CN1823805A - Ground erythromycin enteric micropill and its preparation method - Google Patents
Ground erythromycin enteric micropill and its preparation method Download PDFInfo
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- CN1823805A CN1823805A CN 200510136661 CN200510136661A CN1823805A CN 1823805 A CN1823805 A CN 1823805A CN 200510136661 CN200510136661 CN 200510136661 CN 200510136661 A CN200510136661 A CN 200510136661A CN 1823805 A CN1823805 A CN 1823805A
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- micropill
- dirithromycin
- lauryl sulphate
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Abstract
An enteric micropill of dirithromycin is composed of a micropill prepared from dirithromycin and one or more medicinal excipients, an isolating layer prepared from hydroxypropylmethyl cellulose and medicinal excipient, and an enteric layer prepared from one or more medicinal excipients. Its preparing process is also disclosed.
Description
Technical field
The invention belongs to the Western medicine invention field, relate to good enteric coated preparation of antibiotic dirithromycin in a kind of macrolide and preparation method thereof.
Background technology
Dirithromycin is taken the lead in succeeding in developing by the Thomae company of subsidiary of German Boehinger Ingelheim company, it is the derivant of erythromycin, belong to macrolide antibiotics, be applicable to that the age is more than 12 years old, by the patient of the microbial various infection of sensitivity, because its good curative effect and remarkable safety quite are subjected to various countries clinician and patient's favor.
Dirithromycin is very responsive to acid medium, and is promptly destroyed in very short time in gastric juice, resolves into red mould cyclammonium.Though red mould cyclammonium has antibacterial activity, oral absorption is poor, and bioavailability is low.Side by side erythromycin and red mould cyclammonium easily stimulate stomach, cause gastrointestinal reaction, and in the intestinal juice alkaline environment, dirithromycin is comparatively stablized and easily is absorbed, and company has developed the dirithromycin enteric coatel tablets and gone on the market still.Because the dirithromycin enteric coatel tablets are made by conventional tablet bag film-coat, very easily broken by the teeth when taking and lose enteric solubility, and may appear at when discharging in the intestinal shortcoming such as local excessive concentration by patient.Still company on former basis an enterprising step carry out the improvement of dosage form.The dirithromycin enteric coated micropill that the present invention mentions has overcome above-mentioned deficiency, is a kind of novel good enteric coated preparation of dirithromycin.
Summary of the invention
Purpose of the present invention aims to provide a kind of absorption and not influenced by gastric emptying, and release is even, the bioavailability height, and zest is little, favorable reproducibility dirithromycin enteric coated micropill.
The present invention aims to provide good preparation of a kind of dirithromycin and preparation method thereof, to solve the problems of the technologies described above.It is the dirithromycin enteric coated micropill.
The objective of the invention is to realize by following manner:
Micropill of the present invention comprises the pastille micropill be made up of dirithromycin and one or more pharmaceutically useful excipient, the sealing coat of being made up of hydroxypropyl methylcellulose and other pharmaceutically useful excipient and the enteric layer of being made up of one or more pharmaceutically useful excipient.
Described pastille micropill also can be made by celphere and dirithromycin and one or more pharmaceutically acceptable excipient of being deposited on this celphere.
The excipient that the pastille micropill is adopted is one or more in sodium lauryl sulphate, hydroxypropyl methylcellulose, carboxymethyl starch sodium, polyvidone, microcrystalline Cellulose, starch, carboxymethyl starch sodium, L-arginine, nonreducing sugar such as the sucrose; Described sealing coat contains one or more in Pulvis Talci, magnesium stearate, crosslinked ketopyrrolidine, hydroxypropyl methylcellulose, sodium lauryl sulphate, non-reducing sugar such as the sucrose; Enteric layer contain in the pharmaceutically acceptable excipient of promising crylic acid resin such as methacrylic acid copolymer aqueous dispersion, Pulvis Talci, citric acid triacetic acid, tween 80, the sodium lauryl sulphate one or more.
Contain the 20-300mg dirithromycin in the micropill of the present invention.
It is preferable to contain the 100-280mg dirithromycin in the micropill of the present invention.
Dirithromycin enteric coated micropill of the present invention, it is good containing following composition:
The pastille micropill
Celphere 60-100mg
Dirithromycin 125mg
The sodium lauryl sulphate trace
Hydroxypropyl methylcellulose 3-15mg
Carboxymethyl starch sodium 15-35mg
Sealing coat
Pastille micropill 205-270mg
The sodium lauryl sulphate trace
Hypromellose 5-15mg
Enteric layer
Sealing coat micropill 220-285mg
Methacrylic acid copolymer aqueous dispersion 180-250mg
Pulvis Talci 8-18mg
Triethyl citrate 4-9mg
Tween 80 0.05ml
Sodium lauryl sulphate 4-10g.
Described celphere contains following composition:
Microcrystalline Cellulose 60-100mg
Starch 15-50mg
Hydroxypropyl methylcellulose 5-15mg
Micropill of the present invention contains following composition for best:
The pastille micropill
Celphere 70-90mg
Dirithromycin 125mg
The sodium lauryl sulphate trace
Hydroxypropyl methylcellulose 5-12mg
Carboxymethyl starch sodium 20-30mg
Sealing coat
Pastille micropill 240-258mg
The sodium lauryl sulphate trace
Hypromellose 8-12mg
Enteric layer
Sealing coat micropill 248-270mg
Methacrylic acid copolymer aqueous dispersion 190-230mg
Pulvis Talci 10-15mg
Triethyl citrate 4-9mg
Tween 80 0.05ml
Sodium lauryl sulphate 5-9g.
The preparation method of micropill of the present invention is: A, provide the pastille micropill of being made up of dirithromycin and one or more pharmaceutically useful excipient; B, on the pastille micropill, apply the sealing coat that one deck contains one or more pharmaceutically acceptable excipient; D, on sealing coat, apply the enteric layer that one deck contains hydroxypropyl methylcellulose and one or more pharmaceutically acceptable excipient.
The untoward reaction of dirithromycin is a gastrointestinal reaction, is mainly stomachache, diarrhoea, feels sick etc., and this may be because local excitation or plasma concentration after taking medicine increase sharply caused.The present invention is prepared into enteric coated micropill with advanced preparation process with dirithromycin, then above-mentioned enteric coated micropill is filled in the common enteric coated capsule and is prepared from, can avoid occurring causing the phenomenon that local drug concentration is too high when common enteric dosage form discharges in intestinal, will have significant clinical superiority.
But this dosage form is to the manufacturing technique requirent height, and this medicine is not changed when the stomach by the patient, and can dissolve rapidly and release of active ingredients when it leaves stomach and enters small intestinal.Active component wherein is in the inside of micropill and wraps in thin film or tunicle promptly in " enteric coating ".Described enteric coating is insoluble in sour environment such as stomach, and is soluble in nearly neutral environment such as small intestinal.
Preparation of the present invention has been concentrated the advantage of pellet preparations, two kinds of dosage forms of enteric coated preparation, thereby makes the absorption of medicine not influenced by gastric emptying, and release is even, the bioavailability height, and zest is little, favorable reproducibility.
The specific embodiment
The various compositions and the layer of micropill below will be discussed respectively, and concrete simultaneously the introduction added the method that various compositions progressively make up the dirithromycin enteric coated micropill.
Pastille micropill among the present invention can directly be prepared from dirithromycin and one or more pharmaceutically useful excipient.Also another kind of mode be can adopt, dirithromycin and excipient on celphere, applied.
Preferred pastille micropill is coated on the celphere by the interlayer that will contain dirithromycin and is prepared.Described celphere is that pharmaceutical field can be bought or make by oneself.The most preferred celphere of the present invention be the starch that is used for drug manufacture, microcrystalline Cellulose and hydroxypropyl methylcellulose preparation and the ball core.Yet, the hollow ball core that can use any pharmaceutically acceptable excipient to make, described excipient comprises for example sucrose, wax, plant gum etc.Be primarily characterized in that be inert for the patient of other excipient in dirithromycin and the micropill and this micropill that will take.
The size of pastille micropill depends on the required size of micropill to be produced.Usually, micropill can be as small as 0.1mm, or greatly to 2mm.Preferred nuclear core is 0.2mm to 1.0mm, so as finally to obtain required preferred size, diameter is the micropill of about 0.5-1.5mm.
The amount of used pastille micropill depends on the weight and the thickness of the interpolation layer beyond the pastille micropill, and usually, the pastille micropill accounts for the 10-70% of product.More preferably the pastille micropill accounts for about 15-45% of product.
Preparation process of the present invention comprises three step: A of preparation of dirithromycin pastille micropill, sealing coat coated micropill and enteric coated micropill, the preparation of dirithromycin pastille micropill: with the celphere is carrier, proper auxiliary materials such as sodium lauryl sulphate are dissolved in the suitable quantity of water, the adding dirithromycin stirs to make and is uniformly dispersed, add an amount of dehydrated alcohol, stir; Hydroxypropyl methylcellulose is disperseed with an amount of ethanol, be prepared into solution or suspension with certain bonding force, even spraying is coated in hollow ball core outside, makes that micropill increases under the state of rotation that rolls, drying, forms the pastille micropill.B, the preparation of dirithromycin sealing coat micropill: hydroxypropyl methylcellulose, sodium lauryl sulphate etc. is mixed with coating solution, pastille nuclear core is carried out isolation coat.C, the preparation of dirithromycin enteric coated micropill: Pulvis Talci, triethyl citrate, tween 80 etc. are mixed with enteric coating liquid, will wrap the sealing coat micropill and carry out enteric coating.
Is " powder coating method " with dirithromycin to the method that makes things convenient for that celphere carries out coating, in the method, celphere with thick liquid or binding agent moistening, is made the medicine slurry with the dirithromycin powder of crushing screening and sparged on the celphere, then with the mixture drying.This method is used in the industrialization drug manufacture usually, and suitable device is a usual means.All used this device in many steps of the inventive method, perhaps, available fluidized bed plant or rotating plate device prepare product of the present invention.
The preparation of dirithromycin pastille micropill also can be as follows: proper auxiliary materials such as sodium lauryl sulphate, microcrystalline Cellulose, starch etc. are dissolved in the suitable quantity of water, add dirithromycin and stir to make and be uniformly dispersed, add an amount of dehydrated alcohol, stir; Hydroxypropyl methylcellulose is disperseed with an amount of ethanol, be prepared into solution or suspension with certain bonding force, granulate, sieve, the granule of getting between the 50-60 order is a parent nucleus, rest materials is suspended in the binding agent, even spraying is coated in parent nucleus outside, makes that micropill increases under the state of rotation that rolls, drying, forms the pastille micropill.
Among the present invention various excipient effectively determine it all is that the inventor passes through repeatedly to test, update and the principal agent dirithromycin suitable of the present invention that obtains, can better prepare the proper auxiliary materials of micropill of the present invention.The inventor also further obtains being fit to best proportioning of the present invention by following experiment.Below done experiment, so that determine corresponding auxiliary material of the present invention better by the inventor.
Because roundness, the friability of celphere directly influence drug of topical application effect, thereby influence the content and the quality of pastille micropill, so select suitable blank core ball material extremely important.The inventor considers the microcrystalline Cellulose stable in properties, and good moldability and chance water have expansion, do not influence the release of medicine; Starch has certain mouldability, has certain disintegrate effect concurrently; Sucrose has hygroscopicity to be easy to into granule.Therefore, the inventor drafts from these three kinds of adjuvants the material of screening preparation celphere by experiment, as binding agent, and screens preferable solvent and concentration thereof simultaneously with the fine little element of hydroxypropyl methyl.
The celphere prescription screening
Draft the screening prescription, see Table 1.
The screening prescription of table 1 celphere
Through the above result of analysis-by-synthesis, prescription four is more excellent.
After making the celphere preparation, be that other composition of pastille micropill is determined with that.The inventor considers that with the fine little element of hydroxypropyl methyl be binding agent, and screens its concentration by experiment; The disintegrate of medicine and release for the benefit of, we add the carboxymethyl starch sodium with disintegration in medicated layer, add an amount of sodium lauryl sulphate to increase the lubricity of medicine slurry, produce static when preventing to produce, and help the release of medicine.Screen medicine by experiment and starch the consumption of each component,, purpose ball yield whether bright and clean with balling-up, hardness, the surface of pastille micropill, result of extraction are index, determine the best composition and the ratio of medicine slurry.
The prescription screening of pastille micropill medicinal liquid
Draft the screening prescription, see Table 2:
The screening prescription of table 2 pastille micropill medicinal liquid
Behind the analysis-by-synthesis, found that prescription four is more excellent, and by experiment it is verified.
The inventor determines to have carried out further exploratory development to the prescription of sealing coat.
Because the dirithromycin raw material is stable under alkali condition among the present invention, extremely unstable under acid condition, enteric coating liquid is generally slant acidity, can not directly carry out enteric coatedly, therefore should wrap sealing coat earlier, wraps enteric layer again.The sealing coat of this product adopts film property hydroxypropyl emthylcellulose preferably, sealing coat weightening finish 5%, and the inventor also further screens its suitable concentration by experiment.Phenomenon, film property, yield, dissolution with the coating process of micropill are index, determine the preferred plan of sealing coat.
The screening of sealing coat coating fluid prescription
Draft the screening prescription and see Table 3:
Table 3 sealing coat coating fluid prescription screening table
Comprehensive analysis results is found the prescription three micropill sealing coat best results of wrapping, and yield reaches 98%.
Be that the inventor explores enteric layer prescription screening and research at last.
Concrete condition according to the coating process is improved, with the material state of micropill coating process, film property, 2 hours releases, yields are that index is screened in the phosphate buffer of 1 hour and pH value 6.8 in hydrochloric acid solution (9 → 1000) 900ml, to determine best prescription and technology.
The prescription screening of enteric coating liquid sees Table 4:
The prescription screening table of table 4 enteric coating liquid
5.4 enteric liquid prescription screening the results are shown in Table 5:
Table 5 enteric liquid prescription screening result
The above result of analysis-by-synthesis, gained enteric coated-pellet film property, material whitewashing state is all fine.Take the release of three prescription gained micropills in sour neutralization buffer into consideration, for guaranteeing the quality of the pharmaceutical preparations, the inventor selects to adopt prescription two to be the prescription of this preparation enteric coating coating solution, enteric layer weightening finish 35%.And by experiment it is verified that yield reaches 92%, and gained micropill release in acid is 0.45%, and release is 95.8% in buffer, and the accumulation dissolution is 96.2%, and is effective, reached Expected Results.
Embodiment 1:
125mg dirithromycin enteric-coated pellet capsule
Stock chart
The pastille micropill
Celphere 90mg (30-40 order)
Dirithromycin 125mg
The sodium lauryl sulphate trace
Hydroxypropyl methylcellulose 7.5mg
Carboxymethyl starch sodium 25mg
Sealing coat
Pastille micropill 248mg
The sodium lauryl sulphate trace
Hypromellose 12mg
Enteric layer
Sealing coat micropill 260mg
Methacrylic acid copolymer aqueous dispersion 215mg
Pulvis Talci 12mg
Triethyl citrate 6mg
Tween 80 0.05ml
Sodium lauryl sulphate 6mg.
Take by weighing hydroxypropyl methylcellulose and add absolute ethyl alcohol and stirring and make and be uniformly dispersed, add purified water and make it abundant swelling, sieve, as binding agent.The microcrystalline Cellulose pulverizing is sieved, take by weighing starch and its mix homogeneously, granulate, sieve, the granule of getting between the 50-60 order is a parent nucleus, and rest materials is suspended in the binding agent, crosses 80 mesh sieves, is sprayed on the parent nucleus, and oven dry is sieved, and is the purpose ball with 30-40 order ball core.
Sodium lauryl sulphate is dissolved in the suitable quantity of water, and the dirithromycin that adds crushing screening stirs to make and is uniformly dispersed, and adds an amount of dehydrated alcohol, stirs; In addition hypromellose is disperseed with an amount of ethanol, add carboxymethyl starch sodium and be uniformly dispersed; Above-mentioned two solution stirring are made into the homogeneous system, sieve and make the medicine slurry.Medicine slurry with the suspension sample that obtains is coated on the hollow micropill of microcrystalline Cellulose-starch then.After having applied the dirithromycin suspension of aequum, with pastille micropill drying.
Sodium lauryl sulphate is dissolved in the suitable quantity of water, its aqueous solution is joined in the alcohol dispersion liquid of hydroxypropyl methylcellulose, stirring makes the hydroxypropyl methylcellulose complete swelling to even,
Pulvis Talci, triethyl citrate, tween 80, sodium lauryl sulphate are added homogenate in the pure water successively, suspension after the homogenate is added in the methacrylic acid copolymer aqueous dispersion, stirring makes into uniform suspension, sieve, form with aqueous suspension is coated to enteric layer on the micropill of sealing coat then, behind the suspension that has applied aequum, with the micropill finish-drying.Promptly get enteric coated micropill.
Analyze the content of dirithromycin in the gained micropill, and fill it in the capsulae vacuus to obtain containing the enteric-coated pellet capsule of 125mg dirithromycin.
Embodiment 2:
125mg dirithromycin enteric-coated pellet capsule
Stock chart
The pastille micropill
Sucrose 75mg
Hydroxypropyl methylcellulose 25mg
Dirithromycin 125mg
The sodium lauryl sulphate trace
Polyvidone 5mg
Sealing coat
Pastille micropill 230mg
Magnesium stearate 10mg
Hypromellose 10mg
Enteric layer
Sealing coat micropill 250mg
No. 2 resin 15mg
Pulvis Talci 12mg
Triethyl citrate 6mg
Tween 80 0.05ml
Sucrose, polyvidone etc. is dissolved in the suitable quantity of water, and the adding dirithromycin stirs to make and is uniformly dispersed, and adds an amount of dehydrated alcohol, stirs; Hydroxypropyl methylcellulose is disperseed with an amount of ethanol, be prepared into solution or suspension with certain bonding force, granulate, sieve, the granule of getting between the 50-60 order is a parent nucleus, rest materials is suspended in the binding agent, even spraying is coated in parent nucleus outside, makes that micropill increases under the state of rotation that rolls, drying, forms the pastille micropill.
It is described then to press the foregoing description 1, respectively sealing coat and enteric layer is applied up, is prepared into micropill.
