CN114748702A - Hydrogel coating for eustachian tube balloon dilatation catheter and preparation method thereof - Google Patents

Abstract

The invention discloses a hydrogel coating for a eustachian tube balloon dilatation catheter and a preparation method thereof, belonging to the technical field of medical devices. The method comprises the following steps: (1) carrying out oxygen plasma treatment on the eustachian tube balloon dilatation catheter, soaking the eustachian tube balloon dilatation catheter in a polycarboxylic acid solution, and then taking out and drying the eustachian tube balloon dilatation catheter; (2) coating the alginate solution on the surface of the eustachian tube balloon dilatation catheter obtained in the step (1), and then drying; (3) and (3) soaking the eustachian tube balloon dilatation catheter obtained in the step (2) in a mixed solution of water-soluble chitosan and polycarboxylic acid, taking out and drying to form the hydrogel coating. The hydrogel coating is matched with a eustachian tube balloon dilatation catheter with a drug administration function for use, and when the catheter enters a dry and narrow physiological cavity, such as a pathological eustachian tube, physiological saline can be injected through the drug administration function to moisten the cavity, so that the lubricating effect of the hydrogel coating is improved.

Description

Hydrogel coating for eustachian tube balloon dilatation catheter and preparation method thereof

Technical Field

The invention belongs to the technical field of medical equipment, and particularly relates to a hydrogel coating for a eustachian tube balloon dilatation catheter and a preparation method thereof.

Background

The balloon dilatation catheter is a medical intervention device and generally comprises a multi-cavity pipeline, a balloon and a plurality of connecting pieces. The balloon can be inflated in the body to expand a narrow physiological cavity in the body so as to enable the physiological cavity to be unobstructed or other instruments to pass through. The balloon dilatation catheter is originally used as an interventional therapy device for stenotic coronary arteries, and the clinical application is expanded to the dilatation operation of respiratory, digestive, excretory and genital tracts. The physiological cavities and ducts shrink or even are completely blocked due to pathological changes, inflammation, edema and the like. When the balloon dilatation catheter is inserted into or pulled out of the physiological cavity, the tissue is easy to be damaged due to mechanical friction, and the operation difficulty is improved. The existing common solution is to coat one or more layers of hydrophilic high molecular polymers on the outer surface of the catheter, so as to reduce friction and improve lubricating performance.

For example, CN201410742829 grafts acrylic acid or acrylate, acrylate or vinyl pyrrolidone monomer on the surface of inert polymer by grafting photoinitiator, and carries out ultraviolet polymerization curing to form a hydrophilic gel layer; CN202110623067 forms a swelling adhesive layer on the inner wall of the tracheal catheter by immersing in an isopropanol solution containing a hydrophobic photoinitiator, and forms an ultraviolet light-cured hydrogel adhesive layer by ultraviolet graft polymerization of acrylic acid or N, N-dimethylacrylamide; CN202111511558 deposits the polymer glue solution containing catechol group on the surface of the substrate, and compounds the polymer glue solution with one or more solutions of acrylic acid, methacrylic acid, acrylamide, hydroxyethyl acrylate, hydroxyethyl methacrylate, polyoxyethylene methacrylate, N-isopropyl acrylamide, 2-acrylamido-2-methylpropanesulfonic acid, 2-acrylamido-2-methylpropanesulfonate, methacrylate sulfonate, acrylic acid chitosan ester, methacrylic acid chitosan ester, dimethylaminoethyl methacrylate, sodium alginate methacrylate, methacryloyl ethyl carboxyl betaine and methacryloyl ethyl sulfobetaine, and carries out in-situ polymerization to obtain the substrate modified with the hydrogel lubricating coating.

The existing hydrogel coating is generally prepared by grafting hydrogel monomers on the surface of a substrate and carrying out in-situ polymerization by using a mode of ultraviolet light-initiated graft polymerization. The base layer is often required to be directly contacted with the monomer and the initiator with biological toxicity in the production process, and the high-curvature shape characteristic of the catheter increases the difficulty of removing the residual toxic monomer and the initiator by immersion cleaning. Meanwhile, the ultraviolet light initiated reaction process is complex, and the equipment cost is high.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides a hydrogel coating for a eustachian tube balloon dilatation catheter and a preparation method thereof.

In order to achieve the purpose, the invention adopts the technical scheme that: in a first aspect, there is provided a method of preparing a hydrogel coating for a eustachian tube balloon dilation catheter, comprising the steps of:

(1) carrying out oxygen plasma treatment on the eustachian tube balloon dilatation catheter, soaking the eustachian tube balloon dilatation catheter in a polycarboxylic acid solution, and then taking out and drying the eustachian tube balloon dilatation catheter;

(2) coating the alginate solution on the surface of the eustachian tube balloon dilatation catheter obtained in the step (1), and then drying;

(3) and (3) soaking the eustachian tube balloon dilatation catheter obtained in the step (2) in a mixed solution of water-soluble chitosan and polycarboxylic acid, taking out and drying to form the hydrogel coating.

The invention introduces hydroxyl functional groups on the surface of the eustachian tube balloon dilatation catheter through oxygen plasma treatment, and the polycarboxylic acid is enriched on the surface of the eustachian tube balloon dilatation catheter through hydrogen bond action by soaking in polycarboxylic acid solution and drying.

After the alginate is coated on the surface of the catheter, hydroxyl on a molecular chain of the alginate and the hydroxyl on the surface of the catheter and carboxyl on polycarboxylic acid are subjected to esterification condensation reaction at the temperature of 80-120 ℃, generated water molecules are evaporated at high temperature to enable the reversible reaction to be promoted to the condensation direction, and finally ester bond covalent bonding and fixation are generated between the alginate and the catheter.

And then coating water-soluble chitosan and polycarboxylic acid, carrying out esterification condensation reaction on the water-soluble chitosan and hydroxyl on alginate through carboxyl on the polycarboxylic acid at 60-90 ℃, evaporating generated water molecules at high temperature to push the reversible reaction to the condensation direction, and covalently bonding the water-soluble chitosan to the alginate layer on the surface of the catheter through ester bonds. Meanwhile, ester bonds can be used as chemical crosslinking sites to form a water-soluble chitosan and alginate hydrogel coating, so that the hydrophilicity of the surface of the catheter is improved, and the catheter has a lubricating effect.

Preferably, in the step (1), the mass fraction of the polycarboxylic acid in the polycarboxylic acid solution is 1-5%.

Preferably, in the step (2), the mass fraction of alginate in the alginate solution is 10-15%.

Preferably, in the step (3), the mass fraction of the polycarboxylic acid in the mixed solution of the water-soluble chitosan and the polycarboxylic acid is 0.05-0.1%, and the mass fraction of the water-soluble chitosan is 5-10%.

The invention selects proper mass fraction of polycarboxylic acid solution, alginate solution, and mixed solution of water-soluble chitosan and polycarboxylic acid to further improve the bonding strength, hydrophilicity and lubricating effect of the hydrogel coating.

Preferably, the polycarboxylic acid is at least one of malic acid, citric acid, adipic acid, tartaric acid and succinic acid. Preferably, the polycarboxylic acid is adipic acid.

Preferably, the alginate is at least one of sodium alginate, potassium alginate and ammonium alginate.

Preferably, the water-soluble chitosan is at least one of carboxymethyl chitosan, chitosan hydrochloride, chitosan quaternary ammonium salt and chitosan lactate.

Preferably, the water-soluble chitosan has a molecular weight of 10-30Kda, a degree of deacetylation of 90-100%, and a degree of substitution of 80-90%.

Preferably, the water-soluble chitosan is carboxymethyl chitosan.

The molecular weight, degree of deacetylation and degree of substitution of the specific water-soluble chitosan, as well as the type of polycarboxylic acid, may be selected to further control the bonding strength, hydrophilicity and lubricating effect of the hydrogel coating. Meanwhile, the release effect of the water-soluble chitosan under the condition of the human body cavity can be controlled.

Preferably, in the step (2), the drying temperature is 90-120 ℃, and the drying time is 3-6 h.

Preferably, in the step (3), the drying temperature is 60-90 ℃, and the drying time is 2-4 h.

The esterification condensation reaction is carried out under different heating temperatures and time conditions, which can affect the proceeding degree of the reversible reaction and determine the bonding strength between the water-soluble chitosan, the alginate and the catheter. In the step (2), the reaction is carried out more fully by selecting lower reaction temperature and longer reaction time, so that the bonding strength of the alginate and the catheter is improved, and the coating is prevented from falling off. And (3) selecting a lower reaction temperature and a shorter reaction time, and controlling the bonding strength of the water-soluble chitosan and the alginate so that the ester bond bonded with the water-soluble chitosan can be slowly hydrolyzed at the temperature of 35-40 ℃. When the catheter with the hydrogel coating enters a cavity focus for balloon expansion. The ester bond of the water-soluble chitosan is hydrolyzed under the condition of body temperature, and the water-soluble chitosan is separated from the hydrogel and coated on the cavity focus, thereby playing the physiological functions of analgesia, hemostasis and antibiosis.

Preferably, the eustachian tube balloon dilatation catheter comprises an elongated catheter, wherein the elongated catheter is provided with a front end and a tail end, a connector is fixedly sleeved at the front end, and a balloon is fixedly sleeved at the tail end; wherein the elongated catheter comprises a drug injection tube and an air intake tube; the air inlet pipe is sleeved on the outer side of the medicine injection pipe and is connected with the medicine injection pipe; the length of the medicine injection tube is greater than that of the air inlet tube; the tail end of the air inlet pipe is provided with a plurality of air inlet holes, and the air inlet holes are communicated with the saccule.

The eustachian tube balloon dilatation catheter used by the invention is the eustachian tube balloon catheter in the patent CN 202022250937.

In a second aspect, the invention provides a eustachian tube balloon dilatation catheter hydrogel coating, which is prepared by the preparation method of the first aspect.

The eustachian tube is a narrow passage connecting the nasopharynx part and the middle ear tympanic cavity, the whole length of an adult is 31-38mm, the diameter of the narrowest part is only 1-3mm, wherein the outer 1/3 is a bone part, and the inner 2/3 is a cartilage part. Blockage or blockage of the eustachian tube in pathological conditions can cause lesions in the middle ear system and lead to hearing impairment and head noise. Inflammatory diseases, genetics, infection, allergy, mechanical obstruction, sinusitis, throat reflux, neuromuscular diseases and the like can cause blockage of the eustachian tube. The eustachian tube is more narrow than other physiological tracts and clogged eustachian tubes in diseased states may dry out due to insufficient secretions. The existing hydrophilic lubricating hydrogel coating generally utilizes the water lubricating property of high water content hydrogel to reduce the friction of the contact surface of the catheter and the physiological cavity. The lubricating effect of the hydrogel coating can be obviously reduced for the dry cavity channel in a pathological state.

The hydrogel coating is matched with a eustachian tube balloon dilatation catheter with a drug administration function for use, and when the catheter enters a dry and narrow physiological cavity, such as a pathological eustachian tube, the cavity can be wetted by injecting physiological saline through the drug administration function, so that the lubricating effect of the hydrogel coating is improved.

Compared with the prior art, the invention has the following beneficial effects:

(1) the invention uses nontoxic natural materials of alginate and water-soluble chitosan as main raw materials, and a hydrogel coating is formed on the surface of the eustachian tube balloon dilatation catheter, and the raw materials do not contain toxic monomers and initiators, so that the safety of the coating is improved.

(2) In the hydrogel coating, water-soluble chitosan is combined through ester bonds to form the hydrogel coating, when the eustachian tube balloon dilatation catheter with the hydrogel coating enters a cavity focus to perform balloon dilatation, the ester bonds of the water-soluble chitosan are hydrolyzed under the condition of body temperature, and the water-soluble chitosan is separated from the hydrogel coating and coated on the focus to play the roles of analgesia, hemostasis and antibiosis.

(3) The hydrogel coating is matched with a eustachian tube balloon dilatation catheter with a drug administration function for use, and when the catheter enters a dry and narrow physiological cavity such as a pathological eustachian tube, physiological saline can be injected to moisten the cavity through the drug administration function so as to improve the lubricating effect of the hydrogel coating.

(4) In the preparation process of the hydrogel coating, the ultraviolet light initiation procedure is not involved, the production equipment is simplified, and the production cost is reduced.

Drawings

FIG. 1 is the contact angle of the hydrogel coating obtained in example 1;

fig. 2 is a contact angle of the surface of a eustachian tube balloon catheter used in the present invention.

Detailed Description

To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to the following embodiments.

The eustachian tube balloon dilatation catheter used in the following examples is the eustachian tube balloon catheter in patent CN 202022250937; the eustachian tube balloon catheter comprises an elongated catheter, wherein the elongated catheter is provided with a front end and a tail end, a connector is fixedly sleeved at the front end, and a balloon is fixedly sleeved at the tail end; wherein the elongated catheter comprises a drug injection tube and an air intake tube; the air inlet pipe is sleeved on the outer side of the medicine injection pipe and is connected with the medicine injection pipe; the length of the medicine injection tube is greater than that of the air inlet tube; the tail end of the air inlet pipe is provided with a plurality of air inlet holes, and the air inlet holes are communicated with the saccule.

The water used for the preparation of the aqueous solutions in the following examples was ultrapure water.

Example 1

The embodiment provides a preparation method of a hydrogel coating for a eustachian tube balloon dilatation catheter, which comprises the following steps of:

(1) treating the eustachian tube balloon catheter by using a plasma surface treatment machine for 20min, and soaking the treated eustachian tube balloon catheter in a citric acid aqueous solution for 30min, wherein the mass fraction of citric acid in the citric acid aqueous solution is 3.5%; taking out the soaked eustachian tube balloon catheter, and drying at 45 ℃;

(2) dipping and coating the surface of the eustachian tube balloon catheter obtained in the step (1) with sodium alginate aqueous solution by using a lifting device, wherein the lifting speed is fixed at 10mm/min, the mass fraction of sodium alginate in the sodium alginate aqueous solution is 10%, and drying the eustachian tube balloon catheter in an oven at 95 ℃ for 6 hours after coating;

(3) soaking the eustachian tube balloon catheter obtained in the step (2) in a mixed aqueous solution of carboxymethyl chitosan and adipic acid for 15min, and then drying the soaked eustachian tube balloon catheter in an oven at 80 ℃ for 2h to form a hydrogel coating; wherein the mass fraction of the carboxymethyl chitosan in the mixed aqueous solution of the carboxymethyl chitosan and the adipic acid is 10 percent, and the mass fraction of the adipic acid is 0.05 percent; the molecular weight of carboxymethyl chitosan is 24Kda, the degree of deacetylation is 95%, and the degree of substitution is 85%.

Example 2

The embodiment provides a preparation method of a hydrogel coating for a eustachian tube balloon dilatation catheter, which comprises the following steps of:

(1) treating the eustachian tube balloon catheter by using a plasma surface treatment machine for 20min, and soaking the treated eustachian tube balloon catheter in a malic acid aqueous solution for 60min, wherein the mass fraction of malic acid in the malic acid aqueous solution is 2.0%; taking out the soaked eustachian tube balloon catheter, and drying at 50 ℃;

(2) soaking and coating the surface of the eustachian tube balloon catheter obtained in the step (1) with a sodium alginate aqueous solution by using a pulling device, wherein the pulling speed is fixed at 10mm/min, the mass fraction of sodium alginate in the sodium alginate aqueous solution is 12%, and drying the eustachian tube balloon catheter in an oven at 110 ℃ for 4 hours after coating;

(3) placing the eustachian tube balloon catheter obtained in the step (2) into a mixed aqueous solution of chitosan hydrochloride and citric acid for soaking for 20min, and then drying the soaked eustachian tube balloon catheter in a 75-DEG C drying oven for 3h to form a hydrogel coating; wherein the mass fraction of chitosan hydrochloride in the mixed aqueous solution of chitosan hydrochloride and citric acid is 7%, and the mass fraction of citric acid is 0.08%; the molecular weight of the chitosan hydrochloride is 30Kda, the deacetylation degree is 95%, and the substitution degree is 85%.

Example 3

The embodiment provides a preparation method of a hydrogel coating for a eustachian tube balloon dilatation catheter, which comprises the following steps of:

(1) treating the eustachian tube balloon catheter by using a plasma surface treatment machine for 20min, and soaking the treated eustachian tube balloon catheter in a succinic acid water solution for 40min, wherein the mass fraction of succinic acid in the succinic acid water solution is 4.0%; taking out the soaked eustachian tube balloon catheter, and drying at 50 ℃;

(2) soaking and coating the surface of the eustachian tube balloon catheter obtained in the step (1) with a sodium alginate aqueous solution by using a pulling device, wherein the pulling speed is fixed at 10mm/min, the mass fraction of sodium alginate in the sodium alginate aqueous solution is 10%, and drying the eustachian tube balloon catheter in an oven at 120 ℃ for 3 hours after coating;

(3) soaking the eustachian tube balloon catheter obtained in the step (2) in a mixed aqueous solution of chitosan quaternary ammonium salt and DL-tartaric acid for 20min, and then drying the soaked eustachian tube balloon catheter in an oven at 60 ℃ for 4h to form a hydrogel coating; wherein the mass fraction of the chitosan quaternary ammonium salt in the mixed water solution of the chitosan quaternary ammonium salt and the DL-tartaric acid is 5 percent, and the mass fraction of the DL-tartaric acid is 0.1 percent; the molecular weight of the chitosan quaternary ammonium salt is 15Kda, the deacetylation degree is 95%, and the substitution degree is 85%.

Effect example 1

This effect example tested the hydrophilicity, lubricity and release ability of the water-soluble chitosan of the hydrogel coatings obtained in examples 1 to 3, as follows:

(1) contact Angle test

Characterizing the hydrophilicity of the sample by performing a contact angle test on the hydrogel coating surface using an antennal gauge;

the preparation method of the test sample is the same as the above embodiment, but the sheet material with the same material is used to replace the balloon dilatation catheter;

the test was carried out using a plate of the same material as a control sample without coating treatment;

and (3) placing a flat sample with a proper size on a sample table, adjusting the position of the sample table to a proper position by an observation screen, and starting a microsyringe to vertically dropwise add 5 mu L of purified water to the center of the sample. After the water drop is stabilized on the surface, the photograph is taken and the contact angle is read by image analysis software.

(2) Friction test

A universal mechanical testing machine is matched with a self-made clamp to carry out a friction test on the surface of the hydrogel coating so as to represent the lubricity of the sample;

the test sample was prepared in the same manner as in the above example, with a catheter having a length of 10cm and a diameter of 0.6 mm;

the test was performed using a catheter of the same size and material but without the coating treatment for the control sample;

one end of the sample wetted with purified water was clamped to the sensor of the universal mechanical testing machine, and the other end was vertically dropped into a beaker containing purified water. Fixing the middle part of the sample by using a clamp capable of setting clamping force, wherein the clamping force is 5N; the apparatus pulls the sample at a rate of 100mm/min and repeats 20 times. The friction force was recorded by the test software.

(3) Water soluble chitosan release test

The release capacity of water-soluble chitosan in the hydrogel coating was tested according to 0704 nitrogen assay method in pharmacopoeia of the people's republic of China (2020 edition four).

The test specimens were prepared in the same manner as in the above examples, with the catheter having a length of 10cm and a diameter of 0.6 mm. 5 test samples are soaked in purified water in a 100ml volumetric flask for 30min at the constant temperature of 37 +/-1 ℃ to obtain a test product leaching liquor.

Taking the leaching liquor, precisely weighing and placing in a dry 500ml Kjeldahl flask, then sequentially adding 10g of potassium sulfate and 0.5g of copper sulfate powder, and slowly adding 20ml of sulfuric acid along the wall of the flask. Placing a small funnel at the mouth of the Kjeldahl flask, obliquely placing the Kjeldahl flask at an angle of 45 degrees, slowly heating with direct fire to keep the temperature of the solution below the boiling point, stopping boiling, strongly heating to boil, and cooling after the solution turns to clear green. Slowly adding 250ml of water along the wall of the bottle, shaking for mixing, cooling, adding 75ml of 40% sodium hydroxide solution, allowing the solution to flow to the bottom of the bottle along the wall of the bottle to form a liquid layer, adding several zinc particles, and connecting the Kjeldahl flask with a condenser tube by using a nitrogen balloon; adding 50ml of 2% boric acid solution into a 500ml conical flask, and adding 10 drops of mixed indicator solution of methyl red-bromocresol green; inserting the lower end of a condenser pipe below the liquid level of the boric acid solution, slightly swinging the Kjeldahl flask to uniformly mix the solution, heating and distilling until the total volume of the receiving solution is about 250ml, lifting the tip of the condenser pipe out of the liquid level, flushing steam for about 1 minute, and stopping distillation after rinsing the tip with water; the distillate was titrated with sulfuric acid titrant (0.05mol/L) until the solution changed from blue-green to grayish-purple and the titration results were corrected for by a blank test. Each 1ml of sulfuric acid titration solution (0.05mol/L) corresponded to 1.401mg of N.

The release amount of the water-soluble chitosan in a single catheter is calculated according to the following formula:

in the formula:

omega-the amount released of water-soluble chitosan in milligrams (mg) in the sample to be tested;

v1 — volume of sample tube consumed sulfuric acid titration in milliliters (mL);

v0 — volume of blank tube spent sulfuric acid titration in milliliters (mL);

-the average relative molecular mass of the water-soluble chitosan saccharide units.

The test results are shown in table 1 below and fig. 1-2.

TABLE 1

	Contact angle	Mean friction force (N)	Water-soluble chitosanRelease amount (mg)
				Example 1	7.8°	0.07	6.8
Example 2	9.6°	0.09	5.4
				Example 3	11.5°	0.15	4.3
Uncoated samples	96.4°	0.94	/

As can be seen from table 1 and fig. 1-2, the hydrogel coating of the present invention has excellent hydrophilicity and lubricity, while also having a high water-soluble chitosan releasing ability.

Effect example 2

The effect example examines the influence of temperature on the performance of the hydrogel coating, and sets test groups 1-8, wherein the schemes of the test groups 1-8 are different from the scheme of the example 1 only in that: the drying temperature of only step (2) in the protocols of test groups 1-4 was different, and the drying temperature of only step (3) in test groups 5-8 was different; hydrogel coatings were prepared according to the method of example 1, and the properties of the resulting hydrogel coatings were measured according to the method of effect example 1, and the results of the measurements are shown in table 2 below.

TABLE 2

As can be seen from Table 2, when the drying temperature in step (2) is 90-120 deg.C, and the drying temperature in step (3) is 60-90 deg.C, the hydrogel coating has good hydrophilicity, low friction, and high release amount of water-soluble chitosan.

Effect example 3

The effect example examines the influence of the molecular weight of the water-soluble chitosan on the performance of the hydrogel coating, and sets test groups 9-13, wherein the schemes of the test groups 9-13 are different from the scheme of the example 1 only in that: the molecular weight of the water-soluble chitosan is different; hydrogel coatings were prepared according to the method of example 1, and the properties of the resulting hydrogel coatings were tested according to the method of effect example 1, and the test results are shown in table 3 below.

TABLE 3

From the data in Table 3, it can be seen that the hydrogel coating performed better when the water-soluble chitosan had a molecular weight of 10-30 Kda.

Finally, it should be noted that the above embodiments are intended to illustrate the technical solutions of the present invention and not to limit the scope of the present invention, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims (10)

1. A preparation method of a hydrogel coating for a eustachian tube balloon dilatation catheter is characterized by comprising the following steps of:

(1) carrying out oxygen plasma treatment on the eustachian tube balloon dilatation catheter, soaking the eustachian tube balloon dilatation catheter in a polycarboxylic acid solution, and then taking out and drying the eustachian tube balloon dilatation catheter;

(2) coating the alginate solution on the surface of the eustachian tube balloon dilatation catheter obtained in the step (1), and then drying;

(3) and (3) soaking the eustachian tube balloon dilatation catheter obtained in the step (2) in a mixed solution of water-soluble chitosan and polycarboxylic acid, taking out and drying to form the hydrogel coating.

2. The production method according to claim 1, wherein in the step (1), the mass fraction of the polycarboxylic acid in the polycarboxylic acid solution is 1 to 5%.

3. The method according to claim 1, wherein in step (2), the alginate solution comprises alginate in an amount of 10 to 15% by weight.

4. The production method according to claim 1, wherein in the step (3), the mixed solution of the water-soluble chitosan and the polycarboxylic acid has a mass fraction of 0.05 to 0.1% and a mass fraction of 5 to 10% for the water-soluble chitosan.

5. The method according to claim 1 or 2, wherein the polycarboxylic acid is at least one of malic acid, citric acid, adipic acid, tartaric acid, and succinic acid.

6. The method according to claim 1 or 3, wherein the alginate is at least one of sodium alginate, potassium alginate and ammonium alginate.

7. The method according to claim 1 or 4, wherein the water-soluble chitosan is at least one of carboxymethyl chitosan, chitosan hydrochloride, chitosan quaternary ammonium salt, and chitosan lactate.

8. The method according to claim 1, wherein in the step (2), the drying temperature is 90-120 ℃, and the drying time is 3-6 h; in the step (3), the drying temperature is 60-90 ℃, and the drying time is 2-4 h.

9. The method of claim 1, wherein the eustachian tube balloon dilation catheter comprises an elongated catheter having a front end and a distal end, the front end being fixedly sleeved with a connector, the distal end being fixedly sleeved with a balloon; wherein the elongated catheter comprises a drug injection tube and an air intake tube; the air inlet pipe is sleeved on the outer side of the medicine injection pipe and is connected with the medicine injection pipe; the length of the medicine injection tube is greater than that of the air inlet tube; the tail end of the air inlet pipe is provided with a plurality of air inlet holes, and the air inlet holes are communicated with the saccule.

10. A hydrogel coating produced by the production method according to any one of claims 1 to 9.

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