CN106344519A - Tandospirone enteric-coated mini-pill, and preparation method and application thereof - Google Patents
Tandospirone enteric-coated mini-pill, and preparation method and application thereof Download PDFInfo
- Publication number
- CN106344519A CN106344519A CN201510424689.5A CN201510424689A CN106344519A CN 106344519 A CN106344519 A CN 106344519A CN 201510424689 A CN201510424689 A CN 201510424689A CN 106344519 A CN106344519 A CN 106344519A
- Authority
- CN
- China
- Prior art keywords
- parts
- enteric
- enteric coated
- tandospirone
- coated micropill
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides tandospirone enteric-coated mini-pills and a preparation method thereof. The enteric-coated mini-pills are prepared by adding pharmaceutically acceptable auxiliary materials into an active ingredient, namely the tandospirone or medicinal salt thereof. The invention also provides application of the tandospirone enteric-coated mini-pills to preparation of medicines which are administrated intestinally and can resist anxiety. The tandospirone enteric-coated mini-pills prepared by the method have stable quality, are not disintegrated in a stomach, and have a large distribution area in an intestinal tract, high disintegration and dissolution property, high bioavailability, low irritability on a gastrointestinal mucous membrane, few side effects and high medicine taking compliance of a patient. The tandospirone enteric-coated mini-pills can be used for treating patients suffering from the following diseases: an anxiety state caused by various neuroses, an anxiety state accompanied with body diseases, such as primary hypertension and peptic ulcer, and mild and moderate depression; and the tandospirone enteric-coated mini-pills are particularly suitable for the patients suffering from anxiety caused by digestive system diseases, the patients who suffer from gastric mucosal lesion and are easy to bleed, and senile patients who need to take medicines for a long time to take.
Description
Technical field
The present invention relates to a kind of tandospirone enteric coated micropill and its production and use, belong to drug world.
Background technology
Tandospirone is a kind of novel anxiolytic succeeded in developing by SUMITOMO CHEMICAL Pharmaceutical Co., Ltd, and
It was approved to list first in Japan in 1996, initially enter Chinese market within 2004, anxiety at home
The application of therapy field is increasingly extensive.
Tandospirone can selectively acting in intracerebral 5-ht1a receptor, site of action concentrates in emotion
The cerebral limbic systems such as the Hippocampus of pivot, corpus amygdaloideum are simultaneously projected to the rapheal nuclei that 5-ht can be neural, by swashing
Presynaptic 5-ht1a receptor alive, inhibitory neuron discharges, and reduces the synthesis of 5-ht, simultaneously to synapse
5-ht1a receptor afterwards has partial agonist effect, thus reaching the 5-ht function of comprehensive adjustment synapse,
Play angst resistance effect.Life-time service can also play antidepressant effect simultaneously.With traditional sedative hypnotic
Compare, its angst resistance effect is special, and side effect is less, and sedative-hypnotic effect is weak, no myorelaxant effects,
No according to lazyness and drug withdrawal withdrawal symptom, no accumulate in vivo after prolonged application.Test through long-term clinical application
Card, tandospirone has good result to the anxiety under multiple situations, with the body as feature with anxiety
Heart comorbidity therapy field has a extensive future.
Tandospirone belongs to and acts on central nervous system's class medicine, and oral formulations need to first pass through gastrointestinal tract
It is absorbed into body circulation, then big intracerebral action target spot competence exertion anxiety is distributed to by blood brain barrier
Or antidepressant effect.Blood brain barrier is one layer of defensive barrier of brain, and the transmission of material is had strictly
Restriction effect, active constituents of medicine will enter intracerebral by this layer of barrier, in addition to the permeability of itself,
Also restricted by blood drug level.Clinical data is had to show, health adult is once administered orally tandospirone
After 20mg, in blood plasma, maximum concentration is only 2.9～3.2ng/ml.According to the medication guide principle of tandospirone,
The dosage of generally adult's application Tandospirone Citrate Tablets is that each 10mg is administered orally, and 3 times a day, and often
Daily dose is limited in and must not exceed 60mg.The Film coated tablets sold in the market and two kinds of conventional capsule
Oral formulations are all disintegration time length, the slow conventional formulation of dissolution after disintegrate, have impact on the absorption of medicine,
So it is difficult to improve the blood drug level after being administered orally.If simple to overcome blood drug level to increase medication dose
Low problem, can bring the risk that untoward reaction increases again.
According to pharmacokinetics general knowledge, weak acidic drug free state in sour environment increases, and has
Preferably cell-membrane permeable, therefore weak acidic drug are easier to absorb in gastric acid environment.Citric acid
Tandospirone shows faintly acid, is easier to absorb in stomach, and therefore existing tandospirone listing preparation is equal
For stomach dissolution type preparation, for example: Tandospirone Citrate stomach dissolution type conventional capsule, tandospirone slow releasing tablet
(cn200610021419.0), tandospirone slow-releasing granules (jp2002020291), tandospirone infiltration
The slow controlled release oral dosage formulations such as pump-type controlled release tablet (us5185158, us5330762, us5858407).On
State stomach dissolution type preparation and have ignored a critically important problem: tandospirone is that one kind has irritating chemical combination
Thing, after gastric melts, local dose is very big, and gastric mucosa can be produced stimulates；Separately have document report is
Reach long-time release effect (generally daily only need to take medicine once or twice), their content of dispersion is than general
Port formulation is high 1.5～3 times, if gastric occur prominent release that to will also result in local dose excessive, from
And gastric mucosa is produced and stimulates.
