CN102772413A - Low dose entecavir formulation and use - Google Patents
Low dose entecavir formulation and use Download PDFInfo
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- CN102772413A CN102772413A CN2012101468842A CN201210146884A CN102772413A CN 102772413 A CN102772413 A CN 102772413A CN 2012101468842 A CN2012101468842 A CN 2012101468842A CN 201210146884 A CN201210146884 A CN 201210146884A CN 102772413 A CN102772413 A CN 102772413A
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- 239000000203 mixture Substances 0.000 title claims abstract description 62
- 229960000980 entecavir Drugs 0.000 title claims abstract description 30
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- 238000009472 formulation Methods 0.000 title abstract 2
- 239000013543 active substance Substances 0.000 claims abstract description 21
- 208000002672 hepatitis B Diseases 0.000 claims abstract description 17
- QDGZDCVAUDNJFG-FXQIFTODSA-N entecavir (anhydrous) Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)C1=C QDGZDCVAUDNJFG-FXQIFTODSA-N 0.000 claims description 87
- 239000011159 matrix material Substances 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 24
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Abstract
Compositions containing a low dose of entecavir are administered on a daily basis to treat hepatitis B virus infection and/or co-infections. Formulations for the oral administration of a low dose of entecavir are provided. Other pharmaceutically active substances can be included in the entecavir composition or can be separately administered for the treatment of hepatitis B virus infection or for the treatment of co-infected patients.
Description
The application is that application number is 200810149287.9, the applying date is on August 29th, 2000, denomination of invention is divided an application for " low dose entecavir preparation and application thereof ", and this application of application number 200810149287.9 to be application number be 00126403.6, the dividing an application of August 29 2000 applying date, denomination of invention " low dose entecavir preparation and application thereof ".
Technical field
The application relates to low dose entecavir preparation and application thereof.
Background technology
BMS 200475 (Entecavir), [1S-(1 α, 3 α, 4 β)]-2-amino-1,9-dihydro-9-[4-hydroxyl-3-(methylol)-2-methylene cyclopenta]-6H-purine-6-one,
Be the antiviral agent that is used to treat hepatitis B virus infection, carrying out clinical evaluation at present.
People such as Zahler disclose the application of BMS 200475 and treatment hepatitis B thereof in United States Patent (USP) 5206244.The disclosed effective antiviral dosage oral or parenteral introduction of this patent is about 1.0-50mg/kg body weight, and this required dosage can reasonable time interval administration every day several.
People such as Bisacchi disclose the method for improved synthetic BMS 200475 in W098/09964.
Summary of the invention
The present invention relates to contain the pharmaceutical composition of low dose entecavir and the application that this type low dose group compound is used for safe and effective treatment hepatitis B virus infection.
The invention still further relates to method with the BMS 200475 and the active compound combined treatment hepatitis B virus infection of other drug of low dosage.Other materials that are fit to this purpose comprise other antiviral agent and/or immunomodulator.BMS 200475 and one or more other drug active substances can be combined in in a kind of dosage form or can be separately independently dosage form plan administration simultaneously or sequentially according to prescription.
The invention still further relates to the pharmaceutical composition for oral administration that contains the low-dose drugs active substance.Said composition is to obtain through the surface that the granule that makes pharmaceutically active substance adheres to carrier matrix.Making the method for pharmaceutically active substance calmness on carrier matrix is in order to make active substance/carrier matrix agglomeration of particles be reduced to minimum.
The present invention relates to contain the pharmaceutical composition of the about 25mg low dosage of 0.001mg-antiviral agent BMS 200475 of having an appointment, said composition is administered once and is used to treat the hepatitis B virus infection of adult patient every day.Preferred pharmaceutical composition contains the BMS 200475 of the about 10mg of 0.01mg-that has an appointment, and most preferred pharmaceutical composition contains the about 5mg BMS 200475 of the 0.01-that has an appointment.And the preferred and most preferred pharmaceutical composition of this type is administered once and is used to treat the hepatitis B virus infection of adult patient every day.
The term adult patient be defined as the age be about more than 16 years old or 16 years old and body weight be equal to or higher than 50 kilograms patient.The pharmaceutical composition that contains the low BMS 200475 of limiting the quantity of of above-mentioned scope is suitable for child patient or body weight are lower than patient's administration of 50 kilograms.
The above-mentioned low dose entecavir pharmaceutical composition that is used for administration every day also can be not too regularly to some patient's administration.For example, to treating the controlled patient of hepatitis B virus infection who makes them and can implement and keep therapeutic scheme so that it avoids further infection through taking the low dose entecavir pharmaceutical composition every day.This therapeutic scheme of keeping comprises that every day, deficiency was once taken the low dose entecavir compositions.For example, be administered once or be administered once weekly in per three or four days with regard to it is enough.
Low dose entecavir pharmaceutical composition of the present invention can be mixed with the form through any suitable administration.For example the preferred oral administration compositions can be tablet, capsule, granule or powder type, perhaps can be elixir, solution or form of suspension.According to method well known in the art, the low dose entecavir pharmaceutical composition also can be mixed with the form of non-gastrointestinal, rectum or via intranasal application administration.This type preparation can comprise pharmaceutically acceptable excipient, and said excipient comprises extender commonly used in this based composition, lubricant, disintegrating agent, binding agent etc.The present invention also comprises slow releasing preparation.
Unexpectedly find now, take once low dose entecavir pharmaceutical composition of the present invention every day and can treat hepatitis B virus infection effectively, and can not be created in the harmful side effect that the high dose scheme administration described in the United States Patent (USP) 5206244 brings.
The invention still further relates to method with one or more other drug active substance treatment hepatitis B virus infections of above-mentioned low dose entecavir compositions associating.The other drug active substance that is suitable for this purpose comprises one or more antiviral agent, for example didanosine, lamivudine, abacavir, adefovir; Adefovir dipivoxil; Famciclovir, (2R, 4R)-4-(2; 6-diaminourea-9H-purine-9-yl)-2-methylol-1; 3-dioxolanes (DPAD), hepatitis B immune are regulated albumen (EHT 899 of Enzo Biochem), emtricitabine, 1-(2-deoxidation-2-fluoro-beta-D-arabinofuranosyl base) thymus pyrimidine (FMAU), GLQ-223 (compd A, α-trichosanthin), epvudine (L-dT), epcitabine (L-dC), ribavirin, tenofovir (PMPA), 2 ', 3 '-dideoxy-2 '; 3 '-dideoxy-β-L (-)-5-fluorine cytidine [L (-) Fd4C], and other fluoro L-and D-nucleoside.The pharmaceutically active substance that is suitable for this purpose also comprises-kind or panimmunity regulator, for example alpha-interferon, beta-interferon, pegylated interferon, alpha-Thymosin and Hepatitis B virus vaccine, for example HBV/MF59, Hepagene and Theradigm-HBV.
When the other drug active substance was suitable for oral administration, they can combine to form the tablet or the capsule of single dose with low dose entecavir.If one or more other drug active substances can not with the BMS 200475 compatibility be combined in in a kind of dosage form, for example, if if administering mode is different or administration frequencies are different, then one or more other pharmaceutically active substance can be individually dosed.The dosage of one or more other active substances is that its usual amounts of treating separately perhaps decides the minimizing consumption by the doctor of treatment.Independently dosage form can be planned administration simultaneously or sequentially according to prescription.
The present invention also comprises the method with above-mentioned low dose entecavir combination treatment accompanying infection patient.The accompanying infection patient is except that infecting hepatitis B virus, also suffers from other the infecteds viral or the non-viral disease.Especially, this type Therapeutic Method can be used for the hepatitis B patient of accompanying infection hepatitis C or HIV.This accompanying infection patient preferably uses above-mentioned low dose entecavir compositions and the active compound combined treatment of one or more above-mentioned other drugs.The patient of for example concurrent hepatitis B and hepatitis C also should use the low dose entecavir compositions to treat except that using ribavirin and interferon treat.
On the other hand, the present invention is the pharmaceutical composition that content is less than or equal to about 10mg BMS 200475, especially tablet and capsular method for preparing.This based composition is through can not process evenly good preparation of content with active substance and mixed with excipients simply.Traditional method of granulating also is inappropriate for the biologically active prod of low dosage like this.
The tablet and the capsule preparations that contain the about 10mg BMS 200475 of the 0.001mg-that has an appointment can prepare according to following method, with efficient and the good homogeneous property of guaranteeing product.At first the BMS 200475 calmness is prepared compositions to the surface of carrier matrix.This step is accomplished through following operations: form the solution of BMS 200475 and adhesive material, when the carrier matrix granule keeps motion, use this solution with the mode of spraying or liquid stream then.Controlled condition is so that agglomeration of particles drops to minimum.Subsequently, except that desolvating, be left to adhere to the BMS 200475 on carrier matrix surface from carrier surface.This has prevented that BMS 200475 from separating with substrate and in operation subsequently, make the loss of BMS 200475 drop to minimum.
After the drying, with any other composition that comprises in the carrier matrix granule of BMS 200475 coating and the compositions, for example disintegrating agent and/or mix lubricant.Then with the powder tablet forming that obtains or be filled in the capsule.
During spray step, make the carrier matrix granule keep motion through mechanical agitation or air-flow stirring.In the mechanical agitation method, carrier matrix is put into machinery (high shear) blender stir.The solution that will contain BMS 200475 and adhesion substance is sprayed on the carrier matrix granule under atomizing pressure (0-2 crust) with the speed of controlling.For making BMS 200475 maximum ground calm to carrier, spray round carrier guaranteeing in the position of adjustment sprayer unit.Speed that control is calm and spray pattern are so that agglomeration of particles drops to minimum.In case contain the solution of BMS 200475 on the calmness, in exsiccator, pan dryer or fluidized bed dryer all are suitable for wet BMS 200475/carrier matrix transfer of granules.Remove at elevated temperatures and desolvate.When solvent was water or the water of regulating pH, suitable temperature was about 50 ℃-Yue 80 ℃.
In the air-flow stirring means, carrier matrix is put into the tube that the bottom has fine ga(u)ge screen.Regulate the air-flow that gets into so that the motion of matrix granule keeps constant and mobile.The balance carrier mass makes it reach about 25 ℃-Yue 80 ℃.The solution that will contain BMS 200475 and adhesive material is being sprayed on the carrier matrix granule under the above-mentioned atomizing pressure with control speed.Having, sprays round carrier guaranteeing in the position of adjustment sprayer unit again, and the calm speed of control is so that agglomeration of particles drops to minimum.In case the calm BMS 200475 solution of going up desolvates the temperature rising to remove.When solvent was water or the water of regulating pH, suitable temperature was about 50 ℃-Yue 80 ℃.In the air-flow stirring means, the BMS 200475 calmness on the carrier matrix and remove the two steps operation desolvate and can in same device, carry out, but in the mechanical agitation method, is then needed two kinds of devices.
Said method also has and reduces contacting of operator and BMS 200475 in the facility environment.
Though what top method was described is the preparation of drug combination that contains the about 10mg BMS 200475 of about 0.005mg-, they also can be used for preparing the pharmaceutical composition that contains any soluble agents active substance of low dosage.
Preferred solvent in the said method is water or the water of regulating pH.Can be through adding acid, for example the pH of hydrochloric acid reduction water improves the dissolubility of BMS 200475 in water.
Adhesive material preferably has the polymer of high-consistency.The material that is fit to comprises polyvidone, methylcellulose, hydroxy methocel, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl-cellulose, gelatin, guar gum and xanthan gum, and polyvidone is preferred.The content of adhesive material is preferably about 10% (weight) of about 1%-of compositions gross weight in the whole compositions.
Carrier matrix is to be easy to by spray coating and to be difficult for accumulative pharmaceutically useful material.The material that is fit to comprises microcrystalline Cellulose, calcium phosphate, dextrin, glucose, dextrates, mannitol, sorbitol and sucrose, and microcrystalline Cellulose is preferred.The content of carrier mass is preferably about 95% (weight) of about 80%-of compositions gross weight in the whole compositions.
The disintegrant content that comprises in the whole compositions is preferably about 1%-about 7% of compositions gross weight.The disintegrating agent that is fit to comprises polyvinylpolypyrrolidone, cross-linked carboxymethyl cellulose, PRIMOGEL, pre-gelatinized starch and corn starch, and polyvinylpolypyrrolidone is preferred.
The lubricant content that comprises in the whole compositions is preferably about 0.1%-about 5% of compositions gross weight.The disintegrating agent that is fit to comprises magnesium stearate, stearic acid, stearyl fumarate and sodium lauryl sulfate, and magnesium stearate is preferred.
The tablet of gained or capsule can be the film coatings, so that take.The suitable material that is used for the film coating is polymeric coating materials, pigment, plasticizer, solubilizing agent etc.The coating materials that is fit to comprises hydroxypropyl methylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate etc.Also can comprise Polyethylene Glycol in the film coated composition as plasticizer.Also can use other plasticizer in the film coated composition, for example citric acid diethylester and triethyl citrate.Suitable solubilizing agent comprises polyoxyethylene sorbitan carboxylic ester, especially polysorbate80.Suitable pigment comprises titanium dioxide and various ferrum oxide.
Composition in the coated composition is dispersed in The suitable solvent, in the preferred water.Coated composition can adopt conventional pan coating or spray coating technology to be used for tablet or capsule.
The specific embodiment
The following example is explained low dose entecavir compositions of the present invention.
Embodiment 1
Adopt method for preparing 10 microgram BMS 200475 tablets.
| Composition | Amount % (w/w) | Amount/sheet |
| BMS 200475 | 0.01 | 0.01mg |
| Microcrystalline Cellulose, NF | 93.24 | 93.24mg |
| Polyvinylpolypyrrolidone, NF | 4.00 | 4.00mg |
| Polyvidone, USP | 2.50 | 2.50mg |
| Magnesium stearate, NF | 0.25 | 0.25mg |
| Pure water, USP * | In right amount | --- |
| Amount to | 100.00 | 100.00mg |
* remove through drying.
Embodiment 2
Adopt 10 milligrams of BMS 200475 capsules of method for preparing.
| Composition | Amount % (w/w) | Amount/piece |
| BMS 200475 | 10.00 | 10.00mg |
| Microcrystalline Cellulose, NF | 82.03 | 82.03mg |
| Polyvinylpolypyrrolidone, NF | 4.00 | 4.00mg |
| Polyvidone, USP | 2.50 | 2.50mg |
| Magnesium stearate, NF | 0.25 | 0.25mg |
| Hydrochloric acid | 1.22 | 1.22mg |
| Pure water, USP * | In right amount | --- |
| Amount to | 100.00 | 100.00mg |
Capsule shells----
* remove through drying.
Embodiment 3
Adopt method for preparing 50 microgram BMS 200475 capsules.
| Composition | Amount % (w/w) | Amount/piece |
| BMS 200475 | 0.05 | 0.05mg |
| Dicalcium phosphate, NF | 93.20 | 93.20mg |
| Polyvinylpolypyrrolidone, NF | 4.00 | 4.00mg |
| Hydroxypropyl cellulose, NF | 2.50 | 2.50mg |
| Magnesium stearate, NF | 0.25 | 0.25mg |
| Pure water, USP * | In right amount | --- |
| Amount to | 100.00 | 100.00mg |
Capsule shells----
* remove through drying.
Embodiment 4
Adopt 1 milligram of BMS 200475 tablet of method for preparing.
| Composition | Amount % (w/w) | Amount/sheet |
| BMS 200475 | 1.00 | 1.00mg |
| Mannitol, NF | 90.00 | 90.00mg |
| Cross-linking sodium carboxymethyl cellulose, NF | 4.00 | 4.00mg |
| Methylcellulose, NF | 2.50 | 2.50mg |
| Stearic acid, NF | 2.50 | 0.25mg |
| Pure water, USP * | In right amount | |
| Amount to | 100.00 | 100.00mg |
* remove through drying.
Embodiment 5
To the 100mg tablet that contains the 1.0mg BMS 200475 of the 100mg tablet that contains the 0.01mg BMS 200475 of embodiment 1 and embodiment 4 adopt conventional pan coating or spray coating technology with below the compositions listed carry out the film coating.
* remove through drying.
1Suppose with sheet heavily to be that 100mg calculates.
2Suitable plasticizer is citric acid diethylester and triethyl citrate.
Embodiment 6
Human patients to chronic hbv-infection gives 28 days BMS 200475s, with at random, the safety and the antiviral activity of double blinding, placebo, dose titration test method research BMS 200475.Under all test doses, BMS 200475 all demonstrates effective antiviral activity.Take dose every day respectively and be 0.05,0.1,0.5 and 1.0mg BMS 200475 medicament, the average logarithm of the hepatitis B virus DNA level in the time of the 28th day in the blood reduces and is respectively 2.21,2.25,2.81 and 2.42.BMS 200475 is easy to the tolerance into the patient.
Claims (34)
1. an administration frequency is once a day or is less than the pharmaceutical composition that once is used to treat hepatitis B virus infection and/or accompanying infection, contains pharmaceutically suitable carrier and the about 25mg BMS 200475 of about 0.001mg-.
2. the compositions of claim 1, the content of wherein said BMS 200475 is the about 10mg of about 0.01mg-.
3. the compositions of claim 1, the content of wherein said BMS 200475 is the about 5mg of about 0.01mg-.
4. the compositions of claim 3, the content of wherein said BMS 200475 is about 0.01mg.
5. the compositions of claim 3, the content of wherein said BMS 200475 is about 0.05mg.
6. the compositions of claim 3, the content of wherein said BMS 200475 is about 0.1mg.
7. the compositions of claim 3, the content of wherein said BMS 200475 is about 0.5mg.
8. the compositions of claim 3, the content of wherein said BMS 200475 is about 1.0mg.
9. the compositions of claim 1 is tablet or capsule form.
10. the compositions of claim 1 contains one or more other drug active substances.
11. the oral drug preparation of a low dose entecavir contains the about 10mg BMS 200475 of the about 0.001mg-that is adhered to carrier matrix.
12. the compositions of claim 11; Wherein said carrier matrix is selected from microcrystalline Cellulose, calcium phosphate, dextrin, glucose, dextrates, mannitol, sorbitol and sucrose, and said BMS 200475 adheres on the said substrate through having viscous enough polymeric adhesive property material.
13. the compositions of claim 12, wherein said stickum is selected from polyvidone, methylcellulose, hydroxy methocel, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl-cellulose, gelatin, guar gum and xanthan gum.
14. the compositions of claim 11 comprises lubricant and disintegrating agent.
15. the compositions of claim 14; Wherein said lubricant is magnesium stearate, stearic acid, stearyl fumarate, sodium lauryl sulfate, and said disintegrating agent is selected from polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, PRIMOGEL, pre-gelatinized starch and corn starch.
16. the combination of oral medication of a low dose entecavir contains through BMS 200475, lubricant and the disintegrating agent of stickum coating to the carrier matrix, wherein:
The content of said BMS 200475 is that about 0.001-of said composition weight is about 10%,
The content of said stickum is that about 1-of said composition weight is about 10%,
The content of said carrier is that about 80-of said composition weight is about 95%,
The content of said disintegrating agent is about 1-about 5% of said composition weight.
The content of said lubricant is about 0.1-about 5% of said composition weight.
17. the compositions of claim 16, wherein said stickum is selected from polyvidone, methylcellulose, hydroxy methocel, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl-cellulose, gelatin, guar gum and xanthan gum,
Said carrier matrix is selected from microcrystalline Cellulose, calcium phosphate, dextrin, glucose, dextrates, mannitol, sorbitol and sucrose,
Said disintegrating agent is selected from polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, PRIMOGEL, pre-gelatinized starch and corn starch, and
Said lubricant is selected from magnesium stearate, stearic acid, stearyl fumarate and sodium lauryl sulfate.
18. the compositions of claim 17, wherein said stickum is a polyvidone.
19. the compositions of claim 17, wherein said carrier matrix is a microcrystalline Cellulose.
20. the compositions of claim 17, wherein said disintegrating agent is a polyvinylpolypyrrolidone.
21. the compositions of claim 17, wherein said lubricant is a magnesium stearate.
22. the low dose entecavir tablet composition contains:
About 0.01% BMS 200475,
About 93.24% microcrystalline Cellulose,
About 4.0% polyvinylpolypyrrolidone,
About 2.50% polyvidone and
About 0.25% magnesium stearate, said percent are based on w/w.
23. the low dose entecavir tablet composition contains:
About 1.0% BMS 200475,
About 90.0% mannitol,
About 4.0% cross-linking sodium carboxymethyl cellulose,
About 2.50% methylcellulose and
About 2.50% stearic acid, said percent are based on w/w.
24. the low dose entecavir tablet composition of claim 22 has the outer coatings film.
25. the low dose entecavir tablet composition of claim 23 has the outer coatings film.
26. the low dose entecavir capsule composition contains:
About 10.0% BMS 200475,
About 82.03% microcrystalline Cellulose,
About 4.00% polyvinylpolypyrrolidone,
About 2.50% polyvidone,
About 0.25% magnesium stearate and
About 1.22% hydrochloric acid, said percent are based on w/w.
27. the low dose entecavir capsule composition contains:
About 0.05% BMS 200475,
About 93.20% dicalcium phosphate,
About 4.00% polyvinylpolypyrrolidone,
About 2.50% hydroxypropyl cellulose and
About 0.25% magnesium stearate, said percent are based on w/w.
28. contain the method for preparing of the combination of oral medication of low dosage soluble agents active substance, comprising:
(a) said pharmaceutically active substance and stickum are dissolved in the solvent,
(b) with the solution spray of step (a) to moving carrier matrix simultaneously,
(c) the said coating carrier substrate of drying steps (b) and
(d) the said exsiccant coating carrier substrate of step (c) and other required compositions are mixed and made into said pharmaceutical composition.
29. the method for claim 28, the content of wherein said pharmaceutically active substance account for about 10% (w/w) of about 0.001-of said composition weight.
30. the method for claim 29, wherein said pharmaceutically active substance is a BMS 200475, and said solvent is water or the water with acid pH.
31. the method for claim 28, wherein during spray step (b), said carrier matrix keeps motion through mechanical agitation, and in step (c), said coating carrier substrate is carried out drying in pan dryer or fluidized bed dryer.
32. the method for claim 28, wherein during spray step (b), said carrier matrix stirs through air-flow and keeps motion, and in step (c), said coating carrier substrate also stirs through air-flow carries out drying.
33. an administration frequency is once a day or is less than the pharmaceutical composition that once is used to treat hepatitis B virus infection and/or accompanying infection, contains second kind of pharmaceutically active substance of pharmaceutically suitable carrier, the about 25mg BMS 200475 of about 0.001mg-and effective dose.
34. the compositions that contains pharmaceutically suitable carrier and the about 25mg BMS 200475 of about 0.001mg-is in that to prepare administration frequency be once a day or be less than the application of medicine that is used for treating hepatitis B virus infection and/or accompanying infection once.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18567200P | 2000-02-29 | 2000-02-29 | |
| US60/185,672 | 2000-02-29 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 00126403 Division CN1310999A (en) | 2000-02-29 | 2000-08-29 | Low dose Etikavi Prepn. and the use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102772413A true CN102772413A (en) | 2012-11-14 |
Family
ID=22681972
Family Applications (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 00126403 Pending CN1310999A (en) | 2000-02-29 | 2000-08-29 | Low dose Etikavi Prepn. and the use thereof |
| CN 200810170016 Expired - Lifetime CN101444511B (en) | 2000-02-29 | 2000-08-29 | Low dose entecavir formulation and use |
| CN 200510128719 Ceased CN1813753B (en) | 2000-02-29 | 2000-08-29 | Low dose entecavir formulation and use |
| CNA2008101492879A Pending CN101385732A (en) | 2000-02-29 | 2000-08-29 | Low dose entecavir formulation and use |
| CN2012101468842A Pending CN102772413A (en) | 2000-02-29 | 2000-08-29 | Low dose entecavir formulation and use |
Family Applications Before (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 00126403 Pending CN1310999A (en) | 2000-02-29 | 2000-08-29 | Low dose Etikavi Prepn. and the use thereof |
| CN 200810170016 Expired - Lifetime CN101444511B (en) | 2000-02-29 | 2000-08-29 | Low dose entecavir formulation and use |
| CN 200510128719 Ceased CN1813753B (en) | 2000-02-29 | 2000-08-29 | Low dose entecavir formulation and use |
| CNA2008101492879A Pending CN101385732A (en) | 2000-02-29 | 2000-08-29 | Low dose entecavir formulation and use |
Country Status (4)
| Country | Link |
|---|---|
| CN (5) | CN1310999A (en) |
| HK (1) | HK1040196A1 (en) |
| UY (1) | UY26595A1 (en) |
| ZA (1) | ZA200205900B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20210069115A1 (en) * | 2015-02-01 | 2021-03-11 | Orsenix Holdings Bv | High Surface-Area Lyophilized Compositions Comprising Arsenic For Oral Administration In Patients |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1732944B (en) * | 2005-09-02 | 2013-05-08 | 海南中和药业有限公司 | Entecavir dispersible tablet and its preparation process |
| CN1820744B (en) * | 2006-04-04 | 2011-01-26 | 中国人民解放军军事医学科学院毒物药物研究所 | Oseltamivir phosphate granula and its preparing method |
| CN101371841A (en) * | 2007-08-23 | 2009-02-25 | 浙江医药股份有限公司新昌制药厂 | Crystallization type Entecavir formulation as well as preparation method and use thereof |
| CN101244260B (en) * | 2007-02-14 | 2011-12-28 | 成都地奥九泓制药厂 | Combined medicament for treating chronic hepatitis B |
| CN102578564A (en) * | 2011-11-01 | 2012-07-18 | 江苏江山制药有限公司 | Preparation method for rapid-disintegrating directly-pressed particle mannitol preparation |
| CN102416003A (en) * | 2011-12-08 | 2012-04-18 | 南京优科生物医药有限公司 | Method for preparing entecavir tablets |
| CN102552210B (en) * | 2012-01-10 | 2013-12-11 | 四川海思科制药有限公司 | Entecavir capsule and preparation method thereof |
| KR101285008B1 (en) * | 2012-04-18 | 2013-07-10 | 제일약품주식회사 | A method for preparing oral formulation of low dose entecavir |
| CN112535736B (en) * | 2020-12-14 | 2023-08-29 | 石家庄四药有限公司 | Entecavir composition and preparation method thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4489026A (en) * | 1982-09-07 | 1984-12-18 | The Upjohn Company | Process for preparing solid unit dosage forms of ultra-low dose drugs |
| US5206244A (en) * | 1990-10-18 | 1993-04-27 | E. R. Squibb & Sons, Inc. | Hydroxymethyl (methylenecyclopentyl) purines and pyrimidines |
| PH30929A (en) * | 1992-09-03 | 1997-12-23 | Janssen Pharmaceutica Nv | Beads having a core coated with an antifungal and a polymer. |
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2000
- 2000-08-29 CN CN 00126403 patent/CN1310999A/en active Pending
- 2000-08-29 CN CN 200810170016 patent/CN101444511B/en not_active Expired - Lifetime
- 2000-08-29 CN CN 200510128719 patent/CN1813753B/en not_active Ceased
- 2000-08-29 CN CNA2008101492879A patent/CN101385732A/en active Pending
- 2000-08-29 CN CN2012101468842A patent/CN102772413A/en active Pending
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2001
- 2001-02-23 UY UY26595A patent/UY26595A1/en not_active IP Right Cessation
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2002
- 2002-03-04 HK HK02101639.3A patent/HK1040196A1/en unknown
- 2002-07-23 ZA ZA200205900A patent/ZA200205900B/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20210069115A1 (en) * | 2015-02-01 | 2021-03-11 | Orsenix Holdings Bv | High Surface-Area Lyophilized Compositions Comprising Arsenic For Oral Administration In Patients |
Also Published As
| Publication number | Publication date |
|---|---|
| UY26595A1 (en) | 2001-09-28 |
| HK1040196A1 (en) | 2002-05-31 |
| CN1813753B (en) | 2010-04-07 |
| CN101444511B (en) | 2013-01-02 |
| ZA200205900B (en) | 2004-03-29 |
| CN1813753C (en) | |
| CN1310999A (en) | 2001-09-05 |
| CN101385732A (en) | 2009-03-18 |
| CN1813753A (en) | 2006-08-09 |
| CN101444511A (en) | 2009-06-03 |
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