CN101305997B - Medicament for treating nerve dysfunction after refraining opium type material - Google Patents
Medicament for treating nerve dysfunction after refraining opium type material Download PDFInfo
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- CN101305997B CN101305997B CN2008100586065A CN200810058606A CN101305997B CN 101305997 B CN101305997 B CN 101305997B CN 2008100586065 A CN2008100586065 A CN 2008100586065A CN 200810058606 A CN200810058606 A CN 200810058606A CN 101305997 B CN101305997 B CN 101305997B
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Abstract
The invention relates to a drug for treating the nerve functional disturbance after the withdrawal of opium matters. The drug is a compound preparation which is composed of atropine and baclofen in the mass ratio of 1:1-10. The drug has the main function that the nerve functional disturbance syndrome which is caused by the withdrawal after opioid addiction can be inhibited. The compound preparation can well inhibit the withdrawal syndrome, which is beneficial for the physical recovery. The detoxification drug with the advantages of low use cost, safety, reliability, strong scientificity, and insignificant toxicity and side effects can shorten the withdrawal time relieve or partially remove the nerve functional disturbance syndrome after the withdrawal of the narcotics, and can be used as an ideal detoxification drug.
Description
Technical field
The present invention relates to addiction medicine and neurobiology technical field, specifically a kind of medicine for the treatment of nerve dysfunction after refraining opium type material.
Technical background
The dependency behavior is a series of cognitions, behavior and the physiological signs group that addicted substance acts on the susceptible brain and produced, although being perfectly clear, user use the dependence material can bring tangible problem, but still continue to use, its result has caused relying on symptom and mandatory drug-seeking behavior (compulsive drug seeking behavior) after tolerance, the drug withdrawal.In a single day these symptoms form with regard to long-term existence, even give up the several years even longer, and the possibility [1] that still has intensive drug craving sense and revert to take drugs.Opioid drug is of paramount importance a kind of in the addictive drug, use opioid drug to have brought huge infringement for individual, family, society, cause infectious diseases such as labour force's forfeiture, national quality decline, HIV to propagate, become worldwide public health and social problem.Behavior sensitization process is mediated by awarding the close midbrain-dopamine system of interactively with medicine: DA mediator content raise during ambient induced relied on, and the dopamine neuron discharge increases this type of change triggers behavior sensitization of dopamine neuron.The life-time service dependent drug can make nerve conduction path generation adaptive change, the cAMP compensatory raises, thereby this rise comprises that the activated adenyl cyclase activity makes the rising of cAMP content activate cAMP deopendent protein kinase A and makes respective target albumen generation phosphorylation and bring into play biological action.After the withdrawal, the cAMP path that has been raised is still kept the hyperfunction of its function, relies on symptom [2] accordingly thereby cause body.
Under the physiological status, body function is regulated in have the advantage status performance of sympathetic nervous system, in the refraining opium type material process, and the parasympathetic nervous system status of having the advantage, sympathetic nervous system function is low, causes to bring out a large amount of withdrawal symptoms.
The detoxification medicament categories that opiates relies on is a lot, and following a few class roughly can be arranged:
2. opioid receptor agonist: this is a cross-dependence principle of utilizing similar medicine, and it represents medicine is methadone.This medicine itself is an opioid analgesics, and the oral opiates withdrawal symptom that suppresses continue 24～36 hours, and toxic and side effects is low, does not influence individual daily behavior.General predose 30～40rng/d+ is then with the end of successively decreasing in 2～3 weeks.Methadone used select 30 surplus year, the demonstration of having passed through many countries and regions, effect is clear and definite.But beautiful second ketone only suits to use in the mechanism better in medical condition, that management is strict.In addition, the defective that it also has self as: this is as narcotic, is " with poison for poison " in some sense, for a long time with self easy addiction, runs off easily, forms illegal drug, later stage withdrawal difficulty.
2. opiate receptor partial agonist: it represents medicine is buprenorphin hydrochloride, and this medicine belongs to the opiate receptor partial agonist, and only agent is used for clinical as powerful pain-stopping in beginning.Since the end of the seventies, the research of relevant its opiates withdrawal treatment aspect becomes increasingly active and studies show that buprenorphine can be alleviated the opium withdrawal symptom, but itself has certain dependency.
3. non-opium medicine: mainly refer to maincenter α receptor stimulating agent, represent medicine that clonidine is arranged.Clonidine is a maincenter α receptor stimulating agent, originally be used for resisting hypertension, after discover, it can successfully alleviate withdrawal symptom behind the opiate addiction (as watery nasal discharge, shed tears, suffer from abdominal pain, diarrhoea, skeletal muscle pain, shiver with cold etc.), and the untoward reaction of medicine is common xerostomia, asthenia, dizzy, constipation.
4. traditional medicine method: the theory of Chinese medical science of China has original understanding to the drug problem.In recent years. there are being some progress in China aspect the traditional Chinese medical science drug rehabilitation, developed the medicine of some Chinese medicine method treatment opiate addictions and obtained certain success, but the toxic action of the traditional Chinese medical science is indeterminate in the use that has to a certain degree limited traditional Chinese medical science preparation.
List of references:
[1]Hyman，S.E.；Malenka，R.C.Addiction?and?the?brain：the?neurobiologyof?compulsion?and?its?persistence.Nat.Rev.Neurosci.2：695-703；2001.
[2]Nestler，E.J.；Hope，B.T.；Widnell，K.L.Drug?addiction：a?model?forthe?molecular?basis?of?neural?plasticity.Neuron?11：995-1006；1993.
[3.] Soup Yi Lang, the therapeutic strategy so far of opium drug addiction. Beijing medical science .1999.21 (1) 45-46
Summary of the invention
The purpose of this invention is to provide a kind of medicine for the treatment of nerve dysfunction after refraining opium type material, it can strengthen GABA function of nervous system and suppress the cholinergic nerve function simultaneously, and the synergism of this two system is being brought into play the effect that DA discharges that suppresses jointly.
Technical scheme of the present invention is: is 1: 1～10 compound preparations of forming (anti-additive medicament) by atropine, baclofen according to mass ratio, the nervous dysfunction syndrome of giving up behind the major function inhibition opioid addiction.
Compound preparation of the present invention can be good at suppressing withdrawal symptom, helps physical recovery.Have that use cost is low, safe, reliable, scientific strong, toxic and side effects is little, can obviously shorten the time of giving up and alleviation or part is removed nervous dysfunction symptom after the drugs drug withdrawal, can be used as a kind of ideal anti-additive medicament and use.
Below be the experimental data relevant with drug effect of the present invention:
As shown in Figure 1, shown the influence of atropine to withdrawal symptom;
As shown in Figure 2, shown the influence of baclofen to withdrawal symptom;
As shown in Figure 3, shown atropine and baclofen synergism to withdrawal symptom.
The result: one factor analysis of variance (one-way ANOVA) shows after the continuously injecting animals morphine mouse jump number of times showed increased under the inducing of Allylnoroxymorphone, and to the number of skips inhibitory action, difference has statistical significance under the effect of various dose bromocriptine.Check shows relatively P=0.024＜0.05 of morphine group and normal saline group, and difference has significance, illustrate that the morphine group is given up in the process at Allylnoroxymorphone to induce down number of skips to give up the model establishment apparently higher than the normal saline matched group.Morphine group and 1mg/kg atropine group relatively P=0.572＞0.05 difference do not have significance, as shown in Figure 1.One factor analysis of variance (one-way ANOVA) shows that activity increases after the continuously injecting animals morphine in the baclofen experiment simultaneously, under the effect of various dose baclofen, activity inhibitory action difference had statistical significance, variable remarkable [F (4,34)=3.121, p=0.032] between group.Morphine group and normal saline group be P=0.014＜0.05 relatively, and difference has significance, the morphine abstinence syndrome process be described after morphine group jump behavior apparently higher than the normal saline matched group, show and give up the model establishment.Morphine group and 0.5mg/kg baclofen, 1.0mg/kg baclofen comparing difference do not have significance (P=0.243＞0.05, P=0.089＞0.05), morphine group and 1.5mg/kg baclofen comparing difference have significance (P=0.032＜0.05), effect presents dose-dependence, as shown in Figure 2.The dosage of selecting baclofen unrestraint effect for use in the concertedness experiment is also used the atropine 1mg/kg of unrestraint effect simultaneously as test dose 1mg/kg.Atropine as shown in Figure 3, baclofen to the inductive morphine abstinence syndrome of Allylnoroxymorphone after the influence of jump behavior, comparing difference has the significance difference [F (4 between one-way ANOVA statistics demonstration group, 35)=42.607, p＜0.001], Post hoc (LSD) check shows that morphine group and normal saline group relatively show and give up the modelling success in p＜0.001, morphine group and 1mg/kg bromocriptine group and 1mg/kg baclofen comparing difference do not have significance (p=.0196＜0.05, p=0.393＜0.05), it should be noted that in the administering drug combinations experiment but to produce significant difference (p＜0.001), the reciprocal action of the two result thus obtains fine explanation.
Description of drawings
Fig. 1 is the influence of atropine to withdrawal symptom;
Fig. 2 is the influence of baclofen to withdrawal symptom;
Fig. 3 is atropine and the baclofen synergism to withdrawal symptom.
The specific embodiment
Embodiment 1:
Pharmaceutical formulation:
Atropine: baclofen (according to mass ratio)=1: 1 (atropine and baclofen are the commercially available prod)
Preparation method:
With analytically pure medicine according to atropine: baclofen (according to mass ratio)=respectively be dissolved in normal saline at 1: 1, mixed evenly get final product compound formulation of the present invention.
Embodiment 2:
Pharmaceutical formulation: atropine: baclofen (according to mass ratio)=1: 5
Preparation method is identical with embodiment 1.
Embodiment 3:
Pharmaceutical formulation:
Atropine: baclofen (according to mass ratio)=1: 10
Preparation method is identical with embodiment 1.
Claims (1)
1. one kind by crude drug quality proportioning is: atropine: the application of compound preparation in the medicine of preparation treatment nerve dysfunction after refraining opium type material of baclofen=form at 1: 1.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2008100586065A CN101305997B (en) | 2008-07-01 | 2008-07-01 | Medicament for treating nerve dysfunction after refraining opium type material |
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| CN2008100586065A CN101305997B (en) | 2008-07-01 | 2008-07-01 | Medicament for treating nerve dysfunction after refraining opium type material |
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| CN101305997B true CN101305997B (en) | 2010-08-18 |
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| CN108735291A (en) * | 2018-05-21 | 2018-11-02 | 上海青研科技有限公司 | Drug addiction personnel's drugs craving degree assessment method based on interior hidden test and device |
| CN114214396A (en) * | 2020-06-30 | 2022-03-22 | 宁波市康宁医院(宁波市精神疾病预防控制中心、宁波市微循环与莨菪类药研究所) | Application of GABRD methylation as heroin relapse resisting target |
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Granted publication date: 20100818 Termination date: 20130701 |