CN104147012B - A kind of oral disintegrated preparation containing ftorafur, Gimeracil and oteracil potassium - Google Patents
A kind of oral disintegrated preparation containing ftorafur, Gimeracil and oteracil potassium Download PDFInfo
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- CN104147012B CN104147012B CN201410418922.4A CN201410418922A CN104147012B CN 104147012 B CN104147012 B CN 104147012B CN 201410418922 A CN201410418922 A CN 201410418922A CN 104147012 B CN104147012 B CN 104147012B
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- gimeracil
- ftorafur
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Abstract
The present invention relates to a kind of containing ftorafur, Gimeracil and the oral disintegrated preparation of three kinds of active component of oteracil potassium, it is possibly together with carbohydrate and disintegrating agent.In oral disintegrated preparation of the present invention, the dissolution of active component is higher, it is ensured that the quick acting of medicine；The more important thing is described oral disintegrated preparation good stability；Without surfactant, reduce the zest to human gastrointestinal tract, improve patient medication compliance；Preparation technology is simple, is suitable for industrialized production.
Description
Technical field
The invention belongs to pharmaceutical preparations technology field, be specifically related to a kind of oral cavity containing ftorafur, Gimeracil and oteracil potassium
Disintegrating preparations.
Background technology
Ftorafur (FT, FT207) is one of miazines anticarcinogen, and it is the prodrug of 5-fluorouracil (5-FU), right
Most solid tumors have inhibitory action.The competent biosynthesis disturbing blocking dna, RNA and protein in vivo, thus produce it and resist
Cancer effect.Being proved by medical basic research and clinical observation, ftorafur toxic and side effects is little, and chemotherapeutic index is higher, to immunosuppressant
Act on and the least on the impact about immunity internal organs, be the safe drugs that can use the most continuously.Through gastrointestinal after this product is oral
Road absorbs, and within 1-3 hour, blood level reaches summit.Last longer than intravenously administrable, therefore its preferable therapeutic effect can be played.
It is mainly used in gastric cancer, cancer of bile ducts, rectal cancer, colon cancer, cancer of pancreas, breast carcinoma, pulmonary carcinoma and incidence cancer.Ftorafur is main
Untoward reaction be symptom of digestive tract, bone marrow depression and neurotoxicity etc..
Gimeracil (i.e. gimeracil CDHP) and oteracil potassium (OXO) individually use does not has obvious anticancer work
Property, they are used in combination with ftorafur is to improve curative effect and reducing toxicity.The effect of CDHP is the anticancer treatment for improving FT
Effect, but after the oral entrance of FT is internal, first under the catalysis of liver P450 activating enzymes, it is transformed into 5-FU, afterwards except about 10%
Enter intestinal also outside orotic acid phosphoribosynltransferase (ORTC) catalysis lower generation phosphorylation, remaining 5-FU of about 90% be
Under the catalysis of liver dihydropyrimidine dehydrogenase (DPD), the approach following 5-FU is transformed into triphosphoric acid floxuridine (FUTP) and
Two activated products of phosphoric acid deoxidation fluorouracil glucoside (FdUMP) play antitumaous effect.So, DPD is the main limit of 5-FU degraded
Speed enzyme, DPD activity is depended in the holding of its blood plasma 5-FU level.CDHP is the reversible inhibitor of DPD.Through comparing,
The effect of CDHP suppression DPD activity is 180 times of uracil, thus can effectively suppress the degraded of 5-FU.It is demonstrated experimentally that
When CDHP:FT coordinates with 0.4: 1 (mol ratio), can make 5-FU effect level in tumor tissues keep 12 hours with
On, the toxicity of intestinal will not be made again to increase.The Main Function of OXO is the activity of suppression small intestine ORTC.For adding
In the metabolic process of fluorine, there is the 5-FU of about 10% to enter intestinal tissue, under the catalysis of ORTC, produce phosphorylation, this
Process is considered to produce the main cause of intestinal toxic and side effects.The another one outstanding feature of OXO be oral enter internal after,
The overwhelming majority is distributed in small intestinal cell surface.Only few part enters blood circulation, tumor tissues and other normal structure.Cause
This, OXO mainly suppresses the effect of 5-FU phosphorylation in small intestine, will not affect the activity of 5-FU in tumor tissues.
When OXO: FT (mol ratio) is 1: 1, higher tumor killing effect can be kept, again can reduction intestinal poison by a relatively large margin
Side reaction.
CN101574326A discloses capsule preparations of a kind of tegafur, gimeracil and oteracil potassium and preparation method thereof, and this invention improves stablizing of tegafur, gimeracil and oteracil potassium
Property, but the dissolution of medicine is not improved, and for ensureing Fast Stripping, adds substantial amounts of surfactant, minimum use
Amount reaches 10mg/ grain, relatively big to GI irritation, uses coating of pellets technology simultaneously, and plant manufacturing process is complicated.
CN1660105A discloses prescription and the preparation technology of a kind of tegafur, gimeracil and oteracil potassium oral cavity disintegration tablet, it is possible to cover the bad bitterness of medicine, medicine
The water solublity of thing is not the most improved.CN101843621A discloses a kind of tegafur, gimeracil and oteracil potassium granule, and active constituents of medicine is made ring
The method of cyclodextrin inclusion compound solves, and to improve dissolution and the bioavailability of medicine, but cyclodextrin inclusion compound technique is complex,
Workshop industrialization produces inconvenience.
CN102302499A discloses a kind of capsule preparations containing ftorafur, gimeracil and oteracil potassium, and this invention improves
Tegafur, gimeracil and oteracil potassium dissolution, for ensureing Fast Stripping, adds surfactant, and consumption reaches 0.9-5mg/ grain, adds GI irritation,
Reduce patient medication compliance.
CN201210055279.4 discloses a kind of oral formulations containing ftorafur, gimeracil and oteracil potassium, containing such as
The active component of lower granularity: ftorafur≤180 μm, gimeracil≤150 μm, oteracil potassium≤150 μm.Live without surface
Property agent, but the little improvement effect to disintegrative of particle diameter is the least.
Ftorafur is alkalescent medicine, and poorly water-soluble shows unstability in an acidic solution.Therefore, medicine disintegration speed is improved
While, also should improve principal agent stability, reduce its toxic and side effects.
Summary of the invention
It is an object of the invention to provide a kind of oral disintegrated preparation containing ftorafur, Gimeracil and oteracil potassium.Said preparation
Without surfactant, there is good stability, the rapid feature of disintegrate.The concrete technical scheme of the present invention is as follows:
A kind of oral disintegrated preparation containing ftorafur, Gimeracil and oteracil potassium, it contains:
Preferably, described carbohydrate is selected from chitosan nano, hydrogenated starch hydrolysate, Dextrose monohydrous, mannitol, Portugal
Grape sugar and lactose in one or more；
Preferably, described carbohydrate consumption is 45.0-68.0 part, preferably 55.0-68.0 part.
Preferably, described disintegrating agent consumption is 4.0-15.0 part, preferably 5-10 part.
Preferably, described disintegrating agent is selected from cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium and friendship
One or more in connection polyvidone；It is preferably polyvinylpolypyrrolidone.
Described oral disintegrated preparation can also contain binding agent, and described binding agent is preferably hypromellose.
Described oral disintegrated preparation can also contain lubricant, it is preferable that described lubricant is selected from micropowder silica gel, Pulvis Talci and tristearin
One or more in acid magnesium, preferably magnesium stearate.
Described oral disintegrated preparation can also contain correctives, it is preferable that described correctives is selected from blueberry flavor, honey peach essence, spinach
One or more in trailing plants essence, Fructus Mangifera Indicae essence.
Described oral disintegrated preparation can also comprise cyclodextrin.
A kind of preparation method of the oral disintegrated preparation containing ftorafur, Gimeracil and oteracil potassium, it comprises the steps of:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent are crossed 80 mesh sieves, mix homogeneously, added
Enter appropriate distilled water, pelletize and be dried, 20 mesh sieve granulate, it is subsequently adding recipe quantity lubricant, mix homogeneously, tabletting and get final product.
