CN101422610A - Chemical composite preparation and use thereof - Google Patents
Chemical composite preparation and use thereof Download PDFInfo
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- CN101422610A CN101422610A CNA2007100664159A CN200710066415A CN101422610A CN 101422610 A CN101422610 A CN 101422610A CN A2007100664159 A CNA2007100664159 A CN A2007100664159A CN 200710066415 A CN200710066415 A CN 200710066415A CN 101422610 A CN101422610 A CN 101422610A
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Abstract
The invention relates to a chemical composite preparation and an application thereof, which belong to the technical field of addition medical applications and are characterized in that the chemical composite preparation consists of a GABAB receptor agonist material, an M receptor antagonist material and an auxiliary material (any one of starch, pre-gelatinized starch and dextrin), and the weight proportions of the effective constituents of the materials are as follows: 1 to 40 percent of the GABAB receptor agonist material, 1 to 15 percent of the M receptor antagonist material and 45 to 98 percent of the auxiliary material, and the materials are prepared into tablets according to the conventional method. The chemical composite preparation can be other preparations prepared by the conventional method after changing the auxiliary material. The chemical composite preparation is used for curing opioid type drug dependent patients in the aspects of drug discarding, rehabilitation and drug retaking resistance, and the healing effect is better than that of singly used M receptor antagonist or GABAB receptor agonist, and the invention has significant drug retaking resistant effect.
Description
Technical field:
The present invention relates to (be called for short GABA by m-AChR (abbreviation m receptor) antagonist and γ-An Jidingsuan B receptor
BReceptor) chemical composite preparation and the application thereof of the preparation of agonist and adjuvant belong to the addiction medicine applied technical field.
Background technology:
When opiate receptor action system Medical Biology intervention means enjoyed non-negotiation to have difficulty in taking a step, non-opiate receptor action system compensatory adapted to and the research of anti-opium drug dependence and recurrence medicine receives much concern.Closely during the last ten years, it is found that some chemical substance itself do not have direct effect to opiate receptor, but the generation that can suppress the opium tolerance and rely on.This impels people to begin to other receptor acting system beyond the opiate receptor action system effect in opium relies on to explore.
One, dopamine (DA) receptor stimulating agent is used for opium drug and gives up and the treatment of addiction research
A large amount of studies show that, addiction phase opium drug causes a large amount of releases of DA, human body generation adapt, and after the drug withdrawal, the original DA release function of human body self temporarily can't be replied, be starkly lower than normal level thereby the interior DA level of body occurs, produce a series of behavior reaction sensitization phenomenons (acute withdrawal symptom).
Drug abuse by directly or indirectly activate from the midbrain veutro (ventral tegmental area, VTA) to the DA projection tract of forebrain by a large amount of institute confirmations with generally acknowledge (see figure 1).Most of Drug abuse promote VTA neuron DA to discharge (see figure 2).
As shown in Figure 2, VTA projects the DA neuron of NAc and the GABA serotonergic neuron forms synaptic contact, and as shown in Figure 1 between VTA, NAc, the VP three GABA can form the topology contact by relay cell.Since it is so close to regulate the movable nerve accommodation relation with addictive behavior of the DA serotonergic neuron in this loop, can conclude that equally the activity that directly changes this loop GABA serotonergic neuron also can cause the variation of addictive behavior.This shows that except that the DA system, GABA is the important system of can not ignore.
The reciprocal action of DA energy and GABA energy system is proved [1,2,3,4].There is a reciprocal action [5,6,7] that suppresses each other between GABA serotonergic neuron and the DOPA serotonergic neuron.In the reciprocal action that between GABA serotonergic neuron and DA serotonergic neuron, suppresses mutually, DA D1 and GABA
AThe receptor role is small and weak relatively, and mainly that influence is DA D2 and GABA
BReceptor [8; 9].The d2 dopamine receptor agonist reduces the reaction of postsynaptic to GABA, and dopamine D 1 and D2 receptor can activity brought into play reciprocal regulating action [10] to GABA.The d2 dopamine receptor agonist significantly reduces the aggregate velocity of GABA, and dopamine D 2 receptor antagonists has then strengthened the aggregate velocity of GABA; The d1 dopamine receptor agonist then has no significant effect [11] to the aggregate velocity of GABA.
