Absorbable developing polymer composite material and preparation method thereof

Abstract

The invention belongs to the technical field of medical polymer materials. The invention relates to a polymer composite material, in particular to an absorbable developing polymer composite material and a preparation method thereof. The strontium-doped tricalcium phosphate provided by the invention can be used as a developing agent, and compared with a traditional iodine developing agent, the dissolution time is longer, and the developing effect of an implanted instrument can be maintained for a long time. The invention also provides an absorbable developing material prepared from strontium-doped tricalcium phosphate and a high polymer material. The developing material can be absorbed by a human body, and the problem that the recovery of a patient and the beautifying effect are influenced by tissue fibrosis caused by long-term retention of a traditional embedded metal developing material in the human body is solved. Besides, the absorbable developing material has a good imaging effect, is different from a metal material, can obviously distinguish surrounding tissues in X-ray and CT images after being implanted in vivo, does not have artifacts, cannot interfere with normal tissue imaging, and has good application prospects and values.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medical polymer materials. More specifically, it relates to an absorbable developing polymer composite material and a preparation method thereof. BACKGROUND

[0002] Medical polymer materials, especially absorbable polymer materials, have been increasingly widely used in clinical disease treatment due to their excellent biocompatibility and broad adaptability. However, compared with traditional metal materials, polymer materials have a higher penetration rate to X-rays, resulting in poor developing ability. For non-developable medical devices, especially implantable devices, it is difficult for doctors to achieve accurate positioning and filling during implantation, which not only significantly increases the difficulty and risk of operation, but also may cause harm to patients and increase the risk of operation. In addition, it is also difficult to accurately determine the position and degradation state of the device during postoperative follow-up, which brings challenges to long-term monitoring and efficacy evaluation. Therefore, it is of great clinical significance to improve the developing performance of polymer materials.

[0003] Currently, the main strategies to improve the developing performance of polymer devices include embedding metal components in the devices, or adding developing agents such as barium salts and iodine agents in the material system. For example, Chinese patent CN109925018B discloses a polymer medical device with an embedded metal developing marker, which uses absorbable polymer material polylactic acid to embed titanium clips. However, this method has obvious limitations: the developing components cannot be degraded and remain in the body after the product is degraded / absorbed in the body, which may cause inflammatory reactions or affect tissue repair, causing difficulties for patients and clinical management.

[0004] On the other hand, traditional contrast agent barium is mainly used for esophagus and gastrointestinal contrast as a contrast agent, and it is also difficult to be absorbed as an implant material; while commonly used iodine agents generally have good solubility, are easy to dissolve, have a short contrast imaging time, and have high viscosity, osmotic pressure, and charge problems, which often cause adverse reactions of the contrast agent in the body, causing irreparable harm to the health of patients.

[0005] Therefore, the development of new polymer composite materials with good developing performance and complete absorbability has become an important research direction in the field of biomedical materials. Such materials are expected to realize real-time visualization guidance of implanted devices during surgery and long-term tracking after surgery, and also avoid the potential risks of foreign body residues, which have broad clinical application prospects and transformation value. SUMMARY

[0006] The present application aims to provide a strontium-doped tricalcium phosphate, which can be used as a developing agent to prepare absorbable developing materials with excellent imaging effect.

[0007] The first objective of this invention is to provide a strontium-doped tricalcium phosphate and a method for its preparation.

[0008] A second objective of this invention is to provide applications of the aforementioned strontium-doped tricalcium phosphate.

[0009] A third objective of this invention is to provide an absorbable developing material.

[0010] The above-mentioned objective of this invention is achieved through the following technical solution: This invention provides a method for preparing strontium-doped tricalcium phosphate, comprising the following steps: ... 2+ 、Sr 2+ The ion-mixed solution was added to the phosphate solution and stirred at 70-90℃ for 0.5-1.5 h. The temperature was then raised to 100-120℃ and stirred for another 0.5-1.5 h to obtain the product. After drying, the product was calcined to obtain strontium-doped tricalcium phosphate.

[0011] As an alternative implementation, the phosphate solution is a diammonium hydrogen phosphate solution.

[0012] As an alternative implementation, the concentration of the diammonium hydrogen phosphate solution is 0.1~0.3 mol / L.

[0013] As an alternative implementation, the concentration of the diammonium hydrogen phosphate solution is 0.15~0.25 mol / L.

[0014] As an alternative implementation, the concentration of the diammonium hydrogen phosphate solution is 0.2 mol / L.

[0015] As an alternative implementation, the above-mentioned method for preparing strontium-doped tricalcium phosphate includes the following steps: [The text abruptly ends here, so the translation stops.] 2+ 、Sr 2+ The ion-mixed solution was added to the phosphate solution and stirred at 80°C for 1 h, then heated to 110°C and stirred for another 1 h to obtain the product. The product was dried and then calcined to obtain strontium-doped tricalcium phosphate.

[0016] Preferably, Ca 2+ 、Sr 2+ In ionic mixed solutions, Sr 2+ Ions and Ca 2+ The molar ratio of ions is 1:(1~4).

[0017] As an alternative implementation scheme, Ca 2+ 、Sr 2+ In ionic mixed solutions, Sr 2+ Ions and Ca 2+ The molar ratio of the ions is 1:1.

[0018] As an alternative implementation scheme, Ca 2+ 、Sr 2+ In ionic mixed solutions, Sr 2+ Ions and Ca 2+ The molar ratio of the ions is 1:4.

[0019] As an alternative implementation scheme, Ca 2+ 、Sr 2+ In ionic mixed solutions, Sr 2+ The concentration of ions is 0.06~0.3 mol / L, Ca 2+ The concentration of ions is 0.15~0.24 mol / L.

[0020] Preferably, Ca 2+ 、Sr 2+ The volume ratio of the ion-mixed solution to the phosphate solution is 1:(0.8~1.2).

[0021] More preferably, Ca 2+ 、Sr 2+ The volume ratio of the ion-mixed solution to the phosphate solution is 1:1.

[0022] As an alternative implementation, the Ca 2+ 、Sr 2+ The ion-mixed solution is Sr 2+ Solution and Ca 2+ A mixture of solutions.

[0023] Optionally, Sr 2+ The solution can be a strontium nitrate solution or a strontium chloride solution.

[0024] Optionally, Ca 2+ The solution can be either calcium nitrate solution or calcium chloride solution.

[0025] Optionally, the concentration of the strontium nitrate solution is 0.2~0.4 mol / L (preferably 0.3 mol / L), and the concentration of the calcium nitrate solution is 0.2~0.4 mol / L (preferably 0.3 mol / L).

[0026] As an alternative implementation, the drying is performed at 160~200°C for 8~14 hours.

[0027] As an alternative implementation, the drying is performed at 180°C for 12 hours.

[0028] As an alternative implementation, the calcination treatment is performed at 900~1200℃ for 4~8 h.

[0029] As an alternative implementation, the calcination treatment is performed at 900~1200℃ for 6 hours.

[0030] As an alternative implementation, the calcination treatment is performed by calcining at 1200°C for 6 hours.

[0031] The strontium-doped tricalcium phosphate prepared according to the above preparation method should also be within the scope of protection of this invention.

[0032] This invention provides the application of the above-mentioned strontium-doped tricalcium phosphate as a developer.

[0033] This invention provides the application of the above-mentioned strontium-doped tricalcium phosphate in the preparation of developing materials.

[0034] The present invention also provides an absorbable developing material containing a developing agent and a polymeric material; the developing agent is the above-mentioned strontium-doped tricalcium phosphate, and the polymeric material is at least one selected from poly(ethylene lactide), polylactic acid, polycaprolactone, polyglycolic acid, and polydioxanone.

[0035] As an alternative implementation, the mass ratio of the developer to the polymer material is (1~5):(5~9).

[0036] As an alternative implementation, the mass ratio of the developer to the polymer material is 3:7.

[0037] As an alternative implementation, the mass ratio of the developer to the polymer material is 5:5.

[0038] As an alternative implementation, the absorbable developing material is prepared by mixing a polymer material with the above-mentioned strontium-doped tricalcium phosphate, and the polymer material and the above-mentioned strontium-doped tricalcium phosphate are mixed in a mass ratio of (1~5):(5~9).

[0039] As an alternative implementation, the polymeric material is a blend or copolymer of two or more of poly(lactic acid) glycolide (PLGA), polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), and poly(p-dioxanone) (PPDO).

[0040] The present invention has the following beneficial effects: 1. The absorbable polymer material and the strontium-doped tricalcium phosphate contrast agent used in this invention are both absorbable materials. The composite material made from them can be absorbed by the human body, avoiding the problem of traditional embedded metal contrast materials remaining in the body for a long time, causing tissue fibrosis and affecting patient recovery and cosmetic results.

[0041] 2. The developing agent used in this invention has a longer dissolution time compared to traditional iodine developing agents, and can maintain the developing effect of implanted devices for a longer period of time.

[0042] 3. The absorbable imaging material of the present invention is different from metal materials. After being implanted in the body, it is clearly distinguishable from surrounding tissues in X-ray and CT images, and there are no artifacts that will interfere with the imaging of normal tissues, which can help medical personnel to better judge the efficacy.

[0043] 4. The absorbable imaging material of the present invention can be designed with varying effective imaging time according to different clinical application needs. Attached Figure Description

[0044] Figure 1 The CT value test results for S5 after 24 months of degradation testing.

[0045] Figure 2 The results of X-ray developing performance tests on developing materials are shown (the left side shows the test results for C1 material, and the right side shows the test results for S1 material). Detailed Implementation

[0046] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0047] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0048] Strontium nitrate, chemical formula Sr(NO3)2, CAS number 10042-76-9.

[0049] Calcium nitrate, chemical formula Ca(NO3)2, CAS number 10124-37-5.

[0050] Diammonium hydrogen phosphate, chemical formula (NH4)2HPO4, CAS number 7783-28-0.

[0051] The X-ray impermeability test method refers to the "Pharmaceutical Industry Standard of the People's Republic of China YY / T 0586-2016".

[0052] Polylactic acid (PLA), CAS number 26100-51-6, has the following structural formula: .

[0053] Polycaprolactone (PCL), CAS No. 24980-41-4, structural formula is .

[0054] Poly(p-dioxanone) (PPDO), CAS No. 31621-87-1, structural formula is: .

[0055] Poly(lactic acid-glycolic acid) (PLGA), also known as polylactic acid-glycolic acid copolymer, CAS number: 30846-39-0, structural formula: Purchased from Evonik Specialty Chemicals Ltd. ® (Item number: LG 824 S).

[0056] In the following embodiments, the doping amount is calculated using the molar ratio: Doping amount = Sr 2+ / (Ca 2+ + Sr 2+ ).

[0057] Example 1: Preparation of Strontium-doped tricalcium phosphate I. Solution Preparation Using deionized water as a solvent, prepare 0.3 mol / L strontium nitrate solution, 0.3 mol / L calcium nitrate solution and 0.2 mol / L diammonium hydrogen phosphate solution.

[0058] II. Preparation Method (1) Take 0.3 mol / L strontium nitrate solution and 0.3 mol / L calcium nitrate solution and mix them in a volume ratio of 1:1 to obtain a mixed solution; (2) Under stirring conditions, the mixture was gradually added dropwise to an equal volume of 0.2 mol / L diammonium hydrogen phosphate solution (the volume ratio of the mixture to the diammonium hydrogen phosphate solution was 1:1). After the addition was completed, the temperature was raised to 80°C and stirred for 1 hour. Then the temperature was raised to 110°C and stirred for 1 hour to obtain a paste-like product. (3) After the obtained paste product was vacuum dried at 180°C for 12 h, the product was transferred to a muffle furnace and calcined at 900°C for 6 h to obtain strontium-doped tricalcium phosphate powder (strontium doping amount is 50%).

[0059] Example 2 Preparation of Strontium-doped tricalcium phosphate I. Solution Preparation Using deionized water as a solvent, prepare 0.3 mol / L strontium nitrate solution, 0.3 mol / L calcium nitrate solution and 0.2 mol / L diammonium hydrogen phosphate solution.

[0060] II. Preparation Method (1) Take 0.3 mol / L strontium nitrate solution and 0.3 mol / L calcium nitrate solution and mix them in a volume ratio of 1:1 to obtain a mixed solution; (2) Under stirring conditions, the mixture was gradually added dropwise to an equal volume of 0.2 mol / L diammonium hydrogen phosphate solution (the volume ratio of the mixture to the diammonium hydrogen phosphate solution was 1:1). After the addition was completed, the temperature was raised to 80°C and stirred for 1 hour. Then the temperature was raised to 110°C and stirred for 1 hour to obtain a paste-like product. (3) After the obtained paste product is vacuum dried at 180°C for 12 hours, the product is transferred to a muffle furnace and calcined at 1200°C for 6 hours to obtain strontium-doped tricalcium phosphate powder (strontium doping amount is 50%).

[0061] Example 3 Preparation of Strontium-doped tricalcium phosphate I. Solution Preparation Using deionized water as a solvent, prepare 0.3 mol / L strontium nitrate solution, 0.3 mol / L calcium nitrate solution and 0.2 mol / L diammonium hydrogen phosphate solution.

[0062] II. Preparation Method (1) Take 0.3 mol / L strontium nitrate solution and 0.3 mol / L calcium nitrate solution and mix them in a volume ratio of 1:4 to obtain a mixed solution; (2) Under stirring conditions, the mixture was gradually added dropwise to an equal volume of 0.2 mol / L diammonium hydrogen phosphate solution (the volume ratio of the mixture to the diammonium hydrogen phosphate solution was 1:1). After the addition was completed, the temperature was raised to 80°C and stirred for 1 hour. Then the temperature was raised to 110°C and stirred for 1 hour to obtain a paste-like product. (3) After the obtained paste product is vacuum dried at 180°C for 12 hours, the product is transferred to a muffle furnace and calcined at 1000°C for 6 hours to obtain strontium-doped tricalcium phosphate powder (strontium doping amount is 20%).

[0063] Example 4 Absorbable and developable polymer composite material According to the mass ratio of strontium-doped tricalcium phosphate powder to PPDO = 30:70, the strontium-doped tricalcium phosphate powder prepared in Example 1 was mixed and stirred evenly with PPDO, and then extruded and granulated by a twin-screw extruder, and injection molded into discs with a diameter of 10 mm and a thickness of 1 mm, denoted as S1.

[0064] Example 5 Absorbable and developable polymer composite material According to the mass ratio of strontium-doped tricalcium phosphate powder to PPDO = 30:70, the strontium-doped tricalcium phosphate powder prepared in Example 2 was mixed and stirred evenly with PPDO, and then extruded and granulated by a twin-screw extruder, and injection molded into discs with a diameter of 10 mm and a thickness of 1 mm, denoted as S2.

[0065] Example 6 Absorbable and developable polymer composite material According to the mass ratio of strontium-doped tricalcium phosphate powder to PLGA = 50:50, the strontium-doped tricalcium phosphate powder prepared in Example 2 was mixed and stirred evenly with PLGA, and then extruded and granulated by a twin-screw extruder, and injection molded into round discs with a diameter of 10 mm and a thickness of 1 mm, denoted as S3.

[0066] Example 7 Absorbable and developable polymer composite material According to the mass ratio of strontium-doped tricalcium phosphate powder to polylactic acid (PLA) of 50:50, the strontium-doped tricalcium phosphate powder prepared in Example 3 was mixed and stirred evenly with polylactic acid (PLA), and then extruded and granulated by a twin-screw extruder, and injection molded into round discs with a diameter of 10 mm and a thickness of 1 mm, denoted as S4.

[0067] Example 8: Absorbable and developable polymer composite material According to the mass ratio of strontium-doped tricalcium phosphate powder to PCL = 50:50, the strontium-doped tricalcium phosphate powder prepared in Example 3 was mixed and stirred evenly with PCL, then extruded and granulated by a twin-screw extruder, and injection molded into round discs with a diameter of 10 mm and a thickness of 1 mm, denoted as S5.

[0068] Comparative Example 1 PPDO is extruded and granulated using a twin-screw extruder, and then injection molded into round discs with a diameter of 10 mm and a thickness of 1 mm, denoted as C1.

[0069] Comparative Example 2 PLGA is extruded and granulated using a twin-screw extruder, and then injection molded into round discs with a diameter of 10 mm and a thickness of 1 mm, denoted as C2.

[0070] Comparative Example 3 PLA is extruded and granulated using a twin-screw extruder, and then injection molded into round discs with a diameter of 10 mm and a thickness of 1 mm, denoted as C3.

[0071] Comparative Example 4 PCL is extruded and granulated using a twin-screw extruder, and then injection molded into round discs with a diameter of 10 mm and a thickness of 1 mm, denoted as C4.

[0072] Comparative Example 5 Using deionized water as a solvent, prepare 0.3 mol / L strontium nitrate solution, 0.3 mol / L calcium nitrate solution and 0.2 mol / L diammonium hydrogen phosphate solution.

[0073] I. Preparation of Strontium-doped Tricalcium Phosphate Powder (1) Mix strontium nitrate solution and calcium nitrate solution at a volume ratio of 1:9 to obtain a mixed solution; (2) Under stirring conditions, the mixture was gradually added dropwise to an equal volume of diammonium hydrogen phosphate solution (the volume ratio of the mixture to the diammonium hydrogen phosphate solution was 1:1). After the addition was completed, the temperature was raised to 80°C and stirred for 1 hour. Then the temperature was raised to 110°C and stirred for 1 hour to obtain a paste-like product. (3) After the obtained paste product was vacuum dried at 180°C for 12 hours, the product was transferred to a muffle furnace and calcined at 1000°C for 6 hours to obtain strontium-doped tricalcium phosphate powder (strontium doping amount is 10%).

[0074] II. Preparation of absorbable and developable polymer composite materials Strontium-doped tricalcium phosphate powder (10% strontium doping) was mixed with PCL at a mass ratio of 50:50. The mixture was then extruded and granulated using a twin-screw extruder and injection molded into discs with a diameter of 10 mm and a thickness of 1 mm, denoted as C5.

[0075] Comparative Example 6 Using deionized water as a solvent, prepare 0.3 mol / L strontium nitrate solution and 0.3 mol / L calcium nitrate solution.

[0076] I. Preparation of developing materials (1) Take 0.3 mol / L strontium nitrate solution and 0.3 mol / L calcium nitrate solution and mix them in a volume ratio of 1:1 to obtain a mixed solution; (2) Heat the mixture to 80°C and stir for 1 hour, then continue to heat to 110°C and stir for 1 hour. Transfer the product to 180°C and vacuum dry for 12 hours to obtain the developing material.

[0077] II. Preparation of absorbable and developable polymer composite materials The developing material of this comparative example was mixed with PLGA at a mass ratio of 50:50 and stirred evenly. The mixture was then extruded and granulated using a twin-screw extruder and injection molded into discs with a diameter of 10 mm and a thickness of 1 mm, denoted as C6.

[0078] Comparative Example 7 Using deionized water as a solvent, prepare 0.3 mol / L strontium nitrate solution, 0.3 mol / L calcium nitrate solution and 0.2 mol / L diammonium hydrogen phosphate solution.

[0079] I. Preparation of developing materials (1) Take 0.3 mol / L strontium nitrate solution and 0.3 mol / L calcium nitrate solution and mix them in a volume ratio of 1:1 to obtain a mixed solution; (2) Under stirring conditions, the mixture was gradually added dropwise to an equal volume of 0.2 mol / L diammonium hydrogen phosphate solution (the volume ratio of the mixture to the diammonium hydrogen phosphate solution was 1:1). After the addition was completed, the temperature was raised to 110℃ and the mixture was stirred for 2 hours to obtain a paste-like product. (3) After the obtained paste product is vacuum dried at 180°C for 12 hours, the product is transferred to a muffle furnace and calcined at 1200°C for 6 hours to obtain the developing material.

[0080] II. Preparation of absorbable and developable polymer composite materials The developing material of this comparative example was mixed with PLGA at a mass ratio of 50:50 and stirred evenly. The mixture was then extruded and granulated using a twin-screw extruder and injection molded into round discs with a diameter of 10 mm and a thickness of 1 mm, denoted as C7.

[0081] Comparative Example 8 Using deionized water as a solvent, prepare 0.3 mol / L strontium nitrate solution, 0.3 mol / L calcium nitrate solution and 0.2 mol / L diammonium hydrogen phosphate solution.

[0082] I. Preparation of developing materials (1) Mix 0.3 mol / L strontium nitrate solution and 0.3 mol / L calcium nitrate solution at a volume ratio of 1:1 to obtain a mixed solution; (2) Under stirring conditions, the mixture was gradually added dropwise to a 0.3 mol / L diammonium hydrogen phosphate aqueous solution with a volume of 60% of the volume of the mixture (the volume ratio of the mixture to the diammonium hydrogen phosphate solution was 1:0.6). After the addition was completed, the temperature was raised to 80°C and stirred for 1 hour. Then the temperature was raised to 110°C and stirred for 1 hour to obtain a paste-like product. (3) The obtained paste product was vacuum dried at 180°C for 12 hours to obtain the developing material.

[0083] II. Preparation of absorbable and developable polymer composite materials The developing material of this comparative example was mixed with PLGA at a mass ratio of 50:50 and stirred evenly. The mixture was then extruded and granulated using a twin-screw extruder and injection molded into discs with a diameter of 10 mm and a thickness of 1 mm, denoted as C8.

[0084] Comparative Example 9 Using deionized water as a solvent, prepare solutions of 0.2 mol / L dysprosium nitrate, 0.3 mol / L calcium nitrate, and 0.2 mol / L diammonium hydrogen phosphate.

[0085] I. Preparation of developing materials (1) Mix 0.2 mol / L dysprosium nitrate solution and 0.3 mol / L calcium nitrate solution at a volume ratio of 1:1 to obtain a mixed solution; (2) Under stirring conditions, the mixture was gradually added dropwise to a 0.2 mol / L diammonium hydrogen phosphate aqueous solution (the volume ratio of the mixture to the diammonium hydrogen phosphate solution was 1:1). After the addition was completed, the temperature was raised to 80°C and stirred for 1 hour. Then the temperature was raised to 110°C and stirred for 1 hour to obtain a paste-like product. (3) After transferring the paste product to vacuum drying at 180°C for 12 hours, the product is transferred to a muffle furnace and calcined at 1200°C for 6 hours to obtain dysprosium-doped tricalcium phosphate developing material.

[0086] II. Preparation of absorbable and developable polymer composite materials The dysprosium-doped tricalcium phosphate developing material of this comparative example was mixed with PLGA at a mass ratio of 50:50 and stirred evenly. The mixture was then extruded and granulated using a twin-screw extruder and injection molded into discs with a diameter of 10 mm and a thickness of 1 mm, denoted as C9.

[0087] Comparative Example 10 Using deionized water as a solvent, prepare europium nitrate solution with a concentration of 0.2 mol / L, calcium nitrate solution with a concentration of 0.3 mol / L, and diammonium hydrogen phosphate solution with a concentration of 0.2 mol / L.

[0088] I. Preparation of developing materials (1) Mix 0.2 mol / L europium nitrate solution and 0.3 mol / L calcium nitrate solution at a volume ratio of 1:1 to obtain a mixed solution; (2) Under stirring conditions, the mixture was gradually added dropwise to a 0.2 mol / L diammonium hydrogen phosphate aqueous solution (the volume ratio of the mixture to the diammonium hydrogen phosphate solution was 1:1). After the addition was completed, the temperature was raised to 80°C and stirred for 1 hour. Then the temperature was raised to 110°C and stirred for 1 hour to obtain a paste-like product. (3) After transferring the paste product to vacuum drying at 180°C for 12 hours, the product is transferred to a muffle furnace and calcined at 1200°C for 6 hours to obtain europium-doped tricalcium phosphate developing material.

[0089] II. Preparation of absorbable and developable polymer composite materials Europium-doped tricalcium phosphate developing material of this comparative example was mixed with PLGA at a mass ratio of 50:50 and stirred evenly. The mixture was then extruded and granulated using a twin-screw extruder and injection molded into discs with a diameter of 10 mm and a thickness of 1 mm, denoted as C10.

[0090] Experimental Example 1: In vitro degradation test (I) Experimental Methods In vitro degradation tests were performed on the disc samples prepared in Examples 4-8 and Comparative Examples 1-10. The disc samples from Examples 4-8 and Comparative Examples 1-10 were placed in PBS buffer solution at pH 7.4 (20 mL per sample) and incubated at 37°C. The PBS buffer solution was replaced weekly to ensure pH stability. Sample changes were observed periodically, and the time required for complete dissolution was recorded.

[0091] (II) Experimental Results The results of the in vitro degradation tests are shown in Table 1. The results showed that all samples exhibited good biodegradability and were completely degraded under simulated physiological conditions. However, the degradation rates varied significantly among different formulations, with complete degradation times ranging from 11 weeks to 152 weeks. This indicates that the composition and proportions of the system, as well as processing conditions, can be adjusted to respond to different clinical needs.

[0092] Table 1. Time required for in vitro simulated degradation of radioactive materials.

[0093] Experiment Example 2: CT Value Test (I) Experimental Methods CT value measurement: The CT values ​​of the circular samples in Examples 4-8 and Comparative Examples 1-10 above were measured using a CT scanner, as well as the CT values ​​of each sample after a certain degradation period.

[0094] The specific measurement method is as follows: Place the sample in the pudding / jelly, fix the pudding / jelly on the water mold, use an external laser light for positioning, align the center of the laser light with the approximate center of the pudding / jelly, and use a CT simulation positioning machine for scanning, with a layer thickness of 5mm.

[0095] (II) Experimental Results The CT value test results are shown in Table 2. The initial CT values ​​of materials S1-S5 were approximately 450 HU, while the CT values ​​of the materials described in comparative examples 1-4 were approximately 100 HU. For comparison, the CT values ​​of fat were -90 to -70 HU, water was 0 HU, soft tissue was 6-80 HU, and bone was 1000 HU. In contrast, the initial CT values ​​of comparative examples C1-C4 without contrast agent were only 90-115 HU, close to those of soft tissue, making them difficult to distinguish effectively in images.

[0096] It is noteworthy that, despite prolonged degradation time, the sample from the example studies maintained a high CT value for an extended period. For instance, the S5 sample still maintained a CT value of 300 HU after 24 months of degradation (e.g., Figure 1 As shown in the figure, this indicates that the strontium-doped tricalcium phosphate developer it contains has excellent stability, is not easily dissolved or lost, and has a long-lasting developing effect. In contrast, the comparative samples C6, C7, and C8 are easily dissolved and cannot maintain a developing effect for a long time.

[0097] The imaging material prepared in this embodiment of the invention not only has good initial imaging performance, but also maintains a stable CT signal during long-term degradation. The imaging agent is not easily dissolved, overcoming the defects of traditional iodine-based imaging agents such as easy diffusion and short imaging time. It is suitable for absorbable medical implant materials that require long-term image tracking.

[0098] Table 2 CT value test results of imaging materials

[0099] Note: / indicates that the sample has been completely degraded and cannot be developed for testing.

[0100] Experimental Example 3: X-ray developing performance test (I) Experimental Methods The samples (S1-S5) of Examples 4-8 and the samples of Comparative Examples 1, 5, 9, and 10 (C1, C5, C8, C10) were photographed using a medical X-ray machine (e.g., ...). Figure 2As shown in the figure, the working distance was maintained at 60cm, the voltage at 70KV, the current at 0.55mA, and the imaging time at 0.79ms. The grayscale of the X-ray image was evaluated using ImageJ software, and the grayscale value of the developed image was quantitatively analyzed.

[0101] (II) Experimental Results The X-ray imaging results are shown in Table 3. The results indicate that the composite materials (S1~S5) prepared in this embodiment exhibit significant high-density shadows in X-ray images, with grayscale contrast values ​​ranging from 0.82 to 0.86, averaging approximately 0.84, significantly higher than the background soft tissue, demonstrating excellent X-ray visibility. In contrast, the X-ray grayscale contrast value of cortical bone under these conditions is approximately 0.74. According to industry standard YY / T 0586-2016, a contrast value difference of approximately 0.1 is sufficient to achieve good tissue differentiation. Therefore, the samples in this embodiment have sufficient contrast with bone tissue, enabling clear identification in clinical X-ray examinations and meeting the needs of long-term post-implantation image tracking.

[0102] In contrast, the contrast value of Comparative Example C1 was only 0.23, almost indistinguishable from soft tissue, and therefore unable to achieve effective imaging. The contrast value of Comparative Example C5 was 0.71, which, although showing some imaging ability, was significantly lower than that of the Example samples and was close to the grayscale of bone tissue, making it difficult to distinguish clearly.

[0103] The comparative values ​​of the C9 sample (dysprosium doped) and the C10 sample (europium doped) were 0.73 and 0.71, respectively. Although slightly higher than C5, they were still significantly lower than the sample of the example and were close to the grayness of cortical bone, making it difficult to accurately identify its position and morphology under X-ray.

[0104] Table 3. Test results of grayscale contrast value of X-ray film for developing materials

[0105] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A method for preparing strontium-doped tricalcium phosphate, characterized in that, The steps include: Ca 2+ 、Sr 2+ The ion mixture solution was added to the phosphate solution, and the mixture was stirred at 70-90℃ for 0.5-1.5 h. The temperature was then raised to 100-120℃ and stirred for another 0.5-1.5 h to obtain the product. The product was dried and then calcined to obtain strontium-doped tricalcium phosphate.

2. The preparation method according to claim 1, characterized in that, Ca 2+ 、Sr 2+ In ionic mixed solutions, Sr 2+ Ions and Ca 2+ The molar ratio of ions is 1:(1~4).

3. The preparation method according to claim 1, characterized in that, Ca 2+ 、Sr 2+ In ionic mixed solutions, Sr 2+ The concentration of ions is 0.06~0.3 mol / L, Ca 2+ The concentration of ions is 0.15~0.24 mol / L.

4. The preparation method according to claim 1, characterized in that, The drying process involves drying at 160-200℃ for 8-14 hours.

5. The preparation method according to claim 1, characterized in that, The calcination treatment is performed at 900~1200℃ for 4~8 hours.

6. Strontium-doped tricalcium phosphate prepared by any one of the preparation methods according to claims 1 to 5.

7. The use of the strontium-doped tricalcium phosphate as described in claim 6 as a developer.

8. The application of the strontium-doped tricalcium phosphate as described in claim 6 in the preparation of developing materials.

9. An absorbable developing material, characterized in that, It contains a developer and a polymeric material; the developer is the strontium-doped tricalcium phosphate as described in claim 7, and the polymeric material is at least one of poly(ethylene lactide), polylactic acid, polycaprolactone, polyglycolic acid, and poly(p-dioxanone).

10. The absorbable developing material according to claim 9, characterized in that, The mass ratio of developer to polymer material is (1~5):(5~9).

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