CN101450083B - Use of clostridium butyricum in preparing composition for treating newborn feeding intolerance - Google Patents

Use of clostridium butyricum in preparing composition for treating newborn feeding intolerance Download PDF

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CN101450083B
CN101450083B CN2007101967322A CN200710196732A CN101450083B CN 101450083 B CN101450083 B CN 101450083B CN 2007101967322 A CN2007101967322 A CN 2007101967322A CN 200710196732 A CN200710196732 A CN 200710196732A CN 101450083 B CN101450083 B CN 101450083B
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clostridium butyricum
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CN101450083A (en
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崔云龙
李洪福
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Beijing Puerkang Medical High Technology Co., Ltd.
Qingdao Donghai Pharmaceutical Co., Ltd.
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BEIJING PUERKANG MEDICAL HIGH TECHNOLOGY Co Ltd
QINGDAO EASTSEA PHARMACEUTICAL CO Ltd
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Abstract

The invention discloses an application of butanoic acid clostridium for preparing combination for treating feeding intolerance of newborn baby, especially relates to a new application of butanoic acid clostridium or a joint application of butanoic acid clostridium and one or more of bifidobacteria, coagulated bacillus, lactobacillus, streptococcus and bacillus subtilis for treating feeding intolerance of newborn baby. In which, the combination includes medicine, health food and drink.

Description

The application of clostridium butyricum in preparation treatment newborn feeding intolerance composition
Technical field
The present invention relates to the new medicine use of clostridium butyricum, be specifically related to clostridium butyricum as the application of main active ingredient in preparation treatment newborn feeding intolerance composition, belong to the biological medicament field.
Background technology
Feeding intolerance refers to owing to newborn infant especially premature infant and low Birth Weight intestinal mucosa growth imperfection, the digestive system function developmental immaturity, behind the beginning nutrition, the feeding intolerance problems such as vomiting, abdominal distension, gastric retention often occur, affect neonatal survival rate and life quality.Simultaneously, feeding intolerance newborn infant long period intravenous nutrition, be unfavorable for that the proliferate of newborn infant's intestinal mucosa and digestive system function reach maturity, and be prone to the complication such as cholestasis, hemorrhage, xanthochromia, necrotizing enterocolitis, secondary infection appears in severe patient, inspire multiple organ dysfunction syndrome, premature death rate, disability rate are raise.Main domperidone, metoclopramide, cisapride, Regular Insulin, the erythromycin etc. used promote digestive tract power reinforcing medicine treatment newborn feeding intolerance at present, not only can not promote fast intestinal function to reach maturity, and there are side effects such as extrapyramidal system untoward reaction, heart rate disorder, hypoglycemia, although the low dose of erythromycin of using is not found apparent side effect, but erythromycin belongs to antimicrobial drug, life-time service can cause alteration of intestinal flora and bacterial drug resistance occur, have potential side effect.
" Applied Clinical Pediatrics magazine " [2007 in 2007,22 (2): 138-139], He Xiangying etc. have delivered " golden bifid sheet treatment very low birth weight infant feeding intolerance ", by using bifidus bacillus, lactobacillus bulgaricus and the low Birth Weight feeding intolerance of thermophilus streptococcus treatment, but bifidus bacillus, Bacterium lacticum and thermophilus streptococcus just replenish intestinal beneficial bacterium, recover the intestinal microflora balance, and because bifidus bacillus, Bacterium lacticum and thermophilus streptococcus can not be secreted butyric acid (butyric acid), butyric acid is the energy derive of intestinal mucosa 70%, therefore, can not the promoting digestion system function reach maturity treatment feeding intolerance weak curative effect.
Therefore, searching can effectively promote newborn infant's peptic digestion phylogeny ripe, eliminates feeding intolerance, and safety without any the medicine of toxic side effect be clinical in the urgent need to.The inventor finds that through further investigation clostridium butyricum is different from bifidus bacillus, Bacterium lacticum and thermophilus streptococcus, clostridium butyricum medicine or composition enter enteron aisle can secrete a large amount of butyric acid, intestinal mucosa cells propagation and the required energy of growing are provided, the promoting digestion phylogeny is ripe, eliminates fast feeding intolerance, and safety is without any toxic side effect, it is healthy can not to damage the newborn infant, social effect is huge, and has no the correlative study report, special this patent of invention of application.
Summary of the invention
The present invention provides the application of clostridium butyricum in preparation treatment newborn feeding intolerance composition first, and wherein said pharmaceutical composition comprises medicine, healthcare products and drink etc.
The inventor confirms that after deliberation clostridium butyricum has significant therapeutic effect to newborn feeding intolerance.Described newborn infant comprises premature infant, full-term infants and postmature infant.
The inventor studies show that clostridium butyricum treatment newborn feeding intolerance mainly is by entering a large amount of butyric acid of intestinal secretion, the energy of intestinal mucosa 70% is provided, promote intestinal mucosa cells proliferate and digestive system development ripe, eliminate neonatal feeding by the feeding intolerance problems such as vomiting, abdominal distension, gastric retention often occurring, promote Growth of Neonates.The inventor studies confirm that clostridium butyricum through fermentation culture, can produce the butyric acid up to 40mmol/L.And bifidus bacillus, lactobacillus bulgaricus and thermophilus streptococcus be not owing to produce butyric acid, the short chain fatty acids such as the lactic acid of their secretions, acetic acid also must be converted into butyric acid and could be utilized by the intestinal mucosa cells metabolism, therefore, effectively the promoting digestion phylogeny is ripe, and the treatment newborn feeding intolerance does not far reach the result for the treatment of of clostridium butyricum.But clostridium butyricum can not produce with bifidus bacillus, Bacillus coagulans, Bacterium lacticum, suis, subtilis etc. the probiotic bacterium combined utilization of butyric acid, replenish simultaneously the multiple beneficial bacterium, Rapid Establishment intestinal microflora balance, play synergistic therapeutic action, further improve the curative effect for the treatment of newborn feeding intolerance.And clostridium butyricum, bifidus bacillus, Bacillus coagulans, Bacterium lacticum, suis, subtilis do not have toxic side effect, and its application dose also is that the clinician is easy to grasp and adjust according to the state of an illness.
Clostridium butyricum of the present invention is selected from but is not limited to clostridium butyricum (Clostridium butyricum), CGMCC, preservation numbering 0313.1.
Bifidus bacillus of the present invention is selected from but is not limited to bifidobacteria infantis (Bifidobacterium infantis), CGMCC, preservation numbering 0313.2, bifidus longum bb (Bifidobacterium longum), CGMCC, preservation numbering 0313.5, bifidobacterium breve (Bifidobacterium breve), CGMCC, preservation numbering 0313.6, bifidumbacterium bifidum claims again bifidobacterium (Bifidobacterium bifidum), CGMCC, preservation numbering 0313.7.
Bacillus coagulans of the present invention is selected from but is not limited to Bacillus coagulans (Bacillus coagulans), CGMCC, preservation numbering 1207.
Bacterium lacticum of the present invention is selected from but is not limited to Lactobacterium acidophilum (Lactobacillus acidophilus), CGMCC, preservation numbering 0313.4.
Suis of the present invention is selected from but is not limited to thermophilus streptococcus (Streptococcus thermophilus), CGMCC, preservation numbering 0313.3.
Subtilis of the present invention is selected from but is not limited to subtilis (Bacillus subtilis), CGMCC, preservation numbering 1887.
Clostridium butyricum of the present invention, bifidus bacillus, Bacillus coagulans, Bacterium lacticum, suis, subtilis refer to that living organism is individual.
The present invention is that clostridium butyricum with effective dose is according to top described as medicament active composition, according to certain preparation process, add the excipient substances such as conventional vehicle, seasonings, disintegrating agent, sanitas, lubricant, wetting agent, tamanori, solvent, thickening material, solubilizing agent, make any formulation that is suitable for using clinically, such as formulations such as tablet, capsule, granule, powder, liquid preparation, enemas.
Clostridium butyricum composition of the present invention can be that clostridium butyricum is made active bacteria formulation as active ingredient separately, also can be that active bacteria formulation is made in the combination of one or more in the probiotic bacterium or other active ingredients in clostridium butyricum and bifidus bacillus, Bacillus coagulans, Bacterium lacticum, suis, the subtilis, to play synergistic therapeutic action, improve the result for the treatment of to newborn feeding intolerance.
Indication effective dose of the present invention refers to can not be lower than 1 * 10 with clostridium butyricum according to total viable count that the top described solid live bacteria preparation of making as medicament active composition alone or in combination comprises 6CFU/g is generally 1 * 10 7More than the CFU/g, can reach 1 * 10 12CFU/g or 1 * 10 12More than the CFU/g.
Indication effective dose of the present invention refers to can not be lower than 1 * 10 with clostridium butyricum according to total viable count that the top described liquid active bacteria formulation of making as medicament active composition alone or in combination comprises 6CFU/mL is generally 1 * 10 7More than the CFU/mL, can reach 1 * 10 12CFU/mL or 1 * 10 12More than the CFU/mL.
The preferred preparation process of the present invention is, inoculates bacterial classification in the first liquid medium within, cultivates or multistage amplification cultivation, and is then that liquid culture is centrifugal, collects wet bacterium mud, and described bacterium mud is dry, sieve, obtain dry bacterium powder.The dry bacterium powder of gained is mixed with pharmaceutical carrier, make final formulation.Preparation process is not limited to of the present invention, and other known preparation process is all passable.
Because the present invention discloses the application in preparation treatment newborn feeding intolerance composition take clostridium butyricum as medicament active composition first; therefore; make medicament as medicament active composition and auxiliary material combination alone or in combination with clostridium butyricum; so long as this medicament is used for the treatment of newborn feeding intolerance, all belong to protection scope of the present invention.
Clostridium butyricum of the present invention all has the effect for the treatment of newborn feeding intolerance when making any formulation.Any medicament; prepare patent medicine if contain the clostridium butyricum composition in its component; as long as indicate or prompting has the effect for the treatment of newborn feeding intolerance, then fall within protection scope of the present invention on the signs such as its packing or specification sheets or at other any propaganda materials.
Clostridium butyricum of the present invention can be made healthcare products or drink.Healthcare products or drink with clostridium butyricum is made have the effect for the treatment of newborn feeding intolerance if need only to indicate or point out on the signs such as its packing or specification sheets or at other any propaganda materials, then fall within protection scope of the present invention.
Embodiment
The explanation of medicine preparation example: the preparation of the combined preparation of clostridium butyricum preparation or clostridium butyricum and other probiotic bacteriums is at first to prepare the bacterium powder, then doses as required corresponding auxiliary material and makes according to a conventional method final formulation.Used substratum in the bacterium powder preparation process, the known substratum of the art personnel is all passable.The preparation of the combined preparation of clostridium butyricum preparation of the present invention or clostridium butyricum and other probiotic bacteriums is all passable according to preparation process well known by persons skilled in the art, be not limited to method described below, the present invention specifically is prepared as example with oral clostridium butyricum viable bacteria powder, the preparation method of clostridium butyricum preparation is described, those skilled in the art are according to the preparation process that is easy to grasp the combined preparation of other formulation or clostridium butyricum and other probiotic bacterium of the present invention, be interest of clarity at this, the preparation method of the combined preparation of other formulation and clostridium butyricum and other probiotic bacterium omits, no longer one by one narration explanation.
The preparation of the oral clostridium butyricum viable bacteria of medicine Preparation Example powder
The preparation of 1 bacterium powder
Get one of clostridium butyricum strain tube, being dissolved in sterilizes is equipped with in the 100mL triangular flask of 10mL physiological saline and an amount of granulated glass sphere, 75 ℃ of water-baths activate 10 minutes, draw the 1mL bacteria suspension with the 1mL aseptic straw, inoculation is equipped with in the 250mL triangular flask of 50mL amplification culture medium, putting the interior 37 ℃ of constant temperature oscillations (190rpm) of rocking bed cultivated 24 hours, switching is equipped with in the 450mL amplification culture medium 2500mL plate washer triangular flask, 37 ℃ of constant-temperature shaking culture 24 hours, microscopy is transferred in the seeding tank that the 4.5L amplification culture medium is housed after without miscellaneous bacteria again, anaerobism was cultivated (aeration quantity 3: 1) 24 hours, microscopy is transferred after without miscellaneous bacteria to be had in the fermentor tank of 45L fermention medium, 37 ℃ of anaerobism were cultivated (aeration quantity 3: 1) 24 hours, and microscopy gemma rate reaches more than 80%, stopped to cultivate.Use continuous centrifuge, 12000rpm is centrifugal.Collect wet bacterium mud, weigh, add by 1: 1 (w/v) and freeze in protective material, freeze-drying, porphyrize is crossed 100 mesh sieves, and normal temperature saves backup.
The preparation of 2 finished products
According to the viable count of clostridium butyricum bacterium powder, add in proportion skim-milk, glucose, make viable count be not less than 1 * 10 6CFU/g, then pack.
Clinical observation on the therapeutic effect embodiment explanation: we have carried out the observation of curative effect of clostridium butyricum treatment newborn feeding intolerance, and carry out the curative effect contrast observing with bifidus bacillus, Bacillus coagulans, Bacterium lacticum, suis, subtilis.
Test example clostridium butyricum treatment newborn feeding intolerance observation of curative effect
1 data and method
1.1 data is selected feeding intolerance newborn infant 100 examples, Case definition: the performance of the gastrointestinal motility disorders such as clinical appearance vomiting, abdominal distension, gastric retention, in stomach tube, extract residual milk out before breast-feeding.All infants are all got rid of gi tract congenital malformation, occlusive ileus, anencephaly hepatic and kidney function obstacle and cardiac damage.Man's 48 examples, women 52 examples.By table of random number 100 routine newborn infants are divided into five groups, A group (clostridium butyricum treatment group), B group (clostridium butyricum, bifidus bacillus, Bacterium lacticum and suis treatment group), C group (bifidus bacillus, Bacterium lacticum and suis treatment group), D organize (Bacillus coagulans and subtilis treatment group) and control group.Every group of 20 routine infants, five groups of infant gestational ages, sex, body weight, severe extents are learned processing by statistics, and no significant difference has comparability.
1.2 all infants of method all give routine care, infusion pump fluid infusion, the conventional complex therapys such as treatment protopathy and Parenteral nutrition.
The A group: give oral clostridium butyricum viable bacteria powder (containing clostridium butyricum is 1.0 * 10 for Qingdao DongHai Pharmacy Co., Ltd's production, 500mg/ bag on conventional complex therapy basis 7CFU/g) oral, 1 bag/time, 3 times/d, the rear oral or nasal feeding of breast-feeding, the course for the treatment of is more than 7 days;
The B group: give oral clostridium butyricum, bifidus bacillus, Bacterium lacticum and suis tetragenous viable bacteria powder (Qingdao DongHai Pharmacy Co., Ltd produces on conventional complex therapy basis, the 500mg/ bag, containing clostridium butyricum, bifidus bacillus, Bacterium lacticum and suis respectively is 1.0 * 10 7CFU/g) oral, 1 bag/time, 3 times/d, the rear oral or nasal feeding of breast-feeding, the course for the treatment of is more than 7 days;
The C group: give Oral Bifidobacterium, Bacterium lacticum and suis live triple powder (containing bifidus bacillus, Bacterium lacticum and suis respectively is 1.0 * 10 for Qingdao DongHai Pharmacy Co., Ltd's production, 500mg/ bag on conventional complex therapy basis 7CFU/g) oral, 1 bag/time, 3 times/d, the rear oral or nasal feeding of breast-feeding, the course for the treatment of is more than 7 days:
The D group: give oral Bacillus coagulans and subtilis bigeminy viable bacteria powder (containing Bacillus coagulans and subtilis respectively is 1.0 * 10 for Qingdao DongHai Pharmacy Co., Ltd's production, 500mg/ bag on conventional complex therapy basis 7CFU/g) oral, 1 bag/time, 3 times/d, the rear oral or nasal feeding of breast-feeding, the course for the treatment of is more than 7 days;
Control group: conventional complex therapy, the course for the treatment of is more than 7 days.
1.3 observation index is observed four groups of symptom variation such as Neonatal Abdominal Distension, vomiting, gastric retention and gurgling sound, physiological weight loss returns to the baby weight time, the milk amount increases situation and records the time that the intravenous nutrition of stopping using reaches complete enteral nutritional support, have or not jaundice complication and jaundice time length, every day times of defecation, length of stay and having no adverse reaction.
1.4 curative effect judging standard produce effects: treat 3~5 days abdominal distension, symptoms of emesis and disappear, gurgling sound is normal, and nasal feeding is suckled every 2~3 hours 1 time, can tolerate, and stays without the gastric content storage; Take a turn for the better: treat 5~7 days abdominal distension, symptoms of emesis and alleviate, a little less than the gurgling sound, nasal feeding is suckled every 2~3 hours 1 time, gastric content retention<1/3; Invalid: treat 7 days abdominal distension, symptoms of emesis without improvement, a little less than the gurgling sound, nasal feeding is suckled every 2~3 hours 1 time, and the gastric content storage stays>and 1/3.Produce effects and improvement add up to effectively.
1.5 statistical procedures adopts SPSS11.0 software to carry out statistical procedures.Data all with X is relatively adopted in expression between group 2Check or t check have statistical significance take P<0.05 as difference.
2 results
2.1 four groups of curative effects compare A group produce effects 14 examples, 4 examples that take a turn for the better, invalid 2 examples, total effective rate 90%; B group produce effects 15 examples, 5 examples that take a turn for the better, invalid 0 example, total effective rate 100%; C group produce effects 8 examples, 4 examples that take a turn for the better, invalid 8 examples, total effective rate 60%; D group produce effects 6 examples, 6 examples that take a turn for the better, invalid 8 examples, total effective rate 60%; Control group produce effects 5 examples, 4 examples that take a turn for the better are without 11 effect examples, total effective rate 45%.Learn by statistics check, A group and B group total effective rate are significantly higher than C group, D group and control group, and difference has statistical significance (P<0.01), and B group total effective rate is higher than the A group, and difference has statistical significance (P<0.05).
2.2 two groups of observation index relatively return to the baby weight time, reach the complete enteral nutritional support time, vomiting and abdominal distension extinction time, the jaundice time length, A group and B group and C group, D group and control group are relatively, difference has statistical significance (P<0.01), and the B group compares with the A group, and difference has statistical significance (P<0.05); Every day, times of defecation and length of stay compared, and A organizes and the B group organizes with C group, D and control group compares, and difference has statistical significance (P<0.01), and the B group compares with the A group, and difference has statistical significance (P<0.05) to see Table 1.
Table 1 liang group treatment fore-and-aft observing index comparison (
Figure S2007101967322D00061
± s)
Observation index The A group The B group The C group The D group Control group
Return to the baby weight time (my god) reach (my god) vomiting extinction time (my god) abdominal distension extinction time (my god) jaundice time length (my god) times of defecation every day (inferior) length of stay of complete enteral nutritional support time ?8.36±1.42?14.14±1.56?4.59±1.32?4.65±1.43?14.46±2.48?2.52±0.73?21.58±4.46 ?7.01±1.23?13.03±1.63?3.76±1.43?3.11±1.43?13.21±1.98?3.10±0.65?20.14±3.29 ?9.98±1.83?15.96±1.54?6.45±1.68?6.50±1.58?17.56±1.64?2.31±0.52?24.15±5.76 ?9.87±1.75?15.67±1.85?6.56±1.75?6.70±1.61?17.98±1.76?2.34±0.61?24.41±5.24 ?10.85±2.13?17.32±2.16?7.38±1.49?7.45±1.57?19.55±2.41?2.02±0.67?25.74±5.21
3 discuss
Test-results shows, bifidus bacillus, Bacterium lacticum and suis live triple treatment group and Bacillus coagulans and the subtilis bigeminy viable bacteria treatment group of being better than evident in efficacy of clostridium butyricum treatment newborn feeding intolerance.Can a large amount of butyric acid of specific secretion mainly due to clostridium butyricum, the energy of intestinal mucosa propagation and growth is provided, the promoting digestion phylogeny is ripe, and bifidus bacillus, Bacterium lacticum, thermophilus streptococcus, Bacillus coagulans and subtilis be not owing to produce butyric acid, the short chain fatty acids such as the lactic acid of their secretions, acetic acid also must be converted into butyric acid and could be utilized by the intestinal mucosa cells metabolism, therefore, effectively the promoting digestion phylogeny is ripe, and the treatment newborn feeding intolerance does not far reach the result for the treatment of of clostridium butyricum.But the effect of clostridium butyricum and bifidus bacillus, Bacterium lacticum and suis combined utilization is better than the result for the treatment of that clostridium butyricum is used separately, show that one or more bacterium combined utilization in clostridium butyricum and bifidus bacillus, Bacillus coagulans, Bacterium lacticum, suis, the subtilis have synergistic therapeutic action, acetic acid and the lactic acid of giving birth to mainly due to bifidus bacillus, Bacillus coagulans, Bacterium lacticum, suis, producing bacillus subtilis are utilized by clostridium butyricum, having produced more butyric acid is the intestinal mucosa utilization, has improved result for the treatment of.Utilize clostridium butyricum or clostridium butyricum and bifidus bacillus, Bacillus coagulans, Bacterium lacticum, suis, one or more bacterium combined utilization treatment newborn feeding intolerances in the subtilis are evident in efficacy, and clostridium butyricum, bifidus bacillus, Bacillus coagulans, Bacterium lacticum, suis, subtilis all belongs to probiotics, can not produce any toxic side effect to the newborn infant, therefore, clostridium butyricum or clostridium butyricum and bifidus bacillus, Bacillus coagulans, Bacterium lacticum, suis, one or more bacterium combined utilization treatment neonatal feedings in the subtilis are not anti-to be that newborn feeding intolerance is treated the important breakthrough on the history, significant.
The present invention in implementation process employed microbial strains respectively on July 28th, 1997, on August 23rd, 2004 and on December 15th, 2006 in (No. 13, North No.1 Row, Zhongguancun, Haidian District, Beijing City, China Committee for Culture Collection of Microorganisms common micro-organisms center, Institute of Microorganism, Academia Sinica's postcode 100080) preservation, totally nine following microbial strainss, but clostridium butyricum of the present invention, bifidus bacillus, Bacterium lacticum, suis, Bacillus coagulans, subtilis are not limited to this nine kinds of microbial strainss.
(1) Classification And Nomenclature: clostridium butyricum Clostridium butyricum, preserve numbering 0313.1.
(2) Classification And Nomenclature: bifidobacteria infantis Bifidobacterium infantis, preserve numbering 0313.2.
(3) Classification And Nomenclature: thermophilus streptococcus (Streptococcus thermophilus), preserve numbering 0313.3.
(4) Classification And Nomenclature: Lactobacterium acidophilum (Lactobacillus acidophilus), preserve numbering 0313.4.
(5) Classification And Nomenclature: bifidus longum bb Bifidobacterium longum, preserve numbering 0313.5.
(6) Classification And Nomenclature: bifidobacterium breve Bifidobacterium breve, preserve numbering 0313.6.
(7) Classification And Nomenclature: bifidobacterium Bifidobacterium bifidum, preserve numbering 0313.7.
(8) Classification And Nomenclature: Bacillus coagulans Bacillus coagulans, preserve numbering 1207.
(9) Classification And Nomenclature: subtilis (Bacillus subtilis), preserve numbering 1887.
Above-mentioned nine microbial strainss are through this microorganism Spot detection, and detected result is survival.

Claims (14)

1. the application of clostridium butyricum in preparation treatment newborn feeding intolerance preparation, it is characterized in that described preparation activeconstituents is comprised of clostridium butyricum, or formed by one or more viable bacterias in clostridium butyricum and bifidus bacillus, Bacterium lacticum, suis, Bacillus coagulans, the subtilis.
2. by the described application of claim 1, it is characterized in that described preparation refers to medicine, healthcare products or drink.
3. by the described application of claim 1, it is characterized in that clostridium butyricum, bifidus bacillus, Bacterium lacticum, suis, Bacillus coagulans, subtilis refer to the biont that lives.
4. by the described application of claim 1, it is characterized in that clostridium butyricum is selected from clostridium butyricum CGMCC0313.1 strain.
5. by the described application of claim 1, it is characterized in that bifidus bacillus is selected from bifidobacteria infantis CGMCC0313.2 strain, bifidus longum bb CGMCC0313.5 strain, bifidobacterium breve CGMCC 0313.6 strain, bifidobacterium CGMCC0313.7 strain; Bacillus coagulans is selected from Bacillus coagulans 1207 strains; Bacterium lacticum is selected from Lactobacterium acidophilum CGMCC0313.4 strain; Suis is selected from thermophilus streptococcus CGMCC0313.3 strain; Subtilis is selected from subtilis CGMCC1887 strain.
6. by the described application of claim 1, it is characterized in that the newborn infant refers to premature infant, full-term infants and postmature infant.
7. by the described application of claim 1, it is characterized in that promoting that the newborn infant grows, recover complete enteral nutritional support, control vomiting, abdominal distension and jaundice reduce the hospital stays and recover normal defecation.
8. by the described application of claim 1, it is characterized in that oral or the nasal feeding application.
9. by the described application of claim 1, it is characterized in that the viable count that solid live bacteria preparation that clostridium butyricum is made as medicament active composition alone or in combination contains is not less than 1 * 10 6CFU/g.
10. by the described application of claim 1, it is characterized in that the viable count preferred 1 * 10 that solid live bacteria preparation that clostridium butyricum is made as medicament active composition alone or in combination contains 7More than CFU/g reaches.
11. by the described application of claim 1, it is characterized in that the viable count preferred 1 * 10 that solid live bacteria preparation that clostridium butyricum is made as medicament active composition alone or in combination contains 12More than CFU/g reaches.
12. by the described application of claim 1, it is characterized in that the viable count that liquid active bacteria formulation that clostridium butyricum is made as medicament active composition alone or in combination contains is not less than 1 * 10 6CFU/mL.
13. by the described application of claim 1, it is characterized in that the viable count preferred 1 * 10 that liquid active bacteria formulation that clostridium butyricum is made as medicament active composition alone or in combination contains 7More than CFU/mL reaches.
14. by the described application of claim 1, it is characterized in that the viable count preferred 1 * 10 that liquid active bacteria formulation that clostridium butyricum is made as medicament active composition alone or in combination contains 12More than CFU/mL reaches.
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CN1178703A (en) * 1997-08-06 1998-04-15 北京东方百信生物技术有限公司 Gastrointestinal tract preparation for bady and its producing technology

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