Medical ultrasonic coupling material as well as preparation method and application thereof

Abstract

The invention discloses a medical ultrasonic coupling material and a preparation method and application thereof.The preparation method comprises the steps that clay is dissolved in water and stirred until the clay is dissolved, and a clay solution is prepared; adding sodium hyaluronate into the clay solution, and stirring until the sodium hyaluronate is dissolved to prepare a sodium hyaluronate-clay solution mixed solution; adding a zwitterionic monomer and acrylamide into the sodium hyaluronate-clay solution mixed solution, stirring until the zwitterionic monomer and acrylamide are dissolved, adding a photoinitiator and a cross-linking agent into the pre-polymerized solution, stirring until the photoinitiator and the cross-linking agent are dissolved to prepare the pre-polymerized solution, transferring the pre-polymerized solution into a mold, performing illumination to initiate cross-linking, taking out a sample from the mold, and putting the sample into water for balanced swelling to obtain the solid coupling material. After the medical ultrasonic coupling material is used, the medical ultrasonic coupling material has no residue on tissues, does not need to be wiped and removed, is convenient and sanitary, can accept certain tensile and compressive stress, does not collapse or deform, has good mechanical properties, meets clinical use requirements, can be clamped and fixed on an ultrasonic probe, and does not break.

Description

Technical Field

[0001] The present invention belongs to the field of ultrasonic detection supplies, and particularly relates to a medical ultrasonic coupling material, a preparation method thereof, and an application thereof. Background Art

[0002] With the progress of medical diagnostic technology, ultrasonic diagnostic technology is becoming more and more widely used due to its advantages such as non-invasive, non-ionizing radiation, and relatively simple operation. Ultrasonic waves are a type of sound wave that need to rely on a medium for propagation and generate reflection, refraction, etc. at the interface formed by different media. In order to eliminate the loss caused by ultrasonic wave reflection, a medical coupling material is required to fill the gap between the skin and the ultrasonic probe.

[0003] Currently, the commonly used medical ultrasonic coupling materials in clinics are mostly paste-like or gel-like. During the examination, the coupling agent is applied to the ultrasonic probe or the detection site; after the detection, it is wiped with toilet paper or cleaned with water, which has problems such as cumbersome operation and unsanitary. Especially for superficial or musculoskeletal examinations, because it is close to the radiation surface of the probe, good sound wave superposition cannot be formed, the echo signal is weak, the generated image is not clear, the quality is poor, a imaging blind area is formed, and it lacks clinical diagnostic significance. To avoid the blind area, the probe needs to be separated from the tissue by a certain distance (0.5 - 1 cm), and at the same time, the loss caused by ultrasonic wave reflection, etc. needs to be eliminated to obtain a better-quality image. The paste-like or gel-like coupling materials used clinically have weak mechanical properties and are prone to collapse and deformation after accumulating to a certain extent. Especially when the probe is placed above the coupling agent and pushed, it cannot maintain the original accumulated height. At the same time, with the development of the standardization of scanning, the coupling material needs to be clamped and fixed on the ultrasonic probe to achieve better pushing and scanning at the examination site. Therefore, the material that can be clamped and fixed needs to have good mechanical properties, and the pushing effect after clamping and fixing depends on the lubricating performance of the material. In addition, the coupling material is prone to melting with the increase of temperature under the action of ultrasonic waves on the skin surface and cannot play the role of isolating tissues.

[0004] Currently, the commercially available solid coupling materials have weak mechanical properties, are easy to break, cannot be clamped and fixed on the ultrasonic probe, and have unsatisfactory lubricating performance. When performing ultrasonic examination by attaching to the tissue, it is necessary to spray water many times to improve the lubricating effect. Therefore, it is urgent to develop a new generation of ultrasonic conduction solid coupling materials with good mechanical properties and lubricating performance. Summary of the Invention

[0005] The purpose of this part is to outline some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this part, the abstract of the specification and the title of the invention of the present application to avoid obscuring the purpose of this part, the abstract of the specification and the title of the invention, and such simplifications or omissions cannot be used to limit the scope of the present invention.

[0006] In view of the above and / or problems existing in the prior art, the present invention is proposed.

[0007] Therefore, the object of the present invention is to overcome the deficiencies in the prior art and provide a preparation method of a medical ultrasonic coupling material.

[0008] To solve the above technical problems, the present invention provides the following technical solutions: A preparation method of a medical ultrasonic coupling material, including,

[0009] Dissolve clay in water and stir until dissolved to obtain a clay solution;

[0010] Add sodium hyaluronate to the clay solution and stir until dissolved to obtain a sodium hyaluronate-clay solution mixture;

[0011] Add zwitterionic monomer and acrylamide to the sodium hyaluronate-clay solution mixture and stir until dissolved to obtain prepolymer solution A;

[0012] Add photoinitiator and crosslinking agent to prepolymer solution A and stir until dissolved to obtain prepolymer solution B;

[0013] Transfer the obtained prepolymer solution B into a mold, initiate crosslinking by light irradiation, take out the sample from the mold, and place it in water for equilibrium swelling to obtain a solid coupling material.

[0014] As a preferred embodiment of the preparation method of the present invention, wherein: the clay is one of lithium magnesium silicate and aluminum magnesium silicate.

[0015] As a preferred embodiment of the preparation method of the present invention, wherein: the concentration of the clay solution is 0.01 - 0.015 g / mL, and the water is one of ultrapure water and deionized water.

[0016] As a preferred embodiment of the preparation method of the present invention, wherein: the sodium hyaluronate is one of low molecular weight sodium hyaluronate and enzymatically digested sodium hyaluronate, wherein the molecular weight of low molecular weight sodium hyaluronate is 200 - 400 kDa, and the molecular weight of enzymatically digested sodium hyaluronate is less than 10 kDa.

[0017] As a preferred embodiment of the preparation method of the present invention, wherein: the concentration of sodium hyaluronate in the sodium hyaluronate-clay solution mixture is 0.02 - 0.08 g / mL.

[0018] As a preferred embodiment of the preparation method of the present invention, wherein: the zwitterionic monomer is at least one of carboxylate betaine type zwitterionic monomer, sulfonate betaine type zwitterionic monomer, and phosphate betaine type zwitterionic monomer; the concentration of the zwitterionic monomer in prepolymer solution A is 0.5 - 1.5 mol / L, and the concentration of acrylamide is 2.5 - 4 mol / L.

[0019] As a preferred embodiment of the preparation method of the present invention, wherein: the photoinitiator is one of 1173, α-ketoglutaric acid, and 2959, and the concentration of the photoinitiator is 1-3 mol% of the total molar amount of the monomers; the crosslinking agent is one of N,N'-methylenebisacrylamide, polyethylene glycol diacrylate, and polyethylene glycol dimethacrylate, and the concentration of the crosslinking agent is 0.1-0.2 mol% of the total molar amount of the monomers.

[0020] As a preferred embodiment of the preparation method of the present invention, wherein: for the photo-initiated crosslinking, the wavelength of the light source for light irradiation is 365-405 nm, and the light irradiation time is 3-6 h; for the swelling in water for equilibration, the equilibration swelling time is 3-5 days, and the water is changed every 24 h.

[0021] Another object of the present invention is to overcome the deficiencies in the prior art and provide a medical ultrasonic coupling material prepared by the preparation method. The friction coefficient of the medical ultrasonic coupling material reaches 0.021-0.029, the tensile strain is 189.4-210.7%, the tensile stress is 0.092-0.116 MPa, and the compressive stress is 0.46-0.65 MPa when bearing 90% of the compressive strain. After removing the strain, the coupling material can return to the initial state.

[0022] Another object of the present invention is to overcome the deficiencies in the prior art and provide an application of the medical ultrasonic coupling material in ultrasonic examination. The solid coupling material can be clamped and fixed on the ultrasonic probe without breaking; the solid coupling material is smoothly pushed when clamped and fixed on the ultrasonic probe, and the pushing displacement can reach 35-50 cm.

