CN109464425A - A kind of probiotics embedded particles and preparation method thereof - Google Patents
A kind of probiotics embedded particles and preparation method thereof Download PDFInfo
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- 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
- A61K9/5073—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 having two or more different coatings optionally including drug-containing subcoatings
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
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- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
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- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
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Abstract
The present invention provides a kind of probiotics embedded particles and preparation method thereof, are related to probiotics technical field.Probiotics embedded particles of the present invention include three encapsulating layers outside probiotics core and the probiotics core, and the encapsulating layer is from inside to outside successively are as follows: starch protection layer, film coating separation layer and enteric coat layer.Viable detection is 39~49% after scheme of the present invention embedding；Survival rate after accelerating storage 2 months at 37 DEG C is 18~42%；And the survival rate of 60min is 77~85% in simulated gastric fluid, probiotics is remarkably improved in the viable bacteria content of shelf life, while most of probiotics can also be made to discharge in enteron aisle, to play beneficial effect.
Description
Technical field
The invention belongs to keep probiotic active technical field, and in particular to a kind of probiotics embedded particles and its preparation side
Method.
Background technique
In recent years, probiotics has key effect in human health, has been widely used in multiple product, and by
More and more people approve.Because probiotics preparation be to body and its in environment be provided with benefit viable bacteria, improve human body it is micro-
The ecological balance.Therefore, viable count contained by unit formulation is one of the major criterion for evaluating probiotics preparation.And prebiotic becteriums product
In probiotics raw material viable bacteria stability with regard to most important.Viable count and its time-to-live remove and strain sheet in probiotics preparation
Body has outside the Pass, has very close relationship with dosage form, condition of storage.Since most probiotics are that anaerobism or inclined anaerobism are living
Bacterium, general light, temperature, humidity and pH have a significant impact probiotics, and temperature is higher, and humidity is bigger, and viable bacteria life span is shorter.
In addition, probiotics must reach enteron aisle by gastric environment with a large amount of viable bacteria and be settled in competence exertion on intestinal mucosa
Its physiological function can generate Beneficial Effect to human body by changing intestinal flora balance.However, there is many active probiotics to exist
Just because that gastric acid and bile act on is dead before into enteron aisle, therefore the ability for proliferation of surviving in host is lower, very greatly
Their probiotic effects are affected in degree.Therefore also just become another important finger of probiotic effect in the survival rate of enteron aisle
Mark.
Various probiotics preparation products under normal conditions, to human body generate beneficial functional before, will undergo production process,
Storage process and through intestines and stomach process.Therefore, the viable bacteria stability of the probiotics raw material in prebiotic becteriums product is just to Guan Chong
It wants.
In order to extend the probiotics time-to-live to greatest extent, especially increase survival volume of the probiotics in enteron aisle, very
It researchs and produces personnel more and has carried out embedding techniques in the application study in probiotics field, mainly include following four:
1. spray drying process: by probiotics and with wall material it is miscible with solution in, spray drying.Simple process, but probiotics
Embedding rate is low, and because of dry aqueous solution, at least 60 DEG C or more of drying temperature, although the time is shorter, spray drying temperature is prebiotic
Bacterium does not tolerate, and temperature is positively correlated with yield (i.e. mist flow), and 60 DEG C of spray drying yield is impossible to reach
It is production-scale, although having hermetically sealed spray drying technology now, it can be spray-dried with low-temperature circulating, yield can be improved, only
It is the experimental stage, but also wants 60 DEG C of circulations, and energy consumption greatly improves.
2. fluidized bed embeds: probiotics (mixing other auxiliary materials) powder to be embedded boils in fluidized bed, the spray of packaging material aqueous solution
Mist coated powder, dry simultaneously, though temperature can be reduced to 40 DEG C or so, embedding rate is improved relative to spray drying, embedding
Time is very long (preventing from bonding, mist flow cannot be big, and to dry after embedding).Probiotics is deposited in long-time thermal histories
Motility rate is greatly reduced.
3. extrusion coacervation: it agglomerates different phases to form embedding using physical and chemical principle, but embeds not exclusively densification,
Enteric packaging material is even more it is not possible that (low pH gastric juice is easily penetrated into).
4. high-pressure electrostatic method: making core material and packaging material band difference charge attract each other to form embedding, but this embedding is also not
Fine and close, that is, the leakproofness being isolated from the outside world is very poor, and opposite probiotics will be isolated as far as possible for outside air and moisture, substantially
It is nonsensical, needless to say stop the gastric acid liquid of low pH.
In conclusion improving the stability of probiotics solid material with embedding method, much still belong to experimental stage.Even if having
Production-scale (as squeezed coacervation), can not have both the preservation characteristics and acidproof enteric characteristics of leakproofness.
Summary of the invention
In view of this, being prepared the purpose of the present invention is to provide a kind of probiotics embedded particles and preparation method thereof
Probiotics embedded particles can guarantee viable bacteria content in shelf life, and a certain number of viable bacterias can be made to enter enteron aisle and acted as
With.
In order to achieve the above-mentioned object of the invention, the present invention the following technical schemes are provided:
The present invention provides a kind of probiotics embedded particles, the probiotics embedded particles include probiotics core and described
Three encapsulating layers outside probiotics core, the encapsulating layer is from inside to outside successively are as follows: starch protection layer, film coating separation layer and
Enteric coat layer.
