66108-95-0 Usage
Uses
Used in Pharmaceutical Industry:
Iohexol is used as a raw material for the production of the water-soluble, non-ionic X-CT contrast agent Omnipaque.
Used in Medical Imaging:
Iohexol is used as an imaging agent for CT angiography, urinary system, spinal cord and joint, lymphatic system angiography, and other diagnostic procedures.
Used in Antimicrobial Applications:
Iohexol is used as an antibacterial agent in certain applications.
Overall, Iohexol is a versatile contrast agent with applications in the pharmaceutical industry and medical imaging, as well as potential use in antimicrobial applications.
Non-ionic contrast agent
Iohexol is a non-ionic contrast agent with its pure product appearing as white or light gray powder and having hygroscopicity. In the early 80s of last century, it has been successfully developed by the Nycomed Company (Norwegian) and has first entered into market in 1982 in Norway and Sweden. In 1985, it has obtained the approval of the US Food and Drug Administration (FDA) for entering into US market; in the early 90s, Schering AG and Japan's first pharmaceutical Co., Ltd. were respectively subject to transferee production with product sales in Europe and the Asia-Pacific countries.
The six hydroxyl groups in its molecules are evenly distributed around the benzene ring, effective shielding the lipophilic iodobenzene ring, making it have high hydrophilic, low viscosity, low permeability than ordinary ion-type contrast agent and low toxicity against the nerve system, etc. It is the raw material for the production of water-soluble, non-ionic X-CT contrast agent in pharmaceutical factory. Iohexol is also currently one of the best contrast agents. The developed countries have completely used it to replace ionography agent. It is suitable for myelography, cardiovascular, arteriovenous, lymphatic system, urography and enhanced CT scan. The general dosage is as follows: decision regarding spinal canal imaging is based on the location; lumbar thoracic 24% solution: 8~12ml, neck 24% solution: 10~15ml, CT scan Cisternography 8~12ml.
Pharmacological effects
Iohexol contrast agent belongs to non-ionic water-soluble contrast agent with a similar osmotic pressure with plasma as well as moderate viscosity. It is easily for injection. Clinical angiography and urography have proved less toxic than ionic contrast agents, and can be safely used for myelography. The reason is that the non-ionic contrast agent has weak stimulation on the mast cell with less histamine release and less likely to cause allergic reactions. This product is weak vasodilator, not easy to cause hypotension; it causes very small injury on vascular endothelium, difficult to form thrombosis; small effect on heart and kidney function. It has a lower toxicity than amikacin. This product almost does not penetrate the cell membrane. After intravenous injection, it is mainly distributed in the interstitial cavity without being absorbed by organ and tissue. It is not metabolized by the body and is released mostly with the urine in the prototype form. PBP is smaller than 20%.
Non-ionic intravascular contrast agents: such as iobitridol, ioversol, iodohexol, iopamidol, iopromide and iodixanol.
Clinical application
It can be used for angiography, urography, cerebral angiography, peripheral and various kinds of arterial angiography, venography, digital subtraction and CT enhanced scan. Myelography and the use of subarachnoid injection for brain pool CT scan. It can also be applied to various kinds of body cavity examinations.
Subarachnoid space application
①It should be done of iodine allergy test before the application. Patients of positive result should be disabled. Patients of a history of epilepsy should be disabled.
②Patients having a history of allergies or being suspected allergic to this product, but must be subject to the angiography of this product can choose to apply adrenal cortex hormones and antihistamines before the contrast to prevent. But the spinal cord should be disabled of applying adrenal corticosteroid drugs.
③Patients of local or systemic bacterial infection should not carry out lumbar puncture, of course, can’t use this product for angiography.
④If necessary, it can be given of sedation agents such as diazepam before surgery. Upon severe pain, it can be administrated of analgesics.
⑤Good body fluid condition can reduce the incidence of adverse reactions, therefore it should be prevented of dehydration of patients.
⑥After angiography, allow the patients to sit in bed. The head should be elevated for at least 6 hours. The patient should maintain the supine position for 24 hours without self-move or bending down to prevent the residual contrast agent from flowing into the brain and reduce the leakage of cerebrospinal fluid.
