CN110037991A - Stable China advanced in years is for Buddhist nun's pharmaceutical composition and preparation method thereof - Google Patents
Stable China advanced in years is for Buddhist nun's pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN110037991A CN110037991A CN201910292591.7A CN201910292591A CN110037991A CN 110037991 A CN110037991 A CN 110037991A CN 201910292591 A CN201910292591 A CN 201910292591A CN 110037991 A CN110037991 A CN 110037991A
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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
- A61K31/495—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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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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
- A61K9/2004—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
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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
- A61K9/2004—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
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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
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
A kind of stable China advanced in years is for Buddhist nun's pharmaceutical composition and preparation method thereof, and described pharmaceutical composition includes stepping China to replace Buddhist nun and pharmaceutic adjuvant, and the pharmaceutic adjuvant includes lubricant and filler；It is characterized in that, the lubricant includes magnesium stearate, the filler includes lactose and/or microcrystalline cellulose.The present invention selects microcrystalline cellulose and/or lactose as filler, selects magnesium stearate as lubricant, can be good at solving the problems, such as to step China for sticking of Buddhist nun's pharmaceutical composition in big specification, mass production, while also assuring good quality stability.
Description
Technical field
The present invention relates to a kind of stable China advanced in years for Buddhist nun's pharmaceutical composition and preparation method thereof.
Background technique
Tumour is to threaten the major disease of human health, has 1,200,000 newly-increased patients in China every year.Wherein, lung cancer has been
As the first reason of China's mortality of malignant tumors, there are 600,000 people to die of lung cancer every year.
EGF-R ELISA (epidermal growth factor receptor, EGFR, HER1/erbB1) family
Race is one of most representational receptor in the receptor type tyrosine kinase of cross-film, has extensive biological function.Epidermis
The multiple ligands such as growth factor and transforminggrowthfactor-α extracellularly can partially be combined with EGFR, by mitogenic signals to cell
Interior transmitting promotes injury repair so that cell cycle regulation, adjusts cell normal differentiation.EGFR can also activate blood downstream
Pipe EGF-R ELISA (vascular epidermal growth factor receptor, VEGFR) promotes entity
Tumor capillary network is formed.Therefore EGFR plays important work in the generation of tumour cell, development, differentiation, reparation and transfer
With.Studies have shown that in the tumour of a variety of epithelial cell origins such as breast cancer, colorectal cancer, lung cancer, G. cephalantha and cancer of pancreas
All there is the abnormal activation of EGFR gene, amplification and overexpressions.
Human epidermal growth factor acceptor -2 (human epidermal growth factor receptor, HER2/
Neu, erbB-2) it is a transmembrane receptor, in many Several Epidermal Tumors such as breast cancer, oophoroma, prostate cancer, non-small cell lung
It is over-expressed in cancer, nasopharyngeal carcinoma etc., there are the overexpressions of HER2/neu gene for about 25%~30% primary breast cancer.
It steps China and replaces Buddhist nun (Mefatinib), its chemical name is: 2- crotonaldehyde amino-N- [4- [(the chloro- 4- fluorophenyl of 3-) ammonia
Base] -7- difluoromethyl oxygroup] -6- quinazolyl] -4- (dimethylamino)；Molecular formula: C21H19ClF3N5O2；Structural formula is such as
Under:
It is a kind of irreversible EGFR/HER2 efficient double inhibitor of the second generation, there is high activity, highly-water-soluble feature is right
First generation EGFR kinases is that the drug resistance that the drug of target spot generates has good therapeutic effect (ZL201200785900).
Summary of the invention
It is a kind of advanced in years magnificent for Buddhist nun's pharmaceutical composition, explanation application No. is being provided in the patent application of 201810750822.X
Disclosing in book and stepping China for Buddhist nun's content is 5mg, the tablet formulation and technique that production scale is 5000.Inventor is by further
The study found that when making content of the China advanced in years for Buddhist nun reach 45mg or bigger (such as 80mg, 120mg), if by this patent application
Each component in side directly scales up, and may cause the excessive problem of tablet volume.If but directly increasing the patent application
The percentage composition that China replaces Buddhist nun is stepped in prescription, Yin Maihua has viscosity for Buddhist nun itself, then in formulation process it is possible that
Sticking phenomenon, for example, content be 45mg tablet, pressure less than 10 will sticking, content be 80mg or 120mg sticking phenomenon more
Very.The China advanced in years that the patent application provides is not suitable for carrying out the large-scale production of big specification tablet for Buddhist nun's preparation prescription.
In addition, inventor also found, the tablet that the formula of the pharmaceutical composition of above-mentioned patent application is prepared, in room temperature
After storing 24 months under the conditions of (25 DEG C ± 2 DEG C, RH65% ± 5%), stability decline is embodied in dissolution rate decline.
In order to solve the above technical problems, inventor has found by further in-depth study, using magnesium stearate as profit
Lubrication prescription can effectively solve the problem that using lactose and/or microcrystalline cellulose as filler and step China for Buddhist nun's pharmaceutical composition in big specification
Sticking problem in the large-scale production of tablet, while also assuring good quality stability.
In consideration of it, the present invention, which provides one kind China advanced in years, replaces Buddhist nun's pharmaceutical composition, including advanced in years magnificent for Buddhist nun and pharmaceutic adjuvant, it is described
Pharmaceutic adjuvant includes lubricant and filler；It is characterized in that, the lubricant includes magnesium stearate, the filler includes cream
Sugar and/or microcrystalline cellulose.
Optionally, the filler further includes mannitol；
Optionally, the pharmaceutic adjuvant further includes disintegrating agent, and optionally, the disintegrating agent includes carboxyrnethyl starch sodium or crosslinking
Carmethose.
Optionally, in described pharmaceutical composition each component weight content are as follows: step China replace Buddhist nun 8-99%, be chosen as 15-
80%, it is chosen as 24-60%；Optionally, lubricant 0.1-10% is chosen as 0.5-5%, is chosen as 1-2%；Optionally, it fills out
Agent 0-91.5% is filled, 5-65% is chosen as, is chosen as 30-65%；Optionally, disintegrating agent 0-15% is chosen as 1-10%, optional
For 1-5%.
Optionally, in described pharmaceutical composition each component weight content are as follows: magnesium stearate 0.1-10% is chosen as
0.5-5% is chosen as 1-2%；Optionally, microcrystalline cellulose 0-91.5% is chosen as 5-65%, is chosen as 30-65%；It can
Selection of land, lactose 0-91.5%, is chosen as 5-65%, is chosen as 30-65%；
Optionally, in described pharmaceutical composition each component weight content are as follows: magnesium stearate 1-2%；Microcrystalline cellulose
For 30-65%；Lactose is 30-65%.
Optionally, described pharmaceutical composition is tablet or capsule；Optionally, the tablet is Film coated tablets or sugar-coat
Piece.
Optionally, it is 30-120mg that China is stepped in the unit dosage forms of described pharmaceutical composition for the content of Buddhist nun, is chosen as 45-
80mg, more preferable 60mg.
On the other hand, the present invention also provides the preparation method of aforementioned pharmaceutical compositions, described pharmaceutical composition is tablet, is adopted
Preparation process is pressed disc method after direct compression method or dry granulation；
Described pharmaceutical composition is capsule, the preparation method used for the directly filling capsule of powder or dry granulation after fill
It is encapsulated.
Optionally, the direct compression method or directly filling capsule method include the following steps:
(1) it mixes: taking the China advanced in years of recipe quantity for Buddhist nun and auxiliary material, be added in hopper mixing machine and mix.
(2) tabletting or filling capsule.
Optionally, filling capsule method includes the following steps: after pressed disc method or dry granulation after the dry granulation
(1) it mixes: taking the China advanced in years of recipe quantity for Buddhist nun and auxiliary material, be added in hopper mixing machine and mix；
(2) dry granulation: taking mixed-powder, pelletizes on dry granulating machine；
(3) tabletting or filling capsule.
Optionally, the tablet contains coatings, and the weight of coatings is the 3% of tablet weight.
Coatings are using conventional coating material, such as Opadry.
In addition, application No. is the supplementary material compatibility test of the patent application of 201810750822.X (DSC scanning methods)
In, it discloses China advanced in years and replaces the melting peak of Buddhist nun and magnesium stearate not corresponding for Buddhist nun and the melting peak of magnesium stearate mixture and China advanced in years,
There may be consistency problems for the two；After microcrystalline cellulose is mixed with China advanced in years for Buddhist nun, a new endothermic peak is generated, the two can also
There can be consistency problem.Therefore, magnesium stearate is not recommended to use in the patent application as lubricant, is not recommended to use crystallite
Cellulose is as filler.The present inventor further studies, and China advanced in years is taken to replace for Buddhist nun and magnesium stearate (mass ratio 5:1), China advanced in years
Buddhist nun and microcrystalline cellulose (mass ratio 1:5) physical mixture, in be protected from light, (total illumination is not less than 1.2 × 10 to Qiang Guang6Lux.hr,
Near ultraviolet energy is not less than 200W.hr/m2), high temperature (60 DEG C), place 10 days under the conditions of high humidity (RH90% ± 5%), respectively at
0th day, 5 days and the 10th day sample detection investigates appearance, the situation of change in relation to substance.It high temperature and humidity and is protected from light as the result is shown
Lower no significant change, long-term impurity of placing is without significant change.Big specification, large-scale production are carried out stepping China for Buddhist nun's pharmaceutical composition
Technique in, the control of the environment temperature of production is no more than 30 DEG C, and instantaneous temperature is not also high, therefore can be to avoid China advanced in years for Buddhist nun and hard
The consistency problem of fatty acid magnesium and microcrystalline cellulose.
It is antineoplastic that China, which is stepped, for Buddhist nun, and toxicological study shows that it has certain side effect, mainly shows mucosal toxicity.Cause
This above-mentioned simple film-making or Capsule technologies processed, on the one hand can simplify production technology, improve the versatility of production equipment, adapt to
In mass production；It on the other hand can be with further protection worker from pollution, to reduce the generation of professional risk.
The present invention steps China in Buddhist nun's pharmaceutical composition, selects magnesium stearate as lubricant, lactose and/or microcrystalline cellulose
As filler, China advanced in years has been well solved for sticking problem of Buddhist nun's pharmaceutical composition in big specification, large-scale production, simultaneously
Also assure good quality stability.
Detailed description of the invention
Fig. 1 is the dissolution curve that the resulting China advanced in years of embodiment 3 replaces Buddhist nun's piece.
Specific embodiment
Detailed description of the preferred embodiments below.It should be understood that described herein specific
Being given for example only property of embodiment the present invention will be described, be not intended to restrict the invention.
China is stepped in following embodiment for the specification of Buddhist nun with C21H19ClF3N5O2Meter, prescription throwing amount replace two horse of Buddhist nun to step China
Carry out hydrochlorate C21H19ClF3N5O2·(C4H4O4)2Meter.
Comparative example 1:
China advanced in years is replaced the content of Buddhist nun by 12% by the prescription of embodiment 1 in the application of reference application number 201810750822.X
It is increased to 27%, while the content of lactose is reduced to 70% by 85%, when preparation 45mg steps China for Buddhist nun's piece, sticking feelings occurs
Condition.
Prescription:
Preparation method with application number 201810750822.X embodiment 1, specifically:
(1) it is sieved: taking and step China for Buddhist nun and stearic acid, sieve with 100 mesh sieve respectively.
(2) it weighs: it is spare for Buddhist nun, lactose and stearic acid to weigh recipe quantity China advanced in years.
(3) it premixes: taking the China advanced in years of recipe quantity for Buddhist nun, lactose, be added in hopper mixing machine, speed 24rpm, mixing are set
20min。
(4) dry granulation: taking pre-mix powder, pelletizes on dry granulating machine, parameter setting are as follows: starting pressure 7MPa, eventually
Only pressure 8MPa, 3~10rpm of feeding speed, tabletting 5~10rpm of speed, whole grain 100~150rpm of speed, sieve mesh number 24
Mesh.
(5) total mix: taking the stearic acid of particle and recipe quantity obtained, be added in hopper mixing machine and mix, setting speed
24rpm is mixed 20 minutes, sample detection mixture homogeneity.
(6) fusion treatment: the particle after taking total mix, which is set in constant temperature convection oven, to be merged, and fusion temperature is 70 DEG C, when
Between 1 hour.
(7) whole grain: taking fused particle, carries out whole grain with 24 meshes.
(8) tabletting: selecting the punching of Ф 9.0mm scrobicula, carries out tabletting by theoretical slice weight.
As a result: when being pressed into about 10, start sticking, piece sublist face starts the granular a small amount of deficient phenomena of sesame occur,
And it is increasingly severe.It is unable to complete tabletting.
Embodiment 1:
Prescription:
Preparation method:
(1) mix: it is spare into Polythene Bag for Buddhist nun and auxiliary material to weigh China advanced in years by recipe quantity；By weighed China advanced in years for Buddhist nun and
Auxiliary material pours into hopper mixing machine, and revolving speed 25rpm is arranged, and mixes 20 minutes；
(2) tabletting: using suitable punch die, adjusts filling and piece is thick, tabletting.
As a result: not occurring the phenomenon that tabletting sticking in preparation process, smoothly prepare qualified tablet.
Embodiment 2:
Prescription:
Preparation method:
(1) mix: it is spare into Polythene Bag for Buddhist nun and auxiliary material to weigh China advanced in years by recipe quantity；By weighed China advanced in years for Buddhist nun and
Auxiliary material pours into hopper mixing machine, and revolving speed 25rpm is arranged, and mixes 20 minutes；
(2) tabletting: using suitable punch die, adjusts filling and piece is thick, tabletting；
(3) it is coated: taking 0.75Kg Opadry coating powder, be added in purified water, it is stirring while adding, it is configured to solid content
13% coating solution；The plain piece pressed is put into seed-coating machine, setting inlet air temperature is 70 degree, atomizing pressure 0.2MPa, coating
Weight gain about 3%.
As a result: not occurring the phenomenon that tabletting sticking in preparation process, smoothly prepare qualified tablet.
Embodiment 3:
Prescription:
Preparation method:
(1) mix: it is spare into Polythene Bag for Buddhist nun and auxiliary material to weigh China advanced in years by recipe quantity；By weighed China advanced in years for Buddhist nun and
Auxiliary material pours into hopper mixing machine, and revolving speed 25rpm is arranged, and mixes 20 minutes；
(2) tabletting: using suitable punch die, adjusts filling and piece is thick, tabletting；
(3) it is coated: taking 0.45Kg Opadry coating powder, be added in purified water, it is stirring while adding, it is configured to solid content
13% coating solution；The plain piece pressed is put into seed-coating machine, setting inlet air temperature is 70 degree, atomizing pressure 0.2MPa, coating
Weight gain about 3%.
As a result: not occurring the phenomenon that tabletting sticking in preparation process, smoothly prepare qualified tablet.
Embodiment 4:
Prescription:
Preparation method:
(1) mix: it is spare into Polythene Bag for Buddhist nun and auxiliary material to weigh China advanced in years by recipe quantity；By weighed China advanced in years for Buddhist nun and
Auxiliary material pours into hopper mixing machine, and revolving speed 25rpm is arranged, and mixes 20 minutes；
(2) dry granulation: taking said mixture, is pelletized with dry granulating machine, 24 mesh sieves；
(3) tabletting: using suitable punch die, adjusts filling and piece is thick, tabletting；
(4) it is coated: taking 0.012Kg Opadry coating powder, be added in purified water, it is stirring while adding, it is configured to solid content
13% coating solution；The plain piece pressed is put into seed-coating machine, setting inlet air temperature is 70 degree, atomizing pressure 0.2MPa, coating
Weight gain about 3%.
As a result: not occurring the phenomenon that tabletting sticking in preparation process, smoothly prepare qualified tablet.
Embodiment 5:
Prescription
Preparation method:
It is same as Example 1.
As a result: not occurring the phenomenon that tabletting sticking in preparation process, smoothly prepare qualified tablet.
Embodiment 6:
Prescription:
Preparation method: same as Example 1.
As a result: not occurring the phenomenon that tabletting sticking in preparation process, smoothly prepare qualified tablet.
Embodiment 7:
Prescription
Preparation method: same as Example 1.
As a result: not occurring the phenomenon that tabletting sticking in preparation process, smoothly prepare qualified tablet.
Embodiment 8:
Prescription:
Preparation method:
(1) mix: it is spare into Polythene Bag for Buddhist nun and auxiliary material to weigh China advanced in years by recipe quantity；By weighed China advanced in years for Buddhist nun and
Auxiliary material pours into hopper mixing machine, and revolving speed 25rpm is arranged, and mixes 20 minutes；
(2) suitable capsule shells, filling capsule filling capsule: are used.
Embodiment 9:
Prescription:
Preparation method: same as Example 1.
As a result: not occurring the phenomenon that tabletting sticking in preparation process, smoothly prepare qualified tablet.
Test example 1: dissolution curve test
Experimental method: the resulting China advanced in years of Example 3 replaces Buddhist nun's piece, according to dissolution method (Chinese Pharmacopoeia version in 2015 the
Four 0,931 second methods of general rule), using 900ml pH6.8 buffer as dissolution medium, revolving speed is 50 turns per minute, respectively 5,
10,15,20,30,45,60 minutes when, solution 10ml is taken, while supplementing 10ml dissolution medium, by the sample of taking-up with 0.45 μm
Filter membrane filtration, discards 2ml, subsequent filtrate is taken to be diluted to a certain concentration as test solution.According to UV-VIS spectrophotometry
(four general rules 0401 of Chinese Pharmacopoeia version in 2015) measurement, Detection wavelength 335nm.It separately takes and steps magnificent appropriate for Buddhist nun's reference substance, precision
It is weighed, add dissolution medium to dissolve and every ml is made and replaces 22.2 μ g of Buddhist nun (with C containing China is stepped21H19ClF3N5O2Meter) solution as control
Product solution, is measured in the same method.Every the amount of dissolution is calculated with absorbance by external standard method.With when m- dissolution rate draw dissolution curve, knot
Fruit sees Fig. 1.
As can be seen from Figure 1: China advanced in years of the invention is quick releasing formulation for Buddhist nun's piece, can be with Fast Stripping.
Test example 2: stability contrast experiment
Sample 1: by patent application step China for Buddhist nun's pharmaceutical composition and preparation method thereof (application number 201810750822.X,
The applying date is on July 10th, 2018) in embodiment 1 China advanced in years for being prepared of prescription for Buddhist nun's piece, specific preparation method and place
Side is as follows:
Prescription: (specification: 5mg, with C21H19ClF3N5O2Meter)
[note 1]: with C21H19ClF3N5O2·(C4H4O4)2Meter.
Preparation method:
(1) it is sieved: taking and step China for Buddhist nun and stearic acid, sieve with 100 mesh sieve respectively.
(2) it weighs: it is spare for Buddhist nun, lactose and stearic acid to weigh recipe quantity China advanced in years.
(3) it premixes: taking the China advanced in years of recipe quantity for Buddhist nun, lactose, be added in hopper mixing machine, speed 24rpm, mixing are set
20min。
(4) dry granulation: taking pre-mix powder, pelletizes on dry granulating machine, parameter setting are as follows: starting pressure 7MPa, eventually
Only pressure 8MPa, 3~10rpm of feeding speed, tabletting 5~10rpm of speed, whole grain 100~150rpm of speed, sieve mesh number 24
Mesh.
(5) total mix: taking the stearic acid of particle and recipe quantity obtained, be added in hopper mixing machine and mix, setting speed
24rpm is mixed 20 minutes, sample detection mixture homogeneity.
(6) fusion treatment: the particle after taking total mix, which is set in constant temperature convection oven, to be merged, and fusion temperature is 70 DEG C, when
Between 1 hour.
(7) whole grain: taking fused particle, carries out whole grain with 24 meshes.
(8) tabletting: selecting the punching of Ф 5.0mm scrobicula, carries out tabletting by theoretical slice weight.
Sample 2: it is prepared by embodiment 3
Experimental method: taking sample 1 and sample 2, and the stability for being placed in 25 DEG C of ± 2 DEG C/RH60% ± 5% keeps sample in case, in
24 months sampling and measuring dissolution rates, were compared with 0 month.For dissolution determination method with test example 1, sample time is 30 minutes,
Dissolution determination result see the table below.
Experimental result:
| The dissolution results of 30min | 0 month | 24 months |
| Sample 1 | 84% | 67% |
| Sample 2 | 87% | 87% |
Experiment conclusion: the sample 2 prepared using 3 prescription of embodiment: being stepped China and replace Buddhist nun's piece, after storage 24 months, dissolution rate
Do not decline, and the prescription in application number 201810750822.X is used to prepare resulting sample 1, dissolution rate decline shows this
The China advanced in years of application is more preferable for Buddhist nun's pharmaceutical composition quality stability.
Claims (9)
1. a kind of pharmaceutical composition, including step China and replace Buddhist nun and pharmaceutic adjuvant, the pharmaceutic adjuvant includes lubricant and filler；
It is characterized in that, the lubricant includes magnesium stearate, the filler includes lactose and/or microcrystalline cellulose.
2. pharmaceutical composition according to claim 1, which is characterized in that the filler further includes mannitol.
3. pharmaceutical composition according to claim 1 or 2, which is characterized in that the pharmaceutic adjuvant further includes disintegrating agent, can
Selection of land, the disintegrating agent are selected from carboxyrnethyl starch sodium or cross-linked carboxymethyl cellulose sodium.
4. pharmaceutical composition according to claim 1-3, which is characterized in that following components is in the pharmaceutical composition
Weight content in object: stepping China for Buddhist nun is 8-99%, is chosen as 15-80%, is chosen as 24-60%；Optionally, lubricant is
0.1-10% is chosen as 0.5-5%, is chosen as 1-2%；Optionally, filler 0-91.5% is chosen as 5-65%, optional
For 30-65%；Optionally, disintegrating agent 0-15% is chosen as 1-10%, is chosen as 1-5%.
5. pharmaceutical composition according to claim 1-4, which is characterized in that each component in described pharmaceutical composition
Weight content are as follows: magnesium stearate 0.1-10% is chosen as 0.5-5%, is chosen as 1-2%；Optionally, microcrystalline cellulose is
0-91.5% is chosen as 5-65%, is chosen as 30-65%；Optionally, lactose 0-91.5% is chosen as 5-65%, is chosen as
30-65%；
Optionally, in described pharmaceutical composition each component weight content are as follows: magnesium stearate 1-2%；Microcrystalline cellulose is 30-
65%；Lactose is 30-65%.
6. pharmaceutical composition according to claim 1-5, which is characterized in that described pharmaceutical composition be tablet or
Capsule.
7. pharmaceutical composition according to claim 6, which is characterized in that the tablet is Film coated tablets or sugar coated tablet.
8. pharmaceutical composition according to claim 1-7, which is characterized in that the unit dose of described pharmaceutical composition
It is 30-120mg that China is stepped in type for the content of Buddhist nun, is chosen as 45-80mg, more preferable 60mg.
9. the preparation method of any one of claim 1-8 described pharmaceutical composition, which is characterized in that described pharmaceutical composition is piece
Agent, preparation method are direct compression method or compressing dry granulation；
Alternatively, described pharmaceutical composition is capsule, preparation method is filling capsule after direct filling capsule or dry granulation.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910292591.7A CN110037991B (en) | 2019-04-12 | 2019-04-12 | Stable maihuatinib pharmaceutical composition and preparation method thereof |
| PCT/CN2020/083994 WO2020207441A1 (en) | 2019-04-12 | 2020-04-09 | Stable mefatinib pharmaceutical composition and preparation method therefor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910292591.7A CN110037991B (en) | 2019-04-12 | 2019-04-12 | Stable maihuatinib pharmaceutical composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110037991A true CN110037991A (en) | 2019-07-23 |
| CN110037991B CN110037991B (en) | 2021-07-27 |
Family
ID=67276905
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910292591.7A Active CN110037991B (en) | 2019-04-12 | 2019-04-12 | Stable maihuatinib pharmaceutical composition and preparation method thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN110037991B (en) |
| WO (1) | WO2020207441A1 (en) |
Cited By (2)
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| WO2020207441A1 (en) * | 2019-04-12 | 2020-10-15 | 杭州华东医药集团新药研究院有限公司 | Stable mefatinib pharmaceutical composition and preparation method therefor |
| CN113750059A (en) * | 2020-06-05 | 2021-12-07 | 杭州中美华东制药有限公司 | Mewatinib tablet and preparation method thereof |
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| CN110037991B (en) * | 2019-04-12 | 2021-07-27 | 杭州华东医药集团新药研究院有限公司 | Stable maihuatinib pharmaceutical composition and preparation method thereof |
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| CN104546780A (en) * | 2014-12-12 | 2015-04-29 | 安徽一灵药业有限公司 | Daclatasvir film coating tablet preparation and preparation method thereof |
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| WO2020207441A1 (en) * | 2019-04-12 | 2020-10-15 | 杭州华东医药集团新药研究院有限公司 | Stable mefatinib pharmaceutical composition and preparation method therefor |
| CN113750059A (en) * | 2020-06-05 | 2021-12-07 | 杭州中美华东制药有限公司 | Mewatinib tablet and preparation method thereof |
| CN113750059B (en) * | 2020-06-05 | 2022-11-15 | 杭州中美华东制药有限公司 | Mewatinib tablet and preparation method thereof |
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| Publication number | Publication date |
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| CN110037991B (en) | 2021-07-27 |
| WO2020207441A1 (en) | 2020-10-15 |
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Effective date of registration: 20220318 Address after: 310012 c910, Xihu international science and technology building, No. 391, Wener Road, Xihu District, Hangzhou, Zhejiang Province Patentee after: HANGZHOU HUADONG MEDICINE GROUP PHARMACEUTICAL RESEARCH INSTITUTE Co.,Ltd. Patentee after: Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd Address before: 310011 new drug research institute, No. 866, Moganshan Road, Hangzhou, Zhejiang Patentee before: HANGZHOU HUADONG MEDICINE GROUP PHARMACEUTICAL RESEARCH INSTITUTE Co.,Ltd. |