Medical functional coating, preparation method and implantation intervention medical device

Abstract

The invention provides a medical functional coating, a preparation method and a implantation intervention medical device. The preparation method of the medical functional coating comprises the following steps: obtaining meso-porous silicon nanoparticles loaded with curcumin; adding the meso-porous silicon nanoparticles loaded with the curcumin into a solution of carboxymethyl chitosan and sodium alginate to form a gel solution of the meso-porous silicon nanoparticles loaded with the curcumin; providing a base material, and adsorbing the gel solution on the surface of the base material to form a coating capable of releasing curcumin; tissue regeneration after prostatic hyperplasia resection can be promoted, the antibacterial effect is achieved, the pain of a patient is relieved, and the treatment recovery period is shortened.

Description

TECHNICAL FIELD

[0001] The present application relates to the medical field, in particular to a medical functional coating, a preparation method and an interventional medical device. BACKGROUND

[0002] A urinary catheter is a tube made of rubber, silicone or plastic, which can be inserted into the bladder through the urethra to drain urine. It is a common medical device in medicine, often used for difficult urination, preoperative and postoperative urinary catheterization to drain urine.

[0003] Prostatic hyperplasia is one of the common diseases of elderly men. Although it is not a direct threat to life, it seriously affects the quality of life of patients; with the development of medical technology, surgery is one of the most effective methods for treating prostatic hyperplasia or prostate cancer. The special nature of the prostate surgery and the surgical site (the prostatic part of the urethra is located in the posterior urethra) often causes bleeding, infection, pain, slow wound healing and long course of disease. In the prior art, to solve the above problems, systemic anti-infection, hemostasis and other treatments are usually performed; a large amount of drugs need to be administered, and the therapeutic effect is poor, the patient suffers, and the treatment recovery period is long.

[0004] After prostate surgery, a urinary catheter is needed for urinary catheterization. The existing urinary catheter has many functional cavities in addition to the urinary catheterization function, such as water inlet and outlet cavities for flushing, balloon inflation cavity, etc.; it has good flushing and urinary catheterization effect when used. However, due to the presence of the urinary catheter, it has adverse effects on the postoperative site, such as bacteria, foreign bodies and compression effects, increasing the healing difficulty of the surgical site, thereby increasing the patient's pain and affecting the cure rate and recovery period, thus putting higher requirements on the urinary catheter.

[0005] Therefore, it is of great significance to develop a new, efficient, safe and non-bacterial drug-resistant antibacterial coating applied to the urinary catheter to promote tissue regeneration after prostatic hyperplasia resection. SUMMARY

[0006] The technical problem solved by the present application is to provide a medical functional coating, a preparation method and an interventional medical device, which can promote tissue regeneration after prostatic hyperplasia resection, have antibacterial effect, reduce patient pain and shorten the treatment recovery period.

[0007] The present application provides a preparation method of a medical functional coating, comprising: obtaining curcumin-loaded mesoporous silica nanoparticles; adding the curcumin-loaded mesoporous silica nanoparticles into a solution of carboxymethyl chitosan and sodium alginate to form a gel solution of the curcumin-loaded mesoporous silica nanoparticles; and providing a substrate, and adsorbing the gel solution on the surface of the substrate to form a curcumin-releasable coating.

[0008] Optionally, the method for obtaining the curcumin-loaded mesoporous silica nanoparticles comprises: providing initial mesoporous silica nanoparticles; and sequentially surface treating the initial mesoporous silica nanoparticles with a first treating solution and a curcumin solution to obtain the curcumin-loaded mesoporous silica nanoparticles.

[0009] Optionally, the initial mesoporous silica nanoparticles have a particle size ranging from 50 nm to 100 nm.

[0010] Optionally, the first treating solution is an ethanol solution of amino silane or a dopamine solution, the ethanol solution of amino silane has a concentration ranging from 5 mM to 20 mM, and the dopamine solution has a concentration ranging from 1 mg / ml to 5 mg / ml.