⑦If the patients get nausea, vomiting, it should be applied of intravenous fluids to replace the fluid food; if necessary, it should be given of antiemetic.
⑧Upon myelography failure, it is not appropriate for immediate repeated angiography.
⑨Upon seizures, it should be immediately applied of intravenous injection of 10mg diazepam. To prevent recurrence of epilepsy, it can be applied of intramuscular injection of 0.2 g phenobarbital sodium at 20 to 30 minutes after the stopping of pathogenesis.
⑩The relative density of iohexol injection should be higher than that of cerebrospinal fluid.
Intravascular applications
①Before use, it should be applied of allergy testing. Positive patients should be disabled.
②Patients having a history of allergy, being allergic to iodine, of asthma should be disabled or used with caution.
③Patients of severe liver and kidney dysfunction, severe thyroid disease, bone marrow leukemia should be used with caution; These patients should be disabled upon dehydration. Patients of diabetes having a serum creatinine concentration of more than 0.5mmol /L should be disabled.
④pregnant women should be used with caution. Under conditions that it must be applied, it should be used of the lowest dose.
⑤This product can interfere with thyroid function tests, so that the ability of thyroid tissue? binding to iodine will be reduced, and it should be taken of several days or even two weeks for fully recover.
⑥contrast agent should not be mixed with other drugs for compatibility, instead should be used of a dedicated syringe.
Dosage and Usage
Intrathecal injection: Dose should be according to the check project and the usage technical decisions. It can be referred to the following table.
▼▲
Application items
Concentration (mg/ml)
Usage amount (ml/per time)
Waist, thoracic
angiography
180
240
0~15
8~12
Cervical angiography
CT scan Cisternography
240
180
240
10~12
5~15
4~12
Myelography for children
?
?
<2 years old
2～6 years old
>6 years old
180
180
180
2~6
4~8
6~12
It can be used for cardiovascular, arterial intravenous and urinary tract radiography. The iodine concentration and dosage used should be generally the same as other angiographic contrast agents currently used.
Medicine interactions
1, Patients subjecting to metformin treatment, if subjecting to simultaneous injection of iohexol contrast agent, may get lactic acidosis and acute renal failure.
2, Simultaneous administration of tricyclic antidepressants or monoamine oxidase inhibitors during the intrathecal injection of the drug can reduce the threshold of seizures, and lead to seizures.
3. Patients treated with interleukin-2 within 2 weeks had an increased risk of delayed response (cold-like symptoms and skin reactions).
4, Ⅲ antiarrhythmic drugs such as amiodarone, in the recommended dose, can extend the QT interval. The effect of prolonging the QT interval when combined with this product has additive effect.
This information was edited by lookchem (2015-08-03).
Adverse effects
1. Adverse effects after application in subarachnoid space are generally the same as that of receiving the lumbar puncture, but are mostly mild. The incidence of headache is less than that of using meglumine. Severe headache lasting several days may be intermittent. Other may have nausea, vomiting, dizziness, neck back pain, limb pain and paresthesia. EEG showed no clear short wave.
2. Adverse effects after intravascular administration were significantly lower than those of other ionic contrast agents in frequency and severity, and adverse reactions were similar to that of meglumine. A small number of patients have mild reactions, such as warm feeling, red, nausea, vomiting, mild chest pain, skin itching, urticaria, numbness and lower limbs.
Precautions
1, Patients with allergic history to iodine and allergic constitution should take with caution.
2, Patients of liver and kidney dysfunction, heart and circulatory system dysfunction, physical weakness, cerebral arteriosclerosis, diabetes, goiter and leukemia should take with caution.
3, Patients of severe hyperthyroidism should be disabled.
4, generally it should be prepared well of acute allergic reactions rescue.
Chemical properties
It appears as white or light gray powder with hygroscopicity.
Check Digit Verification of cas no
The CAS Registry Mumber 66108-95-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,6,1,0 and 8 respectively; the second part has 2 digits, 9 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 66108-95:
(7*6)+(6*6)+(5*1)+(4*0)+(3*8)+(2*9)+(1*5)=130
130 % 10 = 0
So 66108-95-0 is a valid CAS Registry Number.
66108-95-0Relevant articles and documents
Contrast medium of the impurity F synthetic method and its impurity G contrast medium, impurity H and impurity M application in the synthesis of
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, (2019/07/05)
The invention relates to a synthesis method of contrast medium impurities, in particular to a contrast medium impurity F synthetic method and its in the contrast medium impurity G, impurity H and M application in the synthesis of the impurity, which belongs to the field of medical technology. The method is to 5 - nitro - 1, 3 - benzene dicarboxylic acid dimethyl ester (formula 2 compound) and 2, 3 - dihydroxy propylamine as raw materials of formula 3 compound, type 3 compound with hydrogen reduction reaction [...] 4 compound, of formula 4 with a compound obtained by reaction of the impurity F [...] contrast medium. The invention relates to 5 - nitro - 1, 3 - benzene dicarboxylic acid dimethyl ester (formula 2 compound) as the starting material, the synthesis of 5 - amino - N, double-N' - (2, 3 - dihydroxy-propyl) - diiodo - 1, 3 - benzene dicarboxylic amide (formula 1 compounds) and then to of formula 1 as the starting material for the synthesis of impurity G, impurity H and impurity M, for the contrast medium quality control to provide acceptable impurity reference substance.
Method for preparing iohexol
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Paragraph 0028-0049, (2019/08/07)
The invention discloses a method for preparing iohexol. The method comprises the following steps: using a compound I: 5-[acetamido]-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-phenyldicarbonamide,glycerol-chlorohydrin or analogues thereof as raw materials, using disodium hydrogen phosphate or dipotassium phosphate as an acid dressing agent, reacting in a solvent, after ending the reaction, acquiring the iohexol through post-treatment. Through using buffer base of the disodium hydrogen phosphate or the dipotassium phosphate as the acid dressing agent, reaction conditions are moderate relatively, and a defect in a reaction process that a pH is unstable is overcome. So the iohexol prepared by the method is less and small in impurity, especially the impurity of alkoxy can be controlled byless than 0.5%, a yield is high, and the yield can reach 90-98%. The method is green and environment-friendly, and simple in operation.
Novel energy-saving environment-friendly continuous preparation method of iohexol
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, (2018/07/28)
The invention relates to a novel energy-saving environment-friendly continuous preparation method of iohexol. The preparation method specifically comprises the following steps: (1) acylation reaction:carrying out a reaction on a compound of a formula [2] with acetic anhydride in an environment of hydrochloric acid to obtain a compound of a formula [3]; (2) transesterification: carrying out a reaction on the compound of the formula [3] with a small-molecule liquid alcohol under an appropriate condition to obtain a compound of a formula [4], (3) alkylation reaction: carrying out a reaction on the compound of the formula [4] with 3-chloro-1,2-propylene glycol under the condition of a mixed solution of methanol and sodium methoxide, carrying out neutralization, filtering and desolvation to obtain an iohexol crude product; (4) purification: purifying the iohexol crude product to obtain an iohexol pure product. The method comprises carrying out the transesterification reaction on the liquidalcohol with 5-acetylamino-2,4,6-triiodo-N,N'-bis(2,3-diacetoxypropyl)-1,3-phthalamide, then carrying out an alkylation reaction with the alkylating reagent 3-chloro-1,2-propylene glycol in a methanol solution of the sodium methoxide, carrying out neutralization by using a methanol solution of hydrochloric acid, carrying out filtering, carrying out desolvation on the obtained filtrate, and thenpurifying the obtained iohexol crude product to obtain the iohexol pure product.
Energy-saving environment-friendly continuous preparation method of iohexol
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, (2018/07/28)
The invention relates to an energy-saving environment-friendly continuous preparation method of iohexol. The preparation method comprises the following steps: (1) acylation reaction: carrying out a reaction on a compound of a formula [2] with acetic anhydride in an environment of hydrochloric acid to obtain a compound of a formula [3]; (2) transesterification: carrying out a reaction on the compound of the formula [3] with a small-molecule liquid alcohol under an appropriate conditions to obtain a compound of a formula [4]; (3) alkylation reaction: carrying out a reaction on the compound of the formula [4] with and 3-chloro-1,2-propanediol under a condition of a mixed solution of methanol and sodium methoxide to obtain an iohexol crude product; and (4) purification: purifying the iohexol crude product to obtain an iohexol pure product. According to method, the transesterification reaction is carried out on the liquid alcohol with 5-acetylamino-2,4,6-triiodo-N,N'-bis(2,3-diacetoxypropyl)-1,3-phthalamide, then the alkylation reaction is carrred out with the alkylation reagent 3-chloro-1,2-propanediol in a methanol solution of the sodium methoxide, and the obtained iohexol crude product is purified to obtain the pure iohexol product.
DESALINATION OF A COMPOSITION COMPRISING A CONTRAST AGENT
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Paragraph 0036, (2013/11/05)
The invention relates to industrial preparation of contrast agents, and further to an improved process for the purification of contrast agents. In particular, it relates to a process for reducing the salt content of compositions comprising an MR contrast agent or an X-ray contrast agent, such as a non-ionic iodinated monomeric compound or a non-ionic iodinated dimeric compound.
DESALINATION OF A COMPOSITION COMPRISING A CONTRAST AGENT
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Page/Page column 12, (2012/07/13)
The invention relates to industrial preparation of contrast agents, and further to an improved process for the purification of contrast agents. In particular, it relates to a process for reducing the salt content of compositions comprising an MR contrast agent or an X-ray contrast agent, such as a non-ionic iodinated monomeric compound or a non-ionic iodinated dimeric compound.
Preparation and Purification of Iodixanol
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Page/Page column 5-6, (2012/11/13)
An improved synthesis method for preparation of iodixanol, and a purification process through macroporous adsorption resin chromatographic column and recrystallization are provided. The synthesis method relates to dimerization of 5-acetamido-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide (compound A) to prepare iodixanol, wherein excessive side reactions such as alkylation are effectively inhibited by controlling the pH of the reaction mixture with a boron-containing acidic substance or salts thereof such as boric acid. In this way, the conversion rate of compound A to iodixanol is 85-90%. The iodixanol crude product is purified by a macroporous adsorption resin chromatographic column, obtaining iodixanol product with recovery of 90-95% and purity of 96-98%. The iodixanol crude product is recrystallized in mixed solvent containing 2-methoxyethanol, obtaining iodixanol product with recovery of 90-95% and purity of greater than 99%.
SYTNHESIS OF IODIXANOL IN METHANOL
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Page/Page column 5, (2011/02/18)
This invention relates to the synthesis of iodixanol (1,3-bis(acetamido)-N,N′-bis[3,5-bis(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl]-2-hydroxypropane), more specifically to the dimerisation of 5-acetamido-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide with methanol as solvent.
PREPARATION AND PURIFICATION OF IODIXANOL
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Page/Page column 15-16, (2011/06/23)
An improved synthesis method for preparation of iodixanol, and a purification process through macroporous adsorption resin chromatographic column and recrystallization are provided. The synthesis method relates to dimerization of 5-acetamido-N, N'-bis(2,3-dihydroxypropyl)-2,4,6- triiodo-isophthalamide (compound A) to prepare iodixanol, wherein excessive side reactions such as alkylation are effectively inhibited by controlling the pH of the reaction mixture with a boron-containing acidic substance or salts thereof such as boric acid. In this way, the conversion rate of compound A to iodixanol is 85-90%. The iodixanol crude product is purified by a macroporous adsorption resin chromatographic column, obtaining iodixanol product with recovery of 90-95% and purity of 96-98%. The iodixanol crude product is recrystallized in mixed solvent containing 2-methoxyethanol, obtaining iodixanol product with recovery of 90-95% and purity of greater than 99%.
Synthesis of iodixanol in methanol
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Page/Page column 7, (2011/02/19)
This invention relates to the synthesis of iodixanol (1,3-bis(acetamido)-N,N'-bis[3,5-bis(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl]-2-hydroxypropane), more specifically to the dimerisation of 5-acetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide with methanol as solvent.
