CN104887641B - Pabuk former times profit cloth gastric floating tablet and preparation method thereof - Google Patents
Pabuk former times profit cloth gastric floating tablet and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to pharmaceutical technology field, is related to a kind of Pabuk former times profit cloth gastric floating tablet and preparation method, described gastric floating tablet each component and its mass percent are：Pabuk former times profit cloth 10% 30%, hydroxypropyl methylcellulose 20% 50%, bleach activator 20% 40%, foaming agent 2% 10%, microcrystalline cellulose 0% 25%, magnesium stearate 0.5 3%.Preparation technology can use dry granulation or wet granulation technology.It is an object of the invention to provide a kind of high bioavilability, in the Pabuk former times profit cloth gastric floating tablet of slow releasing trend, effectively reduction medication total amount.The unique advantage of the present invention is：Gastric floating tablet is prepared using two kinds of different mechanism, obtained tablet can keep the flotation time of more than 10 hours in gastric juice, and the sustained release in pH1.2 hydrochloric acid solutions, medicine is effectively avoided bioavilability is low extremely caused by indissoluble after pH is higher than 4 the problem of, reduce medicining times, mitigate toxic side effect, effectively improve patient's compliance.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of Pabuk former times profit cloth gastric floating tablet and preparation method thereof.
Background technology
Cyclin dependent kinase 4/6 (cyclin-dependent kinase4/6, CDK4/6) inhibitor, can press down
Throwing/threonine kinase is combined with cyclin D, and blocks cellular is changed from the G1 phases to the S phases.CDK4/6 inhibitor is as small point
Sub- targeted drug is antitumor, and advantage is：Selective depression CDK4/6, the cytotoxicity of " general-CDK inhibitor " is not shown,
As bone marrow suppression and enteron aisle are reacted；Because the cyclin D levels of tumour cell are high compared with normal cell, and increase tumour cell pair
The sensitiveness of medicine, and then increase the targeting of medicine.
Pabuk former times profit cloth（palbociclib）It is CDK4/6 selective depressant, chemistry is entitled：6- acetyl group -8- rings
Amyl group -5- methyl -2- [[5- (piperazine -1- bases) pyridine -2- bases] amino] -8H- pyridos [2,3-d] pyrimidin-7-ones.Its structure
Belong to Pyridopyrimidine class, selective depression CDK4 and CDK6, IC50（The ratio between apoptotic cell and whole cell numbers are equal to 50% when institute
Corresponding concentration）Respectively 11 and 15nmol/L, and 10 μm of ol/L are more than to CDK2, CDK1, CDK5 IC50.This product is by Pfizer
Register of company declares, the 2 months 2015 CDK4/6 inhibitor by the first approval of U.S. FDA, for menopausal women late period or
The first-line treatment of metastatic ER+/HER2- breast cancer；Clinical test before listing includes：High-risk early-stage breast cancer（III phase
It is clinical）, liver cancer（II phase is clinical）, epithelial ovarian cancer（II phase is clinical）, leukaemia（The a phases of I b/ II are clinical）Non-small cell lung cancer
（II/III phase is clinical）, Huppert's disease（I/II phase is clinical）, colorectal cancer liver cancer（I phase is clinical）, embryonal-cell lipoma（II phase faced
Bed）, melanoma（I/II phase is clinical）, lymphoma mantle cell（I phase is clinical）, solid tumor（II phase is clinical）.It is glue that it, which lists formulation,
Wafer, specification 75mg, 100mg and 125mg.
Pabuk former times profit is furnished with 2 pKa values, and respectively 3.9 and 7.4.When pH value is less than 4, solubility is high；PH value is higher than 4
When, drug solubility is remarkably decreased, about 0.009mg/ml.The absolute bioavailability of its conventional capsule agent is about 46%, and
Absorb by whether feeding and influenceing, under non-fed conditions, bioavilability is about 13%.Thus, it can be seen that not feeding, cause medicine
Gastric emptying time reduces, and quickly reaches small intestine（Physiological pH is higher than 4）And aiding reduces drug solubility, and then reduce biological utilisation
Degree.