From the point of view of the untoward reaction evidence reported when existing tandospirone preparation Clinical practice, incidence rate is relatively
The untoward reaction for digestive system aspect of high (incidence rate >=1%), comprising: Nausea and vomiting, appetite
Depressed, thirsty, abdominal discomfort sense, stomachache, flatulence, abdominal distention, diarrhoea etc., this is for by digestive system
Disease causes the patient of patient, mucosal lesion or easy bleeding of anxiety, needs the gerontal patient of Long-term taking medicine
Particularly disadvantageous.These patients are not only low to pungent toleration, and easily induction digestive system is bad anti-
Should, lead to Compliance low, and due to digestive tract function imbalance, drug absorption is poor, and medicine is biological
Availability is not high, can have a strong impact on therapeutic effect.
Techniques disclosed above all has and discharges medicine in a large number in stomach, and with or may be with local dose
Excessive feature, stimulates to digestive tract after failing to solve the problems, such as medication.So far, can improve by
Digestive system disease causes the patient of patient, mucosal lesion or easy bleeding of anxiety, needs Long-term taking medicine
The Compliance problem of gerontal patient and therapeutic effect, and it is capable of the tandospirone intestinal of efficient absorption utilization
Solubility preparation has not yet to see report.
Therefore, the existing issue for tandospirone and its conventional formulation and particular patients ' demand it would be highly desirable to
Develop a kind of suitable digestive system disease cause anxiety the patient of patient, mucosal lesion or easy bleeding,
The tandospirone enteric coated preparation needing the gerontal patient of Long-term taking medicine to take and being fully absorbed.
Content of the invention
The technical scheme is that and provide a kind of tandospirone enteric coated micropill and preparation method thereof and use
On the way.
This law is bright to provide a kind of tandospirone enteric coated micropill, and it is to be by tandospirone or its officinal salt
The capsule core of active component preparation, sealing coat, enteric layer and complete layer composition；Wherein, capsule core, sealing coat,
Enteric layer, the percentage by weight of complete layer are:
Capsule core 25～95%, sealing coat 0～15%, enteric layer 5～40%, complete layer 0～20%.
Preferably, described capsule core, sealing coat, enteric layer, the percentage by weight of complete layer are:
Capsule core 50～80%, sealing coat 4～10%, enteric layer 10～27%, complete layer 6～13%.
Wherein, the percentage by weight that in described capsule core, supplementary material accounts for enteric coated micropill is:
The percentage by weight that in described sealing coat, adjuvant accounts for enteric coated micropill is:
Hydroxypropyl methylcellulose 0～12%
Pulvis Talci 0～8%；
The percentage by weight that in described enteric layer, adjuvant accounts for enteric coated micropill is:
The percentage by weight that in described complete layer, adjuvant accounts for enteric coated micropill is:
Preferably, the percentage by weight that in described capsule core, supplementary material accounts for enteric coated micropill is:
The percentage by weight that in described sealing coat, adjuvant accounts for enteric coated micropill is:
Hydroxypropyl methylcellulose 3～7%
Pulvis Talci 1～4%；
The percentage by weight that in described enteric layer, adjuvant accounts for enteric coated micropill is:
The percentage by weight that in described complete layer, adjuvant accounts for enteric coated micropill is:
It is further preferred that the percentage by weight that in described capsule core, supplementary material accounts for enteric coated micropill is:
Wherein, described filler is selected from starch, sucrose, Lactose, Microcrystalline Cellulose, Mannitol, mountain
Pears alcohol, calcium sulfate, calcium hydrogen phosphate or one or more therein of Calcium Carbonate；
Described disintegrating agent is selected from low-substituted hydroxypropyl cellulose, carboxymethylcellulose calcium, cross-linked carboxymethyl
Sodium cellulosate, carboxymethyl starch sodium or one or more therein of Crospovidone；
Described nodularization accelerator is selected from sodium alginate, polyvinyl alcohol, hydroxypropyl cellulose, hydroxypropyl
Cellulose, sodium carboxymethyl cellulose, polyvidone, Macrogol 4000, polyethylene glycol 6000 or micropowder
One or more therein of silica gel；
Described enteric macromolecular material is acrylic resin, hydroxypropyl methylcellulose titanate esters, hydroxypropyl first
Base cellulose acetate succinate (hpmcas), cellulose acetate titanate esters, cellulose acetate benzene three
Acid esters or polyvinyl alcohol titanate esters；
Described plasticizer be selected from triethyl citrate, tributyl citrate, glycerol, glycerol triacetate,
SA dibutyl ester, propylene glycol, Oleum Ricini, cochin oil, Semen Maydis oil, Polyethylene Glycol therein one
Plant or multiple.
