CN105412026B - Acotiamide hydrochloride hydrate piece and preparation method thereof - Google Patents
Acotiamide hydrochloride hydrate piece and preparation method thereof Download PDFInfo
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Abstract
The present invention relates to a kind of acotiamide hydrochloride hydrate pieces and preparation method thereof, the tablet includes: the acotiamide hydrochloride trihydrate of 20~60 parts by weight, the filler of 40~80 parts by weight, the disintegrating agent of 2~20 parts by weight, the adhesive of 1~8 parts by weight, the lubricant of 0.5~6 parts by weight.The present invention enables the acotiamide hydrochloride trihydrate of the indissoluble in 0.01N hydrochloric acid medium more preferably to dissolve out, improves its bioavilability and stability, reduce the excessive dependence to feed preparation process by increasing silica content in reasonable range.And the acotiamide hydrochloride hydrate tablet formulation and preparation is simple, production cost is saved, and improve formulation products quality and therapeutic effect.
Description
Technical field
The invention belongs to field of medicine preparations, specifically, the present invention relates to a kind of acotiamide hydrochloride hydrate piece and its preparations
Method.
Background technique
Acotiamide hydrochloride hydrate is trihydrate (compound shown in Formulas I), is the functional dyspepsia FD treatment of first, the whole world
Medication is developed by Japanese Ze Li new drug Co., Ltd., and in 2 months 2013 in Japan's approval listing.Satisfy suitable for postprandial
Swollen sense, functional dyspepsia FD, upper abdomen is glutted, the treatment of early satiety.
The acotiamide hydrochloride trihydrate oral tablet listed at present mainly passes through in alimentary canal and inhibits acetyl gallbladder
Alkali esterase works, and can promote WeiDongLi Capsule, improves stomach receiving obstacle, the expansion of enhancing stomach bottom.However, since Acotiamide is indissoluble
Property drug, dissolution rate is low, and the dissolution rate of drug directly affects the absorption of drug, causes bioavilability not high, influences drug
Curative effect is played, this not only causes the waste of drug but also large dose oral administration drug is easy to produce many side reactions.
The bulk pharmaceutical chemicals stage usually is being prepared, is being refined, the small crystallization of partial size is selected or raw material is being crushed, is being controlled
Granulation diameter, or by the dissolution rate of the means such as micro mist promotion formulation products, but these physical operations increase operational sequence, lead to
It often will cause the related substance of raw material to increase, crystal form, moisture etc. change, and affect product quality.
Therefore, current Acotiamide pharmaceutical preparation still has much room for improvement.
Summary of the invention
The present invention is directed to solve at least some of the technical problems in related technologies.For this purpose, of the invention
One purpose is to propose a kind of acotiamide hydrochloride hydrate piece, and prescription is advanced, and dissolution rate is high, and preparation is simple, saves
Production cost, and stable product quality.
In one aspect of the invention, the invention proposes a kind of acotiamide hydrochloride hydrate pieces.According to an embodiment of the invention,
According to parts by weight, the acotiamide hydrochloride hydrate piece includes: 20~60 parts by weight of acotiamide hydrochloride trihydrate, filler 40
~80 parts by weight, 2~20 parts by weight of disintegrating agent, 1~8 parts by weight of adhesive, 0.5~6 parts by weight of lubricant.
In one aspect of the invention, the invention proposes a kind of acotiamide hydrochloride hydrate pieces.According to an embodiment of the invention,
According to parts by weight, the acotiamide hydrochloride hydrate piece includes: 30~50 parts by weight of acotiamide hydrochloride trihydrate trihydrate,
40~60 parts by weight of filler, 2~8 parts by weight of disintegrating agent, 1~5 parts by weight of adhesive, 1~5 parts by weight of lubricant.
According to an embodiment of the invention, the filler be selected from mannitol, lactose, sucrose, starch, microcrystalline cellulose,
The combination of pregelatinized starch, sorbierite or calcium phosphate etc. and their mixture, preferably lactose and microcrystalline cellulose.
