CN114699563B - Supported polyether polyurethane film, preparation method and application thereof - Google Patents

Abstract

The invention belongs to the technical field of medical materials, and particularly relates to a supported polyether polyurethane film, a preparation method and application thereof. The supported polyether polyurethane film provided by the invention is characterized in that the medicine is ultrasonically fused with the film base liquid in the manufacturing process, so that the film is molded into a tube shape after being supported on the surface of the film, and the supported polyether polyurethane film is used for slowly releasing hydrophilic medicine in a liquid solvent in the medical process due to hydrophilicity of a supporting agent, so that the catheter is replaced by being reinserted after being taken down and loaded in the prior art, the operation difficulty and the labor capacity of medical staff are reduced, and meanwhile, the pain of a patient is relieved.

Description

A kind of loaded polyether polyurethane film, preparation method and application thereof

Technical field

The invention belongs to the technical field of medical materials, and in particular relates to a loaded polyether polyurethane film, a preparation method and its application.

Background technique

Polyether polyurethane is mainly defined for polyols in polyurethane materials, that is, the polyols used to prepare polyurethane are entirely composed of polyether polyols or account for the vast majority of the system. In the molecular structure of polyether polyol, the ether bond has low cohesive energy and is easy to rotate. Therefore, the polyurethane material prepared by it has good low-temperature flexibility, excellent hydrolysis resistance, low viscosity of the raw material system, and is easy to dissolve isocyanate, additives and other components. , excellent processing performance.

Medical catheters can be roughly classified according to their functions: infusion catheters, hemodialysis catheters, angiography catheters, intravascular interventional therapy catheters, digestive tract catheters, respiratory catheters, urinary system catheters, catheters for the general system, and surgical catheters. Drainage tubes, etc. However, the existing medical catheters have a single function and can only be used for drainage and conduction. When drug injection is required, the existing catheter needs to be taken out, the drug is injected and then reinserted into the catheter. The operation process is cumbersome and the patient feels obvious pain.

Contents of the invention

In order to solve the above technical problems, the present invention provides a loaded polyether polyurethane film, which includes dissolving polyether polyurethane (PEUR) in tetrahydrofuran solvent, adding a loading agent, ultrasonic mixing, and then pouring it into a mold to evaporate the solvent. Solute self-forming elastomer.

Further, the loading agent is one or more of triamcinolone acetonide, mitomycin, gemcitabine, pirarupicin, and BCG.

The invention also provides a method for preparing a loaded polyether polyurethane film, which method includes:

S1. Dissolve the polyether polyurethane PEUR in the tetrahydrofuran solvent, and stir the solute completely with magnetic stirring for 4 days at room temperature to obtain a uniform transparent solution with a concentration of 1g/20ml;

S2. Add the required dose of loading agent to the transparent solution obtained in step S1, and disperse it evenly in the solution by ultrasonic for 30 minutes to obtain a loading agent-polyether polyurethane mixed solution;

S3. Pour the loading agent-polyether polyurethane mixed solution into a glass petri dish, place it horizontally in a fume hood, and evaporate at room temperature for 1 week to initially obtain a loaded polyether polyurethane base film material;

S4. Then place it in a vacuum drying oven to dry for 2 days to completely evaporate the tetrahydrofuran solvent in the material to obtain the required loaded polyether polyurethane film.

Further, in the described step S2, in order to explore the appropriate drug dosage, a gradient design was adopted, and the transparent solution with a concentration of 1g/20ml obtained in step S1 was divided into four groups: PEUR-0, PEUR-1, PEUR-2, and PEUR-4; Add 0, 25, 50, and 100 mg of loading agent to the transparent solutions of PEUR-0, PEUR-1, PEUR-2, and PEUR-4 groups respectively.

Further, in step S3, the diameter of the glass petri dish is 8-10 mm, and the bottom surface is smooth and flat.

Further, in step S4, the temperature inside the vacuum drying oven is 40-50°C.

The invention also provides a loaded polyether polyurethane film for use in the preparation of catheters in the field of medical supplies.

To sum up, compared with the existing technology, the present invention provides a loaded polyether polyurethane film, a preparation method and its application. The loaded polyether polyurethane film includes dissolving polyether polyurethane (PEUR) in After adding the tetrahydrofuran solvent, the loading agent is added and mixed by ultrasonic, and then poured into the mold to evaporate the solvent solute to form a self-formed elastomer. During the manufacturing process, the drug is ultrasonically fused with the film base fluid to load the film surface and then shape into a tube. Since the loading agent is hydrophilic, it is used for the slow release of hydrophilic drugs in liquid solvents during medical processes to replace In the existing technology, the catheter is removed, the medicine is applied, and then the catheter is re-inserted, which reduces the difficulty of the operation and the workload of medical staff, and at the same time reduces the pain of the patient.

Description of drawings

Figure 1 is a flow chart of a preparation method of a loaded polyether polyurethane film provided by the invention;

Figure 2 is a surface morphology diagram of the loaded polyether polyurethane film provided in Embodiment 3 of the present invention as scanned under a scanning electron microscope;

Figure 3 is an X-ray diffraction (XRD) analysis chart of the supported polyether polyurethane film provided in Example 3 of the present invention;

Figure 4 is an infrared spectrum (FTIR) analysis chart of the supported polyether polyurethane film provided in Example 3 of the present invention;

Figure 5 shows four groups of TA/PEUR three-dimensional morphologies observed using a laser confocal 3D microscope of the loaded polyether polyurethane film provided in Embodiment 3 of the present invention;

Figure 6 is a diagram showing the surface wettability observation effect of the water contact angle of the loaded polyether polyurethane film provided in Embodiment 3 of the present invention;

Figure 7 is an observation and analysis chart of the water contact angle and surface wettability of the loaded polyether polyurethane film provided in Example 3 of the present invention;

Figure 8 is a stress-strain test curve obtained by conducting tensile tests on four groups of loaded polyether polyurethane films provided in Embodiment 3 of the present invention;

Figure 9 shows the Young's modulus test chart obtained by conducting tensile tests on four groups of loaded polyether polyurethane films provided in Embodiment 3 of the present invention;

Figure 10 is a tensile strength test chart obtained by conducting tensile tests on four groups of loaded polyether polyurethane films provided in Example 3 of the present invention;

Figure 11 is the ultimate strain test chart obtained by conducting tensile tests on four groups of loaded polyether polyurethane films provided in Example 3 of the present invention.

Detailed ways

In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the present invention and are not intended to limit the present invention.

The invention provides a loaded polyether polyurethane film, a preparation method and an application thereof. The loaded polyether polyurethane film includes dissolving polyether polyurethane (PEUR) in a tetrahydrofuran solvent, then adding a loading agent and mixing with ultrasonic Then, it is poured into a mold to evaporate the solvent solutes to form a self-formed elastomer. During the manufacturing process, the drug is ultrasonically fused with the film base fluid to load the film surface and then shape into a tube. Since the loading agent is hydrophilic, it is used for the slow release of hydrophilic drugs in liquid solvents during medical processes to replace In the existing technology, the catheter is removed, the medicine is applied, and then the catheter is re-inserted, which reduces the difficulty of the operation and the workload of medical staff, and at the same time reduces the pain of the patient.

Example 1

The invention provides a loaded polyether polyurethane film, which includes dissolving polyether polyurethane (PEUR) in tetrahydrofuran solvent, adding a loading agent, ultrasonic mixing, and then pouring it into a mold to evaporate the solvent solute to self-form. Elastomer; in this example polyether polyurethane: thermoplastic polyurethane, Lubrizol Pellethane Lubrizol 2363-80A; Tetrahydrofuran purchased: CAS number: 109-99-9, T103266 Tetrahydrofuran, ACS, ≥99.0% (GC), contains 250ppm BHT as inhibitor, purchased from Aladdin Biochemical Technology Co., Ltd. (Shanghai, China).

Further, the loading agent is one or more of triamcinolone acetonide, mitomycin, gemcitabine, pirarupicin, and BCG.

In this embodiment, the loading agent is triamcinolone acetonide.

Example 2

The invention provides a method for preparing a loaded polyether polyurethane film, wherein the loaded polyether polyurethane film includes the elastomer as described in Example 1, and the preparation method includes:

S1. Dissolve polyether polyurethane (PEUR) in tetrahydrofuran solvent and stir the solute completely at room temperature for 4 days using magnetic stirring to obtain a uniform transparent solution with a concentration of 1g/20ml, because the concentration of 1g/20ml is close to the maximum solubility ;

S2. Add the required dose of loading agent (in this example, the loading agent is triamcinolone acetonide TA) to the transparent solution obtained in step S1, and make it evenly dispersed in the solution by ultrasonic for 30 minutes to obtain the loading agent-polymer. Ether polyurethane mixed solution;

S3. Pour the loading agent-polyether polyurethane mixed solution into a glass petri dish, place it horizontally in a fume hood, and evaporate at room temperature for 1 week to initially obtain a loaded polyether polyurethane base film material; further, glass culture The diameter of the dish is 8-10mm, and the bottom surface is smooth and flat;

S4. Dry the loaded polyether polyurethane base film initially obtained in step S3 in a vacuum drying oven for 2 days to completely evaporate the tetrahydrofuran solvent in the material to obtain the required supported polyether polyurethane film; further, The temperature inside the vacuum drying box is 40-50°C.

Further, in this example, in order to explore the appropriate drug dosage, a gradient design was adopted, and the transparent solution with a concentration of 1g/20ml obtained in step S1 was divided into four groups: PEUR-0, PEUR-1, PEUR-2, and PEUR- 4; Add 0, 25, 50, and 100 mg of triamcinolone acetonide to the four groups of transparent solutions respectively, analyze and observe the loading status of triamcinolone acetonide, and measure the performance of the four groups of loaded polyether polyurethane base membrane materials.

The specific method for analyzing and observing load conditions is:

1. By scanning electron microscope (SEM);

Considering that the material is not conductive during electron microscopy (SEM) scanning, a high-resolution coating instrument (208HR, Cressingon, UK) was used to spray gold on the material surface before observation. The surface morphology of the film was observed by SEM (SUPRA 35, LEO, Germany) at a working distance of 10.7mm, applying a working voltage of 20kv, and at 1000 times and 10000 times respectively. The surface morphology is shown in Figure 2.

2. Component analysis X-ray diffraction (XRD) and infrared spectroscopy (FTIR);

First, the composition and crystallinity of the material were analyzed by X-ray diffraction (XRD, D8 Advance, BRUKER, Germany) at 2θ angle from 5° to 60° at a rate of 0.5 s/step using Cu kαradiation). Infrared (FTIR, Cary630, Agilent, Germany) was further used to analyze the chemical groups within the 4000–400cm ^-1 absorption spectrum range of the material. The X-ray diffraction analysis pattern is shown in Figure 3. The characteristic peak of polyurethane PEUR corresponds to a broad peak with 2θ of 19.7°, indicating that PEUR is in an amorphous state. Among them, the sharp peaks with 2θ of 9.8°, 14.4°, 17.5°, and 24.7° respectively correspond to the characteristic peaks of triamcinolone acetonide TA, indicating that TA has higher crystallinity and larger grains. The TA characteristic peak signals in PEUR-0, 1, 2, and 4 continue to increase, indicating that the TA component in the membrane continues to increase, which is in line with expectations.

The FTIR analysis spectrum is shown in Figure 4, in which 3398, 1663, 1613, and 1055 cm ^-1 are the typical stretching vibration peaks of TA. Among them, 3398cm ^-1 corresponds to the stretching vibration of the hydrogen bonded hydroxyl group, 1663cm ^-1 corresponds to the stretching vibration of the carbonyl group on the fatty ester bond, 1613cm ^-1 corresponds to the stretching vibration of the C=C unsaturated bond, and 1055cm ^-1 corresponds to the stretching vibration of CF vibration. The peak intensity is consistent with the changes in TA content.

3. Surface roughness;

The surface roughness of the material was analyzed by measuring the three-dimensional morphology of the material surface using a laser confocal 3D microscope (Olympus OLS4000, Olympus, Japan). Line roughness measurement Ra and surface roughness measurement Sa of the material were obtained at 50 times magnification, and each sample was measured individually three times.

The results of observing the three-dimensional morphology of four groups of TA/PEUR are shown in Figure 5. Ra corresponds to the line roughness, which reflects the ups and downs of the material at the macro level. Sa corresponds to the surface roughness and reflects the local average undulation of the material. It can be seen from the results that the load of TA can reduce the roughness of the material to a certain extent. The smooth surface is not easy for cells to adhere and grow, and can also improve the actual comfort. The overall roughness of the materials after loading TA is similar.

4. Static water contact angle;

Make the material into a square piece of 10* ^10mm2 , adhere it to the glass slide, and keep it flat. Drop 2 μL of ultrapure water on the surface of the material, and use a contact angle meter (OCA 15PRO, DATAPHYSICS, Germany) to measure the static water contact angle of the material at 10s, 30s, and 60s respectively. Repeat 3 times.

The water contact angle and surface wettability observation and analysis diagrams are shown in Figures 6 and 7. With the loading of TA, the water contact angle of the film will decrease, the hydrophilicity will increase, and the surface wettability will improve. Similarly Will improve material comfort.

5. Conduct tensile tests on four groups of loaded polyether polyurethane films

The material was made into a rectangular shape of 5*25mm. The actual working gauge length was 10mm. Both ends were supported on an electronic universal testing machine (Instron 5848, Instron, America), running at a speed of 15mm/min. The experimental groups were repeated 5 times in each group to obtain the tensile strength, Young's modulus and ultimate strain.

The stress-strain test curve results are shown in Figure 8; the Young's modulus test results are shown in Figure 9; the tensile strength test results are shown in Figure 10; the ultimate strain test results are shown in Figure 11;

Overall, the load of TA will improve the mechanical properties of the material, and the tensile strength, elastic modulus, and elongation at break will all be improved. But when the TA content increases to 0.786 mg/cm ² , the mechanical properties of PEUR-2 reach the highest. The tensile strength increased from 9.89MPa to 14.24MPa, the elastic modulus increased from 0.15MPa to 3 times that of PEUR-0, and the ultimate strain (i.e. elongation at break) increased from 611.87% to 693.61%.

Example 3

The loaded polyether polyurethane film as described in Examples 1 and 2 is used to prepare medical catheter products to load drugs in the catheter. Since the loading agent loaded on the above TA/PEUR, such as the drug triamcinolone acetonide (TA), is Release slowly during treatment. Specifically, when the loading agent is triamcinolone acetonide (TA), it can be used for anti-inflammatory applications in the treatment of skin diseases, mouth ulcers, etc.; when the loading machine is one of mitomycin, gemcitabine, pirarupicin, BCG, or When used in various forms, it can be used to depolymerize DNA, antagonize DNA replication, etc. during tumor treatment, replacing the existing technology of removing the catheter, applying medicine, and then reinserting the catheter, thereby reducing the difficulty of operation and the workload of medical staff. At the same time, It can also reduce the pain of patients.

The above descriptions are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention shall be included in the protection of the present invention. within the range.

Claims (3)

1. A method for reducing the surface roughness of polyether polyurethane film, which is characterized by including: S1. Dissolve polyether polyurethane PEUR in tetrahydrofuran solvent, and stir the solute completely with magnetic stirring for 4 days at room temperature to obtain a uniform transparent solution with a concentration of 1g/20mL; S2. Add the required dose of triamcinolone acetonide to the transparent solution obtained in step S1, and evenly disperse it in the solution by ultrasonic for 30 minutes to obtain a triamcinolone acetonide-polyether polyurethane mixed solution; S3. Pour the triamcinolone acetonide-polyether polyurethane mixed solution into a glass petri dish, place it horizontally in a fume hood, and evaporate at room temperature for 1 week to initially obtain a polyether polyurethane base film material; S4. Then place it in a vacuum drying oven to dry for 2 days to completely evaporate the tetrahydrofuran solvent in the material to obtain the required polyether polyurethane film, which is used to prepare medical catheters; In order to explore the appropriate drug dosage in the described step S2, a gradient design was adopted, and the transparent solution with a concentration of 1g/20mL obtained in step S1 was divided into three groups: PEUR-1, PEUR-2 and PEUR-4; respectively, towards PEUR-1, Add 25, 50, and 100 mg of triamcinolone acetonide to the transparent solutions of PEUR-2 and PEUR-4 groups; In step S3, the diameter of the glass petri dish is 8-10mm, and the bottom surface is smooth and flat; In step S4, the temperature inside the vacuum drying box is 40-50°C. 2. A polyether polyurethane film with reduced surface roughness obtained by the method of reducing the surface roughness of a polyether polyurethane film according to claim 1. 3. The polyether polyurethane film prepared by the method of reducing the surface roughness of the polyether polyurethane film according to claim 1 or the application of the polyether polyurethane film according to claim 2 in the preparation of medical catheters.