Wherein, described enteric coated micropill is to be prepared from by the supplementary material of following weight percentage ratio:
Tandospirone or 10 parts of its officinal salt, 70 parts of Microcrystalline Cellulose, 50 parts of starch, carboxymethyl form sediment
30 parts of powder sodium, 40 parts of sodium carboxymethyl cellulose, 10 parts of micropowder silica gel, 30 parts of hydroxypropyl methylcellulose,
24 parts of Pulvis Talci, 20 parts of hydroxypropyl methylcellulose acetate succinate, 10 parts of SA dibutyl ester, two
4 parts of titanium oxide, 2 parts of river wax；Or
Tandospirone or 10 parts of its officinal salt, 60 parts of Lactose, 30 parts of Mannitol, cross-linked carboxymethyl
40 parts of sodium cellulosate, 30 parts of polyvidone, 10 parts of micropowder silica gel, 38 parts of hydroxypropyl methylcellulose, cunning
28 parts of stone powder, 26 parts of cellulose acetate benzenetricarboxylic acid ester, 12 parts of Polyethylene Glycol, 4 parts of titanium dioxide, bar
2 parts of western palm wax；Or
Tandospirone or 10 parts of its officinal salt, 45 parts of sucrose, 35 parts of Sorbitol, Crospovidone
25 parts, 30 parts of Macrogol 4000,5 parts of micropowder silica gel, 45 parts of hydroxypropyl methylcellulose, Pulvis Talci
36 parts, 40 parts of polyvinyl alcohol titanate esters, 20 parts of glycerol, 7 parts of titanium dioxide, 2 parts of Brazil wax.
Wherein, the particle diameter of described enteric coated micropill is 0.1～2.0mm.
Preferably, the particle diameter of enteric coated micropill is 0.3～1.5mm.
It is further preferred that the particle diameter of enteric coated micropill is 0.5～0.8mm.
Present invention also offers the method preparing tandospirone enteric coated micropill, it comprises the steps:
A. prepare capsule core: tandospirone or its officinal salt, filler are mixed together with disintegrating agent, then
Add nodularization accelerator soft material, soft material is extruded into the sieve plate in 0.5mm aperture diameter is identical, light slips
Close bar, puts and carries out round as a ball in spheronizator, until granule is rolled into microspheric granula, take out, place 40
Carry out freeze-day with constant temperature at DEG C, cross 32 mesh sieves, obtain final product；
B. bag sealing coat: by hydroxypropyl methylcellulose with, after 70 DEG C of hot water dispersing and dissolvings, adding Pulvis Talci,
Make the sealing coat solution that solid content is about 15wt%；Capsule core is placed in coating pan, adjusts inlet temperature
Piece bed tempertaure is made to be 35 DEG C, atomizing pressure is 0.4mpa, rotating speed is 12rpm, carries out sealing coat to capsule core
Coating；
C. bag enteric layer: enteric coating material is added to the water and adds plasticizer, Pulvis Talci, titanium dioxide
It is prepared into the aqueous dispersion that solid content is about 20wt%；Adjusting inlet temperature makes piece bed tempertaure be 30 DEG C, mist
Change pressure is 0.2mpa, and rotating speed is 12rpm, carries out enteric layer coating to capsule core；
D. bag complete layer: by hydroxypropyl methylcellulose with after 70 DEG C of hot water dispersing and dissolvings, add Pulvis Talci and
Titanium dioxide, makes the decorative layer solution that solid content is about 20wt%；Capsule core is placed in coating pan, adjusts
Section inlet temperature makes piece bed tempertaure be 35 DEG C, and atomizing pressure is 0.5mpa, and rotating speed is 14rpm, to capsule core
Carry out decorative layer coating, polishing is waxed, and obtains final product.
The invention provides use in preparing intestinal canal administration medicine antianxity for the tandospirone enteric coated micropill
On the way.
Present invention also offers a kind of tandospirone enteric coated preparation, it is micro- that said preparation includes tandospirone enteric
Ball.
Wherein, described preparation is tablet, capsule or granule.
The tandospirone enteric coated micropill steady quality that the present invention is obtained, in stomach not disintegrate, divides in intestinal
Cloth area is big, and disintegrate stripping property is good, and bioavailability is high, side effect little to alimentary canal mucous membrane zest
Few, patient's Compliance is high.Can be used for treating the patient with following disease: caused by various neurosiss
Anxiety state, the anxiety state that the physical disease such as essential hypertension, peptic ulcer occurs together, light,
Moderate depressive patients；Especially suitable digestive system disease causes patient, mucosal lesion or the easy bleeding of anxiety
Patient, need the gerontal patient of Long-term taking medicine to take.
Brief description
The In-vitro release curves of Fig. 1 different-grain diameter enteric coated micropill
Below by way of specific embodiment, the present invention is described in further detail, but is not intended to limit this
Bright, various changes and replacement that those skilled in the art make according to the present invention, without departing from the present invention
Spirit, scope of the following claims of the present invention all should be belonged to.
