TR2021022259A2 - Acetylcholinesterase Inhibitory Activity of Salt Samples of Imidurea Molecule, Imidurea Isomer Molecule Forms, or Pharmaceutically Accepted Imidurea Isomer Molecular Forms thereof - Google Patents

Abstract

The present invention can be used in the treatment of various diseases or disorders caused by AChE as pharmaceutical composition and functional food and carriers, and containing imidurea or imidurea derivatives or pharmaceutically acceptable salts thereof, which have acetylcholinesterase (AChE) inhibitory property.

Description

DESCRIPTION Salt Samples of Imidurea Isomer Molecular Forms Accepted as Acetylcholinesterase Inhibitor Activity Technical Field to which the Invention Relates: The presented invention contains imidurea (sitafloxacin), imidurea derivatives and their pharmaceutical preparations. composition and functional food and pharmaceutically acceptable salts of acetylcholinesterase (AChE) is related to its inhibitory properties.

Known Status of the Technique: Acetylcholine, an alkaloid, was the first neurotransmitter identified. Located in the central nervous system In addition to being a chemical-transmitter that receives It is located in the parasympathetic nervous system (including humans). For the first time in 1914, the British Acetylcholine, defined by scientist Henry Hallet Dale, is the compound of choline with acetic acid. is the ester. In 1921, frog hearts were discovered by Australian scientist Otto Lewi. This discovery, which was confirmed as a neurotransmitter as a result of his experiments on It brought scientists the Nobel Prize in 1936.

In certain neurons, acetylcholine is separated from choline and acetyl-CoA by the enzyme acetyl esterase. is synthesized. After completing its task by being released into the synaptic space Acetylcholine is converted into acetate, a salt of choline and acetic acid, with the help of the enzyme acetylcholinesterase. It is turned and destroyed. Additionally, acetylcholinesterase, called AChE, has hydrolytic activity. The activity of parasympathetic neurons, especially by forming the choline and acetate group, increases the activity of parasympathetic neurons. It is an enzyme that enables the degradation of the neurotransmitter acetylcholine (ACh).

After AChE is produced in the membrane of the endoplasmic reticulum, it is required to carry out its function. is transported to the cell membrane. AChE is mainly produced in and around cholinergic neurons, especially found at the attachment points of the muscles, as well as in the plasma, liver and other tissues It is an important enzyme.

Generally, acetylcholine is secreted from the membrane at the axon tip towards the synaptic gap and transfers action potential by binding the post-synaptic neuron receptor It is a neurotransmitter. After the stimulus is carried to the neuron, it is degraded to choline and acetate by AChE. It is then used to synthesize new acetylcholine molecules again through reabsorption. is carried back to the nerve endings.

Acetylcholine research has shown that various physical and mental diseases/disorders, acetylcholine mechanism and an abnormal concentration of synthesized acetylcholine. It has been revealed that there is a significant relationship between the decrease in the level of

Acetylcholine is currently implicated in the pathogenesis of Alzheimer's and Parkinson's diseases. It is known that it has an important place in the mechanism. Also known as dementia Alzheimer's disease (AD) is typically the most well-known acetylcholine-related disorder.

The most important symptoms of Alzheimer's disease are memory loss, speech impairment and is dementia. To date, various hypotheses have emerged for the mechanism and pathogenesis of the disease. Atilsa is still not fully known.

In addition, the central nervous systems of patients with Alzheimer's disease generally cannot be repaired, and cholinergic neurons in particular cannot be repaired. With this, Patients suffering from Alzheimer's disease due to failure of cholinergic neurons to repair report that cognitive achievement is deeply related to decline in memory and learning has been done.

Restoration efforts of the cholinergic neuron associated with AD are suggested by the cholinergic hypothesis. is being driven. According to this hypothesis, successful results can be achieved in the treatment of AD disease. towards the restoration of actively damaged cholinergic neurons. The necessity of doing this is stated.

ACh, a cholinergic neurotransmitter, is used to heal irreparable cholinergic neurons. Use of precursor molecule, use of cholinergic receptor agonists or AChE A method to balance the concentration of ACh in the synapse with its inhibitors is implemented. However, since cholinergic receptor agonists are degraded in ViVO, AChE inhibitors are used.

It inhibits the enzyme acetylcholinesterase, as it has a deep connection with acetylcholine deficiency. Some drugs are used to treat diseases such as Alzheimer's disease.

In myasthenia gravis, which is a neuromuscular disease, the body responds to acetylcholine receptors. It is known that it prevents a proper acetylcholine signal transfer by producing antibodies against it. This In the treatment of the disorder, drugs such as Physostigmine, which inhibit the acetylcholinesterase enzyme, are used. is used. Additionally, acetylcholine is a rapid stimulation of the pupil during cataract surgeries. It is used to undergo constriction (shrinkage).

Therapeutic drugs for Alzheimer's that have been approved by the American Food and Drug Administration (FADl) AChE inhibitors used as tacrine (THA, Cognex®), donepezil (Acricept®) and rivastigmaine (Exel0n®), among which are obtained from natural products compounds are galanthamine (Galanthus nivalis), huperzine A (Huperzia serrata) and others.

AChE keeps the concentration of ACh constant by protecting it from ACh degradation Inhibitors have the effect of improving cognitive (judgment, perception) function. However. AChE Inhibitors have many known properties such as hepatotoxicity, short half-life, low biocompatibility. It has a problem. Therefore, many studies have focused on the development of new AChE inhibitors. It is done on.

At the same time, in other pathological studies related to the choline nervous system, gastrointestinal movement is controlled by nerve impulses and acetylcholine increases stomach function has been reported. Therefore, neostigmine, a type of AChE inhibitor, increases abdominal distension due to postoperative ileus (intestinal obstruction after surgery) or In the treatment of dysuria (urinary difficulty) caused by bladder detrusor insufficiency is used.

Additionally, the autoimmune neuromuscular disease myasthenia gravis is associated with post-synaptic neuromuscular disease. neurotransmitter due to the disruption of acetylcholine receptors at their junction points. The simulative (stimulating) effect of acetylcholine is impaired. acetyl such as mestinon or neostigmine It is treated with choline inhibitors. Mestinon is often used in the treatment of myasthenia gravis. is used. Thus, acetylcholine remains on the receptors in the muscle cells. Acetylcholine concentration is increased. Although treatment in a short time seems to be an advantage, Depending on the dose, side effects such as vomiting and abdominal pain may occur. myasthenia Newly developed acetylcholine esterase inhibitors are nicotinic or muscarinic inhibitors in the treatment of gravis. They do not show selectivity for acetylcholine receptors, so muscarinic acetylcholine Undesirable effects occur with stimulation of the receptor. Moreover, their absorption rate is very high. are low and treatment intervals are narrow due to their partial effectiveness.

Glaucoma is a progressive intraocular pressure that causes irreversible vision loss. It is a disease in which the optic nerves are damaged. In this context, according to the information available, acetylcholine Esterase inhibitors ensure the reabsorption of aqueous fluid. Thus intraocular pressure is reduced. However, the issue that needs particular attention is Glaucoma. Risk of catarrh formation if treatment with AChE inhibitors continues for more than 6 months is occurring.

Treatment or treatment of various diseases or disorders associated with low ACh concentration application of precursor ACh molecules to facilitate ACh synthesis in It is recommended as an alternative method. However, without entering the blood brain barrier AChE with ACh hydrolytic activity, such as Tacrin, due to their short-time interactions Medicines are mostly used in treatment.

As mentioned above, currently developed and commercially available AChE Hepatopathy, gastrointestinal distribution (abdominal pain or vomiting), muscle pain It has many side effects such as etc.

As a result of in-Slico calculations, various forms of imidurea were affected by acetylcholine esterase levels. It reduces the activity of the enzyme and even has this effect on the drugs used today as AChE inhibitors. It has been observed that it has a much stronger effect than drugs.

Therefore, the presented invention covers various problems related to the abnormal decrease in aCetylcholine concentration. It proposes a molecule that can be used in the treatment of diseases and disorders. this molecule with imidurea molecule, which has high aceticcholine estrease inhibition activity Technical Problems That the Invention Aims to Solve: The aim of the presented invention is to develop the imidurea molecule with AChE inhibition activity. is to be determined.

Another aim of the present invention is to use various imidurea agents with AChE inhibition activity. It is the determination of isomer molecule forms.

Another object of the present invention is to use the imidurea molecule or various Imidurea isomer molecules. forms or pharmaceuticals capable of inhibiting AChE activity. is to determine the accepted salts.

Another purpose of the presented invention is to treat the weakness of the smooth muscles of the gastrointestinal region. (myasthenia), bladder, in the treatment of neurodegenerative diseases or glaueoma or Providing pharmaceutical composition or pharmaceutically acceptable salts of the imidurea molecule or various forms of the Imidurea isomer molecule is to be determined.

