CN107865891A - A kind of probiotic composition, preparation, bacterium mud and purposes - Google Patents

A kind of probiotic composition, preparation, bacterium mud and purposes Download PDF

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Publication number
CN107865891A
CN107865891A CN201711077820.0A CN201711077820A CN107865891A CN 107865891 A CN107865891 A CN 107865891A CN 201711077820 A CN201711077820 A CN 201711077820A CN 107865891 A CN107865891 A CN 107865891A
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Prior art keywords
probiotics
probiotic
probiotic composition
streptococcus salivarius
gel
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CN107865891B (en
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杜俊蓉
胡英
杨雪琴
黎慧
谈增
薛丽
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Sichuan University
Zhejiang University ZJU
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Sichuan University
Zhejiang Medical College
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs

Abstract

The invention discloses a kind of probiotic composition, including lactobacillus acidophilus, streptococcus salivarius M18, streptococcus salivarius K12.The present invention is advantageous to the Regeneration of Alveolar Bone destroyed, while can suppress the growth of Periodontal Pathogens, and can prevent and treat periodontitis to a certain extent can effectively suppress periodontosis, solve the unsound problem of modern's tooth.

Description

A kind of probiotic composition, preparation, bacterium mud and purposes
Technical field
The present invention relates to field of pharmaceutical biology, and in particular to a kind of probiotic composition, preparation, bacterium mud and purposes.
Background technology
It medically will be around and be covered in periodontal soft tissue being referred to as gum, the acute and chronic for betiding gingiva tissue is scorching Disease is referred to as gingivitis (gingivitis).Bleeding gums are shown as, red and swollen, distending pain, continues development and invades sclerous tissues, produce periodontal Inflammation, including the inflammation of gingiva tissue and general disease are in the performance of gum.
Periodontosis refers to the disease in tooth supporting tissue (periodontium) occurs, including only involves the gingivitis of gingiva tissue With the major class of periodontitis two for involving deep layer periodontium (parodontium, alveolar bone, cementum).Periodontal disease is common oral cavity disease Disease, it is one of the main reason for causing adult's loss of tooth, and endangers the main oral disease of human teeth and whole body health Disease.
The early symptom of periodontosis is not easy to draw attention, and causes periodontium long-term chronic to infect, inflammation recurrent exerbation, no The function of oral cavity masticatory system is only damaged, can also have a strong impact on health.
Therefore, researching and developing a kind of medicine of new treatment tooth portion disease has very real meaning.
The content of the invention
It is an object of the invention to provide a kind of probiotic composition, the probiotic composition is advantageous to the alveolar bone destroyed Regeneration, while the growth of Periodontal Pathogens can be suppressed, can prevent and treat periodontitis to a certain extent can effectively suppress Periodontosis, solves the unsound problem of modern's tooth.Additionally provide a kind of preparation, bacterium mud and purposes.
The present invention is achieved through the following technical solutions：
A kind of probiotic composition, including lactobacillus acidophilus, streptococcus salivarius M18, streptococcus salivarius K12.
In terms of clump count, lactobacillus acidophilus 10-30%, streptococcus salivarius M18 are 10-50%, and streptococcus salivarius K12 is 20-80%.
It is 10% by lactobacillus acidophilus in terms of clump count, streptococcus salivarius M18 is 10%, and streptococcus salivarius K12 is 80% Composition.
A kind of probiotics preparation, it is made up of preceding described probiotic composition and pharmaceutically acceptable carrier or auxiliary material.
Probiotics preparation, it is probiotic gel agent or probiotics buccal piece.
A kind of probiotics bacterium mud, it is made by preceding described probiotic composition through cultivating centrifuge washing.
When probiotics preparation is probiotic gel agent, it is prepared into by preceding described probiotic composition after bacterium mud or through culture Bacterium mud made from centrifuge washing is mixed to prepare with gel-type vehicle afterwards.
Gel-type vehicle is Macromolecule glue material, bioadhesive material, NMF, distilled water composition, described macromolecule Material is the one or more in carbomer, poloxamer, hydroxypropyl cellulose, hydroxypropyl methyl cellulose sodium, chitosan；Institute The bioadhesive material stated is the one or more in Sodium Hyaluronate, hydroxypropyl methyl cellulose, sodium alginate；Described guarantor Humectant is the one or more in glycerine, propane diols polyethylene glycol, glycerine, sorbierite.
When probiotics preparation is probiotics buccal piece, preceding described probiotic composition is prepared into probiotic composition and frozen Dry powder, then direct tablet compressing is made after auxiliary material is mixed with Freeze-dry Powder of Probioctics.
A kind of purposes of foregoing probiotic composition on treatment periodontitis or periodontal medicine is prepared.
The present invention compared with prior art, has the following advantages and advantages：
Present invention mixing probiotics it is mutual excite the oral environment that dental health existence is given with inhibitory action, Probiotics is mixed while harmful bacteria is suppressed, also assigns the effect of positive incentive between each probiotics member so that tooth The oral health environment of growth is balanced, and excites and promote the oral immunisation function of human body, equal to periodontosis and gingivitis There is preventive and therapeutic effect.
Brief description of the drawings
Accompanying drawing described herein is used for providing further understanding the embodiment of the present invention, forms one of the application Point, do not form the restriction to the embodiment of the present invention.In the accompanying drawings：
Fig. 1 is the contrast and experiment mouse Alveolar Bone Loss figure of the present invention.
The anaerobic bacteria that Fig. 2 is the present invention counts figure.
Embodiment
For the object, technical solutions and advantages of the present invention are more clearly understood, with reference to embodiment and accompanying drawing, to this Invention is described in further detail, and exemplary embodiment of the invention and its explanation are only used for explaining the present invention, do not make For limitation of the invention.
Embodiment 1
Lactobacillus acidophilus is 4 × 108CFU, streptococcus salivarius M18 are 4 × 108CFU, streptococcus salivarius K12 be 2 × 108CFU。
Embodiment 2
Lactobacillus acidophilus is 1 × 108CFU, streptococcus salivarius M18 are 1 × 108CFU, streptococcus salivarius K12 be 8 × 108CFU。
Probiotics preparation can be made into by embodiment 1-2 probiotic composition and pharmaceutically acceptable carrier.Embodiment The unit of probiotic composition in 1-2 is not limited to 108CFU, 107CFU~1010CFU。
As one kind is embodied as probiotic gel agent, another kind is embodied as probiotics buccal piece.
To further illustrate beneficial effects of the present invention, inventor has specially been several groups of contrast experiments.It is as follows to contrast content：
With following comparative example group as a comparison.
Comparative example 1
Lactobacillus acidophilus 1 × 108CFU
Comparative example 2
Streptococcus salivarius K12 is 8 × 108CFU
Comparative example 3
Streptococcus salivarius M18 is 1 × 108CFU
Comparative example 4
Lactobacillus acidophilus 3.5 × 108CFU, streptococcus salivarius M18 are 5.5 × 108CFU, streptococcus salivarius K12 be 1 × 108CFU.Experiment content is as follows：
1st, experiment material
1.1 experimental facilities and apparatus
Detest bacteria incubator, desk centrifuge, light microscope, photomicrographic system type, dentistry Special surgical instrument one Set.
1.2 experiment reagent
Anaerobic Blood Agar flat board, PBS PBs, 4% paraformaldehyde solution, methylene blue staining agent.
1.3 experimental method
1.3.1 zoopery and packet
By SPF level C57BL/6 male mices 80,8 groups are randomly divided into i.e.:Blank group (untreated fish group), model group (ligation Solvent group is given after dental floss) and administration group 1-6 (ligation dental floss after give probiotic group；The corresponding comparative example 1 of administration group 1, administration group 2 corresponding comparative examples 2, the corresponding comparative example 3 of administration group 3, the corresponding embodiment 1 of administration group 4, the corresponding embodiment 2 of administration group 5, administration group 6 Corresponding comparative example 4.
