RU2706364C1 - Composition for x-ray diagnostics based on iodinated polymer matrix - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to X-ray diagnostics and consists in creation radioopaque compositions for localizing a pathological focus, located deep in soft tissues (shrapnel wounds, tumor centers, cysts, foreign bodies, ends of bone fragments, etc.) by applying marks directly on body surface. Composition is based on iodated guanidine-containing polymer synthesized by polycondensation in molten hexamethylenediamine and guanidine and diphenyl guanidine hydroiodides at 165–200 °C for 4 hours with subsequent purification by reprecipitation into water, with concentration of 30 g/dl of polymer in dimethyl formamide with a dye.EFFECT: obtaining an X-ray contrast composition, which is highly concentrated colored ointment solution, having antibacterial properties, having high adhesion to living tissues and providing clear visualization on X-ray image; simplification and acceleration of the X-ray diagnostic process using an easy-to-use, accessible external contrast agent.1 cl, 4 ex, 1 dwg

Description

Usage: in medicine for x-ray diagnostics. The essence of the invention is to create a radiopaque composition based on an iodinated polymer matrix for application to the surface of the body in order to localize a pathological focus located deep in the soft tissues (fragmentation wounds, tumor foci, cysts, foreign bodies, ends of bone fragments, etc.). The composition is highly concentrated colored ointment solution with antibacterial properties, high adhesion to living tissues and providing a clear visualization x-ray image.

Currently, for the initial determination of the location of damage using an X-ray device, marks are used from improvised X-ray positive objects, such as metal needles, pins, nets, frames [RF Patent 2183941, AS USSR 1747032], which are attached to the patient’s skin with an adhesive plaster. However, when shooting, a shift of such a mark is possible, which leads to an erroneous determination and, as a result, re-exposure of the patient. Known radiopaque agents (RKS) [Shimanovsky N.L. Contrast media: a guide to rational use / N.L. Shimanovsky. - M .: GEOTAR-Media, 2009. - 464 p.] Used for the study of internal organs, however, there are no similar external agents, and the use of RKS internal applications for external diagnostics is not possible due to a number of factors, among which the absence of a number of necessary characteristics (such as good adhesion, the ability to put indelible mark) and high cost.

An acceptable method for localizing a pathological lesion is to project its location using a coordinate device-frame, consisting of two or more slats of any X-ray contrast material, interconnected with screws and nuts in various versions [RF Patent RF 2033083], which is selected as a prototype . At the same time, a significant drawback of this method is the transfer of the frame and marking of the body surface according to its template, which slows down the diagnostic / treatment process, as a result of long preparation in the manufacture of an individual frame for a specific clinical case, its sterilization and sterilization of marking products, which limits the use of this method in in case of emergency surgery. In addition, the absence of specific recommendations on the marking material can lead to blurring and erasing of landmark marks under the influence of liquid medicines that come into contact with the skin during operations (alcohol, saline solution, disinfectant solution, etc.), as well as physiological fluids.

The purpose of the invention: the creation of a composition based on iodinated guanidino-containing polymer systems for X-ray diagnostics, with the localization of pathological foci located deep in soft tissues, which provides a clear visualization on an X-ray image and allows to increase the reliability and accuracy of this research method.

The inventive method and the creation of compositions based on iodinated polymer matrix carrier, solvent and dye, combining high contrast (due to the presence of iodine atoms), antibacterial activity and good adhesion to the patient's tissues (due to the use of polyguanidines), as well as visual control (dye-labeled label) for the radiological diagnosis of lesions located deep in soft tissues.

To immobilize iodine on a polyguanidine molecule, it is proposed to obtain polyguanidine hydroiodides in which iodine acts as the counterion of a positively charged guanidine group. Despite the fact that the synthesis of hydroiodides can be carried out by replacing the counterions of the common salts of guanidines (chloride, phosphate), this option does not look attractive, since it requires a large consumption of reagents and does not guarantee the required high percentage of substitution. Therefore, to obtain hydroiodides, non-salt forms of guanidines were used.