It is DA energy and GABA energy system that above result of study prompting, the development of novel drug-breaking medicine can not be avoided two neurotransmitter systems, finally reaches the curative effect of drug rehabilitation by the comprehensive adjustment to DA energy and GABA energy system.Yet early-stage Study result shows, though the medicine of DA receptor or raising DA level can be alleviated acute withdrawal symptom to a certain extent in the direct exciting brain, as select for use the medicine that substitutes dopamine, the effect of simulation dopamine medicine, prevent medicine that dopamine decomposes etc., but use this class medicine very limited separately to acute withdrawal symptom therapeutic effect, protracted symptom treatment and anti-reverting to take drugs are not had obviously effect, and DA receptor or the medicine potential risk that improves the DA level are to take for a long time and may produce new drug dependence consequence in the direct exciting brain.
Two, the m receptor antagonist is used for opium drug and gives up and the treatment of addiction research
The medicinal of m receptor antagonist can be traced back to the ancient times in the west, has only medical herbs such as hyoscyami, Semen daturae, Flos Daturae at that time.The effective alkaloid that mainly contains of these medical herbs is scopolamine, atropine, hyoscyamine, and they all are the m receptor antagonisies.The known road of doctor at that time is with hyoscyami treatment opium relevant disease, comprises that as the indication of Flos Daturae opium addiction, Semen daturae are the antidotes of opium etc.In fact this class medicine all have the striatal cholinergic nerve path of blocking-up, suppress dopamine in hyperfunction, the corresponding raising brain of acetylcholine effect, help keeping or recovering the effect characteristics of striatum dopamine (DA) and acetylcholine (Ach) two big mediator system balancings.This shows that the m receptor antagonist has the effect of dopamine level in the indirect raising brain.
Studies show that further m receptor playing the part of important role in the morphine addiction behavior, but wherein the function of M1-M5 receptor subtype is different.Nearest achievement in research provides the most direct proof for the regulation and control that m receptor participates in opium award mechanism.Researcher uses the gene knockout technology to cause M5 receptor defects mice, the mice morphine reward effect position preference behavior of finding M5 acceptor gene disappearance weakens widely, the analgesic effect of morphine and the not at all influence of generation that morphine analgesia is tolerated, infer that the M5 receptor may be as the new treatment target spot [12,13] of opiate addiction.M1 receptor subtype antagonism not only plays therapeutical effect [14] to the acute withdrawal symptom of morphine, and aspects such as anti-pain in morphine addiction and the improvement of condition position preference play important adjustment of treatment effect [15].
Experimentation shows, use the m receptor antagonist to carry out Drug therapy separately, though to give up the vertebral body that causes be outward that the syndrome therapeutic effect is obvious to acute, but limited to sleep improvement, anxiety, weight increase, protracted symptom and the anti-therapeutic effect of reverting to take drugs, and dosage is big, toxic and side effects is more obvious.
Three, GABA
BReceptor stimulating agent is used for opium drug to be given up and the treatment of addiction research
GABA
BComprise GABA
B1a/1b and GABA
B2 two kinds of receptor subtypes, its function and drug dependence, pain, epilepsy, petit mal relevant [16].Studies show that GABA can system play the part of important role [17,18,19], GABA in morphine addiction
BAnd GABA
AReceptor stimulating agent has been proved to be its improvement effect to the morphine withdrawal symptom.GABA
BAnd GABA
AReceptor stimulating agent can significantly reduce the jump behavior of the inductive morphine-addicted rats of naloxone, GABA
BBut not GABA
AReceptor antagonist has then significantly increased the jump behavior of the inductive morphine-addicted rats of naloxone.Show GABA
BReceptor has participated in morphine addiction process [20,21,22].Many experimental results show GABA
BSystem and opiate system exist interaction [18,23].GABA
BThe effect of the acute withdrawal symptom of receptor stimulating agent prevention morphine addiction may with its return function relevant [23,24] to some brain district opium μ receptor.GABA
BReceptor stimulating agent baclofen significance suppresses nauseating, the vomiting phenomenon of morphine induction, shows GABA
BReceptor stimulating agent has participated in vomiting control path, and baclofen also can suppress its position preference in addition, and the analgesic activity that opium μ receptor stimulating agent is produced has strengthening effect [25,26,27].GABA
BReceptor stimulating agent is except its improvement effect to the acute withdrawal symptom of morphine addiction, and many researchs also show its effect [28,29,30,31] to drug dependence and pre-preventing suction again.GABA
BReceptor may become another new treatment target spot of opiate addiction.
Experimentation shows, uses GABA separately
BThough receptor stimulating agent is obvious to sleep improvement, anxiety, weight increase, protracted symptom therapeutic effect, to give up the vertebral body that causes be outward that the syndrome therapeutic effect is limited to acute, and dosage when big toxic and side effects bigger.
Four, m receptor and GABA
BThe interaction relationship research of receptor
The relation that there are parallel action in brain district acetylcholine serotonergic neuron relevant with addiction and GABA serotonergic neuron.The agonist of m receptor can increase the release of GABA, and the antagonist of m receptor can reduce the release [32,33] of GABA.These effects may be relevant with the indirect adjustments and controls of DA energy system.According to co-relation, if only use the antagonist of m receptor will cause the inhibition that GABA can system separately, and if use GABA separately
BThe agonist of receptor will cause the active of acetylcholine system, and both of these case all is undesirable in the drug dependence Comprehensive Treatment process.
Five, the withdrawal and treatment of opium drug
Opium drug mainly comprises morphine, Opium, heroin etc., these class drugs are to suck the most serious, most popular drugs all over the world, these class drugs have a common characteristic, in case the performance of a series of punitive will appear in drug withdrawal exactly, promptly at the various withdrawal symptoms in different time stage.The withdrawal symptom here comprises two layers of meaning, and the ground floor implication is a physical dependence, and the series reaction of each system of health promptly takes place behind the dialysis drugs; Second layer implication is a psychologic dependence, also be addiction, promptly these class drugs have a kind of special euphoriant effect, are that other material institute is non-existent, just go to crave for it after this euphoriant effect, will constantly remove to use its (reverting to take drugs), drug-seeking behavior just or drug craving repeatedly feeling.
Drug rehabilitation be meant the drug addict give up suck, the bad habit and the drug addiction of shoot up.Junkie is carried out drug addiction treatment, mainly comprise three phases: detoxification, rehabilitation, anti-reverting to take drugs.(1) detoxification: cut off the withdrawal symptom that occurs behind the drugs for alleviating junkie, give drug abstainer with Drug therapy or control the process of the withdrawal symptom of its appearance.Detoxification is the first step and the basis of drug addiction treatment.(2) rehabilitation: junkie still exists psychological dependence and certain physical dependence after the detoxification, to drugs crave for and delaying property withdrawal symptom is still wanted last very long, so drug abstainer is carried out the drug rehabilitation treatment on the basis of detoxification,, reduces psychological dependence to consolidate detoxification efficiency.(3) anti-reverting to take drugs: be meant after finishing above-mentioned two stages, improve the ability that it resists the drugs temptation, reduce drugs and crave for degree and relapse rate by Drug therapy.
Various medicines are numerous in the drug addiction treatment, but the cost height, toxic and side effects is big, the single problem of effect is more outstanding.How effectively, safety, low cost, the anti-additive medicament treatment of synthetically carrying out detoxification, rehabilitation, the anti-three phases of reverting to take drugs have become the emphasis that people pay close attention to.
