CN101264107A - Bacillus licheniformis medicinal composition and preparations thereof - Google Patents
Bacillus licheniformis medicinal composition and preparations thereof Download PDFInfo
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- CN101264107A CN101264107A CNA2008100113305A CN200810011330A CN101264107A CN 101264107 A CN101264107 A CN 101264107A CN A2008100113305 A CNA2008100113305 A CN A2008100113305A CN 200810011330 A CN200810011330 A CN 200810011330A CN 101264107 A CN101264107 A CN 101264107A
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- bacillus licheniformis
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Abstract
The invention discloses a bacillus licheniformis drug combination and the preparation, which comprises pharmaceutical live bacteria powder and suitable accessories. The bacillus licheniformis drug combination is characterized in that: living bacteria number of bacillus licheniformis for each g of the combination is 0.5 to 2.5 billion and preferred number is 1 to 2 billion; volume per weight for each suitable accessories are dispersing agent 70% to 95%, adhesive 1% to 20%, disintegrating agent 1% to 6%, lubricant 0.1% to 1% and coating liquid1% to 10% respectively. The drug combination is specific release preparation using bacillus licheniformis as active ingredient. Enteric-coated preparation is preferred and enteric-coated tablet, enteric-coated capsule and enteric-coated granule are more preferred. Survival rate experiments shows that: only 2.17% survives after live bacteria powder is orally taken for 4 hours and 93.7% to 95.2% survives after the preparation is orally taken. So the bacillus licheniformis drug combination has an advantage of overcoming the drawbacks of acid nonresistance and no survival for microecology liver bacteria under gastric-acid environment.
Description
Technical field
The invention belongs to the medical biotechnology field, relate to a kind of little ecological pharmaceutical composition, contain Bacillus licheniformis and suitable adjuvant and can reach the effect that the location discharges.
Background technology
Microbial ecological agent is active bacteria formulation (Biogen), bacteria-promoting agent, probiotics (Probitics) again, it is under little ecological theory instructs, by lactobacillus, bacillus cereus. beneficial microbes such as yeast (PM), biological preparation or the active bacteria formulation produced through special process such as compound cultivation, fermentation, drying, processing, it can replenish the normal microorganism that lacks or lack in the animal intestinal on quantity or kind, adjust or keep microecological balance in the intestinal, improve the also immune function of enhancing body, improve the anti-stress ability of body.
The probiotic bacteria that is applied to human body at present has bacillus bifidus, lactobacillus, enterococcus, escherichia coli, bacillus subtilis, wax sample bud enterobacteria, bacillus licheniformis, Clostridium butyricum and yeast etc.
Microbial ecological agent can be used for preventing and treating the various constipation of treatment, antineoplaston, alleviation, hepatic encephalopathy, chronic hepatitis and liver cirrhosis, the acute pancreatitis of diarrhoea, irritable bowel syndrome, inflammatory bowel, helicobacter pylori clinically.Microbial ecological agent safeguards that to disease preventing and treating human beings'health plays an important role.
But little ecological active bacteria formulation is not acidproof, can not survive under gastric acid environment.Therefore exploitation and development enteric dosage form active bacteria formulation are significant.
Summary of the invention
The object of the present invention is to provide bacillus licheniformis medicinal composition and preparation thereof, the pharmaceutical composition that will contain Bacillus licheniformis and be active component is delivered to site of action with enteric coated preparation, to improve the survival rate of viable bacteria.
A kind of bacillus licheniformis medicinal composition comprises medicinal viable bacteria powder and suitable adjuvant, it is characterized in that containing the Bacillus licheniformis viable count in every gram compositions is 5～2,500,000,000, preferred 10～2,000,000,000.Suitable adjuvant comprises diluent, binding agent, disintegrating agent, lubricant and/or coating materials.Each component volume/weight ratio is respectively: diluent 70～95%, binding agent 1～20%, disintegrating agent 1～6%, lubricant 0.1～1%, coating solution 1～10%.
Said composition discharges medicine for the location, preferred enteric coated preparation, more preferably enteric coated tablet, enteric coated capsule, enteric coated granule.
Bacillus licheniformis is the little ecological active bacteria formulation of active component, enter in the intestinal with viable bacteria formation after Bacillus licheniformis is oral, in growth metabolism, can produce multiple antibacterial substance, as Gramicidin, subtilin, nystatin and cephalosporin etc., so staphylococcus and yeast-like fungus are all had obvious antagonism.Bacillus licheniformis is aerobic double anaerobe, under aerobic, little oxygen and oxygen free condition, can both ramp breed, consume the free oxygen in the ecological environment simultaneously, have ecology and take the oxygen effect by force, cause low-oxygen environment, promote useful physiological flora of intestinal such as growths such as bacillus bifidus, lactobacillus, bacteroid and peptostreptococcus, suppress major part and advocate aerobic pathogenic bacterium growth and breeding, recover intestinal eubiosis, make diarrhoea wait remission or disappearance.
The same with other active bacteria formulation, Bacillus licheniformis also has acid nonfast characteristics, so the present invention compares with enteric dosage form and gastric solubleness dosage form, and the viable bacteria survival rate is higher than the gastric solubleness dosage form far away in the enteric dosage form, makes it to become microbial ecological agent efficiently.
The suitable adjuvant that relates in the above-mentioned composition comprises diluent, binding agent, disintegrating agent, lubricant and coating materials.
Above-mentioned diluent is meant in sweet lactose, pregelatinized Starch, microcrystalline Cellulose, starch, mannitol, polyvinylpolypyrrolidone and the sucrose one or more.Above-mentioned binding agent is meant one or more in acrylic resin, poloxamer, hydroxypropyl emthylcellulose, microcrystalline Cellulose, polyvidone, methylcellulose, ethyl cellulose, carboxymethyl cellulose and the polyvinylpyrrolidone.Above-mentioned disintegrating agent is one or more in methylcellulose, polyvidone, modified starch, hydroxyethylmethyl-cellulose, carboxymethyl starch sodium, the low-substituted hydroxypropyl cellulose.Above-mentioned lubricant is meant one or more in octadecanol, stearic acid, magnesium stearate, Pulvis Talci, Polyethylene Glycol, the micropowder silica gel.Above-mentioned coating materials is meant in titanium dioxide, acrylic resin, methylcellulose, poloxamer, Polyethylene Glycol, polyvidone, polyvinylpyrrolidone, Opadry series, the enteric coating coating materials one or more.
The specific embodiment
The preparation method of present composition enteric coated capsule is: take by weighing Bacillus licheniformis viable bacteria powder, disintegrating agent, diluent according to percentage by weight, add fluidizer behind the crushing screening, mix homogeneously, the enteric coated capsule of packing into.
The preparation method of said composition enteric coated tablet is: take by weighing Bacillus licheniformis viable bacteria powder, disintegrating agent, diluent according to percentage by weight, and mix homogeneously behind the crushing screening, guiding humid medium or binding agent system soft material are granulated, granulate, tabletting, the bag sealing coat, enteric coated.
The preparation method of this enteric coated particles is: take by weighing Bacillus licheniformis viable bacteria powder, disintegrating agent, diluent according to percentage by weight, mix homogeneously behind the crushing screening, guiding humid medium or binding agent system soft material, granulate granulate, bag sealing coat, enteric coated, packing promptly behind the drying and moulding.
This enteric coated granule can also prepare by the following method: take by weighing Bacillus licheniformis viable bacteria powder, disintegrating agent, diluent according to percentage by weight, and mix homogeneously behind the crushing screening, the bag sealing coat, enteric coated.
Following examples are explanation of the invention and explanation, but do not limit the present invention.
Embodiment 1
Get Bacillus licheniformis viable bacteria powder 10kg (contain 30,000,000,000 of viable bacterias in every gram viable bacteria powder, down with), lactose 70kg, starch 170kg pulverized behind 100 mesh sieves behind the mix homogeneously, the enteric coated capsule of packing into, every gram compositions contains 1,200,000,000 of Bacillus licheniformis.
Embodiment 2
Get Bacillus licheniformis viable bacteria powder 18kg, microcrystalline Cellulose 320kg, lactose 120kg, magnesium stearate 36kg pulverized behind 100 mesh sieves behind the mix homogeneously, the enteric coated capsule of packing into, every gram compositions contains 10.9 hundred million of Bacillus licheniformis.
Embodiment 3
Get Bacillus licheniformis viable bacteria powder 10kg, starch 150kg, lactose 40kg, carboxymethyl starch sodium 30kg pulverized mix homogeneously behind 100 mesh sieves, added 2% hydroxypropyl emthylcellulose and made soft material in right amount, 18 order system wet granulars, 40 ℃ of dryings, 16 mesh sieve granulate, add magnesium stearate 0.5kg, behind the mix homogeneously, tabletting wraps sealing coat and enteric coating respectively, promptly, every gram compositions contains 12.1 hundred million of Bacillus licheniformis after the packing.
Embodiment 4
Get Bacillus licheniformis viable bacteria powder 12kg, microcrystalline Cellulose 158kg, spray-dried lactose 44kg, low-substituted hydroxypropyl methylcellulose 15kg, Pulvis Talci 20kg, mix homogeneously behind the crushing screening, direct compression, enteric coated, promptly, every gram compositions contains 14.3 hundred million of Bacillus licheniformis after the packing.
Embodiment 5
Get Bacillus licheniformis viable bacteria powder 18kg, microcrystalline Cellulose 250kg, amylum pregelatinisatum 110kg, hydroxy methocel 20kg, lactose 60kg, magnesium stearate 0.25kg, mix homogeneously behind the crushing screening, direct compression, enteric coated, promptly, every gram compositions contains 11.7 hundred million of Bacillus licheniformis after the packing.
Embodiment 6
Get Bacillus licheniformis viable bacteria powder 10kg, pregelatinized Starch 150kg, lactose 40kg, crospolyvinylpyrrolidone 25kg pulverized mix homogeneously behind 100 mesh sieves, added 8% starch slurry and made soft material in right amount, 18 order system wet granulars, 40 ℃ of dryings, 16 mesh sieve granulate, add micropowder silica gel 0.25kg, behind the mix homogeneously, tabletting, enteric coated, promptly, every gram compositions contains 12.8 hundred million of Bacillus licheniformis after the packing.
Embodiment 7
Get Bacillus licheniformis viable bacteria powder 25kg, microcrystalline Cellulose 200kg, starch 180kg, Sodium Hydroxymethyl Stalcs 9kg pulverized mix homogeneously behind 100 mesh sieves, added 5% polyvidone and made soft material in right amount, 18 order system wet granulars, 40 ℃ of dryings, 16 mesh sieve granulate add magnesium stearate 0.7kg, behind the mix homogeneously, tabletting, enteric coated, every gram compositions contains 18.1 hundred million of Bacillus licheniformis.
Embodiment 8
Get Bacillus licheniformis viable bacteria powder 25kg, starch 310kg, lactose 130kg, low-substituted hydroxypropyl methylcellulose 20kg pulverized mix homogeneously behind 80 mesh sieves, add 10% starch slurry and make soft material in right amount, 20 order system wet granulars, 40 ℃ of dryings, 18 mesh sieve granulate, the enteric coated capsule of packing into, every gram compositions contains 15.5 hundred million of Bacillus licheniformis.
Embodiment 9
Get Bacillus licheniformis viable bacteria powder 25kg, mannitol 50kg, starch 200kg, microcrystalline Cellulose 150kg, crospolyvinylpyrrolidone 27kg, pulverized mix homogeneously behind 80 mesh sieves, and added 4% polyvidone and make soft material in right amount, 20 order system wet granulars, 40 ℃ of dryings, 18 mesh sieve granulate, the enteric coated capsule of packing into, every gram compositions contains 16.5 hundred million of Bacillus licheniformis.
Embodiment 10
Get Bacillus licheniformis viable bacteria powder 1kg, lactose 13.6kg crosses behind 100 mesh sieves behind the mix homogeneously, with Opadry II is that coating solution carries out powder coating, adds the 5.6kg magnesium stearate in granule, packs behind the mixing, get enteric coated particles, every gram compositions contains 14.4 hundred million of Bacillus licheniformis.
Embodiment 11
Get Bacillus licheniformis viable bacteria powder 1.5kg, starch 5kg, microcrystalline Cellulose 15kg, cross behind 100 mesh sieves behind the mix homogeneously, with Opadry II is that coating solution carries out powder coating, adds the 2.0kg micropowder silica gel in granule, packs behind the mixing, get enteric coated particles, every gram compositions contains 19.1 hundred million of Bacillus licheniformis.
Embodiment 12
Get Bacillus licheniformis viable bacteria powder 2.5kg, starch 15kg, lactose 30kg, carboxymethyl starch sodium 1.0kg pulverized behind 80 mesh sieves behind the mix homogeneously, added 10% starch slurry and made soft material in right amount, 20 order system wet granulars, 40 ℃ of dryings, 18 mesh sieve granulate, enteric coated, add the 5.5kg magnesium stearate, pack behind the mixing, get enteric coated particles, every gram compositions contains 12.5 hundred million of Bacillus licheniformis.
Embodiment 13
Get Bacillus licheniformis viable bacteria powder 5.0kg, microcrystalline Cellulose 30kg adds 2% hydroxypropyl methylcellulose and makes soft material in right amount, and is enteric coated, and pack gets enteric coated particles, and every gram compositions contains 1,100,000,000 of Bacillus licheniformis.
Enteric coated preparation of the present invention and viable bacteria powder handled 4h in simulated gastric fluid (pH 1.2) after, viable bacteria survival rate relatively.
Table 1 Bacillus licheniformis enteric coated preparation and the viable bacteria powder acid resistance in simulated gastric fluid relatively
| Dosage form | Former bacterium number | Viable count behind the 4h | Survival rate % |
| The viable bacteria powder | 3.0×10 10 | 6.51×10 8 | 2.17 |
| Embodiment 1 | 1.01×10 9 | 9.50×10 8 | 94.1 |
| Embodiment 2 | 9.1×10 8 | 8.63×10 10 | 94.9 |
| Embodiment 3 | 1.05×10 9 | 1.00×10 9 | 95.2 |
| Embodiment 4 | 1.03×10 9 | 9.65×10 8 | 93.7 |
By table 1 result as can be seen, enteric coated preparation has been avoided gastric acid contact lichens bacillus living, has improved the viable bacteria acid resistance greatly.
Enteric coated preparation of the present invention is carried out release conditions research in simulated intestinal fluid, the results are shown in Table 2.
The viable bacteria release of table 2 Bacillus licheniformis enteric coated preparation in simulated intestinal fluid
| Dosage form | Former bacterium number | Viable count behind the 30min | Release % |
| Embodiment 1 | 1.01×10 9 | 9.99×10 8 | 98.9 |
| Embodiment 2 | 9.1×10 8 | 8.96×10 8 | 98.5 |
| Embodiment 3 | 1.05×10 9 | 1.04×10 9 | 98.7 |
| Embodiment 4 | 1.03×10 9 | 1.02×10 9 | 99.0 |
Table 2 is the result show: enteric coated preparation has played the effect of enteric, makes the Bacillus licheniformis viable bacteria increase and protects barrier together.
Claims (4)
1, a kind of bacillus licheniformis medicinal composition comprises medicinal viable bacteria powder and suitable adjuvant, it is characterized in that containing the Bacillus licheniformis viable count in every gram compositions is 5～2,500,000,000, preferred 10～2,000,000,000.
2, according to the described pharmaceutical composition of claim 1, it is characterized in that being fit to adjuvant and comprise diluent, binding agent, disintegrating agent, lubricant and/or coating materials, each component volume/weight ratio is respectively: diluent 70～95%, binding agent 1～20%, disintegrating agent 1～6%, lubricant 0.1～1%, coating solution 1～10%.
3,, it is characterized in that being fit to diluent in the adjuvant and be meant in lactose, pregelatinized Starch, microcrystalline Cellulose, starch, mannitol, polyvinylpolypyrrolidone and the sucrose one or more according to claim 1 bacillus licheniformis medicinal composition; Binding agent is meant one or more in acrylic resin, poloxamer, hydroxypropyl emthylcellulose, microcrystalline Cellulose, polyvidone, methylcellulose, ethyl cellulose, carboxymethyl cellulose and the polyvinylpyrrolidone; Disintegrating agent is one or more in methylcellulose, polyvidone, modified starch, hydroxyethylmethyl-cellulose, carboxymethyl starch sodium, the low-substituted hydroxypropyl cellulose; Lubricant is meant one or more in octadecanol, stearic acid, magnesium stearate, Pulvis Talci, Polyethylene Glycol, the micropowder silica gel; Coating materials is meant in titanium dioxide, acrylic resin, methylcellulose, poloxamer, Polyethylene Glycol, polyvidone, polyvinylpyrrolidone, Opadry series, the enteric coating coating materials one or more.
4, the described bacillus licheniformis medicinal composition preparation of a kind of claim 1 is characterized in that said composition is that the location discharges medicine, preferred enteric coated preparation, more preferably enteric coated tablet, enteric coated capsule, enteric coated granule.
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2008100113305A CN101264107A (en) | 2008-05-09 | 2008-05-09 | Bacillus licheniformis medicinal composition and preparations thereof |
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| CNA2008100113305A CN101264107A (en) | 2008-05-09 | 2008-05-09 | Bacillus licheniformis medicinal composition and preparations thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101537020B (en) * | 2009-04-24 | 2012-05-02 | 东北制药集团公司沈阳第一制药厂 | Synbiotics of bacillus licheniformis and oligosaccharide class prebiotics and composition and formulation thereof |
| CN103099821A (en) * | 2013-02-01 | 2013-05-15 | 东北制药（沈阳）科技发展有限公司 | High-dose bacillus licheniformis viable bacterium composition as well as preparation method and application thereof |
| CN104206702A (en) * | 2013-09-06 | 2014-12-17 | 郑州后羿制药有限公司 | Veterinary bacillus subtilis microcapsule preparation and preparation method thereof |
| CN109566863A (en) * | 2019-01-18 | 2019-04-05 | 湖北华扬科技发展有限公司 | Feed addictive and its preparation method and application |
| CN111714467A (en) * | 2019-03-21 | 2020-09-29 | 浙江京新药业股份有限公司 | Live bacillus enteric-coated capsule and preparation method thereof |
| US10967011B2 (en) * | 2013-02-04 | 2021-04-06 | Seres Therapeutics, Inc. | Compositions and methods |
-
2008
- 2008-05-09 CN CNA2008100113305A patent/CN101264107A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101537020B (en) * | 2009-04-24 | 2012-05-02 | 东北制药集团公司沈阳第一制药厂 | Synbiotics of bacillus licheniformis and oligosaccharide class prebiotics and composition and formulation thereof |
| CN103099821A (en) * | 2013-02-01 | 2013-05-15 | 东北制药（沈阳）科技发展有限公司 | High-dose bacillus licheniformis viable bacterium composition as well as preparation method and application thereof |
| WO2014117679A1 (en) * | 2013-02-01 | 2014-08-07 | 东北制药集团股份有限公司 | High-dosage bacillus licheniformis viable bacteria composition and preparation method and use thereof |
| US10967011B2 (en) * | 2013-02-04 | 2021-04-06 | Seres Therapeutics, Inc. | Compositions and methods |
| US11730775B2 (en) | 2013-02-04 | 2023-08-22 | Seres Therapeutics, Inc. | Methods for treatment of Clostridium difficile infection or recurrence or symptoms thereof |
| CN104206702A (en) * | 2013-09-06 | 2014-12-17 | 郑州后羿制药有限公司 | Veterinary bacillus subtilis microcapsule preparation and preparation method thereof |
| CN104206702B (en) * | 2013-09-06 | 2016-08-10 | 郑州后羿制药有限公司 | A kind of bacillus subtilis microcapsule formulation for animals and preparation method thereof |
| CN109566863A (en) * | 2019-01-18 | 2019-04-05 | 湖北华扬科技发展有限公司 | Feed addictive and its preparation method and application |
| CN111714467A (en) * | 2019-03-21 | 2020-09-29 | 浙江京新药业股份有限公司 | Live bacillus enteric-coated capsule and preparation method thereof |
| CN111714467B (en) * | 2019-03-21 | 2023-10-24 | 浙江京新药业股份有限公司 | Bacillus licheniformis viable bacteria enteric capsule and preparation method thereof |
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Open date: 20080917 |