阅读说明：本技术 麻黄素应用于治疗帕金森病 (Application of ephedrine in treating Parkinson's disease ) 是由 徐四川 于 2019-04-10 设计创作，主要内容包括：《多巴胺通道理论》认为,多巴胺分子通过多巴胺功能通道,到达多巴胺活性空腔,发挥多巴胺功能作用。《帕金森病科学病理》认为,当多巴胺功能通道被纤维蛋白堵塞,就会出现帕金森病。这是因为多巴胺功能通道被堵塞造成了多巴胺功能化因子减小,功能多巴胺含量减少。我们采用麻黄素分子,具有专一选择通过多巴胺功能通道的功能,发明了应用麻黄素治疗控制帕金森病。实验测定证实麻黄素是具有专一选择通过多巴胺功能通道的物质。老鼠动物实验证实,麻黄素能疏通被±-突触核蛋白堵塞的多巴胺功能通道,具有治疗控制帕金森病的效果。(The theory of dopamine channels states that dopamine molecules pass through dopamine functional channels to reach dopamine active cavities to play a dopamine functional role. The science and pathology of Parkinson's disease states that Parkinson's disease occurs when dopamine functional pathways are blocked by fibrin. This is because occlusion of dopamine functional channels results in a decrease in dopamine-functional factors and a decrease in functional dopamine content. The ephedrine molecule is adopted, so that the function of specifically selecting a functional channel passing through dopamine is realized, and the application of the ephedrine in treating and controlling the Parkinson's disease is invented. Experimental determination proves that the ephedrine is a substance which has a specific selection to pass through a dopamine functional channel. The experiment of the mouse and the animal proves that the ephedrine can dredge the dopamine functional channel blocked by the +/-synuclein and has the effect of treating and controlling the Parkinson's disease.)

1. Ephedrine for treating and controlling Parkinson's disease, with molecular formula of ephedrine C₁₀H₁₅NO, ephedrine chemical name is: (1R,2S) -2-methylamino-phenylpropan-1-ol.

2. The ephedrine is applied to dredging dopamine functional channels blocked by the +/-synuclein fibrin.

1. Field of the invention

Parkinson's disease, ancient times. This Disease is known as Parkinson's Disease because the United kingdom physician JamesParkinson studied the Disease carefully in 1817 and published a paper after which the physician's name Parkinson named the Disease (Parkinson's Disease). At present, about 1000 million Parkinson patients worldwide exist, wherein Chinese Pa patients exceed 200 ten thousand, and the number of the Parkinson patients in three and forty years old in the young is rapidly increased. Parkinson's disease includes four major conditions: (1) resting tremor, (2) muscle rigidity, (3) bradykinesia, (4) abnormal gait and unstable posture, and many possible complications make the life of a patient abnormally hard, often have a feeling of death, but are not easy to die, and are serious, distressing and disabling diseases.

Parkinson's disease is currently considered an incurable, uncontrollable, disabling disease and is also wanting to afflict humans. Obviously, the method is closely related to the fact that the nature of the Parkinson disease is not comprehensively and deeply known, and is obviously related to the fact that the disease causes are not correctly aimed at, proper medicines are not available, and reasonable medicines are not available.

The most essential reason is nigral dopaThe production and release of dopamine molecules into the intercellular spaces by amine cells has not been ignored for a long time. None have studied the sites where dopamine molecules actually act in their receptors, nor have they studied whether dopamine molecule channels are a problem in dopamine receptors. In the intercellular space, there are other various particles including Na⁺,K⁺,Ca²⁺,H₂And O. Each of these particles has a channel, why are the dopamine molecules without channels? How can there be no channel? Clearly, the dopamine molecule should have its channels.

