A prosthesis for spine and a method for preparing the prosthesis

Abstract

The present invention relates to the field of medical devices, and specifically to a prosthesis applied to the spine, comprising a substrate, wherein the outer wall of the substrate is provided with a hole one, and the substrate is provided with a through hole two in a vertical direction. The present invention solves the problem of filling large bone defects through a porous titanium alloy prosthesis. By filling bone cement and drug-loaded gelatin microspheres in hole one, the bone cement is degraded to release anti-infection, anti-tumor, anti-osteoporosis and other drugs to treat the disease while inducing bone cells to grow into the porous metal to achieve faster and stronger fusion. Autologous cancellous bone particles can be filled through hole two, which helps to improve the fusion rate after prosthesis implantation and provide a seed cell basis for bone growth in the porous structure. The reinforcing beams around the prosthesis can meet the patient's initial prosthesis load-bearing requirements after surgery.

Description

Technical Field

[0001] The present invention relates to the field of medical devices, and in particular to a prosthesis applied to a spine and a method for preparing the prosthesis. Background Art

[0002] In clinical practice, when spinal tumors, infections (especially tuberculosis), severe fractures, etc. require vertebral resection and reconstruction surgery, large bone replacement materials are often needed to restore stability and promote later fusion. Existing materials include autologous bone, large allogeneic bone, and titanium mesh. However, the amount and shape of autologous bones such as ribs and iliac bones often cannot meet the requirements of filling large bone defects; with the annual surge in the number of spinal surgeries, large allogeneic bones are increasingly scarce and have no osteogenic activity; and the commonly used titanium mesh lacks anti-tumor and anti-infection activities, and the elastic modulus does not match that of autologous bone, causing sinking. Therefore, there is a thorny problem of no bone available during large vertebral lesion resection. In recent years, technologies such as 3D printing porous titanium alloys have provided new strategies for preoperative customization of orthopedic prostheses. Summary of the invention

[0003] The purpose of the present invention is to solve the problem that the amount and shape of autologous bone often cannot meet the requirements of filling large bone defects, and the commonly used titanium mesh lacks anti-tumor, anti-infection and other activities, and the elastic modulus does not match that of autologous bone, causing sinking. Therefore, there is a thorny problem that no bone is available during large vertebral lesion resection. A method is provided that can resist spinal infection and solve the problem that the amount and shape of autologous bone often cannot meet the requirements of filling large bone defects, especially a prosthesis applied to the spine and a method for preparing the prosthesis.

[0004] The technical problem solved by the present invention can be achieved by adopting the following technical solutions:

[0005] A prosthesis applied to a spine comprises a base body, wherein the outer wall of the base body is provided with a first hole, and the base body is provided with a second through hole in a vertical direction.

[0006] The prosthesis for spinal column according to claim 1 is characterized in that the matrix is ​​made of titanium alloy.

[0007] There are a plurality of holes one, and the holes one are located in the matrix and are all interconnected. The diameter of the hole one is 300-900 μm, and the porosity of the hole one is 60%-95%.

[0008] The base body is provided with two pairs of connection holes, which are respectively located at the upper part and the lower part of the base body.

[0009] The upper part and the lower part of the base are respectively fixed with connecting plates, and at least one positioning hole is opened on the connecting plates.

[0010] At least two reinforcing beams are fixed on the outer wall surface of the base.

[0011] A method for preparing a prosthesis for a spine comprises the prosthesis for a spine and a filler, wherein the filler is located in hole one.

[0012] The filler is formed by mixing bone cement and drug-loaded gelatin microspheres, wherein the drug-loaded gelatin microspheres account for 5-15 wt %.

[0013] The bone cement preparation method is as follows:

[0014] In the first step, calcium carbonate powder and phosphoric acid solution are used as raw materials;

[0015] In the second step, deionized water and calcium carbonate powder are mixed in a molar mass ratio of 50:1 to form a calcium carbonate suspension, and then 1 mol / L of a phosphate buffer solution with a pH value of 6 is added to the calcium carbonate suspension, and stirred at a speed of 100 r / min for 10 minutes to obtain a calcium phosphate suspension with a milky white precipitate;

[0016] The third step is to filter out the aqueous solution in the calcium phosphate suspension obtained in the second step using a filter cloth to obtain a precipitate;

[0017] In the fourth step, the precipitate obtained in the third step is washed and filtered with deionized water and anhydrous ethanol, dispersed with an ultrasonic oscillator, and then dried with an automatic drying bottle until it becomes powder. Finally, the powder is ground with a ball mill to obtain calcium phosphate bone cement powder.

[0018] The preparation method of the drug-loaded gelatin microspheres is as follows:

[0019] The first step is to prepare a 15wt% gelatin solution with distilled water, add anti-tuberculosis drugs, anti-tumor drugs, anti-osteoporosis drugs or antibiotics, stir and heat to 37°C to obtain a drug-containing gelatin solution;

[0020] The second step is to add the gelatin solution obtained in the second step to 5 times the volume of 37°C liquid paraffin, then add the surface dispersant Span-80, the volume ratio of the surface dispersant Span-80 is 1% of the total liquid volume, stir for 10 minutes, quickly cool to 0°C and continue stirring for 10 minutes, add the cross-linking agent genipin with a mass concentration of 1%, the cross-linking agent genipin accounts for one twentieth of the total liquid volume after the surface dispersant Span-80 is added to the liquid paraffin, and stop stirring after pre-curing for 30 minutes to obtain a suspension of drug-loaded gelatin microspheres and liquid paraffin;

[0021] The third step is to dehydrate the suspension obtained in the second step with acetone, wash off the paraffin with anhydrous ether, and dry it with a vacuum pump to obtain drug-loaded gelatin microsphere powder;

[0022] Step 4: The drug-loaded gelatin microsphere powder obtained in step 3 is immersed in a 0.5% mass concentration genipin solution and is kept at 37° C. in the dark for 24 hours to continue cross-linking;

[0023] The morphology of the microspheres was observed under a light microscope before solidification. The particle size of the microspheres was estimated to be less than 100 μm using a scaled cell slide as a reference under a light microscope. The microspheres had a spherical structure and good dispersion.

[0024] Step 5, the cross-linked drug-loaded gelatin microspheres in step 4 are thoroughly washed with anhydrous ethanol and freeze-dried to obtain washed drug-loaded gelatin microsphere powder;

[0025] Step 6: seal the drug-loaded gelatin microsphere powder obtained in step 5 and sterilize it using 60Co radiation for later use.

[0026] The beneficial effects of the present invention are:

[0027] 1. The porous titanium alloy prosthesis solves the problem of filling large bone defects.

[0028] 2. By filling the hole with bone cement and drug-loaded gelatin microspheres, the bone cement can be degraded to release anti-infection, anti-tumor, anti-osteoporosis and other drugs to treat the disease and induce bone cells to grow into the porous metal to achieve faster and stronger fusion.

[0029] 3. Autologous cancellous bone particles can be filled through hole 2, which helps to improve the fusion rate after prosthesis implantation and provide a seed cell basis for bone growth in the porous structure.

[0030] 4. The reinforcing beam around the prosthesis can meet the patient's initial prosthesis load-bearing requirements after surgery. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] The present invention is further described below in conjunction with the accompanying drawings and embodiments.

[0032] Figure 1 It is a structural schematic diagram of the present invention.

[0033] Figure 2 It is a top view of the present invention.

[0034] Figure 3 It is a side view of the connecting plate of the present invention.

[0035] Figure 4 It is a top view of the connecting plate of the present invention.

[0036] In the figure: 1-base; 2-hole one; 3-through hole two; 4-connection hole; 5-connection plate; 6-positioning hole; 7-reinforcement beam; 8-filler. DETAILED DESCRIPTION

[0037] Embodiment 1:

[0038] Reference Figure 1-2, is a schematic structural diagram of Example 1 of the present invention, a prosthesis applied to the spine, comprising a base 1, a hole 2 is formed on the outer wall of the base 1, and a through hole 3 is formed in the vertical direction of the base 1.

