CN1613455A - Targeting microorgan micro-capsules and their preparation - Google Patents

Targeting microorgan micro-capsules and their preparation Download PDF

Info

Publication number
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
Authority
CN
China
Prior art keywords
targeting
probiotic
probiotic microcapsule
microcapsule
microcapsule according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CNA2003101032482A
Other languages
Chinese (zh)
Inventor
崔云龙
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BEIJING PUERKANG MEDICAL HIGH TECHNOLOGY Co Ltd
QINGDAO EASTSEA PHARMACEUTICAL CO Ltd
DONGFANGHAIXIN BIOLOGICAL TECHNOLOGY Co LTDD BEIJING
Original Assignee
BEIJING PUERKANG MEDICAL HIGH TECHNOLOGY Co Ltd
QINGDAO EASTSEA PHARMACEUTICAL CO Ltd
DONGFANGHAIXIN BIOLOGICAL TECHNOLOGY Co LTDD BEIJING
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BEIJING PUERKANG MEDICAL HIGH TECHNOLOGY Co Ltd, QINGDAO EASTSEA PHARMACEUTICAL CO Ltd, DONGFANGHAIXIN BIOLOGICAL TECHNOLOGY Co LTDD BEIJING filed Critical BEIJING PUERKANG MEDICAL HIGH TECHNOLOGY Co Ltd
Priority to CNA2003101032482A priority Critical patent/CN1613455A/en
Publication of CN1613455A publication Critical patent/CN1613455A/en
Pending legal-status Critical Current

Links

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

Targeting probiotic microcapsule and preparation method thereof
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.
CNA2003101032482A 2003-11-04 2003-11-04 Targeting microorgan micro-capsules and their preparation Pending CN1613455A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CNA2003101032482A CN1613455A (en) 2003-11-04 2003-11-04 Targeting microorgan micro-capsules and their preparation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CNA2003101032482A CN1613455A (en) 2003-11-04 2003-11-04 Targeting microorgan micro-capsules and their preparation

Publications (1)

Publication Number Publication Date
CN1613455A true CN1613455A (en) 2005-05-11

Family

ID=34756581

Family Applications (1)

Application Number Title Priority Date Filing Date
CNA2003101032482A Pending CN1613455A (en) 2003-11-04 2003-11-04 Targeting microorgan micro-capsules and their preparation

Country Status (1)

Country Link
CN (1) CN1613455A (en)

