CN105997926A - Bifidobacterium colonic-dissolving soft capsule and preparation method thereof - Google Patents
Bifidobacterium colonic-dissolving soft capsule and preparation method thereof Download PDFInfo
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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Abstract
The invention relates to a bifidobacterium colonic-dissolving soft capsule and a preparation method thereof. The soft capsule comprises contents and a gelatine capsule shell, wherein the capsule shell of the soft capsule is treated to have colonic solubility. The contents in the soft capsule are a stable suspension prepared from freeze-dried bifidobacterium powder, plant oil, a suspending aid and a wetting agent through uniform mixing and stirring. Additionally, the capsule shell of the soft capsule has the colonic solubility due to the fact that the soft capsule is dipped in formaldehyde. The freeze-dried bifidobacterium powder soft capsule with the plant oil as a carrier is encapsulated, has colonic solubility and good stability, is convenient to transport and store and has a longer guarantee period; bifidobacterium and the plant oil act on the colon together, the disordered intestinal flora is improved, bowel relaxing efficacy is realized, and suffering of people from constipation is eliminated. The bifidobacterium colonic-dissolving soft capsule and the preparation method thereof are used for the field of preparation of microbial ecological agents.
Description
Technical field
The invention belongs to microbial ecological agent technical field, relate to a kind of bacillus bifidus colon insoluble capsule and preparation side thereof
Method.
Background technology
Along with the quickening of social life rhythm, diet becomes more meticulous and the burden many impacts such as heavily of people's psychiatric,
Increasing crowd suffers from the bowel problems such as diarrhoea, constipation, irritable bowel syndrome, and wherein constipation has become affects modern life
One of key factor of bioplasm amount.Therefore, the treatment of constipation and research seem and become more and more important.
Constipation belongs to a kind of common gastrointestinal dysfunction disease, is primarily referred to as defecation frequency minimizing, the minimizing of feces amount, defecation
Laborious etc., it is the inducement of many chronic diseases, is also the performance of health aging ahead of time.
So far, the Therapeutic Method for constipation is varied, treats frequently with cathartic on traditional clinical, can be quick
Constipation relieving symptom, but may be with untoward reaction such as stomachache, abdominal distention.Life-time service easily produces drug dependence, very
To increasing the weight of constipation.
Show can effectively slow down constipation symptom, constipation by the dietary fiber in increase meals and probiotic bacteria according to research
Generation and alteration of intestinal flora have much relations.During alteration of intestinal flora, in intestinal, the increase of harmful bacteria quantity is easily caused
Constipation, the generation of the symptoms such as diarrhoea, and when using microbial ecological agent artificially to supplement appropriate probiotic bacteria, it is possible to improve this type of disease
Shape, and do not find its untoward reaction, but due to active bacteria not stomach juice-resistant, bile acid, the effect of digestive enzyme etc. and easily inactivate.
Therefore find one to allow patient there is no a misery for improving constipation, and the method that can fundamentally solve constipation be in the urgent need to
's.
Microbial ecological agent product mostly is the type such as granule, liquid in the market, generally there is shelf life short, is difficult to storage
And transport, it is difficult to ensure that the number of viable in medicine, medicine is difficult to after arriving intestinal through digestive tract environment such as gastric acid, arrives intestinal
Behind road, thalline mortality, it is impossible to play the physiological action of probiotic bacteria.
Summary of the invention
It is an object of the invention to develop one and treat constipation good effect, effect is obvious, safety, the little microbial ecological agent of side effect
Health promoting product, improves the symptom of constipation in terms of physics and biological two, solves constipation problem and brings the misery of people.By one it is
Row research, the research products improving constipation relieving providing safety and Health for society, make the updating and upgrading of a product being similar to, Jin Ergai
The health status of kind modern, strengthens the body constitution of people, improves the quality of life of people, and the health for the mankind makes tribute
Offer.
The present invention studies a kind of bifidobacterium adolescentis soft capsule with colon dissolubility, and it includes soft capsule content and soft
Capsule rubber；Described soft capsule content is made up of bacillus bifidus lyophilized powder, vegetable oil, suspending agent and wetting agent；Described
Soft capsule rubber be made up for 1:0.5:1 in mass ratio of edible Gelatinum oxhide, G & W ratio；Described soft capsule is being made
After impregnating by formalin afterwards, obtain bacillus bifidus colon insoluble capsule.
Preparation method major programme of the present invention is as follows:
A kind of preparation method of bacillus bifidus colon insoluble capsule, it is characterised in that: the composition bag of bacillus bifidus soft capsule
Including soft capsule content and soft capsule rubber, wherein content is by bacillus bifidus lyophilized powder, vegetable oil, suspending agent, wetting agent
Through the stable suspension that mixing, stirring are made.It addition, use certain density formalin to impregnate soft capsule a period of time,
Obtain tying enteric soft capsules.
A kind of preparation method of the bacillus bifidus colon insoluble capsule of the present invention, it follows the steps below:
One, the preparation of soft capsule content:
Take the fermentation liquid of the bacillus bifidus after fermentation, by fermentation liquid centrifugal 15min under 4500r, obtain bacillus bifidus
Bacterium mud, collects bacterium mud, and weighs, and 1:3 in mass ratio mixes with freeze drying protectant, after mixing at-20 DEG C pre-freeze 8h, then vacuum
Lyophilization 12h takes out, and obtains freeze-dried bifidobacteria powder；
Mycopowder after lyophilizing is crossed 120 mesh sieves, and in suspension, the mass ratio of each composition is bacillus bifidus lyophilized powder: soybean oil
It is: with the quality of soybean oil as standard that Cera Flava adds 4%, greatly for 1:3, the suspending agent wherein added and the addition of wetting agent
Fabaceous lecithin adds 6%.
Two, the preparation of soft capsule content suspension: the freeze-dried bifidobacteria powder taking step one crosses 120 mesh sieves, standby；
First being heated by vegetable oil, pour suspending agent into, after making suspending agent completely melted, stop heating, room temperature is cooled to 30 DEG C,
Adding wetting agent, stirring while adding, mix homogeneously, to without precipitation, adds the freeze-dried bifidobacteria powder after sieving, mixing
Uniformly, obtain soft capsule content suspension, standby at a temperature of soft capsule content suspension is placed in 30 DEG C；Described bifid bar
Bacterium lyophilized powder: the mass ratio of vegetable oil is 1:3；The addition (mass ratio) of suspending agent is the 4% of vegetable oil, the interpolation of wetting agent
Amount (mass ratio) is the 6% of vegetable oil；
Three, the preparation of glue:
Gelatin, G & W are weighed according to the ratio that mass ratio is 1:0.5:1；In water pouring into the glue tank that will weigh,
Then add glycerol, be subsequently heated to 70 DEG C and stir, add the gelatin weighed up, stir 3h at a temperature of 75 DEG C, take out
Vacuum removal of air bubbles, 60 DEG C of insulations, standby；
Four, compacting soft capsule:
In pressing process, soft capsule content need to be in 30 DEG C of temperature constant states, and the operating parameter controlling encapsulating machine is:
Glue box temperature is 50-55 DEG C, and rubber thickness is 0.8-0.9mm, and sprinkler body temperature is 40-43 DEG C, then suppresses according to above-mentioned parameter
Soft capsule；
Five, shape and be dried:
After soft capsule is suppressed successfully, carry out preliminarily dried 4h through drying machine, after taking-up, use washes of absolute alcohol soft capsule
Surface, remove oil stain, be then placed in pallet and continue to be dried 12～15h, control the moisture of soft capsule peel 9%～
10%, both obtained bacillus bifidus soft capsule.
Six, colon dissolves soft capsule and must process
Prepared soft capsule is immersed in 1h in the formalin that volumetric concentration is 10%, after taking-up with dehydrated alcohol repeatedly
Clean till formaldehydeless taste, dry, both obtained bacillus bifidus colon insoluble capsule.
Viable bacteria content in the soft capsule obtained is 1 × 109Cfu/g～10 × 109cfu/g。
The temperature of described content is maintained at 30 DEG C, makes suspension not solidify in liquid condition always, and to seal,
The activity of big degree protection thalline.
In the technological process of bifidobacterium adolescentis soft capsule, the temperature of main attention content, i.e. can not too high destruction bacterium
Vigor, again can not be the lowest, cause suspension to solidify, cause machine jams, loading amount is uneven, press not go out capsule, it is also noted that respectively
Ratio between composition, prevents that the state of suspension is uneven causes machine jams.The setting of the most each parameter is also
Determine whether soft capsule can be suppressed successfully.
The present invention includes following beneficial effect:
1, bacillus bifidus and vegetable oil are prepared by mixing into soft capsule by the present invention, it is simple to be stored in transport, and both can
Jointly act on intestinal, by the lubrication of intestinal being combined with vegetable oil, the regulation effect of intestinal microbial population from biology
Produce aperient effects with physics two aspect, treat constipation.
2, in the present invention, soft capsule is processed into colon dissolubility, makes bacillus bifidus arrive disintegrate after colon smoothly, discharges
Bacillus bifidus, it is to avoid the digestive tract environment destructions to bacillus bifidus such as gastric acid bile, plays physiology at intestinal smoothly
Function, playing the effect of regulating intestinal canal flora, the especially treatment to constipation has preferable effect.And thalline is dry by freezing
After dry, can make soft capsule keeps higher number of viable, strengthen the resistivity of thalline environment to external world, significantly increase
Thalline is in shelf-life of low temperature and arrives the survival rate of intestinal.
Accompanying drawing explanation
Fig. 1 is the soft capsule preservation enteric disintegration time figure of 30 days of the formalin process of 10% concentration；
Fig. 2 is number of viable variation diagram in lower 90 days comparison lyophilizing mycopowder of different temperatures, and wherein, A is the viable count of-18 DEG C
Amount variation diagram, B is the number of viable variation diagram of 4 DEG C, and C is the number of viable variation diagram of 25 DEG C；
Fig. 3 is number of viable variation diagram in lower 90 days bacillus bifidus colon insoluble capsules of different temperatures, and wherein, A is-18 DEG C
Number of viable variation diagram, B is the number of viable variation diagram of 4 DEG C, and C is the number of viable variation diagram of 25 DEG C；
Fig. 4 is normal rabbits pellet morphology observation figure；
Fig. 5 is constipation rabbit pellet morphology observation figure；
Fig. 6 feeds soft capsule group rabbit pellet morphology observation figure for filling；
Fig. 7 is positive controls rabbit rabbit pellet morphology observation figure.
Detailed description of the invention
In order to preferably explain and illustrate the feature of the present invention, concrete illustrating in following specific embodiment,
But the present invention is not limited by the following examples.
Detailed description of the invention one: a kind of bacillus bifidus colon insoluble capsule of present embodiment, it includes soft capsule content
Thing and soft capsule rubber；Described soft capsule content is by bacillus bifidus lyophilized powder, vegetable oil, suspending agent and wetting agent system
Become；Described soft capsule rubber is made up for 1:1:0.5 in mass ratio of edible Gelatinum oxhide, G & W ratio；Described flexible glue
After capsule impregnates by formalin after it has been manufactured, obtain bacillus bifidus colon insoluble capsule.
Detailed description of the invention two: present embodiment is unlike detailed description of the invention one: each component of soft capsule content
Consumption is: bacillus bifidus lyophilized powder: the mass ratio of vegetable oil is 1:3, and the addition of suspending agent is the 4% of vegetable oil quality, profit
The addition of humectant is the 6% of vegetable oil quality.Other is identical with detailed description of the invention one.
Detailed description of the invention three: present embodiment is unlike detailed description of the invention one: the viable bacteria content in soft capsule
It is 1 × 109Cfu/g～10 × 109cfu/g.Other is identical with detailed description of the invention one.
Detailed description of the invention four: present embodiment is unlike detailed description of the invention one: described formalin dipping
Referring to impregnate soft capsule 1h by the formalin that volumetric concentration is 10%, taking-up dehydrated alcohol rinses soft capsule, dries, and removes
Residues of formaldehyde, had both obtained bacillus bifidus colon insoluble capsule.Other is identical with detailed description of the invention one.
Detailed description of the invention five: present embodiment is unlike detailed description of the invention one: described suspending agent is Cera Flava；
Described wetting agent is soybean phospholipid.Other is identical with detailed description of the invention one.
Detailed description of the invention six: present embodiment is unlike detailed description of the invention one: described vegetable oil is Semen sojae atricolor
One or more in oil, Oleum Cocois, Semen Maydis oil, Oleum Arachidis hypogaeae semen are in mass ratio for the mixture of 1:1 mixing.Other be embodied as
Mode one is identical.
Detailed description of the invention seven: present embodiment bacillus bifidus described in unlike detailed description of the invention one is the youth
Bacillus bifidus (Bifidobacterium adolescentis).Other is identical with detailed description of the invention one.
Detailed description of the invention eight: the preparation method of present embodiment a kind of bacillus bifidus colon insoluble capsule, it be according to
Following steps are carried out:
One, the preparation of soft capsule content:
Take the fermentation liquid of the bacillus bifidus after fermentation, by fermentation liquid centrifugal 15min under 4500r, obtain bacillus bifidus
Bacterium mud, collects bacterium mud, and weighs, and 1:3 in mass ratio mixes with freeze drying protectant, after mixing at-20 DEG C pre-freeze 8h, then vacuum
Lyophilization 12h takes out, and obtains freeze-dried bifidobacteria powder；
Mycopowder after lyophilizing is crossed 120 mesh sieves, and in suspension, the mass ratio of each composition is bacillus bifidus lyophilized powder: soybean oil
It is: with the quality of soybean oil as standard that Cera Flava adds 4%, greatly for 1:3, the suspending agent wherein added and the addition of wetting agent
Fabaceous lecithin adds 6%.
Two, the preparation of soft capsule content suspension: the freeze-dried bifidobacteria powder taking step one crosses 120 mesh sieves, standby；
First being heated by vegetable oil, pour suspending agent into, after making suspending agent completely melted, stop heating, room temperature is cooled to 30 DEG C,
Adding wetting agent, stirring while adding, mix homogeneously, to without precipitation, adds the freeze-dried bifidobacteria powder after sieving, mixing
Uniformly, obtain soft capsule content suspension, standby at a temperature of soft capsule content suspension is placed in 30 DEG C；Described bifid bar
Bacterium lyophilized powder: the mass ratio of vegetable oil is 1:3；The addition (mass ratio) of suspending agent is the 4% of vegetable oil, the interpolation of wetting agent
Amount (mass ratio) is the 6% of vegetable oil；
Three, the preparation of glue:
Gelatin, G & W are weighed according to the ratio that mass ratio is 1:0.5:1；In water pouring into the glue tank that will weigh,
Then add glycerol, be subsequently heated to 70 DEG C and stir, add the gelatin weighed up, stir 3h at a temperature of 75 DEG C, take out
Vacuum removal of air bubbles, 60 DEG C of insulations, standby；
Four, compacting soft capsule:
In pressing process, soft capsule content need to be in 30 DEG C of temperature constant states, and the operating parameter controlling encapsulating machine is:
Glue box temperature is 50-55 DEG C, and rubber thickness is 0.8-0.9mm, and sprinkler body temperature is 40-43 DEG C, then suppresses according to above-mentioned parameter
Soft capsule；
Five, shape and be dried:
After soft capsule is suppressed successfully, carry out preliminarily dried 4h through drying machine, after taking-up, use washes of absolute alcohol soft capsule
Surface, remove oil stain, be then placed in pallet and continue to be dried 12～15h, control the moisture of soft capsule peel 9%～
10%, both obtained bacillus bifidus soft capsule.
Six, colon dissolves soft capsule and must process
Prepared soft capsule is immersed in 1h in the formalin that volumetric concentration is 10%, after taking-up with dehydrated alcohol repeatedly
Clean till formaldehydeless taste, dry, both obtained bacillus bifidus colon insoluble capsule.
Detailed description of the invention nine: present embodiment is unlike detailed description of the invention eight: described freeze drying protectant group
Being divided into: weight/mass percentage composition is the skimmed milk of 9.51%, weight/mass percentage composition is the glycerol of 1.93%, and weight/mass percentage composition is
The sucrose of 9.28% and the water of surplus.Other is identical with detailed description of the invention eight.
Detailed description of the invention ten: present embodiment is unlike detailed description of the invention eight: the viable bacteria content in soft capsule
It is 1 × 109Cfu/g～10 × 109cfu/g.Other is identical with detailed description of the invention eight.
Detailed description of the invention 11: present embodiment is unlike detailed description of the invention eight: described formalin leaching
Stain refers to impregnate soft capsule 1h by the formalin that volumetric concentration is 10%, and taking-up dehydrated alcohol rinses soft capsule, dries, removes
Remove residues of formaldehyde, both obtain bacillus bifidus colon insoluble capsule.Other is identical with detailed description of the invention eight.
Detailed description of the invention 12: present embodiment is unlike detailed description of the invention eight: described suspending agent is honeybee
Wax；Described wetting agent is soybean phospholipid.Other is identical with detailed description of the invention eight.
Detailed description of the invention 13: present embodiment is unlike detailed description of the invention eight: described vegetable oil is big
One or more in Oleum Glycines, Oleum Cocois, Semen Maydis oil, Oleum Arachidis hypogaeae semen are in mass ratio for the mixture of 1:1 mixing.Other is real with concrete
Execute mode eight identical.
Detailed description of the invention 14: present embodiment bacillus bifidus described in unlike detailed description of the invention eight is blue or green
Spring bacillus bifidus (Bifidobacterium adolescentis).Other is identical with detailed description of the invention eight.
The Integral Thought of the present invention is:
The subject matter faced according to bifidobacterium preparations in the market, is carried out bacillus bifidus at vacuum lyophilization
Reason, keeps higher viable count, is prepared by mixing into soft capsule with vegetable oil, and dissolves process by colon and obtain bacillus bifidus
Colon insoluble capsule, makes bacillus bifidus and vegetable oil pass through disintegrate after stomach reaches colon and discharges, and plays bacillus bifidus
The physiological function of regulating intestinal canal colony balance and the effect of vegetable oil lubrication intestinal, reach loosening bowel to relieve constipation, the purpose for the treatment of constipation.
Solve the puzzlement that the intestinal tract diseases such as constipation are brought.
By following example checking beneficial effects of the present invention:
Embodiment one: the preparation of a kind of bacillus bifidus colon insoluble capsule of the present embodiment, soft capsule is by content and glue
Skin forms.
The constituent of described soft capsule content is: bacillus bifidus is 1:3 with the ratio of vegetable oil, suspending agent Cera Flava
Addition is the 4% of soybean oil, and the addition of wetting agent soybean phospholipid is the 6% of soybean oil, and the viable bacteria content of content is 2.6
×108cfu/g。
In the rubber of described soft capsule, the ratio of each component is: gelatin 40%, water 40%, glycerol 20%.
The preparation method of a kind of bacillus bifidus soft capsule, mainly comprises the steps that
One, the preparation of content:
After fermentation bifidobacterium adolescentis, by fermentation liquid centrifugal 15min under 4500r, obtain the bacterium mud of bifidobacterium adolescentis,
Collecting bacterium mud, and weigh, 1:3 in mass ratio mixes with protective agent, and protective agent formula is: skimmed milk 9.51%, glycerol 1.93%,
Sucrose 9.28%, after mixing in refrigerator at-20 DEG C after pre-freeze 8h, in vacuum freeze drier, lyophilization 12h takes out,
To bifidobacterium adolescentis lyophilizing mycopowder.
Mycopowder after lyophilizing is sieved, crosses 120 mesh sieves.The method can make mycopowder microgranule the most carefully be enough to by encapsulating machine
Liquid injection port, do not result in blocking, it is ensured that loading amount is uniform, due to external force, the activity of bifidobacterium adolescentis will not be caused shadow again
Ring, be one of important step in technological process.
In suspension, the mass ratio of each composition is bifidobacterium adolescentis lyophilized powder: soybean oil is 1:3, the suspending wherein added
The addition of agent and wetting agent is: with the quality of soybean oil as standard, and Cera Flava adds 4%, and soybean phospholipid adds 6%.
Two, the preparation of content suspension: weigh freeze-dried bifidobacteria powder and soybean oil in the ratio of 1:3, first will be big
Oleum Glycines heats, and pours the Cera Flava of 4% into, after making Cera Flava completely melted, stops heating, and room temperature is cooled to 30 DEG C, add 6% big
Fabaceous lecithin, stirring while adding, mix homogeneously, without precipitation, adds the lyophilizing mycopowder weighed up, mix homogeneously, prepared by content
Become, save backup that (temperature of content is maintained at 30 DEG C, makes suspension not solidify in liquid condition, and to seal, maximum always
The activity of degree protection thalline)；
Three, the preparation of glue:
Plasticizer is glycerol, and major ingredient is gelatin, and by gelatin, G & W weighs institute according to the ratio of mass ratio 1:0.5:1
The amount needed, first weighs in water pouring into the glue tank of requirement, and adds the desired amount of glycerol, is heated to 70 DEG C and stirs all
Even, add the gelatin weighed up, 75 DEG C of stirring 3h, make gelatin expand completely, prepare glue, evacuation removes bubble, 60 DEG C
Insulation, standby.
Four, compacting soft capsule:
In pressing process, content need to be in 30 DEG C of temperature constant states, and seal as far as possible, at utmost ensures number of viable,
And the operating parameter controlling encapsulating machine is respectively as follows: glue box temperature between 50-55 DEG C, rubber thickness is at 0.8-0.9mm, sprinkler body
Temperature controls at 40-43 DEG C, prevents the too high activity affecting bacterium of temperature.Soft capsule is suppressed by this operating parameter.
Five, shape and be dried:
After soft capsule is suppressed successfully, preliminarily dried 4h need to be carried out through drying machine, after taking-up, use washes of absolute alcohol flexible glue
The surface of capsule, removes oil stain, is then placed in pallet and continues to be dried 12-15h, controls the moisture of soft capsule peel at 9%-
Between 10%, both obtained product.
In the technological process of bifidobacterium adolescentis soft capsule, the temperature of main attention content, i.e. can not too high destruction bacterium
Vigor, again can not be the lowest, cause suspension to solidify, cause machine jams, loading amount is uneven, press not go out capsule, it is also noted that respectively
Ratio between composition, prevents that the state of suspension is uneven causes machine jams.The setting of the most each parameter is also
Determine whether soft capsule can be suppressed successfully.
The associated verification result of the test of bacillus bifidus colon insoluble capsule of the present invention is as follows:
Test one: the study on the stability of bacillus bifidus colon insoluble capsule enteric solubility
There are some researches show, although the soft capsule after formalin is soaked can have an enteric effect, but over time
Passage, enteric effect may decline, so the present invention need PARA FORMALDEHYDE PRILLS(91,95) to soak after the enteric of bacillus bifidus soft capsule
Stability is verified.According to embodiment one, after being preserved 30 days by soft capsule, investigate disintegration time.
Seeing Fig. 1 to understand, at first 15 days, it is very slow that the enteric disintegration time of soft capsule declines, and preserves preferable colon
Dissolubility, at the 30th day, although enteric disintegration time ratio has declined, but remains at more than 300min disintegration,
Still retain the molten effect of preferable colon.
Test two: the checking of bacillus bifidus colon insoluble capsule colon dissolubility
According to embodiment one, randomly select 6 soft capsules and be placed in disintegration tester, take out after first passing through simulated gastric fluid 2h, few
Amount clear water is cleaned, and continues to put in artificial intestinal fluid and takes out after 2h, and a small amount of clear water is cleaned, and is finally putting into artificial colonic fluid
In, until disintegrate is complete, record final disintegration time.
16 soft capsule disintegration times of table
From result, the disintegration time of average every soft capsule is 7h17min, because medicine normally arrives human colon
The time at position is 5h, so according to the investigation of disintegration in pharmacopeia, it was demonstrated that it is molten that bacillus bifidus soft capsule can reach colon
Effect.
Test three: the study on the stability of viable count under bacillus bifidus colon insoluble capsule different temperatures
Use the soft capsule in the embodiment of the present invention one to be individually positioned in-18 DEG C, 4 DEG C, under 20 DEG C of three kinds of different temperatures, examine
Examine the viable count change of 90 days, use plate dilution method, choose suitable gradient coated plate, within every 7 days, measure once, with HD bifid bar
Bacterium lyophilizing mycopowder compares, and each gradient does 3 Duplicate Samples.
Result sees Fig. 2 and Fig. 3, and in the present invention, in the lyophilizing mycopowder of comparison, initial viable count is 3.72 × 1011Cfu/g,
Initial viable count in embodiment one soft capsule is 2.96 × 108/g.From result, viable count gradually drops over time
Low.After preserving 90 days, at 18 DEG C, in bacillus bifidus soft capsule, viable count have dropped 1.17 orders of magnitude, viable bacteria in lyophilized powder
Number have dropped 2.44 orders of magnitude；At 4 DEG C, in bacillus bifidus soft capsule, viable count have dropped 1.52 orders of magnitude, in lyophilized powder
Viable count have dropped 2.88 orders of magnitude；At 25 DEG C, in bacillus bifidus soft capsule, viable count have dropped 1.90 orders of magnitude, lyophilizing
In powder, viable count have dropped 4.07 orders of magnitude；
So compared with simple lyophilizing mycopowder, at a temperature of each, in soft capsule, the stability of bacterium is all more preferable, and declines
Slower.It addition, soft capsule has more preferable bin stability under the conditions of 18 DEG C.Although with preservation viable count under room temperature
Decline, but still can keep long stability.
Test five: the bacillus bifidus colon insoluble capsule research to constipation rabbit aperient effects
Randomly choose 6 rabbit therein not process as blank group, remain 18 rabbit as constipation modeling
Group, (by 4.0mg/kg weight, the quality that Loperamide Hydrochloride is dissolved in 2mL is divided to fill hello 2mL Loperamide Hydrochloride solution every day
Number is the normal saline of 0.9%), continuous 4d manufactures the Constipation Model of rabbit.Finally judge whether the successful index of modeling, mainly
During record modeling, the feed intake of every rabbit, amount of drinking water, weight increments, defecation grain number, feces water content five
Index, contrasts with blank group, if all declined, it was demonstrated that rabbit constipation modeling success.
At random 18 rabbit after modeling are divided into 3 groups, often group 6, model control group, positive controls and bacillus bifidus
Colon insoluble capsule group, adds blank group totally 4 groups, wherein blank group and model control group normal feed every day material and
Water, in addition to normal feed, feeds positive controls every day two LIVZON CHANGLE hard capsules, bacillus bifidus knot enteric soft for remaining two groups
Capsule group feeds two bacillus bifidus soft capsules prepared according to embodiment one every day, and in capsule, bacteria containing amount is identical, be all 1 ×
108cfu。
Result of the test is as follows:
The observed result of rabbit pellet morphology:
Be can be seen that blank group normal rabbits feces is spherical by accompanying drawing 4 and accompanying drawing 5, size is similar, is neatly as good as
Shape, but modeling group rabbit feces, owing to constipation causes feces less, form is irregular and into strips, and this is likely due to constipation
Time rabbit exert oneself defecation, the feces alteration of form that defecation arduously causes.
Accompanying drawing 6 is the rabbit feces giving HD bacillus bifidus colon insoluble capsule after 7 days, and its shapes and sizes are the most equal
Even, almost with normal rabbits indifference, constipation symptom disappears.Accompanying drawing 7 is the pellet morphology after positive controls is administered, and feces is big
Little close to normal, but also some strip just exists, and constipation symptom is not wholly absent, it was demonstrated that its therapeutic effect to constipation
Poorer than HD bacillus bifidus colon insoluble capsule.
The comparison of table 2 blank group and constipation modeling group indices (N=4)
Note: *. compared with blank group, there is significant difference (P ＜ 0.05).*. compared with blank group, there is pole
Significant difference (P ＜ 0.01)；
Table 2 is during manufacturing Constipation Model, the blank group of record and the physical signs of constipation modeling group rabbit
With defecation index, by contrasting with blank group, it is judged that its whether modeling success.The rabbit of constipation modeling group is searching for food
Significantly reduce in amount and amount of drinking water, therefore cause body weight also to increases slowly, it was demonstrated that constipation modeling group rabbit causes appetite because of constipation
Depressed, poor growth.And the defecation grain number of constipation modeling group rabbit and feces water content are the most notable compared with blank group
Reduce, it was demonstrated that the possible difficult defecation of the rabbit after modeling, have the symptom that feces becomes dry, therefore, may certify that from these five indexs
Modeling success.
3 four groups of differences of table feed thing on constipation rabbit feed intake, amount of drinking water, weight increments impact (N=4)
Note: same column difference letter representation significant difference (P ＜ 0.05), same column same letter represents not notable (the P ＞ of difference
0.05).
Upper table shows in the result of variations that each group of rabbit administration processes tri-indexs of 7d, can obtain HD bacillus bifidus
The feed intake of colon insoluble capsule group rabbit dramatically increase compared with model control group with amount of drinking water and with blank group rabbit
Without significant difference；Compared with positive controls, the feed intake of bacillus bifidus enteric soft capsules group dramatically increases, but amount of drinking water is without aobvious
Writing difference, its weight increments and blank group are also without significant difference.Result proves HD bacillus bifidus colon insoluble capsule
Can significantly improve diet and the drinking-water situation of constipation rabbit, make livelihood restoration normal, do not hinder rabbit to grow, body weight increases,
It is made to live without significant difference with normal rabbits.
4 four groups of differences of table feed thing on the impact of rabbit defecation grain number and feces water content (N=4)
Note: the different letter representation significant difference (P ＜ 0.05) of colleague, colleague's same letter represents not notable (the P ＞ of difference
0.05).
From upper table result, compared with model control group, positive controls and the feces volume of bacillus bifidus soft capsule group
All have and significantly increase, wherein the feces volume of bacillus bifidus soft capsule group and blank group no significant difference, but positive control
Group feces volume compared with blank group does not dramatically increase, and can't recover normal defecation state.Bacillus bifidus soft capsule group
Defecation grain number and the water content of constipation rabbit can be dramatically increased, there is significant aperient effects, and double with in the market
It is more notable that discrimination bacillus hard capsule compares effect.
5 four groups of differences of table feed thing on the impact of Constipation Model Intestinal Flora In Rabbits (N=4)
Note: same column difference letter representation significant difference (P ＜ 0.05), same column same letter represents not notable (the P ＞ of difference
0.05).
Table 5 result shows after starting experiment, modeling success and respectively organizes five kinds of intestinal microbial populations in rabbit intestinal after medicine feed
Situation of change.From result, the various intestinal microflora no significant differences of all rabbit, intestinal microbial population state before modeling
Normally, experiment can be started.After modeling, in addition to blank group, in modeling Intestinal Flora In Rabbits, escherichia coli quantity dramatically increases,
Yeast quantity has the trend of increase but not notable, and additionally the quantity of bacillus bifidus, lactobacillus and dyspepsiacoccus is the most notable
Reduce (P ＜ 0.05), have significant difference, it was demonstrated that in constipation rabbit body, intestinal microbial population gets muddled, and its harmful bacteria increases, useful
Bacterium reduces.After being administered 7 days at each group, in bacillus bifidus colon insoluble capsule group rabbit body, bifidobacteria dramatically increases (P ＜
0.05), there was no significant difference (P ＞ 0.05) compared with blank group, the quantity of dyspepsiacoccus and lactobacillus is the most obvious
Increasing significant difference compared with model control group, colibacillary quantity significantly reduces, it was demonstrated that bacillus bifidus colon insoluble capsule
Constipation Intestinal Flora In Rabbits balance being played regulation effect, makes probiotics increase, harmful bacteria reduces.Rabbit gives positive controls
The quantity of bacillus bifidus, lactobacillus and dyspepsiacoccus in given the test agent rear intestinal the most all increased, but difference does not show
Writing, colibacillary quantity reduces, but compared with bacillus bifidus soft capsule group, the regulating effect to constipation Intestinal Flora In Rabbits
And inconspicuous, result proof bacillus bifidus colon insoluble capsule is to treatment rabbit constipation, and regulating intestinal canal colony balance has significantly
Effect.
Claims (10)
1. a bacillus bifidus colon insoluble capsule, it is characterised in that it includes soft capsule content and soft capsule rubber；Described
Soft capsule content be made up of bacillus bifidus lyophilized powder, vegetable oil, suspending agent and wetting agent；Described soft capsule rubber is
It is made up for 1:0.5:1 in mass ratio of edible Gelatinum oxhide, G & W ratio；Described soft capsule soaks by formalin after it has been manufactured
After stain, obtain bacillus bifidus colon insoluble capsule.
A kind of bacillus bifidus colon insoluble capsule the most according to claim 1, it is characterised in that each group of soft capsule content
Demultiplexing amount is: bacillus bifidus lyophilized powder: the mass ratio of vegetable oil is 1:3, and the addition of suspending agent is the 4% of vegetable oil quality,
The addition of wetting agent is the 6% of vegetable oil quality.
A kind of bacillus bifidus colon insoluble capsule the most according to claim 1, it is characterised in that the viable bacteria in soft capsule contains
Amount is 1 × 109Cfu/g～10 × 109cfu/g。
A kind of bacillus bifidus colon insoluble capsule the most according to claim 1, it is characterised in that described formalin leaching
Stain refers to impregnate soft capsule 1h by the formalin that volumetric concentration is 10%, and taking-up dehydrated alcohol rinses soft capsule, dries, removes
Remove residues of formaldehyde, both obtain bacillus bifidus colon insoluble capsule.
A kind of bacillus bifidus colon insoluble capsule the most according to claim 1, it is characterised in that described suspending agent is honeybee
Wax；Described wetting agent is soybean phospholipid.
A kind of bacillus bifidus colon insoluble capsule the most according to claim 1, it is characterised in that described vegetable oil is big
One or more mixture being mixed by any ratio in Oleum Glycines, Oleum Cocois, Semen Maydis oil, Oleum Arachidis hypogaeae semen.
A kind of bacillus bifidus colon insoluble capsule the most according to claim 1, it is characterised in that described bacillus bifidus is
Bifidobacterium adolescentis (Bifidobacterium adolescentis).
8. the preparation method of a bacillus bifidus colon insoluble capsule, it is characterised in that it follows the steps below:
One, the preparation of soft capsule content:
Take the fermentation liquid of the bacillus bifidus after fermentation, by fermentation liquid centrifugal 15min under 4500r, obtain the bacterium mud of bacillus bifidus,
Collecting bacterium mud, and weigh, 1:3 in mass ratio mixes with freeze drying protectant, after mixing at-20 DEG C pre-freeze 8h, then vacuum freezing
It is dried 12h to take out, obtains freeze-dried bifidobacteria powder；
Mycopowder after lyophilizing is crossed 120 mesh sieves, and in suspension, the mass ratio of each composition is bacillus bifidus lyophilized powder: soybean oil is 1:
3, the suspending agent wherein added and the addition of wetting agent be: with the quality of soybean oil as standard, Cera Flava adds 4%, Semen sojae atricolor phosphorus
Fat adds 6%.
Two, the preparation of soft capsule content suspension: the freeze-dried bifidobacteria powder taking step one crosses 120 mesh sieves, standby；
First being heated by vegetable oil, pour suspending agent into, after making suspending agent completely melted, stop heating, room temperature is cooled to 30 DEG C, then adds
Entering wetting agent, stirring while adding, mix homogeneously, to without precipitation, adds the freeze-dried bifidobacteria powder after sieving, mix homogeneously,
Obtain soft capsule content suspension, standby at a temperature of soft capsule content suspension is placed in 30 DEG C；Described bacillus bifidus freezes
Dry powder: the mass ratio of vegetable oil is 1:3；The addition (mass ratio) of suspending agent is the 4% of vegetable oil, the addition of wetting agent
(mass ratio) is the 6% of vegetable oil；
Three, the preparation of glue:
Gelatin, G & W are weighed according to the ratio that mass ratio is 1:0.5:1；In water pouring into the glue tank that will weigh, then
Add glycerol, be subsequently heated to 70 DEG C and stir, add the gelatin weighed up, at a temperature of 75 DEG C, stir 3h, evacuation
Removing bubble, 60 DEG C of insulations, standby；
Four, compacting soft capsule:
In pressing process, soft capsule content need to be in 30 DEG C of temperature constant states, and the operating parameter controlling encapsulating machine is: glue box
Temperature is 50-55 DEG C, and rubber thickness is 0.8-0.9mm, and sprinkler body temperature is 40-43 DEG C, then suppresses flexible glue according to above-mentioned parameter
Capsule；
Five, shape and be dried:
After soft capsule is suppressed successfully, carry out preliminarily dried 4h through drying machine, after taking-up, with the table of washes of absolute alcohol soft capsule
Face, removes oil stain, is then placed in pallet and continues to be dried 12～15h, control the moisture of soft capsule peel 9%～
10%, both obtained bacillus bifidus soft capsule.
Six, colon dissolves soft capsule and must process
Prepared soft capsule is immersed in 1h in the formalin that volumetric concentration is 10%, repeatedly cleans with dehydrated alcohol after taking-up
Till formaldehydeless taste, dry, both obtained bacillus bifidus colon insoluble capsule.
The preparation method of a kind of bacillus bifidus colon insoluble capsule the most according to claim 8, it is characterised in that described
Freeze drying protectant component is: weight/mass percentage composition is the skimmed milk of 9.51%, and weight/mass percentage composition is the glycerol of 1.93%, quality
Percentage composition is sucrose and the water of surplus of 9.28%.
The preparation method of a kind of bacillus bifidus colon insoluble capsule the most according to claim 8, it is characterised in that formaldehyde is molten
The mass concentration of liquid is 10%, and dip time is 1h.
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| CN106174570A (en) * | 2016-10-17 | 2016-12-07 | 四川东坡中国泡菜产业技术研究院 | A kind of method utilizing Pickles water to make nourishing capsule granule |
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| US20220287965A1 (en) * | 2021-03-11 | 2022-09-15 | North Carolina Agricultural And Technical State University | Oleogels and methods relating thereto |
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