RU2469729C1 - Medication for destructuring atherosclerotic lesions, formed on walls of blood vessels - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: claimed is application of carbon-containing nanoparticles, representing carbon nanocapsule 10 nm in size, containing iron particles, for destructuring atherosclerotic lesions, formed on the walls of blood vessels. It is demonstrated that claimed carbon-containing nanoparticles, applied on the surface of atherosclerotic lesion, are capable of penetrating into its internal layers and modifying its structure: presence of nanoparticles in it combines with presence in it of segments of sparse collagen structures.

EFFECT: invention can be used for creation of novel efficient medication which makes it possible to destructure atherosclerotic lesions, formed on the walls of blood vessels.

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Description

The invention relates to the field of experimental medicine and can be used to create a new effective tool that allows for the destruction of atherosclerotic formations that form on the walls of blood vessels.

It has now been proven that impaired patency of blood vessels due to the formation of atherosclerotic formations on their walls leads to impaired functioning of the internal organs, brain and limbs of a person. In the practice of restoring blood flow through blood vessels, whose lumen is narrowed as a result of atherosclerotic formations, an installation of metal stent frames is used. This method of treatment is widespread in cardiology and vascular surgery [1, 2]. However, the stent installed in the lumen of the vessel does not destruct the atherosclerotic formation, but presses it into the surrounding tissues. Since atherosclerotic formations have a very rigid structure due to the presence of a large number of dense, often calcified collagen masses, their pressing into the surrounding tissues leads to injury to the latter, which provokes the development of secondary restenoses at the ends of stents. This circumstance significantly reduces the effectiveness of the treatment and the possibility of its use in a number of patients.

Thus, the development of tools that allow the destruction of atherosclerotic formations that form on the walls of blood vessels is very important.

An adequate prototype was not found in the studied patent and medical literature.

The objective of the invention is to develop a tool that allows you to destroy the atherosclerotic lesions that form on the walls of blood vessels.

The problem is solved by the use of carbon-containing nanoparticles, allowing to destruct the atherosclerotic formations that form on the walls of blood vessels.

Today it is known that in the nanostate, many materials acquire new, sometimes unique properties. It has been established that a large number of various active centers are localized on the surface of nanoparticles, due to which nanoparticles are able to penetrate through cell membranes and form bulk structures in the form of nanospheres and nanotubes [3]. The properties of nanomaterials continue to be studied, including in the medical aspect.

The nanomaterial used by us was obtained by the method of [4] and, by its structure, represents a carbon nanocapsule ~ 10 nm in size containing iron particles. It has been shown that nanomaterials, including carbon-containing ones, have pronounced adhesive and adsorption properties, in this quality they are increasingly used as catalysts and sorbents in chemical and biotechnological industries [5, 6].

We first discovered that carbon nanomaterials can penetrate into atherosclerotic formations that form on the walls of blood vessels and lead to their destructuring.

No information was found in the patent and medical literature that carbon-containing nanoparticles are able to penetrate atherosclerotic formations and change their structure. This property of carbon-containing nanoparticles does not follow from the prior art in this field and is not obvious to a specialist.

The invention can be used in experimental studies to create a new effective tool that allows for the destruction of atherosclerotic formations that form on the walls of blood vessels

Based on the foregoing, it should be considered that the proposed invention meets the conditions of patentability: “Novelty”, “Inventive step”, “Industrial applicability”.

The invention will be apparent from the following description and the accompanying drawings.

Figure 1 shows a general view of atherosclerotic formations that form on the walls of blood vessels.

a - type of atherosclerotic formation, not treated with nanoparticles before implantation;

b - type of atherosclerotic formation not treated with nanoparticles after explantation;

c - type of explanted atherosclerotic formation treated with carbon-containing nanoparticles;

g - type of explanted atherosclerotic lesions treated with carbon-free nanoparticles.

Figure 2 shows a macroscopic view of the explanted atherosclerotic formation treated with carbon-containing nanoparticles.

1 - the outer surface of the explanted fragment;

2 - a section of a transverse section revealing the inner layers of an atherosclerotic formation.

Figure 3 shows a typical morphological picture of an explanted atherosclerotic formation under a light microscope (stained with 1% methylene blue solution, magnification × 400 and × 1000).

a - atherosclerotic formation, not treated with nanoparticles;

b - an atherosclerotic formation treated with carbon-free nanoparticles;

c - atherosclerotic formation treated with carbon-containing nanoparticles;

3 - groups of nanoparticles in the structure of atherosclerotic formation;

4 - altered structures of atherosclerotic formation, in the form of weakly metachromatic colored intercellular substance.

Figure 4 shows a typical picture of an excilated atherosclerotic formation treated with carbon nanoparticles by electron microscopy.

3 - carbon nanoparticles;

5 - discharged sections of the collagen structure.

The experiments were conducted on 18 male Wistar rats weighing 200-250 g, anesthetized with ketamine (50 mg / kg ip). In sterile conditions, fragments of an atherosclerotic formation 0.8–8 mm ² in size uniformly sprinkled with nanoparticles were implanted under the skin in the interscapular region under sterile conditions. After implantation, the incision was sutured, and after withdrawal from anesthesia, the animals were kept in standard vivarium conditions. After 20 days, reimplantation of an atherosclerotic formation was carried out. Their morphometry and structural studies were carried out using light and electron microscopy.

Example

The study of the ability of carbon nanoparticles to degrade atherosclerotic formations formed on the walls of blood vessels was carried out according to the following scheme. Experimental animals (n = 6) under the skin in the interscapular region were implanted with fragments of an atherosclerotic formation uniformly sprinkled with the studied nanoparticles. To compare the effects obtained, control series were performed (6 animals in each series): 1 - with implantation of fragments of an atherosclerotic formation without nanoparticles and 2 - with implantation of fragments of an atherosclerotic formation treated with carbon nanoparticles of iron.

After 20 days, in each series of experiments, the implanted fragments were removed and their morphometry was performed. The histological structure of the atherosclerotic lesion was examined on semi-thin sections stained with 1% methylene blue solution at optical magnifications of × 400 and × 1000. The ultrastructure of atherosclerotic formation was studied by transmission electron microscopy [7]. Ultrathin sections with a thickness of 60-100 nm were prepared according to the standard procedure on an Ultrotome III ultratome (LKB, Sweden). The obtained preparations were examined in a JEM-100 CXII electron microscope (JEOL, Japan) with an aperture diaphragm of 25-30 μm, at an accelerating voltage of 80 kV.

As can be seen in Fig. 1 (a, b), in the control series, the 20-day implantation of an atherosclerotic formation under the skin of rats did not lead to significant morphometric changes in these fragments, which retained a yellowish-whitish color.

The study of fragments of atherosclerotic formations treated with carbon-containing nanoparticles of Fig. 1 (c) and iron nanoparticles of Fig. 1 (d) did not reveal significant differences in the morphometric study. In both cases, the explanted fragments had a glossy black surface. However, after using carbon-containing nanoparticles in the section of atherosclerotic formations, one could clearly see macroscopically that in Fig. 2 the latter penetrated into the depth of the plaque itself (2), staining its structures in gray and black.

In the study using light microscopy in the control series, no visible differences were detected. The fragments of Fig. 3 (a, b) show a typical structure characteristic of atherosclerotic formations that form on the walls of blood vessels, without any foreign inclusions.

In the experimental series of Fig. 3 (c), on the contrary, single and groups of nanoparticles (3), which are located in the atherosclerotic formation itself, were visible. Around the nanoparticles, areas of atherosclerotic formation with a changed structure (4) are confidently detected in the form of a weakly metachromatic (lilac shade) colored intercellular substance, the area of which significantly exceeds the size of the nanoparticles themselves.

Electron microscopy of atherosclerotic masses (Fig. 4) also showed that in the experimental series nanoparticles (3) in the form of black electron-dense matter are found inside atherosclerotic masses. The presence of nanoparticles is combined with the presence of rarefied collagen structures in their environment (5), which indicates a change in the density of atherosclerotic formations and the development of destructive processes.

Our results indicate that, under the considered conditions, carbon-containing nanoparticles deposited on the surface of an atherosclerotic formation are able to penetrate into its inner layers and modify its structure.

Thus, carbon-containing nanoparticles can be used to destruct the atherosclerotic formations that form on the walls of blood vessels.

Literature

1. Le May M.R., Labiraz M., Davies R.F. et al. Stenting thromlolysis in acute myocardial infarction trial (STAT) // J. Am. Coll Cardiol. 2001, 37, P.985-991.

2. Krylov A.L. Stents containing drugs. New Perspectives // International Journal of Interventional Cardioangiology. 2006, No. 10, p.16-21.

3. Suzdalev I.P. Nanotechnology: physical chemistry of nanoclusters, nanostructures and nanomaterials. - M .: KomKniga, 2006 .-- 592 p.

4. Ermakov A.E., Uimin M.A., Lokteva E.S. et al. The Synthesis, Structure, and Properties of Carbon Containing Nanocomposites Based on Nickel, Palladium, and Iron // Russ. J. Phys. Chem. 2009, A 83, p. 1187-1193.

5. Cooper B.C., Pozdnyakova I.O., Bubble A.P. The use of nanodiamonds for separation and purification of proteins // Solid State Physics. 2004.V. 46. Issue 4. S.737-739.

6. Cooper B.C., Purtov K.V., Bubble A.P. et al. Catalytic activity of nanodiamond particles in organic reactions // Reports of the Russian Academy of Sciences, 2008, vol. 418, No. 2, pp. 267-269.

7. Karunu V.Ya. Electron microscopy. - Kiev: "Vishka school", 1984, p.208.

Claims (1)

The use of carbon-containing nanoparticles, representing a 10 nm carbon nanocapsule containing iron particles, for the destruction of atherosclerotic formations formed on the walls of blood vessels.

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