Preparation method and application of external contrast agent

Abstract

The invention discloses a preparation method and application of an external contrast agent, and belongs to the technical field of contrast agents. The preparation method comprises the following steps: preparing a coupling solvent from PEG 600 and PEG 1000, and mixing the coupling solvent with iopromide to prepare the contrast agent for external use. The external contrast agent prepared by the invention is beneficial to a low-density object, can present a clear structure during CT scanning imaging, and is also beneficial to reconstruction of a three-dimensional structure of the low-density object. The external contrast agent is sprayed to the surface of the low-density object, so that the low-density object can be developed under X-rays, imaging of the low-density object is facilitated, and a precise three-dimensional structure of the low-density object is reconstructed.

Description

Technical Field

[0001] This invention relates to a method for preparing and applying a topical contrast agent, belonging to the field of contrast agent technology. Background Technology

[0002] Currently, medical imaging technology is widely used in the diagnosis and treatment assessment of diseases. Contrast agents are usually introduced into the body through injection (intravenous, arterial, etc.), oral administration, or enema to improve the visibility of specific tissues or organs in imaging examinations such as X-rays and CT scans. Contrast agents play a key role in improving imaging contrast and enhancing the display of lesions.

[0003] Iodine-based contrast agents, such as iopromide and iohexol, are widely used in X-ray and CT imaging examinations due to their good water solubility and X-ray absorption. These contrast agents are primarily designed for in vivo use, administered intravenously or via arterial injection to temporarily alter the density of local tissues, thereby enhancing the imaging contrast between the target structure and surrounding tissues.

[0004] However, the aforementioned contrast agents have limitations. Their application in in vitro object imaging is not ideal, especially in meeting the needs of low-density materials (such as polymer artificial blood vessels, tissue engineering scaffolds, etc.) in three-dimensional imaging, structural analysis, or precision modeling. Furthermore, there are no external contrast agents on the market that can help low-density objects present their precise structures under X-ray or CT scans.

[0005] Therefore, developing a specialized contrast agent suitable for in vitro use, which should have good adhesion to low-density objects and imaging enhancement effects, to support the imaging evaluation and precise replication of artificial structures in the field of medical engineering, has extremely high practical and economic value. Summary of the Invention

[0006] To address the aforementioned issues, this invention first prepares a coupling solvent using PEG 600 and PEG 1000, and then mixes the coupling solvent with iopromide to prepare a topical contrast agent. The topical contrast agent prepared by this invention helps low-density objects to exhibit a clear structure during CT scan imaging and also aids in the reconstruction of the three-dimensional structure of low-density objects.

[0007] The first objective of this invention is to provide a method for preparing a topical contrast agent, comprising the steps of:

[0008] (1) Mix PEG 600 and PEG 1000, let stand, and obtain the coupling solvent;

[0009] The mass ratio of PEG 600 to PEG 1000 is 1-3:1-4.

[0010] (2) Mix the coupling solvent with an aqueous solution of iopromide to obtain a topical contrast agent;

[0011] The mass fraction of the iopromide aqueous solution is 60-80% w / w, and the mass ratio of the coupling solvent to the iopromide aqueous solution is 50:1-2.

[0012] In one embodiment, the mixing and standing in step (1) is performed at 50-60°C and 200-800 rpm, followed by standing for 1-2 hours.

[0013] In one embodiment, the mass ratio of PEG 600 and PEG 1000 in step (1) is 1:1, 3:4, 1:2, or 1:3;

[0014] Optionally, the mass ratio of PEG 600 to PEG 1000 is 1:1 or 3:4.

[0015] In one embodiment, the mixing in step (2) is carried out at 50-60°C, and the mixture is stirred and heated for 1-2 hours.

[0016] A second object of the present invention is to provide a topical contrast agent prepared by any of the methods described above.

[0017] In one embodiment, the above-mentioned external contrast agent is solid at room temperature (25°C) and becomes liquid when heated to 41°C.

[0018] A third object of the present invention is to provide an imaging product containing the aforementioned topical contrast agent.

[0019] A fourth object of the present invention is to provide the application of any of the above-described methods or the above-described topical contrast agents in in vitro contrast imaging and 3D imaging.

[0020] The fifth objective of this invention is to provide a method for improving the in vitro contrast and 3D imaging effects of low-density materials by spraying the aforementioned topical contrast agent onto the surface of the low-density material.

[0021] In one embodiment, the spraying involves first heating the topical contrast agent until it melts, then spraying it onto the surface of a low-density object at a spraying rate of 0.2–0.8 mL / cm². 3 .

[0022] In one embodiment, the low-density material includes polylactic acid-based artificial blood vessels and sponges.

[0023] Beneficial effects of the present invention

[0024] The present invention provides an external contrast agent Z1105-02 obtained by mixing PEG600, PEG1000 and iopromide solution in different mass ratios. When sprayed onto the surface of low-density objects, it can make low-density objects visible under X-rays, which is beneficial for imaging low-density objects and reconstructing their precise three-dimensional structure.

[0025] (1) Z1105-02 is a solid at room temperature (25℃) and a liquid at 35℃. It can quickly adhere to the surface of low-density objects through temperature changes.

[0026] (2) Z1105-02 has a liquid viscosity close to that of water at 35℃, making it suitable for application. Attached Figure Description

[0027] Figure 1 Melting point test diagrams of PEG600 and PEG1000 coupled in different ratios.

[0028] Figure 2 The viscosity curve of Z1105-02 at 35℃ is shown.

[0029] Figure 3 The images show polylactic acid (PLA) artificial blood vessels and their CT imaging and 3D reconstruction results. The images are shown in the CT image; where A represents the PLA artificial blood vessel, B represents the CT angiography, and C represents the 3D imaging.

[0030] Figure 4 The images and 3D reconstructed images of polylactic acid artificial blood vessels after spraying topical contrast agent Z1105-02 (Example 1) under CT are shown in the CT images. Among them, A is the polylactic acid artificial blood vessel, B is the CT angiography, and C is the 3D imaging.

[0031] Figure 5 The images and 3D reconstructed images of polylactic acid (PLA) artificial blood vessels after spraying with iopromide aqueous solution (76.89% w / w) are shown in the CT images. Among them, A is the PLA artificial blood vessel, B is the CT angiography, and C is the 3D imaging.

[0032] Figure 6 The images and 3D reconstructed images under CT are obtained after spraying a 90% w / w iopromide aqueous solution onto a polylactic acid artificial blood vessel (Comparative Example 1). In the images, A is the polylactic acid artificial blood vessel, B is the CT angiography, and C is the 3D imaging.

[0033] Figure 7 The images and 3D reconstructed images of polylactic acid (PLA) artificial blood vessels after spraying with a topical contrast agent prepared using only PEG600 and iopromide (Comparative Example 2) are shown in CT and CT images. In the images, A is the PLA artificial blood vessel, B is the CT contrast agent, and C is the 3D image. Detailed Implementation

[0034] The preferred embodiments of the present invention are described below. It should be understood that the embodiments are for better explanation of the present invention and are not intended to limit the present invention.

[0035] Raw materials used in the examples:

[0036] PEG 600 and PEG 1000 were purchased from: Sinopharm Chemical Reagent Co., Ltd.

[0037] Iopromide was purchased from Bayer AG, Germany.

[0038] Test method:

[0039] CT imaging method: Micro-CT detection conditions: scanning voltage 70KV, X-ray filter Cu0.06mm + Al0.5mm, current 88μA, field of view 18mm, resolution 144μm, scanning mode High Resolution, scanning time 4min, angular increment 1.5°.

[0040] Example 1: Preparation of a topical contrast agent

[0041] A method for preparing a topical contrast agent, comprising the steps of:

[0042] (1) PEG 600 and PEG 1000 were mixed at 60℃ and 750rpm and allowed to stand for 6h to obtain the coupling solvent; wherein the mass ratio of PEG 600 and PEG 1000 was 1:1.

[0043] (2) Mix the coupling solvent with the iopromide aqueous solution, shake and heat at 60°C for 2 hours to obtain the external contrast agent (named Z1105-02); wherein the mass fraction of the iopromide aqueous solution is 76.89% w / w, and the mass ratio of the coupling solvent to the iopromide aqueous solution is 50:1.

[0044] The prepared external contrast agent Z1105-02 is a solid at room temperature (25℃).

[0045] Example 2: Preparation of a topical contrast agent

[0046] Based on Example 1, the mass ratio of coupling solvent to iopromide aqueous solution in step (2) was changed to 50:2 to prepare an external contrast agent.

[0047] Example 3: Changing the ratio of PEG 600 and PEG 1000

[0048] Based on Example 1, while keeping the total amount of PEG 600 and PEG 1000 unchanged, the mass ratio of PEG 600 and PEG 1000 was changed to 3:4, 1:2, and 1:3, respectively, and the remaining steps were the same as in Example 1.

[0049] Melting point test results as follows Figure 1 As shown, the results indicate that the melting point of the prepared external contrast agent changes when the ratio of PEG 600 and PEG 1000 is changed. When the mass ratio is 1:1, the melting point of the external contrast agent is 35℃.

[0050] Testing the melting point and the spraying effect of the contrast agent revealed that when the melting point of the external contrast agent is low, it is not conducive to the rapid adhesion of the external contrast agent to the object surface; when the melting point of the external contrast agent is high, the contrast agent will agglomerate on the object surface and cannot be uniformly adhered to the object surface.

[0051] The viscosity of topical contrast agent Z1105-02 at 35℃ was measured, and the results are as follows: Figure 2 As shown, the results indicate that the liquid viscosity is close to that of water, making it suitable for application.

[0052] Comparative Example 1: Iopromide Concentration

[0053] Based on Example 1, the mass fraction of iopromide was changed to 50% w / w and 90% w / w, while the remaining steps were the same as in Example 1, to prepare a topical contrast agent.

[0054] The test results show that when the mass fraction of iopromide is less than 60% w / w or greater than 80% w / w, the topical contrast agent cannot be effectively and evenly sprayed onto the object surface.

[0055] Comparative Example 2: No PEG 1000 added

[0056] Based on Example 1, without adding PEG 1000, a topical contrast agent was prepared using only PEG 600 and iopromide aqueous solution.

[0057] Example 4: Imaging Effect Detection

[0058] The external contrast agents prepared in Examples 1 and 2, and Comparative Examples 1 and 2 were used to test their contrast effects on low-density materials (e.g., polylactic acid artificial blood vessels, sponges), with iopromide aqueous solution (76.89% w / w) as a control.

[0059] The specific steps for spraying the topical contrast agent onto the surface of a low-density material are as follows:

[0060] Take the external contrast agent Z1105-02 prepared in Example 1, melt it, and then spray 0.2 mL evenly onto a 1 cm³ volume area. 2The low-density object surface was left to stand for 3 minutes and then imaged using Micro-CT.

[0061] Low-density polylactic acid (PLA) artificial blood vessels, without any treatment, produce imaging results as follows: Figure 3 As shown, the results indicate that low-density polylactic acid (PLA) artificial blood vessels cannot be visualized under Micro-CT and have no 3D reconstructed structure.

[0062] After spraying with the topical contrast agent Z1105-02 prepared in Example 1, the contrast and imaging results are as follows: Figure 4 As shown, the results indicate that gray images appear under Micro-CT and the 3D reconstructed structures are clear; similarly, the topical contrast agent prepared in Example 2 also has good effects.

[0063] Using only iopromide aqueous solution to spray polylactic acid artificial blood vessels, the angiography and imaging results are as follows: Figure 5 As shown, the results indicate that artificial blood vessels made of lactic acid cannot be fully imaged.

[0064] The topical contrast agent prepared using a higher concentration of iopromide (90% w / w) as described in Comparative Example 1 was sprayed onto a polylactic acid artificial blood vessel. The angiography and imaging results are as follows: Figure 6 As shown, the results indicate that the artificial blood vessels made of lactic acid exhibit severe imaging defects, and the topical contrast agent shows significant aggregation on the surface of the artificial blood vessels.

[0065] The topical contrast agent prepared in Comparative Example 2 (without PEG 1000) was sprayed onto a polylactic acid artificial blood vessel. The contrast and imaging results are as follows: Figure 7 As shown, the results indicate that the topical contrast agent was unevenly applied to the surface of the artificial blood vessel, resulting in significant imaging defects.

[0066] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Anyone skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. A method for preparing a topical contrast agent, characterized in that, Including the following steps: (1) Mix PEG 600 and PEG 1000, let stand, and obtain the coupling solvent; The mass ratio of PEG 600 to PEG 1000 is 1-3:1-4. (2) Mix the coupling solvent with an aqueous solution of iopromide to obtain a topical contrast agent; The mass fraction of the iopromide aqueous solution is 60-80% w / w, and the mass ratio of the coupling solvent to the iopromide aqueous solution is 50:1-2.

2. The method according to claim 1, characterized in that, In step (1), the mixing and standing are carried out at 50-60℃ and 200-800rpm, and then left to stand for 1-2 hours.

3. The method according to claim 1, characterized in that, In step (1), the mass ratio of PEG 600 and PEG 1000 is 1:1, 3:4, 1:2, or 1:

3. Optionally, the mass ratio of PEG 600 to PEG 1000 is 1:1 or 3:

4.

4. The method according to claim 1, characterized in that, In step (2), the mixing temperature is 50-60℃, and the mixture is stirred and heated for 1-2 hours.

5. The topical contrast agent prepared by the method according to any one of claims 1 to 4.

6. An imaging product, characterized in that, The product contains the external contrast agent as described in claim 4.

7. The application of the method according to any one of claims 1 to 4 or the external contrast agent according to claim 5 in in vitro contrast imaging and 3D imaging.

8. A method for improving the in vitro imaging and 3D imaging effects of low-density materials, characterized in that, The external contrast agent as described in claim 5 is sprayed onto the surface of a low-density material.

9. The method according to claim 8, characterized in that, The spraying process involves first heating the external contrast agent until it melts, then spraying it onto the surface of the low-density object at a rate of 0.2–0.8 mL / cm². 3 .

10. The method according to claim 8, characterized in that, Low-density materials include polylactic acid (PLA) artificial blood vessels and sponges.

Images