CN108409317A - Mesoporous type hydroxylapatite ceramic is percutaneously implantable pass device and preparation method thereof - Google Patents

Abstract

The invention belongs to the field of biomaterial science and technology, and in particular relates to a mesoporous hydroxyapatite ceramic percutaneously implanted access device and a preparation method thereof. In the present invention, the mesoporous hydroxyapatite ceramics prepared by the preparation of the amount of binder, the selection of the pore-forming agent and the adjustment of the ratio, and the determination of the sintering system have excellent mechanical properties under the condition that there are enough pores. ; The mesoporous hydroxyapatite ceramics as a percutaneous implant access device has good biocompatibility, can be embedded in the body for a long time, and has wide application prospects; using the mesoporous hydroxyapatite ceramics of the present invention The percutaneous implantation of hydroxyapatite ceramics is expected to lead to a new drug delivery and treatment method, which uses the pore diffusion of ceramics for active continuous or intermittent drug delivery, which can reduce the toxic side effects of drugs and achieve targeted drug delivery .

Description

Mesoporous hydroxyapatite ceramic percutaneous implant access device and preparation method thereof

technical field

The invention belongs to the field of biomaterial science and technology, and in particular relates to a mesoporous hydroxyapatite ceramic percutaneously implanted access device and a preparation method thereof.

Background technique

A transdermal device refers to an implant that is partly implanted subcutaneously through the skin and maintains part of the skin wound or protrudes from the skin. It can be used as a device for transmitting material information inside and outside the body (can be combined with biosensors), and is an important part of biomaterial science and engineering. an important field of research. The percutaneous device is expected to be used for assisting vocalization, dialysis treatment, catheterization of benign prostatic hyperplasia, and measurement of biological information in vivo. Such as percutaneous catheters for the exchange of nutrients or drugs, skin windows for observation and collection of various information in the body, and intermediate connectors for implantable prostheses.

Since the 1950s, many researchers have tried to use various materials to make transdermal components. Williams first used metal tantalum as a transdermal component; in the 1960s, people began to try materials such as silicone rubber and polyester fiber. In the seventies, a large variety of materials began to be used in transdermal elements. Such as polypropylene, polyurethane collagen and other polymer materials, and copper chromium manganese alloy, titanium, gold and other metal materials. However, there are very serious problems when these materials are used as transdermal components, such as bacterial infection and epithelial descent, which will form a gap between the material and the skin tissue, which will cause the material to fall off from the body and cannot exist for a long time. In the 1980s, with the development and application of dense hydroxyapatite and supersurface hydroxyapatite coatings, a lot of research work on the role of hydroxyapatite in percutaneous components was carried out, especially in the development of oral dental implants. And application fields, usually using dense ceramics, combined with simple means such as surface roughening, have achieved some meaningful results. Professor Aoki from Japan has repeatedly reported that dense HA can form a seal with the skin under static conditions. After 17 months of implantation in the dog's back, the epithelial movement is only 1 mm, and the gap between hydroxyapatite, subcutaneous tissue and skin With good biocompatibility, it can form a tight attachment and combination to effectively prevent the invasion of bacteria.

Wang Jing designed and developed a new type of transdermal component based on liquid silicone rubber-hydroxyapatite composite material. The transdermal component has good biocompatibility and can be implanted in the skin for a long time for internal and external information transmission. The unique air bag switch design of the percutaneous component also makes the percutaneous component not only play the role of the interface between the internal and external pipelines, but also play the role of a control switch. It also proposes that nanoscale HA particles and higher curing pressures can be used to make transdermal devices more widely used.

J.A. Jansen has cultured epidermal cells on the surface of different substrate materials: such as HA, polystyrene, carbonated HA, carbon, gold, titanium and other substances. Hemidesmosome structures, while not formed on metal, suggest that the properties of the substrate material determine the nature and structure of epithelial cell attachment. At the same time, he also studied the interaction of fibroblasts and epithelial cells with the surface of different materials. Fibroblasts grow better on titanium metal, while epithelial cells grow better on carbon surfaces, and the material surface is favorable after glow discharge. Binding of fibroblasts to the material surface.

Contents of the invention

The invention aims at the deficiencies of the prior art and aims to provide a mesoporous hydroxyapatite ceramic percutaneously implanted access device and a preparation method thereof.

For realizing above-mentioned purpose of the invention, the technical scheme that the present invention adopts is:

A method for preparing a mesoporous hydroxyapatite ceramic percutaneously implanted access device, comprising the following steps:

(1) polyvinyl alcohol and deionized water are mixed according to a certain ratio to prepare a polyvinyl alcohol solution;

(2) Take by weighing nano-hydroxyapatite, polyvinyl alcohol solution and nano-carbon powder, mix and grind it into uniform wet powder;

(3) Take the wet powder prepared in step (2) and put it in a mould, carry out calendering and hold the pressure to obtain a green body;

(4) Carefully take out the green bodies, disperse them into rubber gloves, extract the vacuum and seal them; then put the gloves containing the green bodies into an oil pan for cold isostatic pressing to obtain pre-sintered secondary green bodies;

(5) Take out the secondary green body, bury the secondary green body flatly in the alumina powder, put it into a muffle furnace for sintering, and after the sintering is completed, it will be polished with fine sandpaper to obtain the mesoporous hydroxyphosphorus Gray stone ceramic.

In the above solution, the mesoporous pore diameter of the mesoporous hydroxyapatite ceramic percutaneously implanted access device is 20-50 nm.

In the above scheme, the mass concentration of the polyvinyl alcohol solution is 2%-10%.

In the above solution, the mass ratio of nano-hydroxyapatite, polyvinyl alcohol and nano-carbon powder in step (2) is 1000:4-20:5-40.

In the above scheme, the pressure of rolling and holding pressure described in step (3) is 5MPa, and the holding time is 5min.

In the above scheme, the cold isostatic pressing treatment in step (4) is as follows: increasing the pressure by 20 MPa per minute until reaching a maximum pressure of 200 MPa, and maintaining the pressure for 10 minutes.

In the above scheme, the sintering process in step (5) is: 0-200°C, heating time 60min, heat preservation 30min; 200-900°C, heating time 100min, heat preservation 30min; .

The beneficial effects of the present invention are as follows: the mesoporous hydroxyapatite ceramics prepared by the present invention have a uniform mesoporous structure, and also have excellent mechanical properties, and the bending strength is 138Mpa, which basically reaches the strength of human bones; Porous hydroxyapatite ceramics have good biocompatibility when implanted into the body as a percutaneous implant access device, can be implanted in the body for a long time, and have wide application prospects; using the mesoporous hydroxyapatite ceramics of the present invention The percutaneous implantation of access devices is expected to lead to a new drug delivery and treatment method, using the pore diffusion of ceramics for active continuous or intermittent drug delivery, which can reduce the toxic side effects of drugs and achieve targeted drug delivery.

Description of drawings

Figures 1 to 3 are scanning electron microscopes (SEM) of the ceramic section of the mesoporous hydroxyapatite ceramic percutaneously implanted access device prepared in the present invention.

Fig. 4 is a physical figure of the present invention: the physical size on the left side is: d=33.1mm, h=1.6mm, and the physical size on the right side is d=22.5mm, h=3.2mm.

Detailed ways

In order to better understand the present invention, the content of the present invention is further illustrated below in conjunction with the examples, but the content of the present invention is not limited to the following examples.

Example 1

A method for preparing a mesoporous hydroxyapatite ceramic percutaneously implanted access device, comprising the following steps: (1) heating 20ml of deionized water to 90°C to maintain a constant temperature, then weighing 0.4g of polyvinyl alcohol and adding in three times In water and constantly stirring, until polyvinyl alcohol dissolves completely, obtain the polyvinyl alcohol solution that mass fraction is 2%; (2) accurately weigh 10g hydroxyapatite powder and 0.4g nanometer carbon powder, carbon powder is mixed with hydroxyl Mix the apatite powder evenly, then add 2ml vinyl alcohol solution dropwise to the mixed powder, stir while dripping, and then perform ball milling to make it fully mixed to obtain a wet powder; (3) Put the wet powder into the mold three times Carry out calendering into sheets, the pressure is 5MPa, keep the pressure for 5min, get the preliminary green body, then put the green body into the rubber glove to extract the vacuum and seal it, and carry out the cold isostatic pressing treatment: increase the pressure by 20MPa per minute until the maximum pressure is reached 200MPa, and hold the pressure for 10 minutes; at this time, the pre-sintered secondary green body is obtained, and the secondary green body is taken out and buried in alumina powder, and put into a muffle furnace for sintering. The sintering system is 0~ 200°C (heating time 60min) → heat preservation 30min → 200-900°C (heating time 100min) → heat preservation 30min → 900-1200°C (heating time 100min) → heat preservation 120min → cooling with the furnace to obtain mesoporous hydroxyapatite For ceramics, the obtained ceramic sheet is first roughly ground with 600-mesh sandpaper, and then finely polished with 2000-mesh sandpaper to make it smoother, so as to obtain a mesoporous hydroxyapatite ceramic percutaneous implant device. A test strip of 3mm×4mm×28mm was prepared and processed into a mold with a corresponding shape, and the bending strength of the ceramic was measured to be 112MPa.

Example 2

A method for preparing a mesoporous hydroxyapatite ceramic percutaneously implanted access device, comprising the following steps: (1) heating 20ml of deionized water to 90°C to maintain a constant temperature, then weighing 1g of polyvinyl alcohol and adding it to the water three times And constantly stir, until polyvinyl alcohol dissolves completely, obtain the polyvinyl alcohol solution that mass fraction is 5%; (2) accurately weigh 10g hydroxyapatite powder and 0.4g nano carbon powder, carbon powder is mixed with hydroxyphosphorus earlier Mix the limestone powder evenly, then add 2ml of polyvinyl alcohol solution dropwise to the mixed powder, stir while dripping, and then perform ball milling to make it fully mixed to obtain a wet powder; (3) Put the wet powder into the mold three times Carry out calendering into sheets, the pressure is 5MPa, keep the pressure for 5min, get the preliminary green body, then put the green body into the rubber glove to extract the vacuum and seal it, and carry out the cold isostatic pressing treatment: increase the pressure by 20MPa per minute until the maximum pressure is reached 200MPa, and hold the pressure for 10 minutes; at this time, the pre-sintered secondary green body is obtained, and the secondary green body is taken out and buried in alumina powder, and put into a muffle furnace for sintering. The sintering system is 0~ 200°C (heating time 60min) → heat preservation 30min → 200-900°C (heating time 100min) → heat preservation 30min → 900-1200°C (heating time 100min) → heat preservation 120min → cooling with the furnace to obtain mesoporous hydroxyapatite For ceramics, the obtained ceramic sheet is first roughly ground with 600-mesh sandpaper, and then finely polished with 2000-mesh sandpaper to make it smoother, so as to obtain a mesoporous hydroxyapatite ceramic percutaneous implant device. A test strip of 3 mm × 4 mm × 28 mm was prepared and processed into a mold with a corresponding shape, and the bending strength of the ceramic was measured to be 138 MPa.

Example 3

A method for preparing a mesoporous hydroxyapatite ceramic percutaneously implanted access device, comprising the following steps: (1) heating 20ml of deionized water to 90°C to maintain a constant temperature, then weighing 1.6g of polyvinyl alcohol and adding in three times In water and constantly stirring, until polyvinyl alcohol dissolves completely, obtain the polyvinyl alcohol solution that mass fraction is 8%; (2) accurately weigh 10g hydroxyapatite powder and 0.4g nano carbon powder, carbon powder is mixed with hydroxyl Mix the apatite powder evenly, then add 2ml of polyvinyl alcohol solution dropwise to the mixed powder, stir while dripping, and then perform ball milling to make it fully mixed to obtain a wet powder; (3) Put the wet powder into the mold three times Carry out calendering in the middle into sheets, the pressure is 5MPa, and the pressure is kept for 5min to obtain a preliminary green body, then put the green body into a rubber glove to draw a vacuum and seal it, and perform cold isostatic pressing: increase the pressure by 20MPa per minute until it reaches the maximum The pressure is 200MPa, and the pressure is maintained for 10 minutes; at this time, the pre-sintered secondary green body is obtained, and the secondary green body is taken out and buried in alumina powder, and put into a muffle furnace for sintering. The sintering system is 0 ~200°C (heating time 60min) → heat preservation 30min → 200 ~ 900°C (heating time 100min) → heat preservation 30min → 900 ~ 1200°C (heating time 100min) → heat preservation 120min → cooling with the furnace to obtain mesoporous hydroxyapatite For stone ceramics, the obtained ceramic sheet was firstly ground with 600-mesh sandpaper, and then finely polished with 2000-mesh sandpaper to make it smoother, that is, a mesoporous hydroxyapatite ceramic percutaneous implant device was obtained. A test strip of 3 mm × 4 mm × 28 mm was prepared and processed into a mold with a corresponding shape, and the bending strength of the ceramic was measured to be 135 MPa.

Example 4

A method for preparing a mesoporous hydroxyapatite ceramic percutaneously implanted access device, comprising the following steps: (1) heating 20ml of deionized water to 90°C to maintain a constant temperature, then weighing 2g of polyvinyl alcohol and adding it to the water three times And constantly stir, until polyvinyl alcohol dissolves completely, obtain the polyvinyl alcohol solution that mass fraction is 10%; (2) accurately weigh 10g hydroxyapatite powder and 0.4g nano carbon powder, carbon powder is mixed with hydroxyphosphorus earlier Mix the limestone powder evenly, then add 2ml of polyvinyl alcohol solution dropwise to the mixed powder, stir while dripping, and then perform ball milling to make it fully mixed to obtain a wet powder; (3) Put the wet powder into the mold three times Carry out calendering into sheets, the pressure is 5MPa, keep the pressure for 5min, get the preliminary green body, then put the green body into the rubber glove to extract the vacuum and seal it, and carry out the cold isostatic pressing treatment: increase the pressure by 20MPa per minute until the maximum pressure is reached 200MPa, and keep the pressure for 10 minutes, at this time, the pre-sintered secondary green body is obtained; take out the secondary green body and bury it flat in the alumina powder, put it into the muffle furnace for sintering, and the sintering system is 0～ 200°C (heating time 60min) → heat preservation 30min → 200-900°C (heating time 100min) → heat preservation 30min → 900-1200°C (heating time 100min) → heat preservation 120min → cooling with the furnace to obtain mesoporous hydroxyapatite For ceramics, the obtained ceramic sheet is first roughly ground with 600-mesh sandpaper, and then finely polished with 2000-mesh sandpaper to make it smoother, so as to obtain a mesoporous hydroxyapatite ceramic percutaneous implant device. A test strip of 3mm×4mm×28mm was prepared and processed into a mold with a corresponding shape, and the bending strength of the ceramic was measured to be 123MPa.

Example 5

A method for preparing a mesoporous hydroxyapatite ceramic percutaneously implanted access device, comprising the following steps: (1) heating 20ml of deionized water to 90°C to maintain a constant temperature, then weighing 1g of polyvinyl alcohol and adding it to the water three times And constantly stir, until polyvinyl alcohol dissolves completely, obtain the polyvinyl alcohol solution that mass fraction is 5%; (2) accurately weigh 10g hydroxyapatite powder and 0.05g nanometer carbon powder, carbon powder is mixed with hydroxyphosphorus earlier Mix the limestone powder evenly, then add 2ml of polyvinyl alcohol solution dropwise to the mixed powder, stir while dripping, and then perform ball milling to make it fully mixed to obtain a wet powder; (3) Put the wet powder into the mold three times Carry out calendering into sheets, the pressure is 5MPa, keep the pressure for 5min, get the preliminary green body, then put the green body into the rubber glove to extract the vacuum and seal it, and carry out the cold isostatic pressing treatment: increase the pressure by 20MPa per minute until the maximum pressure is reached to 200MPa, and hold the pressure for 10min, at this time the pre-sintered secondary green body is obtained; at this time, the pre-sintered secondary green body is obtained, the secondary green body is taken out and buried in alumina powder flatly, and put into the Sintering in a Furnace, the sintering system is 0-200°C (heating time 60min) → heat preservation 30min → 200-900°C (heating time 100min) → heat preservation 30min → 900-1200°C (heating time 100min) → heat preservation 120min → furnace After cooling, the mesoporous hydroxyapatite ceramics are obtained. The obtained ceramic sheet is first roughly ground with 600-mesh sandpaper, and then finely polished with 2000-mesh sandpaper to make it smoother, and the mesoporous hydroxyapatite is obtained. Ceramic percutaneous implant devices. A test strip of 3mm×4mm×28mm was prepared and processed into a mold with a corresponding shape, and the bending strength of the ceramic was measured to be 156MPa.

Example 6

A method for preparing a mesoporous hydroxyapatite ceramic percutaneously implanted access device, comprising the following steps: (1) heating 20ml of deionized water to 90°C to maintain a constant temperature, then weighing 1g of polyvinyl alcohol and adding it to the water three times And constantly stir, until polyvinyl alcohol dissolves completely, obtain the polyvinyl alcohol solution that mass fraction is 5%; (2) accurately weigh 10g hydroxyapatite powder and 0.2g nano carbon powder, carbon powder is mixed with hydroxyphosphorus earlier Mix the limestone powder evenly, then add 2ml of polyvinyl alcohol solution dropwise to the mixed powder, stir while dripping, and then perform ball milling to make it fully mixed to obtain a wet powder; (3) Put the wet powder into the mold three times Carry out calendering into sheets, the pressure is 5MPa, keep the pressure for 5min, get the preliminary green body, then put the green body into the rubber glove to extract the vacuum and seal it, and carry out the cold isostatic pressing treatment: increase the pressure by 20MPa per minute until the maximum pressure is reached 200MPa, and keep the pressure for 10min. At this time, the pre-sintered secondary green body is obtained. Take out the secondary green body and bury it flat in the alumina powder, put it into the muffle furnace for sintering, and the sintering system is 0～ 200°C (heating time 60min) → heat preservation 30min → 200-900°C (heating time 100min) → heat preservation 30min → 900-1200°C (heating time 100min) → heat preservation 120min → cooling with the furnace to obtain mesoporous hydroxyapatite For ceramics, the obtained ceramic sheet is first roughly ground with 600-mesh sandpaper, and then finely polished with 2000-mesh sandpaper to make it smoother, so as to obtain a mesoporous hydroxyapatite ceramic percutaneous implant device. A test strip of 3 mm × 4 mm × 28 mm was prepared and processed into a mold with a corresponding shape, and the bending strength of the ceramic was measured to be 143 MPa.

The mesoporous hydroxyapatite ceramic percutaneous implantation device prepared by the invention was tested, and Figures 1 to 3 are ceramic cross-sectional scan electrons of the mesoporous hydroxyapatite ceramic percutaneous implantation access device prepared by the present invention Microscope (SEM) pictures, it can be seen from the figure that the mesoporous hydroxyapatite ceramic percutaneous implantation access device has a mesoporous structure, and the distribution of mesopores is uniform, and the pore size of the mesopores is less than 50nm. The mechanical properties of the hydroxyapatite ceramic percutaneous implant device were tested, and the results are shown in Table 1, indicating that the mesoporous hydroxyapatite ceramic percutaneous implant device has good mechanical properties.

Table 1 Pore distribution and mechanical properties of mesoporous hydroxyapatite ceramics

Example Bending strength/MPa Pore distribution 1 112 Evenly distributed and uniform in size 2 138 Evenly distributed and uniform in size 3 135 Evenly distributed and uniform in size 4 123 Evenly distributed and uniform in size 5 156 Uneven distribution, small number of pores 6 143 Uneven distribution, small number of pores

The mesoporous hydroxyapatite ceramic percutaneous implant device prepared by the invention was subjected to a biocompatibility test, and the mesoporous hydroxyapatite ceramic material was soaked in phosphate buffer at a ratio of 0.2 g/mL, and the Extract at (37±1)°C to obtain a material extract, put the solution into a petri dish, extract 1mL of mouse blood and inoculate it into the petri dish, and test it one week later, it is found that the blood cells are in contact with each other and attached to the petri dish. On the inner wall of the petri dish, the shape is good, and there is no rejection and interference phenomenon, which shows that the mesoporous hydroxyapatite ceramic prepared by the present invention has good biocompatibility when used as a percutaneous implant device.

Apparently, the above-mentioned embodiments are only examples for clear illustration, rather than limiting the implementation. For those of ordinary skill in the art, other changes or changes in different forms can be made on the basis of the above description. It is not necessary and impossible to exhaustively list all the implementation manners here. However, the obvious changes or modifications thus extended are still within the scope of protection of the present invention.

Claims (7)

1. A method for preparing a mesoporous hydroxyapatite ceramic percutaneously implanted access device, comprising the steps of: (1) Prepare polyvinyl alcohol solution by mixing polyvinyl alcohol and deionized water according to a certain ratio; (2) Weigh nano-hydroxyapatite, polyvinyl alcohol solution and nano-carbon powder, mix and grind them into uniform wet powder; (3) Put the wet powder prepared in step (2) into a mold, perform rolling under a certain pressure and maintain the pressure to obtain a green body; (4) Carefully take out the green bodies, disperse them into rubber gloves, extract the vacuum and seal them; then put the gloves containing the green bodies into the oil pan for cold isostatic pressing to obtain pre-sintered secondary green bodies; (5) Take out the secondary green body, bury the secondary green body flatly in the alumina powder, put it into the muffle furnace for sintering, after the sintering is completed, and then polish it with fine sandpaper, you can get the mesoporous hydroxyphosphorus Percutaneous implantation of graystone ceramic access devices. 2. The preparation method according to claim 1, wherein the mesoporous pore diameter of the mesoporous hydroxyapatite ceramic percutaneously implanted access device is 20-50 nm. 3. preparation method according to claim 1, is characterized in that, the mass concentration of described polyvinyl alcohol solution is 2%～10%. 4. The preparation method according to claim 1, characterized in that the mass ratio of nano-hydroxyapatite, polyvinyl alcohol and nano-carbon powder in step (2) is 1000:4~20:5~40. 5 . The preparation method according to claim 1 , characterized in that, in step (3), the rolling and holding pressure is 5 MPa, and the holding time is 5 minutes. 6 . The preparation method according to claim 1 , wherein the cold isostatic pressing treatment in step (4) is: increasing the pressure by 20 MPa per minute until reaching a maximum pressure of 200 MPa, and maintaining the pressure for 10 minutes. 7. The preparation method according to claim 1, characterized in that the sintering process in step (5) is: 0~200°C, heating time 60min, heat preservation 30min; 200~900°C, heating time 100min, heat preservation 30min ; 900~1200℃, heating time 100min, holding time 120min.