According to an embodiment of the invention, the disintegrating agent is selected from croscarmellose sodium (CCNa), low substitution hydroxyl
At least one of propyl cellulose (L-HPC), crospovidone, sodium carboxymethyl starch (CMS-Na), preferably low-substituted hydroxypropyl
Cellulose.
According to an embodiment of the invention, described adhesive can be selected from starch slurry, methylcellulose (MC), hydroxypropylcellulose
(HPC), hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (CMC-Na), polyvinylpyrrolidone (PVP), polyethylene glycol
At least one of (PEG), preferred hydroxypropylcellulose.
According to an embodiment of the invention, the lubricant can be selected from one of silica, magnesium stearate, talcum powder or
A combination thereof, preferably silica and magnesium stearate compositions.
According to a particular embodiment of the invention, the silica is preferably 0.5~5 parts by weight, most preferably 2~5 weights
Measure part.
In another aspect of this invention, the method that the present invention also proposes preparation acotiamide hydrochloride hydrate piece comprising wet process system
Grain, specific as follows:
1) it is sieved
20 mesh screens are selected, sieving removal agglomeration obtains uniform particle group, is conducive to the processes such as subsequent granulation, mixing, tabletting
Progress.
2) it mixes
Recipe quantity acotiamide hydrochloride hydrate, filler, disintegrating agent are uniformly mixed.
3) it pelletizes
The mixture that step 2) is obtained adds adhesive softwood, selects the granulation of 20 mesh screens.
4) it dries
The particle that step 3) is obtained is dried in for 50~70 DEG C, controls moisture between 3.0%~6.0%.
5) tabletting
Lubricant is added into the particle that step 4) obtains, is mixed evenly rear tabletting to obtain the final product.
In another aspect of this invention, the method that the present invention also proposes preparation acotiamide hydrochloride hydrate piece comprising powder is straight
Pressure, specific as follows:
1) it is sieved
20 mesh screens are selected, sieving removal agglomeration obtains uniform particle group, conducive to subsequent mixing, the progress of tableting process.
2) it mixes
Recipe quantity acotiamide hydrochloride hydrate, filler, disintegrating agent, mix lubricant is uniform.
3) tabletting
The mixture tabletting obtained to step 3) to get.
Compared with prior art, the present invention having the advantage that
(1) present invention has carried out prescription, the technical study of acotiamide hydrochloride hydrate piece, gained prescription not by both at home and abroad public affairs
It opens；
(2) acotiamide hydrochloride hydrate piece of the invention is low to raw materials requirement, does not need to carry out granularity control to raw material, be prepared
Technique limitation is small, can effectively reduce production cost, and ensure product quality；
(3) dosage for improving silica within the scope of supplementary product consumption is had surprisingly found that in the present invention, can dramatically increase salt
The dissolution of sour Acotiamide tablet, the acotiamide hydrochloride trihydrate beneficial effect obtained to different rotating speeds exquisiteness are deposited
The prescription of silica content is being improved with better In Vitro Dissolution stability, no slack-off phenomenon of dissolution, bioavilability is more
It is high；
(4) according to an embodiment of the invention, the present invention carries out process optimization using wet granulation, acotiamide hydrochloride hydrate is obtained
Piece preparation process, method is easy, easily controllable and stable product quality, it is easy to accomplish industrial-scale production, reduction are produced into
This.
Detailed description of the invention
Fig. 1 is that Examples 1 to 6 simulates dissolution result figure in 0.01N hydrochloric acid medium；
Fig. 2 simulates dissolution result figure in 0.01N for embodiment 7~10 and embodiment 19 in hydrochloric acid medium；
Fig. 3 simulates dissolution result figure in 0.01N for embodiment 11~14 and embodiment 20 in hydrochloric acid medium；
Fig. 4 simulates dissolution result figure in 0.01N for embodiment 15~18 and embodiment 21 in hydrochloric acid medium；
Fig. 5 simulates dissolution result figure in 0.01N for embodiment 22 and embodiment 23 in hydrochloric acid medium.
Specific embodiment
The embodiment of the present invention is described below in detail.The embodiments described below is exemplary, and is only used for explaining this hair
It is bright, and be not considered as limiting the invention.Particular technique or condition are not specified in embodiment, according to text in the art
It offers described technology or conditions or is carried out according to product description.Reagents or instruments used without specified manufacturer,
For can be with conventional products that are commercially available.
Because dosage should not be too many in prescription for silica, at present in view of the country without unified standard, we are in prescription
It is investigated with being no more than 5 parts by weight.
Conventional method
(1) preparation of acotiamide hydrochloride hydrate piece
Wet granule compression tablet:
1) it is sieved
20 mesh screens are selected, sieving removal agglomeration obtains uniform particle group, is conducive to the processes such as subsequent granulation, mixing, tabletting
Progress.
2) it mixes
Recipe quantity acotiamide hydrochloride hydrate, filler, disintegrating agent are uniformly mixed.
3) it pelletizes
The mixture that step 2) is obtained adds adhesive softwood, selects the granulation of 20 mesh screens.
4) it dries
The particle that step 3) is obtained is dried in for 50~70 DEG C, controls moisture between 3.0%-6.0%.
5) tabletting
Lubricant is added into the particle that step 4) obtains, is mixed evenly rear tabletting to obtain the final product.
Direct powder compression:
In another aspect of this invention, the method that the present invention also proposes preparation acotiamide hydrochloride hydrate piece comprising powder is straight
Pressure, specific as follows:
1) it is sieved
Select 20 mesh screens, sieving removal agglomeration obtains uniform particle group, conducive to the processes such as subsequent mixing, tabletting into
Row.
2) it mixes
Recipe quantity acotiamide hydrochloride hydrate, filler, disintegrating agent, mix lubricant is uniform.
3) tabletting
The mixture tabletting obtained to step 3) to get.
(2) measuring method of acotiamide hydrochloride hydrate tablet dissolution
Dissolution determination condition: 37 DEG C, dissolution medium is 0.01N hydrochloric acid, and the second method is paddle method,
Sample time is 5,10,20,30,45,60min, and with membrane filtration, subsequent filtrate is diluted 5 times by reject primary filtrate,
Using ultraviolet spectrophotometry test sample, Detection wavelength 280nm.
(3) content of HPLC method measurement acotiamide hydrochloride hydrate piece and related substance
Instrument: Agilent1100 high performance liquid chromatograph, 1100 UV detector
Chromatographic column: octadecylsilane chemically bonded silica is the chromatographic column of filler；
Mobile phase: phosphate-acetonitrile buffer solution
Dilution: acetonitrile: water=30:70 (v/v)
Reference substance solution: precision weighs hydrochloric Acotiamide trihydrate reference substance about 20mg, accurately weighed, sets
In 100ml measuring bottle, with dilution ultrasonic dissolution and it is diluted to scale, is shaken up.It is parallel to prepare two parts.
Test solution: Acotiamide piece is finely ground, and precision weighs about 20mg powder, sets in 100ml measuring bottle, uses dilution
Ultrasonic dissolution is simultaneously diluted to scale, shakes up.It is parallel to prepare two parts.
The specific embodiment of the invention patent is as follows:
Lot number 1: pass through the acotiamide hydrochloride trihydrate raw material obtained compared with slow-speed of revolution method for refining；
Lot number 2: the acotiamide hydrochloride trihydrate raw material obtained by moderate revolving speed method for refining；
Lot number 3: the acotiamide hydrochloride trihydrate raw material obtained by higher rotation speed method for refining.