[0023] Advantages of the present invention:

[0024] (1) The present invention provides a medical ultrasonic coupling material. After use, there is no residue on the tissue, and it does not need to be wiped off, which is convenient and hygienic; the solid coupling material provided by the present invention can withstand certain tensile and compressive stresses, will not collapse and deform, has good mechanical properties, meets the clinical use requirements, and can be clamped and fixed on the ultrasonic probe without breaking.

[0025] (2) The solid coupling material provided by the present invention has good lubrication performance, the friction coefficient can reach 0.021-0.029, and it is smoothly pushed when clamped and fixed on the ultrasonic probe, and the pushing displacement can reach 35-50 cm.

[0026] (3) The solid coupling material provided by the present invention is less affected by the environmental temperature. After being placed at 40 °C for one day, there is no melting phenomenon and it can still remain stable. Description of the Drawings

[0027] To more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings. Among them:

[0028] Figure 1 Comparison chart of the tensile properties of the sample of Embodiment 1 of the present invention and commercially available products.

[0029] Figure 2 Comparison chart of the compression properties of the sample of Embodiment 1 of the present invention and commercially available products.

[0030] Figure 3 Comparison chart of the changes before and after compression of the sample of Embodiment 1 of the present invention and commercially available products.

[0031] Figure 4 Comparison chart of the ultrasonic images of the sample of Embodiment 1 of the present invention and commercially available products. Specific embodiments

[0032] To make the above objects, features, and advantages of the present invention more obvious and understandable, the following will provide a detailed description of the specific embodiments of the present invention in conjunction with the embodiments of the specification.

[0033] In the following description, many specific details are set forth to fully understand the present invention. However, the present invention can also be implemented in other ways different from those described herein. Those skilled in the art can make similar generalizations without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below.

[0034] Secondly, the so-called "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that can be included in at least one implementation manner of the present invention. The "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor is it a separate or selectively exclusive embodiment from other embodiments.

[0035] In the embodiments of the present invention, the molecular weight of low-molecular-weight sodium hyaluronate is 200 - 400 kDa; the molecular weight of enzymatically digested sodium hyaluronate is less than 10 kDa, and both are purchased through commercial channels; for other raw materials, without special instructions, they are all ordinary commercially available products.

[0036] The specific test conditions in the embodiments of the present invention are as follows:

[0037] Tensile test conditions: Place a rectangular specimen (20 mm × 5 mm × 2 mm) in a tensile fixture and conduct a material tensile test at a speed of 100 mm / min.

[0038] Compression test conditions: The sample is a cylindrical sample with a height of 2 mm and a diameter of 10 mm, and the compression rate is 10% deformation / min.

[0039] Friction performance test conditions: A continuous pressure of 1 N is applied, the single stroke of linear reciprocation is 5 mm, the friction rate is 5 mm / s, and the friction time lasts for 5 min.

[0040] Example 1

[0041] Preparation method of solid coupling material:

[0042] (1) Dissolve lithium magnesium silicate clay in water and stir until dissolved, with a concentration of 0.01 g / mL;

[0043] (2) Add enzymatically digested sodium hyaluronate to (1) and stir until dissolved, with a concentration of 0.02 g / mL;

[0044] (3) Add sulfobetaine-type zwitterionic monomer and acrylamide to (2) and stir until dissolved. The concentration of the zwitterionic monomer is 1 mol / L, the concentration of acrylamide is 4 mol / L, and the stirring time is 1 h;

[0045] (4) Add photoinitiator 1173 and crosslinking agent N,N'-methylenebisacrylamide to (3) and stir until dissolved. The concentration of the initiator is 1 mol% of the total molar amount of the monomers, the concentration of the crosslinking agent is 0.2 mol% of the total molar amount of the monomers, and the stirring time is 3 min;

[0046] (5) Transfer the prepolymer solution obtained in (4) into a mold and irradiate it with a 365 nm light source to initiate crosslinking, with a light irradiation time of 4 h;

[0047] (6) Take out the sample from the mold and place it in water for equilibrium swelling. The swelling time is 3 days. Thus, the solid coupling material can be obtained.

[0048] The tensile properties of the obtained solid coupling material are as Figure 1 shown. The tensile strain is 210.7%, and the tensile stress is 0.116 MPa; the tensile strain of the commercially available product is 69.7%, and the tensile stress is 0.019 MPa.

[0049] The compression properties of the obtained solid coupling material are as Figure 2 shown. When the compression strain reaches 90%, the compression stress is 0.65 MPa, and after removing the strain, the material returns to its initial state. See Figure 3 for details; when the compression deformation of the commercially available product is 37%, the structure of the product changes. As the stress gradually increases, there is a weak trend of decreasing and then increasing. This is because the structure of the commercially available product is damaged. After removing the strain after compression, it can be found that the commercially available product has been damaged and cannot withstand the stress. SeeFigure 3 。

[0050] In addition, when the commercially available product is compressed to 30%, although the appearance of the sample is not damaged, after removing the compressive stress, the sample cannot return to the size of the initial state, with poor resilience, which affects the use. The sample prepared in this example can be clamped and fixed on the ultrasonic probe due to its good mechanical properties and will not break.

[0051] The friction coefficient of the commercially available product is about 0.075, and the friction coefficient of the sample in Example 1 is 0.029, which proves that the lubrication performance of the sample prepared in this example has been greatly improved. When the sample prepared in this example is clamped and fixed on the ultrasonic probe, the pushing is smooth and the pushing displacement reaches 35 cm.

[0052] The ultrasonic image of the sample prepared in this example is clear, and the image result is comparable to that of the commercially available product, as shown in Figure 4 。

[0053] After the sample prepared in this example is placed in the air at 40 °C for one day, no melting phenomenon is observed and it remains stable.

[0054] Example 2

[0055] Preparation method of solid coupling material:

[0056] (1) Dissolve magnesium aluminum silicate clay in water and stir until dissolved, with a concentration of 0.012 g / mL;

[0057] (2) Add low molecular weight sodium hyaluronate to (1) and stir until dissolved, with a concentration of 0.06 g / mL;

[0058] (3) Add carboxybetaine type zwitterionic monomer and acrylamide to (2) and stir until dissolved, where the concentration of the zwitterionic monomer is 0.5 mol / L and the concentration of acrylamide is 3 mol / L, and the stirring time is 0.5 h;

[0059] (4) Add photoinitiator α-ketoglutaric acid and crosslinker polyethylene glycol diacrylate to (3) and stir until dissolved, where the concentration of the initiator is 1 mol% of the total molar amount of the monomers and the concentration of the crosslinker is 0.15 mol% of the total molar amount of the monomers, and the stirring time is 5 min;

[0060] (5) Transfer the prepolymer solution obtained in (4) into a mold and irradiate it with a 405 nm light source to initiate crosslinking, with a light irradiation time of 6 h;

[0061] (6) Take out the sample from the mold and place it in water for equilibrium swelling, with a swelling time of 4 days. The solid coupling material can be obtained.

[0062] The tensile strain of the obtained solid coupling material is 189.4%, and the tensile stress is 0.092 MPa; when the obtained solid coupling material is compressed to 90%, the compressive stress is 0.46 MPa, and after the stress is removed, the material returns to the initial state with good resilience. The sample prepared in this example can be clamped and fixed on the ultrasonic probe due to its good mechanical properties and will not break.

[0063] The friction coefficient of the sample prepared in this example is 0.021, which proves that the lubrication performance of the sample prepared by the present invention has been greatly improved. When the sample prepared in this example is clamped and fixed on the ultrasonic probe, the pushing is smooth and the pushing displacement reaches 50 cm.

[0064] After the sample prepared in this example is placed in the air at 40 °C for one day, no melting phenomenon is observed and it remains stable.

[0065] Example 3

[0066] Preparation method of solid coupling material:

[0067] (1) Dissolve clay magnesium aluminum silicate in water and stir until dissolved, with a concentration of 0.015 g / mL;

[0068] (2) Add low molecular weight sodium hyaluronate to (1) and stir until dissolved, with a concentration of 0.08 g / mL;

[0069] (3) Add phosphate betaine type zwitterionic monomer and acrylamide to (2) and stir until dissolved, where the concentration of the zwitterionic monomer is 1 mol / L and the concentration of acrylamide is 2.5 mol / L, and the stirring time is 1.5 h;

[0070] (4) Add photoinitiator 2959 and crosslinking agent polyethylene glycol dimethacrylate to (3) and stir until dissolved, where the concentration of the initiator is 3 mol% of the total molar amount of the monomers and the concentration of the crosslinking agent is 0.1 mol% of the total molar amount of the monomers, and the stirring time is 4 min;

[0071] (5) Transfer the prepolymer solution obtained in (4) into a mold and irradiate it with a 385 nm light source to initiate crosslinking, with a light irradiation time of 3 h;

[0072] (6) Take out the sample from the mold and place it in water for equilibrium swelling, with a swelling time of 5 days. The solid coupling material can be obtained.

[0073] The tensile strain of the obtained solid coupling material is 195.9%, and the tensile stress is 0.099 MPa; when the obtained solid coupling material is compressed to 90%, the compressive stress is 0.53 MPa, and after the stress is removed, the material returns to the initial state with good resilience. The sample prepared in this example can be clamped and fixed on the ultrasonic probe due to its good mechanical properties and will not break.

[0074] The friction coefficient of the sample prepared in this example is 0.025, which proves that the lubrication performance of the sample prepared by the present invention has been greatly improved.

[0075] When the sample prepared in this example is clamped and fixed on the ultrasonic probe, the pushing is smooth and the pushing displacement reaches 40 cm. After the sample prepared in this example is placed in the air at 40 °C for one day, no melting phenomenon is observed and it remains stable.

[0076] Comparative Example 1

[0077] The experimental steps are similar to those of Example 1, except that steps (1) and (2) are directly combined, and clay and sodium hyaluronate are added to water and stirred simultaneously. It is found that even if the stirring time is extended, neither of them can be completely dissolved in water, and there are still granular substances, and a homogeneous solution cannot be obtained. Continuing the experiment according to the subsequent steps, a homogeneous coupling material cannot be obtained.

[0078] Comparative Example 2

[0079] The experimental steps are similar to those of Example 1, except that step (2) is omitted and sodium hyaluronate digested by enzymes is not added. It is found through testing that the tensile strain of the obtained coupling material is 207.4%, the tensile stress is 0.109 MPa, and the compressive stress is 0.62 MPa when it bears 90% of the compressive strain and it will not break. However, the friction performance of the obtained coupling material decreases, the friction coefficient is 0.135, the pushing displacement is 5 cm, the pushing effect is not good, and multiple water spray lubrications are required.

[0080] Comparative Example 3

[0081] The experimental steps are similar to those of Example 1, except that the content of sodium hyaluronate digested by enzymes is 0.1 g / mL. It is found through testing that the friction coefficient of the obtained coupling material is 0.062, which is equivalent to the friction performance of commercially available products;

[0082] The mechanical properties of the obtained coupling material decrease and it is fragile. When the compressive strain is 40%, the material breaks and cannot be clamped and fixed on the ultrasonic probe.

[0083] Comparative Example 4

[0084] The experimental steps are similar to those of Example 1, except that ordinary sodium hyaluronate with a molecular weight of 1.0×10 6 -1.8×10 6 Da is used;

[0085] It is found through testing that the friction coefficient of the obtained coupling material is 0.079, which is equivalent to the friction performance of commercially available products; the mechanical properties of the obtained coupling material decrease and it is fragile. When the compressive strain is 45%, the material breaks and cannot be clamped and fixed on the ultrasonic probe.

[0086] The present invention provides a medical ultrasonic coupling material. After use, there is no residue on the tissue, and it does not need to be wiped off, which is convenient and hygienic. The solid coupling material provided by the present invention can withstand a certain amount of tensile and compressive stress without collapsing or deforming, has good mechanical properties, meets the clinical use requirements, and can be clamped and fixed on the ultrasonic probe without breaking. The solid coupling material provided by the present invention has good lubrication performance, the friction coefficient can reach 0.021 - 0.029, and it can be smoothly pushed when clamped and fixed on the ultrasonic probe, and the pushing displacement can reach 35 - 50 cm. The solid coupling material provided by the present invention is less affected by the ambient temperature, and there is no melting phenomenon after being placed at 40°C for one day, and it can still remain stable.

[0087] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered within the scope of the present invention.

Claims

1. A method for preparing a medical ultrasonic coupling material, Features: include, Prepare a clay solution by dissolving clay in water and stirring until dissolved; Adding sodium hyaluronate to the clay solution and stirring until dissolved to prepare a sodium hyaluronate-clay solution mixture; Adding zwitterionic monomer and acrylamide to the sodium hyaluronate-clay solution mixture, stirring until dissolved, to prepare prepolymer solution A; Adding a photoinitiator and a crosslinking agent to prepolymer solution A, stirring until dissolved, to obtain prepolymer solution B; The obtained prepolymer solution B is transferred into a mold, and light is irradiated to induce cross-linking. The sample is taken out of the mold and placed in water for equilibrium swelling, thereby obtaining a solid coupling material.

2. The preparation method according to claim 1, Features: The clay is one of lithium magnesium silicate and aluminum magnesium silicate; the concentration of the clay solution is 0.01-0.015 g / mL, and the water is one of ultrapure water and deionized water.

3. The preparation method according to claim 1, Features: The sodium hyaluronate is one of low molecular weight sodium hyaluronate and enzyme-cut sodium hyaluronate, wherein the molecular weight of low molecular weight sodium hyaluronate is 200-400 kDa, and the molecular weight of enzyme-cut sodium hyaluronate is less than 10 kDa.

4. The preparation method according to claim 1, Features: The concentration of sodium hyaluronate in the sodium hyaluronate-clay solution mixture is 0.02-0.08 g / mL.

5. The preparation method according to claim 1, Features: The zwitterionic monomer is at least one of carboxylate betaine zwitterionic monomers, sulfonate betaine zwitterionic monomers, and phosphate betaine zwitterionic monomers; the concentration of the zwitterionic monomer in the prepolymer solution A is 0.5-1.5 mol / L, and the concentration of acrylamide is 2.5-4 mol / L.

6. The preparation method according to claim 1, Features: The photoinitiator is one of 1173, α-ketoglutaric acid, and 2959, and the concentration of the photoinitiator is 1 to 3 mol% of the total molar amount of the monomer; the cross-linking agent is one of N,N'-methylenebisacrylamide, polyethylene glycol diacrylate, and polyethylene glycol dimethacrylate, and the concentration of the cross-linking agent is 0.1 to 0.2 mol% of the total molar amount of the monomer.

7. The preparation method according to claim 1, Features: The light irradiation induces crosslinking, the wavelength of the light source is 365-405nm, and the irradiation time is 3-6h; the equilibrium swelling is carried out in water, wherein the equilibrium swelling time is 3-5 days, and the water is changed every 24h.

8. A medical ultrasonic coupling material obtained by the preparation method according to any one of claims 1 to 7.

9. The medical ultrasonic coupling material according to claim 8, Features: The friction coefficient of the medical ultrasonic coupling material is less than 0.03; The medical ultrasonic coupling material can withstand a tensile strain greater than 100%, and after the strain is removed, the ultrasonic coupling material can return to its initial state; The medical ultrasonic coupling material can withstand a compressive strain greater than 60%, and after the strain is removed, the ultrasonic coupling material can return to its initial state.

10. Use of the medical ultrasonic coupling material according to claim 8 in ultrasonic examination, Features: The solid coupling material can be clamped and fixed on the ultrasonic probe without being broken; The solid coupling material is clamped and fixed on the ultrasonic probe and can be pushed smoothly, and the pushing displacement can reach 35 to 50 cm.

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