Through long-term basic research, under the support of national science foundation projects, two dopamine molecular channels are discovered very fortunately, one is a 'dopamine functional channel', and the other is a 'dopamine protective channel' (actaphys. -chim.sin.2017,23,927; actaphys. -chim.sin.2011,17,2432). Based on a 'dopamine functional channel', the concepts of total dopamine, 'functional dopamine' and non-functional dopamine are defined, and a functional dopamine content formula G is researched and established_D＝f×T_DThus, a dopamine channel theory is established, and the essence of the Parkinson disease is found as follows: the functional dopamine is deficient, and the scientific pathology of Parkinson's disease and the new pathology of Parkinson's disease are proposed. We also scientifically defined parkinson's disease, named: "functional dopamine deficiency syndrome". Based on dopamine channel theory and Parkinson's disease science and pathology, the essential problem of the Parkinson's disease is basically solved on the academic theory. Based on the science and pathology of Parkinson's disease, through the technology for treating the dopamine function conversion factor through the series of treatments and the application of the medicine, the Parkinson's disease becomes a curable or controllable simple disease from difficult, complicated and uncontrollable disabling diseases, and the time for thoroughly controlling the magic of the Parkinson's disease comes early, so that the human is benefited. Since 1817, James Parkinson's doctors carefully observed the disease, at least 5000 million people all over the world suffered from the disease, and the disease is just about to victimize humans, which cannot be ignored, and is the time of stopping.

2. Background of the invention

At present, the research on Parkinson's disease generally adopts ' dopamine function science ' and old dopamine neuron apoptosis pathology. The science of dopamine function states that dopamine molecules in a living body have functions of regulating and controlling movement of the living body and the like by combining different types of dopamine receptors, and are related to the Parkinson disease. Alvurd Carlsson (Arvid Carlsson), Paul Greengard (Paul Greengard) and Eric Kandel (Eric Kandel) have achieved the 2000 nobel prize for signal transduction by dopamine molecules. In 1960, Hornykliewic detected the remains of patients who died in the late stage of Parkinson's disease, and found that the patients died have serious striatal dopamine deficiency. Combined with dopamine function, the parkinson's old pathology appears: the mesencephalic substantia nigra dopaminergic neuron irreversibly undergoes progressive apoptosis, and the Parkinson's disease appears when the dopaminergic cell undergoes apoptosis to a certain degree.

According to the old pathology of apoptosis, the measures currently taken clinically are: (1) exogenous supplement and increase of dopamine (common medicines comprise medobatin, kinine and the like), (2) reduction of dopamine reduction in vivo (common medicines comprise selegiline, rasagiline and safinamide), (3) provision of pseudo dopamine function through an agonist, enhancement of dopamine function (common medicines comprise seforomao, peptidesda and the like), (4) antagonism of acetylcholine receptor function, reduction of acetylcholine function, and achievement of dopamine balance (common medicines comprise amantadine, amban and the like). These drugs only solve the problem of total dopamine, enhance the function of total dopamine, and do not relate to the problem of dopamine-functionalized factor. The principles and concepts of these therapies, limited to the problem of total dopamine, and to the problem of enhancing total dopamine function, are based on the old pathology of parkinson's disease. The principle and thought of the therapies only consider the Parkinson's disease essential problem as the' total dopamine 'problem, but not consider the Parkinson's disease essential problem as the 'functional dopamine' problem. It is clear that these therapies, the anti-parkinson drugs used, although achieving partial relief for a limited period of time, are gradually declining in the presence of parkinson's disease. As the disease ages, the condition of the patient is always worsened and aggravated, causing the condition to become an uncontrollable disabling disease.

3. Summary of the invention

A functional dopamine content formula is established based on our research_D＝f×T_DIt can be seen that the current therapy only solves the total dopamine problem in the functional dopamine problem, namely the total dopamine content and the total dopamine function enhancing problem, namely T in the formula_DThat term, which does not relate to dopamine functionalization factors, is the term fta in the formula. The patent technology and the medicine of the invention are the technology and the medicine for solving the problem of the item f in the formula, and the technology and the medicine for solving the problem of the dopamine functional factor. At present, the clinical measures only solve the problems of total dopamine content and total dopamine function enhancement, but do not relate to the solution of dopamine functional factors. That is, the technology for solving the problem of dopamine-functionalized factor is currently a technical gap in clinical practice. The reason is that the basic scientific research in the past has not reached the understanding that the essential problems of parkinson's disease are: the 'functional dopamine deficiency' problem can not be scientifically recognized and proposed yet. And we, based on the functional dopamine content formula, G_D＝f×T_DThe application of scientific principles such as dopamine channel theory, Parkinson disease science pathology and the like invents a series of technologies and medicines for treating the dopamine function conversion factor.

The invention discloses a technology for dredging a dopamine functional channel blocked by +/-synuclein fibrin by ephedrine (namely ephedrine), and discloses application of ephedrine in treating Parkinson's disease, and treatment of Parkinson's disease and dredging of the dopamine functional channel in an injection or oral ephedrine mode. Dredging dopamine functional channels, repairing and improving dopamine functional factors, recovering and improving functional dopamine content, and achieving the effect of treating and curing Parkinson's disease. In the substantia nigra of the midbrain, the main substance that blocks dopamine-functioning channels is fibrin, the most predominant of which, including alpha (±) synuclein.

4. Description of the drawings

FIG. 1 Experimental determination of Ephedrine (Ephedrine, or Ephedrine) fractionThe change result of free energy of the molecule on the dopamine molecule channel is shown in the middle picture, the ephedrine molecular structure is shown in the middle picture, and the molecular formula is C₁₀H₁₅NO, chemical name: (1R,2S) -2-methylamino-phenylpropan-1-ol.

The results in the figure show that the free energy change of the molecule on the functional channel is 102.3kJ^-1Far less than 157.8kJ. mol change in the dopamine protective channel free energy^-1Or 277.7kJ. mol^-1. The difference between the free energy changes on the functional and protective channels was about 55.5kJ^-1The ratio of the number of molecules of ephedrine passing through a dopamine functional channel to the number of molecules passing through a dopamine protective channel is 2.25 multiplied by 10⁹1 (based on the formula "G ═ R × T × lnK, T ═ 310K). Therefore, the data of the ratio of free energy to the number of molecules obtained from experiments show that the ephedrine molecule has the function of specifically selecting a dopamine functional channel, can dredge the blocked dopamine functional channel, and promote the dopamine molecule to pass through the functional channel to play a functional role, thereby achieving the effect of treating and controlling the Parkinson's disease. In the figure, the Y-axis direction is the direction of the movement of molecules from inside to outside of the cell, and is called a dopamine functional channel. In the figure, the directions of X and Z axes are the directions of molecules moving from the internal structure of the dopamine receptor to the middle membrane layer of the cell membrane, and the molecules are called dopamine protective molecule channels.

5. Detailed description of the preferred embodiments

1) Animal establishment for Parkinson's disease

The + -synuclein contains 140 residues, is a fibrin, and a dimeric structure has been reported so far, as well as a fibrous state [ J Chem Phys,2018,148(12),123322 ]. At present, a plurality of biotechnology companies can well express and purify the +/-synuclein, and the purity of the obtained sample is more than 95%. The use of + -synuclein to generate murine models of Parkinson's disease has been reported in the literature [ Nature 2015,522,340 ]. The literature reports that about 200 g of experimental mice were injected with 2 microgram of + -synuclein into the substantia nigra of the midbrain, and then the spatial distribution of + -synuclein over time was observed by protein fluorescence tracking, and that the experimental mice had very standard parkinson's disease conditions and that apoptosis of dopamine neurons of the experimental mice was observed. The Parkinson disease experimental mice reported in the literature are analyzed by the old pathology of the Parkinson disease based on the dopamine neuron apoptosis mechanism. The observed Parkinson disease experimental mice can not automatically heal and recover health. Results have well demonstrated that + -synuclein, in laboratory mice, cannot be eliminated by its own mechanism, and at the same time, it has also been well demonstrated that laboratory mice cannot cure apoptotic dopamine neuron cells by themselves, thereby restoring health.

We also used ± -synuclein to generate parkinson's disease mice, according to the methods described in the above documents. However, we administered about 200 g of mice, each of which was injected with 5. mu.g of + -synuclein into the substantia nigra of the midbrain, 2.5 times as much as reported in the literature. Injecting 5 microgrammes of +/-synuclein at the substantia nigra part of a mouse, wherein the Parkinson disease of the experimental mouse appears next day, and the Parkinson disease caused by injection reasons and solution reagents is eliminated through a blank test. The next day after injection, the experimental mice did not, and could not develop, a significant amount of dopamine neuron apoptosis, but suffered from severe, standard parkinson's disease conditions. These parkinsonian symptoms can last for more than 2 months. Therefore, our experiments prove that the +/-synuclein can block dopamine functional channels of experimental mice to generate the Parkinson's disease. After the dopamine functional channel is blocked, the +/-synuclein can also produce other effects to cause a great deal of apoptosis of dopamine neurons. The Parkinson disease of the experimental mouse can be analyzed through Parkinson disease scientific pathology and Parkinson disease new pathology. Thus, we refer to the literature methods to uniquely establish standard parkinson's disease condition laboratory mice.

In addition, it is noted that it cannot be assumed that the production of animal models of parkinson's disease necessarily requires massive apoptosis of dopamine neurons. This animal model is based on the old pathology of parkinson's disease. This situation is possible for the later stages of a long-term parkinson's disease patient. However, in the early stage, early stage and middle stage of Parkinson's disease, the patient does not have the condition that large area dopamine neuron really die. Therefore, considering this animal model as a standard animal model of Parkinson's disease for studying Parkinson's disease in different situations has greatly misled and seriously jeopardized the study and treatment of Parkinson's disease. The current definition of parkinson's disease is four major conditions: (1) resting tremor, (2) muscle rigidity, (3) bradykinesia, (4) gait abnormalities and postural instability, and other complications. Therefore, Parkinson's disease is determined by the condition rather than by a particular cause. Massive apoptosis of dopamine neurons is only one cause of parkinson's disease, a condition that is likely to occur later in the long-term in parkinson's patients. Massive apoptosis of dopamine neurons does lead to a decrease in total dopamine content, however, this cannot be regarded as essential for parkinson's disease. A reduction in total dopamine content as a cause of the disease results in: functional dopamine reduction, which is the nature of parkinson's disease. Therefore, the ' functional dopamine ' is used as a standard to judge whether the Parkinson's disease exists or not. The functional dopamine content also comprises dopamine functional factors which are closely related to the smoothness of dopamine functional channels, so that the blockage of the dopamine functional channels is another cause of the Parkinson's disease. The old pathology of the Parkinson disease does not appear, but the old pathology of the Parkinson disease is regarded as an absolute pathology, which obviously brings great pain and life cost to a plurality of patients. The old pathology of the Parkinson disease is regarded as absolute pathology, and obviously, the research and the treatment of the Parkinson disease are greatly misled and seriously damaged, and the invention and the development of the medicine for treating the Parkinson disease are seriously influenced.

2) Effect of ephedrine in the treatment of Parkinson's disease

Our experiments and literature reports that the use of + -synuclein can establish and generate standard Parkinson's disease test mice. Therefore, the Parkinson disease experimental mouse can not be cured by relying on or depending on a self mechanism (namely, no external help is adopted) to recover the health. Thus, the mouse quasi-disease state of the Parkinson's disease experiment can be maintained for a long time, and the disease mouse cannot eliminate the cause of the disease by the self mechanism. We analyzed the cause that the dopamine channel of the experimental rat is blocked by the + -synuclein, and the dopamine neuron cell of the experimental rat is apoptotic by the + -synuclein as reported in the literature. In fact, apoptotic dopamine neuron cells should be difficult to revive, and therefore it should be difficult to restore the health of experimental mice. In addition, in our experiment, about 200 g of experimental mice are injected with 5 micrograms of the sample per mouse in the substantia nigra part of the mice, and the Parkinson's disease appears in the experimental mice the next day. The next day after injection, it is unlikely that the experimental mice will have a significant amount of dopamine neurons that die, but the experimental mice will have severe standard parkinson's disease conditions. These experiments fully demonstrated that the cause was the blockage of functional dopamine channels by + -synuclein in laboratory rats.

Since the etiology of Parkinson's disease is that the functional dopamine channels of laboratory mice are blocked by + -synuclein, if exogenous drugs are used to help the laboratory mice dredge: the functional dopamine channel blocked by the +/-synuclein increases and recovers the content of functional dopamine, and the Parkinson disease of the experimental mouse is cured, so that the health of the experimental mouse can be recovered. Conversely, by injecting the drug into the Parkinson disease experimental mouse, the Parkinson disease symptoms of the experimental mouse are eliminated, and the health of the experimental mouse is recovered, so that the drug helps the experimental mouse to dredge: the functional dopamine channel blocked by the +/-synuclein increases and recovers the content of functional dopamine, thereby achieving the aim of curing the Parkinson's disease.

Based on the standard Parkinson disease experimental mice generated by adopting the +/-synuclein, the experimental mice are injected with 0.6 mg of ephedrine once a day. After about 30 days, the standard Parkinson disease symptoms of the experimental mice can be eliminated, the administration is stopped, and the experimental mice completely recover to be healthy. And the laboratory mice continue to maintain normal health status without any help. Therefore, the ephedrine has the effect of curing the Parkinson's disease through the standard Parkinson's disease mouse experiment.