CN1119154C - Live triple bifidobacteria preparation and preparing method thereof - Google Patents
Live triple bifidobacteria preparation and preparing method thereof Download PDFInfo
- Publication number
- CN1119154C CN1119154C CN98110623A CN98110623A CN1119154C CN 1119154 C CN1119154 C CN 1119154C CN 98110623 A CN98110623 A CN 98110623A CN 98110623 A CN98110623 A CN 98110623A CN 1119154 C CN1119154 C CN 1119154C
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- CN
- China
- Prior art keywords
- viable
- faecalis
- acidophilus
- preparation
- bifidobacterium bifidum
- 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.)
- Expired - Lifetime
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Abstract
The present invention relates to a triple bifidobacteria viable bacterium preparation (Peifeikang), which is prepared from bifidobacteria bifidum (6-1), streptococcus faecalis, lactobacilli and a protective agent. The triple bifidobacteria viable bacterium preparation can be used for treating digestive system diseases, such as dyspepsia, chronic diarrhea, acute diarrhea, flora imbalance, etc., has the purpose of health care, and provides a preparing method.
Description
The invention belongs to microniological proudcts, be specifically related to a kind of Bifid Triple Viable and preparation method.
Bacillus bifidus, lactobacillus and streptococcus faecalis are common normal flora important members in the humans and animals body, concentrate and stick to the lower intestinal tract mucosa, to body performance beneficial effect, can suppress the invasion of foreign nationality pathogen, its metabolite provides the host essential vitamin, participates in and assist the digestion and the absorption of nutrition.The immunologic function of excitating organism reduces the toxic absorption of intestinal source property.Because digestive system disease or use antibiotic and with advancing age in a large number, bacillus bifidus reduces gradually in the body.For keeping the normal level of above-mentioned probiotics, people begin one's study and contain the preparation of these probioticss.As the SANZHU KOUFUYE and the method for making thereof of Chinese patent CN1103584 report, it contains bacillus bifidus, Lactobacillus acidophilus and streptococcus faecalis.But this stability of Oral is poor, and the survival rate of bacterium is low, unsuitable long preservation.
The objective of the invention is to overcome the shortcoming of above-mentioned oral liquid, design the high three bacterium associating goods of a kind of good stability, survival rate easy to use, bacterium.
The invention provides a kind of Bifid Triple Viable (Birid Triple Viable); said preparation is by bifidobacterium bifidum (6-1); lactobacillus and streptococcus faecalis lyophilization viable bacteria powder are formed as active ingredient and protective agent; and can be 0.01～99.99% to be that any proportioning of 99.99～0.01% is formed 100% composition by containing active ingredient with containing protective agent; wherein bifidobacterium bifidum (6-1) and lactobacillus and streptococcus faecalis can be by 1～5: 1～5: 1～5 arbitrary proportion is formed active ingredient, and protective agent can be for containing defatted milk powder 10-20%; isolactose 10-20%; vitamin C-sodium 0.01-0.2%; sodium glutamate 0.01-2%; vitamin E 0.01-2%; beta-schardinger dextrin-6-20%; the arbitrary proportion of starch 6-20% is formed protective agent.
Strain of the present invention source and biological property thereof are as follows:
Strain source and biological property thereof
1, strain source
(1) bifidobacterium bifidum (6-1) is separated, is granted by Inst. of Epidemiology and Microbiology, Chinese Academy of Preventive Medicine (.
Choose fresh excreta 0.5 gram of healthy children (1-5 year), put mixing in 4.5 milliliters of PBS diluents, and do 10 times of serial dilutions, get suitable concn and be coated with the BL flat board, 37 ℃ of anaerobism were cultivated 72 hours.The bacillus bifidus that on the BL flat board, grows, bacterium colony is rounded, and is outstanding slightly, indivedual concaves, color is brown more, and coffee-like canescence or milky are opaque, have smooth or rough type, the about 0.5-2.0 millimeter of diameter.The pure culture of picking colonies typical is also done aerobic test, in numerous colonies typicals, has chosen bacillus bifidus 6-1 strain.Through microscopy, biochemical reactions and in conjunction with the analysis of metabolite is accredited as bifidobacterium bifidum (6-1) (B.bifidum6-1 strain).The results are shown in Table one, qualification result meets: BuchananBL et al (1977): the description of relevant Bifidobacterium bifidum in the Bergeys Mannual of Determimative Bacteriology 8th ed book.
