CN106890326A - A kind of enteric-coated micro-pill and its preparation containing phosphoesterases complex - Google Patents
A kind of enteric-coated micro-pill and its preparation containing phosphoesterases complex Download PDFInfo
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- CN106890326A CN106890326A CN201510968385.5A CN201510968385A CN106890326A CN 106890326 A CN106890326 A CN 106890326A CN 201510968385 A CN201510968385 A CN 201510968385A CN 106890326 A CN106890326 A CN 106890326A
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- Prior art keywords
- enteric
- active medicine
- capsule core
- pill
- coated micro
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Classifications
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
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- A—HUMAN NECESSITIES
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- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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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
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
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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
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- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/03—Phosphoric monoester hydrolases (3.1.3)
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- C12Y301/04—Phosphoric diester hydrolases (3.1.4)
- C12Y301/04001—Phosphodiesterase I (3.1.4.1)
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- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
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- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01002—Beta-amylase (3.2.1.2)
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Abstract
The invention belongs to pharmaceutical technology field, specifically a kind of enteric-coated micro-pill and its preparation containing phosphoesterases complex.Enteric-coated micro-pill is active medicine capsule core, enteric clothing film and parcel separation layer；Active medicine is phosphoesterases complex；Count by weight, active medicine capsule core：Separation layer：Enteric layer is (10~110)：(1~40)：(1~120).Enteric-coated micro-pill of the present invention contains the active medicine capsule core of phosphoesterases complex, and enteric clothing film, and separation layer is wrapped up between active medicine capsule core and enteric clothing film, improves active medicine stability.Capsule or tabletted is inserted after enteric-coated micro-pill is obtained, multiple unit system is obtained.The present invention is enteric multiple unit pharmaceutical preparation, with good release performance, and storage stability.
Description
Technical field
The invention belongs to pharmaceutical technology field, specifically a kind of enteric containing phosphoesterases complex
Micropill and its preparation.
Background technology
With the improvement of people ' s living standards and diet structure change, in life dinner party increase
The alcohol fatty hepatopath for causing is more and more, and the hyperlipidemic caused by the factors such as obesity
The incidence of disease of fatty liver also increasingly increases, and is possible to develop into hepatitis, cirrhosis.
Phosphoesterases complex is a kind of complex enzyme from barley fibrous root separate using biotechnology
Preparation, be bioengineering downstream technique isolate and purify multi-enzyme system (Zhang Yuhong, Wang Xuedong etc.,
The research Shandong medical industry 2000 of phosphoesterases complex extraction process；19：2-3), have
There is phosphate esterase active, containing the important enzyme needed for very abundant human metabolism, such as
Phosphomonoesterase, phosphodiesterase, nucleotidase, amylase, deoxyribonuclease, essence
Propylhomoserin esterase, phospholipase D etc., can promote body metabolism, improve micro-ecological environment, improve
Lipid-metabolism, can accelerate alcohol liver detoxification, remove liver harmful substance, can be with multiple-effect reparation
Hepatic injury, as a kind of useful hepatoprotective agent clinically act on extensively (Li Xiaoyu, Tian Zibin,
He Xigang etc., phosphoesterases complex the Clinical advances world Chinese in hepatopathy field digest
Magazine 2014；22：4424-4429)；Can also improve a poor appetite, build up health so that some
Disease is improved or fully recovers, and is used clinically for coronary heart disease, Collagen chorionitis, children stupid
The auxiliary treatment of solidity psoriasis, alpastic anemia, leukopenia and silicosis (is opened
Space is red, Wang Xuedong etc., the research Shandong medical industry 2000 of phosphoesterases complex extraction process；
19：2-3).
As enzyme preparation, phosphoesterases complex less stable in itself, and the easily quilt in gastric juice
Destruction, it is therefore desirable to which wrapping up enteric coating prevents hydrochloric acid in gastric juice from destroying.Existing compound phosphate ester enzyme preparation
Only enteric coated tablet, formulation is more single.Tableting processes can substantially reduce phosphoesterases complex simultaneously
Potency.
The content of the invention
It is an object of the invention to provide a kind of enteric-coated micro-pill containing phosphoesterases complex and its system
It is standby.
To reach above-mentioned purpose, the present invention can be prepared by following technical solution：
A kind of enteric-coated micro-pill containing phosphoesterases complex：Enteric-coated micro-pill is active medicine capsule core, enteric coating
Film and parcel separation layer；Active medicine is phosphoesterases complex；Count by weight, active drug
Thing capsule core：Separation layer：Enteric layer is (10~110)：(1~40)：(1~120).
The active medicine capsule core is containing blank capsule core or without blank capsule core；
Wherein, the preparation of the active medicine micropellets containing blank capsule core, system is placed in by blank capsule core
In grain seed-coating machine, by way of drug powder lamination, pharmaceutic adjuvant and active medicine are wrapped up
Onto blank capsule core；
The blank capsule core Average Particle Diameters 0.1-1.5mm, preferably 0.2-1.0mm, it is optimal
Select 0.25-0.75mm.Blank capsule core is selected from microcrystalline cellulose capsule core, sucrose capsule core, titanium dioxide
Silicon capsule core.
The preparation of the active medicine micropellets without blank capsule core, active medicine and common medicine are used
Auxiliary material mixes, and by extrusion spheronization machine, the active medicine capsule core without blank capsule core is obtained；
Or, active medicine is mixed with common medicinal supplementary material, by centrifugal granulation or high shear
Granulation is obtained the active medicine capsule core without blank capsule core.
The pharmaceutic adjuvant is in filler, adhesive, antiplastering aid, disintegrant, wetting agent
One or more.
The filler be selected from microcrystalline cellulose, lactose, starch, pregelatinized starch, dextrin,
One kind in calcium monohydrogen phosphate, sucrose, mannitol, calcium carbonate, low-substituted hydroxypropyl cellulose or
It is several；Preferably microcrystalline cellulose, lactose or sucrose；
It is fine that described adhesive is selected from hydroxypropyl methyl cellulose, polyvinylpyrrolidone, hydroxypropyl
Dimension element, methylcellulose, hydroxymethyl cellulose, Arabic gum, hydroxyethyl cellulose, N-
One or more in vinylpyrrolidone；It is preferred that polyvinylpyrrolidone, hydroxypropyl cellulose
Or Hydroxypropyl methylcellulose；
The antiplastering aid is selected from one or more in talcum powder, superfine silica gel powder, magnesium stearate；
Preferably talc powder or superfine silica gel powder；
The disintegrant is selected from PVPP, Ac-Di-Sol, cross-linked carboxymethyl
One or more in sodium starch, low-substituted hydroxypropyl cellulose, starch；
The wetting agent be selected from pure water, isopropanol, propyl alcohol, ethanol or methyl alcohol in one kind or
It is several.
Counted by weight in the active medicine micropellets containing blank capsule core, blank capsule core：
Active medicine：Filler：Adhesive：Antiplastering aid：Disintegrant：Wetting agent is (10~50)：
(10~60)：(0~60)：(0~30)：(0~10)：(0~10)：(10~200).
It is living in the active medicine micropellets of the preparation without blank capsule core by extrusion spheronization machine
Property medicine, filler, adhesive, antiplastering aid, disintegrant, wetting agent are counted by weight,
(20~60)：(0~80)：(0~20)：(0~15)：(0~10)：(40~180).
The use centrifugal granulation is lived in preparing the active medicine micropellets without blank capsule core
Property medicine, filler, adhesive, antiplastering aid, disintegrant, wetting agent are counted by weight,
(40~80)：(0~50)：(0~30)：(0~10)：(0~10)：(30~160).
The parcel separation layer is located between active medicine capsule core and enteric clothing film；Separation layer increases weight
Account for 1%~40% (w/w) of active medicine capsule core；Parcel separation layer be water-soluble polymer with it is auxiliary
Material A compositions；Auxiliary material A is the one kind in plasticizer, antiplastering aid, defoamer, pigment, solvent
Or it is several, count by weight, water-soluble polymer, plasticizer, antiplastering aid, defoamer,
Pigment, the parts by weight ratio of solvent are (10~60)：(5~25)：(0~30)：(0~
15)：(0~10)：(200~1800).
Wherein, polymer is selected from PVP, Arabic gum, hydroxypropyl cellulose, hydroxypropyl first
One or more in base cellulose, sodium carboxymethylcellulose；It is preferred that hydroxypropyl cellulose, hydroxyl
Propyl methocel or PVP.
Plasticizer be selected from triethyl citrate, ATBC, ATEC,
One or more in polyethylene glycols, glyceryl triacetate；It is preferred that polyethylene glycols, lemon
Triethylenetetraminehexaacetic acid ester or glyceryl triacetate；The addition of plasticizer can ensure the film forming of polymer clothing film
Integrality.
The antiplastering aid is selected from one or more in talcum powder, superfine silica gel powder, magnesium stearate.
The defoamer is selected from one or more in dimethicone, vegetable oil, mineral oil.
The pigment is selected from one or more in di-iron trioxide, iron oxide, titanium dioxide；
The solvent is selected from pure water, isopropanol, propyl alcohol, ethanol or methyl alcohol.
Enteric clothing film weightening accounts for 1%~80% (w/w) of isolation ball, clothing film be polymer and
Auxiliary material B is constituted, and auxiliary material B is in plasticizer, antiplastering aid, opacifier, pigment, solvent
Plant or several；Wherein, polymer and plasticizer, antiplastering aid, opacifier, pigment, solvent
Mass fraction ratio is (20~50)：(2~25)：(0~30)：(0~15)：(0~10)
(300~1500).
The enteric clothing film, effect is protection active constituents of medicine, prevents active component by gastric juice
Destruction.Wherein, polymer is selected from acrylic resin, cellulose acetate peptide acid esters, acetate fiber
Plain benzenetricarboxylic acid ester, HP55, acetate succinate cellulose, acetate succinate
One or more in hydroxypropyl methyl cellulose；
Plasticizer be selected from triethyl citrate, ATBC, ATEC,
Polyethylene glycols, glyceryl triacetate, diethyl phthalate, repefral,
One or more in dibutyl phthalate, castor oil, glycerine；It is preferred that polyethylene glycols,
Triethyl citrate or glyceryl triacetate；The addition of plasticizer can ensure that enteric clothing film is complete
Property and certain toughness.
The antiplastering aid is selected from one or more in talcum powder, superfine silica gel powder, magnesium stearate.
The defoamer is selected from one or more in dimethicone, vegetable oil, mineral oil.
The pigment is selected from one or more in di-iron trioxide, iron oxide, titanium dioxide；
The solvent is selected from pure water, ethanol, propyl alcohol, isopropanol or methyl alcohol.
A kind of preparation method of the enteric-coated micro-pill containing phosphoesterases complex:
I) active medicine and pharmaceutic adjuvant are sprayed into blank capsule core by way of powder lamination
On prepare active medicine capsule core；
Or, active medicine is mixed with pharmaceutic adjuvant, by extrusion spheronization method, centrifugal granulation
Or high shear granulation prepares active medicine capsule core, wetting agent volatilizees in preparation process；；
II) each composition of separation layer is dispersed through treatment, then by coating equipment in sugar production line by separation layer bag
Phosphoesterases complex isolation micropill is prepared in the active medicine capsule core wrapped up in；
III each composition of enteric clothing film) is dispersed through treatment, then by coating equipment in sugar production line by enteric
Phosphoesterases complex enteric-coated micro-pill is prepared in the capsule core containing active medicine of layer parcel.
It is described II) in by water-soluble polymer, plasticizer, antiplastering aid, defoamer in separation layer
It is stand-by in the solvent being scattered in separation layer with pigment mixing.
The III) in by polymer in enteric clothing film, plasticizer, antiplastering aid, opacifier and
Pigment dispersion is stand-by in the solvent in enteric clothing film.
Meanwhile, by phosphoesterases complex enteric-coated micro-pill be filled in capsule or with prepare used by tablet
Auxiliary material mixing compacting, obtains final product tablet.
Advantage for present invention：
Phosphoesterases complex enteric-coated micro-pill of the present invention has preferable dissolution rate and bioavilability.
The dissolution rate of invention formulation grinds tablet stabilization than original, fluctuates small, and product property is more stable.
Enteric-coated micro-pill prepared by the present invention is filled in capsule or mixed with other auxiliary materials simultaneously and is pressed into
Tablet, is made enteric multiple unit pharmaceutical preparation, and phosphoesterases complex potency is more in preparation process
Stabilization.
Specific embodiment
Following examples are further described to of the invention, rather than the limit to the scope of the invention
System.
The preparation of active medicine capsule core of the embodiment 1 containing blank capsule core
The composition of the active medicine capsule core containing blank capsule core is as shown in the table,
Preparation process：
Weigh the ethanol water that 12.8g Hydroxypropyl methylcelluloses E5 is dissolved in 254.0g 25% (w/w)
In solution；600.0g microcrystalline cellulose capsule cores are weighed to be placed in centrifugal granulating seed-coating machine；Weigh
640.0g phosphoesterases complexs mix with 25.6g talcum powder be placed in centrifugal granulating seed-coating machine confession
In powder device；Engine speed 250rpm, blow rate required 0.32m are set3/ min, EAT 40 ± 2
DEG C, atomizing pressure 0.18MPa, hydrojet 6 ± 1g/min of speed, for 18 ± 2g/min of powder speed.
After terminating for powder, stop hydrojet and atomization, adjust engine speed 200rpm, polish 3min,
Then micropill is taken out, is placed in 35 DEG C of oven dryings, sieved, obtain particle diameter 0.500~
The active medicine capsule core one of 0.700mm.
The preparation of active medicine capsule core of the embodiment 2 without blank capsule core
The composition of the active medicine capsule core without blank capsule core is as shown in the table,
Preparation process：
Weigh phosphoesterases complex 420.0g, microcrystalline cellulose 390.0g, lactose 105.0g,
Talcum powder 60.0g, PVPP 40.0g, are placed in and mix 10min in blender, then
930.0g 75% (w/w) ethanol water is added to prepare wet softwood；Wet softwood is placed in extruder
In, be placed in the softwood of extrusion in spheronizator by the speed extrusion of 80rpm, and 500rpm is round as a ball
10min, is subsequently placed in drying in 38 ± 2 DEG C of baking oven, and 0.425~0.600mm's of screening is micro-
Ball, obtains active medicine capsule core two.
The preparation of active medicine capsule core of the embodiment 3 without blank capsule core
The composition of the active medicine capsule core without blank capsule core is as shown in the table,
Preparation process：
Weigh phosphoesterases complex 600.0g, microcrystalline cellulose 450.0g, superfine silica gel powder 60.0g,
PVPP 30.0g is placed in and mixes 10min in blender；Weigh PVP K30 45.0g
It is dissolved in the ethanol water of 900.0g 45% (w/w)；Phosphoesterases complex is mixed with auxiliary material
Compound is placed in centrifugal granulating seed-coating machine, sets engine speed 300rpm, the blow rate required
0.35m3/ min, 40 ± 2 DEG C of EAT, atomizing pressure 0.2MPa, hydrojet speed 8 ±
1g/min, hydrojet terminates, and continues round as a ball 5min, then takes out micropill, and in 35 DEG C of bakings
Case is dried, and obtains active medicine capsule core.Sieve to obtain activity of the particle diameter between 0.3~0.6mm
Medicine capsule core three.
The active medicine of embodiment 5 isolates the preparation of ball
The composition of active medicine isolation ball is as shown in the table,
Preparation process：
Weigh 60.0g HPC-L F, 6.0g PEG400s and be dissolved in 1140.0g
Pure water, and 12.0g talcum powder is added, stir.By 600.0g phosphoesterases complexs
Capsule core one is placed in fluid bed, sets (the m of the blow rate required 24 ± 23/ h)/kg, atomizing pressure 5 ±
0.5bar, hydrojet 8 ± 1g/min of speed, 50 ± 2 DEG C of EAT, temperature of charge 35 ± 2
DEG C, after hydrojet terminates, continue to be dried in fluid bed, obtain active medicine isolation ball one.
The active medicine of embodiment 6 isolates the preparation of ball
The composition of phosphoesterases complex isolation ball is as shown in the table,
Preparation process：
Weigh 40.0g Hydroxypropyl methylcellulose E5,4.0g triethyl citrates and be dissolved in 860.0g
Absolute ethyl alcohol, and 8.0g talcum powder is added, stir.By 500.0g phosphoesterases complexs
Capsule core three is placed in fluid bed, sets (the m of the blow rate required 20 ± 23/ h)/kg, atomizing pressure 4.0
± 0.5bar, hydrojet 6 ± 2g/min of speed, 45 ± 2 DEG C of EAT, temperature of charge 35 ±
2 DEG C, after hydrojet terminates, continue to be dried in fluid bed, obtain phosphoesterases complex isolation ball
Two.
The preparation of the phosphoesterases complex enteric coated pill of embodiment 7
The composition of phosphoesterases complex enteric coated pill is as shown in the table,
Preparation process：
Weigh 18.0g triethyl citrates and 36.0g talcum powder, high shear dispersion to 600.0g
In pure water, then mix with Utech L30D55 while stirring；By 600.0g compound phosphoric acids
Esterase isolation ball one is placed in fluid bed, sets (the m of the blow rate required 22 ± 23/ h)/kg, atomization pressure
6.0 ± 0.5bar of power, hydrojet 5 ± 2g/min of speed, 50 ± 2 DEG C of EAT, material temperature
35 ± 2 DEG C of degree, after hydrojet terminates, continues to be dried in fluid bed, obtains phosphoesterases complex
Enteric coated pill one.
The preparation of the phosphoesterases complex enteric coated pill of embodiment 8
The composition of phosphoesterases complex enteric coated pill is as shown in the table,
Preparation process：
Weigh 150.0g Eudragit L100-55s, 15.0g Macrogol 6000s, be dissolved in 900g
Absolute ethyl alcohol, is subsequently adding 15.0g titanium dioxide and stirs,；By 600.0g compound phosphoric acids
Esterase isolation ball one is placed in fluid bed, sets (the m of the blow rate required 22 ± 23/ h)/kg, atomization pressure
5.0 ± 0.5bar of power, hydrojet 7 ± 2g/min of speed, 45 ± 2 DEG C of EAT, material temperature
35 ± 2 DEG C of degree, after hydrojet terminates, continues to be dried in fluid bed, obtains phosphoesterases complex
Enteric coated pill two.
The preparation of the phosphoesterases complex capsulae enterosolubilis of embodiment 9
Preparation process：
Using capsule filling machine, by phosphoesterases complex enteric-coated micro-pill one, with 314 ± 10mg/
Grain, filling 1000.
The preparation of the phosphoesterases complex enteric coatel tablets of embodiment 10
| Phosphoesterases complex enteric-coated micro-pill two | 142g |
| Microcrystalline cellulose PH102 | 318g |
| PVPP | 2g |
| Superfine silica gel powder | 4g |
Preparation process：
Phosphoesterases complex enteric-coated micro-pill two and recipe quantity microcrystalline cellulose PH102, crosslinking are gathered
Dimension ketone, superfine silica gel powder mixing 5min, are placed in rotary pelleting machine compressing tablet and enteric-coated micro-pill matrix are obtained
Agent one, recessed abnormity punching before 14 × 7mm, piece weighs 466 ± 23.3mg, hardness 8kg~12kg.
The titration of embodiment 11
The preparation of phosphoesterases complex plain piece
| Composition | Microcrystalline cellulose | Phosphoesterases complex | Hydroxypropyl methylcellulose E5 | Talcum powder |
| Quality/g | 600.0 | 640.0 | 12.8 | 25.6 |
According to form prescription, using direct compression method, using 9mm punch dies, plain piece hardness
5kg-7kg, compacting 100mg phosphoesterases complex plain pieces A.
Phosphoesterases complex raw material 235mg, phosphoesterases complex plain piece A 5 are taken respectively, lived
The 500mg of property medicine capsule core one, phosphoesterases complex enteric-coated micro-pill matrix agent one 5, put respectively
In mortar, add water a little, grinding is uniform, moves to respectively in 100ml measuring bottles, is diluted with water to
Scale, shakes up, respectively in muddy solution.
9, test tube is taken, 3 one group of test tubes are accurate respectively to add rna solution [to take core
Ribosomal ribonucleic acid (content more than 80%) 1.0g, add water 30ml, shakes up, and is adjusted with sodium hydroxide test solution
Section pH value to 7.0~7.2, add water and be diluted to 50ml] 3ml, trishydroxymethylaminomethane delay
Fliud flushing [takes trishydroxymethylaminomethane 1.2g, after the 50ml that adds water dissolvings, uses 0.1mol/L salt
Acid solution (about 85ml) adjusts pH value to 7.0~7.2, is diluted with water to 200ml] 1.5ml,
The liquor zinci chloridi 0.5ml of 0.01mol/L, is incubated 5 minutes, three groups of examinations in 70 DEG C of water-baths
Pipe is accurate respectively to add need testing solution 1ml, shakes up, and puts accurate response 30 in 70 DEG C of water-baths
Minute, then accurate addition perchloric acid ammonium molybdate test solution (ammonium molybdate 0.25g is taken, plus 70%~72%
Perchloric acid 3.5ml and appropriate amount of water make dissolving, are diluted with water to 100ml) 5ml, shake up, stand
Put in ice bath and cool down 15 minutes, filtration is taken during subsequent filtrate 2ml puts 100ml measuring bottles, plus
Water is diluted to scale, according to AAS, is determined as reference with water at the wavelength of 260nm and inhaled
Receipts degree A, need testing solution is replaced with water 1ml, is operated with method, determines trap A0.Press
Formula is calculated：
A in formula：Sample trap A0：Blank trap
Phosphoesterases complex titration result
| Sample | Per 100mg phosphoesterases complex potency | Potency changes |
| Phosphoesterases complex | 15340 | —— |
| Phosphoesterases complex plain piece A | 13652 | - 11.0% |
| Active medicine capsule core one | 14835 | - 3.2% |
| Phosphoesterases complex enteric-coated micro-pill matrix agent one | 14589 | - 4.8% |
Result shows, after phosphoesterases complex direct tablet compressing, due to the effect of compression force, potency
11% is reduced, and the reduction of the potency of active medicine capsule core only has 3.2%, phosphoesterases complex enteric
Micropill potency reduction by 4.8% after compression.Be prepared into for phosphoesterases complex by above-mentioned as shown by data
Active micropill, relative to reduce influence of the compression force to potency with compressing tablet, active micropill is prepared into
Enteric-coated micro-pill compressing tablet again, potency reduction is less than direct tablet compressing, illustrate that enteric-coated micro-pill resistance to pressure is preferable,
There is certain protective effect to phosphoesterases complex in tableting processes.
Claims (9)
1. a kind of enteric-coated micro-pill containing phosphoesterases complex, it is characterised in that：Enteric-coated micro-pill is active medicine capsule core, enteric clothing film and parcel separation layer；Active medicine is phosphoesterases complex；Count by weight, active medicine capsule core：Separation layer：Enteric layer is (10~110)：(1~40)：(1~120).
2. the enteric-coated micro-pill containing phosphoesterases complex as described in claim 1, it is characterised in that：The active medicine capsule core is containing blank capsule core or without blank capsule core；
Wherein, the preparation of the active medicine micropellets containing blank capsule core, blank capsule core is placed in granulator coater, by way of drug powder lamination, pharmaceutic adjuvant and active medicine is wrapped up onto blank capsule core；
The preparation of the active medicine micropellets without blank capsule core, active medicine is mixed with common medicinal supplementary material, by extrusion spheronization machine, the active medicine capsule core without blank capsule core is obtained；
Or, active medicine is mixed with common medicinal supplementary material, the active medicine capsule core without blank capsule core is obtained by centrifugal granulation or high shear granulation；
The pharmaceutic adjuvant is one or more in filler, adhesive, antiplastering aid, disintegrant, wetting agent.
3. the enteric-coated micro-pill containing phosphoesterases complex as described in claim 2, it is characterised in that：Counted by weight in the active medicine micropellets containing blank capsule core, blank capsule core：Active medicine：Filler：Adhesive：Antiplastering aid：Disintegrant：Wetting agent is (10~50)：(10~60)：(0~60)：(0~30)：(0~10)：(0~10)：(10~200).
4. the enteric-coated micro-pill containing phosphoesterases complex as described in claim 2, it is characterised in that：Active medicine, filler, adhesive, antiplastering aid, disintegrant, wetting agent are counted by weight in the active medicine micropellets of the preparation without blank capsule core by extrusion spheronization machine, (20~60)：(0~80)：(0~20)：(0~15)：(0~10)：(40~180).
5. the enteric-coated micro-pill containing phosphoesterases complex as described in claim 2, it is characterised in that：Active medicine, filler, adhesive, antiplastering aid, disintegrant, wetting agent are counted by weight in the active medicine micropellets of the use centrifugal granulation preparation without blank capsule core, (40~80)：(0~50)：(0~30)：(0~10)：(0~10)：(30~160).
6. the enteric-coated micro-pill containing phosphoesterases complex as described in claim 1, it is characterised in that：The parcel separation layer is located between active medicine capsule core and enteric clothing film；Separation layer weightening accounts for 1%~40% (w/w) of active medicine capsule core；Parcel separation layer is that water-soluble polymer is constituted with auxiliary material A；Auxiliary material A is one or more in plasticizer, antiplastering aid, defoamer, pigment, solvent, is counted by weight, and water-soluble polymer, plasticizer, antiplastering aid, defoamer, pigment, the parts by weight ratio of solvent are (10~60)：(5~25)：(0~30)：(0~15)：(0~10)：(200~1800).
7. the enteric-coated micro-pill containing phosphoesterases complex as described in claim 1, it is characterised in that：The enteric clothing film weightening accounts for 1%~80% (w/w) of isolation ball, and clothing film is that polymer and auxiliary material B are constituted, and auxiliary material B is one or more in plasticizer, antiplastering aid, opacifier, pigment, solvent；Wherein, polymer and plasticizer, antiplastering aid, opacifier, pigment, the mass fraction ratio of solvent are (20~50)：(2~25)：(0~30)：(0~15)：(0~10) (300~1500).
8. the preparation method of the enteric-coated micro-pill containing phosphoesterases complex described in a kind of claim 1, it is characterised in that：
I) active medicine and pharmaceutic adjuvant is sprayed to by way of powder lamination and prepared in blank capsule core active medicine capsule core；
Or, active medicine is mixed with pharmaceutic adjuvant, active medicine capsule core is prepared by extrusion spheronization method, centrifugal granulation or high shear granulation；
II) each composition of separation layer is dispersed through treatment, phosphoesterases complex isolation micropill is prepared in the active medicine capsule core then wrap up separation layer by coating equipment in sugar production line；
III each composition of enteric clothing film) is dispersed through treatment, phosphoesterases complex enteric-coated micro-pill is prepared in the capsule core containing active medicine then wrapped up enteric layer by coating equipment in sugar production line.
9. the preparation method of the enteric-coated micro-pill containing phosphoesterases complex as described in claim 8, it is characterised in that：The phosphoesterases complex enteric-coated micro-pill is filled in capsule or mixes compacting with the auxiliary material prepared used by tablet, obtain final product tablet.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510968385.5A CN106890326A (en) | 2015-12-21 | 2015-12-21 | A kind of enteric-coated micro-pill and its preparation containing phosphoesterases complex |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510968385.5A CN106890326A (en) | 2015-12-21 | 2015-12-21 | A kind of enteric-coated micro-pill and its preparation containing phosphoesterases complex |
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| CN106890326A true CN106890326A (en) | 2017-06-27 |
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| CN201510968385.5A Withdrawn CN106890326A (en) | 2015-12-21 | 2015-12-21 | A kind of enteric-coated micro-pill and its preparation containing phosphoesterases complex |
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| CN (1) | CN106890326A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108294317A (en) * | 2018-01-31 | 2018-07-20 | 无限极（中国）有限公司 | A kind of walnut peptide enteric-coated micro-pill and preparation method thereof |
| EP3975999A4 (en) * | 2019-06-03 | 2023-07-19 | Theriva Biologics, Inc. | ALKALINE PHOSPHATASE FORMULATIONS AND THEIR USES |
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| CN201524268U (en) * | 2009-11-04 | 2010-07-14 | 青岛汉河药业有限公司 | Extended release pills in micro-capsules |
| CN101987081A (en) * | 2010-07-16 | 2011-03-23 | 钟术光 | Controlled release preparation |
| CN104644583A (en) * | 2014-12-25 | 2015-05-27 | 青岛黄海制药有限责任公司 | Dabigatran-containing multi-unit pellet tablet and preparation thereof |
| CN104645322A (en) * | 2014-12-25 | 2015-05-27 | 青岛黄海制药有限责任公司 | Phosphoesterases complex enteric-coated tablet and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN201524268U (en) * | 2009-11-04 | 2010-07-14 | 青岛汉河药业有限公司 | Extended release pills in micro-capsules |
| CN101987081A (en) * | 2010-07-16 | 2011-03-23 | 钟术光 | Controlled release preparation |
| CN104644583A (en) * | 2014-12-25 | 2015-05-27 | 青岛黄海制药有限责任公司 | Dabigatran-containing multi-unit pellet tablet and preparation thereof |
| CN104645322A (en) * | 2014-12-25 | 2015-05-27 | 青岛黄海制药有限责任公司 | Phosphoesterases complex enteric-coated tablet and preparation method and application thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108294317A (en) * | 2018-01-31 | 2018-07-20 | 无限极（中国）有限公司 | A kind of walnut peptide enteric-coated micro-pill and preparation method thereof |
| EP3975999A4 (en) * | 2019-06-03 | 2023-07-19 | Theriva Biologics, Inc. | ALKALINE PHOSPHATASE FORMULATIONS AND THEIR USES |
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Application publication date: 20170627 |