CN109464425B - Probiotic embedded particle and preparation method thereof - Google Patents
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Abstract
The invention provides a probiotic embedded particle and a preparation method thereof, and relates to the technical field of probiotics. The probiotic embedded particle comprises a probiotic core and three embedded layers outside the probiotic core, wherein the embedded layers sequentially comprise from inside to outside: a starch protective layer, a film coating isolation layer and an enteric coating layer. The survival rate of the live bacteria embedded by the scheme is 39-49%; the survival rate after accelerated storage for 2 months at 37 ℃ is 18-42%; the survival rate of the probiotics in the artificial gastric juice for 60min is 77-85%, the viable bacteria content of the probiotics in the shelf life can be obviously improved, and meanwhile, most of the probiotics can be released in the intestinal tract, so that the beneficial effect is exerted.
Description
Technical Field
The invention belongs to the technical field of probiotic activity maintenance, and particularly relates to a probiotic embedded particle and a preparation method thereof.
Background
In recent years, probiotics have a key role in human health, are widely applied to various products and are accepted by more and more people. The probiotic preparation is used for providing beneficial live bacteria for organisms and the internal environment of the organisms and improving the micro-ecological balance of human bodies. Therefore, the number of viable bacteria contained in a unit formulation is one of the important criteria for evaluating probiotic formulations. The stability of the live bacteria of the probiotic raw materials in the probiotic products is very important. The number of live bacteria in the probiotic preparation and the survival time of the live bacteria are closely related to the strain, the dosage form and the storage condition. As most of the probiotics are anaerobic or partial anaerobic viable bacteria, the light, the temperature, the humidity and the pH have obvious influence on the probiotics generally, and the higher the temperature is, the higher the humidity is, and the shorter the living time of the viable bacteria is.
In addition, probiotics must pass through the gastric environment to reach the intestinal tract with a large number of live bacteria and colonize the intestinal mucosa to exert their physiological functions, and can have beneficial effects on the human body by changing the balance of the intestinal flora. However, many active probiotics die from the action of gastric acid and bile before entering the intestinal tract, so that the survival and proliferation capacity of the probiotics in the host body is low, and the probiotic effect of the probiotics is greatly influenced. The survival rate in the intestine is therefore another important indicator of the efficacy of the probiotic.
Generally, various probiotic preparation products undergo a preparation process, a storage process and a gastrointestinal process before they have beneficial effects on human bodies. Therefore, the live stability of the probiotic raw material in the probiotic product is of paramount importance.
In order to prolong the survival time of probiotics to the maximum extent, in particular to increase the survival amount of the probiotics in the intestinal tract, many research and production personnel develop application research of embedding technology in the field of microecologics, which mainly comprises the following four types:
1. spray drying method: mixing the probiotics and the wall material, mixing the mixture with the solution, and spray drying. The process is simple, but the embedding rate of probiotics is low, and because of drying the aqueous solution, the drying temperature is at least more than 60 ℃, although the time is short, the probiotics at the spray drying temperature is not tolerant, and the temperature is in positive correlation with the yield (namely the spray flow), the spray drying yield at 60 ℃ cannot reach the production scale, and the low-temperature circulation spray drying can be realized by the existing fully-sealed spray drying technology, so that the yield can be improved, but only in the experimental stage, the 60 ℃ circulation is required, and the energy consumption is greatly improved.
2. Fluidized bed embedding: probiotic (mixed with other auxiliary materials) powder to be embedded is boiled in a fluidized bed, the powder is coated by spraying a coating material aqueous solution, and the powder is dried at the same time, although the temperature can be reduced to about 40 ℃, the embedding rate is improved relative to spray drying, but the embedding time is very long (the adhesion is prevented, the spraying flow cannot be large, and the drying is carried out after the embedding). The survival rate of the probiotics is greatly reduced in the long-time heating process.
3. Extrusion coacervation method: the embedding is formed by condensing different phases by utilizing a physical and chemical principle, but the embedding is not complete and compact, and the enteric coating material is impossible (the gastric juice with low pH is easy to permeate).
4. High-voltage electrostatic method: the core material and the packing material are mutually attracted to form embedding by different charges, but the embedding is not compact, namely the sealing performance of the embedding is poor, and the embedding is basically meaningless compared with the situation that probiotics need to isolate the external air and moisture as far as possible, namely the embedding is used for blocking low-pH gastric acid.
In conclusion, the embedding method is used for improving the stability of the probiotic solid raw material, and a plurality of probiotics solid raw materials belong to the test stage. Even in the case of production scale (e.g., extrusion coagulation), it is impossible to achieve both the storage property of sealing property and the acid-resistant enteric property.
