Preparation method of nanoparticles, ureteral stent and modification method of ureteral stent
By attaching prepared nanoparticles to the surface of the ureter stent, the liquid component deposition problem is solved, the risk of ureteral tissue damage is reduced, and the longer-term and safe use of the stent is achieved.
Patent Information
- Application Number
- CN202311660119.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-05
- Publication Date
- 2025-06-06
AI Technical Summary
The existing ureteral stents are prone to liquid deposition during use, resulting in impaired stent function and may cause problems such as poor urination and urinary tract infection.
Using a nanoparticle preparation method, nanoparticles with spherical porous structure are formed by ultrasonic dissolving polymers and drugs in organic solutions and ultrasonic vibration or stirring dropwise. These nanoparticles can attach to the surface of the ureteral stent, improving their surfactivity and reducing liquid component deposition.
Through nanoparticle attachment, the possibility of liquid components depositing on the surface of the ureteral stent is significantly reduced, thereby reducing the risk of external invasion and damage to ureteral tissue and reducing the occurrence of problems such as scar or stenosis.
Smart Images
Figure CN120093998A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of medical devices, and in particular to a method for preparing nanoparticles, a ureteral stent and a method for modifying the same. Background Art
[0002] Ureteral stents are commonly used medical devices in interventional surgery. Although the manufacturing process and manufacturing materials of ureteral stents are constantly improving, existing ureteral stents still have many clinical problems. After the ureteral stent is implanted in the human body, the substances in the liquid flowing through the ureteral stent are easily deposited on the surface of the ureteral stent, thus affecting the normal use of the stent. Ureteral stents can be used for short-term retention after lithotripsy to avoid the stimulation of ureteral tissue caused by laser lithotripsy and ureteroscopy, which can directly lead to problems such as ureteral adhesion, edema, and stenosis. Long-term retention of ureteral stents in the urinary system is prone to bacterial deposition and encrustation, which can cause symptoms such as dysuria, urinary tract infection, urinary pain, and irritation.
[0003] Therefore, it is necessary to modify the existing ureteral stents and find suitable modified materials to improve their surface properties and avoid or reduce the deposition of components in the liquid on the surface of the ureteral stent. Summary of the invention
[0004] The present invention aims to solve one of the technical problems in the related art at least to a certain extent. To this end, the present invention provides a method for preparing nanoparticles, comprising the following steps:
[0005] The polymer and the drug having a concentration of 0.1-1% are dissolved by ultrasonic in an organic solution at a ratio of 5:1-1:1;
[0006] After ultrasonic dissolution, the above solution is added dropwise into the polyvinyl alcohol solution for ultrasonic vibration or stirring, and the ultrasonic vibration or stirring time is 20-30 minutes;
[0007] After ultrasonic vibration or stirring, the mixture is pre-frozen for a predetermined time, and then transferred to a freeze dryer, and the nanoparticles are taken out after being completely dried.
[0008] The nanoparticles obtained by the nanoparticle preparation method of the present invention can be attached to the surface of the ureteral stent, avoiding or reducing the deposition of components in the liquid on the stent surface, so that the ureteral stent can reduce the damage to ureteral tissue due to external invasion, the formation of scars or stenosis, and other problems.
[0009] Optionally, the polymer is polylactic acid, polycaprolactone, polyurethane or polydioxanone; the drug is an anti-proliferative drug; and the organic solution is an acetone solution, a chloroform solution or a dichloromethane solution.
[0010] Optionally, the drug is an anti-proliferative drug such as paclitaxel or sirolimus; the concentration of the polyvinyl alcohol solution is 0.03%, and the dripping speed of the polyvinyl alcohol solution is 10 μl / drop / second; the freezing temperature is -20°C, and the predetermined time is 24 hours.
[0011] Optionally, the nanoparticles are spherical porous structures, and the diameter of the nanoparticles is 10-100 nm.
[0012] The present invention also provides a method for modifying a ureteral stent, comprising the following steps:
[0013] S1, after cleaning the ureteral stent, placing it in a first solution, and reacting it at a predetermined temperature and time to form a connection layer on the surface of the ureteral stent, and then placing the ureteral stent in deionized water for ultrasonic cleaning and drying;
[0014] S2, preparing nanoparticles according to any one of the preparation methods of the present invention;
[0015] S3, dissolving a predetermined amount of the nanoparticles prepared in S2 in a polyvinyl alcohol solution to obtain a nanoparticle solution; placing the ureteral stent obtained in S1 in the nanoparticle solution and reacting at a predetermined temperature and time, taking it out and ultrasonically cleaning it in deionized water, and placing it in the nanoparticle solution again, repeating the operation for at least 2 times, and drying it to obtain the ureteral stent loaded with nanoparticles.
[0016] The ureteral stent obtained by the above method can avoid or reduce the adhesion and deposition of components in the liquid on the surface of the stent, so that the ureteral stent can reduce the damage to ureteral tissue due to external invasion, the formation of scars or stenosis, and other problems.
[0017] Optionally, in S1, the first solution is a polydopamine solution, the ureteral stent is cleaned by ultrasound, the concentration of the polydopamine solution is 2 mg / ml, and the predetermined temperature and time are 20-40° C. for 6-12 hours;
[0018] In S2, the second solution is a poly-lysine solution, the concentration of the poly-lysine solution is 0.5-5 mg / ml; the predetermined temperature and time are 20-40° C. for 6-12 hours;
[0019] In S4, the nanoparticle solution is shaken while reacting, and the shaking frequency is 100 rpm; the concentration of the nanoparticle solution is 0.1-10 mg / ml, the predetermined temperature and time are 20-40°C for reaction for 20-30 hours, the ultrasonic cleaning time in deionized water is 20-30 minutes, and the drying method is to place it in a 30-40°C oven for drying for 20-25 hours.
[0020] The present invention also provides a ureteral stent prepared by the modification method of the present invention, comprising: a stent body, a connection layer covered on the surface of the stent body, and a nanoparticle arrangement layer covered on the outer side of the connection layer.
[0021] Optionally, the connecting layer is a polydopamine coating.
[0022] Optionally, the stent body includes a supporting portion and pigtail spiral portions connected to both ends of the supporting portion.
[0023] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the invention. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the invention and, together with the description, serve to explain the principles of the invention.
[0025] Figure 1 is a schematic flow chart of a method for modifying a ureteral stent in one embodiment of the present invention;
[0026] Figure 2 Schematic diagram of the cross-sectional structure of a ureteral stent in one embodiment of the present invention.
[0027] Reference numerals:
[0028] 1-Stent body; 2-Connection layer; 3-Nanoparticle arrangement layer. DETAILED DESCRIPTION
[0029] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.
[0030] This embodiment provides a method for preparing nanoparticles, and the prepared nanoparticles can be attached to a ureteral stent to avoid or reduce the deposition of components in the liquid on the surface of the stent.
[0031] Specifically, the preparation method of nanoparticles mainly includes the following steps: ultrasonically dissolving a polymer with a concentration of 0.1-1% and a drug in an organic solution at a ratio of 5:1-1:1; dripping the above solution dropwise into a polyvinyl alcohol solution for ultrasonic vibration or stirring after ultrasonic dissolution, and the ultrasonic vibration or stirring time is 20-30 minutes; pre-freezing for a predetermined time after ultrasonic vibration or stirring, and then transferring to a freeze dryer, and taking out the nanoparticles after complete drying. The obtained nanoparticles can be attached to the surface of the ureteral stent, improve the surface activity of the ureteral stent, and release the drugs in the nanoparticles into the human body within a specific period, avoiding or reducing the deposition of components in the liquid on the surface of the stent, so that the ureteral stent can reduce the damage to the ureteral tissue due to external invasion and inhibit the stenosis problem caused by surgery.
[0032] In some embodiments, the polymer is polylactic acid, polycaprolactone, polyurethane or polydioxanone; the drug is an anti-proliferative drug; and the organic solution is an acetone solution, a chloroform solution or a dichloromethane solution. Those skilled in the art can select any of the above polymers and organic solutions as needed.
[0033] Furthermore, the drug is an anti-proliferative drug such as paclitaxel or sirolimus; the concentration of the polyvinyl alcohol solution is 0.03%, and the dripping speed of the polyvinyl alcohol solution is 10 microliters / drop / second; the freezing temperature is -20°C, and the predetermined time is 24 hours. Those skilled in the art can make appropriate adjustments based on this data to meet different needs, for example, each of the above parameters can fluctuate within a range of 10%.
[0034] In some embodiments, the nanoparticles are spherical porous structures, and the diameter of the nanoparticles is 10-100 nm.
[0035] In conjunction with the above embodiments, a detailed method for preparing nanoparticles is described below. The prepared nanoparticles are porous structures, and are formed into spheres by blending degradable polymers or non-degradable polymers with drugs. The average size is 10-100nm. The polymer can be polylactic acid, polycaprolactone, polyurethane, polydioxanone, etc., and the drug is an anti-proliferative drug such as paclitaxel and sirolimus. The ratio of the polymer to the drug is 5:1-1:1. The polymer and the drug are dissolved in an organic solution, which has a certain solubility in water and can be acetone, chloroform, dichloromethane, etc. The above mixed solution is added dropwise to an aqueous solution containing polyvinyl alcohol, and after ultrasonic vibration or stirring for 20 minutes, it is transferred to a freeze dryer after being frozen at -20°C for 24 hours, and the nanoparticles are taken out after being completely dried.
[0036] Based on the above-mentioned method for preparing nanoparticles, this embodiment further provides a method for modifying a ureteral stent, the purpose of which includes but is not limited to avoiding or reducing the adhesion and deposition of components in the liquid on the surface of the stent.
[0037] Specifically, the modification method of the ureteral stent mainly includes the following steps:
[0038] S1, after cleaning the ureteral stent, place it in a first solution and react it at a predetermined temperature and time to form a connecting layer on the surface of the ureteral stent, and then place the ureteral stent in deionized water for ultrasonic cleaning and drying; a polydopamine coating is formed on the surface of the stent after treatment, and the polydopamine coating itself has active functional groups that can fix nanoparticles.
[0039] S2, preparing drug-carrying nanoparticles, specifically, the drug-carrying nanoparticles may be prepared according to the preparation method of any of the above embodiments;
[0040] S3, dissolving a predetermined amount of the nanoparticles prepared in S2 in a polyvinyl alcohol solution to obtain a nanoparticle solution; placing the ureteral stent obtained in S1 in the nanoparticle solution and reacting at a predetermined temperature and time, taking it out and ultrasonically cleaning it in deionized water, and placing it in the nanoparticle solution again, repeating the operation for at least 2 times, and drying it to obtain the ureteral stent loaded with nanoparticles.
[0041] The ureteral stent obtained by the above method can avoid or reduce the adhesion and deposition of components in the liquid on the surface of the stent, so that the ureteral stent can reduce the damage to ureteral tissue due to external invasion, the formation of scars or stenosis, and other problems.
[0042] In some embodiments, in S1, the first solution is a polydopamine solution, the ureteral stent is cleaned by ultrasound, the concentration of the polydopamine solution is 2 mg / ml, and the predetermined temperature and time are 20-40° C. for 6-12 hours. It is understood that those skilled in the art can make appropriate adjustments based on this data to meet different needs.
[0043] In S2, the second solution is a poly-lysine solution, and the concentration of the poly-lysine solution is 0.5-5 mg / ml; the predetermined temperature and time are 20-40° C. for reaction for 6-12 hours; those skilled in the art can make appropriate adjustments based on this data to meet different needs.
[0044] In S4, the nanoparticle solution is shaken while reacting, and the shaking frequency is 100 rpm; the concentration of the nanoparticle solution is 0.1-10 mg / ml, the predetermined temperature and time are 20-40°C for reaction for 20-30 hours, the ultrasonic cleaning time in deionized water is 20-30 minutes, and the drying method is placed in a 30-40°C oven for drying for 20-25 hours. For example, the drying method is placed in a 40°C oven for drying for 24 hours.
[0045] The present invention further provides a ureteral stent prepared according to any of the above modification methods, combined with Figure 2 The ureteral stent comprises: a stent body 1, a connection layer 2 is covered on the surface of the stent body 1, and a nanoparticle arrangement layer 3 is covered on the outer side of the connection layer 2.
[0046] In some embodiments, the connecting layer is a polydopamine coating; the stent body includes a supporting portion and a pigtail spiral portion connected to both ends of the supporting portion.
[0047] In the description of the present invention, it is to be understood that the terms “center”, “longitudinal”, “lateral”, “length”, “width”, “thickness”, “up”, “down”, “front”, “back”, “left”, “right”, “vertical”, “horizontal”, “top”, “bottom”, “inside”, “outside”, “clockwise”, “counterclockwise”, “axial”, “radial”, “circumferential”, etc., indicating orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as limiting the present invention.
[0048] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In the description of the present invention, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.
[0049] In the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral one; it can be a mechanical connection, an electrical connection, or communication with each other; it can be a direct connection, or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.
[0050] In the present invention, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may mean that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, a first feature being "above", "above" or "above" a second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. A first feature being "below", "below" or "below" a second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.
[0051] In the present invention, the terms "one embodiment", "some embodiments", "examples", "specific examples", or "some examples" etc. mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the described specific features, structures, materials or characteristics may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.
[0052] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included in the scope of protection of the present invention.
Claims
1. A method for preparing nanoparticles, It is characterized in that The following steps are involved: The polymer and the drug having a concentration of 0.1-1% are dissolved by ultrasonic in an organic solution at a ratio of 5:1-1:1; After ultrasonic dissolution, the above solution is added dropwise into the polyvinyl alcohol solution for ultrasonic vibration or stirring, and the ultrasonic vibration or stirring time is 20-30 minutes; After ultrasonic vibration or stirring, the mixture is pre-frozen for a predetermined time, and then transferred to a freeze dryer, and the nanoparticles are taken out after being completely dried.
2. The preparation method according to claim 1, It is characterized in that The polymer is polylactic acid, polycaprolactone, polyurethane or polydioxanone; the drug is an anti-proliferative drug; and the organic solution is an acetone solution, a chloroform solution or a dichloromethane solution.
3. The preparation method according to claim 2, It is characterized in that The drug is an anti-proliferative drug such as paclitaxel or sirolimus; the concentration of the polyvinyl alcohol solution is 0.03%, and the dripping speed of the polyvinyl alcohol solution is 10 microliters / drop / second; the freezing temperature is -20°C, and the predetermined time is 24 hours.
4. The preparation method according to claim 1, It is characterized in that The nanoparticles are spherical porous structures, and the diameter of the nanoparticles is 10-100 nm.
5. A method for modifying a ureteral stent, It is characterized in that The following steps are involved: S1, after cleaning the ureteral stent, placing it in a first solution, and reacting it at a predetermined temperature and time to form a connection layer on the surface of the ureteral stent, and then placing the ureteral stent in deionized water for ultrasonic cleaning and drying; S2, preparing the nanoparticles according to the preparation method according to any one of claims 1 to 4; S3, dissolving a predetermined amount of the nanoparticles prepared in S2 in a polyvinyl alcohol solution to obtain a nanoparticle solution; placing the ureteral stent obtained in S1 in the nanoparticle solution and reacting at a predetermined temperature and time, taking it out and ultrasonically cleaning it in deionized water, and placing it in the nanoparticle solution again, repeating the operation for at least 2 times, and drying it to obtain the ureteral stent loaded with nanoparticles.
6. The method for modifying a ureteral stent according to claim 5, It is characterized in that In S1, the first solution is a polydopamine solution, and the ureteral stent is cleaned by ultrasound. The concentration of the polydopamine solution is 2 mg / ml, and the predetermined temperature and time are 20-40° C. for 6-12 hours. In S2, the second solution is a poly-lysine solution, and the concentration of the poly-lysine solution is 0.5-5 mg / ml; the predetermined temperature and time are 20-40° C. for reaction for 6-12 hours.
7. The method for modifying a ureteral stent according to claim 5, It is characterized in that In S4, the nanoparticle solution is shaken while reacting, and the shaking frequency is 100 rpm; the concentration of the nanoparticle solution is 0.1-10 mg / ml, the predetermined temperature and time are 20-40°C for reaction for 20-30 hours, the ultrasonic cleaning time in deionized water is 20-30 minutes, and the drying method is to place it in a 30-40°C oven for drying for 20-25 hours.
8. A ureteral stent prepared by the modification method according to any one of claims 5 to 7, It is characterized in that include: The support body has a connection layer on its surface, and a nanoparticle arrangement layer is covered on the outside of the connection layer.
9. The ureteral stent according to claim 8, It is characterized in that The connecting layer is a polydopamine coating.
10. The ureteral stent according to claim 8, It is characterized in that The support body comprises a supporting portion and pigtail spiral portions connected to two ends of the supporting portion.