CN116763975A - Developing medical suture for tissue positioning and preparation method thereof - Google Patents

Abstract

The present invention provides a developing medical suture for tissue positioning and a preparation method thereof. The polymer matrix is crystallized with a contrast agent as a crystal nucleus so that it is closely combined with the contrast agent to form a composite material with developing properties. By first preparing a A polymer mixture doped with developing substances was then used to limit the temperature and pressure and control the diameter, strength and flexibility of the suture, and then processed and extruded it to form the suture, thereby preparing a medical suture with overall developing ability. According to The developed medical suture produced by this method has a tight combination of the developer and the suture, high development intensity, and can be conveniently used for positioning, measurement and monitoring of the implantation site.

Description

A developing medical suture for tissue positioning and its preparation method

Technical field

The present invention relates to the field of medical sutures, and in particular to a developing medical suture for tissue positioning and a preparation method thereof.

Background technique

With the continuous advancement of medical technology, more and more attention has been paid to the refinement of clinical operations. The accurate positioning of target tissues and target sites and in vivo measurement guided by medical images play a crucial role in this process. In orthopedic surgery, imaging tissue positioning implants enable monitoring of anterior cruciate ligament (ACL) graft extension and migration, and follow-up in 3D X-ray based imaging modalities such as radiostereometry analysis (RSA) and CT. The degree of healing of the tendon repair and the length of the repair site of the shoulder joint rotation sleeve are used to determine whether the surgical repair is successful. In addition, in the fields of reshaping the three-dimensional structure of the heart, tracking myocardial motion, local ablation of solid tumors, and radiotherapy positioning, with the assistance of imaging tissue positioning implants, combined with medical imaging methods, high-precision and repeatable medical treatments can be achieved. Modeling and positioning to benefit many doctors and patients.

Current imaging tissue positioning implants are mostly made of metal, including titanium, platinum, gold or stainless steel. Common types include microspheres, rods, rings and threads. However, there are some problems that are difficult to overcome and avoid with metal imaging tissue positioning implants: 1. Metal implants are permanently implanted, non-absorbable, and can only be removed through another surgery. For some, long-term surgery is not required. For imaging-tracked procedures or patients, the implant does not need to be permanently retained. Metal implants that remain in the body for a long time increase the risk of harm to the human body due to material damage and migration. 2. There are metal implants in the body, which is a contraindication when MRI examination is required. For patients who require subsequent MRI examination, long-term retention of metal implants in the body adds unnecessary trouble to their clinical diagnosis and treatment. 3. During the operation, the fixation of metal implants is also a big problem. Metal implants often do not have their own fixation measures and need to be fixed by suturing or other means. Implants are generally small in size, and their fixation during surgery is technically difficult and time-consuming.

In order to solve the problems of current metal-based imaging tissue positioning implants, imaging sutures are considered to be a better choice for tissue positioning. Sutures mostly use polymer materials, which can control their absorbability and degradation and absorption time through polymer chemistry. In addition, the suture itself can be fixed on the tissue through convenient surgical operations, which is beneficial to practical clinical use.

After searching the prior art, it was found that CN215503207U discloses a special developing suture for disposable annulus fibrosus under endoscope. The structure includes a suture and a developing layer, and the developing layer is evenly coated on the surface of the suture. On the basis of the existing annulus fibrosus suture, the surface is covered with a developable coating. When the patient undergoes an X-ray scan after surgery, whether the suture is strong can be found on the image. CN111035793B discloses a development suture that can monitor displacement and a preparation method thereof. The preparation method is to partially develop the core wire and control each of the two adjacent sub-regions, one to be developable under X-rays and the other to be under X-rays. Cannot be developed under light. The development process adopts the method of spraying developer on the core wire at a certain distance and then drying and hardening. The developed sutures produced by this method can monitor whether the sutures slip or have a tendency to slip in the body. CN 106725677A discloses a long-term absorbable suture developed by ; The coat is made of 6 to 8 ordinary single fibers of natural collagen, tightly woven around the inner core. This invention has the characteristics of X-ray development marking. The absorption time of the outer layer of the suture is controlled by the number of layers of the jacket, thereby maintaining different development times.

However, these above-mentioned technologies all have a shortcoming, that is, they all apply developer on the surface of the suture base material by surface coating to achieve the development effect. With this surface coating method, firstly, the binding force between the suture base material and the developer is weak. When implanted in the body, when the suture comes into contact with tissue and body fluids, the developer will disperse quickly and the suture will quickly lose its development. ability, it is difficult to achieve mid- and long-term postoperative monitoring and positioning. Second, the developer only exists on the surface of the suture. Excessive local developer concentration may enhance toxic side effects and affect the biocompatibility of the suture. When the developer concentration is low, the development ability will be affected. In addition, if absorbable sutures are used as the base material, since the developer only exists on the surface of the developing suture, there will be a mismatch between the development time and the suture degradation time, which limits the clinical value of the developing suture to a certain extent.

Contents of the invention

In view of this, the present invention proposes a developing medical suture for tissue positioning and a preparation method thereof to solve the above problems.

The technical solution of the present invention is implemented as follows:

A preparation method for developing medical sutures for tissue positioning, including the following steps:

S1. Synthesis of polymer composite materials containing developing substances: Add 0.4 to 4 parts of contrast agent and 0.05 to 0.5 parts of polyvinylpyrrolidone (PVP) to 10 to 50 parts of solvent, stir at 300 to 800 rpm for 20 to 60 minutes, and then add 1 After ~10 parts of the polymer matrix, continue stirring at room temperature to slowly evaporate the solvent. The polymer matrix crystallizes with the contrast agent as the crystal nucleus so that it is closely combined with the contrast agent to form a composite material with developing properties. Then the composite material is Store under vacuum at room temperature;

S2. Processing and extrusion to form sutures: The composite material is extruded into filaments at a high temperature of 190-250°C and a high pressure of 10-30MPa to control the diameter, strength and flexibility of the sutures.

Further, the solvent of S1 includes but is not limited to tetrahydrofuran, toluene, chloroform, xylene, dimethyl sulfoxide, and methylene chloride.

Further, the contrast agents of S1 include, but are not limited to, diatrizoic acid, diatrizoate meglumine (MD), meglumine, iodiol, iohexol (IHX), iomeprol, iopamidol, iodine Pentol, iopromide, ioversol, ioxilan, iodixanol (IDX) and iotrilan.

Further, the polymer matrix of S1 includes but is not limited to polylactic acid (PLA), polydioxanone (PDO), polyglycolide-caprolactone (PGCL), polylactic acid-glycolic acid copolymer. (PLGA), polypropylene (PP), poly-L-lactide-co-ε-caprolactone (PLCA), polydioxanone or polydioxanone suture (PDS), polyhydroxy Acetic acid (PGA), polyglycol carbonate, polyvinyl acetate (PVA), nylon.

Further, the solvent concentration in S1 is 5-40% w/v.

Further, the concentration of the contrast agent in S1 is 5-40% w/v.

Further, the average molecular weight of the polyvinylpyrrolidone described in S1 is 2000-2000000 Da.

Further, the developed medical suture is prepared according to the above preparation method.

Further, the contrast agent in the developed medical suture is distributed in the polymer matrix in an "island" structure.

Furthermore, the HU value of the developed medical suture in micro-CT can reach 5500.

Compared with the prior art, the beneficial effects of the present invention are:

In preparing the developing medical suture, the present invention first closely combines the contrast agent and the polymer matrix by blending to prepare a developable polymer composite material, and then processes and extruses the obtained developing medical suture. The blending method tightly combines the contrast agent with the polymer matrix. The contrast agent in the developed medical suture is distributed in the polymer matrix in an "island" structure, giving the suture the ability to perform X-ray scanning and CT scan after entering the tissue. The imaging capability is low, the HU value of micro-CT can reach 5500, and the imaging intensity is high. The imaging medical suture still has X-ray imaging capabilities under tissue with a thickness of 4cm, and can be conveniently used to position the implant site. Measurement and monitoring. By regulating the type and molecular weight of the polymer matrix, the absorbability and degradation cycle of the suture can be controlled, which solves the problem of long-term retention of metal implants in the body; at the same time, the developer is evenly distributed throughout the suture, and during the development Sutures exist throughout the entire cycle of the body, and all sutures have developing capabilities. There will be no mismatch between the developing capabilities of the sutures and the degradation cycle.

Description of drawings

Figure 1 is a schematic diagram of the preparation of developed medical sutures;

Figure 2 shows the SEM pattern of composite material PDO/IHX/PVP;

Figure 3 is a micro-CT image showing sutures in deep tissue.

Detailed ways

In order to better understand the technical content of the present invention, specific examples are provided below to further illustrate the present invention.

Unless otherwise specified, the experimental methods used in the examples of the present invention are conventional methods.

Materials, reagents, etc. used in the embodiments of the present invention can be obtained from commercial sources unless otherwise specified.

Example 1

A preparation method for developing medical sutures for tissue positioning, including the following steps:

S1. Synthesis of composite material PDO/IHX/PVP containing the developing substance iohexol (IHX):

Add 0.4 parts of IHX (30% w/v) and 0.01 parts of PVP (8K) to 10 parts of DCM (10% w/v), and continue stirring for 20 min. After adding PDO, continue stirring at room temperature to slowly evaporate the DCM. The PDO matrix crystallizes with IHX as the crystal nucleus so that it closely combines with the contrast agent IHX to form a composite material PDO/IHX/PVP with developing properties. Then PDO/IHX /PVP composite materials are stored in vacuum at room temperature;

S2. Processing and extrusion to form sutures:

The composite material is extruded into filaments at a high temperature of 190°C and a high pressure of 10MPa to obtain developed medical sutures.

Example 2

A preparation method for developing medical sutures for tissue positioning, including the following steps:

S1. Synthesize the composite material PLA/MD/PVP containing the developing substance diatrizoate meglumine (MD):

Add 0.6 parts of MD (30% w/v) and 0.01 parts of PVP (40K) to 10 parts of THF (10% w/v), and continue stirring for 20 min. After adding PLA, continue stirring at room temperature to slowly evaporate THF. The PLA matrix uses MD as the crystal nucleus to crystallize so that it is closely combined with the contrast agent MD to form a composite material PLA/MD/PVP with developing properties. Then PLA/MD /PVP composite materials are stored in vacuum at room temperature.

S2. Processing and extrusion to form sutures:

The composite material is extruded into filaments at a high temperature of 230°C and a high pressure of 15MPa to obtain developed medical sutures.

Example 3

A preparation method for developing medical sutures for tissue positioning, including the following steps:

S1. Synthesis of composite material PGCL/IDX/PVP containing the developing substance iodixanol (IDX):

Add 0.8 parts of IDX (30% w/v) and 0.05 parts of PVP (360K) to 10 parts of DMSO (10% w/v), and continue stirring for 20 min. After adding PGCL, continue stirring at room temperature, slowly evaporate DMSO, and the PLA matrix crystallizes with IDX as the crystal nucleus so that it is closely combined with the contrast agent IDX to form a composite material PGCL/IDX/PVP with developing properties, and then PGCL/IDX /PVP composite materials are stored in vacuum at room temperature.

S2. Processing and extrusion to form sutures:

The composite material is extruded into filaments at a high temperature of 250°C and a high pressure of 20MPa to obtain developed medical sutures.

1. Scanning electron microscope (SEM) analysis of developed medical sutures:

The scanning electron microscope spectrum of the PDO/IHX/PVP composite material produced in Example 1 is shown in Figure 2. Hydrophilic iohexol is dispersed in the hydrophobic PDO matrix in an "island" shape, reducing the surface hydrophobicity of the composite material.

2. Micro-CT analysis of developing medical sutures:

X-ray microcomputed tomography (Bruker SkyScan 1176, USA) was used to evaluate the X-ray imaging capabilities of the developed medical sutures prepared in Examples 1, 2, and 3. The composite materials prepared in Examples 1, 2, and 3 were hot-pressed into sheets with a diameter of 10 mm and a thickness of 1 mm. The scanning parameters were: spatial resolution of 18 μm pixel size, rotation step of 0.8°, voltage of 45 kV, and aluminum filter of 0.20 mm. All data are analyzed and reconstructed using the GPU reconnaissance server software in the micro-CT system. After image reconstruction, the HU value is calculated in the CTAn software of the micro-CT system. The results are as follows in Table 1:

Table 1 Grayscale and HU values of developed sutures

sample Grayscale HU Example 1 100 5553 Example 2 103 5580 Example 3 101 5567

Developed medical sutures have high development intensity and can meet the needs of positioning, measurement and monitoring of implant sites.

3. X-ray imaging of developing sutures in deep tissues:

X-ray imaging of developing suture materials in deep tissue was evaluated using a small animal optical imaging device (In Vivo Xtreme, Bruker, USA). The composite material prepared in Example 1 was hot pressed into slices with a diameter of 10 mm and a thickness of 1 mm. A piece of lean meat was cut into 0.6cm thick slices and placed on the composite slices layer by layer to evaluate the X-ray imaging ability of the polymer under the deep tissue. Set the test parameters as follows: X-ray filter 0.8mm, exposure time 1.2s, field of view 19cm.

As shown in Figure 3, the results show that the developed medical suture has strong developing performance, so that it can still be developed under a tissue thickness of 4cm.

The above descriptions are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included in the present invention. within the scope of protection.

Claims (10)

1. A method for preparing a developing medical suture for tissue positioning, which is characterized in that it includes the following steps: S1. Synthesis of polymer composite materials containing developing substances: Add 0.4 to 4 parts of contrast agent and 0.05 to 0.5 parts of polyvinylpyrrolidone to 10 to 50 parts of solvent, stir at 300 to 800 rpm for 20 to 60 minutes, and then add 1 to 10 parts After the polymer matrix is formed, continue stirring at room temperature. The polymer matrix will crystallize with the contrast agent as the crystal nucleus so that it is closely combined with the contrast agent to form a composite material with developing properties. The composite material is then stored in a vacuum at room temperature; S2. Processing and extrusion to form sutures: The composite material is extruded into filaments at a high temperature of 190-250°C and a high pressure of 10-30MPa to control the diameter, strength and flexibility of the sutures. 2. The preparation method of a developing medical suture for tissue positioning as claimed in claim 1, characterized in that: the solvent of S1 includes but is not limited to tetrahydrofuran, toluene, chloroform, xylene, dimethyl methylene Sulfone, methylene chloride. 3. A method for preparing a developing medical suture for tissue positioning as claimed in claim 1, characterized in that: the contrast agent of S1 includes but is not limited to diatrizoic acid, diatrizoate meglumine, and meglumine meglumine. amine, iodiol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, iodixanol, and iotrilam. 4. A method for preparing medical sutures for tissue positioning according to claim 1, characterized in that: the polymer matrix of S1 includes but is not limited to polysaccharide lactic acid and polydioxanone. , polyglycolide-caprolactone, polylactic acid-co-glycolic acid, polypropylene, polyL-lactide-co-epsilon-caprolactone, polydioxanone or polydioxanone seam Thread, polyglycolic acid, polyglycol carbonate, polyvinyl acetate, nylon. 5. The method for preparing a developed medical suture for tissue positioning according to claim 1, characterized in that: the solvent concentration in S1 is 5-40% w/v. 6. The method for preparing a developing medical suture for tissue positioning according to claim 1, characterized in that: the concentration of the contrast agent in S1 is 5-40% w/v. 7. The method for preparing a developing medical suture for tissue positioning according to claim 1, characterized in that: the average molecular weight of the polyvinylpyrrolidone described in S1 is 2000-2000000 Da. 8. The developed medical suture prepared by the preparation method according to any one of claims 1-5. 9. A method for preparing a developing medical suture for tissue positioning as claimed in claim 8, characterized in that: the contrast agent in the developing medical suture is distributed in the polymer matrix in an "island" structure. middle. 10. A method for preparing a developing medical suture for tissue positioning according to claim 8, characterized in that: the HU value of the developing medical suture in micro-CT can reach 5500.