[0011] Optionally, the amino silane is 3-aminopropyltrimethoxysilane or 3-aminopropyltriethoxysilane.

[0012] Optionally, after the mesoporous silica nanoparticles are surface treated with the first treating solution, the method further comprises repeatedly centrifuging and washing the mesoporous silica nanoparticles with water.

[0013] Optionally, the carboxymethyl chitosan has a mass concentration ranging from 0.4 mg / ml to 8 mg / ml, and the sodium alginate has a mass concentration ranging from 0.4 mg / ml to 8 mg / ml.

[0014] Optionally, the ratio of the mass concentration of the carboxymethyl chitosan to the mass concentration of the sodium alginate ranges from 4:1 to 1:4.

[0015] Optionally, 5 mg to 30 mg of the curcumin-loaded mesoporous silica nanoparticles are contained in 10 mL of the gel solution.

[0016] Optionally, before the gel solution is adsorbed on the surface of the substrate to form a curcumin-releasable coating, the method further comprises forming a polydopamine coating on the surface of the substrate.

[0017] Optionally, the method for forming the polydopamine coating comprises immersing the substrate in a dopamine solution having a concentration ranging from 1 mg / ml to 4 mg / ml and a pH value of 8.5 for 4 hours to 12 hours.

[0018] Optionally, after the gel solution is adsorbed on the surface of the substrate to form a curcumin-releasable coating, the method further comprises cleaning and drying the substrate.

[0019] Optionally, the substrate comprises a medical catheter.

[0020] Optionally, the medical catheter comprises a urinary catheter, a tracheal tube, a drainage tube, a central venous catheter, or a coronary intervention catheter.

[0021] Accordingly, the present application also provides a medical functional coating prepared by the method for preparing a medical functional coating.

[0022] Accordingly, the present application also provides an interventional medical device having at least a part of its surface provided with the medical functional coating.

[0023] Compared with the prior art, the technical scheme of the present application has the following advantages:

[0024] In the method for preparing the medical functional coating, the curcumin-loaded mesoporous silica nanoparticles are added into a solution of carboxymethyl chitosan and sodium alginate to form a gel solution of the curcumin-loaded mesoporous silica nanoparticles, the substrate is placed into the gel solution, and a coating capable of releasing curcumin is formed on the surface of the substrate by adsorption from the gel solution. When the coating on the surface of the substrate contacts a wound, the curcumin can play a role in anti-inflammation and anti-oxidation, thereby promoting the regeneration of wound tissue. The coating can also play a role in antibiosis, avoiding secondary infection of the wound, reducing the pain of the patient, shortening the treatment and recovery period, and having a wide range of applications. The carboxymethyl chitosan and the sodium alginate have opposite charges and can form the gel solution through electrostatic interaction. The gel solution can be blended with the mesoporous nanoparticles, and after being coated on the surface of the substrate, the carboxymethyl chitosan and the curcumin-loaded mesoporous silica nanoparticles can be released, thereby playing a role in promoting wound repair and inhibiting inflammation. The gel solution formed by the carboxymethyl chitosan and the sodium alginate has excellent hydrophilicity and super-slip and super-hydrophilic properties, and the carboxymethyl chitosan also has an antibacterial effect. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 The figure is a flow chart of the formation process of the coating in an embodiment of the present application;

[0026] Figure 2 The figure shows the proliferation of prostate stromal cells on the surfaces of different materials in an embodiment of the present application;

[0027] Figure 3 The figure shows the antioxidant capacity of different samples;

[0028] Figure 4 The figure shows the antibacterial performance of different samples. DETAILED DESCRIPTION

[0029] As the background art, after a prostate hyperplasia resection surgery, a corresponding catheter needs to be inserted into the patient. The presence of the catheter has an adverse effect on the postoperative site, such as bacteria, foreign matter and compression effect, increasing the difficulty of healing of the surgical site, thereby increasing the pain of the patient and affecting the cure rate and recovery period.

