Dual-zone differential melt-mix injection molding method for medical implants and implants

Abstract

This application provides a dual-temperature zone differentiated melt mixing injection molding method for medical implants and an implant, belonging to the field of injection molding technology. The method includes: S1, feeding raw materials into two independently temperature-controlled chambers; the first chamber controls the temperature to fully melt the raw materials, while the second chamber controls the temperature to keep the raw materials in a semi-molten state with solid-liquid coexistence; S2, simultaneously feeding the two states of raw materials into a mixing chamber to mix them, dispersing the semi-molten components within the fully molten matrix to form a mixed melt with a differential distribution of melt degree; S3, injecting the mixed melt into a mold to form the medical implant. This application improves the dimensional stability and structural consistency of the medical implant through differentiated control and stable retention of the initial phase.

Description

Technical Field

[0001] This application belongs to the field of injection molding technology, and particularly relates to a dual-temperature zone differential melt mixing injection molding method for medical implants and the implant itself. Background Technology

[0002] With the increasing prevalence of minimally invasive neurosurgical procedures (such as neuroendoscopic skull base repair), clinical requirements for skull base repair implants have become extremely stringent. To achieve minimally invasive access through narrow orifices, the repair implant needs to be extremely thin to compress its radial dimensions; simultaneously, to ensure efficient closure of the skull base bone window post-operatively, the implant must be able to stably maintain its anatomical and physiological curvature after delivery to the repair area. Currently, medical-grade polycaprolactone (PCL) and other polymeric materials are widely used in precision injection molding technology to prepare these ultrathin implants with complex curvatures.

[0003] However, in existing injection molding processes, to ensure material flowability and surface accuracy within extremely thin cavities (e.g., 0.4mm~0.9mm), process parameters typically prioritize improving melt flow uniformity. But when processing ultra-thin products with specific mechanical requirements, a single process control mode often fails to achieve precise control over the material's phase distribution. This results in the internal structure of ultra-thin products being unable to provide stable support responses after being subjected to compression or bending stress during minimally invasive procedures, easily leading to geometric instability or insufficient shape retention, thus affecting the fit accuracy between the implant and the skull base.

[0004] Because existing technologies lack effective means to intervene in the formation of the material's microstructure during injection molding, the mechanical properties and structural stability of the finished product are extremely sensitive to changes in thickness. How to address the uncontrollable structural formation and insufficient distribution stability of materials during molding, while ensuring the quality of ultra-thin parts, has become a critical technological bottleneck that urgently needs to be solved in the field of high-precision medical device manufacturing. Summary of the Invention

[0005] This application provides a dual-temperature zone differential melt mixing injection molding method for medical implants and an implant, in order to solve the problems of uncontrollable material structure formation and insufficient distribution stability in the preparation of ultra-thin medical implants by existing injection molding processes.

[0006] This application provides a dual-temperature zone differential melt mixing injection molding method for medical implants, comprising the following steps: S1. The pretreated medical polymer raw materials are respectively transported to the first heating chamber and the second heating chamber with independent temperature control. The temperature of the first heating chamber is set to make the medical polymer raw materials inside a fully molten state, and the temperature of the second heating chamber is set to make the medical polymer raw materials inside a semi-molten state with solid and liquid coexistence. S2. Simultaneously transport the medical polymer raw materials in a fully molten state and the medical polymer raw materials in a semi-molten state into the mixing chamber for mixing treatment, so that the semi-molten medical polymer raw materials are dispersed in the fully molten medical polymer raw materials to form a mixed melt with different melting degree distribution. S3. The mixed melt is transported to the injection molding mechanism and injected into the mold cavity for molding to obtain a medical implant.

[0007] As an optional approach in this application, in step S1, the temperature of the first heating chamber is set to be 20°C to 40°C higher than the melting point of the medical polymer raw material and lower than the thermal degradation temperature of the medical polymer raw material. The temperature of the second heating chamber is set within the melting temperature range of the medical polymer raw material, so that the medical polymer raw material in the second heating chamber is in a state of partial melting while retaining part of the solid phase structure.

[0008] As an optional embodiment of this application, in step S2, metering pumps are respectively installed at the outlet ends of the first heating chamber and the second heating chamber. The metering pumps are used to meter and transport the medical polymer raw materials in the fully molten state and the medical polymer raw materials in the semi-molten state, respectively. The mass ratio of the two materials entering the mixing chamber is controlled by adjusting the conveying rate of the metering pumps. The mass ratio of the medical polymer raw materials in the fully molten state to the medical polymer raw materials in the semi-molten state is 3:1 to 7:1.

[0009] As an optional approach in this application, in step 2, when the fully molten medical polymer raw material and the semi-molten medical polymer raw material are mixed in the mixing chamber, the mixing components built into the mixing chamber are used to stir at a low speed of 50 r / min to 300 r / min to obtain a uniformly mixed melt.

[0010] As an optional aspect of this application, during the mixing process, the temperature inside the mixing chamber is controlled to be lower than the temperature of the first heating chamber and within the melting temperature range of the medical polymer raw material.

[0011] As an optional method of this application, in step S3, the mixed melt is injected into the mold cavity at an injection rate of 10-50 mm / s by the injection molding mechanism, and the injection pressure is controlled at 50-90 MPa. After injection, a holding pressure of 30-80 MPa is applied for holding treatment for 30-60 seconds. After holding, the mold is subjected to gradient cooling so that the mixed melt is formed into a medical implant in the mold cavity. The specific method of gradient cooling is as follows: The mold temperature is reduced from the initial temperature to the first temperature and maintained at the first temperature for a set time; the first temperature is set to be within the crystallization temperature range of the medical polymer raw material. After the set time has elapsed, the mold temperature is further reduced to a second temperature for demolding; the second temperature is lower than the first temperature and is a temperature that allows the mixed melt to solidify and meets the demolding conditions.

[0012] As an optional embodiment of this application, the medical polymer raw materials used include medical-grade polycaprolactone powder and nano-hydroxyapatite particles; wherein, the nano-hydroxyapatite particles account for 1% to 3% of the total mass of the medical polymer raw materials; the number average molecular weight of the polycaprolactone powder is 80,000 to 120,000, and the average particle size of the nano-hydroxyapatite particles is 50 nm to 100 nm; and the polycaprolactone powder is vacuum dried before use.

[0013] As an optional approach in this application, the raw material pretreatment prior to step S1 includes high-speed mixing and preparation of medical polymer raw materials: Medical-grade polycaprolactone powder and nano-hydroxyapatite particles are fed into a high-speed mixer. At the same time, 0.1% to 0.3% of medical-grade polyethylene glycol 400 as a dispersant is added as the total mass of the mixture of medical-grade polycaprolactone powder and nano-hydroxyapatite particles. The speed is adjusted to 1800 r / min to 2200 r / min, and the temperature of the mixing chamber is controlled at 40℃ to 50℃. The mixture is continuously mixed for 20 min to 30 min to allow the nano-hydroxyapatite particles to fully penetrate and uniformly disperse in the polycaprolactone matrix, forming a homogeneous composite material with tight interfacial bonding. After mixing, the mixture is removed, sealed, and stored for later use.

[0014] As an optional embodiment of this application, after step S3, post-processing of the formed medical implant is also included: Aseptic trimming and deburring are performed on the initially formed medical implant. Then, a low-temperature annealing process is performed, in which the medical implant is placed at 60℃~100℃ for 1h~2h to eliminate the molding internal stress of the medical implant and improve its dimensional stability. After the annealing process, the medical implant is cleaned, and then cleanliness and biocompatibility are tested. If it passes the test, it is aseptically packaged.

[0015] As an alternative approach to this application, the method is applicable to the preparation of implants for minimally invasive skull base surgery.

[0016] This application also provides an implant for minimally invasive skull base surgery, said implant being prepared according to the dual-temperature zone differential melt mixing injection molding method for medical implants described in any of the above claims.

[0017] Compared with the prior art, the dual-temperature zone differential melt mixing injection molding method for medical implants provided in this application has the following advantages: 1. This application, by setting up independently temperature-controlled first and second heating chambers, ensures that the materials involved in mixing are in a preset state of difference in melting degree at the front end of processing, thereby changing the single path of material state change in traditional processes. This method transforms the structure formation process, which originally relied mainly on the natural evolution during the molding and cooling stages, into a controllable construction process based on the difference in the initial melting state, which helps to improve the controllability of material structure formation during the molding process.

[0018] 2. By simultaneously conveying and mixing materials in both fully molten and semi-molten states, this application enables the formation of structural features with differentiated melt distributions within the mixed melt. This structural feature reduces the dependence of structural formation on a single cooling path during material entry into the mold cavity and subsequent solidification, thus contributing to improved consistency and stability of the internal structural distribution of the material.

[0019] 3. This application utilizes fully molten components to maintain the mold-filling flow capability of materials during injection molding, while introducing semi-molten components to reduce the random fluctuations in structure formation during molding to a certain extent. This helps to improve the stability of the product's structural distribution while ensuring the smooth progress of the molding process. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 A general process flow diagram of the dual-temperature zone differential melt mixing injection molding method for medical implants provided in the embodiments of this application; Figure 2This is a schematic diagram illustrating the principle of the differentiated melting and mixing process in two temperature zones in steps S1 and S2 of the embodiments of this application; Figure 3 This is a schematic diagram of the temperature-time curve of the gradient cooling process in step S3 of the embodiment of this application; Figure 4 This is a comparison diagram of the internal structural features of the implants prepared in Example 1 and the comparative example of this application, wherein: Figure 4 Curve (a) is a schematic diagram of the differential scanning calorimetry (DSC) heat flow curve of the product of Example 1, showing a relatively wide endothermic characteristic; curve (b) is a schematic diagram of the DSC heat flow curve of the comparative example product, showing a single narrow melting peak. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions in the embodiments of this application are described clearly and completely below. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without creative effort are also within the scope of protection of this application.

[0023] Please see Figures 1-4 , Figure 1 A general process flow diagram of the dual-temperature zone differential melt mixing injection molding method for medical implants provided in the embodiments of this application; Figure 2 This is a schematic diagram illustrating the principle of the differentiated melting and mixing process in two temperature zones in steps S1 and S2 of the embodiments of this application; Figure 3 This is a schematic diagram of the temperature-time curve of the gradient cooling process in step S3 of the embodiment of this application; Figure 4 This is a comparison diagram of the internal structural features of the implants prepared in Example 1 and the comparative example of this application, wherein: Figure 4 Curve (a) is a schematic diagram of the differential scanning calorimetry (DSC) heat flow curve of the product of Example 1, showing a relatively wide endothermic characteristic; curve (b) is a schematic diagram of the DSC heat flow curve of the comparative example product, showing a single narrow melting peak.

[0024] like Figure 1 and Figure 2 As shown in the embodiments of this application, a dual-temperature zone differential melt mixing injection molding method for medical implants is provided, comprising the following steps: S1. The pretreated medical polymer raw materials are respectively transported to the first heating chamber and the second heating chamber with independent temperature control. The temperature of the first heating chamber is set to make the medical polymer raw materials inside a fully molten state, and the temperature of the second heating chamber is set to make the medical polymer raw materials inside a semi-molten state with solid and liquid coexistence. S2. Simultaneously transport the medical polymer raw materials in a fully molten state and the medical polymer raw materials in a semi-molten state into the mixing chamber for mixing treatment, so that the semi-molten medical polymer raw materials are dispersed in the fully molten medical polymer raw materials to form a mixed melt with different melting degree distribution. S3. The mixed melt is transported to the injection molding mechanism and injected into the mold cavity for molding to obtain a medical implant.

[0025] In this embodiment, medical polymer raw materials are introduced into the first and second heating chambers respectively, and different temperatures are applied to them, so that one part of the raw material is in a fully molten state, while the other part is in a semi-molten state with solid-liquid coexistence. This treatment method allows the materials participating in subsequent mixing to have different melting characteristics before entering the mixing stage. Compared with heating all materials to a single state, the above treatment allows the materials to form a differentiated physical state basis in the initial stage, thereby providing conditions for the formation of a melt with certain structural characteristics during subsequent mixing. In application, the temperature of the two heating chambers can be adjusted to allow one part of the material to have good fluidity, while the other part retains a certain solid structure to meet the needs of subsequent mixing and molding.

[0026] In step S2 of the above embodiment, two materials in different states are simultaneously transported to a mixing chamber for mixing. During the mixing process, the semi-molten material exists as a dispersed phase within the fully molten continuous phase, resulting in a distribution structure with varying degrees of melting within the mixed melt. Since this structure is formed during the mixing stage, rather than entirely dependent on natural changes during subsequent molding, it reduces the randomness of the material's internal structure formation to some extent. In application, by controlling the synchronicity of the two materials' transport and the mixing process, the semi-molten material can form a relatively uniform dispersion within the fully molten matrix, thus ensuring that the mixed melt already possesses a certain structural distribution foundation before entering the molding stage.

[0027] Furthermore, in step S3, in this embodiment, the aforementioned mixed melt is directly conveyed to the injection molding mechanism and injected into the mold cavity for molding. Since the mixed melt already possesses a distribution characteristic of materials with different melting points before entering the mold cavity, this distribution characteristic can be retained to a certain extent during injection molding and subsequent solidification processes. This results in a more stable internal structure of the final medical implant compared to products formed from traditional single-state melt molding. In practice, the injection molding process can be controlled according to the mold structure and product dimensions, allowing the mixed melt to complete filling and molding within the mold cavity, resulting in a product with a relatively stable structural distribution.

[0028] Furthermore, the dual-temperature zone differentiated melt mixing injection molding method provided in this embodiment controls the initial melt state of the material, enabling the mixed melt to possess a certain structural distribution basis before entering the mold cavity. Since this structural basis can be retained to some extent during subsequent molding, compared to methods that rely entirely on the natural formation of the structure during cooling, this method reduces the sensitivity of the product structure to fluctuations in the cooling environment, thus helping to improve the consistency of the product's structural distribution during mass production. When used to prepare medical implants with high structural stability requirements, it exhibits relatively stable process adaptability.

[0029] Furthermore, in step S1, the temperature of the first heating chamber is set to be 20°C to 40°C higher than the melting point of the medical polymer raw material and lower than the thermal degradation temperature of the medical polymer raw material. The temperature of the second heating chamber is set within the melting temperature range of the medical polymer raw material, so that the medical polymer raw material in the second heating chamber is in a state of partial melting while retaining part of the solid phase structure.

[0030] In this embodiment, by setting the temperature of the first heating chamber to be 20°C to 40°C above the melting point of the raw material but below its thermal degradation temperature, the material within the first heating chamber can achieve good processing fluidity. This temperature range helps the polymer raw material to completely melt, ensuring the melt's ability to fill the mold while avoiding damage to the material's thermal stability due to excessively high temperatures. This control method ensures that the first heating chamber can continuously output a continuous phase melt with a uniform state and stable fluidity, providing a stable process foundation for subsequent molding processes.

[0031] Meanwhile, the temperature of the second heating chamber is set within the melting temperature range of the raw material, with the aim of maintaining this portion of the material in a controlled solid-liquid coexistence phase. The requirement that the temperature of the second heating chamber be set within the melting temperature range means that the temperature must be controlled at the melting point. T m Below the initial melting point (when the material begins to soften and a small number of unstable small grains begin to melt) and above this temperature, the material is not completely fluidized but retains a certain proportion of solid structure, thus forming a non-uniform material characteristic at the processing front end. When subsequently mixed with the melt in the first heating chamber, these retained solid structures can exist in a dispersed form within the fully molten matrix. Through this synergistic limitation of the temperature difference between the two chambers, the present invention improves the controllability of the initial melting state distribution of the material to a certain extent, providing the necessary physical prerequisite for forming a mixed melt with differentiated distribution characteristics.

[0032] In some embodiments, in step S2, metering pumps are respectively installed at the outlet ends of the first heating chamber and the second heating chamber. The metering pumps are used to meter and transport the medical polymer raw materials in the fully molten state and the medical polymer raw materials in the semi-molten state, respectively. The mass ratio of the two materials entering the mixing chamber is controlled by adjusting the conveying rate of the metering pumps. The mass ratio of the medical polymer raw materials in the fully molten state to the medical polymer raw materials in the semi-molten state is 3:1 to 7:1.

[0033] In this embodiment, by setting metering pumps at the outlets of the first and second heating chambers respectively, quantitative control of the process of materials in different molten states entering the mixing chamber is achieved. Since there are certain differences in the fluidity between fully molten and semi-molten materials, adjusting the delivery rate of each metering pump can effectively alleviate the delivery fluctuations caused by inconsistent material viscosity, thus helping to ensure the stability of the component ratio before entering the mixing stage. This dual-pump linkage metering method transforms the component input during the mixing process into controllable process parameters, which helps improve the stability of the phase distribution within the mixed melt and provides a material basis for the subsequent formation of a stable differentiated distribution structure.

[0034] Furthermore, this embodiment limits the mass ratio of fully molten to semi-molten materials to between 3:1 and 7:1, a process detail that balances material flowability and structural distribution stability. When the mass ratio is within this range, the larger proportion of fully molten material constitutes the continuous phase, providing the necessary flowability to support injection molding filling; while the smaller proportion of semi-molten material, as the dispersed phase, is distributed in a dispersed form within the matrix. This avoids both excessively high proportions that would increase the overall melt viscosity and affect mold filling, and excessively low proportions that would weaken the structural function. Through this synergistic limitation of the ratio, this embodiment improves the flow and distribution of the mixed melt to a certain extent, enabling the molded medical implant to maintain a relatively thin wall thickness while achieving a more uniform structural foundation, thereby contributing to improved product consistency.

[0035] In some embodiments, in step 2, when the fully molten medical polymer raw material and the semi-molten medical polymer raw material are mixed after entering the mixing chamber, the mixing components built into the mixing chamber are used to stir at a low speed of 50 r / min to 300 r / min to obtain a uniformly mixed melt.

[0036] In this embodiment, controlling the mixing component to perform low-speed stirring within the rotation speed range of 50 r / min to 300 r / min helps to achieve stable mixing of materials in different states. Since there is a viscosity difference between fully molten and semi-molten materials when they enter the mixing chamber, setting the above-mentioned specific low rotation speed range can generate a moderate shearing effect, guiding the semi-molten components to disperse in the continuous phase matrix, thereby obtaining a mixed system with a relatively uniform component distribution on a macroscopic scale.

[0037] Meanwhile, this low-speed stirring mode limits the energy input of mechanical shear to the material, helping to avoid adverse effects on the phase state of the semi-molten components due to excessively rapid local shear heating, thus maintaining the preset differentiated melting characteristics to a certain extent. Through this gentle mixing control, this embodiment can reduce the risk of unexpected changes in the material state before molding while ensuring the quality of material mixing, thereby helping to improve the controllability of the melt phase distribution during subsequent injection molding.

[0038] In some embodiments, during the mixing process, the temperature inside the mixing chamber is controlled to be lower than the temperature of the first heating chamber and within the melting temperature range of the medical polymer raw material.

[0039] The above embodiments, by controlling the temperature within the mixing chamber to be lower than that of the first heating chamber and within the melting temperature range of the raw materials, help provide a stable temperature environment for the mixing process. Since the fully molten material output from the first heating chamber has a high temperature, if the mixing environment temperature is too high, the semi-molten components dispersed within it are prone to further melting, leading to the loss of the predetermined differentiated structure. By lowering the temperature of the mixing chamber and stabilizing it within the melting temperature range, the impact of the heat carried by the fully molten material on the semi-molten components can be mitigated to some extent, thereby helping to maintain the phase state of the semi-molten components.

[0040] The temperature control method described above helps to suppress unexpected phase transitions of materials during mixing. By maintaining the phase difference between the fully molten and semi-molten states, it ensures the stability of the mixed melt before it enters the injection molding mechanism to a certain extent, which is beneficial to the retention of structural distribution characteristics during subsequent molding.

[0041] In some embodiments, in step S3, the mixed melt is injected into the mold cavity at an injection rate of 10-50 mm / s by the injection molding mechanism, and the injection pressure is controlled at 50-90 MPa. After injection, a holding pressure of 30-80 MPa is applied for holding treatment for 30-60 seconds. After holding, the mold is subjected to gradient cooling so that the mixed melt is formed into a medical implant in the mold cavity. The specific method of gradient cooling is as follows: The mold temperature is reduced from the initial temperature to the first temperature and maintained at the first temperature for a set time; the first temperature is set to be within the crystallization temperature range of the medical polymer raw material. After the set time has elapsed, the mold temperature is further reduced to a second temperature for demolding; the second temperature is lower than the first temperature and is a temperature that allows the mixed melt to solidify and meets the demolding conditions.

[0042] Figure 3 A schematic diagram of the temperature-time curve of the gradient cooling process in step S3 of this embodiment is shown. In this embodiment, limiting the injection rate to 10–50 mm / s and using an injection pressure of 50–90 MPa helps to smoothly fill the mold cavity with the mixed melt. Since the mixed melt has differentiated phase characteristics, a lower injection rate can reduce shearing during the mold filling process, thereby avoiding, to some extent, unintended changes in the preset phase distribution caused by temperature effects due to shearing. After injection molding, applying a holding pressure of 30–80 MPa and maintaining it for 30–60 seconds can compensate for volume shrinkage during material solidification. This holding pressure strategy helps to keep the material in a dense state within the mold, providing a basis for locking in the differentiated distribution characteristics during the initial solidification stage.

[0043] In the subsequent gradient cooling process, lowering the mold temperature to the first temperature within the raw material's crystallization temperature range and maintaining it for a set time is crucial for achieving controlled structure. During this isothermal stage, the crystallization characteristics of the raw material can be utilized, allowing the dispersed semi-molten components to serve as a reference for structural distribution, guiding the material to form a more stable distribution during solidification. Compared to traditional direct cooling methods, this gradient temperature control helps reduce internal stress caused by rapid cooling, positively impacting the uniformity of the product's internal structure.

[0044] After the set time expires, the mold temperature is further reduced to a second temperature that meets the demolding conditions, completing the transition from initial structural locking to final solidification. Because a good structural foundation has been established in the previous stage, the subsequent cooling process has minimal impact on the internal structure of the product, thus ensuring demolding efficiency while better preserving the differentiated distribution characteristics of the initial construction. Through the synergistic effect of injection molding parameters and gradient cooling technology, this invention, to a certain extent, improves the problem of uneven structural distribution in medical implants during molding, contributing to improved geometric accuracy and process consistency of the product.

[0045] In this embodiment, to achieve structural stability control of the mixed melt during the molding process, the first temperature in the gradient cooling process is set within the crystallization temperature range of the medical polymer raw material. This crystallization temperature range is the temperature range in which the material crystallizes during cooling. This temperature range can be obtained by differential scanning calorimetry (DSC) testing or determined based on the thermal performance parameters provided by the material manufacturer. For commonly used biodegradable medical polymer materials in the art, such as polycaprolactone, their crystallization temperature range is typically between 40°C and 60°C, but the specific value can be adjusted according to the different molecular weights and added components of the material.

[0046] During the gradient cooling process, the mold temperature is first reduced from the initial temperature to the crystallization temperature range and maintained within this temperature range for a set time, allowing the mixed melt to undergo controlled crystallization during this stage. Because the semi-molten medical polymer raw material retains some solid-phase structure during the aforementioned dual-temperature melting and mixing process, this portion of the structure can serve as the starting region for crystal growth within the crystallization temperature range, thereby enabling the mixed melt to form a more stable structural distribution on a macroscopic scale.

[0047] After maintaining the set time, the mold temperature is further reduced to a second temperature for cooling and solidification, allowing the overall product to reach the strength required for demolding. This staged cooling method ensures the mixed melt undergoes a controlled crystallization stage and a complete solidification stage during molding, thus avoiding internal stress concentration during rapid cooling and guaranteeing the structural stability and molding consistency of the medical implant.

[0048] Based on the above technical solution, this embodiment introduces a phased controlled gradient cooling process during the injection molding stage. This allows the mold temperature to first decrease to the crystallization temperature range of the medical polymer raw material and maintain this temperature for a set time during the molding process, before further decreasing it to a temperature that meets the demolding requirements. Compared to conventional injection molding processes that use a single cooling rate or rapid cooling and solidification, this technical solution provides controlled crystallization conditions for the mixed melt in the initial cooling stage, allowing it to undergo ordered structural evolution within the crystallization temperature range, rather than directly entering a rapid solidification state.

[0049] Furthermore, since the semi-molten medical polymer raw material retains a portion of its solid phase structure during the aforementioned dual-temperature melting and mixing process, the gradient cooling process enables this portion of the structure to participate in the formation of the material's internal structure during the crystallization stage. This results in a more stable structural distribution in the final medical implant. Compared to the existing method of directly injection molding and rapidly cooling fully molten material, this embodiment achieves full-process control of the material's internal structure formation process through a synergistic control method combining partial solid phase retention with controlled mixing and staged cooling.

[0050] Therefore, this embodiment is not a simple optimized combination of injection parameters or cooling methods in existing injection molding processes. Instead, it uses specific temperature control methods to make the material undergo a controlled crystallization stage and a gradual solidification stage during the molding process under different melting conditions, thereby obtaining a structure formation method that is different from conventional processes.

[0051] In some embodiments, the medical polymer raw materials used include medical-grade polycaprolactone powder and nano-hydroxyapatite particles; wherein, the nano-hydroxyapatite particles account for 1% to 3% of the total mass of the medical polymer raw materials; the number average molecular weight of the polycaprolactone powder is 80,000 to 120,000, and the average particle size of the nano-hydroxyapatite particles is 50 nm to 100 nm; and the polycaprolactone powder is vacuum dried before use.

[0052] In this embodiment, medical-grade polycaprolactone (PCL) powder with a number-average molecular weight of 80,000–120,000 and nano-hydroxyapatite (n-HA) particles of a specific size are selected to provide material support for the subsequent construction of differentiated melt structures. Using PCL powder within this molecular weight range helps to improve the mixing uniformity between components through the physical properties of its powder state while maintaining molding strength, and its flow properties meet the flow requirements during the molding process. The addition of 1%–3% of n-HA particles with an average particle size of 50 nm–100 nm allows them to exist in a dispersed form in the system, thereby forming a relatively uniform distribution.

[0053] During subsequent dual-temperature zone processing, these nanoparticles help maintain the distribution of the dispersed phase. Furthermore, vacuum drying of the PCL powder removes any trace moisture that may be present in the raw material, helping to reduce the risk of material degradation or bubble defects during injection molding. This synergy between component selection and pretreatment improves the component homogeneity and physical stability of the raw material before it enters the heating chamber, thus providing a reliable material basis for forming a stable mixture in subsequent processes.

[0054] In some embodiments, the raw material pretreatment prior to step S1 includes the high-speed mixing and preparation of medical polymer raw materials: Medical-grade polycaprolactone powder and nano-hydroxyapatite particles are fed into a high-speed mixer. At the same time, 0.1% to 0.3% of medical-grade polyethylene glycol 400 as a dispersant is added as the total mass of the mixture of medical-grade polycaprolactone powder and nano-hydroxyapatite particles. The speed is adjusted to 1800 r / min to 2200 r / min, and the temperature of the mixing chamber is controlled at 40℃ to 50℃. The mixture is continuously mixed for 20 min to 30 min to allow the nano-hydroxyapatite particles to fully penetrate and uniformly disperse in the polycaprolactone matrix, forming a homogeneous composite material with tight interfacial bonding. After mixing, the mixture is removed, sealed, and stored for later use.

[0055] In this embodiment, introducing a high-speed mixing pretreatment with specific parameters before step S1 helps improve the distribution of the nano-reinforcing phase in the polymer matrix. Adding 0.1%–0.3% medical-grade polyethylene glycol 400 (PEG400) as a dispersant utilizes its wettability to aid in the dispersion of nano-hydroxyapatite particles in the matrix. The shear force generated under a high rotation speed of 1800–2200 r / min promotes the dispersion of nanoparticles. Simultaneously, controlling the mixing chamber temperature at 40°C–50°C utilizes a mild thermal environment to improve the distribution between components. Through the synergistic effect of physical shearing and temperature control, this invention enables the pre-uniform distribution of inorganic components in the organic matrix before the raw materials enter the heating chamber, providing the necessary component basis for the subsequent formation of a stable mixing system.

[0056] Furthermore, this specific high-speed mixing parameter configuration helps improve the distribution stability of the composite raw materials during subsequent processing. Since the nano-components have already achieved a good initial distribution during the pretreatment stage, the nanoparticles can distribute well with the matrix phase changes when the material enters the fully molten and semi-molten phases in the subsequent S1 step. Especially in the semi-molten phase, this distribution helps reduce the risk of uneven component distribution due to stress in the subsequent S2 mixing stage. Continuous mixing for 20-30 minutes helps ensure good distribution consistency among the various components. This pretreatment method not only helps improve the macroscopic component uniformity of the composite material but also, to a certain extent, ensures the stability of the final product's structural distribution, thus providing a material basis for the quality stability of subsequent products.

[0057] In some embodiments, after step S3, post-processing of the formed medical implant is further included: Aseptic trimming and deburring are performed on the initially formed medical implant. Then, a low-temperature annealing process is performed, in which the medical implant is placed at 60℃~100℃ for 1h~2h to eliminate the molding internal stress of the medical implant and improve its dimensional stability. After the annealing process, the medical implant is cleaned, and then cleanliness and biocompatibility are tested. If it passes the test, it is aseptically packaged.

[0058] In this embodiment, after step S3 is completed, the pre-formed medical implant undergoes aseptic trimming and deburring to remove burrs and flash formed during the forming process, thereby reducing the adverse effects of irregular edge structures on subsequent use. Trimming under aseptic conditions not only improves the boundary morphology of the product, making it more regular, but also helps maintain a relatively clean state before proceeding to subsequent processing steps, providing a stable foundation for subsequent heat treatment.

[0059] Subsequently, the modified medical implant is placed at a temperature of 60℃ to 100℃ and maintained for 1 to 2 hours for low-temperature annealing. Within this temperature range, the material is in a state below its melting temperature and possesses a certain degree of molecular mobility, thereby gradually releasing the internal stress formed during the molding and cooling process. In practical applications, by controlling the annealing temperature and time, the internal structure of the product tends to stabilize, which helps to reduce dimensional changes or local deformations caused by the release of internal stress, thereby improving the dimensional stability of the product.

[0060] After annealing, the product is cleaned, and cleanliness and biocompatibility tests are conducted to confirm its surface condition and safety for use. Once the tests are passed, it is aseptically packaged to maintain relative stability during subsequent storage and transportation, thereby reducing the adverse effects of the external environment on its performance. The synergistic effect of these post-processing steps helps to improve the overall performance of the product in terms of dimensional stability and safety for use.

[0061] The dual-temperature zone differential melt mixing injection molding method provided in the above-described embodiments of this application is applicable to the preparation of implants for minimally invasive skull base surgery.

[0062] In this embodiment, the method is specifically applied to the preparation of implants for minimally invasive skull base surgery, mainly because the aforementioned differentiated melting process can meet the synergistic requirements of ultra-thinness and high stability in skull base repair. In minimally invasive skull base surgery, implants typically need to maintain complex anatomical curvatures with a thickness of 0.4 mm to 0.9 mm. Traditional homogeneous melt molding often struggles to balance thin-wall filling with post-molding shape stability.

[0063] By applying the dual-temperature zone molding process described in this embodiment, the fully molten component provided by the first heating chamber ensures the flow of the melt within the mold cavity, guaranteeing the molding accuracy of the thin-walled structure. Simultaneously, the differentiated distribution characteristics of the solid phase structure retained in the second heating chamber within the mixed melt provide a structural support foundation for the thin-walled product. This process-imposed structural feature helps improve the product's resistance to deformation during demolding and subsequent use, allowing it to better conform to the physiological curvature of the skull base and reducing dimensional deviations caused by stress during minimally invasive approaches. Through a deep integration of process details and clinical needs, the molding method of this embodiment provides a controllable technological means for the high-precision repair of skull base bone defects.

[0064] To further illustrate the implementation process and technical effects of the method described in this embodiment, a detailed description is provided below in conjunction with specific embodiments. In the following embodiments, medical-grade polycaprolactone (PCL) powder (number average molecular weight of 100,000, melting point of approximately 60°C) and nano-hydroxyapatite (n-HA) particles (average particle size of 80 nm) are used as examples of raw materials for illustration.

[0065] It should be noted that in other embodiments, the medical polymer raw material can also be other biodegradable polymer materials with similar melting and crystallization properties. This embodiment is only a preferred implementation method.

[0066] Example 1: Preparation of an ultrathin skull base repair card replica (0.4 mm thick) Raw material pretreatment: Take PCL powder and n-HA particles (n-HA percentage 1%), and add 0.1% PEG400 by mass of the total mixture. Mix in a high-speed mixer at 2000 rpm and 45°C for 25 min. After mixing, vacuum dry.

[0067] Dual-temperature zone melting (S1): The temperature of the first heating chamber is set to 90℃ to ensure that the PCL is in a fully molten state; the temperature of the second heating chamber is set to 59℃ (within the melting temperature range), so that the material is in a semi-molten state where solid and liquid coexist.

[0068] Metering and Mixing (S2): The mass ratio of materials entering the mixing chamber from the first heating chamber and the second heating chamber is controlled at 7:1 by a metering pump. The mixing chamber rotates at 100 r / min, and the chamber temperature is controlled at 58℃.

[0069] Injection molding (S3): Injection rate 30 mm / s, injection pressure 70 MPa. Holding pressure 50 MPa, duration 40 s.

[0070] Gradient cooling: The initial temperature of the mold is reduced to 45℃ (first temperature) and maintained for 45s; then the temperature is reduced to 25℃ (second temperature) for demolding.

[0071] Post-treatment: After trimming, anneal at 80℃ for 1.5h.

[0072] Results: The 0.4mm thick implant was fully filled and had good surface quality. Simulated environmental testing showed that its anatomical curvature was well maintained and its dimensions were stable.

[0073] Example 2: Preparation of a skull defect filler (0.9 mm thick) with high supporting strength Raw material pretreatment: n-HA accounted for 3%, and PEG400 was added at 0.3% of the total mass of the mixture. Mix at 1800 r / min and 50℃ for 30 min.

[0074] Dual-temperature melting (S1): The temperature of the first heating chamber is 85℃; the temperature of the second heating chamber is 58℃, so that it retains a certain proportion of the initial solid phase structure.

[0075] Metering and mixing (S2): The mass ratio is controlled at 3:1. The mixing chamber rotation speed is 250 r / min, and the chamber temperature is 55℃.

[0076] Injection molding (S3): Injection rate 15mm / s, injection pressure 90MPa. Holding pressure 75MPa, duration 60s.

[0077] Gradient cooling: The first temperature is set to 50℃ and maintained for 60 seconds; then the temperature is reduced to 30℃ for demolding.

[0078] Post-treatment: After trimming, anneal at 70℃ for 2 hours.

[0079] Results: The implant exhibited a differentiated phase distribution, resulting in improved compressive strength compared to conventional injection-molded parts, and demonstrated good dimensional stability in simulated environmental testing.

[0080] Example 3: Preparation of a general-purpose skull base auxiliary repair patch (0.6 mm thick) Raw material pretreatment: PCL powder with a number average molecular weight of 100,000 was selected, with n-HA particles accounting for 2%, and PEG400 was added at 0.2% of the total mass of the mixture. In a high-speed mixer, the speed was adjusted to 2200 r / min, the mixing chamber temperature was controlled at 40℃, and the mixture was continuously mixed for 20 min. After mixing, it was sealed and set aside for later use.

[0081] Dual-temperature melting (S1): The pretreated material is conveyed to a dual-temperature chamber. The temperature of the first heating chamber is set to 100℃ (40℃ above the melting point) to completely melt the PCL; the temperature of the second heating chamber is set to 60℃ (within the melting temperature range) to keep the material in a partially melted state while retaining some solid phase structure.

[0082] Metering and Mixing (S2): The mass ratio of fully molten material to semi-molten material entering the mixing chamber is controlled at 5:1 by metering pump. The mixing chamber speed is set to 150 r / min for medium-low speed stirring, and the mixing chamber temperature is controlled at 57℃ to maintain phase differences.

[0083] Injection Molding (S3): The mixed melt is injected into the mold cavity at an injection rate of 50 mm / s, and the injection pressure is controlled at 50 MPa. After injection, a holding pressure of 30 MPa is applied, and the holding time is 30 s.

[0084] Gradient cooling: First, the mold temperature is reduced from the initial temperature to 48℃ (within the crystallization temperature range) and maintained at this temperature for 30 seconds; then the mold temperature is further reduced to 20℃ for demolding.

[0085] Post-processing: The pre-formed implant is aseptically trimmed, then placed at 60°C for 1 hour for low-temperature annealing. After processing, it is cleaned and packaged.

[0086] Results: The 0.6mm implant produced exhibited balanced performance indicators, with relatively stable differential distribution characteristics observed in the internal tissues. Its size fluctuations were small, and its production cycle adaptability was good, which can meet the general clinical application needs of skull base minimally invasive surgery.

[0087] Comparative Example: Conventional Single-Temperature Zone Injection Molding Process The same raw materials and drying conditions as in the above embodiments were used, but the dual-temperature zone control was eliminated. All raw materials were placed in a single heating chamber and heated to 100°C until completely melted, then directly injection molded and rapidly cooled to 25°C using conventional circulating water for demolding.

[0088] Comparative conclusion: The implant prepared in the comparative example is more prone to local shrinkage defects at a thickness of 0.4 mm, and its deformation during subsequent annealing is generally greater than that of the above embodiment. Experimental results show that the dual-temperature zone differentiated melt mixing injection molding method provided in this embodiment, through differentiated control of the initial phase state, reduces the sensitivity of the product structure to cooling environment fluctuations to a certain extent, which helps to improve the consistency of molding quality.

[0089] Process performance and structural characterization testing To further understand the process characteristics and product performance of the dual-temperature zone differentiated melt mixing injection molding method described in this application, process observation and physical performance tests were conducted on the medical implants (cardiops with a thickness of 0.4 mm) prepared in the above embodiments and comparative examples. The test results are recorded in Tables 1 and 2.

[0090] Table 1: Process Observation Records for Different Embodiments and Comparative Examples

[0091] Table 2: Size stability test of implants under simulated physiological environment (37°C saline)

[0092] 1. Characteristic representation of internal structure Figure 4 The figure shows a comparison of the differential scanning calorimetry (DSC) heat flow curves of the implants prepared in Example 1 and the comparative example; where (a) curve is the DSC curve of the product of Example 1, and (b) curve is the DSC curve of the product of the comparative example. Differential scanning calorimetry (DSC) analysis of the implants prepared in Example 1 showed that their heat flow curves exhibited a wide endothermic characteristic within the melting temperature range and showed obvious signs of dual melting peaks. Peak 1 corresponds to the ordered structural basis evolved from the semi-molten components, and peak 2 corresponds to the continuous phase matrix composed of the fully molten matrix. Compared with the single, narrow melting peaks exhibited in the comparative example, Figure 4 The bimodal characteristic objectively reflects the differences in the internal phase composition of the material. This test result indicates that the dual-temperature zone control and mixing process provided in this embodiment helps to form a distribution structure within the product that differs from that of conventional homogeneous melts.

[0093] 2. Microscopic morphological observation The sections from Example 2 were observed using a polarizing microscope (POM). The observations showed that, due to the introduction of semi-molten components during the molding process, a relatively uniform microstructure was formed within the product. Compared to the microstructure formed by rapid cooling in the comparative example, the product prepared in this example exhibited better microstructure distribution characteristics, which corresponds to the dimensional stability performance recorded in Table 2.

