CN105997883A - Solid dispersion and preparation method and application thereof - Google Patents
Solid dispersion and preparation method and application thereof Download PDFInfo
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- CN105997883A CN105997883A CN201610293223.0A CN201610293223A CN105997883A CN 105997883 A CN105997883 A CN 105997883A CN 201610293223 A CN201610293223 A CN 201610293223A CN 105997883 A CN105997883 A CN 105997883A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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Abstract
The invention discloses solid dispersion with the high bioavailability and a preparation method thereof, a medicinal composition containing the solid dispersion and application. The dispersion contains apixaban and a medicinal enteric-coated carrier material, apixaban is amorphous, and the weight ratio of apixaban to the medicinal enteric-coated carrier material is 1:1 to 1:39. The solid dispersion has the advantages of being high in dissolution rate and uniform in active agent dispersion.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to the high solid dispersion of a kind of bioavailability and preparation side thereof
Method, and comprise Pharmaceutical composition and the application of this solid dispersion.
Background technology
Execute your treasured and the anticoagulant of Pfizer's joint development when Eliquis is hundred, directly act on thrombin
Xa, for treatment phlebothrombosis disease including deep venous thrombosis and pulmonary infarction, in May, 2011, the oral Xa of European Union's approval
The factor direct inhibitor ELIQUIS lists, for the adult patients of select a time hip joint or replacement knee in arthroplasty, to prevent vein
Thrombosis.
Chemistry entitled 4,5,6,7-tetrahydrochysene-1-(4-the methoxyphenyl)-7-oxo-6-of Eliquis [4-(2-oxo-
Piperidino) phenyl]-1H-pyrazolo [3,4-c] pyridine-3-carboxamide, structural formula is as follows:
Eliquis dissolubility and dissolution in physiological fluid is low, and the absorption to Eliquis has a huge impact, thus
It is unfavorable for the effect giving full play to this Eliquis at target spot position so that the bioavailability of Eliquis is relatively low.
Patent of invention CN102908324A (2013.02.06 is open) relate to the system of a kind of Eliquis solid dispersion
Preparation Method, melts particularly as follows: polyethylene glycol 6000 is heated to 60 DEG C, adds Eliquis and is stirred vigorously as 10000-
20000r/min；To the fused mass after stirring at cooling and solidifying rapidly；Solidfied material sieves and drying under reduced pressure obtains Eliquis admittedly
Body dispersion.The product that this invention obtains can improve dissolution, but owing to the fusing point of Eliquis is at 237.7 DEG C, at 60 DEG C
In non-melt state, Eliquis pressed powder is also simply dispersed in melted Polyethylene Glycol by the solid dispersion of gained,
For heterogeneous system, the not solid dispersion of real meaning, Eliquis disperses uneven in products obtained therefrom, impact activity
Agent absorption in vivo.
Summary of the invention
In order to solve the deficiency that prior art exists, the invention provides a kind of dissolution height and activating agent is finely dispersed
Solid dispersion and preparation method thereof, and comprise Pharmaceutical composition and the application of this solid dispersion.
First goal of the invention of the present invention is to provide a kind of solid dispersion, and this solid dispersion has higher dissolution
And activating agent is uniformly dispersed.
Adopt the following technical scheme that for completing the first goal of the invention
A kind of solid dispersion, comprises activating agent and medicinal enteric carrier material, and described activating agent is Eliquis, described Ah piperazine
Husky class is amorphous, and structural formula is:
The weight ratio of described Eliquis and medicinal enteric carrier material is 1:1-1:39.
The weight ratio of described Eliquis and medicinal enteric carrier material is preferably 1:2-1:20, more preferably 1:2-1:
10, most preferably 1:5-1:10.
Preferably, described medicinal enteric carrier material is enteric acrylic polymer, acetic acid hypromellose neighbour's benzene
Dicarboxylic acid esters, Hydroxypropyl Methyl Cellulose Phthalate one or more；It is further preferred that described medicinal enteric carrier is enteric third
Olefin(e) acid resinous polymer and acetic acid Hydroxypropyl methyl cellulose phtalate binary complex carrier；Further preferably, enteric propylene
The weight ratio of acid resin polymer and acetic acid Hydroxypropyl methyl cellulose phtalate is 1:1-1:9, preferably 1:1-1:3.
