Method and device for testing uniformity of drug coating of balloon dilatation catheter

Abstract

The invention belongs to the technical field of medical instruments, and particularly relates to a balloon dilatation catheter drug coating uniformity testing method and device.In the preset temperature environment, a balloon dilatation catheter is filled with liquid phase-change shaping filler, then the environment temperature is reduced to the testing temperature, and the uniformity of the balloon dilatation catheter drug coating is tested. According to the method, the phase change shaping filler is solidified and shaped in the balloon dilatation catheter, so that the solidified and shaped balloon dilatation catheter can be axially and / or radially cut at the test temperature to obtain a plurality of to-be-detected sample segments with regular shapes, and the area or length of each part of the to-be-detected sample segments can be conveniently calculated. Meanwhile, according to the type of the medicine attached to the balloon dilatation catheter, the content of the medicine on the sample segment to be detected is detected by utilizing a chemical analysis quantitative detection method, so that the measurement precision of the medicine content is effectively ensured; and evaluating the uniformity of the drug coating according to the area or length of each sample segment to be detected and the measured drug content.

Description

Technical Field

[0001] This invention belongs to the technical field of medical devices, specifically relating to a method and apparatus for testing the uniformity of drug coating on balloon dilation catheters. Background Technology

[0002] Drug-coated balloon dilatation catheters are balloon dilatation catheters with a drug coating such as paclitaxel on their surface. After the balloon reaches the lesion site, it dilates to restore blood flow. The drug is released into the local tissue to inhibit excessive proliferation of smooth muscle cells and reduce the inflammatory response, thereby inhibiting excessive intimal hyperplasia and reducing restenosis. With its "intervention without implantation" treatment concept and increasingly abundant clinical evidence, drug-coated balloons have shown extremely broad application prospects in areas such as in-stent restenosis, small vessel disease, and branch ostial disease.

[0003] The uniformity of the drug coating is a prerequisite for ensuring that the drug can evenly cover the blood vessel wall at the lesion site, and it is also a necessary indicator of product process stability. Current technical documents such as the "Guiding Principles for Registration Review of Drug-Coated Balloon Dilatation Catheters" and ASTM F 3320-18: Standard Guide for Coating Characterization of Drug-Coated Balloons both stipulate that the longitudinal and circumferential uniformity of the coating should be evaluated, but specific test equipment and measurement methods are not provided.

[0004] Existing measurement techniques have the following problems: 1. Due to the light weight of the balloon, the mass method has a large error.

[0005] 2. Because the balloon is made of flexible material and is mostly supplied in a folded state, direct cutting or cutting after inflation cannot detect regular patterns, making it difficult to obtain the area of ​​each part and resulting in large errors.

[0006] 3. The area obtained by using 3D scanning technology after cutting the balloon is more accurate, but the cost is too high.

[0007] 4. The balloon sizes vary widely, with diameters ranging from 1.0mm to 12mm and lengths from 5mm to 300mm. The ability to cut balloons of different sizes using the same device places high demands on the device's adaptability. Summary of the Invention

[0008] To address the aforementioned technical problems, this invention provides a method and apparatus for testing the uniformity of drug coating on balloon dilation catheters. The method utilizes a phase change molding filler to cure and shape the balloon dilation catheter, followed by axial and radial cutting to obtain regular rectangular samples. This facilitates the testing of the uniformity of the balloon drug coating. This invention is easy to promote and apply, improving enterprise R&D efficiency.

[0009] The technical problem to be solved by the present invention is achieved by the following technical solution: a method for testing the uniformity of drug coating on a balloon dilation catheter, comprising the following steps: Step S1: Under a preset temperature environment, fill the balloon dilation catheter with liquid phase change molding filler, and then lower the ambient temperature to the test temperature so that the phase change molding filler solidifies and shapes inside the balloon dilation catheter. The melting point temperature of the phase change molding filler is higher than the test temperature. Step S2: At the test temperature, the solidified balloon dilation catheter is cut along the axial and / or radial direction to obtain multiple regularly shaped sample fragments to be tested. Step S3: Based on the type of drug attached to the balloon dilation catheter, the drug content on the sample fragment to be tested is detected using a chemical analysis quantitative detection method; Step S4: Evaluate the uniformity of the drug coating based on the area or length of each sample fragment to be tested and the measured drug content.

[0010] Preferably, the quantitative detection method for chemical analysis in step S3 of this invention includes the following steps: Step S3.1, Preparation of test solution: Add the test solvent to the test tube. The amount of test solvent added is calculated based on the specifications of the balloon dilation catheter and the labeled drug content to ensure that the drug concentration of the final test solution is within the range of the standard curve. The sample fragment to be tested is immersed in the test solvent, the drug is completely dissolved by sonication, and then vortexed to mix, thus obtaining the test solution; Step S3.2, Preparation of the reference solution: Weigh an appropriate amount of the reference standard into a volumetric flask, dissolve it with the test solvent, and dilute to the mark to obtain the standard stock solution; Transfer the above standard stock solution and dilute it with the test solvent to prepare a series of standard solutions; Step S3.3: Determine the drug content using a chromatographic analysis instrument. The specific solvent used (e.g., methanol, acetonitrile, or other solutions), the volume added, and the ultrasonic duration for different samples should be set according to the detection requirements.

[0011] Preferably, in step S4 of this invention, the specific method for evaluating the uniformity of the drug coating based on the area or length of each sample fragment to be tested and the measured drug content includes: (1) Evaluation of longitudinal uniformity of drug coating: Divide the balloon dilation catheter into N or more equal-length sample segments to be tested, N≥3; The lengths of each sample segment to be tested are L i The drug content of each sample fragment to be tested was analyzed separately to obtain m. i , i=1...N; The expected drug content of each sample fragment to be tested is calculated using the following formula: m i '=L i / * ; The drug content on each sample fragment to be tested is compared with the expected drug content, and calculated as a percentage: The % content of the i-th fragment (Qi) is as follows: (m i / m i ')×100%; (2) Evaluation of drug circumferential uniformity: Divide the balloon dilation catheter into more than M uniform sample segments along the circumference, M≥2; The area of ​​each sample segment to be tested is Sj. The drug content of each sample segment to be tested is analyzed to obtain mj, j=1...N; The expected drug content of each sample fragment to be tested is calculated using the following formula: m j '=S j / * ; The drug content on each sample fragment to be tested is compared with the expected drug content, and calculated as a percentage: For the j-th fragment (Qj), the percentage content is as follows: (m j / m j ')×100%; (3) Simultaneously determine the longitudinal and circumferential uniformity of the drug coating: Divide the balloon dilation catheter into N equal parts along the longitudinal direction and M equal parts along the circumferential direction, for a total of N*M parts, N≥3, M≥2; Calculate the area of ​​each part, S. ij The drug content of each sample fragment to be tested was analyzed separately to obtain m. ij , i=1...N, j=1...M; The masses of each segment of the sample to be tested along the longitudinal direction are m i = The masses of each segment of the sample to be tested along the circumference are m. j = ; The lengths of the sample segments to be tested along the longitudinal direction are L. i The areas of each segment of the sample to be tested along the circumference are S j = ; The remaining steps are the same as those for evaluating the longitudinal uniformity of the drug coating and the circumferential uniformity of the drug.

[0012] Preferably, the phase change shaping filler of this invention is a eutectic mixture with a melting point of 35°C to 45°C. A eutectic mixture refers to a physical mixture in which the melting point is significantly reduced due to changes in intermolecular forces after mixing two or more substances in a specific ratio. By selecting a eutectic mixture with a melting point higher than the test temperature as the phase change shaping filler, the balloon dilation catheter is filled above the melting point of the eutectic mixture. Then, at the test temperature, the balloon dilation catheter maintains a fixed shape under the filling of the eutectic mixture. The phase change temperature of the eutectic mixture is controlled slightly above room temperature, but not too high. For example, around 35°C to 45°C, the mixture is first placed in a water bath slightly above the phase change temperature to make it liquid. The liquid is then drawn up with a syringe and injected into the balloon (this temperature will not be too high to cause balloon deformation or drug denaturation). At room temperature, it gradually solidifies, providing stable support for the balloon and facilitating cutting. (Without support, cutting would cause air leakage and prevent the balloon from being cut into uniform pieces.)

[0013] Preferably, the eutectic mixture of the present invention is a quaternary eutectic mixture of quinic acid-lauric acid-myristic acid-palmitic acid (QA-LA-MA-PA); The specific proportions, calculated by weight percentage, are: 8%-15% decanoic acid + 35%-45% lauric acid + 25%-35% myristic acid + 10%-15% palmitic acid. This quaternary eutectic mixture of decanoic acid, lauric acid, myristic acid, and palmitic acid (QA-LA-MA-PA) is biodegradable, non-toxic (ISO 10993 certified), reusable, and has a melting point of 39-41 degrees Celsius, meeting usage requirements.

[0014] The present invention also discloses a balloon dilation catheter drug coating uniformity testing device for the above-mentioned balloon dilation catheter drug coating uniformity testing method, including a support and a clamping assembly; The clamping assembly includes a left gripper, a right gripper, and a drive mechanism; The left and right grippers are arranged opposite each other and can be slidably mounted on the bracket. The drive mechanism is used to drive the left and right grippers to move relative to each other. The upper end of the left gripper is provided with first gripping comb teeth that are spaced apart from each other. The first gripping comb teeth are arched and the ends of the first gripping comb teeth are provided with concave first gripping surfaces. The upper end of the right gripper is provided with a second gripping comb tooth that is spaced apart from each other. The second gripping comb tooth is arched and the end of the second gripping comb tooth is provided with a concave second gripping surface. The left and right grippers are provided with radial cutting gaps corresponding to their positions, and the first and second gripping surfaces are arranged opposite to each other. Since the first and second gripping combs are arched, the balloon dilation catheter can be suspended and clamped, facilitating the cutting of the balloon dilation catheter along the axial and / or radial direction.

[0015] Preferably, in this invention, the left gripper is provided with an arched first support tooth on the front side of the first gripping comb tooth, and the first support tooth and the first gripping comb tooth are spaced apart. The right gripper is provided with an arched second support tooth on the front side of the second gripping comb tooth, and the second support tooth and the second gripping comb tooth are spaced apart. The first support tooth has an upward-opening first support groove at its end, and the second support tooth has an upward-opening second support groove at its end. The end of the balloon dilation catheter is tapered, so it will not contain any medication or be clamped. To prevent the end of the balloon dilation catheter from falling off during the cutting process and making it difficult to retrieve, the left jaw has an arched first support tooth on the front side of the first clamping comb, and the right jaw has an arched second support tooth on the front side of the second clamping comb. The first support groove with the opening at the end of the first support tooth and the second support groove with the opening at the end of the second support tooth are used to catch the tip of the balloon dilation catheter that has been radially cut off. In addition, the first and second support groove structures provide the necessary space for placement, making it convenient for the operator to hold the balloon dilation catheter between the left and right jaws.

[0016] Preferably, the driving mechanism of the present invention includes a guide rod, a bidirectional screw, and a knob fixedly mounted on the bracket; The guide rod and the bidirectional screw are arranged in parallel. The bidirectional screw has two ends with opposite thread directions, and the left and right jaws are respectively threaded to both ends of the bidirectional screw. The left and right grippers are slidably mounted on the guide rod; The knob is connected to a bidirectional screw and is used to drive the bidirectional screw to rotate. This invention utilizes the bidirectional screw to drive the left and right grippers to move relative to each other, so as to clamp balloon dilation catheters of different sizes. The knob structure allows the operator to control the clamping force on the balloon dilation catheter and avoid excessive clamping force that could cause the drug to fall off.

[0017] Preferably, the present invention further includes an axial cutting mechanism; The axial cutting mechanism includes an axial guide rod, an axial cutting slider, and an axial cutting blade; The axial guide rod is horizontally fixed on the bracket, and the axial cutting slider is slidably mounted on the axial guide rod. The axial cutting blade is vertically mounted on the axial cutting slider and located between the left and right grippers. This invention slidably mounts the axial cutting slider on a horizontally positioned axial guide rod, and mounts the axial cutting blade on the slider. By driving the axial cutting blade through the space between the left and right grippers, the balloon dilation catheter can be cut axially.

[0018] Preferably, the present invention further includes a radial cutting mechanism; The radial cutting mechanism includes a rotating bracket, a radial cutting support plate, and a radial cutting blade; The rotating bracket is vertically mounted on the support, and the end of the radial cutting support plate is pivotally connected to the rotating bracket; The radial cutting blades are spaced apart on the lower end face of the radial cutting support plate, and the radial cutting blades correspond to the radial cutting gap. By rotating the radial cutting support plate, the radial cutting blades below the radial cutting support plate pass through the radial cutting gap, thus completing the radial cutting of the balloon dilation catheter. By setting the gap between two adjacent radial cutting blades, the length of the cut sample along the radial direction of the balloon dilation catheter can be adjusted.

[0019] Compared with existing technologies, the beneficial effects of this invention are as follows: The method for testing the uniformity of drug coating on balloon dilatation catheters involves filling a balloon dilatation catheter with a liquid phase change filler at a preset temperature. Then, the ambient temperature is lowered to the test temperature, allowing the phase change filler to solidify within the balloon dilatation catheter. This enables the solidified balloon dilatation catheter to be cut axially and / or radially at the test temperature, yielding multiple regularly shaped sample fragments for testing. This facilitates the calculation of the area or length of each sample fragment. Furthermore, based on the type of drug adhering to the balloon dilatation catheter, this invention utilizes a chemical analysis and quantitative detection method to detect the drug content on the sample fragments, effectively ensuring the accuracy of drug content measurement. The uniformity of the drug coating can be evaluated based on the area or length of each sample fragment and the measured drug content.

[0020] The balloon dilation catheter drug coating uniformity testing device of the present invention utilizes the first clamping comb tooth of the left jaw and the second clamping comb tooth of the right jaw to achieve precise clamping of drug-eluting balloons of different sizes, and provides radial and axial cutting gaps for radial and axial cutting of the balloon dilation catheter to cut out rectangular sample segments to be tested, which facilitates the calculation of the area of ​​the sample segments to be tested.

[0021] Since both the first and second clamping surfaces are recessed, the balloon dilation catheter remains between the first and second clamping surfaces even after axial cutting, preventing sample loss and drug detachment that could affect test results. Attached Figure Description

[0022] Figure 1 This is a flowchart of the method for testing the uniformity of drug coating on balloon dilation catheters according to the present invention; Figure 2 This is a schematic diagram of the structure of the balloon dilation catheter drug coating uniformity testing device of the present invention. Figure 1 ; Figure 3 This is a schematic diagram of the structure of the balloon dilation catheter drug coating uniformity testing device of the present invention. Figure 2 ; Figure 4 This is a schematic diagram showing the usage state of the balloon dilation catheter drug coating uniformity testing device of the present invention; Figure 5 This is a schematic diagram of an axial cut of the balloon dilation catheter drug coating uniformity testing device of the present invention; Figure 6 This is a longitudinal cut diagram of the balloon dilation catheter drug coating uniformity testing device of the present invention; In the figure, 1 is the bracket, 2 is the clamping assembly, 21 is the left gripper, 22 is the right gripper, and 23 is the drive mechanism; 211 First clamping comb teeth, 212 First clamping surface; 221 Second clamping comb teeth, 222 Second clamping surface; 100 radial cutting gap; 213 First support tooth, 214 First support groove; 223 Second support tooth, 224 Second support groove.

[0023] 231 Guide rod, 232 Two-way screw, 233 Knob; 3-axis cutting mechanism, 31-axis guide rod, 32-axis cutting slider, 33-axis cutting blade; 4. Radial cutting mechanism, 41. Rotary bracket, 42. Radial cutting support plate, 43. Radial cutting blade. Detailed Implementation

[0024] The technical solutions in the embodiments of the present invention will now be clearly and completely described in conjunction with the accompanying drawings.

[0025] For ease of description, balloon dilation catheters can also be simply referred to as balloons.

[0026] like Figure 1 As shown, a method for testing the uniformity of drug coating on a balloon dilation catheter includes the following steps: Step S1: Under a preset temperature environment, fill the balloon dilation catheter with liquid phase change molding filler, and then lower the ambient temperature to the test temperature to allow the phase change molding filler to solidify and shape inside the balloon dilation catheter. The melting point temperature of the phase change molding filler is higher than the test temperature.

[0027] Specifically, the phase change stabilized filler is first placed in a water bath slightly above the phase transition temperature in a container to make it liquid. The liquid is then drawn up with a syringe and injected into the balloon. At room temperature, the phase change stabilized filler gradually solidifies inside the balloon, providing stable support and facilitating cutting. (Without support, air would leak when cut, and it would be impossible to cut into uniform pieces.)

[0028] Step S2: At the test temperature, the cured balloon dilation catheter is cut along the axial and / or radial direction to obtain multiple regularly shaped sample fragments to be tested. For ease of calculation, the balloon dilation catheter is cut uniformly along the axial and radial directions.

[0029] After cutting, the solid phase change sizing filler is separated from the cut sample fragment to be tested, so as to facilitate subsequent testing.

[0030] Step S3: Based on the type of drug attached to the balloon dilation catheter, the drug content on the sample fragment to be tested is detected using a chemical analysis quantitative detection method.

[0031] Step S4: Evaluate the uniformity of the drug coating based on the area or length of each sample fragment to be tested and the measured drug content.

[0032] The quantitative chemical analysis method in step S3 includes the following steps: Step S3.1, Preparation of test solution: Add the test solvent to the test tube. The amount of test solvent added is calculated based on the specifications of the balloon dilation catheter and the labeled drug content to ensure that the drug concentration of the final test solution is within the range of the standard curve.

[0033] The sample fragment to be tested is immersed in the test solvent, sonicated to completely dissolve the drug, and then vortexed to mix, thus obtaining the test solution.

[0034] Step S3.2, Preparation of the reference solution: Weigh an appropriate amount of the reference standard into a volumetric flask, dissolve it with the test solvent, and dilute to the required mark to obtain the standard stock solution.

[0035] Transfer the above-mentioned standard stock solution and dilute it with the test solvent to prepare a series of standard solutions.

[0036] Step S3.3: Determine the drug content using a chromatographic analysis instrument.

[0037] The specific methods for evaluating the uniformity of the drug coating in step S4 based on the area or length of each sample fragment to be tested and the measured drug content include: (1) Evaluation of longitudinal uniformity of drug coating: The balloon dilation catheter is divided into more than N equal-length sample segments to be tested, N≥3.

[0038] The lengths of each sample segment to be tested are L i The drug content of each sample fragment to be tested was analyzed separately to obtain m. i , i=1...N.

[0039] The expected drug content of each sample fragment to be tested is calculated using the following formula: m i '=L i / * .

[0040] The drug content on each sample fragment to be tested is compared with the expected drug content, and calculated as a percentage: The % content of the i-th fragment (Qi) is as follows: (m i / m i ')×100%.

[0041] (2) Evaluation of drug circumferential uniformity: Divide the balloon dilation catheter into more than M uniform sample segments along the circumference, M≥2.

[0042] The areas of each sample segment to be tested are S j The drug content of each sample fragment to be tested was analyzed separately to obtain m. j , j=1...N.

[0043] The expected drug content of each sample fragment to be tested is calculated using the following formula: m j '=S j / * .

[0044] The drug content on each sample fragment to be tested is compared with the expected drug content, and calculated as a percentage: For the j-th fragment (Qj), the percentage content is as follows: (m j / m j ')×100%.

[0045] (3) Simultaneously determine the longitudinal and circumferential uniformity of the drug coating: Divide the balloon dilation catheter into N equal parts along the longitudinal direction and M equal parts along the circumferential direction, for a total of N*M parts, where N≥3 and M≥2.

[0046] Calculate the area of ​​each part, S. ij The drug content of each sample fragment to be tested was analyzed separately to obtain m. ij , i=1...N, j=1...M.

[0047] The masses of each segment of the sample to be tested along the longitudinal direction are mi = The masses of each segment of the sample to be tested along the circumference are m. j = .

[0048] The lengths of the sample segments to be tested along the longitudinal direction are L. i The areas of each segment of the sample to be tested along the circumference are S j = .

[0049] The remaining steps are the same as those for evaluating the longitudinal uniformity of the drug coating and the circumferential uniformity of the drug.

[0050] The phase change shaping filler is a eutectic mixture.

[0051] The eutectic mixture is a quaternary eutectic mixture of quinic acid, lauric acid, myristic acid, and palmitic acid (QA-LA-MA-PA). The formulation has been validated and optimized; the current composition is 8%-15% decanoic acid (C10) + 35%-45% lauric acid (C12) + 25%-35% myristic acid (C14) + 10%-15% palmitic acid (C16), with a melting point of 39℃-41℃.

[0052] Sample determination was performed using the method described in this embodiment (taking paclitaxel as an example): (1) Preparation of test solution: Place the cut balloon samples of equal area into different stoppered test tubes. Add an appropriate volume of acetonitrile. This volume needs to be calculated based on the balloon specifications and the labeled drug content (the above method is a conventional method. For example, if the linear range is 1-100 μg / mL and the labeled drug content of the sample is 1 mg, the added volume can be set to 20 mL, so that the concentration of the target substance in the test solution is 50 μg / mL, which is in the middle of the standard curve). Ensure that the drug concentration of the final prepared test solution is within the range of the standard curve. Immerse the balloon in acetonitrile, sonicate to completely dissolve the drug, and then vortex mix to obtain the test solution.

[0053] (2) Preparation of reference solution: Weigh an appropriate amount of reference standard into a brown volumetric flask, dissolve it in acetonitrile and dilute to the mark to obtain the standard stock solution. Accurately transfer an appropriate amount of the above solution and dilute it with acetonitrile to prepare a series of standard solutions.

[0054] Current drug capsules typically contain paclitaxel or rapamycin. Brown bottles protect the drug from light, further ensuring its stability, which is especially important for photosensitive drugs. Light exposure can cause paclitaxel to polymerize or break down, and rapamycin is easily oxidized when exposed to light for extended periods. In short, light protection is a crucial protective measure.

[0055] (3) Chromatographic conditions Chromatographic column: octadecylsilane-bonded silica column; mobile phase: methanol-water-acetonitrile (23:41:36); column temperature: 35℃; flow rate: 1.0 mL / min; detection wavelength: 227 nm; injection volume: 10 μL.

[0056] (4) Calculation of results Example 1: Example of longitudinal uniformity of drug coating A drug-eluting balloon is divided into three nearly equal parts, A, B, and C, with each segment having a length of L. A L B L C The drug content of each segment was analyzed separately, and the results are as follows: Measured content of segment A: m A ; Measured content in section B: m B Content determined in section C: m C .

[0057] The expected drug content of segment A of the balloon is calculated using the following formula: m A '=L A / (L) A +L B +L C )*(m A +m B +m C ).

[0058] The drug concentration on segment A of the balloon is compared to the expected drug concentration, calculated as a percentage; for example, for segment A (QA), the % concentration is as follows: (m A / m A ')×100%.

[0059] Example 2: Example of drug circumferential uniformity A drug-eluting balloon is cut circumferentially into two parts that are as even as possible. Measure the area: a surface: S a b side: S b .

[0060] Then, the drug content of each side was analyzed separately, and the results are as follows: Drug content measured on side a: m A Content measured on side b: m b The expected drug content on side a is calculated using the following formula: m a '=S a / (S) a +S b )*(m A +m B +m C ).

[0061] The drug content on side A is compared to the expected drug content, calculated as a percentage; for example, for side A (QA), the % content is as follows: (ma / m a ')×100%.

[0062] Example 3: Simultaneous determination of longitudinal and circumferential uniformity of drug coating A single drug-eluting balloon is divided into approximately three equal parts along its longitudinal direction and two equal parts along its circumference, resulting in a total of six parts: Aa, Ab, Ba, Bb, Ca, and Cb.

[0063] Calculate the area of ​​each part, S. Aa S Ab S Ba S Bb S Ca S Cb The drug content of each part was analyzed separately, and the results were as follows: m Aa m Ab m Ba m Bb m Ca m Cb Then, along the longitudinal direction, m are respectively A =(m Aa +m Ab ), m B =(m Ba +m Bb ), m C =(m Ca +m Cb ), along the circumferential direction, are m respectively a =(m Aa +m Ba +m Ca ), m b =(m Ab +m Bb +m Cb S A =S Aa +S Ab S B =S Ba +S Bb ,S C =S Ca +S Cb .

[0064] The expected drug content of part A is calculated using the following formula: m A '=S A / (S) A +S B +S C )*(m A +m B +m C ).

[0065] The drug content in Part A is compared to the expected drug content, calculated as a percentage; for example, for Part A (QA), the % content is as follows: (m A / m A ')×100%, and the calculation of the remaining part is the same as the example above.

[0066] like Figures 2-6 As shown, a balloon dilation catheter drug coating uniformity testing device is used in the above-mentioned balloon dilation catheter drug coating uniformity testing method, including a support 1 and a clamping assembly 2.

[0067] The clamping assembly 2 includes a left gripper 21, a right gripper 22, and a drive mechanism 23.

[0068] The left gripper 21 and the right gripper 22 are arranged opposite to each other and can be slidably mounted on the bracket 1.

[0069] The drive mechanism 23 is used to drive the left gripper 21 and the right gripper 22 to move relative to each other.

[0070] The upper end of the left gripper 21 is provided with first gripping comb teeth 211 that are spaced apart from each other. The first gripping comb teeth 211 are arched and the ends of the first gripping comb teeth 211 are provided with concave first gripping surfaces 212.

[0071] The upper end of the right gripper 22 is provided with second gripping comb teeth 221 that are spaced apart from each other. The second gripping comb teeth 221 are arched and the ends of the second gripping comb teeth 221 are provided with concave second gripping surfaces 222.

[0072] The left gripper 21 and the right gripper 22 are provided with radial cutting gaps 100 corresponding to their positions, and the first clamping surface 212 and the second clamping surface 222 are arranged opposite to each other. Specifically, the first clamping surface 212 and the second clamping surface 222 are two clamping planes that intersect at an obtuse angle.

[0073] The left gripper 21 is provided with an arched first support tooth 213 on the front side of the first gripping comb tooth 211, and the first support tooth 213 and the first gripping comb tooth 211 are spaced apart.

[0074] The right gripper 22 is provided with an arched second support tooth 223 on the front side of the second gripping comb tooth 221, and the second support tooth 223 and the second gripping comb tooth 221 are spaced apart.

[0075] The first support tooth 213 has an upward-opening first support groove 214 at its end, and the second support tooth 223 has an upward-opening second support groove 224 at its end.

[0076] The drive mechanism 23 includes a guide rod 231, a bidirectional screw 232, and a knob 233, which are fixedly mounted on the bracket 1.

[0077] The guide rod 231 and the bidirectional screw 232 are arranged in parallel.

[0078] The bidirectional screw 232 is rotatably mounted on the bracket 1 via bearings. The bidirectional screw 232 has threads at both ends with opposite directions. The left jaw 21 and the right jaw 22 are threadedly connected to both ends of the bidirectional screw 232, respectively.

[0079] The left gripper 21 and the right gripper 22 are slidably mounted on the guide rod 231.

[0080] The knob 233 is connected to the bidirectional screw 232 and is used to drive the bidirectional screw 232 to rotate.

[0081] The balloon dilation catheter drug coating uniformity testing device also includes an axial cutting mechanism 3.

[0082] The axial cutting mechanism 3 includes an axial guide rod 31, an axial cutting slider 32, and an axial cutting blade 33.

[0083] The axial guide rod 31 is horizontally fixed on the bracket 1, and the axial cutting slider 32 is slidably mounted on the axial guide rod 31.

[0084] The axial cutting blade 33 is vertically mounted on the axial cutting slider 32, and the axial cutting blade 33 is located between the left jaw 21 and the right jaw 22.

[0085] The balloon dilation catheter drug coating uniformity testing device also includes a radial cutting mechanism 4.

[0086] The radial cutting mechanism 4 includes a rotating bracket 41, a radial cutting support plate 42, and a radial cutting blade 43.

[0087] The rotating bracket 41 is vertically mounted on the bracket 1, and the radial cutting support plate 42 is pivotally connected at its end to the rotating bracket 41.

[0088] The radial cutting blades 43 are spaced apart on the lower end face of the radial cutting support plate 42, and the radial cutting blades 43 correspond to the radial cutting gap 100.

[0089] The balloon dilation catheter drug coating uniformity testing device in this embodiment has the following advantages: 1. Improved ease of operation and controllability: The drug-eluting balloon is securely clamped by a two-way screw driven by a knob. The operation is simple and the clamping force is controllable.

[0090] Both axial and radial cutting are accomplished through a dedicated guide structure (the pivot shaft between the axial guide rod 31 and the radial cutting support plate 42), which significantly reduces the difficulty and error of manual operation and improves the accuracy and repeatability of the operation.

[0091] 2. Cutting precision and uniformity are significantly improved: The axial cutting structure slides along the axial guide rod 31, while the balloon dilation catheter can rotate between the first clamping surface 212 and the second clamping surface 222, ensuring that the axial cutting blade 33 can accurately achieve axial equal division cutting and the cutting position is accurate.

[0092] The radial cutting structure's axial rotation design, combined with its radial cutting blade 43, can cut the balloon into small segments of identical length at equal intervals.

[0093] The synergistic effect of the dual precision cutting ensures that the outer surface of the expanded balloon becomes a rectangle with strictly equal area, providing a highly uniform sample with consistent geometry for subsequent experiments.

[0094] 3. Standardized sample preparation: This solution provides a highly standardized and repeatable balloon cutting method that overcomes the problems of inconsistent size and shape caused by manual cutting.

[0095] The resulting rectangular samples of equal area are suitable for studying the coating uniformity of drug-eluting balloons.

[0096] 4. Improve experimental efficiency and reliability: The systematic cutting process, which first uses the left gripper 21 and the right gripper 22 to hold the balloon, and then performs axial and radial cutting, reduces human intervention and shortens the sample preparation time.

[0097] Working principle or working process: 1. Clamping the balloon: First, fill and shape the balloon, then place it between the left clamp 21 and the right clamp 22. Rotate the knob to drive the balloon clamp, namely the left clamp 21 and the right clamp 22, through the rotation of the bidirectional screw to firmly clamp the experimental balloon.

[0098] 2. Axial cutting: The axial cutting blade 33 can be slid along the axial guide rod 31 to accurately divide the experimental balloon axially. Rotating the balloon can achieve multiple equal divisions.

[0099] 3. Radial Cutting: Rotating the radial cutting support plate 42 around the axis, the radial cutting blade 43 on it will cut the balloon into several small segments of the same length. At this time, unfolding the outer surface of the balloon will result in rectangles of equal area.

[0100] Application prospects of this invention: 1. Quality control of drug-coated balloon dilation catheters By performing both axial and radial cutting, the balloon is expanded into rectangular segments of equal area. Combined with chromatographic analysis, the uniformity of the drug coating distribution is quantified. This technology resolves the efficacy differences caused by uneven coating in the production of drug-coated balloon dilatation catheters.

[0101] 2. Support for the research and development of new balloon products By revealing coating process defects through multi-segment cutting, companies can be guided to improve their coating technologies. This also provides technical support for the development of complex, novel balloons.

Claims

1. A method for testing the uniformity of drug coating on a balloon dilation catheter, characterized in that, Includes the following steps: Step S1: Under a preset temperature environment, fill the balloon dilation catheter with liquid phase change molding filler, and then lower the ambient temperature to the test temperature so that the phase change molding filler solidifies and shapes inside the balloon dilation catheter. The melting point temperature of the phase change molding filler is higher than the test temperature. Step S2: At the test temperature, the solidified balloon dilation catheter is cut along the axial and / or radial direction to obtain multiple regularly shaped sample fragments to be tested. Step S3: Based on the type of drug attached to the balloon dilation catheter, the drug content on the sample fragment to be tested is detected using a chemical analysis quantitative detection method; Step S4: Evaluate the uniformity of the drug coating based on the area or length of each sample fragment to be tested and the measured drug content.

2. The method for testing the uniformity of drug coating on a balloon dilation catheter according to claim 1, characterized in that: The quantitative chemical analysis method in step S3 includes the following steps: Step S3.1, Preparation of test solution: Add the test solvent to the test tube. The amount of test solvent added is calculated based on the specifications of the balloon dilation catheter and the labeled drug content to ensure that the drug concentration of the final test solution is within the range of the standard curve. The sample fragment to be tested is immersed in the test solvent, the drug is completely dissolved by sonication, and then vortexed to mix, thus obtaining the test solution; Step S3.2, Preparation of the reference solution: Weigh an appropriate amount of the reference standard into a volumetric flask, dissolve it with the test solvent, and dilute to the mark to obtain the standard stock solution; Transfer the above standard stock solution and dilute it with the test solvent to prepare a series of standard solutions; Step S3.3: Determine the drug content using a chromatographic analysis instrument.

3. The method for testing the uniformity of drug coating on a balloon dilation catheter according to claim 1, characterized in that, The specific methods for evaluating the uniformity of the drug coating in step S4 based on the area or length of each sample fragment to be tested and the measured drug content include: (1) Evaluation of longitudinal uniformity of drug coating: Divide the balloon dilation catheter into N or more equal-length sample segments to be tested, N≥3; The lengths of each sample segment to be tested are L i The drug content of each sample fragment to be tested was analyzed separately to obtain m. i , i=1...N; The expected drug content of each sample fragment to be tested is calculated using the following formula: m i '=L i / * ; The drug content on each sample fragment to be tested is compared with the expected drug content, and calculated as a percentage: The % content of the i-th fragment (Qi) is as follows: (m i / m i ')×100%; (2) Evaluation of drug circumferential uniformity: Divide the balloon dilation catheter into more than M uniform sample segments along the circumference, M≥2; The areas of each sample segment to be tested are S j The drug content of each sample fragment to be tested was analyzed separately to obtain m. j , j=1...N; The expected drug content of each sample fragment to be tested is calculated using the following formula: m j '=S j / * ; The drug content on each sample fragment to be tested is compared with the expected drug content, and calculated as a percentage: For the j-th fragment (Qj), the percentage content is as follows: (m j / m j ')×100%; (3) Simultaneously determine the longitudinal and circumferential uniformity of the drug coating: Divide the balloon dilation catheter into N equal parts along the longitudinal direction and M equal parts along the circumferential direction, for a total of N*M parts, N≥3, M≥2; Calculate the area of ​​each part, denoted as Sij. Analyze the drug content of each sample fragment to be tested to obtain m. ij , i=1...N, j=1...M; The masses of each segment of the sample to be tested along the longitudinal direction are m i = The masses of each segment of the sample to be tested along the circumference are m. j = ; The lengths of the sample segments to be tested along the longitudinal direction are L. i The areas of each segment of the sample to be tested along the circumference are S j = ; The remaining steps are the same as those for evaluating the longitudinal uniformity of the drug coating and the circumferential uniformity of the drug.

4. The method for testing the uniformity of drug coating on a balloon dilation catheter according to claim 1, characterized in that: The phase change shaping filler is a eutectic mixture with a melting point of 35℃~45℃.

5. The method for testing the uniformity of drug coating on a balloon dilation catheter according to claim 4, characterized in that: The eutectic mixture is a quaternary eutectic mixture of quinic acid-lauric acid-myristic acid-palmitic acid (QA-LA-MA-PA); The specific proportions, calculated by weight percentage, are: 8%-15% decanoic acid + 35%-45% lauric acid + 25%-35% myristic acid + 10%-15% palmitic acid.

6. A device for testing the uniformity of drug coating on a balloon dilation catheter, used in the method for testing the uniformity of drug coating on a balloon dilation catheter according to any one of claims 1 to 5, characterized in that: Includes a support (1) and a clamping assembly (2); The clamping assembly (2) includes a left jaw (21), a right jaw (22), and a drive mechanism (23); The left gripper (21) and right gripper (22) are arranged opposite to each other and can be slidably mounted on the bracket (1); The drive mechanism (23) is used to drive the left gripper (21) and the right gripper (22) to move relative to each other; The upper end of the left gripper (21) is provided with first gripping comb teeth (211) that are spaced apart from each other. The first gripping comb teeth (211) are arched and the ends of the first gripping comb teeth (211) are provided with concave first gripping surfaces (212). The upper end of the right gripper (22) is provided with a second gripping comb tooth (221) that is spaced apart from each other. The second gripping comb tooth (221) is arched and the end of the second gripping comb tooth (221) is provided with a concave second gripping surface (222). The left jaw (21) and right jaw (22) are provided with radial cutting gaps (100) corresponding to their positions, and the first clamping surface (212) and the second clamping surface (222) are arranged opposite to each other.

7. The balloon dilation catheter drug coating uniformity testing device according to claim 6, characterized in that: The left gripper (21) has an arched first support tooth (213) on the front side of the first gripping comb tooth (211), and the first support tooth (213) and the first gripping comb tooth (211) are spaced apart; The right gripper (22) has an arched second support tooth (223) on the front side of the second gripping comb tooth (221), and the second support tooth (223) and the second gripping comb tooth (221) are spaced apart; The first support tooth (213) has an upward-opening first support groove (214) at its end, and the second support tooth (223) has an upward-opening second support groove (224) at its end.

8. The balloon dilation catheter drug coating uniformity testing device according to claim 6, characterized in that: The drive mechanism (23) includes a guide rod (231), a two-way screw (232), and a knob (233) fixedly mounted on the bracket (1). The guide rod (231) and the bidirectional screw (232) are arranged in parallel; The bidirectional screw (232) has threads at both ends in opposite directions, and the left jaw (21) and right jaw (22) are threadedly connected to both ends of the bidirectional screw (232); The left gripper (21) and right gripper (22) are slidably mounted on the guide rod (231); The knob (233) is connected to the bidirectional screw (232) and is used to drive the bidirectional screw (232) to rotate.

9. The balloon dilation catheter drug coating uniformity testing device according to claim 6, characterized in that: It also includes an axial cutting mechanism (3); The axial cutting mechanism (3) includes an axial guide rod (31), an axial cutting slider (32), and an axial cutting blade (33). The axial guide rod (31) is horizontally fixed on the bracket (1), and the axial cutting slider (32) is slidably mounted on the axial guide rod (31). The axial cutting blade (33) is vertically arranged on the axial cutting slider (32), and the axial cutting blade (33) is located between the left jaw (21) and the right jaw (22).

10. The balloon dilation catheter drug coating uniformity testing device according to claim 6, characterized in that: It also includes a radial cutting mechanism (4); The radial cutting mechanism (4) includes a rotating bracket (41), a radial cutting support plate (42), and a radial cutting blade (43). The rotating bracket (41) is vertically mounted on the bracket (1), and the end of the radial cutting support plate (42) is pivotally connected to the rotating bracket (41); The radial cutting blades (43) are spaced apart on the lower end face of the radial cutting support plate (42), and the radial cutting blades (43) correspond to the radial cutting gap (100).

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