CN110721347B

CN110721347B - Anti-blocking anti-infection shunt pipe and preparation method thereof

Info

Publication number: CN110721347B
Application number: CN201910973636.7A
Authority: CN
Inventors: 赵东升; 别小华
Original assignee: Xian Honghui Hospital
Current assignee: Xian Honghui Hospital
Priority date: 2019-10-14
Filing date: 2019-10-14
Publication date: 2022-05-17
Anticipated expiration: 2039-10-14
Also published as: CN110721347A

Abstract

The invention discloses a blockage-preventing anti-infection shunt pipe and a preparation method thereof, wherein the blockage-preventing anti-infection shunt pipe comprises the following steps: the shunt pipe comprises a sodium citrate and chymotrypsin composite coating and a Shupu deep coating, can effectively prevent blockage caused by blood clots, leucocytes and protein adhesion in the shunt pipe, can also prevent infection of the shunt pipe, and can effectively avoid danger caused by frequent replacement of the shunt pipe.

Description

Anti-blocking anti-infection shunt pipe and preparation method thereof

Technical Field

The invention relates to a medical instrument for hydrocephalus shunt surgery, in particular to an anti-blocking anti-infection shunt tube.

Background

Since Kausch first applied ventricular-peritoneal shunt (V-P shunt) to treat hydrocephalus, along with the development of shunt, the shunt device in V-P shunt is continuously perfected, and the shunt technology is continuously improved, so that the complications of shunt are reduced to the maximum extent. Nevertheless, complications from various shunt failures continue to emerge, making it the biggest obstacle in the treatment of hydrocephalus. When the students reviewed the history of the shunt, they noted that the 1-year failure rate of the shunt was 40% and the 2-year failure rate was 50%. The most common causes of shunt failure are shunt blockage, shunt infection, and over-shunting, respectively, where shunt blockage is the leading site and shunt infection can be life threatening.

Clinically, the blockage of the shunt tube can be treated only by pulling out the shunt tube and replacing the shunt tube. When the shunt tube is pulled out, the risk of rebleeding exists, when a new shunt tube is placed, the risk of secondary brain injury and cerebral hemorrhage exists, if the shunt tube is blocked again along with the lapse of time, one patient may need to change the shunt tube for many times, so that the medical cost is increased, and the operation risk is increased. It has been reported that the incidence of epilepsy was 5.9% when one hit was performed without repeated puncture and 24.2% when the shunt was inserted by two punctures during ventricular puncture. For the treatment of shunt tube infection, the shunt tube can only be pulled out, the drainage is carried out outside the cerebrospinal fluid, the anti-infection treatment is enhanced, the shunt tube is placed again after the cerebrospinal fluid is normal, the process is not only long, but also the life of a patient is possibly threatened. How to solve the problems of blockage and infection of the shunt pipe is always a difficult problem which puzzles the hydrocephalus shunt operation.

Chinese patent ' multidirectional valve hydrocephalus shunt tube with antibacterial and anticoagulant functions and preparation and use methods thereof ' (CN103007422A) proposes an antibacterial and anticoagulant coating technology for the shunt tube, which points out that the surface of the shunt tube is sequentially treated with rifampicin and/or nitrofurazone as antibacterial agents and heparin sodium as anticoagulant agents to carry out antibacterial and anticoagulant treatment, thereby being convenient for long-term implantation, effectively preventing infection and blockage and solving two complications of the present hydrocephalus shunt operation '. However, according to clinical effects, the shunt tube coated with heparin sodium is still difficult to avoid blockage, which is mainly reflected in cerebrospinal fluid drainage, and cerebrospinal fluid with slow flow rate (lower than blood flow rate) cannot clear clots formed in the shunt tube. The shunt tube coated with rifampicin and nitrofurazone has a narrow antibacterial spectrum, so that the effect of preventing infection of the shunt tube is obviously insufficient, and the aggregation of clots in the shunt tube also causes the aggravation of infection.

The sulbactam sodium is developed and produced by a pyroxene company, the antibacterial component of the sulbactam sodium is cefoperazone, the compound preparation is a third-generation cephalosporin and enzyme inhibitor compound preparation, the compound preparation has a synergistic antibacterial effect on various bacteria, the sulbactam sodium is an only antibacterial drug with the drug resistance rate of less than 35 percent of all common bacteria in a drug resistance monitoring report, and the sulbactam sodium is good in safety and tolerance.

The sodium citrate is the most important citrate, is mainly generated by fermenting starch substances and then neutralizing with alkali substances, and has the following characteristics: 1) is safe and nontoxic; 2) is biodegradable; 3) can complex with metal ions (such as Ca)²⁺) (ii) a 4) Is easily dissolved in water; 5) the pH can be adjusted. The sodium citrate also has the retarding performance, and can play a role in preventing blood coagulation by adding the disinfected sodium citrate when fresh blood is clinically taken, so the sodium citrate is called as anticoagulant.

Chymotrypsin is a proteolytic enzyme secreted by pancreas, is used for enzymolysis of peptide chains and specially hydrolyzes peptide bonds, and belongs to endopeptidase. Generally, the protein can be rapidly decomposed and denatured, has the similar action and application as trypsin, and has stronger decomposition capability, lower toxicity and less adverse reaction compared with the trypsin.

At present, the main problems faced by the coating technology of an anticoagulant and antibacterial shunt tube are as follows: aiming at the flowing liquid environment in the shunt pipe, how to enable the coating at the liquid-solid interface to achieve the expected anti-blocking and anti-infection functions is not clear, namely, no clear basis is available for selecting the components of the coating. Meanwhile, at present, reports of using sodium citrate and chymotrypsin to manufacture the composite coating shunt pipe are not found.

Disclosure of Invention

The invention aims to provide an anti-blocking anti-infection shunt pipe and a preparation method thereof, which can effectively prevent the shunt pipe from being blocked and prevent the shunt pipe from being infected.

In order to achieve the purpose, the invention adopts the following technical scheme:

the utility model provides an anti-blocking anti-infection shunt tubes, this shunt tubes include the shunt tubes body and set up the antibacterial coating on the internal surface and the surface of shunt tubes body, the last anticoagulant coating that is provided with of antibacterial coating, wherein, anticoagulant coating is selected from the composite coating of sodium citrate and chymotrypsin.

Preferably, the components of the antibacterial coating comprise a compound preparation of cefoperazone and sulbactam (e.g., sulbactam).

Preferably, the surface of the antibacterial coating is modified by plasma sputtering.

The preparation method of the anti-blocking anti-infection shunt pipe comprises the following steps:

1) preparing an antibacterial coating on the shunt tube body;

2) after the step 1), performing plasma sputtering on the antibacterial coating on the shunt tube body, and preparing a composite coating of sodium citrate and chymotrypsin on the antibacterial coating after modifying the surface of the antibacterial coating by using the plasma sputtering; or, after the step 1), directly preparing the composite coating of the sodium citrate and the chymotrypsin on the antibacterial coating.

Preferably, the step 1) specifically comprises the following steps: soaking the shunt tube body in a Shupu deep solution for 24-48 hours, wherein the concentration of Shupu deep in the solution is 1-2 g/L, and the soaking temperature is 20-40 ℃; taking out and drying after soaking.

Preferably, in the step 2), the preparation of the composite coating of sodium citrate and chymotrypsin specifically comprises the following steps: soaking the shunt tube body with the antibacterial coating in a mixed solution of sodium citrate and chymotrypsin for 24-48 hours, wherein the concentration of the sodium citrate in the solution is 30-35 g/L, the concentration of the chymotrypsin is 1-10 g/L, the soaking temperature is 20-40 ℃, and taking out and drying after soaking; or after plasma sputtering is carried out on the shunt tube body with the antibacterial coating, the shunt tube body is soaked in the sodium citrate-chymotrypsin mixed solution for 24-48 hours at the soaking temperature of 20-40 ℃, and the shunt tube body is taken out and dried after soaking.

The invention has the beneficial effects that:

the invention provides the shunt tube with the sodium citrate and chymotrypsin composite coating by considering the actual conditions (including clot formation cause and cerebrospinal fluid flow rate) of the shunt tube during draining cerebrospinal fluid, and the shunt tube can continuously play an anti-blocking role in drainage (the clot can be effectively removed by the flowing of the cerebrospinal fluid), so that the danger caused by frequent replacement of the shunt tube is avoided. Meanwhile, the antibacterial coating is reserved between the composite coating of the sodium citrate and the chymotrypsin and the shunt tube body, and the antibacterial coating and the composite coating attached to the antibacterial coating are mutually cooperated, so that the infection risk aggravated by clot and bacterial adhesion in the shunt tube is reduced, and the infection of the shunt tube is effectively prevented.

Furthermore, the invention adopts Shupu as the drug effect component of the antibacterial coating, thereby obviously reducing the occurrence of shunt tube infection.

Drawings

Fig. 1 is a schematic structural diagram of a shunt tube used in a shunt simulation experiment device (an oblique fracture indicates that the shunt tube is a slender tube body);

in the figure: 1. a liquid inlet; 2. a shunt tube body part.

Detailed Description

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

Shunt tube coating design

Through model experiments and clinical data analysis, the invention finds that the main reasons for blockage of the shunt tube are erythrocyte coagulation, adhesion of leukocytes and protein accumulation, so that the shunt tube is gradually narrowed until the shunt tube is blocked. While the effect of most Cell Adhesion Molecules (CAM) depends on divalent cations, such as Ca²⁺，Mg²⁺. The mechanism of action of cell adhesion molecules is in three modes: mutual recognition and binding (homophilic adhesion) between homogeneous CAM molecules on the surfaces of two adjacent cells; mutual recognition and binding (affinity binding) between different types of CAM molecules on the surfaces of two adjacent cells; the same CAM molecule on the surface of two adjacent cells is extracellularlyThe linker molecules of (a) recognize and bind to each other.

Meanwhile, shunt infection can be caused by gram-positive bacteria or gram-negative bacteria, which are the main pathogenic bacteria causing nosocomial infection, accounting for 71.6 percent, most commonly enterobacter, and secondly acinetobacter and pseudomonas aeruginosa.

Based on the above experimental and analytical results, in combination with analysis of the composition (e.g., the presence of oozing blood, inflammation, etc. physiological or pathological conditions that are likely to induce clot formation) and flow characteristics of the fluid (cerebrospinal fluid) in the shunt tube, the present invention finally screens and determines coating compositions different from those of the existing shunt tube (e.g., chinese patent CN 103007422A). The invention uses the sodium citrate and chymotrypsin composite coating as the anticoagulation coating, uses Shupu as the main component of the antibacterial coating, and uses the plasma sputtering modification technology to process the shunt tube before the anticoagulation treatment, thus being beneficial to increasing the bonding strength of the anticoagulation medicament (sodium citrate and chymotrypsin) and the shunt tube wall with the antibacterial coating, and leading the anticoagulation coating to keep more lasting effect in drainage.

(II) preparation of the coating

Referring to fig. 1, in the experiment, a silica gel shunt tube is used as a treatment object, one end of a shunt tube body 2 is provided with a radial hole as a liquid inlet 1, and the other end of the shunt tube body is used for allowing cerebrospinal fluid to flow out, so that drainage is realized. The specific treatment process comprises the following steps:

1) antibacterial treatment

Taking normal saline as a solvent, dissolving a certain amount of Shupu deep, and preparing 1-2 g/L Shupu deep-normal saline solution; soaking the silica gel shunt tube in Shupu deep-normal saline solution for 24 hours, controlling the soaking temperature to be 20-25 ℃ by using water bath, taking out and drying (70-80 ℃);

2) plasma sputtering modification

Placing the antibacterial silica gel shunt tube in a plasma immersion ion injection device, vacuumizing, and introducing nitrogen at the gas pressure of 40-50P; controlling the radio frequency discharge power to be 1000-1200W; the amplitude of the loaded pulse high-voltage power supply is 50-100 kV, the frequency is 20000-40000 Hz, and the duty ratio is 50-80%; the heating temperature is 120-200 ℃, and the treatment is carried out for 3-5 h.

3) Anticoagulation treatment

Dissolving a certain amount of sodium citrate (Shanghai, Biotechnology Co., Ltd.) and chymotrypsin (Shanghai, first Biochemical pharmaceutical Co., Ltd.) in physiological saline to obtain a mixed solution, wherein the concentration of the sodium citrate and the concentration of the chymotrypsin are respectively 32.1g/L and 1g/L, soaking the silica gel shunt tube subjected to antibacterial treatment and plasma sputtering modification in the mixed solution for 24 hours, controlling the soaking temperature to be 20-25 ℃ by using a water bath, taking out, and drying (70-80 ℃).

4) And (3) packaging the silica gel shunt tube treated in the step 3) by adopting a paper-plastic bag, and sterilizing by using ethylene oxide to obtain a finished product (namely the shunt tube with the antibacterial coating and the anticoagulant coating).

Through using normal saline, the shunt tube after treatment can be more suitable to be implanted into a body for use, the influence of the shunt tube coating on the cerebrospinal fluid for drainage is reduced, and the clot occurrence probability is reduced.

(III) functional test of coating

Experiment 1

Using shunt tubes (denoted as T) and common shunt tubes (untreated silica gel shunt tubes, denoted as C) having an antibacterial coating (inner coating) and an anticoagulant coating (outer coating) prepared by the present invention, 30 shunt tubes were each divided into two groups, rabbit venous blood was used to fill each shunt tube (forming an accelerated clot model), the standing was performed for 1h, 2h, and 3h, and then the unobstructed degree of the shunt tubes was observed (if venous blood could be completely evacuated, the unobstructed degree was denoted as unobstructed, if it could not be evacuated, the obstructed degree was denoted as blocked), and the results are shown in table 1.

TABLE 1 results of experiment 1

From the results of experiment 1, the anticoagulant coating prepared by the invention has obvious anti-blocking effect. From the results of experiment 1, it was also found that: the main reason for the blockage of the shunt is the formation of clots inside the shunt that block the shunt due to blood clotting (e.g., red blood cell coagulation), inflammatory cell (e.g., white blood cell) adhesion, and protein adhesion, and the complex formation of clots places a high demand on the anticoagulant coating (which is also the reason for the poor anti-blockage effect of pure blood anticoagulant ingredients such as heparin sodium).

Experiment 2

After the experiment 1, the component flow tubes are flushed with normal saline (simulated cerebrospinal fluid) for 24 hours, the flushing process adopts a mode of hanging and filling an injection bottle, the drainage state (slow flow rate and the like) of the actual cerebrospinal fluid is simulated as much as possible, the rabbit venous blood is injected again after the normal saline is flushed, and the experiment 1 is repeated, wherein the results are shown in table 2.

TABLE 2 results of experiment 2

Experiment 3

After experiment 2, the component flow tubes were flushed again with normal saline for 72 hours, and after flushing with normal saline, the rabbit venous blood was again injected, and experiment 1 was repeated, with the results shown in table 3.

TABLE 3 results of experiment 3

In experiments 2 and 3, the ordinary shunt tube group cannot reach a smooth result again through flushing all the time after the blockage of the first experiment. From the results of experiments 2 and 3, it can be seen that although the flow of cerebrospinal fluid (simulated by normal saline) in the shunt tube has a certain influence on the coating effect, the shunt tube coating prepared by the invention can continuously play a role in removing clots in the drainage of cerebrospinal fluid, and effectively ensures that the shunt tube is not blocked.

Further experiments show that the anticoagulant coating not only has the anticoagulant effect, but also has the anti-inflammatory effect, so that the anticoagulant coating can effectively remove clots formed by aggregated cells and other cerebrospinal fluid components which are easy to adhere, has the continuous anti-blocking effect, and is matched with the antibacterial coating to obviously reduce the risk of infection of the shunt tube.

Claims

1. An anti-blocking anti-infection shunt tube, which is characterized in that: the shunt tube comprises a shunt tube body and antibacterial coatings arranged on the inner surface and the outer surface of the shunt tube body, wherein an anticoagulant coating is arranged on the antibacterial coatings, the anticoagulant coating is selected from a composite coating of sodium citrate and chymotrypsin, the composite coating is prepared by using a mixed solution of the sodium citrate and the chymotrypsin, and the mixed solution of the sodium citrate and the chymotrypsin contains 30-35 g/L of sodium citrate and 1-10 g/L of chymotrypsin dissolved in physiological saline;

the antibacterial coating comprises a compound preparation of cefoperazone and sulbactam, and is prepared by using 1-2 g/L sulbactam deep-normal saline solution.

2. An anti-clogging, anti-infective shunt according to claim 1 wherein: the surface of the antibacterial coating is modified by plasma sputtering.

3. A preparation method of an anti-blocking anti-infection shunt pipe is characterized by comprising the following steps: the method comprises the following steps:

1) preparing an antibacterial coating on the shunt tube body;

2) after the step 1), performing plasma sputtering on the antibacterial coating on the shunt tube body, and preparing a composite coating of sodium citrate and chymotrypsin on the antibacterial coating after modifying the surface of the antibacterial coating by using the plasma sputtering; or, after the step 1), directly preparing a composite coating of sodium citrate and chymotrypsin on the antibacterial coating;

in the step 2), the preparation of the composite coating of sodium citrate and chymotrypsin specifically comprises the following steps: dissolving a certain amount of sodium citrate and chymotrypsin in physiological saline, soaking the shunt tube body with the antibacterial coating in a mixed solution of the sodium citrate and the chymotrypsin for 24-48 hours, wherein the concentration of the sodium citrate in the solution is 30-35 g/L, the concentration of the chymotrypsin is 1-10 g/L, the soaking temperature is 20-40 ℃, and taking out and drying after soaking; or after plasma sputtering is carried out on the shunt tube body with the antibacterial coating, soaking the shunt tube body in the sodium citrate-chymotrypsin mixed solution for 24-48 hours at the soaking temperature of 20-40 ℃, and taking out and drying after soaking;

the step 1) specifically comprises the following steps: dissolving a certain amount of Shupu in normal saline as a solvent, and soaking the shunt tube body in the Shupu deep solution for 24-48 hours, wherein the concentration of the Shupu in the solution is 1-2 g/L, and the soaking temperature is 20-40 ℃; taking out and drying after soaking.