[0039] In actual use:

[0040] In this embodiment, a prosthesis applied to the spine is applied to the vertebrae. First, the CT or MRI data of the patient's defective spine is collected before surgery, and the required external and internal structures of the matrix 1 are reconstructed with the help of three-dimensional modeling software. At the same time, the medical staff's three-dimensional structure design plan is integrated into the virtual model, and then the matrix 1 is printed out and then implanted into the defective part.

[0041] In order to facilitate the ingrowth and fusion of new bone tissue, a hole 2 is opened outside the matrix 1 to facilitate the ingrowth and fusion of new bone tissue.

[0042] The through hole 23 is convenient for filling with autogenous cancellous bone particles during surgery, which helps to improve the fusion rate after prosthesis implantation and provides a basis for bone growth in the porous structure.

[0043] Embodiment 2:

[0044] Based on Example 1, Figure 1-4 : The substrate 1 is made of titanium alloy.

[0045] In actual use: porous titanium alloy material provides a good bone replacement material, provides short-term stability and provides space for long-term bone graft fusion.

[0046] Embodiment 3:

[0047] Based on Example 1, Figure 1-4 : There are a plurality of holes 2, and the plurality of holes 2 are located in the substrate 1 and are interconnected. The diameter of the hole 2 is 300-900 μm, and the porosity of the hole 2 is 60%-95%.

[0048] In actual use: the ideal micropore size of bone tissue engineering scaffold is 300-900μm, and the porosity is between 60% and 95%. Therefore, the diameter of hole 2 is 300-900μm, and the porosity of hole 2 is 60%-95%, which is conducive to the growth and fusion of new bone tissue.

[0049] Embodiment 4:

[0050] Based on Example 1, Figure 1 The base body 1 is provided with two pairs of connection holes 4, which are respectively located at the upper part and the lower part of the base body 1.

[0051] In actual use: the connecting hole 4 is used to facilitate intraoperative fixation to the adjacent vertebrae, thereby increasing the stability of the base 1. When the bone density of the adjacent vertebrae is good, titanium alloy screws can be inserted obliquely upward or downward through the connecting hole 4 to achieve temporary fixation of the prosthesis.

[0052] Embodiment 5:

[0053] Based on Example 1, Figure 3-4 A connecting plate 5 is fixed to the upper and lower parts of the base 1 respectively, and at least one positioning hole 6 is formed on the connecting plate 5.

[0054] In actual use: the positioning holes on the connecting plate 5 are used to facilitate intraoperative fixation to the adjacent vertebrae. Depending on the location of the patient's lesion, when the bone density of the adjacent vertebrae is poor or other reasons cause the connecting hole 4 to fail to meet the fixation strength, the positioning holes 6 and screw structure on the connecting plate 5 are used to enhance the fixation effect.

[0055] Embodiment 6:

[0056] Based on Example 1, Figure 1-4 : At least two reinforcing beams 7 are fixed to the outer wall surface of the base 1.

[0057] In actual use: the early load-bearing capacity of the porous titanium alloy prosthesis can be improved by reinforcing the beam 7.

[0058] This embodiment uses three reinforcing beams 7 .

[0059] Embodiment 7:

[0060] A method for preparing a prosthesis for a spine includes a prosthesis for a spine and a filler 8, wherein the filler is located in a hole 2.

[0061] In actual use: the filler 8 is a degradable calcium phosphate bone cement material or other degradable material that is filled with different drugs for sustained release according to different lesions of the patient.

[0062] Embodiment 8:

[0063] Based on Example 7, the difference of this example is that the filler is a mixture of bone cement and drug-loaded gelatin microspheres, and the drug-loaded gelatin microspheres account for 5-15wt%.

[0064] In actual use: bone cement can fully exert its functions of both bone conduction and drug loading.

[0065] For example, for spinal tuberculosis lesions, drug-loaded gelatin microspheres containing anti-tuberculosis drugs such as rifampicin and isoniazid are prepared. During surgery, the drug-loaded microspheres are mixed with calcium phosphate bone cement and then injected into the porous structure of the prosthesis. As the bone cement degrades, rifampicin, isoniazid and other anti-tuberculosis drugs are gradually released, forming a higher concentration around the lesion, thereby achieving an anti-tuberculosis effect. In postoperative imaging follow-up, the signals of bone edema, sclerosis, abscesses, etc. in the lesion area gradually disappear.

[0066] Embodiment 9:

[0067] On the basis of Example 8, this embodiment is characterized in that the bone cement preparation method is as follows:

[0068] In the first step, calcium carbonate powder and phosphoric acid solution are used as raw materials;

[0069] In the second step, deionized water and calcium carbonate powder are mixed in a molar mass ratio of 50:1 to form a calcium carbonate suspension, and then 1 mol / L of a phosphate buffer solution with a pH value of 6 is added to the calcium carbonate suspension, and stirred at a speed of 100 r / min for 10 minutes to obtain a calcium phosphate suspension with a milky white precipitate;

[0070] The third step is to filter out the aqueous solution in the calcium phosphate suspension obtained in the second step using a filter cloth to obtain a precipitate;

[0071] In the fourth step, the precipitate obtained in the third step is washed and filtered with deionized water and anhydrous ethanol, dispersed with an ultrasonic oscillator, and then dried with an automatic drying bottle until it becomes powder. Finally, the powder is ground with a ball mill to obtain calcium phosphate bone cement powder.

[0072] In actual use: calcium phosphate bone cement powder and drug-loaded gelatin microspheres are mixed, with the drug-loaded gelatin microspheres accounting for 5-15wt%, and then mixed with quick-setting blending liquid sodium dihydrogen phosphate into a toothpaste-like state for easy use, with a powder-liquid ratio of / g / ml: 1:2. The mixed toothpaste-like bone cement is loaded into a syringe and then poured into the porous structure hole 1 2 of the prosthesis. After the hollow structure hole 2 3 is filled with autologous cancellous bone particles, the prosthesis is implanted in the bone defect and fixed.

[0073] Embodiment 10:

[0074] On the basis of Example 8, this embodiment is characterized in that the preparation method of the drug-loaded gelatin microspheres is as follows:

[0075] The first step is to prepare a 15wt% gelatin solution with distilled water, add anti-tuberculosis drugs, anti-tumor drugs, anti-osteoporosis drugs or antibiotics, stir and heat to 37°C to obtain a drug-containing gelatin solution;

[0076] The second step is to add the gelatin solution obtained in the second step to 5 times the volume of 37°C liquid paraffin, then add the surface dispersant Span-80, the volume ratio of the surface dispersant Span-80 is 1% of the total liquid volume, stir for 10 minutes, quickly cool to 0°C and continue stirring for 10 minutes, add the cross-linking agent genipin with a mass concentration of 1%, the cross-linking agent genipin accounts for one twentieth of the total liquid volume after the surface dispersant Span-80 is added to the liquid paraffin, and stop stirring after pre-curing for 30 minutes to obtain a suspension of drug-loaded gelatin microspheres and liquid paraffin;

[0077] The third step is to dehydrate the suspension obtained in the second step with acetone, wash off the paraffin with anhydrous ether, and dry it with a vacuum pump to obtain drug-loaded gelatin microsphere powder;

[0078] Step 4: The drug-loaded gelatin microsphere powder obtained in step 3 is immersed in a 0.5% mass concentration genipin solution and is kept at 37° C. in the dark for 24 hours to continue cross-linking;

[0079] The morphology of the microspheres was observed under a light microscope before solidification. The particle size of the microspheres was estimated to be less than 100 μm using a scaled cell slide as a reference under a light microscope. The microspheres had a spherical structure and good dispersion.

[0080] Step 5, the cross-linked drug-loaded gelatin microspheres in step 4 are thoroughly washed with anhydrous ethanol and freeze-dried to obtain washed drug-loaded gelatin microsphere powder;

[0081] Step 6: seal the drug-loaded gelatin microsphere powder obtained in step 5 and use 60 Co irradiation sterilized for future use.

[0082] In actual use: mix calcium phosphate bone cement powder and drug-loaded gelatin microspheres, with the drug-loaded gelatin microspheres accounting for 5-15wt%, and then use quick-setting blending liquid sodium dihydrogen phosphate to blend into a toothpaste-like state for easy use, with a powder-liquid ratio / g / ml: 1:2.

[0083] The above is a detailed description of the embodiments of the present invention in conjunction with the accompanying drawings, but the present invention is not limited to the above embodiments. Within the knowledge scope of ordinary technicians in the field, various changes can be made without departing from the purpose of the present invention, which are all within the protection scope of this technology.

Claims

1. A method for preparing a prosthesis for a spine, characterized in that: A prosthesis for use in a spinal column, comprising a base (1) and a filler (8), wherein the base (1) has a first hole (2) formed on its outer wall, and a second through hole (3) formed in a vertical direction of the base (1); The substrate (1) is made of titanium alloy; There are a plurality of holes one (2), and the plurality of holes one (2) are located in the substrate (1) and are interconnected. The diameter of the hole one (2) is 300-900 μm, and the porosity of the hole one (2) is 60%-95%. The base body (1) is provided with two pairs of connection holes (4), and the two pairs of connection holes (4) are respectively located at the upper part and the lower part of the base body (1); The filler (8) is located in hole one (2); The filler (8) is made of a mixture of bone cement and drug-loaded gelatin microspheres, wherein the drug-loaded gelatin microspheres account for 5-15 wt %; The bone cement preparation method is as follows: In the first step, calcium carbonate powder and phosphoric acid solution are used as raw materials; In the second step, deionized water and calcium carbonate powder are mixed in a molar mass ratio of 50:1 to form a calcium carbonate suspension, and then 1 mol / L of a phosphate buffer solution with a pH value of 6 is added to the calcium carbonate suspension, and stirred at a speed of 100 r / min for 10 minutes to obtain a calcium phosphate suspension with a milky white precipitate; The third step is to filter out the aqueous solution in the calcium phosphate suspension obtained in the second step using a filter cloth to obtain a precipitate; The fourth step is to wash and filter the precipitate obtained in the third step with deionized water and anhydrous ethanol, disperse the precipitate with an ultrasonic oscillator, dry it with an automatic drying bottle until it becomes powder, and finally grind the powder with a ball mill to obtain calcium phosphate bone cement powder; The preparation method of the drug-loaded gelatin microspheres is as follows: The first step is to prepare a 15wt% gelatin solution with distilled water, add anti-tuberculosis drugs or anti-tumor drugs, anti-osteoporosis drugs, and antibiotics, and stir and heat to 37° C. to obtain a drug-containing gelatin solution; The second step is to add the gelatin solution obtained in the second step to 5 times the volume of 37°C liquid paraffin, and then add the surface dispersant Span-80, the volume ratio of the surface dispersant Span-80 is 1% of the total liquid volume, stir for 10 minutes, quickly cool to 0°C and continue stirring for 10 minutes, add 1% mass concentration of cross-linking agent genipin, the cross-linking agent genipin accounts for one twentieth of the total liquid volume after adding the surface dispersant Span-80 to the liquid paraffin, and stop stirring after pre-curing for 30 minutes to obtain a suspension of drug-loaded gelatin microspheres and liquid paraffin; The third step is to dehydrate the suspension obtained in the second step with acetone, wash off the paraffin with anhydrous ether, and dry it with a vacuum pump to obtain drug-loaded gelatin microsphere powder; Step 4: The drug-loaded gelatin microsphere powder obtained in step 3 is immersed in a 0.5% mass concentration genipin solution and is kept at 37°C in the dark for 24 hours to continue cross-linking; The morphology of the microspheres was observed under a light microscope before solidification. The particle size of the microspheres was estimated to be less than 100 μm using a scaled cell slide as a reference under a light microscope. The microspheres had a spherical structure and good dispersion. Step 5, the cross-linked drug-loaded gelatin microspheres in step 4 are thoroughly washed with anhydrous ethanol and freeze-dried to obtain washed drug-loaded gelatin microsphere powder; Step 6: seal the drug-loaded gelatin microsphere powder obtained in step 5 and use 60 Co irradiation sterilized for future use.

2. The method for preparing a prosthesis for a spine according to claim 1, characterized in that: The upper and lower parts of the base body (1) are respectively fixed with connecting plates (5), and at least one positioning hole (6) is formed on the connecting plate (5).

3. The method for preparing a prosthesis for a spine according to claim 1, characterized in that: At least two reinforcement beams (7) are fixed to the outer wall surface of the base body (1).

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