Specific embodiment
The preparation of embodiment 1 tandospirone enteric coated capsule
Prepare 1000 capsules altogether
Preparation technology:
(1) capsule core preparation: tandospirone or its officinal salt, filler are mixed together with disintegrating agent, then plus
Enter nodularization accelerator soft material, soft material is extruded into the sieve plate in 0.5mm aperture diameter is identical, smooth densification
Bar, put and carry out round as a ball in spheronizator, until granule is rolled into microspheric granula, take out, place 40 DEG C
Under carry out freeze-day with constant temperature, cross 32 mesh sieves, obtain final product；
(2) bag sealing coat: by hydroxypropyl methylcellulose with, after 70 DEG C of hot water dispersing and dissolvings, adding Pulvis Talci,
Make the sealing coat solution that solid content is about 15wt%；Capsule core is placed in coating pan, adjusts inlet temperature
Piece bed tempertaure is made to be 35 DEG C, atomizing pressure is 0.4mpa, rotating speed is 12rpm, carries out sealing coat to capsule core
Coating；
(3) bag enteric layer: enteric coating material is added to the water and adds plasticizer, Pulvis Talci, titanium dioxide system
Standby one-tenth solid content is about the aqueous dispersion of 20wt%；Adjusting inlet temperature makes piece bed tempertaure be 30 DEG C, atomization
Pressure is 0.2mpa, and rotating speed is 12rpm, carries out enteric layer coating to capsule core；
(4) bag decorative layer: by hydroxypropyl methylcellulose with after 70 DEG C of hot water dispersing and dissolvings, add Pulvis Talci and
Titanium dioxide, makes the decorative layer solution that solid content is about 20wt%；Capsule core is placed in coating pan, adjusts
Section inlet temperature makes piece bed tempertaure be 35 DEG C, and atomizing pressure is 0.5mpa, and rotating speed is 14rpm, to capsule core
Carry out decorative layer coating, polishing is waxed；
(5) filling: take above-mentioned prepared micropill, insert in capsulae vacuuses, obtain final product.
The preparation of embodiment 2 tandospirone enteric coated capsule
Prepare 1000 capsules altogether
Preparation technology: with embodiment 1.
The preparation of embodiment 3 tandospirone enteric coated capsule
Prepare 1000 capsules altogether
Preparation technology: with embodiment 1.
The preparation of embodiment 4 tandospirone enteric coated capsule
Prepare 1000 capsules altogether
Preparation technology: with embodiment 1.
The preparation of embodiment 5 tandospirone enteric coated capsule
Prepare 1000 capsules altogether
Preparation technology: with embodiment 1.
The preparation of embodiment 6 tandospirone enteric coated capsule
Prepare 1000 capsules altogether
Preparation technology: with embodiment 1.
The preparation of embodiment 7 tandospirone enteric coated capsule
Prepare 1000 capsules altogether
Preparation technology: with embodiment 1.
The preparation of embodiment 8 tandospirone enteric coated capsule
Prepare 1000 capsules altogether
Preparation technology: with embodiment 1.
The preparation of embodiment 9 tandospirone enteric coated capsule
Prepare 1000 capsules altogether
Preparation technology: with embodiment 1.
The preparation of embodiment 10 tandospirone enteric coated capsule
Prepare 1000 capsules altogether
Preparation technology: with embodiment 1.
Prove beneficial effects of the present invention below by way of specific experiment.
Experimental example 1 tandospirone enteric coated capsule releasing effect of the present invention measures:
Prepare the enteric coated micropill of 8 kinds of different-grain diameters with reference to embodiment 4, and filling Capsuleses, make Chinese holly
Rafter acid tandospirone drug content is the capsule of 10mg/ grain.
1000 capsules respectively prepared by each prescription.
Preparation technology:
(1) capsule core preparation: Tandospirone Citrate, filler are mixed together with disintegrating agent, adds nodularization
Accelerator soft material, the sieve plate of soft material respective aperture is extruded into diameter is identical, smooth fine and close bar,
Put and carry out round as a ball in spheronizator, until granule is rolled into microspheric granula, take out, at placing 40 DEG C, carry out constant temperature
It is dried, sieve, obtain final product；
(2) bag sealing coat: by hydroxypropyl methylcellulose with, after 70 DEG C of hot water dispersing and dissolvings, adding Pulvis Talci,
Make the sealing coat solution that solid content is about 15wt%；Capsule core is placed in coating pan, adjusts inlet temperature
Piece bed tempertaure is made to be 35 DEG C, atomizing pressure is 0.4mpa, rotating speed is 12rpm, carries out sealing coat to capsule core
Coating；
(3) bag enteric layer: enteric coating material is added to the water and adds plasticizer, Pulvis Talci, titanium dioxide system
Standby one-tenth solid content is about the aqueous dispersion of 20wt%；Adjusting inlet temperature makes piece bed tempertaure be 30 DEG C, atomization
Pressure is 0.2mpa, and rotating speed is 12rpm, carries out enteric layer coating to capsule core；
(4) bag decorative layer: by hydroxypropyl methylcellulose with after 70 DEG C of hot water dispersing and dissolvings, add Pulvis Talci and
Titanium dioxide, makes the decorative layer solution that solid content is about 20wt%；Capsule core is placed in coating pan, adjusts
Section inlet temperature makes piece bed tempertaure be 35 DEG C, and atomizing pressure is 0.5mpa, and rotating speed is 14rpm, to capsule core
Carry out decorative layer coating, polishing is waxed；
(5) filling: take above-mentioned prepared micropill, insert in capsulae vacuuses, obtain final product.
