CN101028273A - Improved Enticawer suspension granules and their preparation - Google Patents
Improved Enticawer suspension granules and their preparation Download PDFInfo
- Publication number
- CN101028273A CN101028273A CN 200710026684 CN200710026684A CN101028273A CN 101028273 A CN101028273 A CN 101028273A CN 200710026684 CN200710026684 CN 200710026684 CN 200710026684 A CN200710026684 A CN 200710026684A CN 101028273 A CN101028273 A CN 101028273A
- Authority
- CN
- China
- Prior art keywords
- entecavir
- weight portions
- order
- weight portion
- agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
An improved mixed particle of entecavir for treating various hepatitides is proportionally prepared from entecavir, suspending aid, flavouring, pigment and adhesive through pulverizing, sieving and granulating.
Description
Technical field
The present invention relates to a kind of medicine and preparation method thereof, particularly a kind of improved Entecavir mix suspension grain that is used for the treatment of various hepatitis and preparation method thereof.
Background technology
Chronic viral hepatitis B is a kind of serious disease that is caused by hepatitis B viruses (HBV), also be high incidence and high mortality in the world disease it.This virus can cause lifelong infection, hepatic fibrosis or sclerosis, hepatocarcinoma, liver failure and death.Estimate that according to the U.S. CDC U.S. has the infected HBV virus of 1,250,000 people approximately, have every year and die from hepatitis B more than 5000 people and infect relevant disease, also increase 100,000 cases in addition every year newly with HBV; Europe has 1,000,000-2,000,000 people to infect HBV every year approximately, 90,000 people is wherein arranged approximately by persistent infection, has 2.2 ten thousand people finally to die from liver cirrhosis or primary hepatocarcinoma approximately; The whole world has 3.5 hundred million hepatitis B virus carrierss approximately, mainly be distributed in Asia, Africa and area, Latin America, the annual primary hepatocarcinoma that has 1,000,000-2,000,000 people to die from hepatitis B or cause approximately by chronic viral hepatitis B, occupy the 9th of disease death reason: the chronic viral hepatitis B patient of 10%-30% can develop into liver cirrhosis through 10-30, and the patient of about 1%-5% can develop into hepatocarcinoma through 20-40; The male mother of HBsAg can make infections in infants HBV by vertical transmission, wherein becomes the positive carrier of chronic HBsAg more than 90%, thereby has a strong impact on follow-on health.Therefore, effectively treat chronic viral hepatitis B, to reduce the HBV infection rate be the task of top priority of global the world of medicine.
Anti-HBV is the main means of treatment chronic viral hepatitis B, i.e. blocking-up or suppress hepatitis B viruses (HBV) duplicating in vivo lastingly, thereby alleviate or stop liver inflammation, necrosis and fibrosis lesion, stop pathological changes to lose compensatory, liver cirrhosis, liver failure and hepatocarcinoma development to liver function.The active drug of treatment chronic viral hepatitis B commonly used has interferon injection, oral antiviral drugs lamivudine and lamivudine and other antiviral drugs such as kurarinone etc.
Entecavir (entecavi :) is the light carbon deoxidation of an epoxy bird battalion, is a kind of deoxidation bird nuclear battalion analog that can effectively suppress hepatitis B virus duplication, has stronger anti-HBV effect.The chemical name of Entecavir is a 2-amino-1,9-dihydro-9[(15,3R, 4S foretell the light base-3-of 4-(through methyl rises 2-methylene Pentamethylene. fore-telling 6H-he cry of certain animals-6-ketone, monohydrate. molecular formula is C12H15NSO3.HZO, and molecular weight 295.3. structural formula is as follows:
Entecavir is as the general analog of nuclear that suppresses hbv replication, and its indication is the adult chronic viral hepatitis B active stage patient of the HBVDNA positive and HBeAg positive or negative and the patient invalid to lamivudine therapy.Recommended dose is: 1 of Zhi Liao the hepatitis B patient patient of general analogue treatment (do not accept nuclear) every day first, every 0.5mg; The drug-fast patient of lamivudine therapy (lamivudine therapy inefficacy patient) is 1 of every day, every 1.0mg.The patient is all good to the toleration of two kinds of therapeutic doses of Entecavir.Use Entecavir and treat the patient that the virus mutation that causes only occurs in the strain of infection lamivudine resistance mutated viruses, and aberration rate low (5.8%).
The pharmacokinetics evaluation experimental shows that this medicine oral absorption is good, and peak plasma concentration and AUC value all are dose dependent to be increased.Blood drug level is two index decreased, and average t1/2 is 55h, and the thing of taking medicine is eliminated from urine with the prototype medicament forms more than 50%.Tubular secretion is the main path of eliminating, and renal clearance is in the scope of 300-600ml/min.Entecavir health adult in, pharmacokinetics index between the severe hepatic injury patient is similar.In, severe liver injury patient need not to adjust dosage when using Entecavir.
Mix suspension grain is a kind of quick-effective preparation that development in recent years is got up, because its distinctive advantage more and more is subjected to people's attention.
Mix suspension grain (chewable tablets) definition: can even suspendible in adding entry.Normal sucrose, Herba Menthae, the flavorants etc. of adding are suitable for child administration to adjust taste, make mix suspension grain for the medicine of disintegrate difficulty and can help absorbing.Specification requirement: 1. mouthfeel, epigranular are good; 2. loss on drying must not surpass 2.0% 3. the settling volume ratio should be not less than 0.90 4. other should meet general rule requirement under the granule item.
Since mix suspension grain require water-soluble back suspendible evenly, good mouthfeel, to the oral mucosa nonirritant.Therefore the selection to supplementary product kind and performance thereof is the key of preparation mix suspension grain.
At present, it is rapid that extensive patients presses for a kind of absorption, can effectively improve the bioavailability and the blood drug level of Entecavir, improves the Entecavir mix suspension grain of Entecavir off-odor, taking convenience, few side effects simultaneously.The present invention has realized this purpose.
Summary of the invention
The inventor finds unexpectedly, if with the following technical scheme of the present invention, can make absorb fast, bioavailability is high, taking convenience, intestinal are residual less, few side effects and the good Entecavir mix suspension grain of mouthfeel.This purpose also of the present invention just.
Improvement Entecavir mix suspension grain of the present invention is made up of the effective amount of actives Entecavir and the adjuvant that pharmaceutically can prepare mix suspension grain.Adjuvant is any pharmaceutically acceptable auxiliaries that is fit to make mix suspension grain, and they can comprise suspending agent, correctives, odor mask, coloring agent etc.
The composition of mix suspension grain by weight, active ingredient entecavir 0.001-25 weight portion; Preferred 0.01-5 part; 0.05-0.1 part most preferably.
The adjuvant of preparation mix suspension grain is optional from suspending agent, correctives, coloring agent, binding agent, wetting agent; Mix suspension grain prescription of the present invention is counted with weight portion:
Entecavir 0.01-5 part, suspending agent 0.1-11 part, correctives 50-96 part, coloring agent 0.001-0.5 part, binding agent 0.01-20 part.Can regulate according to actual needs and delete.
In the present invention's prescription, the weight portion of each composition is preferably: Entecavir 0.05-0.1 part, suspending agent 1-5 part, correctives 80-96 part, coloring agent 0.02-0.05 part, binding agent 2-8 part.
Suspending agent of the present invention is selected from one or more the mixture in glycerol, syrup, mucialga of arabic gummy, sodium alginate, agar, methylcellulose, sodium carboxymethyl cellulose, xanthan gum, hydroxypropyl emthylcellulose, sodium hydroxyethyl cellulose, polyvidone, polyvinyl alcohol, kieselguhr, veegum and the aluminium stearate.Preferred hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, methylcellulose.
Correctives of the present invention is selected from sucrose, lactose, mannitol, aspartame, sorbitol, xylitol, glycyrrhizin, disodium glycyrrhizinate, trisodium glycyrrhetinate, from Rhizoma et radix valerianae, Fructus Pruni pseudocerasi, Fructus Vitis viniferae, Fructus Citri tangerinae, Fructus Citri Limoniae, Herba Menthae, careless Pueraria lobota, Fructus Musae, Fructus Ananadis comosi, honey peach essence, maltose alcohol, saccharin sodium, protein sugar, sucrose, aspartame and Flos Chrysanthemi one or more the mixture in former times.Preferably sucrose, disodium glycyrrhizinate, flavoring orange essence, lactose, aspartame, glycyrrhizin, honey peach essence.
Coloring agent of the present invention is selected from one or more the mixture in chlorophyll, caramel, sunset yellow, cocoa pigment, sodium-iron-chlorophyllin, lemon yellow, amaranth, carmine, indigo, red scarlet, orange, light blue and the fast blue.Preferred red scarlet, orange.
Binding agent of the present invention is selected from one or more the mixture in syrup, polyvidone aqueous solution, polyvidone ethanol liquid, carboxymethylcellulose sodium solution, aqueous gelatin solution and the starch slurry.Preferred syrup, starch slurry.
The present invention also provides good preparation method, and it comprises the steps:
(1), makes soft material after adding binding agent again with Entecavir and suspending agent, correctives, coloring agent and wetting agent mix homogeneously; Perhaps, add wetting agent system soft material again with Entecavir elder generation and suspending agent, correctives, coloring agent, binding agent mix homogeneously;
(2) the wet grain of system back oven dry, to particle drying weightlessness below 2.0%, stop oven dry, granulate, screening, packing are promptly.
One of preferred manufacturing procedure is:
Prescription (in weight portion): 0.5 part of Entecavir, 500 parts of sucrose, 5 parts of disodium glycyrrhizinates, 0.5 part of flavoring orange essence, red scarlet 0.25 part, 10 parts of hydroxypropyl emthylcelluloses, 15 parts in syrup;
Preparation process comprises: (1) with 200 order Entecavir powder and 150 order cane sugar powders, equivalent increases progressively, mix homogeneously; With disodium glycyrrhizinate, hydroxypropyl emthylcellulose, flavoring orange essence and red scarletly dissolve in right amount with wetting agent 95% ethanol, add in the mixed-powder of above-mentioned Entecavir and sucrose, add syrup again and make soft material; (2) above-mentioned soft material is dried after with 16,18 or 20 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop oven dry, reuse 12-40 order is two to be sieved.
A preferred manufacturing procedure is again:
Prescription (in weight portion): 0.25 part of Entecavir, 200 parts of lactose, 50 parts of aspartames, 2.5 parts of glycyrrhizins, 2.5 parts in honey peach essence, orange 0.12 part, 12 parts of sodium carboxymethyl cellulose, 18 parts of starch slurries;
Preparation process comprises: (1) is with 200 order Entecavir powder and the 200 order aspartame equivalent mix homogeneously that progressively increases, again with the 100 order lactose equivalent mix homogeneously that progressively increases, again with glycyrrhizin, honey peach essence, orange, the sodium carboxymethyl cellulose equivalent mix homogeneously that progressively increases, add starch slurry at last and stir, add wetting agent system soft material; (2) above-mentioned soft material is dried after with 16,18 or 20 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop oven dry, reuse 12-40 order is two to be sieved.
A preferred manufacturing procedure is again:
Prescription (in weight portion): 0.5 part of Entecavir, 500 parts of sucrose, 5 parts of disodium glycyrrhizinates, 0.5 part of flavoring orange essence, red scarlet 0.25 part, 15 parts of sodium carboxymethyl cellulose, 28 parts in syrup;
Preparation process comprises: (1) with Entecavir powder (200 order) and cane sugar powder (150 order), equivalent increases progressively, mix homogeneously; With disodium glycyrrhizinate, sodium carboxymethyl cellulose, flavoring orange essence and red scarletly dissolve in right amount with wetting agent 95% ethanol, add in raw material and the sucrose mixed-powder, add syrup again and make soft material; (2) with drying behind the 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop oven dry, reuse 12 order to 40 orders are two to be sieved.
A preferred manufacturing procedure is again:
Prescription (in weight portion): 0.25 part of Entecavir, 200 parts of lactose, 50 parts of aspartames, 2.5 parts of glycyrrhizins, 2.5 parts in honey peach essence, orange 0.12 part, 18 parts of hydroxypropyl emthylcelluloses, 24 parts of starch slurries;
Preparation process comprises: (1) is with Entecavir powder (200 order) and aspartame (200 order) the equivalent mix homogeneously that progressively increases, again with lactose (100 order) the equivalent mix homogeneously that progressively increases, again with glycyrrhizin, honey peach essence, the orange equivalent volumes mix homogeneously that progressively increases, add starch slurry at last and stir, add wetting agent and make soft material; (2) with drying behind the 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop oven dry, reuse 12 order to 40 orders are two to be sieved.
Entecavir mix suspension grain of the present invention in each oral formulations unit, contains Entecavir 0.001-25mg, and preferred dose is 0.01-10mg, and more preferred dose is 0.01-5mg.
The invention provides the pharmaceutic adjuvant and the consumption thereof that are fit to the Entecavir mix suspension grain, wherein used suspending agent has increased the weight and volume of mix suspension grain, is convenient to the molding and the divided dose of preparation; Used correctives makes this preparation produce fragrant and sweet happy people's mouthfeel, and correctives not only played the important function of flavoring, has also played stronger taste masking effect, has covered the bad strange taste of Entecavir, has improved the mouthfeel of mix suspension grain greatly; The coloring agent that the present invention is an amount of makes granule produce pleasing visual appearance, can eliminate the bored patient who takes medicine and resist emotion; Entecavir mix suspension grain of the present invention improves patient's drug compliance especially easily.The suitable amount of adhesive that the present invention adds has increased the granularity of Entecavir mix suspension grain.
Mix suspension grain suspendible of the present invention is even, and main advantage is: 1. absorption is fast, bioavailability is high, and the treatment hepatitis B is had better therapeutic; 2. intestinal is residual few, few side effects; 3. mouthfeel is good; 4. taking convenience.
The specific embodiment
Embodiment 1 (1000 bags)
Prescription: Entecavir 0.5g, sucrose 500g, disodium glycyrrhizinate 5g, flavoring orange essence 0.5g, red scarlet 0.25g, sodium carboxymethyl cellulose 15g, syrup 28g.
Make each: (1) with Entecavir powder (200 order) and cane sugar powder (150 order), equivalent increases progressively, mix homogeneously; With disodium glycyrrhizinate, sodium carboxymethyl cellulose, flavoring orange essence and red scarletly dissolve in right amount with wetting agent 95% ethanol, add in raw material and the sucrose mixed-powder, add syrup again and make soft material; (2) with drying behind the 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop oven dry, the two screening of reuse 12 order to 40 orders both must.
Embodiment 2 (1000 bags)
Prescription: Entecavir 0.25g, lactose 200g, aspartame 50g, glycyrrhizin 2.5g, honey peach essence 2.5g, orange 0.12g, hydroxypropyl emthylcellulose 18g, starch slurry 24g.
Preparation: (1) is with Entecavir powder (200 order) and aspartame (200 order) the equivalent mix homogeneously that progressively increases, again with lactose (100 order) the equivalent mix homogeneously that progressively increases, again with glycyrrhizin, honey peach essence, the orange equivalent volumes mix homogeneously that progressively increases, add starch slurry at last and stir, add wetting agent and make soft material; (2) with drying behind the 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop oven dry, the two screening of reuse 12 order to 40 orders both must.
Embodiment 3 (1000 bags)
Prescription: Entecavir 0.5g, sucrose 500g, disodium glycyrrhizinate 5g, flavoring orange essence 0.5g, red scarlet 0.25g, hydroxypropyl emthylcellulose 10g, syrup 15g;
Preparation: (1) with 200 order Entecavir powder and 150 order cane sugar powders, equivalent increases progressively, mix homogeneously; With disodium glycyrrhizinate, hydroxypropyl emthylcellulose, flavoring orange essence and red scarletly dissolve in right amount with wetting agent 95% ethanol, add in the mixed-powder of above-mentioned Entecavir and sucrose, add syrup again and make soft material; (2) for above-mentioned soft material is dried after with 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop to dry, reuse 12-40 order pair sieves.
Embodiment 4 (1000 bags)
Prescription: Entecavir 0.25g, lactose 200g, aspartame 50g, glycyrrhizin 2.5g, honey peach essence 2.5g, orange 0.12g, sodium carboxymethyl cellulose 12g, starch slurry 18g;
Preparation: (1) is with 200 order Entecavir powder and the 200 order aspartame equivalent mix homogeneously that progressively increases, again with the 100 order lactose equivalent mix homogeneously that progressively increases, again with glycyrrhizin, honey peach essence, orange, the sodium carboxymethyl cellulose equivalent mix homogeneously that progressively increases, add the starch slurry system soft material that stirs at last; (2) for above-mentioned soft material is dried after with 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop to dry, reuse 12-40 order pair sieves.
Embodiment 5 (1000 bags)
Prescription: Entecavir 0.005g, lactose 325g, aspartame 50g, glycyrrhizin 12.25g, honey peach essence 12.25g, orange 0.005g, sodium carboxymethyl cellulose 0.5g, starch slurry 100g;
Preparation: (1) is with 200 order Entecavir powder and the 200 order aspartame equivalent mix homogeneously that progressively increases, again with the 100 order lactose equivalent mix homogeneously that progressively increases, again with glycyrrhizin, honey peach essence, orange, the sodium carboxymethyl cellulose equivalent mix homogeneously that progressively increases, add the starch slurry system soft material that stirs at last; (2) for above-mentioned soft material is dried after with 16 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop to dry, reuse 12 orders pair sieve.
Embodiment 6 (1000 bags)
Prescription: Entecavir 0.05g, lactose 400g, aspartame 50g, glycyrrhizin 10g, honey peach essence 12.45g, orange 2.5g, sodium carboxymethyl cellulose 5g, starch slurry 20g;
Preparation: (1) is with 200 order Entecavir powder and the 200 order aspartame equivalent mix homogeneously that progressively increases, again with the 100 order lactose equivalent mix homogeneously that progressively increases, again with glycyrrhizin, honey peach essence, orange, the sodium carboxymethyl cellulose equivalent mix homogeneously that progressively increases, add the starch slurry system soft material that stirs at last; (2) for above-mentioned soft material is dried after with 20 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop to dry, reuse 40 orders pair sieve.
Embodiment 7 (1000 bags)
Prescription: Entecavir 25g, lactose 375g, aspartame 10g, glycyrrhizin 12.5g, honey peach essence 12.5g, orange 0.1g, sodium carboxymethyl cellulose 25g, starch slurry 40g;
Preparation: (1) is with 200 order Entecavir powder and the 200 order aspartame equivalent mix homogeneously that progressively increases, again with the 100 order lactose equivalent mix homogeneously that progressively increases, again with fragrant sticking, orange, the sodium carboxymethyl cellulose equivalent of glycyrrhizin, the honey peach mix homogeneously that progressively increases, add the starch slurry system soft material that stirs at last; (2) for above-mentioned soft material is dried after with 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop to dry, reuse 18 orders pair sieve.
Embodiment 8 (1000 bags)
Prescription: Entecavir 0.25g, sucrose 465g, disodium glycyrrhizinate 12.5g, flavoring orange essence 2.0g, red scarlet 0.15g, hydroxypropyl emthylcellulose 10g, syrup 10g;
Preparation: (1) with 200 order Entecavir powder and 150 order cane sugar powders, equivalent increases progressively, mix homogeneously; With disodium glycyrrhizinate, hydroxypropyl emthylcellulose, flavoring orange essence and red scarletly dissolve in right amount with wetting agent 95% ethanol, add in the mixed-powder of above-mentioned Entecavir and sucrose, add syrup again and make soft material; (2) for above-mentioned soft material is dried after with 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop to dry, reuse 30 orders pair sieve.
Embodiment 9 (1000 bags)
Prescription: Entecavir 0.5g, sucrose 440g, disodium glycyrrhizinate 7.20g, flavoring orange essence 2.0g, red scarlet 0.25g, hydroxypropyl emthylcellulose 50g, syrup 0.05g;
Preparation: (1) with 200 order Entecavir powder and 150 order cane sugar powders, equivalent increases progressively, mix homogeneously; With disodium glycyrrhizinate, hydroxypropyl emthylcellulose, flavoring orange essence and red scarletly dissolve in right amount with wetting agent 95% ethanol, add in the mixed-powder of above-mentioned Entecavir and sucrose, add syrup again and make soft material; (2) for above-mentioned soft material is dried after with 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop to dry, reuse 12-40 order pair sieves.
Embodiment 10 (1000 bags)
Prescription: Entecavir 5g, lactose 200g, aspartame 50g, glycyrrhizin 2.5g, honey peach essence 2.5g, orange 0.12g, sodium carboxymethyl cellulose 12g, starch slurry 18g;
Preparation: (1) is with 200 order Entecavir powder and the 200 order aspartame equivalent mix homogeneously that progressively increases, again with the 100 order lactose equivalent mix homogeneously that progressively increases, again with glycyrrhizin, honey peach essence, orange, the sodium carboxymethyl cellulose equivalent mix homogeneously that progressively increases, add the starch slurry system soft material that stirs at last; (2) for above-mentioned soft material is dried after with 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop to dry, reuse 12-40 order pair sieves.
Embodiment 11 (1000 bags)
Prescription: Entecavir 25g, lactose 200g, aspartame 45g, glycyrrhizin 2.5g, honey peach essence 2.5g, orange 2.5g, sodium carboxymethyl cellulose 50g, starch slurry 100g;
Preparation: (1) is with 200 order Entecavir powder and the 200 order aspartame equivalent mix homogeneously that progressively increases, again with the 100 order lactose equivalent mix homogeneously that progressively increases, again with glycyrrhizin, honey peach essence, orange, the sodium carboxymethyl cellulose equivalent mix homogeneously that progressively increases, add the starch slurry system soft material that stirs at last; (2) for above-mentioned soft material is dried after with 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop to dry, reuse 12-40 order pair sieves.
Claims (10)
1. improved Entecavir mix suspension grain is characterized in that being made up of the effective amount of actives Entecavir and the adjuvant that pharmaceutically can prepare mix suspension grain.
2. a kind of improved Entecavir mix suspension grain of claim 1, it is formed in weight portion, described active ingredient entecavir 0.001-25 weight portion.
3. a kind of improved Entecavir mix suspension grain of claim 2, wherein said entecavir 0.01-5 weight portion.
4. a kind of improved Entecavir mix suspension grain of claim 3 is characterized in that the described adjuvant that pharmaceutically can prepare mix suspension grain is selected from suspending agent, correctives, coloring agent, binding agent, wetting agent; The composition of mix suspension grain is counted with weight portion: Entecavir 0.01-5 part, suspending agent 0.1-11 part, correctives 50-96 part, coloring agent 0.001-0.5 part, binding agent 0.01-20 part.
5. a kind of improved Entecavir mix suspension grain of claim 4 is characterized in that forming and counts with weight portion: Entecavir 0.05-0.1 part, suspending agent 1-5 part, correctives 80-96 part, coloring agent 0.02-0.05 part, binding agent 2-8 part.
6. a kind of improved Entecavir mix suspension grain of claim 4 is characterized in that described suspending agent is selected from one or more the mixture in glycerol, syrup, mucialga of arabic gummy, sodium alginate, agar, methylcellulose, sodium carboxymethyl cellulose, xanthan gum, hydroxypropyl emthylcellulose, sodium hydroxyethyl cellulose, polyvidone, polyvinyl alcohol, kieselguhr, veegum and the aluminium stearate; Described correctives is selected from sucrose, lactose, mannitol, aspartame, sorbitol, xylitol, glycyrrhizin, disodium glycyrrhizinate, trisodium glycyrrhetinate, from Rhizoma et radix valerianae, Fructus Pruni pseudocerasi, Fructus Vitis viniferae, Fructus Citri tangerinae, Fructus Citri Limoniae, Herba Menthae, careless Pueraria lobota, Fructus Musae, Fructus Ananadis comosi, honey peach essence, maltose alcohol, saccharin sodium, protein sugar, sucrose, aspartame and Flos Chrysanthemi one or more the mixture in former times; Described coloring agent is selected from one or more the mixture in chlorophyll, caramel, sunset yellow, cocoa pigment, sodium-iron-chlorophyllin, lemon yellow, amaranth, carmine, indigo, red scarlet, orange, light blue and the fast blue; Described binding agent is selected from one or more the mixture in syrup, polyvidone aqueous solution, polyvidone ethanol liquid, carboxymethylcellulose sodium solution, aqueous gelatin solution and the starch slurry.
7. claim 4 or 5 a kind of improved Entecavir mix suspension grain is characterized in that described suspending agent is selected from hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, methylcellulose; Described correctives is selected from one or more in sucrose, disodium glycyrrhizinate, flavoring orange essence, lactose, aspartame, glycyrrhizin, the honey peach essence; Described coloring agent be selected from red scarlet, Fructus Citri tangerinae is yellow; Described binding agent is selected from syrup, starch slurry.
8. the preparation method of any improved Entecavir mix suspension grain among the claim 1-7 comprises the steps:
(1) with Entecavir and suspending agent, correctives, coloring agent and wetting agent mix homogeneously, adds binding agent system soft material again; Perhaps, add binding agent or wetting agent system soft material again with Entecavir elder generation and suspending agent, correctives, coloring agent mix homogeneously;
(2) the wet grain of system back oven dry, to particle drying weightlessness below 2.0%; Stop oven dry, granulate, screening, packing.
9. the preparation method of claim 8 is characterized in that containing in the per unit preparation Entecavir 0.01mg-5mg.
10. claim 8 or 9 preparation method is characterized in that it being following method A, B, C or B:
Method A
Prescription: Entecavir 0.5 weight portion, sucrose 500 weight portions, disodium glycyrrhizinate 5 weight portions, flavoring orange essence 0.5 weight portion, red scarlet 0.25 weight portion, hydroxypropyl emthylcellulose 10 weight portions, syrup 15 weight portions;
Preparation process comprises: (1) with 200 order Entecavir powder and 150 order cane sugar powders, equivalent increases progressively, mix homogeneously; With an amount of wetting agent 95% dissolve with ethanol of disodium glycyrrhizinate, hydroxypropyl emthylcellulose, flavoring orange essence and red scarlet usefulness, add in the mixed-powder of above-mentioned Entecavir and sucrose, add syrup again and make soft material; (2) above-mentioned soft material is dried after with 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop oven dry, reuse 12-40 order is two to be sieved;
Method B
Prescription: Entecavir 0.25 weight portion, lactose 200 weight portions, aspartame 50 weight portions, glycyrrhizin 2.5 weight portions, honey peach essence 2.5 weight portions, orange 0.12 weight portion, sodium carboxymethyl cellulose 12 weight portions, starch slurry 18 weight portions;
Preparation process comprises: (1) is with 200 order Entecavir powder and the 200 order aspartame equivalent mix homogeneously that progressively increases, again with the 100 order lactose equivalent mix homogeneously that progressively increases, again with glycyrrhizin, honey peach essence, orange, the sodium carboxymethyl cellulose equivalent mix homogeneously that progressively increases, add the starch slurry system soft material that stirs at last; (2) above-mentioned soft material is dried after with 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop oven dry, reuse 12-40 order is two to be sieved;
Method C
Prescription: Entecavir 0.5 weight portion, sucrose 500 weight portions, disodium glycyrrhizinate 5 weight portions, flavoring orange essence 0.5 weight portion, red scarlet 0.25 weight portion, sodium carboxymethyl cellulose 15 weight portions, syrup 28 weight portions;
Preparation process comprises: (1) with 200 order Entecavir powder and 150 order cane sugar powders, equivalent increases progressively, mix homogeneously; With disodium glycyrrhizinate, sodium carboxymethyl cellulose, flavoring orange essence and red scarletly dissolve in right amount with wetting agent 95% ethanol, add in raw material and the sucrose mixed-powder, add syrup again and make soft material; (2) with drying behind the 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop oven dry, reuse 12 order to 40 orders are two to be sieved;
Method D
Prescription: Entecavir 0.25 weight portion, lactose 200 weight portions, aspartame 50 weight portions, glycyrrhizin 2.5 weight portions, honey peach essence 2.5 weight portions, orange 0.12 weight portion, hydroxypropyl emthylcellulose 18 weight portions, starch slurry 24 weight portions;
Preparation process comprises: (1) is with 200 order Entecavir powder and the 200 order aspartame equivalent mix homogeneously that progressively increases, again with the 100 order lactose equivalent mix homogeneously that progressively increases, again with glycyrrhizin, honey peach essence, the orange equivalent volumes mix homogeneously that progressively increases, add starch slurry at last and stir and make soft material; (2) with drying behind the 18 mesh sieve system wet granulars, to particle drying weightlessness below 2.0%, stop oven dry, reuse 12 order to 40 orders are two to be sieved.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710026684 CN101028273A (en) | 2007-02-02 | 2007-02-02 | Improved Enticawer suspension granules and their preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710026684 CN101028273A (en) | 2007-02-02 | 2007-02-02 | Improved Enticawer suspension granules and their preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101028273A true CN101028273A (en) | 2007-09-05 |
Family
ID=38713924
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200710026684 Pending CN101028273A (en) | 2007-02-02 | 2007-02-02 | Improved Enticawer suspension granules and their preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101028273A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102389400A (en) * | 2011-11-02 | 2012-03-28 | 谢安云 | Entecavir granule formulation and preparation method thereof |
| CN103908436A (en) * | 2012-12-29 | 2014-07-09 | 安徽贝克生物制药有限公司 | Quick-release type entecavir composition |
-
2007
- 2007-02-02 CN CN 200710026684 patent/CN101028273A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102389400A (en) * | 2011-11-02 | 2012-03-28 | 谢安云 | Entecavir granule formulation and preparation method thereof |
| CN103908436A (en) * | 2012-12-29 | 2014-07-09 | 安徽贝克生物制药有限公司 | Quick-release type entecavir composition |
| CN103908436B (en) * | 2012-12-29 | 2016-02-10 | 安徽贝克生物制药有限公司 | A kind of quick-releasing type entecavir composite |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1191262C (en) | Cranesbill total flavonoid extract and use in preparation of anti-virus medicine | |
| CN1965853A (en) | Application of gentiopicroside in preparation of antiviral medicament | |
| CN101028273A (en) | Improved Enticawer suspension granules and their preparation | |
| CN1903183A (en) | Dispersion tablets of telbivudine and its prepn. method | |
| CN1781485A (en) | Improved entecavir oral disintegrating tablet and its preparing method | |
| WO2005039561A1 (en) | Micronized bicyclol and the orally administered controlled release formulation | |
| CN1709451A (en) | Underleaf pearl formulation for treatig liver-gallbladder diseases and its preparing method | |
| CN100348199C (en) | Silicibinin-N-methylglucamine disperser for treating hepatitis, and its prepn. method | |
| CN1931138A (en) | Entecavir granule and its prepn process | |
| CN101254177A (en) | Dantrolene sodium chewable tablet and method of preparing the same | |
| CN1857684A (en) | Compound Chinese medicine preparation for removing toxic matter, dispersing blood clots and strengthing body's resistance and its preparaing process | |
| CN1220495C (en) | Traditional Chinese medicine for treating upper respiratory tract infection and its preparation method | |
| CN1245154C (en) | Mouth cavity fast disintegrating tablet of Chinese medicine or natural medical matters and its preparing method | |
| CN1927372A (en) | Antiviral dispersant tablet and method for making same | |
| CN101057851A (en) | Improved entecavir effervescent tablet and its preparation method | |
| CN101028272A (en) | Enticawer chewing tablets and their preparation | |
| CN1857683A (en) | Compound Chinese medicine preparation for eliminating heat, promoting urination and dispersing blood clots and its preparing process | |
| CN1220513C (en) | Proprietury Chinese medicine for stopping blood, analgesia, removing blood stasis and engender new and its preparation method | |
| CN1695728A (en) | Oral taking preparation of Chinese traditional medicine for nourishing the kidney and the lung | |
| CN112891482B (en) | A composition for treating coronavirus infection | |
| CN1439371A (en) | Matrine sustained releasing agent and its preparing process | |
| CN103933037B (en) | Dehydrocavidine-containing pharmaceutical composition and preparation method thereof | |
| CN1785247A (en) | Disintegrant tablets, and its prepn. method | |
| CN101057906A (en) | Traditional Chinese medicinal composition for treating hepatitis and its preparation method and medicinal preparation | |
| CN103919743B (en) | Pharmaceutical composition containing cavidine total alkali and preparation method of pharmaceutical composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |