CN107260718A - Verapamil is used to prepare the purposes for suppressing to relapse medicine after drug rehabilitation - Google Patents
Verapamil is used to prepare the purposes for suppressing to relapse medicine after drug rehabilitation Download PDFInfo
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- CN107260718A CN107260718A CN201710496170.7A CN201710496170A CN107260718A CN 107260718 A CN107260718 A CN 107260718A CN 201710496170 A CN201710496170 A CN 201710496170A CN 107260718 A CN107260718 A CN 107260718A
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- verapamil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
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- Chemical & Material Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
The invention belongs to technical field of medicine, and in particular to a kind of Verapamil is used to prepare the purposes for suppressing to relapse medicine after drug rehabilitation.The present invention chooses nearly primate species tree shrew as model animal, explores the regulatory mechanism relapsed after L types calcium channel is given up for long-time by the induction of medication related thread, and then suppress Relapse behavior using L type calcium ion channel blockors Verapamil.As a result show, Verapamil, which can effectively suppress the medication induced by medication related thread of the tree shrew after long-time is given up, to be craved for, so as to suppress Relapse behavior；And tree shrew has very high homology on nervous system related protein gene with primate, therefore Verapamil is relapsed with important clinical value applied to treatment.
Description
Technical field
The invention belongs to technical field of medicine, and in particular to a kind of Verapamil, which is used to prepare, to be suppressed to relapse after quitting drug abuse
The purposes of medicine.
Background technology
At present, drug abuse is considered as the mankind " the third-largest killer " for being only second to heart disease and cancer, and drug rehabilitation problem is ground
Study carefully turns into one of whole world focus of attention.Drug abuse not only has serious harm to the body and mind of people, and threatens whole society
The harmony of meeting is stabilized.The main Types of China's drug abuse are opiates, and opioid dependence is a kind of complicated clinical syndrome, is
Chronic opium after caused by a kind of change for the use of behavior and neural plasticity, including body relies on and psychological dependence：Body
Body, which is relied on, is mainly shown as different degrees of abstinence reaction and/or sign；Psychological dependence is then mainly shown as the different heart of degree
Reason craving and mandatory medication.
Conventional drug rehabilitation method mainly has natural drug withdrawal (not provide the medicine specially quit drug abuse to drug addict, firmly at present
Property stop taking drugs, allow withrawal symptom organic growth, spontaneous regression), drug withdrawal method (be exactly using various anti-withrawal symptom medicines
To mitigate pain of the drug addict during giving up, or carried out with other similar drugs substituting descending treatment) and spirit
Method is given up, the methadone that drug withdrawal method includes Western medicine class substitutes diminishing method, opium diminishing method, buprenorphine diminishing method, cola
Determine the multiple formulations such as detoxicity method and peaceful, the golden deficient honeydew of peace monarch of Chinese medicine class.But either Western medicine or Chinese medicine can not be from
The drug addiction of patient is fundamentally eliminated, is easily relapsed after being discontinued.
Refer to that addict experienced after prolonged give up even if being relapsed after drug rehabilitation, (make when exposed to medication related thread
With utensil, medication environment etc.) when, strong medication craving can be still produced, and then trigger the process relapsed.Once drug abstainer
Appearance relapses symptom, and the withdrawal of its drug addiction can be more difficult, so treatment relapses and also becomes the maximum for solving the problems, such as drug addiction and choose
War.
The content of the invention
Therefore, the technical problems to be solved by the invention be to provide a kind of Verapamil be used for prepare suppress to answer after drug rehabilitation
Inhale the purposes of medicine.
Suppress to relapse medicine after quitting drug abuse in order to solve the above technical problems, being used to prepare the invention discloses described Verapamil
The purposes of thing.
It is preferred that, the Verapamil is verapamil hydrochloride.
Suppress the medicine that relapses after drug rehabilitation the invention also discloses a kind of, the medicine by chief active of Verapamil into
Point.
It is preferred that, the Verapamil is verapamil hydrochloride.
More excellent, the amount of the Verapamil is contained in the pharmaceutical units preparation, is 160- according to amount of formulation is taken day
Calculate within 180mg/ days.
Unit formulation of the present invention refers to that every capsule of capsule formulation, tablet are per tablet preparation, injection 10ml/
The 25g/ bags of branch or granule.
