CN1613455A - Targeting microorgan micro-capsules and their preparation - Google Patents
Targeting microorgan micro-capsules and their preparation Download PDFInfo
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- CN1613455A CN1613455A CNA2003101032482A CN200310103248A CN1613455A CN 1613455 A CN1613455 A CN 1613455A CN A2003101032482 A CNA2003101032482 A CN A2003101032482A CN 200310103248 A CN200310103248 A CN 200310103248A CN 1613455 A CN1613455 A CN 1613455A
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Abstract
A microsoftgel of target useful bacteria is composed of the useful bacteria and/or protecting agent, and three protecting layers. The first protecting layer is prepared from the protein cross-linked with transglutaminase for wrapping the useful bacteria to form microsoftgel. The second protecting layer is prepared from the hydrogenated oil. The third protecting layer is the release controlling coating material. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to the targeting probiotic microcapsule, is a kind of microcapsule targeting preparation with probiotic bacteria of three-layer protection layer specifically.The present invention also relates to the preparation method of said preparation simultaneously.
Background technology
Microecology studies show that, with the bacillus bifidus is " probiotic bacteria " of representative, it has the important physical function to body, comprise the effects such as growth, reduction cholesterol in serum content, activating immune system and active anticancer that suppress pathogenic entero becteria, along with domestic and international people deepen continuously to the understanding of " probiotic bacteria ", increasing probiotic composition is being applied aspect medical treatment, health care and the nutrition.
But probiotic composition mainly is an active bacteria formulation, belongs to obligate anaerobe mostly, very easily is subjected to the influence of external environment factors such as temperature, oxygen, moisture and soda acid, the active difficulty that keeps of normal conditions.The probiotic products of Xiao Shouing for guaranteeing its viable count before the deadline, generally adopt 2~8 ℃ of low temperature storage, but the low temperature storage condition has limited the accumulating and the market sale of product in the market.In addition, the problem of probiotic composition maximum be probiotic products when oral, be subjected to the effect of gastric acid easily, viable count can descend significantly before arriving onset position intestinal, thereby influences the curative effect or the health-care effect of probiotic products.
In order to overcome the problems referred to above, the research method of a lot of probiotic microcapsuleizations has been proposed in medicine and field of food industry, European patent EP 0634167A1 discloses capsule manufacture technology, described and adopted three layers of squeezing and pressing method: with immobilising hydrophobic substance under the room temperature as core, the bacillus bifidus mycopowder is suspended in the core, the wall material is higher than the oils and fats of body temperature, 2. a certain proportion of gelatin and pectin for 1. fusing point.Core and wall material enter the inner, middle and outer layer of three layers of nozzle respectively, splash into the Bifidobacterium capsule that forms diameter 2.5mm in the cold oil then simultaneously.
Japan Patent JP57-33543 discloses a kind of technology of preserving bacillus bifidus.Described the employing fusing point at 35 ℃, temperature is lower than 35 ℃ of solidified oils and fatss, and the bacillus bifidus mycopowder is suspended in the liquid fat, and cooling is solidified oils and fats again, envelopes the technology of bacillus bifidus.
Chinese patent CN1310016A discloses another kind of production technology, utilizes the viable bacteria microgranule of bacillus bifidus, and capsule clothing liquid is compound enteric solubility material, makes the active Bifidobacterium acid resistant enteric coated capsule by the fluidisation nebulization.
The principle of above-mentioned these methods all is to coat probiotic bacteria by some materials, make it with outside air in oxygen, water separation from, reducing the external environment factor influences it, thereby improves probiotic bacteria stability under room temperature and acid-base condition.But the disclosed method of EP0634167A1 can't be avoided the influence (gelatin and pectin technology are moisture) of water, and removes the complex process of cold oil, easily influences the probiotic bacteria survival; The disclosed method process conditions of JP57-33543 harshness is difficult to directly apply to production; The disclosed method of CN1310016A is owing to directly adopt the fluidisation nebulization, and thalline easily damages in encapsulation process, thereby influences the stability of probiotic bacteria.Therefore, all there is certain defective in the method aspect probiotic microcapsule.On the other hand, develop the probiotic bacteria dissociant of peracid, high temperature tolerance both at home and abroad by biotechnology, construct the method that new bacterial strain improves probiotic bacteria stability by genetic engineering, but this method needs a large amount of time and higher cost, also possible simultaneously safety dispute does not also have product to be applied at present.
Summary of the invention
The inventor at present in the existing probiotic microcapsule shortcoming of medicine and field of food industry, thereby outside probiotic bacteria, adopt the three-layer protection layer effectively to overcome above-mentioned shortcoming, finished the present invention.
So; one object of the present invention has just provided the microcapsule of targeting probiotic bacteria; it can effectively protect probiotic bacteria; be subjected to the bactericidal action of gastric juice when prolonging the probiotic bacteria time-to-live at ambient temperature and avoiding oral; and make the probiotic bacteria organs such as intestinal that arrive safe and sound, the directed performance curative effect that discharges.
Another purpose of the present invention also provides the preparation method of this targeting probiotic microcapsule.
Targeting probiotic microcapsule of the present invention is made up of probiotic bacteria and/or protective agent and three-layer protection layer, and the ground floor protective layer is with biocompatibility fabulous protein and the crosslinked back embedding of T-5398 probiotics viable bacteria body, formation primary microcapsules; Second layer protective layer is to coat elementary capsule with fusing point at 30 ℃-40 ℃ hydrogenated oil and fat to form secondary microcapsule; The three-layer protection layer is with release controlling coating material secondary microcapsule to be carried out encapsulation according to different needs, forms final targeting microcapsule.
In the trilamellar membrane of targeting probiotic microcapsule of the present invention, the existence of ground floor protective layer has reduced the influence to probiotic bacteria of temperature in the fluidized coating process, air; Second layer protective layer utilizes hydrogenated oil and fat coating probiotic bacteria to completely cut off oxygen and moisture; The three-layer protection layer can protect probiotic bacteria to avoid the gastric juice effect, and the probiotic bacteria in will being coated on is in the directed release of specific paries such as intestinal.
In description of the present invention, term " probiotic bacteria " refers to people, animals and plants bacteria beneficial are comprised Lactobacillus, bacillus, Enterococcus, Bifidobacterium.In the present invention, with one or more to human body beneficial's bacterial strain as the probiotic bacteria among the present invention, preferred bacterial strain is selected from Lactobacillus, Bifidobacterium.
Can be that probiotic bacteria or probiotic bacteria and one or more are selected from following protectant mixture in the targeting probiotic microcapsule among the present invention: inorganic salts such as milk powder, defatted milk powder, trehalose, sodium chloride, pentite, amino acids and its esters, glycerol, lactose, starch, sodium isoascorbate, phosphate, particularly preferred be milk powder, defatted milk powder, trehalose, sodium chloride, glycerol.
Among the present invention probiotic bacteria and protectant ratio be preferably 1: 0.1~1: 20, particularly preferred is 1: 0.5~1: 10.
Among the present invention; the protective agent consumption is by primary microcapsules weight; be preferably defatted milk powder 1~30%, trehalose 2~30%, sodium chloride 0.1~3%, glycerol 0.1~1%, particularly preferred is defatted milk powder 2~20%, trehalose 2.5~20%, sodium chloride 0.5~3%, glycerol 0.1~0.9%.
Preferred crosslinkable protein is gelatin, milk protein, soybean protein, corn protein and collagenic protein, particularly preferably is gelatin, milk protein, soybean protein.
Can be T-5398 preferably for crosslinked enzyme.Preferred protein has good film property, and can form layer protective layer after the probiotic bacteria mixing drying around probiotic bacteria, but because onrelevant between the protein molecule, protective layer has the space around the probiotic bacteria.As want between the protein molecule to form void-free crosslinked, adopt formaldehyde, glutaraldehyde etc. as cross-linking agent usually.But these materials have adverse effect to health; and easily cause probiotic active forfeiture; T-5398 is the enzyme of acyl group transfer reaction between the γ-Carboxylamide group of glutamine in the catalysis peptide chain; when proteinic lysine formed acyl acceptor, the T-5398 effect formed intermolecular cross-linked structure ε-(γ-Glu)-Lys.Adopt T-5398 as cross-linking agent, course of reaction is without heating process and add other materials, nontoxic, particularly preferably is the T-5398 that derives from microorganism.
According to the present invention, preferred protein consumption is the 1-20% of used primary microcapsules weight, and particularly preferred protein consumption is the 3-10% of used primary microcapsules weight.
The consumption of used cross-linking agent T-5398 is the 0.01-3% of used primary microcapsules weight among the present invention, and particularly preferred consumption is the 0.05-2% of used primary microcapsules weight.
The crosslinked temperature of protein enzyme is preferably 20-70 ℃ among the present invention, and particularly preferred is 30-50 ℃.
In the present invention, primary microcapsules is mixed with the suitable dilution agent, refers to primary microcapsules and one or more are selected from the mixture of following material: starch, dextrinosan, milk powder, defatted milk powder, lactose, glucose, lactose, microcrystalline Cellulose, sucrose, dextrin, sodium starch phosphate, sodium chloride, pregelatinized starch, mannitol and xylitol.
Among the present invention the ratio of primary microcapsules and diluent be preferably 1: 1~1: 200, particularly preferred is 1: 5~1: 100.
Preferred hydrogenated oil and fat refers to fusing point at 30 ℃-40 ℃ hydrogenated oil and fat, and promptly temperature surpasses 30 ℃-40 ℃, and oils and fats presents melting state, and the quasi-grease that solidifies when being lower than 30 ℃ of temperature.
The method that preferred hydrogenated oil and fat coats is finished by the fluidized coating machine.Concretely, preferred equipment comprises the centrifugal encapsulation machine of BZJ type fluidisation of Changzheng Tianmin High Science ﹠ Technology Co., Ltd., Beijing, the XLB type rotary fluid pill coating machine of good the granulation drying equipment in changzhou factory, LDP type fluidized granulation coating machine.The granulating coated machine of jet flowization at the bottom of the LXB type centrifugal fluidization pill coating machine of Wujin, Jiangsu Taihu Lake, city granulation drying equipment company and the DLB type.When using described fluidized coating machine, the oils and fats temperature that is preferably sprayed into floater remains on 30 ℃~100 ℃.Because probiotic bacteria can be damaged when temperature surpasses 55 ℃, therefore the oils and fats temperature that is preferably sprayed into floater remains between 30 ℃~55 ℃, the air themperature that preferably is imported into simultaneously remains between 20 ℃~40 ℃, and oils and fats can be solidified rapidly around seed.The consumption of preferred hydrogenated oil and fat is the 1-80% that needs the primary microcapsules weight of coating, and particularly preferred consumption is the 5-40% that needs the primary microcapsules weight of coating.
Among the present invention, refer to the final different demands of using of targeting probiotic microcapsule goods according to different needs.For example: if oral, the microcapsule goods stomach that then needs the enteric material encapsulation is insoluble and dissolve rapidly in intestinal portion; If be applied in reproductive tract, then need dissolved coating material encapsulation in the sour environment; If arrive specific targeting moiety, then need encapsulation to have the material of targeting moiety.
Among the present invention, preferred release controlling coating material comprises: release controlling coating material, particularly enteric-coating material that drug world is commonly used; Perhaps expansile coating material and other release controlling coating material, more specifically, the zein extract is arranged, sodium alginate, acrylic acid, acrylic resin, Lac, hydroxypropyl emthylcellulose (HPMC), hydroxypropyl emthylcellulose phthalic acid fat (HPMCP), hydroxypropyl emthylcellulose acetic acid amber acid ester (HPMCAS), carboxymethyl cellulose (CMC), hydroxypropyl cellulose (HPC), cellulose acetate phthalic acid fat (CAP), ethyl cellulose (EC), methylcellulose (MC), soybean protein, guar gum, tracasol, xanthan gum, arabic gum, sodium carboxymethyl cellulose, pectin, casein, gelatin, cellulose, OY-P-7171 (Shanghai Colorcon Coating Technology Co., Ltd's enteric coatings agent), LE enteric coatings agent (Tianjin Ai Leyi medical material scientific ﹠ technical corporation), LE floating type coating materials (Tianjin Ai Leyi medical material scientific ﹠ technical corporation), SLUS film coating agent (Tianjin Si Lusen medical material scientific ﹠ technical corporation).
Preferably carry out the method for encapsulation, finish by the fluidized coating machine with release controlling coating material.Concretely, preferred equipment comprises the centrifugal coating machine of BZJ type fluidisation of Changzheng Tianmin High Science ﹠ Technology Co., Ltd., Beijing, the XLB type rotary fluid pill coating machine of changzhou good granulation drying equipment factory, LDP type fluidized granulation coating machine, the granulating coated machine of jet flowization at the bottom of the LXB type centrifugal fluidization pill coating machine of Wujin, Jiangsu Taihu Lake, city granulation drying equipment company and the DLB type.When using described fluidized coating machine, the temperature that preferably is imported into air remains on 20-70 ℃, because the microcapsule products temperature is when surpassing 55 ℃, probiotic bacteria can be damaged, and therefore preferably in whole process the microcapsule products temperature is remained on 20-55 ℃.
The consumption of preferred release controlling coating material is the 1-20% of final targeting microencapsulated product weight, and particularly preferred consumption is the 1-15% of final targeting microencapsulated product weight.
The solvent of preferred release controlling coating material is one or more in water or the organic solvent.Concretely, comprising: water, ethanol, acetone, acetonitrile, dichloromethane, ether, hexane, 1,4-dioxane, oxolane, dimethyl sulfoxine, ethyl acetate and methyl acetate.If desired, use the pH regulator agent, pH value is transferred to required scope, improve the coating material dissolubility thus as acetic acid, hydrochloric acid, phosphoric acid, citric acid, tartaric acid, malic acid etc.
In carrying out encapsulation process, if desired, use to be selected from one or more following plasticizers: Polyethylene Glycol, propylene glycol, glycerol, triethyl citrate, glycerol triacetate, spermaceti acid and stearyl alcohol.In the case, the consumption of preferred plasticizer is the 1-50% of used coating material weight.
The preparation method of targeting probiotic microcapsule of the present invention comprises the following steps: the protein that at first adopts biocompatibility fabulous; with the crosslinked back embedding of T-5398 probiotics viable bacteria body; around thalline, form the ground floor protective layer; make primary target to microcapsule through lyophilization; again primary target is coated at 30 ℃-40 ℃ hydrogenated oil and fat with fusing point in the fluidized coating machine to microcapsule and form second layer protective layer; make secondary target to microcapsule; carry out encapsulation according to different needs with release controlling coating material at last and form the three-layer protection layer, thereby obtain final targeting microencapsulated product.
The targeting probiotic microcapsule that adopts the present invention to make can effectively be protected probiotic bacteria, is subjected to the bactericidal action of gastric juice when prolonging the probiotic bacteria time-to-live at ambient temperature and avoiding oral, and makes the probiotic bacteria target organs such as intestinal that arrive safe and sound.
Explain the preparation method of targeting probiotic microcapsule goods involved in the present invention below more specifically.
Adopt the crosslinked protein of T-5398 will contain the probiotic bacteria embedding, the reuse freeze drying process is made the targeting primary microcapsules; With primary target to microcapsule with after the suitable dilution agent mixes, in the fluidized coating machine, make secondary target to microcapsule 30 ℃-40 ℃ hydrogenated oil and fat coating with fusing point, carry out encapsulation according to different needs with release controlling coating material at last, obtain final targeting microencapsulated product.
With more specific description the present invention, it should be understood that described embodiment only is for the present invention is described by the following example and experimental example, and the scope that does not limit the present invention in any way.
Embodiment 1
The preparation of targeting bifid bacterium microcapsule goods
1. primary target prepares to microencapsulated product
The preparation of a. compound embedding liquid
Get the 100ml deionized water, add the trehalose of 10g, the defatted milk powder of 10g, the glycerol of 0.5g, the soybean protein of 5g, the dissolving mix homogeneously adds T-5398, and mixing stirred 10 minutes, and constant temperature is 40 minutes in 37 ℃ of water-baths, makes compound embedding liquid.
The fermentation liquid that b. will contain bacillus bifidus places the centrifugal collection thalline of tubular type (4000-7000rpm) centrifuge for 12 kilograms, per kilogram obtains wet bacterium mud and adds the compound embedding liquid of 10ml, mixing is placed in the vacuum freeze drier, dry 28-72 hour, makes lyophilizing bacillus bifidus primary microcapsules 70g.
2. secondary target prepares to microencapsulated product
A.60g bacillus bifidus embedding mycopowder and 540g adjuvant (including the 324g glucose, 108g dextrinosan, 108g milk powder) are pressed and are waited times dilution method mix homogeneously standby.
B. said mixture is placed by (the BZT360 type of Changzheng Tianmin High Science ﹠ Technology Co., Ltd., Beijing) in the fluidized coating machine, hydrogenated oil and fat (39 ℃ of fusing points) thawing is heated to 60 ℃, said mixture is carried out the embedding operation.
The controlled condition that the fluidisation oils and fats coats the microcapsule goods is: mix mycopowder 300g, engine speed 100rpm, oils and fats nozzle flow 10L/h, fluidization air flow 1.0M
3/ min, nozzle air pressure 0.2M
3/ hr, the coating time is 30 minutes.Make the bacillus bifidus secondary target to microencapsulated product by above-mentioned condition.
3. release controlling coating material encapsulation
A. release controlling coating material prescription: Lac 200g, sodium carboxymethyl cellulose 20g, magnesium stearate 20g is dissolved in 80% ethanol, is settled to 1000ml.
B. the microcapsule goods that oils and fats is coated place (the BZT360 type of Changzheng Tianmin High Science ﹠ Technology Co., Ltd., Beijing) in the fluidized coating machine, are the capsule heart with above-mentioned microcapsule goods, adopt fluidisation system capsule to carry out encapsulation.
The controlled condition of fluidisation microencapsulation microcapsule goods is: oils and fats coats microcapsule goods 300g, engine speed 100rpm, spray capsule flow quantity 4.5-5L/hr, fluidization air flow 1.0M
3/ min, nozzle air pressure 0.2M
3/ hr, makes final targeting bifid bacterium microcapsule goods by above-mentioned condition at 2 hours encapsulation time.
Embodiment 2
The preparation of targeting bacillus acidophilus microencapsulated product
1. primary target prepares to microencapsulated product
The preparation of a. compound embedding liquid
Get the 100ml deionized water, add the trehalose of 10g, the defatted milk powder of 10g, the glycerol of 0.5g, the soybean protein of 5g, the dissolving mix homogeneously adds T-5398, and mixing stirred 10 minutes, and constant temperature is 40 minutes in 37 ℃ of water-baths, makes compound embedding liquid.
The fermentation liquid that b. will contain the bacillus acidophilus places the centrifugal collection thalline of tubular type (4000-7000rpm) centrifuge for 10 kilograms, per kilogram obtains wet bacterium mud and adds the compound embedding liquid of 10ml, mixing is placed in the vacuum freeze drier, dry 28-72 hour, make lyophilizing targeting bacillus acidophilus primary microcapsules 60g.
2. the secondary microencapsulated product preparation of targeting
A.60g bacillus acidophilus's embedding mycopowder and 540g adjuvant (including the 324g glucose, 108g dextrinosan, 108g milk powder) are pressed and are waited times dilution method mix homogeneously standby.
B. said mixture is placed in the fluidized coating machine, hydrogenated oil and fat (37 ℃ of fusing points) thawing is heated to 55 ℃, said mixture is carried out the embedding operation.
The controlled condition that the fluidisation oils and fats coats the microcapsule goods is: mix mycopowder 300g, engine speed 100rpm, oils and fats nozzle flow 10L/h, fluidization air flow 1.0M
3/ min, nozzle air pressure 0.2M
3/ hr, the coating time is 30 minutes.Make the secondary microencapsulated product of targeting bacillus acidophilus by above-mentioned condition.
3. release controlling coating material encapsulation
A. release controlling coating material prescription: acrylic resin 190g, sodium carboxymethyl cellulose 16g, magnesium stearate 22g is dissolved in 80% ethanol, is settled to 1000ml.
B. the microcapsule goods that oils and fats is coated place (the BZT360 type of Changzheng Tianmin High Science ﹠ Technology Co., Ltd., Beijing) in the fluidized coating machine, are the capsule heart with above-mentioned microcapsule goods, adopt fluidisation system capsule to carry out encapsulation.
The controlled condition of fluidisation microencapsulation microcapsule goods is: oils and fats coats microcapsule goods 300g, engine speed 100rpm, spray capsule flow quantity 4.5-5L/hr, fluidization air flow 1.0M
3/ min, nozzle air pressure 0.2M
3/ hr, makes final targeting bacillus acidophilus microencapsulated product by above-mentioned condition at 2 hours encapsulation time.
Claims (25)
1. targeting probiotic microcapsule, it is characterized in that it is made up of probiotic bacteria and/or protective agent and three-layer protection layer, wherein the ground floor protective layer is with biocompatibility fabulous protein and the crosslinked back embedding of T-5398 probiotics viable bacteria body formation primary microcapsules; Second layer protective layer is to coat primary microcapsules with fusing point at 30 ℃-40 ℃ hydrogenated oil and fat to form secondary microcapsule; The three-layer protection layer is to carry out the secondary microcapsule of encapsulation according to different needs with release controlling coating material to form final targeting probiotic microcapsule.
2. according to the described targeting probiotic microcapsule of claim 1, wherein said probiotic bacteria is selected from one or more bacterial strains in Lactobacillus, the Bifidobacterium.
3. according to the described targeting probiotic microcapsule of claim 1, wherein said protective agent is from selecting one or more the group down: inorganic salts such as milk powder, defatted milk powder, trehalose, sodium chloride, pentite, amino acids and its esters, glycerol, lactose, starch, sodium isoascorbate, phosphate.
4. targeting probiotic microcapsule according to claim 3, wherein probiotic bacteria and protectant ratio are 1: 0.1~1: 20.
5. targeting probiotic microcapsule according to claim 4, wherein probiotic bacteria and protectant ratio are 1: 0.5~1: 10.
6. targeting probiotic microcapsule according to claim 3, wherein primary microcapsules weight is counted defatted milk powder 1~30%, trehalose 2~30%, sodium chloride 0.1~3%, glycerol 0.1~1%.
7. targeting probiotic microcapsule according to claim 6, wherein primary microcapsules weight is counted defatted milk powder 2~20%, trehalose 2.5~20%, sodium chloride 0.5~3%, glycerol 0.1~0.9%.
8. targeting probiotic microcapsule according to claim 1, wherein protein is gelatin, milk protein, soybean protein, corn protein or collagenic protein.
9. targeting probiotic microcapsule according to claim 8, wherein said proteinic consumption are the 1-20% of used mycopowder weight.
10. targeting probiotic microcapsule according to claim 1, wherein said enzyme is a T-5398.
11. targeting probiotic microcapsule according to claim 10, the consumption of wherein said enzyme are the 0.01-3% of used primary microcapsules weight.
12. according to claim 1,10 or 11 described targeting probiotic microcapsules, wherein said enzyme crosslinking temperature is 20-70 ℃.
13. targeting probiotic microcapsule according to claim 1, wherein said hydrogenated oil and fat refers to fusing point at 30 ℃-40 ℃ hydrogenated oil and fat, temperature surpasses 30 ℃-40 ℃, and oils and fats presents flow regime, and temperature forms a quasi-grease of solid forms when being lower than 30 ℃.
14. targeting probiotic microcapsule according to claim 13, wherein said to make the method that secondary microcapsule adopts with hydrogenated oil and fat be to finish by the fluidized coating machine.
15. according to claim 13 or 14 described targeting probiotic microcapsules, the consumption of wherein said hydrogenated oil and fat is the 1-80% that needs the primary microcapsules weight of coating.
16. targeting probiotic microcapsule according to claim 1, wherein said primary microcapsules is mixed with the suitable dilution agent, refers to primary microcapsules and one or more are selected from the mixture of following substance: starch, dextrinosan, milk powder, defatted milk powder, lactose, glucose, lactose, microcrystalline Cellulose, sucrose, dextrin, sodium starch phosphate, sodium chloride, pregelatinized starch, mannitol, xylitol.
17. targeting probiotic microcapsule according to claim 16, wherein the ratio of primary microcapsules and diluent is 1: 1~1: 200.
18. targeting probiotic microcapsule according to claim 17, wherein the ratio of primary microcapsules and diluent is 1: 5~1: 100.
19. targeting probiotic microcapsule according to claim 1, wherein said release controlling coating material are the mixture that is selected from one or more materials of following material: the zein extract, sodium alginate, acrylic acid, acrylic resin, Lac, hydroxypropyl emthylcellulose, hydroxypropyl emthylcellulose phthalic acid fat, hydroxypropyl emthylcellulose acetic acid amber acid ester, carboxymethyl cellulose, hydroxypropyl cellulose, cellulose acetate phthalic acid fat, ethyl cellulose, methylcellulose, soybean protein, guar gum, tracasol, xanthan gum, arabic gum, sodium carboxymethyl cellulose, pectin, casein, gelatin, cellulose, OYP-7171, the agent of LE enteric coatings, LE floating type coating materials, the SLUS film coating agent.
20. targeting probiotic microcapsule according to claim 19, wherein said release controlling coating material consumption are the 1-20% of whole microencapsulated product weight.
21. targeting probiotic microcapsule according to claim 20, wherein said release controlling coating material solvent for use is one or more in the following material: water, ethanol, acetone, acetonitrile, dichloromethane ether, hexane, 1,4-dioxane, oxolane, dimethyl sulfoxine, ethyl acetate and methyl acetate.
22. targeting probiotic microcapsule according to claim 1 wherein uses to be selected from one or more following materials as plasticizer: Polyethylene Glycol, propylene glycol, glycerol, triethyl citrate, glycerol triacetate, spermaceti acid and stearyl alcohol.
23. targeting probiotic microcapsule according to claim 22, wherein said plasticizer consumption are the 1-50% of coating material.
24. the preparation method of any one described targeting probiotic microcapsule among the claim 1-23, its feature comprise the following steps: (1) protein after adopting T-5398 crosslinked with probiotic bacteria and/the protective agent embedding, and adopt lyophilization to make primary microcapsules; (2) with primary microcapsules with after the suitable dilution agent mixes, in the fluidized coating machine, coat at 30-40 ℃ hydrogenated oil and fat and make secondary microcapsule with fusing point; (3) secondary microcapsule is carried out encapsulation with release controlling coating material, obtain final microencapsulated product.
25. the preparation method of targeting probiotic microcapsule according to claim 24, wherein the temperature of complete process is 20 ℃-70 ℃ in the fluidized coating machine.
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2003
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