RU2817994C1 - Method of producing radiopaque composition - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to silicone-based radiopaque compositions. Disclosed is a method of producing a radiopaque composition containing the following in wt.%: 58.3–78.3 of silicone, 20–40 of barium sulphate with particle size of less than 0.1 mm, 1.5 of ultramarine and 0.2 of a vulcanisation catalyst, by loading components into a mixer – first silicone, then successively in three equal portions of barium sulphate, ultramarine and then vulcanizer, wherein the components are loaded into the mixing chamber with rotating rotors and at temperature of 55–60 °C with subsequent rolling of composition on cold rollers at 30 °C.

EFFECT: preventing premature vulcanisation and formation of barium sulphate agglomerates in the X-ray contrast composition.

1 cl, 1 dwg, 3 tbl, 5 ex

Description

The invention relates to the field of producing radiopaque compositions based on silicone, used for the manufacture of products, including medical purposes.

A method for producing a radiopaque composition is known from the prior art [patent RU 2083609 C1. IPC C08L 23/06, C08K 13/06. Application No. 93053351/04 dated November 30, 1993, publ. 07/10/1997], during which a polyethylene-based filler containing bismuth oxychloride is preliminarily subjected to heat treatment. Heat treatment is carried out in the range from 0.25 to 2 hours at a temperature from 600 to 800°C.

The disadvantage of this method is the need for preliminary heat treatment at high temperatures of the composition at the manufacturing stage.

Also known is a radiopaque composition containing barium sulfate and obtained by dissolving citric acid, potassium sorbate and flavoring in approximately 15 liters of water [patent US3784681A. IPC A61K 27/08. Application No. 206169 dated 12/08/1971, publ. 12/18/1970]. An anionic polysaccharide is added to the resulting solution. Barium sulfate is mixed with a solution of sodium polyalkylaryl sulfonate in a mixer until smooth, after which the polysaccharide solution is added. The suspension thus obtained is diluted with water to 100 l, then pasteurized at a temperature of about C and homogenized in a colloid mill. The suspension can be converted into a dry preparation in a known manner, for example by spray drying or roller drying. A suspension prepared from such a dry preparation has the same properties as the original suspension and can be diluted with water without the formation of sediment.

This method has the following disadvantage: the preparation of the composition occurs in several stages, which complicates the process of obtaining a suspension.

The closest to the proposed technical solution is a method for producing an X-ray contrast agent, which consists of mixing 20 g of barium sulfate powder with 80 g of aubazidan aqueous solution and dispersing the resulting composition in a tissue micro-pulverizer or other dispersant for 2 minutes at 5000 rpm [SU 568438 A. MPK A61K 29/02. Application No. 2028559/13 dated May 28, 1974, publ. 08/15/1977 in Bull. No. 30].

The disadvantage of this method is the need to use a high-speed mixer providing a mixing speed of 5000 rpm.

The technical result of the proposed invention is to prevent premature vulcanization and the formation of barium sulfate agglomerates.

The technical result is achieved by the fact that the method of producing an x-ray contrast composition by mixing silicone, barium sulfate, ultramarine and a vulcanization catalyst in the following ratio of components, in wt. %:

silicone 58.3 - 78.3 barium sulfate 20 - 40 ultramarine 1.5 vulcanization catalyst 0.2,

includes

loading silicone into the mixer for min, followed by lowering the upper press, heating and homogenization at a temperature of 40°C for 3 minutes at a rotor speed of 30 - 40 rpm,

introducing 1/3 of barium sulfate into the solution at a rotor speed of 40 rpm, followed by lowering the upper press and increasing the rotor speed to 60 rpm for 5 minutes at a mixing temperature of 50°C,

introducing the second third of barium sulfate into the solution at a rotor speed of 40 rpm, followed by lowering the upper press and increasing the rotor speed to 60 rpm for 5 minutes at a mixing temperature of 55-60°C,

introducing the remaining third of barium sulfate into the solution at a rotor speed of 40 rpm, followed by lowering the upper press and increasing the rotor speed to 60 rpm for 5 minutes at a mixing temperature of 55-60°C,

introducing ultramarine into the solution and stirring the solution for 5 minutes at a rotor speed of 60 rpm at a temperature of 60°C,

introduction of the catalyst into the solution at a rotor speed of 60 rpm at a temperature of 60°C,

rolling of the composition, which is carried out on cold rollers with a roll temperature of no more than 30°C.

Disclosure of the Invention

When implementing the method, a closed type mixer is used, which is a device for the cyclic production of homogeneous mixtures of polymers, elastomers, ceramic or other materials by mixing. The mixer consists of a mixing chamber, a loading device, a frame with rotors and a drive and auxiliary electrical equipment.

The choice of mixing temperature is determined by the need to slightly soften the silicone for uniform mixing and distribution of barium sulfate. Carrying out mixing at higher temperatures can negatively affect the properties of the composition - scorching will occur.

The choice of mixing speeds in the range of 40-60 rpm is due to the need for uniform distribution of barium sulfate in the polymer matrix.

Barium sulfate was chosen as a radiopaque component because, according to preliminary estimates, it is more compatible and more uniformly distributed in the polymer matrix. In addition, based on a literature review of radiopaque compounds, it was revealed that barium sulfate is most often used as an X-ray positive agent, including in various medical studies [Shah, Tilak M. “Radiopaque Polymer Formulations for Medical. Devices.” Medical Device and Diagnostic Industry, Mar. 2000].

The choice of the amount of barium sulfate in the compositions (from 20 to 40 wt%) is determined by determining the minimum possible threshold for the visibility of the composition on an X-ray machine. In addition, a radiopaque mark in medical products should not reduce or have a minimal effect on the physical and mechanical characteristics of the finished product.

Initially, the degree of dispersion of barium sulfate in the compositions was assessed visually - the absence of lumps and transparent (clean) areas of silicone.

After a preliminary visual assessment of the compatibility of the components during the manufacture of the compositions, the compatibility of the components, namely the uniformity of distribution of the barium sulfate powder, was assessed on the X-ray photographs shown in the figure, where 1 - 4 are barium sulfate samples depending on their dispersion.

A preliminary assessment of the compatibility of the components took place at a barium sulfate concentration of 20% by weight.

Component compatibility studies were carried out using the X-ray diagnostic complex KRD - "OKO". Rg shooting mode - automatic “With exposure meter”. The experiment was carried out at room temperature plus 21 - 23°C and humidity 50 - 55%.

The thickness of the composition samples was 1.5 mm.

When using barium sulfate, analytical grade. (GOST 3158-75) agglomeration of particles in the polymer matrix and their uneven distribution in the polymer composition were observed (figure, samples 1 and 2). This is primarily due to the initial particle size of barium sulfate (from 2-3 mm to 0.1 mm). When using barium sulfate of a finer fraction (less than 0.1 mm, figure, samples 3 and 4), a uniform distribution of X-ray contrast agent particles in the polymer matrix is observed and the entire sample acquires X-ray positive properties.

When the barium sulfate content was more than 40% by weight, “crumbling” of the material was observed due to large agglomerates in the polymer matrix.

Subsequently, to assess the radiographic visibility of the resulting compositions, the manufactured radiopaque polymer compositions were molded to specified sizes, simulating insertion into medical devices - bundles with a diameter of 1 and 2 mm.

With the introduction of barium sulfate, it was noted that the kinetics of vulcanization of the final compositions does not change relative to the vulcanization of “pure” silicone (silicon with a vulcanization catalyst) and the optimum vulcanization at 180°C is 14 ± 3 minutes.

In addition to barium sulfate and silicone, the composition includes a vulcanization catalyst (1.5 wt% by weight of silicone) and a pigment (ultramarine, 0.2 wt% by weight of silicone) for more complete modeling of the behavior of the manufactured samples in the mixer.

Examples of implementation of the invention

The silicone chosen for the polymer base was ELASTOSIL® R plus 4305/60, a two-component silicone rubber developed specifically for extrusion processing and cured by an addition mechanism on a platinum catalyst. After the second stage of vulcanization, this silicone is approved for contact with food.

To visually control the presence of an X-ray label, ultramarine is introduced from the proposed composition to stain it blue.

Barium sulfate in the form of the drug "Bar-VIPS", introduced into the composition, promotes its uniform distribution in the polymer matrix due to the particle size of barium sulfate - less than 0.1 mm.

The proportional ratios of the components of the developed composition options are presented in Table 1.

X-ray contrast compositions were prepared in a laboratory micromixer with a loading chamber volume of 0.1 l, produced by Polimermash Group LLC.

Laboratory micromixer type “RS-0.1” is intended for the production of rubber compounds and polymer compositions. The technical characteristics of the micromixer are given in Table 2.

The initial components of the compositions were introduced in the following order: first silicone, then X-ray contrast filler (barium sulfate), pigment (ultramarine) and then vulcanizer. The components were loaded according to the conditions of the claimed method into the loading funnel of the mixing chamber with the rotors rotating and pressed with a loading device. The rotors rotated in the mixing chamber housing in opposite directions at different frequencies. As a result, the direction of the forces acting on the mixture located between the rotors constantly changed, promoting intense mixing. In accordance with the stage, the heating temperature of the mixing chamber and the rotation speed of the rotors were set. After the mixing cycle was completed, the loading device was removed, the fastening handles were unscrewed, the chamber was removed and the resulting composition was unloaded.

The indicators of the composition variants prepared in accordance with the described method, confirming the receipt of the declared technical result, are summarized in Table 3.

The declared technical result is achieved by lower energy costs for the production of the composition due to the temperature-time conditions of production.

An effective technical result of a relatively close analogue is achieved by a simplified technology for manufacturing the composition with improved visualization of the material when irradiated with X-rays - greater X-ray contrast.

Thanks to the developed method for producing a radiopaque composition, namely the mixing mode, the formation of agglomerates is prevented during the production of the composition itself, as well as during its further molding into medical products.

Table 1 Components Composition, mass. % (options) 1 2 3 4 5 Silicone (ELASTOSIL® R plus 4305/60) 78.3 73.3 68.3 63.3 58.3 Barium sulfate 20 25 thirty 35 40 Vulcanization catalyst 1.5 Ultramarine 0.2

Table 2 - Technical characteristics of the micromixer type “RS-0.1” Chamber volume without rotors, cm ³ 115 Chamber volume with rotors, cm ³ 100 Rotor type non-meshing four-blade Rotation speed of high-speed rotor, rpm 25 - 90 Rotation speed of low-speed rotor, rpm 13 - 60 Speed regulation stepless (frequency) Friction 1:1.5 Geared motor power, kW 1.1

Table 3 Composition quality indicators Analogue 1 Options 1 2 3 4 5 Prevention of premature vulcanization, min Absent 16:32 16:41 16:54 17:05 17:21

Claims (10)

A method for producing an X-ray contrast composition by mixing silicone, barium sulfate, ultramarine and a vulcanization catalyst at the following ratio of components in wt.%: silicone 58.3-78.3 barium sulfate with particle size less than 0.1 mm 20-40 ultramarine 1.5 vulcanization catalyst 0.2, consisting in loading silicone into the mixer, followed by lowering the upper press, heating and homogenizing at a temperature of 40°C for 3 minutes at a rotor speed of 30-40 rpm, introducing 1/3 of barium sulfate into the solution at a rotor speed of 40 rpm, followed by lowering the upper press and increasing the rotor speed to 60 rpm for 5 minutes at a mixing temperature of 50°C, introducing the second third of barium sulfate into the solution at a rotor speed of 40 rpm, followed by lowering the upper press and increasing the rotor speed to 60 rpm for 5 minutes at a mixing temperature of 55-60°C, introducing the remaining third of barium sulfate into the solution at a rotor speed of 40 rpm, followed by lowering the upper press and increasing the rotor speed to 60 rpm for 5 minutes at a mixing temperature of 55-60°C, introducing ultramarine into the solution and stirring the solution for 5 minutes at a rotor speed of 60 rpm at a temperature of 60°C, introducing the catalyst into the solution at a rotor speed of 60 rpm at a temperature of 60°C, rolling of the composition, which is carried out on cold rollers with a roll temperature of no more than 30°C.