The medicine adds customary adjuvant according to common process, and clinically acceptable oral preparations are made.
Specifically, the preparation includes tablet, capsule, pill, pill, granule, powder.
The auxiliary material is included in filler, disintegrant, lubricant, adhesive, flavouring, suspending agent, preservative or matrix
One or more of mixtures.
The filler include but is not limited to starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose,
One or more mixtures in sucrose；
The disintegrant includes but is not limited to starch, PVPP, hydroxypropyl cellulose, sodium carboxymethylcellulose, carboxylic
One or more mixtures in methyl starch sodium；
One kind that the lubricant includes but is not limited in magnesium stearate, talcum powder, silica, lauryl sodium sulfate
Or a variety of mixtures；
The suspending agent includes but is not limited to polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methyl
One or more mixtures in cellulose；
One kind that described adhesive includes but is not limited in starch slurry, polyvinylpyrrolidone, hydroxypropyl methyl cellulose
Or a variety of mixtures；
The flavouring includes but is not limited to sweetener and/or essence；The sweetener is saccharin sodium, aspartame, sugarcane
One or more mixtures in sugar, honey element；
The preservative include but is not limited in parabens, benzoic acid, sodium benzoate, sorbic acid, sorbate one
Plant or a variety of mixtures；
The matrix includes the mixture of one or both of PEG, insect wax.
It should be noted that the customary adjuvant includes but is not limited to the above-mentioned scope enumerated, those skilled in the art can
The selection and adjustment of adaptability are done according to actual conditions.
The invention also discloses a kind of method for preparing the medicine, i.e., each raw material components are measured according to selected prescription,
Selected auxiliary material is added, clinically acceptable formulation is made according to common process.
Verapamil has been used to the treatment heart in the eighties in last century and twisted as a kind of L-type calcium ion channel blockor
Bitterly, heart disease etc., and side effect is smaller.Scheme of the present invention relapses medicine using Verapamil as after preparing suppression drug rehabilitation
Active component, the Relapse behavior after drug rehabilitation can effectively be suppressed to a certain extent by inquiring into and demonstrating it.
The present invention chooses nearly primate species tree shrew as model animal, explores L-type calcium channel for for a long time
The regulatory mechanism relapsed is induced by medication related thread after giving up, and then utilizes the suppression of L-type calcium ion channel blockor Verapamil
Relapse behavior processed.As a result show, Verapamil can effectively suppress tree shrew by long-time give up after by medication related thread
The medication craving of induction, so as to suppress Relapse behavior；And tree shrew has very on nervous system related protein gene with primate
High homology, therefore Verapamil is relapsed with important clinical value applied to treatment.
Brief description of the drawings
In order that present disclosure is more likely to be clearly understood, specific embodiment and combination below according to the present invention
Accompanying drawing, the present invention is further detailed explanation, wherein,
Fig. 1 be tree shrew of the present invention long-time give up relapse model set up situation；Wherein, A is tree shrew self administration model
Foundation, N=7, * * * p<0.001, effective nose touches number compared with invalid nose touches number；B is to give up (LW) by 45 days long-term,
Effective nose touches number and gives up the situation of change for giving up (SW) on the 1st day in short term, N=7, * * p<0.01, give up for a long time with guarding against in short term
It is disconnected to compare；
Fig. 2 is the two subtype C av1.2 and Cav1.3 of L-type calcium channel at nucleus accumbens septi of the present invention with the time of giving up
The protein expression situation of extension；Wherein, A be Cav1.2 when giving up the 45th day, compared to give up the 1st day expression quantity change feelings
Condition, N=4, * p<0.05；B is that Cav1.3 is giving up the 1st day and giving up the expression quantity situation of 45 days, N=4；
Fig. 3 is the influence that L-type calcium-ion channel antagonists Verapamil is craved for for medication；Wherein, A is to be noted at nucleus accumbens septi
Penetrate the influence that Verapamil suppresses (LW) and short time after giving up for a long time and gives up (SW) medication craving, N=5；*p<0.05；B is
Influence of the Verapamil (10ug) to the autogenic movement behavior of animal is injected at nucleus accumbens septi；C is that intracerebroventricular injection Verapamil has
Effect suppresses the medication craving result after giving up for a long time, N=3；*p<0.05, medication intervention (WD is given up for a long time>30) with it is long when
Between give up after baseline compare；D effectively suppresses the medication craving result after giving up for a long time, N for intraperitoneal injection Verapamil
=3, * * p<0.01, medication intervention (WD is given up for a long time>30) compared with the baseline after being given up with long-time.
Embodiment
The tablet of embodiment 1
Verapamil hydrochloride 100g is taken, starch, talcum powder, microcrystalline cellulose, the hydroxypropyl methyl cellulose of dosage of getting it filled
And sucrose is auxiliary material, and tablet is made according to common process.Content per the hydrochloric Verapamil of tablet preparation is 80mg, and 1 tablet once,
2 times a day.
The capsule of embodiment 2
Verapamil hydrochloride 100g is taken, microcrystalline cellulose, PVPP, magnesium stearate, the polyethylene pyrrole of dosage of getting it filled
Pyrrolidone, sorbic acid are auxiliary material, and capsule is made according to common process.The content of the hydrochloric Verapamil of every capsule is
180mg, 1 every time, one time a day.
The tablet of embodiment 3
Verapamil hydrochloride 100g is taken, the PVPP for dosage of getting it filled, magnesium stearate, microcrystalline cellulose, hydroxypropyl first
Base cellulose and honey element are auxiliary material, and tablet is made according to common process.Often the content of the hydrochloric Verapamil of tablet preparation is
90mg, 1 tablet once, and 2 times a day.
Experimental example
1st, tree shrew gives up the foundation for relapsing model for a long time
First, tactile this self administration row of acquisition medicine of nose is passed through according to the model training tree shrew association shown in A in Fig. 1
For.After the administrations training of 7 days, medication related thread is exposed again giving up the 1st day and give up the 45th day by animal respectively
But medicine is not provided, craving degree of the number detection tree shrew to medicine is touched according to nose.Result as shown in B in Fig. 1 shows that tree shrew passes through
Cross after cocaine medication, tree shrew nose touches number apparently higher than giving up the 1st day after 45 days give up, show to use after giving up for a long time
Medicine craving degree enhancing, craving degree, which is compared to give up the 1st day, after 45 days give up is remarkably reinforced, and then causes Relapse behavior.
2nd, L-type calcium channel with the increase for the time of giving up the protein expression content status at nucleus accumbens septi
Because nucleus accumbens septi is the crucial brain area that intracerebral regulates and controls the corelation behaviours such as award, motivation, in order to explore calcium channel
Given up in long-time and the mechanism relapsed is induced by medication clue, this research, which compares constantly to give up time point, (gives up the 1st day and ring
Disconnected 45th day) main two subtype C a of L-type calcium channel albumenv1.2 and Cav1.3 expression in nucleus accumbens septi.
As result is shown in Fig. 2, compared to giving up the 1st day, Cav1.2 expression contents have after giving up 45 days significantly to be risen
High (A in Fig. 2), and Cav1.3 change less (B in way 2) with the increase for the time of giving up.Result above is pointed out, L-type calcium
Ion channel, particularly Cav1.2 hypotypes, play an important role in craving behavior.
3rd, the medication that Verapamil can effectively suppress to be induced by medication clue after giving up for a long time is craved for
In order to verify that L-type calcium channel, for the effect relapsed, is tested respectively at giving up craving in the 1st day and the 45th day
Before, micro at nucleus accumbens septi (10ug) injection L-type calcium ion channel blockor Verapamil.
Result as shown in Figure 3 shows that Verapamil can significantly inhibit the craving behavior given up the 45th day, and to giving up
1st day without influence (A in such as Fig. 3).Also, Verapamil does not influence the autogenic movement behavior (B in such as Fig. 3) of animal.In addition,
Respectively at telocoele (100ug), abdominal cavity (10mg/kg) injection Verapamil (C and D in such as Fig. 3) after tree shrew is given up for a long time,
As a result show, Verapamil suppresses the effect that medication is craved in nervous system or peripherally administered equal can reach.
Result above proves that Verapamil can effectively suppress the medication craving after giving up for a long time, and in animal
Have no apparent side effect.
Obviously, above-described embodiment is only intended to clearly illustrate example, and the not restriction to embodiment.It is right
For those of ordinary skill in the art, can also make on the basis of the above description it is other it is various forms of change or
Change.There is no necessity and possibility to exhaust all the enbodiments.And the obvious change thus extended out or
Among changing still in the protection domain of the invention.
Claims (9)
1. Verapamil is used to prepare the purposes for suppressing to relapse medicine after drug rehabilitation.
2. purposes according to claim 1, it is characterised in that the Verapamil is verapamil hydrochloride.
3. a kind of medicine for suppressing to relapse after drug rehabilitation, it is characterised in that the medicine is using Verapamil as main active.
4. medicine according to claim 3, it is characterised in that the Verapamil is verapamil hydrochloride.
5. the medicine according to claim 3 or 4, it is characterised in that contain the Verapamil in the pharmaceutical units preparation
Amount, according to take day amount of formulation for 160-180mg/ days calculating.
6. the medicine according to claim any one of 3-5, it is characterised in that the medicine adds customary adjuvant according to routine
Technique, is made clinically acceptable oral preparations.
7. medicine according to claim 6, it is characterised in that the preparation include tablet, capsule, pill, pill,
Granule, powder.
8. the medicine according to claim 6 or 7, it is characterised in that the auxiliary material include filler, disintegrant, lubricant,
One or more of mixtures in adhesive, flavouring, suspending agent, preservative or matrix.
9. a kind of method for preparing any one of the claim 3-8 medicines, it is characterised in that measured respectively according to selected prescription
Raw material components, add selected auxiliary material, clinically acceptable formulation are made according to common process.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710496170.7A CN107260718A (en) | 2017-06-26 | 2017-06-26 | Verapamil is used to prepare the purposes for suppressing to relapse medicine after drug rehabilitation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710496170.7A CN107260718A (en) | 2017-06-26 | 2017-06-26 | Verapamil is used to prepare the purposes for suppressing to relapse medicine after drug rehabilitation |
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| Publication Number | Publication Date |
|---|---|
| CN107260718A true CN107260718A (en) | 2017-10-20 |
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|---|---|---|---|
| CN201710496170.7A Pending CN107260718A (en) | 2017-06-26 | 2017-06-26 | Verapamil is used to prepare the purposes for suppressing to relapse medicine after drug rehabilitation |
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Citations (8)
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|---|---|---|---|---|
| CN1559397A (en) * | 2004-03-12 | 2005-01-05 | 中国药科大学 | Chrono-slow-releasing prepn. hydrochloride verapamil |
| CN1565437A (en) * | 2003-06-30 | 2005-01-19 | 北京正大绿洲医药科技有限公司 | Verapamil hydrochloric acid drop pill and its preparation method |
| CN1568961A (en) * | 2004-05-13 | 2005-01-26 | 南昌弘益科技有限公司 | Dripping pills of verapamil hydrochloride and its preparation |
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2017
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Patent Citations (8)
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| CN1565437A (en) * | 2003-06-30 | 2005-01-19 | 北京正大绿洲医药科技有限公司 | Verapamil hydrochloric acid drop pill and its preparation method |
| CN1559397A (en) * | 2004-03-12 | 2005-01-05 | 中国药科大学 | Chrono-slow-releasing prepn. hydrochloride verapamil |
| CN1568961A (en) * | 2004-05-13 | 2005-01-26 | 南昌弘益科技有限公司 | Dripping pills of verapamil hydrochloride and its preparation |
| CN1785170A (en) * | 2004-12-08 | 2006-06-14 | 北京双鹤药业股份有限公司 | Method for preparing delayed-release verapamil hydrochloride |
| CN101422453A (en) * | 2008-11-10 | 2009-05-06 | 河南帅克制药有限公司 | Verapamil hydrochloride delayed-release capsule and preparation method thereof |
| CN102614141A (en) * | 2011-12-02 | 2012-08-01 | 内蒙古元和药业股份有限公司 | Verapamil hydrochloride delayed-release tablet and its preparation method |
| CN103211797A (en) * | 2012-01-18 | 2013-07-24 | 北京天衡药物研究院 | Verapamil hydrochloride film-controlled slow-release pellet capsule |
| CN103520115A (en) * | 2013-09-27 | 2014-01-22 | 内蒙古医科大学 | Verapamil hydrochloride sustained release microsphere and preparation method thereof |
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Application publication date: 20171020 |