CN103286053B - Biomedical material and preparation method thereof - Google Patents

Abstract

The invention discloses a biomedical material and a preparation method thereof. The preparation method of the material of the present invention includes the following main steps: 1) melting and forming, 2) anodic polarization, 3) cathodic deposition, 4) heat treatment, and 5) coating. The material of the present invention includes a pure magnesium or magnesium alloy substrate and a functional film covering the surface of the substrate with both degradation protection and self-degradation properties. The material as a whole has controllable and complete degradation and absorption characteristics, which meets the stringent requirements for the ideal characteristics of degradable biomaterials. The present invention provides an optimal solution for solving the contradiction between the utilization of biodegradation characteristics and degradation rate control of absorbable biomedical materials, especially medical magnesium alloys. The materials and technologies involved are not only applicable to ordinary medical equipment products, but also to high-end medical equipment products such as Implantable devices, especially "secondary surgery-free" implants, have more competitive advantages.

Description

A kind of biomedical material and preparation method thereof

technical field

The invention belongs to the technical field of manufacturing and application of biomedical new materials and medical device products, and in particular relates to a biomedical new material and a preparation method thereof.

Background technique

With the development of social economy and the improvement of living standards, human beings are paying unprecedented attention to their own medical and health undertakings. The increasing pressure of survival, the accelerated pace of life, the intensification of environmental pollution, the frequent occurrence of food, transportation and production safety accidents, local wars, and natural disasters have caused diseases and traumas to become the ever-lingering haze of human beings. As an important means of modern medicine—an important basis and component of medical devices, biomaterials are used for the diagnosis and treatment of diseases, the repair, replacement or function enhancement of tissues and organs, so that a large number of patients who are struggling on the verge of disability and death can be treated. recover. In recent years, the global medical device industry has developed rapidly, with an average annual growth rate more than twice that of the national economy during the same period. Known as a "sunrise industry", it has become a very active new economic growth point in the 21st century. Taking my country as an example, the growth rate of my country's medical device market in 2010 was as high as 23%, and the market scale exceeded 100 billion yuan for the first time, becoming the second largest medical device market in the world after the United States. billion. Because of the huge social and economic value of biological materials, its research and development work has increasingly attracted the attention of governments, industries and science and technology circles all over the world, and has been included in the development of high-tech key new materials by the governments of the United States, Germany, Japan, Australia and my country. plan.

There are many kinds of biological materials. So far, more than a thousand kinds have been studied, and nearly a hundred kinds are widely used in medicine. Among them, metal materials have become the most widely used load-bearing implant materials in medical clinics, especially in orthopedics (such as spinal orthopedics, fractured bone joints, and skull repairs) due to their advantages such as high strength and fracture toughness, and easy processing and forming. However, existing medical metal materials such as stainless steel, cobalt-chromium alloy, nickel alloy, and titanium alloy have common problems: in addition to being expensive, the mechanical compatibility, biocompatibility, and biodegradability are not satisfactory. Taking titanium alloy, which has been widely used in clinical medicine, as an example, its main performance defects include: (1) Due to the mismatch of elastic modulus, the load transfer from the implant to the adjacent bone tissue is hindered, that is, "stress "shielding" effect, making it unavoidable as an implant (such as inhibiting bone healing, leading to osteoporosis, bone resorption or bone atrophy, or even secondary fractures, etc.); (2) The degradation of pure titanium in the body will lead to Allergies and even death, both Al and V in the typical titanium alloy Ti6Al4V are cytotoxic, among which V can cause chronic inflammation, and the combination of Al and inorganic phosphorus can lead to phosphorus deficiency and induce Alzheimer's disease at the same time; (3) due to poor biodegradability , After the functional reconstruction of the damaged tissue/organ is completed, the implant must be taken out by a second operation, thus blocking the patient's recovery process and increasing the patient's physical and mental pain and economic burden. Based on the above reasons, searching for new materials and technologies with better comprehensive performance under the premise of ensuring safety has always been the focus and hotspot of biomaterials research. It is against this background that magnesium alloys have jumped into the field of vision of material scientists, clinical medical experts and high-tech medical equipment companies with their many advantages.

The use of magnesium alloy as a biomedical material has a series of unique inherent advantages: (1) The advantage of biodegradability. Magnesium metal is chemically active. Under the action of aggressive physiological environment (Cl ^- , organic acids, proteins, enzymes and cells, etc.), magnesium implants can be gradually biodegraded to disappear completely during service, overcoming the metal body Complications caused by long-term persistence in the human body make it possible for patients to avoid the suffering of secondary surgery, and at the same time mean that multiple interventions can be performed at the same lesion site. (2) Advantages of biocompatibility. Magnesium is a non-alien component of the human body and one of the constant elements in the human body (Mg ²⁺ is the fourth cation in the human body after Na ⁺ , K ⁺ and Ca ²⁺ , and the second cation in cells after K ⁺ ; the average content of magnesium per unit body weight of the human body is 0.3-0.4g/kg), participates in a series of metabolic processes, and is closely related to the maintenance of life and the health of the body. It plays an important role in healing and the proper functioning of nerves, muscles, heart, etc. Therefore, magnesium metal is essentially non-biologically toxic. When used as a biological material, as long as the release rate of magnesium ions is effectively controlled, its degradation will be beneficial and harmless to the host (the daily demand for magnesium by the human body: 40-70mg/d for infants, children 250mg/d, adult 300-700mg/d). (3) Advantages of mechanical compatibility. The Young's elastic modulus of magnesium is the closest to the corresponding parameters of human bones (10-40GPa), which is beneficial to reduce or even eliminate the potential "stress shielding" effect of implants on human bone tissue, and promote bone growth and healing. (4) Advantages of biological activity. Publicly reported results of animal experiments and clinical trials show that magnesium has excellent osteoinductivity. (5) Conventional performance advantages. Magnesium has "one low" (low density), "two highs" (high specific strength and specific stiffness), "three good" (good casting and machinability, dimensional stability and recyclability) and "four strong" (Electromagnetic shielding ability, shock absorption and noise reduction ability, and strong thermal and electrical conductivity), so it enjoys the reputation of "green engineering materials in the 21st century" and has great significance in many fields, especially in "lightweight" and "environmental protection". Significance or fields with special technical requirements, such as aerospace, automotive, IT electronics, communications, national defense and military industries, the development and application of magnesium alloys as structural materials has attracted great attention internationally. (6) Resource and price advantages. Magnesium resources are very rich on the earth. The relative content of magnesium in the crustal metal elements is 10.63%, second only to aluminum (31.51%) and iron (22.02%), ranking third, which is 4.37 times that of titanium (2.43%). Among them, there is "inexhaustible and inexhaustible" magnesium in seawater alone - the concentration of magnesium is 1.1kg/m ³ , and the total content is as high as 2.1×10 ¹⁵ tons. Abundant resources and the rapid development of smelting, forming and other technologies have resulted in the price of magnesium metal and its products being very low compared to titanium. Taking raw materials as an example, the latest domestic market quotation statistics show that at present, the average price of 99.95% primary magnesium ingots (about 17.0 yuan/kg) is only about 10% of that of TA0 titanium ingots (about 160.0 yuan/kg). Based on the above advantages, magnesium alloy is expected to become an ideal biomedical new metal material for orthopedic internal fixation devices including (1) bone plate, bone nail and bone mesh, (2) artificial bone, (3) vascular stent and ( 4) Manufacture of many high value-added medical device products including tissue engineering stents.

Unfortunately, the thermodynamic stability of magnesium itself is poor (E ⁰ =-2.37V NHE), the self-oxidized film on the surface is thin (~10nm) and loose (because of PBR=0.80) and has no "self-healing" ability, so it cannot repair the substrate. Provide effective protection. It is reported that the mass loss of pure magnesium is as high as 99% after being eroded by HBSS (Hank's balanced salt solution) for 225 hours. Therefore, the biomedical application of magnesium alloys not only does not benefit from its unique biodegradation characteristics, but has been suffering from a series of problems caused by too fast degradation, such as: a) The service performance of the material product, especially the premature mechanical integrity Attenuation or even failure, b) endangering biocompatibility, c) rapid release of large doses of potentially biotoxic alloying elements, d) increasing the stress on host magnesium metabolism, and even triggering hypermagnesemia, e) causing a sharp rise in local pH , and f) local tissue gas accumulation, etc. Based on the above reasons, the development of new materials, especially new composite materials based on magnesium or magnesium alloys, can enhance the controllability of biodegradation of materials (not only biodegradable, but also the degradation rate can be adjusted according to needs), while improving the biocompatibility of materials It is of great significance to meet the stringent requirements of clinical medicine for the comprehensive performance of materials, and it has become an important topic in the field of biomedical new materials and medical devices.

So far, with biomedicine as the application background, the development of surface-modified magnesium and magnesium alloy matrix composite materials has achieved fruitful results. The main surface modification technologies involved include: (1) Conventional Micro-arc Oxidation (MAO) technology (referring to the MAO technology that uses non-degradable or almost non-degradable MAO ceramic membranes as the preparation object, the same below), (2) based on conventional MAO composite technology, such as MAO/organic coating, MAO/chemical deposition, etc., (3) organic coating, (4) chemical conversion, (5) biomimetic passivation, (6) cathode deposition, (7) anode deposition, (8) IBAD (Ion Beam Assisted Deposition), (9) Sol-Gel Method, (10) Silane Modification, (11) Ion Implantation, (12) Ion Plating, (13) Electrochemical Polymerization, and (14) Hydrothermal method, etc. Although the above-mentioned technologies and the composite materials produced have their own advantages, they also have serious defects: or focus on the inhibition of matrix biodegradability and the improvement of biocompatibility, not only do not consider the surface modification layer in damaged tissue/ After the completion of the functional reconstruction of the organ, the issue of biodegradation is "retire after success". On the contrary, in order to improve the modification effect, efforts have been made to synthesize/apply a dense and non-degradable modification layer according to the conventional thinking; or although taking into account the The biodegradability of the modified layer, but the comprehensive service performance is not ideal. As far as the former is concerned, taking the use of MAO treatment on the substrate to realize the preparation of composite materials as an example, since conventional electrolytes (such as silicate, phosphate, and fluoride-based electrolytes) are used, the main components of the obtained MAO film are almost impossible. Silicates, phosphates or fluorides that degrade or are poorly degradable. This is undoubtedly impeccable for non-medical magnesium alloys, but it constitutes a serious contradiction with the biggest bright spot of magnesium alloys in biomedicine—the utilization of biodegradability. In other words, when it is used as a "secondary operation-free" implant device or tubular/luminal tissue/organ scaffold material such as vascular stent, even in the service environment, the matrix can be gradually degraded and absorbed as expected, and the non-degradable shell ( The long-term existence of surface modified film layers such as MAO film) or its peeled off fragments will also make all efforts to avoid permanent foreign body reactions in the body useless, and even bring catastrophic consequences (such as blockage of blood vessels). As far as the latter is concerned, taking the preparation of composite materials by coating degradable polymer materials on the surface of the substrate as an example, there are the following main problems: (1) The potential hazards of acidic degradation products of polymer materials are not considered, such as a. The acidification of the local physiological environment then triggers aseptic inflammation, b. Accelerates the degradation of the magnesium alloy matrix, so no specific countermeasures/prevention measures have been proposed; (2) Polymer materials are used in isolation or only in combination with non-degradable HA ( Hydroxyapatite) used in combination, which limits its modification effect and application scope; (3) Coating/substrate bonding force is not ideal, etc.

Contents of the invention

The purpose of the present invention is to provide a new biomedical material and a preparation method thereof for the outstanding problems existing in the existing biomedical materials and their application technologies.

The present invention is achieved through the following technical solutions:

A preparation method of a biomedical material, comprising the following main steps:

a) Smelting and forming: smelting pure magnesium or magnesium alloy, and performing forming to obtain the product matrix;

b) Anodic polarization: immerse the product matrix obtained in step a) into a water-based solution of sodium chloride with a concentration of 20.0mg/L-100.0g/L after surface treatment, and use an equal-area product of the same material as the counter electrode , power on for processing;

c) Cathodic deposition: immerse the substrate of the product treated in step b) in a water-based solution of magnesium chloride with a concentration of 0.5-150.0g/L, and conduct treatment with electricity to obtain a functional film bottom layer with both degradation protection and self-degradation characteristics Front layer;

d) Heat treatment: perform heat treatment on the product substrate treated in step c) to obtain a functional film bottom layer with both degradation protection and self-degradation properties, wherein the heat treatment temperature is 350-550°C, and the holding time is 1-24h;

e) Coating: including the following main steps:

e-1) Preparation of solution:

1# solution: an organic solvent-based solution of PLLA, PLGA or their mixture, with a concentration of 0.2-75.0g/L;

2# solution: use magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or two or more of them as the solid dispersed phase, and use water, acetone, ethanol, n-butanol or two or more of them The mixture is a liquid suspension, wherein the concentration of the solid dispersed phase is 0.5-45.0 g/L;

3# solution: it uses magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or two or more of them as the solid dispersed phase, and PLLA, PLGA or the organic solvent-based solution of their mixture as the liquid Suspension, wherein the concentration of the PLLA, PLGA or mixture thereof is 0.2-75.0g/L, and the mass of the solid dispersed phase accounts for 0.5%-40% of the total mass of the solid dispersed phase and PLLA, PLGA or the mixture of PLLA and PLGA ;

e-2) Coating of coating: Coating the product substrate treated in step d) to obtain a functional film surface layer with both degradation protection and self-degradation properties. The coating treatment adopts the following three schemes Do more than one of:

Option 1: Use the 1# solution and 2# solution prepared in step e-1) in combination, follow the order of using 1# solution first, then 2# solution, and then 1# solution, and carry out more than one round of coating;

Scheme 2: Independently use the 3# solution prepared in step e-1) for more than one round of coating;

Scheme 3: Combined use of 1# solution, 2# solution and 3# solution prepared in step e-1), follow the order of using 1# solution first, then 2# solution, and then 3# solution, and carry out more than one round of coating.

The sodium chloride described in step b) uses sodium nitrate, sodium sulfate, lithium chloride, lithium nitrate, lithium sulfate, potassium chloride, potassium nitrate, potassium sulfate, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate , magnesium sulfate or a mixture of two or more of them is partially or completely replaced; the magnesium chloride in step c) is partially or completely replaced by magnesium nitrate, magnesium sulfate or a mixture thereof.

The organic solvent of 1# solution and 3# solution described in step e-1) is one of A solvent and B solvent, wherein A solvent is more than one of epichlorohydrin, dichloromethane or chloroform, B The solvent is a mixture obtained by uniformly mixing A solvent with more than one of acetone, ethanol or n-butanol; the pure magnesium and magnesium alloy in the 2# solution and 3# solution described in step e-1) are powdery, granular shape, flake, filament, ribbon, tube or whisker, and its open circuit potential in any same environmental medium is not higher than that of pure magnesium or magnesium alloy in the product matrix.

The 1# solution described in the step e-1) is replaced with molten PLLA, molten PLGA or a mixture of molten PLLA and molten PLGA; the 3# solution described in the step e-1) is used for magnesium oxide, magnesium hydroxide , pure magnesium, magnesium alloy, β-TCP, CPP or a mixture of two or more of them is a solid dispersed phase, replaced by a liquid suspension of molten PLLA, molten PLGA, or a mixture of molten PLLA and molten PLGA, wherein The mass of the solid dispersed phase accounts for 0.5%-40% of the total mass of the solid dispersed phase and PLLA, PLGA or the mixture of PLLA and PLGA.

One of the 1# solution and 2# solution described in Scheme 1 in step e-2) is replaced by 3# solution; the coating method described in step e-2) includes dip coating, brush coating, spin coating or spray coating.

After coating the coating containing PLLA or PLGA, carry out natural curing or artificial curing treatment, and after the coating is partially or completely cured, the subsequent coating is carried out; when coating magnesium oxide, magnesium hydroxide, pure After magnesium, magnesium alloy, β-TCP, CPP or a mixture of two or more thereof, drying treatment is carried out.

A biomedical material prepared by the above preparation method, which includes a pure magnesium or magnesium alloy substrate and a functional film covering the surface of the substrate with both degradation protection and self-degradation properties, wherein the functional film includes a bottom layer and a surface layer; the bottom layer It is mainly composed of magnesium oxide or a mixture of magnesium oxide and magnesium hydroxide; the surface layer includes at least one of No.1 coating and No.2 coating; the No.1 coating is made of magnesium oxide, hydroxide Magnesium, pure magnesium, magnesium alloy, β-TCP, CPP or a mixture of two or more of them is a degradable polymer material layer in the sandwich layer; the No.2 coating is made of magnesium oxide, magnesium hydroxide, pure magnesium, magnesium Alloy, β-TCP, CPP or a mixture of two or more of them is a degradable polymer material-based composite material layer as a reinforcing phase, wherein the mass of the reinforcing phase accounts for 0.5%-40% of the mass of the composite material; the No.1 The degradable polymer material in coating and No.2 coating is PLLA, PLGA or their mixture.

The No.1 coating and the No.2 coating have more than one layer respectively, and the composition, structure and thickness of different layers are the same or different; the degradable polymer materials on both sides of the sandwich layer in the No.1 coating The composition, structure and thickness of the layers are the same or different; the sandwich layer in the No.1 coating is replaced by the No.2 coating; the degradable polymer material layer on both sides of the sandwich layer in the No.1 coating At least one layer shall be replaced with No.2 coating.

The pure magnesium and magnesium alloys in the No.1 coating and No.2 coating are in the form of powder, granule, flake, wire, ribbon, tube or whisker, and they are in any same environmental medium The open circuit potential is not higher than the open circuit potential of the base pure magnesium or magnesium alloy.

The smelting and forming of step a) of the material preparation method of the present invention can be carried out by any known or commercially available techniques, such as melting under protective atmosphere, casting, forging, extrusion or cutting, etc. The role of smelting is to obtain a high-quality melt (metal or alloy liquid) with chemical composition, inclusions (such as oxide inclusions), gas content (such as hydrogen) and other control levels that meet the requirements; forming includes direct forming using the above melt ( Such as casting) or indirect forming (that is, the billet is first obtained from the above melt, such as ingot, and then the billet is processed, such as forging, extrusion and cutting, etc.).

The purpose of surface finishing in step b) of the material preparation method of the present invention is to remove burrs, dirt, scale, etc. remaining or generated on the surface of the product during processing, storage and transportation, so as to obtain a surface quality that meets the requirements of subsequent treatment. Surface finishing can be carried out by any known or commercially available physical and/or chemical techniques, such as: sandpaper/grinding wheel grinding, polishing cloth polishing, organic solvents including absolute ethanol, acetone, etc., directly or under the action of external fields such as ultrasonic waves, degreasing, Alkaline washing, pickling, water washing, etc.

The main purpose of anodic polarization in step b) of the material preparation method of the present invention is to realize the dual treatment of "deactivation" and surface roughening of the substrate material, while improving the corrosion resistance of the material, it is the coating/substrate. Tight integration lays a solid structural foundation. The so-called "deactivation" refers to the use of the selective dissolution of anodic polarization to dissolve and "dig out" the micro-anode with higher electrochemical activity on the surface of the substrate, leaving a micro-cathode with stronger electrochemical inertness. When anodizing, the power supply can be selected from DC, AC or pulse power supply. Although it is also possible to use inert materials such as stainless steel, graphite or platinum sheets as counter electrodes according to conventional practices, the strategy of "using products of the same material of equal area as counter electrodes", that is, "peer bipolar", can avoid The potential pollution hazard of the heterogeneous counter electrode to the electrolyte, and under the action of a symmetrical AC or pulse power supply, can ensure that the workpieces of the two poles can be synchronously obtained almost the same treatment effect, and the efficiency of anodic polarization treatment can be doubled, so as to realize the maximum The purpose of saving energy and increasing efficiency. The article used as the counter electrode may have the same or different geometry as the workpiece. Of course, when the same material as that of the workpiece is used as the counter electrode material, the area of the counter electrode may be different from the area of the workpiece. Specific process parameters such as voltage/current amplitude, frequency and its duty cycle, and processing time during anodic polarization can be flexibly controlled according to different requirements for processing effects. The concentration of sodium chloride in the anodic polarization electrolyte is too low, even if high current density/high voltage is used for a long time, satisfactory treatment effect cannot be obtained; if the concentration is too high, the cost of raw materials will increase and the treatment effect will be improved at the same time There is no obvious benefit, therefore, it is advisable to control the concentration of sodium chloride in the range of 20.0mg/L-100.0g/L. During anodic polarization, the temperature of the solution can be controlled at 1-85°C; the processing time can be flexibly controlled according to the magnitude of the applied electric parameters, the concentration of the electrolyte, and the specific requirements of the degree of surface roughness.

The purpose of cathodic deposition in step c) of the material preparation method of the present invention is to prepare the pre-layer of the bottom layer of the functional film on the surface of the substrate after anodic polarization. For cathode deposition, the counter electrode can be made of inert materials such as platinum, stainless steel and graphite, or the same material as the cathode (ie, pure magnesium or magnesium alloy). When the concentration of cathodic deposition electrolyte is too low or too high, the deposition rate and deposition effect will be adversely affected. The cathodic deposition electrolyte can also be replaced by an ethanol-based solution of magnesium chloride, magnesium nitrate, magnesium sulfate or a mixture thereof. The electrical parameter control mode of cathodic deposition includes constant current, constant voltage (constant electrode potential), or dynamic potential linear scanning or circular scanning within a certain electrode potential interval at a certain scanning rate. During cathodic deposition, the temperature of the electrolyte should be controlled at 2-60°C. The selection of other specific process parameters such as current density, electrode potential, scanning rate and action time should be determined according to the requirements of performance indicators such as deposition layer thickness and density.

The main purpose of the heat treatment in step d) of the material preparation method of the present invention is to realize the conversion of magnesium hydroxide, the main product of cathode deposition, into magnesium oxide, and at the same time play a certain sintering effect on the existing film layer, thereby obtaining a more compact structure. bottom layer of the membrane. The conversion of magnesium hydroxide to magnesium oxide (or decomposition to produce magnesium oxide) starts at 340°C and ends at 490°C. Therefore, by adjusting the heat treatment temperature level within the range of 350-550°C, the degree of conversion of magnesium hydroxide to magnesium oxide can be controlled. If the heat treatment temperature is controlled between 350-489°C, part of the magnesium hydroxide will be converted to magnesium oxide, and the bottom layer of the functional film is composed of a mixture of magnesium oxide and magnesium hydroxide; when the heat treatment temperature is between 490-550°C, the magnesium hydroxide will be completely transformed For magnesium oxide, the bottom layer of the functional film is only composed of magnesium oxide. Heat treatment can be carried out in atmospheric environment or vacuum environment by any known or commercially available techniques and equipment. When carried out in an aerobic environment, heat treatment can also promote the thermal oxidation of the surface metal of the product to a certain extent, thereby further increasing the thickness of the bottom layer of the functional film.

After anodic polarization, cathodic deposition and heat treatment, it is best to clean and dry the materials respectively, including rinsing with tap water and/or distilled water, deionized water, drying with hot air or compressed air or drying in a heating furnace, or volatile Rinse with organic solvents such as ethanol, acetone, etc. and then dry. The purpose of cleaning and drying is to remove non-target products adsorbed on the surface of the workpiece, including anodic polarization by-products, anodic polarization and cathodic deposition electrolytes, etc., to avoid cross-contamination of solutions and affect subsequent treatment effects.

The main purpose of liquefying (preparing into solution or melting for use) various coating materials in step e) of the material preparation method of the present invention is to facilitate coating and ensure uniform coating effect. The organic solvents of the PLLA and PLGA can be preferably selected from A solvent, B solvent and any other known or commercially available solvents according to specific requirements such as dissolution rate, curing mode and rate, and coating porosity. When used as an organic solvent-based solution, if the concentration of the degradable polymer material is too low, the thickness of the coating obtained in a single coating is too thin, and the coating efficiency is too low; Conducive to coating and poor coating uniformity. The specific concentration of degradable polymer materials can be controlled according to the requirements of coating rate and coating quality (such as uniformity, porosity, etc.). When magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or their mixtures are used as the reinforcing phase of the degradable polymer matrix composite material, the modification effect will not be obvious if the dosage is too low; If the coating is high, the overall performance of the composite coating, including cohesion, bonding with the matrix, and degradation protection performance, will be significantly deteriorated. When magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloys, β-TCP, CPP, or mixtures thereof are used as 1) a suspension in an organic solvent-based solution of PLLA, PLGA, or a mixture thereof, or 2) PLLA in a molten state , When the solid dispersed phase of molten PLGA or the mixture of molten PLLA and molten PLGA is a liquid suspension, its quality is controlled at 0.5% of the total mass of the solid dispersed phase and PLLA, PLGA or PLLA and PLGA mixture- 40%, it is to ensure that the required composite coating is obtained. When preparing the 2# solution, control the concentration of the solid dispersed phase to 0.5-45.0g/L, for two reasons: first, if the concentration is too low, the thickness of the film layer obtained by a single coating is too thin, and the coating efficiency is too low ; Second, if the concentration is too high, the difficulty of uniform dispersion of the solid dispersed phase increases and the stability of the solution becomes poor, which is not conducive to coating and poor film quality. In order to obtain a high-quality suspension, the dispersion of the magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP can be carried out under stirring conditions such as mechanical, ultrasonic or compressed air. During the coating operation, the specific coating times of each coating material are controlled according to the needs of the coating structure and thickness. When using the same coating material for multiple coats, the solution used for each coat can be the same or different. For the same coating solution, the obtained coating thickness is positively correlated with the number of coatings.

The coating method of magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or their mixtures described in the present invention can be replaced by techniques such as electrophoretic deposition, magnetron sputtering or ion beam assisted deposition.

It is worth noting that there may be an autoxidation film between the cathode deposition layer and the substrate in the material of the present invention, that is, the substrate and the surrounding environment (including the atmosphere, cleaning solutions such as water, absolute ethanol, alkali washing solution or pickling solution, etc., and the anode electrode The surface layer is naturally oxidized when it is in contact with the chemical solution, cathodic deposition solution, etc.), and the film layer is mainly composed of the oxide, hydroxide (such as magnesium oxide, magnesium hydroxide) or a mixture of the substrate. This "self-oxidation film" is the inevitable product of most metals and their alloys in conventional manufacturing environments (corresponding to special manufacturing environments such as vacuum). The impact on general service performance is basically negligible.

The magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP used in the material of the present invention and its preparation method can be commercially available or self-made products of any shape, size and crystallinity. Among them, pure magnesium and magnesium alloys are preferably powdery, granular, flake, filamentary, ribbon, tubular or whisker-like. In order to enhance the stability of pure magnesium and magnesium alloy in the coating, it can be surface modified according to known or commercially available techniques before use. Control the preparation method and the open circuit potential of pure magnesium or magnesium alloy in the prepared coating is not higher than the open circuit potential of pure magnesium or magnesium alloy in the matrix, the purpose is to obtain the required coating and ensure that the coating components in service state are not As a cathodic component accelerates the degradation of the matrix, it is better to degrade preferentially over the matrix (eg as a sacrificial anode).

No.1 coating and No.2 coating are designed to be more than one layer in the material of the present invention, and different layers (here " different layers " refer to No.1 coating or No.2 coating as structural unit composition (such as: magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP or CPP dosage; type of polymer material and its molecular weight, etc.), structure (such as density, porosity, surface roughness Degree, etc.) and thickness are the same or different. In addition, the composition (type and molecular weight, etc.), structure and thickness of the polymer material layers on both sides of the sandwich layer in the No.1 coating are the same or different. The purpose is to make full use of the different The characteristics of the material constituent units are used to achieve the successful control of the overall comprehensive performance of the material, especially the biodegradability, biocompatibility, coating/matrix binding force, coating cohesion, etc. The specific thickness of the No.2 coating and the sandwich layer in the No.1 coating and the polymer material layers on both sides can be flexibly controlled according to actual use needs. In the preparation of No.1 coating, in order to enhance the bonding force between the sandwich layer and the polymer material layers on both sides, the coating of the sandwich layer should be carried out before the first layer of polymer material layer is completely cured, or the sandwich layer should be properly controlled. The porosity of the polymer material layer on both sides of the layer, or heat treatment with appropriate specifications after the coating application process.

In the material of the present invention and its preparation method, PLLA and PLGA can be partially or completely replaced by any other known or commercially available polymer materials with biodegradable properties, such as natural degradable polymers such as collagen, gelatin and chitosan materials, and other synthetic degradable polymer materials. β-TCP and CPP can also be partially or completely replaced by any other known or commercially available degradable inorganic biomaterials.

It should be pointed out that the pure magnesium referred to in the present invention includes: 1) magnesium metal with different purity levels, 2) pure magnesium products, and 3) products containing pure magnesium parts (components). The magnesium alloy referred to in the present invention includes: 1) magnesium-based alloys with different alloy components and alloying levels, 2) magnesium-based composite materials, and 3) magnesium alloy products, and 4) magnesium-containing alloy parts (components) products.

Compared with prior art, advantage of the present invention is many-sided, and outstanding performance is in following two aspects:

(1) The material integrates ideal characteristics. As far as the bottom part of the functional film of the material of the present invention is concerned, since the thermodynamic stability of magnesium oxide and magnesium hydroxide is higher than that of atomic magnesium, the bottom layer of the functional film is relatively stable to pure magnesium or magnesium alloy substrates. It must have degradation protection ability, which can be used as a physical shielding layer to protect the matrix from excessive degradation to a certain extent; on the other hand, according to the Pourbaix theory, even magnesium hydroxide with higher thermodynamic stability among magnesium oxide and magnesium hydroxide, The pH range in which it can stably exist in water-based solutions is also above 11.475, while the pH value of normal body fluids is 7.40 or even lower. Therefore, the bottom layer of the functional film can be gradually degraded under the erosion of body fluids, that is, it has self-degradation characteristics. And its degradation rate can be adjusted by crystallinity, density and so on. As far as the surface layer of the functional film of the material of the present invention is concerned, the degradable polymer material is not only magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, It is an ideal "binder" for non-bulk materials such as β-TCP and CPP, and has the characteristics of good cold/hot formability, flexible and controllable thickness, density and degradation; among them, magnesium oxide, magnesium hydroxide, Pure magnesium, magnesium alloys, β-TCP and CPP not only have biodegradability, but also the degradation products are nutrients needed by the human body. On the other hand, magnesium oxide, magnesium hydroxide, pure magnesium and magnesium alloys also have the ability to neutralize the acidic degradation products of degradable polymer materials (such as the intermediate product of PLLA degradation, lactic acid, and the final products of carbon dioxide and water). / Eliminate its prominent role in potential hazards (such as sterile inflammation, etc.). In addition, as the reinforcing phase of polymer matrix composites, magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloys, β-TCP and CPP can not only improve the mechanical properties of the matrix to a certain extent, but also can Improve the coating/substrate bonding force and the degradation protection performance of the coating and adjust the degradation rate of the coating. Based on the above analysis, the functional film in the material of the present invention not only has excellent biocompatibility and degradation resistance (to the matrix), but also has controllable biodegradability—it can effectively prevent Break the action channel of the erosive medium in the environment, form a tight protection for the matrix (degradation protection), and gradually degrade itself (self-degradation) with the functional reconstruction of the damaged tissue/organ, and finally expose the matrix to facilitate its natural degradation. Absorption, and its degradation protection ability and self-degradation rate can be regulated by the composition, structure and thickness of the film layer. For example, under the same premise of other parameters, the thicker the functional film is, the stronger its degradation protection ability is; the looser the functional film structure is, the weaker its degradation protection ability is; The slower the rate. And the matrix part of the material of the present invention—pure magnesium or magnesium alloy has biocompatibility, mechanical compatibility, biodegradability and bioactivity, and its degradation rate can be optimized through composition, microstructure such as alloying, crystal grain fine-tuning and other techniques. Therefore, the material of the present invention has obvious advantages as a whole - it is expected to completely eliminate the common existing materials or damage biocompatibility or mechanical integrity due to one-sided emphasis on biodegradability, or damage biodegradation due to one-sided emphasis on degradation protection. Therefore, it provides an ideal solution for the contradiction between the utilization of biodegradable properties of degradable biomaterials and the control of degradation rate.

(2) Technology synergy realizes the optimized preparation of materials , cathodic deposition, heat treatment and organic/inorganic coating technology, the coating/matrix, coating/coating are closely combined on the surface of the substrate, and the composition, structure and thickness can be adjusted, so the degradation protection and self-degradation characteristics are controllable, and at the same time The multiple defense system with excellent biocompatibility and bioactivity provides a new idea for the preparation of biomedical controllable fully degradable materials. Specifically, anodic polarization treatment is performed in an electrolyte solution containing corrosive ions such as chloride ions, nitrate ions or sulfate ions, and the surface metal atoms of pure magnesium or magnesium alloys will be ionized, that is, anodic dissolution will occur. Due to the inhomogeneity of composition, microstructure, etc., the dissolution process of the matrix micro-area is not uniform, and the anodic dissolution shows selectivity, that is, the micro-anode area is preferentially dissolved. Therefore, objectively, anodic polarization has not only "deactivation" effect on the matrix "Effect, and has a significant roughening effect, which can form a large number of microscopic "anchor points", thereby creating conditions for the tight combination between the bottom layer of the functional film/substrate. As an integrated technology of coating synthesis and coating preparation, electrochemical cathodic deposition has the advantages of nonlinearity, low temperature operability, good controllability, and low cost, and is one of the ideal technologies for surface modification of materials. The cathodic deposition process can realize the in-situ synthesis of magnesium hydroxide on the surface of the substrate, and the heat treatment process can realize the conversion of magnesium hydroxide to magnesium oxide and the sintering of the existing film layer. The formation of the bottom layer of the functional film is to cover the substrate with a protective film with self-degradation characteristics internally, and to become an ideal substrate for the subsequent coating (functional film surface layer) externally with its rough and porous microstructure. When magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP and CPP are used independently as coating materials, there are outstanding problems such as difficult coating and poor bonding force, and they are used as a sandwich layer of an organic coating or When the dispersed phase (reinforcing phase) of the polymer-based composite material is used, the above problems can be easily solved. Therefore, using the technology provided by the invention, the optimal preparation of controllable and fully degradable biomaterials can be realized.

Description of drawings

Fig. 1 is a process flow chart of the material preparation method in the embodiment;

Fig. 2 is a schematic diagram of a cross-sectional structure of a material in an embodiment;

Fig. 3 is a schematic diagram of the cross-sectional structure of the material functional film surface layer in the embodiment;

In the figure: 1-substrate, 2-bottom layer of functional film, 3-surface layer of functional film, a-degradable polymer material layer, b-magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or Among them, two or more mixture layers, c-degradable polymer material layer, d-degradable polymer material with magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or two or more of them as the reinforcing phase Molecular material based composite layer.

Detailed ways

The specific implementation of the present invention will be further described below in conjunction with the accompanying drawings and examples, but the implementation and protection scope of the present invention are not limited thereto.

As shown in Figure 1, it is a process flow chart of the material preparation method of the present invention. The preparation method of the biomedical material of the present invention consists of five main steps of smelting, forming→anodic polarization→cathode deposition→heat treatment→coating. Among them, the purpose of smelting and forming is to obtain the product matrix that meets the requirements of material (chemical and phase composition, microstructure, grain size, etc.), shape and size; the main function of anodic polarization is to realize the "deactivation" of the surface of the product matrix " and "roughening" double treatment; the function of cathodic deposition is to obtain the product layer of magnesium hydroxide, that is, the front layer of the bottom layer of the functional film; the main function of heat treatment is to realize the transformation of the cathodic deposition product into magnesium oxide and the transformation of the existing film layer. Sintering to obtain the bottom layer of the functional film; the function of coating is to "reinforce" the bottom layer of the self-degradable functional film on the one hand, and to construct the surface layer of the functional film on the other hand.

As shown in Fig. 2, it is a schematic diagram of the cross-sectional structure of the material of the present invention. The controllable fully degradable biological material of the present invention is integrally constructed by a pure magnesium or magnesium alloy substrate 1, a functional film bottom layer 2 covering the surface of the substrate 1 and adjacent to the substrate 1, and a functional film surface layer 3 adjacent to the functional film bottom layer 2.

As shown in Figure 3, it is a schematic diagram of the cross-sectional structure of the functional film surface layer of the material of the present invention. Wherein a coating, b coating and c coating are superimposed together and belong to No.1 coating in the present invention, and b coating belongs to the sandwich layer of No.1 coating. Wherein the d coating belongs to the No.2 coating of the present invention.

The above-mentioned features of the present invention will be further described in detail below in conjunction with preferred embodiments of the present invention.

Materials used in the examples include high-purity magnesium (purity 99.9%), magnesium alloys AZ31, AZ91, WE43 and ZK60. Smelting and shaping are carried out according to the material composition to obtain test pieces. Among them, melting conditions: temperature 750-760 ℃, 0.3vol%SF ₆ +50vol%CO ₂ mixed gas protection with air, melt holding time 30min. Forming techniques include metal mold casting (high purity magnesium and all the above magnesium alloys), die casting (magnesium alloys AZ31 and AZ91), forging (magnesium alloy WE43) and hot extrusion (magnesium alloy AZ31), in which metal mold casting conditions: 710-720°C ;Die-casting conditions: pouring temperature 660°C, mold temperature 220°C, injection specific pressure 50MPa, injection speed 40m/s; forging conditions: cylindrical ingot as blank, free forging, initial forging temperature 400°C, final forging temperature 320°C, forging ratio 1.87, heat preservation at 420°C for 2 hours before each forging; hot extrusion conditions: cylindrical ingot as billet, extrusion temperature 350°C, extrusion ratio 20, extrusion speed 1.5m/min. The above test piece was cut by wire to obtain a test sample with a size of 20mm×15mm×2.5mm. Finish the surface of the sample according to the following specifications: alkali washing→water washing→acid washing→water washing→water abrasive paper grinding from coarse to fine→water washing→ultrasonic cleaning with absolute ethanol→hot air drying→reserve, among which the alkali cleaning condition: 40.0g Compound solution of /L sodium hydroxide, 10.0g/L sodium phosphate and 0.2g/L sodium dodecylbenzenesulfonate, 95°C, 15min; pickling conditions: 20.0g/L nitric acid, 50.0g/L nitric acid Composite solution of magnesium and 50.0g/L absolute ethanol, 25°C, 15sec; washing conditions: rinse with tap water and distilled water in sequence.

Example 1

The sample of AZ91 magnesium alloy in mold casting state was taken as the research object. Using distilled water as solvent, prepare 20.0g/L sodium chloride solution as anodic polarization electrolyte. Connect the equal-area samples of the same material to the wires, then connect them to the two output ports of the sinusoidal AC power supply, and immerse them in the above-mentioned electrolyte with a temperature control of 25°C, keep the distance between the samples at 3cm, and treat with a constant current of 1.0mA/cm2 ^at 50Hz After 30 minutes, it was found that the surface of the sample was uniformly distributed with fine pits of the same size and depth visible to the naked eye. The washed and dried anodized sample and the stainless steel cylinder form an electrode pair, the sample is connected to the negative pole of the DC power supply, and the stainless steel cylinder is connected to the positive pole of the DC power supply, respectively immersed in 50.0g/L magnesium chloride solution prepared with deionized water, A constant current of 1.5mA/cm ² was applied for 45 minutes, and a complete and uniform layer of earth gray film (the pre-layer of the bottom layer of the functional film) was formed on the surface of the sample. The washed and dried cathodic deposition sample was placed in a muffle furnace, heated to 450°C for 12 hours, and then cooled to room temperature with the furnace. It was found that the density of the film layer (the bottom layer of the functional film) was significantly improved.

Using dichloromethane as solvent, prepare 40.0g/LPLLA solution, marked as S ₀₁ ; use n-butanol as dispersant (liquid), add 10.0g/L magnesium oxide (solid dispersed phase) and stir evenly to obtain a suspension , marked as S ₀₂ ; using a homogeneous mixture of epichlorohydrin and acetone (mixing volume ratio 2:1) as solvent, first prepare 25.0g/LPLLA solution (liquid), then add 5.0g/L magnesium oxide (solid dispersed phase ) and stir well to obtain a suspension, labeled S ₀₃ . Carry out 3 rounds of dip-coating treatment on the heat-treated sample after washing and drying according to the following specifications: immerse the sample in the solution S ₀₁ , take it out after 7 sec, immerse the sample in the suspension S ₀₂ after the coating is cured, take it out after 15 sec, and After the cold wind blows dry, immerse the sample in solution S ₀₁ and take it out after 3 seconds. After the coating is cured, immerse the sample in solution S ₀₃ and take it out after 10 seconds. After the coating is naturally cured, immerse the sample in solution S ₀₁ and take it out after 7 seconds. Allow the coating to cure. Results A uniform composite coating (functional film surface layer) was obtained on the surface of the heat-treated sample, which was composed of 1) PLLA coating with MgO as the sandwich layer, and 2) MgO/PLLA composite material as the sandwich layer PLLA coatings are stacked sequentially.

Take SBF (simulated body fluid) as the test medium (see Table 1 for the comparison of its composition and the chemical composition of human plasma), control the volume-to-surface ratio (that is, the ratio of the solution volume to the surface area of the sample) to 24ml/cm ² , and the solution renewal interval is 24h. Under the test temperature of 37°C, the in vitro biodegradation performance tests were carried out on the above samples respectively. The results show that the substrate of the sample begins to have visible corrosion marks after about 42 days, compared with the blank sample (that is, the sample with only surface finishing but no anodic polarization, cathodic deposition, heat treatment and coating treatment) after immersion That is to say, the result of the beginning of corrosion, its initial anti-degradation ability is obviously enhanced, indicating that the functional film has a good biodegradation protection ability for the substrate; the functional film basically disappears after about 97 days, indicating that it has good self-degradation characteristics; After 182d, it was completely degraded, indicating that the material as a whole has full degradation characteristics.

Example 2

The sample of high-purity magnesium as cast metal was taken as the research object. Except that the concentration of sodium chloride was changed to 100.0g/L, the other conditions of anodic polarization were controlled the same as in Example 1. It was found that, except that the area of a single pit increased, the density of pits and their distribution uniformity decreased, the others were the same as in the implementation example 1. Except that the concentration of magnesium chloride was changed to 0.5g/L, other conditions and results of cathodic deposition were the same as in Example 1. Except that the temperature is changed to 350°C and the time is changed to 24h, the control and results of other heat treatment conditions are the same as in Example 1. Using chloroform as solvent, first prepare four parts of 30.0g/LPLLA solution, then add 10.0g/L magnesium hydroxide, pure magnesium powder (spherical, median particle size d ₅₀ =47μm), β-TCP and CPP respectively, and stir Homogenously, suspensions are obtained, labeled as solutions S ₀₄ , S ₀₅ , S ₀₆ and S ₀₇ . Carry out two rounds of dip-coating treatment on the heat-treated sample after washing and drying according to the following specifications: immerse the sample in solution S ₀₄ and take it out after 15 sec. After the coating is cured, immerse the sample in solution S ₀₅ and take it out after 15 sec. After the coating is cured, the sample is immersed in the solution S ₀₆ , and taken out after 15 sec. After the coating is cured, the sample is immersed in the solution S ₀₇ , and the coating is cured. As a result, a uniform composite coating (functional film surface layer) was obtained on the surface of the sample, which was successively stacked by PLLA-based composite coatings with magnesium hydroxide, pure magnesium, β-TCP and CPP as reinforcement phases . The in vitro biodegradability test of the material was carried out the same as in Example 1, and the results showed that the substrate of the sample began to have visible corrosion marks after about 39 days, indicating that the functional film had good biodegradation protection ability for the substrate; Almost completely disappeared, indicating that it has good self-degradation characteristics; the sample is completely degraded after about 250d, indicating that the material as a whole has full degradation characteristics.

Example 3

The sample of AZ31 magnesium alloy in mold casting state was taken as the research object. Except that the concentration of sodium chloride was changed to 20.0 mg/L, other conditions of anodic polarization were controlled as in Example 1. It was found that the treatment effect was the same as in Example 1 except that the density and depth of pits were reduced. Except that the concentration of magnesium chloride was changed to 150.0g/L, other conditions and results of cathodic deposition were the same as in Example 1. Except that the temperature was changed to 550° C. and the time was changed to 1 h, the control and results of other heat treatment conditions were the same as in Example 1. Use chloroform as solvent to prepare 75.0g/LPLLA solution, marked as solution S ₀₈ ; use ethanol as dispersant (liquid), add 0.5g/L magnesium hydroxide (solid dispersed phase), stir well to obtain suspension, marked as solution S ₀₉ . Using dichloromethane as a solvent, first prepare a 75.0 g/L PLLA solution, then add 0.377 g/L magnesium oxide and stir evenly to obtain a suspension, which is marked as solution S ₁₀ . Dip-coat the heat-treated sample after washing and drying according to the following specifications: immerse the sample in solution S ₀₈ , take it out after 7 seconds, immerse the sample in solution S ₀₉ after the coating is cured, take it out after 30 seconds, and wait for the coating to dry Finally, immerse the sample in solution S ₀₈ , and take it out after 7 sec. After the coating is cured, immerse the sample in solution S ₁₀ , take it out after 20 sec, and wait for the coating to be cured. Results A uniform composite coating (functional film surface layer) was obtained on the surface of the sample, which was composed of 1) PLLA coating with magnesium hydroxide as the sandwich layer, and 2) magnesium oxide/PLLA composite coating. The in vitro biodegradability test of the material was carried out the same as in Example 1, and the results showed that the substrate of the sample began to have visible corrosion marks after about 21 days, indicating that the functional film had a certain biodegradation protection ability for the substrate; Almost completely disappeared, indicating that it has good self-degradation characteristics; the sample is completely degraded after about 102d, indicating that the material as a whole has full degradation characteristics.

Example 4

The ZK60 magnesium alloy sample in metal mold casting state was taken as the research object. Anode polarization, cathode deposition and heat treatment condition control and results are the same as in Example 1. The preparation of solution S ₀₈ was the same as in Example 3 except that the concentration of PLLA was changed to 0.2 g/L. The preparation of solution S ₀₉ was the same as in Example 3 except that the concentration of magnesium hydroxide was changed to 45.0 g/L. The preparation of solution _S10 was the same as in Example 3 except that the concentration of PLLA was changed to 0.2g/L and the concentration of magnesium oxide was changed to 0.133g/L. Carry out dip-coating treatment to the heat-treated sample after washing and drying with embodiment 3, the result is the same as embodiment 3. The in vitro biodegradability test of the material was carried out the same as in Example 1, and the results showed that the substrate of the sample began to have visible corrosion marks after about 17 days, indicating that the functional film had a certain biodegradation protection ability for the substrate; Almost completely disappeared, indicating that it has good self-degradation characteristics; the sample is completely degraded after about 77 days, indicating that the material as a whole has full degradation characteristics.

Example 5

The sample of WE43 magnesium alloy in mold casting state was taken as the research object. Anode polarization, cathode deposition and heat treatment condition control and results are the same as in Example 1. The preparation of solution S ₀₁ is the same as in Example 1. Using acetone as dispersant (liquid), add 10.0g/L magnesium hydroxide, pure magnesium powder (spherical, median particle size d ₅₀ =47μm), β-TCP and CPP respectively, stir well to obtain a suspension, and mark them separately are solutions S ₁₁ , S ₁₂ , S ₁₃ and S ₁₄ . Dip-coat the heat-treated sample after washing and drying according to the following specifications: Immerse the sample in solution S ₀₁ and take it out after 10 sec. After the coating is cured, immerse the sample in solution S ₁₁ and take it out after 35 sec. Finally, immerse the sample in solution S ₀₁ and take it out after 10 sec. After the coating is cured, immerse the sample in solution S ₁₂ and take it out after 35 sec. After the coating is dry, immerse the sample in solution S ₀₁ and take it out after 10 sec. After curing, immerse the sample in solution S ₁₃ and take it out after 35 sec. After the coating is dry, immerse the sample in solution S ₀₁ and take it out after 10 sec. After the coating is cured, immerse the sample in solution S ₁₄ and take it out after 35 sec. After the layer is dry, immerse the sample in the solution S ₀₁ , take it out after 10 sec, and wait for the coating to solidify. As a result, a composite coating (functional film surface layer) was obtained in which PLLA coatings with magnesium hydroxide, pure magnesium, β-TCP and CPP as sandwich layers were stacked in sequence. The in vitro biodegradability test of the material was carried out the same as in Example 1, and the results showed that: the substrate of the sample began to have visible corrosion marks after about 26 days, indicating that the functional film had a certain biodegradation protection ability for the substrate; Almost completely disappeared, indicating that it has good self-degradation characteristics; the sample is completely degraded after about 125d, indicating that the material as a whole has full degradation characteristics.

Example 6

The forged WE43 magnesium alloy sample was taken as the research object. In addition to changing the sodium chloride in the electrolyte into sodium nitrate, sodium sulfate, lithium chloride, lithium nitrate, lithium sulfate, potassium chloride, potassium nitrate, potassium sulfate, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, Except for magnesium nitrate or magnesium sulfate, the control and results of other conditions of anodic polarization are the same as in Example 1. Except that the magnesium chloride in the electrolytic solution was changed into magnesium nitrate or magnesium sulfate respectively, other condition control and results of cathodic deposition were the same as in Example 1. Heat treatment condition control and result are with embodiment 1. Carry out the preparation of solution _S03 with embodiment 1. Use this solution to brush, spin and spray the heat-treated samples after washing and drying to obtain a uniform magnesium oxide/PLLA composite material coating (functional film surface layer) with an area density of 1.72mg/ ^cm2 . The in vitro biodegradability test of the material was carried out the same as in Example 1. The results showed that the substrate began to have visible corrosion marks after about 44 days, indicating that the functional film had a good biodegradation protection ability for the substrate; Almost completely disappeared, indicating that it has good self-degradation characteristics; the sample is completely degraded after about 182d, indicating that the material as a whole has full degradation characteristics.

Example 7

The die-cast AZ31 magnesium alloy sample was taken as the research object. Anode polarization, cathode deposition and heat treatment condition control and results are the same as in Example 1. Carry out the preparation of solution _S02 with embodiment 1. The PLLA solid particles are heated to a completely molten state and kept at 210°C, which is marked as solution S ₁₅ . Dip-coat the heat-treated sample after washing and drying according to the following specifications: immerse the sample in solution S ₁₅ and take it out after 30 sec. After the coating is cured, immerse the sample in solution S ₀₂ and take it out after 15 sec. Afterwards, the sample is immersed in the solution S ₁₅ , taken out after 2 sec, and the coating is cured. As a result, a uniform PLLA coating (functional film surface layer) with magnesium oxide as the sandwich layer was obtained on the surface of the sample. The in vitro biodegradability test of the material was carried out the same as in Example 1, and the results showed that the substrate of the sample began to have visible corrosion marks after about 15 days, indicating that the functional film had a certain biodegradation protection ability for the substrate; Almost completely disappeared, indicating that it has good self-degradation characteristics; the sample is completely degraded after about 130d, indicating that the material as a whole has full degradation characteristics.

Example 8

The extruded AZ31 magnesium alloy sample was taken as the research object. Anode polarization, cathode deposition and heat treatment condition control and results are the same as in Example 1. Heat 190.0g of PLLA solid particles to a completely molten state and keep it warm at 210°C, add a mixture of 5.0g of magnesium oxide and 5.0g of magnesium hydroxide, and stir evenly to obtain a suspension, which is marked as solution S ₁₆ . Dip-coat the heat-treated sample after washing and drying according to the following specifications: Immerse the sample in solution S ₁₆ and take it out after 45 sec. After the coating is cured, immerse the sample in solution S ₁₆ and take it out after 3 sec. . Results A uniform PLLA-based composite coating with magnesium oxide and magnesium hydroxide as reinforcing phases was obtained on the surface of the sample. The in vitro biodegradability test of the material was carried out the same as in Example 1, and the results showed that the substrate of the sample began to have visible corrosion marks after about 23 days, indicating that the functional film had a certain biodegradation protection ability for the substrate; Almost completely disappeared, indicating that it has good self-degradation characteristics; the sample is completely degraded after about 157d, indicating that the material as a whole has full degradation characteristics.

Example 9

The die-cast AZ91 magnesium alloy sample was taken as the research object. Anode polarization, cathode deposition and heat treatment condition control and results are the same as in Example 1. The preparation of solutions S ₀₁ , S ₀₂ and S ₀₃ was carried out as in Example 1. Dip-coat the heat-treated sample after washing and drying according to the following specifications: immerse the sample in solution S ₀₃ , take it out after 60 sec, immerse the sample in solution S ₀₂ after the coating is cured, take it out after 15 sec, and wait for the coating to dry Finally, immerse the sample in solution S ₀₃ and take it out after 20 sec. After the coating is cured, immerse the sample in solution S ₀₂ and take it out after 15 sec. Immerse the sample in solution S ₀₁ and take it out after 30 sec. Results A composite coating (functional film surface layer) was obtained on the surface of the cathodically deposited sample, which consisted of 1) MgO/PLLA composite coating with MgO as the sandwich layer, and 2) MgO as the sandwich layer, The two sides are superimposed by magnesium oxide/PLLA composite material coating and PLLA coating respectively. The in vitro biodegradability test of the material was carried out the same as in Example 1, and the results showed that the substrate of the sample began to have visible corrosion marks after about 10 days, indicating that the functional film had a certain biodegradation protection ability for the substrate; Almost completely disappeared, indicating that it has good self-degradation characteristics; the sample is completely degraded after about 140d, indicating that the material as a whole has full degradation characteristics.

Further referring to the ISO 10993 standard for biological evaluation of medical devices, the titanium alloy Ti6Al4V widely used in medical clinics was used as a negative control, and each sample in Example 1-Example 9 was subjected to biological tests represented by hemolysis rate and in vitro cytotoxicity. Compatibility test, the results show that: each sample shows good biocompatibility comparable to Ti6Al4V.

Table 1: Comparison of test medium and human plasma chemical composition

Claims (9)

1. A preparation method for biomedical materials, characterized in that it comprises the following main steps: a) Smelting and forming: smelting pure magnesium or magnesium alloy, and performing forming to obtain the product matrix; b) Anodic polarization: immerse the product matrix obtained in step a) into a water-based solution of sodium chloride with a concentration of 20.0mg/L-100.0g/L after surface treatment, and use an equal-area product of the same material as the counter electrode , power on for processing; c) Cathodic deposition: immerse the substrate of the product treated in step b) in a water-based solution of magnesium chloride with a concentration of 0.5-150.0g/L, and conduct treatment with electricity to obtain a functional film bottom layer with both degradation protection and self-degradation characteristics Front layer; d) Heat treatment: perform heat treatment on the product substrate treated in step c) to obtain a functional film bottom layer with both degradation protection and self-degradation properties, wherein the heat treatment temperature is 350-550°C, and the holding time is 1-24h; e) Coating: including the following main steps: e-1) Preparation of solution: 1# solution: an organic solvent-based solution of PLLA (poly-L-lactic acid), PLGA (poly-lactic-glycolic acid) or their mixture, with a concentration of 0.2-75.0g/L; 2# solution: magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP (β-tricalcium phosphate), CPP calcium polyphosphate or two or more of them are the solid dispersed phase, water, acetone, Ethanol, n-butanol or a suspension in which two or more mixtures are liquid, wherein the concentration of the solid dispersed phase is 0.5-45.0 g/L; 3# solution: it uses magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or two or more of them as the solid dispersed phase, and PLLA, PLGA or the organic solvent-based solution of their mixture as the liquid Suspension, wherein the concentration of the PLLA, PLGA or mixture thereof is 0.2-75.0g/L, and the mass of the solid dispersed phase accounts for 0.5%-40% of the total mass of the solid dispersed phase and PLLA, PLGA or the mixture of PLLA and PLGA ; e-2) Coating of coating: Coating the product substrate treated in step d) to obtain a functional film surface layer with both degradation protection and self-degradation properties. The coating treatment adopts the following three schemes Do more than one of: Option 1: Use the 1# solution and 2# solution prepared in step e-1) in combination, follow the order of using 1# solution first, then 2# solution, and then 1# solution, and carry out more than one round of coating; Scheme 2: Independently use the 3# solution prepared in step e-1) for more than one round of coating; Scheme 3: Combined use of 1# solution, 2# solution and 3# solution prepared in step e-1), follow the order of using 1# solution first, then 2# solution, and then 3# solution, and carry out more than one round of coating. 2. The preparation method of biomedical materials according to claim 1, characterized in that: sodium nitrate, sodium sulfate, lithium chloride, lithium nitrate, lithium sulfate, potassium chloride, Potassium nitrate, potassium sulfate, ammonium chloride, ammonium nitrate, ammonium sulfate, magnesium chloride, magnesium nitrate, magnesium sulfate or a mixture of two or more thereof are partially or completely replaced; the magnesium chloride described in step c) is replaced by magnesium nitrate, magnesium sulfate or a mixture thereof partially or fully replaced. 3. The preparation method of biomedical materials according to claim 1, characterized in that: the organic solvent of the 1# solution and the 3# solution in step e-1) is one of A solvent and B solvent, wherein A solvent is more than one of epichlorohydrin, dichloromethane or chloroform, and B solvent is a mixture obtained by uniformly mixing A solvent with one or more of acetone, ethanol or n-butanol; the step e-1) The pure magnesium and magnesium alloys in the above-mentioned 2# solution and 3# solution are in the form of powder, granule, flake, filament, ribbon, tube or whisker, and its open circuit potential in any same environment medium is not high The open circuit potential of pure magnesium or magnesium alloy in the product matrix. 4. The method for preparing biomedical materials according to claim 1, characterized in that: the 1# solution in step e-1) is replaced by molten PLLA, molten PLGA or a mixture of molten PLLA and molten PLGA The 3# solution described in step e-1) is used for magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or two or more mixtures thereof as solid dispersed phase, in molten state PLLA, molten state PLGA or the mixture of molten PLLA and molten PLGA is replaced by a liquid suspension, wherein the mass of the solid dispersed phase accounts for 0.5%-40% of the total mass of the solid dispersed phase and PLLA, PLGA or the mixture of PLLA and PLGA. 5. The preparation method of biomedical materials according to claim 1, characterized in that: in step e-2), one of the 1# solution and 2# solution described in scheme 1 is replaced by 3# solution; step e-2 ) The coating methods described in include dipping, brushing, spin coating or spraying. 6. the preparation method of biomedical material according to claim 1 is characterized in that: after being coated with the coating containing PLLA or PLGA, carry out natural curing or artificial curing treatment, after the coating is partially or fully cured, Then carry out the coating of the subsequent coating; after coating magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or a mixture of two or more thereof, dry treatment is carried out. 7. A biomedical material prepared by the preparation method according to claim 1, characterized in that it comprises a pure magnesium or magnesium alloy substrate and a functional film covering the surface of the substrate with both degradation protection and self-degradation properties, wherein the functional film Including a bottom layer and a surface layer; the bottom layer is mainly composed of magnesium oxide or a mixture of magnesium oxide and magnesium hydroxide; the surface layer includes at least one of No.1 coating and No.2 coating; the No.1 The coating is a degradable polymer material layer with magnesium oxide, magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or a mixture of two or more of them as the sandwich layer; the No.2 coating is made of magnesium oxide , magnesium hydroxide, pure magnesium, magnesium alloy, β-TCP, CPP or a mixture of two or more thereof is a degradable polymer-based composite material layer as a reinforcing phase, wherein the quality of the reinforcing phase accounts for 0.5% of the mass of the composite material -40%; the degradable polymer material in the No.1 coating and the No.2 coating is PLLA, PLGA or a mixture thereof. 8. The biomedical material according to claim 7, characterized in that: said No.1 coating and No.2 coating are respectively more than one layer, and the composition, structure and thickness of different layers are the same or different; The composition, structure and thickness of the degradable polymer material layers on both sides of the sandwich layer in the No.1 coating are the same or different; the sandwich layer in the No.1 coating is replaced by the No.2 coating; the No. .1 At least one of the degradable polymer material layers on both sides of the sandwich layer in the coating is replaced by No.2 coating. 9. The biomedical material according to claim 7, characterized in that: the pure magnesium and magnesium alloys in the No.1 coating and the No.2 coating are powdery, granular, flake, filamentous, Ribbon, tube or whisker shape, and its open circuit potential in any same environmental medium is not higher than that of the base pure magnesium or magnesium alloy.