Release in vitro measures:
From drug release determination method first method in Chinese Pharmacopoeia version annex xd in 2010, with 900ml phosphorus
Hydrochlorate buffer solution (ph 6.8) be release medium, rotating speed be 100 revs/min, predetermined point of time (5,
10,15,20,25,30,35,40,45min) sample, measure tandospirone concentration.With the time
(min) it is abscissa, accumulative releasing degree (%) is vertical coordinate, draws release profiles.Release result is shown in
Table 1 and Fig. 1.
Table 1
Be may certify that by table 1 releasing result and Fig. 1 release profiles, particle diameter is the present invention of 0.1～2.0mm
In enteric coated micropill 45min, vitro release all reaches more than 95%, meets the requirement to enteric coated preparation for the pharmacopeia.
Wherein, particle diameter is that in the enteric coated micropill 45min of the present invention of 0.5～0.8mm, release in vitro is not only complete, and
And discharge more uniform, drug absorption fluctuation can be made less.But, tandospirone enteric coated micropill particle diameter
During<0.1mm or particle diameter>2.0mm, in 45min, vitro release is decreased obviously, and discharges the uniformity
Bad.
The relevant substance-measuring of experimental example 2 tandospirone capsule of the present invention:
With reference to high performance liquid chromatography: Chinese Pharmacopoeia two annex vd of version in 2010 measure.
Chromatographic condition and system suitability: it is filler with octadecylsilane chemically bonded silica,
0.01mol/l potassium dihydrogen phosphate-acetonitrile (60:40) is mobile phase, and Detection wavelength is 243nm,
Number of theoretical plate is calculated by tandospirone peak and should be not less than 5000.
Take tandospirone or its officinal salt content about in 50mg about sample, plus flowing phased soln mistake
Filter, filtrate is transferred in 100ml measuring bottle, and is diluted to scale with mobile phase, shakes up, as test sample
Solution；Take relevant material a reference substance appropriate, plus mobile phase makes the comparison containing about 2.5 μ g in every 1ml
Solution.Precision measures contrast solution 20 μ l, injects chromatograph of liquid, adjusts detection sensitivity, makes main one-tenth
The peak height of color separation spectral peak is about the 20～25% of full scale；Precision measures need testing solution and contrast solution again
Each 20 μ l, are injected separately into chromatograph of liquid, 2 times of record chromatogram to main constituent peak retention time.For
Impurity peaks in test sample solution chromatogram must not cross the main peak area (0.5%) in contrast solution chromatogram.
Testing result is shown in Table 2.
Table 2
Experimental example 3 tandospirone capsule preparations evaluation test of the present invention:
Measure with reference to Chinese Pharmacopoeia version annex x d the second method in 2010: measure 0.1mol/l hydrochloric acid solution
750ml, injects each stripping rotor, treats that dissolution medium temperature constant, at 37 DEG C ± 0.5 DEG C, capsule is put into
Turn in basket, setting speed is measured for 100 revs/min, sample in regulation sample point after 2 hours and locate
Reason, as need testing solution.Separately precision weighs Tandospirone Citrate reference substance in right amount and processes, as
Reference substance solution.Precision measures each 50 μ l of above two solution, injects chromatograph of liquid, records chromatogram；
By external standard method with the stripping quantity of calculated by peak area every, and then calculate release (%)；Then in above-mentioned acid
The buffering that the 0.2mol/l sodium radio-phosphate,P-32 solution 250ml that temperature is 37 DEG C ± 0.5 DEG C obtains ph6.8 is added in liquid
Liquid, appropriate in regulation sample point draw solution after the 45min that remains in operation, survey according to the method in above-mentioned acid solution
Determine release (%).
Chromatographic condition and system suitability: with octadecylsilane chemically bonded silica as filler, with 0.1
% heptane sulfonic acid sodium salt (with phosphoric acid tune ph value to 3.0)-acetonitrile (7:3) is mobile phase, and Detection wavelength is
239nm, sets column temperature as 40 DEG C, and adjustment flow velocity makes tandospirone peak retention time be about 6 minutes, reason
Calculate by tandospirone peak by plate number and should be not less than 3000, tailing factor should be not more than 2.0.Measurement result
It is shown in Table 3.
Table 3
May certify that from table 3 experimental result, tandospirone capsule of the present invention is low in stomach release, in intestinal
In road, distribution area is big, disintegrate stripping property good such that it is able to improve bioavailability, reduction is to digestive tract
Irritation on mucous membrane and side effect, improve patient's Compliance.
The experimental example 4 tandospirone capsule of the present invention clinic test of pesticide effectiveness:
During studying, patient is prohibited from using other tranquilizer, anti-inflammatory agent, muscle relaxant, depressor, resists
Chlorpromazine, antidepressants or antianxiety drugss.Parallel right using polycentric random, double blinding, placebo
According to the clinical trial of research, patient's total number of cases are 240 people, are randomly divided into 12 groups, and the age is from 24～65
In year, inclusion criteria is the slight anxious patients to moderate and meets with digestive system disease, gastric mucosa damage
Wound or easy bleeding, more than 50 years old age wherein at least one condition.Take respectively tandospirone conventional capsule,
Embodiment 1～10 enteric coated capsule, dosage is 60mg/ day.After medication 30 days, carry out curative effect (anti-
Anxiety curative effect carries out evaluation analysis according to Hamilton anxiety scale) and untoward reaction evaluation.Result is listed in
Table 4.
Table 4
Result shows, tandospirone conventional capsule group and embodiment 1～10 enteric coated capsule group and placebo group
Compare, all show obvious curative effects.And than tandospirone conventional capsule, this enteric coated capsule quality is more steady
Fixed, more preferably, its effective percentage is obviously higher than tandospirone conventional capsule group for dissolving out capability；In addition enteric glue
Capsule has the property just starting release medicine in intestinal, solves tandospirone and upon administration digestive tract is produced
The raw problem stimulating, damages few, the few side effects bringing, Compliance is high, no to alimentary canal mucous membrane
Good response rate is significantly lower than tandospirone conventional capsule；It is more suitable for treating the anxiety caused by various neurosiss
State, the anxiety state that the physical disease such as essential hypertension, peptic ulcer occurs together, light, moderate suppression
Strongly fragrant disease；Especially suitable digestive system disease cause anxiety the patient of patient, mucosal lesion or easy bleeding,
The gerontal patient needing Long-term taking medicine takes；More patients can be made to be benefited.
Claims (14)
1. a kind of tandospirone enteric coated micropill it is characterised in that: it is by tandospirone or its officinal salt
For the capsule core of active component preparation, sealing coat, enteric layer and complete layer composition；Wherein, capsule core, isolation
Layer, enteric layer, the percentage by weight of complete layer are:
Capsule core 25～95%, sealing coat 0～15%, enteric layer 5～40%, complete layer 0～20%.
2. enteric coated micropill according to claim 1 it is characterised in that: described capsule core, sealing coat,
Enteric layer, the percentage by weight of complete layer are:
Capsule core 50～80%, sealing coat 4～10%, enteric layer 10～27%, complete layer 6～13%.
3. enteric coated micropill according to claim 1 and 2 it is characterised in that: described capsule core Central Plains
The percentage by weight that adjuvant accounts for enteric coated micropill is:
The percentage by weight that in described sealing coat, adjuvant accounts for enteric coated micropill is:
Hydroxypropyl methylcellulose 0～12%
Pulvis Talci 0～8%；
The percentage by weight that in described enteric layer, adjuvant accounts for enteric coated micropill is:
The percentage by weight that in described complete layer, adjuvant accounts for enteric coated micropill is:
4. enteric coated micropill according to claim 3 it is characterised in that: supplementary material in described capsule core
The percentage by weight accounting for enteric coated micropill is:
The percentage by weight that in described sealing coat, adjuvant accounts for enteric coated micropill is:
Hydroxypropyl methylcellulose 3～7%
Pulvis Talci 1～4%；
The percentage by weight that in described enteric layer, adjuvant accounts for enteric coated micropill is:
The percentage by weight that in described complete layer, adjuvant accounts for enteric coated micropill is:
5. enteric coated micropill according to claim 4 it is characterised in that: supplementary material in described capsule core
The percentage by weight accounting for enteric coated micropill is:
6. the enteric coated micropill according to claim 3-5 any one it is characterised in that: described fills out
Fill agent and be selected from starch, sucrose, Lactose, Microcrystalline Cellulose, Mannitol, Sorbitol, calcium sulfate, phosphoric acid
Hydrogen calcium or one or more therein of Calcium Carbonate；
Described disintegrating agent is selected from low-substituted hydroxypropyl cellulose, carboxymethylcellulose calcium, cross-linked carboxymethyl
Sodium cellulosate, carboxymethyl starch sodium or one or more therein of Crospovidone；
Described nodularization accelerator is selected from sodium alginate, polyvinyl alcohol, hydroxypropyl cellulose, hydroxypropyl
Cellulose, sodium carboxymethyl cellulose, polyvidone, Macrogol 4000, polyethylene glycol 6000 or micropowder
One or more therein of silica gel；
Described enteric macromolecular material is acrylic resin, hydroxypropyl methylcellulose titanate esters, hydroxypropyl first
Base cellulose acetate succinate (hpmcas), cellulose acetate titanate esters, cellulose acetate benzene three
Acid esters or polyvinyl alcohol titanate esters；
Described plasticizer be selected from triethyl citrate, tributyl citrate, glycerol, glycerol triacetate,
SA dibutyl ester, propylene glycol, Oleum Ricini, cochin oil, Semen Maydis oil, Polyethylene Glycol therein one
Plant or multiple.
7. enteric coated micropill according to claim 6 it is characterised in that: described enteric coated micropill be by
The supplementary material of following weight percentage ratio is prepared from:
Tandospirone or 10 parts of its officinal salt, 70 parts of Microcrystalline Cellulose, 50 parts of starch, carboxymethyl form sediment
30 parts of powder sodium, 40 parts of sodium carboxymethyl cellulose, 10 parts of micropowder silica gel, 30 parts of hydroxypropyl methylcellulose,
24 parts of Pulvis Talci, 20 parts of hydroxypropyl methylcellulose acetate succinate, 10 parts of SA dibutyl ester, two
4 parts of titanium oxide, 2 parts of river wax；Or
Tandospirone or 10 parts of its officinal salt, 60 parts of Lactose, 30 parts of Mannitol, cross-linked carboxymethyl
40 parts of sodium cellulosate, 30 parts of polyvidone, 10 parts of micropowder silica gel, 38 parts of hydroxypropyl methylcellulose, cunning
28 parts of stone powder, 26 parts of cellulose acetate benzenetricarboxylic acid ester, 12 parts of Polyethylene Glycol, 4 parts of titanium dioxide, bar
2 parts of western palm wax；Or
Tandospirone or 10 parts of its officinal salt, 45 parts of sucrose, 35 parts of Sorbitol, Crospovidone
25 parts, 30 parts of Macrogol 4000,5 parts of micropowder silica gel, 45 parts of hydroxypropyl methylcellulose, Pulvis Talci
36 parts, 40 parts of polyvinyl alcohol titanate esters, 20 parts of glycerol, 7 parts of titanium dioxide, 2 parts of Brazil wax.
8. the enteric coated micropill according to claim 1～7 any one it is characterised in that: described intestinal
The particle diameter of molten micropill is 0.1～2.0mm.
9. enteric coated micropill according to claim 8 it is characterised in that: the grain of described enteric coated micropill
Footpath is 0.3～1.5mm.
10. enteric coated micropill according to claim 9 it is characterised in that: the grain of described enteric coated micropill
Footpath is 0.5～0.8mm.
11. preparation claim 1-10 any one described in enteric coated micropill methods it is characterised in that:
It comprises the steps:
A. prepare capsule core: tandospirone or its officinal salt, filler are mixed together with disintegrating agent, then
Add nodularization accelerator soft material, soft material is extruded into the sieve plate in 0.5mm aperture diameter is identical, light slips
Close bar, puts and carries out round as a ball in spheronizator, until granule is rolled into microspheric granula, take out, place 40
Carry out freeze-day with constant temperature at DEG C, cross 32 mesh sieves, obtain final product；
B. bag sealing coat: by hydroxypropyl methylcellulose with, after 70 DEG C of hot water dispersing and dissolvings, adding Pulvis Talci,
Make the sealing coat solution that solid content is about 15wt%, capsule core is placed in coating pan, adjust inlet temperature
Piece bed tempertaure is made to be 35 DEG C, atomizing pressure is 0.4mpa, rotating speed is 12rpm, carries out sealing coat to capsule core
Coating；
C. bag enteric layer: enteric coating material is added to the water and adds plasticizer, Pulvis Talci, titanium dioxide
It is prepared into the aqueous dispersion that solid content is about 20wt%；Adjusting inlet temperature makes piece bed tempertaure be 30 DEG C, mist
Change pressure is 0.2mpa, and rotating speed is 12rpm, carries out enteric layer coating to capsule core；
D. bag complete layer: by hydroxypropyl methylcellulose with after 70 DEG C of hot water dispersing and dissolvings, add Pulvis Talci and
Titanium dioxide, makes the decorative layer solution that solid content is about 20wt%；Capsule core is placed in coating pan, adjusts
Section inlet temperature makes piece bed tempertaure be 35 DEG C, and atomizing pressure is 0.5mpa, and rotating speed is 14rpm, to capsule core
Carry out decorative layer coating, polishing is waxed, and obtains final product.
Enteric coated micropill described in 12. claim 1～10 any one is preparing intestinal canal administration medicine antianxity
Purposes in thing.
A kind of 13. tandospirone enteric coated preparation, the enteric that it contains described in claim 1-9 any one is micro-
Ball.
14. tandospirone enteric coated preparation according to claim 13 it is characterised in that: described system
Agent is tablet, capsule, granule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510424689.5A CN106344519B (en) | 2015-07-17 | 2015-07-17 | A kind of Tandospirone enteric-coated micro-pill and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510424689.5A CN106344519B (en) | 2015-07-17 | 2015-07-17 | A kind of Tandospirone enteric-coated micro-pill and its preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106344519A true CN106344519A (en) | 2017-01-25 |
| CN106344519B CN106344519B (en) | 2018-11-06 |
Family
ID=57843044
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510424689.5A Active CN106344519B (en) | 2015-07-17 | 2015-07-17 | A kind of Tandospirone enteric-coated micro-pill and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106344519B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109745323A (en) * | 2017-11-01 | 2019-05-14 | 四川科瑞德制药股份有限公司 | Azapirone compound improves the active purposes of parasympathetic nerve |
| WO2021129340A1 (en) * | 2019-12-25 | 2021-07-01 | 四川科瑞德制药股份有限公司 | Tandospirone pharmaceutical composition, preparation method therefor and use thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001076557A1 (en) * | 2000-04-10 | 2001-10-18 | Sumitomo Pharmaceuticals Co., Ltd. | Sustained release preparations |
| CN1899287A (en) * | 2006-07-19 | 2007-01-24 | 四川科瑞德制药有限公司 | Slow release medicinal composition for treating anxiety and its preparing method |
| CN1915216A (en) * | 2006-08-30 | 2007-02-21 | 四川科瑞德制药有限公司 | New usage of tandospirone and its derivative, and composition containing tandospirone |
| CN104706614A (en) * | 2013-12-16 | 2015-06-17 | 四川科瑞德制药有限公司 | Tandospirone micropore osmotic pump preparation |
-
2015
- 2015-07-17 CN CN201510424689.5A patent/CN106344519B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001076557A1 (en) * | 2000-04-10 | 2001-10-18 | Sumitomo Pharmaceuticals Co., Ltd. | Sustained release preparations |
| CN1899287A (en) * | 2006-07-19 | 2007-01-24 | 四川科瑞德制药有限公司 | Slow release medicinal composition for treating anxiety and its preparing method |
| CN1915216A (en) * | 2006-08-30 | 2007-02-21 | 四川科瑞德制药有限公司 | New usage of tandospirone and its derivative, and composition containing tandospirone |
| CN104706614A (en) * | 2013-12-16 | 2015-06-17 | 四川科瑞德制药有限公司 | Tandospirone micropore osmotic pump preparation |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109745323A (en) * | 2017-11-01 | 2019-05-14 | 四川科瑞德制药股份有限公司 | Azapirone compound improves the active purposes of parasympathetic nerve |
| WO2021129340A1 (en) * | 2019-12-25 | 2021-07-01 | 四川科瑞德制药股份有限公司 | Tandospirone pharmaceutical composition, preparation method therefor and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106344519B (en) | 2018-11-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5956475B2 (en) | Orally disintegrating tablets containing bitter mask granules | |
| JPH0753365A (en) | Pharmaceutical chemistry composition that has control release ability by gamma. - hydroxy butyric acid salt | |
| CN105338970B (en) | Medicament capsule compound formulation comprising Tadalafei and Tamsulosin | |
| WO2019130749A1 (en) | Novel fine particle coating (drug-containing hollow particle and method for manufacturing same) | |
| CN101366876A (en) | Traditional Chinese medicine preparation for treating throat irritation and preparation method thereof | |
| CN106344519A (en) | Tandospirone enteric-coated mini-pill, and preparation method and application thereof | |
| CN106963736A (en) | Dextromethorphan hydrobromide sustained-release dry suspensoid agent and preparation method thereof | |
| CN108685870A (en) | Jamaicin and its can forming salt enteric-coated micro-pill, its prepare and application | |
| CN105496967B (en) | Ranitidine hydrochloride controlled release dry suspensoid agent and preparation method thereof | |
| CN102085344A (en) | Aplotaxis carminative sustained-release preparation and preparation method thereof | |
| Mutalik et al. | Chitosan and enteric polymer based once daily sustained release tablets of aceclofenac: in vitro and in vivo studies | |
| CN101099762B (en) | Blood pressue lowering sustained-release preparation with chrysanthemum flower and pearl | |
| WO2013189305A1 (en) | Valsartan-amlodipine compound solid preparation and preparation method therefor | |
| CN102293759A (en) | Dextral ibuprofen sustained release tablet preparation and preparation method thereof | |
| CN106176659B (en) | A kind of Tandospirone enteric coatel tablets and preparation method thereof | |
| CN109646417A (en) | A kind of Trimetazidine sustained release tablets and preparation method thereof | |
| CN101658507B (en) | Glyceryl guaiacolate and pseudoephedrine compound sustained release preparation | |
| CN104220064B (en) | A kind of joint product containing synephrine and Topiramate | |
| Chaturvedi et al. | Comparative Evaluation Of Natural And Semisynthetic Superdisintegrants In The Formulation Of Orodispersible Tablets of Norfloxacin | |
| CN105726503A (en) | Levofloxacin hydrochloride tablet | |
| CN108096251B (en) | Gefitinib pharmaceutical composition and preparation method thereof | |
| CN105250233B (en) | (S)-ibuprofen enteric-coated sustained-release tablet and preparation method thereof | |
| Choudhury | Formulation and Statistical Optimisation of Bilayer Sublingual Tablets of Levocetrizine Hydrochloride & Ambroxol Hydrocholoride | |
| CN1306949C (en) | Tendon relaxing and dampness removing traditional Chinese medicine compound preparation and preparation method thereof | |
| Pandurangan et al. | Fast dissolving tablets-An overview |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |