CN103948559A - Telbivudine tablet and preparation method thereof - Google Patents
Telbivudine tablet and preparation method thereof Download PDFInfo
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- CN103948559A CN103948559A CN201410150874.5A CN201410150874A CN103948559A CN 103948559 A CN103948559 A CN 103948559A CN 201410150874 A CN201410150874 A CN 201410150874A CN 103948559 A CN103948559 A CN 103948559A
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Abstract
The invention relates to a telbivudine tablet composition. The core of the telbivudine tablet composition is prepared from the following components in parts by weight: 100-600 parts of telbivudine, 50-250 parts of microcrystalline cellulose, 50-100 parts of starch, 15-30 parts of carboxymethyl starch sodium, 1-5 parts of magnesium stearate, 100-400ml of 50% ethanol solution containing 5% povidone K30. The telbivudine tablet has the advantages of good curative effect, simple operation, small pollution and low cost, and is suitable for industrial production.
Description
Invention field
The present invention relates to a kind of pharmaceutical preparation for the treatment of hepatitis B and preparation method thereof, be specifically related to a kind of Sebivo sheet and preparation method thereof.
Background of invention
Thereby hepatitis B is the pathogeny of the sick hepatitis B of the hepatitis b virus infected common transmittable that causes be after hepatitis B virus infection human body virus itself directly do not cause hepatocellular pathological changes just in hepatocyte existence copy its antigen presentation copying immune system of exciting human on liver plasma membrane and recognize and occur to attack and cleaning reaction to infecting.Wherein acute hepatitis b is that the immunologic function of body perfects and after immune system is activated, identifies hepatitis B virus and attack and infected viral hepatocyte and removed it; Chronic viral hepatitis B is that after hepatitis B virus invasion, but the immunologic function of body is activated but repeatedly attacks the hepatic tissue chronic inflammatory disease that causes that can not remove completely again and repeatedly show effect infecting viral hepatocyte in low or tolerance status body.
Chronic hepatitis is defined as the course of disease at least 6 months, and the state of an illness is without continuing or recurrent hepatitis of improving.Chronic hepatitis has numerous causes of disease, and China is current is mainly chronic hepatitis B.China not only thumping majority of chronic hepatitis causes by hepatitis B virus (HBV), and other chronic hepatopathys of great majority, comprise liver cirrhosis and hepatocarcinoma (HCC), also by chronic HBV infection, are made progress.By the chronic hepatitis B of acute hepatitis B chronicity seldom, the acute stage that transfers chronic hepatitis to is often light disease.The acute hepatitis B of sharply falling ill is chronicity seldom; The fulminant hepatitis B surviving almost all can recover completely.Seldom counting chronic hepatitis B is transformed by acute hepatitis B delay; The overwhelming majority is developed by Chronic Asymptomatic HbsAg carrier (AsC), in this regard, can think that it is " incubation period " of chronic hepatitis B that Chronic Asymptomatic carries; But also having morbidity is the so-called primary chronic hepatitis B of chronic hepatitis B performance.The performance that HBV infects is all over the world different.China infects immunologic tolerance because of how at infantile period, viremia over a long time of performance and pathological changes is slight.Clinical stable patient also can be recurred and increase the weight of, often relevant with virus sweep to the conversion of HBe serum.Chronic hepatitis B often shows " silence ", and clinical manifestation is often not consistent with the severe of pathological changes.Even if developed into, lose compensatory chronic hepatopathy, also the normal past medical histroy without acute attack.
The time that HBeAg and HBVDNA exist in serum is longer, make progress for the probability of hepatic fibrosis larger.Therefore must strengthen antiviral therapy, prevention hepatic fibrosis formation and development.The sure antiviral drugs of curative effect has two large class--interferon and nucleoside analogs at present.
The nucleoside analog that approved is treated for anti-HBV both at home and abroad at present comprises lamivudine (LAM) and Entecavir (ETV), and nucleotide analog adefovir ester (ADV).Existing nucleoside analog can effectively suppress virus replication, taking convenience and few side effects in a short time; But treatment time one is long, the complexity between virus and host and dynamic relation has determined the necessity that drug resistance occurs.So research and develop a kind of antiviral drugs fast and effectively, reduce drug resistance odds as far as possible, be main target in current anti-hepatitis B research.
Sebivo is a kind of novel nucleoside analog, by Switzerland Novartis Co.,Ltd, in 07 year, introduces China, is carrying out at present III phase clinical research.This test, for random, double blinding, dual analog test, is used the therapeutic effect of Sebivo or Sebivo to carry out two-year contrast to 332 adult chronic hepatitis B patients.In this test, most of patient is friend eAg positive (290).
Sebivo is obviously being better than lamivudine aspect antiviral and clinical efficacy.Sebivo can significantly reduce virus levels (HBV DNA), and fall is 6.22log10, compares with the fall 5.4log10 of Sebivo, almost exceeds 1,000,000 times (p=0.0004).In addition, accepting body inner virus carrying capacity in the patient of Sebivo treatment reaches lower than the ratio that can detect virus levels also considerably beyond using the patient of Sebivo treatment (to be respectively 70% and 43%; P < 0.0001).Compare with using the patient of Sebivo treatment, the treatment of accepting the patient of Sebivo treatment replys that degree is obviously higher (is respectively 87% and 54%; P<0.0001).Treatment is replied and is defined as HBV DNA level to be reduced to 5log10 copy/mL below horizontal, and with HBeAg turn out cloudy or ALT normal again.
In the patient who uses Sebivo, the multiple normal ratio of liver enzyme (ALT) (is respectively 89% and 76% higher than the patient who uses Sebivo to treat; P=0.0033).In addition, statistics shows, uses HBeAg in Sebivo treatment group to turn out cloudy the ratio of (only limiting to HBeAg positive patient, is that a kind of potential furuncle of controlling is for a long time replied index) also higher than using the treatment group of Sebivo (to be respectively 31% and 20%; P=0.0473).The frequence of seroconversion of Sebivo treatment group (only for HBeAg positive patient) is 25%, and Sebivo is 18%.The ratio Sebivo that in treatment, drug resistance occurs is 4.5%, and lamivudine is 10%.
The Data support that this test draws Sebivo there is the conclusion of good safety.And the Sebivo that this test shows and the overall security of lamivudine are very approaching with the GLOBE result of study of announcing recently.Aspect clinical adverse, the result of two treatment groups of Sebivo and lamivudine is similar, all lower.Common untoward reaction comprises nasopharyngitis, upper respiratory tract infection and weak.Shown in GLOBE result of study, to compare with Sebivo, the ratio that the patient's of use lamivudine therapy Serum ALT raises is higher; Compare with Sebivo, the ratio of the Serum Creatine Kinase rising of use lamivudine therapy (without changing therapeutic regimen) is higher.Through retrieval and inquisition, domestic having no with Sebivo tablet of the present invention, also has no relevant report.
Yet in clinical practice, find, its disintegrate effect of commercial preparation is unsatisfactory.In order to find the more rapid effectively Sebivo preparation of a kind of disintegrate, special proposition the present invention.The object of the present invention is to provide a kind of new Sebivo sheet and preparation technology thereof, good effect, simple to operate, pollute less, with low cost, be applicable to suitability for industrialized production.
Summary of the invention
The object of the present invention is to provide a kind of new Sebivo sheet and preparation technology thereof, and through repetition test, each component screening is arrived to weight ratio of the present invention, and being surprised to find that the tablet quality obtaining is stable, stripping is fast, in body, distribute rapidly, bioavailability is high.
On the one hand, the invention provides a kind of Sebivo sheet, wherein, described Sebivo tablet composition label is prepared from by following composition: 50% alcoholic solution 100～400ml of 100～600 parts of Sebivos, 50～250 parts of microcrystalline Cellulose, 50～100 parts of starch, 15～30 parts of carboxymethylstach sodium, 1～5 part of magnesium stearate, 5% PVP K30.
In other embodiments, Sebivo sheet of the present invention, wherein, described Sebivo sheet label is prepared from by following composition: 50% alcoholic solution 200～300ml of 600 parts of Sebivos, 100～250 parts of microcrystalline Cellulose, 50～100 parts of starch, 15～30 parts of carboxymethylstach sodium, 1～5 part of magnesium stearate, 5% PVP K30.
In other embodiments, Sebivo sheet of the present invention, wherein, described Sebivo tablet composition label is prepared from by following composition: 50% alcoholic solution 300ml of 600 parts of Sebivos, 250 parts of microcrystalline Cellulose, 100 parts of starch, 20 parts of carboxymethylstach sodium, 3 parts of magnesium stearate, 5% PVP K30.
Some embodiments therein, Sebivo sheet of the present invention, wherein, described tablet composition label also has coatings outward, described coatings is that 85% alcoholic solution of 6% Opadry is made, described coatings weight be label weight be 2%～5%.
On the other hand, the present invention relates to a kind of preparation method of Sebivo sheet of the present invention, wherein, described tablet composition preparation method is: sieve (1); (2) binding agent preparation: take PVP K30,50% alcoholic solution of preparation 5% PVP K30, standby; (3) mix: take Sebivo, starch, part microcrystalline Cellulose and part carboxymethylstach sodium, mix to obtain mixed-powder; (4) granulate: by 5/7 of the mixed-powder total amount of step (3) join 5% PVP K30 50% alcoholic solution total amount 8/13 in soft material processed, granulate, dry, granulate obtains primary granule; Primary granule, the mixed-powder of remaining step (3) and 50% alcoholic solution of 5% PVP K30 are further granulated in fluid bed, until without residual powder, dry, granulate obtains intermediate grain; (5) always mixed: the intermediate grain that step (4) is obtained, magnesium stearate, residue microcrystalline Cellulose and carboxymethylstach sodium mix; (6) measure the qualified rear calculating of Sebivo content and answer tabletting weight; (7) tabletting wrap coatings; (8) after full inspection, packing and get final product.
Some embodiments therein, preparation method of the present invention, wherein, taking part microcrystalline Cellulose described in step (3) is 2/3 of microcrystalline Cellulose total amount, part carboxymethylstach sodium is 5/7 of carboxymethylstach sodium total amount.
Some embodiments therein, preparation method of the present invention, wherein, described primary granule particle diameter 200～250 orders of step (4), described intermediate grain particle diameter 150～200 orders.
Some embodiments therein; preparation method of the present invention; wherein; described in step (5), be mixed into first the granule that carboxymethylstach sodium and step (4) are obtained and mix, and then mix joining after microcrystalline Cellulose, magnesium stearate mix homogeneously in the mixture of granule and microcrystalline Cellulose.
Some embodiments therein, preparation method of the present invention, wherein, sieves as crossing 80 mesh sieves described in step (1).
Some embodiments therein, preparation method of the present invention, wherein, the described bag coatings of step (7) is 85% alcoholic solution with 6% Opadry coating materials, it is 2～5% of label weight that air flow is sprayed to coatings weight continuously, is dried.
Technical scheme of the present invention has following advantage:
(1) the present invention writes out a prescription rationally, and tablet disintegrate is rapid, and outward appearance is good;
(2) preparation method provided by the present invention can further improve the result of extraction of product, has strengthened the performance of drug effect.
The specific embodiment
Below in conjunction with embodiment, further explain the present invention, but embodiment does not limit in any form to the present invention.
Embodiment 1
The 50% alcoholic solution 300ml that gets Sebivo 600g, microcrystalline Cellulose 250g, starch 100g, carboxymethylstach sodium 20g, magnesium stearate 3g, 5% PVP K30, makes 1000.Get above-mentioned adjuvant and cross 80 mesh sieves, get PVP K30, prepare 50% alcoholic solution of 5% PVP K30, standby, take Sebivo, starch, 2/3 microcrystalline Cellulose and 5/7 the carboxymethylstach sodium of recipe quantity, mix homogeneously is made mixed-powder, get 5/7 of mixed-powder weight, add soft material processed in 50% alcoholic solution of 8/13 5% PVP K30 preparing, granulate, dry, granulate obtains primary granule, particle diameter approximately 200～250 orders.The polyvidone alcoholic solution of the mixed-powder of primary granule, residue 2/7 and residue 5/13 is continued to granulate in fluid bed, complete to residual powder and the consumption of polyvidone alcoholic solution, make intermediate grain, dry and granulate, particle diameter 150～200 orders.Intermediate grain is added to remaining carboxymethylstach sodium, mix, and then add magnesium stearate and remaining microcrystalline Cellulose, mix homogeneously.Measure the qualified rear calculating of Sebivo content and answer tabletting weight, tabletting, does film-coat agent with 85% alcoholic solution of 6% Opadry coating materials, and with air flow, being sprayed to continuously film gain in weight is 3% of label weight, full inspection, pack after and get final product.
Embodiment 2
The 50% alcoholic solution 200ml that gets Sebivo 600g, microcrystalline Cellulose 200g, starch 80g, carboxymethylstach sodium 15g, magnesium stearate 3g, 5% PVP K30, makes 1000.Get above-mentioned adjuvant and cross 90 mesh sieves, get PVP K30, prepare 50% alcoholic solution of 5% PVP K30, standby, take Sebivo, starch, 2/3 microcrystalline Cellulose and 5/7 the carboxymethylstach sodium of recipe quantity, mix homogeneously is made mixed-powder, get 5/7 of mixed-powder weight, add soft material processed in 50% alcoholic solution of 8/13 5% PVP K30 preparing, granulate, dry, granulate obtains primary granule, particle diameter approximately 200～250 orders.The polyvidone alcoholic solution of the mixed-powder of primary granule, residue 2/7 and residue 5/13 is continued to granulate in fluid bed, complete to residual powder and the consumption of polyvidone alcoholic solution, make intermediate grain, dry and granulate, particle diameter 150～200 orders.Intermediate grain is added to remaining carboxymethylstach sodium, mix, and then add magnesium stearate and remaining microcrystalline Cellulose, mix homogeneously.Measure the qualified rear calculating of Sebivo content and answer tabletting weight, tabletting, does film-coat agent with 85% alcoholic solution of 6% Opadry coating materials, and with air flow, being sprayed to continuously film gain in weight is 4% of label weight, full inspection, pack after and get final product.
Embodiment 3
The 50% alcoholic solution 150ml that gets Sebivo 600g, microcrystalline Cellulose 150g, starch 100g, carboxymethylstach sodium 30g, magnesium stearate 4g, 5% PVP K30, makes 1000.Get above-mentioned adjuvant and cross 95 mesh sieves, get PVP K30, prepare 50% alcoholic solution of 5% PVP K30, standby, take Sebivo, starch, 10/13 microcrystalline Cellulose and 5/7 the carboxymethylstach sodium of recipe quantity, mix homogeneously is made mixed-powder, get 5/7 of mixed-powder weight, add soft material processed in 50% alcoholic solution of 8/13 5% PVP K30 preparing, granulate, dry, granulate obtains primary granule, particle diameter approximately 200～250 orders.The polyvidone alcoholic solution of the mixed-powder of primary granule, residue 2/7 and residue 5/13 is continued to granulate in fluid bed, complete to residual powder and the consumption of polyvidone alcoholic solution, make intermediate grain, dry and granulate, particle diameter 150～200 orders.Intermediate grain is added to remaining carboxymethylstach sodium, mix, and then add magnesium stearate and remaining microcrystalline Cellulose, mix homogeneously.Measure the qualified rear calculating of Sebivo content and answer tabletting weight, tabletting, does film-coat agent with 85% alcoholic solution of 6% Opadry coating materials, and with air flow, being sprayed to continuously film gain in weight is 5% of label weight, full inspection, pack after and get final product.
Biological test
The present invention also provides following test example, so that the present invention is further described:
Comparative Study on Dissolution
This test example has detected result of extraction provided by the invention, and detection method is carried out with reference to 2005 editions the 2nd appendix XC dissolution method the second method of < < Chinese Pharmacopoeia > >.
Take distilled water as dissolution medium, rotating speed 50rpm, 30min sampling, injection liquid chromatography, records chromatogram, and gets reference substance solution injection liquid chromatography, records chromatogram.With external standard method, calculate Sebivo stripping quantity in test sample.Each sample carries out under the same conditions, and the same terms repeats 50 calculating mean values.
Wherein sample 1 is the embodiment of the present invention 1 product, and 2 is embodiment 2 products, and 3 is embodiment 3 products, reference reagent: commercially available Sebivo sheet (Beijing Novartis, specification: 600mg).
The different sample dissolutions of table 1
| Sample | 5min | 10min | 15min | 30min | 45min |
| Embodiment 1 | 98.2 | 98.9 | 99.4 | 99.9 | 100.26 |
| Embodiment 2 | 97.7 | 98.4 | 99.2 | 99.8 | 100.12 |
| Embodiment 3 | 97.9 | 98.5 | 99.4 | 99.8 | 100.20 |
| Marketed tablet | 75.6 | 80.6 | 89.7 | 95.4 | 99.5 |
By table 1 data, can find that the inventive method prepares tablet and more can improve the dissolution of product than commercially available ordinary tablet, as adopted the sample 1-3 of preparation method of the present invention, its dissolution is apparently higher than commercially available Sebivo sheet.And the prescription of the embodiment of the present invention 1 makes dissolution reach optimum.
This test is for fear of error effect, special each sample respectively got to 10 batches, and every batch of duplicate detection 10 times, averages.Learn and calculate by statistics, P < 0.05, this test has statistical significance.
And take oral form of medication according to Sebivo tablet, this Sebivo sheet provided by the present invention is beneficial to the performance of this medicine effect more, has greatly strengthened its bioavailability.
Accelerate 6 months stability tests
The Sebivo sheet of blister package (embodiment 1) is put under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5% and placed six months, outcome quality is stable, and indices is as shown in table 2.
Six months accelerated test testing results of table 2 Sebivo sheet
| Inspection batch | Outward appearance | Related substance % | Dissolution % | Content % |
| Batch 1 | White is smooth | 0.20 | 100.26 | 100.24 |
| Batches 2 | White is smooth | 0.25 | 100.12 | 100.14 |
| Batches 3 | White is smooth | 0.22 | 100.20 | 100.20 |
Claims (10)
1. a Sebivo sheet, wherein, described Sebivo tablet composition label is prepared from by following composition: 50% alcoholic solution 100～400ml of 100～600 parts of Sebivos, 50～250 parts of microcrystalline Cellulose, 50～100 parts of starch, 15～30 parts of carboxymethylstach sodium, 1～5 part of magnesium stearate, 5% PVP K30.
2. Sebivo sheet according to claim 1, wherein, described Sebivo tablet composition label is prepared from by following composition: 50% alcoholic solution 200～300ml of 600 parts of Sebivos, 100～250 parts of microcrystalline Cellulose, 50～100 parts of starch, 15～30 parts of carboxymethylstach sodium, 1～5 part of magnesium stearate, 5% PVP K30.
3. Sebivo sheet according to claim 2, wherein, described Sebivo tablet composition label is prepared from by following composition: 50% alcoholic solution 300ml of 600 parts of Sebivos, 250 parts of microcrystalline Cellulose, 100 parts of starch, 20 parts of carboxymethylstach sodium, 3 parts of magnesium stearate, 5% PVP K30.
4. according to the Sebivo sheet described in claim 1～3 any one, wherein, described tablet composition label also has coatings outward, and described coatings is that 85% alcoholic solution of 6% Opadry is made, described coatings weight be label weight be 2%～5%.
5. a preparation method for Sebivo sheet described in claim 1～4 any one, wherein, described tablet composition preparation method is: sieve (1); (2) binding agent preparation: take PVP K30,50% alcoholic solution of preparation 5% PVP K30, standby; (3) mix: take Sebivo, starch, part microcrystalline Cellulose and part carboxymethylstach sodium, mix to obtain mixed-powder; (4) granulate: by 5/7 of the mixed-powder total amount of step (3) join 5% PVP K30 50% alcoholic solution total amount 8/13 in soft material processed, granulate, dry, granulate obtains primary granule; Primary granule, the mixed-powder of remaining step (3) and 50% alcoholic solution of 5% PVP K30 are further granulated in fluid bed, until without residual powder, dry, granulate obtains intermediate grain; (5) always mixed: the intermediate grain that step (4) is obtained, magnesium stearate, residue microcrystalline Cellulose and carboxymethylstach sodium mix; (6) measure the qualified rear calculating of Sebivo content and answer tabletting weight; (7) tabletting wrap coatings; (8) after full inspection, packing and get final product.
6. preparation method according to claim 5, wherein, taking part microcrystalline Cellulose described in step (3) is 2/3 of microcrystalline Cellulose total amount, part carboxymethylstach sodium is 5/7 of carboxymethylstach sodium total amount.
7. preparation method according to claim 5, wherein, described primary granule particle diameter 200～250 orders of step (4), described intermediate grain particle diameter 150～200 orders.
8. preparation method according to claim 5; wherein; described in step (5), be mixed into first the granule that carboxymethylstach sodium and step (4) are obtained and mix, and then mix joining after microcrystalline Cellulose, magnesium stearate mix homogeneously in the mixture of granule and microcrystalline Cellulose.
9. preparation method according to claim 5, wherein, sieves as crossing 80 mesh sieves described in step (1).
10. preparation method according to claim 5, wherein, the described bag coatings of step (7) is 85% alcoholic solution with 6% Opadry coating materials, it is 2～5% of label weight that air flow is sprayed to coatings weight continuously, is dried.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107550866A (en) * | 2016-06-30 | 2018-01-09 | 康普药业股份有限公司 | A kind of Sebivo preparation |
| CN107655982A (en) * | 2016-07-23 | 2018-02-02 | 复旦大学附属华山医院 | A kind of method of Sebivo content in detection blood plasma |
| CN110680806A (en) * | 2018-07-04 | 2020-01-14 | 郑州泰丰制药有限公司 | Preparation method of telbivudine particles |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102327249A (en) * | 2011-09-02 | 2012-01-25 | 山东罗欣药业股份有限公司 | Lamivudine tablet composition and preparation method thereof |
| AU2013203196A1 (en) * | 1998-08-10 | 2013-05-02 | Centre National De La Recherche Scientifique | Beta-L-2'-Deoxy Nucleosides for the Treatment of Hepatitis B |
-
2014
- 2014-04-15 CN CN201410150874.5A patent/CN103948559A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2013203196A1 (en) * | 1998-08-10 | 2013-05-02 | Centre National De La Recherche Scientifique | Beta-L-2'-Deoxy Nucleosides for the Treatment of Hepatitis B |
| CN102327249A (en) * | 2011-09-02 | 2012-01-25 | 山东罗欣药业股份有限公司 | Lamivudine tablet composition and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 无: "《http://www.fda.gov/downloads/drugs/drugsafety/ucm135934.pdf》", 《HTTP://WWW.FDA.GOV/DOWNLOADS/DRUGS/DRUGSAFETY/UCM135934.PDF》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107550866A (en) * | 2016-06-30 | 2018-01-09 | 康普药业股份有限公司 | A kind of Sebivo preparation |
| CN107655982A (en) * | 2016-07-23 | 2018-02-02 | 复旦大学附属华山医院 | A kind of method of Sebivo content in detection blood plasma |
| CN110680806A (en) * | 2018-07-04 | 2020-01-14 | 郑州泰丰制药有限公司 | Preparation method of telbivudine particles |
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