CN106491558A - Acotiamide hydrochloride hydrate film controlling type slow releasing preparation and preparation method thereof - Google Patents
Acotiamide hydrochloride hydrate film controlling type slow releasing preparation and preparation method thereof Download PDFInfo
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- CN106491558A CN106491558A CN201611125204.3A CN201611125204A CN106491558A CN 106491558 A CN106491558 A CN 106491558A CN 201611125204 A CN201611125204 A CN 201611125204A CN 106491558 A CN106491558 A CN 106491558A
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- Prior art keywords
- hydrochloride hydrate
- acotiamide hydrochloride
- preparation
- slow releasing
- controlling type
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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Abstract
The invention provides a kind of acotiamide hydrochloride hydrate film controlling type slow releasing preparation and preparation method thereof, acotiamide hydrochloride hydrate intermediate is prepared using solid dispersion technology, it is coated using slow-release material again and makes film controlling type slow releasing preparation, the slow releasing preparation has good slow release effect.
Description
Technical field
The invention belongs to chemicals medicine technical field, and in particular to a kind of acotiamide hydrochloride hydrate film controlling type slow releasing preparation and its
Preparation method.
Background technology
Functional dyspepsia referred to from gastroduodenal region, with post-prandial fullness discomfort, early satiety, epigastrium pain or
Epigastrium burn feeling is one group of clinical syndrome of main performance, function of dominant gastrointestinal disease category.The disease is clinically common
Disease and frequently-occurring disease, proportion highest in gastropathy, the course of disease are long, easily repeatedly.Foreign Epidemic disease is learned research and is shown：Functional digestive
Bad prevalence between 20% ~ 40%, account for Gastroenterology Clinic with indigestion symptom clients in China 25% ~ 40%, and
Its sickness rate is in rising trend in China, and therefore functional dyspepsia is always the study hotspot in disease for digest field.
Hydrochloric acid Ah impersonates amine piece, English name or latin name：Acofide (Acotiamide Hydrochloride
Hydrate Tablets)；CAS：403651-06-9；Chinese chemical name：N-【2-（Isopropylamino）Ethyl】-2-（2- hydroxyl -4,
5- dimethoxybenzoyl amino）Thiazole -4-carboxamide hydrochlorate trihydrate.Its structural formula：C21H30N4O5S·HCl·
3H2O；Molecular weight：541.06.By day intrinsic safety Si Telaisi, drugmaker is developed with Ze Li new drugs K.K. Union, in 2013
On June 6, in takes the lead in Japan's listing.Listing dosage form is conventional tablet, specification 100mg/ piece, and the indication of approval is：After the meal
Feeling of repletion, functional dyspepsia, epigastrium are glutted, early satiety.
It is global first functional dyspepsia medicine for treatment that hydrochloric acid Ah impersonates amine piece, mainly by suppressing acetyl gallbladder
Alkali esterase works, and can promote gastric motility, improves stomach receiving obstacle, strengthens the expansion of stomach bottom.Pharmacokinetic shows, orally
Acotiamide hydrochloride hydrate piece needs to be administered three times a day to maintain effective blood drug concentration.Therefore, existing acotiamide hydrochloride hydrate preparation
Usage and dosage for a day three times, each 100mg is bfore meals.Patient needs frequently to take medicine, and needs control in taking medicine before meal
With, it is very easy to forget, compliance is poor.And drug design is prepared into slow releasing preparation and can solve the problem that this problem.
Content of the invention
It is an object of the invention to provide a kind of acotiamide hydrochloride hydrate film controlling type slow releasing preparation and preparation method thereof, with good
Good slow release effect, and preparation process is simple, to equipment without particular/special requirement.
For achieving the above object, the present invention is adopted the following technical scheme that：
A kind of acotiamide hydrochloride hydrate film controlling type slow releasing preparation, by the acotiamide hydrochloride hydrate intermediate and coating constituents structure of high-dissolvability
Into；Including following raw material：Acotiamide hydrochloride hydrate 10-30wt%, lubricant 0-10wt%, adjuvant 40-90wt%.