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Summary of the invention:
The objective of the invention is to overcome the deficiency of prior art, and the chemical composite preparation of a kind of detoxification that is used for the opium drug dependent patients, rehabilitation, the anti-Comprehensive Treatment of reverting to take drugs is provided.
My years of researches exploration discovery: the condition that ideal comprehensive anti-additive medicament should possess is m receptor antagonism and GABA
BThe activated comprehensive adjustment of system.The present invention is by m receptor antagonism and GABA
BThe comprehensive regulation of receptor activation finally reaches the therapeutic effect (see figure 3) of opium drug detoxification, rehabilitation, the anti-three phases of reverting to take drugs.Its curative effect not only is better than the m receptor antagonist or the GABA of single use
BReceptor stimulating agent, but also have the significantly anti-effect of reverting to take drugs.
M receptor antagonist of the present invention is meant the chemical compound that can work as the m receptor antagonist in vivo, and the used m receptor antagonist of the present invention comprises following nine kinds: atropine (Atropine), hyoscyamine (Scopolamine), pirenzepine (Pirenzepine), trihexyphenidyl (Trihexyphenidyl), hundred are than stopping ingot (Biperiden), telenzepine (Telenzepine), Mei Suotuoming (Methoctramine), diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt (4-DAMP), Tropicamide (Tropicamide).
GABA of the present invention
BReceptor stimulating agent is meant can be in vivo as GABA
BThe chemical compound that receptor stimulating agent works, the GABA that the present invention is used
BReceptor stimulating agent comprises following five kinds: 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)), baclofen (4-amino-3-(4-chlorophenyl) butanoic acid (Baclofen)), 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)), 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)), γ-amino-beta--4-(4-chlorphenyl) nitropropane (3-amino-2-(4-chlorophenyl)-1-nitropropane).
Chemical composite preparation of the present invention is prepared by conventional method, and is specific as follows:
The raw material that preparation adopts is: a kind of GABA
BReceptor stimulating agent crude drug, a kind of m receptor antagonist crude drug, adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BThe receptor stimulating agent crude drug is 1～40%, m receptor antagonist crude drug is 1～15%, adjuvant is 45～98%, makes tablet according to a conventional method.Also change other preparation of making according to a conventional method behind the adjuvant.
The invention has the advantages that: the many usefulness of a medicine, can comprehensively play opium drug detoxification (acute withdrawal symptom), rehabilitation (protracted abstinence symptom (psa)), reduce drugs and crave for degree therapeutic effect such as (anti-reverting to take drugs).
Description of drawings:
Fig. 1 is for participating in the nervous pathway of medicine and non-medicine award.
Fig. 2 promotes the action site that DA discharges for Drug abuse.
Fig. 3 is m receptor antagonism and GABA
BActivate the cooperative effect of Comprehensive Treatment drug addiction.
Fig. 4,5,6,7,8 gives up the skip test result for mice.
Fig. 9,10,11,12,13 is a mice conditioned place preference animal test results.
The specific embodiment:
The chemical composite preparation that present embodiment uses is tablet.During actual the use, this chemical composite can be arbitrary dosage form of routine.
Embodiment 1:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug baclofen, m receptor antagonist crude drug atropine (Atropine), adjuvant (in starch, pregelatinized Starch, the dextrin any); The effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug baclofen is 1～40%, m receptor antagonist crude drug atropine (Atropine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 2:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug baclofen, m receptor antagonist crude drug hyoscyamine (Scopolamine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug baclofen is 1～40%, m receptor antagonist crude drug hyoscyamine (Scopolamine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 3:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug baclofen, m receptor antagonist crude drug pirenzepine (Pirenzepine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug baclofen is 1～40%, m receptor antagonist crude drug pirenzepine (Pirenzepine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 4:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug baclofen, m receptor antagonist crude drug trihexyphenidyl (Trihexyphenidyl), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug baclofen is 1～40%, m receptor antagonist crude drug trihexyphenidyl (Trihexyphenidyl) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 5:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug baclofen, m receptor antagonist crude drug hundred are than stopping ingot (Biperiden), adjuvant (in starch, pregelatinized Starch, the dextrin any), and the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug baclofen is 1～40%, ingot (Biperiden) is 1～15% to m receptor antagonist crude drug hundred than stopping, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 6:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug baclofen, m receptor antagonist crude drug telenzepine (Telenzepine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug baclofen is 1～40%, m receptor antagonist crude drug telenzepine (Telenzepine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 7:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug baclofen, m receptor antagonist crude drug Mei Suotuoming (Methoctramine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug baclofen is 1～40%, m receptor antagonist crude drug Mei Suotuoming (Methoctramine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 8:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug baclofen, m receptor antagonist crude drug diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt (4-DAMP), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug baclofen is 1～40%, m receptor antagonist crude drug diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt (4-DAMP) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 9:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug baclofen, m receptor antagonist crude drug Tropicamide (Tropicamide), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug baclofen is 1～40%, m receptor antagonist crude drug Tropicamide (Tropicamide) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 10:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)), m receptor antagonist crude drug atropine (Atropine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)) is 1～40%, m receptor antagonist crude drug atropine (Atropine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 11:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)), m receptor antagonist crude drug hyoscyamine (Scopolamine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)) is 1～40%, m receptor antagonist crude drug hyoscyamine (Scopolamine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 12:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)), m receptor antagonist crude drug pirenzepine (Pirenzepine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)) is 1～40%, m receptor antagonist crude drug pirenzepine (Pirenzepine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 13:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)), m receptor antagonist crude drug trihexyphenidyl (Trihexyphenidyl), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)) is 1～40%, m receptor antagonist crude drug trihexyphenidyl (Trihexyphenidyl) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 14:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)), m receptor antagonist crude drug hundred are than stopping ingot (Biperiden), adjuvant (in starch, pregelatinized Starch, the dextrin any), and the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)) is 1～40%, ingot (Biperiden) is 1～15% to m receptor antagonist crude drug hundred than stopping, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 15:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)), m receptor antagonist crude drug telenzepine (Telenzepine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)) is 1～40%, m receptor antagonist crude drug telenzepine (Telenzepine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 16:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)), m receptor antagonist crude drug Mei Suotuoming (Methoctramine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)) is 1～40%, m receptor antagonist crude drug Mei Suotuoming (Methoctramine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 17:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)), m receptor antagonist crude drug diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt (4-DAMP), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)) is 1～40%, m receptor antagonist crude drug diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt (4-DAMP) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 18:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)), m receptor antagonist crude drug Tropicamide (Tropicamide), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl (methyl) hypophosphorous acid (3-aminopropyl (methyl) phosphinic acid (SKF-97541)) is 1～40%, m receptor antagonist crude drug Tropicamide (Tropicamide) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 19:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)), m receptor antagonist crude drug atropine (Atropine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)) is 1～40%, m receptor antagonist crude drug atropine (Atropine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 20:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)), m receptor antagonist crude drug hyoscyamine (Scopolamine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)) is 1～40%, m receptor antagonist crude drug hyoscyamine (Scopolamine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 21:
The raw material that preparation adopts is:
Receptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)), m receptor antagonist crude drug pirenzepine (Pirenzepine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)) is 1～40%, m receptor antagonist crude drug pirenzepine (Pirenzepine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 22:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)), m receptor antagonist crude drug trihexyphenidyl (Trihexyphenidyl), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)) is 1～40%, m receptor antagonist crude drug trihexyphenidyl (Trihexyphenidyl) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 23:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)), m receptor antagonist crude drug hundred are than stopping ingot (Biperiden), adjuvant (in starch, pregelatinized Starch, the dextrin any), and the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)) is 1～40%, ingot (Biperiden) is 1～15% to m receptor antagonist crude drug hundred than stopping, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 24:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)), m receptor antagonist crude drug telenzepine (Telenzepine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)) is 1～40%, m receptor antagonist crude drug telenzepine (Telenzepine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 25:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)), m receptor antagonist crude drug Mei Suotuoming (Methoctramine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)) is 1～40%, m receptor antagonist crude drug Mei Suotuoming (Methoctramine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 26:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)), m receptor antagonist crude drug diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt (4-DAMP), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)) is 1～40%, m receptor antagonist crude drug diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt (4-DAMP) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 27:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)), m receptor antagonist crude drug Tropicamide (Tropicamide), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid (4-amino-3-(5-chloro-2-thienyl) butanoic acid (BCTG)) is 1～40%, m receptor antagonist crude drug Tropicamide (Tropicamide) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 28:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)), m receptor antagonist crude drug atropine (Atropine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)) is 1～40%, m receptor antagonist crude drug atropine (Atropine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 29:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)), m receptor antagonist crude drug hyoscyamine (Scopolamine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)) is 1～40%, m receptor antagonist crude drug hyoscyamine (Scopolamine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 30:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)), m receptor antagonist crude drug pirenzepine (Pirenzepine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)) is 1～40%, m receptor antagonist crude drug pirenzepine (Pirenzepine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 31:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)), m receptor antagonist crude drug trihexyphenidyl (Trihexyphenidyl), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)) is 1～40%, m receptor antagonist crude drug trihexyphenidyl (Trihexyphenidyl) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 32:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)), m receptor antagonist crude drug hundred are than stopping ingot (Biperiden), adjuvant (in starch, pregelatinized Starch, the dextrin any), and the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)) is 1～40%, ingot (Biperiden) is 1～15% to m receptor antagonist crude drug hundred than stopping, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 33:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)), m receptor antagonist crude drug telenzepine (Telenzepine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)) is 1～40%, m receptor antagonist crude drug telenzepine (Telenzepine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 34:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)), m receptor antagonist crude drug Mei Suotuoming (Methoctramine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)) is 1～40%, m receptor antagonist crude drug Mei Suotuoming (Methoctramine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 35:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)), m receptor antagonist crude drug diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt (4-DAMP), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)) is 1～40%, m receptor antagonist crude drug diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt (4-DAMP) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 36:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)), m receptor antagonist crude drug Tropicamide (Tropicamide), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
BReceptor stimulating agent crude drug 3-aminopropyl hypophosphorous acid (3-aminopropylphosphonic acid (3-APPA)) is 1～40%, m receptor antagonist crude drug Tropicamide (Tropicamide) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 37:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane (3-amino-2-(4-chlorophenyl)-1-nitropropane), m receptor antagonist crude drug atropine (Atropine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
B(3-amino-2-(4-chlorophenyl)-1-nitropropane) is 1～40% to receptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane, m receptor antagonist crude drug atropine (Atropine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 38:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane (3-amino-2-(4-chlorophenyl)-1-nitropropane), m receptor antagonist crude drug hyoscyamine (Scopolamine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
B(3-amino-2-(4-chlorophenyl)-1-nitropropane) is 1～40% to receptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane, m receptor antagonist crude drug hyoscyamine (Scopolamine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 39:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane (3-amino-2-(4-chlorophenyl)-1-nitropropane), m receptor antagonist crude drug pirenzepine (Pirenzepine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
B(3-amino-2-(4-chlorophenyl)-1-nitropropane) is 1～40% to receptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane, m receptor antagonist crude drug pirenzepine (Pirenzepine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 40:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane (3-amino-2-(4-chlorophenyl)-1-nitropropane), m receptor antagonist crude drug trihexyphenidyl (Trihexyphenidyl), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
B(3-amino-2-(4-chlorophenyl)-1-nitropropane) is 1～40% to receptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane, m receptor antagonist crude drug trihexyphenidyl (Trihexyphenidyl) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 41:
The raw material that preparation adopts is: GABA
B(3-amino-2-(4-chlorophenyl)-1-nitropropane), m receptor antagonist crude drug hundred are than stopping ingot (Biperiden), adjuvant (in starch, pregelatinized Starch, the dextrin any), and the effective ingredient weight ratio of raw material is: GABA for receptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane
B(3-amino-2-(4-chlorophenyl)-1-nitropropane) is 1～40% to receptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane, ingot (Biperiden) is 1～15% to m receptor antagonist crude drug hundred than stopping, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 42:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane (3-amino-2-(4-chlorophenyl)-1-nitropropane), m receptor antagonist crude drug telenzepine (Telenzepine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
B(3-amino-2-(4-chlorophenyl)-1-nitropropane) is 1～40% to receptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane, m receptor antagonist crude drug telenzepine (Telenzepine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 43:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane (3-amino-2-(4-chlorophenyl)-1-nitropropane), m receptor antagonist crude drug Mei Suotuoming (Methoctramine), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
B(3-amino-2-(4-chlorophenyl)-1-nitropropane) is 1～40% to receptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane, m receptor antagonist crude drug Mei Suotuoming (Methoctramine) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 44:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane (3-amino-2-(4-chlorophenyl)-1-nitropropane), m receptor antagonist crude drug diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt (4-DAMP), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
B(3-amino-2-(4-chlorophenyl)-1-nitropropane) is 1～40% to receptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane, m receptor antagonist crude drug diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt (4-DAMP) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
Embodiment 45:
The raw material that preparation adopts is: GABA
BReceptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane (3-amino-2-(4-chlorophenyl)-1-nitropropane), m receptor antagonist crude drug Tropicamide (Tropicamide), adjuvant (in starch, pregelatinized Starch, the dextrin any), the effective ingredient weight ratio of raw material is: GABA
B(3-amino-2-(4-chlorophenyl)-1-nitropropane) is 1～40% to receptor stimulating agent crude drug γ-amino-beta--4-(4-chlorphenyl) nitropropane, m receptor antagonist crude drug Tropicamide (Tropicamide) is 1～15%, adjuvant is 45～98%, makes tablet with conventional production facility and technology.
The animal experiment of medicine of the present invention:
Prescription with above-mentioned crude drug is formed has carried out animal experiment and clinical trial respectively, and the result is as follows.
1, the mice naloxone is urged and is given up the jump animal experiment
Classical mice naloxone urgency is given up the skip test result and is shown: by GABA
BThe complex that receptor stimulating agent and m receptor antagonist are formed can both the urgency of significance reduction mice naloxone be given up number of skips (seeing Fig. 4,5,6,7,8) in effective dosage ranges.
2, mice conditioned place preference animal experiment
Classical mice conditioned place preference result shows: the complex of being made up of GABAB receptor stimulating agent and m receptor antagonist can both reduce mice in the time of staying of positive case (seeing Fig. 9,10,11,12,13) by significance in effective dosage ranges.
The clinical trial of medicine of the present invention:
Animal pharmacodynamics experiment screening by mice compares, in above-claimed cpd, and the preferred especially trihexyphenidyl (Trihexyphenidyl) of m receptor antagonist crude drug, GABA
BThe preferred especially baclofen (4-amino-3-(4-chlorophenyl) butanoic acid (Baclofen)) of receptor stimulating agent crude drug.Make the tablet of 100mg with above-mentioned two kinds of crude drug, carry out clinical trial.
1, acute withdrawal symptom and protracted symptom clinical trial
Tested is 52 routine severe heroin male smokers, and the age, sucks heroin for the last time and is no more than 8 hours between year at 21-55.Every day, taking dose was 3～9, take three times, took five days continuously.Compare by medicine group and 35 routine placebo group statistical analysiss to indexs such as withdrawal symptom marking scales, anxiety rating scale (HAMA), untoward reaction marking scales, protracted symptom marking scales, the result shows: the second day withdrawal symptom scoring significance of taking medicine reduces (P＜0.05); The 3rd day Manifest Anxiety Scale scoring significance of taking medicine reduces (P＜0.05); Before taking medicine with the five day every day of the untoward reaction scoring there was no significant difference (P〉0.05) relatively of taking medicine; Above result shows that the acute withdrawal symptom toxic and side effects of this Drug therapy is little, detoxification efficiency is obvious.
Take medicine 2～6 every day during the protracted symptom outbreak, and protracted symptom scoring significance reduced (P＜0.05) in second day, showed that this medicine also has the effect of anti-protracted symptom.
2, the anti-clinical trial of reverting to take drugs
Tested is 63 routine severe heroin male smokers, and the age, between year, the mode of sucking was intravenous injection at 24-51, and history of drug abuse all more than December, reintegrates into society after compulsory rehabilitation center finishes physiology detoxification and rehabilitation.Select 33 examples to be placebo group at random for drug study group, 30 examples.The urine examination positive was defined as the person of reverting to take drugs, the urine examination feminine gender is defined as personal integrity person regularly to the tested morphine urine qualitative detection of carrying out in per 15 days.Take medicine tested every month, every day, taking dose was 2～6 course of treatment, took 10 days course of treatment three times.Drug study group relapse rate is 72.7% after 12 months, and placebo group then is 93.3%.Show that this medicine has certain anti-effect of reverting to take drugs.
Clinical test results shows: chemical composite preparation energy of the present invention Comprehensive Treatment opium drug detoxification (acute withdrawal symptom), rehabilitation (protracted abstinence symptom (psa)), reduction drugs are craved for degree symptoms such as (anti-reverting to take drugs), and its therapeutic effect is preferable.
Claims (5)
1, a kind of chemical composite preparation is characterized in that this chemical composite preparation is by a kind of GABA
BReceptor stimulating agent crude drug, a kind of m receptor antagonist crude drug, adjuvant (in starch, pregelatinized Starch, the dextrin any) are formed, and the effective ingredient weight ratio of raw material is: GABA
BThe receptor stimulating agent crude drug is 1～40%, m receptor antagonist crude drug is 1～15%, adjuvant is 45～98%, makes tablet according to a conventional method.Also change other preparation of making according to a conventional method behind the adjuvant.
2, the described chemical composite preparation of claim 2 is characterized in that:
A.M receptor antagonist crude drug comprises: atropine, hyoscyamine, pirenzepine, trihexyphenidyl, hundred are than stopping ingot, telenzepine, Mei Suotuoming, diphenyl acetic acid-4-piperidines ester iodomethane quaternary ammonium salt, Tropicamide;
B.GABA
BThe receptor stimulating agent crude drug comprises: 3-aminopropyl (methyl) hypophosphorous acid, baclofen, 4-amino-3-(5-chloro-2-thiophene) aminobutyric acid, 3-aminopropyl hypophosphorous acid, γ-amino-beta--4-(4-chlorphenyl) nitropropane.
3, the application of claim 1 and 2 described chemical composite preparations is characterized in that this chemical composite preparation gives up application with the addiction therapy medicine as opium drug.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100664159A CN101422610A (en) | 2007-12-04 | 2007-12-04 | Chemical composite preparation and use thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100664159A CN101422610A (en) | 2007-12-04 | 2007-12-04 | Chemical composite preparation and use thereof |
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| CN101422610A true CN101422610A (en) | 2009-05-06 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103298473A (en) * | 2010-10-25 | 2013-09-11 | 曼尼托巴大学 | Therapeutic compositions for diabetic symmetrical polyneuropathy |
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2007
- 2007-12-04 CN CNA2007100664159A patent/CN101422610A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103298473A (en) * | 2010-10-25 | 2013-09-11 | 曼尼托巴大学 | Therapeutic compositions for diabetic symmetrical polyneuropathy |
| CN103298473B (en) * | 2010-10-25 | 2015-07-29 | 曼尼托巴大学 | For the therapeutic composition of diabetes symmetry polyneuropathy |
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