Disclosure of Invention
In view of the above, the present invention provides a probiotic embedded particle and a preparation method thereof, and the prepared probiotic embedded particle can ensure the content of viable bacteria in the shelf life and can make a certain amount of viable bacteria enter the intestinal tract to act.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a probiotic embedded particle, which comprises a probiotic core and three embedded layers outside the probiotic core, wherein the embedded layers sequentially comprise from inside to outside: a starch protective layer, a film coating isolation layer and an enteric coating layer.
Preferably, the diameter of the probiotic core is 180-380 μm; the thickness of the starch protective layer is 40-80 mu m; the thickness of the film coating isolation layer is 5-10 mu m; the thickness of the enteric coating layer is 6-12 mu m.
Preferably, the species of probiotic of the probiotic core include: lactobacillus plantarum, lactobacillus acidophilus, lactobacillus casei, lactobacillus paracasei, lactobacillus rhamnosus, lactobacillus fermentum, lactobacillus salivarius, lactobacillus helveticus, lactobacillus reuteri, lactobacillus gasseri, lactobacillus crispatus, lactobacillus johnsonii, lactobacillus bulgaricus, streptococcus thermophilus, bifidobacterium lactis, bifidobacterium longum, bifidobacterium breve, bifidobacterium infantis, bifidobacterium bifidum and bifidobacterium adolescentis.
The invention also provides a preparation method of the probiotic embedded particle, which comprises the following steps: (1) using the probiotic powder as a core, and sequentially embedding the probiotic powder layer by using starch and water until the weight of the probiotic powder is increased by 1-3 times to obtain starch-embedded probiotic particles;
(2) performing film coating on the starch-embedded probiotic particles by using a film coating premix until the weight of the starch-embedded probiotic particles is increased by 8-20%, so as to obtain film-coated probiotic particles;
(3) and (3) carrying out enteric coating on the film-coated probiotic particles by using an enteric coating solution until the weight of the film-coated probiotic particles is increased by 8-30%, and drying to obtain probiotic embedded particles.
Preferably, during the embedding in the step (1), after the starch and the water are embedded into one layer, the next layer of starch and water is embedded after the starch and the water are dried.
Preferably, the water content of the dried embedded particles is less than or equal to 3 percent.
Preferably, the type of starch comprises porous starch or resistant starch.
Preferably, the material temperature in the film coating in the step (2) is 30-37 ℃.
Preferably, the enteric coating solution comprises the following raw materials in percentage by weight: the ratio of the enteric material to the plasticizer to the anticaking agent is 1: 0.05-0.2: 0.25-0.5.
Preferably, the material temperature during the enteric coating is 30-35 ℃.
The invention provides a probiotic embedded particle, which comprises a probiotic core and three embedded layers outside the probiotic core, wherein the embedded layers sequentially comprise from inside to outside: a starch protective layer, a film coating isolation layer and an enteric coating layer. The starch protective layer can play a role in thermal protection, can simultaneously avoid direct contact of probiotics and moisture as much as possible, isolate the high-temperature environment in the embedding process as much as possible, and ensure the living environment of the probiotics; the film coating isolation layer has sealing performance, so that the stability of viable bacteria in a shelf life can be improved, and the influence of an enteric coating material on the activity of the probiotic bacteria in the next step can be prevented; the enteric coating layer can enable a certain amount of active probiotics to enter the intestinal tract to play a role due to the enteric effect of the enteric coating layer.
The invention also provides a preparation method of the probiotic embedded particles, and different embedding methods are utilized to enable different embedding layers to meet different weight increasing requirements, so that the probiotic core layer is embedded layer by layer, and the activity of probiotics and the amount of the probiotics entering small intestines are obviously improved.
Drawings
Fig. 1 is a schematic cross-sectional view of a probiotic embedded particle according to the invention.
Detailed Description
The invention provides a probiotic embedded particle, which comprises a probiotic core and three embedded layers outside the probiotic core, wherein the embedded layers sequentially comprise from inside to outside: a starch protective layer, a film coating isolation layer and an enteric coating layer.
The structure of the probiotic embedded particle disclosed by the invention is shown in figure 1, and comprises a probiotic core and three embedded layers outside the probiotic core, wherein the embedded layers sequentially comprise from inside to outside: a starch protective layer, a film coating isolation layer and an enteric coating layer. The diameter of the probiotic core is preferably 180-380 mu m. The thickness of the starch protective layer is preferably 40-80 mu m. The thickness of the film coating isolation layer is preferably 5-10 mu m. The thickness of the enteric coating layer is preferably 6-12 μm.
The probiotic species of the probiotic core of the present invention preferably include: lactobacillus plantarum, lactobacillus acidophilus, lactobacillus casei, lactobacillus paracasei, lactobacillus rhamnosus, lactobacillus fermentum, lactobacillus salivarius, lactobacillus helveticus, lactobacillus reuteri, lactobacillus gasseri, lactobacillus crispatus, lactobacillus johnsonii, lactobacillus bulgaricus, streptococcus thermophilus, bifidobacterium lactis, bifidobacterium longum, bifidobacterium breve, bifidobacterium infantis, bifidobacterium bifidum and bifidobacterium adolescentis.
The invention also provides a preparation method of the probiotic embedded particle, which comprises the following steps: (1) using the probiotic powder as a core, and sequentially carrying out layer-by-layer embedding by using starch and water until the weight of the probiotic powder is increased by 1-3 times to obtain starch-embedded probiotic particles;
(2) performing film coating on the starch-embedded probiotic particles by using a film coating premix until the weight of the starch-embedded probiotic particles is increased by 8-20%, so as to obtain film-coated probiotic particles;
(3) and (3) carrying out enteric coating on the film-coated probiotic particles by using an enteric coating solution until the weight of the film-coated probiotic particles is increased by 8-30%, and drying to obtain probiotic embedded particles.
According to the preparation method, the probiotic powder is used as a core, and starch and water are sequentially embedded layer by layer until the weight of the probiotic powder is increased by 1-3 times, so that the starch-embedded probiotic particles are obtained. The granularity of the bacterial powder is preferably 40-80 meshes. The method of the present invention for the encapsulation is not particularly limited, and a centrifugal pellet mill or a fluidized bed coating granulator is preferably used, and a centrifugal pellet mill is more preferably used. The method for embedding by using the centrifugal pellet mill or the fluidized bed coating granulator is not particularly limited, and a conventional method in the field can be used. In the embodiment of the present invention, the starch embedding operation is performed by using a centrifugal pellet mill, and preferably includes: placing the bacterial powder into a centrifugal pelleting machine, firstly adjusting the rotating speed of a rotary drum and the inclination angle of a baffle plate at 18-25 ℃ to ensure that the material in the pelleting machine is stably dispersed in a largest fan-shaped rotating surface, then sequentially coating a layer of starch and a layer of water, and simultaneously keeping the rotary drum temperature of the pelleting machine at 30 +/-2 ℃. The addition of starch is to uniformly attach the granules to rotate every time, and the degree of starch fine powder is reduced as much as possible. Adding water quantity each time to enable the particles to be loose and rotate without adhesion, and reducing the starch subdivision falling degree as much as possible; and when the next layer is packed, the previous layer must be dried. And (4) continuously embedding and granulating layer by layer until the weight of the fed bacterial powder is increased by 1-3 times. After the starch embedding and granulating are finished, drying is not needed. Can be directly used as the feeding of the next operation. The water content of the particles embedded in the starch layer is less than or equal to 3 percent. The starch of the present invention preferably comprises conventional starch, resistant starch or porous starch. The starch protective layer obtained after the starch embedding can become a protective layer for blocking moisture finally, and meanwhile, the starch has larger heat capacity, can increase the heat resistance of the probiotics, especially porous starch or resistant starch, and is more favorable for the heat protection of the probiotics in the granulating or embedding process of the subsequent step; but also can avoid the adverse effect of other coating layers on the probiotics.
According to the invention, the starch-embedded probiotic particles are subjected to film coating by using a film coating premix until the weight of the starch-embedded probiotic particles is increased by 8-20%, so as to obtain the film-coated probiotic particles. The film coating premix is preferably water-soluble film coating premix which comprises the following raw materials in parts by weight: 82-88 parts of HPMC (hydroxy propyl methyl cellulose), 60005-10 parts of polyethylene glycol, 2-6 parts of copovidone and 1-5 parts of talcum powder. In the film coating, a film coating premix is preferably adopted, and the film coating premix is preferably prepared by mixing pure water and a film coating premix according to the weight ratio of 1: 5-20 to prepare coating slurry and stirring. The stirring of the invention preferably comprises a first stirring (slightly rapid stirring) and a second stirring (slow stirring), wherein in the process of preparing the film-coating premix solution, the speed of the first stirring is preferably 100-150 rpm, and the time of the first stirring is preferably 3-5 min (the film-coating premix is completely added in the time). In the present invention, preferably, after the film coating premix is completely dissolved, the first stirring is terminated, and the second stirring is performed at a speed of preferably 30 to 60rpm for 45 to 60 min. The method of coating the film is not particularly limited in the present invention, and the coating is preferably carried out by a fluidized bed coating granulator or a high performance granule film coater, more preferably by a high performance granule film coater. The present invention is not particularly limited to the method for operating the fluidized bed coating granulator or the high efficiency granule film coater, and preferably, when the high efficiency granule film coater is used, the weight ratio of the pure water to the film coating premix is preferably 1: 5-10; and then starting the high-efficiency coating machine to check whether the machine is good or not, setting the air inlet temperature to be 78-88 ℃ and the air outlet temperature to be 38-42 ℃, pouring particles, adjusting the rotating speed of a coating pot to be 2-3 rpm, adjusting the position of a spray gun to be about 30-40 cm away from a bed, and starting preheating the materials. And (3) starting coating when the temperature of the material is 32-38 ℃ and the pressure of the spraying air is 0.5-0.6 MPa, and gradually increasing the rotating speed of a coating pot and increasing the flow (taking the non-adhesion between particles as a degree) after coating for 20-30 min. And in the coating process, continuously stirring the coating liquid, spraying the whole slurry as soon as possible until the weight is increased, keeping the running state of the hot air fan at the moment, drying for a few minutes, then closing the hot air fan, starting cooling to room temperature, and discharging.
When a fluidized bed coating machine is adopted for granulation, the weight ratio of the pure water to the film coating premix is preferably 1: 8-20; meanwhile, setting the material temperature to be 30-35 ℃ (the air inlet temperature is adjusted according to the material temperature); the spraying air pressure is 0.05-0.2 MPa; the blowing frequency is 25-45 Hz (the minimum total boiling degree of all materials is used); the spray flow is such that no agglomeration occurs and the particles in the bed continue to flow. During the coating process, the coating solution is continuously stirred. And (5) spraying and coating the isolating layer film until the weight is increased, stopping spraying, and keeping the temperature of the material to be continuously and rotationally dried until the water content of the particles is less than 3%.
The film coating layer can block air and moisture, hermetically block air and moisture from entering, maintain low water content, keep the activity of probiotics, and simultaneously can increase the heat protection effect on the probiotics and the influence of an enteric coating material on the activity of the probiotics.
According to the invention, the film-coated probiotic particles are subjected to enteric coating by using an enteric coating solution until the weight of the film-coated probiotic particles is increased by 8-30%, and then dried to obtain probiotic embedded particles. The enteric coating solution preferably comprises the following raw materials in weight ratio, wherein the weight ratio of enteric materials to plasticizers to anticaking agents is 1: 0.05-0.2: 0.25-0.5. The enteric material of the present invention preferably comprises: eudragit L100-55 (corresponding to the domestic II resin), Eudragit L30D-55 (copolymer of methacrylic acid and ethyl acrylate 1: 1) or kollicoat SR30D-55 (polyvinyl acetate). The plasticizer of the invention comprises triethyl citrate (TEC), polyethylene glycol, diethyl phthalate (DEP) or dibutyl sebacate (DBS). The anticaking agent comprises talcum powder and glycerin monostearate. In the present invention, the source of each raw material in the solution coating solution is not particularly limited, and conventional commercially available products in the art may be used. The preparation method of the enteric coating solution is not particularly limited, and the conventional technical means in the field can be utilized.
In the present invention, when enteric coating is performed using a fluidized bed coating granulator, it is preferably set to: the material temperature is 30-35 ℃ (the air inlet temperature is adjusted according to the material temperature); the pressure of the spraying air is 0.1-0.3 MPa (adjusted according to the spraying flow); the blowing frequency is 25-45 Hz (the blowing frequency is related to the size of the production batch, and the minimum total boiling degree of all materials is used); the spray flow was observed through the observation window to a degree that no agglomeration occurred and the particles in the bed continued to flow. After the weight gain of the spray liquid coating is reached, stopping spraying, keeping the material temperature and the blowing frequency, and carrying out fluidized drying until the water content of the coated particles is less than 3%.
In the present invention, when the enteric coating operation is performed using a centrifugal pellet mill, it is preferably set to: and (3) putting the film-coated probiotic particles into a centrifugal pelleting machine, firstly adjusting the speed of the rotary drum and the inclination angle of the baffle at room temperature to ensure that the materials in the pelleting machine are stably dispersed in a maximum fan-shaped rotating surface, and simultaneously keeping the temperature of the rotary drum of the pelleting machine at 35 +/-2 ℃. The spray is started to rotate for preparing pills, and the spray amount is enough to enable the particles to rotate loosely and not to have viscosity. The coating solution is kept to be stirred at a constant speed in the coating process, and the stirring speed at the constant speed is not particularly limited, and preferably, no precipitate is generated. In the process of preparing the pellets, the operation sequence of spraying and drying is not particularly limited, and the pellets can be continuously sprayed, dried or sprayed intermittently, and then sprayed after drying to prevent sticking. Stopping spraying after the weight of the spray pill is increased to the required weight, and continuously drying until the water content is less than 3 percent; and (6) discharging.
The enteric coating layer obtained by the enteric coating can ensure that the probiotics are not inactivated in gastric juice with low pH and are completely released after reaching the small intestine so as to fully play the balance role of the probiotics in regulating intestinal flora.
The coated probiotic granule and the preparation method thereof provided by the present invention will be described in detail with reference to the following examples, which should not be construed as limiting the scope of the present invention.
Example 1
Embedding weight gain proportion of each layer: the weight of the starch protective layer is increased by 2 times; the weight of the film coating isolation layer is increased by 18 percent; the weight of the enteric coating layer is increased by 10 percent.
Proportioning:
500g of probiotics: the probiotic bacteria are mixed of three probiotics of Lactobacillus Plantarum (LP), Lactobacillus Rhamnosus (LR) and Lactobacillus Fermentum (LF), and the viable bacteria index content is as follows: 1000 hundred million/g;
1000g of starch: is porous starch;
270g of isolating layer film coating premix: HPMC, copovidone, polyethylene glycol 6000 and talcum powder are used as main materials to form a water-based transparent film coating premix;
177g of enteric coating material: wherein Eudragit L100-55: 102g, TEC: 25g, talc: 50 g.
1. Protective layer starch coated pellet operation (centrifugal pellet mill):
placing the mixed probiotics LP, LR and LF in a centrifugal pill making machine, placing 40-80 bacteria powder in the centrifugal pill making machine, firstly adjusting the rotating speed of a rotary drum and the inclination angle of a baffle plate at room temperature to enable materials in the pill making machine to be stably dispersed in a largest fan-shaped rotating surface, then sequentially coating a layer of starch and a layer of water, and simultaneously keeping the temperature of the rotary drum of the pill making machine to be 30 +/-2 ℃. The addition of starch is carried out every time in order to uniformly attach the granules to rotate and minimize the subdivision degree of starch. The water is added every time to enable the particles to be loose and rotate without adhesion, and the degree of starch subdivision and falling is reduced as much as possible. The next layer in each package must be dried before the previous layer. And (4) continuously embedding and granulating layer by layer until the weight of the granules is 2 times of that of the fed probiotics, namely the total weight of the granules reaches 1500 g. Stopping coating, and rotary drying until the water content of the particles is below 3%. And (6) discharging.
2. Isolation layer film coating operation (fluid bed coating granulator):
preparing coating slurry according to the proportion of the film coating premix to water being 1kg to 10L, adding 18 percent of coating weight, putting the water into a mixing barrel, gradually pouring the film coating premix into the mixing barrel while slightly and quickly stirring, and slowly stirring for 45min after the film coating premix is completely added within 5min to prepare the film coating liquid.
Carrying out isolation layer film coating by using a fluidized bed coating granulator, and setting: material temperature: 32 +/-2 ℃;
air blowing frequency: 25-45 Hz; according to the specific gravity of the materials in the fluidized bed (due to different water contents), the adjustment is carried out at any time.
Liquid spraying flow rate: the particles in the bed were observed through the observation window to a degree of no agglomeration and continuous flow.
Spraying the isolating layer film to increase weight, stopping spraying, and rotary drying until the water content of the granule is less than 3%.
3. Enteric coating operation (centrifugal pill making machine)
25g of plasticizer was weighed out and dissolved in water for further use. And weighing 102g of Eudragit L100-55, slowly adding into water, stirring for 7min, suspending in water, adding the prepared plasticizer solution under stirring, slowly dropwise adding 1mol/LNaOH solution (the amount of NaOH is 1.4% of that of the enteric coating material), continuously stirring for 30min, adding talcum powder, stirring with water, diluting to 30% of the solid content of the coating material, and sieving with a 80-mesh sieve to prepare the enteric coating material which is 18% of the total volume of the solution.
And (3) putting the intermediate body coated by the isolating layer into a centrifugal pill making machine, firstly adjusting the speed of the rotary drum and the inclination angle of the baffle at room temperature to ensure that the materials in the pill making machine are stably dispersed in a maximum fan-shaped rotating surface, and simultaneously keeping the temperature of the rotary drum of the pill making machine at 35 +/-2 ℃. The spray rotation is started to prepare pills, the spray is carried out while drying, and the spray amount is enough to enable the particles to be loose and rotate and not to have adhesion. The coating liquid is kept stirring at a constant speed in the coating process to prevent precipitation. During the period, the coating liquid is not necessarily sprayed continuously, but can be sprayed intermittently, and is sprayed after being dried to prevent adhesion. After the weight of the spray pill is increased by 10 percent. After spraying is stopped, continuously drying until the water content is less than 3 percent; and (6) discharging.
Example 2
Embedding weight gain proportion of each layer: the weight of the protective layer is increased by 1.5 times; the weight of the isolating layer is increased by 18 percent; the weight of the enteric coating layer is increased by 28 percent.
Proportioning:
500g of probiotics: is a mixture of three probiotics of Bifidobacterium Lactis (BLA), Lactobacillus Rhamnosus (LR) and Lactobacillus Paracasei (LPC), and the content of viable bacteria indexes is as follows: 1000 hundred million/g;
750g of starch: is porous starch;
isolation layer embedding premix 225 g: the water-based transparent film coating premix is prepared from HPMC, copovidone, polyethylene glycol 6000 and talcum powder as main materials;
295g of enteric coating material: wherein Eudragit L100-55: 195g, TEC: 30g, talcum powder: 70 g.
Preparation:
1. protective layer starch coated pellet operation (centrifugal pellet mill):
placing the mixed probiotics BLA, LR and LPC into a centrifugal pill making machine, placing 40-80 bacteria powder into the centrifugal pill making machine, firstly adjusting the rotating speed of a rotary drum and the inclination angle of a baffle plate at room temperature to enable materials in the pill making machine to be stably dispersed in a largest fan-shaped rotating surface, then sequentially coating a layer of starch and a layer of water, and simultaneously keeping the temperature of the rotary drum of the pill making machine to be 30 +/-2 ℃. The addition of starch is carried out every time in order to uniformly attach the granules to rotate and minimize the subdivision degree of starch. The water is added every time to enable the particles to be loose and rotate without adhesion, and the degree of starch subdivision and falling is reduced as much as possible. The next layer in each package must be dried before the previous layer. The particles are embedded layer by layer until the weight of the particles is 1.5 times of that of the fed probiotics, namely the total weight of the particles reaches 1250 g. Stopping coating, and rotary drying until the water content of the particles is below 3%. And (6) discharging.
2. Isolation layer film coating operation (high efficiency granule film coater):
and (3) according to the ratio of the film coating premix to water being 1: 8, putting the water into a mixing barrel according to the proportion of the coating weight increment being 18%, gradually pouring the film coating premix into the mixing barrel while slightly and quickly stirring, and slowly stirring for 60min after the film coating premix is completely added within 4 min.
Opening the high-efficiency coating pan to check whether the machine is good, setting the air inlet temperature and the opening degree of an air inlet and exhaust air door to adjust proper negative pressure, pouring particles, adjusting the rotating speed of the coating pan to 2 r/min, adjusting the position of a spray gun to a position about 30cm away from a bed, and starting preheating materials. Coating is started until the material temperature is about 35 +/-2 ℃, the spraying air pressure is about 0.5MPa, and the rotating speed of a coating pan and the flow rate are gradually increased (to ensure that the particles are not adhered) after the coating is carried out for 20 min. In the coating process, the coating liquid is continuously stirred, and the whole serous fluid is sprayed as soon as possible until the weight is increased. Keeping the hot air fan running for drying for a few minutes, then closing the hot air fan, starting cooling to room temperature, and discharging. Coating operation parameters are as follows:
air outlet temperature: set to 40 ℃; air inlet temperature: 80 ℃;
material temperature: set to 35 ℃. + -. 2 ℃.
3. Enteric coating operation (fluid bed coating granulator)
And weighing the plasticizer according to the proportion, and dissolving the plasticizer in the reclaimed water for later use. And slowly adding Eudragit L100-55 weighed according to the proportion into water, stirring for 5-10 min to suspend in the water, adding a prepared plasticizer solution under the stirring state, slowly dropwise adding 1mol/L NaOH solution (the NaOH amount is 1.4 percent of the enteric coating material), continuously stirring for 30min, adding talcum powder, stirring with water to dilute until the solid content of the coating material is 30 percent, and sieving with a 80-mesh sieve to prepare the enteric coating material with the concentration of 15 percent of the total solution.
Enteric coating with fluidized bed coating granulator
Material temperature: 32 +/-2 ℃ (inlet temperature is adjusted according to material temperature)
Spray air pressure: 0.2MPa (adjusted according to spray flow)
Air blowing frequency: the general formula is as follows: and (4) adjusting the frequency of 25-45 Hz at any time according to the specific gravity (different water content) of the materials in the fluidized bed.
Liquid spraying flow rate: the particles in the bed were observed through the observation window to a degree of no agglomeration and continuous flow. During the coating process, the enteric coating solution is continuously stirred.
After the weight gain of the spray coating reaches 28%, stopping spraying, keeping the material temperature and the blowing frequency, and carrying out fluidized drying until the water content of the coated particles is less than 3%. And (6) discharging.
Example 3
Embedding weight gain proportion of each layer: the weight of the protective layer is increased by 3 times; the weight of the isolating layer is increased by 10 percent; the weight of the enteric coating layer is increased by 12 percent.
Proportioning:
500g of probiotics: is a mixture of three probiotics of Bifidobacterium Lactis (BLA), Lactobacillus Casei (LC) and Lactobacillus Plantarum (LP), and the content of viable bacteria indexes is as follows: 1000 hundred million/g;
1500g of starch: is porous starch;
isolation layer embedding premix 200 g: the water-based transparent film coating premix is prepared from HPMC, copovidone, polyethylene glycol 6000 and talcum powder as main materials;
264g of enteric coating material: wherein 510g of Eudragit L30D-55 aqueous dispersion and 170g of kollicoat SR30D-55 aqueous dispersion (the solid content is 30 percent); TEC: 10g of a mixture; talc powder: 50 g.
Preparation:
1. protective layer starch coated pellet operation (centrifugal pellet mill):
placing the mixed probiotics BLA, LC and LP in a centrifugal pill making machine, placing 40-80 bacteria powder in the centrifugal pill making machine, firstly adjusting the rotating speed of a rotary drum and the inclination angle of a baffle plate at room temperature to enable materials in the pill making machine to be stably dispersed in a largest fan-shaped rotating surface, then sequentially coating a layer of starch and a layer of water, and simultaneously keeping the temperature of the rotary drum of the pill making machine to be 30 +/-2 ℃. The addition of starch is carried out every time in order to uniformly attach the granules to rotate and minimize the subdivision degree of starch. The water is added every time to enable the particles to be loose and rotate without adhesion, and the degree of starch subdivision and falling is reduced as much as possible. The next layer in each package must be dried before the previous layer. Embedding layer by layer until the weight of the particles is 3 times of that of the fed probiotics, namely the total weight of the particles reaches 2000 g. Stopping coating, and rotary drying until the water content of the particles is below 3%. And (6) discharging.
2. Isolation layer film coating operation (high efficiency granule film coater):
and (3) according to the ratio of the film coating premix to water being 1: 8, putting water into a mixing barrel according to the proportion of the coating weight increment being 10%, gradually pouring the film coating premix into the mixing barrel while slightly and quickly stirring, and slowly stirring for 60min after the film coating premix is completely added within 4 min.
Opening the high-efficiency coating pan to check whether the machine is good, setting the air inlet temperature and the opening degree of an air inlet and exhaust air door to adjust proper negative pressure, pouring particles, adjusting the rotating speed of the coating pan to 2 r/min, adjusting the position of a spray gun to a position about 30cm away from a bed, and starting preheating materials. Coating is started when the temperature of the materials is 35 +/-2 ℃ and the pressure of the spraying air is about 0.5MPa, and the rotating speed of a coating pot and the flow rate are gradually increased (by taking the non-adhesion between particles as a degree) after the coating is carried out for 20 min. In the coating process, the coating liquid is continuously stirred, and the whole serous fluid is sprayed as soon as possible until the weight is increased. Keeping the hot air fan running for drying for a few minutes, then closing the hot air fan, starting cooling to room temperature, and discharging. Coating operation parameters are as follows:
air outlet temperature: set at 38 ℃; air inlet temperature: 80 ℃;
material temperature: set to 35 ℃. + -. 2 ℃.
3. Enteric coating operation (centrifugal pill making machine)
Respectively weighing Eudragit L30D-55 aqueous dispersion (with solid content of 30%) and kollicoat SR30D-55 aqueous dispersion according to the proportion, respectively adding a proper amount of water to dilute and stir, then mixing the two dispersions, and stirring uniformly. And adding a proper amount of water into the plasticizer TEC and the talcum powder which are weighed according to the proportion, homogenizing for 10min by a high-shear homogenizer to obtain a suspension, pouring the suspension into the mixed water dispersion diluent, diluting to the solid content required by the enteric coating material, stirring for 30min, filtering by a 80-mesh screen, and preparing the enteric coating liquid, wherein the preparation concentration is that the enteric coating material accounts for 15% of the total solution.
And (3) putting the intermediate body coated by the isolating layer into a centrifugal pill making machine, firstly adjusting the speed of the rotary drum and the inclination angle of the baffle at room temperature to ensure that the materials in the pill making machine are stably dispersed in a maximum fan-shaped rotating surface, and simultaneously keeping the temperature of the rotary drum of the pill making machine at 35 +/-2 ℃. The spray rotation is started to prepare pills, the spray is carried out while drying, and the spray amount is enough to enable the particles to be loose and rotate and not to have adhesion. The coating liquid is kept stirring at a constant speed in the coating process to prevent precipitation. During the period, the coating liquid is not necessarily sprayed continuously, but can be sprayed intermittently, and is sprayed after being dried to prevent adhesion. After the weight gain of the spray pill reaches 12 percent. After spraying was stopped, drying was continued until the water content was less than 3%. And (6) discharging.
Experiments were carried out on the probiotic embedded particles prepared in examples 1-3 above:
the theoretical viable count after embedding, the loss rate, the accelerated test viable count and the viable count in a gastric juice environment of examples 1 to 3 were measured, and the specific test results are shown in table 1:
TABLE 1 statistics of viable counts for examples and comparative experiments
Note: [1]: after embedding, the product prepared by triple embedding in the patent is referred to;
[2]: relative to the theoretical viable count of the embedding material after dilution;
[3]: detecting the viable count result in an environment at 37 ℃ after 2 months;
[4]: relative to the number of live bacteria after embedding;
[5]: and detecting the viable count result after 60min in an artificial gastric juice environment at 37 ℃. The artificial gastric juice is prepared according to a pharmacopoeia method, and the pH value is about 2.
As shown in Table 1, the survival rate of the three embodiments of the invention is 39-49%; the storage is carried out for 2 months at the temperature of 37 ℃, and the survival rate is 18-42%.
The invention provides probiotic embedded particles and a preparation method thereof, wherein the survival rate of live bacteria after embedding is 39-49%; the survival rate after accelerated storage for 2 months at 37 ℃ is 18-42%; the survival rate of the probiotics in the artificial gastric juice for 60min is 77-85%, the viable bacteria content of the probiotics in the shelf life can be obviously improved, and meanwhile, most of the probiotics can be released in the intestinal tract, so that the beneficial effect is exerted.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (8)
1. The preparation method of the probiotic embedded particles is characterized by comprising the following steps: (1) using the probiotic powder as a core, and sequentially carrying out layer-by-layer embedding by using starch and water until the weight of the probiotic powder is increased by 1-3 times to obtain starch-embedded probiotic particles;
(2) performing film coating on the starch-embedded probiotic particles by using a film coating premix until the weight of the starch-embedded probiotic particles is increased by 8-20%, so as to obtain film-coated probiotic particles;
(3) enteric coating the film-coated probiotic particles with an enteric coating solution until the weight of the film-coated probiotic particles is increased by 8-30%, and drying to obtain probiotic embedded particles;
the probiotic embedded particles are composed of a probiotic core and three embedded layers outside the probiotic core, wherein the embedded layers sequentially comprise from inside to outside: a starch protective layer, a film coating isolating layer and an enteric coating layer;
the starch is porous starch.
2. The preparation method according to claim 1, wherein the diameter of the probiotic core is 180-380 μm; the thickness of the starch protective layer is 40-80 mu m; the thickness of the film coating isolation layer is 5-10 mu m; the thickness of the enteric coating layer is 6-12 mu m.
3. The method of claim 1, wherein the species of probiotic bacteria of the probiotic core include: lactobacillus plantarum, lactobacillus acidophilus, lactobacillus casei, lactobacillus paracasei, lactobacillus rhamnosus, lactobacillus fermentum, lactobacillus salivarius, lactobacillus helveticus, lactobacillus reuteri, lactobacillus gasseri, lactobacillus crispatus, lactobacillus johnsonii, lactobacillus bulgaricus, streptococcus thermophilus, bifidobacterium lactis, bifidobacterium longum, bifidobacterium breve, bifidobacterium infantis, bifidobacterium bifidum and bifidobacterium adolescentis.
4. The method according to claim 1, wherein the embedding in step (1) is carried out by embedding a layer of starch and water in water, drying the layer, and embedding the next layer of starch and water in water.
5. The method of claim 4, wherein the moisture content of the dried encapsulated particles is less than or equal to 3%.
6. The preparation method according to claim 1, wherein the material temperature in the film coating in the step (2) is 30 to 37 ℃.
7. The preparation method according to claim 1, wherein the enteric coating solution comprises the following raw materials in parts by weight: the ratio of the enteric material to the plasticizer to the anticaking agent is 1: 0.05-0.2: 0.25-0.5.
8. The method according to claim 1 or 7, wherein the temperature of the material for the enteric coating is 30 to 35 ℃.
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| CN113170894B (en) * | 2021-05-14 | 2022-08-09 | 南昌大学 | Preparation method of particle-type probiotics capable of being delivered by gastrointestinal tract |
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