阅读说明：本技术 含聚己内酯/聚维酮碘表层的载碘钛合金医用部件及其制作方法 (Iodine-loaded titanium alloy medical component containing polycaprolactone/povidone iodine surface layer and manufacturing method thereof ) 是由 叶招明 滕王锶源 刘安 王翊凯 方亮 于 2020-06-19 设计创作，主要内容包括：本发明提供了一种抗菌的含聚己内酯/聚维酮碘表层的载碘钛合金医用部件及其制作方法,本发明通过微弧氧化反应及表面碘修饰的方法将含碘涂层固定至钛合金上,并在此结构之上构建一层高聚合物复合结构,从而获得稳定的抗菌性能；通过此工艺制得的材料具有较为明显的广谱抗菌作用,抗菌有效成分为碘；此外,通过构建聚己内酯/聚维酮碘表层结构解决了材料表面碘不稳定、易挥发的缺点,保障了材料抗菌性能的稳定性；并且随着表层结构的逐步降解,其下的碘被逐步释放,这在一定程度上也延长了材料的有效抗菌时长；本发明可有效降低目前在使用钛合金植入物的外科手术后出现的早期感染及其相关并发症。(The invention provides an antibacterial iodine-carrying titanium alloy medical component containing a polycaprolactone/povidone iodine surface layer and a manufacturing method thereof, wherein an iodine-containing coating is fixed on a titanium alloy by a micro-arc oxidation reaction and surface iodine modification method, and a high polymer composite structure is constructed on the structure, so that stable antibacterial performance is obtained; the material prepared by the process has obvious broad-spectrum antibacterial action, and the antibacterial active ingredient is iodine; in addition, the defects that the iodine on the surface of the material is unstable and volatile are overcome by constructing the surface layer structure of polycaprolactone/povidone iodine, and the stability of the antibacterial performance of the material is guaranteed; and along with the gradual degradation of the surface layer structure, the iodine below the surface layer structure is gradually released, so that the effective antibacterial duration of the material is prolonged to a certain extent; the invention can effectively reduce the early infection and the related complications which appear after the surgical operation using the titanium alloy implant.)

1. The iodine-carrying titanium alloy medical component is characterized in that a titanium alloy base material, a porous iodine modification layer and a polycaprolactone/povidone iodine surface layer are sequentially arranged from inside to outside;

the preparation method of the iodine-carrying titanium alloy medical component comprises the following steps:

(1) immersing the titanium alloy base material subjected to surface pretreatment into an electrolytic bath solution for electrochemical treatment to form a surface porous film structure; the electrochemical treatment is anodic oxidation or micro-arc oxidation; the electrolytic cell solution comprises: 1-20g/L of calcium acetate, 1-20g/L of monocalcium phosphate, 10-20g/L of ethylene diamine tetraacetic acid disodium salt, 1-20g/L of calcium glycerophosphate and deionized water as a solvent;

(2) performing surface iodine modification on the titanium alloy material with the porous film structure on the surface obtained in the step (1) by using an electrochemical method;

(3) and (3) immersing the titanium alloy material modified by the iodine in the step (2) into the polycaprolactone/povidone iodine dip-coating solution, reacting for 5-20s, and volatilizing to obtain the iodine-carrying titanium alloy medical component containing the polycaprolactone/povidone iodine surface layer.

2. The iodine-carrying titanium alloy medical component as claimed in claim 1, wherein in the electrochemical reaction process in the step (1), the titanium alloy substrate is placed on a titanium alloy hook or a mesh basket as an anode, a pure titanium plate is used as a cathode, the distance between the anode and the cathode is 10-30cm, the voltage is controlled to be 200-700V, the frequency is controlled to be 100-500HZ, the duty ratio is 10-30%, the temperature is controlled to be 20-40 ℃, and the reaction time is 2-15 min.

3. The iodine-carrying titanium alloy medical member as set forth in claim 1, wherein in the step (2) of the production method, the operating conditions for the surface iodine modification are as follows: taking potassium iodide aqueous solution as electrolyte, placing the material on a titanium alloy hook or a mesh basket as an anode under the conditions of normal temperature and constant pressure of 15-60V in the dark, taking a pure titanium plate as a cathode, and reacting for 10-70min, wherein the distance between the anode and the cathode is 10-20 cm; the concentration of the potassium iodide aqueous solution is 0.01-0.05 mol/L.

4. The iodine-carrying titanium alloy medical member as set forth in claim 1, wherein in said step (3) of the production method, the operation of immersing the material in the dip-coating solution for reaction is repeated 2 to 3 times; in the polycaprolactone/povidone iodine dip-coating liquid, the concentration of polycaprolactone is 0.5-15g/dL, the concentration of povidone iodine is 0.5-2g/dL, and the solvent is dichloromethane.

5. The use of the iodine-bearing titanium alloy medical component of claim 1 as an orthopedic internal-external fixation and implant.

Technical Field

The invention relates to an iodine-carrying titanium alloy medical component containing a polycaprolactone/povidone iodine surface layer and a manufacturing method thereof.

Background

With the development of medical material technology, the application range and the use amount of the medical internal implant are gradually increased year by year in the global range. Therefore, the related infection caused by the internal implant also becomes a problem which is difficult to avoid and troublesome for the present clinician. At this stage, the treatment of such infections is mainly done clinically by systemic application of antibiotics. However, this treatment requires the application of sufficient amounts of antibiotics for a long period of time, which can cause the normal flora of the human body to become dysregulated, presenting a superinfection, and in severe cases being life threatening. In addition, in the case of internal implant-related infection, local blood supply at the infection focus is generally poor and bacteria often form a biofilm inhibiting drug permeation, resulting in low blood concentration at and near the infection focus and difficulty in exerting antibiotic effect. Therefore, the modification treatment of the surface of the internal implant to make the surface have the anti-infection property is an effective method for solving the related infection of the internal implant.

The micro-arc oxidation method is a novel surface modification method. The metal surface coating formed by micro-arc oxidation is an extremely thin oxidation insulation layer immediately generated on the metal surface after electrification. The electrolytic ions of the reaction solution can participate in the physical and chemical reaction of the micro-arc reaction discharge area, break down the oxide film and deposit in the coating. Therefore, researchers have utilized this phenomenon to introduce calcium and phosphorus elements into the coating, and have achieved the goal of improving the bioactivity of the coating. The literature proves that the titanium dioxide coating prepared on the titanium substrate by utilizing the micro-arc oxidation technology not only has the characteristic of inducing the growth of hydroxyapatite on the surface of the material, but also has good cell adhesion characteristic. The invention also applies the solution containing calcium and phosphorus to carry out micro-arc oxidation, and the surface area of the material is increased to increase the iodine adhesion area, and simultaneously the base material has certain biological activity.

Polycaprolactone is a high polymer with good biological safety and biodegradability, and the degradation product is CO₂And H₂And O. The literature reports that after the molecular fragments of polycaprolactone degraded in vivo are phagocytized by phagocytes, the degraded products in cells can be excreted out of the body by random normal metabolism. At present, polycaprolactone is widely applied to the fields of medicine and biology, such as the construction of controllable drug release carriers, cell and tissue culture pedestals, the manufacture of completely degradable plastic surgical sutures, medical modeling materials and the like.

Iodine and iodine compounds have strong antibacterial performance. At present, a plurality of iodine and compounds thereof are used in the medical disinfection field including skin and partial mucosa, and have good biological safety. The method of modifying iodine and its compound on the surface of material can endow the material with reliable bacteriostasis performance.

According to the invention, the copolymer surface layer of Polycaprolactone (PCL)/povidone iodine (PVP-I) is constructed on the iodine-carrying titanium alloy part, so that the original high biological safety of PCL is maintained, the material is endowed with early antibacterial performance, and the problem that iodine generated by simply carrying iodine on the surface of the titanium alloy is difficult to stably and continuously exist is solved. In addition, when the PCL/PVP-I copolymerization layer on the surface layer is continuously degraded, the iodine of the iodine modification layer below the PCL/PVP-I copolymerization layer is slowly released, and the effect of prolonging the bacteriostatic effective time is further achieved. Meanwhile, the material surface can also show certain osteogenic activity along with the gradual increase of the exposure proportion of the micro-arc oxidation layer.

Disclosure of Invention

The invention aims to provide an iodine-carrying titanium alloy medical component with a polycaprolactone/povidone iodine surface layer and antibacterial property and a manufacturing method thereof, aiming at the problem of implant infection caused by the use of a titanium alloy medical material in the field of orthopedic surgery.

The invention uses PCL/PVP-I and potassium iodide solution to carry out modification treatment on the surface of the micro-arc titanium oxide alloy, and mainly comprises three steps of constructing a porous iodine-carrying layer, modifying the iodine surface and constructing a polycaprolactone/povidone iodine surface layer on the surface.

The technical scheme of the invention is as follows:

an iodine-carrying titanium alloy medical component comprises a titanium alloy base material, a porous iodine modification layer and a polycaprolactone/povidone iodine surface layer from inside to outside in sequence;

the preparation method of the iodine-carrying titanium alloy medical component comprises the following steps:

(1) immersing the titanium alloy base material subjected to surface pretreatment into an electrolytic bath solution for electrochemical treatment to form a surface porous film structure;

specifically, the surface pretreatment method comprises the following steps: polishing, sand blasting and impurity removing are carried out on the material, and the impurity removing comprises the following steps: washing with acetone (more than or equal to 99.5%), ethylene glycol (more than or equal to 99.5%) and ultrapure water in sequence, then acid washing, and finally ultrasonic cleaning; the acid cleaning adopts HF and HNO₃、H₃PO₄The acid washing time of the mixed acid solution is 5-25 min; the ultrasonic cleaning comprises the following steps: cleaning the material in ultrapure water for 5 min/time, and circulating for 3 times;

the electrochemical treatment is anodic oxidation or micro-arc oxidation; the electrolytic cell solution comprises: 1-20g/L of calcium acetate, 1-20g/L of monocalcium phosphate, 10-20g/L of ethylene diamine tetraacetic acid disodium salt, 1-20g/L of calcium glycerophosphate and deionized water as a solvent; in the electrochemical reaction process, the titanium alloy base material is placed on a titanium alloy hook or a mesh basket to be used as an anode, a pure titanium plate is used as a cathode, the distance between the anode and the cathode is 10-30cm, the voltage is controlled to be 200-700V in the reaction period, the frequency is controlled to be 100-500HZ, the duty ratio is 10-30%, the temperature is controlled to be 20-40 ℃, and the reaction time is 2-15 min;

the thickness of the obtained porous film is 5-20 μm;