The synthesis of guanidine hydroiodides (GHI) and definylguanidine (DPHGI), as precursors for the polymer component of the composition, is carried out by reacting the corresponding pure guanidines with freshly prepared hydroiodic acid:

The synthesis was carried out as follows: in a flask mounted on a magnetic stirrer, with constant stirring, a weighed portion of pure guanidine (guanidine, grade chd (R = H) and diphenylguanidine, grade chd (R = Ph)) weighing 2 g was added and then a stoichiometric amount was added hydroiodic acid. The obtained colored substances (GGI - red-brown, DFGGI - yellow) were dried in air to constant weight.

The structure of the obtained hydroiodides is confirmed by IR spectroscopy and X-ray phase analysis.

Then, on the basis of the obtained hydroiodides (GHI, DPHGI), polymers were synthesized by polycondensation in a melt with hexamethylenediamine (HMDA) at 165-200 ° C according to the following scheme:

Samples synthesized for 4 hours are a hygroscopic resinous mass of red-brown (yellow) color, readily soluble in DMF, DMSO, insoluble in water.

The polymers were purified by precipitating their solutions in DMF into water and further drying.

The structure of the obtained polymers was studied by IR spectroscopy.

To establish the contrasting properties of substances, their various concentrations were studied.

Example 1

0.5 g of dry polymer is dissolved in 10 ml of DMF. The resulting solution is checked for the presence of contrasting properties in X-rays on a PhilipsDualDiagnost X-ray apparatus at an exposure dose of radiation of E = 0.04 mZV. This concentration does not appear in the image.

Example 2

1 g of dry polymer is dissolved in 10 ml of DMF. The resulting solution is checked for the presence of contrasting properties in X-rays on a PhilipsDualDiagnost X-ray apparatus at an exposure dose of radiation of E = 0.04 mZV. This concentration is characterized by the appearance of a mild unsatisfactory imaging on the x-ray.

Example 3

3 g of dry polymer are dissolved in 10 ml of DMF. The resulting solution is checked for the presence of contrasting properties in X-rays on a PhilipsDualDiagnost X-ray apparatus at an exposure dose of radiation of E = 0.04 mZV. A clear visualization of the substance on the x-ray is observed.

Example 4

4 g of dry polymer are dissolved in 10 ml of DMF. The resulting solution is checked for the presence of contrasting properties in X-rays on a PhilipsDualDiagnost X-ray apparatus at an exposure dose of radiation of E = 0.04 mZV. A clear visualization of the substance on the x-ray is observed.

Thus, the optimal concentration of the substance is selected, which is 30 g / dts, which is necessary for its clear visualization in an x-ray. All hydroiodides also contrasted at a given concentration of solutions in DMF (figure).

As dyes, it is proposed to use a wide range of non-toxic colored compounds, such as the food coloring lycopene (E160d), which provides a red color.

The presented figure clearly demonstrates the radiopaque properties of the obtained substances. On the radiograph under item "A" - a solution of guanidine hydroiodide in DMF 3 g / dl; "B" - a solution of diphenylguanidine hydroiodide in DMF, a concentration of 3 g / DL; “B” - DMF, “G” - a solution of iodinated guanidine-based polymer in DMF, concentration 3 g / dl; "D" - a solution of iodinated polymer based on guanidine in DMF, a concentration of 4 g / DL; “D” - a solution of iodinated diphenylguanidine-based polymer in DMF, concentration 3 g / dl.

Claims (1)

X-ray contrast composition for the process of radiographic diagnosis in the localization of a pathological lesion by applying labels directly to the surface of the body based on an iodinated guanidine-containing polymer synthesized by polycondensation in a melt of geaxamethylenediamine and guanidine and diphenylguanidine hydroiodides at 165-200 ° C for 4 hours followed by re-purification with water for 4 hours, followed by water purification , with a concentration of 30 g / dl of the polymer in dimethylformamide with a dye.

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