Blood vessel contrast agent for corpses and preparation method of blood vessel contrast agent
By combining iodine-containing polymers, iodobenzene ring compounds, and triethyl glycerol, along with dimer acids and liquid paraffin, a stable angiography agent is formed, solving the problems of permeability and imaging quality of cadaveric angiography agents over long periods of time, and achieving excellent angiography results over a longer period of time.
Patent Information
- Application Number
- CN202511453132.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-13
- Publication Date
- 2025-11-07
- Estimated Expiration
- 2045-10-13
AI Technical Summary
Existing post-mortem angiography agents have high requirements for the time of death of the sample. The angiography effect decreases after the time of death exceeds 24 hours, and there are permeability problems, making it difficult to maintain the stability and imaging quality of blood vessels for a long time.
The formulation employs a combination of iodine-containing polymers, iodobenzene ring compounds, and triethyl glycerol. The iodine-containing polymers form micelles, which, combined with dimer acids, form a water-based isolation membrane on the vascular intima, enhancing the stability of the contrast agent within the blood vessel. Triethyl glycerol provides viscosity support at low temperatures, and combined with liquid paraffin, it forms a suitable vascular contrast agent.
It achieves stability within blood vessels and good imaging results over a longer period of time (e.g., within 72 hours), solving the problems of permeability and image quality degradation of traditional contrast agents after a long period of time, and is suitable for cadavers with a long time of death.
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Figure CN120899953A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application belongs to the technical field of angiographic agents, and particularly relates to a kind of angiographic agents for cadavers and a preparation method thereof. BACKGROUND
[0002] In traditional cadaver dissection, the search for vascular lesions and injuries is one of the technical problems that have puzzled the forensic community. In traditional cadaver dissection, if thin-layer sectioning of blood vessels is used for blood vessel search, not only a large amount of manpower and material resources are consumed, but also due to the limitations of naked eye observation, it often leads to missed detection, and even misdiagnosis. With the development of cadaver angiography technology, this problem has been improved and even solved. Cadavers lack the blood circulation of living bodies, so whole-body angiography of cadavers is extremely challenging. In addition, the dosage of angiographic agents for cadavers is large, and the current clinical use of iodine contrast agents, such as iodized oil, is relatively expensive, and there is a problem of incomplete angiography or pseudo-image caused by viscosity mismatch. Compared with conventional angiographic agents, angiographic agents for cadavers have their own characteristics, such as increased vascular wall permeability due to loss of physiological activity in cadaver blood vessels, which can easily lead to extravasation of contrast agents and affect the quality of imaging. Therefore, cadaver contrast agents need to have high viscosity and liposolubility to slow down the penetration rate and stabilize the filling of blood vessels.
[0003] Iohexol is a commonly used component of angiographic agents for cadavers in clinical use. For example, CN114010804A discloses a kind of angiographic agent for cadavers, which includes iohexol, sorbitol and water. The content of iohexol in the angiographic agent is 20-60 mg / mL, and the content of sorbitol in the angiographic agent is 700-800 mg / mL. Iohexol can easily penetrate through the cadaver blood vessel wall and extravasate into the surrounding tissue, resulting in blurred blood vessel boundaries, decreased contrast quality, and insufficient contrast density of iohexol, which cannot meet the requirements of long-term stable influence of cadaver blood vessels.
[0004] CN111840580A discloses a kind of angiographic agent for cadavers, which includes an iodinated benzene ring compound and a specific viscosity liposoluble solvent, and the iodinated benzene ring compound is mixed with the specific viscosity liposoluble solvent to obtain a liposoluble iodine solution. US20130045168A1 discloses an angiographic agent that can be used for autopsy, which includes iodized oil and a non-polar component, and the non-polar component is paraffin oil or liquid paraffin, and the two are mixed to obtain a liposoluble iodine solution. However, the above-mentioned contrast agent using small-molecule organic iodide has poor flowability at low temperature, cannot be used in a wide range of temperature, and has the problem of incomplete contrast during the contrast process.
[0005] The more important problem of the existing corpse angiographic agent is that the existing angiographic agent has a high requirement for the sample death time, which is 12h, and the best angiographic effect is generally not more than 24h. The blood vessels are complete within 12h of death. With the passage of time, the permeability of the blood vessels of the corpse increases, affecting the filling of the vascular filling agent, and permeation is prone to occur. SUMMARY
[0006] In order to solve the defect that the existing angiographic agent for corpses and autopsies has a high requirement for the sample death time (the death time is generally not more than 48h, preferably not more than 24h), and the angiographic effect decreases when the death time is more than 3 days, the present application provides a corpse angiographic agent and a preparation method thereof. The corpse angiographic agent provided by the present application contains iodine-containing polymer, iodinated benzene ring compound and glyceryl triacetate. The present application adopts the compounding of iodine-containing polymer and iodinated benzene ring compound. The iodine-containing polymer forms micelles at a verified concentration, providing more excellent angiographic effect and better low-temperature fluidity, and without causing problems such as vascular permeation. The diacid can form a water-based isolation film on the inner surface of the blood vessel, hindering the permeation of the angiographic agent outside the blood vessel, and enhancing the stability of the angiographic agent components in the blood vessel. The glyceryl triacetate as a low-temperature plasticizer can provide the angiographic agent with suitable viscosity at low temperature, and can also have ideal angiographic effect on corpses with long death time in cooperation with the iodine-containing polymer. Specifically, the present application provides the following technical solutions to solve the above technical problems: A corpse angiographic agent, comprising the following components in mass parts: 20-35 parts of iodine-containing polymer, 30-50 parts of iodinated benzene ring compound, 90-150 parts of glyceryl triacetate, 30-40 parts of diacid, and 600-800 parts of liquid paraffin; the iodine-containing polymer is obtained by copolymerization of (meth) acrylic acid alkyl ester, polyethylene glycol diacrylate and iodine-containing monomer; the alkyl carbon chain length in the (meth) acrylic acid alkyl ester is 4-6; the iodine-containing monomer is selected from at least one of 3-iodo-acrylic acid ethyl ester, 3-iodo-acrylic acid methyl ester and (meth) acrylic acid iodinated benzyl ester.
[0007] Further, the iodinated benzene ring compound is at least one of mono-iodinated benzene ring compound, di-iodinated benzene ring compound, tri-iodinated benzene ring compound, tetra-iodinated benzene ring compound, penta-iodinated benzene ring compound and hexa-iodinated benzene ring compound; preferably, the di-iodinated benzene ring compound. Further, the di-iodinated benzene ring compound is selected from at least one of 1,2-diiodobenzene, 1,3-diiodobenzene and 1,4-diiodobenzene.
[0008] Further, the molar ratio of (meth) acrylic acid alkyl ester, polyethylene glycol diacrylate and iodine-containing monomer is 6-10:0.5-0.8:3-5.
[0009] Further, the (meth)acrylic acid iodo benzyl ester is selected from at least one of (meth)acrylic acid 3,4,5-triiodobenzyl ester, (meth)acrylic acid 3-iodobenzyl ester, (meth)acrylic acid 2-iodobenzyl ester, (meth)acrylic acid 3,5-diiodobenzyl ester.
[0010] Further, the (meth)acrylic acid iodo benzyl ester is prepared by esterification reaction of (meth)acrylic acid and iodo benzyl alcohol, and the iodo benzyl alcohol is selected from at least one of 3,4,5-triiodobenzyl alcohol, 3-iodobenzyl alcohol, 2-iodobenzyl alcohol, 3,5-diiodobenzyl alcohol.
[0011] Further, the preparation method of the (meth)acrylic acid iodo benzyl ester comprises the following steps: under inert atmosphere, (meth)acrylic acid and iodo benzyl alcohol are added into aromatic hydrocarbon organic solvent, and the product (meth)acrylic acid iodo benzyl ester is obtained by fully reacting under the presence of concentrated sulfuric acid catalyst and polymerization inhibitor at 70-110℃. The generated water is removed by water trap during the reaction, and after the reaction is completed, neutralization, liquid separation, extraction and reduced pressure distillation are performed; the neutralization is adjusted to pH 6-7 by sodium bicarbonate to neutralize the excess acid; the extraction is performed by ethyl acetate.
[0012] Preferably, the molar ratio of (meth)acrylic acid and iodo benzyl alcohol is 1-1.2:1; the aromatic hydrocarbon organic solvent is selected from at least one of benzene, toluene and ethylbenzene; the inert atmosphere is nitrogen, the amount of concentrated sulfuric acid catalyst is 2-5wt% of the mass of (meth)acrylic acid, and the polymerization inhibitor is selected from at least one of hydroquinone, p-hydroxyanisole, p-methoxyphenol and tert-butyl catechol, and the amount of polymerization inhibitor is 0.3-1wt% of the mass of (meth)acrylic acid.
[0013] Further, the (meth)acrylic acid alkyl ester is selected from at least one of (meth)acrylic acid propyl ester, (meth)acrylic acid butyl ester, (meth)acrylic acid pentyl ester and (meth)acrylic acid hexyl ester; the inventors have also tried to use (meth)acrylic acid C1-3 ester, but the effect is not good, the carbon chain length is insufficient, and at least (meth)acrylic acid butyl ester is needed to obtain a good effect; however, the carbon chain length cannot be too long, otherwise the solubility is not good and the iodine-containing polymer cannot be well dispersed in liquid paraffin. The number average molecular weight of the PEG segment of the polyethylene glycol diacrylate is 200-400 g / mol.
[0014] Further, the iodine-containing polymer is prepared by a preparation method comprising the following steps: under inert atmosphere, (meth)acrylic acid C3-6 alkyl ester, polyethylene glycol diacrylate and iodine-containing monomer are added into an organic solvent, an initiator is slowly added while being heated to 70-80℃, and the reaction is performed for 6-10h; after the reaction is completed, the reaction solution is poured into methanol, the polymer is precipitated, washed and dried to obtain the iodine-containing polymer.
[0015] Further, the organic solvent is selected from at least one of tetrahydrofuran, ethyl acetate, butyl acetate; the initiator is an azo initiator, and is specifically selected from at least one of azobisisobutyronitrile, azobisisoheptyl nitrile, dimethyl azobisbutyrate, the amount of initiator is 1-3wt% of the total mass of monomers; the washing is washing with methanol for 3-5 times, and the drying is vacuum drying.
[0016] Further, the acid value of the dimer acid is 180-210 mgKOH / g, the viscosity at 25 DEG C is 4000-7000 mPa s, and the viscosity of the liquid paraffin at 25 DEG C is 10-40 mPa s.
[0017] The application further provides a preparation method of the angiographic agent for corpses. (S1) accurately weighing each material, stirring and uniformly mixing the iodobenzene ring compound and the liquid paraffin to obtain liquid phase A; (S2) uniformly mixing the iodine-containing polymer, glyceryl triacetate and dimer acid under heating at 50-60 DEG C to obtain liquid phase B; (S3) uniformly mixing liquid phase A and liquid phase B under stirring at 300-600 rpm, vacuum defoaming to obtain the angiographic agent for corpses, and sealing and storing in the dark.
[0018] Further, the uniformly ultrasonic mixing is stirring or oscillation under ultrasonic conditions, the ultrasonic power is 200-300 W, and the ultrasonic frequency is 60-200 kHz; the vacuum defoaming is under 0.01-0.1 MPa for 0.5-2 h.
[0019] The iodine-containing polymer prepared by the application can realize excellent angiographic effect on corpses in cooperation with the iodobenzene ring compound, and the angiographic agent of the application can still achieve ideal angiographic effect for corpses with a longer death time, such as 72h≤death time≤84h, and the conventional angiographic agent for corpses has no effect. BRIEF DESCRIPTION OF DRAWINGS
[0020] Figure 1 is an angiographic image of the arterial arch part of a human corpse with a death time of 12h using the angiographic agent of example 1; Figure 2 is an angiographic image of the arterial arch part of a human corpse with a death time of 72h using the angiographic agent of example 1. DETAILED DESCRIPTION
[0021] The technical solutions of the application are further explained and described below with specific examples.
[0022] The acid value of the dimer acid is 196 mgKOH / g, and the viscosity at 25℃ is 4700 mPa·s; the viscosity of liquid paraffin at 25℃ is 10 mPa·s.
[0023] Preparation Example 1-1 Under nitrogen atmosphere, 1.1 mole fraction of methacrylic acid and 1 mole fraction of 3,4,5-triiodobenzyl alcohol were added into solvent toluene, 3wt% concentrated sulfuric acid of the mass of methacrylic acid was added as a catalyst, 0.6wt% hydroquinone of the mass of methacrylic acid was added as a polymerization inhibitor, the temperature was raised to 100℃ and reacted for 12h, the water was separated by a water separator, and the water phase was neutralized to pH=7 with 5wt% sodium bicarbonate aqueous solution, the liquid was separated, the water phase was extracted with ethyl acetate, the organic phases were combined, and the solvent was distilled off under reduced pressure to obtain the product 3,4,5-triiodobenzyl methacrylate.
[0024] Preparation Example 1-2 The same as Preparation Example 1-1, except that 3,4,5-triiodobenzyl alcohol was replaced by 3,5-diiodobenzyl alcohol of equal molar amount, and the product was 3,5-diiodobenzyl methacrylate.
[0025] Preparation Example 1-3 The same as Preparation Example 1-1, except that 3,4,5-triiodobenzyl alcohol was replaced by 3-iodobenzyl alcohol of equal molar amount, and the product was 3-iodobenzyl methacrylate.
[0026] Preparation Example 2-1 Under nitrogen atmosphere, butyl acrylate, polyethylene glycol diacrylate (PEG segment number average molecular weight 200) and the 3,4,5-triiodobenzyl methacrylate prepared in Preparation Example 1 were added into solvent ethyl acetate according to the molar ratio of 6:0.8:5, and 5wt% azobisisobutyronitrile ethyl acetate solution was slowly added dropwise while heating, and the amount of azobisisobutyronitrile was 1wt% of the total mass of monomers (the sum of isopropyl acrylate, polyethylene glycol diacrylate and 3,4,5-triiodobenzyl methacrylate). The temperature was raised to 80℃ and reacted for 10h. After the reaction was completed, the reaction solution was poured into methanol, and the polymer was precipitated, washed with tetrahydrofuran for 3 times, and vacuum dried to obtain iodine-containing polymer 1.
[0027] Preparation Example 2-2 The same as Preparation Example 2-1, except that the 3,4,5-triiodobenzyl methacrylate prepared in Preparation Example 1 was replaced by the 3,5-diiodobenzyl methacrylate prepared in Preparation Example 1-2, and finally iodine-containing polymer 2 was prepared.
[0028] Preparation Example 2-3 The other conditions are the same as those in Preparation Example 2-1, except that the 3,4,5-triiodobenzyl methacrylate prepared in Preparation Example 1 is replaced with an equal molar amount of 3-iodobenzyl methacrylate prepared in Preparation Example 1-3, and finally iodine-containing polymer 3 is prepared.
[0029] Preparation Example 2-4 The other conditions are the same as those in Preparation Example 2-1, except that the molar ratio of butyl acrylate, polyethylene glycol bisacrylate, and 3,4,5-triiodobenzyl methacrylate is changed to 10:0.5:3, and finally iodine-containing polymer 4 is prepared.
[0030] Preparation Example 2-5 The other conditions are the same as those in Preparation Example 2-1, except that butyl acrylate is replaced with an equal molar amount of propyl acrylate, and finally iodine-containing polymer 5 is prepared.
[0031] Preparation Example 2-6 The other conditions are the same as those in Preparation Example 2-1, except that butyl acrylate is replaced with an equal molar amount of hexyl acrylate, and finally iodine-containing polymer 6 is prepared.
[0032] Preparation Example 2-7 The other conditions are the same as those in Preparation Example 2-1, except that the number-average molecular weight of the PEG segment of the polyethylene glycol bisacrylate is 600, and finally iodine-containing polymer 7 is prepared.
[0033] Preparation Example 2-8 The other conditions are the same as those in Preparation Example 2-1, except that butyl acrylate is replaced with an equal molar amount of methyl acrylate, and finally iodine-containing polymer 8 is prepared.
[0034] Preparation Example 2-9 The other conditions are the same as those in Preparation Example 2-1, except that the polyethylene glycol bisacrylate is replaced with ethylene glycol diacrylate, and finally iodine-containing polymer 9 is prepared.
[0035] Preparation Example 2-10 The other conditions are the same as those in Preparation Example 2-1, except that the polyethylene glycol bisacrylate is not added, and finally iodine-containing polymer 10 is prepared.
[0036] Preparation Example 2-11 The other conditions are the same as those in Preparation Example 2-1, except that butyl acrylate is not added, and finally iodine-containing polymer 11 is prepared.
[0037] Example 1
[0038] (S1) 40 parts by mass of 1,4-diiodobenzene was stirred and mixed uniformly with 800 parts by mass of liquid paraffin to obtain liquid phase A; (S2) 30 parts by mass of the iodine-containing polymer 1 prepared in Preparation Example 2-1, 120 parts by mass of glycerol triacetate, and 40 parts by mass of dimer acid were mixed uniformly under the condition of 60°C heating, 200W, and 120kHz ultrasonic, to obtain liquid phase B; (S3) Liquid phase A and liquid phase B were mixed uniformly under the condition of 400rpm stirring, and vacuum degassing for 1h under the condition of 0.1MPa, to obtain the angiographic agent for corpse, which was stored in a dark place.
[0039] Figure 1 is an angiographic image of the arterial arch of a human corpse which died 12h ago, using the angiographic agent of Example 1. Figure 2 is an angiographic image of the arterial arch of a human corpse which died 72h ago, using the angiographic agent of Example 1. It can be seen that even after 72h, the angiographic agent of the present application still has a good angiographic effect.
[0040] Example 2
[0041] The other conditions were the same as in Example 1, except that the iodine-containing polymer 1 prepared in Preparation Example 2-1 was replaced by the iodine-containing polymer 2 prepared in Preparation Example 2-2.
[0042] Example 3
[0043] The other conditions were the same as in Example 1, except that the iodine-containing polymer 1 prepared in Preparation Example 2-1 was replaced by the iodine-containing polymer 3 prepared in Preparation Example 2-3.
[0044] Example 4
[0045] The other conditions were the same as in Example 1, except that the iodine-containing polymer 1 prepared in Preparation Example 2-1 was replaced by the iodine-containing polymer 4 prepared in Preparation Example 2-4.
[0046] Example 5
[0047] The other conditions were the same as in Example 1, except that the iodine-containing polymer 1 prepared in Preparation Example 2-1 was replaced by the iodine-containing polymer 5 prepared in Preparation Example 2-5.
[0048] Example 6 The other conditions were the same as in Example 1, except that the iodine-containing polymer 1 prepared in Preparation Example 2-1 was replaced by the iodine-containing polymer 6 prepared in Preparation Example 2-6.
[0049] Example 7
[0050] The other conditions were the same as in Example 1, except that the iodine-containing polymer 1 prepared in Preparation Example 2-1 was replaced by the iodine-containing polymer 7 prepared in Preparation Example 2-7.
[0051] Example 8
[0052] (S1) 50 parts by mass of 1,4-diiodobenzene was mixed with 800 parts by mass of liquid paraffin to obtain liquid phase A; (S2) 20 parts by mass of the iodine-containing polymer 1 prepared in Preparation Example 2-1, 120 parts by mass of triacetin, and 10 parts by mass of dimer acid were mixed under the condition of 60°C heating and 200W, 120kHz ultrasonic to obtain liquid phase B; (S3) Liquid phase A and liquid phase B were mixed under the condition of 400rpm stirring, and vacuum degassing was performed under the condition of 0.1MPa for 1h to obtain the angiographic agent for cadavers, which was stored in the dark after sealing.
[0053] Example 9
[0054] (S1) 30 parts by mass of 1,4-diiodobenzene was mixed with 800 parts by mass of liquid paraffin to obtain liquid phase A; (S2) 35 parts by mass of the iodine-containing polymer 1 prepared in Preparation Example 2-1, 120 parts by mass of triacetin, and 30 parts by mass of dimer acid were mixed under the condition of 60°C heating and 200W, 120kHz ultrasonic to obtain liquid phase B; (S3) Liquid phase A and liquid phase B were mixed under the condition of 400rpm stirring, and vacuum degassing was performed under the condition of 0.1MPa for 1h to obtain the angiographic agent for cadavers, which was stored in the dark after sealing.
[0055] Comparative Example 1 The other conditions were the same as in Example 1, except that the iodine-containing polymer 1 prepared in Preparation Example 2-1 was replaced by the iodine-containing polymer 8 prepared in Preparation Example 2-8.
[0056] Comparative Example 2 The other conditions were the same as in Example 1, except that the iodine-containing polymer 1 prepared in Preparation Example 2-1 was replaced by the iodine-containing polymer 9 prepared in Preparation Example 2-9.
[0057] Comparative Example 3 The other conditions were the same as in Example 1, except that the iodine-containing polymer 1 prepared in Preparation Example 2-1 was replaced by the iodine-containing polymer 10 prepared in Preparation Example 2-10.
[0058] Comparative Example 4 The other conditions were the same as in Example 1, except that the iodine-containing polymer 1 prepared in Preparation Example 2-1 was replaced by the iodine-containing polymer 11 prepared in Preparation Example 2-11.
[0059] Comparative Example 5 70 parts by mass of 1,4-diiodobenzene, 120 parts by mass of triacetin, 40 parts by mass of dimer acid, and 800 parts by mass of liquid paraffin were mixed to obtain the mixture, which was stored in the dark. That is, compared with Example 1, no iodine-containing polymer was added, and the same mass of 1,4-diiodobenzene was added instead.
[0060] Comparative Example 6 The other conditions are the same as in Example 1, except that the triglyceride is replaced with an equal mass of Span-20.
[0061] Application examples Adult rabbits were randomly divided into 28 groups of 4 rabbits each. For each contrast agent used in the above-described examples and comparative examples, two groups of rabbits were tested: one group underwent angiography within 12 hours of death, and the other group underwent angiography between 72 and 84 hours after death. Rabbits were euthanized by intravenous injection of 20% chloral hydrate (3 ml / kg) at the ear vein. After euthanasia, the left common carotid artery was cannulated and the right common carotid artery was ligated. Using a high-pressure injector, 20 mL was injected into each rabbit via the cannulated common carotid artery at a flow rate of 0.2 mL / s at room temperature. PMCT scans were performed in situ once before and once after injection (scanning parameters: tube voltage 120 kV, tube current automatic, slice thickness 1.0 mm). Three segments (upper, middle, and lower) of the aortic arch lumen were selected from each rabbit, and a region of interest (ROI) was randomly selected within each segment. CT values were recorded, and the results are shown in Table 1 below.
[0062] Table 1. Angiographic effects of cadaveric contrast agents on rabbits at different times of death.
[0063] As can be seen from the data in Table 1, the contrast agent provided by this invention is very suitable for autopsy use, exhibiting excellent contrast effects within 12 hours of death, and maintaining good contrast effects even after 72 hours of death. This is attributed to the use of an iodine-containing polymer in this invention, which is a copolymer of (meth)acrylate C4-6 alkyl ester, polyethylene glycol diacrylate, and an iodine-containing monomer. The absence of any one of these monomers, or a change in the monomer type, would not achieve the goal of maintaining excellent contrast effects even at longer death times. Furthermore, triglycerides in the contrast agent also play an important role.
Claims
1. A radiopaque agent for cadavers, characterized by comprising a mixture of a radiopaque agent and a biodegradable polymer. The composition comprises the following components by mass: 20-35 parts of iodine-containing polymer, 30-50 parts of iodinated benzene ring compound, 90-150 parts of glycerol triacetate, 30-40 parts of dimer acid, 600-800 parts of liquid paraffin; the iodine-containing polymer is obtained by copolymerization of (meth) acrylate alkyl ester, polyethylene glycol diacrylate and iodine-containing monomer; the alkyl carbon chain length of (meth) acrylate alkyl ester is 4-6; the iodine-containing monomer is selected from at least one of 3-iodine-acrylic acid ethyl ester, 3-iodine-acrylic acid methyl ester and (meth) acrylate iodinated benzyl ester.
2. The radiological contrast medium for cadavers according to claim 1, characterized in that, The iodinated benzene ring compound is at least one of mono-iodinated benzene ring compound, di-iodinated benzene ring compound, tri-iodinated benzene ring compound, tetra-iodinated benzene ring compound, penta-iodinated benzene ring compound and hexa-iodinated benzene ring compound.
3. The radiological contrast medium for cadavers according to claim 1, characterized in that, The iodinated benzene ring compound is di-iodinated benzene ring compound, and the di-iodinated benzene ring compound is at least one of 1,2-di-iodobenzene, 1,3-di-iodobenzene and 1,4-di-iodobenzene.
4. The radiological contrast medium for cadavers according to claim 1, characterized in that The molar ratio of (meth) acrylate alkyl ester, polyethylene glycol diacrylate and iodine-containing monomer is 6-10:0.5-0.8:3-5.
5. The radiological contrast medium for cadavers according to claim 1, wherein The (meth) acrylate iodinated benzyl ester is at least one of (meth) acrylate 3,4,5-tri-iodobenzyl ester, (meth) acrylate 3-iodobenzyl ester, (meth) acrylate 2-iodobenzyl ester and (meth) acrylate 3,5-di-iodobenzyl ester.
6. The radiological contrast medium for cadavers according to claim 5, characterized in that, The (meth) acrylate iodinated benzyl ester is obtained by esterification of (meth) acrylate and iodinated benzyl alcohol, and the iodinated benzyl alcohol is at least one of 3,4,5-tri-iodobenzyl alcohol, 3-iodinated benzyl alcohol, 2-iodinated benzyl alcohol and 3,5-di-iodinated benzyl alcohol.
7. The radiological contrast medium for cadavers according to claim 1, wherein The (meth) acrylate alkyl ester is at least one of (meth) acrylate butyl ester, (meth) acrylate pentyl ester and (meth) acrylate hexyl ester; and the number average molecular weight of the PEG segment in the polyethylene glycol diacrylate is 200-400 g / mol.
8. The radiological contrast medium for cadavers according to claim 1, wherein The iodine-containing polymer is obtained by a preparation method comprising the following steps: under inert atmosphere, (meth) acrylate alkyl ester, polyethylene glycol diacrylate and iodine-containing monomer are added into an organic solvent, an initiator is slowly added while being heated to 70-80 DEG C for 6-10 hours, after the reaction is completed, the reaction solution is poured into methanol, the polymer is precipitated, washed and dried to obtain the iodine-containing polymer.
9. The radiological contrast medium for cadavers according to claim 1, wherein The dimer acid has an acid value of 180-210 mgKOH / g and a viscosity of 4000-7000 mPa·s at 25 DEG C; and the liquid paraffin has a viscosity of 10-40 mPa·s at 25 DEG C.
10. The method of preparing a radiological contrast agent for cadavers according to any one of claims 1 to 9, characterized in that, The method comprises the following steps: (S1) accurately weighing each material, stirring and uniformly mixing the iodinated benzene ring compound and the liquid paraffin to obtain liquid phase A; (S2) under heating at 50-60 DEG C, uniformly mixing the iodine-containing polymer, glycerol triacetate and dimer acid by ultrasonic mixing to obtain liquid phase B; (S3) uniformly mixing liquid phase A and liquid phase B under stirring at 300-600 rpm, vacuum degassing to obtain the angiographic agent for cadavers, and sealing and storing in the dark.
Citation Information
Patent Citations
Blood vessel contrast agent for corpses and preparation method of blood vessel contrast agent
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