Gastric floating tablet（floating tablets）Also known as gastric stagnation tablets, floating drug delivery system or hydrodynamic equilibrium system
System, after referring to orally autologous density can be kept to be less than gastric content density（1.004~1.01g/cm3）, and in floating in gastric juice
The preparation of state, the floating preparation mainly designed according to hydrodynamically balanced system.Different according to floating mechanism, it can divide
For effervescence type and non-effervescence type.Effervescence type gastric floating tablet is mainly by main ingredient, hydrophilic gel and foaming agent（Carbonate etc.）Composition；It is non-
Effervescence type gastric floating tablet is mainly realized using the bleach activator such as fatty alcohol, aliphatic acid etc. of autologous density less than gastric juice density.For up to
To optimal flotation property, the present invention applies both floating mechanism simultaneously.Therefore, Pabuk former times profit cloth gastric floating tablet is developed,
Portion on the gastrointestinal tract can be extended（Physiological pH is less than 4）Holdup time, make medicine as far as possible discharge, fully absorb into vivo, and then
Effectively avoid being decreased obviously for bioavilability.
The domestic and international patent about Pabuk former times profit cloth includes compound patent（CN101001857B, CN101906104B
Deng）, technique patent（CN101511829A）, use patent（CN102231984A etc.）, composition patent（US2014/
0080838A1 etc.）.Temporarily without formulation patent.
The content of the invention
The present invention for Pabuk former times profit cloth pH value higher than 4 extremely indissoluble and the problem of be in low bioavilability, there is provided one
Kind Pabuk former times profit cloth gastric floating tablet and preparation method thereof.Obtained Pabuk former times profit cloth gastric floating tablet passes through effervescence type and non-effervesce
Two kinds of floating mechanismic designs of type form.Its rise drift the time be less than 15min, persistently the flotation time be higher than 10h, effectively facilitate medicine and exist
Stomach and duodenum release and absorption, reach constant complete, the raising bioavilability that releases the drug, reduce medication dose, raising trouble
Person's compliance.Also, dry granulation tabletting or wet granule compression tablet technique can be used to be prepared as gastric floating tablet, step is succinct, can
Industrialized production.
Pabuk former times profit cloth gastric floating tablet provided by the invention is using Pabuk former times profit cloth as active component, with hypromellose
Element, bleach activator, foaming agent are floating and slow-release material, using microcrystalline cellulose and magnesium stearate as excipient, specific component
And its mass percent is as follows：
Pabuk former times profit cloth 10%-30%, hydroxypropyl methylcellulose 20%-50%, bleach activator 20%-40%, foaming agent 2%-10%,
Microcrystalline cellulose 0%-25%, magnesium stearate 0.5%-3%.
Hydroxypropyl methylcellulose in described Pabuk former times profit cloth gastric floating tablet, model preferably are selected from K4M（Dow Chemical company
Product, trade name：METHOCELTMK4M Premium CR, 2% average viscosity are about 4000 mPa.s, and methoxyl content exists
In the range of 19.0% ~ 24.0%, hydroxypropoxy content is 4.0% ~ 12.0%）、K15M（Dow Chemical Products, trade name：
METHOCELTMK15M Premium CR, 2% average viscosity are 15,000 cps, and methoxyl content is in 19.0% ~ 24.0% scope
Interior, hydroxypropoxy content is 4.0% ~ 12.0%）And K100M（Dow Chemical Products, trade name：METHOCELTM
K100M Premium CR, 2% average viscosity are 100,000, and in the range of 19.0% ~ 24.0%, propoxyl contains methoxyl content
Amount is 4.0% ~ 12.0%）In one or more.Hydroxypropyl methylcellulose as hydrophilic gel material, can water absorption and swelling, volume increases
Add, there is provided the buoyancy for maintaining tablet persistently to float, while tablet volume increases and extends the gastric emptying time；And sustained release can be used as
Material, sustained drug is set slowly to discharge.
