CN107455757A - A kind of probiotic composition for adjusting enteron aisle - Google Patents
A kind of probiotic composition for adjusting enteron aisle Download PDFInfo
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- CN107455757A CN107455757A CN201710598382.6A CN201710598382A CN107455757A CN 107455757 A CN107455757 A CN 107455757A CN 201710598382 A CN201710598382 A CN 201710598382A CN 107455757 A CN107455757 A CN 107455757A
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- probiotic composition
- stabilizer
- accelerator
- enteron aisle
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- 239000006041 probiotic Substances 0.000 title claims abstract description 38
- 235000018291 probiotics Nutrition 0.000 title claims abstract description 38
- 239000000203 mixture Substances 0.000 title claims abstract description 36
- 230000000529 probiotic effect Effects 0.000 title claims abstract description 32
- 239000003381 stabilizer Substances 0.000 claims abstract description 22
- 239000002994 raw material Substances 0.000 claims abstract description 20
- 241001608472 Bifidobacterium longum Species 0.000 claims abstract description 11
- 241000218588 Lactobacillus rhamnosus Species 0.000 claims abstract description 11
- 229940009291 bifidobacterium longum Drugs 0.000 claims abstract description 11
- 235000021255 galacto-oligosaccharides Nutrition 0.000 claims abstract description 11
- 150000003271 galactooligosaccharides Chemical class 0.000 claims abstract description 11
- 239000000843 powder Substances 0.000 claims abstract description 11
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- 239000008187 granular material Substances 0.000 claims description 5
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- 230000000694 effects Effects 0.000 abstract description 6
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 4
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- 238000010521 absorption reaction Methods 0.000 description 2
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
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- 210000000056 organ Anatomy 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 241000304886 Bacilli Species 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
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- 230000008855 peristalsis Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 235000013406 prebiotics Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
- A23V2400/175—Rhamnosus
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/51—Bifidobacterium
- A23V2400/533—Longum
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Molecular Biology (AREA)
- Botany (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
It is made of the raw material of following parts by weight the invention discloses a kind of probiotic composition for adjusting enteron aisle：30 50 parts of bifidobacterium longum, 40 60 parts of Lactobacillus rhamnosus, 5 10 parts of stabilizer, 68 parts of accelerator, 35 parts of galactooligosaccharide, 20 30 parts of skimmed milk powder.Present invention regulation enteron aisle probiotic combinations composition formula is reasonable, sugar content is low, edible safety, without any adverse side effect, and be adapted to diabetes patient.
Description
Technical field
The invention belongs to field of health care products, and in particular to a kind of probiotic composition for adjusting enteron aisle.
Background technology
Enteron aisle is the maximum immune organ of human body, and the toxin expelling organ that human body is maximum.If enteron aisle there is a problem, intestines
It is an incremental process that road, which is raised, and whole maintenance process should follow enteron aisle self cycle period, be had every about two weeks
The improvement of one matter.Then on the basis of improvement, a new cycle is again introduced into, then is further improved, is so followed
Ring is reciprocal, whole to raise process helically formula situation rising, until enteron aisle complete recovery of health.
Since 20th century mankind to Tiny ecosystem research so far, microecology has achieved significant progress, especially its
Extensive attention is obtained in the application of the prevention, treatment, health care of disease etc., numerous studies show：In human body intestinal canal just
The digestion and absorption of the nutrition of normal flora and human body have substantial connection, and normal flora has participated in cholesterol, steroids, fat, egg
The absorption and metabolism of white matter, lipoid, amino acid and some drugses.If certain factor influences and subtracts the probiotics in enteron aisle
Few, harmful bacteria amount reproduction, enteral microecological balance is broken, and will cause the various clinical symptoms such as diarrhoea.It is clinically usual
Broad-spectrum antibiotic can be largely used, although harmful bacteria can be killed effectively, can also kill beneficial bacterium simultaneously, cause gut flora to lose
Adjust, so as to cause disease.For intestinal bacilli illness person, oral help probiotics preparation is directly effectively to adjust doing for gut flora
Method.The composition of adjustment host intestine microorganism that can be directly or indirectly, activates host's endogenous microbes group or siberian crabapple
The activity of system realizes prebiotic effect.
Although probiotic food has many benefits to body, probiotics is constant relatively difficult, and the shelf-life is short, storage
Cost of transportation is high, while sour taste is afraid of to adapt to consumer by manufacturer, and substantial amounts of sugar or flavoring essence are added in manufactured goods,
And probiotics species is various.Therefore, it is badly in need of that a kind of strain collocation is reasonable, sugar content is low, the improvement function of intestinal canal of long shelf-life, carries
The probiotics health products of high immunity of organisms, after dietotherapy is combined with medicine, gradually make people's group energy of modern life rhythm quickening
The impaired stomach of enough renewal and reparation.
The content of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of formula is reasonable, sugar content is low, long shelf-life regulation intestines
The probiotic composition in road.
The purpose of the present invention is achieved by the following technical solution：
A kind of probiotic composition for adjusting enteron aisle, is made of the raw material of following parts by weight：Bifidobacterium longum 30-50 parts,
Lactobacillus rhamnosus 40-60 parts, stabilizer 5-10 parts, accelerator 6-8 parts, galactooligosaccharide 3-5 parts, skimmed milk powder 20-30 parts；
The stabilizer is according to 1 by Momordica grosvenori, sea-buckthorn, myrobalan, radix polygonati officinalis and mulberries：0.2-0.4：0.1-0.3：0.6-0.8：
Made from 0.4-0.6 weight ratio；
The accelerator is according to 1 by garlic polysaccharide and blueberry anthocyanin：Made from 0.5-0.9 weight ratio.
Preferably, a kind of probiotic composition for adjusting enteron aisle, is made of the raw material of following parts by weight：Long bifid bar
40 parts of bacterium, 50 parts of Lactobacillus rhamnosus, 8 parts of stabilizer, 7 parts of accelerator, 4 parts of galactooligosaccharide, 25 parts of skimmed milk powder.
Preferably, the stabilizer is according to 1 by Momordica grosvenori, sea-buckthorn, myrobalan, radix polygonati officinalis and mulberries：0.3：0.2：0.7：0.5
Weight ratio made from.
Preferably, the accelerator is according to 1 by garlic polysaccharide and blueberry anthocyanin：Made from 0.7 weight ratio.
After each raw material of probiotic composition weighs by weight, tablet, capsule, particle is conventionally made
Agent or pill.
Preferably, the formulation of the probiotic composition is granule.
Lactobacillus rhamnosus used in the present invention is the Lactobacillus rhamnosus product of high-purity, and purity is more than 40%.
Eating method：With warm water or warm milk（Less than 37 DEG C）Instant Drinks.
Points for attention：Need interval 2 hours can invented food after taking antibiotic.
In the present invention, bifidobacterium longum and Lactobacillus rhamnosus make the composition of gut flora occur, beneficial to change, to improve people
Body gastrointestinal function, recover colony balance in human body intestinal canal, form antibacterial biological barrier, safeguard health, while can also press down
The breeding of spoilage organisms processed, toxin caused by spoilage organisms is cleared up, remove enteron aisle rubbish.Accelerator is to bifidobacterium longum and rhamnose breast
The growth and breeding of bacillus has facilitation, and metabolism of the probiotics to stabilizer has facilitation, and stabilizer can stablize long bifid
Bacillus and the activity of Lactobacillus rhamnosus, extend the shelf life, three is mutually coordinated in enteron aisle；Meanwhile stabilizer and accelerator
Gastrointestinal peristalsis can be promoted, accelerate lipolysis, in time efficiently excrete the toxin being detained in enteron aisle, improve human body intestines
Road flora provides body environment and ensured, and then improves immunity of organisms.
Inventive formulation is reasonable, sugar content is low, edible safety, without any adverse side effect, and is adapted to diabetes patient.
Embodiment
With reference to embodiment, the present invention is described further.
Raw material used is commercially available convenient source in following embodiments.
Lactobacillus rhamnosus used is the Lactobacillus rhamnosus product of high-purity, and purity is more than 40%.
Embodiment 1
A kind of probiotic composition for adjusting enteron aisle, is made of the raw material of following parts by weight：50 parts of bifidobacterium longum, sandlwood
Sugared 40 parts of lactobacillus, 10 parts of stabilizer, 8 parts of accelerator, 5 parts of galactooligosaccharide, 20 parts of skimmed milk powder；
The stabilizer is according to 1 by Momordica grosvenori, sea-buckthorn, myrobalan, radix polygonati officinalis and mulberries：0.2： 0.3： 0.8：0.4 weight ratio
It is obtained；
The accelerator is according to 1 by garlic polysaccharide and blueberry anthocyanin：Made from 0.9 weight ratio.
Above-mentioned each raw material adds pharmaceutically acceptable auxiliary material and conventionally prepares piece agent, 1.5g/ pieces.
Embodiment 2
A kind of probiotic composition for adjusting enteron aisle, is made of the raw material of following parts by weight：45 parts of bifidobacterium longum, sandlwood
Sugared 45 parts of lactobacillus, 9 parts of stabilizer, 7 parts of accelerator, 4 parts of galactooligosaccharide, 23 parts of skimmed milk powder；
The stabilizer is according to 1 by Momordica grosvenori, sea-buckthorn, myrobalan, radix polygonati officinalis and mulberries：0.3：0.2：0.7：0.5 weight is than system
；
The accelerator is according to 1 by garlic polysaccharide and blueberry anthocyanin：Made from 0.8 weight ratio.
Above-mentioned each raw material adds pharmaceutically acceptable auxiliary material and is conventionally prepared into capsule, 1.5g/ grains.
Embodiment 3
A kind of probiotic composition for adjusting enteron aisle, is made of the raw material of following parts by weight：40 parts of bifidobacterium longum, sandlwood
Sugared 50 parts of lactobacillus, 8 parts of stabilizer, 7 parts of accelerator, 4 parts of galactooligosaccharide, 25 parts of skimmed milk powder.
The stabilizer is according to 1 by Momordica grosvenori, sea-buckthorn, myrobalan, radix polygonati officinalis and mulberries：0.3：0.2：0.7：0.5 weight
Than obtained；
The accelerator is according to 1 by garlic polysaccharide and blueberry anthocyanin：Made from 0.7 weight ratio.
Above-mentioned each raw material adds pharmaceutically acceptable auxiliary material and is conventionally prepared into granule, 1.5g/ bags.
Embodiment 4
A kind of probiotic composition for adjusting enteron aisle, is made of the raw material of following parts by weight：35 parts of bifidobacterium longum, sandlwood
Sugared 55 parts of lactobacillus, 7 parts of stabilizer, 7 parts of accelerator, 4 parts of galactooligosaccharide, 28 parts of skimmed milk powder；
The stabilizer is according to 1 by Momordica grosvenori, sea-buckthorn, myrobalan, radix polygonati officinalis and mulberries：0.3：0.2：0.7：0.5 weight is than system
；
The accelerator is according to 1 by garlic polysaccharide and blueberry anthocyanin：Made from 0.6 weight ratio.
Above-mentioned each raw material adds pharmaceutically acceptable auxiliary material and is conventionally prepared into granule, 1.5g/ bags.
Embodiment 5
A kind of probiotic composition for adjusting enteron aisle, is made of the raw material of following parts by weight：30 parts of bifidobacterium longum, sandlwood
Sugared 60 parts of lactobacillus, 5 parts of stabilizer, 6 parts of accelerator, 3 parts of galactooligosaccharide, 30 parts of skimmed milk powder；
The stabilizer is according to 1 by Momordica grosvenori, sea-buckthorn, myrobalan, radix polygonati officinalis and mulberries： 0.4：0.1：0.6：0.6 weight ratio
It is obtained；
The accelerator is according to 1 by garlic polysaccharide and blueberry anthocyanin：Made from 0.5 weight ratio.
Above-mentioned each raw material adds pharmaceutically acceptable auxiliary material and is conventionally prepared into pill, 1.5g/ balls.
Comparative example
A kind of probiotic composition for adjusting enteron aisle, is made of the raw material of following parts by weight：40 parts of bifidobacterium longum, sandlwood
Sugared 50 parts of lactobacillus, 4 parts of galactooligosaccharide, 25 parts of skimmed milk powder.
Above-mentioned each raw material adds pharmaceutically acceptable auxiliary material and is conventionally prepared into granule, 1.5g/ bags.
Human experimentation
According to the principle of voluntariness, select to be not suffering from gastrointestinal disease in nearly one month, do not take antibiotic, the age between 20-65 year,
The whole normal volunteers 120 of physical examination index.
Patient is randomly divided into 6 groups, every group of 20 people, each group general information comparing difference is counted without Tong and learns Yi Yi ﹙ P>0.05 ﹚,
With comparativity.Experimental group 1-5 takes sooner or later each edible a piece of/grain/bag/ball of probiotic composition of embodiment 1-3 preparations, right
The probiotic composition of comparative example preparation is taken according to group, it is sooner or later each edible one bag, continuously take 20 days.
Original eating habit and habits and customs, normal diet are not changed during experiment.
Experimental group and control group are after taking tested material and continuously taking tested material 20 days, and aseptic collection excrement carries out 10 respectively
It is serially diluted again, selects suitable dilution factor, be seeded on various culture mediums, cultivated on request respectively, then to culture
Thing carries out bacterium colony（Enterobacteria, enterococcus, Bifidobacterium, lactobacillus, bacteroid and Bacillus perfringens）Count, as a result such as table 1
It is shown.
Table 1 foretastes front and rear flora situation and compared（cfu/g）
As shown in Table 1, compared with control group, experimental group 1-5 Bifidobacterium and the quantity of lactobacillus dramatically increase, intestines bar
Bacterium, enterococcus, bacteroid and Bacillus perfringens quantity decrease.From the foregoing, the probiotic composition of the present invention
Have the function that to adjust gut flora balance.
Probiotic composition prepared by the present invention and comparative example is natural（Normal temperature）Under the conditions of deposit 18 months, the present invention production
The organoleptic indicators such as color, character, smell and the quality of product are normal, no generation significant change, every sense organ of comparative example product
There is slight abnormality in index, illustrates that probiotic composition stability prepared by the present invention is good.
Experiment in vitro
Mice pancreatic is damaged by the way of alloxan is injected intraperitoneally, so that blood glucose rise.Blood glucose value ＞ 10mM/L's
Mouse, it is believed that be hyperglycaemia mouse.Choose 20 hyperglycaemia mouse and be randomly divided into two groups, one group is experimental group, and one group is control
Group, two groups of general information comparing differences are counted without Tong and learn Yi Yi ﹙ P>0.05 ﹚, there is comparativity.The μ L sheets of experimental group continuous gavage 200
Invent the probiotic composition prepared（Final mass fraction is 20%）30 days；The μ L physiological saline 30 of control group continuous gavage 200
My god.In whole experiment process, every the body weight between the two groups of mouse of detection in 7 days, feed intake, amount of drinking water, change of blood sugar and small
The dynamic change of mouse gut flora.Animal test results show that body weight, feed intake and the drinking-water situation of experimental mice obtain
Obvious to improve, typical " three-many-one-little " symptom of diabetes gradually disappears；Compared to control group, the gut flora of experimental mice
Middle bacteroid quantity is reduced, and bifidobacteria increase.Adjusted it is thus regarded that the probiotic composition for inventing preparation not only has
Intestinal microflora is saved, the effect of strengthening immunity of organisms, also there is certain hypoglycemic function, be adapted to diabetic's food
With.
Claims (6)
1. a kind of probiotic composition for adjusting enteron aisle, it is characterised in that be made of the raw material of following parts by weight：Long bifid
Bacillus 30-50 parts, Lactobacillus rhamnosus 40-60 parts, stabilizer 5-10 parts, accelerator 6-8 parts, galactooligosaccharide 3-5 parts, degreasing
Milk powder 20-30 parts；
The stabilizer is according to 1 by Momordica grosvenori, sea-buckthorn, myrobalan, radix polygonati officinalis and mulberries：0.2-0.4：0.1-0.3：0.6-0.8：
Made from 0.4-0.6 weight ratio；
The accelerator is according to 1 by garlic polysaccharide and blueberry anthocyanin：Made from 0.5-0.9 weight ratio.
2. probiotic composition according to claim 1, it is characterised in that be made of the raw material of following parts by weight：
40 parts of bifidobacterium longum, 50 parts of Lactobacillus rhamnosus, 8 parts of stabilizer, 7 parts of accelerator, 4 parts of galactooligosaccharide, skimmed milk powder 25
Part.
3. probiotic composition according to claim 2, it is characterised in that the stabilizer is by Momordica grosvenori, sea-buckthorn, scolded
Son, radix polygonati officinalis and mulberries are according to 1：0.3：0.2：0.7：Made from 0.5 weight ratio.
4. probiotic composition according to claim 2, it is characterised in that the accelerator is by garlic polysaccharide and blueberry
Anthocyanidin is according to 1：Made from 0.7 weight ratio.
5. according to the probiotic composition any one of claim 1-4, it is characterised in that the probiotic composition is each
After raw material weighs by weight, pulvis, tablet, capsule, granule or pill is conventionally made.
6. probiotic composition according to claim 5, it is characterised in that the formulation of the probiotic composition is particle
Agent.
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| CN108142928A (en) * | 2017-12-25 | 2018-06-12 | 北京数果科技有限公司 | For the compound probiotic composition of intestinal canal regulating and its application |
| CN109393097A (en) * | 2018-12-10 | 2019-03-01 | 朱宇 | A kind of slim tea of relax bowel and defecation |
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| CN109393097A (en) * | 2018-12-10 | 2019-03-01 | 朱宇 | A kind of slim tea of relax bowel and defecation |
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Application publication date: 20171212 |