated by an alumina film based on atomic layer deposition, the alumina film prepared by ALD is not completely isolated, and is provided with a nano channel, and the nano channel can provide a diffusion path for the antibiotics, so that the antibiotics are released from the porous medium layer through the nano channel, and the effect of slowly releasing the antibiotics is achieved.

Inventors

  • MA CHUNHUI
  • ZHUANG LIWEI
  • CUI YUMENG
  • YAN ZUOQIN
  • ZHANG XIN
  • LV QI
  • MA TIANLE

Assignees

  • 上海市老年医学中心
  • 华东理工大学
  • 上海科技大学
  • 上海市徐汇区中心医院

Dates

Publication Date
20260512
Application Date
20260227

Claims (12)

  1. 1. An endoplant material capable of slowly releasing antibiotics, characterized in that the surface of the endoplant material is a porous medium layer, the porous medium layer can absorb and/or contain antibiotics, the porous medium layer absorbing and/or containing the antibiotics is covered and/or encapsulated by an alumina film based on atomic layer deposition, and the antibiotics are released from the porous medium layer through nano channels of the alumina film.
  2. 2. The endophyte material of claim 1, wherein the endophyte material comprises a medical metal matrix, a polymer or a ceramic biomaterial, further wherein the medical metal matrix comprises titanium or a titanium alloy, 316L stainless steel.
  3. 3. The endophyte material of claim 1, wherein the thickness of the alumina film is 27nm-65nm, and further wherein the number of layers of the alumina film is 200-500.
  4. 4. A process for the preparation of a slow-release antibiotic-containing endophytic material as claimed in any one of claims 1 to 3, characterized by the following specific steps: S10, dissolving antibiotics with deionized water, preparing saturated antibiotic solution, and soaking plant materials in the saturated antibiotic solution for 6-24 hours; S20, placing the soaked and naturally air-dried internal plant material into a reactor for waiting for film coating; s30, introducing a first precursor into the reactor, wherein the first precursor is trimethylaluminum; s40, purging with inert gas; s50, introducing a second precursor into the reactor, wherein the second precursor is water; S60, purging with inert gas; And S70, repeating the steps of S30-S60, and alternately introducing the first precursor and the second precursor for a plurality of times in a circulating way until the surface of the inner plant material absorbing the antibiotics is coated to form the alumina film with a specific thickness.
  5. 5. The method of claim 4, wherein the antibiotic is a water-soluble antibiotic, further wherein the antibiotic is vancomycin.
  6. 6. The method of claim 4, wherein the first precursor and the second precursor are both fed into the reaction chamber of the reactor in a gas pulse, and further wherein the reaction chamber has a temperature of 65-85 ℃.
  7. 7. The method according to claim 4, wherein in step S30, the flow rate of the first precursor introduced into the reactor is 25sccm and the introduction time is 0.5S, and in step S50, the flow rate of the first precursor introduced into the reactor is 25sccm and the introduction time is 0.5S.
  8. 8. The method according to claim 4, wherein the inert gas purge time is 15S in step S40, and the inert gas purge time is 12S in step S60.
  9. 9. The method of claim 4, wherein the inert gas is nitrogen.
  10. 10. The method according to claim 4, wherein the steps S30 to S60 are repeated 200 to 500 times.
  11. 11. A medical material prepared from the endoplant material of any one of claims 1 to 3 or the endoplant material prepared by the method of any one of claims 4 to 10.
  12. 12. Use of the medical material according to claim 11 for the preparation of a product for the prevention and treatment of poor bone healing.

Description

Endophytic material capable of slowly releasing antibiotics and preparation method and application thereof Technical Field The invention belongs to the application fields of atomic layer deposition and medical antibacterial, and particularly relates to an endophyte material capable of slowly releasing antibiotics, and a preparation method and application thereof. Background Orthopedic endophytic infections (e.g., artificial joint infections, fracture endoprosthesis infections, cosmetic endoprosthesis infections) are serious postoperative complications that can cause local tissue destruction, long-term pain, loss of function in patients, amputation in severe cases, and life-threatening systemic infections in more severe cases. Common methods for reducing the related infection of the endophyte include controlling the operation time and bleeding amount, pulse cleaning wound surfaces in the operation, mixed implantation of composite antibacterial drug materials and the like, but the method cannot reduce the probability of forming a biological film on the surface of the endophyte. The treatment of endophytic infection is very challenging, antibiotics play a key role in the endophytic infection, but the endophytic infection has a plurality of problems in practical clinical application, namely (1) the treatment period is long, patient compliance is poor, the endophytic infection generally needs intravenous antibiotic treatment for 4-6 weeks, oral administration is added for 3-6 months, long-term antibacterial treatment is partially needed until healing is achieved, and liver and kidney function damage caused by long-term use of the antibiotics is a non-negligible side effect. (2) The cost is high, and the cost of the multi-time debridement operation and the revision operation is high and is usually 2-3 times of that of the primary operation. (3) The effects are repeated, because the drug permeability is insufficient, a fiber wrapping layer is easy to form around the metal/macromolecule inner plant, the antibiotics are difficult to permeate to an infection focus, the blood supply of the tissue around the inner plant is poor, the drug concentration is possibly lower than the minimum antibacterial concentration, the antibacterial effect is poor, and the disease is repeated. (4) The medication contraindication of special people is that the control of endophyte infection is more difficult for diabetics, the amputation risk is obviously increased, the renal function of the old is reduced, the toxicity risk of vancomycin/aminoglycoside is increased, and the like, thus causing a certain difficulty for clinical treatment of diabetics. The onset of orthopedic endophyte surgical infection depends on the ability of bacteria to adhere to the material surface and form biofilms, and many studies in recent years have been directed to developing novel endophyte surface anti-infective coatings by which the surface properties of the endophyte are altered to reduce or avoid bacterial adhesion or to reduce the risk of infection formation by releasing bactericidal components from the coating. The current method for improving the antibacterial capability of the endophyte is to modify the surface coating, but the combination of the antibacterial coating and the matrix limits the clinical application of the endophyte, and due to the limitation of the thickness of the coating, the antibacterial component of the endophyte often has insufficient content, and the release time is too short, so that the antibacterial effect is influenced. The effect of antibacterial adhesive coatings depends on their firmness and durability on the implant surface, but most of these coatings crosslink antibacterial drugs with very different physicochemical properties to the metal surface, and the stability and slow release effect often do not reach clinical needs and can only stay in experimental stages, just like "hanging rice soup on chopsticks", because of the separation of the coatings caused by the different elastic moduli of the "endophyte-coating and coating-bone interface". Therefore, the treatment of endophytic infection is not only a medical problem, but also a health crisis involving multiple dimensions of physiology, psychology, economy and the like. Comprehensive intervention in combination with surgical debridement, rational antibiotics, plus local antibiotic delivery systems may be a direction of future intra-treatment plant infection. Accurate use and control of the release rate of antibiotics is central to the therapeutic strategy of endophyte infection. Although some materials are now pre-mixed with antibiotics, such as bone cements containing antibiotics, to prevent infection, the effective bacteriostatic concentration of antibiotics is maintained for a short period of time and the materials suitable for this are single. Controlling the release rate in plant material within an antibiotic (e.g., vancomycin) and locally extending the time to mai