1~embodiment of embodiment 6 investigates silica to acotiamide hydrochloride trihydrate made from Different Preparation
The influence of raw material dissolution:
Embodiment 1
1 acotiamide hydrochloride trihydrate raw material 100mg of lot number
Silica 0mg
Embodiment 2
1 acotiamide hydrochloride trihydrate raw material 100mg of lot number
Silica 5mg
Embodiment 3
2 acotiamide hydrochloride trihydrate raw material 100mg of lot number
Silica 0mg
Embodiment 4
2 acotiamide hydrochloride trihydrate raw material 100mg of lot number
Silica 5mg
Embodiment 5
3 acotiamide hydrochloride trihydrate raw material 100mg of lot number
Silica 0mg
Embodiment 6
3 acotiamide hydrochloride trihydrate raw material 100mg of lot number
Silica 5mg
The prescription of 1~embodiment of embodiment 6 is subjected to dissolution test, in 5,10,20,30,45,60min sampling, filtering,
Reject primary filtrate, by ultra-violet analysis after sample is diluted 5 times, the results are shown in Table 1 for simulation dissolution:
1 1~embodiment of embodiment 6 of table simulation dissolution result
As a result: the experimental results showed that silica can increase the dissolution of the acotiamide hydrochloride trihydrate of different batches,
It is in particular in 60min, the simulation dissolution of the raw material of lot number 1 is only 69%, and 5% silica is added, the amount of dissolution
Rise to 95%；The simulation dissolution of the raw material of lot number 2 is only 75%, and 5% silica is added, and the amount of dissolution rises to
98%；The simulation dissolution of the raw material of lot number 3 is only 78%, and 5% silica is added, and the amount of dissolution rises to 100%.
The investigation of 7~embodiment of embodiment 10 uses the acotiamide hydrochloride trihydrate of lot number 1 for raw material, using wet process system
Grain carries out different prescription proportion preparation acotiamide hydrochloride hydrate pieces:
Embodiment 7
Embodiment 8
Embodiment 9
Embodiment 10
The investigation of 11~embodiment of embodiment 14 uses the acotiamide hydrochloride trihydrate of lot number 2 for raw material, using wet process
Granulation carries out different prescription proportion preparation acotiamide hydrochloride hydrate pieces:
Embodiment 11
Embodiment 12
Embodiment 13
Embodiment 14
The investigation of 15~embodiment of embodiment 18 uses the acotiamide hydrochloride trihydrate of lot number 3 for raw material, using wet process
Granulation carries out different prescription proportion preparation acotiamide hydrochloride hydrate pieces:
Embodiment 15
Embodiment 16
Embodiment 17
Embodiment 18
The investigation of 19~embodiment of embodiment 21 uses the acotiamide hydrochloride trihydrate of 3 lot numbers for raw material, and use is wet
Legal system grain carries out different filler proportion preparation acotiamide hydrochloride hydrate pieces:
Embodiment 19
Embodiment 20
Embodiment 21
Embodiment 22 and 23 investigation uses the acotiamide hydrochloride trihydrate of lot number 1 for raw material, using powder vertical compression into
The different prescription proportion preparation acotiamide hydrochloride hydrate pieces of row:
Embodiment 22
Embodiment 23
Acotiamide hydrochloride hydrate tablet dissolution investigates test:
It is formulated according to provided by embodiment 7~21 and makes 1000 respectively, taken 6 in each embodiment: existing respectively
5min, 10min, 20min, 30min, 45min, 60min sampling and testing correspond to the dissolution rate of acotiamide hydrochloride hydrate piece, calculate 6
Average value, as a result as shown in the table:
2 7~embodiment of embodiment 21 of table accumulates dissolution results
Acotiamide hydrochloride hydrate tablet stability investigates test:
Choosing the different prescriptions of lot number 1~3 and matching acotiamide hydrochloride hydrate piece obtained is investigation object, is existed according to silica
Sample spot is arranged in dosage endpoint value in prescription, carries out stability test.
Sample: by embodiment 7, embodiment 10, embodiment 11, embodiment 14, embodiment 15, embodiment 18, embodiment 22,
Acotiamide hydrochloride hydrate piece obtained by embodiment 23.
24 hot test of embodiment
Sample is taken, is placed in the thermostatic drying chamber that temperature is 60 DEG C and places 10 days, sampled respectively at 10 days, to character, contain
The investigations project such as amount, related substance, dissolution rate is measured, and the results are shown in Table 3.
3 high temperature influence factor test result of table
As a result: compared with Example 7, embodiment 14 is compared with embodiment 11, embodiment 18 and embodiment 15 for embodiment 10
It compares, embodiment 23, as can be seen that improving silica content, can improve prescription dissolution rate, simultaneously compared with embodiment 22
Prescription stability under the high temperature conditions is not influenced.
25 high humidity test of embodiment
Sample is taken, is placed in 25 DEG C, humidity is placed 10 days under conditions of being 92.5%, was sampled respectively at 10 days, to character, is contained
The investigations project such as amount, related substance, dissolution rate is measured, and the results are shown in Table 4.
4 high humidity influence factor test result of table
As a result: compared with Example 7, embodiment 14 is compared with embodiment 11, embodiment 18 and embodiment 15 for embodiment 10
It compares, embodiment 23, as can be seen that improving silica content, can improve prescription dissolution rate, simultaneously compared with embodiment 22
Prescription stability under conditions of high humidity is not influenced.
26 exposure experiments to light of embodiment
Sample is taken, illumination 10 days under 4500LX are placed in, was sampled respectively at 10 days, to character, content, related substance, dissolution
The investigations projects such as degree are measured, and the results are shown in Table 5.
5 illumination effect factor result of table
As a result: compared with Example 7, embodiment 14 is compared with embodiment 11, embodiment 18 and embodiment 15 for embodiment 10
It compares, embodiment 23, as can be seen that improving silica content, can improve prescription dissolution rate compared with embodiment 22.In light
According under the conditions of, the tablet in embodiment turns yellow, but related substance does not increase, still good in illumination condition stability inferior.
27 accelerated test of embodiment
Take this product (by embodiment 7, embodiment 10, by obtained by embodiment 11, embodiment 14, embodiment 15, embodiment 18
Tablet), placed 6 months under conditions of temperature is 40 ± 2 DEG C, relative humidity is 75 ± 5%, in 0,1,2,3,6 the end of month point
It does not sample, is measured to character, dissolution rate, in relation to the investigations project such as substance and labelled amount, the results are shown in Table 6.
6 accelerated test result of table
Test result shows that this product is placed 6 months under the conditions of temperature is 40 ± 2 DEG C, relative humidity is 75 ± 5%, point
It is not sampled in the stipulated time, observation character, measurement moisture, content, accumulation dissolution rate etc., without significant change in accelerator,
In accelerator, Silica Example (embodiment 10, embodiment 14, embodiment 18, embodiment 23) is added and relatively compares in fact
Example (embodiment 7, embodiment 11, embodiment 15, embodiment 22) is applied compared to still keeping better dissolution rate.With comparative example
(embodiment 7, embodiment 11, embodiment 15, embodiment 22) related substance compares, and variation tendency is same in accelerator is not added two
The prescription (embodiment 7, embodiment 11, embodiment 15, embodiment 22) of silica.Illustrate that the present invention not only can increase dissolution rate
And efficiency, it has good stability simultaneously.
Influence of 28 acotiamide hydrochloride hydrate of embodiment to rat gastric emptying
Experimental program: water is can't help in healthy male Wistar rat fasting 24 hours.