Embodiment 3:
125mg dirithromycin enteric-coated pellet capsule
Stock chart
The pastille micropill
Celphere (sucrose 80mg, hydroxypropyl methylcellulose 5mg) 30-40 order
Dirithromycin 125mg
The sodium lauryl sulphate trace
Hydroxypropyl methylcellulose 25mg
Sealing coat
Pastille micropill 235mg
Magnesium stearate 6mg
Titanium dioxide 8mg
Hypromellose 8mg
Enteric layer
Sealing coat micropill 257mg
Enteric resin 20mg
Pulvis Talci 12mg
Triethyl citrate 6mg
Embodiment 4
The pastille micropill
Microcrystalline Cellulose 80mg
Starch 25mg
Hydroxypropyl methylcellulose 12mg
Dirithromycin 125mg
The sodium lauryl sulphate trace
Hydroxypropyl methylcellulose 5mg
Carboxymethyl starch sodium 20mg
Sealing coat
Pastille micropill 267mg
The sodium lauryl sulphate trace
Hypromellose 8mg
Enteric layer
Sealing coat micropill 275mg
Methacrylic acid copolymer aqueous dispersion 190mg
Pulvis Talci 10mg
Triethyl citrate 4mg
Tween 80 0.05ml
Sodium lauryl sulphate 5mg
Embodiment 5
Celphere
Microcrystalline Cellulose 30mg
Starch 50mg
Hydroxypropyl methylcellulose 10mg
The pastille micropill
Celphere 90mg
Dirithromycin 125mg
The sodium lauryl sulphate trace
Hydroxypropyl methylcellulose 10mg
Carboxymethyl starch sodium 28mg
Sealing coat
Pastille micropill 253mg
The sodium lauryl sulphate trace
Hypromellose 12mg
Enteric layer
Sealing coat micropill 265mg
Methacrylic acid copolymer aqueous dispersion 230mg
Pulvis Talci 15mg
Triethyl citrate 9mg
Tween 80 0.05ml
Sodium lauryl sulphate 9g.
Other step is substantially with embodiment 1.
Embodiment 6
The pastille micropill
Sucrose 30mg
Starch 60mg
L-arginase 12 0mg
Dirithromycin 125mg
The sodium lauryl sulphate trace
Hydroxypropyl methylcellulose 10mg
Carboxymethyl starch sodium 25mg
Sealing coat
Pastille micropill 270mg
The sodium lauryl sulphate trace
Hypromellose 15mg
Enteric layer
Sealing coat micropill 285mg
Methacrylic acid copolymer aqueous dispersion 220mg
Pulvis Talci 15mg
Triethyl citrate 9mg
Tween 80 0.05ml
Sodium lauryl sulphate 9g.
Substantially can prepare this product by the foregoing description 1 method therefor.Gained micropill and capsule administration field method commonly used detects, and the equal quality of sample is stable.
Clinical and experimental study shows, micropill of the present invention and capsule not only have the characteristics of conventional enteric coated preparation, when also having the generic condition that micropill touches small intestinal, can discharge contained dirithromycin rapidly equably, thereby solve the too high problem of local drug concentration that general enteric dosage form is run into.
Embodiment 7
The pastille micropill
Celphere 60mg
Dirithromycin 125mg
The sodium lauryl sulphate trace
Hydroxypropyl methylcellulose 3mg
Carboxymethyl starch sodium 35mg
Sealing coat
Pastille micropill 223mg
The sodium lauryl sulphate trace
Hypromellose 5mg
Enteric layer
Sealing coat micropill 228mg
Methacrylic acid copolymer aqueous dispersion 180mg
Pulvis Talci 8mg
Triethyl citrate 4mg
Tween 80 0.05ml
Sodium lauryl sulphate 4g.
Other step is substantially with embodiment 1.
Embodiment 8
The pastille micropill
Celphere 100mg
Dirithromycin 125mg
The sodium lauryl sulphate trace
Hydroxypropyl methylcellulose 15mg
Carboxymethyl starch sodium 15mg
Sealing coat
Pastille micropill 255mg
The sodium lauryl sulphate trace
Hypromellose 15mg
Enteric layer
Sealing coat micropill 270mg
Methacrylic acid copolymer aqueous dispersion 250mg
Pulvis Talci 18mg
Triethyl citrate 9mg
Tween 80 0.05ml
Sodium lauryl sulphate 10g.
Other step is substantially with embodiment 1.
Claims (10)
1, a kind of dirithromycin enteric coated micropill, it is characterized in that it comprises the pastille micropill of being made up of dirithromycin and one or more pharmaceutically useful excipient, sealing coat of forming by hydroxypropyl methylcellulose and other pharmaceutically acceptable excipient and the enteric layer of forming by one or more pharmaceutically useful excipient.
2, dirithromycin enteric coated micropill according to claim 1 is characterized in that described pastille micropill can and be deposited on dirithromycin on this celphere and one or more pharmaceutically acceptable excipient be made by celphere.
3, dirithromycin enteric coated micropill according to claim 1 is characterized in that: the excipient that the pastille micropill is adopted is one or more in sodium lauryl sulphate, hydroxypropyl methylcellulose, carboxymethyl starch sodium, polyvidone, microcrystalline Cellulose, starch, carboxymethyl starch sodium, L-arginine, nonreducing sugar such as the sucrose; Described sealing coat contains one or more in Pulvis Talci, magnesium stearate, crosslinked ketopyrrolidine, hydroxypropyl methylcellulose, sodium lauryl sulphate, non-reducing sugar such as the sucrose; Enteric layer contain in the pharmaceutically acceptable excipient of promising crylic acid resin such as methacrylic acid copolymer aqueous dispersion, Pulvis Talci, citric acid triacetic acid, tween 80, the sodium lauryl sulphate one or more.
4, a kind of preparation that contains any described enteric dirithromycin micropill among a large amount of claim 1-3.
5, dirithromycin enteric coated micropill according to claim 4 is characterized in that containing the 20-300mg dirithromycin.
6, dirithromycin enteric coated micropill according to claim 4 is characterized in that containing the 100-280mg dirithromycin.
7, dirithromycin enteric coated micropill according to claim 4 is characterized in that containing following composition:
The pastille micropill
Celphere 60-100mg
Dirithromycin 125mg
The sodium lauryl sulphate trace
Hydroxypropyl methylcellulose 3-15mg
Carboxymethyl starch sodium 15-35mg
Sealing coat
Pastille micropill 205-270mg
The sodium lauryl sulphate trace
Hypromellose 5-15mg
Enteric layer
Sealing coat micropill 220-285mg
Methacrylic acid copolymer aqueous dispersion 180-250mg
Pulvis Talci 8-18mg
Triethyl citrate 4-9mg
Tween 80 0.05ml
Sodium lauryl sulphate 4-10g.
8, dirithromycin enteric coated micropill according to claim 7, it is characterized in that: described celphere contains following composition:
Microcrystalline Cellulose 60-100mg
Starch 15-50mg
Hydroxypropyl methylcellulose 5-15mg
9, dirithromycin enteric coated micropill according to claim 7 is characterized in that containing following composition:
The pastille micropill
Celphere 70-90mg
Dirithromycin 125mg
The sodium lauryl sulphate trace
Hydroxypropyl methylcellulose 5-12mg
Carboxymethyl starch sodium 20-30mg
Sealing coat
Pastille micropill 240-258mg
The sodium lauryl sulphate trace
Hypromellose 8-12mg
Enteric layer
Sealing coat micropill 248-270mg
Methacrylic acid copolymer aqueous dispersion 190-230mg
Pulvis Talci 10-15mg
Triethyl citrate 4-9mg
Tween 80 0.05ml
Sodium lauryl sulphate 5-9g.
10, the preparation method of the described dirithromycin enteric coated micropill of claim 1 is characterized in that step is: A, provide the pastille micropill of being made up of dirithromycin and one or more pharmaceutically useful excipient; B, on the pastille micropill, apply the sealing coat that one deck contains one or more pharmaceutically acceptable excipient; D, on sealing coat, apply the enteric layer that one deck contains hydroxypropyl methylcellulose and one or more pharmaceutically acceptable excipient.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101366618A CN100488515C (en) | 2005-12-31 | 2005-12-31 | Ground erythromycin enteric micropill and its preparation method |
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|---|---|---|---|
| CNB2005101366618A CN100488515C (en) | 2005-12-31 | 2005-12-31 | Ground erythromycin enteric micropill and its preparation method |
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| CN1823805A true CN1823805A (en) | 2006-08-30 |
| CN100488515C CN100488515C (en) | 2009-05-20 |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101502491B (en) * | 2009-03-09 | 2011-06-29 | 山东省医药工业研究所 | Dirithromycin enteric-coated formulation |
| CN102145008A (en) * | 2010-12-29 | 2011-08-10 | 山东鲁抗辰欣药业有限公司 | Dirithromycin medicinal composition and preparation method thereof |
| CN101596164B (en) * | 2008-06-06 | 2011-12-28 | 海南皇隆制药股份有限公司 | Dirithromycin enteric coatel granule and preparation method thereof |
| CN102349870A (en) * | 2011-10-18 | 2012-02-15 | 胡昌勤 | New preparation of erythrocin and relevant drug thereof and preparation method of new preparation |
| CN102846577A (en) * | 2012-09-27 | 2013-01-02 | 天津红日药业股份有限公司 | Medical composition containing erythromycin cydocarbonate |
| CN102908317A (en) * | 2011-08-01 | 2013-02-06 | 浙江丽水众益药业有限公司 | Macrolide antibiotics enteric-coated pellets and coating solution thereof |
| CN104546733A (en) * | 2013-10-21 | 2015-04-29 | 广东东阳光药业有限公司 | Benproperine taste-masking pellet |
| CN109893511A (en) * | 2017-12-11 | 2019-06-18 | 湖北舒邦药业有限公司 | A kind of Dirithromycin enteric coatel tablets enteric coating, preparation method and a kind of Dirithromycin enteric coatel tablets |
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- 2005-12-31 CN CNB2005101366618A patent/CN100488515C/en not_active Expired - Fee Related
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101596164B (en) * | 2008-06-06 | 2011-12-28 | 海南皇隆制药股份有限公司 | Dirithromycin enteric coatel granule and preparation method thereof |
| CN101502491B (en) * | 2009-03-09 | 2011-06-29 | 山东省医药工业研究所 | Dirithromycin enteric-coated formulation |
| CN102145008B (en) * | 2010-12-29 | 2013-06-05 | 辰欣药业股份有限公司 | Dirithromycin medicinal composition and preparation method thereof |
| CN102145008A (en) * | 2010-12-29 | 2011-08-10 | 山东鲁抗辰欣药业有限公司 | Dirithromycin medicinal composition and preparation method thereof |
| CN102908317B (en) * | 2011-08-01 | 2014-08-20 | 浙江众益制药股份有限公司 | Macrolide antibiotics enteric-coated pellets and coating solution thereof |
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| CN102349870A (en) * | 2011-10-18 | 2012-02-15 | 胡昌勤 | New preparation of erythrocin and relevant drug thereof and preparation method of new preparation |
| CN102349870B (en) * | 2011-10-18 | 2015-12-16 | 胡昌勤 | Preparation of a kind of erythromycin and related drugs thereof and preparation method thereof |
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| CN102846577A (en) * | 2012-09-27 | 2013-01-02 | 天津红日药业股份有限公司 | Medical composition containing erythromycin cydocarbonate |
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| CN109893511B (en) * | 2017-12-11 | 2022-07-12 | 湖北舒邦药业有限公司 | Dirithromycin enteric-coated tablet enteric-coated coating, preparation method thereof and dirithromycin enteric-coated tablet |
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| CN100488515C (en) | 2009-05-20 |
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Address after: 410005, Hunan, Changsha province Furong Road, No. 368 BOBO world city CTA wealth center, 24 floor Patentee after: HUNAN JIUDIAN PHARMACEUTICAL CO., LTD. Address before: 410011, 7 building, Xin Tian mansion, No. 78 North Shaoshan Road, Hunan, Changsha Patentee before: Hunan Jiudian Pharmaceutical Co., Ltd. |
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