Active agents in thermoplastic polymer compositions and methods for producing them
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2026-05-15
- Publication Date
- 2026-08-14
Smart Images
Figure 2026131618000001_ABST
Abstract
Description
Technical Field
[0001] The present invention generally relates to a formulated polyurethane composition for medical devices having antibacterial, antithrombotic, and / or anti-inflammatory properties. In particular, the present invention relates to a melt-processable polyurethane composition for medical devices having antibacterial, antithrombotic, and / or anti-inflammatory properties. [Citation of Related Applications] This application is a claim of priority application to U.S. Provisional Patent Application No. 63 / 295,132, filed on December 30, 2021, which is incorporated herein by reference in its entirety.
Background Art
[0002] Medical devices are commonly used to facilitate the care and treatment of patients undergoing surgical procedures. Examples of such devices include catheters, grafts, stents, sutures, and the like. Unfortunately, microorganisms such as bacteria and fungi may infiltrate these medical devices and / or form biofilms on the medical devices, and such biofilms can be difficult to treat. As a result of such contamination, infections can occur, along with discomfort or disease.
[0003] Generally, it is known that using medical devices with antibacterial properties in various medical devices can reduce the incidence of patient infections. Typically, an antibacterial agent is applied as a coating to a conventional medical device, or the conventional medical device is immersed in a solution of the antibacterial agent so that the antibacterial agent is injected into the medical device. In these conventional and other methods of introducing an antibacterial agent into a medical device, this extra coating or immersion step is time-consuming and increases costs.
[0004] In addition to the added steps and increased production time, coating or immersion cannot achieve relatively high antibiotic concentrations in the base material of medical devices. For relatively short procedures lasting a few hours, this relatively low antibiotic concentration may be sufficient. However, for longer procedures lasting several days, the antibiotics present in conventional devices may be insufficient. Therefore, these conventional devices must be replaced frequently when the antibiotic level falls below an effective level. [Overview of the Initiative] [Problems that the invention aims to solve]
[0005] Therefore, there is a need to provide antimicrobial medical devices and methods for introducing antimicrobial agents into medical devices that can solve, at least to some extent, the shortcomings described herein. [Means for solving the problem]
[0006] In one respect, the above requirements are largely met by the present invention, which provides a polymer that is compounded with an active drug component (API) for use in medical devices, and a method for compounding the polymer and the API.
[0007] One embodiment of the present invention relates to a method for integrating an active ingredient (API) with a thermoplastic polymer. The method comprises the steps of supplying the thermoplastic polymer and the API into a first feed port of a multi-screw extruder, or supplying the thermoplastic polymer into a first feed port of a twin-screw extruder, transporting the thermoplastic polymer along a heated multi-screw extruder, and heating the thermoplastic polymer to a melting temperature of 160°C to 280°C before the thermoplastic polymer is transported past a second feed port, wherein the second feed port supplies the API into the heated multi-screw extruder and mixes it with the molten thermoplastic polymer to produce a compound containing 85 to 100% of the initial API content, and the method further comprises the steps of extruding the compound from the outlet of the heated multi-screw extruder, and cooling the extruded compound by passing it through an air cooling device so that the extruded compound contains 85 to 100% of the initial API content.
[0008] Another embodiment of the present invention relates to a medical device. The medical device comprises a thermoplastic polymer integrated with an active drug component (API). A method for integrating an API with a thermoplastic polymer includes the steps of supplying the thermoplastic polymer and the API into a first feed port of a twin-screw extruder, or supplying the thermoplastic polymer into a first feed port of a twin-screw extruder, transporting the thermoplastic polymer along a heated multi-screw extruder, and heating the thermoplastic polymer to a melting temperature of 160°C to 280°C before the thermoplastic polymer is transported past a second feed port, the second feed port supplying the API into the heated multi-screw extruder to mix with the molten thermoplastic polymer, thereby producing a compound containing 85 to 100% of the initial API content, the method further includes the steps of extruding the compound from the outlet of the heated multi-screw extruder, and cooling the extruded compound by passing it through an air cooling device so that the extruded compound contains 85 to 100% of the initial API content.
[0009] Thus, in order to enable a better understanding of the present invention and to enable a better recognition of its contribution to the art, some embodiments of the present invention have been described in a rather broad manner. Naturally, there are additional embodiments of the present invention that are described below and that constitute the subject matter of the claims appended to this specification.
[0010] In this regard, before describing in detail at least one embodiment of the present invention, it should be understood that the uses of the present invention are not limited to the details of the configuration and arrangement of the components described or illustrated below. The present invention can take on various embodiments in addition to those described and can be embodied and implemented in various ways. It should also be understood that the words and terms used in this specification and abstract are for the purpose of describing the present invention and should not be considered to limit the present invention.
[0011] Therefore, those skilled in the art will understand that the technical idea upon which the present invention is based can be readily used as a basis for designing other structures, methods, and systems that achieve some of the objectives of the present invention. Importantly, the claims are deemed to include such equivalent configurations, provided they do not deviate from the true spirit and scope of the present invention. [Brief explanation of the drawing]
[0012] [Figure 1] This is a schematic diagram of a system in which a thermopolymer is combined with an active ingredient (API). [Figure 2] This graph illustrates the relationship between API content and resin composition. [Figure 3] This is a graph showing the amount of API eluted over time. [Figure 4] This graph illustrates the relationship between API content and resin composition. [Figure 5] This is a graph showing the API content over time. [Figure 6] This is a graph showing the API content over time. [Figure 7] This is a graph showing the API content over time. [Figure 8] This is a high-performance liquid chromatography diagram showing the analytical values at a wavelength of 280 nm for chlorhexidine diacetate (CHA) heated to 210°C over 10 minutes. [Figure 9] This is a high-performance liquid chromatography diagram showing the analytical values of unheated CHA at a wavelength of 280 nm. [Figure 10] This is a high-performance liquid chromatography diagram showing the analytical values at a wavelength of 280 nm for chlorhexidine dihydrochloride (CHD) heated to a temperature of 210°C over 10 minutes. [Figure 11] This is a high-performance liquid chromatography diagram showing the analytical values of unheated CHD at a wavelength of 280 nm. [Figure 12] This is a simplified diagram of an extruder and air cooling system as one embodiment of the present invention. [Figure 13] This plot shows the relationship between the actual API percentage after compounding and water cooling and different polymer formulations. [Figure 14] This is a plot of the API percentage after mixing and air cooling. [Figure 15] This is a plot of the API percentage after mixing and air cooling. [Modes for carrying out the invention]
[0013] Embodiments of the present invention provide systems and apparatus for incorporating active drug components (APIs) into polymers. Examples of APIs include active antibacterial agents, antithrombotic agents, and anti-inflammatory agents. Specific examples of suitable antibacterial agents include biguanides, such as chlorhexidine and alexidine. Examples of suitable polymers include thermoplastic polymers with a melting temperature of 160°C to 280°C.
[0014] When formulating APIs in an extruder, such as a two - or multi - screw extruder, the thermoplastic polymer is heated to the melting temperature of the polymer. Once melted, the polymer remains in a molten state until this temperature drops to the solidification temperature. Depending on the polymer, there may be a few degrees Celsius that separate these states. As described herein, the API is introduced downstream from the polymer inlet. This has the advantage of introducing the API into the molten polymer in a part of the screw extruder that is not actively heating the polymer to the melting temperature, and can be at a lower temperature than the upstream part of the extruder. Additionally, by subjecting the API to the elevated temperature of the molten polymer for a short duration, thermal degradation of the API may be reduced.
[0015] The formulated polymer and API are rapidly cooled after thorough mixing and extrusion. However, surprisingly, it has been found that in some water - based cooling methods, a significant amount of the API can be lost from the formulated polymer. For the purposes of this disclosure, a significant loss of API is a loss of 15% or more of the API. In addition to the additional cost of the lost API, increasing the initial amount of API added to the polymer can have adverse effects, such as cloudiness, crystallization, etc. of the API. For example, when water is used for cooling, it is necessary to minimize the exposure time to prevent a significant loss of the API. As a variant, it has been found that, advantageously, by using a sufficient amount of air cooling, the same cooling performance can be obtained while retaining the API in the formulated polymer.
[0016] Figure 1 is a schematic view of a system 10 for formulating a thermopolymer with an active pharmaceutical ingredient (API). As shown in Figure 1, system 10 includes an extruder 12 with a body 14, a motor 16 for rotating an internal screw (not shown), and a heater 18. The body 14 has a first port 20 for introducing the polymer 22. The body 14 has a second port 24 for introducing the API 26. As shown, the API 26 is introduced downstream from the first port 20 and the heater 18. In some embodiments, the second port 24 is provided at least halfway along the length of the body 14.
