CN1899287A - Slow release medicinal composition for treating anxiety and its preparing method - Google Patents
Slow release medicinal composition for treating anxiety and its preparing method Download PDFInfo
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- CN1899287A CN1899287A CN 200610021419 CN200610021419A CN1899287A CN 1899287 A CN1899287 A CN 1899287A CN 200610021419 CN200610021419 CN 200610021419 CN 200610021419 A CN200610021419 A CN 200610021419A CN 1899287 A CN1899287 A CN 1899287A
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Abstract
The present invention provides a kind of slow released medicinal composition for treating anxiety, and features that the slow released medicinal composition is slow released medicinal preparation with tadosporin citrate in effective quantity as the active component and pharmaceutically acceptable supplementary material. By means of the action of the slow releasing material, tadosporin citrate is released slowly to generate slow and smooth blood medicine level without peak valley phenomenon and with raised patient compliance. The present invention has reduced medicine taking times and convenient taking.
Description
Technical field
The present invention relates to slow releasing preparation and the preparation method of SM-3997 (tandospirone citrate), belong to field of medicaments.
Background technology
SM-3997 is a kind of 5-HT receptor stimulating agent, is used for the treatment of the medicine of generalized anxiety disorder and mixed type anxiety depression.Do not see any slow releasing preparation report both at home and abroad.And existing commercially available ordinary preparation is taken 3 every day, and each consumption is 10mg, and blood concentration fluctuation is big, and patient takes poor compliance.So it is necessary that preparation 12h can keep the slow releasing preparation of blood drug level.The SM-3997 oral absorption is good, and peak time is 0.5-2h.(1-Pyrimidiny1-piperazine, 1-PP), the concentration of metabolite is higher about 2～8 times than the concentration of its parent compound to be metabolized to the 1-pyrimidylpiperazine in vivo.The SM-3997 elimination half-life in vivo is 2～3h, and the elimination half-life of its metabolite is 3-5h, after the taking medicine continuously of long period, does not have in vivo and accumulates.Medicine nearly 70% is drained from urine after the metabolism in vivo, has only 0.1% to be the original shape medicine, has 21% to discharge from feces in addition.At present, Chang Yong slow-release material comprises: one, the less high molecular polymer of water insoluble or water solublity.Common have ethyl cellulose, polyethylene, polypropylene, poly-silica ball, ethylene-vinyl acetate copolymer and a polymethyl methacrylate etc.Two, bioerodable section bar material.Commonly used have stearic acid, Brazil wax, glyceryl monostearate, a stearyl alcohol etc.Three, hydrophilic gel class material.Be meant and meet water and Digestive system expands, form the gel barrier and control the hydrophilic polymer of medicine stripping.Mainly contain natural gum class such as sodium alginate, agar, tragcanth; Cellulose derivative class such as methylcellulose, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose etc.
Because the character of medicine, clinical consumption and specifically at the indication analysis-by-synthesis, whether can be prepared into slow releasing preparation, reach the effect of slow releasing preparation, be unpredictable.
Summary of the invention
The technical problem that the present invention solves has provided a kind of SM-3997 preparation of sustained-release administration.The present invention also provides the preparation method of said preparation.
The invention provides a kind of sustained release pharmaceutical composition for the treatment of anxiety neurosis, it is that SM-3997 by effective dose is an active component, add the slow-releasing agent that pharmaceutically acceptable slow-release material, adhesive, filler, lubricant, fluidizer, coloring agent are prepared from, described SM-3997, structural formula is as follows:
Because SM-3997 is molten in the water part omitted, slow-release material preferred for this invention is a hydrophilic gel class material, is meant to meet water or Digestive system expands, and forms the gel barrier and controls the hydrophilic polymer of medicine stripping.Mainly contain natural gum class such as sodium alginate, agar, tragcanth; Cellulose derivative class such as methylcellulose, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose etc.
The present invention is cellulose derivative more preferably, comprises in methylcellulose, hydroxy methocel, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose (HPMC), carboxymethyl cellulose, carboxyethyl cellulose, the microcrystalline Cellulose one or more.
Further, hydroxypropyl emthylcellulose more preferably comprises among HPMC A4M, HPMC K4M, HPMCE4M, HPMC K15M, HPMC K50M, the HPMC K100M one or more.
HPMC K4M preferably.
