阅读说明：本技术 一种基于阴离子树脂的输尿管支架抗结壳涂层的制造方法 (Method for manufacturing ureteral stent anti-crusting coating based on anionic resin ) 是由 向彬 谭骏毅 舒杰 张艳 刘庄 吴俊� 于 2021-08-03 设计创作，主要内容包括：本发明公开了一种基于阴离子树脂的输尿管支架抗结壳涂层的制造方法,该方法是将抗结壳的有效成分阴离子树脂制成涂层溶液以溶液浸渍、喷涂或辊轮涂镀的方式在涂层基底形成涂层,经干燥固化后以共价键的形式结合于作为涂层基底的输尿管支架上。本发明的方案通过在输尿管支架表面涂镀一层基于阴离子树脂的稳定涂层,实现减少结壳数量,减轻支架拔除困难的目的。该涂层方法成本较低,工艺简易,适合大规模生产,主要成分生物相容性较好,有临床应用价值。(The invention discloses a method for preparing an anti-incrustation coating of a ureteral stent based on anionic resin, which is characterized in that the anionic resin which is an anti-incrustation effective component is prepared into a coating solution to form a coating on a coating substrate in a solution dipping, spraying or roller coating mode, and the coating is combined on the ureteral stent which is taken as the coating substrate in a covalent bond mode after drying and curing. According to the scheme of the invention, the stable coating based on the anionic resin is coated on the surface of the ureteral stent, so that the aims of reducing the crusting quantity and relieving the difficulty in stent removal are fulfilled. The coating method has the advantages of low cost, simple process, suitability for large-scale production, good biocompatibility of the main components and high clinical application value.)

1. A method for manufacturing an anti-incrustation coating of a ureteral stent based on an anionic resin is characterized by comprising the following steps:

(1) putting the anion resin into pure water, and violently stirring by a magnetic stirrer to disperse the anion resin into dispersion liquid;

(2) adding an activating agent into the dispersion liquid, and continuously stirring to form an activated emulsion;

(3) then slowly adding the waterborne polyurethane coating into the activated emulsion, and violently stirring to fully mix the waterborne polyurethane coating and the activated emulsion to form a coating solution;

(4) taking a ureteral stent as a coating substrate, forming a coating on the coating substrate by using a coating solution in a solution dipping, spraying or roller coating mode, and then drying and curing to form an anti-crusting coating on the surface of the coating substrate; the anionic polymer as the main effective component of the anti-crusting coating is bonded on the ureteral stent as the coating substrate in a covalent bond mode.

2. The method of claim 1, wherein: the anion resin is resin which contains sulfonic side chain groups and takes carbon-carbon bonds as a main chain.

3. The method of claim 2, wherein: the anion resin is polyethylene sulfonate resin.

4. The method of claim 3, wherein: the molecular weight of the anion resin is between 120K and 2500K, the functional group of the Lewis acid is deprotonated to become sodium salt, potassium salt and the like, and the components are insoluble in water.

5. The method of claim 2, wherein: the backbone conformation of the anionic resin is a random conformation.

6. The method of claim 1, wherein: the anti-crusting coating thickness is between 0.1 and 0.5 mm.

7. The method of claim 1, wherein: the activator is an aziridine activator.

8. The method of claim 1, wherein: and (4) forming a coating on the coating substrate in a solution dipping mode, which specifically comprises the following steps: and slowly immersing the ureteral stent made of polyether type thermoplastic polyurethane into the coating solution, standing for 30s after the ureteral stent is completely immersed, and slowly withdrawing the ureteral stent from the liquid surface at the speed of 1 cm/s.

9. The method of claim 1, comprising the steps of:

(1) taking 4.0g of random sodium polyvinyl sulfonate high polymer with the molecular weight of 200K, putting the random sodium polyvinyl sulfonate high polymer into 12mL of pure water, and violently stirring the mixture by using a magnetic stirrer to disperse the mixture to form dispersion liquid;

(2) adding 0.6g of aziridine activating agent into the dispersion, and continuously stirring for 20min to form activated emulsion;

(3) then, 20g of waterborne polyurethane coating is slowly added into the activated emulsion, and is slowly added into the activated emulsion containing the sodium polyvinyl sulfonate high polymer, and the mixture is stirred vigorously for 30min to be fully mixed

(4) Taking the ureteral stent made of polyether type thermoplastic polyurethane, slowly immersing the ureteral stent into a coating solution, standing for 30s after the ureteral stent is completely immersed, and slowly withdrawing the ureteral stent from the liquid surface at the speed of 1 cm/s; and (3) putting the soaked ureteral stent into a 65-DEG C drying oven to dry for 2.5h to obtain a finished ureteral stent product with an anti-crusting coating.

Technical Field

The invention relates to the technical field of medical treatment, in particular to a method for manufacturing a ureteral stent anti-crusting coating based on anionic resin.

Background

The ureter bracket is a medical appliance used for auxiliary treatment of urolithiasis, and is used for relieving benign or malignant obstruction of the ureter, promoting recovery of the ureter and treating urine extravasation. The ureteral stent is usually made of high polymer or metal, and after being implanted into a patient, the upper end of the ureteral stent is started and fixed on a renal pelvis and extends into a bladder along the ureter, so that the ureteral stent plays a role in expanding the ureter. During the time the ureteral stent is in place, it is often the case that significant urinary salt deposits (encrustation) and urethral stones are produced at the surface due to prolonged contact with urine. The crusting on the surface of the ureteral stent can obviously increase the resistance in the removal process, reduce the success rate of the removal operation and simultaneously increase the infection risk of the ureter/urethra of a patient after the operation.

In order to reduce the amount of incrustation generated on the surface of the ureteral stent during indwelling, the coating of the functional coating on the surface of the ureter is the most common strategy. Some instruments have coated the ureteral surface with a hydrophilic hydrogel coating, such as polyvinylpyrrolidone (PVP) or Polyacrylamide (PAM), which claims to reduce the adherence of urine salts and microorganisms to the stent surface, but in practice hydrogel coatings are susceptible to rapid erosion and exfoliation in the presence of urine with very high ionic strength and a drastic change in composition. The damaged hydrogel coating is more beneficial to the accumulation of microorganisms and urine salt due to uneven surface, and the generation of crusting is promoted.

Another strategy for preventing ureteral stent incrustation is to load phenolic antibiotics (such as triclosan and the like) or buffer substances (such as phosphate buffer and the like) into the coating, so that the phenolic antibiotics or buffer substances are slowly released in the using process, and the functions of killing microorganisms in urine and preventing urine salt deposition are achieved. However, on one hand, the abuse of antibiotics can aggravate the prevalence of drug-resistant bacteria such as antibiotic-resistant staphylococcus aureus (MRSA) in hospital environment, and on the other hand, the urine environment with extremely high salt concentration and large pH fluctuation can completely make the release rate of effective substances of the slow-release/buffer coatings uncontrollable, so that the ureteral stent coatings gradually lose the original effects in the later stage of long-term retention.

In addition, an apparatus manufacturer forms a diamond-like inert coating on the surface of the ureteral stent, the coating can greatly reduce the bonding of hydrophilic substances, mineral salts, microorganisms and the like in urine to the surface of the stent due to covalent bonds or intermolecular forces, the coating has good corrosion resistance, can be kept in the urine for a long time without change, and has good biocompatibility. However, the technology has the disadvantages of high cost, expensive processing machine, complex process and difficult popularization.

Disclosure of Invention

In view of the above, the technical problem to be solved by the present invention is to provide a method for manufacturing an anion resin-based ureteral stent anti-crusting coating, which is used for coating a stable anion resin-based coating on the surface of a ureteral stent, so as to achieve the purposes of reducing the number of crusts and reducing the difficulty in stent removal. The coating method has the advantages of low cost, simple process, suitability for large-scale production, good biocompatibility of the main components and high clinical application value.

Therefore, the invention discloses the following technical scheme:

a method for manufacturing an anionic resin-based ureteral stent anti-crusting coating comprises the following steps:

(1) putting the anion resin into pure water, and violently stirring by a magnetic stirrer to disperse the anion resin into dispersion liquid;

(2) adding an activating agent into the dispersion liquid, and continuously stirring to form an activated emulsion;

(3) then slowly adding the waterborne polyurethane coating into the activated emulsion, and violently stirring to fully mix the waterborne polyurethane coating and the activated emulsion to form a coating solution;

(4) taking a ureteral stent as a coating substrate, forming a coating on the coating substrate by using a coating solution in a solution dipping, spraying or roller coating mode, and then drying and curing to form an anti-crusting coating on the surface of the coating substrate; the anionic polymer as the main effective component of the anti-crusting coating is bonded on the ureteral stent as the coating substrate in a covalent bond mode.

Preferably, the anionic resin is a resin with a carbon-carbon bond as a main chain containing sulfonic acid side chain groups.

More preferably, the anionic resin is a polyethylene sulfonate resin.

Preferably, the molecular weight of the anion resin is between 120K and 2500K, the functional group of the Lewis acid is deprotonated to become sodium salt, potassium salt and the like, and the components are insoluble in water.

Preferably, the backbone conformation of the anionic resin is a random conformation.

Preferably, the anti-crusting coating thickness is between 0.1 and 0.5mm

Preferably, the activator is an aziridine activator.

Preferably, step (4) forms a coating on the coated substrate by solution dipping, specifically: and slowly immersing the ureteral stent made of polyether type thermoplastic polyurethane into the coating solution, standing for 30s after the ureteral stent is completely immersed, and slowly withdrawing the ureteral stent from the liquid surface at the speed of 1 cm/s.

As a preferred embodiment of the invention, the method for manufacturing the anti-crusting coating of the ureteral stent based on the anionic resin comprises the following steps:

(1) taking 4.0g of random sodium polyvinyl sulfonate high polymer with the molecular weight of 200K, putting the random sodium polyvinyl sulfonate high polymer into 12mL of pure water, and violently stirring the mixture by using a magnetic stirrer to disperse the mixture to form dispersion liquid;

(2) adding 0.6g of aziridine activating agent into the dispersion, and continuously stirring for 20min to form activated emulsion;

(3) then, 20g of waterborne polyurethane coating is slowly added into the activated emulsion, and is slowly added into the activated emulsion containing the sodium polyvinyl sulfonate high polymer, and the mixture is stirred vigorously for 30min to be fully mixed

(4) Taking the ureteral stent made of polyether type thermoplastic polyurethane, slowly immersing the ureteral stent into a coating solution, standing for 30s after the ureteral stent is completely immersed, and slowly withdrawing the ureteral stent from the liquid surface at the speed of 1 cm/s; and (3) putting the soaked ureteral stent into a 65-DEG C drying oven to dry for 2.5h to obtain a finished ureteral stent product with an anti-crusting coating.

For the ureteral stent finished product with the anti-crusting coating, whether the anionic resin is successfully grafted or not can be verified through the dyeing of a 1% cresol red solution on the coating on the surface of the ureteral stent or a photoelectron spectroscopy test.

Compared with the prior art, the scheme disclosed by the invention at least comprises the following beneficial effects:

1. the anionic high polymer serving as the main anti-crusting active ingredient of the coating has better stability in urine, and is not easy to corrode or fall off in the urine environment compared with a common hydrophilic coating (such as polyvinylpyrrolidone);

2. the anionic polymer serving as the main anti-crusting effective component of the coating can play a certain local buffering role due to the fact that the anionic polymer contains more Lewis acid groups, and can reduce urine salt deposition caused by severe pH change of urine;

3. the anionic polymer as the main anti-crusting effective component of the coating can definitely reduce the deposition of urinary salts such as calcium oxalate and the like on the surface of the substrate in-vitro tests;

4. anionic polymers (such as calcium polyvinyl sulfonate) have been used in humans as drugs to reduce blood potassium. Most of the high polymers do not participate in the metabolic process of human bodies, do not cause heat sources and immune reactions, and have good biocompatibility;

5. the coating technology has the advantages of low raw material cost and simple process, and is suitable for large-scale production and popularization.

Detailed Description

The present invention will be described in further detail with reference to examples. The following examples are intended to illustrate the invention only and are not intended to limit the scope of the invention. The method of carrying out the process without specifying the conditions in the examples is usually carried out in a conventional manner.

The invention discloses a method for manufacturing a ureteral stent anti-crusting coating based on anionic resin, which comprises the following steps:

(1) putting the anion resin into pure water, and violently stirring by a magnetic stirrer to disperse the anion resin into dispersion liquid;

(2) adding an activating agent into the dispersion liquid, and continuously stirring to form an activated emulsion;

(3) then slowly adding the waterborne polyurethane coating into the activated emulsion, and violently stirring to fully mix the waterborne polyurethane coating and the activated emulsion to form a coating solution;

(4) taking a ureteral stent as a coating substrate, forming a coating on the coating substrate by using a coating solution in a solution dipping, spraying or roller coating mode, and then drying and curing to form an anti-crusting coating on the surface of the coating substrate; the anionic polymer as the main effective component of the anti-crusting coating is bonded on the ureteral stent as the coating substrate in a covalent bond mode.

Among them, the anion resin is preferably a resin having a carbon-carbon bond as a main chain and having a sulfonic acid side chain group. More preferably, the anionic resin is a polyethylene sulfonate resin.

The molecular weight of the anionic resin is 120-2500K, the functional group of the Lewis acid is deprotonated to become sodium salt, potassium salt and the like, and the components are insoluble in water. The backbone conformation of the anionic resin is a random conformation. In order to achieve a good anti-crusting effect as quickly as possible, the anti-crusting coating thickness is between 0.1 and 0.5mm

As a preferred embodiment of the invention, the method for manufacturing the anti-crusting coating of the ureteral stent based on the anionic resin comprises the following steps:

(1) taking 4.0g of random sodium polyvinyl sulfonate high polymer with the molecular weight of 200K, putting the random sodium polyvinyl sulfonate high polymer into 12mL of pure water, and violently stirring the mixture by using a magnetic stirrer to disperse the mixture to form dispersion liquid;

(2) adding 0.6g of aziridine activating agent into the dispersion, and continuously stirring for 20min to form activated emulsion;

(3) then, 20g of waterborne polyurethane coating is slowly added into the activated emulsion, and is slowly added into the activated emulsion containing the sodium polyvinyl sulfonate high polymer, and the mixture is stirred vigorously for 30min to be fully mixed

(4) Taking the ureteral stent made of polyether type thermoplastic polyurethane, slowly immersing the ureteral stent into a coating solution, standing for 30s after the ureteral stent is completely immersed, and slowly withdrawing the ureteral stent from the liquid surface at the speed of 1 cm/s; and (3) putting the soaked ureteral stent into a 65-DEG C drying oven to dry for 2.5h to obtain a finished ureteral stent product with an anti-crusting coating.

For the ureteral stent finished product with the anti-crusting coating, whether the anionic resin is successfully grafted or not can be verified through the dyeing of a 1% cresol red solution on the coating on the surface of the ureteral stent or a photoelectron spectroscopy test.

Compared with the prior art, the scheme disclosed by the invention at least comprises the following beneficial effects:

1. the anionic high polymer serving as the main anti-crusting active ingredient of the coating has better stability in urine, and is not easy to corrode or fall off in the urine environment compared with a common hydrophilic coating (such as polyvinylpyrrolidone);

2. the anionic polymer serving as the main anti-crusting effective component of the coating can play a certain local buffering role due to the fact that the anionic polymer contains more Lewis acid groups, and can reduce urine salt deposition caused by severe pH change of urine;

3. the anionic polymer as the main anti-crusting effective component of the coating can definitely reduce the deposition of urinary salts such as calcium oxalate and the like on the surface of the substrate in-vitro tests;

4. anionic polymers (such as calcium polyvinyl sulfonate) have been used in humans as drugs to reduce blood potassium. Most of the high polymers do not participate in the metabolic process of human bodies, do not cause heat sources and immune reactions, and have good biocompatibility;

5. the coating technology has the advantages of low raw material cost and simple process, and is suitable for large-scale production and popularization.

The present invention will be described in further detail with reference to examples.

Example 1: 4.0g of a random sodium polyvinylsulfonate high polymer having a molecular weight of 200K was taken and put into 12mL of pure water, and vigorously stirred with a magnetic stirrer to disperse the polymer. To the dispersion was added 0.6g of aziridine activator (DSM)^TMCX-100 crosslinking agent) and stirring is continued for 20 min. Then 20g of aqueous polyurethane coating (DSM)^TMNEOREZ-R9621) is slowly added into the emulsion containing the sodium polyvinyl sulfonate high polymer, and stirred vigorously for 30min to mix thoroughly. Taking a ureteral stent of polyether type thermoplastic polyurethane with the specification of 6Fr, slowly immersing the ureteral stent into the coating solution, standing for 30s after the ureteral stent is completely immersed, and slowly withdrawing the ureteral stent from the liquid surface at the speed of 1 cm/s. The soaked ureter stent is put into a 65 ℃ oven to be dried for 2.5h,and obtaining the finished product of the ureteral stent with the anti-crusting coating.

Example 2: the coating on the surface of the ureteral stent can be used for verifying whether the anionic resin is successfully grafted or not by dyeing with a 1% cresol red solution or testing through photoelectron spectroscopy. From the detection results, successful grafting can be realized by adopting the ureteral stent finished product obtained by the scheme in example 1. And the clinical use effect is also excellent.

The above disclosure is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the scope of the present invention, therefore, the present invention is not limited by the appended claims.