Not tally bacillus bifidus of table one and bifidobacterium bifidum (6-1)
The physicochemical characteristics comparison sheet of strain
(2) source of Lactobacillus acidophilus and streptococcus faecalis
| The bacterial strain project | Bifidobacterium bifidum | Bifidobacterium bifidum (6-1) |
| Gram | G + | G + |
| Power | - | - |
| Catalase test | - | - |
| U.S. blue milk test | - | - |
| The milk setting test | + | + |
| The 6.5%NaCl meat extract | - | - |
| Gelatin liquefaction test | - | - |
| Sugar fermentating test | ||
| Glucose | + | + |
| Lactose | + | + |
| Maltose | - | + |
| Raffinose | - | + |
| Sucrose | - | - |
| Sorbitol | - | - |
| Mannitol | - | - |
| 45 ℃ of anaerobism are cultivated | - | - |
| 45 ℃ of aerobic cultivations | - | - |
Lactobacillus acidophilus (L.acidophilus YIT2004) and streptococcus faecalis (Strep.faecalis YIT0027) are all given by Gifu, Japan pharmaceutical university.
2, biological property
(1) cultural characteristic and thalli morphology
37～38 ℃ of optimum growth temperatures, PH6.5-7.4 are grown in (6-1) strain of A bifidobacterium bifidum (Bifidobacterium bifidum) under anaerobism or little oxygen condition.72 hours bacterium colony of anaerobism or little oxygen cultivation is rounded on the BL flat board, projection, milky, smooth, toughness, not of uniform size.
Gram-positive, painted inhomogeneous, no brood cell, no pod membrane, atrichia, thalline is straight shape or bending, the forked of " Y " or " V " type can occur, and is bar-shaped etc. polymorphic.
B Lactobacillus acidophilus Lactobacillus acidophilus YIT2004 is facultative anaerobe, and 37～40 ℃ of optimum growth temperatures can be grown optimal pH 5.5-6.5 under 45 ℃ of conditions.48 hours bacterium colony of aerobic cultivation is rounded on the BL flat board, protuberance, milky, smooth, about 1 millimeter of diameter.
Gram-positive, the quarter butt of no brood cell, no pod membrane, atrichia, the blunt circle in two ends or club shape, single or become double row.
C streptococcus faecalis Streptococcus Faecalis YIT 0027 is facultative anaerobe, and 37～40 ℃ of optimum growth temperatures can well be grown under 45 ℃ of conditions, optimal pH 6.5-7.6, and 24 hours bacterium colony of aerobic cultivation is rounded, protruding on the BL flat board.Canescence, smooth.
Gram-positive, no brood cell, no pod membrane, atrichia, oval become double row more, also become short chain.
The stability test result of Bifid Triple Viable of the present invention (Birid Triple Viable) is as follows:
The table 2 Birid Triple Viable capsule measurement result that keeps sample
Conclusion:
| Lot number | Storage period | Former viable bacteria amount B.B CFU/G L.A CFU/G S.F CFU/G | Measurement result viable bacteria amount B.B CFU/G L.A CFU/G S.F CFU/G | ||||
| 1 | 6 months | 1.00E+09 | 8.00E+07 | 1.50E+07 | 1.00E+09 | 2.50E+07 | 1.60E+07 |
| 2 | 6 months | 1.00E+09 | 8.00E+07 | 2.00E+07 | 1.00E+09 | 3.00E+07 | 1.00E+07 |
| 3 | 6 months | 1.00E+09 | 6.00E+07 | 4.00E+06 | 1.00E+08 | 3.10E+07 | 1.60E+06 |
| 4 | 6 months | 3.00E+09 | 2.50E+07 | 4.00E+07 | 2.00E+09 | 1.00E+07 | 1.30E+07 |
| 5 | 6 months | 1.50E+09 | 2.00E+08 | 6.00E+07 | 3.00E+08 | 3.00E+07 | 2.00E+07 |
| 6 | 6 months | 8.00E+08 | 8.00E+07 | 4.00E+07 | 3.00E+08 | 2.00E+07 | 2.00E+07 |
Birid Triple Viable its total viable count when dispatching from the factory is 1.9～6.5 hundred million CFU/g.Put in the refrigerator and preserved 1 year, its total viable count can reach 6,700,000～3,000 ten thousand CFU/g.
Table 3 bacillus bifidus lyophilized powder stability test result (reserve temperature 2-8 ℃)
| Lot number | Storage period | Initial viable count CFU/G | Measure viable count CFU/G | Situation of change |
| 1 | 1 year | 3.5E+09 | 1.00E+10 | No change |
| 2 | 6 months | 2.20E+09 | 2.70E+09 | No change |
| 3 | 6 months | 1.70E+10 | 2.70E+09 | E+01 falls |
| 4 | 1 year | 3.00E+07 | 1.00E+07 | No change |
| 5 | 1 year | 1.00E+07 | 1.10E+07 | No change |
| 6 | 1 year | 300E+07 | 2.40E+06 | E+01 falls |
Table 4 lactobacillus lyophilized powder stability test result (reserve temperature 2-8 ℃)
| Lot number | Storage period | Initial viable count CFU/G | Measure viable count CFU/G | Situation of change |
| 1 | 1 year | 4.6×10 9 | 1×10 8 | E+01 falls |
| 2 | 1 year | 3.0×10 9 | 1.7×10 8 | E+01 falls |
| 3 | 1 year | 1.7×10 9 | 5.0×10 7 | E+02 falls |
| 4 | 10 months | 3.0×10 9 | 2.0×10 8 | E+01 falls |
| 5 | 6 months | 1.0×10 11 | 8×10 10 | E+01 falls |
| 6 | 6 months | 2.0×10 10 | 1.0×10 10 | No change |
Table 5 streptococcus faecalis lyophilized powder stability test result (reserve temperature 2-8 ℃)
| Lot number | Storage period | Initial viable count CFU/G | Measure viable count CFU/G | Situation of change |
| 1 | 1 year | 3.0×10 10 | 3.0×10 9 | E+01 falls |
| 2 | 1 year | 3.0×10 10 | 2.8×10 9 | E+01 falls |
| 3 | 1 year | 2.0×10 10 | 1.5×10 9 | E+01 falls |
| 4 | 11 months | 6.0×10 9 | 3.5×10 8 | E+01 falls |
| 5 | 6 months | 3.0×10 10 | 5×10 9 | E+01 falls |
| 6 | 6 months | 3.0×10 10 | 2.2×10 10 | No change |
It is as follows that the general pharmacology of Bifid Triple Viable of the present invention (Birid Triple Viable) is learned the development test result: one, material and method: animal: three of Canis familiaris L.s are respectively 10Kg, 12Kg, 12Kg.Be numbered 1#, 2#, 3#.Medicine: (every contains the 210mg mycopowder to the Birid Triple Viable capsule, includes bifidobacterium bifidum (6-1) 4 * 10
6CFU, Lactobacillus acidophilus 4 * 10
6CFU, streptococcus faecalis 2 * 10
7CFU).Route of administration: observation acute observation that is administered once after three days in oral three days.Drug dose: 1#, 210mg * 50 (be people's dosage 50 times); 210mg * 24 (be people's dosage 20 times); 3#, 210mg * 12 (be people's dosage 10 times).Three, conclusion:
Three oral Birid Triple Viable capsules of Canis familiaris L. (large, medium and small dosage) back ANOMALOUS VARIATIONS all do not occur to nervous system, cardiovascular system and respiratory frequency and the degree of depth.
The pharmacodynamic study result of the test of Bifid Triple Viable of the present invention (Birid Triple Viable) is as follows:
For inquiring into Bifid Triple Viable (Birid Triple Viable) mechanism of action and the antagonism of pathogenic entero becteria are renderd a service.We add excrement chain bacterium and finished product preparation with the bifidobacterium bifidum in the preparation (6-1), Lactobacillus acidophilus respectively, and the antagonism of Song Nei Shi and shigella flexneri has been carried out preliminary study.
Material 1, strain and preparation:
Bifidobacterium bifidum (6-1) (B.bifidum 6-1),
Lactobacillus acidophilus (L.acidophilus YIT 2004),
Streptococcus faecalis (Strep.faecalis YIT 0072),
Bacillus ceylonensis A (Shigella sonnei 73)
Shigella flexneri (Shigella flexneri 301),
Bifid Triple Viable (Birid Triple Viable, 970107,970721) 2, culture medium lot number::
PYG soup, BL agar, LB agar.3, other:
Aerobic, anaerobism culture apparatus, test tube, suction pipe, triangular flask, plate.
Method
In process of the test, used strain needs to cultivate under same environmental condition.Through pilot study, we have selected PYG soup for use is culture fluid, has verified used strain well-grown all under 37 ℃, anaerobic condition.And done the logarithmic growth curves of various bacterium respectively with this condition.One, bifidobacterium bifidum (6-1) is to the antagonism of bacillus ceylonensis A: 1, the preparation of Song Salmonella liquid:
Inoculation Song Salmonella (inoculum concentration about 10 in the triangular flask that contains 100ml PYG soup
3CFU/ml), put 37 ℃, anaerobic condition cultivation 5 hours (being the mid-log phase of this bacterium this moment) down.Get the every pipe 6ml of 12 Boiling tubes of this culture fluid packing, packet numbering is: O, A, B, C, every group of tee pipe.2, the preparation of bacillus bifidus liquid:
Inoculating bifidobacterium is (inoculum concentration about 10 in the triangular flask that contains 50ml PYG soup
3CFU/ml), put 37 ℃, anaerobic condition cultivation 16 hours (mid-log phase of this bacterium at this moment) down, make bacterium liquid (1).With PYG bacterium liquid (1) is done 10 times, 100 times dilutions and make bacterium liquid (2), (3).3, Mixed culture:
Get bacterium liquid (1), (2), (3) and A, B, C respectively and respectively organize Song Salmonella mixed in equal amounts in the test tube; In 0 group of tee pipe, add 6ml PYG soup respectively as contrast.Get O group bacterium liquid this moment and be coated with the dull and stereotyped count plate of LB, respectively organize Song Salmonella value in the test tube when being zero; Get bacterium liquid (1) and be coated with the dull and stereotyped count plate of BL, A, B, C respectively organize the bacillus bifidus value in the test tube when conversing zero.
Above four groups of 12 test tubes are put cultivation under 37 ℃ of anaerobic conditions, and the different time sampling is coated with LB plate count Song Salmonella value.Two, the Lactobacillus acidophilus adds streptococcus faecalis to the antagonism 1 of bacillus ceylonensis A, the preparation of Song Salmonella liquid: the preparation of (same) 2, lactobacillus and streptococcus faecalis:
Inoculating lactobacillus and streptococcus faecalis (inoculum concentration about 10 in the triangular flask that contains 50ml PYG soup respectively
3CFU/ml), put under 37 ℃, anaerobic condition, cultivate 11 and make two kinds of bacterium liquid 5 hours (this moment be respectively the two mid-log phase) respectively, get that the two equivalent is mixed makes bacterium liquid (1), with PYG soup bacterium liquid (1) is done 10 times, 100 times dilutions and make bacterium liquid (2), (3).3, Mixed culture: (class is same) three, Bifid Triple Viable (Birid Triple Viable) are to the preparation of antagonism 1, Song Shi and the good fortune Salmonella liquid of Song Nei Shi and shigella flexneri: the preparation of (class is same) 2, preparation suspension:
The aseptic powder 5g that takes by weighing in the preparation adds in the 45ml PYG soup mixing and makes suspension (1), with PYG soup (1) liquid is done 10 times of dilutions and makes serial suspension.3, Mixed culture: (class is same)
The result
In vitro, Bifid Triple Viable all has tangible antagonism to Song Nei Shi and shigella flexneri, but internal energyly kills above-mentioned two kinds of bacterium fully in 48 hours, and its minimum inhibitory concentration is 0.5-1mg/ml.
Three kinds of bacterium in the preparation embody time sequencing (the antibacterial usefulness of the preferential performance of streptococcus faecalis and Lactobacillus acidophilus is followed by bifidobacterium bifidum (6-1)) and cooperative effect in antibacterial process.
The animal toxicity test result of Bifid Triple Viable of the present invention (Birid Triple Viable) is as follows: 1, general toxicity test:
Get preparation and dilute cold one-tenth suspension with physiological saline solution, respectively footpath tail vein injection, lumbar injection, filling stomach, (be equivalent to more than 4,000 times of people's per kilogram consumption for the dosage that every group every mice contains 1,600,000 viable bacterias, computational methods are seen below), (three groups, 20 mice/groups, body weight 20-25 gram, male and female half and half), observed seven days.2, seven days continuous toxicity tests:
With bifidobacterium bifidum (6-1) liquid, give the dosage of 2,900,000 viable bacterias of every white mice (be equivalent to 7,000 times of people's per kilogram consumption, computational methods are with 1) through irritating stomach.The triple bifidobacteria bacteria preparation is through irritating the dosage that stomach contains 3,600 ten thousand bacterium for every mice (be equivalent to 90,000 times of people's per kilogram consumption, computational methods are with 1).Establish normal saline matched group (every group of 20 Mus, body weight 20-25 gram, male and female half and half) simultaneously and give seven days continuously by above-mentioned dosage every day.(kunming mice grinds animal housing of institute by preventive medicine academy of science stream and provides).3, toxicity test result:
Animal ingestion in the process of the test, movable normal, have no adverse reaction, body weight rises, and test group and control animals body weight gain amplitude do not have marked difference.During off-test, general toxicity test, none only death of continuous each treated animal of toxicity test in seven days.Above result proves, the bifidobacterium bifidum in the Bifid Triple Viable (6-1), Lactobacillus acidophilus and the equal avirulence of streptococcus faecalis.
The result that Bifid Triple Viable of the present invention (Birid Triple Viable) is studied the safety of bifidobacterium fermentation by animal experiment and human trial shows:
One, this milk product is to the Switzerland white mice, Shanghai white No. 1/F 26+13 white mice, and NIH closed colony white mice, SD pure lines rat and Japanese white big ear rabbit do not have acute toxicity, cumulative toxicity and zest.
Three mutagenicity tests are all negative, show that bacillus bifidus does not have mutagenicity.
Two, from this milk product 24 trial volunteers are tried the human trial in January and the result in 1 year of tracing study as can be known, human body healthy and safe do not found ill effect.
The result is as follows in Bifid Triple Viable of the present invention (Birid Triple Viable) clinical research: one, MethodsThe cases enrolled
1, adult's acute diarrhea: (1) light-duty or plain edition acute bacillary dysentery:
*Light-duty--body temperature is below 38 ℃, and clinical symptoms is not obvious, and the diarrhoea number of times is no more than 4-5 time/day, The stool is completely mashed, naked eyes lose pus and blood, cultivate positive.
*About plain edition--body temperature 38-39 ℃, leukocyte＜20,000/ml has slight tenesmus, defecates 5-15 time/day, band mucus or pus and blood, conscious, no drowsiness, convulsions, cardiovascular function is good, breathes steadily.(2) agnogenio acute diarrhea (comprise bacillary and viral etc.); Onset is anxious, and unclean dietary history is arranged, diarrhoea water just＞3 time/day, and the stool outward appearance does not have pus and blood, microscopy high power field leukocyte＜15.
2, adult's chronic diarrhea: stool＞2-3 time/day, the stool character is undesired, continues more than 2-3 month, shows effect repeatedly and guilty party again in the recent period.
3, the adult is constipation: stool＞2-3 days/time, and dry stool is dry and hard, and difficult defecation is arranged, and often needs to rely on glycerin or intestine moistening agent, and symptom continues above person of 1 week.
4,0 of acute and chronic diarrhoea of the various causes of disease of children's (infectious and non-infectious) or constipation
+--the outpatient service of 13 one full year of life or the sick child that is in hospital.
Two, research method
Intend separating tests and contrast two groups carrying out, compare treatment with Birid Triple Viable and lactasinum with double blinding and open matching type.Research approach is formulated according to " medicine for digestive system clinical research guideline " and " specification requirement of new biological product anthroposcopy " that Ministry of Public Health bureau of drug administration issues by Beijing Friendship Hospital's Digestive System Department and clinical pharmacology chamber, and participates in clinical research unit and pass through discussion through each.Constituent parts is in strict accordance with the requirement of scheme, by unified charting.The qualified case that data is complete can be decided to be can estimate case.
Statistical procedures adopts X 2 test and Ridit to analyze according to data with different.
Three, medication and dosage patient inactive other medicines (antibiotic, hormone, other diarrhea or intestine moistening agent) before treatment, the random packet administration; The double blinding group is given identical Birid Triple Viable and the lactasinum capsule of profile.The adult: 5/time, 2-3 time/day; Child: 0
+--1 years old 1/time, 2/time of 1--6 years, 3/time of 6--13 years, 3 times/day.The peelable capsule that comes unglued of child is poured out the powder warm boiled water.
