CN106074545B - A kind of clopidogrel tablet and preparation method thereof that magnetic disturbance is stable - Google Patents
A kind of clopidogrel tablet and preparation method thereof that magnetic disturbance is stable Download PDFInfo
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- CN106074545B CN106074545B CN201610681016.2A CN201610681016A CN106074545B CN 106074545 B CN106074545 B CN 106074545B CN 201610681016 A CN201610681016 A CN 201610681016A CN 106074545 B CN106074545 B CN 106074545B
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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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
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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
- A61K9/2009—Inorganic 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
Abstract
The present invention proposes a kind of clopidogrel tablet that magnetic disturbance is stable.It is characterized in that by the clopidogrel tablet of magnetic micro-powder silica gel interference stability, the raw material composition including following parts by weight: 75 parts of the pharmaceutically acceptable salt of clopidogrel, 10 ~ 80 parts of D-sorbite, 1 ~ 10 part of magnetic micro-powder silica gel, 0.1 ~ 5 part of vitamin B, 0.5 ~ 10 part of sustained release agent, 1 ~ 15 part of disintegrating agent, 1 ~ 10 part of lubricant.By carrying out magnetic modification to superfine silica gel powder, stabilizer as clopidogrel, it is effective that clopidogrel dextroisomer is inhibited to be converted into laevoisomer, ensure safety of the clopidogrel tablet in the stability and medicine use process during storage, it made more effectively to play therapeutic effect, at the same tablet it is oral after due to that can be enriched with by magnetic particle, absorb clopidogrel quickly, it prevents from being lost, improves the validity of clopidogrel, reduce its toxic side effect.Clopidogrel tablet producing technology of the present invention is simple, and particularly suitable for industrialized production, and the preparation prepared is with good performance.
Description
Technical field
The invention belongs to pharmaceutical technology field, it is related to a kind of pharmaceutical preparation and preparation method thereof, more particularly to a kind of magnetic
Clopidogrel tablet of interference stability and preparation method thereof.
Background technique
Clopidogrel, its chemical name is (+)-(S)-α-(2- Chloro-O-Phenyl) -6,7- dihydro-thiophene simultaneously [3,2-c] pyrroles
Pyridine -5 (4H)-methyl acetate is a kind of platelet aggregation inhibitor of inductivity, by inhibiting platelet aggregation to reduce artery
The chance of obstruction has the function that inhibition platelet aggregation, pre- anti-stroke and heart attack curative effect is played, at present in clinic
On be mainly used for treat atherosclerosis disease, acute coronary artery syndrome, prevention coronary stenting after-poppet in again
Narrow and thrombotic complications etc..
Clopidogrel is a kind of sticky grease, therefore salt use is generally prepared as in preparation process, such as hydrochloride, sulphur
Sour hydrogen salt and benzene sulfonate etc..Contain ester bond and chiral carbon in clopidogrel molecule structure, to light, heat, wet, high pH value is equal
More sensitive, being easy to happen Degradation and Transformation is clopidogrel acid, chiral inversion also easily occurs in preparation process, i.e., from dextroisomer
The problems such as being easier to be converted into laevoisomer, and generating compatibility with auxiliary material.Existing report shows the left-handed different of clopidogrel
Structure body is almost without the effect of anti-platelet aggregation, and its toxicity is apparently higher than the dextroisomer of clopidogrel, therefore chlorine pyrrole
The content of Gray's laevoisomer has increased slightly, and just has a great impact to the success of operation, close association the life of patient
Health.So the content of laevoisomer and the clopidogrel acid of strict control clopidogrel is the important finger for controlling the quality of production
Mark.For the problem present on, the prior art uses a variety of methods and attempts to solve.
China Patent Publication No. CN101721410A discloses a kind of stable solid composite medicament, contains I crystal sulfuric acid
Clopidogrel hydrogen, Macrogol 6000 and superfine silica gel powder, and the disintegrating agent selected from low-substituted hydroxypropyl cellulose and selected from micro-
The filler of one or more of crystalline cellulose, dextrin and pregelatinized starch, wherein in terms of composition weight, I crystal form sulfuric acid
The content of clopidogrel hydrogen is 15%~50%, and the content of polyethylene glycol is 1%~25%, the content of superfine silica gel powder is 3.5~
5%, the content of disintegrating agent is 2%~5%, and the content of filler is 40%~60%.
It discloses in Chinese patent application CN1935119A and is replaced using glycerol palmitic, stearic rouge and superfine silica gel powder
Magnesium stearate effectively increases the stability of solid pharmaceutical preparation, but the mobility of particle can be made to decline, and causes to be stranded to tableting processes
It is difficult.And polyglycerol stearate is hydrophobic auxiliary, with the dissolution for being likely to influence main ingredient after main ingredient granulation.
China Patent Publication No. CN 102058550A discloses clopidogrel bisulfate tablet and preparation method thereof, with chlorine pyrrole
The bisulfate clopidogrel of Gray's meter, further includes filler, disintegrating agent, solubilizer, glidant and lubricant.Using in prescription
The method that granular microcrystalline cellulose and the superfine silica gel powder handled through air-flow crushing is added, so that the simple process of dry granulation can
Row, favorable reproducibility, prepared product stability is high, can meet the needs being continuously mass produced.
In conclusion the technology for solving clopidogrel stability difference at present mainly adds lubricant or coating agent, such as add
Superfine silica gel powder or the mixture with other auxiliary agents is added not to solve fundamentally although the stability of clopidogrel can be improved
The problem of clopidogrel salt configuration converts.
Summary of the invention
In view of the deficiencies of the prior art, the present invention proposes a kind of clopidogrel tablet that magnetic disturbance is stable and its preparation sides
Method.The clopidogrel tablet is equipped with D-sorbite, vitamin B, sustained release using clopidogrel pharmaceutically acceptable salt as main ingredient
Agent, disintegrating agent, lubricant and magnetic micro-powder silica gel, it is mixed with clopidogrel salt by carrying out magnetic modification to superfine silica gel powder
It closes, inhibits the conversion of clopidogrel isomer using magnetic interference, solve clopidogrel dextrorotation in clopidogrel solid pharmaceutical preparation
Isomers is converted into the problem of laevoisomer, it is ensured that stability and medicine of the clopidogrel tablet during storage used
Safety in journey makes it more effectively play therapeutic effect, at the same tablet it is oral after due to that can be enriched with by magnetic particle, make
Clopidogrel quickly absorbs, and prevents from being lost, and improves the validity of clopidogrel, reduces its toxic side effect.
To solve the above problems, the invention adopts the following technical scheme:
A kind of clopidogrel tablet that magnetic disturbance is stable, it is characterised in that by the chlorine pyrrole lattice of magnetic micro-powder silica gel interference stability
Thunder tablet, the raw material composition including following parts by weight: 75 parts of the pharmaceutically acceptable salt of clopidogrel, 10 ~ 80 parts of D-sorbite, magnetic
Property 1 ~ 10 part of superfine silica gel powder, 0.1 ~ 5 part of vitamin B, 0.5 ~ 10 part of sustained release agent, 1 ~ 15 part of disintegrating agent, 1 ~ 10 part of lubricant.
The magnetic micro-powder silica gel is core-shell structure, and kernel is magnetic ferrites nanoparticle of the partial size in 1 ~ 100nm,
Shell is superfine silica gel powder.
The pharmaceutically acceptable salt of the clopidogrel is selected from clopidogrel hydrochloride, clopidogrel hydrogenesulphate, chlorine pyrrole
Gray's benzene sulfonate, clopidogrel maleate, clopidogrel amino-acid salt, any one in clopidogrel hydrobromate.
The sustained release agent is polyethylene glycol/polylactic acid copolymer, hydroxypropyl methyl cellulose, magnesium stearate, carboxymethyl
The mixture of one or both of sodium starch.
The disintegrating agent is crosslinked polyvinylpyrrolidone.
The lubricant is talcum powder, any one in olive oil.
A kind of preparation method for the clopidogrel tablet that magnetic disturbance is stable, it is characterised in that it is specific the preparation method is as follows:
(1) by superfine silica gel powder be sieved choose 100 ~ 200 mesh, be added in anhydrous cyclohexane organic solvent, superfine silica gel powder with
The mass volume ratio of anhydrous cyclohexane is 1:40~80, and microwave oscillation reacts 10 ~ 20min, is dispersed in superfine silica gel powder
In organic solvent；70 ~ 85 DEG C are warming up to, amino silicane coupling agent is slowly added dropwise, constant temperature 3 ~ 8h of reflux is added magnetic ferrites and receives
Rice corpuscles reacts 1 ~ 3h with 500 ~ 800rpm mixing speed, and filtration drying obtains magnetic micro-powder silica gel；
(2) 75 portions of pharmaceutically acceptable salt of clopidogrel are weighed and cross 100 ~ 200 meshes, be proportionally added into D-sorbite 10 ~
1-10 parts of magnetic micro-powder silica gel mixing obtained in step (1) are added in 80 parts, 0.1 ~ 5 part of vitamin B, 0.5 ~ 10 part of sustained release agent
Gained tablet grinding and sieving is pelletized in uniform tabletting；
(3) particle for obtaining step (2) and 1 ~ 15 part of disintegrating agent, 1 ~ 10 part of lubricant direct pressing after mixing,
Up to a kind of clopidogrel tablet that magnetic disturbance is stable.
The amino silicane coupling agent be phenylaminomethyl trimethoxy silane, phenylaminomethyl triethoxysilane,
Any one in aminoethylaminopropyl trimethyl silane, dosage are the 0.5 ~ 3% of superfine silica gel powder dosage.
Mass percentage of the magnetic ferrites nanoparticle in magnetic micro-powder silica gel is 30 ~ 65%.
A kind of clopidogrel tablet and preparation method thereof that magnetic disturbance is stable of the present invention protrudes compared with prior art
The characteristics of and excellent effect be:
1, stabilizer of the addition magnetic micro-powder silica gel as clopidogrel in the present invention, it is effective to inhibit clopidogrel dextrorotation
Isomers is converted into laevoisomer, it is ensured that clopidogrel tablet is in the stability and medicine use process during storage
Safety makes it more effectively play therapeutic effect, at the same tablet it is oral after due to that can be enriched with by magnetic particle, make chlorine pyrrole lattice
Thunder quickly absorbs, and prevents from being lost, and improves the validity of clopidogrel, reduces its toxic side effect.
2, clopidogrel tablet formulation of the present invention is reasonable, and each component compatibility is good, and obtained tablet quality is stablized, and reappears
Property is good；It solves the problems, such as the sticking in production process, is suitble to industrial production.
3, the present invention uses direct tablet compressing method, and simple process is easy to industrialized production, prepared clopidogrel tablet
Meet drug registration standard, does not find apparent configuration Transformation Phenomenon.
Specific embodiment
The present invention is explained in detail below in conjunction with specific embodiment, is not restricted to the present invention.It is not departing from
In the case where above method thought of the present invention, the various replacements made according to ordinary skill knowledge and customary means or change
Into should all be included in the protection scope of the present invention.
Embodiment 1
Component proportion:
| Material name | Dosage |
| Clopidogrel hydrochloride | 75 parts by weight (in terms of clopidogrel free alkali) |
| D-sorbite | 10 parts by weight |
| Vitamin B | 0.1 parts by weight |
| Polyethylene glycol/polylactic acid copolymer | 1.5 parts by weight |
| Crosslinked polyvinylpyrrolidone | 1 parts by weight |
| Talcum powder | 1 parts by weight |
| Magnetic micro-powder silica gel | 1 parts by weight |
Preparation method:
(1) by superfine silica gel powder be sieved choose 100 ~ 200 mesh, be added in anhydrous cyclohexane organic solvent, superfine silica gel powder with
The mass volume ratio of anhydrous cyclohexane is 1:40, and microwave oscillation reacts 20min, is dispersed in superfine silica gel powder organic molten
In agent；85 DEG C are warming up to, phenylaminomethyl trimethoxy silane is slowly added dropwise, magnetic ferrites nanometer is added in constant temperature reflux 3h
Particle reacts 1h with 800rpm mixing speed, and filtration drying obtains magnetic micro-powder silica gel；
(2) it weighs clopidogrel hydrochloride and crosses 100 ~ 200 meshes, be proportionally added into D-sorbite, vitamin B, poly- second two
Alcohol/copolymer of poly lactic acid is added magnetic micro-powder silica gel obtained in step (1) and is uniformly mixed tabletting, after gained tablet is crushed
Sieving granulation；
(3) particle for obtaining step (2) and talcum powder and crosslinked polyvinylpyrrolidone direct pressing after mixing,
Up to a kind of clopidogrel tablet that magnetic disturbance is stable.
Embodiment 2
Component proportion:
| Material name | Dosage |
| Clopidogrel hydrogenesulphate | 75 parts by weight (in terms of clopidogrel free alkali) |
| D-sorbite | 20 parts by weight |
| Vitamin B | 1 parts by weight |
| Polyethylene glycol/polylactic acid copolymer | 2 parts by weight |
| Sodium carboxymethyl starch | 2 parts by weight |
| Crosslinked polyvinylpyrrolidone | 1 parts by weight |
| Talcum powder | 2 parts by weight |
| Magnetic micro-powder silica gel | 2 parts by weight |
Preparation method:
(1) by superfine silica gel powder be sieved choose 100 ~ 200 mesh, be added in anhydrous cyclohexane organic solvent, superfine silica gel powder with
The mass volume ratio of anhydrous cyclohexane is 1:50, and microwave oscillation reacts 20min, is dispersed in superfine silica gel powder organic molten
In agent；70 DEG C are warming up to, phenylaminomethyl trimethoxy silane is slowly added dropwise, magnetic ferrites nanometer is added in constant temperature reflux 8h
Particle reacts 3h with 500rpm mixing speed, and filtration drying obtains magnetic micro-powder silica gel；
(2) it weighs clopidogrel hydrogenesulphate and crosses 100 ~ 200 meshes, be proportionally added into D-sorbite, vitamin B, poly- second
Glycol/copolymer of poly lactic acid and sodium carboxymethyl starch are added magnetic micro-powder silica gel obtained in step (1) and are uniformly mixed tabletting,
Gained tablet grinding and sieving is pelletized；
(3) particle for obtaining step (2) and talcum powder and crosslinked polyvinylpyrrolidone direct pressing after mixing,
Up to a kind of clopidogrel tablet that magnetic disturbance is stable.
Embodiment 3
Component proportion (clopidogrel content 75mg/ piece):
| Material name | Dosage |
| Clopidogrel benzene sulfonate | 75 parts by weight (in terms of clopidogrel free alkali) |
| D-sorbite | 40 parts by weight |
| Vitamin B | 2 parts by weight |
| Hydroxypropyl methyl cellulose | 4 parts by weight |
| Magnesium stearate | 3 parts by weight |
| Crosslinked polyvinylpyrrolidone | 2 parts by weight |
| Olive oil | 4 parts by weight |
| Magnetic micro-powder silica gel | 5 parts by weight |
Preparation method:
(1) by superfine silica gel powder be sieved choose 100 ~ 200 mesh, be added in anhydrous cyclohexane organic solvent, superfine silica gel powder with
The mass volume ratio of anhydrous cyclohexane is 1:60, and microwave oscillation reacts 15min, is dispersed in superfine silica gel powder organic molten
In agent；75 DEG C are warming up to, phenylaminomethyl triethoxysilane is slowly added dropwise, magnetic ferrites nanometer is added in constant temperature reflux 5h
Particle reacts 2h with 800rpm mixing speed, and filtration drying obtains magnetic micro-powder silica gel；
(2) it weighs clopidogrel benzene sulfonate and crosses 100 ~ 200 meshes, be proportionally added into D-sorbite, vitamin B, hydroxypropyl
Ylmethyl cellulose and magnesium stearate are added magnetic micro-powder silica gel obtained in step (1) and are uniformly mixed tabletting, by gained tablet
Grinding and sieving granulation；
(3) particle for obtaining step (2) and olive oil and crosslinked polyvinylpyrrolidone direct pressing after mixing,
Up to a kind of clopidogrel tablet that magnetic disturbance is stable.
Embodiment 4
Component proportion (clopidogrel content 75mg/ piece):
| Material name | Dosage |
| Clopidogrel maleate | 75 parts by weight (in terms of clopidogrel free alkali) |
| D-sorbite | 50 parts by weight |
| Vitamin B | 3 parts by weight |
| Magnesium stearate | 5 parts by weight |
| Sodium carboxymethyl starch | 4 parts by weight |
| Crosslinked polyvinylpyrrolidone | 2 parts by weight |
| Talcum powder | 6 parts by weight |
| Magnetic micro-powder silica gel | 8 parts by weight |
Preparation method:
(1) by superfine silica gel powder be sieved choose 100 ~ 200 mesh, be added in anhydrous cyclohexane organic solvent, superfine silica gel powder with
The mass volume ratio of anhydrous cyclohexane is 1:80, and microwave oscillation reacts 10min, is dispersed in superfine silica gel powder organic molten
In agent；80 DEG C are warming up to, aminoethylaminopropyl trimethyl silane is slowly added dropwise, magnetic ferrites nanometer is added in constant temperature reflux 3h
Particle reacts 2h with 600rpm mixing speed, and filtration drying obtains magnetic micro-powder silica gel；
(2) it weighs clopidogrel maleate and crosses 100 ~ 200 meshes, be proportionally added into D-sorbite, vitamin B, tristearin
Sour magnesium and sodium carboxymethyl starch are added magnetic micro-powder silica gel obtained in step (1) and are uniformly mixed tabletting, gained tablet is crushed
Sieving granulation afterwards；
(3) particle for obtaining step (2) and talcum powder and crosslinked polyvinylpyrrolidone direct pressing after mixing,
Up to a kind of clopidogrel tablet that magnetic disturbance is stable.
Embodiment 5
Component proportion:
| Material name | Dosage |
| Clopidogrel amino-acid salt | 75 parts by weight (in terms of clopidogrel free alkali) |
| D-sorbite | 60 parts by weight |
| Vitamin B | 4 parts by weight |
| Sodium carboxymethyl starch | 8 parts by weight |
| Polyethylene glycol/polylactic acid copolymer | 8 parts by weight |
| Crosslinked polyvinylpyrrolidone | 4 parts by weight |
| Olive oil | 8 parts by weight |
| Magnetic micro-powder silica gel | 8 parts by weight |
Preparation method:
(1) by superfine silica gel powder be sieved choose 100 ~ 200 mesh, be added in anhydrous cyclohexane organic solvent, superfine silica gel powder with
The mass volume ratio of anhydrous cyclohexane is 1:40, and microwave oscillation reacts 20min, is dispersed in superfine silica gel powder organic molten
In agent；75 DEG C are warming up to, aminoethylaminopropyl trimethyl silane is slowly added dropwise, magnetic ferrites nanometer is added in constant temperature reflux 4h
Particle reacts 2h with 800rpm mixing speed, and filtration drying obtains magnetic micro-powder silica gel；
(2) it weighs clopidogrel amino-acid salt and crosses 100 ~ 200 meshes, be proportionally added into D-sorbite, vitamin B, carboxylic first
Base sodium starch and polyethylene glycol/polylactic acid copolymer are added magnetic micro-powder silica gel obtained in step (1) and are uniformly mixed tabletting,
Gained tablet grinding and sieving is pelletized；
(3) particle for obtaining step (2) and olive oil and crosslinked polyvinylpyrrolidone direct pressing after mixing,
Up to a kind of clopidogrel tablet that magnetic disturbance is stable.
Embodiment 6
Component proportion (clopidogrel content 75mg/ piece):
| Material name | Dosage |
| Clopidogrel hydrobromate | 75 parts by weight (in terms of clopidogrel free alkali) |
| D-sorbite | 80 parts by weight |
| Vitamin B | 5 parts by weight |
| Hydroxypropyl methyl cellulose | 6 parts by weight |
| Magnesium stearate | 1 parts by weight |
| Sodium carboxymethyl starch | 3 parts by weight |
| Polyethylene glycol/polylactic acid copolymer | 10 parts by weight |
| Crosslinked polyvinylpyrrolidone | 5 parts by weight |
| Olive oil | 10 parts by weight |
| Magnetic micro-powder silica gel | 10 parts by weight |
Preparation method:
(1) by superfine silica gel powder be sieved choose 100 ~ 200 mesh, be added in anhydrous cyclohexane organic solvent, superfine silica gel powder with
The mass volume ratio of anhydrous cyclohexane is 1:40, and microwave oscillation reacts 20min, is dispersed in superfine silica gel powder organic molten
In agent；85 DEG C are warming up to, phenylaminomethyl triethoxysilane is slowly added dropwise, magnetic ferrites nanometer is added in constant temperature reflux 3h
Particle reacts 1h with 800rpm mixing speed, and filtration drying obtains magnetic micro-powder silica gel；
(2) it weighs clopidogrel hydrobromate and crosses 100 ~ 200 meshes, be proportionally added into D-sorbite, vitamin B, hydroxypropyl
Ylmethyl cellulose, magnesium stearate, sodium carboxymethyl starch and polyethylene glycol/polylactic acid copolymer are added obtained in step (1)
Magnetic micro-powder silica gel is uniformly mixed tabletting, and gained tablet grinding and sieving is pelletized；
(3) particle for obtaining step (2) and olive oil and crosslinked polyvinylpyrrolidone direct pressing after mixing,
Up to a kind of clopidogrel tablet that magnetic disturbance is stable.
Beneficial effects of the present invention are illustrated below by detection.
One, Testing index and method
Using ovomucoid bonding spherical silica gel as filler, with acetonitrile -0.01mol/L potassium dihydrogen phosphate (25:
75) it is mobile phase, under conditions of 220nm Detection wavelength, accelerate and long-term stable experiment, detection clopidogrel are left-handed
The content of isomers.The content of national regulation, clopidogrel laevoisomer is no more than 1%.
Two, embodiment sample and prior art reference substance testing result
1, accelerated stability test
2, long-term stable experiment
The above test results show that magnetic micro-powder silica gel of the invention can effectively inhibit clopidogrel dextroisomer
It is converted into laevoisomer, improves the stability of clopidogrel, while improving clinical safety.
Claims (4)
1. a kind of clopidogrel tablet that magnetic disturbance is stable, it is characterised in that by the clopidogrel of magnetic micro-powder silica gel interference stability
Tablet, the raw material composition including following parts by weight: 75 parts of the pharmaceutically acceptable salt of clopidogrel, 10~80 parts of D-sorbite, magnetic
Property 1~10 part of superfine silica gel powder, 0.1~5 part of vitamin B, 0.5~10 part of sustained release agent, 1~15 part of disintegrating agent, lubricant 1~10
Part；
The magnetic micro-powder silica gel is core-shell structure, and kernel is magnetic ferrites nanoparticle of the partial size in 1~100nm, outside
Shell is superfine silica gel powder；
The sustained release agent is polyethylene glycol/polylactic acid copolymer, hydroxypropyl methyl cellulose, magnesium stearate, carboxymethyl starch
The mixture of one or both of sodium；
The disintegrating agent is crosslinked polyvinylpyrrolidone；
The lubricant is talcum powder, any one in olive oil.
2. a kind of stable clopidogrel tablet of magnetic disturbance according to claim 1, it is characterised in that the chlorine pyrrole lattice
The pharmaceutically acceptable salt of thunder is selected from clopidogrel hydrochloride, clopidogrel hydrogenesulphate, clopidogrel benzene sulfonate, clopidogrel
Any one in maleate, clopidogrel hydrobromate.
3. a kind of preparation method for the clopidogrel tablet that magnetic disturbance described in claim 1 is stable, it is characterised in that specific system
Preparation Method is as follows:
(1) by superfine silica gel powder be sieved choose 100~200 mesh, be added in anhydrous cyclohexane organic solvent, superfine silica gel powder with it is anhydrous
The mass volume ratio of hexamethylene is 1:40~80, and microwave oscillation reacts 10~20min, has been dispersed in superfine silica gel powder
In solvent；70~85 DEG C are warming up to, amino silicane coupling agent is slowly added dropwise, constant temperature 3~8h of reflux is added magnetic ferrites and receives
Rice corpuscles reacts 1~3h with 500~800rpm mixing speed, and filtration drying obtains magnetic micro-powder silica gel；The amino silicone
Alkane coupling agent is phenylaminomethyl trimethoxy silane, phenylaminomethyl triethoxysilane, aminoethylaminopropyl trimethyl silicane
Any one in alkane, dosage are the 0.5~3% of superfine silica gel powder dosage；
(2) 75 portions of pharmaceutically acceptable salt of clopidogrel are weighed and cross 100~200 meshes, are proportionally added into D-sorbite 10~80
1-10 parts of magnetic micro-powder silica gel mixing obtained in step (1) are added in part, 0.1~5 part of vitamin B, 0.5~10 part of sustained release agent
Gained tablet grinding and sieving is pelletized in uniform tabletting；
(3) particle for obtaining step (2) and 1~15 part of disintegrating agent, 1~10 part of lubricant direct pressing after mixing, i.e.,
Obtain a kind of clopidogrel tablet that magnetic disturbance is stable.
4. a kind of preparation method of the stable clopidogrel tablet of magnetic disturbance according to claim 3, it is characterised in that step
Suddenly mass percentage of the magnetic ferrites nanoparticle in magnetic micro-powder silica gel described in (1) is 30~65%.
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| CN101766573A (en) * | 2010-02-05 | 2010-07-07 | 上海安必生制药技术有限公司 | Preparation process of clopidogrel bisulfate solid preparation |
| CN104367582A (en) * | 2014-05-20 | 2015-02-25 | 南京海纳医药科技有限公司 | Tablet containing clopidogrel sulfate and aspirin active compositions and preparation method thereof |
| CN105362243A (en) * | 2015-12-18 | 2016-03-02 | 重庆福安药业(集团)股份有限公司 | Clopidogrel hydrogen sulfate oral administration solid medicine composition and preparation method thereof |
-
2016
- 2016-08-18 CN CN201610681016.2A patent/CN106074545B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101766573A (en) * | 2010-02-05 | 2010-07-07 | 上海安必生制药技术有限公司 | Preparation process of clopidogrel bisulfate solid preparation |
| CN104367582A (en) * | 2014-05-20 | 2015-02-25 | 南京海纳医药科技有限公司 | Tablet containing clopidogrel sulfate and aspirin active compositions and preparation method thereof |
| CN105362243A (en) * | 2015-12-18 | 2016-03-02 | 重庆福安药业(集团)股份有限公司 | Clopidogrel hydrogen sulfate oral administration solid medicine composition and preparation method thereof |
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Effective date of registration: 20211111 Address after: 257092 building 10, No. 38, Huanghe Road, economic development zone, Dongying City, Shandong Province Patentee after: Dongying University Science Park Development Co., Ltd Address before: 610091 block 4, Donghai Road, Jiaolong industrial port, Qingyang District, Chengdu, Sichuan Patentee before: Chengdu Xinkeli Chemical Technology Co., Ltd |