[0030] On this basis, the application provides a preparation method of a medical functional coating, wherein the curcumin-loaded mesoporous silicon nanoparticles are added into a solution of carboxymethyl chitosan and sodium alginate to form a gel solution of the curcumin-loaded mesoporous silicon nanoparticles, the substrate is placed into the gel solution, and the coating capable of releasing curcumin is formed on the surface of the substrate by adsorption of the gel solution; when the coating on the surface of the substrate contacts with a wound, the curcumin can play a role of anti-inflammation and anti-oxidation, so as to promote the regeneration of the wound tissue, the coating can play a role of antibiosis to avoid secondary infection of the wound, the pain of the patient is reduced, the treatment recovery period is shortened, and the application range is wide.

[0031] In order to make the above objectives, characteristics and advantages of the present application more obvious and easy to understand, the specific embodiments of the present application are described in detail below with reference to the drawings.

[0032] Figure 1 The process flow chart of the coating formation in an embodiment of the present application is shown in Figure 1 Firstly, step S1 is performed to obtain the curcumin-loaded mesoporous silicon nanoparticles.

[0033] In the embodiment, the method for obtaining the curcumin-loaded mesoporous silicon nanoparticles comprises the steps of providing initial mesoporous silicon nanoparticles, and sequentially treating the surface of the initial mesoporous silicon nanoparticles by a first treatment solution and a solution of curcumin to obtain the curcumin-loaded mesoporous silicon nanoparticles.

[0034] In the embodiment, the particle size of the initial mesoporous nanoparticles ranges from 50 nm to 100 nm.

[0035] Specifically, the initial mesoporous nanoparticles are mesoporous silicon dioxide nanoparticles.

[0036] In the embodiment, the first treatment solution is an ethanol solution of amino silane or a solution of dopamine, the concentration of the ethanol solution of amino silane ranges from 5 mM to 20 mM, and the concentration of the solution of dopamine ranges from 1 mg / ml to 5 mg / ml.

[0037] In the embodiment, the amino silane is 3-aminopropyltrimethoxysilane or 3-aminopropyltriethoxysilane.

[0038] In the embodiment, after the surface treatment of the mesoporous silicon nanoparticles by the first treatment solution, the mesoporous silicon nanoparticles are further subjected to repeated centrifugal water washing.

[0039] Specifically, the initial mesoporous nanoparticles of 50-100 nm are dispersed in the amino silane ethanol solution of 5-20 mM or the dopamine solution of 1-5 mg / ml to form an intermediate mesoporous silica nanoparticle solution of 1 mg / ml, and the intermediate mesoporous silica nanoparticles are obtained by fully reacting for 4-12 hours and repeatedly centrifuging and washing with water. The modified intermediate mesoporous silica nanoparticles are further dispersed in the curcumin solution of 2-10 mg / ml, fully adsorbed for 1-4 hours, and dried by centrifugation to obtain the curcumin-loaded mesoporous silica nanoparticles.

[0040] The step S2 is performed: the curcumin-loaded mesoporous silica nanoparticles are added to a solution of carboxymethyl chitosan and sodium alginate to form a gel solution of the curcumin-loaded mesoporous silica nanoparticles.

[0041] In the embodiment, the mass concentration of the carboxymethyl chitosan ranges from 0.4 mg / ml to 8 mg / ml, and the mass concentration of the sodium alginate ranges from 0.4 mg / ml to 8 mg / ml.

[0042] In the embodiment, the ratio of the mass concentration of the carboxymethyl chitosan to the mass concentration of the sodium alginate ranges from 4:1 to 1:4.

[0043] In the embodiment, the solution of carboxymethyl chitosan and sodium alginate is formed by mixing a solution of carboxymethyl chitosan and a solution of sodium alginate in a certain ratio.

[0044] Specifically, the solution of carboxymethyl chitosan and sodium alginate is formed by providing a carboxymethyl chitosan solution with a mass concentration of 2-10 mg / ml and a sodium alginate solution with a mass concentration of 2-10 mg / ml, and the volume ratio of the carboxymethyl chitosan solution to the sodium alginate solution is 4-1:1-4, such as 4:1, 3:1, 1:1, 1:2, 1:3, 1:4, and the like.

[0045] In other embodiments, the solution of carboxymethyl chitosan and sodium alginate can also be formed by adding carboxymethyl chitosan solid and sodium alginate solid to a solvent.

[0046] In the embodiment, the carboxymethyl chitosan and the sodium alginate have opposite charges and can form the gel solution through electrostatic interaction. This gel solution can be blended with mesoporous nanoparticles, and after being coated on the surface of the substrate, the carboxymethyl chitosan and the curcumin-loaded mesoporous silica nanoparticles can be released, thereby promoting wound repair and inhibiting inflammation. The gel solution formed by the carboxymethyl chitosan and the sodium alginate itself has excellent hydrophilicity and super-slip and super-hydrophilic properties, and the carboxymethyl chitosan also has antibacterial effect.

[0047] In the embodiment, 5mg-30mg of the curcumin-loaded mesoporous silica nanoparticles are contained in every 10mL of the gel solution.

[0048] Step S3 is performed: providing a substrate, and adsorbing the gel solution on the surface of the substrate to form a curcumin-releasable coating.

[0049] In the embodiment, the substrate includes medical catheters, including urinary catheters, tracheal tubes, drainage tubes, central venous catheters, and coronary intervention catheters.

[0050] Specifically, the medical catheter uses the urinary catheter.

[0051] In the embodiment, a polydopamine coating is formed on the surface of the substrate.

[0052] In the embodiment, the method for forming the polydopamine coating is: immersing the substrate in a dopamine solution with a concentration ranging from 1mg / ml to 4mg / ml and a pH value of 8.5 for 4-12 hours, and then washing and drying to obtain a substrate with a polydopamine coating on the surface.

[0053] In the embodiment, the substrate is immersed in the gel solution for sufficient adsorption and reaction for 1-4 hours.

[0054] In the embodiment, after the curcumin-releasable coating is formed on the surface of the substrate, the substrate is subjected to washing and drying treatment.

[0055] In the embodiment, after the polydopamine coating is formed on the surface of the substrate, the surface of the substrate has good bioadhesion, adhesion, antioxidant capacity, and strong chemical reactivity, so that the curcumin-releasable coating is more easily formed on the surface of the substrate.

[0056] In the embodiment, after the curcumin-releasable coating is formed on the surface of the substrate, the coating can release curcumin, which can play an anti-inflammatory and antioxidant role to promote wound tissue regeneration, and the coating can also play an antibacterial role to avoid secondary infection of the wound, reduce the pain of the patient, shorten the treatment and recovery period, and have a wide range of applications. In addition, the carboxymethyl chitosan and the sodium alginate have opposite charges and can form the gel solution through electrostatic interaction. This gel solution can be blended with mesoporous nanoparticles, and after being coated on the surface of the substrate, it can release the carboxymethyl chitosan and the curcumin-loaded mesoporous silica nanoparticles, thereby playing a role in promoting wound repair and inhibiting inflammation. The gel solution formed by the carboxymethyl chitosan and the sodium alginate itself has excellent hydrophilicity and super-slip and super-hydrophilic properties, and the carboxymethyl chitosan also has antibacterial effects.

[0057] Correspondingly, the application further provides a medical functional coating prepared by the preparation method.

[0058] In the embodiment, the medical functional coating can release curcumin which can play an anti-inflammatory and antioxidant role to promote wound tissue regeneration, and the coating can play an antibacterial role to avoid secondary infection of the wound, reduce the pain of the patient, shorten the treatment recovery period, and expand the use range of the medical functional coating.

[0059] Correspondingly, the application further provides an implant interventional medical device having the coating on at least part of the surface.

[0060] In the embodiment, since the implant interventional medical device has the medical functional coating on at least part of the surface, since the medical functional coating can release curcumin which can play an anti-inflammatory and antioxidant role to promote wound tissue regeneration, and the coating can play an antibacterial role to avoid secondary infection of the wound, reduce the pain of the patient, the implant interventional medical device can have a wider use range.

[0061] The technical solutions of the application are further described below through specific embodiments.

[0062] Embodiment 1: Human prostate stromal cells are cultured and inoculated on the surfaces of different modified materials, cultured at 37℃ and 5% CO2 for 1 day, 3 days and 5 days respectively, the proliferation of the cells is detected by using the CCK-8 evaluation method, and the obtained results are as shown in Figure 2

[0063] Figure 2 ​​The results can be seen that the proliferation of normal cells (NC) is good, while the silicone surface (silicone) lacks effective bioactivity, and the proliferation activity of cells is consistent. After the preparation of carboxymethyl chitosan / sodium alginate (CS / SA) coating on the silicone surface, the proliferation performance is improved to a certain extent due to the promotion of cell adhesion and growth by carboxymethyl chitosan. Then, after adding hydrogen peroxide (H2O2) in the cells, the proliferation of the cells is improved to a certain extent, and the cell activity is significantly less than that of normal cells. If H2O2 is added during the culture of the CS / SA coating modified sample and cells, the proliferation of the cells is improved to a certain extent, but due to the addition of H2O2, the proliferation activity of the cells is less than that of the CS / SA coating modified sample without the addition of H2O2, indicating that the addition of H2O2 inhibits the growth of the cells to a certain extent. When H2O2 is added in the CS / SA coating loaded with curcumin nanoparticles (H2O2+Cur) for co-culture, due to the antioxidant bioactivity of curcumin, the proliferation performance of the cells is obviously improved, indicating the antioxidant effect of curcumin, which helps to promote the healing of the damaged tissue.

[0064] Example 2: The antioxidant capacity of different samples was detected by using a commercial total antioxidant capacity (T-AOC) detection kit, and the results are shown in Figure 3

[0065] As can be seen from Figure 3 , the antioxidant capacity of silicone rubber and materials added with hydrogen peroxide is weak, while the antioxidant capacity of CS / SA and CS / SA coating modified samples loaded with curcumin nanoparticles is improved, even in the presence of hydrogen peroxide (H2O2), especially the material loaded with curcumin, which has excellent antioxidant capacity, which helps to promote the proliferation of cells, thereby promoting the rapid healing of the tissue after prostate surgery.

[0066] ​Example 3: Bacterial inhibition experiment. Bacterial inhibition experiments were conducted on unmodified silica gel samples (silicone), silica gel samples modified with a CS / SA coating (CS / SA), and samples modified with a CS / SA coating loaded with curcumin nanoparticles (Cur-CS / SA). Typical Gram-positive bacteria (Escherichia coli) and typical Gram-negative bacteria (Staphylococcus aureus) were selected as test bacteria. Escherichia coli (or Staphylococcus aureus) were cultured overnight in liquid culture medium (LB broth, 25 g / L). 10 mL of the bacterial solution was aspirated and centrifuged at 1300 rpm for 5 minutes to assess bacterial survival and count. The bacterial solution was re-shaken and diluted to an absorbance of approximately 0.01. After the sample surface was sterilized, it was placed in a 12-well plate. 500 μL of the diluted bacterial solution was aspirated and added dropwise to the sample surface. The plates were incubated at 37°C for 30 minutes. Then, 1500 μL of sterile deionized water was added to each plate and the culture was continued at 37°C for 24 hours. 50 μL of bacterial solution from the sample plate was added dropwise to the surface of solid culture medium (LB nutrient agar, 40 g / L) and evenly spread. After incubation at 37°C overnight, photos were taken and the antibacterial properties were evaluated by analyzing the number of colonies. Figure 4 shown.

[0067] Depend on Figure 4 It can be seen that the effect of the unmodified silica gel sample is poor, whether it is Escherichia coli or Staphylococcus aureus. Due to the good antibacterial effect of carboxymethyl chitosan, the number of bacteria in the sample modified by CS / SA coating is significantly reduced, showing excellent antibacterial performance; after further adding curcumin-loaded nanoparticles, the antibacterial performance of the material is further improved, and almost no bacterial growth is observed, indicating the excellent antibacterial performance of the material.

[0068] Although the present invention is disclosed as above, the present invention is not limited thereto. Any person skilled in the art can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be based on the scope defined by the claims.

Claims

1. A method for the production of a medical functional coating, characterized in that The method comprises the following steps: obtaining curcumin-loaded mesoporous silica nanoparticles; adding the curcumin-loaded mesoporous silica nanoparticles into a solution of carboxymethyl chitosan and sodium alginate to form a gel solution of curcumin-loaded mesoporous silica nanoparticles; providing a substrate, and adsorbing the gel solution on the surface of the substrate to form a curcumin-releasable coating.

2. The method of claim 1, wherein the functional coating is a medical functional coating. The method for obtaining the curcumin-loaded mesoporous silica nanoparticles comprises the following steps: providing initial mesoporous silica nanoparticles; surface-treating the initial mesoporous silica nanoparticles with a first treatment solution and a curcumin solution in sequence to obtain the curcumin-loaded mesoporous silica nanoparticles.

3. The method of claim 2, wherein the functional coating is applied to the medical device by a method selected from the group consisting of: dip coating, spray coating, spin coating, and combinations thereof. The particle size of the initial mesoporous silica nanoparticles ranges from 50 nm to 100 nm.

4. The method of claim 2, wherein the functional coating is applied to the medical device by a method selected from the group consisting of: plasma spraying, sputtering, and thermal evaporation. The first treatment solution is an ethanol solution of amino silane or a dopamine solution, the concentration of the ethanol solution of amino silane ranges from 5 mM to 20 mM, and the concentration of the dopamine solution ranges from 1 mg / ml to 5 mg / ml.

5. The method of producing a medical functional coating according to claim 4, wherein The amino silane is 3-aminopropyltrimethoxysilane or 3-aminopropyltriethoxysilane.

6. The method for preparing a medical functional coating according to claim 2, wherein: After the mesoporous silica nanoparticles are surface-treated by the first treatment solution, the method further comprises repeatedly centrifuging and washing the mesoporous silica nanoparticles with water.

7. The method for preparing a medical functional coating according to claim 1, wherein: The mass concentration of the carboxymethyl chitosan ranges from 0.4 mg / ml to 8 mg / ml, and the mass concentration of the sodium alginate ranges from 0.4 mg / ml to 8 mg / ml.

8. The method for preparing a medical functional coating according to claim 1, wherein: The ratio of the mass concentration of the carboxymethyl chitosan to the mass concentration of the sodium alginate ranges from 4:1 to 1:

4.

9. The method for preparing a medical functional coating according to claim 1, wherein: Each 10 mL of the gel solution contains 5 mg-30 mg of the curcumin-loaded mesoporous silica nanoparticles.

10. The method for preparing a medical functional coating according to claim 1, wherein: Before the gel solution is adsorbed on the surface of the substrate to form the curcumin-releasable coating, the method further comprises forming a polydopamine coating on the surface of the substrate.

11. The method of producing a medical functional coating according to claim 10, wherein The method for forming the polydopamine coating is that the substrate is immersed in a dopamine solution with a concentration ranging from 1 mg / ml to 4 mg / ml, for 4 hours to 12 hours, and the pH value of the dopamine solution is 8.

5.

12. The method for preparing a medical functional coating according to claim 1, wherein: After the curcumin-releasable coating is formed on the surface of the substrate, the method further comprises cleaning and drying the substrate.

13. The method for preparing the medical functional coating according to claim 1, wherein: The substrate comprises a medical catheter.

14. The method of producing a functional coating for medical use according to claim 13, wherein The medical catheter comprises a urinary catheter, a trachea, a drainage tube, a central venous catheter, and a coronary intervention catheter.

15. A medical functional coating prepared by the method for preparing a medical functional coating according to any one of claims 1 to 14.

16. An implantable medical device, characterized in that: At least part of the surface of the medical device has the medical functional coating according to claim 15.

Images