[0017] The mixture for formulating Polymer 22 and API 26 is pushed towards outlet 28 while being mixed. Once mixed and extruded from outlet 28, the formulated mixture 30 is cooled through air-cooling device 32. In some embodiments, the air-cooling device 32 has one or more air rings. In other embodiments, the air-cooling device 32 has one or more fans. Optionally, the system 10 may include a conveyor belt 34 for transporting the formulated mixture 30 from outlet 28. The chilled platen 36 may be configured to cool the conveyor belt 34, thereby facilitating the cooling of the formulated mixture 30. In various embodiments, the conveyor belt 34 may be made of a thermally conductive material, such as stainless steel. The chilled platen 36 may have tubes for the flow of cold water or coolant, or alternatively, the chilled platen 36 may have a piezoelectric chiller to enable cooling.
[0018] In some embodiments, the formulated mixture 30 is extruded in the form of a medical device, such as medical tubing, a stent, or a catheter. In other embodiments, the formulated mixture 30 is processed into pellets and further processed into the form of a medical device.
[0019] Specifically, the present invention relates to a medical device, which is composed of a material that enables the medical device to provide long-term antibacterial, antithrombotic, and anti-inflammatory effects due to the API released from the medical device over the period of staying in the body for clinical applications. This medical device is configured by using a method of incorporating antibacterial biguanide drugs (chlorhexidine, alexidine, octenidine) and hydrophilic materials, such as polyether polyurethane or polyether block amide materials containing PEG, which promote the release of antibacterial drugs from the medical device, into a bulk device polymer matrix and combining them into one.
[0020] The polymers are aromatic polyurethanes (Tecothane, Isoplast) and aliphatic polyurethanes (e.g., Tecoflex, Carbothane, Quadrathane), and the antimicrobial agents are chlorhexidine, alexidine, octenidine, and hydrophilic polymers (e.g., PEBAX® = polyether block amide (polymer) material, Tecophillic® = polyether polyurethane with PEG as the polyol). A device is provided consisting of a polymer matrix composed of one of the following combinations that allows for controlled release of the antimicrobial agent over a long period of time. Some examples of suitable polyurethane API mixtures include aliphatic polyurethane + antimicrobial agent + polyether block amide, aromatic polyurethane + antimicrobial agent + polyether block amide, aliphatic polycarbonate polyurethane + antimicrobial agent + polyether block amide, aromatic polycarbonate polyurethane + antimicrobial agent + polyether block amide, and aromatic polycarbonate silicone polyurethane + antimicrobial agent + polyether block amide.
[0021] A suitable medical device for the formulation mixture of the present invention is preferably designed to come into contact with blood vessels or lumens in the body. A suitable polymer is preferably an aromatic or aliphatic polyurethane containing a bulk-dispersed antimicrobial formulation with a melting point exceeding 200°C, with an antimicrobial amount of 0.5-15.0 wt / wt%, and a bulk-dispersed hydrophilic polymer of 5-35 wt / wt%, resulting in hygroscopicity by the device, thereby providing both antithrombotic and antimicrobial effects from the device. Examples of antimicrobial agents include biguanide class antimicrobial agents with a melting point exceeding 200°C, such as CHX-DH (chlorhexidine dihydrochloride) or ALX-DH (alexidine dihydrochloride). The antimicrobial agent preferably includes a biguanide class antimicrobial agent that remains stable and does not degrade at temperatures below 200°C.
[0022] To control the elution rate of the formulated API, the bulk distributed hydrophilic polymer preferably has a moisture absorption rate of at least 15-50%, resulting in a moisture absorption rate of 5-35% from the device. In this way, the medical device facilitates the release of at least 1% of the total amount of API added. In preferred embodiments, the medical device is constructed using a formulation process that maintains the temperature below 200°C.
[0023] As described herein, the compounding process includes a coolant or process for removing water. As described herein, when water is used to cool the compound mixture, as a result, about 50% of the API is lost from the compound mixture. Therefore, air cooling is a preferred means or process for cooling the extruded material to a temperature that is favorable for forming a medical device or cutting it into pellet form.
[0024] Example 1: Tecothane + ALX + PEBAX (0%, 20%, 40%) - Formulation composition, content, elution amount, antimicrobial efficacy Tecothane polyurethane material was compounded with 5% alexidine, and then extruded to form a 7-French 3-lumen catheter. This material was then tested for content, elution rate, and efficacy. The resulting alexidine content was 887 μg / cm³. When these catheters were tested for antimicrobial efficacy, their performance was poor, due to low elution rates. To promote alexidine elution, a hydrophilic material, namely PEBAX, was added during the compounding process at ratios of 20% and 40%. Figure 2 shows the content of each blend. Figure 3 shows the results of the elution test. The addition of 20% and 40% PEBAX accelerated the elution rate of alexidine. Table 1 shows the results of efficacy tests against C. albicans, E. faecalis, and K. pneumoniae, with 20% and 40% showing a greater reduction rate than 4 log on the 14-day challenge. JPEG2026131618000002.jpg104154
[0025] Example 2: Tecoflex + ALX + PEBAX (0%, 20%) - Formulation, content, elution amount, antimicrobial efficacy Tecoflex polyurethane material was compounded with 2.5% alexidine and 20% PEBAX, and then extruded to form a 7-French 3-lumen catheter. This material was then tested for content, elution, and efficacy. The content results are shown in Figure 4, the elution results in Figure 5, and the efficacy results in Table 2. The results in Table 2 show that this catheter tested for at least 4 log of all eight microorganisms tested. 10 It showed a decrease. JPEG2026131618000003.jpg72153
[0026] Example 3: Pellethane + ALX (2%, 3%) + PEBAX (0%, 20%) - Formulation composition, content, elution amount, antimicrobial efficacy Pellethane polyurethane material was compounded with 2% or 3% alexidine and 20% PEBAX, and then extruded to form single-lumen catheter extension line extruders, which were then tested for content, elution, and efficacy. The content results are shown in Figure 6, the elution results are shown in Figure 7, and the efficacy results are shown in Table 3. The results in Table 3 show that the efficacy resulted in at least 4 log for three of the three microorganisms. 10 This indicates that it caused the extinction of the species. JPEG2026131618000004.jpg50153
[0027] Example 4: Evaluation of the thermal stability of CHA (chlorhexidine diacetate), CHD (chlorhexidine dihydrochloride), and ALX-D (alexidine dihydrochloride) The antibiotic was placed in an oven set to 210°C for 10 minutes (simulating the conditions under which the antibiotic is exposed to heat during the compounding and extrusion processes). Another set of the same antibiotic was not exposed to heat at all. Next, the unheated and heated samples were examined by HPLC for the presence of degradation products (extra peaks). The results for CHA and CHD are shown in Figures 8, 9, 10, and 11. The CHA results in Figure 8 are for the heated sample, and compared to the unheated sample in Figure 9, several extra peaks were present from degradation products detected along the baseline. Figures 10 and 11 show the heated and unheated samples of CHD, respectively. Neither sample showed any extra peaks, demonstrating the thermal stability of CHD and therefore its suitability for inclusion in the instrument throughout the compounding process. Similar to CHD, ALX-D also proved stable at 210°C for 10 minutes and was found to be suitable for inclusion in the instrument during the compounding process.
[0028] Example 5: Cooling during the compounding process The formulation of the API into the polyurethane polymer was performed by an external vendor. This vendor used standard formulation procedures as well as a submersible pelletization setup. As shown in Figure 12, approximately 50% of the agent incorporated into the polymer matrix was lost.
[0029] Example 6: Air Cooling System In this embodiment, the amount of API leaching from the compound polymer was reduced by eliminating the water tank and cooling the extruder with multiple air rings. In the first experiment, the extruder was cooled using two air rings, but the extruder was not cooled enough to cut in the pelletizer. In the next experiment, more air rings were added to the base and jig, and the placement of the air rings was adjusted to an appropriate distance. The starting % alexidine in this experiment was 3%. Figure 12 shows the air ring setup.
[0030] As shown in Figure 12, the compound mixture 30 is extruded from the extruder 12. In this embodiment, the air cooling device 32 is a series of air rings 40 provided in an adjustable jig 42, supplying pressurized air via an air supply source 44. Once cooled, the compound mixture 30 is fed into a pelletizer 46. The pelletizer 46 is configured to cut the compound mixture and form it into pellets 50. As a result, after the air rings were implemented, the loss of alexidine was reduced to 20%, compared to the 50% loss observed with the water cooling method.
[0031] Example 7: API supply position in the extruder In the inventors' previous attempts at compounding alexidine into polyurethane, the base polyurethane resin, hydrophilic resin, and alexidine were supplied through the same feed port. As a result of this method, a portion of the powder adhered to the screw as a cake and did not flow through the compounder with the resin. To solve this problem, alexidine was introduced into the polymer melt flow downstream of the polymer feed port. This was found to be effective in reducing the measured API loss during the extrusion process. Figure 14 is a graph showing that the measured API% is between 10% theoretical% and 15% theoretical% during the compounding process.
[0032] Example 8: Use of an ionizer to reduce API deposition on the metal surface of an extruder While several improvements were observed in the compounding process to reduce alexidine loss, the problem of alexidine adhering to the metal parts of the feeder and supply port persisted, and it was observed that alexidine was not well distributed in the polymer bulk. To solve this problem, an ionizer was attached to the extruder to eliminate static electricity and prevent alexidine from adhering to the metal parts. A small increase in alexidine content was observed when the ionizer was used. This occurred because the fan was able to aerosolize the alexidine into the air.
[0033] Many features and advantages of the present invention are evident from the detailed description, and thus the claims are intended to include all such features and advantages of the present invention, which fall within the true spirit and scope of the invention. Furthermore, since many modifications and variations are readily conceivable to those skilled in the art, it is not desirable to limit the present invention to the configuration and operation illustrated and described, and therefore all suitable modifications and equivalents falling within the scope of the present invention can be conceived.
Claims
1. A method for integrating an active drug component (API) with a thermoplastic polymer, The step includes supplying the thermoplastic polymer and the API into a first supply port of a multi-screw extruder. Alternatively, the process includes the step of supplying the thermoplastic polymer into a first supply port of a multi-screw extruder. The step includes transporting the thermoplastic polymer along the heated multi-screw extruder, The process includes heating the thermoplastic polymer to a melting temperature of 160°C to 280°C before the thermoplastic polymer is transported past the second supply port. The second supply port supplies the API into the heated multi-screw extruder and mixes it with the molten thermoplastic polymer, thereby producing a compound mixture containing 85-100% of the initial API content. The step of extruding the aforementioned compound mixture from the outlet of the heated multi-screw extruder is included. A method comprising the step of passing the extruded formulation through an air cooling device to cool the extruded formulation so that the extruded formulation contains 85 to 100% of the initial API content.
2. The method according to claim 1, wherein the second supply port is located at least halfway along the length of the multi-screw extruder.
3. The method according to claim 1, wherein the air cooling device provides an airflow at a flow velocity of 2 to 20 meters per second.
4. The steps include: transporting the aforementioned blended mixture from the outlet using a conveyor belt; The method according to claim 1, further comprising the step of cooling the compound mixture by cooling at least one of the conveyor belt and air in contact with the compound mixture with a chilled platen.
5. The method according to claim 1, wherein the cooled compound mixture is pelletized, and as a result the pellets contain 85 to 100% of the initial API content.
6. The method according to claim 1, wherein the API is a thermally stable antibacterial agent, antithrombotic agent, and / or anti-inflammatory agent in the temperature range of 200°C to 280°C.
7. The method according to claim 6, wherein the API is a salt of a biguanide agent that is thermally stable in the temperature range of 200°C to 280°C.
8. The method according to claim 7, wherein the API is a chlorhexidine salt that is thermally stable in the temperature range of 200°C to 280°C.
9. The method according to claim 7, wherein the API is a thermally stable alexidine salt in the temperature range of 200°C to 280°C.
10. The method according to any one of claims 1 to 9, wherein the thermoplastic polymer includes a thermoplastic polyurethane polymer.
11. The method according to any one of claims 1 to 10, wherein the thermoplastic polymer comprises a hydrophilic polyurethane polymer having a water absorption rate of 5 to 40%.
12. It is a medical device, A medical device comprising a formulated thermoplastic polymer exhibiting a bulk distribution of an active drug component (API) by the method described in any one of claims 1 to 11.
13. The medical device according to claim 12, further comprising a second thermoplastic polymer that does not contain APIs, wherein the compounded thermoplastic polymer containing the bulk-distributed API is co-extruded with the second thermoplastic polymer that does not contain APIs.
14. The medical device according to claim 13, wherein the formulated thermoplastic polymer containing the bulk-distributed API is extruded onto the inner portion of the medical device, and the second thermoplastic polymer not containing the API is extruded onto the outer portion of the medical device.
15. The medical device according to claim 13, wherein the formulated thermoplastic polymer containing the bulk-distributed API is extruded along a first longitudinal portion of the medical device, and the second thermoplastic polymer not containing the API is extruded along a second longitudinal portion of the medical device, and the second thermoplastic polymer not containing the API is configured to be transparent so as to serve as an observation port for a user to view the inside of the medical device.
16. The medical device according to claim 13, wherein the formulated thermoplastic polymer containing the bulk-distributed API is extruded along a first axial portion of the medical device, and the second thermoplastic polymer not containing the API is extruded along a second axial portion of the medical device, and the second thermoplastic polymer not containing the API is configured to be transparent so as to serve as an observation port for a user to view the inside of the medical device.
17. It is a medical device, A thermoplastic polymer integrated with an active drug component (API) is included, and a method for integrating the API with the thermoplastic polymer is: The step includes supplying the thermoplastic polymer and the API into a first supply port of a twin-screw extruder. Alternatively, the process includes the step of supplying the thermoplastic polymer into a first supply port of a twin-screw extruder. The step includes transporting the thermoplastic polymer along the heated multi-screw extruder, The process includes heating the thermoplastic polymer to a melting temperature of 160°C to 280°C before the thermoplastic polymer is transported past the second supply port. The second supply port supplies the API into the heated multi-screw extruder and mixes it with the molten thermoplastic polymer, thereby producing a compound mixture containing 85-100% of the initial API content. The step of extruding the aforementioned compound mixture from the outlet of the heated multi-screw extruder is included. A medical device comprising the step of passing the extruded compound mixture through an air cooling device to cool the extruded compound mixture so that the extruded compound mixture contains 85 to 100% of the initial API content.
18. The medical device according to claim 17, wherein the second supply port is located at least halfway along the length of the multi-screw extruder.
19. The medical device according to claim 17, wherein the air cooling device provides an airflow at a flow rate of 2 to 20 meters per second.
20. A conveyor belt for transporting the aforementioned blended mixture from the outlet, The medical device according to claim 17, further comprising a chilled platen configured to facilitate the cooling of the compound mixture by cooling at least one of the conveyor belt and air that are in contact with the compound mixture.
21. The medical device according to claim 17, wherein the cooled compound mixture is pelletized, and as a result the pellet contains 85 to 100% of the initial API content.
22. The medical device according to claim 17, wherein the API is a thermally stable antibacterial agent, antithrombotic agent, and / or anti-inflammatory agent in the temperature range of 200°C to 280°C.
23. The method according to claim 22, wherein the API is a salt of a biguanide agent that is thermally stable in the temperature range of 200°C to 280°C.
24. The method according to claim 23, wherein the API is a chlorhexidine salt that is thermally stable in the temperature range of 200°C to 280°C.
25. The method according to claim 23, wherein the API is a thermally stable alexidine salt in the temperature range of 200°C to 280°C.
26. The method according to claim 17, wherein the thermoplastic polymer includes a thermoplastic polyurethane polymer.
27. The method according to claim 17, wherein the thermoplastic polymer comprises a hydrophilic polyurethane polymer having a water absorption rate of 5 to 40%.
28. The medical device according to claim 17, further comprising a second thermoplastic polymer.
29. The medical device according to claim 28, further comprising a second thermoplastic polymer that does not contain APIs, wherein the compounded thermoplastic polymer containing the bulk-distributed API is co-extruded with the second thermoplastic polymer that does not contain APIs.
30. The medical device according to claim 28, wherein the formulated thermoplastic polymer containing the bulk-distributed API is extruded onto the inner portion of the medical device, and the second thermoplastic polymer not containing the API is extruded onto the outer portion of the medical device.
31. The medical device according to claim 28, wherein the formulated thermoplastic polymer containing the bulk-distributed API is extruded along a first longitudinal portion of the medical device, and the second thermoplastic polymer not containing the API is extruded along a second longitudinal portion of the medical device, and the second thermoplastic polymer not containing the API is configured to be transparent so as to serve as an observation port for a user to view the inside of the medical device.
32. The medical device according to claim 28, wherein the formulated thermoplastic polymer containing the bulk-distributed API is extruded along a first axial portion of the medical device, and a second thermoplastic polymer not containing the API is extruded along a second axial portion of the medical device, and the second thermoplastic polymer not containing the API is configured to be transparent so as to serve as an observation port for a user to view the inside of the medical device.
33. The medical device is a catheter, according to any one of claims 17 to 32.
34. The medical device according to claim 33, wherein the catheter is inserted into a body cavity to provide access for treatment, nutritional intake, fluid drainage, blood gas monitoring, blood sampling, and other interventional medical procedures.