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100382792C (en) * 2005-09-12 2008-04-23 大连三仪动物药品有限公司 Water soluble microcapsule for medicine and its production process
CN102302160A (en) * 2011-09-07 2012-01-04 黑龙江省乳品工业技术开发中心 Preparation method of Bifidobacterium infantis microcapsules
CN101595976B (en) * 2008-06-04 2012-09-26 东北农业大学 Method for embedding and protecting bifidobacteria by lactalbumin epoxy resin
CN102960599A (en) * 2012-11-19 2013-03-13 陕西科技大学 Method for preparing bifidobacterium microcapsules containing prebiotics
CN103160489A (en) * 2011-12-12 2013-06-19 润盈生物工程(上海)有限公司 Preparation method and application of daily chemical microencapsulated probiotic
CN103347395A (en) * 2010-12-06 2013-10-09 德嘉玛贝里尔有限公司 Composition and method for improving stability and extending shelf life of probiotic bacteria and food products thereof
CN103458709A (en) * 2011-01-21 2013-12-18 凡赛尔医药股份有限公司 Microencapsulated probiotic substance and process of manufacture
CN103704719A (en) * 2013-12-23 2014-04-09 安徽大学 Preparation method for probiotics microcapsule with high viable count
CN104053366A (en) * 2011-11-11 2014-09-17 基普库尔有限公司 Layering and microencapsulation of thermal sensitive biologically active material using heat absorbing material layers having increasing melting points
CN104351938A (en) * 2014-10-21 2015-02-18 吉林农业大学 Method for preparing food-grade enteric-soluble microcapsule
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
CN104560937A (en) * 2014-09-30 2015-04-29 天津生机集团股份有限公司 Method for preparing lactobacillus plantarum microcapsule
CN104894093A (en) * 2015-06-17 2015-09-09 东北农业大学 Method for protecting lactobacillus by soy isolate protein obtained through transglutaminase crosslinking
CN106723233A (en) * 2016-11-28 2017-05-31 沈阳师范大学 Probiotic microcapsule and preparation method with protein masses polysaccharide as wall material
US9833485B2 (en) 2014-10-21 2017-12-05 Ningxia Risingmark Intellectual Property Consulting Co., Ltd Lactobacillus plantarum capsule for poultry and use thereof
US9961910B2 (en) 2007-11-26 2018-05-08 DeGama Products, Ltd Process for preparing bakeable probiotic food
CN108245670A (en) * 2018-02-08 2018-07-06 艾伯尔生物科技(重庆)有限公司 The preparation method and applications of antibacterial protein microcapsules
CN108379565A (en) * 2018-02-08 2018-08-10 艾伯尔生物科技(重庆)有限公司 The preparation method and applications of antibacterial protein microcapsules
CN108524552A (en) * 2018-03-08 2018-09-14 江苏微康生物科技有限公司 A kind of preparation method of probiotics controlled release dripping pill
CN109717481A (en) * 2018-12-27 2019-05-07 广州智特奇生物科技股份有限公司 A kind of preparation process of coating probiotics
CN110771898A (en) * 2019-11-08 2020-02-11 厦门九和良方医药科技有限公司 Probiotic microcapsule, preparation method and application thereof
CN111134330A (en) * 2018-11-06 2020-05-12 内蒙古蒙牛乳业(集团)股份有限公司 Method for preparing probiotic microcapsules by extrusion granulation method and product thereof
CN111134334A (en) * 2018-11-06 2020-05-12 内蒙古蒙牛乳业(集团)股份有限公司 Probiotic microcapsule soft particles and preparation method thereof
CN111134331A (en) * 2018-11-06 2020-05-12 内蒙古蒙牛乳业(集团)股份有限公司 Probiotic microcapsule and preparation method thereof
CN111134332A (en) * 2018-11-06 2020-05-12 内蒙古蒙牛乳业(集团)股份有限公司 Method for preparing probiotic microcapsules by fluidized bed spray granulation method and product thereof
CN111150068A (en) * 2018-11-06 2020-05-15 内蒙古蒙牛乳业(集团)股份有限公司 Probiotic microcapsule taking composite material as wall material and preparation method thereof
CN111436612A (en) * 2020-04-22 2020-07-24 绵阳市润土农业科技开发有限公司 In-vivo enzyme, preparation method thereof and application of in-vivo enzyme in inhibiting novel viruses
CN111529511A (en) * 2020-04-28 2020-08-14 北京诺康达医药科技股份有限公司 Probiotic microcapsule and preparation method and application thereof
CN111956676A (en) * 2020-08-24 2020-11-20 天津现代创新中药科技有限公司 A microecological preparation containing Ginseng radix extract and probiotic bacteria, and its preparation method and application
CN111991370A (en) * 2020-08-20 2020-11-27 四川大学 Intestinal-targeting double-cavity calcium alginate-based composite microcapsule with pumping and constant-speed drug release characteristics and preparation method thereof
CN112292118A (en) * 2018-04-20 2021-01-29 波利凯普斯控股有限公司 Moisture-resistant probiotic granules and production method thereof
CN112516113A (en) * 2019-09-02 2021-03-19 江苏省农业科学院 Preparation method of pleurotus eryngii triterpenoid nano microcapsule
CN115074288A (en) * 2022-07-04 2022-09-20 福建益昕葆生物制药有限公司 Anti-diarrhea egg yolk antibody coated lactobacillus preparation, preparation method and application thereof
WO2022266840A1 (en) * 2021-06-22 2022-12-29 天津大学 Probiotic microcapsule, and preparation method therefor and use thereof
CN115812824A (en) * 2022-12-13 2023-03-21 南昌大学 Probiotics bead-popping soft sweets and preparation method thereof

Cited By (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100382792C (en) * 2005-09-12 2008-04-23 大连三仪动物药品有限公司 Water soluble microcapsule for medicine and its production process
US9961910B2 (en) 2007-11-26 2018-05-08 DeGama Products, Ltd Process for preparing bakeable probiotic food
CN101595976B (en) * 2008-06-04 2012-09-26 东北农业大学 Method for embedding and protecting bifidobacteria by lactalbumin epoxy resin
CN103347395B (en) * 2010-12-06 2016-08-10 德嘉玛贝里尔有限公司 For the stability improving probiotic bacteria and food product thereof the compositions that extends the shelf life and method
US11039637B2 (en) 2010-12-06 2021-06-22 Degama Berrier Ltd. Composition and method for improving stability and extending shelf life of probiotic bacteria and food products thereof
CN103347395A (en) * 2010-12-06 2013-10-09 德嘉玛贝里尔有限公司 Composition and method for improving stability and extending shelf life of probiotic bacteria and food products thereof
CN103458709B (en) * 2011-01-21 2017-10-03 凡赛尔医药股份有限公司 Microencapsulation prebiotic substances and its manufacture method
CN103458709A (en) * 2011-01-21 2013-12-18 凡赛尔医药股份有限公司 Microencapsulated probiotic substance and process of manufacture
CN102302160B (en) * 2011-09-07 2013-03-27 黑龙江省乳品工业技术开发中心 Preparation method of Bifidobacterium infantis microcapsules
CN102302160A (en) * 2011-09-07 2012-01-04 黑龙江省乳品工业技术开发中心 Preparation method of Bifidobacterium infantis microcapsules
CN104053366A (en) * 2011-11-11 2014-09-17 基普库尔有限公司 Layering and microencapsulation of thermal sensitive biologically active material using heat absorbing material layers having increasing melting points
CN103160489B (en) * 2011-12-12 2015-01-14 润盈生物工程(上海)有限公司 Preparation method and application of daily chemical microencapsulated probiotic
CN103160489A (en) * 2011-12-12 2013-06-19 润盈生物工程(上海)有限公司 Preparation method and application of daily chemical microencapsulated probiotic
CN102960599A (en) * 2012-11-19 2013-03-13 陕西科技大学 Method for preparing bifidobacterium microcapsules containing prebiotics
CN103704719A (en) * 2013-12-23 2014-04-09 安徽大学 Preparation method for probiotics microcapsule with high viable count
CN104560937A (en) * 2014-09-30 2015-04-29 天津生机集团股份有限公司 Method for preparing lactobacillus plantarum microcapsule
US9833485B2 (en) 2014-10-21 2017-12-05 Ningxia Risingmark Intellectual Property Consulting Co., Ltd Lactobacillus plantarum capsule for poultry and use thereof
CN104351938A (en) * 2014-10-21 2015-02-18 吉林农业大学 Method for preparing food-grade enteric-soluble microcapsule
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
CN104894093A (en) * 2015-06-17 2015-09-09 东北农业大学 Method for protecting lactobacillus by soy isolate protein obtained through transglutaminase crosslinking
CN106723233A (en) * 2016-11-28 2017-05-31 沈阳师范大学 Probiotic microcapsule and preparation method with protein masses polysaccharide as wall material
CN106723233B (en) * 2016-11-28 2019-03-12 沈阳师范大学 Using protein masses-polysaccharide as the probiotic microcapsule of wall material and preparation method
CN108245670A (en) * 2018-02-08 2018-07-06 艾伯尔生物科技(重庆)有限公司 The preparation method and applications of antibacterial protein microcapsules
CN108379565A (en) * 2018-02-08 2018-08-10 艾伯尔生物科技(重庆)有限公司 The preparation method and applications of antibacterial protein microcapsules
CN108524552A (en) * 2018-03-08 2018-09-14 江苏微康生物科技有限公司 A kind of preparation method of probiotics controlled release dripping pill
CN112292118A (en) * 2018-04-20 2021-01-29 波利凯普斯控股有限公司 Moisture-resistant probiotic granules and production method thereof
CN111150068A (en) * 2018-11-06 2020-05-15 内蒙古蒙牛乳业(集团)股份有限公司 Probiotic microcapsule taking composite material as wall material and preparation method thereof
CN111134334A (en) * 2018-11-06 2020-05-12 内蒙古蒙牛乳业(集团)股份有限公司 Probiotic microcapsule soft particles and preparation method thereof
CN111134333A (en) * 2018-11-06 2020-05-12 内蒙古蒙牛乳业(集团)股份有限公司 Food or health product containing probiotic microcapsules and preparation method thereof
CN111134331A (en) * 2018-11-06 2020-05-12 内蒙古蒙牛乳业(集团)股份有限公司 Probiotic microcapsule and preparation method thereof
CN111134332A (en) * 2018-11-06 2020-05-12 内蒙古蒙牛乳业(集团)股份有限公司 Method for preparing probiotic microcapsules by fluidized bed spray granulation method and product thereof
CN111134334B (en) * 2018-11-06 2023-08-29 内蒙古蒙牛乳业(集团)股份有限公司 Probiotics microcapsule soft particles and preparation method thereof
CN111134330A (en) * 2018-11-06 2020-05-12 内蒙古蒙牛乳业(集团)股份有限公司 Method for preparing probiotic microcapsules by extrusion granulation method and product thereof
CN109717481A (en) * 2018-12-27 2019-05-07 广州智特奇生物科技股份有限公司 A kind of preparation process of coating probiotics
CN109717481B (en) * 2018-12-27 2022-04-26 广州智特奇生物科技股份有限公司 Preparation process of coated probiotics
CN112516113A (en) * 2019-09-02 2021-03-19 江苏省农业科学院 Preparation method of pleurotus eryngii triterpenoid nano microcapsule
CN110771898A (en) * 2019-11-08 2020-02-11 厦门九和良方医药科技有限公司 Probiotic microcapsule, preparation method and application thereof
CN111436612A (en) * 2020-04-22 2020-07-24 绵阳市润土农业科技开发有限公司 In-vivo enzyme, preparation method thereof and application of in-vivo enzyme in inhibiting novel viruses
CN111529511B (en) * 2020-04-28 2022-04-15 北京诺葆营养科技有限公司 Probiotic microcapsule and preparation method and application thereof
CN111529511A (en) * 2020-04-28 2020-08-14 北京诺康达医药科技股份有限公司 Probiotic microcapsule and preparation method and application thereof
CN111991370B (en) * 2020-08-20 2021-06-08 四川大学 Intestinal-targeting double-cavity calcium alginate-based composite microcapsule with pumping and constant-speed drug release characteristics and preparation method thereof
CN111991370A (en) * 2020-08-20 2020-11-27 四川大学 Intestinal-targeting double-cavity calcium alginate-based composite microcapsule with pumping and constant-speed drug release characteristics and preparation method thereof
CN111956676A (en) * 2020-08-24 2020-11-20 天津现代创新中药科技有限公司 A microecological preparation containing Ginseng radix extract and probiotic bacteria, and its preparation method and application
WO2022266840A1 (en) * 2021-06-22 2022-12-29 天津大学 Probiotic microcapsule, and preparation method therefor and use thereof
CN115074288A (en) * 2022-07-04 2022-09-20 福建益昕葆生物制药有限公司 Anti-diarrhea egg yolk antibody coated lactobacillus preparation, preparation method and application thereof
CN115812824A (en) * 2022-12-13 2023-03-21 南昌大学 Probiotics bead-popping soft sweets and preparation method thereof

Similar Documents

Publication Publication Date Title
CN1613455A (en) Targeting microorgan micro-capsules and their preparation
Martín et al. Microencapsulation of bacteria: A review of different technologies and their impact on the probiotic effects
US6890561B1 (en) Microencapsulated and controlled-release formulations of isoflavone from enriched fractions of soy and other plants
JP5950938B2 (en) Microencapsulated probiotic material and production method
EP0762873B1 (en) Stabilized biologically active compounds contained in coated microgranules which can be suspended in alimentary fluids
CN1139657C (en) Electric coated microgranules for stabilizing lactic acid bacteria
AU2008337269B2 (en) Formulations comprising exine shells
JP5771601B2 (en) Particulate composition
US20090130196A1 (en) Bacteriophage composition
KR100473422B1 (en) A composition for an enteric coating of natural product containing lectin
CN107362154A (en) With the microcapsules for improving shell
KR20030060105A (en) Microsphere of pancreatic enzymes with high stability and production method thereof
CN107484878B (en) Preparation method of microbial microcapsule and application of microbial microcapsule in feed
EP2117354A1 (en) A dry food product containing live probiotic
JP2003517470A (en) Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
MX2007000955A (en) Multiparticle pharmaceutical dosage form for a low-soluble active substances and method for producing said pharmaceutical dosage form.
AU2011248293A1 (en) Micropellet compositions comprising pancreatin containing digestive enzyme mixtures
US20140127307A1 (en) Micropellet compositions comprising pancreatin containing digestive enzyme mixture
TW200944216A (en) Agent for suppressing elevation in blood phosphorus level
CN110973369A (en) Slow-release sodium butyrate suitable for aquatic animals and preparation method thereof
HRP20030036A2 (en) Particulate composition of eletriptan
JPH04364123A (en) Coating material and enteric granule produced by using the same
EP4108095A1 (en) Microcapsules containing gamma-aminobutyric acid
GB2394416A (en) Targeted delivery of microbially encapsulated drugs
CN101647782A (en) Vinpocetine oral administration self-microemulsifying pellet as well as preparation method and application thereof

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C57 Notification of unclear or unknown address
DD01 Delivery of document by public notice

Addressee: Yan Shucui

Document name: Notice of conformity

C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C57 Notification of unclear or unknown address
DD01 Delivery of document by public notice

Addressee: Yan Shucui

Document name: Notification of the application for patent for invention to go through the substantive examination procedure

C02 Deemed withdrawal of patent application after publication (patent law 2001)
WD01 Invention patent application deemed withdrawn after publication