Rat takes in 1.5g test food in 10min, is divided into 7 groups, every group 6.It is molten that isodose is given respectively
Coal gives the Acotiamide or Acotiamide and silica mixture of Examples 1 to 6, then rat is placed in iron cage and puts
It 60min clock is set, 60 minutes under etherization, is immediately disconnected out stomach, and gastric content is recycled to and is pre-dried and weighs
It permeates in cup.The amount for remaining gastric content under one's belt is that dry gastric content subtracts the weight for permeating cup with the total weight for permeating cup
It measures to obtain the final product.It is calculated by formula: gastric emptying (%)=[1- (weight/intake of dried object)] × 100.Gastric emptying result in following table
For the average value of place group.
7 Acotiamide of table increases stomach discharge rate result
Remarks: tablet is not suitable for rat administration, thus only selection example 1~6 is tested.
Test result shows compared with vehicle control group, acotiamide hydrochloride hydrate can obviously increase be strapped in it is big in cage
The gastric content emptying ability of mouse；(implement when adding with silica group (embodiment 2,4,6) and the corresponding silica group that is not added
Example 1,3,5) compare, it is stronger to increase gastric emptying ability.
In the description of the present invention, it is to be understood that, term " first ", " second " are used for description purposes only, and cannot
It is interpreted as indication or suggestion relative importance or implicitly indicates the quantity of indicated technical characteristic.Define as a result, " the
One ", the feature of " second " can explicitly or implicitly include one or more of the features.In the description of the present invention,
The meaning of " plurality " is two or more, unless otherwise specifically defined.
In the description of this specification, reference term " one embodiment ", " some embodiments ", " example ", " specifically show
The description of example " or " some examples " etc. means specific features, structure, material or spy described in conjunction with this embodiment or example
Point is included at least one embodiment or example of the invention.In the present specification, schematic expression of the above terms are not
It must be directed to identical embodiment or example.Moreover, particular features, structures, materials, or characteristics described can be in office
It can be combined in any suitable manner in one or more embodiment or examples.In addition, without conflicting with each other, the skill of this field
Art personnel can tie the feature of different embodiments or examples described in this specification and different embodiments or examples
It closes and combines.
Although the embodiments of the present invention has been shown and described above, it is to be understood that above-described embodiment is example
Property, it is not considered as limiting the invention, those skilled in the art within the scope of the invention can be to above-mentioned
Embodiment is changed, modifies, replacement and variant.
Claims (11)
1. a kind of acotiamide hydrochloride hydrate piece characterized by comprising
The acotiamide hydrochloride trihydrate of 20~60 parts by weight,
The filler of 40~80 parts by weight,
The disintegrating agent of 2~20 parts by weight,
The adhesive of 1~8 parts by weight,
The silica of 2~5 parts by weight.
2. acotiamide hydrochloride hydrate piece according to claim 1 characterized by comprising
The acotiamide hydrochloride trihydrate of 30~50 parts by weight,
The filler of 40~60 parts by weight,
The disintegrating agent of 2~8 parts by weight,
The adhesive of 1~5 parts by weight,
The silica of 2~5 parts by weight.
3. acotiamide hydrochloride hydrate piece according to claim 1, which is characterized in that the filler is selected from lactose, sweet dew
At least one of alcohol, microcrystalline cellulose and starch.
4. acotiamide hydrochloride hydrate piece according to claim 3, which is characterized in that the filler is lactose and microcrystalline cellulose
The combination of element.
5. acotiamide hydrochloride hydrate piece according to claim 1, which is characterized in that the disintegrating agent is selected from cross-linked carboxymethyl
At least one of sodium cellulosate, low-substituted hydroxypropyl cellulose, crospovidone and sodium carboxymethyl starch.
6. acotiamide hydrochloride hydrate piece according to claim 5, which is characterized in that the disintegrating agent is low-substituted hydroxypropyl fiber
Element.
7. acotiamide hydrochloride hydrate piece according to claim 1, which is characterized in that described adhesive is selected from starch slurry, first
In base cellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone and polyethylene glycol
It is at least one.
8. acotiamide hydrochloride hydrate piece according to claim 7, which is characterized in that described adhesive is hydroxypropylcellulose.
9. a kind of method for preparing the described in any item acotiamide hydrochloride hydrate pieces of claim 1-8, comprising:
1) it is sieved:
Acotiamide hydrochloride trihydrate, filler, disintegrating agent, adhesive and silica were subjected to 20 meshes respectively, with
Just removal agglomeration；
2) it mixes:
The acotiamide hydrochloride trihydrate of recipe quantity, filler and disintegrating agent are uniformly mixed；
3) it pelletizes:
The softwood processed after the adhesive of addition recipe quantity into the mixture being prepared in step 2), and select 20 mesh screen systems
Grain；
4) it dries:
Particle obtained in step 3) is dried at 50~70 DEG C and obtains dry particle, the water content of the dry particle is
3.0%~6.0 weight %；
5) tabletting:
The silica of recipe quantity is added into the dry particle obtained in step 4), is mixed evenly rear tabletting up to described
Acotiamide hydrochloride hydrate piece.
10. a kind of method for preparing the described in any item acotiamide hydrochloride hydrate pieces of claim 1-8, comprising:
1) it is sieved:
20 mesh screens are selected, sieving removal agglomeration obtains uniform particle group, conducive to subsequent mixing, the progress of tableting process；
2) it mixes:
Recipe quantity acotiamide hydrochloride hydrate, filler, disintegrating agent, silica are uniformly mixed；
3) tabletting:
The mixture tabletting obtained to step 3) to get.
11. the purposes of the described in any item acotiamide hydrochloride hydrate pieces of claim 1-8 in medicine preparation, the drug is for promoting
Into WeiDongLi Capsule, improve stomach receiving obstacle, the expansion of enhancing stomach bottom, increase stomach discharge.
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| CN107228909B (en) * | 2016-03-24 | 2021-05-28 | 中美华世通生物医药科技(武汉)股份有限公司 | Method for measuring acotiamide hydrochloride raw material medicine and related substances in preparation thereof by using HPLC |
| CN106074407A (en) * | 2016-06-12 | 2016-11-09 | 佛山市腾瑞医药科技有限公司 | A kind of acotiamide hydrochloride hydrate dispersible tablet and preparation method thereof |
| CN105919967A (en) * | 2016-06-12 | 2016-09-07 | 佛山市腾瑞医药科技有限公司 | Acotiamide hydrochloride preparation and application thereof |
| CN106918659A (en) * | 2017-01-22 | 2017-07-04 | 合肥拓锐生物科技有限公司 | About the analysis method of material in a kind of acotiamide hydrochloride hydrate raw material and its preparation |
| CN110384670A (en) * | 2018-04-17 | 2019-10-29 | 北京泰德制药股份有限公司 | A kind of composition and preparation method thereof containing acotiamide hydrochloride hydrate |
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|---|---|---|---|---|
| CN103387552A (en) * | 2012-05-10 | 2013-11-13 | 上海医药工业研究院 | Method for preparing acotiamide hydrochloride |
| CN103610657A (en) * | 2013-11-20 | 2014-03-05 | 北京康立生医药技术开发有限公司 | Acotiamide sustained-release preparation |
| CN103622929A (en) * | 2013-12-05 | 2014-03-12 | 安徽省先锋制药有限公司 | Acotiamide hydrochloride sustained release tablet and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103387552A (en) * | 2012-05-10 | 2013-11-13 | 上海医药工业研究院 | Method for preparing acotiamide hydrochloride |
| CN103610657A (en) * | 2013-11-20 | 2014-03-05 | 北京康立生医药技术开发有限公司 | Acotiamide sustained-release preparation |
| CN103622929A (en) * | 2013-12-05 | 2014-03-12 | 安徽省先锋制药有限公司 | Acotiamide hydrochloride sustained release tablet and preparation method thereof |
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