RU62008U1 - MEANS FOR EMBOLIZATION OF VESSELS - Google Patents

Abstract

The utility model relates to means for embolization of blood vessels in order to stop bleeding and reduce blood supply to organs and can be used in cardiovascular and endovascular surgery. The technical result of the proposed utility model is to increase the effectiveness of the tool for embolization of blood vessels due to its increased elasticity, which helps to restore the original form after possible deformations, which the tool undergoes when passing through the catheter to the site of embolization. This is achieved by the fact that the tool is made in the form of a sphere of polymer material obtained during suspension polymerization of a dispersed phase solution containing hydroxyethyl methacrylate (HEMA), ethylene glycol dimethacrylate (EHDMA), N, N, N ', N' - tetramethylethylenediamine (TMEDA), persulfate ammonium (PSA), azoisobutyronitrile (AIBN), 1-dodecanol, cyclohexanol suspended in a solution of the dispersion phase, including polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), ammonium persulfate (PSA) and distilled water, for no more than 120 at a temperature of not higher than 70 ° S.Sredstvo may be in the form of spheres with a diameter 0.1-1.2 mm.

Description

The utility model relates to means for embolization of blood vessels in order to stop bleeding and reduce blood supply to organs and can be used in cardiovascular and endovascular surgery.

One of the main purposes of embolizing agents is their use in oncological practice for the treatment of tumors of parenchymal organs. Intraorgan arterial occlusion causes ischemic necrosis of the tumor, restricts the ability of viable tumor cells, as well as their decay products to enter the general bloodstream during nephrectomy surgery, reduces the likelihood of metastasis and reduces intoxication of the body. For patients with locally advanced and generalized forms of tumor diseases, this treatment is often the only way to prolong life and improve their condition.

The effectiveness of intraorgan arterial occlusion performed in this process largely depends on the quality of the used embolizing agents.

Known means for embolization of blood vessels, made of a material containing silicone rubber - low molecular weight polydimethylsiloxane, tetraethoxysisalan, tin octoate and fine tantalum powder (SU 1106509 A, 07.08.84).

A disadvantage of the known agent is its high viscosity, which does not allow it to be inserted through thin catheters into vessels of small diameter, for example, for the treatment of cerebral aneurysm.

Known means for embolization of blood vessels, made of a polymeric material formed from a solution containing dimethylmethyl vinyl polysiloxane, carbonyl iron,

platinum hydrochloric acid, oligohydridesiloxane and oligodimethylsiloxane (RU 2073529, 02.20.1997).

The tool is prepared immediately before introducing it into the vascular bed of the patient’s tumor organ. When the solution is mixed, spatially cross-linked polymer structures are formed that firmly retain carbonyl iron particles within themselves. The presence of oligodimethylsiloxane, which plays the role of a plasticizer, reduces the viscosity that dimethylmethylvinylpolysiloxane had in the finished composition while maintaining it in air for 20-25 minutes. Then there is a rapid increase in the viscosity of the composition with the formation within 2 hours of an elastic polymer such as a soft sponge and turning off the affected organ from the general bloodstream.

Due to the fact that when using the known tool is prepared immediately before the operation, any deviation from the claimed parameters and technological methods can lead to unpredictable changes in the properties of the obtained funds. This is a significant disadvantage of the known means.

The present invention was a means for embolization of blood vessels with the creation of a complete, reliable occlusion of the tumor, leading to total necrosis of it and excluding the possibility of the entry of single viable tumor cells into the general bloodstream, which would reduce the likelihood of dissemination of the tumor and subsequent metastasis.

The technical result of the proposed utility model is to increase the effectiveness of the tool for embolization of blood vessels due to its increased elasticity, which helps to restore the original form after possible deformations, which the tool undergoes when passing through the catheter to the site of embolization.

The increased effectiveness of the proposed tool is due to the use of a polymeric material with a porous structure. Due to which the agent is capable of swelling, thereby providing a reliable obturation of the embolized vessel.

The proposed tool due to the properties of the material used has the ability to sorb blood elements on the surface, increasing platelet aggregation, contributing to the formation of thrombotic masses at the site of embolization.

In addition, it is able to hold onto itself a blood clot reinforced with a porous mass of polymer, and over long periods it sprouts with connective tissue, providing a stable obturation effect that precludes recanalization of the bloodstream of the vessel.

This is achieved by the fact that the means for embolization of blood vessels is made in the form of a sphere of polymer material obtained during suspension polymerization of a dispersed phase solution containing hydroxyethyl methacrylate (HEMA), ethylene glycol dimethacrylate (EHDMA), N, N, N ', N' - tetramethylethylenediamine (TMEDA) ), ammonium persulfate (PSA), azoisobutyronitrile (AIBN), 1-dodecanol, cyclohexanol suspended in a dispersion phase solution including polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), ammonium persulfate (PSA) and distilled water , for no more than 120 minutes at a temperature not exceeding 70 ° C.

