KR20190076107A - Kit for Diagnosis to Measure Heavy Metal Magnetism in Human Body and Production Method of Nano diamond Complex for Eliminating Heavy Metal Magnetism - Google Patents

Abstract

The present invention relates to a kit for measuring a magnetism level of a heavy metal in a human body for early diagnosis and prevention of nervous diseases, and a method for preparing a nanodiamond complex for removing a heavy metal magnetic substance thereof, and more particularly, to a kit for determining whether a binding material between at least one transition metal selected from the group consisting of aluminum, manganese, nickel, and iron in a sample is present as a magnetic substance by thermally treating at least one sample selected from the group consisting of blood, cerebrospinal fluid (CSF), hair, and urine of a human body. Accordingly, the magnetism level of a heavy metal in a human body can be measured by a complex when the kit of the present invention is used, and a magnetic substance of a heavy metal in vivo can be removed by using the nanodiamond complex of the present invention.

Description

TECHNICAL FIELD [0001] The present invention relates to a kit for measuring the degree of magnetization of heavy metals in human body for early diagnosis and prevention of neurological diseases such as dementia, and a method for producing the nanodiamond complex Complex for Eliminating Heavy Metal Magnetism}

The present invention relates to a kit for measuring the degree of magnetization of a heavy metal in a human body for the early diagnosis and prevention of neurological diseases such as dementia and a method for preparing the nanodiamond complex for removing the heavy metal magnetic substance. More particularly, To an early diagnosis method and a method for manufacturing a nanodiamond composite for removing a heavy metal magnetic substance for treating a nervous system disease by removing the magnetic heavy metal.

According to the 2014 statistics, more than 600,000 of the elderly in Korea are suffering from dementia, and as the aging process progresses, it becomes even worse. By 2030, there will be more than 1 million people. The loss is expected to be more than a trillion won. In the United States, more than 3 million people, more than 30 million people worldwide with dementia, is the science of the 21st century.

Dementia is a word derived from Latin and has the meaning of being "lost in spirit." When the intellectual ability is not enough from birth, it is called "mental retardation", whereas the person who has normal life of dementia gradually decreases the cognitive function as the brain function is impaired. . Here, cognitive function refers to various intellectual abilities such as memory, language ability, time and space grasp ability, judgment ability and abstract thinking ability, and each cognitive function is closely related to a specific brain region.

The causes of clinical syndrome such as dementia are about 70 cases. Among the various dementias, Alzheimer's disease and vascular dementia are the most common. However, degenerative brain diseases such as Lewy bodies dementia and Parkinson's disease and dementia can be caused by various causes such as hydrocephalus, head trauma, brain tumor, drug poisoning and infectious diseases.

Alzheimer's disease (AD), a representative example of senile dementia, can be caused by a variety of causes. The human brain weighs about 1.5 kg and has about 10 billion (10 ¹¹ ) neurons. The gap between these neurons is connected by synapses, and the number of these synapses is 10 It reaches 100 trillion (10 ¹⁴ ). Neurons in the neurons are called axons, and the lobes have a bundle structure consisting of microtubules (microtubules) as a pathway for communication between neurons. A substance called tau protein is called a microtubule structure .

The tau protein is a protein-binding joint (T-shaped) in the tube and regulates Ca ²⁺ transport function. However, when Alzheimer's occurs, tau protein, which acts like a T-shaped fastening bolt, breaks away from a microtubule, and these detached tau proteins condense to form a neurofibrillary tangle. The breakdown of tau protein is associated with the deposition of beta amyloid.

Amyloid does not have a significant effect on the solubility in the case of monomers but when they form amyloid fibrils and form plaques, they become insoluble toxins, And can break the axon.

The brain is very vulnerable to the oxidizing atmosphere, and oxidative damage causes blood circulation disorders.

Calcium channel in microtubule is an important element of information transmission, but calcium channel abnormalities are known to cause tauopathy such as Alzheimer's dementia (AD) and frontotemporalobar degeneration (FTLD). Typically, Ca-dependent processes, redox active metal-rich catalytic iron, auto-oxidation of monoamines, glutamate excitotoxicity, limited antioxidant and repair capacity (low catalase, mitochondria lack catalase) And the production of ROS and cyto-toxicity.

In the old age, unlike the mature stage, in addition to the lateral nucleus, the tau protein is also found to be phosphorylated in the striatum, which is involved in motor function and decision making. The tau protein binds to a large amount of phosphate molecules, The microtubule swells up, fails to function, comes with a breakdown of the neurite, and the broken protein is transformed into a fibrous mass. (&Quot; Molecular Neurodegeneration ", dated October 31, 2014).

So far, the cause of dementia has been linked to the phosphorylation of beta amyloid and tau protein and has been focused on eliminating or reducing them. In other words, they can concentrate on genetic variation of protein. However, by tracking the onset of twin Alzheimer 's disease, environmental factors as well as genetic factors are important. Dementia caused by genetic mutation is about 5%, and genetic factors are caused by the fact that human beings survive on the earth for millions of years while genetic feat is caused by the principle of survival of the fittest And the environmental factors seem to play a larger role in the present.

On the other hand, when the brain is blocked from the outside and thoroughly protected, the importance of the blood brain barrier (BBB) has already been confirmed from the 19th century by staining all the organs except for the brain, The structure was confirmed to pass only some substances such as sugar, oxygen, water, Na and K ions, and growth hormone. Mammalian brain structures are basically similar, and anatomical studies of rabbits, sheep, and rats show that cerebrovascular (BBB) - oxygen and nutrients from the capillary are supplied and cerebral spinal fluid (CSF) It is a structure that covers and protects the entire brain.

In humans, CSF produces about 500 ml per day (a pet bottle) per day, washing the brain about four times a day, and CSF is connected to the kidney along the lymph nodes that are connected to another CSF-lymphatic barrier. For example, the dopamine precursor L-dopa, a treatment for Parkinson's disease (PD), is less toxic than 2% of the BBB transit rate in brain drug delivery It is important to secure an alternative drug delivery system.

In addition, studies have shown that dissociating the brains of Alzheimer's patients results in higher levels of essential ionic metals, such as copper, iron, and zinc, than healthy individuals, and acts as a risk factor for Alzheimer's disease (Lee et al., 2002 (2006), and Barnham & Bush (2008). The results of this study are as follows. In particular, copper ions accumulate in the brain hypothalamus and hippocampal region of AD patients. In the case of PD, iron ions accumulate in the substantia nigra producing dopamine.

In the case of AD patients, osteoporosis accompanied by hip fracture is the most vulnerable hip fracture in the skeleton, making normal life more difficult. As a result of dissecting the pelvis bone, aluminum prevents bone loss and bone loss, Of the population.

Skepticism is emerging around a protein called beta amyloid, the cause of dementia. According to the recent world-renowned cranial nerve research and pharmaceutical industry, the existing hypothesis that beta amyloid plaque is the main cause of dementia is being questioned.

When the brain of a patient with dementia is dissected, copper, iron, and aluminum are accumulated, and beta amyloid and tau protein are present above a certain level. There have been many studies that manganese and aluminum will cause neurological diseases, but the cause of the harm is not clear. In particular, phosphorus is deposited around the tau protein, which may be the cause of lack of calcium and lack of nutrients such as sugar supplied to the brain. Furthermore, what is the cause of the electrochemical reaction in the brain that causes dementia? Has been studied extensively in many countries around the world, but there are not many magnetic or electrochemical studies.

The binding of amyloid protein to the transition metal in the brain has been shown to promote the phosphorylation and fibrosis of iron (Fe) or aluminum in combination with aluminum. In particular, the marked progression of phosphorylation to amyloid proteins bound to aluminum shows a close relationship between AD progression and aluminum metal. (S. Bollognin, et al., 2011)

Amylotrophic lateral sclerosis (ALS) or motor neuron disease (ALS) occurs in the southern Kii Peninsula in Japan. This region is rich in calcium and magnesium in the soil and high in manganese and aluminum, Many patients with ALS are known. This phenomenon is known to have occurred in the southern part of Guam and the US territory of the Pacific. In other words, there is a lot of accumulation of aluminum in common, and manganese is also analogous to some action. It is also known that the proportion of dementia patients in Jeju Island is high.

A study in Bangladesh has reported that children with drinking manganese-rich drinking water have been inhibited in their brain development (Wasserman et al., 2006). Similar studies in Canada have shown that when manganese accumulates in a child's hair, (ADHD), and manganese accumulation in children is adversely affected by calcium and iron metabolism, which can damage the blood brain barrier, leading to severe brain It has been reported that it can cause disease. (Bouchard et al., 2007)

On the other hand, there are three symptoms of delirium, depression, and dementia in patients with brain injuries. Although the cause of delirium has not yet been clearly elucidated, it is reported that it is associated with heavy metals (Hg, Pb, As, Cd) (Lactoferrin) is found to be a large amount of iron ions can have a bad influence on neurons can be guessed. (Kawamata et al., 1993; Leveugle et al., 1994; Faucheux et al., 1995)

 All neurons are connected to the brain, and signaling within the cell must activate the calcium channel. If the axon that carries the information (movement of the actual electron) is abnormal, the neuron does not function properly If false information is given, apoptosis of neuronal cells, loss of bone in bone regeneration, destruction of rheumatoid cartilage in the knee joint, cancer of major organs, It is presumed to be the cause.

Accordingly, the present invention has been made in view of the fact that a trace amount of heavy metals in the human body can cause dementia, Parkinson's disease, depression, and the like by disturbing the nervous system by becoming a binding magnetic body. (NiFeMnAl complex) and iron (Fe), or a metal aqueous solution such as those in which the heavy metal is adsorbed to a gelled or manganese porous material, may become amorphous, such as an alloy state, A diagnostic kit for measuring the accumulated amount of a substance in a human body, and a nanodiamond composite for removing the magnetic substance, and using the same for early diagnosis / prevention of various neurological diseases, the present invention has been completed.

It is an object of the present invention to provide a neuroprotective agent capable of inducing various types of neurological diseases that can occur in the human body, such as dementia, Parkinson's disease, depression, as well as a high degree of life phenomenon such as Down syndrome which is a chromosome amyotrophic abnormality, Is also the cause of disease.

Another object of the present invention is to provide an industrial application method of nano-heavy metals such as iron, manganese, and aluminum ferromagnets produced by heat treatment of blood, and to provide an eco-friendly medical waste treatment method.

Specifically, the object of the present invention is to provide a kit for measuring the degree of magnetization of a heavy metal in a human body and a method for preparing the nanodiamond composite for removing the heavy metal magnetic substance for early diagnosis and prevention of neurological diseases.

In order to achieve the above object, the present invention provides a method of treating a sample comprising at least one sample selected from the group consisting of aluminum, manganese, nickel and iron in the sample by heat treating one or more samples selected from the group consisting of blood of a human body, CSF, hair and urine A kit for judging whether or not a binding substance between two or more transition metals is present as a magnetic substance is provided.

The present invention also relates to a method for preparing a chitosan or curcumin, which comprises preparing chitosan or curcumin as a hollow porous spherical substance to remove a magnetic compound in the human body, or preparing a nitrogen doped nano diamond frame as an injectable material and coating or mixing the chitosan or curcumin, An injecting agent for eliminating heavy metals is provided.

1) introducing nitrogen into a detonation diamond; 2) heat treating the nitrogen-injected nano-diamond in air at 700 ° C for 1 hour to separate impurities from nitrogen-doped diamond (NDD); 3) preparing porous nanodiamond by mixing the NDD and diamondoids (diamondoids) into a nanogel; 4) In the frame of the porous nano diamond, removing a heavy metal in the body including a substance useful for the human body including a natural dyeing material selected from the group consisting of chitosan, gardenia, chitosan, curcumin, The present invention provides a method for producing an injectable therapeutic agent for a neurological disease.

The present invention also provides an apparatus for injecting heavy metal removal injecting agent into a blood using a green laser and tracking whether the nanodiamond is effectively chelated by binding to heavy metals in brain or human body .

The present invention relates to a method for treating a sample comprising at least one substance selected from the group consisting of aluminum, manganese, nickel, and iron in the sample by heat treating one or more samples selected from the group consisting of blood of a human body, CSF, hair and urine, Is provided as a magnetic body.

In a kit according to the present invention, the kit may be used for the treatment and / or prophylaxis of neurological diseases including senile dementia, senile dementia, depression, cerebral apoplexy, cerebral neuropathy including autism and asthma, and osteoporosis, renal failure (CKD), atopy, diabetes type 2, It is preferable to diagnose at least one disease selected from the group consisting of diseases that can be caused by abnormalities of the metabolism or biochemical function of the body including rheumatism.

In addition, in the kit of the present invention, the kit is characterized in that the binding substance between the transition metals acts on physiologically active substances including acetylcholine, insulin, calcium ion regulatory factor calcinarin, Reelin cerebral neuronal cell growth promoting factor, It is preferable to utilize the sample as a bio-marker for judging whether or not it interferes with the normal activity of the body, and the sample is heated by heating the sample at 80 DEG C or less for 5 hours or more, , And then heat-treated at 300 to 400 ° C for about 4 hours in an electric furnace to decompose the protein.

The present invention also relates to a method for preparing a chitosan or curcumin, which comprises preparing chitosan or curcumin as a hollow porous spherical substance to remove a magnetic compound in the human body, or preparing a nitrogen doped nano diamond frame as an injectable material and coating or mixing the chitosan or curcumin, An injecting agent for eliminating heavy metals is provided.

1) introducing nitrogen into a detonation diamond; 2) heat treating the nitrogen-injected nano-diamond in air at 700 ° C for 1 hour to separate impurities from nitrogen-doped diamond (NDD); 3) preparing porous nanodiamond by mixing the NDD and diamondoids (diamondoids) into a nanogel; 4) placing a beneficial material including a natural dye selected from the group consisting of chitosan, gum, chitosan, curcumin, jojoba and safflower into the frame of the porous nano-diamond to remove heavy metals in the body The present invention provides a method for preparing a therapeutic injection.

In the method for preparing a therapeutic agent for treating neuropathy according to the present invention, the nanodiamond is preferably 5 nm in size, and the nanodiamond is preferably prepared by a nitrogen ion implantation method.

In addition, in the method of manufacturing an injection for treating a neurological disease according to the present invention, the porous nanodiamond in the step 3) is coated with a platinum group catalyst containing Pd and Ru in a porous frame to smoothly metabolize the brain desirable.

The present invention also provides an apparatus for injecting heavy metal removal injecting agent into a blood using a green laser and tracking whether the nanodiamond is effectively chelated by binding to heavy metals in brain or human body .

In the device of the present invention, the device preferably tracks the presence of nanodiamonds in cerebrospinal fluid.

In addition, the present invention provides a diagnostic kit and apparatus for use in early diagnosis of AD, which comprises the step of separating the nucleus, amyloid protein, or red blood cells and albumin from the blood, do.

The present invention sees that the cause of the dementia may be caused by some kind of malfunction of the working principle of the nerve cell that transmits various signals of the brain or the body. It is a substance which can interfere with malfunction or nerve activity, We have identified the magnetizable material as one of the causes.

Specifically, the present invention describes the effects of heavy metal manganese, copper, iron, and aluminum on human brain, especially in the brain, from the viewpoint of material science, information transfer (actual electron movement) Treating blood of a patient by measuring a trace amount of heavy metal magnetic substance which can be a magnetic substance, thereby diagnosing neurological diseases early, and providing a method for developing and treating such a magnetic heavy metal removal technique.

One of the methods of the present invention is to replace substances such as plaque or gelled substances in the brain that are dangerous to become magnetic substances by cleaning or ionizing them into essential protein useful for the body. A porous nanodiamond composite is prepared by mixing chitosan and curcumin to clean the brain while capturing heavy metals.

<Blood analysis>

Since the magnetic body in the brain seems to accumulate because it can not pass through the BBB, the present invention is based on the assumption that heavy metal magnetic substances are accumulated in the brain and a magnetic component is present in a small amount in the blood. Especially, manganese aluminum (MnAl) and copper aluminum ) Are thought to be in the form of ions such as red blood cells and ferritin (nano cage protein for Fe ion). In the ferritin nano cage, divalent metals such as Cu ⁺² , Mn ⁺² , Zn ⁺² , Pb ⁺² , and Cd ⁺² are stored, and the aluminum in the blood of AD seems to accumulate in the ferritin. Especially, hemoglobin (Hgb) in the red blood cells is not magnetic in the oxygen-absorbed artery, but it can be absorbed iron, aluminum and manganese ions because it is magnetic in the vein. Analysis of morphology of blood erythrocyte (RBC) in AD patients shows that there is a problem that oxygen supply is not adequately provided due to severe deformation. As shown in FIG. 2, the donor-shaped healthy person's red blood cells are about 15% longer in length than the red blood cells. major effects on the morphology of erythrocytes in Alzheimer's disease J. Bester 2013)

One of the key points of the present invention is the heat treatment of blood, in which about 3 ml of blood is heated at 80 ° C or less for 5 hours or more, the water is completely evaporated and then heat-treated in an electric furnace at 300 to 400 ° C for about 4 hours to decompose proteins do. In this way, a small amount of distilled water is added to the as-heat-treated ash to separate the moving material from the magnet.

As the material which can be magnetized in the material heat-treated with blood, erythrocyte iron is the most important substance. Specifically, the oxides include iron, manganese oxides (Fe ₂ O ₃ , Fe ₃ O ₄ , MnO ₂ ) and intermetallic compounds such as iron, copper, manganese and aluminum compounds such as Heusler compounds (FeMnAl, Cu 2 MnAl) FePO ₄ , FeAlPO _4, Fe ₃ S _4, and the like. As a result of X-ray diffraction (XRD) analysis of magnetic metallic materials, Ni (FeMn) Al ferromagnetic Magnetic Heusler compound was mixed with ferrihydrite (Fh) in the form of iron dissolved in distilled water (See Figure 1 below).

(Ash) with natural dyes (eg, gardenia, chitosan, curcumin, safflower, and jojoba), and coloring chromaticity can be quantified with a light analyzer (CIE). Iron, copper, and aluminum act as a mordant, and anionic hydroxyl groups such as chitosan accelerate bonding with metal ions to facilitate coloration. A natural substance known to be good for Parkinson's disease such as adamantane and sodium safflower is a chelating agent that can capture a metal ion. One of the present invention is a protein that binds to a metal ion To normalize the enzymatic and catalytic functions of the enzyme and regenerate vital life phenomena.

Magnetic flux density is measured by Mossbauer, SQUID, etc. However, since it is required to cool down to near absolute temperature, it is expensive and it takes much time to obtain measurement data. Therefore, we tried to measure the intensity of magnetic materials by measuring the polarization of light in the magnetic field. To understand the components of the MnAl super-ferromagnetic substance, a phenomenon in which the magnetic substance is polarized in accordance with the intensity of the magnetic field under the magnetic field is applied so that the magnetic substance powder has the nitrogen atom of the amine group on the polyacrylamide (PA) And the shape of the deformed elliptical shape can be observed.

According to one recent experiment, when a small amount of aluminum hydroxide (Al (OH) ₃ ) is added after mixing iron ions (Fe ⁺³ ) with amyloid beta protein, iron ions are reduced to two from trivalent by the catalytic action of aluminum Iron ions can be in the form of a mixture of bivalent and trivalent and have magnetite (Fe ₃ O _4, magnetic). (J. of the Royal Society; Evert et al., 2014).

Aluminum is known to penetrate well into the body to perform the major organs or functions of life phenomena such as brain, bone, red blood cells, and nucleus nuclei. In particular, aluminum entering the brain was found to adhere well to the DNA of the neuronal nuclei in the hippocampus, damaging the DNA repair function. (C. McLachlan Review; Aluminum and Alzheimer disease; 1986) It is also known that the concentration of aluminum in the ferritin of AD patients is five times higher than that of healthy individuals. (F. Joshi: Ferritin: isolation of aluminum-ferritin complex from brain. Proc Natl Acad Sci USA 1987)

Aluminum enters the calcium ion site in the nucleus and damages the DNA break. In particular, DNA damage occurs intensely in the Guanine rich sequence, and DNA fragments appear in the urine.

Aluminum is atomic number 13, and there are three electrons in the p orbit, which can be weak magnetic material. Aluminum ions dissolve in water and are absorbed well into the brain by alkaline aluminum hydroxide (Al (OH) ^-4 ).

Manganese ions also pass through the BBB and enter the brain. Manganese (Mn) has no magnetic property when manganese is bonded to each other, but it is bound to other transition metal (s) Strong magnetism can occur in the poem, which can interfere with electrochemical reactions in the brain.

There is much controversy about the safety of vaccines, especially in the United States. In other words, the safety of the vaccine is a problem, and there is a resistance from the parents whether they should fit their child. Aluminum adjuvants, which are essential for the vaccine, have been considered as indispensable for some function of the immune system, such as maintaining the efficacy of the vaccine for a long time. Since the vaccine was first applied to smallpox in the 1920s, hepatitis AB , Diphtheria and other infectious diseases have been used for more than 80 years, but in recent years, the growing number of autism children in the United States is arguing that aluminum is the cause of the vaccine supplements. There was much controversy about the Gulf War Syndrome (GWS) in the Gulf War soldiers in the United States. These soldiers were said to have received 17 inoculations, which seems to be caused by the injection of excess aluminum in the vaccine bell. According to the World Health Organization (WHO) 2001 report, ginseng saponin has been studied as a substitute, but it has not been found to be equivalent to aluminum hydroxide (Al (OH) ₃ ) as an adjuvant in terms of efficacy and price .

In a recent experiment, a nitrogen-doped nanodiamond (NVD) was applied to an aluminum supplemented vaccine and injected into a mouse, which was found to accumulate in the brain 21 days later (Fluorescent nanodiamonds as a relevant tag The experiment showed that the injected aluminum adjuvant vaccine in the muscle spontaneously spread from the spleen to the whole body and slowly accumulates in the brain, albeit in small quantities. Lord, it seems to be an important experiment. In addition, it is very meaningful that it is very difficult for many therapeutic drugs to pass through the BBB, which shows the possibility of passing the BBB through the nanodiamond.

<Nervous system brain diseases such as depression>

Another achievement of the present invention is that the Ni (FeMn) Al superparamagnetic Magnetic Heusler compound is seen in hematological analysis in both patients with dementia and depression, and that such a ferromagnetic substance may cause various brain diseases such as depression It is a proven thing. According to the World Health Organization (WHO), there are estimated 120 million depressive patients worldwide by 2013.

When a transition metal such as iron (Fe) or manganese (Mn) is bonded to aluminum, the electron spin state of the outer d-orbital may be changed to become ferromagnetic. Especially in the case of Cu ₂ MnAl, for example, in the case of Cu ₂ MnAl, each element does not have magnetism. However, due to the mutual influence of the external electrons of the atom, it becomes a ferromagnetic substance called Heusler compound.

The manganese (Mn) element is an atomic number 25 transition metal, and there are five electrons in the d orbit. Each of these five external electrons occupies orbits and can have a strong spin, but in the natural state manganese (Mn ⁺² ) ions combine to form a stable structure (no magnetism) by filling 10 electrons in the d orbit It has a strong property and eventually tends to become a massive form. For example, manganese nodules in the Pacific Ocean (5000 m; 500 atm) are expected to grow to 10 ㎝, taking several hundreds of millions of years and aggregating less than 1 nm per year. The components include copper, nickel, iron, aluminum and silica SiO ₂ sand content) is about 5%.

The natural magnetite is sintered at about 700 ° C. since the compound starts to form at a temperature of 300 ° C. or higher, and the synthesis temperature of manganese aluminum (MnAl) is also 150 ° C. Therefore, It can be considered that as time elapses, it gradually grows into crystals and grows. At the ends of the actual synaptic neuron, 10 or more copper and zinc ions, like a battery, maintain their electromotive force.

In the case of senile dementia, at the age of 70 years, it is estimated that dozens of iron or manganese atoms were assembled into a porous composite. In this case, the manganese may be aggregated or combined with iron hydroxide to have a cluster-like porous structure, and it is presumed that divalent metals such as Cu, Fe, and Zn are filled in these pores. In ionic receptors such as blood (more than 70% of blood), it tends to become a gel state, and these metal ions are presumed to be adhered to pores in the aqueous solution. (See FIG. 3)

Aluminum ions (Al ⁺³ ) are similar in size to iron ions (Fe ⁺³ ) and manganese ions (Mn ⁺³ ) Position is substituted with Al ion and is similar to the crystal structure of the iron hydrate. Parkinson's disease is a neurological disease caused by toxicity due to the combination of aluminum and manganese ions. Parkinson's disease (PD) is slowed down by dopamine deficiency and is accompanied by motor neuron damage such as hand tremor, excessive aluminum and manganese accumulate in the substantia nigra, a dopamine-producing nerve cell in the brain, (Parkinson, 2003). In Korea, the number of patients with Parkinson's disease is estimated by the National Health Insurance Corporation (NHIC) in 2014. According to this patent, ADHD is a neurological disorder that occurs in dopaminergic neurons in patients with autism, which is less severe than AD patients, which are reported to be 80,000 or more. In other words, the cause seems to be the same.

The intermetallic complexes are not usually conditions that can cause a chemical reaction at room temperature, but they may have magnetic properties like amorphous crystals like ferrihydrite dissolved in water, It can be said that it can move like a compound without a reaction, and therefore, if it becomes a magnetic substance substance which can interfere with the surrounding biochemical action, it can disrupt the elaborate electronic information exchange action in the brain.

The aluminum transition metal compound, which is well attached to the DNA chain structure in the brain, especially the nerve cell nucleus, causes various damages to DNA and confuses the channel Ca ^{+ 2} , It eventually breaks the ion balance of neurons, interferes with the intracellular signal transduction mechanism, tau protein relaxation → calcium channel collapse → accumulation of beta amyloid protein.

In addition to autism and epileptic seizure, which are mostly seen in children, central nervous system abnormalities such as depression, bipolar disease, and schizophrenia are slightly different depending on the site of expression The cause of similar brain disease symptoms that interfere with intellectual activity seems to be the brain's vulnerability to the oxidative stress environment. Recently, epilepsy (commonly called epilepsy) is known to be an incurable disease, but actual genetic cause is less than 1%, which causes many abnormalities in the brain's electrical current, causing seizures, seizures, and stunning. There is a small capillary rupture (a kind of microstroke).

Down syndrome (DS) is a chromosome 21 at the time of meiosis should be a pair of normal chromosome 3 is expressed in the abnormal phenomenon and delayed life is not known to be over 40 years. It is also characterized by leukemia (leukaemia) and symptoms similar to AD, which is a neurological disease. The aluminum absorption of parents of DS patients was 6 times higher than that of healthy individuals. Biol Psychiatry A unique phenomenon is that the high absorption of aluminum by these parents is associated with chromosome 21, which is associated with the digestive system, and this chromosome 21 is associated with the digestive system There is also an expression of amyloid protein.

Chromosomes are usually self-repairing and have been known to repair some of the damage themselves. The number of causes that can cause irreversible damage to the chromosome may be numerous, but the present invention is concerned with damage caused by heavy metals, particularly aluminum, which is well penetrated into the DNA of the nucleus. There are hundreds of thousands of mitochondria in the oocyte, and the process of rearranging DNA double helix seems to cause anomalous magnetic phenomena in the process of high electric and electron transfer.

&Lt; Acetylcholine resistance &

It is known that the concentration of acetylcholine (ACh) in the brain of dementia patients is about 50% higher than that of healthy people, and that the core substance of brain information transmission is absolutely insufficient. Actual AD dementia can be a major index for the early diagnosis of AD disease, with its onset gradually spreading beyond the ACh starting from the hippocampus toward the frontal lobe associated with memory storage.

Referring to FIG. 8, it is shown that there is a close relationship with the decrease of acetylcholine (ACh) neuronal activity, which diffuses from the hippocampus, which is the basal portion of the brain, to the frontal lobe.

Alzheimer's (AD) dementia has been regarded as a toxic protein beta amyloid plaque (SP) formed on the surface of nerve cells, but this is a result of other causes due to many problems in the hypothesis. (The Pathogenesis of Alzheimer's Disease: A Reevaluation of the "Cascade Hypothesis" by R. Armstrong 2011)

The ACh resistive phenomenon appears to be caused by a problem in the signaling pathway in the ACh receptor on the cell wall, which is not properly transmitted or is caused by a false signal. The production of beta amyloid protein also appears to be the same concept. (Fisher A. Cholinergic modulation of amyloid precursor protein processing with emphasis on M1 muscarinic receptor: perspectives and challenges in treatment of Alzheimer's disease. J Neurochem 2012)

In other words, beta amyloid protein is formed due to imperfections or fatal defects of various biochemical reactions occurring in nerve cells, which appear to accumulate on the surface of nerve cells. In this respect, although there have been many studies under the hypothesis that ACh choline resistive is related to progress of dementia, it is difficult to measure acetylcholine in the blood and thus it is difficult to use it as a bio-marker. In the present invention, We will use the VAChT (Vesicular acetylcholine transporter) measurements in the transporter sector, which are known to be the most vulnerable during storage → transport → regeneration, and here we will use the role and activity of mitochondria as bio-markers. The importance of mitochondria is emphasized here because the mitochondria involve acetylcholine transport (S. EFANGE, et al., Vesicular Acetylcholine Transporter Density and Alzheimer's Disease 1997) A DNVMRI method using doped nanodiamond as a contrast agent, and the like can be used.

Mitochondria is responsible for energy production, which is the basis of life phenomena. Mitochondria are believed to have come from the genetic evolution of primitive life forms, such as iron bacteria, which are symbiotic with life forms of animals, and of course have their own nucleotides and genomes (DNA) It is known that the process itself (ATP production), which is very fragile and decomposes the sugar and produces energy, is a highly chemical process and therefore very vulnerable to surrounding conditions. In particular, synapses at the nerve endings, which are responsible for the supply of energy (electrons) for all activities that produce, transmit, and transmit neurotransmitters, are exposed to severe oxidative stress in the cell, have. (P. Coskun Systemic mitochondrial dysfunction and the etiology of Alzheimer's disease and Down syndrome dementia. J Alzheimers Disease 2010)

Mitochondrial DNA (mtDNA) is found to be much more vulnerable to oxidative environment than DNA in the nucleus, and apoptosis (programmed cell death) is a phenomenon in which calcium enters into cells and mitochondria are degraded, Most of the copper and manganese present (as active oxygen scavenging enzyme (MnSOD)) accumulates in the brain and appears to cause serious problems.

On the other hand, the microglia cell (MG), which is mainly located in the brain, performs the function of repairing and repairing axon of the neuron while having immunity function such as leukocyte, Were found to be more than normal. In particular, the accumulation of microglia in the core base of the brain from the hippocampus to the limbic system is significant, and in 2011, according to Yale University, amyloid precursor (APP) attached to the capillaries of the brain, And a microstroke that gradually spreads to the entire brain.

Copper, zinc and manganese trace metals in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS), more commonly known as lugeer's disease, were found to be higher than those of normal controls. The reason for the high copper ion is presumed that the cytochrome c due to mitochondrial cell death is decomposed, resulting in a large amount of copper ions. (Melo et al. 2003, Manganese, copper, Zinc in CSF of Multiple Sclerosis, J. of Biological Trace Element Research)

Another example of excessive accumulation of iron and copper is bipolar disease and schizophrenia. It has been reported that iron and copper ions are accumulated in oligodendrocyte (OL), a kind of glial cells in brain of these patients. OL plays a protective role of neurons in the myelination (coating of copper wires), which causes the microglia to attack the brain nerve cells excessively (R. Blaylock, Aluminum Induced Immuno-excitotoxicity in Neurodevelopmental and Neuro-degenerative Disorders 2012) seems to be linked to oligodendrocyte cell death, which leads to synergistic disease. Especially in childhood when growth is terminated, brain cerebral fluid barrier (BCFB) is weak in the early childhood, the brain barrier (BBB) is weakened, seems to be in childhood.

<Calcium homeostasis>

Calcium ions (Ca (+2)) are known to be high in the blood and cells of AD patients. Calcium ions in the body are bound to 99% protein and only about 1% is in the form of free Ca (+2) ion. Increasing free Ca (+2) ion is fatal to cells. Calcium ions are used as a signaling pathway between intracellular nuclei and extracellular blood, as well as bone formation, and as a major component of the calcium channel (calcium channel) in neurons, as well as biochemical enzymes. Calcium ions have to be tightly controlled, and calcineurin (CN) physiologically active substances play the most important role in regulating the calcium in the cells. In the case of AD patients, calcium and CN in the cells are present in excess , Which can cause macrophages (immune cell T cells) to become autoimmune abnormal states that attack stimulating neurons.

In the early stage of AD, CN is expressed intensively in the hippocampus, and NFAT1 (Nuclear Factor Activated T cell 1) is also expressed in many of the immune system inducing apoptosis. In addition, the over-production of beta amyloid protein, which is an important problem of dementia, is mainly related to Golgi-ER-DNA of neurons. Especially ER (endoplasmic reticulum) stores mainly calcium. And a vicious cycle in which an excess of calcium in the cells comes along with the generation of beta amyloid. (K. Cheung, Mechanism of Ca2 + disruption in Alzheimer's disease by presenilin regulation of InsP3 receptor channel gating 2008) (L. Reese et al. A Role for Calcineurin in Alzheimer's disease 2011) K. Baumgartel et al. Neural functions of calcineurin in synaptic plasticity and memory 2012)

It is known that the DS disease is usually accompanied by AD symptoms similar to those before 40 years of age and the condition is worsened. DS patients do not have cancer, whereas in the case of kidney transplant patients, It is said that it does not get dementia when administering CNI (calcineurin inhibitor). This suggests that an adequate level of immune system is important for maintaining health. On the other hand, in patients with DS, serum calcium ion concentration and CN level are higher than those of AD patients. Unusual phenomenon is that the calcium regulator is located on chromosome 21 in question. (M. Mattson et al., 2002) .beta-amyloid precursor protein metabolites and loss of neuronal Ca2 + homeostasis in Alzheimer's disease 1993)

The main point of the present invention is to diagnose and prevent the onset of AD as early as possible. In this respect, it is suggested to measure the factors related to calcium ions such as blood, hair, urine and the like and to diagnose the onset of AD disease early. (A. Jawarska et al., Analysis of calcium homeostasis in fresh lymphocytes from patients with sporadic Alzheimer's disease or mild cognitive impairment 2013)

Many studies have found that aluminum accumulates intensively in the hippocampus of AD patients. In particular, there is DNA deformation in the motor neurons of the hippocampus, and deformation is observed in the region where the guanine expression is concentrated in the helical structure of DNA. (Al ⁺³ ) radius of 54 ppm, which is less than the calcium ion radius (64 ppm), which can easily be substituted, and a strong electron affinity It is believed that when aluminum is incorporated into calcium, which plays a role in strongly condensing DNA in the nucleus, and becomes magnetized, it is likely to cause transformation into DNA structure. Studies have also shown that chemicals such as glyphosate, a major component of herbicides, add toxicity more when added.

As described above, the aluminum ion is similar to the iron ion, so when it enters the place of the iron ion, the iron ion changes from +2 to +3 and biochemically acts, whereas the aluminum ion is +3, followed by oxidation- It causes a problem that it becomes an obstructing factor. In addition, if Ni and Cu free ions combine to form a magnetic body, they can cause serious problems. In addition, there are many Mn ions in the brain. Therefore, in order to use the degree of damage of DNA as a bio-marker in the present invention, a lymphocyte is separately cultured and toxicity test according to calcium ion change is performed.

In addition, the lymphocyte has a nucleus and a blood-treated metallic powder is injected. In particular, we want to observe the response of chromosome 21. It can be used not only for early diagnosis of AD but also for prevention of DS (see Fig. 12).

<Osteoporosis, renal failure, atopic dermatosis>

Osteoporosis (osteoporosis) is a common symptom in AD patients due to loss of bone tissue. Anomalies such as diving sickness and fractures, which occur well in divers who are professionally submerged in deep seas (10 to 20 meters), are also likely to be the same. The bones of osteoporosis patients are dissected, and the photographs showing the incisions can be seen on the aluminum-precipitated photographs. In other words, when more than 70% of aluminum is deposited in the bone (G. Crisponi et al. 2011), aluminum enters the iron ion site and interferes with the biochemical action, This leads to bone loss.

In addition to osteoporosis, it is known that CKD (Chronic kidney disease), which is caused by loss of function of the kidney, is also common in AD patients and pathological symptoms of CKD patients are similar. The majority of patients with CKD are worsened by cardiovascular disease (CVD), which is a mineral bone disturbance that causes calcification (fibroblast regeneration) Which is caused by the hardening of the wall of the blood vessel. (MBC-CKD) 2013). In the present study, we evaluated the relationship between pulmonary arterial pressure (PWV)

In another example where the bone marrow is directly associated with the brain, medical results have been reported that administration of acetylcholinesterase inhibitor (AChEI) to AD patients with injured pelvic bones improved bone regeneration. Acetylcholinesterase inhibitors and healing of hip fractures in Alzheimer's disease patients 2013 (ACh resistive) is considered to be the cause of AD because of the abnormality in the signaling pathway in the cell .

Similarly, atopic dermatitis is caused by a skin barrier system that is irritating to the immune system caused by heavy metals such as chemicals, nickel, lead, and mercury in the skin barrier system. .

Atopy dermatitis is a disease that has not yet been elucidated. So far, the cause is known to be an autoimmune disease leading to a genetic mutation of the filagrin knot binding protein that constitutes the skin barrier and skin cell destruction caused by immune system disruption such as immunoglobulin (IgE).

Tight junctions (TJ) and filaggrin, which are the major parts of the skin barrier, are the deformation of the Golgi body in the cell, which is electrochemically highly sensitive and transformed into cell keratin It is essentially a tissue cell sensitive to the surrounding electromagnetic environment. The BBB, which is the brain barrier, and the kidney corpuscle, as well as the collapse of the barrier wall, can cause serious diseases. In other words, kidneys can become kidney failure dialysis patients, and in the brain nervous system, depression can cause severe diseases such as bipolar disorder, autism, and asthenia.

In conclusion, atopic dermatosis seems to be caused by secondary infections in addition to various primary causes of damage to skin barrier, especially when children grow up, especially when they grow up, because skin barrier is easily opened to external stimuli such as chemicals.

According to the National Health Insurance Corporation data, the number of atopic patients in Korea is estimated to be about 930,000 (about 2% of the population), which accounts for about 50% of children under 12 years of age. It has recently been reported that adult atopic skin patients due to environmental factors such as fine dust exposure have been on an increasing trend.

The human skin is supposed to function as a primary defense against ultraviolet ray damage, but it also seems to be supplemented with a nickel atom protection mechanism. (The only mechanism that can absorb UV ultraviolet light is that the nickel atom is the only mechanism in the human body)

If the skin barrier is irritated and the skin barrier is damaged, it may cause atopic skin disease. Therefore, the atomic nickel-aluminum magnetic body complex, which is a key point of the present invention, is one of the causes of damage to the skin barrier This is a presumption that there is a trace amount of nickel element in the skin of atopic skin patients and also that in the treatment of atopic skin patients, coal tar was applied to the lesion in the past. In the coal tar, diamondoids (diamondoid) , Which separates this material and is used in Parkinson's disease (also known as adamantane) and acts as a chelating agent for heavy metals. In other words, the cause of illness can be considered to be the same.

<Similarity between Alzheimer's Dementia and Rheumatic Disease>

Calcinerin, an adequate regulator of calcium ions, appears in the hippocampus and frontal lobe of AD patients. It has been reported that patients with rheumatoid arthritis have abnormal cervical neuronal signaling, and that they are characterized by inflammatory cytokines and MMPs (Abdul AM, Cognitive decline in Alzheimer's disease associated with selective changes in calcineurin / NFAT signaling. J Neuroscience 2009)

Rheumatoid arthritis (RA) is a common disease that accounts for about 1% of the adult population and is known to be an immune system adverse event, but it is still a refractory disease with no clear cause of the disease (Braunwald et al., 2001) (The pathogenesis of rheumatoid arthritis I. Mclnnes et al, 2011),

The number of patients in Korea is estimated to be about 270,000 by 2015, and Japan is estimated to have about 700,000 people. Fibroblast like synoviocytes (FLS) are attached to knee cartilage As the disease progresses, the immune T cells and B cells develop due to the immune system attacking the self tissue, resulting in severe angiogenesis, (cancer) level of serious illness at present, prevention is the best way to prevent disease.

The bone marrow derived chondrocyte begins to fall off the bone at a very slow rate, and at first the round shape gradually transforms into a flat fibroblast (FB), which turns into a synovial membrane. Chondrocytes are transformed into fibroblasts (FBs) that support cartilage tissue. Originally, stem cells function in FB cells, which are stimulated by external stimuli. Is a pathogen of rheumatism.

Synovial fibroblasts from patients with rheumatoid arthritis have the ability to produce matrix metalloprotein (MMP) and cytokines such as IL-1β, IL-6 and IL-8, and many Studies have shown that mitochondria of chondrocytes are much weaker than normal and that they have been damaged by DNA damage. (V. Grishko et al.) Diminished mitochondrial DNA integrity and repair capacity in OA chondrocytes. Osteoarthritis and Cartilage 2009)

The iron and copper ions in the synovial fluids of patients with RA were found to be more than two times more than the normal ones. In other words, the mechanism of RA was destroyed by heavy metals in the early stage, The disease seems to worsen as the system works.

The cartilage is composed of about 80% water, so the liberated iron ions become ferritic when they are in ferrihydrite state, so they start to attack the cartilage by stimulating the FB and the disease seems to progress. The accumulation of excessive iron and copper ions may cause oxidative damage to the cells. Therefore, ceruloplasmin, ferritin, It is possible to measure the number and prevent disease. The excessive accumulation of iron and copper ions in the joint bones can stimulate the immune system and lead to excessive responses of the T cell, and the body as a whole can be used for brain, kidney, liver, spleen, etc. These data can be used as bio-markers. (Nanoparticles and Colloids as Contributing Factors in Neurodegenerative Disease Stephen C. Bondy 2011)

<Mitochondrial and early dementia screening>

Mitochondrial DNA (mtDNA) in AD patients has been known to cause many damages and cause apoptosis of neurons. (R. Steve et al.) Mitochondrial dysfunction and molecular pathways of disease 2007 Analysis of blood or urine in AD patients Mitochondria and inflammation-related proteins can be examined to determine the progression of inflammation.

Mitochondria are very vulnerable to the CO ₂ gas, excess CO ₂ gas around mitochondria, if soluble in water, as shown in the following reaction process, creating a cytoplasmic weak acid cause mitochondrial cell death (apoptosis), severe cell damage (cell damage) Lt; / RTI &gt;

CO ₂ + 2H ₂ O = HCO ₃ ^- + H ₃ O ⁺

When the cells in the body digest glucose and produce energy, carbon dioxide (CO ₂ ) and nitrogen oxide (NO) are produced as waste, and carbonic anhydrase (CA enzyme) _{2 &lt; / RTI &gt;} gas. The rest are transported by serum, some are recycled by adding calcium to bone regeneration, and are known to be used in the process of converting ammonia gas to urea in the liver.

Nitrogen oxides (NO species), like ROS, also have a negative effect on cells. Recently, a study by Nottingham University in England reported that CA II was found in the brain of PD patients (Amelia Pollard et al. , 2016). In other words, if the CO ₂ gas and the nitrogen oxide waste are not properly removed, the CA II enzyme appears to be spontaneously generated in the brain. If it is not sufficiently operated, serious brain cell damage will occur and epilepsy, AD, PD, ALS And the brain can cause such diseases.

It has been shown that platelets and DNA in AD patients are also severely impaired (P. Mecocci et al., Lymphocyte Oxidative DNA Damage and Plasma Antioxidants in Alzheimer Disease 2002) It can be said that the nerve cells are maintained by producing much. Many studies have shown that glucose metabolism has fallen to a significant level before normal amyotrophy. (Haxby JV et al., Neocortical metabolic abnormalities preceded non-memory cognitive defects in early Alzheimer's dementia. Arch Neurol 1986)

Around 360 million people worldwide are suffering from type 2 diabetes, and many people with dementia are known to have chronic kidney disease (CKD).

The above type 2 diabetes and CKD seem to be caused by abnormality in the signaling pathway in the cell. In the early diagnosis method, blood is centrifuged to separate red blood cells, platelets, lymphocytes and albumin, the ability to chelate and DNA damage caused by metal in order to diagnose / prevent dementia as early as possible and make it a bio-marker.

Platelet platelets are separated from megakaryocytes in bone marrow and lungs and transformed into amyloid protein precursors (APP) by degradation into macrophages after activity in blood for about 10 days (Figure 9 Reference)

On the other hand, the brain itself produces amyloid precursor (APP), which induces and protects neural cell growth in the fetus / infancy and is used for nerve cell repair as an adult. The amyloid precursor (APP) appears to be a metal chelating agent that secretes excess Cu (+2) and Fe (+2) out of the cell.

The amyloid protein in the brain is fundamentally similar in structure and function to APP isolated from platelets.

As shown in FIG. 10, the E2 domain also binds Fe (+2), Al (+3) and the like. Compared with the absence of Cu (+2) ions in the neurons, the extracellular copper ions and beta amyloid proteins are clustered, presumably due to the role of the free iron efflux transporter. The cleavage of the C-termianal domain across the cell membrane by secretase (scissors) results in the production of β-amyloid by APP misfolding, mainly due to ER stress and DNA transcription abnormalities.

The amount of beta-amyloid protein used as a bio-marker is usually very low (ng / ml), which is difficult and expensive to measure.

To solve this problem, the amyloid precursor protein (APP 770) was separated from the platelets of similar structure and function based on the above description. The heavy metal solution from the first blood analysis was used to bind the amyloid protein of the aluminum magnetic Heusler complex ion Is observed with an optical microscope (see Figs. 9 and 10)

Platelets and lymphocytes are derived from the bone marrow. In particular, the megakaryocytes, which are platelet-derived cells, have biochemical characteristics such as neurons, which can confirm the amyloid progenitor protein (APP) integrity. Therefore, for the early diagnosis of AD disease, cell activity can be tested with a magnetic substance detected in primary blood analysis by separating fibroblast, amyloid protein and DNA from platelets and lymphocytes in blood (see FIG. 11).

In addition, the blood lymphocyte has a nucleus, so DNA can be isolated from it to indirectly confirm the degree of DNA damage. In particular, it can be used as a biomarker to analyze the concentration of heusler magnetic bodies on chromosome 21, and can be used as a risk measure for Down syndrome (DS) (see FIG. 12) (Genotoxic effects of aluminum chloride in cultured human lymphocytes treated in different phases of cell cycle, P. Lima et al. 2007)

A health checkup can be done in the following way.

In the first step, the magnetic body in the blood is inspected using the kit of the present invention. Observe the metal complex attracted to the magnet by the naked eye. At this time, natural coloring agents such as gardenia, chitosan, curcumin, safflower, and jojoba can measure the degree of coloring with CIE color.

(II), Fe (II), and Fe (II) ions were investigated in the second step, and trace metals (trace element Fe, Cu, Zn, Mn, Ni, Co, Se) and toxic heavy metals Pb, Hg, Cd, (RBC) and albumin health and serum calcium and calcineurin concentrations in the blood. In addition, fibroblast culturing / calcium ion variation resistance is examined. Other tests include antioxidant capacity tests such as inflammation-related proteins (such as IL-6), glutathione and vitamin B ₁₂ , binding of aluminum ions to amyloid precursor protein (APP) isolated from blood platelets, blood urine nitrogen and creatinine counts, damage from DNA of the nuclei isolated from blood lymphocytes, and a detailed investigation of mitochondrial mtDNA damage (mtDNA degradation fragment in urine and Uric acid crystallization test), microglia and mitochondrial health. If the second overhaul is out of the reference value, the third overhaul will be performed (see Fig. 13).

The third stage is the CSF extraction, heavy metal and autoradiography test, the S-100 B protein level test, microglia and mitochondrial health test, DNV-MRI examination of major body organs (brain, kidney, pancreas, etc.) .

<Brain scavenging agent>

In the brain of AD patients, acetylcholine levels are low and damage to nerve cells using acetylcholine is prominent (see Figure 8).

The root cause of this phenomenon is the slow movement of acetylcholine transporase (ACheT), which transports polarized choline, to produce acetylcholine in the brain. Dementia treatment is one of the ways to increase the acetylcholine level. It is used mainly as an acetylcholine esterase inhibitor (ACheEI), but it inhibits the decomposition of acetylcholine. .

Skepticism is emerging around a protein called beta amyloid, the cause of dementia. Based on the hypothesis that pharmaceutical companies can treat dementia by inhibiting beta amyloid in the absence of a fundamental therapeutic agent, the research focused on the development of a dementia treatment targeting beta amyloid plaques, but failed clinical validity tests, Skepticism is gaining momentum as research has shown that beta amyloid is not the cause of dementia.

The human brain consumes the most oxygen and glucose in the human body, and the glutathione, which performs antioxidative functions in the brain itself, is produced and copes with the oxidative radical species (ROS) that can occur in the brain such as stress. However, this is known to be very vulnerable and can easily hurt ROS.

Accordingly, the present invention relates to a method for replacing substances having a risk of becoming plaque or gelled into a magnetic substance by cleaning or ionizing them into essential proteins beneficial to the body, thereby facilitating the passage of BBB, while mixing essential substances chitosan and curcumin The processed porous nanocomposites are prepared to clean the brain while capturing heavy metals.

To facilitate passage of BBB, a glycerol component or the like is attached to the surface of the nanodiamond so as to enable passage of BBB. Memantine, one of the real dementia treatments, is a type of diamondoids and has a metal chelating function (see Figure 15).

In India, it is known that patients with dementia are fewer than other countries. It is known that curcumin (curry), a favorite Indian food, has excellent ability to capture heavy metals in the brain, thus maintaining a healthy brain. Curcumin is a water-insoluble substance, so it has attracted a lot of research to try to use it as a heavy metal capturing agent and antioxidant while passing hydroxyl radical through the brain barrier BBB. However, 99% of curcumin is filtered out in the kidney, . Meanwhile, chitosan is an essential substance in the brain, so it is easy to pass through BBB, so it is excellent in biocompatibility, and it is tried to pass BBB by mixing chelating agents such as vitamin D and the like.

It is known that zeolite (silica and aluminum compound is often used as a petroleum refining catalyst) adsorbs heavy metals. As a US company used 20 meals for meals in 2012, it reported that 70% of As was emitted, 40% of Al, Pb, Cs and 30% of Ni were discharged by purging heavy metals in the body. In the present invention, a patent application for a method for producing porous silica by treating a rice husk at a low temperature has been filed.

Cisplatin (Pt (Cl ₂ ) ₂ (NH ₃ ) ₂ ), which is used as an anticancer drug, induces apoptosis of cancer cells that enter the cancer cell DNA and infinitely proliferates. Platinum catalyst is actually used in human body This is an example. One of the objects of the present invention is to make it possible to carry out a complex function of attaching a platinum catalyst on the surface of a nanodiamond composite, DNA repair, decomposition of a platelet deposit, and so on.

Nanodiamond is a biosensor that captures heavy metals. Diamond is widely used as a biosensor because it is chemically inert and therefore has good bio compatibility. Especially, when boron (B) or nitrogen (N) is doped in a small amount, For example, there are boron doped diamond (BDD) and nitrogen doped diamond (NDD). The vacancy right next to the NDD nitrogen has a quantum effect, so that magnetic fields appear when the magnetic field is applied. (Lee et al., 2006; Barnham & Bush, 2008). In this paper, we present the results of the study. Recently, Alzheimer's b-amyloid aggregation has been shown to be effective in reducing the aggregation of amyloid proteins by light irradiation with beta amyloid (Photo-induced inhibition of Alzheimer's b-amyloid aggregation in vitro by rose bengal, JS Lee et al. , KAIST 2015)

Nitrogen-doped diamond nanotubes (NVD) are used to remove substances that may become magnetic in the brain as well as to be used as a drug carrier for adhesion to nano- contrast, attaching platinum to the NVD surface, acting as a physiologically active substance or a nanobot, and radiating light to enhance the activity of the brain. The nanodiamonds are hydrophilic and can be formulated as mixed injections or spray formulations in distilled water.

In conclusion, the main object of the present invention is early diagnosis of disease, and its theoretical background is that Cu, Fe, Al, Zn, Fe (OH) _3, and the like. Specifically, dementia may be caused by Ni, Al, and the like. The diagnostic method of the present invention uses XRD as a blood analysis, and it can be used as a first screening to confirm whether there is any attraction to the magnet. The second screening is to identify specific diseases (dementia, rheumatism, etc.). In addition to the conventional methods, the magnetic body detected in the first screening is applied to lymphocytes, platelets and red blood cells separated from the blood, How to respond to chromosomes is used as a basis for judging progress of dementia. In the treatment method of the present invention, the nanodiamond is put into a disease site (for example, brain (specifically, cerebrospinal fluid)), and the magnetic substance is grabbed with an injection agent and discharged out. In the present invention, diseases to be diagnosed and treated include dementia, Alzheimer's (one of the causes is beta amyloid), rheumatic (autoimmune), Down's syndrome, Parkinson's disease, and brain immune cells (microglia).

In the present invention, when a metal bond (for example, NiFeAl, Cu2Fe, or Cu2MnAl magnetic metal complex) becomes a strong magnetic substance, it confuses the calcium channel, which is a pathway for information transmission, and eventually breaks the ion balance in the brain. It is to provide a method for proving and treating the progression of channel collapse → accumulation of beta amyloid protein.

Studies measuring interleukin-3 or beta amyloid protein have been conducted at home and abroad, but are far from dementia treatment. Prior to the experiment in the brain of living animals, the present invention first took the blood (or cerebrospinal fluid) to measure the degree of magnetization of the blood to determine the progress of dementia.

When nitrogen is doped into the nanodiamonds, a vacancy is created next to the nitrogen atoms to emit light by a quantum tunnel. The sensor is fabricated by applying this principle. Also, BDD sensor was also developed to apply the principle that the current intensity changes when a magnetic substance is attached to BDD. The method and apparatus for manufacturing BDD / NDD for the production of biosensors are based on the data of patent application (Korean National Publication No. 2017-0027112, September 2015; applicant, ChangSang Koo) and the study of nanodiamond drug delivery system The method developed so far is used.

It is difficult to change the shape of a diamond because of its strength. The diamond of about 5 nm produced by the TNT detonation developed in the former Soviet Union has a problem in that it is difficult to handle because it aggregates on the basis of nano characteristics and continues to aggregate after explosion. In the present invention, the structure of the nanodiamond complex is such that atomic-level diamondoids are formed outside the spherical nanomaterial spheres such as nano gel to form porous spheres having an outer angle of 7 nm or less , And then mixed in a mixed solution of chitosan and curcumin. The nanodiamond complex is prepared by combining commercial nanodiamonds with 1 to 2 nm sized nanodiamonds with nitrogen implant doping to create a porous bucket of 5 to 7 nm in size. Followed by secondary treatment.

Boron (boron) is an Al group element belonging to Group 13 and Group 2 of the periodic table. It is mainly present as an oxide or an oxide salt rather than a single element in nature. The boron oxide of the present invention is selected from the group consisting of BO ₃ , B ₂ O ₃ , B ₃ O ₄ , B ₂ O, B ₆ O, B ₇ O, B ₁₂ O ₂ , B ₁₃ O ₂ , BO and BO ₂ B ₂ O ₃ is more preferable. Is introduced into the ethanol reaction container and is brought into contact with ethanol, and the contact forms a boron doped diamond (BDD).

The silica is generally amorphous three-dimensional porous silica obtained from coal obtained by pyrolyzing rice husk at a temperature of 400 to 600 ° C in Spouted Bed Reactor. The present invention can also be made by pulverizing less ripe rice seeds and producing ethanol.

The rice seeds developed the nano silica structure as a way to build a self defense system to prevent the invasion of insect pests even in a hot and humid climate. The nanocomposite of rice seed has a fractal structure of about 4 nm in size, and 4 nm can pass through only air and water without passing the virus.

Generally, diamonds have very high thermal conductivity, which can dissipate heat quickly and reduce the amount of platinum used as a carrier for the catalyst, but the electrical conductivity is very low. However, the conductivity of the fluorine-doped diamond is not very high, and the conductivity of the boron-doped diamond according to the present invention is about 10 S / cm. However, titanium nitride (TiN) is high at about 10 ⁵ S / cm. In the present invention, TiCN is coated to improve the electrical conductivity of the doped diamond, thereby improving the electrical conductivity of the dopant-doped diamond by a quantum tunnelling effect at the nano-scale.

The fluorine-doped diamond according to the present invention has high electrical conductivity and is used in the field of decomposing refractory environmental wastes such as phenol, and is resistant to acidity, so it is applicable to fuel cells and lithium secondary batteries.

Thereafter, a step of coating the surface of the nanodiamond with a catalyst component while performing a surface treatment is performed to obtain a catalyst comprising the nanodiamond of the present invention as a carrier. The catalyst may be a platinum-based catalyst. The platinum-based catalyst may be any one including platinum, but it is more preferably CoPdPt.

The platinum catalyst of the present invention can be coated by a conventional method, and preferably annealed at about 700 ° C.

The platinum-based catalyst using the nano-diamond as a carrier according to the present invention uses a dopant-doped nano diamond having excellent durability against acid and alkali at a high temperature as a carrier and thus can be used for a lithium secondary battery, a fuel cell, It can be used as an electrode for various batteries and can also be used as a catalyst material for the decomposition of phenol and the modification of a bunker oil containing a large amount of aromatic compounds.

As an example of bunker oil reforming, Bunker A oil has conventionally been converted to a diesel oil at about 300 ° C. by using a platinum / iridium catalyst using a zeolite carrier. However, the boron-doped diamond according to the present invention is used as a carrier and TiCN and CoPdPt , The conversion rate of the diesel oil passage is improved by about 30% at a high temperature as well as at a high temperature, and the amount of the aromatic compound contained in the bunker oil It is possible to modify divalent linkage into a single bond or loosen the ring to improve its cetane number because it is possible to modify it by paraffin system so that it is possible to manufacture diesel oil having improved productivity and performance even when using bunker oil as a raw material.

It can be used as a substitute for various platinum electrodes having similar basic principles such as electrodes for bio-sensor measurement.

On the other hand, it is very difficult to produce nitrification or hydrocarbons such as Fe ₄ N and Fe ₄ C from the viewpoint of the recycling of waste materials after analyzing the blood. However, since hemoglobin is already bound in the form of Fe ₄ N in the blood, Industrially useful materials such as motors for electric vehicles, power transformers, and the like.

As described above, the present invention is to clarify the possibility of magnetization of heavy metal manganese, copper, aluminum, iron and the like in the human body, and to clarify the mechanism of causing dementia from the electrochemical viewpoint of the effect of magnetic material on neuronal cells, A diagnostic kit for measurement and a capsule for prevention and treatment of neurological diseases are used to remove heavy metals in the human body and to prevent neurological diseases such as dementia as well as premature diseases such as Parkinson's disease, rheumatism, renal failure, depression, autism and epilepsy Diagnosis and treatment.

Figure 1 shows the results of XRD analysis of blood samples from Hewlett-Packard samples, patients with dementia and patients with depression.
2 is an electron micrograph of the morphology of normal and demented patients.
3 is an electron microscope TEM photograph of the porous manganese oxide.
Figure 4 is a graph showing beta amyloid accumulation and the onset of dementia / Down syndrome.
FIG. 5 shows FT-IR analysis results of dementia patients and depressed patients.
FIG. 6 is a graph illustrating the relationship between NDD (nitrogen) -doped nanodiamond (NDD) produced by ion implantation of nitrogen ions on a 5 nm-diameter nano diamond using the principle of magnetic generation when a vacancy occurs in a magnetic field, Is attracted to the magnet is a photograph of a nano diamond DNV fine powder reacting to a magnet. Because nanodiamond is hydrophilic, it is easy to make injections with distilled water, which can be injected into the blood vessels in the body or sprayed in the nasal mucosa. Within 5 minutes after the injection, DNV will become a magnetic body, so the DNV adsorption mixture can be discharged from the cerebrospinal fluid (CSF) to the lymphatic system because there is no such magnetism at the end of the MRI irradiation after adsorbing the magnetic substance in the brain.
7 is a schematic diagram showing that a nitrogen-doped nano diamond is converted to a red color by a green laser.
Figure 8 shows changes in the concentration of acetylcholine in Alzheimer's patients in the brain.
Figure 9 is a schematic diagram related to platelets and amyloid protein precursors .
10 is a schematic diagram showing the structure of brain-derived amyloid protein.
11 is a schematic diagram showing formation of amyloid cell membrane ion channels
(Source: Aluminum-induced conformational changes in beta Amyloid protein and pathogenesis of Alzheimer ^, s diseases 2003 M. Kawahara Kyushu U.).
12 is a schematic diagram related to DNA damage caused by aluminum.
13 shows a diagnostic method according to an embodiment of the present invention.
14 is an animal experiment according to an embodiment of the present invention.
Fig. 15 shows an example of a drug for treating dementia.

Hereinafter, the present invention will be described in more detail with reference to Examples. It will be apparent to those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

The test set of the present invention is a simple and easy-to-handle test set, and it is intended to examine the health of the people including the process of collecting and examining blood during a health examination. However, the blood component is different from the state in the brain, and CSF can be additionally measured as a way to more accurately view the health of the central nervous system such as dementia or depression.

The present invention relates to a method for diagnosing and analyzing the possibility of magnetizing these heavy metals, which can induce dementia, Parkinson's disease, depression and the like, acting on the nervous system as a trace amount of heavy metal in the human body becomes a magnetic body, bottles and it relates to a method of treating neurological disorders, and more particularly, of manganese aluminum (MnAl), copper-aluminum (CuAl) and copper manganese aluminum compound magnet (Cu ₂ MnAl complex) and iron (Fe) or gelled to pores of these heavy metals A kit for diagnosing to measure the amount of these magnetizable substances accumulated in the body, such as adsorbed on a substance, and the production of a nanopolymer composite or a nanodiamond composite for removing the magnetic substance.

Example 1: Patients with dementia

 Analysis of the blood of patients with dementia revealed that a substantial portion of the magnet attracted was a mixture of Ni (FeMn) Al ferromagnetic Magnetic Heusler compound with ferrihydrite (Fh) in the form of iron dissolved in distilled water (see FIG. 1 below) ).

As shown by X-ray diffraction (XRD), the peak at around 32 °, which is the NiAl XRD characteristic in the graph, is a NiMnFeAl Heusler compound. On the other hand, when the content of Mn and Fe increases, the peak around 46 degrees becomes high.

The results of XRD analysis of Husler compound NiAl prepared for industrial use in FIG. 1 are similar. (Conference on Advanced Material Technology, Magnetic evolution in Ni-Al alloy substitution of Mn and Fe, Notonnegoro et al. , 2016).

The level of ferritin in the blood is maintained at a certain level in healthy people, but it is known that the inflammatory disease such as AD, PD, and cancer is elevated in the ferritin level. The rate of erythrocyte sedimentation in the blood , And the results of this experiment are the same as those of the general trend. Blood analysis results suggest that trace metals in the brains of patients with dementia may be caused by aluminum mediated magnetization.

Example 2: Neurological diseases such as depression

As shown in FIG. 1, in the blood treatment samples of patients suffering from depression, it can be seen that the magnetic material showing Ni-Al alloy Heusler compound characteristics is seen from the XRD analysis results.

Parkinson's disease, which is similar to dementia, autism, seizures and schizophrenia are also the same causes.

Infrared (FTIR) analysis of patients with dementia and depression showed that there is a difference in the absorption rate of the normal person and the infrared ray in the vicinity of the wave number of 1200 / cm to 500 / cm (see FIG. 5).

In the case of PD, substantia nigria, which is the production site of dopamine neurotransmitter, is accumulated and iron (+3) is converted to iron (+2) I think there will be.

Example 3: Patients with renal failure dialysis

Pb, As, and Al levels of blood in patients with chronic kidney disease (CKD) are known to be higher than those in healthy individuals. (2001) Not only iron ions but also various other metals such as aluminum are accumulated and ferritin itself is increasing. Several studies have shown associations between CKD and AD patients. C. Harrington et al. Alzheimer's changes in tau protein processing: association with aluminum accumulation in brains of renal dialysis patients 1994) (J. Candy et al. Aluminum accumulation in relation to senile plaque and neurofibrillary tangle formation in the brains of patients with renal failure 1992)

Example 4 Atopic dermatosis

       Tight junctions (TJ) and filaggrin, which are the major parts of the skin barrier, are the deformation of the Golgi body in the cell, which is electrochemically highly sensitive and transformed into cell keratin It is essentially a tissue cell sensitive to the surrounding electromagnetic environment. The BBB, which is the brain barrier, and the kidney corpuscle, as well as the collapse of the barrier wall, can cause serious diseases.

Example 5 Rheumatoid arthritis

       It is known that trace elements such as Fe, Cu, Zn, Ni, Cr, and Al in the blood and knee joint synovial fluid of rheumatism patients are more than twice as high as those in healthy individuals. Niedermeier et al., 1962). Iron accumulation, especially accumulated, can be distinguished by Prussian blue staining method. (Muirden and Senator 1968)

&Lt; Example 6 > Production of nanodiamonds

The capsule for preventing and treating dementia by removing the heavy metals in the human body according to the present invention can form an innovative drug delivery system by coating the nanodiamond with chitosan or the like and flowing it into the brain.

Accordingly, in the present invention, a detonation diamond having a size of about 5 to 7 nm is subjected to a nitrogen ion implantation method (see FIG. 6 in which a nitrogen-doped nanodiamond is attracted to a magnet (below the aluminum foil) And the magnet moving in the vicinity of the magnet was separated and mixed with NDD three-dimensional porosity with chitosan, curcumin or the like to prepare a nanodiamond composite.

Animal experiments were conducted to demonstrate efficacy and safety (see Figure 14).

The present invention consists of manufacturing nanodiamonds, measuring magnetic bodies in blood components, separating ionic metals from blood (if needed, spinal fluid), measuring the degree of magnetization, and identifying the causal relationship between brain malfunctions in vivo.

The present invention activates the electrochemical reaction in the brain by inserting a platinum-based catalyst into the human body of a patient with dementia, and removes metallic copper, manganese and aluminum which are the causative substances of the magnetic body. Drug delivery of diamond complexes can be applied not only to dementia but also to whole brain diseases, and also to cancer treatment.

The blood brain barrier (BBB) protects the cranial nervous system so that substances that can pass through the BBB pass through only Na, K ions and only a few proteins except sugar, water, and oxygen needed for the brain . In addition to patients with dementia (AD), drug delivery to the brain remains a major challenge in order to treat brain diseases such as Parkinson's disease (PD) and epilepsy. Parkinson's disease, Alzheimer's disease, stroke, lysosomal storage disease, and many other diseases have the task of passing the BBB. Nanomaterials and fluorene (C 60) have been studied and are still under development, but they have not been successful in terms of toxicity and drug delivery.

In the case of dementia, the necessary drug and bioactive substance are put into a three-dimensional porous diamond to carry the required drug to activate the electrochemical reaction of the brain, and then the drug is carried into the brain. Accordingly, the present invention has attempted to form a nanodiamond capsule composite not only to remove heavy metals but also to perform various functions. In order to restore the original shape of the aggregated amyloid protein (the aggregated state is toxic) and the tau protein, which are essential proteins in the body, if the tau protein is not aggregated, It is anticipated that by delivering antioxidants in a nanodiamond, which is also a special means of transporting nanodiamonds that can pass through the BBB in order to supply, the effect of the treatment is expected to be enhanced.

Example 7 Nanodiamond Tracking Apparatus and Animal Experiment

The present invention relates to an in vitro biosensor in which a green laser is injected into a CSF circulation region between a neck and a brain for tracking a nanodiamond implanted in a cerebrospinal fluid (CSF), thereby tracking the degree of emission of the nanodiamond Device development. By doing so, it is possible to investigate whether or not the magnetic substance is aggregated in CSF. (See FIG. 7 where the green laser is converted to red by nitrogen vacancy)

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, This is possible.

Claims (15)

Wherein at least one sample selected from the group consisting of blood of a human body, cerebrospinal fluid (CSF), hair and urine is heat-treated so that a binding substance between at least one transition metal selected from the group consisting of aluminum, manganese, And determining whether or not it exists. The method according to claim 1,
The kit may be used for the treatment or prophylaxis of metabolic or biochemical processes of the body, including senile neurological diseases including Alzheimer's disease, depression, brain metastasis, cerebral neurological disorders including autism and asthma, and osteoporosis, renal failure (CKD), atopy, diabetes type 2, And diagnosing at least one disease selected from the group consisting of diseases which can be caused by abnormal function. The method according to claim 1,
The kit can be used to determine whether the binding material between the transition metals acts on physiologically active substances, including acetylcholine, insulin, calcium ion regulatory factor calcinarin, and Reelin cerebral cortical growth factor, to interfere with the immune system's disruption or normal body activity Lt; RTI ID = 0.0 &gt; bio-marker. &Lt; / RTI &gt; The method according to claim 1,
Wherein the sample is heated at 80 DEG C or lower for 5 hours or more, completely evaporated, and then heat-treated at 300-400 DEG C for 4 hours in an electric furnace to decompose the protein. In order to remove magnetic compounds in the human body, chitosan or curcumin is prepared as a hollow porous spherical material, or a nitrogen-doped nano diamond frame is prepared as an injection, and coated or mixed with the chitosan or curcumin, . 1) implanting nitrogen into a detonation diamond;
2) heat treating the nitrogen-injected nano-diamond in air at 700 ° C for 1 hour to separate impurities from nitrogen-doped diamond (NDD);
3) preparing porous nanodiamond by mixing the NDD and diamondoids (diamondoids) into a nanogel;
4) Into the frame of the porous nano diamond, a substance which is beneficial for the human body including natural dye selected from the group consisting of chitosan, gum, curcumin, cabbage and safflower is put into the frame of the porous nano diamond. &Lt; / RTI &gt; The method according to claim 6,
Wherein the nanodiamond has a size of 5 nm. The method according to claim 6,
Wherein the nanodiamond is prepared by a nitrogen ion implantation method. The method according to claim 6,
Wherein the porous nanodiamond in step 3) is coated with a porous frame using a platinum group or transition metal catalyst including Pd and Ru to facilitate metabolism by electron supply in the brain. A device for injecting heavy metal removing injectable agent according to claim 5 into a blood using a green laser and effectively detecting whether the nanodiamond binds to heavy metals in the brain or human body to effectively chelate the magnetic material. A device for injecting heavy metal removing injectable agent according to claim 5 into a blood using a green laser and effectively detecting whether the nanodiamond binds to heavy metals in the brain or human body to effectively chelate the magnetic material. To isolate the nucleus from the blood lymphocytes and inject the heavy metal powder of the magnetic substance of the first paragraph into the separated nucleus and observe the reaction of chromosome 21 to determine the degree of DAN damage and to use it for the early diagnosis of AD and the prevention of Down syndrome (DS) Diagnostic kits and devices. The amyloid protein was separated from the blood platelet and the amyloid protein of the first item was added to the separated amyloid protein and the chelate of the copper ion was observed to judge whether the protein was misfolded. And a diagnostic kit. A method of separating erythrocytes and albumin from blood, injecting the magnetic substance powder of the magnetic substance of claim 1 into the separated erythrocytes and albumin, observing the chelate of copper and iron ions, . A method for the recycling of analytical blood waste, wherein the nanomaterial of iron nitride or carbide is separated from the waste material after analysis of the blood.

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