CN1634043A - Zolmitriptan quick-release formulation - Google Patents
Zolmitriptan quick-release formulation Download PDFInfo
- Publication number
- CN1634043A CN1634043A CN 200410096169 CN200410096169A CN1634043A CN 1634043 A CN1634043 A CN 1634043A CN 200410096169 CN200410096169 CN 200410096169 CN 200410096169 A CN200410096169 A CN 200410096169A CN 1634043 A CN1634043 A CN 1634043A
- Authority
- CN
- China
- Prior art keywords
- zolmitriptan
- quick
- prescription
- disintegrating agent
- starch
- 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.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a Zolmitriptan quick-release formulation which can further improve the dissolving degree of the main medicament, greatly increase the absorbing velocity of the medicament in stomach and intestine, thus making the curative effect exert completely. Based on the physics and chemistry nature of the Zolmitriptan, adjuvant having specific disintegration and dissolving boosting actions for grease solving Zolmitriptan is selected from a plurality of medicinal findings through experiment.
Description
Affiliated technical field
The invention belongs to pharmaceutical preparations technology.
Background technology
Migraine is one of common clinical, frequently-occurring disease, and its incidence rate is about 10%.International headache association is defined as intermittent headache outbreak with migraine and with autonomic imbalance.Show as paroxysmal headache clinically: often with dizzy, hearing disability etc.The migrainous sickness rate of China is 4.2%～14.6%, and M-F is 1: 4.With the quickening pace of modern life with the increase of operating pressure, migraine presents the situation of continuous rising at the sickness rate of China, has become puzzlement people's commonly encountered diseases, frequently-occurring disease.3377 people have been visited in domestic investigation sampling altogether, find that 9.7% people suffers from migraine.Epidemiological study is found: have 6% male and 17% women to suffer from migraine approximately, the multiple age is 25～55 years old.Migraine has had a strong impact on patient's quality of life and work efficiency, causes huge burden for family and society.The shortage of migrainous high incidence and efficient medicine makes that the market of migraine treatment medicine is huge, has a extensive future.This shows, develop effective migraine treatment medicine, be significant, also is very urgent and necessary.
Clinical acute migraine commonly used outbreak medicine has: the nonsteroidal antiinflammatory and analgesic medicine, as aspirin, ibuprofen, indometacin etc.; The Ergotamine preparation is as gynergen and compound preparation thereof etc.; The 5-HT1 receptor stimulating agent.Wherein, analgesic can increase the weight of usually to feel sick and wait simultaneous phenomenon, and analgesic and antimigraine drug share and can cause headache more violent sometimes; The Ergotamine preparation is effective vasoconstrictor, and acting duration is also longer, but cerebrovascular is not had selectivity, and blood plasma level and biological activity are lower, and side effect is more.
Zolmitriptan (zolmitriptan, Zomig), the development of Britain Glaxo Wellcome company, it is the 5-HT1B/1D receptor stimulating agent of a high selectivity, be used for the treatment of various migrainous acute attacks, its mechanism of action makes the unusual expansible vasoconstriction of brain and pachymeninx for by directly stimulating the 5-HT1B/1D receptor of intracranial vessel system, also may act on nervi trigeminus nucleus tail side and trifacial synapse, suppress the release of inflammatory neurotransmitter.All there were sale in European Union member Germany, Finland and Denmark etc. in U.S.'s listing in 1998 in Britain's Initial Public Offering in 1997.Specification has 2.5mg and two kinds of tablets of 5mg.The pharmacological action of Zolmitriptan
Zolmitriptan is a kind of medicine of novel, efficient, specific treatment acute migraine, is the 5HT of high selectivity
1B/1DReceptor stimulating agent is by exciting 5-HT
1Receptor causes vasoconstriction and suppresses the release of neuropeptide, thereby alleviates migrainous outbreak.The pharmaceutical research result shows: Zolmitriptan is may command brain PBF not only, and can act on the pain maincenter of brain, thereby plays the migrainous effect of treatment.Studies show that: when stimulating trigeminal ganglion or migraine, cerebral blood flow increases, and calcitonin-gene-related peptide (CGRP) discharges, and CGRP and VIP (vasoactive intestinal peptide) increase in the external jugular vein.Zolmitriptan has periphery and maincenter dual function, optionally shrink particularly cranium tremulous pulse of intracranial vessel, control brain PBF, release such as CGRP, neurotransmitter A and the P material that can suppress vaso-active substance in addition, the cerebral dura mater arteries is shunk, reduce aseptic inflammation, play the migrainous effect of treatment.