In oral disintegrated preparation of the present invention, the dissolution of active component is higher, it is ensured that the quick acting of medicine；The more important thing is described
Oral disintegrated preparation good stability, and without surfactant, reduce the zest to human gastrointestinal tract, improve patient medication
Compliance；Preparation technology is simple, is suitable for industrialized production.
Detailed description of the invention
It is to be appreciated that for those skilled in the art, in an embodiment of the present invention, it is evident that and can
To be easy to make other embodiment of the scope and spirit without departing from the invention described above and amendment, it is all contained in the guarantor of the present invention
In the range of protecting.Therefore, the scope that should not be construed as claims is limited in following example.
Embodiment 1
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 2
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 3
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 4
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, the binding agent hypromellose adding recipe quantity is pelletized, and adds appropriate distilled water, pelletizes and is dried, and 20 mesh sieves are whole
Grain, is subsequently adding recipe quantity lubricant, mix homogeneously, tabletting and get final product.
Embodiment 5
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, carbohydrate, arachidic acid, menthol, disintegrating agent and rectify
80 mesh sieves, mix homogeneously are crossed in taste agent, add appropriate distilled water, pelletize and are dried, 20 mesh sieve granulate, are subsequently adding recipe quantity lubrication
Agent, mix homogeneously, tabletting and get final product.
Embodiment 6
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, the binding agent hypromellose adding recipe quantity is pelletized, and adds appropriate distilled water, pelletizes and is dried, and 20 mesh sieves are whole
Grain, is subsequently adding recipe quantity lubricant, mix homogeneously, tabletting and get final product.
Embodiment 7
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 8
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 9
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 10
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 11
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 12
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 13
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 14
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 15
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 16
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 17
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 18
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Embodiment 19
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and carbohydrate, disintegrating agent and correctives cross 80 mesh sieves,
Mix homogeneously, adds appropriate distilled water, pelletizes and is dried, 20 mesh sieve granulate, is subsequently adding recipe quantity lubricant, mix homogeneously,
Tabletting and get final product.
Comparative example 1
Prescription:
Preparation method:
Ftorafur, Gimeracil and oteracil potassium cross 100 mesh sieves, and hydroxypropylβ-cyclodextrin crosses 80 mesh sieves, adds after mix homogeneously
Enter a small amount of ethanol to be fully ground, after drying, add the mannitol of 80 mesh sieves, carboxymethyl starch sodium and Fructus Citri Limoniae essence, mix homogeneously,
The dried recipe quantity mix lubricant that adds is uniform, tabletting and get final product.
Comparative example 2
Prescription:
Active component granularity be respectively as follows: 80 μm≤ftorafur≤180 μm, 50 μm≤Gimeracil≤150 μm,
50 μm≤oteracil potassium≤150 μm.
Preparation method:
1) dispensing: by prescription weigh lactose, ftorafur, Gimeracil, oteracil potassium, polyvinylpolypyrrolidone, mannitol, polyvidone,
Magnesium stearate.
2) premix: be sequentially added into lactose, ftorafur, Gimeracil, oteracil potassium, friendship in HLSH2-6A type wet granulator
Connection polyvidone, polyvidone, mannitol.Set incorporation time 7 minutes, mixing speed 250 revs/min, cutting knife speed 1500 turns
/ minute.Start wet granulator and start premix.
3) soft material processed: set 3 minutes soft material time processed, mixing speed 250 revs/min, cutting knife speed 1500 revs/min.Unlatching sets
Standby, under stirring, add water or water-ethanol (1: 1 volume ratio) mixed solution makes suitable soft material in right amount.
4) wet granulate: select 5mm × 4mm screen cloth by wet for prepared soft material granulate, set granulate speed 800 revs/min.
5) it is dried: wet granular is added fluidized bed and is dried, controls pellet moisture in the range of≤1.0%.
6) dry granulate: select the screen cloth of aperture 1.2mm, carry out dry granulate.
7) always mix: dry granulate gained granule and magnesium stearate are placed in hopper mixer, mix 5 minutes.
8) corresponding dosage form is prepared: will always mix gained granulation or fill capsule or be distributed into the convenient oral dosage forms such as granule.
The effect of the present invention is further illustrated below by way of experimental example:
1, stability: have an investigation of related substance:
1. influence factor's experiment: preparation is placed under high temperature (60 DEG C), high humidity (92.5%), high light (4500lx ± 500lx) 10
My god, the investigation carrying out having related substance for the 10th day.Related substance is had to use HPLC method to be measured.
2. Acceleration study: store 6 months, in the 6th in preparation is placed under commercially available back the climatic chamber being placed in 40 DEG C/RH75%
The investigation having related substance is carried out during the moon.The results are shown in Table 1.
Table 1. study on the stability result
During influence factor and Acceleration study, in each embodiment, appearance character and the content of sample substantially do not change.By
The result of table 1 is it can be seen that the preparation of the present invention is substantially less than comparative example at the related substance that has of influence factor's experiment and Acceleration study.
Illustrate that the preparation prepared by the present invention can improve the stability of medicine, extend the shelf life of preparation, be conducive to controlling the bad of medicine
Reaction.
2, dissolution is investigated: dissolution method (Chinese Pharmacopoeia two annex XC the first methods of version in 2010), with 0.1mol/L
Aqueous hydrochloric acid solution be dissolution medium, rotating speed is 50 revs/min, and temperature is 37 ± 0.5 DEG C and operates in accordance with the law, when 15 minutes, inhale
Take dissolution fluid 5ml, supplement the dissolution medium of equivalent simultaneously, by the dissolution fluid membrane filtration of 0.45 μm, use high-efficient liquid phase color
Spectrometry measures dissolution, and limit is the 85% of labelled amount, carries out molten as stated above by above-described embodiment and comparative example gained preparation
Go out feature to investigate.
Experimental result shows, raw material need not micronization, and the various embodiments of the present invention dissolution when 6 minutes has all reached 96%
Above, complete dissolution in 9 minutes.Comparative example 1 dissolution 80% in 12 minutes, complete dissolution in 23 minutes；Comparative example 2 is at 15 points
Clock dissolution only 95%.
Claims (9)
1. one kind contains ftorafur, Gimeracil and the oral disintegrated preparation of oteracil potassium, it is characterised in that in parts by weight,
It contains:
One or more in chitosan nano, hydrogenated starch hydrolysate, Dextrose monohydrous of described carbohydrate；
Described disintegrating agent is low-substituted hydroxypropyl cellulose；Described Orally disintegrated dosage form is formed by wet granule compression tablet.
The most according to claim 1, oral disintegrated preparation, it is characterised in that in parts by weight, described carbohydrate consumption is
45.0-68.0 part.
The most according to claim 2, oral disintegrated preparation, it is characterised in that in parts by weight, described carbohydrate consumption is
55.0-68.0 part.
Oral disintegrated preparation the most according to claim 1, it is characterised in that it is possibly together with binding agent.
Oral disintegrated preparation the most according to claim 4, it is characterised in that described binding agent is hypromellose.
The most according to claim 1, oral disintegrated preparation, it is characterised in that it is possibly together with lubricant, described lubricant is selected from micro-
One or more in powder silica gel, Pulvis Talci and magnesium stearate.
Oral disintegrated preparation the most according to claim 6, it is characterised in that described lubricant is magnesium stearate.
The most according to claim 1, oral disintegrated preparation, it is characterised in that it is possibly together with correctives, described correctives is selected from indigo plant
One or more in certain kind of berries essence, honey peach essence, flavoring pineapple essence and Fructus Mangifera Indicae essence.
9. the preparation side of the oral disintegrated preparation containing ftorafur, Gimeracil and oteracil potassium as claimed in claim 1
Method, it is characterised in that it comprises the steps of: ftorafur, Gimeracil and oteracil potassium sieve, carbohydrate,
Disintegrating agent crosses 80 mesh sieves, mix homogeneously, adds appropriate distilled water, pelletizes and is dried, and 20 mesh sieve granulate are subsequently adding prescription
Amount lubricant, mix homogeneously, tabletting and get final product.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510186063.5A CN104840464A (en) | 2014-08-22 | 2014-08-22 | Oral disintegrating preparation containing tegafur, gimeracil and potassium oxonate |
| CN201410418922.4A CN104147012B (en) | 2014-08-22 | 2014-08-22 | A kind of oral disintegrated preparation containing ftorafur, Gimeracil and oteracil potassium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410418922.4A CN104147012B (en) | 2014-08-22 | 2014-08-22 | A kind of oral disintegrated preparation containing ftorafur, Gimeracil and oteracil potassium |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510186063.5A Division CN104840464A (en) | 2014-08-22 | 2014-08-22 | Oral disintegrating preparation containing tegafur, gimeracil and potassium oxonate |
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| Publication Number | Publication Date |
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| CN104147012A CN104147012A (en) | 2014-11-19 |
| CN104147012B true CN104147012B (en) | 2016-08-24 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201510186063.5A Pending CN104840464A (en) | 2014-08-22 | 2014-08-22 | Oral disintegrating preparation containing tegafur, gimeracil and potassium oxonate |
| CN201410418922.4A Active CN104147012B (en) | 2014-08-22 | 2014-08-22 | A kind of oral disintegrated preparation containing ftorafur, Gimeracil and oteracil potassium |
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| CN201510186063.5A Pending CN104840464A (en) | 2014-08-22 | 2014-08-22 | Oral disintegrating preparation containing tegafur, gimeracil and potassium oxonate |
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| CN115025056A (en) * | 2022-06-27 | 2022-09-09 | 郑州大学第一附属医院 | Orally disintegrating preparation containing tegafur, gimeracil and oteracil potassium |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1660105A (en) * | 2004-12-23 | 2005-08-31 | 鲁南制药股份有限公司 | Disintegration piece taken through oral cavity containing Gimeracil and Oteracil Potassium with fluorine being added |
| CN101683324A (en) * | 2008-09-27 | 2010-03-31 | 张晓芳 | Oral disintegrative tablet of sildenafil citrate and preparation method thereof |
| CN102895212A (en) * | 2011-07-25 | 2013-01-30 | 大鹏药品工业株式会社 | Dry pressed coating tablet containing tegafur, gimeracil and oteracil potassium |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102614183B (en) * | 2012-03-05 | 2013-10-30 | 齐鲁制药(海南)有限公司 | Oral preparation containing tegafur, gimeracil and oteracil potassium |
-
2014
- 2014-08-22 CN CN201510186063.5A patent/CN104840464A/en active Pending
- 2014-08-22 CN CN201410418922.4A patent/CN104147012B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1660105A (en) * | 2004-12-23 | 2005-08-31 | 鲁南制药股份有限公司 | Disintegration piece taken through oral cavity containing Gimeracil and Oteracil Potassium with fluorine being added |
| CN101683324A (en) * | 2008-09-27 | 2010-03-31 | 张晓芳 | Oral disintegrative tablet of sildenafil citrate and preparation method thereof |
| CN102895212A (en) * | 2011-07-25 | 2013-01-30 | 大鹏药品工业株式会社 | Dry pressed coating tablet containing tegafur, gimeracil and oteracil potassium |
Non-Patent Citations (1)
| Title |
|---|
| Development of a Pharmacokinetic Model to Optimize the Dosage Regimen of TS-1, a Combination Preparation of Tegafur, Gimeracil and Oteracil Potassium;Saori Inoue等;《Drug Metab. Pharmacokinet》;20071231;第22卷(第3期);162-168 * |
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| Publication number | Publication date |
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| CN104147012A (en) | 2014-11-19 |
| CN104840464A (en) | 2015-08-19 |
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