The ingredients of the solutions are taken in the following content, in wt.%:

dispersed phase solution

GEMA 38.52-40.4 EGDMA 1.22-1.63 TMEDA 2.99-3.45 AIBN 0.23-0.29 1-dodecanol 4.77-7.36 cyclohexanol 50.32-50.33

dispersion phase solution

PVA 0.5-0.75 PVP 0.5-0.75 PSA 3.6-4.67 distilled water rest

The tool is made in the form of a sphere with a diameter of 0.1-1.2 mm.

The tool is made as follows.

Example 1

Into a 400 ml polymerization reactor. 200 ml are placed. an aqueous solution containing 1.5 g (0.75%) of polyvinylpyrrolidone (PVP) (mol. m. 160,000) and 1.5 g (0.75%) of polyvinyl alcohol (PVA). After starting the paddle mixer (100-120 rpm), the mixture is heated to 70 ° C. Upon reaching the set temperature, 50 ml is introduced into the reactor. An 18% solution of ammonium persulfate (PSA) and then 51.49 g of a reaction mixture of the following composition: 2-hydroxyethyl methacrylate (HEMA) - 20.82 g (40.4%), ethylene glycol dimethacrylate (EHDMA) - 0.63 g (1.22%), N, N, N ', N'-tetramethylethylenediamine (TMEDA) - 1.54 g (2.99%), azoisobutyronitrile (AIBN) - 0.12 g (0.23%), 1-dodecanol - 2.45 g (4.77%), cyclohexanol - 25.92 g . (50.33%). The polymerization process proceeds within 90 minutes. At the end, the polymer product is filtered off and eight times washing with distilled water is carried out with stirring and heating (70-80 ° C). The ratio of polymer product / distilled water is 1/10 (vol.). After that, the polymer product is filtered off, placed in cups with permeable walls and washed with ethyl alcohol under reflux in a Soxhlet extractor for 3-3.5 hours. Then, at room temperature, it is washed with acetone (3 × 200 ml) and then with ether (4 × 150 ml). The final product is dried and fractionated on a sieve. In this example, the following diameter distribution (% vol.) Is obtained: 0.2-0.5 mm. (28%), 0.5-0.9 mm. (43%), 0.9-1.2 mm. (14%) and 15% - the rest. The obtained fractions are subjected to swelling in distilled water, washed again, packaged and sterilized.

Example 2

Into a 600 ml polymerization reactor. place 230 ml. an aqueous solution containing 0.75% PVP (mol. m, 160,000) and 0.75% PVA. After

starting a paddle mixer (120-130 rpm), the mixture was heated to 70 ° C. Upon reaching the set temperature, 70 ml is introduced into the reactor. 20% PSA solution and then 66.85 g of the reaction mixture consisting of: HEMA 25.75 g (38.52%), EGDM 1.05 g (1.57%), TMEDA 2.31 g (3.45%), AIBN 0.18 g (0.27%) ), 1-dodecanol 4.92 g (7.36%), cyclohexanol 32.64 g (48.83%). After this, the polymerization proceeds within 120 minutes. The polymer product is processed as described in example 1. Distribution by fractions (% by volume): 0.1-0.3 mm. (26%), 0.3-0.6 mm. (43%), 0.6-0.8 mm. (19%), 12% - the rest.

Example 3

Into a 400 ml polymerization reactor. 200 ml are placed. an aqueous solution containing 0.75% PVP and 0.75% g. PVA. After starting the paddle mixer (100-110 rpm), the mixture was heated to 70 ° C. Upon reaching the set temperature, 50 ml is introduced into the reactor. 20% PSA solution and then 51.5 g of the reaction mixture consisting of HEMA 20.6 g (39.98%), EGDMA 0.84 g (1.63%), TMEDA 1.54 g (2.99%), AIBN 0.15 g (0.29%), 1-dodecanol 2.46 g (4.78%), cyclohexanol 25.92 g (50.32%). After this, the polymerization proceeds within 90 minutes. The polymer product is processed as described in example 1. Distribution by fractions (% by volume): 0.3-0.6 mm. (23%), 0.6-1.0 mm. (38%), 1.0-1.3 mm. (12%), 27% - the rest.

As can be seen from the examples, a sequential system for initiating the polymerization process was used for the manufacture of the proposed agent, the primary initiation being the PSA / TMEDA system, and the further process is ensured by an internal initiator, AIBN. This allows you to get a tool for embolization of spherical vessels, and during the process to prevent the merging of droplets of the dispersed phase. This effect is based on the fact that the initial initiation of the process occurs at the interface between the dispersed and dispersed phases with

the formation of a shell around the dispersed phase. The process is based on the effect of accelerating the decay of the initiator (PSA) by the initiation activator (TMED) {"Polyetheracrylates", A.A. Berlin, T.Ya. Kefeli, G.V. Korolev, "Nauka" M. 1967 p. 244) . A further polymerization process takes place inside the formed sphere due to the thermal decomposition of AIBN. The elasticity is controlled by the content of the crosslinking agent EGDM in the process conditions.

Thus, the proposed tool for embolization of blood vessels is made in the form of a sphere with predetermined diameters from a polymer elastic material with a porous structure. Due to the material used, the proposed tool for vascular embolization has high elasticity and, when used, the tool does not exert pressure on the walls of the embolized vessel and does not cause destructive changes in adjacent tissues, contributes to reliable thrombus formation in the lumen of the vascular bed. In addition, due to the spherical form of execution, high elasticity and the absence of adhesion, this tool is easily passed through a catheter and occludes vessels. The product meets all medical requirements for drugs used in vascular surgery.

The proposed tool, when used, is sterilized and implanted in patients with vascular occlusion in order to stop bleeding, as well as with endovascular embolization during the treatment of various neoplasms.

To confirm the technical result indicated by the applicant, a specific example of the use of the proposed tool is proposed.

Patient A., 17 years old. Received with complaints of a pulsating formation of the left half of the face, pain, periodic bleeding from the gingival surface of the upper teeth on the left. Sick from birth. Diagnosed with arteriovenous hemangioma of the left half of the face. At the age of 7 years, the external carotid artery was ligated on the left with a good primary effect. After a year, a relapse of the disease was noted, removal of hemangiomas was recognized impossible. Upon admission to the hospital, the state is close to satisfactory, in the region of the left half of the face pulsating

tumor formation, when examining the oral cavity, an angiomatically changed plus-tissue is revealed in the projection of the hard palate on the left, with a touch of fibrin. Palpation over the projection of the formation of systolic trembling. During auscultation, intense systolic-diastolic murmur is determined.

When ultrasound dopplerography is determined, an increase in the linear velocity of blood flow in the common carotid arteries on the right is up to 63 cm / sec, on the left is up to 83 cm / sec. The volumetric blood flow velocity on the right is 237 ml / min, on the left is 890 ml / min. In several stages, the patient underwent selective arteriography of all brachiocephalic arteries to identify afferent branches.

According to arteriography revealed: the external carotid artery on the left is bandaged at the mouth. Participation in the blood supply to the angiomatous tissue of the branches of the external carotid artery to the right, inter-arterial anastomoses from the basin of the internal carotid artery to the left, branches of the thyroid trunk to the left. The last of these sources was the most significant.

The diagnosis was established: Congenital arteriovenous angiodysplasia of the left half of the face and the hard palate on the left, macrophytous form. Recurrent bleeding from angiomatous tissue in the projection of the hard palate.

Since the radical removal of angiomatous tissues is considered impossible. In several stages, the patient underwent REO of afferent vessels with embryos from a spherical hydrogel and transcatheter sclerotherapy with 96% ethanol solution.

During control arteriography of afferent artery pools, a full embolization effect was noted. The course of the post-embolization period is smooth, only insignificant episodes of hyperthermia up to 37.3-37.8 ° C are noted.

Only interarterial anastomoses from the pool of the left internal carotid artery were not embolized, due to the high risk of embolic complications in the cerebral artery pool and the development of critical ischemia of angiomatous tissue in the region of the hard palate and subsequent necrotic

changes. Objectively, the disappearance of the pulsation of the formation, the absence of systolic tremor was noted; during auscultation, systolic-diastolic noise was not determined. The patient was discharged in satisfactory condition.

Claims (3)

1. The tool for embolization of blood vessels, characterized in that it made in the form of a sphere of polymer material obtained during suspension polymerization of a dispersed phase solution containing hydroxyethyl methacrylate (HEMA), ethylene glycol dimethacrylate (EHDMA), N, N, N ', N'-tetramethylethylenediamine (TMEDA), ammonium persulfate (PSA), azoisobenzoisobenzo (AIBN), 1-dodecanol, cyclohexanol suspended in a dispersion phase solution including polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), ammonium persulfate (PSA) and distilled water, for no more than 120 minutes at a temperature not exceeding 70 ° С . 2. The tool according to claim 1, characterized in that the ingredients of the solutions are taken in the following content, wt.%: dispersed phase solution GEMA 38.52-40.4 EGDMA 1.22-1.63 TMEDA 2.99-3.45 AIBN 0.23-0.29 1-dodecanol 4.77-7.36 Cyclohexanol 50.32-50.33 dispersion phase solution PVA 0.5-0.75 PVP 0.5-0.75 PSA 3.6-4.67 Distilled water Rest 3. The tool according to claims 1 and 2, characterized in that the diameter of the sphere is 0.1-1.2 mm.