The application is that application number is the division that 201010170021.X, name are called " treatment amphetamines dependence syndrome and with the medicine of opioid mixed dependence disease " application for a patent for invention, and the applying date of original bill is on May 12nd, 2010.
Summary of the invention
The purpose of this invention is to provide a kind of non-opium composition of medicine that is used for the treatment of amphetamines dependence syndrome, amphetamines and opioid mixed dependence disease.
The object of the present invention is achieved like this: by by antipsychotic drug, α
23 adrenergic receptor agonists or and anticholinergic agent or and nonopioid analgesic or and benzene phenodiazine
the class medicine is combined and is provided solution.
The antipsychotic drug that the combination medicine for the treatment of amphetamines dependence syndrome of the present invention, amphetamines and opioid mixed dependence disease is 2-95% by percentage by weight and the α of 0.001-5%
23 adrenergic receptor agonists forms.
Also can be respectively in aforementioned pharmaceutical compositions or add the anticholinergic agent that percentage by weight is 0-5%, the nonopioid analgesic of 0-80% and the benzene phenodiazine of 0-10% simultaneously
the class medicine.
In above-mentioned medicine components:
Antipsychotic drug can be one or more in following medicine: olanzapine, penfluridol, paroxetine, risperidone, Aripiprazole, trifluoperazine, mirtazapine, perphenazine, fluphenazine.
α
23 adrenergic receptor agonists can be one or more in following medicine: BA-168, chlorine vinegar amine miaow, clonidine, lofexidine.
Anticholinergic agent can be one or more in following medicine: Semen daturae, Anisodamine, scopolamine, atropine, benzetropine, probanthine, benactyzine, benzoglycolic acid quinine ester, benzhexol, diphenhydramine, Anisodine, Pirenzepine, propyl group dibenzoyl choline chlormethine, kemadrin, K toxin.
Nonopioid analgesic can be one or more in following medicine: tetrahydropalmatine, tramadol, benzoxazocine, Dicentrine, rotundine, four nitrogen Zhuos, tetrahydropalmatine.
The benzene phenodiazine
the class medicine can be one or more in following medicine: stable, estazolam, nitrodiazepam, fludiazepam, flunitrazepan, flurazepam, oxazepan, L0, clonazepam, chlorine nitrogen
alprazolam, etizolam, Midazolam, Convertal etc.
Combine with any suitable excipient with prescription of the present invention and can make the above dosage form of any pharmaceutics.
Analeptic such as abuse amfetamine etc., photis, the auditory hallucination that the patient occurs, suspect, many mental symptoms such as fear, delusion of persecution, anxiety, pessimism, suicide, need the application high-titer, hang down the antipsychotic medications of side effect.
The analeptic such as abuse amfetamine, the patient there will be blood pressure to increase, and causes the internal organs ischemia, causes the diseases such as cerebral palsy, myocardial ischemia, needs application α
23 adrenergic receptor agonists carries out Treatment of Hypertension, can treat the refraining opium type material symptom that merges the misuser simultaneously.
The side effect such as vertebral body is outward can occur in the antipsychotic drug of high-titer, need application anticholinergic agent antagonism.
Most of drug abuse person often merges the abuse opioid, and more serious stomachache, extremities joint pain and whole body pain etc. are arranged in opioid dependent's withdrawal symptom, needs the treatment of application nonopioid analgesic.
Most of drug abuse person often merges the medicines such as abuse triazolam, and meeting epilepsy between During The Withdrawal Period, need application benzene phenodiazine
the class Drug therapy.
Pharmaceutical composition of the present invention is for the abuse analeptic such as amfetamine or when merging above-mentioned symptom that the patient of abuse opioid occurs and being treated, reached comparatively ideal effect, can control rapidly, significantly withdrawal symptom, the detoxification cure rate reaches more than 90%.
The each oral 1-4 grain of tablet, capsule and pill, the each oral 10-40 milliliter of unguentum and syrup, spray sprays the 10-40 milliliter in abdomen, the external of skin of back place at every turn, and every kind of dosage form is all used 1-2 time every day, within 7-10 days, is a course for the treatment of.
The clinical experiment visual report
One, materials and methods
(1) object of observation
20 routine amphetamines dependents, 20 routine amphetamines and opioid mixed dependence person are observed in this checking, and inclusion criteria is as follows:
1, the clinical criteria that meets Ministry of Public Health " amphetamines relies on the diagnoses and treatment guideline "; Merge the clinical criteria that opioid mixed dependence person meets Ministry of Public Health " opioid drug relies on the diagnoses and treatment guideline ";
2, get rid of mental disorder, the heart, liver, kidney disease and other serious physical diseases;
3, during the treatment, nothing continues to use analeptic or the opioids such as amphetamine.
(2) research method
All cases are only used pharmaceutical composition of the present invention for medicine, tightly completely cut off analeptic or the opioids such as amphetamine.
1, efficacy assessment standard and method
This research is strictly evaluated by related standards and the method for Ministry of Public Health regulation.According to " withdrawal symptom is observed table day by day " (OWS scale), whole day nursing observation, and shown effect to patient's withdrawal symptom, the record of marking day by day by the special messenger 15 to 16 o'clock every days.After observing medication, within 10th, stop.
2, toxicity untoward reaction evaluation criteria and method
(1) according to " new drug untoward reaction observe scale " whole day nursing observation, and be responsible for medication person's the untoward reaction record of marking day by day by the special messenger 15 to 16 o'clock every days.After observing medication, within 10th, stop.
(2) Examine observe: all patient is carried out to general vital sign observation every day before treatment starts and during treatment, record faithfully in progress note.
3, detoxification standard
(1) stop using pharmaceutical composition of the present invention 10 days courses for the treatment of to the;
(2) the acute withdrawal symptom is eliminated substantially;
(3) merge the 8th day course for the treatment of of opioid dependent, naloxone urges addiction experiment (0.4 milligram of intramuscular injection) feminine gender, urine morphine to detect negative.
4, medication
Supervise then and there and take medicine one by one by the medical worker.Warm water takes, and dosage, according to the abuse time of experimenter's amphetamines or opioid, the use amount of nearly a week, reaches withdrawal symptom and controls degree and determine, and directs consumption concretely and is:
Two, observed result
(1) to controlling the observation of curative effect of withdrawal symptom
1, to the control rate of withdrawal symptom
Administration time is apart from the last time average of taking drugs: the amphetamines dependent is 8.6 hours, and amphetamines and opioid mixed dependence person are 11.9 hours.
Before administration, obvious withdrawal symptom all appears in all cases, and the scoring mean: the amphetamines dependent is 50.2 ± 5.8; Amphetamines and opioid mixed dependence person are 52.3 ± 5.6.
After taking pharmaceutical composition of the present invention, withdrawal symptom is all obviously alleviated (referring to table 1).
The scoring of table 1. withdrawal symptom changes the mean table day by day
Annotate: variance analysis, relatively front with treatment
From table 1: pharmaceutical composition administration of the present invention same day, withdrawal symptom is obviously controlled, after medication before withdrawal symptom scoring every day and medication relatively, difference has significance.
2, the occurrence rate of withdrawal symptom
During treating, pharmaceutical composition of the present invention can be controlled withdrawal symptom obviously, effectively, and for strict this medicine of estimating, to eliminating or alleviate the difference on effect of different withdrawal symptoms, we observe and add up the occurrence rate of various withdrawal symptoms:
Table 2. withdrawal symptom occurrence rate (n=20)
From table 2: the amphetamines dependent, except 3 examples occur anxiety symptom, other symptoms all can be controlled fully.
Amphetamines and opioid mixed dependence person, except anxiety, extremities joint pain, yawn and fatigue and weak control are undesirable, other symptoms all can be fully or basic controlling, and these several symptoms all belong to the addiction initial stage, a lighter withdrawal symptom, take pharmaceutical composition of the present invention to the patient immediately, these several withdrawal symptoms all are effectively controlled, and diarrhoea, vomiting, paroxysmal tic etc. come across to be sent out the addiction middle and late stage stage, comparatively serious withdrawal symptom and also can not occur.
(2) toxicity and untoward reaction
During treating, untoward reaction situation statistics is as follows:
Table 3. untoward reaction occurrence rate (n=20)
Table 4. untoward reaction scoring changes the mean table day by day
From table 3,4: the untoward reaction main manifestations is dizzy, weak.Untoward reaction and dosage are proportionate, and within first 3 days, dosage is larger, and the side reaction scoring is also higher, and along with the minimizing of dosage, side reaction also alleviates gradually, after drug withdrawal, disappear fully.
Three, conclusion
(1) pharmaceutical composition control withdrawal symptom effect of the present invention is remarkable
From table 1,2: as long as dosage holds water, all medication persons' withdrawal symptom all obviously being controlled without exception.
(2) pharmaceutical composition control withdrawal symptom of the present invention effect is rapid
In actual observation, medication is about 30 minutes, and withdrawal symptom is controlled.
(3) side effect of pharmaceutical composition of the present invention is less
From table 3,4: the untoward reaction of this medicine is less, and, along with the minimizing of dosage, side reaction also alleviates gradually, after drug withdrawal, disappears fully.
(4) pharmaceutical composition of the present invention is taken safety
This medicine is not containing any poisonous substances, and all the components is all the Chinese medicine and western medicine kind that state-promulgated pharmacopoeia is recorded, safer.
The specific embodiment
Below in conjunction with embodiment, the invention will be further described:
Embodiment 1:
The percentage by weight of medicine components is: 92% olanzapine, 3% chlorine vinegar amine miaow, 5% diphenhydramine, by after the adjuvants such as starch, Pulvis Talci and said medicine raw material blending, by the method for prior art, make capsule (200 milligrams every).
Embodiment 2:
The percentage by weight of medicine components is: 85% mirtazapine, 2% lofexidine, 5% scopolamine, 8% flunitrazepan, by after the adjuvants such as starch, Pulvis Talci and said medicine raw material blending, by the method for prior art, make tablet (200 milligrams every).
Embodiment 3:
The percentage by weight of medicine components: 90% Aripiprazole, 5% BA-168,5% benzhexol, will after the adjuvants such as starch, Pulvis Talci and said medicine raw material blending, by the method for prior art, make capsule (200 milligrams every).
Embodiment 4:
The percentage by weight of medicine components: 32% Paroxetine, 3% BA-168,5% Radix Anisodi Acutanguli, 60% tramadol, will make pill (200 milligrams every) by the method for prior art after the adjuvants such as starch, Pulvis Talci and said medicine raw material blending.
Embodiment 5:
The percentage by weight of medicine components: 95% penfluridol, 5% clonidine, will after the adjuvants such as 95% ethanol, laurocapram and said medicine raw material blending, by the method for prior art, make spray.
Embodiment 6:
The percentage by weight of medicine components: 90% risperidone, 5% BA-168,5% Semen daturae, will after the adjuvants such as syrup and said medicine raw material blending, by the method for prior art, make unguentum.
Embodiment 7:
The percentage by weight of medicine components: 84% fluphenazine, 5% lofexidine, 3% atropine, 8% fludiazepam, by after the adjuvants such as starch, Pulvis Talci and said medicine raw material blending, by the method for prior art, make capsule (200 milligrams every).
Embodiment 8:
The percentage by weight of medicine components: 74% trifluoperazine, 5% chlorine vinegar amine miaow, 3% benzetropine, 8% rotundine, 10% chlorine nitrogen
to after the adjuvants such as monosaccharide and said medicine raw material blending, by the method for prior art, make syrup.
Embodiment 9:
The percentage by weight of medicine components: 10% perphenazine, 2% BA-168,80% tetrahydropalmatine, 8% clonazepam, by after the adjuvants such as starch, Pulvis Talci and said medicine raw material blending, by the method for prior art, make tablet (200 milligrams every).
Embodiment 10:
The percentage by weight of medicine components: 85% haloperidol, 5% chlorine vinegar amine miaow, 10% estazolam, will after the adjuvants such as 95% ethanol, laurocapram and said medicine raw material blending, by the method for prior art, make spray.