TR2023001681A2 - A MEMBRANE AND PARTICULATE SYSTEM THAT CLEANSES HEAVY METAL FROM BODY LIQUIDS OR ORGANS - Google Patents

Abstract

The invention relates to a system that cleans heavy metal chelation from body blood or other fluids without exposing the kidneys and other organs to redistribution and side effects of chelators. (Figure 1)

Description

DESCRIPTION A MEMBRANE AND PARTICULATE SYSTEM THAT CLEARS HEAVY METAL FROM BODY FLUIDS OR ORGANS Technical Field The invention relates to a system that cleans heavy metal chelation from body blood or other fluids without exposing the kidneys and other organs to redistribution and side effects of chelators. . Background of the Invention In recent years, exposure to heavy metals of hydrogeological origin (e.g. arsenic, lead, cadmium, mercury and copper) has caused a global public health concern due to their harmful effects on human health. The World Health Organization and the International Agency for Research on Cancer define arsenic and cadmium metals as group 1 human carcinogens. Arsenic is the world's second leading cause of waterborne death. Metalloids such as arsenic often fall into the heavy metals category due to their similarities with heavy metals. Arsenic, cadmium and other toxic metals have been associated with bladder, kidney, liver and skin cancer. Even at lower levels of these toxic metals, widespread adverse effects can occur. There is a lot of evidence regarding the association of toxic metals with cardiovascular diseases, infertility, neurological diseases. Metal ions entering the body from the environment can bind to many molecules in body tissues, including proteins and polysaccharides. Moreover, most of these metals are biologically active and participate in a variety of different physiological and pathophysiological reactions. The effects of toxic metals also depend on the amount, nutritional status, age and gender. The amount and route of exposure to the metal, tissue distribution, achieved concentration and excretion rate are among the determinants of toxicity. Toxicity mechanisms also include inhibition of enzyme activity and protein, changes in nucleic acid synthesis and function, and changes in cell membrane permeability. All organs and organic systems in the body can be affected by heavy metals. Metal accumulations, especially in young developing organisms, can cause irreversible damage. People with high heavy metal levels are treated with medications called "chelators." These drugs bind to metals in the bloodstream; This metal-chelator compound is then eliminated in the urine. The main purpose of chelation therapy is; It transforms the toxic metal complex into a new non-toxic complex with biological ligands and makes it excretable from the organism. Although chelators are valuable drugs, they have side effects that limit their use with several medical conditions, especially those involving heavy metal toxicity due to lead, mercury, arsenic, and iron. In the context of medical therapeutics, chelation is a process in which organic chelator molecules are delivered into the blood and bind target metal ions with high affinity. The chelator and metal ion complex remain in the blood until filtered by the kidney or excreted by the liver, thus removing the metal ions from the body. Edetate disodium, a synthetic chelating agent first synthesized in Germany in the 1930s, has up to six binding sites to retain and entrap metal ions. Although metal chelation treatments in coronary heart diseases have controversial results, they have been tried before and are still on the agenda. The pharmacokinetic data, clinical uses and side effects of most chelating drugs used in humans are different for each chelating drug. Some chelating drugs with worldwide application are: dimercaprol (BAL), succimer (meso-DMSA), Monoisoamyl DMSA (MiADMSA), Monomethyl DMSA (MmDMSA), Monocyclohexyl DMSA (MchDMSA), unithiol (DMPS), D-penicillamine (DPA). , N-acetyl-Dpenicillamine (NAPA), Nitrilotriacetic Acid (NTA), calcium disodium ethylenediaminetetraacetate (CaNa2EDTA), calcium trisodium or zinc trisodium diethylenetriaminepentaacetate (CaNa3DTPA, ZnNa3DTPA), deferoxamine (DFO), deferiprone (L1), triethylenetetraamine (trientine), N-acetylcysteine (NAC) and Prussian blue (PB). Several novel synthetic homologues and experimental chelating agents have been designed and tested in vivo for metal binding. The effect of these chelators on the tissue and serum distribution of metals has not yet been demonstrated as a regular pattern. Toxic elements retained in bone and soft tissues are not completely immobilized. When heavy metals are withdrawn from the blood with chelators, they may redistribute to sensitive organs through the blood and cause secondary toxic effects. Observation of redistribution to the liver, kidney, brain and heart after the chelators collect heavy metals from the tissues constitutes a serious problem and eliminates the beneficial effects of chelation therapy. While hydrophilic chelators remain limited to extracellular metal pools and increase renal excretion; lipophilic chelators can access and reduce intracellular stores but redistribute toxic metals to sensitive compartments. With chelating agents, heavy metals in the plasma are eliminated quite rapidly within a few hours or days. Toxic heavy metals, on the other hand, compartmentalize in various parts of the body in different time periods and are not equally accessible to chelating agents. Generally, a chelating agent removes the most readily mobilized metals, typically in the plasma, kidney, liver, and then to a lesser extent bone and central nervous system. It is very important to have long-term chelators that will absorb and buffer heavy metal in the blood during redistribution after cleaning in the blood, but existing chelators cannot provide this. This situation creates a vital effectiveness-security paradox. Repeated exposure of the kidneys to a filterable but reabsorbable metal or chelate causes nephrotoxicity. Similarly, enterohepatic circulation can result in ongoing gastrointestinal exposure to a metal, ligand, or chelate, producing organ toxicity. Although radioactive elements can occur naturally in the environment, most harmful radionuclides are of anthropogenic origin, released from military, industrial or medical processes. Nuclear reactor accidents can result in worker exposure. Reports after the Chernobyl and Fukushima accidents revealed that radioisotopes 137Cs and 131l constituted large amounts of harmful pollutants in airborne distribution and fallout. Future terrorist attacks that could contaminate drinking water could expose larger populations to radionuclides. Accidental exposure to radioactive sources used in medicine and industry is an important cause of intoxication. The primary goal of emergency treatment after ingestion of radionuclides is to minimize the radiation dose to contaminated individuals. Uranium; Significant exposure may occur through industrial milling, mining and environmental remediation of refined uranium-contaminated soil, mines or waste, and nuclear fuel production and processing. Exposure to uranium in the natural environment most commonly occurs orally from contaminated food or drinking water. Prussian blue, which can be used in the treatment of thallium and cesium poisoning, was approved by the FDA in 2003. In 2004, the FDA approved calcium DTPA and zinc DTPA to enhance the elimination of various radioactive nuclides, including plutonium, americium, or curium. Currently used chelating agents have serious side effects such as renal failure, arrhythmias, tetany, hypotension, bone marrow depression, thrombocytopenia, leukocytopenia, prolonged bleeding time, convulsions, respiratory arrest, and decreases in the amount of calcium, zinc, copper and manganese. These agents are generally contraindicated in pregnancy, active kidney diseases, anuria and hepatitis. Therefore, there is an urgent need to develop chelators that are less toxic and more effective for chelation, other than chelators that bind heavy metals in the blood, that will prevent enterohepatic heavy metal circulation. In the literature, in the Chinese patent application numbered CN107141468, the circulating iron chelator is created by connecting good biocompatible polyethylene glycol monomethyl ether and deferoxamine through a pH-sensitive chemical bond. The invention further discloses a method of preparation of long-circulation iron chelator, and the method of preparation includes the steps of coupling polyethylene glycol monomethyl ether with carboxybenzaldehyde through an esterification reaction and allowing an intermediate to react with deferoxamine through a schiff base to prepare "Compared with Deferoxamine, a long-circulation iron chelator with pH response properties, the disclosed iron chelator has the characteristics of long action and response to the acid microenvironment of the lesion location, and has a potential application value in the treatment of diseases related to iron overload." A long-circulation iron chelator with reaction properties is disclosed. Also in the literature, the Chinese patent document numbered CN107281498 explains the preparation method on the subject. The preparation method is prepared from polyethylene glycol derivatives with good biocompatibility and deferoxamine. "It involves the step of preparing the polyethylene glycol modified iron ionic chelator by covalent bonding of polyethylene glycol monomethyl ether with deferoxamine. Compared with deferoxamine, the iron ionic chelator has the advantages of long action and low toxicity, and has potential application value in the treatment of iron overload-related diseases." In the mentioned application, the structure of Polyethylene glycol modified iron ionic chelator is explained. Also in the literature, the Russian patent document numbered RU2696981 deals with the determination of human erythrocyte sensitivity to lysis by complement system activation. For human erythrocytes, susceptibility to lysis is assessed when the complement system is activated in a thrombin pathway using citrate plasma with high thrombin activity associated with fibrin. To inhibit complement activation by one of three known pathways (classical, alternative or lectin), sodium citrate is used as a chelator to bind Ca and Mg. In the presence of high fibrin-associated thrombin activity, the CS component is activated and a membrane-attack complex is formed, determined by lysis of human erythrocytes. The degree of HE lysis is determined from a calibration curve where 100% lysis is complete lysis of human erythrocytes with the addition of water and the erythrocyte control for spontaneous lysis is 0% lysis. The parallel is determined by the standard HE blood group technique. The human erythrocytes most sensitive to lysis are human erythrocytes with blood group A, second are HE with blood group AB, and third are HE with blood group B. The most stable are human erythrocytes with blood group O. EFFECT: This test can be used for personalized prediction of the severity of reperfusion syndrome by complement activation of the complement system via thrombin, as well as for the selection of treatment approaches in given pathological conditions." method is disclosed. Due to the reasons mentioned above, a new system that cleans heavy metal from body fluids or organs is needed. Purpose of the Invention Based on this position of the technique, the aim of the invention is to introduce a new system that eliminates the existing disadvantages and cleans heavy metal from body fluids or organs. Another aim of the invention is to provide a structure that eliminates the limitation and toxicity problems of the agents recommended for heavy metal chelation by preventing various cases of heavy metal poisoning and eliminating the disadvantages such as numerous side effects, non-specific binding and difficulty in application. is to reveal. Another aim of the invention is to introduce a structure that eliminates the risk of exposure of the kidneys to high radiation during excretion, even if deporporation (therapeutic removal of the radioactive substance absorbed by the body) is successful. Explanation of the Drawings Figure - 1 A representative view of the membrane system that cleans heavy metal from body fluids or organs, which is the subject of the invention. Figure - 2 A representative view of another system, which cleans heavy metal from body fluids or organs, which is the subject of the invention, with particles that bind heavy metal. Figure - 3. Another representative view of the particle system that cleans heavy metal from the body fluids or organs that are the subject of the invention Figure - 4 Another representative view of the membrane system that cleans heavy metal from the body fluids or organs that is the subject of the invention Reference Numbers 1. Membrane 2. Sphere Detailed Description of the Invention In this detailed explanation , the innovation that is the subject of the invention is explained only with examples that will not create any limiting effect on a better understanding of the subject. The invention is a system that cleans heavy metal chelation from body blood or other fluids without exposing the kidneys and other organs to redistribution and side effects of chelators, and its feature is; It is characterized by containing a heavy metal-binding membrane (1) and/or filtration spheres (2) through which body fluids are passed. Figure - 1 depicts a representative view of the membrane (1) structure that adsorbs heavy metals from body fluids or organs that are the subject of the invention. Meet; It contains heavy metal binding membrane (1) or filtration beads (2) through which body fluids will be passed, which clears heavy metal chelation from body blood or other fluids without exposing the kidneys and other organs to redistribution and side effects of chelators. Body fluids containing heavy metal are passed over the membrane (1) or beads (2) and are isolated by passively adsorbing the heavy metal in them. Heavy metal cleaning can also be done in the system by using a heavy metal adsorbent membrane (1) cleaner. Blood or body fluids to be cleaned of heavy metals are passed through the membrane (1) and the heavy metals in it are adsorbed and separated by the membrane (1). Multiple membranes (1) with selective affinity for single or different heavy metals can also be used in the system. With the addition of heavy metal adsorbent bead (2) cleaners in the system, the body fluids to be cleaned of heavy metal are passed through the beads (2) and the heavy metals in the liquid are adsorbed by the beads (2) and heavy metal cleaning is carried out. Spheres (2) may have different affinities for different heavy metals. In the system subject to the invention, body fluids to be cleaned of heavy metal are passed through the membrane (1) with the heavy metal adsorbent membrane (1), and heavy metal cleaning is carried out by adsorbing the heavy metals in the liquid by the membrane (1). In another alternative, the body fluids to be cleaned of heavy metal are passed through the beads (2) with heavy metal adsorbent beads (2), and heavy metal cleaning is carried out by adsorbing the heavy metals in the liquid by the beads (2). Multiple membranes (1) with selective affinity for single or different heavy metals can also be used in the system. TR TR

Claims (1)

1. CLAIMS The invention is a system that cleans heavy metal chelation from body blood or other fluids without exposing the kidneys and other organs to redistribution and side effects of chelators, and its feature is; It is characterized by containing a heavy metal-binding membrane (1) and/or filtration spheres (2) through which body fluids are passed. TR TR