Preparation method of 5-fluorouracil / high impact polystyrene anti-tumor implant stent

Abstract

The invention discloses a preparation method of a 5-fluorouracil / high impact polystyrene anti-tumor implantation stent. The preparation method comprises the following steps: S1, uniformly mixing 5-fluorouracil with the mass fraction of 0.5%-1% and high impact polystyrene granules with the mass fraction of 99%-99.5%; s2, a screw extruder and a traction machine are cooperatively used, and the raw materials obtained in the step S1 are prepared into a uniform and smooth wire rod with the specific diameter through the hot melt extrusion technology; and S3, printing an anti-tumor stent entity by using the wire obtained in the step S2 through a 3D printing technology. The prepared 5-fluorouracil / high impact polystyrene anti-tumor implant stent has certain biocompatibility, high drug bioavailability and certain slow release effect, can effectively induce death of cancer cells and inhibit growth of tumors, and meanwhile, reduces toxic and side effects of anti-cancer drugs.

Description

Technical Field

[0001] The invention relates to the technical field of medical orthopedic materials, and in particular to a method for preparing an anti-tumor composite material bracket. Background Art

[0002] In the treatment of malignant tumors, common methods include chemotherapy, radiotherapy, immunotherapy, surgical resection, etc.

[0003] Common drugs used in systemic chemotherapy in conventional chemotherapy include doxorubicin and high-dose methotrexate, but the drugs are not very selective, and tumor cells are not synchronized in the division cycle, which affects the effect of chemotherapy; if the drug concentration is low, it will cultivate drug resistance in tumor cells, and if the drug concentration is high, it will cause great harm to the body. Radiotherapy is not selective and has poor effects. It can only be used as an auxiliary treatment for bone tumors. Immunotherapy cannot be widely used due to the limited source of interferon. Therefore, surgical removal of the tumor and chemotherapy are the main methods at present.

[0004] However, surgical resection carries the risk of tumor cell spread, which indicates that we urgently need to invent an implant that can fill the vacant part after bone tumor removal, which not only has the corresponding mechanical properties and provides certain structural support, but also can place therapeutic drugs locally near the tumor, increase the drug concentration near the tumor, kill the residual bone tumor cells and avoid the drug causing greater damage to the whole body. Summary of the invention

[0005] Purpose of the Invention

[0006] The purpose of the present invention is to provide a method for preparing a 5-fluorouracil / high-impact polystyrene anti-tumor implant scaffold, which can fill the vacant part after the bone tumor is removed, has corresponding mechanical support performance, and can place therapeutic drugs near the tumor, increase the drug concentration near the tumor, kill residual bone tumor cells and avoid the drug causing greater damage to the whole body.

[0007] Technical Solution

[0008] A method for preparing a 5-fluorouracil / high-impact polystyrene anti-tumor implant stent comprises the following steps:

[0009] S1: uniformly mixing 0.5% to 1% by mass of 5-fluorouracil and 99% to 99.5% by mass of high-impact polystyrene pellets;

[0010] S2 uses a screw extruder and a tractor together to prepare the raw material obtained in step S1 into a wire with a specific diameter and uniform smoothness through hot melt extrusion technology;

[0011] S3 uses the wire obtained in step S2 to print out an anti-tumor stent entity through 3D printing technology.

[0012] Preferably, when the raw material obtained in step S1 is fed into the screw extruder, the extrusion temperature is controlled at 200°C to 220°C, the screw speed is 50r / min, the speed of the traction machine is 10mm / s, and the diameter range of the wire is 1.7 to 1.8mm.

[0013] Preferably, the anti-tumor stent entity is a disc with a porous structure, and the diameter of the disc is 10 mm and the thickness is 1 mm.

[0014] 5-Fluorouracil (5-FU) is a fluoride of pyrimidine, which is white or off-white crystals or crystalline powder. It is an antimetabolite and antitumor drug. 5-FU can be converted into 5-fluorouracil deoxynucleotide in the body, which inhibits DNA synthesis by blocking deoxyuracil nucleotides and deoxythymine nucleotides, inhibiting thymine nucleotide synthase, and inducing tumor cell apoptosis. 5-FU also has a certain inhibitory effect on RNA synthesis. 5-Fluorouracil can generate F-dUMP and FUMP through different pathways. The former can covalently bind to the active center of thymidylate synthase, inhibit the activity of this enzyme, and cause deoxynucleotide deficiency and DNA synthesis disorders. In addition, the metabolites of 5-FU can also enter RNA and DNA in the form of metabolites, affecting cell function and producing cytotoxicity. 5-Fu can be used for systemic medication, intracavitary medication and intratumoral medication, and plays an important role in the treatment of various malignant tumors such as lung cancer, colon cancer, and cervical cancer.

[0015] High impact polystyrene (HIPS) is a new type of polystyrene material that is made by grafting polystyrene polymer molecules onto rubbers such as cis-1,4-dimethyl-1-butyl rubber or styrene-butadiene rubber, thereby improving its elasticity. HIPS has both the large-size performance of ordinary polystyrene (GPPS) and good impact hardness and rigidity. The density range of HIPS is 1.04-1.06, and the thermal deformation working temperature is 70-84°C. The maximum tensile hardness of HIPS is 15-30MPa, and the maximum tensile factor is 35%-60%. When exposed to water, acid and dilute inorganic acid, the chemical properties of HIPS are not negatively affected. At the same time, HIPS has the advantages of good chemical stability, electrical insulation and easy processing and molding. Compared with ordinary polystyrene materials, its improved toughness is a great feature.

[0016] Beneficial Effects

[0017] The 5-fluorouracil / high-impact polystyrene anti-tumor implant stent prepared by the present invention has certain biocompatibility, high drug bioavailability, certain sustained-release effect, can effectively induce cancer cell death, inhibit tumor growth, and reduce the toxic side effects of anti-cancer drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 It is a step logic diagram of the present invention;

[0019] Figure 2 This is a diagram of a stent sample prepared according to an embodiment of the present invention. DETAILED DESCRIPTION

[0020] In order to enable those skilled in the art to better understand the content of the present invention, the present invention is further described in conjunction with the accompanying drawings and specific implementation methods.

[0021] Example 1

[0022] A method for preparing a 5-fluorouracil / high-impact polystyrene anti-tumor implant stent comprises the following steps:

[0023] S1: uniformly mixing 0.5% by mass of 5-fluorouracil and 99.5% by mass of high-impact polystyrene pellets;

[0024] S2 uses a screw extruder and a tractor to prepare the raw material obtained in step S1 into a wire with a specific diameter and uniform smoothness through hot melt extrusion technology. The wire diameter is 1.8 mm. The temperature of the screw extruder is controlled at 200° C., the screw speed is 50 r / min, and the speed of the tractor is 10 mm / s.

[0025] S3 builds a digital 3D model through the 3D modeling software Solidworks, and then converts the digital 3D model into a printing instruction for the 3D printer through the 3D slicing software Cura. First import the STL file, then adjust the model. After selecting the model, activate the toolbar, set the model size, scale, position, mirror and other model settings to the software default settings, and set the rotation angle to 0. Considering that the printing platform needs to be taped and glued, the model automatically fits the platform in the default state, removes the Z-axis limit, and avoids the general push and pull Z axis to make the model drop to a negative number. After slicing, only the part above the platform will be printed. Select the "Expert" expert mode in the slicing model and select the default slicing settings in the configuration file. When setting the slicing parameters, select 0.12mm layer height for the quality parameter to ensure printing accuracy. When setting the filling parameters, set the filling density to 95% and the filling pattern to a cube to ensure mechanical requirements and reduce warping. When setting the material parameters, set the nozzle temperature to 210℃ and the hot bed temperature to 35℃ during printing. When setting the speed parameters, set the printing speed to 40mm / s. When setting the movement parameters, set the retraction distance to 2.0mm, the retraction speed to 50mm / s, and check "Z-axis lift during retraction" to reduce wire drawing and avoid the nozzle touching the printed object during printing. Select the "Skirt" mode for the printing platform attachment method, "Normal support" for the support parameters, "Sawtooth" for the support pattern, and set the support Z distance to 0.1mm. To improve the printing quality and avoid "zippers" on the surface of the bracket, select "Sharpest corner" for "Z seam alignment" when setting the Cura parameters, and set the "Seam preference setting" to "Hide seams". The final printed bracket entity is a disc with a hole structure. The diameter of the disc is 10mm and the thickness is 1mm.

[0026] Example 2

[0027] A method for preparing a 5-fluorouracil / high-impact polystyrene anti-tumor implant stent comprises the following steps:

[0028] S1: uniformly mixing 1% by mass of 5-fluorouracil and 99% by mass of high-impact polystyrene pellets;

[0029] S2 uses a screw extruder and a tractor to prepare the raw material obtained in step S1 into a wire with a specific diameter and uniform smoothness through hot melt extrusion technology. The wire diameter is 1.7 mm. The temperature of the screw extruder is controlled at 220° C., the screw speed is 50 r / min, and the speed of the tractor is 10 mm / s.

[0030] S3 builds a digital 3D model through the 3D modeling software Solidworks, and then converts the digital 3D model into a printing instruction for the 3D printer through the 3D slicing software Cura. First import the STL file, then adjust the model. After selecting the model, activate the toolbar, set the model size, scale, position, mirror and other model settings to the software default settings, and set the rotation angle to 0. Considering that the printing platform needs to be taped and glued, the model automatically fits the platform in the default state, removes the Z-axis limit, and avoids the general push and pull Z axis to make the model drop to a negative number. After slicing, only the part above the platform will be printed. Select the "Expert" expert mode in the slicing model and select the default slicing settings in the configuration file. When setting the slicing parameters, select 0.2mm layer height for the quality parameter to ensure printing accuracy. When setting the filling parameters, set the filling density to 95% and the filling pattern to a cube to ensure mechanical requirements and reduce warping. When setting the material parameters, set the nozzle temperature to 210℃ and the hot bed temperature to 35℃ during printing. When setting the speed parameters, set the printing speed to 40mm / s. When setting the movement parameters, set the retraction distance to 2.0mm, the retraction speed to 50mm / s, and check "Z-axis lift during retraction" to reduce wire drawing and avoid the nozzle touching the printed object during printing. Select the "Skirt" mode for the printing platform attachment method, "Normal support" for the support parameters, "Sawtooth" for the support pattern, and set the support Z distance to 0.1mm. To improve the printing quality and avoid "zippers" on the surface of the bracket, select "Sharpest corner" for "Z seam alignment" when setting the Cura parameters, and set the "Seam preference setting" to "Hide seams". The final printed bracket entity is a disc with a hole structure. The diameter of the disc is 10mm and the thickness is 1mm.

[0031] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

The preparation method of 1.5-fluorouracil / high-impact polystyrene anti-tumor implant stent is characterized in that: The following steps are involved: S1: uniformly mixing 0.5% to 1% by mass of 5-fluorouracil and 99% to 99.5% by mass of high-impact polystyrene pellets; S2 uses a screw extruder and a tractor together to prepare the raw material obtained in step S1 into a wire with a specific diameter and uniform smoothness through hot melt extrusion technology; S3 uses the wire obtained in step S2 to print out an anti-tumor stent entity through 3D printing technology.

2. The method for preparing the 5-fluorouracil / high-impact polystyrene anti-tumor implant stent according to claim 1, characterized in that: When the raw material obtained in step S1 is fed into the screw extruder, the extrusion temperature is controlled at 200°C to 220°C, the screw speed is 50r / min, the speed of the traction machine is 10mm / s, and the diameter range of the wire is 1.7 to 1.8mm.

3. The method for preparing the 5-fluorouracil / high-impact polystyrene anti-tumor implant stent according to claim 1, characterized in that: The anti-tumor stent entity is a disc with a porous structure, and the diameter of the disc is 10 mm and the thickness is 1 mm.

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