Preferably, the diameter of the probiotics core is 180~380 μm；The starch protection layer with a thickness of 40~80 μ
m；The film coating separation layer with a thickness of 5~10 μm；The enteric coat layer with a thickness of 6~12 μm.
Preferably, the probiotics type of the probiotics core includes: lactobacillus plantarum, lactobacillus acidophilus, cheese cream bar
Bacterium, lactobacillus paracasei, Lactobacillus rhamnosus, lactobacillus fermenti, Lactobacillus salivarius, Lactobacillus helveticus, lactobacillus reuteri, lattice
Family name's lactobacillus, Lactobacillus crispatus, Yue Shi lactobacillus, lactobacillus bulgaricus, streptococcus thermophilus, bifidobacterium lactis, long bifid bar
Two or more mixing in bacterium, bifidobacterium breve, bifidobacterium infantis, bifidobacterium bifidum and bifidobacterium adolescentis
Strain.
The present invention also provides the preparation methods of above-mentioned probiotics embedded particles, comprising the following steps: (1) will be described prebiotic
The bacterium powder of bacterium is successively embedded as core with starch and water layer by layer, until obtaining starch embedding after 1~3 times of bacterium powder weight gain
Probiotic granulate；
(2) the starch embedding probiotic granulate is subjected to film coating with film-coating premixing material, until the starch packet
After burying probiotic granulate weight gain 8~20%, film coating probiotic granulate is obtained；
(3) by the film coating probiotic granulate enteric coating liquid, enteric coating is carried out, until the film coating is beneficial
It is dry that prebiotic bacterium bag buries particle after raw bacterium weight gain 8~30%.
Preferably, when step (1) described embedding, after one layer of starch and water embedding, next layer of starch is carried out again after drying
With the embedding of water.
Preferably, embedded particles water content≤3% after drying.
Preferably, the type of starch includes porous-starch or resistant starch.
Preferably, temperature of charge when step (2) described film coating is 30~37 DEG C.
It preferably, include the raw material of following weight ratio: enteric material: plasticizer: anticaking agent=1 in the enteric coating liquid
: 0.05~0.2: 0.25~0.5.
Preferably, the temperature of charge when enteric coating is 30~35 DEG C.
The present invention provides a kind of probiotics embedded particles, the probiotics embedded particles include probiotics core and described
Three encapsulating layers outside probiotics core, the encapsulating layer is from inside to outside successively are as follows: starch protection layer, film coating separation layer and
Enteric coat layer.Starch protection layer of the present invention can play heat protective effect, while probiotics can be avoided as far as possible direct with moisture
Contact, as far as possible hot environment of the isolation in embedding process, guarantee probiotics living environment；The film coating separation layer tool
There is leakproofness, the viable bacteria stability in shelf life can be improved and stops enteric-coating material in lower step living to probiotics
Property influence；The enteric coat layer can make a certain amount of active probiotic enter enteron aisle to play work since its enteric acts on
With.
The present invention also provides the preparation methods of the probiotics embedded particles to make difference using different embedding methods
Encapsulating layer reaches different weight gain requirements, so that probiotics core be embedded layer by layer, significantly improves the activity and entrance of probiotics
The amount of small intestine.
Detailed description of the invention
Fig. 1 is the schematic cross-section of probiotics embedded particles of the present invention.
Specific embodiment
The present invention provides a kind of probiotics embedded particles, the probiotics embedded particles include probiotics core and described
Three encapsulating layers outside probiotics core, the encapsulating layer is from inside to outside successively are as follows: starch protection layer, film coating separation layer and
Enteric coat layer.
The structure of probiotics embedded particles of the present invention is as shown in Figure 1, include probiotics core and the prebiotic sclerotium
Three encapsulating layers outside core, the encapsulating layer is from inside to outside successively are as follows: starch protection layer, film coating separation layer and enteric coating
Layer.The diameter of probiotics core of the present invention is preferably 180~380 μm.The thickness of starch protection layer of the present invention is preferred
It is 40~80 μm.The thickness of film coating separation layer of the present invention is preferably 5~10 μm.Enteric coat layer of the present invention
Thickness is preferably 6~12 μm.
The probiotics type of probiotics core of the present invention preferably includes: lactobacillus plantarum, lactobacillus acidophilus, cheese cream
Bacillus, lactobacillus paracasei, Lactobacillus rhamnosus, lactobacillus fermenti, Lactobacillus salivarius, Lactobacillus helveticus, lactobacillus reuteri,
Lactobacillus gasseri, Lactobacillus crispatus, Yue Shi lactobacillus, lactobacillus bulgaricus, streptococcus thermophilus, bifidobacterium lactis, long bifid
Two or more mixed in bacillus, bifidobacterium breve, bifidobacterium infantis, bifidobacterium bifidum and bifidobacterium adolescentis
Combined bacteria kind.
The present invention also provides the preparation methods of above-mentioned probiotics embedded particles, comprising the following steps: (1) will be described prebiotic
The bacterium powder of bacterium is successively embedded as core with starch and water layer by layer, until obtaining starch embedding after 1~3 times of bacterium powder weight gain
Probiotic granulate；
(2) the starch embedding probiotic granulate is subjected to film coating with film-coating premixing material, until the starch packet
After burying probiotic granulate weight gain 8~20%, film coating probiotic granulate is obtained；
(3) the film coating probiotic granulate is subjected to enteric coating with enteric coating liquid, until the film coating is beneficial
It is dry that prebiotic bacterium bag buries particle after raw bacterium weight gain 8~30%.
In the preparation process in accordance with the present invention, using the bacterium powder of the probiotics as core, layer is successively carried out with starch and water
Layer embedding, until obtaining starch embedding probiotic granulate after 1~3 times of bacterium powder weight gain.The granularity of bacterium powder of the present invention is preferably
40~80 mesh.There is no particular determinations for method of the present invention to the embedding, preferably by centrifugal pellet processing machine or fluidized bed packet
Clothing granulator, more preferably with centrifugal pellet processing machine.The present invention is to the utilization centrifugal pellet processing machine or fluidized bed coating granulator
There is no particular determinations for method when being embedded, utilize the conventional method of this field.In embodiments of the present invention, it utilizes
It is centrifuged pellet processing machine and carries out starch embedding operation, preferably include: that bacterium powder is placed in centrifugation pellet processing machine, first at 18~25 DEG C,
Drum rotating speed and baffle tilt angle are adjusted, so that the material in pellet processing machine is scattered in maximum fan-shaped surfaces of revolution stabilization, then
One layer of starch, one layer of water, successively coating, while keeping 30 ± 2 DEG C of pellet processing machine rotary drum temperature.Each starch dosage is uniformly attached with energy
Upper particle rotation reduces starch dust to the greatest extent as degree.Addition water cannot be adhered every time with that particle can be made loosely to rotate, to the greatest extent
Amount reduces starch subdivision and falls as degree；And when every packet later layer, it is necessary to dry to preceding layer.Continuously embedding granulation layer by layer, until
The bacterium powder that feeds intake increases weight 1~3 times.After the completion of starch embedding granulation, it is not necessarily to re-dry.It can feed intake directly as next step operation.This
Particle water content≤3% after inventing the stratum granulosum embedding.Starch of the present invention preferably includes normal starch, resistant starch
Or porous-starch.The starch protection layer obtained after starch embedding of the present invention can become the protective layer of last barrier moisture, together
When starch thermal capacity it is larger, can increase the heat resistance of probiotics, especially porous-starch or resistant starch, be more advantageous to subsequent step
To probiotics by Thermal protection in rapid granulation or embedding process；But also it can be to avoid other encapsulating layers to the unfavorable of probiotics
It influences.
The starch embedding probiotic granulate is carried out film coating with film-coating premixing material by the present invention, until the starch
After embedding probiotic granulate weight gain 8~20%, film coating probiotic granulate is obtained.Film-coating premixing material of the present invention is preferred
For thin, water soluble film coating premix, the raw material including following parts by weight: 82~88 parts of HPMC, Macrogol 6000 5~10
Part, 2~6 parts and 1~5 part of talcum powder of copolyvidone.The present invention is when carrying out the film coating, it is preferred to use film coating is pre-
Mixed liquid, the film-coating premixing liquid are preferably that pure water and film-coating premixing material are prepared packet according to the weight ratio of 1 ︰ 5~20
Clothing slurries, are stirred to obtain the final product.Stirring of the present invention preferably includes the first stirring (slightly quickly stirring) and the second stirring (is stirred at a slow speed
Mix), during configuring the film-coating premixing liquid, the speed of first stirring is preferably 100~150rpm, described
The time of first stirring is preferably 3~5min (all adding film-coating premixing material within this time).The present invention preferably exists
The film-coating premixing material all after dissolution, terminates the first stirring, carries out the second stirring, and the speed of second stirring is preferred
Time for 30~60rpm, second stirring is preferably 45~60min.The present invention to the method for the film coating not
There is particular determination, it is more preferably thin using high-efficient granule preferably by fluidized bed coating granulator or high-efficient granule film coater
Film coating machine is coated.The present invention to the operating method of the fluidized bed coating granulator or high-efficient granule film coater simultaneously
It is not particularly limited, preferably when using high-efficient granule film coater, the weight ratio of pure water and film-coating premixing material is excellent
It is selected as 1:5~10；Whether good it is then turned on high-efficiency coating machine inspection machine, setting inlet air temperature is 78~88 DEG C, out wind-warm syndrome
Degree be 38~42 DEG C, pour into particle, coating pan revolving speed be adjusted to 2~3rpm, Burners Positions be adjusted to separation from bed about 30~
At 40cm, start preheating material.To 32~38 DEG C of temperature of charge, spray air pressure starts to be coated in 0.5~0.6MPa, packet
Coating pan revolving speed and enlargement discharge are gradually increased after 20~30min of clothing (be not adhered between particle as degree).In coating process, hold
Continuous stirring coating solution, has sprayed whole slurries as early as possible, until requiring gain in weight, keeps the operating condition of air-heater at this time, drying is several
Air-heater is turned off after minute, is opened cooling wind and is cooled to room temperature, discharges.
When using fluidized-bed coating machine granulation, the weight ratio of pure water and film-coating premixing material of the present invention is preferably
1:8~20；It is 30~35 DEG C (inlet air temperature is adjusted according to temperature of charge) that temperature of charge is arranged simultaneously；Spray air pressure is
0.05~0.2MPa；Air blast frequency be 25~45Hz (with all materials can bottom line all boiling be spend)；Hydrojet flow
Not agglomerate, bed endoparticle constant flow is degree.In coating process, coating solution is persistently stirred.Isolated layer film spray coating
To gain in weight is required, stop by spraying, temperature of charge being kept persistently to rotarily dry to particle water content less than 3%.
Based calcium of the present invention can obstruct air and moisture, and sealing stops partition air and moisture to enter, maintains
Low water content keeps probiotic active, while also can increase to the heat protective effect and enteric-coating material of probiotics to prebiotic
Bacterium activity influence.
The film coating probiotic granulate is carried out enteric coating with enteric coating liquid by the present invention, until the film coating
It is dry that prebiotic bacterium bag buries particle after probiotic granulate weight gain 8~30%.Preferably included in enteric coating liquid of the present invention with
The raw material of lower weight ratio, wherein enteric material: plasticizer: anticaking agent=1: 0.05~0.2: 0.25~0.5.Intestines of the present invention
Molten material preferably includes: EudragitL100-55 (being equivalent to domestic II resin), Eudragit L30D-55 (methacrylic acid
With 1: 1 copolymer of ethyl acrylate) or kollicoatSR30D-55 (polyvinyl acetate).Plasticizer of the present invention includes
Lemon triethylenetetraminehexaacetic acid ester (TEC), polyethylene glycol, diethyl phthalate (DEP) or dibutyl sebacate (DBS).It is of the present invention
Anticaking agent includes talcum powder and glycerin monostearate.The present invention to the sources of the various raw materials in the molten coating solution not
Particular determination utilizes the conventional commercial product of this field.The present invention to the preparation method of the enteric coating liquid not
Particular determination utilizes ordinary skill in the art means.
In the present invention, it when carrying out enteric coating using fluidized bed coating granulator, is preferable to provide are as follows: temperature of charge
30~35 DEG C (inlet air temperature is adjusted according to temperature of charge)；0.1~0.3MPa of spray air pressure (is adjusted) according to mist flow；
25~45Hz of air blast frequency (air blast frequency is related with Production Batch Size, with all materials can bottom line all boiling be
Degree)；Hydrojet flow is observed by observation window, not agglomerate, bed endoparticle constant flow is degree.Hydrojet is coated the increasing for reaching requirement
After weight, stop by spraying, keeping temperature of charge and air blast frequency, fluidized drying to coated granule water content is less than 3%.
In the present invention, it when carrying out enteric coating operation using centrifugal pellet processing machine, is preferable to provide are as follows: by institute
Film coating probiotic granulate is stated, is set in centrifugation pellet processing machine, first room temperature adjusts drum speed and baffle tilt angle, makes pellet processing machine
In material scatter in maximum fan-shaped surfaces of revolution stabilization, while keeping 35 ± 2 DEG C of pellet processing machine rotary drum temperature.Start spraying rotation system
Ball, spray amount cannot be adhered with that particle can be made loosely to rotate as degree.Coating process coating solution remains a constant speed stirring, the present invention
The speed at the uniform velocity stirred is not particularly limited, precipitating is not preferably generated.When pill of the present invention, to spraying and
There is no particular determinations for dry operation order, can be in continuous be sprayed, can also be to be dried with intermittent spraying with drying
Spraying again afterwards, prevention is adhered.Spraying pill, which reaches, to be stopped after the gain in weight of requirement spraying, is continued drying out to water content less than 3%；
Discharging.
The enteric coat layer that enteric coating of the present invention obtains can be such that probiotics is not deactivated in the gastric juice of low pH,
And by whole releases after reaching small intestine, to give full play to the balanced action of the adjusting intestinal flora of probiotics.
Probiotics coated granule provided by the invention and preparation method thereof is described in detail below with reference to embodiment,
But they cannot be interpreted as limiting the scope of the present invention.
Embodiment 1
Each layer embeds weight gain ratio: starch protection layer increases weight 2 times；Film coating separation layer weight gain 18%；Enteric coat layer
Weight gain 10%.
Proportion:
Probiotics 500g: prebiotic for three kinds of lactobacillus plantarum (LP), Lactobacillus rhamnosus (LR) and lactobacillus fermenti (LF)
The mixing of bacterium, viable bacteria index content: 100,000,000,000/g；
Starch 1000g: for porous-starch；
Isolated layer film is coated premix 270g: with HPMC, copolyvidone, Macrogol 6000, talcum powder for main material
Material composition aqueous transparent film coating pre-mix dose；
Enteric-coating material 177g: wherein EudragitL100-55:102g, TEC:25g, talcum powder: 50g.
1. protective layer starch sheath particles operation (centrifugation pellet processing machine):
Mixing probiotics LP, LR and LF are set in centrifugation pellet processing machine, 40~80 bacterium powder are set in centrifugation pellet processing machine, first room
Temperature adjusts drum rotating speed and baffle tilt angle, so that the material in pellet processing machine is scattered in maximum fan-shaped surfaces of revolution stabilization, so
Later layer starch, one layer of water, successively coating, while keeping 30 ± 2 DEG C of pellet processing machine rotary drum temperature.Each starch dosage is uniform with energy
Particle rotation is enclosed, reduces starch degree of being subdivided into the greatest extent.Addition water cannot be adhered every time with that particle can be made loosely to rotate,
Starch subdivision is reduced to the greatest extent to fall as degree.Every packet later layer, it is necessary to dry to preceding layer.Continuously embedding granulation layer by layer, until
Grain weight is to feed intake 2 times of probiotics, i.e. particle total weight reaches 1500g.Stop covering, rotary drying to particle water content
3% or less.Discharging.
2. isolated layer film coating operations (fluidized bed coating granulator):
In film coating pre-mix dose: the ratio of water=1kg: 10L prepares coating slurries, will by 18% coating weight gain amount
Water is set in mixer, then film coating pre-mix dose is gradually poured into mixer by side, and side is slightly quickly stirred, to film coating in 5min
After pre-mixing agent all adds, then 45min is mixed slowly, prepares film coating liquid.
Isolated layer film coating is carried out with fluidized bed coating granulator, is arranged: temperature of charge: 32 ± 2 DEG C；
Air blast frequency: 25~45Hz；According to material specific gravity in fluidized bed (because of water content difference), adjust at any time.
Hydrojet flow: being observed by observation window, and not agglomerate, bed endoparticle constant flow is degree.
Isolated layer film spray coating stops by spraying, keeping temperature of charge persistently to rotarily dry is to gain in weight is required
Grain water content is less than 3%.
3. enteric material coating operations (centrifugation pellet processing machine)
It weighs 25g plasticizer and is dissolved in middle water, it is spare.102g Eudragit L100-55 will separately be weighed and be slowly added into water
In, stirring 7min is suspended in water, and the plasticizer solution prepared in advance is added under stirring, it is molten that 1mol/LNaOH is slowly added dropwise
Liquid the 1.4% of enteric packaging material (NaOH dosage be), and continue to stir 30min, then plus talcum powder and water agitation and dilution to being coated material
The solid content of material 30% crosses 80 meshes, prepares 18% that enteric-coating material is total solution volume.
Spacer layer coating intermediate is set in centrifugation pellet processing machine, first room temperature adjusts drum speed and baffle tilt angle, makes
Material in pellet processing machine scatters in maximum fan-shaped surfaces of revolution stabilization, while keeping 35 ± 2 DEG C of pellet processing machine rotary drum temperature.Start spraying
Pill is rotated, side is spraying, and side is dry, and spray amount cannot be adhered can rotate particle loosely as degree.Coating process coating solution
Remain a constant speed stirring, prevention precipitating.Period coating solution is not necessarily continuously spraying, can intermittent spraying, spraying again after to be dried, prevention
It is adhered.After spraying pill reaches 10% gain in weight.After stopping by spraying, continue drying out to water content less than 3%；Discharging.
Embodiment 2
Each layer embeds weight gain ratio: protective layer increases weight 1.5 times；Separation layer weight gain 18%；The weight gain of enteric material coatings
28%.
Proportion:
Probiotics 500g: for three kinds of bifidobacterium lactis (BLA), Lactobacillus rhamnosus (LR) and lactobacillus paracasei (LPC)
The mixing of probiotics, viable bacteria index content: 100,000,000,000/g；
Starch 750g: for porous-starch；
Separation layer embeds premix 225g: being using HPMC, copolyvidone, Macrogol 6000, talcum powder as main material
Form aqueous transparent film coating pre-mix dose；
Enteric-coating material 295g: wherein EudragitL100-55:195g, TEC:30g, talcum powder: 70g.
Preparation:
1. protective layer starch sheath particles operation (centrifugation pellet processing machine):
Mixing probiotics BLA, LR and LPC are set in centrifugation pellet processing machine, 40~80 bacterium powder are set in centrifugation pellet processing machine, first
Room temperature adjusts drum rotating speed and baffle tilt angle, and the material in pellet processing machine is made to scatter in maximum fan-shaped surfaces of revolution stabilization,
Right later layer starch, one layer of water, successively coating, while keeping 30 ± 2 DEG C of pellet processing machine rotary drum temperature.Each starch dosage is equal with energy
It is even to enclose particle rotation, reduce starch degree of being subdivided into the greatest extent.Addition water cannot have glutinous every time can rotate particle loosely
Even, starch subdivision is reduced to the greatest extent to fall as degree.Every packet later layer, it is necessary to dry to preceding layer.It embeds layer by layer, until particle weight
It is 1.5 times of the probiotics that feeds intake, i.e. particle total weight reaches 1250g.Stop covering, rotary drying to particle water content 3% with
Under.Discharging.
2. isolated layer film coating operations (high-efficient granule film coater):
By film coating pre-mix dose: water=1: 8, in the ratio of coating weight gain 18%, water is set in mixer, then side will be thin
Film coating pre-mixing agent is gradually poured into mixer, and side is slightly quickly stirred, after film coating pre-mix dose all adds in 4min, then slowly
Speed stirring 60min, for use.
It whether good opens high-efficiency coating pot inspection machine, then inlet air temperature is set and into air draft throttle opening to adjust
Suitable negative pressure, pours into particle, and coating pan revolving speed is adjusted to 2 turns/min, Burners Positions be adjusted to separation from bed about 30cm at, open
Beginning preheating material.To 35 DEG C ± 2 DEG C DEG C of temperature of charge or so, spray air pressure starts to be coated in 0.5MPa or so, coating
Coating pan revolving speed and enlargement discharge are gradually increased after 20min (be not adhered between particle as degree).It is lasting to stir in coating process
Coating solution has sprayed whole slurries, until requiring gain in weight as early as possible.It closes, opens cold after keeping air-heater to operate dry a few minutes
Air-cooled to room temperature, discharging.Coating operations parameter:
Leaving air temp: 40 DEG C are set as；Inlet air temperature: 80 DEG C；
Temperature of charge: 35 DEG C ± 2 DEG C are set as.
3. enteric coating operates (fluidized bed coating granulator)
The plasticizer weighed according to the ratio is dissolved in middle water, spare.It separately will weighed EudragitL100-55 be slowly according to the ratio
It is added to the water, 5~10min of stirring is suspended in water, and the plasticizer solution prepared in advance is added under stirring, is slowly added dropwise
1mol/L NaOH solution (NaOH dosage is the 1.4% of enteric packaging material), and continue to stir 30min, then plus talcum powder simultaneously water stirring
The solid content for being diluted to coating material is 30%, crosses 80 meshes, and compound concentration is that enteric-coating material accounts for total solution 15%.
Enteric coating is carried out with fluidized bed coating granulator
Temperature of charge: 32 DEG C ± 2 DEG C (inlet air temperature is adjusted according to temperature of charge)
Spray air pressure: 0.2MPa (is adjusted) according to mist flow
Air blast frequency: general are as follows: 25~45Hz is adjusted at any time according to material specific gravity in fluidized bed (because of water content difference).
Hydrojet flow: being observed by observation window, and not agglomerate, bed endoparticle constant flow is degree.In coating process, hold
Continuous stirring enteric coating liquid.
After hydrojet coating reaches 28% gain in weight, stop by spraying, keeping temperature of charge and air blast frequency, fluidized drying is extremely
Coated granule water content is less than 3%.Discharging.
Embodiment 3
Each layer embeds weight gain ratio: protective layer increases weight 3 times；Separation layer weight gain 10%；Enteric material coatings weight gain 12%.
Proportion:
Probiotics 500g: for three kinds of bifidobacterium lactis (BLA), Lactobacillus casei (LC) and lactobacillus plantarum (LP) probiotics
Mixing, viable bacteria index content: 100,000,000,000/g；
Starch 1500g: for porous-starch；
Separation layer embeds premix 200g: being using HPMC, copolyvidone, Macrogol 6000, talcum powder as main material
Form aqueous transparent film coating pre-mix dose；
Enteric-coating material 264g: wherein Eudragit L30D-55 aqueous dispersion 510g and kollicoatSR30D-55
Aqueous dispersion 170g (solid content is all 30%)；TEC:10g；Talcum powder: 50g.
Preparation:
1. protective layer starch sheath particles operation (centrifugation pellet processing machine):
Mixing probiotics BLA, LC and LP are set in centrifugation pellet processing machine, 40~80 bacterium powder are set in centrifugation pellet processing machine, first room
Temperature adjusts drum rotating speed and baffle tilt angle, so that the material in pellet processing machine is scattered in maximum fan-shaped surfaces of revolution stabilization, so
Later layer starch, one layer of water, successively coating, while keeping 30 ± 2 DEG C of pellet processing machine rotary drum temperature.Each starch dosage is uniform with energy
Particle rotation is enclosed, reduces starch degree of being subdivided into the greatest extent.Addition water cannot be adhered every time with that particle can be made loosely to rotate,
Starch subdivision is reduced to the greatest extent to fall as degree.Every packet later layer, it is necessary to dry to preceding layer.It embeds layer by layer, until particle weight is
It feeds intake 3 times of probiotics, i.e. particle total weight reaches 2000g.Stop covering, rotary drying to 3% or less particle water content.Out
Material.
2. isolated layer film coating operations (high-efficient granule film coater):
By film coating pre-mix dose: water=1: 8, in the ratio of coating weight gain 10%, water is set in mixer, then side will be thin
Film coating pre-mixing agent is gradually poured into mixer, and side is slightly quickly stirred, after film coating pre-mix dose all adds in 4min, then slowly
Speed stirring 60min, for use.
It whether good opens high-efficiency coating pot inspection machine, then inlet air temperature is set and into air draft throttle opening to adjust
Suitable negative pressure, pours into particle, and coating pan revolving speed is adjusted to 2 turns/min, Burners Positions be adjusted to separation from bed about 30cm at, open
Beginning preheating material.To 35 DEG C ± 2 DEG C of temperature of charge, spray air pressure starts to be coated in 0.5MPa or so, after being coated 20min
Coating pan revolving speed and enlargement discharge is gradually increased (be not adhered between particle as degree).In coating process, coating solution is persistently stirred,
Whole slurries have been sprayed as early as possible, until requiring gain in weight.It is closed after keeping air-heater to operate dry a few minutes, opens cooling wind and be cooled to
Room temperature, discharging.Coating operations parameter:
Leaving air temp: 38 DEG C are set as；Inlet air temperature: 80 DEG C；
Temperature of charge: 35 DEG C ± 2 DEG C are set as.
3. enteric coating operation (centrifugation pellet processing machine)
Weigh Eudragit L30D-55 aqueous dispersion (solid content 30%) and kollicoatSR30D-55 according to the ratio respectively
Aqueous dispersion, respectively plus appropriate amount of water dilution is stirred, then two kinds of dispersions are mixed, and is stirred evenly.It separately will weighed increasing according to the ratio
It moulds agent TEC and suitable quantity of water is added in talcum powder, be homogenized 10min with the equal pulp grinder of high shear, obtain suspension, which is poured into above-mentioned
In mix moisture granular media dilution, and it is diluted to the solid content of enteric packaging material requirement, stirs 30min, 80 mesh net filtrations are prepared
Enteric coating liquid, compound concentration are that enteric-coating material accounts for total solution 15%.
Spacer layer coating intermediate is set in centrifugation pellet processing machine, first room temperature adjusts drum speed and baffle tilt angle, makes
Material in pellet processing machine scatters in maximum fan-shaped surfaces of revolution stabilization, while keeping 35 ± 2 DEG C of pellet processing machine rotary drum temperature.Start spraying
Pill is rotated, side is spraying, and side is dry, and spray amount cannot be adhered can rotate particle loosely as degree.Coating process coating solution
Remain a constant speed stirring, prevention precipitating.Period coating solution is not necessarily continuously spraying, can intermittent spraying, spraying again after to be dried, prevention
It is adhered.After spraying pill reaches 12% gain in weight.After stopping by spraying, continue drying out to water content less than 3%.Discharging.
The probiotics embedded particles that above-described embodiment 1~3 is prepared are tested:
Theoretical viable count, loss late, accelerated test viable count and gastric juice ring after the embedding of measurement Examples 1 to 3 respectively
Viable count in border, specific test result are as shown in table 1:
The viable count of 1 embodiment of table and comparative experiments statistics
Note: [1]: after embedding, refer to the product after the preparation of three re coating of this patent；
[2]: relative to theoretical viable count after embedded material dilution；
[3]: 37 DEG C of environment detect viable count result after 2 months；
[4]: relative to viable count after embedding；
[5]: viable count result is detected after 37 DEG C of simulated gastric fluid environment, 60min.Simulated gastric fluid is matched by official method
System, pH are 2 or so.
As shown in Table 1, the survival rate of three embodiments of the invention is 39~49%；It stores 2 months, survives under 37 DEG C of environment
Rate is 18~42%.
The present invention provides a kind of probiotics embedded particles and preparation method thereof, after embedding Viable detection be 39~
49%；Survival rate after accelerating storage 2 months at 37 DEG C is 18~42%；And the survival rate of 60min is 77 in simulated gastric fluid
~85%, probiotics is remarkably improved in the viable bacteria content of shelf life, while most of probiotics can also be made to discharge in enteron aisle,
To play beneficial effect.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of probiotics embedded particles, which is characterized in that the probiotics embedded particles include probiotics core and the benefit
Three encapsulating layers outside raw sclerotium core, the encapsulating layer is from inside to outside successively are as follows: starch protection layer, film coating separation layer and intestines
Molten coatings.
2. probiotics embedded particles according to claim 1, which is characterized in that the diameter of the probiotics core be 180~
380μm；The starch protection layer with a thickness of 40~80 μm；The film coating separation layer with a thickness of 5~10 μm；The intestines
Molten coatings with a thickness of 6~12 μm.
3. probiotics embedded particles according to claim 1, which is characterized in that the probiotics type packet of the probiotics core
It includes: lactobacillus plantarum, lactobacillus acidophilus, Lactobacillus casei, lactobacillus paracasei, Lactobacillus rhamnosus, lactobacillus fermenti, saliva
Lactobacillus, Lactobacillus helveticus, lactobacillus reuteri, lactobacillus gasseri, Lactobacillus crispatus, Yue Shi lactobacillus, bulgarian milk bar
Bacterium, streptococcus thermophilus, bifidobacterium lactis, bifidobacterium longum, bifidobacterium breve, bifidobacterium infantis, bifidobacterium bifidum and blueness
Two or more mixed bacteria in spring Bifidobacterium.
4. the preparation method of any one of claims 1 to 3 probiotics embedded particles, which comprises the following steps:
(1) it using the bacterium powder of the probiotics as core, is successively embedded layer by layer with starch and water, until the bacterium powder increases weight 1~3 times
Afterwards, starch embedding probiotic granulate is obtained；
(2) the starch embedding probiotic granulate is subjected to film coating with film-coating premixing material, until the starch embedding is beneficial
After raw bacterium weight gain 8~20%, film coating probiotic granulate is obtained；
(3) the film coating probiotic granulate is subjected to enteric coating with enteric coating liquid, until the film coating probiotics
It is dry that prebiotic bacterium bag buries particle after weight gain 8~30%.
5. preparation method according to claim 4, which is characterized in that when step (1) described embedding, starch and water embed one layer
Afterwards, the embedding of next layer of starch and water is carried out again after drying.
6. preparation method according to claim 5, which is characterized in that embedded particles water content≤3% after drying.
7. preparation method according to claim 4 or 5, which is characterized in that the type of the starch includes porous-starch or resists
Property starch.
8. preparation method according to claim 4, which is characterized in that temperature of charge when step (2) described film coating is
30~37 DEG C.
9. preparation method according to claim 4, which is characterized in that include the original of following weight ratio in the enteric coating liquid
Material: enteric material: plasticizer: anticaking agent=1: 0.05~0.2: 0.25~0.5.
10. according to the preparation method of claim 4 or 9, which is characterized in that the temperature of charge when enteric coating is 30~
35℃。
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109999010A (en) * | 2019-04-23 | 2019-07-12 | 河北地邦动物保健科技有限公司 | A kind of probiotics coating pellet and preparation method thereof |
| CN111011867A (en) * | 2019-12-25 | 2020-04-17 | 光明乳业股份有限公司 | Probiotic embedded particle and preparation method thereof |
| CN112868913A (en) * | 2020-12-17 | 2021-06-01 | 杭州康德权饲料有限公司 | Microencapsulated feed enzyme preparation and preparation method thereof |
| CN113170894A (en) * | 2021-05-14 | 2021-07-27 | 南昌大学 | Device and method for preparing particle type probiotics capable of being delivered through gastrointestinal tract |
| CN114642649A (en) * | 2022-03-22 | 2022-06-21 | 安徽安生生物化工科技有限责任公司 | Preparation method of probiotic enteric-coated granules resistant to cold and heat treatment |
| CN115590939A (en) * | 2022-07-28 | 2023-01-13 | 四川豪运药业股份有限公司（Cn） | Ginseng and plum stomach nourishing granule clear paste powder and preparation method and application thereof |
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0634167A1 (en) * | 1993-07-08 | 1995-01-18 | Morishita Jintan Co., Ltd. | Process for producing capsule and capsule obtained thereby |
| TW201129694A (en) * | 2010-02-26 | 2011-09-01 | Univ Hungkuang | Multi-coating macro-granule structure comprising probiotics and manufacturing method thereof |
| CN102755589A (en) * | 2012-07-28 | 2012-10-31 | 赵振华 | Preparation method of Bifidobacterium microcapsules |
| CN103142659A (en) * | 2013-03-18 | 2013-06-12 | 齐鲁制药有限公司 | Film coating tablet containing staphylococcus neisseria |
| CN103283975A (en) * | 2013-03-27 | 2013-09-11 | 广州格拉姆生物科技有限公司 | A method of using spray drying for preparing probiotics micro-capsules |
| CN103327990A (en) * | 2010-12-28 | 2013-09-25 | 日清药业股份有限公司 | Capsule for delivering bifidobacterium into large intestine and method for producing same |
| CN104546946A (en) * | 2014-12-17 | 2015-04-29 | 内蒙古双奇药业股份有限公司 | Preparation method of room-temperature preserved bifidobacteria enteric microcapsule |
| CN107307429A (en) * | 2017-07-04 | 2017-11-03 | 北京英茂药业有限公司 | Film coating pre-mix dose of probiotics preparation and preparation method thereof, application |
-
2018
- 2018-12-29 CN CN201811635102.5A patent/CN109464425B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0634167A1 (en) * | 1993-07-08 | 1995-01-18 | Morishita Jintan Co., Ltd. | Process for producing capsule and capsule obtained thereby |
| TW201129694A (en) * | 2010-02-26 | 2011-09-01 | Univ Hungkuang | Multi-coating macro-granule structure comprising probiotics and manufacturing method thereof |
| CN103327990A (en) * | 2010-12-28 | 2013-09-25 | 日清药业股份有限公司 | Capsule for delivering bifidobacterium into large intestine and method for producing same |
| CN102755589A (en) * | 2012-07-28 | 2012-10-31 | 赵振华 | Preparation method of Bifidobacterium microcapsules |
| CN103142659A (en) * | 2013-03-18 | 2013-06-12 | 齐鲁制药有限公司 | Film coating tablet containing staphylococcus neisseria |
| CN103283975A (en) * | 2013-03-27 | 2013-09-11 | 广州格拉姆生物科技有限公司 | A method of using spray drying for preparing probiotics micro-capsules |
| CN104546946A (en) * | 2014-12-17 | 2015-04-29 | 内蒙古双奇药业股份有限公司 | Preparation method of room-temperature preserved bifidobacteria enteric microcapsule |
| CN107307429A (en) * | 2017-07-04 | 2017-11-03 | 北京英茂药业有限公司 | Film coating pre-mix dose of probiotics preparation and preparation method thereof, application |
Non-Patent Citations (4)
| Title |
|---|
| 姚卫蓉: "多孔淀粉包埋益生菌的工艺研究", 《广州食品工业科技》 * |
| 孙波: "植物乳杆菌多孔淀粉直接包埋工艺的研究", 《工业微生物》 * |
| 李维凤、陈有亮主编: "《药学专业知识（二）第七版》", 28 February 2013, 中国医药科技出版社 * |
| 胡崇茂编著: "《药用辅料 薄膜包衣预混剂生产和应用》", 31 May 2014, 中国医药科技出版社 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| CN109999010B (en) * | 2019-04-23 | 2021-06-15 | 河北地邦动物保健科技有限公司 | Probiotic coated pellet and preparation method thereof |
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| CN113170894A (en) * | 2021-05-14 | 2021-07-27 | 南昌大学 | Device and method for preparing particle type probiotics capable of being delivered through gastrointestinal tract |
| CN114642649A (en) * | 2022-03-22 | 2022-06-21 | 安徽安生生物化工科技有限责任公司 | Preparation method of probiotic enteric-coated granules resistant to cold and heat treatment |
| CN115590939A (en) * | 2022-07-28 | 2023-01-13 | 四川豪运药业股份有限公司（Cn） | Ginseng and plum stomach nourishing granule clear paste powder and preparation method and application thereof |
| CN117814488A (en) * | 2023-12-27 | 2024-04-05 | 善恩康生物科技（苏州）有限公司 | Antioxidant multilayer embedded probiotic granule and preparation method thereof |
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