CN107281160A - A kind of berberine enteric-coated micro-pill and preparation method thereof, application - Google Patents
A kind of berberine enteric-coated micro-pill and preparation method thereof, application Download PDFInfo
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- CN107281160A CN107281160A CN201710628558.8A CN201710628558A CN107281160A CN 107281160 A CN107281160 A CN 107281160A CN 201710628558 A CN201710628558 A CN 201710628558A CN 107281160 A CN107281160 A CN 107281160A
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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
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—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
- 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
- A61K31/4375—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 containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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Abstract
A kind of berberine enteric-coated micro-pill and preparation method thereof, application, are related to field of medicine preparations.A kind of berberine enteric-coated micro-pill, including capsule core, separation layer and enteric layer, separation layer are coated on capsule core, and enteric layer is coated on separation layer.The raw material of capsule core includes berberine, diluent, disintegrant and wetting agent.The raw material of separation layer includes the first coating agent, ethanol solution and the first antitackiness agent, and the raw material of enteric layer includes enteric solubility acrylic resin.It can cover the bitter taste of berberine, and the active ingredient of berberine enteric-coated micro-pill can effectively discharge at enteron aisle, stomach will not be caused to stimulate, reduce the adverse reaction of medicine.A kind of preparation method of berberine enteric-coated micro-pill, including：Capsule core is mixed into the first Cotton seeds of progress, dry separation layer capsule core with separation layer solution, separation layer capsule core is mixed with enteric coating liquid and carries out the second Cotton seeds, drying.This method is simple to operate, and the smooth berberine enteric-coated micro-pill of rounding can be made.
Description
Technical field
The present invention relates to field of medicine preparations, and more particularly to a kind of berberine enteric-coated micro-pill and preparation method thereof, application.
Background technology
Berberine also known as jamaicin, are the main alkaloids in Chinese Drug Rhizomes of Coptis, golden cypress, barberry, are widely distributed in buttercup
In the Chinese medicines such as section, Berberidaceae, Papaveraceae, bitter is used as clearing heat and detoxicating and treatment intestines bacterium property always clinical for a long time
Anti-diarrhea drug is used.In the last few years with the pharmacological further investigation to jamaicin, its clinical application is from simple antibacterial
Anti-diarrhea effect extend to be used for the angiocardiopathy such as illness such as arrhythmia cordis, refractory heart failure and hypertension and glycolipid
The treatment of the metabolic syndrome such as illness such as diabetes, high fat of blood and diabetic complication.
It is largely bad in order to cover in currently available technology berberine micro-pills product because berberine taste is extremely bitter
Smell, prevents from discharging in the oral cavity, and is typically to be discharged in gastric juice.But berberine has certain excitant to stomach, it can influence
Application clinically.
The content of the invention
The first object of the present invention is to provide a kind of berberine enteric-coated micro-pill, can cover the bitter taste of berberine, berberine
The active ingredient of enteric-coated micro-pill effectively can discharge at enteron aisle, stomach will not be caused to stimulate, reduce the adverse reaction of medicine,
And active drug concentration at enteron aisle is higher, the availability of medicine is added.
The second object of the present invention is to provide a kind of preparation method of berberine enteric-coated micro-pill, and this method is simple to operate,
The smooth berberine enteric-coated micro-pill of rounding can be made.
The third object of the present invention is to provide a kind of application of berberine enteric-coated micro-pill, and berberine enteric-coated micro-pill not only may be used
As finished product, can also be used as middle product.
The present invention is solved its technical problem and realized using following technical scheme.
The present invention proposes a kind of berberine enteric-coated micro-pill, including weight ratio is 100:5-25:15.5~87.5 capsule core, every
Absciss layer and enteric layer, separation layer are coated on capsule core, and enteric layer is coated on separation layer.
Capsule core is mainly made up of the first raw material, and the first raw material includes the first major ingredient and the first auxiliary material, and the first major ingredient includes Huang
Lian Su, the first auxiliary material includes diluent, disintegrant and wetting agent；The weight ratio of berberine, diluent and disintegrant is 10-75:
20-85:3-10；The weight ratio of wetting agent and the first raw material is 0.2-3:1；Diluent includes microcrystalline cellulose, lactose and sweet dew
Alcohol.
Separation layer is mainly made up of the second raw material, and the second raw material includes the second major ingredient and the second auxiliary material, and the second major ingredient includes
The weight ratio of first coating agent and ethanol solution, ethanol and capsule core is 0.4-2:1；Second auxiliary material includes the first antitackiness agent, first
The weight ratio of coating agent and the first antitackiness agent is 40-80:10-45；First coating agent includes hydroxypropyl methyl cellulose, polyethylene
Pyrrolidones and ethyl cellulose, at least one of zein.
Enteric layer is mainly made up of the 3rd raw material, and the 3rd raw material includes the second coating agent, and the second coating agent includes enteric solubility
Acrylic resin.
A kind of preparation method of berberine enteric-coated micro-pill, including：Capsule core is mixed into progress first with separation layer solution to be coated
Processing, dry separation layer capsule core, the temperature of the first Cotton seeds step is 25-40 DEG C, and atomizing pressure is 0.05-0.4MPa,
Jet speed is 10-30mL/min.Separation layer capsule core is mixed into the second Cotton seeds of progress, drying, second with enteric coating liquid
The temperature of Cotton seeds step is 25-40 DEG C, and atomizing pressure is 0.05-0.4MPa, and jet speed is 5-30mL/min.Capsule core master
To be made by following steps：First major ingredient and the first auxiliary material are mixed and obtain softwood, is carried out after softwood is extruded round as a ball, dry
It is dry.
A kind of application of berberine enteric-coated micro-pill, it can be used for capsule, granule or supensoid agent.
The beneficial effect of the embodiment of the present invention is：A kind of berberine enteric-coated micro-pill, it includes capsule core, separation layer and enteric
Diluent in layer, capsule core is controllable for the release of active ingredient in berberine enteric-coated micro-pill.Diluent includes crystallite
Cellulose, lactose and mannitol, because the hygroscopicity of lactose is larger, the stickiness of material is unfavorable than larger after wetting agent is added
In ball process, so the selection addition less mannitol of hygroscopicity is mixed with microcrystalline cellulose, lactose and used as diluent.
And lactose and mannitol are soluble in water, the dissolving of capsule core is also beneficial to.Disintegrant can make berberine enteric-coated micro-pill rapid in enteron aisle
The material of fine particle is broken into, is conducive to release of the berberine at enteron aisle, wetting agent is used for berberine, diluent and collapsed
The powder mixing for solving agent carries out round as a ball shaping.Make the coating material of enteric layer using enteric solubility acrylic resin, coating process is easy
Operation, Coating times are controlled well, and film-formation result is good.But because berberine is a kind of season ammonia type alkaloid, in an acidic solution, lose
De-electromation exists with quaternary ammonium form, and its solubility is extremely low, can influence to absorb.And contain in enteric solubility Eudragit coatings material
There is acidic-group carboxyl, it is directly enteric coated to influence the solubility and stability of medicine, therefore the present invention is in enteric layer and ball
Separation layer is coated between core, increases the stability of preparation, while coating the smooth rounding in capsule core surface after separation layer, it is possible to reduce
The loss of medicine in enteric coating.First coating agent of separation layer dissolves in enteron aisle, and separation layer is coated on capsule core, by it is interior to
It is made up of outside capsule core, separation layer, enteric layer, can preferably ensures that capsule core positions release in enteron aisle, improve bioavilability.
A kind of preparation method of berberine enteric-coated micro-pill, this method is simple to operate, and it utilizes round as a ball expressing technique, can be made
The smooth berberine enteric-coated micro-pill of rounding.
A kind of application of berberine enteric-coated micro-pill, berberine enteric-coated micro-pill acts not only as finished product, in can also being used as
Between product use.
Brief description of the drawings
In order to illustrate the technical solution of the embodiments of the present invention more clearly, below will be attached to what is used required in embodiment
Figure is briefly described, it will be appreciated that the following drawings illustrate only certain embodiments of the present invention, therefore is not construed as pair
The restriction of scope, for those of ordinary skill in the art, on the premise of not paying creative work, can also be according to this
A little accompanying drawings obtain other related accompanying drawings.
Fig. 1 release result figures in different medium for the berberine enteric-coated micro-pill in test example of the present invention.
Embodiment
, below will be in the embodiment of the present invention to make the purpose, technical scheme and advantage of the embodiment of the present invention clearer
Technical scheme be clearly and completely described.Unreceipted actual conditions person, builds according to normal condition or manufacturer in embodiment
The condition of view is carried out.Agents useful for same or the unreceipted production firm person of instrument, are the conventional production that can be obtained by commercially available purchase
Product.
Below to a kind of berberine enteric-coated micro-pill of the embodiment of the present invention and preparation method thereof, using being specifically described.
A kind of berberine enteric-coated micro-pill, including weight ratio are 100:5-25:15.5~87.5 capsule core, separation layer and enteric
Layer, separation layer is coated on capsule core, and enteric layer is coated on separation layer.
Capsule core is mainly made up of the first raw material, and the first raw material includes the first major ingredient and the first auxiliary material, and the first major ingredient includes Huang
Lian Su, the first auxiliary material includes diluent, disintegrant and wetting agent；The weight ratio of berberine, diluent and disintegrant is 10-75:
20-85:3-10；The weight ratio of wetting agent and the first raw material is 0.2-3:1；Diluent includes microcrystalline cellulose, lactose and sweet dew
Alcohol.
Diluent is not only formed into the moulding material of berberine enteric-coated micro-pill, and in berberine enteric-coated micro-pill effectively into
The release divided is controllable.In the present embodiment of the present invention, diluent includes microcrystalline cellulose, lactose and mannitol.By
Larger in the hygroscopicity of lactose, the stickiness of material is unfavorable for ball process than larger after wetting agent is added, so selection is added
The less mannitol of hygroscopicity is mixed with microcrystalline cellulose, lactose to be used as diluent.And lactose and mannitol are soluble in water,
It is also beneficial to the dissolving of capsule core.Preferably, it is 1-3 that diluent, which includes weight ratio,:1:1-2 microcrystalline cellulose, lactose and sweet dew
Alcohol.Microcrystalline cellulose, lactose and mannitol by the use of the ratio is as the raw material of capsule core, and the round as a ball shaping of capsule core is preferable, and the coptis
Releasing degree of the active ingredient at enteron aisle is preferable in plain enteric-coated micro-pill.
Disintegrant, refers to the material that the capsule core of berberine enteric-coated micro-pill can be enable to be broken into fine particle rapidly in enteron aisle.
In conjunction with the effect of diluent, it may be such that the berberine composition in capsule core can be effectively absorbed in enteron aisle.Preferably, disintegrant
Including in sodium carboxymethyl starch, sodium carboxymethylcellulose, Ac-Di-Sol and PVPP extremely
Few one kind.In an embodiment of the present invention, disintegrant is sodium carboxymethyl starch, sodium carboxymethylcellulose, cross-linked carboxymethyl fiber
One kind in plain sodium and PVPP.Wherein, PVPP, English abbreviation is PVPP.
Wetting agent, refers to itself without stickiness, but can soak and induce the liquid of medicinal powder stickiness.Wetting agent is mainly used in
One raw material is effectively mixed, and is conducive to follow-up round as a ball shaping.In an embodiment of the present invention, wetting agent includes water or ethanol.It is excellent
Selection of land, the mass concentration of ethanol is 40%-85%.
Further, the first auxiliary material also includes weight ratio≤3 of binder, binder and berberine:5.Binder may be such that
Bond more preferably between first major ingredient and the first auxiliary material, be conducive to the capsule core of berberine enteric-coated micro-pill to be molded.Preferably, binder
Including hydroxypropyl methyl cellulose or high substitution hydroxypropyl methyl cellulose.
Enteric layer is mainly made up of the 3rd raw material, and the 3rd raw material includes the second coating agent, and the second coating agent includes enteric solubility
Acrylic resin.
It is used as the coating material of enteric layer using acrylic resin, coating process is easy to operate, and Coating times are controlled well, film forming
Effect is good.Enteric layer can cover the bitter taste of drug of capsule core, and each component of enteric layer melts at enteron aisle to be dissolved so that berberine enteric
The active ingredient of micropill discharges in enteron aisle, improves local drug concentration, increases drug availability, and compliance is good, it is possible to reduce medicine
The adverse reaction of thing.Acrylic resin, English entitled Eudragit, in some embodiments of the invention, acrylic resin bag
EudragitL100, EudragitL100-55, EudragitL30D-55 and Eudragit S 100 at least one is included,
EudragitL100 can dissolve in pH value is 6.0-7.5 medium, and Eudragit S 100 can be molten in the medium of pH value >=7
Solution.Preferably, it is 2 that the second coating agent, which includes weight ratio,:0.5-1 EudragitL100 and Eudragit S 100, the ratio
The second coating agent may be such that berberine enteric layer micropill in small intestine preferably completely release, improve drug effect.
Further, the 3rd raw material also includes plasticizer, the second antitackiness agent and coating solvent, the second coating agent, plasticizer
Weight ratio with the second antitackiness agent is 40-85:1-10:The weight ratio of 1-15, coating solvent and capsule core is 52.5-250:100.
Plasticizer can increase the flexibility of enteric layer coating, reduce the intermolecular active force of filmogen, and increase by second is wrapped
The mobility of polymer molecular chain in clothing agent, can preferably film forming.Preferably, plasticizer includes triethyl citrate, propane diols
At least one of with polyethylene glycol.In an embodiment of the present invention, plasticizer is triethyl citrate, propane diols and poly- second two
One kind in alcohol.
Second antitackiness agent can reduce by the second coating agent in coating solvent the problem of adhesion, can be preferably by the second bag
Clothing agent is dispersed in coating solvent, is conducive to preferably film forming.Preferably, the second antitackiness agent includes talcum powder and magnesium stearate list
At least one of tristerin.In an embodiment of the present invention, the second antitackiness agent is that talcum powder or magnesium stearate list are stearic
Acid glyceride.
Further, the 3rd raw material also includes weight ratio≤1 of stabilizer, stabilizer and the second coating agent:8.Preferably,
Stabilizer includes the sodium hydroxide that mass concentration is 4%.
But inventors herein have recognized that, berberine is a kind of season ammonia type alkaloid, in slant acidity solution, loses electricity
Son exists in the form of quaternary ammonium salt, and its solubility is low.And contain acidic-group carboxyl in enteric solubility Eudragit coatings material,
Directly cladding enteric layer can influence the solubility and stability of medicine outside capsule core, therefore the present invention is between enteric layer and capsule core
Coat separation layer.Berberine enteric-coated micro-pill contains capsule core, separation layer, enteric layer from inside to outside, in alimentary canal, utilizes pH's
Sensitivity, enables invention formulation preferably to position release in enteron aisle, improves bioavilability.
Separation layer is mainly made up of the second raw material, and the second raw material includes the second major ingredient and the second auxiliary material, and the second major ingredient includes
The weight ratio of first coating agent and ethanol solution, ethanol and capsule core is 0.4-2:1；Second auxiliary material includes the first antitackiness agent, first
The weight ratio of coating agent and the first antitackiness agent is 40-80:10-45；First coating agent includes hydroxypropyl methyl cellulose, polyethylene
Pyrrolidones and ethyl cellulose, at least one of zein.
First coating agent includes hydroxypropyl methyl cellulose, polyvinylpyrrolidone and ethyl cellulose, zein extremely
Few one kind, this is several to dissolve in enteron aisle.Because there is larger individual difference, separation layer in PH diversity and gastric emptying time
Capsule core is coated on, acrylic resin in particular cases enteric layer can be also prevented effectively from and be acted on hydrochloric acid in gastric juice, influence insoluble drug release speed
The generation of degree and stability, equally also ensure that the active ingredient of capsule core is most of and is discharged all in enteron aisle..Wherein, hydroxypropyl
Methylcellulose, English abbreviation is HPMC, in some embodiments of the invention, preferably HPMC E5.
The first coating agent in separation layer is dissolved in ethanol, after treatment can film forming.First coating agent has certain
Stickiness, can reduce the adhesion problems of the first coating agent in ethanol by adding the first antitackiness agent, can be preferably by the
One coating agent is dispersed in ethanol solution, is conducive to preferably film forming.Make in addition, the first antitackiness agent also functions to certain isolation
With, when being coated for enteric layer easily operation a bit.Preferably, the first antitackiness agent includes talcum powder, magnesium stearate and titanium dioxide
At least one of titanium.
Further, the second auxiliary material also includes weight ratio≤1 of polyethylene glycol, polyethylene glycol and the first coating agent:8.
Polyethylene glycol has good lubricity, moisture retention and dispersiveness.Be conducive to preferably disperseing the first coating agent
In ethanol.
A kind of preparation method of berberine enteric-coated micro-pill, including：Capsule core is mixed into progress first with separation layer solution to be coated
Processing, dry separation layer capsule core, the temperature of the first Cotton seeds step is 25-40 DEG C, and atomizing pressure is 0.05-0.4MPa,
Jet speed is 10-30mL/min, and air intake frequency is 20-35HZ, and EAT is 30-60 DEG C, and leaving air temp is 25-35 DEG C,
Drying time is 15-35min.
Capsule core is mainly made by following steps：First major ingredient and the first auxiliary material are mixed and obtain softwood, softwood is squeezed
Carried out after going out round as a ball, dry.
Wherein, in the first major ingredient berberine and the diluent in the first auxiliary material, disintegrant, the granularity of binder are 80-
100 mesh.Raw material is so conducive to be well mixed, berberine is mutually adsorbed with unclassified stores, is conducive to the release of active ingredient.
In embodiments of the invention, first berberine, diluent, disintegrant and binder are well mixed in efficient wet granulator
Afterwards, add wetting agent stirring 20-40min and obtain softwood.
Then softwood is put into extrusion device, the orifice plate for being 0.4-1.5mm with aperture extrusion.By the wet thing of the strip of extrusion
Material is placed in spheronizator and extruded, and is then dried under conditions of 40-65 DEG C to moisture≤3%, screens the capsule core between 18-24 mesh
It is stand-by.Wherein, extruded velocity is that 20-50 turns/min, and round as a ball rotating speed is that 550-1300 turns/min, and the round as a ball time is 5-30min.Profit
Smooth, the forming with capsule core rounding made from this method.
Wherein, separation layer solution is mainly made by following steps：It is anti-glutinous with first after first coating agent is mixed with ethanol
Agent is mixed.
Obtained separation layer capsule core is mixed into the second Cotton seeds of progress, drying, the second Cotton seeds with enteric coating liquid
The temperature of step is 25-40 DEG C, and atomizing pressure is 0.05-0.4MPa, and jet speed is 5-30mL/min, and air intake frequency is 20-
35HZ, EAT is 30-60 DEG C, and leaving air temp is 25-35 DEG C.Enteric layer film forming is good, the forming of berberine enteric-coated micro-pill, circle
It is whole smooth.
Wherein, enteric coating liquid is mainly made by following steps：After second coating agent is mixed with coating solvent again with increasing
Mould agent, the mixing of the second antitackiness agent.
A kind of application of berberine enteric-coated micro-pill, it can be used for capsule, granule or supensoid agent.Berberine enteric-coated micro-pill
Finished product is acted not only as, can also be used as middle product.
The feature and performance to the present invention are described in further detail with reference to embodiments.
Embodiment 1
A kind of berberine enteric-coated micro-pill, including capsule core, separation layer and enteric layer.Capsule core and separation layer, the weight of enteric layer
Than for 100:5:15.5.
It is 20 that the raw material of capsule core, which includes weight ratio,:20:5:90 berberine, diluent, disintegrant and wetting agent.Wherein,
It is 3 that diluent, which includes weight ratio,:1:2 microcrystalline cellulose, lactose and mannitol.Disintegrant is PVPP.
Wetting agent is the ethanol that mass concentration is 40%-85%.
It is 10 that the raw material of separation layer, which includes weight ratio,:3 the first coating agent and the first antitackiness agent, and capsule core weight 0.5
Ethanol again.Wherein, the first coating agent is HPMC E5, and the first antitackiness agent is talcum powder.
It is 60 that the raw material of enteric layer, which includes weight ratio,:2:1 the second coating agent, plasticizer and the second antitackiness agent, Yi Jiyu
Capsule core weight ratio is 52.5:100 coating solvent.Wherein, the second coating agent is EudragitL100, and plasticizer is citric acid three
Ethyl ester, the second antitackiness agent is magnesium stearate glycerin monostearate, and coating solvent is water.
The preparation method of the berberine enteric-coated micro-pill, including：Take the berberine of 80-100 mesh, diluent, disintegrant, bonding
Agent, is put into efficient wet granulator and mixes, and then adds wetting agent, and stirring 20min prepares softwood.Then softwood is put into crowded
Go out in device, the orifice plate for being 0.4-1.5mm with aperture extrusion.The strip wet stock of extrusion is placed in spheronizator and extruded, then
Dried under conditions of 50 DEG C to moisture≤3%, the capsule core screened between 18-24 mesh is stand-by.Wherein, extruded velocity be 40 turns/
Min, round as a ball rotating speed is 600 turns/min, and the round as a ball time is 5-30min.
First coating agent and ethanol are mixed after fully dissolving, the first antitackiness agent is added and mixes to obtain separation layer solution.Will be upper
The capsule core stated carries out the first Cotton seeds by fluid bed, and separation layer solution contacts keeping temperature with capsule core for 30 DEG C, wherein, the
The atomizing pressure of one Cotton seeds is 0.05-0.4MPa, and air intake frequency is 20-35HZ, and EAT is 40 DEG C, and leaving air temp is
25 DEG C, jet speed is 10-30mL/min, has sprayed dry 15-35min after separation layer solution and has obtained separation layer capsule core, has isolated layered pills
Core is than capsule core weightening 5%.
Second coating agent and coating solvent are mixed after fully dissolving, plasticizer, the second antitackiness agent is added and stirs
Enteric layer solution.Above-mentioned separation layer capsule core is placed in fluid bed and carries out the second Cotton seeds, enteric layer solution is with isolating layered pills
Core contact keeping temperature is 25 DEG C, and the atomizing pressure of the second Cotton seeds is 0.05-0.4MPa, and air intake frequency is 20-35HZ, is entered
Air temperature is 30 DEG C, and leaving air temp is 25 DEG C, and jet speed is 5-30mL/min, has sprayed dry berberine after enteric layer solution
Enteric-coated micro-pill, berberine enteric-coated micro-pill is than capsule core weightening 15.5%.
Embodiment 2
A kind of berberine enteric-coated micro-pill, including capsule core, separation layer and enteric layer.Capsule core and separation layer, the weight of enteric layer
Than for 50:5:16.
It is 30 that the raw material of capsule core, which includes weight ratio,:40:3:109.5 berberine, diluent, disintegrant and wetting agent.Its
In, it is 2 that diluent, which includes weight ratio,:1:2 microcrystalline cellulose, lactose and mannitol.Disintegrant is sodium carboxymethyl starch.Wetting
Agent is the ethanol that mass concentration is 40%-85%.
It is 70 that the raw material of separation layer, which includes weight ratio,:20：2 the first coating agent, the first antitackiness agent and polyethylene glycol, and
The ethanol that 0.8 times of capsule core weight.Wherein, the first coating agent is polyvinylpyrrolidone, and the first antitackiness agent is magnesium stearate.
It is 70 that the raw material of enteric layer, which includes weight ratio,:3:5 the second coating agent, plasticizer and the second antitackiness agent, Yi Jiyu
Capsule core weight ratio is 4:5 coating solvent.Wherein, the second coating agent is Eudragit S 100, and plasticizer is propane diols, second
Antitackiness agent is talcum powder.Coating solvent is the ethanol that mass concentration is 40wt%.
The preparation method of the berberine enteric-coated micro-pill, including：Take the berberine of 80-100 mesh, diluent, disintegrant, bonding
Agent, is put into efficient wet granulator and mixes, and then adds wetting agent, and stirring 40min prepares softwood.Then softwood is put into crowded
Go out in device, the orifice plate for being 0.4-1.5mm with aperture extrusion.The strip wet stock of extrusion is placed in spheronizator and extruded, then
Dried under conditions of 65 DEG C to moisture≤3%, the capsule core screened between 18-24 mesh is stand-by.Wherein, extruded velocity be 20 turns/
Min, round as a ball rotating speed is 1300 turns/min, and the round as a ball time is 5-30min.
First coating agent and ethanol are mixed after fully dissolving, the first antitackiness agent is added and mixes to obtain separation layer solution.Will be upper
The capsule core stated carries out the first Cotton seeds by fluid bed, and separation layer solution contacts keeping temperature with capsule core for 25 DEG C, wherein, the
The atomizing pressure of one Cotton seeds is 0.05-0.4MPa, and air intake frequency is 20-35HZ, and EAT is 60 DEG C, and leaving air temp is
35 DEG C, jet speed is 10-30mL/min, has sprayed dry 15-35min after separation layer solution and has obtained separation layer capsule core, has isolated layered pills
Core is than capsule core weightening 10%.
Second coating agent and coating solvent are mixed after fully dissolving, plasticizer, the second antitackiness agent is added and stirs
Enteric layer solution.Above-mentioned separation layer capsule core is placed in fluid bed and carries out the second Cotton seeds, enteric layer solution is with isolating layered pills
Core contact keeping temperature is 40 DEG C, and the atomizing pressure of the second Cotton seeds is 0.05-0.4MPa, and air intake frequency is 20-35HZ, is entered
Air temperature is 60 DEG C, and leaving air temp is 35 DEG C, and jet speed is 5-30mL/min, has sprayed dry berberine after enteric layer solution
Enteric-coated micro-pill, berberine enteric-coated micro-pill is than capsule core weightening 32%.
Embodiment 3
A kind of berberine enteric-coated micro-pill, including capsule core, separation layer and enteric layer.Capsule core and separation layer, the weight of enteric layer
Than for 100:25:87.5.
It is 10 that the raw material of capsule core, which includes weight ratio,:30:6:86.4:6 berberine, diluent, disintegrant, wetting agent and glutinous
Mixture.Wherein, it is 1 that diluent, which includes weight ratio,:1:2 microcrystalline cellulose, lactose and mannitol.Disintegrant is CMS
Sodium, wetting agent is the ethanol that mass concentration is 40%-85%.Binder is hydroxypropyl methyl cellulose.
It is 8 that the raw material of separation layer, which includes weight ratio,:2:1 the first coating agent, the first antitackiness agent and polyethylene glycol, and ball
The ethanol that 0.4 times of core weight.Wherein, the first coating agent is ethyl cellulose, and the first antitackiness agent is titanium dioxide.
It is 50 that the raw material of enteric layer, which includes weight ratio,:5:8 the second coating agent, plasticizer and the second antitackiness agent, Yi Jiyu
Capsule core weight ratio is 1:1 coating solvent.Wherein, the second coating agent is that weight ratio is 2:1 EudragitL100 and
Eudragit S 100, plasticizer is polyethylene glycol, and the second antitackiness agent is talcum powder.Coating solvent is that mass concentration is 85wt%
Ethanol.
The preparation method of the berberine enteric-coated micro-pill, including：Take the berberine of 80-100 mesh, diluent, disintegrant, bonding
Agent, is put into efficient wet granulator and mixes, and then adds wetting agent, and stirring 30min prepares softwood.Then softwood is put into crowded
Go out in device, the orifice plate for being 0.4-1.5mm with aperture extrusion.The strip wet stock of extrusion is placed in spheronizator and extruded, then
Dried under conditions of 40 DEG C to moisture≤3%, the capsule core screened between 18-24 mesh is stand-by.Wherein, extruded velocity be 50 turns/
Min, round as a ball rotating speed is 550 turns/min, and the round as a ball time is 5-30min.
First coating agent and ethanol are mixed after fully dissolving, the first antitackiness agent is added and mixes to obtain separation layer solution.Will be upper
The capsule core stated carries out the first Cotton seeds by fluid bed, and separation layer solution contacts keeping temperature with capsule core for 40 DEG C, wherein, the
The atomizing pressure of one Cotton seeds is 0.05-0.4MPa, and air intake frequency is 20-35HZ, and EAT is 30 DEG C, and leaving air temp is
25 DEG C, jet speed is 10-30mL/min, has sprayed dry 15-35min after separation layer solution and has obtained separation layer capsule core, has isolated layered pills
Core is than capsule core weightening 25%.
Second coating agent and coating solvent are mixed after fully dissolving, plasticizer, the second antitackiness agent is added and stirs
Enteric layer solution.Above-mentioned separation layer capsule core is placed in fluid bed and carries out the second Cotton seeds, enteric layer solution is with isolating layered pills
Core contact keeping temperature is 25 DEG C, and the atomizing pressure of the second Cotton seeds is 0.05-0.4MPa, and air intake frequency is 20-35HZ, is entered
Air temperature is 30 DEG C, and leaving air temp is 25 DEG C, and jet speed is 5-30mL/min, has sprayed dry berberine after enteric layer solution
Enteric-coated micro-pill, berberine enteric-coated micro-pill is than capsule core weightening 87.5%.
Embodiment 4
A kind of berberine enteric-coated micro-pill, including capsule core, separation layer and enteric layer.Capsule core and separation layer, the weight of enteric layer
Than for 100:15:49.5.
It is 50 that the raw material of capsule core, which includes weight ratio,:60:7:118:1 berberine, diluent, disintegrant, wetting agent and glutinous
Mixture.Wherein, it is 1 that diluent, which includes weight ratio,:1:1 microcrystalline cellulose, lactose and mannitol.Disintegrant is carboxymethyl cellulose
Plain sodium, wetting agent is water.Binder is high substitution hydroxypropyl methyl cellulose.
It is 60 that the raw material of separation layer, which includes weight ratio,:30:1 the first coating agent, the first antitackiness agent and polyethylene glycol, and
The ethanol that 1 times of capsule core weight.Wherein, the first coating agent is polyvinylpyrrolidone, and the first antitackiness agent is talcum powder.
It is 40 that the raw material of enteric layer, which includes weight ratio,:4:3:5 the second coating agent, plasticizer, the second antitackiness agent and stably
Agent, and with capsule core weight ratio be 6:5 coating solvent.Wherein, the second coating agent is that weight ratio is 4:1 EudragitL100
With Eudragit S 100, plasticizer is polyethylene glycol, and the second antitackiness agent is talcum powder.Stabilizer is that mass concentration is 4%
Sodium hydroxide.Coating solvent is the ethanol that mass concentration is 50wt%.
The preparation method of the berberine enteric-coated micro-pill, including：Take the berberine of 80-100 mesh, diluent, disintegrant, bonding
Agent, is put into efficient wet granulator and mixes, and then adds wetting agent, and stirring 35min prepares softwood.Then softwood is put into crowded
Go out in device, the orifice plate for being 0.4-1.5mm with aperture extrusion.The strip wet stock of extrusion is placed in spheronizator and extruded, then
Dried under conditions of 50 DEG C to moisture≤3%, the capsule core screened between 18-24 mesh is stand-by.Wherein, extruded velocity be 40 turns/
Min, round as a ball rotating speed is 800 turns/min, and the round as a ball time is 5-30min.
First coating agent and ethanol are mixed after fully dissolving, the first antitackiness agent is added and mixes to obtain separation layer solution.Will be upper
The capsule core stated carries out the first Cotton seeds by fluid bed, and separation layer solution contacts keeping temperature with capsule core for 35 DEG C, wherein, the
The atomizing pressure of one Cotton seeds is 0.05-0.4MPa, and air intake frequency is 20-35HZ, and EAT is 40 DEG C, and leaving air temp is
30 DEG C, jet speed is 10-30mL/min, has sprayed dry 15-35min after separation layer solution and has obtained separation layer capsule core, has isolated layered pills
Core is than capsule core weightening 15%.
Second coating agent and coating solvent are mixed after fully dissolving, plasticizer, the second antitackiness agent and stabilizer is added and stirs
Mix uniform enteric layer solution.By above-mentioned separation layer capsule core be placed in fluid bed carry out the second Cotton seeds, enteric layer solution with
Separation layer capsule core contact keeping temperature is 35 DEG C, and the atomizing pressure of the second Cotton seeds is 0.05-0.4MPa, and air intake frequency is
20-35HZ, EAT is 40 DEG C, and leaving air temp is 30 DEG C, and jet speed is 5-30mL/min, has sprayed and has been done after enteric layer solution
Dry to obtain berberine enteric-coated micro-pill, berberine enteric-coated micro-pill is than capsule core weightening 49.5%.
Embodiment 5
A kind of berberine enteric-coated micro-pill, including capsule core, separation layer and enteric layer.Capsule core and separation layer, the weight of enteric layer
Than for 50:10:31.
It is 60 that the raw material of capsule core, which includes weight ratio,:70:8:100.1:5 berberine, diluent, disintegrant, wetting agent and
Binder.Wherein, diluent is 1.5:1:1 microcrystalline cellulose, lactose and mannitol.Disintegrant is sodium carboxymethylcellulose,
Wetting agent is water.Binder is hydroxypropyl methyl cellulose.
It is 2 that the raw material of separation layer, which includes weight ratio,:1 the first coating agent and the first antitackiness agent element, and 2 times of capsule core weight
Ethanol.Wherein, the second coating agent is polyvinylpyrrolidone, and the first antitackiness agent is talcum powder.
It is 65 that the raw material of enteric layer, which includes weight ratio,:6:12:3 the second coating agent, plasticizer, the second antitackiness agent and stably
Agent, and with capsule core weight ratio be 3:2 coating solvent.Wherein, the second coating agent is Eudragit S 100, and plasticizer is poly-
Ethylene glycol, the second antitackiness agent is talcum powder.Stabilizer is the sodium hydroxide that mass concentration is 4%.Coating solvent is mass concentration
For 60wt% ethanol.
The preparation method of the berberine enteric-coated micro-pill, including：Take the berberine of 80-100 mesh, diluent, disintegrant, bonding
Agent, is put into efficient wet granulator and mixes, and then adds wetting agent, and stirring 28min prepares softwood.Then softwood is put into crowded
Go out in device, the orifice plate for being 0.4-1.5mm with aperture extrusion.The strip wet stock of extrusion is placed in spheronizator and extruded, then
Dried under conditions of 48 DEG C to moisture≤3%, the capsule core screened between 18-24 mesh is stand-by.Wherein, extruded velocity be 35 turns/
Min, round as a ball rotating speed is 1000 turns/min, and the round as a ball time is 5-30min.
First coating agent and ethanol are mixed after fully dissolving, the first antitackiness agent is added and mixes to obtain separation layer solution.Will be upper
The capsule core stated carries out the first Cotton seeds by fluid bed, and separation layer solution contacts keeping temperature with capsule core for 32 DEG C, wherein, the
The atomizing pressure of one Cotton seeds is 0.05-0.4MPa, and air intake frequency is 20-35HZ, and EAT is 48 DEG C, and leaving air temp is
30 DEG C, jet speed is 10-30mL/min, has sprayed dry 15-35min after separation layer solution and has obtained separation layer capsule core, has isolated layered pills
Core is than capsule core weightening 20%.
Second coating agent and coating solvent are mixed after fully dissolving, plasticizer, the second antitackiness agent and stabilizer is added and stirs
Mix uniform enteric layer solution.By above-mentioned separation layer capsule core be placed in fluid bed carry out the second Cotton seeds, enteric layer solution with
Separation layer capsule core contact keeping temperature is 35 DEG C, and the atomizing pressure of the second Cotton seeds is 0.05-0.4MPa, and air intake frequency is
20-35HZ, EAT is 48 DEG C, and leaving air temp is 30 DEG C, and jet speed is 5-30mL/min, has sprayed and has been done after enteric layer solution
Dry to obtain berberine enteric-coated micro-pill, berberine enteric-coated micro-pill is than capsule core weightening 62%.
Embodiment 6
A kind of berberine enteric-coated micro-pill, including capsule core, separation layer and enteric layer.Capsule core and separation layer, the weight of enteric layer
Than for 100:18:47.5.
It is 70 that the raw material of capsule core, which includes weight ratio,:80:9:65.2:4 berberine, diluent, disintegrant, wetting agent and glutinous
Mixture.Wherein, diluent is 1.5:1:2 microcrystalline cellulose, lactose and mannitol.Disintegrant is crosslinked polyethylene pyrrolidines
Ketone, wetting agent is water.Binder is hydroxypropyl methyl cellulose.
It is 55 that the raw material of separation layer, which includes weight ratio,:25:3 the first coating agent, the first antitackiness agent and polyethylene glycol, and
The ethanol that 1.2 times of capsule core weight.Wherein, the first coating agent is polyvinylpyrrolidone, and the first antitackiness agent is titanium dioxide.
It is 80 that the raw material of enteric layer, which includes weight ratio,:8:15:4 the second coating agent, plasticizer, the second antitackiness agent and stably
Agent, and with capsule core weight ratio be 5:2 coating solvent.Wherein, the second coating agent is that weight ratio is 2:0.7
EudragitL100 and Eudragit S 100, plasticizer is triethyl citrate, and the second antitackiness agent is talcum powder.Stabilizer is
Mass concentration is 4% sodium hydroxide.Coating solvent is the ethanol that mass concentration is 70wt%.
The preparation method of the berberine enteric-coated micro-pill, including：Take the berberine of 80-100 mesh, diluent, disintegrant, bonding
Agent, is put into efficient wet granulator and mixes, and then adds wetting agent, and stirring 32min prepares softwood.Then softwood is put into crowded
Go out in device, the orifice plate for being 0.4-1.5mm with aperture extrusion.The strip wet stock of extrusion is placed in spheronizator and extruded, then
Dried under conditions of 53 DEG C to moisture≤3%, the capsule core screened between 18-24 mesh is stand-by.Wherein, extruded velocity be 48 turns/
Min, round as a ball rotating speed is 1100 turns/min, and the round as a ball time is 5-30min.
First coating agent and ethanol are mixed after fully dissolving, the first antitackiness agent is added and mixes to obtain separation layer solution.Will be upper
The capsule core stated carries out the first Cotton seeds by fluid bed, and separation layer solution contacts keeping temperature with capsule core for 37 DEG C, wherein, the
The atomizing pressure of one Cotton seeds is 0.05-0.4MPa, and air intake frequency is 20-35HZ, and EAT is 52 DEG C, and leaving air temp is
28 DEG C, jet speed is 10-30mL/min, has sprayed dry 15-35min after separation layer solution and has obtained separation layer capsule core, has isolated layered pills
Core is than capsule core weightening 18%.
Second coating agent and coating solvent are mixed after fully dissolving, plasticizer, the second antitackiness agent and stabilizer is added and stirs
Mix uniform enteric layer solution.By above-mentioned separation layer capsule core be placed in fluid bed carry out the second Cotton seeds, enteric layer solution with
Separation layer capsule core contact keeping temperature is 37 DEG C, and the atomizing pressure of the second Cotton seeds is 0.05-0.4MPa, and air intake frequency is
20-35HZ, EAT is 52 DEG C, and leaving air temp is 30 DEG C, and jet speed is 5-30mL/min, has sprayed and has been done after enteric layer solution
Dry to obtain berberine enteric-coated micro-pill, berberine enteric-coated micro-pill is than capsule core weightening 47.5%.
Embodiment 7
A kind of berberine enteric-coated micro-pill, including capsule core, separation layer and enteric layer.Capsule core and separation layer, the weight of enteric layer
Than for 100:22:70.8.
It is 40 that the raw material of capsule core, which includes weight ratio,:50:4:116.4:3 berberine, diluent, disintegrant, wetting agent and
Binder.Wherein, diluent is 2:1:1.5 microcrystalline cellulose, lactose and mannitol.Disintegrant is crosslinked polyethylene pyrrolidines
Ketone, wetting agent is water.Binder is hydroxypropyl methyl cellulose.
It is 65 that the raw material of separation layer, which includes weight ratio,:35:4 the first coating agent, the first antitackiness agent and polyethylene glycol, and
The ethanol that 1.5 times of capsule core weight.Wherein, the first coating agent is zein, and the first antitackiness agent is magnesium stearate.
It is 17 that the raw material of enteric layer, which includes weight ratio,:2:2:1 the second coating agent, plasticizer, the second antitackiness agent and stably
Agent, and with capsule core weight ratio be 17:10 coating solvent.Wherein, the second coating agent is that weight ratio is 2:0.6
EudragitL100 and Eudragit S 100, plasticizer is triethyl citrate, and the second antitackiness agent is talcum powder.Stabilizer is
Mass concentration is 4% sodium hydroxide.Coating solvent is the ethanol that mass concentration is 50wt%.
The preparation method of the berberine enteric-coated micro-pill, including：Take the berberine of 80-100 mesh, diluent, disintegrant, bonding
Agent, is put into efficient wet granulator and mixes, and then adds wetting agent, and stirring 32min prepares softwood.Then softwood is put into crowded
Go out in device, the orifice plate for being 0.4-1.5mm with aperture extrusion.The strip wet stock of extrusion is placed in spheronizator and extruded, then
Dried under conditions of 53 DEG C to moisture≤3%, the capsule core screened between 18-24 mesh is stand-by.Wherein, extruded velocity be 50 turns/
Min, round as a ball rotating speed is 900 turns/min, and the round as a ball time is 5-30min.
First coating agent and ethanol are mixed after fully dissolving, the first antitackiness agent is added and mixes to obtain separation layer solution.Will be upper
The capsule core stated carries out the first Cotton seeds by fluid bed, and separation layer solution contacts keeping temperature with capsule core for 35 DEG C, wherein, the
The atomizing pressure of one Cotton seeds is 0.05-0.4MPa, and air intake frequency is 20-35HZ, and EAT is 50 DEG C, and leaving air temp is
28 DEG C, jet speed is 10-30mL/min, has sprayed dry 15-35min after separation layer solution and has obtained separation layer capsule core, has isolated layered pills
Core is than capsule core weightening 22%.
Second coating agent and coating solvent are mixed after fully dissolving, plasticizer, the second antitackiness agent and stabilizer is added and stirs
Mix uniform enteric layer solution.By above-mentioned separation layer capsule core be placed in fluid bed carry out the second Cotton seeds, enteric layer solution with
Separation layer capsule core contact keeping temperature is 37 DEG C, and the atomizing pressure of the second Cotton seeds is 0.05-0.4MPa, and air intake frequency is
20-35HZ, EAT is 52 DEG C, and leaving air temp is 30 DEG C, and jet speed is 5-30mL/min, has sprayed and has been done after enteric layer solution
Dry to obtain berberine enteric-coated micro-pill, berberine enteric-coated micro-pill is than capsule core weightening 70.8%.
Embodiment 8
A kind of berberine enteric-coated micro-pill, including capsule core, separation layer and enteric layer.Capsule core and separation layer, the weight of enteric layer
Than for 100:12:28.8.
It is 75 that the raw material of capsule core, which includes weight ratio,:85:10:52.8:2 berberine, diluent, disintegrant, wetting agent and
Binder.Wherein, diluent is 2:1:2 microcrystalline cellulose, lactose and mannitol.Disintegrant is crosslinked polyethylene pyrrolidines
Ketone, wetting agent is the ethanol that mass concentration is 40%-85%.Binder is hydroxypropyl methyl cellulose.
It is 25 that the raw material of separation layer, which includes weight ratio,:15:1 the first coating agent, the first antitackiness agent and polyethylene glycol, and
The ethanol that 1.8 times of capsule core weight.Wherein, the first coating agent is polyvinylpyrrolidone, and the first antitackiness agent is talcum powder.
It is 55 that the raw material of enteric layer, which includes weight ratio,:1:6:2 the second coating agent, plasticizer, the second antitackiness agent and stably
Agent, and with capsule core weight ratio be 2:1 coating solvent.Wherein, the second coating agent is Eudragit L100, and plasticizer is lemon
Lemon triethylenetetraminehexaacetic acid ester, the second antitackiness agent is talcum powder.Stabilizer is the sodium hydroxide that mass concentration is 4%.Coating solvent is quality
Concentration is 60wt% ethanol.
The preparation method of the berberine enteric-coated micro-pill, including：Take the berberine of 80-100 mesh, diluent, disintegrant, bonding
Agent, is put into efficient wet granulator and mixes, and then adds wetting agent, and stirring 32min prepares softwood.Then softwood is put into crowded
Go out in device, the orifice plate for being 0.4-1.5mm with aperture extrusion.The strip wet stock of extrusion is placed in spheronizator and extruded, then
Dried under conditions of 53 DEG C to moisture≤3%, the capsule core screened between 18-24 mesh is stand-by.Wherein, extruded velocity be 50 turns/
Min, round as a ball rotating speed is 900 turns/min, and the round as a ball time is 5-30min.
First coating agent and ethanol are mixed after fully dissolving, the first antitackiness agent is added and mixes to obtain separation layer solution.Will be upper
The capsule core stated carries out the first Cotton seeds by fluid bed, and separation layer solution contacts keeping temperature with capsule core for 35 DEG C, wherein, the
The atomizing pressure of one Cotton seeds is 0.05-0.4MPa, and air intake frequency is 20-35HZ, and EAT is 50 DEG C, and leaving air temp is
28 DEG C, jet speed is 10-30mL/min, has sprayed dry 15-35min after separation layer solution and has obtained separation layer capsule core, has isolated layered pills
Core is than capsule core weightening 12%.
Second coating agent and coating solvent are mixed after fully dissolving, plasticizer, the second antitackiness agent and stabilizer is added and stirs
Mix uniform enteric layer solution.By above-mentioned separation layer capsule core be placed in fluid bed carry out the second Cotton seeds, enteric layer solution with
Separation layer capsule core contact keeping temperature is 37 DEG C, and the atomizing pressure of the second Cotton seeds is 0.05-0.4MPa, and air intake frequency is
20-35HZ, EAT is 50 DEG C, and leaving air temp is 30 DEG C, and jet speed is 5-30mL/min, has sprayed and has been done after enteric layer solution
Dry to obtain berberine enteric-coated micro-pill, berberine enteric-coated micro-pill is than capsule core weightening 28.8%.
Comparative example
The berberine enteric-coated micro-pill of comparative example is with the berberine enteric-coated micro-pill component in embodiment 1, with when preparation method
Essentially identical, it the difference is that only the diluent only microcrystalline cellulose of comparative example.
Test example 1
Dissolution test：Release to the berberine enteric-coated micro-pill of embodiment 1 is tested, test according to《Middle traditional Chinese medicines
Allusion quotation》2015 editions the 4th paddle method recorded determine the tablets in vitro rate of micropill, using human gastrointestinal tract physiological pH ladder, by surveying
It is scheduled on releasing research its release in vitro performance in corresponding pH value.The final berberine micro-pills enteric coated preparations that determine are respectively in artificial stomach
Liquid is containing pepsin (pH=1.0) and simulated intestinal fluid containing pancreatin (pH=6.4,6.8,7.4,8.0) and in purifying aqueous medium
The release of medicine.
Test procedure：The berberine enteric-coated micro-pill of Example 1 on request, according to《Chinese Pharmacopoeia》0,931 in 4th
Two methods are determined, and its simulated gastric fluid (containing pepsin) is with 0.1mol/L hydrochloric acid solutions (pH=1) for dissolution medium；Simulated intestinal fluid
(containing pancreatin) is using the phosphate buffer of pH=6.0,6.8,7.4,8.0 as dissolution medium；Purified water (pH=5.8) is preheated with 1L
It is dissolution medium to 37 ± 0.5 DEG C of purified waters.In rotating speed 100r/min, 37 ± 0.5 DEG C of temperature is operated in accordance with the law, carries out the coptis
Plain enteric-coated micro-pill dissolution test, samples 5ml solution respectively at 5,10,15,30,45,60,75,90,105,120min, filters,
Take subsequent filtrate 20ul to inject high performance liquid chromatograph, record chromatogram, medicine cumulative release is gone out with calculated by peak area by external standard method
Amount.The berberine enteric-coated micro-pill of embodiment 1 in different medium release result as shown in table 1 and Fig. 1.
The berberine enteric-coated micro-pill of the embodiment 1 of table 1 release result in different medium
From the data of table 1 and Fig. 1 can be seen that the berberine enteric-coated micro-pill of embodiment 1 in water it is insoluble, pH=1's
Almost insoluble in acid medium, its medicament contg is less than the 10% of labelled amount, and in simulated intestinal fluid pH=6.8,7.4, has very
Good concentration release, drug release rate can completely discharge in 90%-102% in enteron aisle in enteron aisle.Illustrate by this
The each component of the berberine enteric-coated micro-pill of inventive embodiments, with when manufacture craft, can obtain in the high Huang of enteron aisle release
Connect plain enteric-coated micro-pill.
Test example 2
The berberine enteric-coated micro-pill for taking appropriate embodiment 1,2,3,4,6 and comparative example to prepare, according to release in test example 1
Method of testing determine berberine enteric-coated micro-pill 1h in pH=6.8 phosphate buffers release.Its result is recorded in table 2
In.
The embodiment 1-4 of table 2,6 and comparative example berberine enteric-coated micro-pill pH=6.8 release
As shown in Table 2, releasing after being only individually coated in Examples 1 and 2 using EudragitL100 and EudragitS100
Degree of putting speed does not have to mix the release being coated in embodiment 3,4,6 using EudragitL100 and EudragitS100 enteric materials
Spend.By a certain percentage by two kinds of coating materials be used in mixed way can after 15min minutes release ＞ 90%, and do not influence effectively
The content of composition.From embodiment 1-4,6 and comparative example release result, it is evident that alone microcrystalline cellulose is used as dilution
The pellet core of agent, its release is compared compared with the present invention program, and its rate of release, burst size are substantially relatively low.
Test example 3
Accelerated stability test：Berberine enteric-coated micro-pill prepared by Example 1-3 is placed in temperature for 40 ± 2 DEG C in right amount,
Relative humidity sampled to be placed 6 months in 75% ± 5% incubator respectively at 0,1,2,3 and 6 months, and determination sample
Character, about material and release, acid resistance content, content.It the results are shown in Table 3.
The embodiment 1-3 acceleration for stabilization of table 3 is tested
Embodiment 1-3 berberine enteric-coated micro-pill is at 40 ± 2 DEG C it can be seen from the result of table 3, and relative humidity is 75%
Carry out 6 months Acceleration studies under the conditions of ± 5%, the character of its sample, about material, acid resistance, release, content and 0 month
Compare with batch sample, as a result unanimously, without significant changes.
In summary, the berberine enteric-coated micro-pill of the embodiment of the present invention, it includes capsule core, separation layer and enteric layer, capsule core
In diluent be controllable for the release of active ingredient in berberine enteric-coated micro-pill.Diluent include microcrystalline cellulose,
Lactose and mannitol, because the hygroscopicity of lactose is larger, the stickiness of material is unfavorable for round as a ball place than larger after wetting agent is added
Reason, so the selection addition less mannitol of hygroscopicity is mixed with microcrystalline cellulose, lactose and used as diluent.And lactose and
Mannitol is soluble in water, is also beneficial to the dissolving of capsule core.Disintegrant can be such that berberine enteric-coated micro-pill is broken into rapidly carefully in enteron aisle
Short grained material, is conducive to release of the berberine at enteron aisle, and wetting agent is used for the powder of berberine, diluent and disintegrant
Material mixing carries out round as a ball shaping.It is used as the coating material of enteric layer using acrylic resin, coating process is easy to operate, Coating times
Good control, film-formation result is good.Separation layer is coated between enteric layer and capsule core, increases the stability of preparation, while coating isolation
The smooth rounding in capsule core surface after layer, it is possible to reduce the loss of medicine in enteric coating.First coating agent of separation layer exists
Enteron aisle dissolves, and separation layer is coated on capsule core, is made up of from inside to outside capsule core, separation layer, enteric layer, can preferably ensure that capsule core exists
Positioning release in enteron aisle, improves bioavilability.The preparation method of the berberine enteric-coated micro-pill of the embodiment of the present invention, this method behaviour
Make simple, it utilizes round as a ball expressing technique, and the smooth berberine enteric-coated micro-pill of rounding can be made.
The application of the berberine enteric-coated micro-pill of the embodiment of the present invention, berberine enteric-coated micro-pill acts not only as finished product,
It can be used as middle product.
Embodiments described above is a part of embodiment of the invention, rather than whole embodiments.The reality of the present invention
The detailed description for applying example is not intended to limit the scope of claimed invention, but is merely representative of the selected implementation of the present invention
Example.Based on the embodiment in the present invention, what those of ordinary skill in the art were obtained under the premise of creative work is not made
Every other embodiment, belongs to the scope of protection of the invention.
Claims (10)
1. a kind of berberine enteric-coated micro-pill, it is characterised in that including weight ratio be 100:5-25:15.5~87.5 capsule core, every
Absciss layer and enteric layer, the separation layer are coated on the capsule core, and the enteric layer is coated on the separation layer；
The capsule core is mainly made up of the first raw material, and first raw material includes the first major ingredient and the first auxiliary material, first master
Material includes berberine, and first auxiliary material includes diluent, disintegrant and wetting agent；The berberine, the diluent and institute
The weight ratio for stating disintegrant is 10-75:20-85:3-10；The weight ratio of the wetting agent and first raw material is 0.2-3:1；
The diluent includes microcrystalline cellulose, lactose and mannitol；
The separation layer is mainly made up of the second raw material, and second raw material includes the second major ingredient and the second auxiliary material, described second
Major ingredient includes the first coating agent and ethanol solution, and the weight ratio of the ethanol and the capsule core is 0.4-2:1；Second auxiliary material
Including the first antitackiness agent, the weight ratio of first coating agent and first antitackiness agent is 40-80:10-45；First bag
Clothing agent includes hydroxypropyl methyl cellulose, polyvinylpyrrolidone and ethyl cellulose, at least one of zein；
The enteric layer is mainly made up of the 3rd raw material, and the 3rd raw material includes the second coating agent, the second coating agent bag
Include enteric solubility acrylic resin.
2. berberine enteric-coated micro-pill according to claim 1, it is characterised in that it is 1-3 that the diluent, which includes weight ratio,:
1:1-2 microcrystalline cellulose, lactose and mannitol；Preferably, the disintegrant includes sodium carboxymethyl starch, carboxymethyl cellulose
At least one of sodium, Ac-Di-Sol and PVPP；Preferably, the wetting agent includes water
Or ethanol.
3. berberine enteric-coated micro-pill according to claim 1, it is characterised in that first auxiliary material also includes binder,
Weight ratio≤3 of the binder and the berberine:5；Preferably, the binder includes hydroxypropyl methyl cellulose or height
Replace hydroxypropyl methyl cellulose.
4. berberine enteric-coated micro-pill according to claim 1, it is characterised in that first antitackiness agent include talcum powder,
At least one of magnesium stearate and titanium dioxide.
5. berberine enteric-coated micro-pill according to claim 1, it is characterised in that second auxiliary material also includes poly- second two
Alcohol, weight ratio≤1 of the polyethylene glycol and first coating agent:8.
6. berberine enteric-coated micro-pill according to claim 1, it is characterised in that the 3rd raw material also include plasticizer,
Second antitackiness agent and coating solvent, the weight ratio of second coating agent, the plasticizer and second antitackiness agent is 40-
85:1-10:The weight ratio of 1-15, the coating solvent and the capsule core is 52.5-250:100.
7. berberine enteric-coated micro-pill according to claim 6, it is characterised in that the plasticizer includes lemon triethylenetetraminehexaacetic acid
At least one of ester, propane diols and polyethylene glycol；Preferably, second antitackiness agent includes talcum powder and magnesium stearate list is hard
At least one of glycerol；Preferably, the coating solvent includes water or ethanol.
8. a kind of preparation method of berberine enteric-coated micro-pill as described in claim any one of 1-7, it is characterised in that including：
The capsule core is mixed into the first Cotton seeds of progress, dry separation layer capsule core, first Cotton seeds with separation layer solution
The temperature of step is 25-40 DEG C, and atomizing pressure is 0.05-0.4MPa, and jet speed is 10-30mL/min；By the separation layer
Capsule core mixes the second Cotton seeds of progress, drying with enteric coating liquid, and the temperature of the second Cotton seeds step is 25-40
DEG C, atomizing pressure is 0.05-0.4MPa, and jet speed is 5-30mL/min；The capsule core is mainly made by following steps：By institute
State the first major ingredient and first auxiliary material mixes and obtains softwood, carried out after the softwood is extruded round as a ball, dry.
9. the preparation method of berberine enteric-coated micro-pill according to claim 8, it is characterised in that in the extrusion step
Extruded velocity is that the round as a ball rotating speed that 20-50 turns in/min, the spheronization step is that 550-1300 turns/min, and the round as a ball time is 5-
30min。
10. the application of a kind of berberine enteric-coated micro-pill as described in claim any one of 1-7, it is characterised in that it can be used for
Capsule, granule or supensoid agent.
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| CN114617856A (en) * | 2021-09-07 | 2022-06-14 | 辽宁格林希尔医疗科技有限公司 | Solid-liquid suspension traditional Chinese medicine preparation and preparation method thereof |
| CN114831222A (en) * | 2022-05-24 | 2022-08-02 | 上海美农生物科技股份有限公司 | Coated tannin pellet feed additive and preparation method thereof |
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| CN114831222A (en) * | 2022-05-24 | 2022-08-02 | 上海美农生物科技股份有限公司 | Coated tannin pellet feed additive and preparation method thereof |
| CN114831222B (en) * | 2022-05-24 | 2023-10-13 | 上海美农生物科技股份有限公司 | Coated tannin micropill feed additive and preparation method thereof |
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Application publication date: 20171024 |