CN1437936A - Libaweilin slow-released pill - Google Patents
Libaweilin slow-released pill Download PDFInfo
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- CN1437936A CN1437936A CN 03100542 CN03100542A CN1437936A CN 1437936 A CN1437936 A CN 1437936A CN 03100542 CN03100542 CN 03100542 CN 03100542 A CN03100542 A CN 03100542A CN 1437936 A CN1437936 A CN 1437936A
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Abstract
The present invention relates to a sustained release medication form of antiviral medicine, in particular, it relates to a slow-released pillet of ribavirin, its preparation method and sustained release medication made up by using said pillet.
Description
Technical field:
The present invention relates to the slow-release pill and preparation method thereof of a kind of slow release formulation of antiviral drugs, particularly ribavirin and the slow releasing preparation made from this piller.
Background technology:
Ribavirin is a kind of ucleosides broad-spectrum antiviral drug, and chemical compound was applied for a patent in 1971, and U.S. Patent number is: US3798209.This product can suppress the growth of deoxyribose type virus and ribotype virus, and its structure is similar with inosine to guanosine, participates in the guanine metabolism in human body, disturbs the biosynthesis of guanine, GMPC-guanosine 5-monophosphate, stops duplicating of viral RNA or DNA.Proved that ribavirin has inhibitory action to multiple virus, as: respiratory syncytial virus, first, Influenza B virus, encephalitis b virus, parainfluenza virus, herpes simplex virus, hepatitis A virus (HAV), epidemic haemorrhagic fever virus, adenovirus etc.Recently, it is found that, ribavirin also has inhibitory action to human immunodeficiency virus (HIV), when share with alpha-interferon hepatitis C virus is had fine inhibitory action, Chinese patent CN99808596.0, CN96195591.0, CN00808831.4, CN99814344.8, CN98809350.2, CN99815897.6 have described these discoveries and the purposes of ribavirin.
More to the research of ribavirin preparation both at home and abroad, dosage form is also a lot, mainly contain tablet, oral liquid, capsule, injection, aerosol, eye drop, nasal drop, liniment, ribavirin chewing gum, aerosol, compound recipe solution etc., Chinese patent CN98812485.8 has described a kind of oral dosage form that can rapid dissolved ribavirin compressed compositions, and this product is not made into the report of slow release formulation.
Summary of the invention:
The common oral solid formulation of ribavirin, it is all shorter that peak reaching time of blood concentration and blood plasma are eliminated the half-life; Because of accumulating in erythrocyte, biological half-life is longer, and heavy dose of ribavirin that uses has harmful effect to liver function and hemogram.Because the antiviral activity of antiviral drugs was directly proportional with medicine and the time that virus contacts, the long more antiviral efficacy of holding time is high more.
For giving full play to the curative effect of ribavirin, the present invention makes slow releasing preparation with ribavirin, prolong peak reaching time of blood concentration and blood plasma and eliminated the half-life, help improving antiviral activity, reduce the toxic and side effects of medicine, and can make medicining times by reducing to every day of ordinary preparation every day 1-2 time for 3-4 time, improved compliance of patients.
An object of the present invention is to provide a kind of new pharmaceutical preparation of ribavirin, said preparation can provide the slow release of ribavirin, and said preparation is made by the ribavirin slow-release pill.
Another object of the present invention provides a kind of ribavirin slow-release pill and preparation method thereof.Ribavirin slow-release pill of the present invention prepares by the following method: elder generation makes ribavirin and contains pill core with suitable diluent, binding agent, wrap one deck sustained release coating layer again.The size of the slow-release pill that makes is between the 12-32 order.
For the above pill core that contains, its preparation method comprises powder lamination method, extrudes spheronizator, fluidized bed granulation method, and the equipment that is adopted can be centrifugal coating pelletizing machine, extrudes spheronizator, fluidized-bed coating machine etc.
Preferably, contain pill core with kind of a nuclear addition process preparation.Promptly on the basis of blank pill nuclear, further add layer ribavirin and suitable diluent, binding agent at its skin.Blank pill is endorsed to be water-insoluble or water miscible, and the former contains single or blended different oxide, cellulose, organic polymer and other materials, and the latter is contained single or blended different organic salt, sugar and other materials.
It is preceding to add layer (bed device of granulating or spray coating as using/add) at blank pill nuclear, and ribavirin is mixed with binding agent and other compositions.Described other compositions can be single or blended binding agent, surfactant, filler or other pharmaceutically acceptable components.
Contain binding agent in the pill core and comprise that hydroxypropyl emthylcellulose, polyvinylpyrrolidone, syrup, starch slurry and other have the pharmaceutically acceptable material of adhesion characteristic.Its consumption is the 1%-20% (percetage by weight) of medicated layer total amount.
Contain diluent in the pill core and comprise a kind of in microcrystalline Cellulose, starch, lactose, the Icing Sugar or their mixture.Its consumption is the 10%-90% (percetage by weight) of medicated layer total amount.
Coatings: one or more sustained release coating materials are comprised dispersions such as cellulose acetate, ethyl cellulose, hydroxypropyl emthylcellulose, Eudragit NE30D, Eudragit RL100, Eudragit RS100 be dissolved in the water or appropriate organic solvent in, adopt suitable packaging technique, coat above-mentioned containing on the pill core.For making coatings obtain necessary mechanical strength, generally need to add plasticizer and include but not limited to phthalic acid ester, Polyethylene Glycol, spermol or other plasticizers.Also can increase antitack agent such as Pulvis Talci, antistatic additive such as sodium lauryl sulphate, dispersant, coloring agent etc.
Ribavirin discharges fully at the appointed time in the preparation in order to make, and has slow release effect again.The coatings weightening finish should be controlled at the 3%-30% (percetage by weight) that contains pill core.
Final preparation: with the above-mentioned slow-release pill that makes by specification be filled into capsule slow releasing capsule, be filled into aluminium foil bag sustained-release granular formulation, wherein the consumption of ribavirin is 50-1000mg in every dose.Described every dose is meant the dosage of at every turn taking, or the amount of every bag of granule or every capsules.
Advantage of the present invention and good effect:
1. be uniformly distributed in gastrointestinal tract after entering in the body, thus little to gastrointestinal irritation, and uniform absorption and complete, the bioavailability height.
2. safe, the drug release behavior of slow-release pill belongs to the collective behavior of each piller, so the drug release behavior to whole preparation out of control of indivedual pillers does not have influence, so relative unit delivery system, this product safety is higher.
3. ribavirin slow-release pill of the present invention can increase and reaches the stable state time, helps improving antiviral activity, reduces administration number of times, reduces toxic and side effects, improves patient's compliance.
Therefore tool of the present invention has great advantage and potentiality, has the very strong market competitiveness.
Description of drawings:
Fig. 1 is the release profiles of product ribavirin sustained-release granular formulation of the present invention; Vertical coordinate is stripping (release) degree, and unit is %, and abscissa is the time, and unit is hour.
Fig. 2 is the release profiles of product ribavirin slow releasing capsule of the present invention; Vertical coordinate is stripping (release) degree, and unit is %, and unit is %, and abscissa is the time, and unit is hour.
The specific embodiment:
By the following examples the present invention is further elaborated:
The preparation of embodiment 1 ribavirin slow-release pill and sustained-release granular formulation:
The every bag of granule of filling a prescription contains ribavirin 0.25g
1. contain the pill core prescription
Ribavirin (120 order) 300g
Microcrystalline Cellulose (120 order) 280g
Ball nuclear (40-60 order) 280g
3% hydroxypropyl methylcellulose is an amount of
Make 1000 bags
2. coating fluid prescription: every 500g contains the pill core consumption
Eudragit NE 30D 156.7g
Pulvis Talci (1250 order) 48.57g
Sodium lauryl sulphate 0.392g
Water 186.5ml preparation technology 1. moldings
Taking by weighing microcrystalline Cellulose puts and starts centrifugal coating pelletizing machine by following parameter in the centrifugal coating pelletizing machine.Engine speed 200rpm, air blast flux 20 * 20L/min, jet flow 15-20L/min, whiff pressure 0.5Mpa, spray pump rotating speed 65rpm.With 3% hydroxypropyl methylcellulose (HPMC) aqueous solution is to be 4 minutes the binding agent whitewashing time, and polishing time is 2 minutes, keeps pump speed 2rpm during polishing, and the granular ball nuclear of 40-60 order is chosen in the back 60 ℃ of oven dry that take the dish out of the pot, screening.2. contain the preparation of pill core
Take by weighing 40-60 order parent nucleus, the material of putting centrifugal coating pelletizing machine is indoor, and will write out a prescription in addition ratio ribavirin medicated powder and microcrystalline Cellulose mixed-powder (120 order) are put in the solid feed hopper.3% hydroxypropyl methylcellulose aqueous solution is a binding agent, starts centrifugal coating pelletizing machine, engine speed 150-200rpm by following parameter.Spray pump rotating speed 15-25rpm, for powder speed 15-35rpm, polishing time 6min, the same molding of all the other parameters, treat pill take the dish out of the pot when growing to 20-32 order size 60 ℃ of oven dry the pastille micropill.3. coating
Take by weighing 20-32 order pastille micropill 500g, put in the centrifugal coating pelletizing machine.Other gets Eudragit NE 30D aqueous dispersion 156.7g, adds Pulvis Talci (1250 order) 48.57g, and sodium lauryl sulphate 0.392g adds water 186.5ml.Stir as coating solution.Start centrifugal coating pan by following parameter and carry out coating.Spray pump rotating speed 10-25rpm, engine speed 150rpm, other parameter is with playing mold technique.Treat to stop when coating solution has sprayed.In 40 ℃ of baking ovens, wear out after taking the dish out of the pot and got final product in 24 hours.4. pack
The above-mentioned piller that makes is filled the normal aluminium foil bag promptly.
Record the drug release determination method of other kinds with reference to 2000 editions two ones of Chinese Pharmacopoeias the granule that embodiment 1 prepares is carried out drug release determination; Medium is a water.Sampling time point is defined as 2 hours; 4 hours; The preparation prescription of 8 hours.Its release profiles is seen Fig. 1. embodiment, 3 Libaweilin slow-released pills and Duracaps contains the pill core prescription: Ribavirin (120 order) 250g microcrystalline cellulose (120 order) 7.5g ball nuclear (32-40 order) an amount of 3% HPMC is made 1000 2 coating fluid prescription in right amount: every 500g pastille micropill consumption Eudragit NE 30D 83.33g talcum powder (1250 order) 25.83g lauryl sodium sulfate 0.21g water 99.16ml preparation technology 1. molding technological operations are with embodiment 1, and 32-40 purpose graininess parent nucleus is chosen in screening. 2. contain pill core preparation technology technological operation with embodiment 1, when pill grows to 18-24 order size, take the dish out of the pot.3. the art for coating technological operation is with embodiment 1.4. filled capsules fills the above-mentioned piller that makes with conventional capsule promptly.
Getting the capsule of embodiment 3 methods preparation, according to dissolution method (two appendix XC second methods of Chinese Pharmacopoeia version in 2000), is solvent with water 900ml, and rotating speed is that per minute 50 changes, operation in accordance with the law.2,6,8 hours its releases.Its release profiles is seen Fig. 2.Description of drawings: Fig. 1 is the release profiles of ribavirin slow-releasing granules,
Fig. 2 is the release profiles of ribavirin slow releasing capsule.
Claims (10)
1, a kind of ribavirin slow-release pill is characterized in that, by containing pill core and coatings constitutes, wherein:
A, contain and contain ribavirin and adjunct ingredient in the pill core,
Contain pharmaceutically acceptable sustained release coating material in b, the coatings.
2, the slow-release pill of claim 1, the adjunct ingredient that wherein contains in the pill core comprises binding agent and diluent, and binding agent is selected from hydroxypropyl emthylcellulose, polyvinylpyrrolidone, syrup, starch slurry, diluent and is selected from microcrystalline Cellulose, starch, lactose, Icing Sugar.
3, the slow-release pill of claim 1, the sustained release coating material that wherein contains in the coatings is selected from cellulose acetate, ethyl cellulose, hydroxypropyl emthylcellulose, EudragitNE30D, EudragitRL100, Eudragit RS100.
4, the slow-release pill of claim 1, wherein the size of slow-release pill is between the 12-32 order.
5, the slow-release pill of claim 1, the adjunct ingredient adhesive consumption in the wherein said ball core is the 1%-20% of medicated layer total amount, and the consumption of diluent is the 10%-90% of medicated layer total amount, and the weight of coatings is the 3%-30% that contains pill core weight.
6, the slow-release pill of claim 1, wherein said contain pill core by powder lamination method, extrude the preparation of spheronization, fluidized bed granulation method.
7, use the pharmaceutical preparation of the slow-release pill preparation of claim 1.
8, preparation according to claim 7 is a capsule.
9, preparation according to claim 7 is a granule.
10, preparation according to claim 7, wherein the amount of ribavirin is 50-1000mg in every dose.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB03100542XA CN1191825C (en) | 2003-01-16 | 2003-01-16 | Libaweilin slow-released pill |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB03100542XA CN1191825C (en) | 2003-01-16 | 2003-01-16 | Libaweilin slow-released pill |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1437936A true CN1437936A (en) | 2003-08-27 |
| CN1191825C CN1191825C (en) | 2005-03-09 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB03100542XA Expired - Fee Related CN1191825C (en) | 2003-01-16 | 2003-01-16 | Libaweilin slow-released pill |
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| CN (1) | CN1191825C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108626569A (en) * | 2017-03-23 | 2018-10-09 | 中国石油化工股份有限公司 | A kind of hydrogen adsorption storing and releasing system and its application |
| CN111184703A (en) * | 2018-11-15 | 2020-05-22 | 哈尔滨医大药业股份有限公司 | Arsenic trioxide slow-release pill and preparation method thereof |
-
2003
- 2003-01-16 CN CNB03100542XA patent/CN1191825C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108626569A (en) * | 2017-03-23 | 2018-10-09 | 中国石油化工股份有限公司 | A kind of hydrogen adsorption storing and releasing system and its application |
| CN108626569B (en) * | 2017-03-23 | 2020-10-16 | 中国石油化工股份有限公司 | Hydrogen adsorption, storage and release system and application thereof |
| CN111184703A (en) * | 2018-11-15 | 2020-05-22 | 哈尔滨医大药业股份有限公司 | Arsenic trioxide slow-release pill and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN1191825C (en) | 2005-03-09 |
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