Except that medicine and slow-release material, also contain medicated premix, these additives comprise one or several in adhesive, filler, lubricant, fluidizer, the coloring agent.
Wherein preferred adhesive is selected from one or several in ethanol, water, dextrin, the starch slurry.
Preferred filler is selected from one or more in lactose, sucrose, mannitol, the corn starch.
Preferred lubricant is selected from one or several in magnesium stearate, Pulvis Talci or the silicon dioxide.
Preferred fluidizer is selected from silica gel and/or Pulvis Talci.
Wherein the consumption of SM-3997 is every 10mg-100mg of preparation unit.Further, every preparation unit contains SM-3997 15mg-55mg.Further, every preparation unit contains SM-3997 15mg-30mg.Described every preparation unit is meant every of tablet, every capsules of capsule, every bag (1g) of granule.The interior blood drug level 12h of back body that takes medicine can maintain in 1.0 ± 0.2～3.2 ± 0.6 (ng/ml) scope.
Wherein, the proportioning of described SM-3997 and slow-release auxiliary material is 1: 0.15-10, all the other are pharmaceutically acceptable adhesive, filler, lubricant, fluidizer and coloring agent.
So the present invention more preferably, the proportioning of SM-3997 and slow-release auxiliary material is 1: 0.15-4, all the other are pharmaceutically acceptable adhesive, filler, lubricant, fluidizer and coloring agent.
Studies show that in many factors that influences slow release effect, the ratio of SM-3997 and slow-release material is extremely important factor.When the use amount of SM-3997 fixedly the time, want to reach the slow release effect of certain hour, the slow-release auxiliary material difference of being arranged in pairs or groups, then the proportioning ratio is also different.For example, experimental result shows, in order to obtain comparatively close pharmacokinetics parameter, reaches the purpose of slow release 12h.When agar and tragcanth were united as slow-release auxiliary material, the ratio of SM-3997 and agar, tragcanth was 1: 0.15 o'clock effectively slow release 12h, effective slow release 12h when the ratio of SM-3997 and hydroxypropyl emthylcellulose is 1: 4.Though but use which kind of slow-release material, when ratio surpasses more than 1: 10, releasing effect is too slow, does not reach the purpose of slow release 12h.So SM-3997 of the present invention is 1 with the ratio of slow-release material: 0.15-10; Preferred SM-3997 is 1 with the ratio of slow-release material: 0.15-4.
Wherein adhesive, filler, lubricant, fluidizer and coloring agent are not all to contain in the middle of every kind of preparation.Adhesive commonly used comprises distilled water, ethanol, starch slurry, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methylcellulose, ethyl cellulose, hypromellose, 5%～20% gelatin solution, 50%～70% sucrose solution, 3%～5% polyethylene adjoin the aqueous solution of pyrrolidone (PVP) or alcoholic solution etc.Filler commonly used comprises starch, Icing Sugar, dextrin, lactose, amylum pregelatinisatum, microcrystalline Cellulose, inorganic salts, mannitol etc.Lubricant commonly used comprises magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, polyethylene glycols and magnesium laurylsulfate etc.Fluidizer mainly comprises silica gel and Pulvis Talci.Coloring agent commonly used comprises capsanthin, red yeast rice, Rhizoma Curcumae Longae, Gardenia Yellow, chrysanthemum etc.
Described adjuvant also contains adhesive, filler, lubricant, fluidizer, coloring agent, and its weight proportion is:
1 part of SM-3997
Slow-release auxiliary material 0.15-10 part
Adhesive 0-5 part
Filler 0-25 part
Lubricant 0-2 part
Fluidizer 0-2 part
Coloring agent 0-2 part.
Further, it is the medicament that is prepared from by following weight proportion raw material and adjuvant:
1 part of SM-3997
Slow-release auxiliary material 0.15-4 part
Adhesive 0-5 part
Filler 0-25 part
Lubricant 0-2 part
Fluidizer 0-2 part
Coloring agent 0-2 part.
The dosage form of the present composition can be: the dosage form of using always on the pharmaceuticss such as tablet, capsule, granule, pill, suppository, soft capsule, oral liquid, suspensoid, injection.Preferred dosage form is tablet and capsule.Tablet is coating further.
SM-3997 slow releasing preparation of the present invention makes the rate of release of SM-3997 slack-off by the effect of slow-release material, produces slowly, blood drug level more stably, avoids peak valley phenomenon, improves compliance of patients simultaneously.The slow releasing preparation administration number of times of SM-3997 of the present invention reduces to 1 day for 3 times from administration in 1 day and only needs administration 2 times, and administration number of times reduces, and conveniently takes.
Following examples only supply the usefulness of elaboration, rather than best proportioning ratio, neither be used for limiting its claim.
The specific embodiment
Embodiment 1
SM-3997 16.2g
Hydroxypropyl emthylcellulose (HPMC K4M) 64.8g
75% ethanol 12ml
Lactose 110g
Magnesium stearate 3g
Pulvis Talci 6g
Preparation technology: with SM-3997 crude drug and hydroxypropyl emthylcellulose, lactose, mix homogeneously, sieve, add 75% alcoholic solution system soft material, cross 20 mesh sieve system wet granulars, oven dry in about 50 ℃, 20 mesh sieve granulate, add magnesium stearate and Pulvis Talci, tabletting behind the mix homogeneously.The heavy 0.2g of sheet makes 1000 altogether.
Zoopery: get 12 of new zealand rabbits, male and female half and half, body weight (4.5-5) kg is divided into 2 groups at random, and fasting 18h before the administration is with 10mg SM-3997/kg administration.Rabbit ear edge vein is got blood, records pharmacokinetic parameter, and the result shows: the slow releasing preparation peak time (t that compares with ordinary preparation
Peak) obviously prolong peak concentration (C
Max) obviously reduce, area under curve (AUC) obviously increases.See Table 1
Table 1 is slow releasing tablet and ordinary tablet pharmacokinetic parameter comparison sheet (x ± s)
| t peak(h) | C max(ng/ml) | AUC(ng.h/ml) | |
| The slow releasing tablet ordinary tablet | 3.5±1.2 * 0.9±0.3 | 1.5±0.9 * 3.3±1.8 | 45.6±12.0 * 11.3±9.5 |
*Compare P＜0.05 with conventional tablet
Side effect situation: do not see that any side effect takes place.
Embodiment 2
SM-3997 30g
Hydroxypropyl emthylcellulose (HPMC K15M) 50g
Methylcellulose 50g
75% ethanol 13ml
Lactose 70g
Magnesium stearate 5g
Pulvis Talci 7g
Preparation technology: with SM-3997 crude drug and hydroxypropyl emthylcellulose, methylcellulose, lactose, mix homogeneously, sieve, add 75% alcoholic solution system soft material, cross 20 mesh sieve system wet granulars, oven dry in about 50 ℃, 20 mesh sieve granulate add magnesium stearate and Pulvis Talci, tabletting behind the mix homogeneously.The heavy 0.2g of sheet makes 1000 altogether.
Animal experiment method such as example 1 the results are shown in Table 2
Table 2 slow releasing tablet and ordinary tablet pharmacokinetic parameter comparison sheet (x ± s)
| t peak(h) | C max(ng/ml) | AUC(ng.h/ml) | |
| The slow releasing tablet ordinary tablet | 3.4±3.1 * 0.8±0.5 | 1.7±0.8 * 3.5±1.3 | 44.7±12.3 * 13.1±3.5 |
*Compare P＜0.05 with conventional tablet
Side effect situation: do not see that any side effect takes place.
Embodiment 3
SM-3997 10g
Sodium alginate 25g
Methylcellulose 50g
Carboxymethyl cellulose 25g
75% alcoholic solution 10ml
Corn starch 100g
Preparation technology: with SM-3997 crude drug and sodium alginate, methylcellulose, carboxymethyl cellulose, corn starch mix homogeneously, sieve, add 75% alcoholic solution system soft material, cross 20 mesh sieve system wet granulars, tabletting.The heavy 0.2g of sheet makes 1000 altogether.
Animal experiment method such as example 1 the results are shown in Table 3
Table 3 slow releasing tablet and ordinary tablet pharmacokinetic parameter comparison sheet (x ± s)
| t peak(h) | C max(ng/ml) | AUC(ng.h/ml) | |
| The slow releasing tablet ordinary tablet | 3.9±1.4 * 1.1±1.2 | 1.4±0.3 * 3.4±2.1 | 43.2±10.3 * 11.4±6.5 |
*Compare P＜0.05 with conventional tablet
Side effect situation: do not see that any side effect takes place.
Embodiment 4
SM-3997 60g
Agar 4g
Tragcanth 5g
75% alcoholic solution 9ml
Corn starch 70g
Lactose 60g
Magnesium stearate 4g
Pulvis Talci 3g
Preparation technology: with SM-3997 crude drug and corn starch, lactose mix homogeneously, sieve, add agar, tragcanth and 75% alcoholic solution system soft material, cross 20 mesh sieve system wet granulars, adding magnesium stearate and Pulvis Talci, tabletting behind the mix homogeneously.The heavy 0.2g of sheet makes 1000 altogether.
Animal experiment method such as example 1 the results are shown in Table 4
Table 4 slow releasing tablet and ordinary tablet pharmacokinetic parameter comparison sheet (x ± s)
| t peak(h) | C max(ng/ml) | AUC(ng.h/ml) | |
| The slow releasing tablet ordinary tablet | 3.4±1.3 * 1.0±0.6 | 1.7±1.2 * 3.1±2.0 | 43.4±11.2 * 12.1±5.3 |
*Compare P＜0.05 with conventional tablet
Side effect situation: do not see that any side effect takes place.
Embodiment 5 bolus of drug of the present invention
SM-3997 15g
Tragcanth 20g
75% ethanol 6ml
Corn starch 60g
Preparation technology: with SM-3997 crude drug and corn starch mix homogeneously, add tragcanth, in general ball pot, make fine pellet core with 75% ethanol, take out, drying is got the dry ball core that makes, weigh after removing fine powder, place coating pan to rotate,, coating solution is sprayed on above the mobile ball core, the blowing hot-air drying, spraying, drying are taken out when coatings reaches constant weight so repeatedly again, place in room temperature and spend the night.
Animal experiment method such as example 1 the results are shown in Table 5
Table 5 slow releasing pill and ordinary pill pharmacokinetic parameter comparison sheet (x ± s)
| t peak(h) | C max(ng/ml) | AUC(ng.h/ml) | |
| The slow releasing pill ordinary pill | 3.9±1.2 * 1.7±0.5 | 1.3±0.9 * 3.1±1.2 | 42.5±11.3 * 13.0±6.2 |
*Compare P＜0.05 with ordinary pill
Side effect situation: do not see that any side effect takes place.
Embodiment 6 medicine capsules of the present invention
SM-3997 55g
Hydroxypropyl emthylcellulose (HPMC K100M) 50g
Methylcellulose 45g
75% ethanol 8ml
Preparation technology: with SM-3997 crude drug and hydroxypropyl emthylcellulose (HPMC K100M), methylcellulose, mix homogeneously, sieve, add 75% alcoholic solution system soft material, cross 20 mesh sieve system wet granulars, drying, granulate, encapsulated.
Animal experiment method such as example 1 the results are shown in Table 6
Table 6 slow releasing capsule and conventional capsule pharmacokinetic parameter comparison sheet (x ± s)
| t peak(h) | C max(ng/ml) | AUC(ng.h/ml) | |
| The slow releasing capsule conventional capsule | 4.1±2.1 * 1.6±0.7 | 1.2±0.8 * 2.9±1.2 | 43.6±23.2 * 12.2±4.6 |
*Compare P＜0.05 with conventional capsule
Side effect situation: do not see that any side effect takes place.
Embodiment 7
SM-3997 100g
Hydroxypropyl emthylcellulose (HPMC K100M) 50g
Methylcellulose 45g
Brazil wax 45g
Polyethylene 50g
75% ethanol 20ml
Preparation technology: with SM-3997 crude drug and hydroxypropyl emthylcellulose (HPMC K100M), methylcellulose, polyethylene mix homogeneously, sieve, add Brazil wax, with 75% alcoholic solution system soft material, mistake 20 mesh sieve system wet granulars, tabletting.The heavy 0.3g of sheet makes 1000 altogether.
Animal experiment method such as example 1 the results are shown in Table 7
Table 7 slow releasing tablet and conventional tablet pharmacokinetic parameter comparison sheet (x ± s)
| t peak(h) | C max(ng/ml) | AUC(ng.h/ml) | |
| The slow releasing tablet conventional tablet | 3.2±1.2 * 1.4±0.6 | 1.4±0.6 * 2.8±1.4 | 41.6±22.2 * 15.2±3.5 |
*Compare P＜0.05 with conventional tablet
Side effect situation: do not see that any side effect takes place.
Embodiment 8 medicinal granules of the present invention
SM-3997 100g
Hydroxypropyl emthylcellulose (HPMC K100M) 50g
Methylcellulose 45g
Stearic acid 100g
Brazil wax 45g
Polyethylene 50g
Lactose 200g
Mannitol 200g
Corn starch 200g
75% ethanol 60ml
Preparation technology: with SM-3997 crude drug and hydroxypropyl emthylcellulose (HPMC K100M), methylcellulose, stearic acid, polyethylene, lactose, Brazil wax, mannitol, corn starch mix homogeneously, sieve, with 75% alcoholic solution system soft material, cross 20 mesh sieve system wet granulars.Drying is made granule.The heavy 1.0g of bag makes 1000 bags altogether.
Animal experiment method such as example 1 the results are shown in Table 8
Table 8 sustained-release granular formulation and plain particles agent pharmacokinetic parameter comparison sheet (x ± s)
| t peak(h) | C max(ng/ml) | AUC(ng.h/ml) | |
| The slow-releasing granules plain particles | 3.5±1.4 * 1.6±0.9 | 1.7±0.4 * 2.9±1.6 | 45.6±27.2 * 14.2±3.6 |
*Compare P＜0.05 with the plain particles agent
Side effect situation: do not see that any side effect takes place.
Following preferred by concrete evidence excipient substance of the present invention.
The optimization experiment of natural gum class and cellulose family in test example 1 slow-release auxiliary material
Experimental technique and result:
Get the hydroxyethyl-cellulose and the sodium alginate of Isodose respectively, each 10 parts,, add 75% alcohol granulation, tabletting with the SM-3997 mixing.Under equal conditions, measure the cumulative release degree, investigate the influence of slow-release material drug release rate.The results are shown in Table 9.
Table 9 hydroxyethyl-cellulose and sodium alginate are to the influence of SM-3997 cumulative release degree (x ± s)
| Time (h) cumulative release degree of putting (%) | Hydroxyethyl-cellulose | Sodium alginate |
| 0 1 2 3 4 5 6 7 8 | 0.0±0.0 9.4±2.1 15.2±1.6 22.3±5.3 28.4±4.5 33.2±6.2 39.3±5.1 43.5±4.5 49.5±6.7 | 0.0±0.0 11.5±2.3 16.2±1.5 27.3±5.6 34.5±5.5 * 39.3±5.1 * 43.3±4.7 * 49.4±3.8 * 65.5±7.1 * |
*Compare P＜0.05 with the hydroxyethyl-cellulose group
Analyze by statistics, hydroxyethyl-cellulose is compared with sodium alginate, and there is significant difference (P＜0.05) in the cumulative release degree during 4-8h. and this experimental result shows that hydroxyethyl-cellulose is preferable as slow-release material than sodium alginate.
The selection experiment of the plain class slow-release auxiliary material of test example 2 iatric fibers of the present invention kind:
Experimental technique and result:
Get the hydroxypropyl emthylcellulose (HPMC K15M) and the hydroxyethyl-cellulose of Isodose respectively, each 10 parts,, add 75% alcohol granulation, tabletting with the SM-3997 mixing.Under equal conditions, measure the cumulative release degree, investigate the influence of slow-release material drug release rate.The results are shown in Table 10:
Table 10HPMC K15M and hydroxyethyl-cellulose are to the influence of SM-3997 cumulative release degree (x ± s)
| Time (h) accumulation discharges degree of putting (%) | HPMC K15M | Hydroxyethyl-cellulose |
| 0 1 2 3 4 5 6 7 8 | 0.0±0.0 3.4±1.3 5.2±1.2 10.5±2.1 13.2±3.2 17.4±5.5 19.7±3.6 21.8±1.3 23.2±6.5 | 0.0±0.0 9.4±2.1 * 15.2±1.6 * 22.3±5.3 * 28.4±4.5 * 33.2±6.2 * 39.3±5.1* 43.5±4.5 * 49.5±6.7 * |
*Compare P＜0.05 with HPMC K15M group
Analyze by statistics, there are significant difference (P＜0.05) in HPMCK15M and hydroxyethyl-cellulose 1-8h, cumulative release degree.This experimental result shows that hydroxypropyl emthylcellulose is preferable as slow-release material than hydroxyethyl-cellulose.
Best model screening experiment in test example 3 hydroxypropyl emthylcelluloses
Because commercially available hydroxypropyl emthylcellulose model is more, the present invention has selected for use four kinds of models to experimentize in conjunction with practical situation, to determine the optimum selection scheme.
Experimental technique and result
Get HPMC K4M, HPMC K15M, the HPMC K100M of Isodose respectively, HPMC A4M, with the SM-3997 mixing, adds 75% alcohol granulation, tabletting by each 10 parts.Under equal conditions, measure the cumulative release degree, investigate the influence of slow-release material drug release rate.The results are shown in Table 11
The experiment of best model in the table 11 screening hydroxypropyl emthylcellulose (x ± s)
| Time (h) cumulative release degree (%) | HPMC K4M | HPMC K15M | HPMC K100M | HPMC A4M |
| 0 1 2 3 4 5 6 7 8 | 0.0±0.0 3.1±1.0 4.2±1.5 8.5±2.1 9.2±1.1 10.4±2.1 11.5±2.5 15.8±1.9 17.8±2.3 | 0.0±0.0 3.4±1.3 5.2±1.2 10.5±2.1 13.2±3.2 * 17.4±5.5 * 19.7±3.6 * 21.8±1.3 * 23.2±6.5 * | 0.0±0.0 3.2±1.1 5.3±1.6 10.3±2.0 13.5±2.1 * 16.7±2.8 * 19.5±2.8 * 22.1±1.4 * 25.1±1.9 * | 0.0±0.0 3.2±1.3 5.7±1.5 10.8±2.7 14.5±2.0 * 17.5±2.8 * 19.7±2.7 * 21.9±1.6 * 25.8±1.8 * |
*P＜0.05 of comparing with HPMC K4M that there were significant differences
This experimental result shows that HPMC K4M is preferable as slow-release material than its excess-three kind hydroxypropyl emthylcellulose.So preferred HPMC K4M of the present invention.
The cumulative in vitro release experiment of test example 4 specific embodiments
Prescription 1 is formed: (1000) hydrophilic gel class
SM-3997 16.2g
Hydroxypropyl emthylcellulose (HPMC K4M) 64.8g
75% ethanol 12ml
Lactose 130g
Magnesium stearate 3g
Pulvis Talci 6g
Prescription 2 is formed: (1000) water-insoluble material
SM-3997 16.2g
Polyethylene 64.8g
75% ethanol 12ml
Lactose 130g
Magnesium stearate 3g
Pulvis Talci 6g
The cumulative in vitro release experiment of table 12 specific embodiment
| Time (hour) cumulative release degree (%) | Prescription 1 | Prescription 2 |
| 1 2 4 6 8 10 12 | 7.4 17.5 36.6 53.1 77 88 97 | 0.5 3.2 6.5 8.7 9.8 11 11 |
This shows that prescription 1 release is even and the interior drug release of 12h is abundant, the release of prescription 2 reaches capacity when 10h, and can not fully discharge medicine.So slow-release material selects the hydrophilic gel class to be better than the water-insoluble material.
Above-mentioned test explanation, for a person skilled in the art, the present invention is used to prepare slow releasing preparation with SM-3997, the consumption and the indication of suitable SM-3997, and the slow-release auxiliary material of selecting reaches best slow release medication purpose.Though the character of each slow-release auxiliary material is certain, because which kind of adjuvant the special chemical physical property of SM-3997 selects for use, can reach best slow release effect, it is unpredictable using up the consumption that reduces slow-release auxiliary material to greatest extent.The slow release effect which kind of proportioning various slow-release auxiliary material and SM-3997 adopt just to reach 12h also is unpredictable.Above-mentioned 2 all is impossible conspicuous for a person skilled in the art, and therefore, slow releasing preparation of the present invention provides a kind of new selection for the clinical treatment anxiety neurosis.
Claims (10)
1, a kind of sustained release pharmaceutical composition for the treatment of anxiety neurosis is characterized in that: it is that the SM-3997 of mountain effective dose is an active component, adds the slow-releasing agent that acceptable accessories is prepared from.
2, the sustained release pharmaceutical composition of treatment anxiety neurosis according to claim 1 is characterized in that: every preparation unit contains SM-3997 10mg-100mg, described SM-3997, and structural formula is as follows:
3, according to the sustained release pharmaceutical composition of claim 2 treatment anxiety neurosis, it is characterized in that: every preparation unit contains SM-3997 15mg-55mg.
4, according to the sustained release pharmaceutical composition of each described treatment anxiety neurosis of claim 1-3, it is characterized in that: it contains the SM-3997 of following weight proportioning and the medicament that slow-release auxiliary material is prepared from:
The proportioning of SM-3997 and slow-release auxiliary material is 1: 0.15-10;
Described slow-release auxiliary material is: insoluble material, bioerodable section bar material, hydrophilic gel material.
5, the sustained release pharmaceutical composition of treatment anxiety neurosis according to claim 4 is characterized in that: it contains the SM-3997 of following weight proportioning and the medicament that slow-release auxiliary material is prepared from:
The proportioning of SM-3997 and slow-release auxiliary material is 1: 0.15-4;
Described slow-release auxiliary material is a hydrophilic gel material, comprises natural gum class, cellulose derivative class.
6, according to the sustained release pharmaceutical composition of claim 4 or 5 described treatment anxiety neurosis, it is characterized in that: described adjuvant also contains adhesive, filler, lubricant, fluidizer, coloring agent, and its weight proportion is:
1 part of SM-3997
Slow-release auxiliary material 0.15-10 part
Adhesive 0-5 part
Filler 0-25 part
Lubricant 0-2 part
Fluidizer 0-2 part
Coloring agent 0-2 part.
7, the sustained release pharmaceutical composition of treatment anxiety neurosis according to claim 6 is characterized in that: it is the medicament that is prepared from by following weight proportion raw material and adjuvant:
1 part of SM-3997
Slow-release auxiliary material 0.15-4 part
Adhesive 0-5 part
Filler 0-25 part
Lubricant 0-2 part
Fluidizer 0-2 part
Coloring agent 0-2 part.
8, according to the sustained release pharmaceutical composition of each described treatment anxiety neurosis of claim 4-7, it is characterized in that: described natural gum class be sodium alginate, agar, tragcanth one or more; Described cellulose derivative class is one or more in methylcellulose, hydroxy methocel, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose HPMC, carboxymethyl cellulose, carboxyethyl cellulose, the microcrystalline Cellulose.
9, the sustained release pharmaceutical composition of treatment anxiety neurosis according to claim 8, it is characterized in that: described cellulose derivative is a hydroxypropyl emthylcellulose, comprises among HPMC A4M, HPMC K4M, HPMC E4M, HPMCK15M, HPMC K50M, the HPMC K100M one or more.
10, according to the sustained release pharmaceutical composition of each described treatment anxiety neurosis of claim 1-9, it is characterized in that: described medicament is: tablet, capsule, granule, pill, suppository, soft capsule, oral liquid, suspensoid, injection.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344519A (en) * | 2015-07-17 | 2017-01-25 | 四川科瑞德制药股份有限公司 | Tandospirone enteric-coated mini-pill, and preparation method and application thereof |
| CN106619481A (en) * | 2015-10-30 | 2017-05-10 | 四川科瑞德制药股份有限公司 | Long-acting 5-HT1A receptor stimulant and preparation method thereof |
| 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 |
| CN113440491A (en) * | 2021-08-17 | 2021-09-28 | 江苏百奥信康医药科技有限公司 | Tandospirone controlled-release orally disintegrating tablet and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001246861A1 (en) * | 2000-04-10 | 2001-10-23 | Sumitomo Pharmaceuticals Co. Ltd. | Sustained release preparations |
-
2006
- 2006-07-19 CN CN2006100214190A patent/CN1899287B/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344519A (en) * | 2015-07-17 | 2017-01-25 | 四川科瑞德制药股份有限公司 | Tandospirone enteric-coated mini-pill, and preparation method and application thereof |
| CN106619481A (en) * | 2015-10-30 | 2017-05-10 | 四川科瑞德制药股份有限公司 | Long-acting 5-HT1A receptor stimulant and preparation method thereof |
| CN106619481B (en) * | 2015-10-30 | 2021-07-13 | 四川科瑞德制药股份有限公司 | Long-acting 5-HT1A receptor agonist and preparation method thereof |
| 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 |
| CN113440491A (en) * | 2021-08-17 | 2021-09-28 | 江苏百奥信康医药科技有限公司 | Tandospirone controlled-release orally disintegrating tablet and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1899287B (en) | 2010-09-29 |
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