It is described to help and bleach activator mass percent is preferably 25%-35% in described Pabuk former times profit cloth gastric floating tablet formula
Drift agent preferably is selected from the one or more in aliphatic acid, fatty alcohol and fatty ester,；Such bleach activator relative density is smaller, and is fat
Fat class, it can play and help drift and sustained release double action, belong to one of composition of non-effervescence type stomach floating system.
And the preferred stearic acid of aliphatic acid in being formulated, the preferred hexadecanol of selected fatty alcohol, selected fatty ester are preferably single
Tristerin.
Foaming agent preferably is selected from one kind in sodium acid carbonate, sodium carbonate and sodium citrate in Pabuk former times profit cloth gastric floating tablet formula
It is or a variety of.When foaming agent contacts with hydrochloric acid in gastric juice, carbon dioxide is produced so that tablet floats, and belongs to effervescence type stomach floating system
One of composition.
In described Pabuk former times profit cloth gastric floating tablet, every contains Pabuk former times profit cloth 50mg ~ 200mg.
The described Pabuk former times profit cloth gastric floating tablet drift time is less than 15min, and the lasting flotation time is higher than 10h.Because combining
Non- effervescence type and effervescence type stomach floating mechanism, Pabuk former times profit cloth play that the drift time is quick, reached less than 5min when playing drift
Between, so that after tablet is oral, quickly floated in stomach, avoid the rapid gastric emptying under fasting conditions, and stomach can not be played
The effect of interior delay.After tablet plays drift, more than 10h flotation time can be maintained, allows more Pabuk former times profit cloth to be discharged in stomach,
Formed solution, and pH less than 4 gastrointestinal tract environment in absorb, avoid to small intestine, Pabuk former times Li Buyin indissolubles and separate out, nothing
Method is absorbed into vivo.
The preparation technology of Pabuk former times profit cloth gastric floating tablet of the present invention includes dry granulation tabletting or wet granulation pressure
Piece, preferably dry granulation tablet forming technique.
Specifically, dry granulation tabletting prepares Pabuk former times profit cloth gastric floating tablet and comprised the following steps：
（1）By the mass percent of component in Pabuk former times profit cloth gastric floating tablet, each component is weighed；
（2）The Pabuk former times profit cloth weighed be crushed into 100 mesh sieves, hydroxypropyl methylcellulose and bleach activator cross 60 mesh sieves respectively,
Then it is mixed uniformly, dry granulation；
（3）Particle obtained above and microcrystalline cellulose, lubricant are mixed, tabletting.
Or wet granule compression tablet technique prepares Pabuk former times profit cloth gastric floating tablet, comprises the following steps：
（1）By the mass percent of component in Pabuk former times profit cloth gastric floating tablet, each component is weighed；
（2）The Pabuk former times profit cloth weighed be crushed into 100 mesh sieves, hydroxypropyl methylcellulose, bleach activator and microcrystalline cellulose point
60 mesh sieves are not crossed, are then mixed uniformly；
（3）Dry particl is made in mixed powder wet granulation obtained above, wet granular drying, sieving with wetting agent；It is described wet
Profit agent is preferably purified water or ethanol water, the ethanol water preferably 75% ethanol water；
（4）Dry particl obtained above and lubricant are mixed, tabletting.
The beneficial effect that the present invention is reached：Compared with the existing unique formulation capsule listed, with similar existing phase
Pass technology is compared, and Pabuk former times profit cloth gastric floating tablet of the present invention and preparation method thereof has advantages below：
1. being formed using two kinds of floating mechanismic designs of effervescence type and non-effervescence type, drift can be quickly played in the solution, when playing drift
Between be less than 15min, majority, which be formulated, to be floated the time and is less than 5min；
2. being formed using two kinds of floating mechanismic designs of effervescence type and non-effervescence type, each functional auxiliary materials can be effectively reduced（Hydroxypropyl
Methylcellulose, bleach activator and foaming agent）Dosage, and then reduce piece weight, be easy to patient and swallow；
3. HPMC and bleach activator usage ratio are about 1:1, while stomach floating effect is played, make respectively
For hydrophilic skeleton slow-release material（Hydroxypropyl methylcellulose）With erodible matrix slow-release material（Bleach activator）, effectively control medicine to release
Speed is put, reaches slow constant release, final release, release rate completely are up to more than 95%；
4. compared with conventional capsule formulation, absorb and be mainly less than 4 gastrointestinal tract site in pH, avoid being higher than in pH 4 intestines
Pabuk former times profit cloth separates out and improves bioavilability in road environment；
5. compared with conventional capsule agent, Pabuk former times profit cloth floating tablet can reach more than 10h slow constant speed release medicine, avoid blood
Side effect caused by concentration fluctuation.
Brief description of the drawings
Fig. 1 is releasing curve diagrams of the embodiment 1-5 in pH1.2 hydrochloric acid solutions.
Embodiment
The invention will be further described below in conjunction with the accompanying drawings.Following examples are only used for clearly illustrating the present invention
Technical scheme, and can not be limited the scope of the invention with this.
Tester in embodiment is as follows：
A, Determination of Hardness：YD-1 tablet hardness testers
B, drug release determination：RC806 digestion instruments
C, assay：752C ultraviolet specrophotometers
Embodiment 1：
Pabuk former times profit cloth gastric floating tablet prescription is：
| Supplementary material | G/100 pieces |
| Pabuk former times profit cloth | 5 |
| Hydroxypropyl methylcellulose | 15 |
| Bleach activator | 17.5 |
| Foaming agent | 2 |
| Microcrystalline cellulose | 10 |
| Magnesium stearate | 0.5 |
Described hydroxypropyl methylcellulose, model K4M.
Described bleach activator is aliphatic acid, and described aliphatic acid is stearic acid.
Described foaming agent is sodium acid carbonate.
Preparation method：Pabuk former times profit cloth be crushed into 100 mesh sieves, hydroxypropyl methylcellulose and bleach activator cross 60 mesh sieves respectively,
Then it is mixed uniformly；Pressure is large stretch of（Hardness is 2 ~ 3kg/mm2）, cross 20 mesh sieves and be prepared into dry particl；Add the micro- of recipe quantity
Crystalline cellulose and magnesium stearate, it is well mixed, tabletting produces.
Embodiment 2：
Pabuk former times profit cloth gastric floating tablet prescription is：
| Supplementary material | G/100 pieces |
| Pabuk former times profit cloth | 20 |
| Hydroxypropyl methylcellulose | 20 |
| Bleach activator | 13.3 |
| Foaming agent | 4.7 |
| Microcrystalline cellulose | 6.6 |
| Magnesium stearate | 2 |
Described hydroxypropyl methylcellulose, model K4M and K100M.Wherein HPMC K4M is 6.7g, hydroxypropyl first
Cellulose K100M is 13.3g,
Described bleach activator is fatty alcohol, and described fatty alcohol is hexadecanol.
Described foaming agent is sodium carbonate.
Preparation method：Pabuk former times profit cloth be crushed into 100 mesh sieves, hydroxypropyl methylcellulose, bleach activator and microcrystalline cellulose point
60 mesh sieves are not crossed, are then mixed uniformly；With 75% ethanol water wet granulation, drying, sieve and dry particl is made；Will be upper
The particle for stating to obtain mixes with lubricant, tabletting.
Embodiment 3：
Pabuk former times profit cloth gastric floating tablet prescription is：
| Supplementary material | G/100 pieces |
| Pabuk former times profit cloth | 12.5 |
| Hydroxypropyl methylcellulose | 31.25 |
| Bleach activator | 12.5 |
| Foaming agent | 5.63 |
| Magnesium stearate | 0.63 |
Described hydroxypropyl methylcellulose, model K4M.
Described bleach activator is fatty ester, and described fatty alcohol is glycerin monostearate.
Described foaming agent is sodium citrate.
Preparation method：Pabuk former times profit cloth be crushed into 100 mesh sieves, hydroxypropyl methylcellulose and bleach activator cross 60 mesh sieves respectively,
Then it is mixed uniformly；Pressure is large stretch of（Hardness is 2 ~ 3kg/mm2）, cross 20 mesh sieves and be prepared into dry particl；Add the hard of recipe quantity
Fatty acid magnesium, it is well mixed, tabletting produces.
Embodiment 4：
Pabuk former times profit cloth gastric floating tablet prescription is：
| Supplementary material | G/100 pieces |
| Pabuk former times profit cloth | 15 |
| Hydroxypropyl methylcellulose | 15 |
| Bleach activator | 30 |
| Foaming agent | 1.5 |
| Microcrystalline cellulose | 11.25 |
| Magnesium stearate | 2.25 |
Described hydroxypropyl methylcellulose, model K15M.
Described bleach activator is aliphatic acid, and described aliphatic acid is stearic acid.
Described foaming agent is sodium acid carbonate.
Preparation method：Pabuk former times profit cloth be crushed into 100 mesh sieves, hydroxypropyl methylcellulose and bleach activator cross 60 mesh sieves respectively,
Then it is mixed uniformly；Pressure is large stretch of（Hardness is 2 ~ 3kg/mm2）, cross 20 mesh sieves and be prepared into dry particl；Add the micro- of recipe quantity
Crystalline cellulose and magnesium stearate, it is well mixed, tabletting produces.
Embodiment 5：
Pabuk former times profit cloth gastric floating tablet prescription is：
| Supplementary material | G/100 pieces |
| Pabuk former times profit cloth | 7.5 |
| Hydroxypropyl methylcellulose | 13.125 |
| Bleach activator | 7.5 |
| Foaming agent | 3.75 |
| Microcrystalline cellulose | 5.25 |
| Magnesium stearate | 0.375 |
Described hydroxypropyl methylcellulose, model K4M and K15M.Wherein HPMC K4M is 5.625g, hydroxypropyl first
Cellulose K15M is 7.5g,
Described bleach activator is aliphatic acid, and described fatty alcohol is stearic acid.
Described foaming agent is sodium carbonate.
Preparation method：Pabuk former times profit cloth be crushed into 100 mesh sieves, hydroxypropyl methylcellulose, bleach activator and microcrystalline cellulose point
60 mesh sieves are not crossed, are then mixed uniformly；With 75% ethanol water wet granulation, drying, sieve and dry particl is made；Will be upper
The particle for stating to obtain mixes with lubricant, tabletting.
Result of the test
Specifically, the sample prepared in Example, pH1.2 dilute hydrochloric acid solution 900ml is dissolution medium, using turning basket
Method, rotating speed are 100 turns/min, 37 ± 1 DEG C of temperature, drug release rate are measured by sampling in 1h, 3h, 5h, 8h, 10h and 12h.
The sample of Example 2, Rotating shaker, rotating speed 100 are used by dissolution medium of pH4.0 acetate buffers 900ml
Turn/min, 37 ± 1 DEG C of temperature, drug release rate is measured by sampling in 1h, 3h, 5h, 8h, 10h and 12h.
Conventional capsule is taken, using Rotating shaker, rotating speed is 100 turns/min, 37 ± 1 DEG C of temperature, respectively with pH1.2 watery hydrochloric acid
Solution, or pH4.0 acetate buffers, or pH6.8 phosphate buffers pH900ml are dissolution medium, are surveyed in 1h and 3h samplings
Determine drug release rate.
Pabuk former times profit cloth gastric floating tablet made from above-described embodiment is taken, it is investigated and plays drift time, flotation time and pH1.2 salt
Release profiles are obtained in acid solution.Conventional capsule with same specification simultaneously（Major auxiliary burden is：Lactose, microcrystalline cellulose, carboxymethyl form sediment
Powder sodium, silica and magnesium stearate）Stripping curve be compared.
The release of the embodiment 1-5 of table 1 and conventional capsule in pH1.2 hydrochloric acid solutions
Take Pabuk former times profit cloth gastric floating tablet and conventional capsule made from above-described embodiment 2, simulation two kinds of formulations are in vivo
Gastrointestinal tract environment, determines release profiles of the embodiment 1 in pH1.2 and p4.0, and measure conventional capsule is molten in pH4.5 and pH6.8
Go out curve.
The release of the embodiment 2 of table 2 and conventional capsule in different pH dissolution mediums
By above-mentioned experimental result, embodiment 1-5 risen in pH1.2 hydrochloric acid solutions drift the time be below 15min, float
The floating time can maintain more than 10h, and burst size is above 90% after 12h.Embodiment 2 can be tieed up in pH4.0 acetate buffers
Hold more than 10h to be sustained, final burst size is about 84%；By comparison, conventional capsule need to be in full intestinal absorption, but it is in pH6.8 phosphorus
Burst size is obtained in phthalate buffer and is less than 20%.Therefore, gastric floating tablet can be predicted to release completely in pH4.0 gastrointestinal tract environment
Put and absorbed；And conventional capsule is orally to small intestine（PH is higher than 4.5）Afterwards, because solubility drastically declines, and can not dissolution, less
It can be absorbed by the body.
In summary, Pabuk former times profit cloth gastric floating tablet and common glue made from proportioning and processing technology provided by the present invention
Capsule is compared, and can effectively improve drug bioavailability, and can slow constant release.
Described above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, without departing from the technical principles of the invention, some improvement and deformation can also be made, these are improved and deformation
Also it should be regarded as protection scope of the present invention.
Claims (10)
1. a kind of Pabuk former times profit cloth gastric floating tablet, it is characterised in that each component and its mass percent are in the gastric floating tablet：
Pabuk former times profit cloth 10%-30%, hydroxypropyl methylcellulose 20%-50%, bleach activator 20%-40%, foaming agent 2-10%, microcrystalline cellulose
Plain 0%-25%, magnesium stearate 0.5%-3%.
A kind of 2. Pabuk former times profit cloth gastric floating tablet according to claim 1, it is characterised in that the quality hundred of the bleach activator
It is 25%-35% to divide ratio.
3. a kind of Pabuk former times profit cloth gastric floating tablet according to claim 1, it is characterised in that the bleach activator is selected from fat
One or more in acid, fatty alcohol and fatty ester.
4. a kind of Pabuk former times profit cloth gastric floating tablet according to claim 3, it is characterised in that the aliphatic acid is tristearin
Acid, the fatty alcohol are hexadecanol, and the fatty ester is glycerin monostearate.
A kind of 5. Pabuk former times profit cloth gastric floating tablet according to claim any one of 1-4, it is characterised in that the foaming agent
One or more selected from sodium acid carbonate, sodium carbonate and sodium citrate.
A kind of 6. Pabuk former times profit cloth gastric floating tablet according to claim 5, it is characterised in that every Pabuk former times profit cloth stomach drift
Floating piece contains Pabuk former times profit cloth 50mg-200mg.
A kind of 7. Pabuk former times profit cloth gastric floating tablet according to claim 6, it is characterised in that the Pabuk former times profit cloth stomach drift
The floating piece drift time is less than 15min, and the lasting flotation time is higher than 10h.
8. the method for Pabuk former times profit cloth gastric floating tablet as claimed in claims 6 or 7 is prepared, including dry granulation tabletting or wet method
Pelletizing press sheet, it is characterised in that the dry granulation tabletting comprises the following steps：
（1）By the mass percent of component in Pabuk former times profit cloth gastric floating tablet, each component is weighed；
（2）The Pabuk former times profit cloth weighed be crushed into 100 mesh sieves, hydroxypropyl methylcellulose and bleach activator cross 60 mesh sieves respectively, then
It is mixed uniformly, dry granulation；
（3）Particle obtained above and microcrystalline cellulose, magnesium stearate are mixed, tabletting.
9. the method according to claim 8 for preparing Pabuk former times profit cloth gastric floating tablet, it is characterised in that the wet granulation
Tabletting comprises the following steps：
（1）By the mass percent of component in Pabuk former times profit cloth gastric floating tablet, each component is weighed；
（2）The Pabuk former times profit cloth weighed be crushed into 100 mesh sieves, hydroxypropyl methylcellulose, bleach activator and microcrystalline cellulose mistake respectively
60 mesh sieves, then it is mixed uniformly；
（3）Dry particl is made in mixed powder wet granulation obtained above, wet granular drying, sieving with wetting agent；
（4）Dry particl obtained above and magnesium stearate are mixed, tabletting.
10. the method according to claim 9 for preparing Pabuk former times profit cloth gastric floating tablet, it is characterised in that the wetting agent
For purified water or ethanol water.
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| CN201510162791.2A CN104887641B (en) | 2015-04-08 | 2015-04-08 | Pabuk former times profit cloth gastric floating tablet and preparation method thereof |
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Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105816437B (en) * | 2016-03-29 | 2018-08-03 | 深圳市药欣生物科技有限公司 | A kind of pharmaceutical preparation and preparation method thereof of Pabuk former times profit cloth |
| US10449195B2 (en) | 2016-03-29 | 2019-10-22 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical formulation of palbociclib and a preparation method thereof |
| CN106038505A (en) * | 2016-05-27 | 2016-10-26 | 郑州思辩科技有限公司 | Colloidal bismuth pectin intragastric floating sustained release tablet and preparation method thereof |
| CN108014343A (en) * | 2017-12-21 | 2018-05-11 | 孟斯琴 | A kind of pharmaceutical composition for treating breast cancer and preparation method thereof |
| CN108066312B (en) * | 2017-12-29 | 2020-03-20 | 山东裕欣药业有限公司 | Palbociclib pharmaceutical composition and preparation method thereof |
| CN108066303A (en) * | 2017-12-31 | 2018-05-25 | 湖南博隽生物医药有限公司 | A kind of anticancer pharmaceutical composition and preparation method thereof |
| CA3100144C (en) | 2018-05-14 | 2023-10-03 | Pfizer Inc. | Oral solution formulation of palbociclib in malic or lactic acid buffer |
| CN109288806A (en) * | 2018-08-22 | 2019-02-01 | 深圳市华力康生物医药有限公司 | A kind of effervescent tablet of Pabuk former times benefit cloth and its application |
| CN109258963A (en) * | 2018-09-18 | 2019-01-25 | 浙江汇能生物股份有限公司 | A kind of calcium polycarbophil stomach floating particle and the application on livestock and poultry |
| CN114306245A (en) | 2020-09-29 | 2022-04-12 | 深圳市药欣生物科技有限公司 | Pharmaceutical composition of amorphous solid dispersion and preparation method thereof |
| CN115444831B (en) * | 2022-10-25 | 2023-08-22 | 南京康川济医药科技有限公司 | Epalrestat gastric floating tablet and preparation method thereof |
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| CN102231984A (en) * | 2008-10-01 | 2011-11-02 | 北卡罗来纳大学查珀尔希尔分校 | Hematopoietic protection against chemotherapeutic compounds using selective cyclin-dependent kinase 4/6 inhibitors |
| CN103054828A (en) * | 2012-12-26 | 2013-04-24 | 蚌埠丰原涂山制药有限公司 | Ranitidine bismuth citrate intra-gastric floating sustained-release tablet and preparation method thereof |
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