Another purpose of the presented invention is to treat the weakness of the smooth muscles of the gastrointestinal region. (myasthenia), bladder, in the treatment of neurodegenerative diseases or glaucoma or Providing pharmaceutical composition or pharmaceutically acceptable salts of the imidurea molecule or various forms of the imidurea isomer molecule is to use.

Another purpose of the presented invention is to treat the weakness of the smooth muscles of the gastrointestinal region. (myasthenia), bladder, in the treatment of neurodegenerative diseases or glaucoma or Providing pharmaceutical composition or pharmaceutically acceptable products for the protection of salts of the imidurea molecule or various forms of the imidurea isomer molecule is to use.

Imidurea molecule or various imidurea isomer molecule forms or pharmaceutically Accepted salts are potent acetylcholine esterase inhibitors of AChE activity. It is an inhibitor. Thus, by being included in the pharmaceutical composition or carrier, weakness of the smooth muscles of the gastrointestinal tract (myasthenia), bladder, neurodegenerative pharmaceutical composition for the treatment or prevention of diseases or glaucomamine providing or using the pharmaceutically acceptable imidurea molecule or various Imidurea It is the use of salts of isomer molecule forms.

Description of the invention: Unless otherwise defined, technical and scientific terms used herein are commonly used to describe the invention. the same understanding as is generally understood by a person of ordinary skill in the technical field has.

In the present invention, imidurea molecule or various imidurea isomer molecule forms are used. or salts of various imidurea isomer molecule forms that provide AChE inhibition It is reported to have activity.

The presented invention is based on the hydrolytic activity of acetylcholine esterase, also known as AChE. It degrades the neurotransmitter acetylcholine, forming choline and acetate groups with the help of acetyl It is related to an enzyme that can cause profound changes in choline concentration. ischemic Neurodegenerative diseases such as brain disease, myasthenia gravis, memory defects, alcohol addiction diseases, myasthenasr (weakening) of gastrointestinal smooth muscle or glaucoma or urinary tract various diseases associated with abnormal decrease in acetylcholine concentration, such as in the bladder It can be used to treat diseases or disorders.

Some imidurea isomer molecular forms or their pharmaceutically acceptable imidurea Salts of isomeric forms of the molecule show higher potential AChE inhibitory activity. They may have the feature.

In the present invention, imidurea molecule or various imidurea isomer molecule forms are used. or salts of various imidurea isomer molecule forms Ischemic brain disease, myasthenia gravis, memory defects, neurodegenerative diseases such as alcohol addiction, gastrointestinal flatulence abnormalities such as myasthenas (weakening) of the muscle or glaucoma or urinary tract (bladder) Various diseases or disorders associated with decreased acetylcholine concentration can be used in treatment.

Imidurea isomer molecule forms shown in Figure 1 is an antibiotic. In the presented invention, It also includes pharmaceutically acceptable salts of the imidurea molecule.

Unless otherwise specified, pharmaceutical salts of Imidurea or the addition of basic groups on imidurea. or may contain acidic salts. Examples of acidic or basic groups are hydroxyl groups, sodium, potassium, calcium, potassium salts and hydrobromide salts, amidogen groups, amino groups p-toluene sulfonate (Tosylatel and methane sulfonate (mesylatel madelate, lactate, tartrate, citrate, succinate, acetate, dihydrogen phosphate, hydrogen phosphate, using background methods or processes with phosphate, hydrosulfate groups can be prepared.

In addition, the free acid and the acid added salt are pharmaceutically acceptable. It can be used for its soluble salts. Acid-added salt, with a large amount of acid solution soluble compounds, followed by water-soluble compounds such as methanol, ethanol, acetone, or acetonitrile. followed by precipitation of the acidic salts with organic solvents. Compounds with similar molar amounts and acids in alcohol or water, such as glycol monoethyl ether, can be heated and then obtained The resulting mixture can be evaporated or dried, or the precipitated salt can be filtered by suction.

Organic acid or inorganic acid can be used as free acid. Examples of organic acids hydrochloric acid, phosphoric acid, nitric acid or tartaric acid, examples of inorganic acids are methane sulfonic acid, p-toluene, sulfonic acid, acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, fumaric acid, mandelic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorpic acid, carbonic acid, vanillic acid, hydroiodic acid and the like.

The formation of pharmaceutical metal salts with base can be used for the presented invention. alkaline or alkaline earth metal salts, compound in alkaline metal hydroxide or alkaline earth metal dissolving in salts, filtering and evaporating compounds from insoluble salts It can be obtained by traditional methods by filtering and drying.

Sodium potassium calcium salts may be preferred and are formed by the reaction of sodium with potassium. prepared silver salts or calcium salts with appropriate silver salts (e.g. silver nitrate) preferable.

The present invention relates to the decrease in ACh concentration by AChE activity. such as ischemic brain disease, myasthenia gravis, memory defects, alcohol habit neurodegenerative diseases, myasthenia (weakening) of gastrointestinal smooth muscle, or decreased abdominal acetylcholine concentration, such as glaucoma or urinary tract (bladder) in the treatment of or protection against diseases/disorders related to Provides pharmaceutical compound.

The pharmaceutical composition of the present invention may be used with pharmaceutically acceptable carriers and/or substance added to medicines to be prepared to give them a suitable shape or a pleasant taste It can form formulations with (excipient). Examples of suitable carriers and excipients lactose, dextrose, sorbitol, mannitol, xylitol, maltitol, starch, acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxy benzonate, propylhydroxybenzolate, talc, magnesium cetarate and mineral oil.

Exceptionally, the compound of the invention may be anticoagulant and protective.

The pharmaceutical composition of the presented invention can be used in oral, nebulized, topical (buccal, sublingual, including dermal and intraocular pathways), parenteral (subcutaneous, intradermal, intraocular) periodontal, intracerobrospiral, intramuscular, intravascular and intraarticular routes) or Although it is applied transdermally, it is not limited to these methods only.

However, the composition of the present invention cannot be used alone or with an AChE inhibitor background. It can be used together with other medications. Examples of acetylcholine esterase inhibitors, Aricept (donepezil hydrochloride capsule commercialized by Eisai), Amirine (Nikken), SM- Zifrosilone (Marion Merrel D0W). These acetylcholine inhibitors Brufani et al. (Alzheimer's Schmidt et al. (Alzheimer Disease: From Molecular Biology to Therapy, eds. Becker et al., Patented by.

The presented invention composition is used for ischemic brain disease, myasthenia gravis, memory defects, neurodegenerative diseases such as alcohol dependence, myasthenas of gastrointestinal smooth muscle (weakening) or in the early stages of diseases such as glaucoma or urinary cavity (bladder) It can even be used in the later stages of the disease. can be given, but there is no limit. Again, Ischemic brain disease, myasthenia gravis, memory defects, neurodegenerative diseases such as alcohol dependence, gastrointestinal smooth muscle diseases such as myasthenas (weakening) or glaucoma or urinary tract (bladder) can be used for protection. The presented invention composition can be repeated as many times as necessary. is applicability. For example, daily or 1-12 weeks depending on the clinical need of the patient. in the range, preferably 3-8 weeks, but not depending on these limits, at appropriate intervals or It can be applied according to the daily clinical needs of the patient.

The composition of the presented invention provides the release or rapid release of active ingredients. can be formulated. These formulations are tablet, powder, suspension, emulsion, solution, syrup, aerosol, sterile injectable solution, hard capsule, sterile powder and so on is possible. It is preferable to provide the composition of the presented project in single dose form. is to be done.

The composition of the present invention can be administered in a therapeutically effective amount. therapeutically The effective amount can be expressed as the dose that can treat the disease or disorder.

The composition of the present invention, its therapeutically effective amount, variety of patient symptoms, period of treatment, rate of excretion, route of administration, time of administration, food, individual patient Various factors, including breed, reaction sensitivity, health, weight, age and treatment conditions. defined in the light of factors. The doses given above will cover all treatments. It does not cover. For example, for animals other than humans, the composition of the invention is unique The most preferred is 500-1000 IU/kg. Further, a single dose of the composition of the invention for humans It can be applied regardless of body weight.

On the other hand, the presented invention relates to methods to be used for protection or ischemic brain Neurodegenerative diseases such as disease, myasthenia gravis, memory defects, alcohol addiction diseases, myasthenas (weakening) of gastrointestinal smooth muscle or glaucoma or urinary tract various diseases associated with abnormal decrease in acetylcholine concentration, such as in the bladder imidurea molecule or imidurea isomer in the treatment of diseases or disorders molecular forms or their imidurea isomer molecules, which are considered pharynoceutic Salts of these forms can be used.

The terms prevention and treatment used herein refer to prevention or protection methods and therapeutic methods. refers to measurements. Thus, the presented invention can treat the sample in need of treatment in the environment. Such as ischemic brain disease, myasthenia gravis, memory defects, alcohol addiction neurodegenerative diseases, myasthenia (weakening) of gastrointestinal smooth muscle, or It can be used to protect against diseases such as glaucoma or urinary tract (bladder). Here The living thing defined as an example means humans, primates and cats in need of treatment. dog, pig, horse dog etc. It includes mammals such as.

Another embodiment is healthy food or food products for which the presented invention can be used for preservation. diseases/disorders acetylcholine concentration by acetylcholine esterase activity Ischemic brain disease, myasthenia gravis, memory defects, alcohol associated with a decrease in Neurodegenerative diseases such as addiction, weakening of gastrointestinal smooth muscle (myasthena) or abnormal acetylcholine concentration, such as glaucoma or urinary tract (bladder) in the treatment or protection against diseases/disorders related to decreased It is related to the pharmaceutical compound that may be used.

The healthy food imidurea molecule or imidurea isomer molecule forms of the presented invention or salts thereof in pharmaceutically acceptable imidurea isomer molecular forms It can be consumed alone or with other foods. Find more healthy food can be used according to traditional methods. The ratio of ingredients in food depends on the intended use (protection, health or treatment of diseases). In general, imidurea molecule or imidurea isomer molecule forms or their pharmaceutically acceptable Salt samples of the imidurea isomer molecular forms are 10% or less by weight. Preferably 5% or less can be added to food or beverage preparation. However, your health For long-term food intake, lower amounts of the active ingredient are recommended for protection. may contain. In addition, if the presented invention does not cause any harmful effects, More active material than known amount may be used.

There is no limit to the variety of healthy foods. Imidurea with which Examples of healthy food can be mixed molecule or imidurea isomer molecule forms or their pharmaceutically acceptable Salt samples of imidurea isomer molecular forms are found in foods, sausages, bread, chocolate, candies, candies, pizza, gummies, ice cream Etc. daily products such as, in various soups, It can be used in beverages, tea, alcoholic beverages and vitamin composition. Presented The foods of the invention are comparable to all types of conventional/commercially available health foods. can be added.

If the food of the presented invention is healthy drinks, healthy drinks contain various sweetening agents, It may contain natural hydrocarbons or an added component similar to commercial beverages.

Natural hydrocarbons include monosaccharides such as glucose or fructose, maltose and sucrose. in disaccharides, natural sweeteners such as cyclodextrin or dextrin or saccharin or There may be synthetic sweeteners such as aspartame. The ratio of natural hydrocarbons in healthy drinks In addition, the food of the presented invention contains various food additives, vitamins, electrolytes, dyeing agents, protective agents, pectic acid and its salts, alginic acid and its salts, organic acid, preservatives, pH controlling agents, stabilizers, glycerin, alcohol and Carbonizing agents can be used for carbonated products. However, offered The food of the invention is fresh for natural fruit juice, fruit juice drinks and vegetable juice drinks. Fruits and vegetables can be chosen. The proportions of the specified additives are not very critical and are generally It can be selected as one percent of the weight of the food.

Claims (1)

CLAIMS . It is an application based on bringing an effective amount of molecules into contact with cells, and its feature is; The molecule or its isomer molecule forms or its pharmaceutically accepted salts have acetyl choline esterase (AChE) inhibitor (AChEI) activity in their natural or synthetic forms. . The common cause of ischemic brain disease, myasthenia gravis, memory defects, neurodegenerative diseases such as alcohol addiction, Alzheimer's disease, Parkinson's disease, myasthena (weakening) of the gastrointestinal smooth muscle or glaucoma or urinary space (bladder) diseases is related to AChE, and its feature is; The claim is that the said molecules and molecule forms have AChEI activity that can be used in the treatment of diseases. . The substance specified as a molecule in the claim is the imidurea molecule of the present invention and its feature is; It has AChEI activity. . The invention presented in the claim is a natural or synthetic form of the imidurea molecule or pharmaceutically acceptable salts of the molecule, and its feature is; The natural or synthetic form of the imidurea molecule or pharmaceutically acceptable salts of the molecule have AChEI activity. . The imidurea molecule and pharmaceutical salts of the molecule presented in the request are as follows; Hydroxyl groups, sodium, potassium, calcium, potassium salts and hydrobromide salts, amino groups containing basic groups or acidic salts, p-toluene sulfonate (Tosylate), methane sulfonate (mesylate) madelate, lactate, tartrate, citrate, succinate, acetate, dihydrogen phosphate It has hydrogen phosphate, phosphate and hydrosulfate groups. . The invention imidurea molecule presented in Claim 1 and its forms specified in Claim 4 or 5 can be used in the treatment of diseases on living creatures, and its feature is; It has AChEI activity of imidurea molecules or pharmaceutically acceptable salts in an effective amount (dose) that can be used in the treatment of the diseases specified in Claim 2, in reducing the effects of the disease or in treating the disorders resulting from the disease. . The cause of the diseases mentioned above in living beings is related to AChE, and its feature is; The invention presented in Claim 3 is that the imidurea molecule and its forms specified in Claim 4 or 5 have a therapeutic effect by contacting them with the help of a technique in an effective amount as specified in Claim 1. Mammals specified as intentional creatures; human, dog, cat, cow, ox, buffalo, sheep, lamb, ram, goat, poultry; It is in contact with chickens, budgies, pigeons, parrots and turkeys and the therapeutic molecules of the diseases specified in Claim 2, and its feature is; The invention presented in Claim 3 is that the imidurea molecule or its forms specified in Claim 4 or 5 have a therapeutic effect as stated in Claim 7 due to the AChEI effect on living beings. The treatment of the diseases specified in claim 27 is the in vivo contact of therapeutic molecules and cells, and its feature is; The present invention is that the imidurea molecule and its forms specified in Claim 4 or 5 have the ability to be used as a therapeutic agent. The invention presented in Claim 3 is the imidurea molecule or the forms specified in Claim 4 or 5, the diseases specified in Claim 2, the therapeutic agents as stated in Claim 9, and its feature is; AChEI has the ability to be administered in the same formulation in its therapeutic use. The imidurea molecule presented in Claim 3 or the forms specified in Claim 4 or 5 are therapeutic active molecules for the diseases specified in Claim 2 as specified in Claim 9, and its feature is; AChEI has the ability to be applied in different formulations when used as a therapeutic standard. The invention presented in Claim 3 in the treatment of the diseases specified in Claim 2 or in the prevention of diseases is the imidurea molecule or the molecule with AChE activity in the forms specified in Claim 4 or Site, and its feature is; The present invention shown in the pharmaceutical composition has the imidurea molecule or at least one of its forms as specified in claim 4 or 5. The invention imidurea molecule presented in Claim 5 or its forms specified in Claim 4 or 5 has AChEI effect in the treatment of the diseases specified in Claim 2 or in the protection from diseases, and its feature is; It has the feature of being applied as a supplement (supporter or additive) for therapeutic purposes. It contains at least one of the imidurea molecule, imidurea isomer molecule forms or salt samples of their pharmaceutically accepted imidurea isomer molecule forms in the pharmaceutical composition for the treatment or protection of the diseases specified in the claim, and its feature is; It has the ability to be used in foods as specified in claim 3. The invention imidurea molecule presented in claim 3 and the forms specified in claim 4 or 5 are used together with drugs that have AChEI effect, and its feature is; When used together, the synergistic effect has stronger activity than when used individually. The invention presented in claim 3 is present in a composition containing the imidurea molecule or its forms specified in claims 4 or 5, a pharmaceutically acceptable carrier, excipient or diluent, and its feature is; It has the ability to transport molecules and preserve their properties without deterioration. The presented invention is the confinement of the imidurea molecule or its forms specified in Claim 4 or Site by using carriers and coatings, and its feature is; It has the ability to be transported in the body of living things and has ACHEI activity. The invention presented in claim 3 is important in protecting and transporting the ACHEI activity of the imidurea molecule and its forms specified in claim 4 or 5, and its feature is; The substances specified as carriers in claim 16 or 17 must have any liposome, chitosan, quantum dotI chemical carriers and their nano-micro sized derivatives. The invention presented in Claim 3 is the imidurea molecule and the ACHEI activity of the forms specified in Claim 4 or 5, and its feature is; The pharmaceutical composition of the molecules used as therapeutic agents has the ability to be applied orally, nebulized, topically (including buccal, sublingual, dermal and intraocular route), parenteral (subcutaneous, intradermal, intraperiodontal, intracerobrospiral; intramuscular, intravascular and intraarticular route) or transdermally. is to have. The invention imidurea molecule presented in Claim 3 or the forms specified in Claim 4 or Site can be carried in the body as stated in Claim 17 or 19 and used in the treatment of the diseases specified in Claim 2, and its feature is; Therapeutic molecules have the ability to be applied in the form of capsules, dragees, powders and creams.