The pharmacokinetics of Zolmitriptan and pharmacodynamics characteristics
The Zolmitriptan oral administration biaavailability is about 40%～60%, not influenced by feed; The average out to peak time is 1.25 hours, and the absorption stage of stable development of 4～6h is arranged subsequently; The Zolmitriptan major part is through liver metabolism.
Zolmitriptan treatment effective percentage is 56%～71%.That common adverse reactions has is nauseating, photophobia, fear sound etc., and degree is dependency with dosage to be increased.The acute attack of Zolmitriptan treatment cluster headache has better curative effect.124 patients are studied, and wherein 73% patient is acute attack, and 27% is chronic.The result shows: the curative effect of 10mg Zolmitriptan and placebo treatment acute attack is respectively 47% and 29% (p=0.02), and there were significant differences.The outbreak of Zolmitriptan 10mg, 5mg and placebo treatment acute migraine, 30 minutes remission rates or cure rate are respectively 60%, 57% and 42% (p≤0.01), and for chronic patients, 5mg or 10mg Zolmitriptan and placebo effect do not have significant difference.
Better according to Zolmitriptan to cluster headache acute attack curative effect, and to the relatively poor characteristics of chronic patients curative effect, the patient absorbs rapidly after taking Zolmitriptan, reaching effective blood drug level is the key factor that influences Zolmitriptan treatment acute migraine attack curative effect, and the conventional tablet bioavailability of existing Zolmitriptan is relatively low, just reached the peak value of blood drug level after 1 hour, this treatment for acute migraine attack is very disadvantageous.
Summary of the invention
Characteristic according to Zolmitriptan, the invention provides a kind of quick releasing formulation of Zolmitriptan, it can further improve the principal agent dissolubility, promptly meet water and can form even viscosity suspension rapidly, can be dispersed into fine particle in the rapid disintegrate of gastrointestinal tract, the medicine distribution area is increased, absorption point increases, improved the speed of medicine greatly in gastrointestinal absorption, avoided shortcomings such as, stimulating gastrointestinal mucosa too high, reduced untoward reaction in the gastrointestinal tract local drug concentration, have taking convenience, absorb characteristics such as fast, bioavailability height, and make things convenient for the patient to take.
Zolmitriptan is a kind of fat-soluble medicine, dissolubility in water is relatively poor, this may be the principal element that influences its infiltration rate and degree, its bioavailability is relatively low, it is more rapid to develop a kind of onset, the dosage form of the Zolmitriptan that bioavailability is higher is vast acute migraine outbreak patient at the back relief of symptoms rapidly of taking medicine, and is very necessary and has market prospect.The crude drug price of Zolmitriptan is more expensive relatively, be the best medicine that is used for the treatment of cluster headache and acute migraine attack of curative effect up to now, but its bioavailability and the infiltration rate in gastrointestinal tract have restricted its curative effect rapidly and farthest performance.
Can make Zolmitriptan disintegrate and stripping rapidly under one's belt, so that make it bring into play drug effect in the shortest time, be important feature of the present invention.The present invention and oral instant-dissolving tablet are compared, has the low significant advantage of production cost, and the present invention reaching the degree suitable with oral liquid aspect infiltration rate and the bioavailability, do not have very significant difference with oral instant-dissolving tablet, and effect is suitable.Because the water solublity of Zolmitriptan is relatively poor, the tablet that uses some conventional adjuvants to be prepared into is to reach disintegrate at a terrific speed that the present invention has and result of extraction.We grope to have selected following adjuvant according to the physicochemical property of Zolmitriptan from numerous pharmaceutically acceptable auxiliaries in experiment, find that they have specific short disintegrate and short stripping to fat-soluble Zolmitriptan.They comprise: one or more in the disintegrating agents such as starch, pregelatinized Starch, carboxymethyl starch sodium, microcrystalline Cellulose, hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, hydroxypropyl starch, sodium alginate, hydroxy acid cellulose, sodium carboxymethyl cellulose, methacrylic acid, divinylbenzene copolyesters, IRP-88, guar gum, Herba Xanthii glue, glucosan, carboxymethylcellulose calcium.
The specific embodiment
The invention will be further elaborated below by embodiment.
Embodiment (recipe quantity is 1000):
Eight kinds of concrete prescriptions:
Prescription A:
Zolmitriptan 0.2g
Hydroxypropyl cellulose (disintegrating agent) 115.8g
Micropowder silica gel (lubricant) 4g
Preparation technology: principal agent is crossed 100 mesh sieves, and disintegrating agent is crossed 80 mesh sieves, takes by weighing principal agent, the disintegrating agent mix homogeneously of recipe quantity, adds the lubricant of recipe quantity, mixing, and tabletting, promptly.Dispersible tablet is limited to 1.0min when disperseing.
Prescription B:
Zolmitriptan 0.6g
Hydroxypropyl cellulose (disintegrating agent) 168g
10% starch slurry (binding agent) 100g
Magnesium stearate (lubricant) 2g
Preparation technology: principal agent is crossed 100 mesh sieves, and disintegrating agent is crossed 80 mesh sieves, takes by weighing principal agent, the disintegrating agent mix homogeneously of recipe quantity, adds binding agent and granulates in right amount, and dry back adds recipe quantity lubricant mixing, and tabletting promptly.Dispersible tablet is limited to 1.2min when disperseing.
Prescription C:
Zolmitriptan 0.8g
Microcrystalline Cellulose (disintegrating agent) 200g
Preparation technology: principal agent is crossed 100 mesh sieves, and disintegrating agent is crossed 80 mesh sieves, takes by weighing principal agent, the disintegrating agent mix homogeneously of recipe quantity, and direct compression promptly.Dispersible tablet is limited to 0.6min when disperseing.
Prescription D:
Zolmitriptan 2g
Crospolyvinylpyrrolidone (disintegrating agent) 80g
Microcrystalline Cellulose (fluidizer) 110g
5%PVP
K30Ethanol solution (binding agent) 140g
Magnesium stearate (lubricant) 3g
Preparation technology is with prescription B.Dispersible tablet is limited to 0.8min when disperseing.
Prescription E:
The general 3g of assistant rice-koji
Hydroxypropyl cellulose (disintegrating agent) 40g
Crospolyvinylpyrrolidone (disintegrating agent) 40g
10% starch slurry (binding agent) 160g
Magnesium stearate (lubricating) 4g
Preparation technology is with prescription B.Dispersible tablet is limited to 0.7min when disperseing.
Prescription F:
Zolmitriptan 4g
Carboxymethylcellulose calcium (disintegrating agent) 15g
Crospolyvinylpyrrolidone (disintegrating agent) 15g
Microcrystalline Cellulose (filler) 140g
10% starch slurry (binding agent) 200g
Magnesium stearate (lubricant) 6g
Preparation technology is with prescription B.Dispersible tablet is limited to 1.5min when disperseing.
Prescription G:
Zolmitriptan 8g
Carboxymethyl starch sodium (disintegrating agent) 30g
Hydroxypropyl cellulose (disintegrating agent) 50g
5%PVP
K30Aqueous solution (binding agent) 300g
Magnesium stearate (lubricant) 8g
Preparation technology is with prescription B.Dispersible tablet is limited to 1.4min when disperseing.
Prescription H:
Zolmitriptan 12g
Crospolyvinylpyrrolidone (disintegrating agent) 14g
Microcrystalline Cellulose (filler) 160g
4%PVP
K30Aqueous solution (binding agent) 400g
Magnesium stearate (lubricant) 10g
Preparation technology is with prescription B.Dispersible tablet is limited to 1.3min when disperseing.
Prescription I:
Zolmitriptan 25g
Pregelatinized Starch (disintegrating agent) 300g
Micropowder silica gel (lubricant) 10g
Preparation technology: principal agent is crossed 100 mesh sieves, and disintegrating agent is crossed 80 mesh sieves, takes by weighing principal agent, the disintegrating agent mix homogeneously of recipe quantity, adds dehydrated alcohol and granulates in right amount, and dry back and the even tabletting of mix lubricant are promptly.Dispersible tablet is limited to 0.9min when disperseing.
Prescription J:
Zolmitriptan 22g
Crosslinked carboxymethyl fecula sodium (disintegrating agent) 120g
Microcrystalline Cellulose (fluidizer) 70g
5%PVP
K30Ethanol solution (binding agent) 140g
Magnesium stearate (lubricant) 3g
Preparation technology is with prescription B.Dispersible tablet is limited to 1.2min when disperseing.
Prescription K
Zolmitriptan 0.6g
Hydroxypropyl starch (disintegrating agent) 168g
10%PVPk30 alcoholic solution (binding agent) 100g
Magnesium stearate (lubricant) 2g
Preparation technology is with prescription B.Dispersible tablet is limited to 0.8min when disperseing.
Prescription L
Zolmitriptan 0.6g
Sodium carboxymethyl cellulose (disintegrating agent) 168g
Sodium alginate (disintegrating agent) 30g
10%PVPk30 alcoholic solution (binding agent) 100g
Magnesium stearate (lubricant) 2g
Preparation technology is with prescription B.Dispersible tablet is limited to 0.7min when disperseing.
Prescription M
Zolmitriptan 0.8g
Hydroxy acid cellulose (disintegrating agent) 200g
Guar gum (disintegrating agent) 50g
Preparation technology: principal agent is crossed 100 mesh sieves, and disintegrating agent is crossed 80 mesh sieves, takes by weighing principal agent, the disintegrating agent mix homogeneously of recipe quantity, adds dehydrated alcohol and granulates in right amount, and dry back tabletting promptly.Dispersible tablet is limited to 0.9min when disperseing.
Zolmitriptan dispersible tablet dispersing uniformity and dissolution in vitro inspection
1, Zolmitriptan dispersible tablet dispersing uniformity is checked
The Zolmitriptan dispersible tablet (A～M), its dispersing uniformity experimental technique is as follows for prescription: get 2 of this product, put jolting in the 100ml water, and in 20 ℃ ± 1 ℃ water, all disintegrates and sieve in 3 minutes by No. 2.See table explanation 1～13 for details.
2, the mensuration of Zolmitriptan dispersible tablet dissolution in vitro
The Zolmitriptan dispersible tablet (prescription A～M), its dissolution in vitro experimental technique is as follows: get this product according to dissolution method (two appendix X of Chinese Pharmacopoeia version in 2000 C, first method) device, with water 900ml is solvent, and rotating speed is that per minute 100 changes, operation in accordance with the law, in the time of 30 minutes, get solution 10ml, filter, get subsequent filtrate 5ml and place the 100ml measuring bottle, be diluted with water to scale, as need testing solution.According to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A), measure trap at 269nm wavelength place; In addition precision takes by weighing that to put the Zolmitriptan reference substance of constant weight through 105 ℃ of dryings an amount of, with water dissolution and quantitatively dilution make the solution that contains 10 μ g among every 1ml, measure trap with method, calculate every stripping quantity, limit is 80% of a labelled amount, should be up to specification.See table 1～13 for details.
Table 1: the cumulative in vitro dissolution of prescription A
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????82 | ????89 | ????93 | ????97 | ????99 | ????99 |
| Disperse the time limit | 1.0min disintegrate, and can be all by No. 2 sieves | |||||
Table 2: the cumulative in vitro dissolution of prescription B
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????69 | ????77 | ????85 | ????92 | ????99 | ????99 |
| Disperse the time limit | 1.2min disintegrate, and can be all by No. 2 sieves | |||||
Table 3: the cumulative in vitro dissolution of prescription C
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????93 | ????95 | ????97 | ????97 | ????99 | ????99 |
| Disperse the time limit | 0.6min disintegrate, and can be all by No. 2 sieves | |||||
Table 4: the cumulative in vitro dissolution of prescription D
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????80 | ????93 | ????97 | ????97 | ????98 | ????99 |
| Disperse the time limit | 0.8min disintegrate, and can be all by No. 2 sieves | |||||
Table 5: the cumulative in vitro dissolution of prescription E
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????87 | ????95 | ????99 | ????99 | ????99 | ????99 |
| Disperse the time limit | 0.7min disintegrate, and can be all by No. 2 sieves | |||||
Table 6: the cumulative in vitro dissolution of prescription F
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????63 | ????74 | ????81 | ????90 | ????93 | ????96 |
| Disperse the time limit | 1.5min disintegrate, and can be all by No. 2 sieves | |||||
Table 7: the cumulative in vitro dissolution of prescription G
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????65 | ????75 | ????83 | ????91 | ????95 | ????99 |
| Disperse the time limit | 1.4min disintegrate, and can be all by No. 2 sieves | |||||
Table 8: the cumulative in vitro dissolution of prescription H
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????70 | ????85 | ????91 | ????96 | ????99 | ????99 |
| Disperse the time limit | 1.3min disintegrate, and can be all by No. 2 sieves | |||||
Table 9: the cumulative in vitro dissolution of prescription I
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????80 | ????89 | ????93 | ????96 | ????99 | ????99 |
| Disperse the time limit | 0.9min disintegrate, and can be all by No. 2 sieves | |||||
Table 10: the cumulative in vitro dissolution of prescription J
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????76 | ????89 | ????93 | ????97 | ????99 | ????99 |
| Disperse the time limit | 1.2min disintegrate, and can be all by No. 2 sieves | |||||
Table 11: the cumulative in vitro dissolution of prescription K
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????81 | ????89 | ????93 | ????96 | ????99 | ????99 |
| Disperse the time limit | 0.8min disintegrate, and can be all by No. 2 sieves | |||||
Table 12: the cumulative in vitro dissolution of prescription L
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????86 | ????91 | ????96 | ????97 | ????99 | ????99 |
| Disperse the time limit | 0.7min disintegrate, and can be all by No. 2 sieves | |||||
Table 13: the cumulative in vitro dissolution of prescription M
| Time (min) | ????5 | ????10 | ????15 | ????20 | ????25 | ????30 |
| Accumulation dissolution (%) | ????71 | ????84 | ????91 | ????96 | ????98 | ????99 |
| Disperse the time limit | 0.9min disintegrate, and can be all by No. 2 sieves | |||||
Claims (5)
1, a kind of immediate release drug dosage form of Zolmitriptan, it is characterized in that containing in its preparation prescription Zolmitriptan and disintegrating agent, described disintegrating agent is one or more in starch, pregelatinized Starch, carboxymethyl starch sodium, microcrystalline Cellulose, hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, hydroxypropyl starch, sodium alginate, hydroxy acid cellulose, sodium carboxymethyl cellulose, methacrylic acid, divinylbenzene copolyesters, IRP-88, guar gum, Herba Xanthii glue, glucosan, the carboxymethylcellulose calcium.
2, Zolmitriptan quick-release formulation as claimed in claim 1 is characterized in that also containing in its preparation prescription binding agent, lubricant or fluidizer.
3, quick releasing formulation as claimed in claim 2 is characterized in that described binding agent is PVPk30 ethanol solution, PVPk30 alcoholic solution, PVPk30 aqueous solution or starch slurry; Described lubricant or fluidizer are hard magnesium, micropowder silica gel or microcrystalline Cellulose.
4, Zolmitriptan quick-release formulation as claimed in claim 1, the content that it is characterized in that every middle Zolmitriptan is 0.2～25mg.
5, Zolmitriptan quick-release formulation as claimed in claim 1, the content that it is characterized in that every middle disintegrating agent is 2～99.6%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100961698A CN100341504C (en) | 2004-12-01 | 2004-12-01 | Zolmitriptan quick-release formulation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100961698A CN100341504C (en) | 2004-12-01 | 2004-12-01 | Zolmitriptan quick-release formulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1634043A true CN1634043A (en) | 2005-07-06 |
| CN100341504C CN100341504C (en) | 2007-10-10 |
Family
ID=34847845
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100961698A Active CN100341504C (en) | 2004-12-01 | 2004-12-01 | Zolmitriptan quick-release formulation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100341504C (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103340854A (en) * | 2013-06-24 | 2013-10-09 | 成都天台山制药有限公司 | Stable zolmitriptan tablet |
| US8962650B2 (en) | 2011-04-18 | 2015-02-24 | Eisai R&D Management Co., Ltd. | Therapeutic agent for tumor |
| US9334239B2 (en) | 2012-12-21 | 2016-05-10 | Eisai R&D Management Co., Ltd. | Amorphous form of quinoline derivative, and method for producing same |
| US9945862B2 (en) | 2011-06-03 | 2018-04-17 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
| US10259791B2 (en) | 2014-08-28 | 2019-04-16 | Eisai R&D Management Co., Ltd. | High-purity quinoline derivative and method for manufacturing same |
| US10517861B2 (en) | 2013-05-14 | 2019-12-31 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| US11090386B2 (en) | 2015-02-25 | 2021-08-17 | Eisai R&D Management Co., Ltd. | Method for suppressing bitterness of quinoline derivative |
| US11369623B2 (en) | 2015-06-16 | 2022-06-28 | Prism Pharma Co., Ltd. | Anticancer combination of a CBP/catenin inhibitor and an immune checkpoint inhibitor |
| US11547705B2 (en) | 2015-03-04 | 2023-01-10 | Merck Sharp & Dohme Llc | Combination of a PD-1 antagonist and a VEGF-R/FGFR/RET tyrosine kinase inhibitor for treating cancer |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6024981A (en) * | 1997-04-16 | 2000-02-15 | Cima Labs Inc. | Rapidly dissolving robust dosage form |
| GB9928578D0 (en) * | 1999-12-03 | 2000-02-02 | Zeneca Ltd | Pharmaceutical formulations |
| US20020001617A1 (en) * | 2000-05-26 | 2002-01-03 | Chang-Hyun Lee | Rapidly disintegrating tablet and process for the manufacture thereof |
| CN1506043A (en) * | 2002-12-11 | 2004-06-23 | 成都博瑞医药科技开发有限公司 | Quickly disintegrating tablet containing cadotril |
-
2004
- 2004-12-01 CN CNB2004100961698A patent/CN100341504C/en active Active
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8962650B2 (en) | 2011-04-18 | 2015-02-24 | Eisai R&D Management Co., Ltd. | Therapeutic agent for tumor |
| US9945862B2 (en) | 2011-06-03 | 2018-04-17 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
| US11598776B2 (en) | 2011-06-03 | 2023-03-07 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
| US9334239B2 (en) | 2012-12-21 | 2016-05-10 | Eisai R&D Management Co., Ltd. | Amorphous form of quinoline derivative, and method for producing same |
| US10517861B2 (en) | 2013-05-14 | 2019-12-31 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| CN103340854B (en) * | 2013-06-24 | 2014-10-15 | 成都天台山制药有限公司 | Stable zolmitriptan tablet |
| CN103340854A (en) * | 2013-06-24 | 2013-10-09 | 成都天台山制药有限公司 | Stable zolmitriptan tablet |
| US10407393B2 (en) | 2014-08-28 | 2019-09-10 | Eisai R&D Management Co., Ltd. | High-purity quinoline derivative and method for manufacturing same |
| US10822307B2 (en) | 2014-08-28 | 2020-11-03 | Eisai R&D Management Co., Ltd. | High-purity quinoline derivative and method for manufacturing same |
| US11186547B2 (en) | 2014-08-28 | 2021-11-30 | Eisai R&D Management Co., Ltd. | High-purity quinoline derivative and method for manufacturing same |
| US10259791B2 (en) | 2014-08-28 | 2019-04-16 | Eisai R&D Management Co., Ltd. | High-purity quinoline derivative and method for manufacturing same |
| US11090386B2 (en) | 2015-02-25 | 2021-08-17 | Eisai R&D Management Co., Ltd. | Method for suppressing bitterness of quinoline derivative |
| US11547705B2 (en) | 2015-03-04 | 2023-01-10 | Merck Sharp & Dohme Llc | Combination of a PD-1 antagonist and a VEGF-R/FGFR/RET tyrosine kinase inhibitor for treating cancer |
| US12083112B2 (en) | 2015-03-04 | 2024-09-10 | Eisai R&D Management Co., Ltd. | Combination of a PD-1 antagonist and a VEGFR/FGFR/RET tyrosine kinase inhibitor for treating cancer |
| US11369623B2 (en) | 2015-06-16 | 2022-06-28 | Prism Pharma Co., Ltd. | Anticancer combination of a CBP/catenin inhibitor and an immune checkpoint inhibitor |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100341504C (en) | 2007-10-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100341504C (en) | Zolmitriptan quick-release formulation | |
| CN101073563A (en) | Chiral composition containing dextrothyroxine buprofenli and levomethadyl cysteliqin and its double slow-releasing tablet | |
| CN1911209A (en) | Quick-disintegration tablets of calcium atovastatine, and its prepn. method | |
| CN1287792C (en) | Dispersive tablet of montelukast sodium | |
| CN1883480A (en) | A pharmaceutical composition containing rupatatine | |
| CN1732953A (en) | Dispersible tablet for treating hypertension | |
| CN1485037A (en) | Medication comprising nicotinic acid and tatin-like medicine | |
| CN1316978C (en) | Compound glucosamine sulfate dispersible tablet formulation and its preparation method | |
| CN1270712C (en) | Felodipine controlled-release preparation | |
| CN1443535A (en) | Tegasevod maleate oral preparation and its preparation process-for curing intestinal irritability syndrome | |
| CN1868466A (en) | Buluoweima slow-release tablet and its preparing method | |
| CN1919185A (en) | Compound ammonium glycyrrhizinato S dispersed tablet and its preparing process | |
| CN1175811C (en) | Slow-releasing Anixitan tablet | |
| CN1303990C (en) | Sodium ferulate oral disintegrating tablet and its preparation process | |
| CN1742726A (en) | Piperazine ferulate oral cavity disintegrating tablet and preparing method | |
| CN1309387C (en) | Cresol powder with dissolution increased and its preparing method-analgesic, antipyretic and anti-inflammatory agent | |
| CN100337625C (en) | Anastrozole dispersed tablet formulation | |
| CN1193755C (en) | Fast disintegrated and stripped oral cilostazol table and its prepn process | |
| CN1634066A (en) | Dispersible tablet of alfuzosin hydrochloride | |
| CN1726916A (en) | Oral disintegration tablet for dropping blood sugar and preparation method | |
| CN1957942A (en) | External preparation of Levocetirizine hydrochloric acid | |
| CN1628646A (en) | Dispersed tablet of tartaric acid tolterodine tartrate | |
| CN101066252A (en) | Aminoglucose calcium tablet and its prepn process | |
| CN1778325A (en) | Disperse tablet for activating bood and stopping pain and its preparation | |
| CN1287795C (en) | Acipimox Dispersible tablet |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |