Development of Organism Detoxication Method by Means of Hemosorption Using Magnetic Adsorbents
Tech Area / Field
- MED-DRG/Drug Discovery/Medicine
3 Approved without Funding
Institute of Biochemical Physics, Russia, Moscow
- Cleveland Clinic Foundation, Lerner Research Institute, USA, OH, Cleveland\nFlorida State University / Biomagnetic Engineering Lab, College of Engineering, USA, FL, Tallahassee
Project summaryDetoxication of the human organism by elimination of toxic substances from its blood is important modern medicine technology. A variety of efferent methods of organism detoxication from endo- and exotoxicants are currently used in the clinical practice. The most widely used methods include hemodialysis, hemofiltration and hemosorption. Whereas the first two are used for elimination of low-molecular water-soluble toxicants, hemosorption allows to eliminate not only low-molecular toxicants, but also high-molecular fat-soluble toxicants, viruses and bacteria.
Above all hemosorption is applied in cases of acute poisoning of different drugs including soporific, psychotropic, anti-tuberculosis and anti-arrhythmic ones, as well as other chemicals for industries and agriculture applications, including organophosphorus compounds and chlorinated hydrocarbons. Hemosorption is the most efficient method of treatment in 30% events of acute poisoning.
Hemosorption successfully helps at endotoxicosis accompanying various diseases both surgical type (pancreatic, peritonitis, sepsis, purulent - destructive defeats), and therapeutic type (immunological and allergic disease, psoriasis, arteriosclerosis, mental diseases). Detoxication is also needed during treatment of oncologic diseases in order to decrease the consequences of poisoning resulted by chemotherapy and exposure.
By estimation more than 100,000 procedures of hemosorption in the world and more than 10,000 of them in Russia are carried out annually. Cost of the procedure achieves several thousands of dollars in some cases. Therefore there is multi-millions market of hemosorption operations and a great perspective in this area.
The standard hemosorption technique involves the withdrawal of a significant amount of the patient's blood from the organism to fill a sorption column, which can contain different types of adsorbents. Form elements of blood (especially thrombocytes) are often damaged up to 5-10% in the sorption column and blood pumps. The reduction of the adsorbent particle size leads to an increase in sorption capacity and efficiency of the column, but also increases its hydraulic resistance and cause further damage of the blood cells. Therefore, sizes of adsorbent particles applicable in hemosorption columns are limited. This leads to conclusion that existing methods of human organism detoxication by traditional hemosorption have imperfection due to damage cellular elements of blood, reducing oxygen capacity of blood, a level of antibodies and arterial pressure.
To avoid these problems, we propose a new method of biological fluid detoxication with the application of ferromagnetic particles of micron and sub-micron size, coated with carbon or other adsorbent. Such ferro-carbon particles due to their small size have very high sorption capacity and fast sorption kinetics, as all volume of particles is used in sorption simultaneously. Additionally they can be moved and confined by a magnetic field.
The processing of a blood by a magnetic hemosorption is carried out extracorporally. Blood, withdrawn from an artery (or a vein), is mixed with a suspension of ferro-carbon particles. After the sorption process is completed in the mixture, the particles of adsorbent containing the toxicants are removed by a magnetic separator and the purified blood is returned to the organism. Removing toxicants from blood results in purifying different organs of the human body as well.
Applications of the magnetic Hemosorptionare are looking forward to disaster medicine (industrial catastrophes, acts of terrorism using chemical or biological weapons) when the large amount of patients is poisoned and should be treated all simultaneously. This method allows to develop portable equipment for these tasks.
Authors of the idea of the magnetic hemosorption (patent № 1836105. 30.03.1990 и 2008929. 28.06.1991of the Russian Federation) participate in the current project. Method and its technical realization have been successfully tested on models and animals and have shown high efficiency in removing lowmolecular (barbiturate), middle (vitamin B12), and high molecular weight (myoglobine) toxicants. At the moment low funds have caused research termination.
The objective of the project is the creation of the new Magnetic Hemosorption method based on the described principle and carrying-out of its clinical trials. Furthermore, it is supposed to study the magnetic adsorbents and develop the optimal ones for the Magnetic Hemosorption in order to adsorb both wide range of toxicants and some denger toxicants and microorganisms.
The project contains three interconnected parts.
The first task is « Development of magnetic adsorbents ». It includes the following stages:
1. Development of the manufacturing technology of submicron ferromagnetic particles containing iron - carbon or iron - silicon dioxide composition.
2. Development of the technology of particles modification including covering by protein or polymeric molecules for attaching to particles of biological compatibility and opportunity of selective adsorption.
3. Study and optimization of magnetic and sorption properties of obtained particles, in order to define the best parameters of the manufacturing technology and at the same time to reach high adsorptive capacity and optimum magnetic properties of particles.
4. Testing efficiency of toxicants sorption in vitro on model suspensions, plasma and donor blood.
5. Manufacture of optimized magnetic adsorbents for preclinical testing and target usage.
Particles will be obtained using the original plasma-chemical technology and in some cases using the new technology of superadiabatic compression as well. In order to define the optimal parameters of the manufacturing technology and combine high sorption capacity and optimal magnetic properties of particles screening by testing of properties of the obtained particles is strongly required.
The second task is «Development of magnetic devices»:
1. Development of magnetic separators.
2. Development a blood channels system and input device of magnetic adsorbents.
3. Development of external magnetic system.
4. Studying of a magnetic separator efficiency, and kinetics of a separator operation depending on its filling, in vitro, on model suspensions, plasma and donor blood.
It is supposed, that the external magnetic field of magnetic devices will be formed by a set of permanent magnets, without electromagnets. A magnetic separator and blood channels system for a magnetic hemosorption will be of one-time usage.
The third task is «Trial of efficiency of a method of a magnetic hemosorption» includes stages of model experiments on animal and all necessary preclinical trials, for obtaining the resolution for carrying out of clinical trials:
1. Testing toxicological safety of magnetic adsorbents on practically healthy animal also include an estimation of safety of adsorbent and magnetic separator on the following parameters: hemocompatibility, clinical biochemistry, system of coagulation of a blood, gas composition of a blood, electrolytes of a blood, physiological exponents, histological structure of animal organs.
2. Testing efficiency of a magnetic hemosorption on animal with model of a pathology (poisoning with various reference toxicants).
3. Preclinical trials of the prototypes of both magnetic adsorbents and separator and obtaining of the resolution for clinical trials.
In process of development of a magnetic hemosorption method, all probable types of diseases and poisonings giving in to treatment by new technology will be determined.
As a result of the project execution, the substantially effective prototype and medical technology for a magnetic hemosorption will be created, and also the preclinical trials of the designed prototype on animal and preparation for clinical trials will be carried out.
The new method of a magnetic hemosorption will have essential advantages in performance of the procedure, namely, the level of exogenous and endogenous toxicants, myoglobine and free hemoglobin of a blood will be reduced in several times and the duration of the procedure is twice reduced. Therefore, application range and augmentation of the prescribed procedures of a magnetic hemosorption at its implantation in clinical practice will be considerably increased (in our estimations 50-100% in comparison with modern application of traditional hemosorptions).
Economic benefit of a magnetic hemosorption in clinical practice can be very large (up to 50% of costs dropping). This will be consequence of reduction of the operation duration, spent adsorbent, cost of necessary equipment and also reduction of treatment period of patients in hospitals.
The research group includes, mainly, scientists of Institute of Biochemical Physics of RAS. Within the framework of the created temporary working collective, as researchers and consultants will be involved the research fellows of Institute of Chemical Physics of RAS, lab. № 33 of State Scientific Research Institute of Chemistry and Technology of Organoelement Compounds (GNIIChTEOS) (Saratov), and Sklifosovsky Emergency Research Center. The performance of the team-work design can bring in the essential contribution into development of new methods detoxication of a blood. Most of participants of the project were earlier connected with the military industry, and have necessary competence in the field of manufacture submicron ferromagnetic particles, development of magnetic systems for medical purposes, studying processes of a sorption and desorption, in the field of a hemodynamic, toxicology and medicine of extreme situations.
The project has practical importance for implementation of the ISTC purposes, as it grants to Russian weapon scientist and experts possibility for reorientation of the abilities on peace activity; encourages their integration in international scientific community; supports applied researches and development of technologies in the field of public health services.
Role of Foreign Collaborators:
– information exchange in the course of project implementation;
– cross-checks of results obtained in the course of project implementation;
– testing and evaluation of equipment/technologies developed in the course of the project;
– conduction of joint seminars and workshops;
– carrying out of joint experiments on basis of Collaborators.
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