WO2024030085A1 - A device for cleaning heavy metal-bound mediators in body fluids and organs - Google Patents
A device for cleaning heavy metal-bound mediators in body fluids and organs Download PDFInfo
- Publication number
- WO2024030085A1 WO2024030085A1 PCT/TR2022/050824 TR2022050824W WO2024030085A1 WO 2024030085 A1 WO2024030085 A1 WO 2024030085A1 TR 2022050824 W TR2022050824 W TR 2022050824W WO 2024030085 A1 WO2024030085 A1 WO 2024030085A1
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- WO
- WIPO (PCT)
- Prior art keywords
- heavy metal
- chelator
- blood
- heavy
- isolation device
- Prior art date
Links
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3618—Magnetic separation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3679—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption
Definitions
- the invention relates to a device that cleaning heavy metal-bound mediators in body fluids or organs.
- the invention relates to a device that removes heavy metal chelation from body blood or other fluids without exposing the kidneys and other organs to redistribution and the side effects of chelators.
- arsenic is the world's second leading cause of waterborne death.
- Metalloids such as arsenic often fall into the heavy metals category because of their similarity to 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 be seen. There is a lot of evidence about the relationship of toxic metals with cardiovascular diseases, infertility and neurological diseases.
- Metal ions entering the body from the environment can bind to many molecules in body tissues, including proteins and polysaccharides. Moreover, many 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 metal exposure, tissue distribution, the concentration achieved and the rate of excretion are also among the determinants of toxicity. Toxicity mechanisms 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 developing young organisms, can cause irreversible damage.
- chelators drugs that bind to metals in the bloodstream; this metal-chelator compound is then eliminated in the urine.
- chelation therapy The main purpose of chelation therapy is; converting the toxic metal complex to a new non-toxic complex with biological ligands and making it excretable from the organism. While chelators are valuable drugs, they have side effects that limit their use, especially with a few medical conditions that include heavy metal toxicity due to lead, mercury, arsenic, and iron.
- chelation is a process in which organic chelator molecules are introduced into the blood and bind target metal ions with high affinity. The chelator and metal ion complex remains in the blood until it is filtered by the kidney or excreted by the liver, so that the metal ions are removed from the body.
- Edetate disodium a synthetic chelating agent first synthesized in Germany in the 1930s, has up to six binding sites to trap and envelop metal ions.
- 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 trientramine (L) ) and Prussian blue (PB).
- BAL dimercaprol
- me-DMSA Monoisoamyl DMSA
- MmDMSA Monomethyl DMSA
- MchDMSA Monocyclohexyl
- hydrophilic chelators are 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 removed quite rapidly within a few hours or days. Toxic heavy metals, on the other hand, are compartmentalized in various parts of the body over different time periods and are not equally accessible to chelating agents.
- a chelating agent removes most readily mobilized metals, typically in the form of 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 the heavy metal in the blood during redistribution after cleaning, but the existing chelators cannot provide this. This situation creates a vital efficacy-safety paradox. Continuous exposure of the kidneys to a filterable but reabsorbable metal or chelate causes nephrotoxicity. Similarly, enterohepatic circulation may result in continued gastrointestinal exposure to a metal, ligand, or chelate, resulting in organ toxicity.
- radioactive elements can be found 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 1311 formed large amounts of harmful pollutants in the air dispersion and fallout. Terrorist attacks that may contaminate drinking water in the future may result in radionuclide exposure of larger populations. 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 of contaminated individuals.
- Uranium can generate significant exposure through industrial grinding, mining, and environmental remediation of soil, mines or wastes contaminated with refined uranium, and nuclear fuel production and processing. Uranium exposure in the natural environment most commonly occurs by mouth from contaminated food or drinking water. Prussian blue, which can be used to treat 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.
- chelating agents have serious side effects such as renal failure, arrhythmias, tetany, hypotension, bone marrow depression, thrombocytopenia, leukocytopenia, prolonged bleeding time, convulsions, respiratory arrest, decreases in calcium, zinc, copper, manganese levels. These agents are generally contraindicated in pregnancy, active kidney disease, anuria and hepatitis. Therefore, there is an urgent need to develop chelates of low toxicity and more effective for chelation.
- the invention discloses a long circulation iron chelator with a pH response characteristic.
- the long circulation iron chelator is formed by connecting polyethylene glycol monomethyl ether with good biocompatibility and deferoxamine through a pH sensitive chemical bond.
- the invention further discloses a preparation method of the long circulation iron chelator, and the preparation method comprises the steps of connecting polyethylene glycol monomethyl ether with carboxybenzaldehyde through an esterification reaction, and enabling an intermediate product to react with the deferoxamine through a schiff base to prepare the long circulation iron chelator with the pH response characteristic.
- the disclosed iron chelator Compared with the deferoxamine, the disclosed iron chelator has the characteristics of long effect and response to an acid microenvironment of a lesion location, and has a potential application value in the treatment of iron overload related diseases.” statements are included. In said application, a long circulation iron chelator with pH response property is disclosed.
- the invention discloses a polyethylene glycol modified iron ionic chelator and a preparation method thereof.
- the iron ionic chelator is prepared from derivatives of polyethylene glycol with good biocompatibility and deferoxamine.
- the preparation method comprises the step of preparing the polyethylene glycol modified iron ionic chelator by covalent binding of carboxylated polyethylene glycol monomethyl ether or formylated polyethylene glycol monomethyl ether with deferoxamine.
- the iron ionic chelator Compared with deferoxamine, the iron ionic chelator has the advantages of long action and low toxicity, and has potential application value in treatment of iron overload related diseases.” statements are included.
- the invention invention refers to clinical immunology and haemostasiology and concerns determining human erythrocyte sensitivity to lysis with complement system activation on thrombin pathway. For ohuman erythrocytes sensitivity to lysis is evaluated when the complement system is activated on a thrombin path using citrate plasma with high thrombin activity associated with fibrin. To inhibit complement activation by one of the known three routes (classical, alternative or lectin), sodium citrate is used as a chelator for binding Caand Mg.
- component C5 is activated and a membrane-attack complex is formed, which is determined by lysis of human erythrocytes.
- Degree of HE lysis is determined from a calibration curve, where 100 % lysis is complete lysis of human erythrocytes with water addition, and erythrocyte control for spontaneous lysis - 0 % lysis.
- Parallel is determined by the standard HE blood group technique. Most sensitive to lysis are human erythrocytes with blood group A, second place HE with blood group AB, in third place HE with blood group B. Most stable are human erythrocytes with 0 blood group. EFFECT: this test can be used for personified prediction of severity of reperfusion syndrome with complement activation by thrombin pathway of complement system, as well as for selection of treatment approach in given pathological situations.” statements are included.
- the aim of the invention is to present a device that cleans body fluids and heavy metal-bound mediators in organs.
- Another aim of the invention is to prevent various heavy metal poisoning cases and to present a structure that eliminates the problem of limitation and toxicity to the agents recommended for heavy metal chelation.
- Another aim of the invention is to provide a fast and effective structure that can remove toxic metal from blood and soft tissues immediately.
- Another aim of the invention is to provide a structure that eliminates the disadvantages such as numerous side effects, non-specific binding and application difficulties.
- Another aim of the invention is to present a structure that eliminates the problems caused by ions such as calcium, magnesium, manganese, and zinc that are excreted uncontrolled from the body through the kidney with chelators administered orally or intravenously.
- Another object of the invention is to provide a structure that eliminates the risk of high radiation exposure of the kidneys during excretion, even if decorporation (therapeutic removal of the radioactive substance absorbed by the body) is successful.
- Another aim of the invention is to reveal a structure that allows the use of new generation chelators more comfortably and safely, as it takes the body fluid out and returns the fluid to the body after cleaning with superparamagnetic particles and the chelators attached to them.
- FIG - 1 Representative view of an application of the heavy metal isolation device that is the subject of the invention
- the invention is a heavy metal isolation device (A) that cleans heavy metal chelation from body blood or other fluids without exposing kidney and other organs to redistribution and side effects of chelators, characterized in that, comprises, heavy metal separation tube (1) positioned outside the body, through which blood or body fluid containing heavy metals enters the entry of blood or body fluids containing heavy metals (1.1), the magnet (2), which is positioned at a distance from the said heavy metal separation tube (1) to affect the magnetic field, and which cleans the body fluid by attracting the chelator-coated superparamagnetic particles with different properties and configurations that bind the heavy metals together with the heavy metals attached to them.
- A heavy metal isolation device
- FIG - 1 shows representative view of an application of the heavy metal isolation device (A), which is the subject of the invention.
- FIG - 2 shows representative view of another application of the heavy metal isolation device (A), which is the subject of the invention.
- the heavy metal isolation device (A) consists main parts of, heavy metal separation tube (1) positioned outside the body, through which blood or body fluid containing heavy metals enters the entry of blood or body fluids containing heavy metals (1.1), the magnet (2), which is positioned at a distance from the said heavy metal separation tube (1) to affect the magnetic field, and which cleans the body fluid by attracting the chelator-coated superparamagnetic particles with different properties and configurations that bind the heavy metals together with the heavy metals attached to them, heavy metal-free blood or body fluid outlet (1.2), which is the outlet end of said heavy metal separation tube (1), positioned as the place where the cleaned blood or body fluid is returned to the patient, heavy metal bonded chelator-coated superparamagnetic particle outlet (1 .3), which is the outlet where the chelator-coated superparamagnetic particles are positioned and evacuated, to which the heavy metal attracted by the magnets (2) is connected and a rotating magnet bearing (3) positioned zero to zero in said heavy metal separation tube (1), rotating
- the invention is a heavy metal isolation device (A) that removes heavy metal chelation from body blood or other fluids without exposing kidneys and other organs to redistribution and the side effects of chelators.
- the basic working principle of the mentioned heavy metal isolation device (A) is based on isolating chelator-coated superparamagnetic particles with different properties and configurations that bind heavy metals from blood, plasma or other body fluids and return blood or other body fluids. It is taken from the entry of blood or body fluids containing heavy metals (1.1) to the heavy metal separation tube (1) outside the body.
- the mentioned heavy metal isolation device (A) basically uses the paramagnetic effect and separates the chelators coated with superparamagnetic substances and the heavy metals they bind by attracting them with permenant or electromagnets.
- the separation process is in an embodiment of the invention; blood or body fluid is passed through the heavy metal separation tube (1), which has a T-shaped projection between the magnets (2). While heavy metals bound to the chelator- coated superparamagnetic substance in the body fluid pass through the heavy metal separation tube (1), they are positioned in front of the heavy metal bonded chelator- coated superparamagnetic particle outlet (1 .3) with magnets (2). It is separated by pulling to the heavy metal bonded chelator-coated superparamagnetic particle outlet (1.3), which is formed as a T protrusion. Thus, clean blood or fluid goes back to the body from heavy metal-free blood or body fluid outlet (1 .2).
- magnets (2) positioned as permanent or electromagnets rotate circularly on the rotating magnet bearing (3) and it isolates the chelator agents and heavy metals attached to the chelator-coated superparamagnetic particles that have bound the heavy metals in the body fluid passing through the Y-shaped heavy metal separation tube (1).
- Said heavy metal isolation device (A) can be used in different device and application combinations.
- the chelator-coated superparamagnetic particles are given to the patient for heavy metal removal from tissues and organs, after staying in the body for a while, they are taken out of the body with the patient's blood and anticoagulant is added to the blood (heparin, bivaluridin, etc.) and the blood is mentioned heavy metal isolation device (A) in a closed system, the heavy metal separation tube (1) passes through it.
- chelator-coated superparamagnetic particles are given intravenously to the patient for tissue and organ cleaning, allowing them to reach the whole body. After a while, the patient's blood is taken out of the body and kept on the mixer in the heavy metal isolation device (A) intermittently.
- the magnets (2) in the mixing unit collect all the chelator-coated superparamagnetic particles from the large amount of blood and are cleaned together with the heavy metals attached to them. After cleaning, it is given back to the blood intermittently by adding the necessary essential elements to the body.
- the heavy metal isolation device (A) when chelator-coated supermagnetic particles are not wanted to be given to the patient intravenously and to the whole body, the patient's blood is taken intermittently by being anticoagulated into the heavy metal separation tube (1) of the heavy metal isolation device (A).
- the blood is mixed with chelator-coated superparamagnetic particles. After a certain period of mixing, heavy metals in the blood are retained by chelator-coated superparamagnetic particles, permenant or electromagnetic magnets (2) are activated and bound heavy metals are taken back from the blood.
- the chelator- coated superparamagentic particles and the blood cleaned from heavy metals are returned to the body intermittently by adding the necessary essential elements.
Abstract
The invention is a heavy metal isolation device (A) that cleans heavy metal chelation from body blood or other fluids without exposing kidney and other organs to redistribution and side effects of chelators.
Description
DESCRIPTION
A DEVICE FOR CLEANING HEAVY METAL-BOUND MEDIATORS IN BODY FLUIDS AND ORGANS
Technical Field
The invention relates to a device that cleaning heavy metal-bound mediators in body fluids or organs.
In particular, the invention relates to a device that removes heavy metal chelation from body blood or other fluids without exposing the kidneys and other organs to redistribution and the 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) raises 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 I human carcinogens. Arsenic is the world's second leading cause of waterborne death. Metalloids such as arsenic often fall into the heavy metals category because of their similarity to 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 be seen. There is a lot of evidence about the relationship of toxic metals with cardiovascular diseases, infertility and neurological diseases.
Metal ions entering the body from the environment can bind to many molecules in body tissues, including proteins and polysaccharides. Moreover, many 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 metal exposure, tissue distribution, the concentration achieved and the rate of excretion are also among the
determinants of toxicity. Toxicity mechanisms 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 developing young organisms, can cause irreversible damage.
People with high heavy metal levels are treated with drugs 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; converting the toxic metal complex to a new non-toxic complex with biological ligands and making it excretable from the organism. While chelators are valuable drugs, they have side effects that limit their use, especially with a few medical conditions that include 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 introduced into the blood and bind target metal ions with high affinity. The chelator and metal ion complex remains in the blood until it is filtered by the kidney or excreted by the liver, so that the metal ions are removed from the body. Edetate disodium, a synthetic chelating agent first synthesized in Germany in the 1930s, has up to six binding sites to trap and envelop metal ions. Although metal chelation treatments have produced controversial results in coronary heart diseases, they have been tried before and have not fallen off the agenda.
The pharmacokinetic data, clinical use and side effects of most of the 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 trientramine (L) ) 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 model. Toxic elements retained in bone and soft tissues are not completely immobilized. When heavy metals are removed from the blood with chelators, they may redistribute to sensitive organs through blood and cause secondary toxic effects. Observation of redistribution to liver, kidney, brain and heart after chelators collect heavy metals from tissues creates a serious problem and eliminates the beneficial effects of chelation therapy.
While hydrophilic chelators are 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 removed quite rapidly within a few hours or days. Toxic heavy metals, on the other hand, are compartmentalized in various parts of the body over different time periods and are not equally accessible to chelating agents.
Generally, a chelating agent removes most readily mobilized metals, typically in the form of 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 the heavy metal in the blood during redistribution after cleaning, but the existing chelators cannot provide this. This situation creates a vital efficacy-safety paradox. Continuous exposure of the kidneys to a filterable but reabsorbable metal or chelate causes nephrotoxicity. Similarly, enterohepatic circulation may result in continued gastrointestinal exposure to a metal, ligand, or chelate, resulting in organ toxicity.
Although radioactive elements can be found 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 1311 formed large amounts of harmful pollutants in the air dispersion and fallout. Terrorist attacks that may contaminate drinking water in the future may result in radionuclide exposure of larger populations. 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 of contaminated individuals. Uranium; can generate significant exposure through industrial grinding, mining, and environmental remediation of soil, mines or wastes contaminated with refined uranium, and nuclear fuel production and processing. Uranium exposure in the natural environment most commonly occurs by mouth from contaminated food or drinking water. Prussian blue, which can be used to treat 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, decreases in calcium, zinc, copper, manganese levels. These agents are generally contraindicated in pregnancy, active kidney disease, anuria and hepatitis. Therefore, there is an urgent need to develop chelates of low toxicity and more effective for chelation.
In the Chinese patent application numbered CN107141468 in the literature, “The invention discloses a long circulation iron chelator with a pH response characteristic. The long circulation iron chelator is formed by connecting polyethylene glycol monomethyl ether with good biocompatibility and deferoxamine through a pH sensitive chemical bond. The invention further discloses a preparation method of the long circulation iron chelator, and the preparation method comprises the steps of connecting polyethylene glycol monomethyl ether with carboxybenzaldehyde through an esterification reaction, and enabling an intermediate product to react with the deferoxamine through a schiff base to prepare the long circulation iron chelator with the pH response characteristic. Compared with the deferoxamine, the disclosed iron chelator has the characteristics of long effect and response to an acid microenvironment of a lesion location, and has a potential application value in the treatment of iron overload related diseases.” statements are included.
In said application, a long circulation iron chelator with pH response property is disclosed.
Again in the literature, in the Chinese patent document numbered CN107281498, “The invention discloses a polyethylene glycol modified iron ionic chelator and a preparation method thereof. The iron ionic chelator is prepared from derivatives of polyethylene glycol with good biocompatibility and deferoxamine. The preparation method comprises the step of preparing the polyethylene glycol modified iron ionic chelator by covalent binding of carboxylated polyethylene glycol monomethyl ether or formylated 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 treatment of iron overload related diseases.” statements are included.
In the mentioned application, Polyethylene glycol modified iron ionic chelate structuring is explained.
Again in the literature, in the Russian patent document numbered RU2696981 , “The invention invention refers to clinical immunology and haemostasiology and concerns determining human erythrocyte sensitivity to lysis with complement system activation on thrombin pathway. For ohuman erythrocytes sensitivity to lysis is evaluated when the complement system is activated on a thrombin path using citrate plasma with high thrombin activity associated with fibrin. To inhibit complement activation by one of the known three routes (classical, alternative or lectin), sodium citrate is used as a chelator for binding Caand Mg. In the presence of high thrombin activity associated with fibrin, component C5 is activated and a membrane-attack complex is formed, which is determined by lysis of human erythrocytes. Degree of HE lysis is determined from a calibration curve, where 100 % lysis is complete lysis of human erythrocytes with water addition, and erythrocyte control for spontaneous lysis - 0 % lysis. Parallel is determined by the standard HE blood group technique. Most sensitive to lysis are human erythrocytes with blood group A, second place HE with blood group AB, in third place HE with blood group B. Most stable are human erythrocytes with 0 blood group. EFFECT: this test can be used for personified prediction of severity of reperfusion syndrome with complement activation by thrombin pathway of
complement system, as well as for selection of treatment approach in given pathological situations.” statements are included.
In the aforementioned patent, the method of determining the sensitivity of human erythrocyte to lysis by the activation of the complement system on the thrombin pathway is disclosed.
For the reasons mentioned above, a new device was needed to clean the body fluids and heavy metal-bound mediators in the organs.
Purpose of the Invention
Based on this position of the technique, the aim of the invention is to present a device that cleans body fluids and heavy metal-bound mediators in organs.
Another aim of the invention is to prevent various heavy metal poisoning cases and to present a structure that eliminates the problem of limitation and toxicity to the agents recommended for heavy metal chelation.
Another aim of the invention is to provide a fast and effective structure that can remove toxic metal from blood and soft tissues immediately.
Another aim of the invention is to provide a structure that eliminates the disadvantages such as numerous side effects, non-specific binding and application difficulties.
Another aim of the invention is to present a structure that eliminates the problems caused by ions such as calcium, magnesium, manganese, and zinc that are excreted uncontrolled from the body through the kidney with chelators administered orally or intravenously.
Another object of the invention is to provide a structure that eliminates the risk of high radiation exposure of the kidneys during excretion, even if decorporation (therapeutic removal of the radioactive substance absorbed by the body) is successful.
Another aim of the invention is to reveal a structure that allows the use of new generation chelators more comfortably and safely, as it takes the body fluid out and returns the fluid to the body after cleaning with superparamagnetic particles and the chelators attached to them.
Explanation of Figures
Figure - 1 Representative view of an application of the heavy metal isolation device that is the subject of the invention
Figure - 2 Representative view of another application of the heavy metal isolation device, which is the subject of the invention
Reference Numbers
A- Heavy Metal Isolation Device
1 . Heavy Metal Separation Tube
1 .1 Entry of Blood or Body Fluids Containing Heavy Metals
1 .2 Heavy Metal-Free Blood or Body Fluid Output
1 .3 Heavy Metal Bonded Chelator Coated Superparamagnetic Particle Output
2. Magnet
3. Rotating Magnet Bearing
Detailed Description of the Invention
In this detailed explanation, the innovation that is the subject of the invention is only explained with examples that will not have any limiting effect for a better understanding of the subject.
The invention is a heavy metal isolation device (A) that cleans heavy metal chelation from body blood or other fluids without exposing kidney and other organs to redistribution and side effects of chelators, characterized in that, comprises, heavy metal separation tube (1) positioned outside the body, through which blood or body fluid containing heavy metals enters the entry of blood or body fluids containing heavy metals (1.1), the magnet (2), which is positioned at a distance from the said
heavy metal separation tube (1) to affect the magnetic field, and which cleans the body fluid by attracting the chelator-coated superparamagnetic particles with different properties and configurations that bind the heavy metals together with the heavy metals attached to them.
Figure - 1 shows representative view of an application of the heavy metal isolation device (A), which is the subject of the invention.
Figure - 2 shows representative view of another application of the heavy metal isolation device (A), which is the subject of the invention.
The heavy metal isolation device (A) according to invention, consists main parts of, heavy metal separation tube (1) positioned outside the body, through which blood or body fluid containing heavy metals enters the entry of blood or body fluids containing heavy metals (1.1), the magnet (2), which is positioned at a distance from the said heavy metal separation tube (1) to affect the magnetic field, and which cleans the body fluid by attracting the chelator-coated superparamagnetic particles with different properties and configurations that bind the heavy metals together with the heavy metals attached to them, heavy metal-free blood or body fluid outlet (1.2), which is the outlet end of said heavy metal separation tube (1), positioned as the place where the cleaned blood or body fluid is returned to the patient, heavy metal bonded chelator-coated superparamagnetic particle outlet (1 .3), which is the outlet where the chelator-coated superparamagnetic particles are positioned and evacuated, to which the heavy metal attracted by the magnets (2) is connected and a rotating magnet bearing (3) positioned zero to zero in said heavy metal separation tube (1), rotating circularly in an evenly spaced order on said magnets (2).
The invention; is a heavy metal isolation device (A) that removes heavy metal chelation from body blood or other fluids without exposing kidneys and other organs to redistribution and the side effects of chelators.
The basic working principle of the mentioned heavy metal isolation device (A) is based on isolating chelator-coated superparamagnetic particles with different properties and configurations that bind heavy metals from blood, plasma or other
body fluids and return blood or other body fluids. It is taken from the entry of blood or body fluids containing heavy metals (1.1) to the heavy metal separation tube (1) outside the body.
Different chelators connected with superparamagnetic substances and the heavy metals they bind are attracted to the heavy metal separation tube (1) outside the body by magnets (2) located at a distance to affect the magnetic field, so the body fluid is cleaned, the cleaned body fluid is given back to the patient through the heavy metal-free blood or body fluid outlet (1 .2).
Heavy metal, chelator-coated superparamagnetic particles in the body fluid cleaned by heavy metal bonded chelator-coated superparamagnetic particle outlet (1.3), thereby eliminating the chelator toxicity.
The mentioned heavy metal isolation device (A) basically uses the paramagnetic effect and separates the chelators coated with superparamagnetic substances and the heavy metals they bind by attracting them with permenant or electromagnets.
The separation process is in an embodiment of the invention; blood or body fluid is passed through the heavy metal separation tube (1), which has a T-shaped projection between the magnets (2). While heavy metals bound to the chelator- coated superparamagnetic substance in the body fluid pass through the heavy metal separation tube (1), they are positioned in front of the heavy metal bonded chelator- coated superparamagnetic particle outlet (1 .3) with magnets (2). It is separated by pulling to the heavy metal bonded chelator-coated superparamagnetic particle outlet (1.3), which is formed as a T protrusion. Thus, clean blood or fluid goes back to the body from heavy metal-free blood or body fluid outlet (1 .2).
In another application, magnets (2) positioned as permanent or electromagnets rotate circularly on the rotating magnet bearing (3) and it isolates the chelator agents and heavy metals attached to the chelator-coated superparamagnetic particles that have bound the heavy metals in the body fluid passing through the Y-shaped heavy metal separation tube (1).
Said heavy metal isolation device (A) can be used in different device and application combinations. The chelator-coated superparamagnetic particles are given to the patient for heavy metal removal from tissues and organs, after staying in the body for a while, they are taken out of the body with the patient's blood and anticoagulant is added to the blood (heparin, bivaluridin, etc.) and the blood is mentioned heavy metal isolation device (A) in a closed system, the heavy metal separation tube (1) passes through it.
While blood passes through the heavy metal separation tube (1) containing T-shaped protrusions in the section of the heavy metal isolation device (A) containing strong magnets (2), chelator-coated superparmagnetic particles and heavy metals are attracted to the T-piece bulge -shaped heavy metal bonded chelator-coated superparamagnetic particle outlet (1 .3) by the attraction of the magnets (2) and the other part of the blood is given back to the body through the heavy metal-free blood or body fluid outlet (1 .2), which is purified from heavy metals and is cleaned from the chelator attached to the superparamagnetic particles and heavy metals. According to the needs of the patient, essential elements can also be given to the returned blood
In another configuration of the aforementioned heavy metal isolation device (A), chelator-coated superparamagnetic particles are given intravenously to the patient for tissue and organ cleaning, allowing them to reach the whole body. After a while, the patient's blood is taken out of the body and kept on the mixer in the heavy metal isolation device (A) intermittently.
The magnets (2) in the mixing unit collect all the chelator-coated superparamagnetic particles from the large amount of blood and are cleaned together with the heavy metals attached to them. After cleaning, it is given back to the blood intermittently by adding the necessary essential elements to the body.
In another configuration of the heavy metal isolation device (A), when chelator-coated supermagnetic particles are not wanted to be given to the patient intravenously and to the whole body, the patient's blood is taken intermittently by being anticoagulated into the heavy metal separation tube (1) of the heavy metal isolation device (A). The blood is mixed with chelator-coated superparamagnetic particles. After a certain
period of mixing, heavy metals in the blood are retained by chelator-coated superparamagnetic particles, permenant or electromagnetic magnets (2) are activated and bound heavy metals are taken back from the blood. The chelator- coated superparamagentic particles and the blood cleaned from heavy metals are returned to the body intermittently by adding the necessary essential elements.
Claims
1. The invention is a heavy metal isolation device (A) that cleans heavy metal chelation from body blood or other fluids without exposing kidney and other organs to redistribution and side effects of chelators, characterized in that, comprises, heavy metal separation tube (1) positioned outside the body, through which blood or body fluid containing heavy metals enters the entry of blood or body fluids containing heavy metals (1.1), the magnet (2), which is positioned at a distance from the said heavy metal separation tube (1) to affect the magnetic field, and which cleans the body fluid by attracting the chelator- coated superparamagnetic particles with different properties and configurations that bind the heavy metals together with the heavy metals attached to them.
2. A heavy metal isolation device (A) according to claim 1 ; comprises heavy metal-free blood or body fluid outlet (1 .2), which is the outlet end of said heavy metal separation tube (1), positioned as the place where the cleaned blood or body fluid is returned to the patient.
3. A heavy metal isolation device (A) according to any preceding claims; comprises heavy metal bonded chelator-coated superparamagnetic particle outlet (1 .3), which is the outlet where the chelator-coated superparamagnetic particles are positioned and evacuated, to which the heavy metal attracted by the magnets (2) is connected.
4. A heavy metal isolation device (A) according to any preceding claims; comprises a rotating magnet bearing (3) positioned zero to zero in said heavy metal separation tube (1), rotating circularly in an evenly spaced order on said magnets (2).
5. A heavy metal isolation device (A) according to any preceding claims; comprises T-piece-shaped bulge positioned as a part of the heavy metal separation tube (1) attracted by the mentioned magnets (2) of the heavy metal
bound chelator-coated Superparamagnetic particles formed between the said magnets (2). A heavy metal isolation device (A) according to any preceding claims; after the permenant or electromagnetic magnets (2) rotate circularly on the rotating magnet bearing (3), chelator-coated paramagnetic particles that bind the heavy metals in the body fluid passing through the heavy metal separation tube (1) and the Y-shaped heavy metal-bonded chelator-coated superparamagnetic particle output that insulates them. (1.3) and heavy metal- free blood or body fluid outlet (1 .2).
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| PCT/TR2022/050824 WO2024030085A1 (en) | 2022-08-05 | 2022-08-05 | A device for cleaning heavy metal-bound mediators in body fluids and organs |
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| PCT/TR2022/050824 WO2024030085A1 (en) | 2022-08-05 | 2022-08-05 | A device for cleaning heavy metal-bound mediators in body fluids and organs |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002026292A1 (en) * | 2000-09-28 | 2002-04-04 | Affina Immuntechnik Gmbh | Circulatory device for separating substances in bodily fluids, especially blood, and the use of said device |
| US20150132312A1 (en) * | 2012-05-14 | 2015-05-14 | Children's Medical Center Corporation | Systems and methods for extracorporeal blood modification |
| US20150246170A1 (en) * | 2011-06-14 | 2015-09-03 | Hangzhou Everlong Biotechnics, Co., Ltd. | Target-directed, magnetically enhanced system for detoxification of patients |
| CN107141468A (en) | 2017-06-16 | 2017-09-08 | 四川大学华西医院 | A kind of long circulating iron chelator responded with pH |
| CN107281498A (en) | 2017-06-16 | 2017-10-24 | 四川大学华西医院 | A kind of polyethyleneglycol modified iron chelator |
| RU2696981C1 (en) | 2019-05-24 | 2019-08-08 | федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр профилактической медицины" Министерства здравоохранения Российской Федерации (ФГБУ "НМИЦ ПМ" Минздрава России) | Determining human erythrocyte sensitivity to lysis with complement system activation on thrombin pathway |
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| WO2002026292A1 (en) * | 2000-09-28 | 2002-04-04 | Affina Immuntechnik Gmbh | Circulatory device for separating substances in bodily fluids, especially blood, and the use of said device |
| US20150246170A1 (en) * | 2011-06-14 | 2015-09-03 | Hangzhou Everlong Biotechnics, Co., Ltd. | Target-directed, magnetically enhanced system for detoxification of patients |
| US20150132312A1 (en) * | 2012-05-14 | 2015-05-14 | Children's Medical Center Corporation | Systems and methods for extracorporeal blood modification |
| CN107141468A (en) | 2017-06-16 | 2017-09-08 | 四川大学华西医院 | A kind of long circulating iron chelator responded with pH |
| CN107281498A (en) | 2017-06-16 | 2017-10-24 | 四川大学华西医院 | A kind of polyethyleneglycol modified iron chelator |
| RU2696981C1 (en) | 2019-05-24 | 2019-08-08 | федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр профилактической медицины" Министерства здравоохранения Российской Федерации (ФГБУ "НМИЦ ПМ" Минздрава России) | Determining human erythrocyte sensitivity to lysis with complement system activation on thrombin pathway |
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