Second goal of the invention of the present invention is to provide the preparation method of a kind of solid dispersion: by activating agent and pharmaceutical carrier
Mix homogeneously, hot-melt extruded.
Concrete preparation method comprises the following steps:
1) respectively by Eliquis and pharmaceutical carrier powder mix homogeneously by a certain percentage, physical mixture is made；
2) setting the extrusion temperature of screw extruder as 120-160 DEG C, temperature starts screw rod, by step 1) gained after being raised to definite value
Physical mixture is added in extruder, through hot melt, squeezes out bands；
3), after bands cooling, pulverize, cross 20-100 mesh sieve, obtain the solid dispersion of Eliquis.
Preferably, described step 1) pharmaceutical carrier is medicinal enteric carrier, more preferably the polymerization of enteric acrylic resin
Thing and acetic acid Hydroxypropyl methyl cellulose phtalate binary complex carrier.
Preferably, described step 2) extrusion temperature is preferably 130-150 DEG C.
Preferably, described step 3) preferably crosses 40-80 mesh sieve.
3rd goal of the invention of the present invention is to provide a kind of pharmaceutical composition comprising Eliquis solid dispersion, described
Pharmaceutical composition can comprise Eliquis solid dispersion provided by the present invention and pharmaceutically acceptable excipient, it is possible to only
For containing Eliquis solid dispersion, said composition is widely used in treatment or medicine for preventing nonvalvular atrial (AF) patient's apoplexy, complete
Body thromboembolism or venous thromboembolism.
The Advantageous Effects of the present invention:
Solid dispersion of the present invention, containing activating agent Eliquis and medicinal enteric carrier material, wherein Eliquis
It is highly dispersed in enteric solubility carrier material and in amorphous state, by substantial amounts of it is demonstrated experimentally that solid dispersion of the present invention has
Higher dissolution and activating agent Eliquis is had to be uniformly dispersed；On the other hand, Eliquis is alkalescence, higher at pH value
Small intestinal in be more beneficial for absorb.
Further, applicant finds through substantial amounts of test, activating agent Eliquis in solid dispersion of the present invention
Also it is the key factor that the present invention controls with the formula of the weight ratio of medicinal enteric carrier, medicinal enteric carrier, when solid disperses
Containing enteric acrylic polymer, the binary enteric carrier material of acetic acid Hydroxypropyl methyl cellulose phtalate in body
Time, the particularly weight ratio at enteric acrylic polymer, acetic acid Hydroxypropyl methyl cellulose phtalate is 1:1-1:
9, in solid dispersion, the dissolution of Eliquis is higher, and within 10 minutes, dissolution can reach more than 90%, complete within 45 minutes
Portion's dissolution；Particularly Eliquis and medicinal enteric vehicle weight ratio are during for 1:5-1:10, just reach whole dissolution at 30 minutes.
Enteric acrylic polymer quickly can discharge at intestinal and with lower portion, and acetic acid Hydroxypropyl methyl cellulose phtalate is at pH
Quickly discharge under the conditions of >=5.5, inventor through great many of experiments it follows that use enteric acrylic polymer and acetic acid
The binary complex carrier of Hydroxypropyl methyl cellulose phtalate, also has synergic adjustment Eliquis dissolution rate and promotes molten
The effect gone out, fully absorbing of whole dissolutions of activating agent Eliquis, beneficially medicine；And the Eliquis solid of correspondence
Dispersion still maintains amorphous state under the conditions of accelerated stability test, and enteric acrylic polymer and acetic acid are described
The binary complex carrier of Hydroxypropyl methyl cellulose phtalate, in storage process, also has the effect that suppression is crystal formation,
Gained solid dispersion good stability.
Preparation method of the present invention, technique is simple, and technological parameter is easily-controllable, is suitable for industrial-scale production.This method
The solid dispersion prepared for raw material with the Eliquis of crystal formation, verifies after testing, and Eliquis is with amorphous state high uniformity
It is dispersed in enteric carrier in homogeneous system, increases surface area, thus increase the dissolution of Eliquis；At 120-160
DEG C, Eliquis and enteric carrier are molten condition, it is simple to preferably carry out dispersibility mixing, thus homogeneously melted
Thing so that while increasing Eliquis dissolution, add Eliquis dispersing uniformity in solid dispersion, thus
Make the effective blood drug concentration kept relative stability in medicine process in leaching in vivo, beneficially Eliquis suction in vivo
Receive.
The pharmaceutical composition comprising Eliquis solid dispersion of the present invention, owing to solid dispersion has well
Dissolution and the scattered uniformity of activating agent, corresponding pharmaceutical composition also has the most excellent performance, can extensively use
In terms for the treatment of or prevention medicine for preventing nonvalvular atrial (AF) patient's apoplexy, systemic embolism or venous thromboembolism medicine.
Accompanying drawing explanation
Fig. 1: Eliquis, embodiment 1 physical mixture, the DSC curve figure of embodiment 1 solid dispersion；
Fig. 2: Eliquis, the X-powder diagram of embodiment 1 solid dispersion；
Fig. 3: Eliquis, embodiment 1 physical mixture, the In Vitro Dissolution curve chart of embodiment 1～8 gained solid dispersion.
Detailed description of the invention
Enteric acrylic polymer (Eudragit S100, L100, L100-55) is purchased from Degussa；
Acetic acid Hydroxypropyl methyl cellulose phtalate (HP-50, HP-55) is purchased from Shin-Etsu Chemial Co., Ltd of Japan；
Other adjuvants and reagent city the most in conventional manner available from；
In solid dispersion raw material of the present invention, Eliquis is crystal formation, and its X-powder diagram corresponds to Fig. 2.
Embodiment 1
Solid dispersion raw material:
Eliquis 4g
Eudragit L100 10g
HP-50 10g
Preparation method:
1) respectively Eliquis and medicinal enteric powder being added three-dimensional mixer mixing 5min according to the above ratio, rotating speed is
30rpm, makes physical mixture；
2) setting the extrusion temperature of screw extruder as 130 DEG C, temperature starts screw rod, by step 1) gains after being raised to 130 DEG C
Reason mixture is added in extruder, through hot melt, squeezes out bands；
3), after bands cooling, pulverize, cross 80 mesh sieves, obtain the solid dispersion of Eliquis.
Embodiment 2
Solid dispersion raw material:
Eliquis 2g
Eudragit S100 5g
HP-55 15 g
Preparation method:
1) respectively Eliquis and medicinal enteric powder being added three-dimensional mixer mixing 15min according to the above ratio, rotating speed is
10rpm, makes physical mixture；
2) setting the extrusion temperature of screw extruder as 150 DEG C, temperature starts screw rod, by step 1) gains after being raised to 150 DEG C
Reason mixture is added in extruder, through hot melt, squeezes out bands；
3), after bands cooling, pulverize, cross 40 mesh sieves, obtain the solid dispersion of Eliquis.
Embodiment 3
Solid dispersion raw material:
Eliquis 2 g
Eudragit L100-55 4g
HP-50 36g
Preparation method:
1) respectively Eliquis and medicinal enteric powder being added three-dimensional mixer mixing 10min according to the above ratio, rotating speed is
12rpm, makes physical mixture；
2) setting the extrusion temperature of screw extruder as 120 DEG C, temperature starts screw rod, by step 1) gains after being raised to 120 DEG C
Reason mixture is added in extruder, through hot melt, squeezes out bands；
3), after bands cooling, pulverize, cross 100 mesh sieves, obtain the solid dispersion of Eliquis.
Embodiment 4
Solid dispersion raw material:
Eliquis 10g
Eudragit L100 10g
HP-50 10g
Preparation method:
1) respectively Eliquis and medicinal enteric powder being added three-dimensional mixer mixing 5min according to the above ratio, rotating speed is
30rpm, makes physical mixture；
2) setting the extrusion temperature of screw extruder as 130 DEG C, temperature starts screw rod, by step 1) gains after being raised to 130 DEG C
Reason mixture is added in extruder, through hot melt, squeezes out bands；
3), after bands cooling, pulverize, cross 80 mesh sieves, obtain the solid dispersion of Eliquis.
Embodiment 5
Solid dispersion raw material:
Eliquis 2.5g
HP-55 97.5g
Preparation method:
1) respectively Eliquis and medicinal enteric powder being added three-dimensional mixer mixing 8min according to the above ratio, rotating speed is
8rpm, makes physical mixture；
2) setting the extrusion temperature of screw extruder as 160 DEG C, temperature starts screw rod, by step 1) gains after being raised to 160 DEG C
Reason mixture is added in extruder, through hot melt, squeezes out bands；
3), after bands cooling, pulverize, cross 20 mesh sieves, obtain the solid dispersion of Eliquis.
Embodiment 6
Solid dispersion raw material:
Eliquis 3g
Eudragit L100 15g
Preparation method is with embodiment 1
Embodiment 7
Solid dispersion raw material:
Eliquis 10g
HP-55 10g
Preparation method is with embodiment 2
Embodiment 8
Solid dispersion raw material:
Eliquis 10g
Enteric acrylic polymer 12g
HP-50 14g
Hydroxypropyl Methyl Cellulose Phthalate 14g
Preparation method is with embodiment 3
Checking embodiment 1
By gained physical mixture in the Eliquis solid dispersion of preparation, embodiment 1 preparation method step 1) in embodiment 1
And Eliquis crude drug carries out differential scanning calorimetric analysis (DSC) experiment, Fig. 1 is shown in by corresponding collection of illustrative plates；
Differential scanning calorimetric analysis method:
Instrument: NETZSCH DSC 204 type differential thermal analyzer
Temperature range: 40-280 DEG C, heating rate: 10 DEG C/min.
As shown in Figure 1: the spectral line of Eliquis crude drug exists obvious Eliquis endothermic peak；This peak is in embodiment
It is obviously reduced in gained physical mixture in 1 preparation method step 1), but still exists；The Eliquis of preparation in embodiment 1
In the spectral line of solid dispersion, this peak is wholly absent；The hot-melt extruded solid dispersion of technical solution of the present invention gained Eliquis
Middle Eliquis disperses evenly in carrier material.
By embodiment 2-8 is verified, it is possible to draw same conclusion.
Checking embodiment 2
Embodiment 1-8 gained solid dispersion is carried out X-powder diffraction respectively, and result is that in solid dispersion, Eliquis is equal
For amorphous, it is shown in Table 1.Figure it is seen that embodiment 1 raw material is Eliquis crystal formation, it is without fixed in solid dispersion
Shape；By embodiment 2-8 is verified, it is possible to draw same conclusion.
Checking embodiment 3
Dissolution determination:
The most accurate weighting raw materials, physical mixture, Eliquis solid dispersion appropriate (being equivalent to medicine about 10mg) shine
Dissolution method (Chinese Pharmacopoeia two annex XC the second methods of version in 2010), with pH6.8 phosphate buffer as solvent, rotating speed
For 50r/min, operate in accordance with the law, respectively at 5min, 10min, 20min, 30min, 45min, take solution 10ml, as test sample
Solution.Use octadecylsilane chemically bonded silica chromatographic column；With 10mM ammonium acetate: acetonitrile (65: 35) is for flowing phase；Flow velocity is
1.0ml per minute；Detection wavelength is 280nm；Column temperature is 25 DEG C, by external standard method with the dissolution of calculated by peak area solid dispersion
Degree.Eliquis crude drug, physical mixture and embodiment 1～8 gained solid dispersion are carried out dissolution experiment, corresponding data
Be shown in Table 1, Fig. 3.
It can be seen that embodiment of the present invention 1-8 from table 1, Fig. 3, Eliquis dissolution is rapid, within 10 minutes, just can reach molten
Go out more than 85%, substantially all dissolution after 45 minutes, in embodiment 1-4, more than 90% within 10 minutes, can be reached, complete after 45 minutes
Full dissolution, particularly embodiment 1-2, after 30 minutes with regard to complete dissolution, reason is containing enteric acrylic polymer, vinegar
The binary complex carrier of acid Hydroxypropyl methyl cellulose phtalate has regulation Eliquis dissolution rate and promotes dissolution
Effect, beneficially Eliquis fully absorbing in vivo.
Physical mixture described in step 1) in embodiment 1, does not forms solid dispersion, and dissolution is poor, crude drug Ah piperazine
The dissolution of husky class is the most poor.
Confirmatory experiment example 4 accelerated stability is tested
The Eliquis solid dispersion of embodiment of the present invention 1-8 gained is sealed, is placed on acceleration environment (40 DEG C/75%RH)
Under, preserve 3 months, and measure corresponding dissolution situation respectively, and measure the crystal formation of sample, experimental result such as table 2:
In conjunction with table 1,2 it can be seen that activating agent Eliquis is in whole accelerated test mistake in solid dispersion of the present invention
Journey remaining, amorphous state, i.e. stability are preferable, the most also there is higher dissolution.
Embodiment 9
Embodiment 1 gained solid dispersion 18g
Microcrystalline Cellulose 6g
Pulvis Talci 0.3g
Solid dispersion raw material is crossed 40 mesh sieves, after adjuvant crosses 80 mesh sieves, weighs supplementary material, mix homogeneously by recipe quantity, load
Capsule.
Embodiment 10
By embodiment 5 gained solid dispersion, directly load capsule.
Embodiment 11
Embodiment 1 gained solid dispersion 50g
Lactose 15g
Microcrystalline Cellulose 12g
Polyvinylpolypyrrolidone 5g
Magnesium stearate 0.5g
Silicon dioxide 0.5g
Solid dispersion raw material is crossed 40 mesh sieves, after adjuvant crosses 80 mesh sieves, weighs supplementary material by recipe quantity, mix homogeneously, directly
Tabletting.
The formulation compositions beyond the region of objective existence prepared except above-described embodiment 9-11, it is also possible to solid dispersion of the present invention is used for
Prepare the common formulations such as granule, suspensoid, pill solution, and be widely used in treatment or prevention medicine for preventing nonvalvular atrial
(AF) patient's apoplexy, systemic embolism or venous thromboembolism medicine aspect.
Embodiments above is only explanation of the invention, and it is not limitation of the present invention, art technology
The present embodiment can be made after reading this specification by personnel as required does not has the amendment of creative contribution, but as long as
All protected by Patent Law in scope of the presently claimed invention.
Claims (10)
1. a solid dispersion, it is characterised in that described dispersion comprises Eliquis and medicinal enteric carrier material, described
Eliquis is amorphous, and the weight ratio of described Eliquis and medicinal enteric carrier material is 1:1-1:39.
Solid dispersion the most according to claim 1, it is characterised in that described Eliquis and medicinal enteric carrier material
Weight ratio be 1:2-1:20.
Solid dispersion the most according to claim 2, it is characterised in that described Eliquis and pharmaceutical carrier enteric material
Weight ratio be 1:5-1:10.
Solid dispersion the most according to claim 1, it is characterised in that described medicinal enteric carrier is enteric acrylic acid tree
Lipopolymer and acetic acid Hydroxypropyl methyl cellulose phtalate binary complex carrier.
Solid dispersion the most according to claim 4, it is characterised in that described enteric acrylic polymer and acetic acid
The weight ratio of Hydroxypropyl methyl cellulose phtalate is 1:1-1:9.
6. according to the preparation method of the solid dispersion described in any one of claim 1-5, it is characterised in that comprise following step
Rapid:
1) respectively by Eliquis and medicinal enteric support powder mix homogeneously by a certain percentage, physical mixture is made；
2) setting the extrusion temperature of screw extruder as 120-160 DEG C, temperature starts screw rod, by step 1) gained after being raised to definite value
Physical mixture is added in extruder, through hot melt, squeezes out bands；
3), after bands cooling, pulverize, cross 20-100 mesh sieve, obtain the solid dispersion of Eliquis.
The preparation method of solid dispersion the most according to claim 6, it is characterised in that step 2) in temperature be 130-
150℃。
The preparation method of solid dispersion the most according to claim 6, it is characterised in that cross 40-80 mesh sieve in step 3).
9. the pharmaceutical composition containing the solid dispersion described in any one of claim 1-5.
10. pharmaceutical composition described in a claim 9 is preparation treatment or prevention medicine for preventing nonvalvular atrial (AF) patient soldier
In, systemic embolism or the application of venous thromboembolism medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201610293223.0A CN105997883A (en) | 2016-05-06 | 2016-05-06 | Solid dispersion and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201610293223.0A CN105997883A (en) | 2016-05-06 | 2016-05-06 | Solid dispersion and preparation method and application thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107648231A (en) * | 2016-07-25 | 2018-02-02 | 江苏豪森药业集团有限公司 | R-lansoprazole pharmaceutical preparation |
| CN108743554A (en) * | 2018-06-20 | 2018-11-06 | 北京阳光诺和药物研究有限公司 | A kind of toluenesulfonic acid Yi Dushaban tablets and preparation method thereof |
| CN110037990A (en) * | 2019-04-15 | 2019-07-23 | 海正药业(杭州)有限公司 | A kind of preparation process of Eliquis solid amorphous dispersions |
| CN112791057A (en) * | 2021-02-07 | 2021-05-14 | 齐飞 | Slow release preparation containing edoxaban and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102908324A (en) * | 2012-10-31 | 2013-02-06 | 南京正科制药有限公司 | Apixaban tablet |
| CN103491964A (en) * | 2011-03-08 | 2014-01-01 | 扎里卡斯药品有限公司 | Solid dispersion formulations and methods of use thereof |
-
2016
- 2016-05-06 CN CN201610293223.0A patent/CN105997883A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103491964A (en) * | 2011-03-08 | 2014-01-01 | 扎里卡斯药品有限公司 | Solid dispersion formulations and methods of use thereof |
| CN102908324A (en) * | 2012-10-31 | 2013-02-06 | 南京正科制药有限公司 | Apixaban tablet |
Non-Patent Citations (2)
| Title |
|---|
| ANONYMOUSLY: "Amorphous Formulations of Apixaban by hot Melt Extrusion", 《RESEARCH DISCLOSURE》 * |
| 邢俊豪等: "阿哌沙班衍生物的合成及Xa因子抑制活性", 《中国药科大学学报》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107648231A (en) * | 2016-07-25 | 2018-02-02 | 江苏豪森药业集团有限公司 | R-lansoprazole pharmaceutical preparation |
| CN107648231B (en) * | 2016-07-25 | 2021-07-16 | 江苏豪森药业集团有限公司 | Dexlansoprazole medicinal preparation |
| CN108743554A (en) * | 2018-06-20 | 2018-11-06 | 北京阳光诺和药物研究有限公司 | A kind of toluenesulfonic acid Yi Dushaban tablets and preparation method thereof |
| CN110037990A (en) * | 2019-04-15 | 2019-07-23 | 海正药业(杭州)有限公司 | A kind of preparation process of Eliquis solid amorphous dispersions |
| CN110037990B (en) * | 2019-04-15 | 2023-03-28 | 海正药业(杭州)有限公司 | Preparation process of apixaban solid amorphous dispersion |
| CN112791057A (en) * | 2021-02-07 | 2021-05-14 | 齐飞 | Slow release preparation containing edoxaban and preparation method thereof |
| CN112791057B (en) * | 2021-02-07 | 2022-03-18 | 齐飞 | Slow release preparation containing edoxaban and preparation method thereof |
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Application publication date: 20161012 |