A drug-coated sinus stent and method of testing

Abstract

The application provides a drug-coated sinus stent and a test method, and relates to the technical field of sinus stents, comprising a stent body made of a biocompatible material with mechanical support characteristics, capable of keeping the middle meatus open and preventing the middle turbinate from adhering to the lateral wall of the nasal cavity, and the surface of the stent body is coated with mometasone furanoate drugs which are released in a targeted manner at the lesion site. The application can accurately describe the drug release curve by using high-performance liquid chromatography to analyze the drug concentration in the release medium, fitting zero-order, first-order and multiple drug kinetics equations, thereby providing data support for drug release mechanism research and stent design optimization, and the fitting curve determination coefficient (R 2 ) is greater than or equal to 0.95, and the least square method is used to calculate the relationship between the drug release rate and time, so that the high-precision simulation of the drug release process can be ensured, and the reliability and reproducibility of the experimental data can be improved.

Description

Technical Field

[0001] This invention relates to the field of sinus stent technology, and more particularly to a drug-coated sinus stent and a testing method thereof. Background Technology

[0002] In the field of modern medicine, sinus diseases, especially chronic sinusitis, have become a common disease. Although existing treatments, including drug therapy and surgical treatment, can alleviate symptoms to some extent, they still face some insurmountable problems, such as poor local drug release, excessively long treatment time, and drug side effects. Therefore, how to achieve continuous and targeted drug release at the lesion site has become a key challenge in the treatment of sinus diseases. Currently, most research on drug delivery systems focuses on targeted drug delivery and sustained-release technologies. Existing drug-coated sinus stents mostly use traditional release methods, which are unstable and result in the inability to maintain drug efficacy for an extended period. In particular, existing technologies have not been able to fully address the issue of precise control over the drug release rate and duration in terms of the drug coating on the stent. Therefore, the research and development of a sinus stent with a longer drug release period and the ability to release drugs stably has become an urgent technical problem to be solved. In addition, the testing methods for drug-coated sinus stents are also an important problem. Existing drug release testing methods are usually difficult to test the drug release behavior realistically and efficiently under different physiological environmental conditions. Traditional testing methods have not fully considered the influence of fluid dynamics on the drug release rate and lack the means to dynamically control the drug release process, which makes it difficult for the drug release data to accurately reflect the release characteristics in actual use. Summary of the Invention

[0003] The purpose of this invention is to address the shortcomings of existing technologies. Currently, research on drug delivery systems mostly focuses on targeted drug delivery and sustained-release technologies. Existing drug-coated sinus stents mostly use traditional release methods, which are unstable and result in the inability to maintain drug efficacy for an extended period. In particular, existing technologies have failed to adequately address the issue of precise control over the drug release rate and duration in terms of the drug coating on the stent. Therefore, researching and developing a sinus stent with a longer drug release period and the ability to release drugs stably has become an urgent technical problem to be solved. In addition, the testing methods for drug-coated sinus stents are also an important problem. Existing drug release testing methods are usually difficult to test the drug release behavior realistically and efficiently under different physiological environmental conditions. Traditional testing methods have not fully considered the influence of fluid dynamics on the drug release rate and lack the means to dynamically control the drug release process, which makes it difficult for the drug release data to accurately reflect the release characteristics in actual use.

[0004] To achieve the above objectives, the present invention adopts the following technical solution: a drug-coated sinus stent, comprising a stent body, wherein the stent body is made of a biocompatible material having mechanical support properties, capable of keeping the middle nasal meatus open and preventing adhesion between the middle turbinate and the lateral wall of the nasal cavity, and the surface of the stent body is coated with mometasone furoate drug that is released directionally at the lesion site, wherein the biocompatible material is one or more combinations of polylactic acid, polyvinyl alcohol or polyurethane, and the coated drug has sustained-release properties, capable of phased release over a certain period of time.

[0005] A method for testing drug-coated sinus stents, employing the flow cell method for drug release testing, includes the following steps: a) Assemble a flow cell, the flow cell comprising a vertically placed flow cell with glass beads and rubies at the bottom; b) Fix the drug-coated stent body at a specific position within the flow cell; c) The release medium is flowed from bottom to top through the sample at a certain flow rate using a precision pump to form a gentle and uniform laminar flow, and the temperature, pH value and ionic strength are controlled to simulate the drug release behavior under different physiological conditions.

[0006] In a preferred embodiment, during the dissolution process of the coating on the surface of the stent body, solutions of bioactive molecules of different concentrations are introduced to simulate the release behavior of drugs under different physiological conditions. The concentration of the bioactive molecule solution is 1-10 mg / mL.

[0007] As a preferred implementation, in the initial stage of the drug release test, a temperature, pH and ionic strength control system is set up to ensure that the drug release behavior of the drug-coated sinus stent is simulated under different physiological conditions during the experiment. The multi-layer coating design during the release phase enables the drug to be released in stages at different time periods.

[0008] As a preferred embodiment, the stent body is placed in the flow cell in two ways: horizontally and vertically. The horizontal angle is 0°±5° and the vertical angle is 90°±5°, in order to examine the effect of different placement methods on the drug release rate.

[0009] In one preferred embodiment, the placement of the stent body in the flow cell is either horizontal or vertical, and the effect of the placement method on the drug release rate is investigated.

[0010] In a preferred embodiment, the release medium is an aqueous solution of SDS with different concentrations, with a volume of 1000 mL, which is filtered through a filter membrane after automatic sampling and then analyzed by high performance liquid chromatography.

[0011] In a preferred embodiment, the drug release curve is fitted using zero-order release kinetics, first-order release kinetics, the Higuchi equation, the Korsmeyer-Peppas equation, and the Weibull equation. During the fitting process, the least squares method is used to calculate the relationship between the drug release rate and time to describe the drug release behavior over a certain period of time. Based on the obtained fitted curve, the relationship between the drug release rate, release amount, and time is calculated.

[0012] As a preferred embodiment, the coefficient of determination (R²) of the fitted curve 2 The value should be no less than 0.95 to ensure high-precision simulation of the drug release process.

[0013] Compared with the prior art, the advantages and positive effects of the present invention are as follows: In this invention, the stent body is made of a biocompatible material with mechanical support properties, which can keep the middle nasal meatus open, thereby preventing adhesion between the middle turbinate and the lateral wall of the nasal cavity, improving the safety and comfort of the stent after surgery. By coating the stent surface with mometasone furoate and using a sustained-release coating design, the drug can be released directionally at the lesion site, effectively reducing local inflammatory response and improving treatment efficacy. By using the flow cell method to test drug release, combined with a temperature, pH, and ionic strength control system, the drug release behavior under different physiological conditions can be simulated, providing a scientific basis for drug coating design and ensuring the stability and controllability of drug release. By introducing bioactive molecule solutions of different concentrations to assist in the drug coating dissolution process, the dissolution behavior under different physiological conditions can be simulated. By studying drug release behavior under physiological conditions, the realism and predictability of experimental simulations are enhanced. Through multi-layered coating design and phased release control, continuous drug release at different time points can be achieved, prolonging the duration of efficacy, reducing dosing frequency, and improving patient compliance. By examining the horizontal and vertical placement of the stent in the flow cell, combined with drug release rate analysis, the impact of stent placement on drug release can be optimized, ensuring uniform and controllable drug release during clinical application. High-performance liquid chromatography (HPLC) analysis of drug concentration in the release medium, combined with zero-order, first-order, and multiple pharmacokinetic equations, can accurately describe the drug release curve, providing data support for drug release mechanism research and stent design optimization. The coefficient of determination (R²) of the fitted curve is used to... 2 With a value ≥0.95, combined with the least squares method to calculate the relationship between drug release rate and time, it can ensure high-precision simulation of the drug release process and improve the reliability and reproducibility of experimental data. Attached Figure Description

[0014] Figure 1 This invention presents a schematic diagram of a drug-coated sinus stent and its testing method.

[0015] Legend: 1. Support frame body. Detailed Implementation

[0016] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0017] Example like Figure 1 As shown, the present invention provides a technical solution: a drug-coated sinus stent, comprising a stent body 1, characterized in that: the stent body 1 is made of a biocompatible material with mechanical support properties, capable of keeping the middle nasal meatus open and preventing adhesion between the middle turbinate and the lateral wall of the nasal cavity; the surface of the stent body 1 is coated with mometasone furoate drug that is released directionally at the lesion site; the biocompatible material is one or more combinations of polylactic acid, polyvinyl alcohol or polyurethane, and the coated drug has sustained-release properties, capable of phased release within a certain time period.

[0018] A method for testing drug-coated sinus stents, employing the flow cell method for drug release testing, includes the following steps: a) Assemble the flow cell, which includes a vertically placed flow cell filled with glass beads and rubies at the bottom; b) Fix the drug-coated stent body 1 at a specific position within the flow cell; c) The release medium is flowed from bottom to top through the sample at a certain flow rate using a precision pump to form a gentle and uniform laminar flow, and the temperature, pH value and ionic strength are controlled to simulate the drug release behavior under different physiological conditions. During the dissolution process of the coating on the surface of the scaffold body 1, solutions of bioactive molecules of different concentrations are introduced to simulate the release behavior of drugs under different physiological conditions; The concentration of the bioactive molecule solution is 1-10 mg / mL; In the initial stage of drug release testing, a temperature, pH, and ionic strength control system was set up to ensure that the drug release behavior of the drug-coated sinus stent under different physiological conditions was simulated during the experiment. The multi-layer coating design during the release phase enables the drug to be released in stages at different time periods; The placement of the stent body 1 in the flow cell is divided into horizontal and vertical placement, with the horizontal placement angle being 0°±5° and the vertical placement angle being 90°±5°, in order to investigate the effect of different placement methods on the drug release rate. The placement of the stent body 1 in the flow cell is divided into horizontal and vertical positions, and the effect of the placement method on the drug release rate is investigated. The release medium was an aqueous solution of SDS with different concentrations, with a volume of 1000 mL. After automatic sampling, the solution was filtered through a filter membrane and then analyzed by high performance liquid chromatography. The drug release curves were fitted using zero-order release kinetics, first-order release kinetics, the Higuchi equation, the Korsmeyer-Peppas equation, and the Weibull equation. During the fitting process, the least squares method was used to calculate the relationship between the drug release rate and time to describe the drug release behavior over a certain period of time. Based on the fitted curves, the relationship between the drug release rate and release amount and time was calculated. The coefficient of determination (R²) of the fitted curve 2 The value should be no less than 0.95 to ensure high-precision simulation of the drug release process; Through the above embodiments, by making the stent body from a biocompatible material with mechanical support properties, the middle nasal meatus can be kept open, thereby preventing adhesion between the middle turbinate and the lateral wall of the nasal cavity, improving the safety and comfort of the stent in postoperative application. By coating the stent surface with mometasone furoate and using a sustained-release coating design, the drug can be released directionally at the lesion site, effectively reducing local inflammatory response and improving treatment efficacy. By using the flow cell method to test drug release, combined with a temperature, pH, and ionic strength control system, the drug release behavior under different physiological conditions can be simulated, providing a scientific basis for drug coating design and ensuring the stability and controllability of drug release. By introducing bioactive molecule solutions of different concentrations to assist in the drug coating dissolution process, the dissolution process can be simulated. By studying drug release behavior under different physiological conditions, the realism and predictability of experimental simulations can be improved. Through multi-layered coating design and staged release control, continuous drug release at different time points can be achieved, prolonging the duration of drug effect, reducing dosing frequency, and improving patient compliance. By examining the horizontal and vertical placement of the stent in the flow cell, combined with drug release rate analysis, the impact of stent placement on drug release can be optimized, ensuring uniform and controllable drug release during clinical application. High-performance liquid chromatography (HPLC) analysis of drug concentration in the release medium, combined with zero-order, first-order, and multiple pharmacokinetic equations, can accurately describe the drug release curve, thus providing data support for drug release mechanism research and stent design optimization. The coefficient of determination (R²) of the fitted curve is used to... 2With a value ≥0.95, combined with the least squares method to calculate the relationship between drug release rate and time, it can ensure high-precision simulation of the drug release process and improve the reliability and reproducibility of experimental data.

[0019] Working principle: like Figure 1 As shown, the scaffold body 1 is fabricated in this embodiment using a biocompatible material with mechanical support properties. This material effectively maintains the opening of the middle nasal meatus and prevents adhesion between the middle turbinate and the lateral wall of the nasal cavity. The biocompatible material used can be polylactic acid (PLLA), polyvinyl alcohol (PVA), polyurethane (PU), or combinations thereof. The scaffold design ensures good structural support and biocompatibility. The drug-eluting coating is constructed by coating the surface of the stent body 1 with a drug, mometasone furoate, which has anti-inflammatory properties. The coating employs a multi-layered structural design with sustained-release capability, ensuring the drug is released in stages over a specific time period to achieve targeted release at the lesion site. The drug-eluting coating uses a biodegradable material to ensure stable release in vivo and avoid instantaneous drug release. The flow cell system was assembled and configured by placing a vertically positioned flow cell and filling the bottom with glass beads and rubies to stabilize the flow field. This flow cell provides a uniform and controllable experimental environment for simulating drug release processes, ensuring the reliability and stability of drug release behavior. The installation of drug-coated sinus stents involves fixing the main body 1 of the drug-coated sinus stent in a designated position within the flow chamber. During installation, the stent can be positioned horizontally (0°±5°) or vertically (90°±5°) to investigate the effect of different positioning methods on the drug release rate. The flow control of the drug release medium involves using a precision pump to flow the release medium (such as SDS aqueous solutions of different concentrations, each with a volume of 1000 mL) from bottom to top across the sample at a constant flow rate, creating a gentle and uniform laminar flow. During the fluid flow, temperature, pH, and ionic strength are controlled to simulate drug release behavior under different physiological conditions in the human body. The introduction of bioactive molecule solutions aims to simulate drug release behavior under different physiological conditions. These solutions, with concentrations ranging from 1 to 10 mg / mL, are introduced during drug release to further enhance the physiological relevance of the experiment. The concentration range of these solutions is used to simulate the influence of the in vivo environment on drug release. Drug sample collection and analysis involve periodically collecting samples using an automated sampling system during the drug release process. After filtration through a filter membrane, the samples are sent to a high-performance liquid chromatography (HPLC) system for analysis to accurately determine drug concentration and release rate. This process allows for the acquisition of drug release data at different time points. Drug release kinetics modeling and fitting were performed, using zero-order release kinetics, first-order release kinetics, the Higuchi equation, the Korsmeyer-Peppas equation, and the Weibull equation to fit drug release data. The least squares method was used to calculate the relationship between drug release rate and time, establishing a drug release model to describe its release behavior at different time points. Evaluation and analysis of the fitted curve: Based on the fitting results, the relationship between drug release rate, release amount, and time is calculated. This is achieved through the coefficient of determination (R²). 2 To evaluate the accuracy of the fitted curve, ensure Ri 2 The value is not less than 0.95 to ensure high-precision simulation of the drug release process. Finally, the drug release performance of the drug-coated sinus stent is comprehensively evaluated based on the fitted data.

[0020] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any other way. Any person skilled in the art may make changes or modifications to the above-disclosed technical content to create equivalent embodiments for application in other fields. However, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the protection scope of the present invention.

Claims

1. A drug-coated sinus stent, comprising a stent body (1), characterized in that: The stent body (1) is made of a biocompatible material with mechanical support properties, which can keep the middle nasal meatus open and prevent the middle turbinate from adhering to the lateral wall of the nasal cavity. The surface of the stent body (1) is coated with mometasone furoate drug that is released in a targeted manner at the lesion site. The biocompatible material is one or more combinations of polylactic acid, polyvinyl alcohol or polyurethane, and the coated drug has sustained-release properties.

2. A method for testing a drug-coated sinus stent, characterized in that: Drug release testing was performed using the flow-through cell method, which includes the following steps: a) Assemble a flow cell, the flow cell comprising a vertically placed flow cell with glass beads and rubies at the bottom; b) Fix the drug-coated stent body (1) in a specific position within the flow cell; c) The release medium is flowed from bottom to top through the sample at a certain flow rate using a precision pump to form a gentle and uniform laminar flow, and the temperature, pH value and ionic strength are controlled to simulate the drug release behavior under different physiological conditions.

3. The method for testing a drug-coated sinus stent according to claim 2, characterized in that: During the dissolution process of the surface coating of the scaffold body (1), solutions of bioactive molecules of different concentrations are introduced to simulate the release behavior of drugs under different physiological conditions. The concentration of the bioactive molecule solution is 1-10 mg / mL.

4. The method for testing a drug-coated sinus stent according to claim 2, characterized in that: In the initial stage of drug release testing, a temperature, pH, and ionic strength control system was set up to ensure that the drug release behavior of the drug-coated sinus stent under different physiological conditions was simulated during the experiment. The multi-layer coating design during the release phase enables the drug to be released in stages at different time periods.

5. The method for testing a drug-coated sinus stent according to claim 2, characterized in that: The main body of the support (1) is placed in the flow pool in two positions: horizontal and vertical. The horizontal angle is 0°±5° and the vertical angle is 90°±5°.

6. The method for testing a drug-coated sinus stent according to claim 2, characterized in that: The placement of the main body of the stent (1) in the flow cell is divided into horizontal and vertical placement, and the effect of the placement method on the drug release rate is investigated.

7. The method for testing a drug-coated sinus stent according to claim 2, characterized in that: The release medium is an aqueous solution of SDS with different concentrations, with a volume of 1000 mL. After automatic sampling, the solution is filtered through a filter membrane and then analyzed by high-performance liquid chromatography.

8. The method for testing a drug-coated sinus stent according to claim 2, characterized in that: The drug release curve was fitted using zero-order release kinetics, first-order release kinetics, the Higuchi equation, the Korsmeyer-Peppas equation, and the Weibull equation. During the fitting process, the least squares method was used to calculate the relationship between the drug release rate and time, describing the drug release behavior over a certain period of time. Based on the obtained fitted curve, the relationship between the drug release rate, release amount, and time was calculated.

9. The method for testing a drug-coated sinus stent according to claim 8, characterized in that: The coefficient of determination (R²) of the fitted curve 2 The value should be no less than 0.95 to ensure high-precision simulation of the drug release process.

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