(2) performing surface iodine modification on the titanium alloy material with the porous film structure on the surface obtained in the step (1) by using an electrochemical method, wherein the operation conditions are as follows: taking a potassium iodide aqueous solution as an electrolyte, placing the material on a titanium alloy hook or a mesh basket as an anode under the conditions of normal temperature (20-30 ℃) and constant pressure of 15-60V in a dark place, taking a pure titanium plate as a cathode, wherein the distance between the anode and the cathode is 10-20cm, and the reaction time is 10-70 min;

the concentration of the potassium iodide aqueous solution is 0.01-0.05 mol/L;

(3) immersing the titanium alloy material modified by the iodine in the step (2) into the polycaprolactone/povidone iodine dip coating solution, reacting for 5-20s, and volatilizing to obtain the iodine-carrying titanium alloy medical component containing the polycaprolactone/povidone iodine surface layer;

the operation of immersing the material in the dip-coating solution for reaction can be repeated for 2-3 times;

in the polycaprolactone/povidone iodine dip-coating solution, the concentration of polycaprolactone (with molecular weight of 5-8 ten thousand) is 0.5-15g/dL, the concentration of povidone iodine is 0.5-2g/dL, and the solvent is dichloromethane;

the operation method of the volatilizing comprises the following steps: and placing the material after dip coating in a vacuum exhaust device for 10-18h to exhaust residual dichloromethane.

The iodine content of the surface of the prepared polycaprolactone/povidone iodine-containing surface iodine-loaded titanium alloy medical component containing the surface layer is 0.5-2 wt%, and the application of the product of the invention includes but is not limited to the range of internal and external fixation and implants of orthopedics. The titanium alloy medical component has obvious bacteriostatic action on common infectious strains of surgical operations, such as staphylococcus aureus, escherichia coli and the like, the effective bacteriostatic components of the titanium alloy medical component are iodine and iodine compounds, including iodine simple substance and povidone iodine, and polycaprolactone with good biological safety and biodegradability is introduced to the surface of the titanium alloy to form a copolymer with the povidone iodine.

The invention has the advantages that:

the invention utilizes iodine with good biological safety and iodine compounds with strong antibacterial performance, and constructs the polycaprolactone/povidone iodine copolymer surface layer on the iodine-carrying titanium alloy component, thereby not only retaining the original high biological safety of polycaprolactone, but also endowing the material with early antibacterial performance, and simultaneously solving the problem that iodine which is only carried on the surface of the titanium alloy is difficult to stably and continuously exist.

In addition, when the PCL/PVP-I copolymerization layer on the surface layer is continuously degraded, the iodine of the iodine modification layer below the PCL/PVP-I copolymerization layer is slowly released, and the effect of prolonging the bacteriostatic effective time is further achieved. Meanwhile, the material surface can also present certain osteogenic activity along with the gradual increase of the exposure proportion of the micro-arc oxidation layer.

The preparation method has the advantages of simple preparation process, proper reaction conditions, high efficiency, low cost and good repeatability, and the obtained titanium alloy medical component has a very obvious antibacterial effect.

Drawings

FIG. 1: the material prepared by the invention has a schematic main structure, wherein a is a PCL/PVP-I structure layer, b is an iodine modification area, c is a porous micro-arc oxidation layer, and d is a titanium alloy layer.

FIG. 2: EDS analysis results of the surface of the iodine-carrying titanium alloy material containing the polycaprolactone/povidone iodine surface layer.

FIG. 3: and (3) performing micro-arc oxidation and PCL/PVP-I dip-coating drying on the surface of the material, wherein the magnification is 5000 times, a is an electron microscope observation image of the surface structure of the micro-arc oxidation layer, and b is a PCL/PVP-I copolymerization surface layer electron microscope observation image.

FIG. 4: the detection result of the eluent after the bacteria culture on the surface of the material is as follows: a is a comparison group made of common titanium alloy material; b is an experimental group, namely an iodine-carrying titanium alloy material containing a polycaprolactone/povidone iodine surface layer.

FIG. 5: after the three materials are placed in a light environment for 1 day and 3 days, the surface bacteriostasis effect detection is carried out: the reference group is a common titanium alloy sample sheet; group A is sample wafer for direct anodic oxidation iodine-carrying treatment; group B is the PCL/PVP-I surface layer modified sample prepared according to example 1.

Detailed Description

The present invention is further illustrated by the following specific examples, but the scope of the invention is not limited thereto.