CN106562945A - Drug for treating Parkinson disease - Google Patents
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- CN106562945A CN106562945A CN201510653772.XA CN201510653772A CN106562945A CN 106562945 A CN106562945 A CN 106562945A CN 201510653772 A CN201510653772 A CN 201510653772A CN 106562945 A CN106562945 A CN 106562945A
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Abstract
The Parkinson disease is called ''chronic cancer'' and is a common incurable disabling disease. At present, a main drug used in clinic is levodopa, namely, the content of dopamine in cells is increased by adopting an exogenous method to relieve the Parkinson disease, and serious side effects are generated, so that patients are painful. A novel drug for treating the Parkinson disease is invented; and the Parkinson disease is treated by dredging a dopamine functional molecule channel. Raw materials of the drug originate from plant extraction separation, an alkaloid compound is obtained through a two-step chemical reaction, and separation is performed by adopting a chiral separation column to obtain a chiral compound, so that the novel drug is prepared. A biological assay experiment proves that drug molecules can dredge the dopamine functional molecule channel, thereby facilitating more dopamine in a biosystem to exert normal function effects. A mouse experiment verifies that the drug has the effect of treating the Parkinson disease and is a safe and efficient drug.
Description
Technical field
Parkinson disease are referred to as " chronic cancer ", are currently a kind of common disabling condition that can not be cured.In China's Mainland, 2,000,000 parkinson patients are had more than at present, and is increased with annual 100000 new number of patients.Parkinson disease also present the trend of rejuvenation in recent years, and the patient in thirty or forty year gradually increases.As parkinson disease are a kind of disabling conditions that can not be cured, minimal invasive treatment can not take care of oneself, and its hazardness is only second to tumor, cardiovascular and cerebrovascular disease.At present, Parkinsonian high potency drugs are also directed to, patient was lived and quality of life is all excessively poor in the painful stage.Therefore, develop efficient medicine to be used to treat parkinson disease is all an important target all the time.In order to develop efficient medicine, the blood brain barrier in consideration brain is needed, because many medicines do not arrive the position of the treatment at all.In addition, because the various complexity of the parkinson disease state of an illness, also lacking the understanding of clear pathology at present.Dopamine (DA) is a kind of important neurotransmitter of intracerebral.Dopamine regulates and controls motor function, cognitive activities by different subtype dopamine receptor, relevant with various physiology, pathological process.Parkinsonian preventing and treating is all closely related with DA systems, and achievement in research is included：Gloomy (the Arvid of A Erweide karrs
Carlsson), dopamine small molecule obtains Bel's Medicine in 2000 as physiology, the pathological process such as signal transduction and regulation and control motor function, cognitive activities and drug dependence if finding for Borrow's Greengard (Paul Greengard) and Eric Kan Deer (Eric Kandel).Their result of study can reveal that the basic cause of Parkinsonian symptoms, be to lack dopamine due to the brain of patient, it is understood that the important function that dopamine is played in brain, it is meant that can effectively be treated by medicine.
Background technology
At present, alleviate the levodopa that Parkinsonian key agents or nineteen sixty-eight find（Commercially available medicine name：Madopar）, the centesimal amount of levodopa of suction enters cell through blood brain barrier, and then the decarboxylation of decarboxylase generates dopamine molecule in the cell, improves intracellular middle DOPAMINE CONTENT IN RABBIT to alleviate the parkinson state of an illness.This employing external source method increases the medicine of DOPAMINE CONTENT IN RABBIT, the ability that cell itself can be suppressed in the cell to generate dopamine, inhibits then the activity of cell so that the efficacy stability phase is very short；A large amount of uncontrollable dopamine molecules are generated under extracellular decarboxylation in the extracellular levodopa for having 99%, very big Side effect is caused, is increased the pain of patient.In terms of surgical intervention, using brain pacemaker, also known as Deep brain stimulation, the main electrode by performing the operation in implantation brain, electric pulse electricity irritation related neural core group is provided, so as to reach the purpose of dysregulation nerve, alleviates Parkinsonian three cardinal symptoms：Tremble, stiff and bradykinesia, such as improve starting and stand up difficulty etc..In order to reach stimulation therapy effect, need to open brain in patients unilateral or bilateral skull, need heavy installation cost and Operation Fee, put alien material electrode in brain into, heavy financial burden is brought not only to patient, but also the danger of very big reality and potentiality is brought, and effect is there is no, even if having.
The content of the invention
Many studies have shown that the parkinson disease cause of disease is lacking for central nervous system's dopamine.Our research then shows that function dopamine lacks the blocking for being mostly derived from Dopamine molecular channel between neurocyte in nervous system.The dopamine produced in neurocyte, through its function of cells play, will become function dopamine, just becomes a kind of important neurotransmitter by Dopamine molecular channel.But, there is gap between neurocyte and neurocyte, just as the seam in twice cliff, dopamine molecule are named as synapse synapse by little cliff prominent on neuron membrane, skip this road seam and be passed on.Synapse bulk composition is exactly various types of dopamine receptors, and our research finds dopamine molecule passage is there is in dopamine receptor protein structure.Our long campaigns study dopamine receptor protein structure and its application in drug development, and it is theoretical to establish dopamine molecule passage.According to dopamine molecule passage viewpoint, we can have an X-rayed the main pathology of parkinson disease is：The blocking of Dopamine molecular channel.In human brain tissue cell, do not lack dopamine under normal circumstances, do not lack receptor and the space of storage dopamine yet, so whether dopamine can be to cause Parkinsonian key by the effect of Dopamine molecular channel function.Briefly parkinson disease pathology is exactly that Dopamine molecular channel plugs.Because only that the dopamine acted on by Dopamine molecular channel function can just become " function dopamine ", function dopamine just plays a part of neurotransmitter, function dopamine lack cause control motor capacity weaken and cause parkinson disease, function dopamine lacks degree and decides Parkinsonian severity extent.Therefore, although parkinson disease different phase, the disease and the state of an illness of different individual patients is ever-changing, but in view of parkinson disease pathology, main cause is exactly the blocking of Dopamine molecular channel, causes Parkinson disease, makes the condition of illness feature with four standards：(1) static tremor, (2) muscular rigidity, (3) bradykinesia, (4) abnormal gait and posture are unstable.As long as the Dopamine molecular channel of blocking can be got through, in view of pathology, can necessarily cure Parkinsonian symptoms.A class treatment of Parkinson disease novel drugs are we have invented, can be dredged and be guided dopamine by way of functional molecular passage and technology, treat and control Parkinsonian symptoms.Such novel drugs is alkaloid compound, is initially come from plant, obtains this kind of alkaloid compound by separating to plant extraction, again by two step chemical reactions, then obtains chiral compound by chiral separation post separation, and formula is prepared into novel drugs.Proved by biological test experiment, this kind of medicine can get through Dopamine molecular channel, and help guides dopamine molecule function to act on, thus can treat Parkinsonian symptoms.Confirmed by mouse zoopery, such medicine has the effect for the treatment of Parkinsonian symptoms.Because this kind of novel drugs are by dredging Dopamine molecular channel, repairing and keep the function of dopamine balance, it is possible to reach the purpose for fundamentally treating Parkinsonian symptoms.Due to the medicine and the unimpeded dopamine passage of the used identical of normal person, rather than it is free from side effects in the range of the dosage of safety using the normal dopamine channel system mode of destruction, therefore the type medicine, is a kind of safe, efficient medicine.At present, there is no the report of related such medicine, also using the present invention used by technology, i.e., dredge and guide dopamine by functional molecular passage by way of and technology, treat and control Parkinsonian symptoms.
4
, description of the drawings
Fig. 1 is that biotic experiment determines novel drugs molecule Gibbs free result figure on dopamine molecule passage.Result in figure shows that free energy change of the drug molecule on Dopamine molecular channel turns to 99 kJ.mol-1, 164 kJ.mol are turned to much smaller than in dopamine protection molecular channel free energy change-1.Therefore, the drug molecule of the application can dredge Dopamine molecular channel so that a large amount of dopamine can reach treatment and control the effect of Parkinsonian symptoms by functional molecular passage, function effect.In figure, Y direction is that dopamine and drug molecule pass through dopamine receptor internal structure, extracellular movement direction, referred to as Dopamine molecular channel is reached from cell.In figure, X and Z-direction are that dopamine and drug molecule move to cell membrane middle film layer direction, referred to as dopamine protection molecular channel from dopamine receptor internal structure.Determination experiment in figure proves that the application drug molecule can dredge Dopamine molecular channel, and Dopamine and system can be made to run well.
5
, specific embodiment
1）Synthetic line：Demethylation ephedrine and demethylation pseudoephedrine（Or ephedrine and pseudoephedrine, these compounds extracted from Herba Ephedrae are purchased in market）+ 45% HI solution of+red phosphorus, oil bath backflow, room temperature cooling, plus distilled water sucking filtration, filtrate add NaOH solution to be adjusted to neutrality, and toluene extraction merges organic faciess, plus HCl solution acidifying, and vacuum distilling obtains product.2）Chiral separation：The alkaloid amphetamine product of synthesis splits into S chirality type alkaloid amphetamines and R chirality type alkaloid amphetamine products by chiral separation post and high phase liquid chromatography technology.The application medicine is the R chirality type alkaloid amphetamine compounds of chiral purity.Compound molecule formula is R-C6H5CH2CH(CH3) NHR, wherein R=H, CH3, OH, SH etc..3）Biological test experiment：Using 1- palmityls -2- oleoyls-lecithin (POPC) raw material composition Lipid bilayer membranes, mice dopamine D 3 receptor is from the abundant bio tech ltd's purchase of upper Hisense, set up D3 receptor-POPC duplicatures and determine system, determined in the middle of duplicature respectively by glass electrode, duplicature inside and outside hydrogen ion concentration and gradient, determine Gibbs free of the drug molecule by dopamine molecule passage process（Proc. Natl. Acad. Sci.
1980, 77(4), 2038）.Measurement result shows in fig. 1.This is a kind of classical assay method, with reliability, also similar to the result acquired by other assay methods.Biological test experiment proves that the application drug molecule can dredge Dopamine molecular channel such that it is able to make Dopamine and its system run well.4）Mouse animal experiment, one has the test of four classes.(1) haloperidol and novel drugs mouse zoopery：Haloperidol (Sigma companies) is dissolved in normal saline, is configured to the storing solution of 4 mg/ml, using the Working dilutions for being front diluted to 1mg/ml.Novel drugs are also arranged to the storing solution of 4 mg/ml, are prepared with 5% G/W, using the new drug thing liquid for being front diluted to 1mg/ml.Kun Ming mice 20（20 ± 2g）Purchase in Kunming Medical University's animal center, it is divided into two groups, one group is matched group 10, every 0.5 ml haloperidol diluent of Mus gavage, adds 0.3 ml of gavage, 5% G/Ws after half an hour daily, and another set is 10 white mice of experimental group, every 0.5 ml haloperidol diluent of Mus gavage, adds 0.3 ml new drug thing liquids of gavage after half an hour daily.Continuous day-to-day test 6 days, daily identical test step.Experimental result is：10 mices of experimental group do not have Parkinson's disease to occur, mice bouncing；, there is in succession Parkinson's disease, die off in 10 mices of matched group.Document report haloperidol acts on dopamine receptor system.Before haloperidol and novel drugs mouse zoopery is carried out, we employ Kun Ming mice 6, according to white mice individual variation, using appropriate amount haloperidol medicine gavage, by the nervous system Dopamine molecular channel for blocking white mouse, so that this 6 white mice can become parkinsonian rat model, meet the parkinson condition of illness feature of four standards：(1) static tremor, (2) muscular rigidity, (3) bradykinesia, (4) abnormal gait and posture are unstable.6 tests on white mice checking haloperidol are acted on Dopamine molecular channel.(2) clozapine and novel drugs mouse zoopery：Clozapine (the great Bioisystech Co., Ltd in Shanghai) is dissolved in normal saline, is configured to the storing solution of 4 mg/ml, using the Working dilutions for being front diluted to 1mg/ml.Novel drugs are also arranged to the storing solution of 4 mg/ml, are prepared with 5% G/W, using the new drug thing liquid for being front diluted to 1mg/ml.Kun Ming mice 20（20 ± 2g）It is divided into two groups, one group is matched group 10, daily every 0.5 ml clozapine diluent of Mus gavage, add 0.3 ml of gavage, 5% G/Ws after half an hour, another set is 10 white mice of experimental group, daily every 0.5 ml clozapine diluent of Mus gavage, adds 0.3 ml new drug thing liquids of gavage after half an hour.Long run test 10 days every other day, each identical test step.Experimental result is：10 mices of experimental group do not have Parkinson's disease to occur, mice bouncing；, there is in succession Parkinson's disease, die off in 10 mices of matched group.Document report clozapine is also to act on dopamine receptor system.Before clozapine and novel drugs mouse zoopery is carried out, we employ Kun Ming mice 6, according to white mice individual variation, using appropriate amount clozapine medicine gavage, by the nervous system Dopamine molecular channel for blocking white mouse so that this 6 white mice can become parkinsonian rat model.Parkinsonian rat model meets the parkinson condition of illness feature of four standards：(1) static tremor, (2) muscular rigidity, (3) bradykinesia, (4) abnormal gait and posture are unstable.6 tests on white mice checking clozapines are acted on Dopamine molecular channel.(3) chlorpromazine and novel drugs mouse zoopery：Chlorpromazine hydrochloride (sigma-aldrich companies) is dissolved in normal saline, is configured to the storing solution of 4 mg/ml, using the Working dilutions for being front diluted to 1mg/ml.Novel drugs are also arranged to the storing solution of 4 mg/ml, are prepared with 5% G/W, using the new drug thing liquid for being front diluted to 1mg/ml.Kun Ming mice 20（20 ± 2g）It is divided into two groups, one group is matched group 10, daily every 0.5 ml chlorpromazine diluent of Mus gavage, add 0.3 ml of gavage, 5% G/Ws after half an hour, another set is 10 white mice of experimental group, daily every 0.5 ml chlorpromazine diluent of Mus gavage, adds 0.3 ml new drug thing liquids of gavage after half an hour.Continuous day-to-day test 6 days, each identical test step.Experimental result is：10 mices of experimental group do not have Parkinson's disease to occur, but die off；10 mices of matched group, also no Parkinson's disease appearance, but it is also to die off.Document report chlorpromazine is to act on the non-dopamine system such as 5-hydroxy tryptamine system.Before clozapine and novel drugs mouse zoopery is carried out, we employ Kun Ming mice 6, according to white mice individual variation, using appropriate amount chlorpromazine medicine gavage, but can not all cause this 6 white mice to become Parkinsonian symptoms Mus, the amount even if this 6 white mice, due to increasing chlorpromazine gavage, it is all dead, cannot also become parkinsonian rat model.The test proves that chlorpromazine is not acting on dopamine receptor system, it is impossible to make white mice produce Parkinsonian symptoms.Because chlorpromazine is not acting on dopamine receptor system, all there are not Parkinsonian symptoms in novel drugs test group and matched group mouse, and die off.Novel drugs simply act on dopamine receptor system, can not produce impact to the impact that chlorpromazine is produced.
(4) haloperidol and madopar mouse zoopery：Haloperidol (Sigma companies) is dissolved in normal saline, is configured to the storing solution of 4 mg/ml, using the working solution for being front diluted to 1mg/ml.Madopar (Shanghai company limited of Roche Group is purchased in strong good pharmacy) is configured to the madopar liquid of 10 mg/ml with 5% G/W.Kun Ming mice 20（20 ± 2g）It is divided into two groups, one group is matched group 10, daily every 0.5 ml haloperidol diluent of Mus gavage, add 0.3 ml of gavage, 5% G/Ws after half an hour, another set is 10 white mice of experimental group, daily every 0.5 ml haloperidol diluent of Mus gavage, adds 0.3 ml madopar liquid of gavage after half an hour.Continuous day-to-day test 6 days, daily identical test step.Experimental result is：There is Parkinson's disease in 10 mices of experimental group, and die off；10 mices of matched group, and there is in succession Parkinson's disease, and die off.Should be it is demonstrated experimentally that madopar be unable to the Dopamine molecular channel of dredge blockage, therefore it is very low to treat the effect of Parkinsonian symptoms.Comprehensive mouse zoopery, it was demonstrated that：Novel drugs act on dopamine system, are capable of the Dopamine molecular channel of dredge blockage, can play the remarkable result that Parkinsonian symptoms are cured in treatment.
Claims (2)
1.R types chirality amfetamine is used to treating and controlling the medicine of Parkinsonian symptoms for the compound and its derivant of agent structure, and compound molecule formula is R-C6H5CH2CH(CH3)NHR´,
Wherein R=H, CH3, OH, SH etc..
2. the technology and its medicine of Parkinsonian symptoms are treated and are controlled by dredging Dopamine molecular channel mode.
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| CN111803473A (en) * | 2019-04-10 | 2020-10-23 | 云南帕精生物科技有限公司 | Application of nortriptyline in treating Parkinson's disease |
Citations (4)
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|---|---|---|---|---|
| CN1898201A (en) * | 2003-10-21 | 2007-01-17 | 森蒂有限公司 | Carbamoyl esters that inhibit cholinesterase and release pharmacologically active agents |
| US20100034873A1 (en) * | 2008-08-06 | 2010-02-11 | Delprete Keith | Transdermal ricinoleic acid compositions |
| CN102170874A (en) * | 2008-08-06 | 2011-08-31 | 高思福斯中心（控股）有限公司 | Compositions and methods for treating psychiatric disorders |
| CN104940224A (en) * | 2014-03-25 | 2015-09-30 | 林信涌 | Inhalation type pharmaceutical composition for treating Parkinson's disease and preparation method thereof |
-
2015
- 2015-10-11 CN CN201510653772.XA patent/CN106562945A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1898201A (en) * | 2003-10-21 | 2007-01-17 | 森蒂有限公司 | Carbamoyl esters that inhibit cholinesterase and release pharmacologically active agents |
| US20100034873A1 (en) * | 2008-08-06 | 2010-02-11 | Delprete Keith | Transdermal ricinoleic acid compositions |
| CN102170874A (en) * | 2008-08-06 | 2011-08-31 | 高思福斯中心（控股）有限公司 | Compositions and methods for treating psychiatric disorders |
| CN104940224A (en) * | 2014-03-25 | 2015-09-30 | 林信涌 | Inhalation type pharmaceutical composition for treating Parkinson's disease and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| 卞富永 等: "多巴胺在受体膜蛋白中分子通道理论透视帕金森疾病病理", 《中国化学会成立80周年中国化学会第二届全国生物物理化学会议（NCBPC2）暨国际华人生物物理化学发展论坛会议论文集》 * |
| 张继伟 等: "多巴胺在POPC磷脂双层膜中扩散和透过过程的分子动力学模拟", 《物理化学学报》 * |
| 王丹 等: "苯丙氨透过POPC磷脂双层膜过程分子动力学模拟", 《中国化学会第29届学术年会摘要集》 * |
| 苏闻 等: "丙炔苯丙胺治疗帕金森病多中心、随机、对照开放临床研究", 《中华神经科杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111803473A (en) * | 2019-04-10 | 2020-10-23 | 云南帕精生物科技有限公司 | Application of nortriptyline in treating Parkinson's disease |
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