Four, conclusion:
1, this clinical research is with light, the medium-sized acute diarrhea of Birid Triple Viable treatment adult or child and agnogenic chronic diarrhea totally 401 examples; With lactasinum contrast treatment 139 examples.Comprehensive therapeutic effect: test group, obvious effective rate are 58.6%, effective percentage is 38.9%, total effective rate is 87.5%; Matched group the three be respectively: 28.1%50.4% 22.3%.Two groups of curative effects relatively have significant difference (P＜0.05), illustrate that Birid Triple Viable treatment diarrhoea is better than lactasinum.Contrast is respectively organized curative effect as can be seen, and the effect of Birid Triple Viable treatment acute diarrhea is better than treating chronic diarrhea (the two curative effect has been compared significant difference P＜0.05).The total effective rate of treatment adult and acute diarrhea in children is respectively 92.3% and 90.7% (wherein produce effects person accounts for the master, is respectively 76.9% and 59.0%); Total effective rate to chronic diarrhea then is respectively: 80.0% and 76.3% (wherein produce effects person is respectively: 43.6% and 39.0%).
2, Birid Triple Viable is except can be used for treating the agnogenic diarrhoea, and is still effective in cure to infectious diarrhea (cause of disease comprises: dysentery bacterium, Salmonella, coliform, campylobacter jejuni, Aeromonas and rotavirus etc. cause a disease).Detect pathogen (antibacterial class) before 52 example treatments are arranged in the test group, have 8 examples to detect rotavirus, have 50 examples (96.2%) to turn out cloudy in 52 examples of treatment back, though do not do virus examination behind the 8 routine rotaviral enteritis patient treatments, whole produce effects.The negative conversion rate of matched group pathogen only 50%, two group notable difference (P＜0.01) is relatively arranged.
Though 3, Birid Triple Viable not as good as to acute diarrhea, truly has certain effect to the curative effect of chronic diarrhea.All have before most chronic diarrhea patients test in various degree clothes other drug and do not have positive effect, or be diagnosed as " irritable bowel syndrome " for a long time, take behind the Birid Triple Viable child patient recovery from illness of 80.0% adult and 76.3% or take a favorable turn.
4, the true tool of Birid Triple Viable is adjusted the function of intestinal microbial population.From testing result to 19 example adults and the forward and backward main intestinal flora of 16 routine children's diarrhae patient treatments, treat preceding patient all in various degree have an intestinal flora disorder, mainly show: enterobacteria etc. are aerobic or facultative anaerobe is higher, anaerobe such as bacillus bifidus are on the low side, the treatment back is along with the disappearance above-mentioned condition of clinical symptoms improves, and it is normal that intestinal flora recovers substantially.
5, Birid Triple Viable has 4 examples effectively in these research 6 examples aspect the treatment constipation.
6, this clinical trial finds to take the person that has the apparent side effect behind the Birid Triple Viable, confirms that these product are safe.
Another object of the present invention has provided the preparation method of above-mentioned Bifid Triple Viable (Birid Triple Viable), and this method comprises the following steps:
The yeast extract of the aqueous solution of defatted milk powder 3.5～4.0% and 1.0% glucose and 3% was placed in the pressure cooker 121 ℃ of sterilizations 10 minutes; be cooled to 37～38 ℃ of bifidobacterium bifidums (6-1) that place in three jars respectively and under aseptic condition, inoculate 10% amount respectively; streptococcus faecalis and lactobacillus; then at 37～38 ℃; intrinsic pressure 0.3～0.6 kg/cm fermentation of jar; wherein bifidobacterium bifidum (6-1) is for filling the nitrogen anaerobic fermentation; streptococcus faecalis and lactobacillus are the filtrated air fermentation; the centrifugal bacterium mud that gets of fermentation back 2000rpm; add the equivalent protective agent; lyophilization; lyophilized powder, then the lyophilized powders of three bacterium is mixed the back and adds starch and pregelatinized Starch and cross 40 mesh sieves and mix back fill capsule (210mg/ grain) or make granule according to a conventional method; tablet.
Bifid Triple Viable of the present invention (Birid Triple Viable) is through Ministry of Public Health pharmaceutical biological product calibrating, and it is as follows that newspaper examine and determine by institute: strain identification (form, dyeing, cultural characteristic, oxytolerant test, biochemical reaction): qualified count plate: qualified escherichia coli counting: the qualified bacterium number of always mixing: qualified safety test: qualified potency test: qualified general comment: qualified
Bifid Triple Viable of the present invention (Birid Triple Viable) can be used for the treatment of digestive system disease such as dyspepsia, acute and chronic diarrhea, dysbacteriosis, and health purpose is arranged, and good social benefit and economic worth are arranged.
Example one, preparation Bifid Triple Viable Capsule
In three jars, add defatted milk powder 7kg respectively, glucose 12kg, yeast powder 500g is dissolved in the 200kg water, transfers about PH6.5.121 ℃; sterilization in 10 minutes; in each jar, inoculate 10% bifidobacterium bifidum (6-1), 18 hours postcooling of 37 ℃ of cultivations of anaerobism then respectively; Lactobacillus acidophilus and streptococcus faecalis; cultivate 20 hours postcooling at aerobic 37 ℃, centrifugal respectively getting about bacterium mud 8kg adds the protective agent mixing; freeze cool-drying at-40 ℃, get about mycopowder 5kg.Above-mentioned three mycopowder are mixed, add amylum pregelatinisatum 20kg, magnesium stearate 400 grams, cross 40 mesh sieves, directly the fill capsule.
Protective agent prescription: defatted milk powder 2kg, sodium glutamate 400 grams, isolactose 3kg, be dissolved in the water of the 12kg left and right sides, sterilized 15 minutes for 121 ℃.
Example two, preparation Birid Triple Viable tablet
Defatted milk powder 10kg, glucose 2kg, yeast powder 1kg, ammonium sulfate 500 grams, potassium dihydrogen phosphate 150g, dipotassium hydrogen phosphate 300g is dissolved in the 200kg water, regulates PH7.0.
121 ℃, example one operation is pressed in sterilization in 10 minutes then, will obtain adding beta-schardinger dextrin-2kg after three lyophilizing mycopowder mix and pulverize, and adds amylum pregelatinisatum 20kg, lactose 2kg, mixes 24 mesh sieves, tabletting.
The protective agent prescription is 2.: defatted milk powder 2kg, vitamin E2 0g, isolactose 3kg, sodium ascorbate 30g, water 12kg, 121 ℃, sterilization in 10 minutes.
Example three, preparation Birid Triple Viable granule
Defatted milk powder 7kg, glucose 1.2kg, yeast powder 500g, water 200kg regulate PH7.0, and 121 ℃, sterilization in 10 minutes.Press example one operation then, after three lyophilizing mycopowder that obtain are mixed, make granulated milk powder 17kg, mix, cross 12 mesh sieves with mycopowder with 0.1%HPMC solution, aluminum-plastic packaged.
Protective agent prescription (with 1.).
Example four, preparation Birid Triple Viable tablet
Defatted milk powder 8kg, glucose 2kg, yeastex powder 1.0kg, water 200kg.Regulate PH6.5,121 ℃, sterilization in 10 minutes.Press example 1 operation then, will make three kinds of lyophilizing mycopowder, sneak into beta-schardinger dextrin-2kg, amylum pregelatinisatum 16kg, lactose 4kg, ethyl cellulose 4kg, mixed 24 mesh sieves, tabletting.
Protective agent (with 2.)
Example five, preparation Bifid Triple Viable Capsule
Defatted milk powder 7kg, glucose 1.2kg, yeast powder 500g, water 200kg regulate PH6.5, and 121 ℃, sterilization in 10 minutes.Other is with example one.
Example six, preparation Birid Triple Viable granule
Defatted milk powder 10kg, glucose 2kg, yeast powder 1.0kg, ammonium sulfate 500g, potassium dihydrogen phosphate 150g, dipotassium hydrogen phosphate 300g is dissolved in the 200kg water, regulates about PH7.0,121 ℃, sterilization in 10 minutes.Press example one operation then, will make three kinds of lyophilizing mycopowder and mix, sneak into beta-schardinger dextrin-2kg, add and use the milk powder 17kg of 0.1%HPMC solution granulation mixed, cross 12 mesh sieves, make granule, aluminum-plastic packaged.
Protective agent (with 2.).
Claims (4)
1, a kind of Bifid Triple Viable; it is characterized in that said preparation is made up of as active ingredient and protective agent bifidobacterium bifidum (6-1), Lactobacillus acidophilus (L.acidophilus YIT2004) and streptococcus faecalis (Strep.faecalis YIT0027) lyophilization viable bacteria powder, the ratio of wherein said bifidobacterium bifidum (6-1), Lactobacillus acidophilus (L.acidophilus YIT2004) and streptococcus faecalis (Strep.faecalis YIT0027) is 1-5: 1-5: 1-5.
2, a kind of Bifid Triple Viable according to claim 1 is characterized in that wherein said protective agent is defatted milk powder 10-20%, isolactose 10-20%, vitamin C-sodium 0.01-0.2%, sodium glutamate 0.01-2%, vitamin E 0.01-2%, beta-schardinger dextrin-6-20%, starch 6-20%.
3, a kind of method for preparing the Bifid Triple Viable of claim 1 or 2 is characterized in that this method comprises the following steps:
The aqueous solution of 3.5-4.0% defatted milk powder and the yeast extract of 1.0% glucose and 3% are placed in the pressure cooker; sterilize 121 ℃ 10 minutes; after being cooled to 37-38 ℃; place respectively in three jars; and under aseptic condition; in three jars, inoculate the bifidobacterium bifidum (6-1) of 10% amount respectively; Lactobacillus acidophilus (L.acidophilus YIT2004) and streptococcus faecalis (Strep.faecalis YIT0027); then at 37-38C; the intrinsic pressure 0.3-0.6 kg/cm fermentation of jar; the centrifugal bacterium mud that gets of fermentation back 2000rpm; add the equivalent protective agent; lyophilization gets lyophilized powder; after the lyophilized powder mixing with three bacterium, add starch and pregelatinized Starch then, cross 40 mesh sieves and mix back fill capsule or make tablet according to a conventional method; granule.
4, the preparation method of Bifid Triple Viable according to claim 3, it is characterized in that wherein said bifidobacterium bifidum (6-1) adopts fills the nitrogen anaerobic fermentation, and Lactobacillus acidophilus (L.acidophilus YIT2004) and streptococcus faecalis (Strep.faecalis YIT0027) adopt filtrated air to ferment.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98110623A CN1119154C (en) | 1998-01-20 | 1998-01-20 | Live triple bifidobacteria preparation and preparing method thereof |
| GB9901267A GB2338244B (en) | 1998-01-20 | 1999-01-20 | A microbe composition, a method to prepare the same and uses thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98110623A CN1119154C (en) | 1998-01-20 | 1998-01-20 | Live triple bifidobacteria preparation and preparing method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1223865A CN1223865A (en) | 1999-07-28 |
| CN1119154C true CN1119154C (en) | 2003-08-27 |
Family
ID=5220654
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN98110623A Expired - Lifetime CN1119154C (en) | 1998-01-20 | 1998-01-20 | Live triple bifidobacteria preparation and preparing method thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN1119154C (en) |
| GB (1) | GB2338244B (en) |
Cited By (4)
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| CN100400649C (en) * | 2006-05-12 | 2008-07-09 | 河北农业大学 | Composite protective agent for direct injection type pure bifidobacterium freeze-dried starter |
| CN101244090B (en) * | 2007-02-16 | 2011-12-28 | 信谊药厂 | Long bifidobacterium culture medium, preparation and technique |
| CN103079581A (en) * | 2010-05-28 | 2013-05-01 | 热尔韦·达诺尼公司 | Probiotic strains for use in improving transepithelial resistance |
| CN101244089B (en) * | 2007-02-16 | 2013-09-25 | 信谊药厂 | Lactobacillus acidophilus/enterococcus faecalis culture medium, preparations and technique |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100400649C (en) * | 2006-05-12 | 2008-07-09 | 河北农业大学 | Composite protective agent for direct injection type pure bifidobacterium freeze-dried starter |
| CN101244090B (en) * | 2007-02-16 | 2011-12-28 | 信谊药厂 | Long bifidobacterium culture medium, preparation and technique |
| CN101244089B (en) * | 2007-02-16 | 2013-09-25 | 信谊药厂 | Lactobacillus acidophilus/enterococcus faecalis culture medium, preparations and technique |
| CN103079581A (en) * | 2010-05-28 | 2013-05-01 | 热尔韦·达诺尼公司 | Probiotic strains for use in improving transepithelial resistance |
| CN103079581B (en) * | 2010-05-28 | 2015-08-05 | 热尔韦·达诺尼公司 | Probiotic strains for improved transepithelial resistance |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1223865A (en) | 1999-07-28 |
| GB9901267D0 (en) | 1999-03-10 |
| GB2338244B (en) | 2003-04-30 |
| GB2338244A (en) | 1999-12-15 |
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