Wherein, the acotiamide hydrochloride hydrate intermediate is dissolved in 1-2.5 times of volume ethanol with acotiamide hydrochloride hydrate, is added
The water-soluble material carrier of melting, cools down after mix homogeneously rapidly and is vacuum dried or acotiamide hydrochloride hydrate obtained in lyophilization
Solid dispersion；Acotiamide hydrochloride hydrate is 1 with the mass ratio of water-soluble material carrier:0.5-3.
The water-soluble material carrier be Myrj 45, the one kind or its mixture in Polyethylene Glycol.
Another object of the present invention is to a kind of method for preparing above-mentioned acotiamide hydrochloride hydrate film controlling type slow releasing preparation is provided,
Its pastille label, load medicine micropill specific make step are：
（1）The preparation of pastille label：The acotiamide hydrochloride hydrate intermediate of obtained high-dissolvability is added lubricant grinding, is sieved
Mix homogeneously with adjuvant afterwards, by mixing after powder through soft material processed, granulation, drying, sieve, granulate, tabletting are made containing tablet
Core, is coated with coating material；
（2）Carry the preparation of medicine micropill：The acotiamide hydrochloride hydrate intermediate of obtained high-dissolvability is added lubricant grinding, is sieved
Mix homogeneously with adjuvant afterwards, by mixing after powder soft material after using extrusion spheronization method prepare carry medicine micropill, use coating material
It is coated.
Wherein, the coating material is ethyl cellulose and its aqueous dispersion, accounts for the 0.1% ~ 20% of coating solution gross weight；Used
Coating solvent is one or more in acetone, ethanol, isopropanol, dichloromethane or chloroform.
The present invention compared with prior art, with advantages below：Insoluble drug is prepared into slow releasing preparation and is often difficult to
Discharged in expeced time completely, therefore this product improves dissolubility and the dissolution of acotiamide hydrochloride hydrate first by solid dispersion technology
Degree, then slow releasing preparation is prepared into, can guarantee that medicine discharges within the scheduled time and meet the requirements.
Description of the drawings
Fig. 1 acotiamide hydrochloride hydrate slow releasing preparation In-vitro release curves.
Specific embodiment
Embodiment one：
A kind of acotiamide hydrochloride hydrate film controlling type slow releasing preparation, by the acotiamide hydrochloride hydrate intermediate and coating constituents structure of high-dissolvability
Into；Including following raw material：
Table 1 prepares the formula of 1000 pastille labels
Its preparation technology is：
（1）The preparation of the acotiamide hydrochloride hydrate intermediate of high-dissolvability：Acotiamide hydrochloride hydrate is dissolved in 2.5 times of volume ethanols molten
In liquid, the Myrj 45 melted in 60 ~ 70 DEG C of water-baths, mixing and stirring is added to be placed in 40 DEG C of vacuum drying ovens
24h is inside dried；
（2）The preparation of pastille label：Take out step（1）The acotiamide hydrochloride hydrate intermediate of gained high-dissolvability, adds recipe quantity
Micropowder silica gel is ground（Micropowder silica gel is used as lubricant, it is possible to reduce loss of the solid dispersion in process of lapping）, cross 80 mesh
After sieve, mix homogeneously with Lactose, add 2% hypromellose aqueous solution appropriate, soft material processed, granulation are dried, sieved, granulate,
Add magnesium stearate mix homogeneously, tabletting.It is coated with above-mentioned coating material, its release is controlled by gain in weight.
Embodiment two：
A kind of acotiamide hydrochloride hydrate film controlling type slow releasing preparation, by the acotiamide hydrochloride hydrate intermediate and coating constituents structure of high-dissolvability
Into；Including following raw material：
Table 2 prepares the formula of 1000 load medicine micropills
Its preparation technology is：
（1）The preparation of the acotiamide hydrochloride hydrate intermediate of high-dissolvability：Acotiamide hydrochloride hydrate is dissolved in 1.5 times of volume ethanols molten
In liquid, the Polyethylene Glycol melted in 60 ~ 70 DEG C of water-baths, mixing and stirring is added to be placed in 40 DEG C of vacuum drying ovens and dry
24h；
（2）Carry the preparation of medicine micropill：Take out step（1）The acotiamide hydrochloride hydrate intermediate of gained high-dissolvability, adds recipe quantity
Micropowder silica gel is ground, and after crossing 80 mesh sieves, and Lactose, Microcrystalline Cellulose are progressively increased method mix homogeneously using equivalent, add 2% hydroxypropyl first
Appropriate cellulose aqueous solution, soft material processed, extrusion spheronization method are prepared and carry medicine micropill.It is coated with above-mentioned coating material, by increasing
Weight control its release.Slow-release micro-pill is obtained final product, capsule is directly loadable into.
Embodiment three：
A kind of acotiamide hydrochloride hydrate film controlling type slow releasing preparation, by the acotiamide hydrochloride hydrate intermediate and coating constituents structure of high-dissolvability
Into；Including following raw material：
Table 3 prepares the formula of 1000 load medicine micropills
Its preparation technology is：
Add binding agent appropriate Microcrystalline Cellulose, soft material processed, using extrusion spheronization method, prepares celphere（Or directly adopt
Commercially available celphere）；Acotiamide hydrochloride hydrate is dissolved in the ethanol solution of 1 times of volume, treats Polyethylene Glycol in 60 ~ 70 DEG C of water
After melting is heated in bath, mixes, stir, add and stir in 2% hypromellose aqueous solution, using fluid bed
Medicinal liquid is sprayed on celphere surface by coating method, is prepared and is carried medicine micropill；After drying, then it is coated with above-mentioned coating material, is led to
Cross gain in weight and control its release.Slow-release micro-pill is obtained final product, capsule is directly loadable into.
Comparative example：
A kind of regular hydrochloric acid Acotiamide preparation, its composition are as follows：
Table 4 prepares the formula of 1000 acotiamide hydrochloride hydrates
Its preparation technology is：
After by acotiamide hydrochloride hydrate micropowder, and Lactose, Microcrystalline Cellulose are progressively increased method mix homogeneously using equivalent, add 2% hydroxypropyl
Methylcellulose aqueous solution is appropriate, soft material processed, and extrusion spheronization method is prepared and carries medicine micropill.It is coated with above-mentioned coating material, is passed through
Gain in weight controls its release.Slow-release micro-pill is obtained final product, capsule is directly loadable into.
Drug release determination：
According to《Chinese Pharmacopoeia》2010 editions two the first methods of annex XC are determined, and take acotiamide hydrochloride hydrate slow releasing capsule, with 0.1mol/
L hydrochloric acid solutions 900ml is dissolution medium, and rotating speed is 75r/min, respectively at 1,2,4,6,8,10,12h, take solution 5ml, while
The distilled water of mutually synthermal, same volume is added, samples taken is centrifuged immediately, take supernatant measure.Take reference substance appropriate, by outer
Mark method calculates release.Its release profiles is as shown in Figure 1；Test result indicate that, the accumulative releasing degree of the present invention is higher than conventional salt
Sour Acotiamide preparation, illustrates first to contribute to carrying the acotiamide hydrochloride hydrate intermediate that acotiamide hydrochloride hydrate is prepared into high-dissolvability
Rise its dissolubility.
The foregoing is only presently preferred embodiments of the present invention, all impartial changes that is done according to scope of the present invention patent with
Modification, should all belong to the covering scope of the present invention.
Claims (5)
1. a kind of acotiamide hydrochloride hydrate film controlling type slow releasing preparation, it is characterised in that in the middle of the acotiamide hydrochloride hydrate of high-dissolvability
Body and coating constituents are constituted；Which includes following raw material：Acotiamide hydrochloride hydrate 10-30wt%, lubricant 0-10wt%, adjuvant
40-90wt%.
2. a kind of acotiamide hydrochloride hydrate film controlling type slow releasing preparation according to claim 1, it is characterised in that hydrochloric acid Ah
Examining for amine intermediate is dissolved in 1-2.5 times of volume ethanol with acotiamide hydrochloride hydrate, adds the water-soluble material carrier of melting, is mixed
Cooled down after closing uniformly rapidly and be vacuum dried or acotiamide hydrochloride hydrate solid dispersion obtained in lyophilization；Wherein hydrochloric acid Ah examining
Mass ratio for amine and water-soluble material carrier is 1:0.5-3.
3. a kind of acotiamide hydrochloride hydrate film controlling type slow releasing preparation according to claim 2, it is characterised in that the water solublity
Material support is Myrj 45, the one kind or its mixture in Polyethylene Glycol.
4. a kind of method for preparing acotiamide hydrochloride hydrate film controlling type slow releasing preparation as claimed in claim 1, it is characterised in that institute
State film controlling type slow releasing preparation be pastille label, carry medicine micropill in one kind；Its specific make step is：
(1) preparation of pastille label：The acotiamide hydrochloride hydrate intermediate of obtained high-dissolvability is added lubricant grinding, is sieved
Mix homogeneously with adjuvant afterwards, by mixing after powder through soft material processed, granulation, drying, sieve, granulate, tabletting are made containing tablet
Core, is coated with coating material；
(2) preparation of medicine micropill is carried：The acotiamide hydrochloride hydrate intermediate of obtained high-dissolvability is added lubricant grinding, is sieved
Mix homogeneously with adjuvant afterwards, by mixing after powder soft material after using extrusion spheronization method prepare carry medicine micropill, use coating material
It is coated.
5. the preparation method of a kind of acotiamide hydrochloride hydrate film controlling type slow releasing preparation according to claim 4, it is characterised in that
The coating material is ethyl cellulose and its aqueous dispersion, accounts for the 0.1%-20% of coating solution gross weight；Coating solvent used is third
One or more in ketone, ethanol, isopropanol, dichloromethane or chloroform.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611125204.3A CN106491558A (en) | 2016-12-09 | 2016-12-09 | Acotiamide hydrochloride hydrate film controlling type slow releasing preparation and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201611125204.3A CN106491558A (en) | 2016-12-09 | 2016-12-09 | Acotiamide hydrochloride hydrate film controlling type slow releasing preparation and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109999003A (en) * | 2019-05-14 | 2019-07-12 | 湖南华纳大药厂股份有限公司 | Acotiamide hydrochloride hydrate oral disintegrating tablet and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102665693A (en) * | 2009-10-27 | 2012-09-12 | 鲁平有限公司 | Solid dispersion of rifaximin |
| 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 |
| CN106511291A (en) * | 2016-09-24 | 2017-03-22 | 济南康和医药科技有限公司 | Acotiamide hydrochloride controlled release tablet and preparation method thereof |
-
2016
- 2016-12-09 CN CN201611125204.3A patent/CN106491558A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102665693A (en) * | 2009-10-27 | 2012-09-12 | 鲁平有限公司 | Solid dispersion of rifaximin |
| 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 |
| CN106511291A (en) * | 2016-09-24 | 2017-03-22 | 济南康和医药科技有限公司 | Acotiamide hydrochloride controlled release tablet and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109999003A (en) * | 2019-05-14 | 2019-07-12 | 湖南华纳大药厂股份有限公司 | Acotiamide hydrochloride hydrate oral disintegrating tablet and preparation method thereof |
| CN109999003B (en) * | 2019-05-14 | 2022-03-25 | 湖南华纳大药厂股份有限公司 | Acotiamide hydrochloride orally disintegrating tablet and preparation method thereof |
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Application publication date: 20170315 |
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