CN115400231A - Conductive medical adhesive and preparation method and application thereof - Google Patents

Abstract

The invention provides a conductive medical adhesive, its preparation method and application. The raw materials for the preparation of the conductive medical adhesive include the following components in parts by weight: 15-50 parts of gelatin, 0.1-3 parts of a conductive agent and 20-50 parts of a modifier. The preparation method comprises the following steps: (1) mixing gelatin, a conductive agent and water and solidifying to obtain a hydrogel; (2) modifying the hydrogel obtained in step (1) and a modifying agent to obtain the hydrogel The above-mentioned conductive medical adhesive glue. The conductive medical adhesive glue prepared by the invention has better conductivity and adhesion, and better biocompatibility, and is suitable for use as a wound sealing material or a bonding repair material for peripheral nerve damage.

Description

A kind of conductive medical adhesive and its preparation method and application

technical field

The invention belongs to the technical field of biomedical materials, and in particular relates to a conductive medical adhesive and its preparation method and application.

Background technique

With the rapid development of the economy and the promotion of medical and health services, patients' demand for surgical services and the appearance of postoperative wounds continues to increase. In recent years, the research and development and industrialization of biomedical adhesives have developed rapidly. The medical adhesive can be closely inlaid with the wound surface, can firmly maintain the joint state of the wound, reduce the bleeding and infection chance of the wound, and has the functions of controlling bleeding, closing the wound and inhibiting scar hyperplasia.

CN110960724A discloses a medicinal hydrogel and its preparation method. The medicinal hydrogel is obtained by uniformly dispersing raw materials including methacrylated gelatin, polydopamine hyaluronic acid and the first nano-particles for cross-linking reaction; the weight of methacrylated gelatin and polydopamine hyaluronic acid The ratio is (1-5):1, and the weight of the first nanoparticle accounts for 0.05%-0.2% of the total weight of methacrylated gelatin and polydopamine hyaluronic acid; the first nanoparticle is modified by β-cyclodextrin Graphene oxide and N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine are dispersed in an organic solvent according to the weight ratio 1:(1.5-2.5), and the reaction is stirred in the dark After standing still for 8-20h, it is obtained. The hydrogel prepared by this technical solution has the functions of being able to fit the wound and stop bleeding as the shape of the wound changes, but the preparation process is relatively complicated.

CN111420125A discloses a medical hydrogel and its preparation method. The preparation method comprises the following steps: providing an acidic aqueous solution of gelatin; adding a coupling agent to the acidic aqueous solution of gelatin to perform a first crosslinking reaction to obtain a gelatin/coupling agent solution, wherein the coupling agent contains Amino and/or epoxy bonded silane coupling agents; the gelatin/coupling agent solution is left standing at 1-4°C to obtain gelatin/silica hybrid hydrogel; the gelatin/silica The silicon hybrid hydrogel is soaked in a specific salt solution for 1-2 days, and dried at room temperature for 2-3 days to obtain a gelatin/silicon dioxide toughened hydrogel, wherein the specific salt solution is sulfate, A salt solution formed of monohydrogen phosphate, dithiosulfate anions, ammonium ions, and sodium ions. The hydrogel prepared by this technical scheme has good mechanical properties and biocompatibility, but the preparation process is relatively complicated.

In addition, peripheral nerve injury caused by accidental trauma or iatrogenic injury can easily lead to loss of local sensation, perception, and motor function, and even cause permanent disability, seriously affecting the quality of life of patients and causing a heavy economic burden to patients' families. Peripheral nerve injury is one of the most common difficult diseases in clinical surgery. It is a very challenging problem to select appropriate treatment methods to promote nerve regeneration and repair clinically.

Gel has a naturally formed interconnected network structure and flexibility close to soft tissue, so it is of great advantage to choose natural or synthetic polymer cross-linked to form a physical and chemically stable flexible adhesive gel for repairing nerve defects. For example, CN111001036A discloses a single-walled carbon nanotube composite conductive nerve sleeve and its preparation method and application. The single-wall carbon nanotube composite conductive nerve sheath is composed of a tube body and a coating covering the surface of the tube body; the tube body is a carboxyl-containing single-wall carbon nanotube; the coating and the The tubes are combined through physical adsorption and chemical bonding; the coating is a composite hydrogel. The conductive nerve sheath prepared by the invention has excellent characteristics such as good biocompatibility and electrical conductivity, and realizes the effect of repairing a large segment of nerve defect and promoting the repair of peripheral nerve damage.

In addition, electrical stimulation can promote the proliferation of neurons and glial cells and the growth of axons, thereby stimulating the regeneration of neural tissue. Introducing conductive materials into adhesives has great research significance for the repair of nerve defects. Its conductivity can stimulate the growth and function of nerve cells, and biological interactions with nerve cells occur in various ways. The rupture repair of peripheral nerve tissue and the realization of treatment provide a new idea.

Based on the influence of conductivity on nerve regeneration function, how to provide a medical adhesive with good conductivity and adhesion has become an urgent technical problem to be solved.

Contents of the invention

Aiming at the deficiencies in the prior art, the object of the present invention is to provide a conductive medical adhesive and its preparation method and application. In the present invention, through the design of the raw material components of the conductive medical adhesive adhesive, and further use of conductive agents and modifiers, the prepared medical adhesive adhesive has better conductivity and adhesion, and has better biological properties. Compatibility, suitable for use as wound sealing material or adhesive repair material for peripheral nerve injury.

For reaching this purpose, the present invention adopts following technical scheme:

In a first aspect, the present invention provides a conductive medical adhesive, the raw materials for the preparation of the conductive medical adhesive include the following components in parts by weight: 15-50 parts of gelatin, 0.1-3 parts of a conductive agent and a modifier 20-50 servings.

In the present invention, through the design of the raw material components of the conductive medical adhesive glue, and further use of conductive agents and modifiers, the medical adhesive glue has better conductivity and adhesion, and is suitable for use as wound sealing materials or Adhesive repair materials for peripheral nerve injuries.

In the present invention, by using the conductive agent and controlling the content of the conductive agent within a specific range, the medical adhesive has better conductivity. If the content of the conductive agent is too small, the conductivity of the prepared medical adhesive will be poor; The production cost of the adhesive.

In the present invention, the parts by weight of the gelatin can be 15 parts, 18 parts, 20 parts, 22 parts, 25 parts, 27 parts, 30 parts, 33 parts, 36 parts, 38 parts, 40 parts, 42 parts, 46 parts copies or 50 copies etc.

The parts by weight of the conductive agent can be 0.1 part, 0.2 part, 0.5 part, 0.7 part, 1 part, 1.3 part, 1.5 part, 1.8 part, 2 parts, 2.2 parts, 2.5 parts, 2.7 parts or 3 parts.

The parts by weight of the modifying agent can be 20 parts, 22 parts, 25 parts, 27 parts, 30 parts, 33 parts, 36 parts, 38 parts, 40 parts, 42 parts, 46 parts or 50 parts, etc.

The following are preferred technical solutions of the present invention, but not as limitations on the technical solutions provided by the present invention. Through the following preferred technical solutions, the purpose and beneficial effects of the present invention can be better realized.

As a preferred technical solution of the present invention, the conductive agent is selected from any one or a combination of at least two of silver nanowires, carbon nanotubes, graphene and MXene.

It should be noted that MXene is a class of two-dimensional inorganic compounds in materials science, composed of transition metal carbides, nitrides or carbonitrides with a thickness of several atomic layers. In the present invention, the silver nanowires and carbon nanotubes used in the process of preparing conductive medical adhesive are respectively commercially available silver nanowire solutions and carbon nanotube solutions, and the MXene used in the present invention is MXene nanosheet colloidal solution , exemplarily including but not limited to Ti ₃ C ₂ -MXene nanosheet colloidal solution.

Preferably, the silver nanowires have a diameter of 20-60nm, such as 20nm, 22nm, 25nm, 27nm, 30nm, 33nm, 36nm, 40nm, 42nm, 46nm, 50nm, 52nm, 55nm, 57nm or 60nm.

Preferably, the carbon nanotubes have a length of 10-30 μm, such as 10 μm, 12 μm, 14 μm, 16 μm, 18 μm, 20 μm, 22 μm, 24 μm, 26 μm, 28 μm or 30 μm.

Preferably, the carbon nanotubes have a diameter of 5-15nm, for example, 5nm, 6nm, 7nm, 8nm, 9nm, 10nm, 11nm, 12nm, 13nm, 14nm or 15nm.

Preferably, the number of layers of the graphene is 1-5 layers, such as 1 layer, 2 layers, 3 layers, 4 layers or 5 layers.

As a preferred technical solution of the present invention, the mass percentage of the modifier in the modifier solution is 10%-40%, for example, it can be 10%, 12%, 15%, 18%, 20%, 22% , 25%, 27%, 30%, 33%, 35%, 38% or 40%, etc.

Preferably, the modifier comprises a combination of modifier A and modifier B.

Preferably, the modifier A is sodium citrate.

Preferably, the modifier B is selected from any one or a combination of at least two of aluminum chloride, ammonium chloride or ammonium sulfate.

Preferably, the mass ratio of the modifier A to the modifier B is (1.8-2.2):1, such as 1.8:1, 1.84:1, 1.88:1, 1.92:1, 1.96:1, 2 :1, 2.04:1, 2.08:1, 2.12:1, 2.16:1 or 2.2:1 etc.

As a preferred technical solution of the present invention, the raw materials for the preparation of the conductive medical adhesive also include 50-85 parts of water, such as 50 parts, 52 parts, 55 parts, 57 parts, 60 parts, 63 parts, 65 parts , 68, 70, 72, 75, 78, 80, 83 or 85 etc.

In a second aspect, the present invention provides a method for preparing the conductive medical adhesive as described in the first aspect, the preparation method comprising the following steps:

(1) gelatin, conductive agent and water are mixed and solidified to obtain a hydrogel;

(2) modifying the hydrogel obtained in step (1) and a modifying agent to obtain the conductive medical adhesive.

In the present invention, the hydrogel is first prepared by gelatin, conductive agent and water, and then the surface of the hydrogel is modified by a modifier to prepare a medical adhesive with good conductivity and adhesion. And the prepared conductive medical adhesive has good biocompatibility.

Specifically, in the present invention, the modifier is selected from the combination of modifier A and modifier B, and through the reaction between modifier A sodium citrate and aluminum ions or ammonium ions in modifier B, citric acid is generated. Aluminum complex or ammonium citrate complex, and then modify the surface of the hydrogel through the generated complex to obtain a conductive medical adhesive with good adhesion.

As a preferred technical solution of the present invention, the mixing temperature in step (1) is 60-100°C, such as 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C or 100°C etc.

Preferably, the mixing time in step (1) is 0.5-1.5h, such as 0.5h, 0.6h, 0.7h, 0.8h, 0.9h, 1h, 1.1h, 1.2h, 1.3h, 1.4h or 1.5h and so on.

Preferably, the solidification method described in step (1) is standing at low temperature.

Preferably, the temperature for standing at low temperature is 4-10°C, for example, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C or 10°C.

Preferably, the time for standing at low temperature is 0.5-1h, for example, it may be 0.5h, 0.6h, 0.7h, 0.8h, 0.9h or 1h.

As a preferred technical solution of the present invention, after the mixing in step (1) is completed, a post-processing step is also included.

Preferably, the post-treatment method is defoaming at 60-100°C, such as 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C or 100°C.

It should be noted that there is no limitation on the defoaming method in the present invention, which exemplarily includes but not limited to static defoaming at 60-100°C. If no defoaming treatment is performed, the hydrogel prepared in step (1) contains air bubbles, which will cause defects in the finally prepared conductive medical adhesive, which will adversely affect its conductivity and adhesion.

As a preferred technical solution of the present invention, the modification method in step (2) is to immerse the hydrogel in a modifier for modification.

Preferably, the modification time is 0.5-1 h, such as 0.5 h, 0.6 h, 0.7 h, 0.8 h, 0.9 h or 1 h.

As a preferred technical solution of the present invention, the preparation method specifically includes the following steps:

(1) Mix gelatin, conductive agent and water at 60-100°C for 0.5-1.5h, then let stand to defoam, then lower the temperature to 4-10°C, let stand and solidify for 0.5-1h to obtain hydrogel;

(2) Soak the hydrogel obtained in the step (1) in the modifier solution for 0.5-1 hour, and modify it to obtain the conductive medical adhesive.

In a third aspect, the present invention provides an application of the conductive medical adhesive as described in the first aspect in the preparation of wound sealing materials or adhesive repair materials for peripheral nerve injuries.

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

In the present invention, through the design of the conductive medical adhesive raw material components, the use of a conductive agent and a modifier, the use of modifier A and modifier B, and further control of the content of the conductive agent within a specific range, Make the medical adhesive have better conductivity and adhesion, its resistivity is 0.3-790Ω·m, and the adhesion strength is 356-800N/m; it is suitable for wound sealing material or adhesive repair of peripheral nerve injury Material.

Description of drawings

FIG. 1 is a physical diagram of the conductive medical adhesive provided in Example 1 of the present invention.

Detailed ways

The technical solutions of the present invention will be further described below in conjunction with the accompanying drawings and through specific implementation methods. It should be clear to those skilled in the art that the embodiments are only for helping to understand the present invention, and should not be regarded as specific limitations on the present invention.

Part raw material component source is as follows in following embodiment and comparative example:

Gelatin: Sigma-Aldrich;

Silver nanowires: Beijing Deke Island Gold Technology Co., Ltd.;

Carbon nanotubes: Nanjing Xianfeng Nano Material Technology Co., Ltd.;

Graphene: Nanjing Xianfeng Nano Material Technology Co., Ltd.;

Ti ₃ C ₂ -MXene nanosheet colloidal solution: prepared according to the method described in CN110098326A.

Example 1

The present embodiment provides a kind of conductive medical adhesive glue and preparation method thereof, and its actual figure is as shown in Figure 1, and the preparation raw material of described conductive medical adhesive glue comprises the following components by weight: 40 parts of gelatin, graphene 1 part, 40 parts of modifier solution and 59 parts of water;

The mass percentage of the modifier in the modifier solution is 30%, and the modifier is composed of sodium citrate and aluminum chloride in a mass ratio of 2:1.

The preparation method of above-mentioned conductive medical adhesive glue is as follows:

(1) At 70°C, mix gelatin, graphene and water for 1 hour, let stand to defoam, then lower the temperature to 4°C, let stand to solidify for 1 hour, and obtain a hydrogel;

(2) Soak the hydrogel obtained in step (1) in a modifier solution for 30 minutes to modify it to obtain the conductive medical adhesive.

Example 2

This embodiment provides a conductive medical adhesive and its preparation method and application. The raw materials for the preparation of the conductive medical adhesive include the following components in parts by weight: 30 parts of gelatin, 0.2 parts of carbon nanotubes, modifier 30 parts of solution and 70 parts of water;

The mass percentage of the modifier in the modifier solution is 10%, and the modifier is composed of sodium citrate and ammonium chloride in a mass ratio of 15:8.

The preparation method of above-mentioned conductive medical adhesive glue is as follows:

(1) At 60°C, mix gelatin, carbon nanotubes and water for 1.5 hours, let stand to defoam, then cool down to 10°C, let stand and solidify for 1 hour to obtain a hydrogel;

(2) Soak the hydrogel obtained in the step (1) in a modifier solution for 40 minutes to modify it to obtain the conductive medical adhesive.

Example 3

This embodiment provides a conductive medical adhesive and its preparation method and application. The raw materials for the preparation of the conductive medical adhesive include the following components in parts by weight: 15 parts of gelatin, 3 parts of silver nanowires, modifier 20 parts of solution and 85 parts of water;

The mass percentage of the modifier in the modifier solution is 20%, and the modifier is composed of sodium citrate and ammonium sulfate in a mass ratio of 1.8:1.

The preparation method of above-mentioned conductive medical adhesive glue is as follows:

(1) At 100°C, mix gelatin, silver nanowires and water for 0.5h, let stand to defoam, then cool down to 6°C, let stand and solidify for 40min to obtain a hydrogel;

(2) Soak the hydrogel obtained in the step (1) in a modifier solution for 50 minutes to modify it to obtain the conductive medical adhesive.

Example 4

This embodiment provides a conductive medical adhesive and its preparation method and application. The raw materials for the preparation of the conductive medical adhesive include the following components in parts by weight: 50 parts of gelatin, Ti ₃ C ₂ -MXene nanosheet colloid 0.1 part of solution, 50 parts of modifier solution and 50 parts of water;

The mass percentage of the modifier in the modifier solution is 40%, and the modifier is composed of sodium citrate and aluminum chloride in a mass ratio of 2.2:1.

The preparation method of above-mentioned conductive medical adhesive glue is as follows:

(1) At 80°C, mix gelatin, Ti ₃ C ₂ -MXene nanosheet colloid solution, and water for 35 minutes, let stand to defoam, then cool down to 7°C, let stand and solidify for 40 minutes to obtain a hydrogel;

(2) Soak the hydrogel obtained in the step (1) in the modifier solution for 1 hour to modify it to obtain the conductive medical adhesive.

Example 5

This embodiment provides a conductive medical adhesive and its preparation method. The only difference from Embodiment 1 is that the graphene content is 0.1 part by weight, and other conditions are the same as Embodiment 1.

Example 6

This embodiment provides a conductive medical adhesive and a preparation method thereof. The difference from Embodiment 1 is that the graphene content is 3 parts by weight, and other conditions are the same as in Embodiment 1.

Example 7

This embodiment provides a conductive medical adhesive and its preparation method. The only difference from Embodiment 1 is that the modifying agent is sodium citrate, and other conditions are the same as Embodiment 1.

Comparative example 8

This embodiment provides a conductive medical adhesive and its preparation method. The only difference from Embodiment 1 is that the modifying agent is aluminum chloride, and other conditions are the same as Embodiment 1.

Comparative example 1

This comparative example provides a conductive medical adhesive and its preparation method. The only difference from Example 1 is that the graphene content is 0.05 parts by weight, and other conditions are the same as in Example 1.

Comparative example 2

This comparative example provides a conductive medical adhesive and its preparation method. The only difference from Example 1 is that the graphene content is 5 parts by weight, and other conditions are the same as in Example 1.

The performance of the conductive medical adhesive glue provided by the above-mentioned embodiments and comparative examples is tested, and the test standard is as follows:

Resistivity: Test the resistivity of the conductive medical adhesive glue provided by the above-mentioned embodiments and comparative examples by an RTS-9 type double electric measuring four-probe tester, wherein the thickness of the conductive medical adhesive glue is 1mm;

Adhesion strength: according to the T-peel test (ASTM D903), the conductive medical adhesives provided in the above examples and comparative examples were peeled off from the glass to test the adhesion strength.

The test results of the conductive medical adhesive glue performance that above-mentioned embodiment and comparative example provide are as shown in table 1:

Table 1

As can be seen from the data in Table 1, the present invention adopts a conductive agent and a modifier through the design of the raw material components of the conductive medical adhesive adhesive, and further controls the conductive agent through the combined use of the modifier A and the modifier B. The content is within a specific range, so that the medical adhesive has better conductivity and adhesion, its resistivity is 0.3-790Ω·m, and the adhesion strength is 356-800N/m; it is suitable for wound sealing materials or adhesive repair materials for peripheral nerve injuries.

Compared with Example 1, if the modifier only adopts sodium citrate (Example 7) or the modifier only adopts aluminum chloride (Example 8) in the preparation raw material of medical adhesive, then the prepared conductive medical Adhesive glue has poor adhesion. It can be seen that the conductive medical adhesive prepared by the present invention has better adhesion through the combined use of the modifier A and the modifier B.

Compared with Example 1, if the content of the conductive agent in the preparation raw material of the conductive medical adhesive is too little (comparative example 1), the conductivity of the prepared conductive medical adhesive is relatively poor, and its resistivity is larger. 2900Ω·m; if the content of the conductive agent in the preparation raw materials of the medical adhesive is too much (comparative example 2), although the prepared medical adhesive has good conductivity, the phenomenon of "powder dropping" will occur, And can increase the production cost of medical adhesive glue. It can be seen that, by controlling the content of the conductive agent in the present invention within a specific range, the conductive medical adhesive prepared by the present invention has better conductivity, and "powder dropping" will not occur.

In summary, the present invention adopts a conductive agent and a modifier through the design of the raw material components of the conductive medical adhesive, and uses the modifier A and the modifier B together to further control the content of the conductive agent. Within a specific range, the medical adhesive has good electrical conductivity and adhesion, and is suitable for use as a wound sealing material or an adhesive repair material for peripheral nerve damage.

The applicant declares that the present invention illustrates the detailed process flow of the present invention through the above-mentioned examples, but the present invention is not limited to the above-mentioned detailed process flow, that is, it does not mean that the present invention must rely on the above-mentioned detailed process flow to be implemented. Those skilled in the art should understand that any improvement of the present invention, the equivalent replacement of each raw material of the product of the present invention, the addition of auxiliary components, the selection of specific methods, etc., all fall within the scope of protection and disclosure of the present invention.

Claims (10)

1. The conductive medical adhesive is characterized by comprising the following raw materials in parts by weight: 15-50 parts of gelatin, 0.1-3 parts of conductive agent and 20-50 parts of modifier.

2. The conductive medical adhesive according to claim 1, wherein the conductive agent is selected from any one of or a combination of at least two of silver nanowires, carbon nanotubes, graphene and MXene;

preferably, the diameter of the silver nanowire is 20-60nm;

preferably, the length of the carbon nanotube is 10-30 μm;

preferably, the diameter of the carbon nano tube is 5-15nm;

preferably, the number of layers of the graphene is 1-5.

3. The electrically conductive medical adhesive according to claim 1 or 2, wherein the modifier is a modifier solution;

preferably, the mass percentage of the modifier in the modifier solution is 10-40%;

preferably, the modifier comprises a combination of modifier a and modifier B;

preferably, the modifier A is sodium citrate;

preferably, the modifier B is selected from any one of aluminum chloride, ammonium chloride or ammonium sulfate or a combination of at least two of the aluminum chloride, the ammonium chloride and the ammonium sulfate;

preferably, the mass ratio of the modifier A to the modifier B is (1.8-2.2): 1.

4. The conductive medical adhesive glue according to any one of claims 1 to 3, wherein the raw materials for preparing the conductive medical adhesive glue further comprise 50 to 85 parts of water.

5. The preparation method of the conductive medical adhesive glue according to any one of claims 1 to 4, characterized in that the preparation method comprises the following steps:

(1) Mixing gelatin, a conductive agent and water, and solidifying to obtain hydrogel;

(2) And (2) modifying the hydrogel obtained in the step (1) and a modifier to obtain the conductive medical adhesive.

6. The method according to claim 5, wherein the temperature of the mixing in the step (1) is 60 to 100 ℃;

preferably, the mixing time of the step (1) is 0.5-1.5h;

preferably, the solidification method in the step (1) is low-temperature standing;

preferably, the temperature of the low-temperature standing is 4-10 ℃;

preferably, the low-temperature standing time is 0.5-1h.

7. The method according to claim 5 or 6, wherein the step (1) further comprises a post-treatment step after the mixing;

preferably, the post-treatment method is defoaming at 60-100 ℃.

8. The method according to any one of claims 5 to 7, wherein the modification in step (2) is carried out by immersing the hydrogel in a modifying agent;

preferably, the time for the modification is 0.5 to 1h.

9. The method according to any one of claims 5 to 8, comprising in particular the steps of:

(1) Mixing gelatin, conductive agent and water at 60-100 deg.C for 0.5-1.5 hr, removing bubbles, cooling to 4-10 deg.C, standing for 0.5-1 hr, and coagulating to obtain hydrogel;

(2) And (2) soaking the hydrogel obtained in the step (1) in a modifier solution for 0.5-1h for modification to obtain the conductive medical adhesive.

10. Use of the electrically conductive medical adhesive of any one of claims 1-4 in the preparation of wound sealing materials or adhesive repair materials for peripheral nerve injury.

Images