Each group mouse is not treated with 4% chloraldurate (0.1ml/10g, intraperitoneal injection) anesthesia, Normal group as intervention It is revived, and remaining 7 groups are ligatured using silk thread around upper left second molar.Blank group fed with water does not do other from experimental day Processing；Model group gives solvent 0.07ml/ times, twice a day；
1.3.2 ligation positioning
Mouse ligatures second molar on the left of the upper jaw with silk thread, while opposite side does not process, as bone elevation carrection base Line, and keep the whole silk thread of experiment not fall off.Per silk thread of weekly check, the mouse for losing silk thread is marked and tied again Prick, all mouse are observed 4 weeks altogether, and mouse was put to death at the 4th week, and observation enamel cementum circle takes silk to crest of alveolar ridge distance Line culture bacterium.
1.3.3 bone loss is observed
Mouse is put to death, its maxilla is taken and is fixed on after microscope goes down its soft tissue in 4% paraformaldehyde solution solid After fixed, tooth dyes in 1% methylenum careuleum.In Nikon SMZ800 microscope 40 × light Microscopic observation bone loss situations, i.e. glaze tooth Sclerotin circle is to the distance of crest of alveolar ridge, while photo record mouse maxillary bone loses situation.
1.3.4 bacteria-measuring
Experiment mice is put to death, removes after silk thread rinses out swill with PBS phosphate buffers, adds 1ml PBS Centrifugation.It will be planted again after bacterium extract solution diluting several times in blood agar culture-medium, cultivate 7d under 37 DEG C of anaerobic environments, record CFU data, length computation CFU/mm is corresponded to by silk thread.
1.3.5 data analysing method
Using InStat variance analyses and multiple comparative test method, the difference for comparing bone information between each group is examined using t.With P<0.05 is that difference is statistically significant.
2 experimental results
2.1 Level of Alveolar Bone absorb result
Fig. 1 shows that blank group rat periodontium is normal, and the distance of enamelo-cemental junction to crest of alveolar ridge is very low, and mould Compared with blank group, second molar Level of Alveolar Bone absorbs apparently higher than baseline values type group.Its glaze cementum of administration group 1,2,3,6 Boundary to the distance of crest of alveolar ridge has certain reduction compared with model group, administration group 4,5 compared with model group enamelo-cemental junction to tooth The distance on groove ridge top greatly reduces.Enamelo-cemental junction to the distance of crest of alveolar ridge compared with administration 4,5 of administration group 1,2,3 substantially increases Add, the distance increase of administration group 6 enamelo-cemental junction to crest of alveolar ridge compared with administration group 4,5 is a lot, illustrates first：Embodiment 1 There is significant beneficial effect relative to single component with 2 probiotic compositions provided；Second, non-invention ratio range Composition might not can reach the effect of one-component because administration group 6 compared with administration group 2 enamelo-cemental junction to alveolar ridge The distance on top increased.
2.2 count of bacteria
By Fig. 2, administration group 1-6 anaerobic bacteria quantity is relatively low, and wherein there were significant differences (* P ＜ 0.05) for administration group 1,3,6, gives Medicine group 2,4,5 has pole significant difference (* * P ＜ 0.01), and administration group 4,5 fungistatic effects are optimal, and administration group shows stronger Periodontal anaerobism pathogenic bacteria inhibitory action.
Contrast experiment more than summarizes, and periodontitis is one kind caused by bacterium plaque bio-film with bone information, soft Tissue inflammation is chronic, the destructive disease mainly showed, and treatment not in time, ultimately results in tooth and pulled out.This experiment has carried out 4 The zoopery in week, the method that the left maxillary second molar neck portion of mouse is ligatured by silk thread create model, observe Level of Alveolar Bone Degree of absorption.Experiment includes 8 groups：Blank group, model group and administration group 1-6, at the 4th week and compare each group enamelo-cemental junction to tooth Index of the distance on groove ridge top as Alveolar Bone Loss.Administration group enamelo-cemental junction to crest of alveolar ridge distance compared with model group Substantially reduce, especially administration group (1 group of embodiment), there were significant differences for administration group 5 (2 groups of embodiment), it is seen that mixing probiotics Combining the mouse Alveolar Bone Loss for ligaturing induction to silk thread has significant mitigation, alveolar bone is regenerated.
Furthermore, it has been established that Periodontal Pathogens include porphyromonas gingivalis, with unwrapping wire aggregation bacillus, Fu Saitan Salmonellas, The anaerobic bacterias such as actinomyces viscosus, treponema denticola, Fusobacterium nucleatum, Prevotella intermedia.The anaerobic bacteria quantity of administration group is compared with model Group anaerobic bacteria quantity greatly reduces, it is seen that mixing probiotic combinations have stronger inhibitory action to the anaerobic bacteria in murine oral. Result is probably as appearance, and different probiotics are different to oral cavity harmful bacteria inhibitory action in combination, the mixing of different proportion Synergy between probiotics is also each variant, in the range of certain proportion, mixes the interphase interaction of probiotics, mutually promotees Enter, play the synergy of colony so that it suppresses antibacterial work of the growth and breeding effect than probiotics is used alone of harmful bacteria With greatly enhancing, the oral environment of dental health existence is given.
In summary, mixing probiotic combinations are advantageous to the Regeneration of Alveolar Bone destroyed, while can suppress Periodontal Pathogens Growth, can prevent and treat periodontitis to a certain extent.
The probiotic gel agent of embodiment 5
A kind of preparation method of probiotic gel agent, it is characterised in that comprise the following steps：
(1) preparation of probiotics bacterium mud：Probiotics strain is taken in BHI fluid nutrient mediums, 5%CO2, under the conditions of 37 DEG C, Cultivate 12h in anaerobic environment, probiotic's culture liquid centrifuges 10min with 3000r/min rotating speed, repeatedly with brine, Obtain probiotics bacterium mud.
(2) gel-type vehicle：Gel-type vehicle is made up of Macromolecule glue material, bioadhesive material, NMF, distilled water, Described high polymer material is in carbomer, poloxamer, hydroxypropyl cellulose, hydroxypropyl methyl cellulose sodium, chitosan It is one or more of；Described bioadhesive material be Sodium Hyaluronate, hydroxypropyl methyl cellulose, one kind in sodium alginate or It is several；Described NMF is the one or more in glycerine, propane diols polyethylene glycol, glycerine, sorbierite.
Table 1
Composition Dosage/part
Bacterium mud 10
Carbomer 500
Triethanolamine 1
Glycerine 50
Hyaluronic acid 20
Distilled water 1000
(1) preparation of probiotics bacterium mud：Probiotics strain is taken in BHI fluid nutrient mediums, 5%CO2, under the conditions of 37 DEG C, Cultivate 12h in anaerobic environment, probiotic's culture liquid centrifuges 10min with 3000r/min rotating speed, repeatedly with brine, Obtain probiotics bacterium mud.
(2) gel-type vehicle：Carbomer dispersion is swelled in distilled water, concentration 1-10%, is added triethanolamine and is adjusted pH extremely 4-12, glycerine is added, add hyaluronic acid, stir, obtain gel-type vehicle.
(3) probiotics bacterium mud is disperseed with distilled water, is mixed in gel-type vehicle, stir, obtain probiotic gel.
Embodiment 6
Table 2
(1) preparation of probiotics bacterium mud：Probiotics strain is taken in BHI fluid nutrient mediums, 5%CO2, under the conditions of 37 DEG C, Cultivate 12h in anaerobic environment, probiotic's culture liquid centrifuges 10min with 3000r/min rotating speed, repeatedly with brine, Obtain probiotics bacterium mud.
(2) gel-type vehicle：Poloxamer, which is scattered in distilled water, to be swelled, concentration 1-10%, adds glycerine, is added transparent Matter acid, stirs, obtains gel-type vehicle.
(3) probiotics bacterium mud is disperseed with distilled water, is mixed in gel-type vehicle, stir, obtain probiotic gel.
Embodiment 7
Table 3
Composition Dosage/part
Bacterium mud 10
Poloxamer 500
Glycerine 50
Hydroxypropyl methyl cellulose 20
Distilled water 1000
(1) preparation of probiotics bacterium mud：Probiotics strain is taken in BHI fluid nutrient mediums, 5%CO2, under the conditions of 37 DEG C, Cultivate 12h in anaerobic environment, probiotic's culture liquid centrifuges 10min with 3000r/min rotating speed, repeatedly with brine, Obtain probiotics bacterium mud.
(2) gel-type vehicle：Poloxamer, which is scattered in distilled water, to be swelled, concentration 1-10%, adds glycerine, adds hydroxypropyl Ylmethyl cellulose, stirs, and obtains gel-type vehicle.
(3) probiotics bacterium mud is disperseed with distilled water, is mixed in gel-type vehicle, stir, obtain probiotic gel.
Embodiment 8
Table 4
(1) preparation of probiotics bacterium mud：Probiotics strain is taken in BHI fluid nutrient mediums, 5%CO2, under the conditions of 37 DEG C, Cultivate 12h in anaerobic environment, probiotic's culture liquid centrifuges 10min with 3000r/min rotating speed, repeatedly with brine, Obtain probiotics bacterium mud.
(2) gel-type vehicle：Carbomer dispersion is swelled in distilled water, concentration 1-10%, is added triethanolamine and is adjusted pH extremely 4-12, glycerine is added, add hydroxypropyl methyl cellulose, stir, obtain gel-type vehicle.
(3) probiotics bacterium mud is disperseed with distilled water, is mixed in gel-type vehicle, stir, obtain probiotic gel.
Determine the viable bacteria content of probiotic gel agent obtained in embodiment 5-8.
Gained probiotic gel agent in Example 5-8 respectively, adds 50ml physiological saline, static after tablet dissolved 5min, with physiological saline gradient dilution to suitable concn, cultivated on MRS agar mediums, 5%CO2, anaerobism under the conditions of 37 DEG C Culture 24 hours, carry out bacterium colony counting.
The viable bacteria content measurement result of table 5
Group Viable bacteria content (cfu/g)
Embodiment 5 3.1×108
Embodiment 6 2.3×108
Embodiment 7 4.9×108
Embodiment 8 3.6×108
The light transmittance for determining probiotic gel agent obtained in embodiment 5-8 is investigated.
Gained probiotic gel agent, normal temperature preserve 1 month, 2 months, 3 months, 4 months, 5 in Example 5-8 respectively The moon, after 6 months, determine light transmittance.
Table 6
Group Light transmittance
Embodiment 5 92%
Embodiment 6 90%
Embodiment 7 95%
Embodiment 8 92%
The Viable detection for determining probiotic gel agent obtained in embodiment 5-8 is investigated
Gained probiotic gel agent, normal temperature preserve 1 month, 2 months, 3 months, 4 months, 5 in Example 5-8 respectively The moon, after 6 months, determine viable bacteria content.
Table 7
The probiotics buccal piece of embodiment 9
Group method is as follows：
(1) preparation of Freeze-dry Powder of Probioctics：Probiotic's culture liquid centrifuges 10min with 3000r/min rotating speed, obtains prebiotic Bacterium bacterium mud；It is freeze drying protectant that skimmed milk power is added in probiotics bacterium mud, concentration 1-10%；Lyophilized thickness is 1.5-2cm, - 80 DEG C, pre-freeze 4h are cooled to, freeze-drying process；Outlet, obtain Freeze-dry Powder of Probioctics；
(2) pharmaceutic adjuvant：Following components is prepared by weight, wherein auxiliary material be respectively isomaltoketose, mannitol, Microcrystalline cellulose, magnesium stearate, silica, Steviosin, mint extract；
(3) direct powder compression：The auxiliary material be crushed into 80 mesh sieves, Freeze-dry Powder of Probioctics crosses 80 mesh sieves, will after sieving Auxiliary material is with probiotic powder by weight 5:100-1 is mixed, and the raw material of directly compressible is obtained after mixing；
(4) tabletting：The raw material of mixing is put into tabletting machine, regulation pressure is 20-60kN, obtains probiotic tablet.
It is embodied as：
(1) preparation of pharmaceutic adjuvant：Prepare by weight, wherein 50 parts of isomalt, 30 parts of mannitol, crystallite are fine 10 parts of dimension element, 4 parts of mint extract, 4 parts of Steviosin, 1 part of magnesium stearate, silica 1 part；
(2) raw material mixes：The auxiliary material be crushed into 80 mesh sieves, Freeze-dry Powder of Probioctics crosses 80 mesh sieves, by auxiliary material after sieving Mixed with probiotic powder by weight 50-1, the raw material of directly compressible is obtained after mixing；
(3) tabletting：The raw material of mixing is put into tabletting machine, regulation pressure is 20kN, obtains probiotic tablet.
Embodiment 10:
A kind of buccal piece containing oral cavity probiotics, its preparation method comprise the following steps：
(1) preparation of pharmaceutic adjuvant：Prepare by weight, wherein 20 parts of isomalt, 50 parts of mannitol, crystallite are fine 20 parts of dimension element, 4 parts of mint extract, 4 parts of Steviosin, 0.5 part of magnesium stearate, silica 1 .5 parts；
(2) raw material mixes：The auxiliary material be crushed into 80 mesh sieves, Freeze-dry Powder of Probioctics crosses 80 mesh sieves, by auxiliary material after sieving Mixed with probiotic powder by weight 50-1, the raw material of directly compressible is obtained after mixing；
(3) tabletting：The raw material of mixing is put into tabletting machine, regulation pressure is 20kN, obtains probiotic tablet.
Embodiment 11:
A kind of buccal piece containing oral cavity probiotics, its preparation method comprise the following steps：
(1) preparation of pharmaceutic adjuvant：Prepare by weight, wherein 40 parts of isomalt, 20 parts of mannitol, crystallite are fine 30 parts of dimension element, 4 parts of mint extract, 4 parts of Steviosin, 1.5 parts of magnesium stearate, 0.5 part of silica；
(2) raw material mixes：The auxiliary material be crushed into 80 mesh sieves, Freeze-dry Powder of Probioctics crosses 80 mesh sieves, by auxiliary material after sieving Mixed with probiotic powder by weight 100-1, the raw material of directly compressible is obtained after mixing；
(3) tabletting：The raw material of mixing is put into tabletting machine, regulation pressure is 40kN, obtains probiotic tablet.
Embodiment 12:
A kind of buccal piece containing oral cavity probiotics, its preparation method comprise the following steps：
(1) preparation of pharmaceutic adjuvant：Prepare by weight, wherein 50 parts of isomalt, 15 parts of mannitol, crystallite are fine 25 parts of dimension element, 4 parts of mint extract, 4 parts of Steviosin, 1 part of magnesium stearate, silica 1 part；
(2) raw material mixes：The auxiliary material be crushed into 80 mesh sieves, Freeze-dry Powder of Probioctics crosses 80 mesh sieves, by auxiliary material after sieving Mixed with probiotic powder by weight 100-1, the raw material of directly compressible is obtained after mixing；
(3) tabletting：The raw material of mixing is put into tabletting machine, regulation pressure is 40kN, obtains probiotic tablet.
Determine the viable bacteria content of buccal piece obtained in embodiment 9-12.
Gained buccal piece in Example 9-12 respectively, adds 50ml physiological saline, after tablet dissolved, static 5min, With physiological saline gradient dilution to suitable concn, cultivated on MRS agar mediums, 5%CO2, Anaerobic culturel under the conditions of 37 DEG C 24 hours, carry out bacterium colony counting.
The viable bacteria content measurement result of table 8
Group Viable bacteria content (cfu/ pieces)
Embodiment 9 2.2×108
Embodiment 10 3.5×108
Embodiment 11 2.7×108
Embodiment 12 4.1×108
EXPERIMENTAL EXAMPLE 2：
Determine the study on the stability of buccal piece obtained in embodiment 9-12
Gained buccal piece in Example 9-12 respectively, normal temperature preserve 1 month, 2 months, 3 months, 4 months, 5 months, 6 After individual month, according to method in EXPERIMENTAL EXAMPLE 2, the viable bacteria content in tablet is determined.
The study on the stability of table 9
Embodiment 9 Embodiment 10 Embodiment 11 Embodiment 12
1 month 2.1×108 3.1×108 2.5×108 4.0×108
2 months 1.7×108 2.9×108 2.1×108 3.6×108
3 months 1.4×108 2.3×108 1.8×108 3.3×108
4 months 1.3×108 1.8×108 1.4×108 2.1×108
5 months 0.9×108 1.1×108 1.1×108 1.8×108
6 months 0.3×108 1.0×108 0.7×108 1.6×108
Above-described embodiment, the purpose of the present invention, technical scheme and beneficial effect are carried out further Describe in detail, should be understood that the embodiment that the foregoing is only the present invention, be not intended to limit the present invention Protection domain, within the spirit and principles of the invention, any modification, equivalent substitution and improvements done etc., all should include Within protection scope of the present invention.

Claims (10)

1. a kind of probiotic composition, it is characterised in that including lactobacillus acidophilus, streptococcus salivarius M18, streptococcus salivarius K12.
2. probiotic composition according to claim 1, it is characterised in that in terms of clump count, lactobacillus acidophilus 10- 30%, streptococcus salivarius M18 are 10-50%, and streptococcus salivarius K12 is 20-80%.
3. probiotic composition according to claim 1, it is characterised in that in terms of clump count, be by lactobacillus acidophilus 10%, streptococcus salivarius M18 are 10%, and streptococcus salivarius K12 is 80% composition.
4. a kind of probiotics preparation, it is characterised in that as the probiotic composition described in claim any one of 1-3 and pharmaceutically Acceptable carrier or auxiliary material are made.
5. probiotics preparation according to claim 4, it is characterised in that be probiotic gel agent or probiotics buccal Piece.
6. probiotics preparation according to claim 4, it is characterised in that when probiotics preparation is probiotic gel agent, by Probiotic composition described in claim any one of 1-3 be prepared into after bacterium mud or after culture bacterium mud made from centrifuge washing with Gel-type vehicle is mixed to prepare.
7. probiotics preparation according to claim 6, it is characterised in that gel-type vehicle is Macromolecule glue material, biology Adhesion material, NMF, distilled water composition, described high polymer material are carbomer, poloxamer, hydroxypropyl cellulose, hydroxyl One or more in propyl methocel sodium, chitosan；Described bioadhesive material is Sodium Hyaluronate, hydroxypropyl first One or more in base cellulose, sodium alginate；Described NMF is glycerine, propane diols polyethylene glycol, glycerine, sorb One or more in alcohol.
8. probiotics preparation according to claim 4, it is characterised in that, will when probiotics preparation is probiotics buccal piece Probiotic composition described in claim any one of 1-3 is prepared into probiotic composition freeze-dried powder, then by auxiliary material and probiotics Direct tablet compressing is made after freeze-dried powder mixing.
9. a kind of probiotics bacterium mud, as the probiotic composition described in claim any one of 1-3 after culture centrifuge washing system .
10. a kind of probiotic composition as described in claim any one of 1-3 is preparing treatment periodontitis or periodontal medicine On purposes.
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CN111235063A (en) * 2020-03-09 2020-06-05 天津小优科技有限公司 Preparation process and application of oral probiotic dry powder
CN111558033A (en) * 2020-05-14 2020-08-21 广州中昱医学生物科技有限公司 Oral cavity cleaning composition and application thereof
IT202100001169A1 (en) 2021-01-27 2022-07-27 Alfasigma Spa BUCCAL MUCOADHESIVE GEL CONTAINING PROBIOTICS FOR USE IN THE PREVENTION AND TREATMENT OF PERIODONTAL DISEASES.
IT202100010802A1 (en) 2021-05-03 2022-11-03 Alfasigma Spa SOLID MUCOADHESIVE FORMULATION INCLUDING PROBIOTICS FOR USE IN THE PREVENTION AND TREATMENT OF ORAL DYSBIOSIS.

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