CN106539777A - A kind of methanesulfonic acid Da Lafeini slow releasing tablet and preparation method thereof - Google Patents
A kind of methanesulfonic acid Da Lafeini slow releasing tablet and preparation method thereof Download PDFInfo
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- CN106539777A CN106539777A CN201611112050.4A CN201611112050A CN106539777A CN 106539777 A CN106539777 A CN 106539777A CN 201611112050 A CN201611112050 A CN 201611112050A CN 106539777 A CN106539777 A CN 106539777A
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- lafeini
- methanesulfonic acid
- slow releasing
- releasing tablet
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
Abstract
A kind of methanesulfonic acid Da Lafeini slow releasing tablet, it is obtained by following supplementary material：1 part of methanesulfonic acid Da Lafeini, 0.3～0.9 part of sustained-release matrix material, 0.05～0.11 part of fluidizer, 1.1～3.1 parts of filler, 1～6 part of binding agent, slowly discharge according to methanesulfonic acid Da Lafeini slow releasing tablet principal agent methanesulfonic acid Da Lafeini obtained in the present invention, deenergized period is up to 12 hours, therefore this product can be reduced compared with conventional capsules agent and take number of times；This product principal agent methanesulfonic acid Da Lafeini slowly discharges, steady, lasting effective blood drug concentration can be provided, avoid or reduce blood drug level peak valley phenomenon, be conducive to improving the safety that medicine is used, meanwhile, this product good stability, shelf life are up to 24 months, preparation method simple possible, is worth marketing application.
Description
Technical field
The invention mainly relates to pharmaceutical technology field, and in particular to a kind of slow release of main component for methanesulfonic acid Da Lafeini
Piece and preparation method thereof.
Background technology
Cutaneous melanoma is most aggressive form in all skin carcinomas.Although it only accounts for the 4% of all cancers,
But its sickness rate persistently rises in the whole world, its speed has exceeded all other cancer.It is expected every year about in the whole world
132000 people will be diagnosed with melanoma, and expection has about 37 every year, and 000 people dies from the disease.
For Buddhist nun's class medicine be in recent years research and development and in the molecule targeted drug of clinical success application, such medicine is main
For the treatment of the cancers such as nonsmall-cell lung cancer, breast carcinoma, cancer of pancreas, renal carcinoma, melanoma, chronic myelocytic leukemia, its
Main to suppress tumour growth by activity that is selectively targeted and suppressing tyrosine kinase, its antitumous effect is good.Wherein,
Imatinib was listed in calendar year 2001, and clinical indication is chronic myelocytic leukemia, was approved within 2002 treating transitivity
Or the gastrointestinal malignant stromal tumors that operation cannot cut off.Gefitinib was approved by the fda in the United States for treating chemotherapy in May, 2003
The advanced Non-small cell lung of failure, and it is approved listing in China in March, 2005.Lapatinib is ground by GlaxoSmithKline PLC company
Send out, listed by U.S. FDA approval in 2007, combined with Capecitabine for treating late period or metastatic breast cancer.E Luo is replaced
Buddhist nun was listed in 2004, for treating nonsmall-cell lung cancer, expanded indication to cancer of pancreas within 2007.List at present
There are Dasatinib, Sutent, AMN107 etc. for Buddhist nun's class medicine.In addition, domestic warp-wise CFDA submits new drug Shen to
The Suo Fan that has please replaces Buddhist nun, furan quinoline for Buddhist nun, Ah handkerchief for Buddhist nun etc..2009～2013 years, have 14 domestic pharmacy corporations and submitted and replace
The clinical application of a kind new medicine of Buddhist nun's class medicine, is related to 23 kinds.For Buddhist nun's class medicine because its anticancer spectrum is wide, determined curative effect, gradually
Become the fiest-tire medication for treating various cancers.In May, 2013, food and medicine Surveillance Authority of the U.S. have approved new drug Da Lafeini
(Tafinlar) for treat metastasis melanin tumor and can not row operative treatment melanoma patient.
The existing preparation with methanesulfonic acid Da Lafeini as main component is mainly capsule, methanesulfonic acid Da Lafeini capsules
Though agent can voluntarily oral administration, at least need to take 2 times daily, take loaded down with trivial details, and there may be as medicining times are too many
And situations such as forget clothes and miss, serious harm patient health.Based on case above, we provide a kind of methanesulfonic acid Da Lafeini slow release
Piece, only need to be taken 1 time daily, and number of times is taken in reduction, facilitates patient to take.
The content of the invention
It is an object of the invention to provide a kind of medication convenience, the methanesulfonic acid Da Lafeini slow releasing tablet of persistent.
Another object of the present invention is to provide the preparation method of above-mentioned methanesulfonic acid Da Lafeini slow releasing tablet.
The purpose of the present invention is realized by following technical measures：
A kind of methanesulfonic acid Da Lafeini slow releasing tablet, it is obtained by the supplementary material of following weight proportion, it is characterised in that：First
It is 1 part of sulfonic acid Da Lafeini, 0.3～0.9 part of sustained-release matrix material, 0.05～0.11 part of fluidizer, 1.1～3.1 parts of filler, viscous
1～6 part of mixture, wherein the sustained-release matrix material is ethyl cellulose, 30 POVIDONE K 30 BP/USP 90, hydroxypropyl methylcellulose, alginic acid
One or more in sodium, agar, Lactose, galactose；The fluidizer is micropowder silica gel, Pulvis Talci, in magnesium stearate one
Plant or several；The filler is starch, Microcrystalline Cellulose, sodium carboxymethyl cellulose, pregelatinized Starch, the one kind in Mannitol
Or it is several；Adhesive therefor is sucrose water, ethanol, starch slurry, one or more in water.
Inventor is had found in research process, if control is bad, the release of methanesulfonic acid Da Lafeini slow releasing tablet is not ideal enough, is
This problem is solved, above-mentioned methanesulfonic acid Da Lafeini slow releasing tablet includes 1 part of the methanesulfonic acid Da Lafeini of weight meter, hydroxypropyl
0.32～0.76 part of cellulose, 0.05～0.52 part of Lactose, 0.03～0.11 part of sodium alginate, magnesium stearate 0.06～0.10
Part, 1.3～1.9 parts of pregelatinized Starch, 0.7～1.6 part of Microcrystalline Cellulose, the ethanol solution 2 that volume fraction is 30%～50%
～5 parts.
Further, above-mentioned slow releasing tablet include 1 part of the methanesulfonic acid Da Lafeini of weight meter, hydroxypropyl methylcellulose 0.35～
0.51 part, 0.16～0.25 part of Lactose, 0.06～0.09 part of sodium alginate, 0.07～0.09 part of magnesium stearate, pregelatinized Starch
1.5～1.8 parts, 0.9～1.3 part of Microcrystalline Cellulose, 3～5 parts of the ethanol solution that volume fraction is 35%～45%.
A kind of preparation method of methanesulfonic acid Da Lafeini slow releasing tablet, is carried out as follows：
1. fine powder will be ground into after methanesulfonic acid Da Lafeini, sustained-release matrix material, filler mixing (all to sieve by No. 5
And can pass through No. 6 sieve amounts must not be less than total amount 95%), sieve；
2. add binding agent, mixing granulation (to cross 24 mesh sieve extrusion granulators), the wet granular by made by is placed in hot-air oven
In, 40～60 DEG C of temperature being set, is dried to pellet moisture≤3%, granulate (crosses 18 mesh sieves), standby；
3. lubricant was crushed into 100 mesh sieves, in adding the granule after granulate, mix homogeneously；
4. compress tablet coating：Regulate tablet machine, tabletting (specification 0.3g/ piece), by the slow releasing tablet bag protection against the tide clothing of compacting；Coating
Material is OPADRY, and coating weight gain amount is the 2%～3% of total weight of tablet；
5. packaging is obtained final product.
It is optimum, a kind of methanesulfonic acid Da Lafeini slow releasing tablet be the supplementary material of following weight proportion prepare as follows and
：1 part of methanesulfonic acid Da Lafeini, 0.45 part of hydroxypropyl methylcellulose, 0.21 part of Lactose, 0.07 part of sodium alginate, magnesium stearate
0.08 part, 1.6 parts of pregelatinized Starch, 1.1 parts of Microcrystalline Cellulose, 5 parts of the ethanol solution that volume fraction is 40%；Take recipe quantity
Methanesulfonic acid Da Lafeini, hydroxypropyl methylcellulose, Lactose, sodium alginate, pregelatinized Starch, Microcrystalline Cellulose are ground into after mixing
Fine powder (amount that No. 6 sieves are all sieved and can passed through by No. 5 must not be less than the 95% of total amount), sieves；To in above-mentioned mixed-powder
The volume fraction for adding recipe quantity is 40% ethanol solution, and mixing granulation (crosses 24 mesh sieve extrusion granulators), wet by made by
Grain, is placed in hot-air oven, arranges 40～60 DEG C of temperature, is dried to pellet moisture≤3%, and granulate (crosses 18 mesh sieves), standby；Will
The magnesium stearate of recipe quantity crushed 100 mesh sieves, in adding the granule after granulate, mix homogeneously；Tablet machine is regulated, by granulate
Granule afterwards carries out tabletting (piece weight 0.3g), by the slow releasing tablet bag protection against the tide clothing of compacting；Coating material is OPADRY, coating weight gain amount
For the 2%～3% of total weight of tablet；Packaging is obtained final product.
Supplementary material needed for above-mentioned is well known to those skilled in the art, and is commercially available on market.
The present invention has following beneficial effect：
Methanesulfonic acid Da Lafeini slow releasing tablet principal agent methanesulfonic acid Da Lafeini of the present invention is up to 12 into slow release, deenergized period
Hour, therefore this product can be reduced compared with conventional capsules agent and take number of times；This product principal agent methanesulfonic acid Da Lafeini slowly discharges, and can provide
Steadily, lasting effective blood drug concentration, it is to avoid or reduce blood drug level peak valley phenomenon, be conducive to improving the safety that medicine is used
Property, meanwhile, this product good stability, shelf life are up to 24 months, preparation method simple possible, are worth marketing application.
Description of the drawings
Fig. 1：Embodiment 1 is obtained the release profiles of methanesulfonic acid Da Lafeini slow releasing tablet；
Fig. 2：Embodiment 2 is obtained the release profiles of methanesulfonic acid Da Lafeini slow releasing tablet；
Fig. 3：Embodiment 3 is obtained the release profiles of methanesulfonic acid Da Lafeini slow releasing tablet.
In above figure, B, C, D, E, F, G represent different pieces in embodiment 1, embodiment 2, embodiment 3.
Specific embodiment
The present invention is specifically described below by embodiment, it is necessary to it is pointed out here that be that following examples are only used
In being further described to the present invention, it is impossible to be interpreted as limiting the scope of the invention, without departing substantially from spirit of the invention
In the case of essence, the modification made to the inventive method, step or condition or replacement belong to the scope of the present invention.
Embodiment 1
A kind of methanesulfonic acid Da Lafeini slow releasing tablet, is obtained according to the following steps：
Label is constituted：
Coating is constituted：
Preparation process：
(1) take the methanesulfonic acid Da Lafeini of recipe quantity, hydroxypropyl methylcellulose, Lactose, sodium alginate, pregelatinized Starch,
Fine powder is ground into after Microcrystalline Cellulose mixing, and (amount of No. 6 sieves that all sieved by No. 5 and can be passed through must not be less than total amount
95%), sieve；
(2) in above-mentioned mixed-powder, add the ethanol solution of recipe quantity, mixing granulation (to cross 24 mesh sieve extrusion granulators), will
Made by wet granular, be placed in hot-air oven, 40～60 DEG C of temperature be set, be dried to pellet moisture≤3%, granulate (crosses 18 mesh
Sieve), it is standby；
(3) magnesium stearate of recipe quantity was crushed into 100 mesh sieves, in adding the granule after granulate, mix homogeneously；
(4) tablet machine is regulated, the granule after granulate is carried out into tabletting (piece weight 0.3g), the slow releasing tablet bag of compacting is moistureproof
Clothing；Coating material is OPADRY, and coating weight gain amount is the 2%～3% of total weight of tablet；
(5) packaging is obtained final product.
(1) measure of release
Slow releasing tablet obtained above is taken as sample, according to release inspection technique (2010 editions two annex X D of Chinese Pharmacopoeia
One method), using the device of the first method of dissolution method, with water 900ml as release medium, rotating speed is 100 turns per minute, in accordance with the law
Operation, Jing 1,2,4,6,8,12 hours take release solution 5ml, are filtered with 0.45 μm of microporous filter membrane, take subsequent filtrate as confession examination
Product solution, and supplementary release medium 5ml in process container in time.Another precision weighs methanesulfonic acid Da Lafeini reference substance about 20mg
Put in 50ml measuring bottles, with water dissolution and be diluted to scale, shake up, as reference substance solution.Precision measures above-mentioned reference substance respectively
Solution and each 20 μ l of need testing solution, determine according to following chromatographic conditions.Calculate the release (referring to Accumulation dissolution) per piece.
Chromatographic condition
Instrument：Agilent 1200LC
Mobile phase: methanol-water=60: 40
Detection wavelength：254nm
Chromatographic column：250*4.6Agilent C18
Flow velocity：1.0ml/min
(1) measurement result of the release of slow releasing tablet sample of the present invention is shown in Table 1, Fig. 1 (having done six sample determinations).
1 slow releasing tablet sample release (%) of the present invention of table
Result of the test：
Outward appearance：Film coated tablets, any surface finish.
Release：Methanesulfonic acid Da Lafeini slow releasing tablet principal agent methanesulfonic acid Da Lafeini can meet slow releasing tablet into slow release
Requirement.(2) a kind of methanesulfonic acid Da Lafeini slow releasing tablet stability experiments of the invention
Experiment material：
Methanesulfonic acid Da Lafeini slow releasing tablet：It is obtained for embodiment 1.
Acceleration study method：By methanesulfonic acid Da Lafeini slow releasing tablet obtained in embodiment 1 by listing packaging, Acceleration study is put
In case, certain hour sampling is tested to investigation project.
Acceleration study temperature：40±2℃
Humidity：RH75% ± 5%
The investigation time：0th, 1,2,3, June
Inspection target：
Character, moisture, relevant material, release, content, microbial limit
Accelerated test stability is recorded：
Acceleration study result shows：Accelerate June sample suitable with 0 month sample items Testing index quality, show that this product adds
Speed experiment June, quality keep stable, and this product stability is preferable.
Long-term experiment method：By methanesulfonic acid Da Lafeini slow releasing tablet obtained in embodiment 1 by listing packaging, put and keep sample for a long time
In case, certain hour sampling is tested to investigation project.
Long-term experiment temperature：25±2℃
Humidity：RH60% ± 10%
The investigation time：0th, 3,6,9,12,18,24 months
Character, moisture, relevant material, release, content, microbial limit
Long term test stability is recorded：
Long term test shows：This product long term test character, moisture, relevant material, release, content, microorganism in 24 months
Limit without significant changes, meets every relevant regulations of production quality standard draft.24 lunar geology of this product long term test
Amount is stable, therefore this product effect duration is minimum 24 months, and long term test is still during continuing to investigate.
Embodiment 2
A kind of methanesulfonic acid Da Lafeini slow releasing tablet, is obtained according to the following steps：
Label is constituted：
Coating is constituted：
Preparation process：It is obtained according to the preparation technology of embodiment 1.
(1) measure of release
Determine according to 1 drug release determination method of embodiment, the measurement result of its release is shown in Table 2, Fig. 2 and (has made six samples
Determine).
2 slow releasing tablet sample release (%) of the present invention of table
Result of the test：
Outward appearance：Film coated tablets, any surface finish.
Release：Methanesulfonic acid Da Lafeini slow releasing tablet principal agent methanesulfonic acid Da Lafeini can meet slow releasing tablet into slow release
Requirement.
(2) a kind of methanesulfonic acid Da Lafeini slow releasing tablet stability experiments of the invention
Experiment material：
Methanesulfonic acid Da Lafeini slow releasing tablet：It is obtained for embodiment 2.
Acceleration study method：By methanesulfonic acid Da Lafeini slow releasing tablet obtained in embodiment 2 by listing packaging, Acceleration study is put
In case, certain hour sampling is tested to investigation project.
Acceleration study temperature：40±2℃
Humidity：RH75% ± 5%
The investigation time：0th, 1,2,3, June
Inspection target：
Character, moisture, relevant material, release, content, microbial limit
Accelerated test stability is recorded：
Acceleration study result shows：Accelerate June sample suitable with 0 month sample items Testing index quality, show that this product adds
Speed experiment June, quality keep stable, and this product stability is preferable.
Long-term experiment method：By methanesulfonic acid Da Lafeini slow releasing tablet obtained in embodiment 2 by listing packaging, put and keep sample for a long time
In case, certain hour sampling is tested to investigation project.
Long-term experiment temperature：25±2℃
Humidity：RH60% ± 10%
The investigation time：0th, 3,6,9,12,18,24 months
Character, moisture, relevant material, release, content, microbial limit
Long term test stability is recorded：
Long term test shows：This product long term test character, moisture, relevant material, release, content, microorganism in 24 months
Limit without significant changes, meets every relevant regulations of production quality standard draft.24 lunar geology of this product long term test
Amount is stable, therefore this product effect duration is minimum 24 months, and long term test is still during continuing to investigate.
Embodiment 3
A kind of methanesulfonic acid Da Lafeini slow releasing tablet, is obtained according to the following steps：
Label is constituted
Coating is constituted：
Preparation process：It is obtained according to the preparation technology of embodiment 1.
(1) measure of release
Determine according to 1 drug release determination method of embodiment, the measurement result of its release is shown in Table 3, Fig. 3 and (has made six samples
Determine).
3 slow releasing tablet sample release (%) of the present invention of table
Result of the test：
Outward appearance：Film coated tablets, any surface finish.
Release：Methanesulfonic acid Da Lafeini slow releasing tablet principal agent methanesulfonic acid Da Lafeini can meet slow releasing tablet into slow release
Requirement.
(2) a kind of methanesulfonic acid Da Lafeini slow releasing tablet stability experiments of the invention
Experiment material：
Methanesulfonic acid Da Lafeini slow releasing tablet：It is obtained for embodiment 3.
Acceleration study method：By methanesulfonic acid Da Lafeini slow releasing tablet obtained in embodiment 3 by listing packaging, Acceleration study is put
In case, certain hour sampling is tested to investigation project.
Acceleration study temperature：40±2℃
Humidity：RH75% ± 5%
The investigation time：0th, 1,2,3, June
Inspection target：
Character, moisture, relevant material, release, content, microbial limit
Accelerated test stability is recorded：
Acceleration study result shows：Accelerate June sample suitable with 0 month sample items Testing index quality, show that this product adds
Speed experiment June, quality keep stable, and this product stability is preferable.
Long-term experiment method：By methanesulfonic acid Da Lafeini slow releasing tablet obtained in embodiment 3 by listing packaging, put and keep sample for a long time
In case, certain hour sampling is tested to investigation project.
Long-term experiment temperature：25±2℃
Humidity：RH60% ± 10%
The investigation time：0th, 3,6,9,12,18,24 months
Character, moisture, relevant material, release, content, microbial limit
Long term test stability is recorded：
Long term test shows：This product long term test character, moisture, relevant material, release, content, microorganism in 24 months
Limit without significant changes, meets every relevant regulations of production quality standard draft.24 lunar geology of this product long term test
Amount is stable, therefore this product effect duration is minimum 24 months, and long term test is still during continuing to investigate.
Embodiment 4-8：
For treat metastasis melanin tumor and can not row operative treatment melanoma methanesulfonic acid Da Lafeini slow release
Piece, by following medicine material, other are same as Example 1；In terms of weight proportion.Obtained slow releasing tablet Film coated tablets, table
Face is bright and clean；Its principal agent methanesulfonic acid Da Lafeini release behavior meets the requirement of slow releasing tablet after testing；While principal agent first sulphur of the present invention
Sour Da Lafeini is into slow release, therefore this product can be reduced compared with conventional formulation and take number of times；This product principal agent methanesulfonic acid Da Lafeini delays
On The Drug Release, can provide steady, lasting effective blood drug concentration, it is to avoid or reduce blood drug level peak valley phenomenon, be conducive to improving
The safety that medicine is used.
Sample obtained by embodiment 4,5,6,7,8 carries out release inspection and stability test, release inspection knot
Fruit shows that the sample release behavior obtained by embodiment 4,5,6,7,8 is up to 12 hours into slow release release time, therefore
This product meets patient requests by only needing daily to take once.Stability test result shows, obtained by embodiment 4,5,6,7,8
Sample accelerate June and long-term 24 months sample qualities stable, therefore this product shelf life at least 24 months.
Embodiment 9～11：
On the basis of methanesulfonic acid Da Lafeini slow releasing tablet of the present invention, controlled trial group (lack part adjuvant), tool are prepared
Body testing program see the table below, and preparation method is with embodiment 1：
9,10,11 result of the test of embodiment shows：Embodiment 9 discharges and all discharges within 4 hours complete, it is impossible to meet slow releasing tablet
Requirement, embodiment 10 discharge 3 hours all release it is complete, it is impossible to meet the requirement of slow releasing tablet, embodiment 11 discharge 6 hours it is complete
Portion's release is complete, it is impossible to meet the requirement of slow releasing tablet.
Claims (5)
1. a kind of methanesulfonic acid Da Lafeini slow releasing tablet, it is characterised in that it is obtained by the supplementary material of following weight proportion：First sulphur
1 part of sour Da Lafeini, 0.3～0.9 part of sustained-release matrix material, 0.05～0.11 part of fluidizer, 1.1～3.1 parts of filler, bonding
1～6 part of agent, wherein the sustained-release matrix material be ethyl cellulose, 30 POVIDONE K 30 BP/USP 90, hydroxypropyl methylcellulose, sodium alginate,
One or more in agar, Lactose, galactose；The fluidizer is micropowder silica gel, Pulvis Talci, the one kind in magnesium stearate or
It is several；The filler is starch, Microcrystalline Cellulose, sodium carboxymethyl cellulose, pregelatinized Starch, the one kind or several in Mannitol
Kind；Adhesive therefor be sucrose water, ethanol, starch slurry, one or more in water.
2. a kind of methanesulfonic acid Da Lafeini slow releasing tablet as claimed in claim 1, it is characterised in that the methanesulfonic acid Da Lafeini
Slow releasing tablet includes 1 part of the methanesulfonic acid Da Lafeini of weight meter, 0.32～0.76 part of hydroxypropyl methylcellulose, Lactose 0.05～0.52
Part, 0.03～0.11 part of sodium alginate, 0.06～0.10 part of magnesium stearate, 1.3～1.9 parts of pregelatinized Starch, Microcrystalline Cellulose
0.7～1.6 part, 2～5 parts of the ethanol solution that volume fraction is 30%～50%.
3. a kind of methanesulfonic acid Da Lafeini slow releasing tablet as claimed in claim 1 or 2, it is characterised in that the methanesulfonic acid is up to drawing
Non- Buddhist nun's slow releasing tablet include 1 part of the methanesulfonic acid Da Lafeini of weight meter, 0.35～0.51 part of hydroxypropyl methylcellulose, Lactose 0.16～
0.25 part, 0.06～0.09 part of sodium alginate, 0.07～0.09 part of magnesium stearate, 1.5～1.8 parts of pregelatinized Starch, crystallite it is fine
Dimension plain 0.9～1.3 part, 3～5 parts of the ethanol solution that volume fraction is 35%～45%.
4. the preparation method of a kind of methanesulfonic acid Da Lafeini slow releasing tablet as described in any one of claims 1 to 3, its feature exist
In it comprises the steps to be obtained：
A. fine powder will be ground into after methanesulfonic acid Da Lafeini, sustained-release matrix material, filler mixing, is sieved, fine powder can be whole
The amount of No. 6 sieves that sieved by No. 5 and can be passed through is more than or equal to the 95% of total amount；
B. binding agent, mixing granulation is added to cross 24 mesh sieve extrusion granulators, the wet granular by made by is placed in hot-air oven, is arranged
40～60 DEG C of temperature, is dried to pellet moisture≤3%, crosses 18 mesh sieve granulate, standby；
C. lubricant was crushed into 100 mesh sieves, in adding the granule after granulate, mix homogeneously；
D. compress tablet coating：Regulate tablet machine, tabletting, specification 0.3g/ piece, by the slow releasing tablet bag protection against the tide clothing of compacting；Coating material
For OPADRY, coating weight gain amount for total weight of tablet 2%～3%；
E. packaging is obtained final product.
5. a kind of methanesulfonic acid Da Lafeini slow releasing tablet, it is characterised in that it is by following side by the supplementary material of following weight proportion
Method is prepared：1 part of methanesulfonic acid Da Lafeini, 0.45 part of hydroxypropyl methylcellulose, 0.21 part of Lactose, 0.07 part of sodium alginate,
0.08 part of magnesium stearate, 1.6 parts of pregelatinized Starch, 1.1 parts of Microcrystalline Cellulose, 5 parts of the ethanol solution that volume fraction is 40%；Take
The methanesulfonic acid Da Lafeini of recipe quantity, hydroxypropyl methylcellulose, Lactose, sodium alginate, pregelatinized Starch, Microcrystalline Cellulose mixing
After be ground into fine powder, sieve, fine powder all can be sieved by No. 5 and the amounts of can pass through No. 6 sieves must not be less than the 95% of total amount；
The volume fraction that recipe quantity is added in above-mentioned mixed-powder is 40% ethanol solution, and mixing granulation, the extrusion of 24 mesh sieves excessively are made
Grain, the wet granular by made by, is placed in hot-air oven, arranges 40～60 DEG C of temperature, is dried to pellet moisture≤3%, crosses 18 mesh
Sieve granulate, it is standby；The magnesium stearate of recipe quantity was crushed into 100 mesh sieves, in adding the granule after granulate, mix homogeneously；Adjust
Granule after granulate is carried out tabletting piece weight 0.3g by good tablet machine, by the slow releasing tablet bag protection against the tide clothing of compacting；Coating material is Europe bar
Generation, coating weight gain amount for total weight of tablet 2%～3%；Packaging is obtained final product.
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2019008487A1 (en) * | 2017-07-05 | 2019-01-10 | Novartis Ag | Novel pharmaceutical composition |
| CN110831582A (en) * | 2017-07-05 | 2020-02-21 | 诺华股份有限公司 | Novel pharmaceutical compositions |
| AU2018297656B2 (en) * | 2017-07-05 | 2021-09-16 | Novartis Ag | Novel pharmaceutical composition |
| RU2779429C2 (en) * | 2017-07-05 | 2022-09-07 | Новартис Аг | New pharmaceutical composition |
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| CN110831582B (en) * | 2017-07-05 | 2023-08-11 | 诺华股份有限公司 | Pharmaceutical composition |
| AU2021221451B2 (en) * | 2017-07-05 | 2023-08-17 | Novartis Ag | Novel pharmaceutical composition |
| CN113941001A (en) * | 2021-12-09 | 2022-01-18 | 宁夏医科大学 | Application of CRAF inhibitor in preparation of anti-tumor medicine |
| CN113941001B (en) * | 2021-12-09 | 2023-09-08 | 宁夏医科大学 | Application of CRAF inhibitor in preparation of antitumor drugs |
| CN117257804A (en) * | 2023-10-17 | 2023-12-22 | 深圳市新阳唯康科技有限公司 | Darafenib pharmaceutical composition as well as preparation method and application thereof |
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