[0094] 3. Conclusion Experimental data and characterization results show that this embodiment, through differentiated control of the initial phase of the material, combined with appropriate mixing and cooling processes, improves the phase distribution stability of the ultrathin implant during the molding process to a certain extent. Compared with conventional homogeneous molding processes, the method of this embodiment helps to improve the shape retention capability of the product under complex stress environments, providing a feasible process for the preparation of precision medical implants.

[0095] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.

Claims

1. A method for dual-temperature zone differential melt mixing injection molding of medical implants, characterized in that, Includes the following steps: S1. The pretreated medical polymer raw materials are respectively transported to the first heating chamber and the second heating chamber with independent temperature control. The temperature of the first heating chamber is set to make the medical polymer raw materials inside a fully molten state, and the temperature of the second heating chamber is set to make the medical polymer raw materials inside a semi-molten state with solid and liquid coexistence. S2. Simultaneously transport the medical polymer raw materials in a fully molten state and the medical polymer raw materials in a semi-molten state into the mixing chamber for mixing treatment, so that the semi-molten medical polymer raw materials are dispersed in the fully molten medical polymer raw materials to form a mixed melt with different melting degree distribution. S3. The mixed melt is transported to the injection molding mechanism and injected into the mold cavity for molding to obtain a medical implant.

2. The dual-temperature zone differential melt mixing injection molding method for medical implants according to claim 1, characterized in that, In step S1, the temperature of the first heating chamber is set to be 20°C to 40°C higher than the melting point of the medical polymer raw material and lower than the thermal degradation temperature of the medical polymer raw material. The temperature of the second heating chamber is set within the melting temperature range of the medical polymer raw material, so that the medical polymer raw material in the second heating chamber is in a state of partial melting while retaining part of the solid phase structure.

3. The dual-temperature zone differential melt mixing injection molding method for medical implants according to claim 2, characterized in that, In step S2, metering pumps are installed at the outlets of the first heating chamber and the second heating chamber, respectively. The metering pumps meter and transport the medical polymer raw materials in the fully molten state and the medical polymer raw materials in the semi-molten state, respectively. The mass ratio of the two materials entering the mixing chamber is controlled by adjusting the transport rate of the metering pumps. The mass ratio of the medical polymer raw materials in the fully molten state to the medical polymer raw materials in the semi-molten state is 3:1 to 7:

1.

4. The dual-temperature zone differential melt mixing injection molding method for medical implants according to any one of claims 1-3, characterized in that, In step 2, when the fully molten medical polymer raw materials and the semi-molten medical polymer raw materials are mixed in the mixing chamber, the mixing components built into the mixing chamber are used to stir at a low speed of 50 r / min to 300 r / min to obtain a uniformly mixed melt.

5. The dual-temperature zone differential melt mixing injection molding method for medical implants according to claim 4, characterized in that, During the mixing process, the temperature inside the mixing chamber is controlled to be lower than that of the first heating chamber and within the melting temperature range of the medical polymer raw material.

6. The dual-temperature zone differential melt mixing injection molding method for medical implants according to claim 4, characterized in that, In step S3, the mixed melt is injected into the mold cavity at an injection rate of 10-50 mm / s through the injection molding mechanism, and the injection pressure is controlled at 50-90 MPa. After injection, a holding pressure of 30-80 MPa is applied for holding treatment for 30-60 seconds. After holding, the mold is subjected to gradient cooling so that the mixed melt is formed into a medical implant in the mold cavity. The specific method of gradient cooling is as follows: The mold temperature is reduced from the initial temperature to the first temperature and maintained at the first temperature for a set time; the first temperature is set to be within the crystallization temperature range of the medical polymer raw material. After the set time has elapsed, the mold temperature is further reduced to a second temperature for demolding; the second temperature is lower than the first temperature and is a temperature that allows the mixed melt to solidify and meets the demolding conditions.

7. The dual-temperature zone differential melt mixing injection molding method for medical implants according to claim 4, characterized in that, The medical polymer raw materials used include medical-grade polycaprolactone powder and nano-hydroxyapatite particles; wherein, nano-hydroxyapatite particles account for 1% to 3% of the total mass of the medical polymer raw materials; the number average molecular weight of polycaprolactone powder is 80,000 to 120,000, and the average particle size of nano-hydroxyapatite particles is 50 nm to 100 nm; and the polycaprolactone powder is vacuum dried before use.

8. The dual-temperature zone differential melt mixing injection molding method for medical implants according to claim 7, characterized in that, The raw material pretreatment prior to step S1 includes the high-speed mixing and preparation of medical polymer raw materials: Medical-grade polycaprolactone powder and nano-hydroxyapatite particles are fed into a high-speed mixer. At the same time, 0.1% to 0.3% of medical-grade polyethylene glycol 400 as a dispersant is added as the total mass of the mixture of medical-grade polycaprolactone powder and nano-hydroxyapatite particles. The speed is adjusted to 1800 r / min to 2200 r / min, and the temperature of the mixing chamber is controlled at 40℃ to 50℃. The mixture is continuously mixed for 20 min to 30 min to allow the nano-hydroxyapatite particles to fully penetrate and uniformly disperse in the polycaprolactone matrix, forming a homogeneous composite material with tight interfacial bonding. After mixing, the mixture is removed, sealed, and stored for later use.

9. The dual-temperature zone differential melt mixing injection molding method for medical implants according to any one of claims 5-8, characterized in that, Following step S3, post-processing of the formed medical implant is also included: Aseptic trimming and deburring are performed on the initially formed medical implant. Then, a low-temperature annealing process is performed, in which the medical implant is placed at 60℃~100℃ for 1h~2h to eliminate the molding internal stress of the medical implant and improve its dimensional stability. After the annealing process, the medical implant is cleaned, and then cleanliness and biocompatibility are tested. If it passes the test, it is aseptically packaged.

10. An implant for minimally invasive skull base surgery, characterized in that, The implant is prepared by the dual-temperature zone differential melt mixing injection molding method for medical implants according to any one of claims 1-9.

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