CN106071027A - A kind of compound antibacterial chewing gum and preparation method thereof - Google Patents
A kind of compound antibacterial chewing gum and preparation method thereof Download PDFInfo
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- CN106071027A CN106071027A CN201610423697.2A CN201610423697A CN106071027A CN 106071027 A CN106071027 A CN 106071027A CN 201610423697 A CN201610423697 A CN 201610423697A CN 106071027 A CN106071027 A CN 106071027A
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- chewing gum
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- compound antibacterial
- gum
- stirring
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- LJYRLGOJYKPILZ-UHFFFAOYSA-N murexide Chemical compound [NH4+].N1C(=O)NC(=O)C(N=C2C(NC(=O)NC2=O)=O)=C1[O-] LJYRLGOJYKPILZ-UHFFFAOYSA-N 0.000 description 1
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- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
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- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G4/00—Chewing gum
- A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
- A23G4/12—Chewing gum characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G4/00—Chewing gum
- A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G4/00—Chewing gum
- A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
- A23G4/068—Chewing gum characterised by the composition containing organic or inorganic compounds containing plants or parts thereof, e.g. fruits, seeds, extracts
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G4/00—Chewing gum
- A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
- A23G4/14—Chewing gum characterised by the composition containing organic or inorganic compounds containing peptides or proteins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
The invention discloses a kind of compound antibacterial chewing gum and preparation method thereof, compound antibacterial chewing gum is made up of by mass percentage following raw material: cecropin D 7:1.0%, CPC:1.5%, Herba Dendranthematis indici extract: 1.5%, glycerol: 0.2～0.8%, Sorbitol: 30%～40%, xylitol: 30%～40%, gum base: 20%～30%, Oleum menthae: 0.1%～1%, acesulfame potassium: 0.1%～0.5%, arabic gum: 0.1%～0.5%, titanium dioxide: 0.1%～0.5%, Brazil wax: 0.01%～0.05%, the mass percent sum of raw material is 100%.This compound antibacterial chewing gum can be stablized, discharge antimicrobial component lentamente, without obvious acute toxic reaction and anaphylaxis；Can obviously reduce the formation of rat dental caries and alleviate dental caries damage destructiveness, there is preferable anticaries action；Also can reduce the gingival hemorrhage index of slight experimental animal model of periodontitis, plaque index, Periodontal Probing Depth and frontal resorption value, effective to slight periodontitis.
Description
Technical field
The invention belongs to biomedicine technical field, be specifically related to a kind of novel compound antibacterial chewing gum and preparation side thereof
Method, this compound antibacterial chewing gum of preparation can be used for the preventing and treating of oral cavity acute infectious diseases.
Background technology
Dental caries and periodontal disease are common disease in oral cavity, and the oral cavity of people or even the health of whole body in serious harm.Pin
Situation to China's oral cavity medical personnel's wretched insufficiency, the prevention of dental caries and periodontal disease has more significance.Oral cavity bacterium
Constantly building up in dental plaque is the pathogenesis of this kind of disease, no matter is dental caries or periodontal disease, and its performance of relying is caused a disease
The microenvironment of function is all Dental plaque biofilm, and Streptococcus mutans is the main cariogenic bacteria of dental caries.Its main pathogenic property is
It produces acid, acid-fast ability.The pathogenic bacterium of periodontal disease are the LPS that the gram-negative bacteria in dental plaque produces, owing to causing
Physicochemical property that pathogenic bacteria is showed in bacterial plaque group, toxicity, gene expression characteristics etc. all differ markedly from floating state, are in
Pathogenic bacterium in plaque bio-film, higher to the adaptation ability of surrounding, therefore the infection caused by dental plaque, treatment means one
The most limited.Prevent at present and treat the method for this type of disease include mechanical removal dental plaque or use antibacterials to control tooth bacterium
Speckle.Gargarism or the sodium fluoride japanning etc. that have contained antibacterials such as chlorhexidine, cetylpyridinium chloride are used for suppressing facing tooth
The formation of bacterial plaque.But these gargarism, the time of staying in the oral cavity of painting are shorter, drug effect is difficult to maintain, and once gargles or rushes
Wash stopping, it is easy to recurrence, need frequent medication；And these medicines are difficult to penetrate bacterial plaque barrier, limited use.
Occur in that the preventing and treating for dental plaque related oral disease of some novel Antibacterial Constituents in recent years, as antibacterial
Peptide, cationic surfactant and natural antibacterial Chinese herbal medicine extract etc., it has the advantage that conventional antimicrobial medicine is incomparable,
Selectivity is relatively strong, does not easily cause bacterial resistance；And its molecular weight is little, it is possible to enter the bacterial plaque formed, play antibacterial
And neutralization, change bacterial plaque structure, weaken bacterial plaque function, thus reach to suppress dental caries, the pathogenetic purpose of periodontal.
The one of periodontal local application has been become now with the development of slow controlled release drug delivery system, local sustained release and controlled release medication
The trend of kind.
Chewing gum volume is little, lightweight, easy to carry, it is simple to use, and its time of staying in oral cavity is longer (general
15 minutes can be chewed), can slowly discharge content therein, chew gum also has the effect of refreshment.Therefore, mouth is fragrant
Sugar is by the ideal carrier of oral administration, is particularly well-suited to the special environment condition not possessing holding oral hygienes such as brushing teeth
Under be engaged in the practitioner of work, such as, the oral cavity of rescue and relief work personnel when meeting major natural disasters and the disaster area people etc. is defended
Raw health care needs.
Summary of the invention
It is an object of the invention to, it is provided that a kind of compound antibacterial chewing gum and preparation method thereof.
In order to realize above-mentioned task, the present invention takes following technical solution:
A kind of compound antibacterial chewing gum, it is characterised in that this prepared antimicrobial gums is pressed percent mass by following raw material
Than composition:
Cecropin D-7:1.0%, CPC:1.5%, Herba Dendranthematis indici extract: 1.5%, glycerol: 0.2～0.8%, Sorbitol:
30%～40%, xylitol: 30%～40%, gum base: 20%～30%, Oleum menthae: 0.1%～1%, acesulfame potassium: 0.1%～
0.5%, arabic gum: 0.1%～0.5%, titanium dioxide: 0.1%～0.5%, Brazil wax: 0.01%～0.05%,
The mass percent sum of raw material is 100%.
Wherein cecropin D-7 uses Fmoc solid-phase synthesis, synthesizes, the polypeptide sequence of this cecropin D-7 on mbha resin
It is classified as KKVVFWVKFK-NH2, purity is 95%, and molecular weight is 1308.7.
The preparation method of above-mentioned compound antibacterial chewing gum, it is characterised in that prepare as follows:
S1: feed intake stirring
1. by xylitol, Sorbitol the most finely ground mistake 100 mesh sieve, xylitol sugar is obtained with appropriate purified water moistening respectively
Slurry, sorbitol syrup；And by the arabic gum of appropriate xylitol syrup and formula ratio and titanium dioxide under the conditions of 80 DEG C all
It is even that to be prepared by mixing into coatings standby；
2. the gum base weighing recipe quantity is placed in oven heat, makes its uniformly softening at a set temperature；
3. taking out in gum base puts into blender the glycerol being stirred and adding recipe quantity half after softening, stirring softens
5min, obtains the first material；
4. adding the sorbitol syrup of recipe quantity half in the first material, 4min is to being thoroughly mixed in stirring；Add surplus
Remaining glycerol is lubricated stirring, adds the Oleum menthae of recipe quantity half, CPC and Flos Chrysanthemi Indici extract, continue stirring after 2min
5min, obtains the second material；
5. second material adds remaining sorbitol syrup, residue xylitol, the acesulfame potassium of formula ratio and antibacterial peptide
D-7, mixing, stir 4min, obtain 3 material；
6. in 3 material, finally add remaining Oleum menthae stirring 6min, stop stirring, take out stirring material；
S2: molding, quenched
By stirring material stripping and slicing and cool down, putting into extrusion in forming machine material receiving port, the label mass average value of molding controls
At 0.90g/ grain, label be placed in low temperature and low humidity quenched in quenched aging more than 24h；
S3: coating
After quenched aging end, the label that precise is good is positioned in coating pan, keeps coating pan to continue, evenly
Rotate, continually add coatings and be coated, till the coated cores mass average value of molding reaches 1.40 grams/,
Coated cores takes the dish out of the pot；
S4, quenched
Coated cores be positioned over low temperature and low humidity quenched in quenched aging more than 24h；
S5, polishing
Precise coated cores well is positioned in polishing pot, keeps polishing pot to continue, rotate evenly and add
The Brazil wax of recipe quantity is polished, and obtains compound antibacterial chewing gum.
Wherein, the mass ratio of described coatings and sheet sandwich layer is 10:1.
The compound antibacterial chewing gum of gained of the present invention, illumination (4500LX), high temperature (60 DEG C) and high humidity (temperature 25 DEG C+
RH 92.5%) under the conditions of place 10 days, the content of the outward appearance of product, dissolution and cecropin D-7 has no significant change；By city
Selling packaging, place six months under the conditions of accelerated test, the indices of product all meets the requirements, and the character of product is described more
Stable；Under the conditions of long term test, in 24 months, indices still conforms to requirement, has no significant change, shows product stability
Preferably, the effect duration of antimicrobial gums fixes tentatively is 24 months.
The compound antibacterial chewing gum of gained, the component outside removing glue base is carried out after being configured to solution by each component ratio of chewing gum
Acute toxicity test and hypersensitive test, without obvious acute toxic reaction and anaphylaxis, show that this antimicrobial gums toxicity is low,
Clinical administration is safe and reliable.
Through our experiments show that, the compound antibacterial chewing gum of gained may be used for oral cavity acute infectious diseases medicine
Application.
Described oral cavity acute infectious diseases is dental caries, the formation of dental caries and alleviates dental caries damage destructiveness；Gingival sulcus is hemorrhage
Index, plaque index, Periodontal Probing Depth and frontal resorption value, slight periodontitis.
In test, the component outside compound antibacterial chewing gum removing glue base is configured to molten by each component ratio of chewing gum by applicant
Carry out the test of pesticide effectiveness after liquid, can obviously reduce the formation of rat dental caries and alleviate dental caries damage destructiveness, there is preferable preventing decayed tooth and make
With；Gingival hemorrhage index, plaque index, Periodontal Probing Depth and the frontal resorption of slight experimental animal model of periodontitis can be reduced
Value is effective to slight periodontitis.
The compound antibacterial chewing gum of the present invention compared with prior art, at least has the advantage that
1) compared with conventional chewing gum, the present invention will have the cecropin D-7 of antibacterial activity, surfactant CPC and open country
Flos Chrysanthemi extract adds to chewing gum, it is possible to more efficiently prevention of oral infections.
2) this compound antibacterial chewing gum has portable, easy-to-use, has a broad antifungal spectrum, and antibacterial action is rapid, does not produce drug resistance, nothing
The advantages such as side effect, use it for the preventing and treating of dental caries and periodontal disease and have good economy, society, environmental benefit.
Accompanying drawing explanation
Fig. 1 is the mass spectrum of cecropin D-7；
Fig. 2 is the chromatogram of cecropin D-7；
Fig. 3 is the release profiles of cecropin D-7 in different CPC specification chewing gum；
Fig. 4 is the chromatogram of antimicrobial gums sample；
Fig. 5 is the chromatogram of blank gum sample；
Fig. 6 is the gingival hemorrhage index map of each group, and wherein A is compound antibacterial chewing gum group, and B is blank auxiliary group, and C is chlorine
Oneself determines group, and D is distilled water group；* p < 0.01 in figure, represents and has significant difference compared with D, and #p < 0.01 represents and has compared with B
Significant difference.
Fig. 7 is the plaque index figure of each group, and wherein A is compound antibacterial chewing gum group, and B is blank auxiliary group, and C is chlorhexidine
Group, D is distilled water group；* p < 0.01 in figure, represents and has significant difference compared with D, and #p < 0.01 represents and has compared with A significantly
Sex differernce
Fig. 8 is the pocket probe depth map of each group, and wherein A is compound antibacterial chewing gum group, and B is blank auxiliary group, and C is
Chlorhexidine group, D is distilled water group；* p < 0.01 in figure, represents and has significant difference compared with D, and #p < 0.01 represents compared with A
There is significant difference
Fig. 9 is the frontal resorption value figure of each group, and wherein A is compound antibacterial chewing gum group, and B is blank auxiliary group, and C is chlorine
Oneself determines group, and D is distilled water group；* p < 0.01 in figure, represents and has significant difference compared with D, and #p < 0.01 represents and has compared with B
Significant difference
Below in conjunction with drawings and Examples and experiment the present invention is described in further detail.
Detailed description of the invention
The present invention intends with a kind of small peptide D-7 with stronger antibacterial activity and cationic surfactant cetylpyridinium chloride
(Cetylpyridnium Chloride, CPC) and Flos Chrysanthemi Indici extract combine, with chewing gum as pharmaceutical carrier, and exploitation one
Can the oral health new product of effective prevention of oral infections, stable, slowly release antimicrobial component natural to imitate body
Defense molecule is at intraoral biological action, it is possible to achieve:
The most effectively under prevention special environment, oral cavity acute infectious diseases develops；
2. strengthen and supplement the natural defense mechanism of body opposing oral pathology substance；
3. contribute to maintaining oral cavity and the composition of intestinal microbial population and ecological balance；
4. the generation of drug resistance bacterium is reduced；
5. infiltrate through and destroy Dental Plaque biomembrane.
This antimicrobial gums is made up of by mass percentage following raw material:
Cecropin D-7:1.0%, CPC:1.5%, Herba Dendranthematis indici extract: 1.5%, glycerol: 0.2～0.8%, Sorbitol:
30%～40%, xylitol: 30%～40%, gum base: 20%～30%, Oleum menthae: 0.1%～1%, acesulfame potassium: 0.1%～
0.5%, arabic gum: 0.1%～0.5%, titanium dioxide: 0.1%～0.5%, Brazil wax: 0.01%～0.05%,
The mass percent sum of raw material is 100%.
Above-mentioned cecropin D-7 uses Fmoc solid-phase synthesis to synthesize on mbha resin, the peptide sequence of this cecropin D-7
For KKVVFWVKFK-NH2, purity is 95%, and molecular weight is 1308.7.This cecropin D-7 has stronger broad-spectrum antibacterial action,
The different strains such as the pathogenic bacterium common to oral cavity and saliva of buccal cavity mixed cell all have preferable antibacterial activity.
The formulation and technology of compound antibacterial chewing gum is optimized by applicant by single factor exploration and Orthogonal Experiment and Design,
Then carry out stability study, acute toxicity test and hypersensitive test, finally carry out caries-prevent effect test and pre-preventing parodontitis medicine
Effect test.Demonstrate this compound antibacterial chewing gum and may be used for the application of oral cavity acute infectious diseases medicine, be mainly used in pressing down
Dental caries processed, hence it is evident that reduce the formation of dental caries and alleviate dental caries damage destructiveness, there is preferable anticaries action；Slight periodontal can be reduced
Scorching gingival hemorrhage index, plaque index, Periodontal Probing Depth and frontal resorption value is effective to slight periodontitis.
The present invention is described in further detail for the embodiment be given below in conjunction with inventor, and these embodiments are only used for
Help understands the present invention, the invention is not restricted to these embodiments.
Embodiment 1: the synthesis of cecropin D-7
The synthesis of cecropin D-7 uses Fmoc solid-phase synthesis, synthesizes on mbha resin.At TBTU/DMF/NMP solution
In, Fmoc-amino acid derivativges is covalently bonded on resin according to the sequence order of antibacterial peptide.At the next aminoacid of crosslinking
Before, Piperidine (DMF solution of 20%v/v) is all used to remove N-terminal Fmoc amino protecting group.Cross-linking reaction
Complete to detect by Kaiser method.After synthetic reaction completes, with 95% trifluoroacetic acid, antibacterial peptide is eluted from resin, and
Use Vydac C18Chromatographic column RP-HPLC color method (RP-HPLC) purification, finally with MALDI-TOF MASS mass spectral analysis
The purity of method detection purification antibacterial peptide.Final cecropin D-7 obtained, the peptide sequence of this cecropin D-7 is KKVVFWVKFK-
NH2, lyophilised after ,-20 DEG C save backup.
Fig. 1 and Fig. 2 is mass spectrum and the chromatogram of cecropin D-7, and as seen from the figure, the molecular weight of cecropin D-7 is 1308.7,
Purity is 95%.
Embodiment 2: the antibacterial activity detection of cecropin D-7
Media dilution method is used to measure antibacterial peptide bacterium different to oral cavity common pathogen and saliva of buccal cavity mixed cell etc.
The minimal inhibitory concentration of strain and minimal bactericidal concentration.
Test method is as follows: take the antibacterial being in exponential phase of fresh cultured, and in 4 DEG C, 4000rpm is centrifuged 15min,
Resuspended with 2 × culture fluid, adjust to 4 × 106CFU/mL.Use coubling dilution that the concentration of antibacterial peptide is adjusted to 200～3.13 μ
g/mL.Each to antibacterial peptide aqueous solution and bacteria suspension 100 μ L are joined in 96 orifice plates.96 orifice plates are at 37 DEG C, aerobic or 5%～10%
CO2Under the conditions of hatch 24-48 hour.The 96 each holes of the orifice plate absorption value at 600nm wavelength is measured with Plate Reader.Test weight
Multiple three times.It addition, negative control (without the aseptic aqueous solution of antibacterial peptide) and positive control (the ammonia benzyl west of 10 μ g/mL are set up in test
Woods aqueous solution).It is MIC that reading value is significantly higher than the corresponding concentration of culture medium, from limpid hole (>=MIC) take 50 μ L paving blood put down
Plate, hatches 24-48 hour, and the corresponding concentration of the longest antibacterial is MBC.
Table 1 :-7 pairs of oral cavity common pathogens of cecropin D and MIC and MBC of saliva of buccal cavity mixed cell
| Test strain | MIC(μg/ml) | MBC(μg/ml) |
| Staphylococcus aureus | 25 | 100 |
| Escherichia coli | 6.25 | 25 |
| Candida albicans | 12.5 | 50 |
| Bacillus acidophilus | 3.13 | 25 |
| Lactobacillus casei | 3.13 | 12.5 |
| Streptococcus sanguis | 3.13 | 25 |
| Streptococcus mutans | 3.13 | 25 |
| Form streptococcus | 25 | 50 |
| Streptococcus sobrinus | 6.25 | 25 |
Result shows, cecropin D-7 all has the most antibacterial and bactericidal activity to above-mentioned bacterium etc., shows that cecropin D-7 has
There is potent broad-spectrum antibacterial action.
Embodiment 3: the determination of cecropin D-7 ratio
The mass ratio of fixing CPC is 1.5%, and the mass ratio of Flos Chrysanthemi Indici extract is 1.5%, prepares different size and resists
The compound antibacterial chewing gum of bacterium PEPD-7 (0.2%, 0.5%, 1%, 1.5%, 2%), is placed in external chaw simulation device and releases
Put.Test parameters is set to: temperature 37 DEG C, and chewing frequency is 50 ± 2 times/min, and total artificial saliva amount is 20ml, chew time
For 20min.Take supernatant after off-test respectively to join MH nutrient broth medium and carry out fungistatic effect compare for examination bacterium.
Result shows, when cecropin D-7 ratio is more than 1%, compound antibacterial chewing gum dissolution fluid to multiple oral cavity common pathogen and
Saliva of buccal cavity mixed cell etc. all has bacteriostatic activity.Therefore 1% polypeptide specification is selected to carry out follow-up investigation.
Table 2: the screening of cecropin D-7 ratio
Note: "-" represents without antibacterial activity, "+" represent have antibacterial activity
Embodiment 4: the determination of Flos Chrysanthemi Indici extract ratio
The mass ratio of fixing CPC is 1.5%, and the mass ratio of cecropin D-7 is 1%, prepares different size Flos Chrysanthemi Indici
The compound antibacterial chewing gum of extract (0.2%, 0.5%, 1%, 1.5%, 2%), is placed in external chaw simulation device and releases
Put.Test parameters is set to: temperature 37 DEG C, and chewing frequency is 50 ± 2 times/min, and total artificial saliva amount is 20ml, chew time
For 20min.Take supernatant after off-test respectively to join MH nutrient broth medium and carry out fungistatic effect compare for examination bacterium.
Result shows, when the ratio of Flos Chrysanthemi Indici extract is more than 1.5%, and the cause common to multiple oral cavity of compound antibacterial chewing gum dissolution fluid
Pathogenic bacteria and saliva of buccal cavity mixed cell etc. all have bacteriostatic activity.Therefore 1.5% Flos Chrysanthemi Indici extract specification is selected to carry out follow-up examining
Examine.
Table 3: the screening of Flos Chrysanthemi Indici extract ratio
Note: "-" represents without antibacterial activity, "+" represent have antibacterial activity
The determination of embodiment 5:CPC ratio
Owing to cecropin D-7 and chewing gum base absorption affinity are relatively strong, need to add surfactant CPC and promote it from gum base
Middle release, therefore with the burst size of cecropin D-7 as index, investigates the addition of CPC.The mass ratio of fixing cecropin D-7
Being 1%, the mass ratio of Flos Chrysanthemi Indici extract is 1.5%, prepares answering of different size CPC (0.5%, 1%, 1.5%, 2%)
Side's antimicrobial gums, is placed in external chaw simulation device and carries out release dynamics test.Test parameters is set to: temperature 37 DEG C,
Chewing frequency is 50 ± 2 times/min, and total artificial saliva amount is 20ml.Take supernatant 400 μ L at special time, supplement simultaneously and wait body
Long-pending fresh dissolution medium, RP-HPLC measures the burst size of cecropin D-7.
High performance liquid chromatography (Chinese Pharmacopoeia four general rules 0512 of version in 2015) is used to measure the content of cecropin D-7,
Method is as follows:
5.1 solution preparations:
1. the preparation of acetate buffer weighs 0.14g sodium acetate and measures 0.48ml acetic acid in 100ml volumetric flask, uses
Pure water dilution is settled to scale and get final product.
2. the preparation precision of cecropin D-7 contrast solution weighs 15mg cecropin D-7 in 25ml volumetric flask, with 0.1M,
The dilution of pH4.0 acetate buffer is settled to scale, ultrasonic and shaking extremely dissolving repeatedly.Under the conditions of 13000r/min, 10min
After Li Xin, take supernatant 20 μ l and inject chromatograph of liquid, record chromatogram.
3. the preparation of need testing solution takes the release in vitro liquid of above-mentioned chewing gum, under the conditions of 13000r/min, 10min from
After the heart, take supernatant 20 μ l and inject chromatograph of liquid, record chromatogram.
5.2 chromatographic conditions and system suitability:
It is filler with octadecylsilane chemically bonded silica, phase composition of flowing: A phase (100% water+1 ‰ trifluoroacetic acid), B
Phase (100% acetonitrile+1 ‰ trifluoroacetic acid), gradient 0～20min (B phase 20%～30%, A phase 80%～70%), column temperature 25 DEG C,
Detection wavelength 215nm.Number of theoretical plate is calculated by cecropin D-7 peak should be not less than 2000, and main peak should accord with the separating degree of adjacent peak
Close requirement.
The calculating of 5.3 cecropin Ds-7 cumulative release percentage rate R (%):
R (%)=WRelease/WAlways× 100%
From the figure 3, it may be seen that when CPC ratio less than 1.5% time, the release of polypeptide be less than 70%, when its ratio reach 1.5% with
Time upper, polypeptide is when 120min releasable more than 90%, and the ratio therefore selecting CPC is 1.5%.
Therefore according to the experimental result of embodiment 3-5, the specification of this antimicrobial gums is set to every containing cecropin D-7
1%, containing Flos Chrysanthemi Indici extract 1.5%, containing CPC1.5%.
Embodiment 6: the determination of chewing gum formulations
With the outward appearance of chewing gum, mouthfeel, dissolution as inspection target, the optimization formula of screening chewing gum.
6.1 sugar alcohol proportionings and the selection of addition
6.1.1 the determination of sugar alcohol proportioning
In compound antibacterial chewing gum, the proportioning of sugar alcohol and addition affect the local flavor of chewing gum, mouthfeel, quality and dissolution
Degree etc..In various sugar alcohols, the sugariness of xylitol is the highest, and suitable with sucrose, xylitol metabolism in vivo need not simultaneously
Insulin participates in, and does not the most make blood glucose value raise, is most suitably adapted for the auxotype sugar substitute of patients with diabetes mellitus, is also
Good anti-caries sweeting agent.Xylitol is highly soluble in water, can absorb a lot of energy when it is dissolved in water, is in all sugar alcohol sweeteners
Heat absorption maximum.The mouthfeel of a kind of nice and cool similar Herba Menthae is had time edible.Sorbitol has refrigerant sweet taste, and sugariness is about sucrose
Half, calorific value is close with sucrose.Its Financial cost comprehensive and health care, use xylitol, Sorbitol to carry out proportioning examination
Test (gum base 35g, D-7 1.4g, Flos Chrysanthemi Indici extract 2.1g, CPC 2.1g, sugar alcohol 100g).The results are shown in Table 4.
Table 4: sugar alcohol proportioning is on product quality and the impact of dissolution
| Xylitol: Sorbitol | Mouthfeel | Quality | Dissolution |
| 3:1 | Entrance is salubrious, ice-cold, the sweetest | The softest | 75.6% |
| 2:1 | Entrance is salubrious, refrigerant, sweeter | Softer | 76.9% |
| 1:1 | Entrance is salubrious, refrigerant, sugariness is agreeable to the taste | Neither too hard, nor too soft | 88.3% |
| 1:2 | Refrigerant sense is general, and sugariness is agreeable to the taste | Harder | 71.2% |
| 1:3 | The most refrigerant sense, sweet taste is thin | The hardest | 64.5% |
As seen from table, in sugar alcohol, xylitol is appropriate when being 1:1 with the ratio of Sorbitol.
6.1.2 the determination of sugar alcohol addition
Using mixing sugar alcohol (xylitol: Sorbitol=1:1) is sweeting agent, carry out sugar alcohol addition to product special flavour and
The test of dissolution impact.With gum base 35g, D-7 1.4g, based on Flos Chrysanthemi Indici extract 2.1g, CPC 2.1g, add respectively
The sugar alcohol of 90g, 95g, 100g, 105g, 110g is tested, and with subjective appreciation and dissolution as standard, determines the consumption of sugar alcohol.
The results are shown in Table 5.
Table 5: sugar alcohol addition is on product special flavour and the impact of dissolution
| Sugar alcohol addition/g | Product special flavour | Dissolution/% |
| 90 | Sweet taste is not enough, entrance is lightly seasoned | 85.3 |
| 95 | Sweet taste is slightly owed, entrance is thin | 89.2 |
| 100 | Sweet taste appropriateness, entrance are comfortable | 92.4 |
| 105 | Sweet taste appropriateness, entrance are comfortable | 94.3 |
| 110 | Sweet taste skips over, entrance is the most greasy | 90.6 |
As seen from the above table, when sugar alcohol addition is 100g～105g, product sweet taste appropriateness, entrance is comfortable, and dissolution symbol
Close requirement.
The determination of 6.2 gum base consumptions
Gum base is most basic material in chewing gum, and its ratio in formula directly influences compound antibacterial chewing gum
Mouthfeel and quality.In order to obtain chewing toughness, viscoelasticity, plasticity is good and dissolution is qualified chewing gum, in trial test
In, with D-7 1.4g, based on Flos Chrysanthemi Indici extract 2.1g, CPC 2.1g, sugar alcohol 100g (xylitol: Sorbitol=1:1),
Add 25 respectively, 30,35g, 40g gum base test, with subjective appreciation and dissolution as standard, determine the consumption of gum base.Knot
Fruit is shown in Table 6.
Table 6: gum base consumption boil on the nape opposite the mouth perfume (or spice) saccharic amount and the impact of dissolution
| Gum base consumption/g | Product quality | Dissolution/% |
| 25 | Eke out a living, stick to one's teeth | 80.3 |
| 30 | Do not eke out a living, do not stick to one's teeth, chew toughness general | 88.6 |
| 35 | Do not eke out a living, do not stick to one's teeth, chew toughness preferable | 92.1 |
| 40 | Quality is harder, chews toughness poor | 70.4 |
As shown in Table 6, gum base consumption is that 35g is appropriate, and the chewing gum product of gained is not eked out a living, do not stuck to one's teeth, and chews toughness
Preferably, mouthfeel, elasticity, hardness are moderate, and dissolution meets the requirements.
The impact on chewing gum local flavor of the 6.3 essence consumptions
Essence has tax fragrant in compound antibacterial chewing gum and softens two effects, the essence quality to compound antibacterial chewing gum
Also play a decisive role, mainly affect the pliability of chewing gum, viscoelasticity etc..With gum base 35g, D-7 1.4g, Flos Chrysanthemi Indici extracts
Based on thing 2.1g, CPC 2.1g, sugar alcohol 100g (xylitol: Sorbitol=1:1), add 1 respectively, 2,5,10g essence (thin
Lotus oil) test, with subjective appreciation and dissolution as standard, determine the consumption of essence.
Table 7: essence consumption boil on the nape opposite the mouth perfume (or spice) saccharic amount and the impact of dissolution
| Essence consumption/g | Product quality | Dissolution/% |
| 1 | Quality is harder, and it is poor to chew toughness, and mouthfeel is poor | 52.3 |
| 2 | Not eking out a living, do not stick to one's teeth, chew toughness typically, mouthfeel is slightly worse | 78.5 |
| 5 | Do not eke out a living, do not stick to one's teeth, chew toughness preferably, in good taste | 93.6 |
| 10 | Eking out a living, stick to one's teeth, mouthfeel is the strongest | 94.3 |
As shown in Table 7, essence consumption is that 5g is appropriate, and the chewing gum product of gained is not eked out a living, do not stuck to one's teeth, and chews toughness relatively
Good, mouthfeel, elasticity, hardness are moderate, and dissolution meets the requirements.
6.4 the determination of formula
On the basis of single factor experiment, fixing xylitol is 1:1 with the proportioning of Sorbitol, chooses sugar alcohol addition
(A), gum base consumption (B) and essence consumption (C) be experimental factor, D is blank column, the orthogonal test of design Three factors-levels,
Chewing gum formulations is optimized, with the organoleptic indicator of compound antibacterial chewing gum and the dissolution of D-7 as inspection target, combines
Close scoring.Comprehensive grading=organoleptic indicator × 0.4+ dissolution × 0.6.Experimental design presses L9(34) orthogonal table carries out.
Wherein the methods of marking of organoleptic indicator is as follows: use mathematics method, by 9 professionals from the color and luster of product,
The aspects such as quality, mouthfeel, abnormal smells from the patient carry out subjective appreciation.Using hundred-mark system, color and luster accounts for 20 points, and quality accounts for 15 points, and mouthfeel accounts for 25 points,
Abnormal smells from the patient accounts for 40 points.The assay method of cecropin D-7 dissolution is with embodiment 5.
Table 8:L9(34) orthogonal test factor level table
| Level | A sugar alcohol addition | B gum base consumption | C essence consumption |
| 1 | 100 | 33 | 3 |
| 2 | 103 | 35 | 5 |
| 3 | 106 | 37 | 7 |
Table 9:L9(34) orthogonal and result
Table 10: the results of analysis of variance
| Factor | SS | V | MS | F | Significance |
| A | 5.677 | 2 | 2.376 | 19.000 | |
| B | 265.826 | 2 | 111.271 | 19.000 | * |
| C | 38.240 | 2 | 16.007 | 19.000 | |
| Error | 2.39 | 2 |
Note: marginal value F0.05(2,2)=19.00, * p < 0.05
It can be seen that the varying level of each factor organoleptic indicator on chewing gum and the impact of dissolution from table 8-10
Be followed successively by: B2 B1 > B3, C2 > C3 > C1, A3 > A1 > A2, B > C > A, i.e. gum base consumption be to chewing gum organoleptic indicator and dissolution
Impact maximum, next to that essence consumption, sugar alcohol addition for chewing gum organoleptic indicator compares the above two with dissolution
Little.
As shown in Table 10, gum base consumption the impact of chewing gum organoleptic indicator and dissolution is had significant difference (p <
0.05).According to Orthogonal experiment results, optimum process be combined as A3B2C2, i.e. gum base consumption is 35g, and gum base consumption is 5g, sugar
Alcohol addition is 106g.
6.5 the confirmatory experiment result of Optimizing Technical
Table 11: orthogonal result verification (n=3)
| Experiment numbers | Organoleptic indicator | Dissolution/% | Comprehensive grading |
| 1 | 89 | 89.6 | 89.36 |
| 2 | 88 | 90.8 | 89.68 |
| 3 | 89 | 88.9 | 88.94 |
| Mean±SD | 89.33±0.37 |
3 factors selected by result explanation of variance analysis have 2 factors to chewing gum sense in the level each set
The impact of official's index and dissolution does not have statistical significance, therefore combines set formulation and technology, prepares according to best prescription
The organoleptic indicator of compound antibacterial chewing gum and dissolution comprehensive grading meansigma methods be 89.33, and relatively stable, illustrate to optimize
Prescription repeatability good.
Embodiment 7: the preparation technology of compound antibacterial chewing gum
Compound antibacterial chewing gum in the present embodiment is adopted and is prepared with the following method:
7.1 feed intake stirring:
1. xylitol, Sorbitol the most finely ground mistake 100 mesh sieve, obtains xylitol sugar with appropriate purified water moistening respectively
Slurry, sorbitol syrup；And by the arabic gum of appropriate xylitol syrup and formula ratio and titanium dioxide under the conditions of 80 DEG C all
It is even that to be prepared by mixing into coatings standby；
2. the gum base weighing recipe quantity is placed in oven heat, at a temperature of setting (summer and autumn 55 DEG C, winter-spring season 65 DEG C)
It is made to soften the most equably；
3. taking out in gum base puts into blender the glycerol being stirred and adding recipe quantity half after softening, stirring softens
5min, obtains material 1；
4. adding the sorbitol syrup of recipe quantity half in material 1,4min is to being thoroughly mixed in stirring；Add remaining
Glycerol is lubricated stirring, adds the Oleum menthae of recipe quantity half, CPC, Flos Chrysanthemi Indici extract after 2min, continues stirring 5min,
Obtain material 2；
5. adding remaining sorbitol syrup in material 2, remain xylitol, the acesulfame potassium of formula ratio, cecropin D-7 mixes
Close, stir 4min, obtain material 3；
6. last material 3 adds remaining Oleum menthae stirring 6min, stops stirring, take out stirring material.
7.2 molding, quenched:
By stirring material stripping and slicing and carry out of short duration cooling, put into extrusion molding label in forming machine material receiving port, quality control
In 0.90g/ grain (meansigma methods), molding label be placed in low temperature and low humidity quenched in quenched aging more than 24h.
7.3 coatings:
4, the label that precise is good is positioned in coating pan, keep coating pan continue, evenly rotate and constantly
Adding coatings to be coated, till label quality reaches 1.40 grams/(meansigma methods) set, label takes the dish out of the pot.Wherein.
The mass ratio of coatings and sheet sandwich layer is 10:1.
7.4 is quenched:
Coated cores be positioned over low temperature and low humidity quenched in quenched aging 24h and above time.
7.5 polishings:
Precise coated cores well is positioned in polishing pot, keeps polishing pot to continue, rotate evenly and add
The Brazil wax of recipe quantity is polished, and obtains compound antibacterial chewing gum.
Embodiment 8: the assay of D-7 in antimicrobial gums
8.1 solution preparations
The preparation method of acetate buffer and cecropin D-7 contrast solution is with embodiment 5
The extracting method of D-7 and the preparation of need testing solution in 8.2 compound antibacterial chewing gum
Precision weighs compound antibacterial gum sample 0.5165g, is placed in 50ml tool plug centrifuge tube.Add 500 μ l glycerol
After, 60 DEG C of heating in water bath 15min become aging 3h after liquid.Accurate addition 10ml acetonitrile/DMF mixed liquor (1:1, v/v), uses glass again
Glass rod is smashed to pieces powdered, acutely after shaking 15min, adds the 0.1M acetate buffer (pH=4.0) of 10ml, then will be mixed
Fit system the most acutely shakes 30min, and then centrifugal 20min under the conditions of 3500r/min, collects supernatant to another
In plastic centrifuge tube；After adding 500 μ l glycerol again in residue, 60 DEG C of heating in water bath 15min become liquid, are subsequently added into 10ml vinegar
Phthalate buffer (0.1M, pH 4.0), the most acutely shakes 30min, then at 3500r/min bar by mixed system
Under part, centrifugal 20min, merges the supernatant of twice, i.e. prepares compound antibacterial chewing gum need testing solution.Centrifugal
After (13000r/min × 10min), take supernatant 20 μ l and inject chromatograph of liquid, record chromatogram.Chromatographic condition is with embodiment 5.
8.3 blank auxiliary interference tests
Take the blank chewing gum according to the preparation of Orthogonal Experiment and Design preferred best prescription, process sample as follows.
Precision weighs blank chewing gum 0.5165g, is placed in 50ml tool plug centrifuge tube.Sample treatment is with 8.2, and prepare is upper
After clear liquid centrifugal (13000r/min × 10min), take supernatant 20 μ l and inject chromatograph of liquid, record chromatogram.Chromatographic condition is same
Embodiment 5.
The content (%) of 8.4 cecropin Ds-7 calculates
Cecropin D-7 (%)=(ASample×CRight×30)/(ARight× m) × 100%
Wherein, ASamplePeak area for sample solution；CRightConcentration for contrast solution；ARightPeak area for contrast solution；M is
The quality of chewing gum.
From Fig. 4 and Fig. 5, blank auxiliary not interference measurement result, specificity is good.Measure three batches of gum sample,
Being calculated D-7 and indicating content is 96.42 ± 0.062%.
Embodiment 9: the stability test of antimicrobial gums
9.1 influence factor's tests
Take test sample a collection of (lot number: 130816) and put in surface plate, respectively at strong illumination (4500LX), high temperature (60 DEG C)
And place 10 days under the conditions of high humidity (RH92.5%) etc., sampling and measuring respectively in the 5th, 10 days time, and with 0 day with batch sample data
Relatively, result of the test is shown in Table 12.
Table 12: compound antibacterial chewing gum influence factor's experiment investigation result (n=6)
Above result of the test shows: this product is investigated 10 days under illumination, high temperature and super-humid conditions, the equal nothing of every quality index
Significant change.
9.2 accelerated stability test
Take three batches of compound recipe antimicrobial gums of test sample (130816,130823,130906), by commercially available back, in temperature 40
DEG C ± 2 DEG C, place 6 months under conditions of relative humidity 75% ± 5%.Take respectively at the 0th, 1,2,3,6 the end of month of period testing
Sample once, is carried out detecting (table 13) by detection projects such as outward appearance, dissolution and sign content.
Table 13: compound antibacterial chewing gum accelerated stability test investigates result (n=6)
Result shows, by commercially available back, places six months under the conditions of accelerated test, and the indices of product all conforms to
Ask, illustrate that the character of compound antibacterial chewing gum product is relatively stable.
9.3 long term test
Take three batches of compound recipe antimicrobial gums of test sample (130816,130823,130906), by commercially available back, in temperature 25
DEG C ± 2 DEG C, under conditions of relative humidity 60% ± 10% place 30 months, first 12 months every 3 months sampling once, i.e. respectively at
0, sampling in 3,6,9,12 months, after 12 months, respectively at sampling in 18,24,30 months, by outward appearance, dissolution and sign content
Detect Deng detection project.Result was compared with 0 month, to determine the effect duration of this compound antibacterial chewing gum product.Such as three
Batch statistic analysis result difference is less, then take its meansigma methods is effect duration, if difference is relatively big, then takes it the shortest for effect duration.
Table 14: compound antibacterial chewing gum long-time stability development test result (lot number 130816, n=6)
Table 15: compound antibacterial chewing gum long-time stability development test result (lot number 130823, n=6)
Table 16: compound antibacterial chewing gum long-time stability development test result (lot number 130906, n=6)
Result shows, commercially available back pressed by compound antibacterial chewing gum, and under the conditions of long term test, in 24 months, indices is still
Meet the requirements, have no significant change, show that product stability is preferable.
This compound antibacterial chewing gum, according to commercially available back, carries out stability test investigation, and result shows that product is accelerating
Place six months under experimental condition (temperature 40 DEG C ± 2 DEG C, relative humidity 75% ± 5%), long term test condition (temperature 25 DEG C ±
2 DEG C, relative humidity 60% ± 10%) under place 24 months, its outward appearance, dissolution, sign content all meet the requirements, relevant parameter
Have no significant change.Therefore being fixed tentatively by product holding conditions as sealing, less than 25 DEG C preservations, it is 1 year that effect duration fixes tentatively.For entering
One step determines the expiry date of compound antibacterial chewing gum, and stability test also will continue to 30 months.
Embodiment 10: the acute toxicity test of compound antibacterial chewing gum
Take 40 mices, male and female half and half, be grouped into the 1st group (the blank auxiliary solution outside removing glue base) and the 2nd group by body weight
(the compound antibacterial chewing gum solution outside removing glue base), overnight fasting, can't help water, with maximum can gavage concentration gastric infusion, blank
Adjuvant group is: purification used before use by the adjuvant (each adjunct ingredient ratio is identical with ratio in compound antibacterial chewing gum) outside removing glue base
Water is made into 1.022g/ml solution, compound antibacterial chewing gum group: chewing gum component (each component ratio and the antibacterial mouth outside removing glue base
In fragrant sugar, ratio is identical) it is made into 1.554g/ml (being calculated as 20.18mg/ml with KSL-W) solution by purified water before use.40ml/
Kg, is administered 3 times in 1 day, time interval 4 hours.After administration, normal material material is raised, and freely drinks water, after administration with following table at once
The general activity situation of close observation animal in 2 weeks and survival condition, record mice poisoning symptom and death condition, Continuous Observation
14, weigh when 7 days, after within 14th, weighing put to death animal, to be poisoned to death animal and put to death animal perform an autopsy on sb., naked eyes see
Examining the pathological changes situation of main organs, if there being ANOMALOUS VARIATIONS, carrying out pathologic examination.
After gavage gives ICR mice, mice is movable normal, abnormal without cry, tremble, faint from fear, sialorrhea, shed tears, rhinorrhea,
The phenomenons such as dyspnea, diarrhoea, constipation, intestinal tympanites occur.During test, compound antibacterial chewing gum treated animal body weight is auxiliary with blank
Material group does not occurs that significance changes (p > 0.05), the results are shown in Table.Compound antibacterial chewing gum group Mouse Weight balanced growth
21.5%.Be administered and observe in 14 days, without 1 animal dead, by only putting to death mice, dissect, the perusal heart, liver, spleen, lung,
Kidney, adrenal gland, thymus, Stomach duodenum, colon, seminal vesicle, prostate, testis, ovary, each internal organs of bladder, the most without exception
Existing.
Table 17: the compound antibacterial chewing gum oral administration impact on the weight of animals
The above results explanation compound antibacterial chewing gum toxicity is the lowest, and clinical administration is safe and reliable.
Embodiment 11: the hypersensitive test of antimicrobial gums
Take Cavia porcellus 18, be randomly divided into 3 groups by body weight sex, often group 6: compound antibacterial chewing gum group is (outside removing glue base
Antimicrobial gums solution), blank auxiliary group (the blank auxiliary solution outside removing glue base), 2,4-dinitro-chloro-benzene positive controls
Group, wherein in compound antibacterial chewing gum group and blank auxiliary group solution concentration with embodiment 10.Dosage is:
1. compound antibacterial chewing gum group 0.2ml/ is only；
2. blank auxiliary group 0.2ml/ is only；
3. 2,4-dinitro-chloro-benzene acetone soln (w/v) the matched group 0.2ml/ of 1% is only.
Hair 3 × 3cm on the left of guinea pig back is cut off, by 2 (3 × 3) cm after 24h before test2Clean filter paper is placed on Cavia porcellus
On the skin of unhairing of left side, the scraps of paper drip 0.2ml test sample and is allowed to drenched, then cover with one layer of oilpaper and two-layer gauze, then
Using nonirritant immobilization with adhesive tape, make sure test sample and contact skin 6h, the 7th day repeated to contact sensitization with the 14th day, totally 3 times.End
Secondary contact sensitization is after 14 days, on the right side of Cavia porcellus on skin of unhairing by method smear 0.2ml test sample respectively and excite contact, positive right
According to medicinal 1%2,4-dinitro-chloro-benzene acetone soln.Remove test sample, i.e. observable after 6h, and in 24,48,72h sees again
Examine and after smearing, have useless pawl to scratch the anaphylaxiss such as nose, sneeze, perpendicular hair, tic, dyspnea, gatism, shock and death.
Compound antibacterial chewing gum group excites with blank auxiliary group Cavia porcellus after contacting 6h and observes, and skin is existing without erythema and edema
As, its sensitization rate is 0, and positive controls sensitization rate is 100%.The results are shown in Table 18.
Table 18: antimicrobial gums excites guinea pig skin anaphylaxis situation after contact 6h
Embodiment 12: the preventing decayed tooth experimental study of compound antibacterial chewing gum
1. packet is tested
This experiment is divided into 4 groups, respectively distilled water group (negative control group), compound antibacterial chewing gum group (test group), empty
White adjuvant group (blank group) and chlorhexidine group (positive controls), often 10 SPF-SD rats of group.
2. the foundation of dental caries animal model
Choose big SPF-SD rat 40 (male and female half and half) in 18d age, all without dental caries.Feed with the cariogenic feedstuff of Keyes 2000#
With 5% aqueous sucrose solution 2d, (concentration is respectively to be separately added into ampicillin Mus age 20～22d in drinking-water and normal diet
400U/mL and 4mg/g), Mus 23d in age takes rat saliva of buccal cavity with aseptic cotton carrier, is coated with flat board, observes antibiotic fungistatic effect, mesh
Be for antibacterial original in killing rat oral cavity after, carry out the inoculation of S.sobrinus international standard strain.
Mus recovers to give cariogenic feedstuff 2000 age 24～28d#And continue to experiment to terminate, and in rat molar gingiva portion even
The S.sobrinus 6715 of continued access kind fresh cultured 18h, concentration is 2 × 109Colony-forming units (CFU/mL), every Mus mouth
Chamber aseptic cotton carrier is coated with wipes bacterium solution 200 μ L, is coated with and wipes different fasting in rear 2h, inoculates 1 time after the 30min of interval.Inoculation
(i.e. Mus 23d and 29d in age) 10 rats of random acquisition before and after S.sobrinus antibacterial, the buccal surface ground one's teeth in sleep Mus with aseptic cotton carrier and
Tooth closes face and presses unified method wiping bacterial plaque, is placed on by cotton swab after shaking up in 1ml sterile saline test tube, takes suspension in containing
The M-S culture plate of streptomycin, 37 DEG C of Anaerobic culturel 72h, whether antibacterial inoculates successfully in detection.Rat is divided by Mus 29d in age at random
Group #, 64d takes 10 rat dental plaques the most at random, and dilution is placed on BHI blood agar (recording total clump count) and MSB agar
(record S.sobrinus clump count) is cultivated, and seeks both ratios i.e. S.sobrinus level.
S.sobrinus level=(S.sobrinus clump count/total clump count) × 100%
Start to dip sterile distilled water, antimicrobial gums solution, blank auxiliary solution, chlorhexidine with aseptic cotton carrier from 30d
Solution smears each face of each group of rat oral mucosa and tooth, and for guaranteeing that medicinal liquid puts in place, every rat is taken out with blunt nosed syringe
Take 1mL injecting liquid drug keeps 10s to gargle in oral cavity, different fasting in 2h after process.
3. dental caries are damaged rank scores by Keyes method
Put to death rat, disconnected cranium after 61d, take mandibular bone on it, after removing soft tissue, jawbone is immersed 2.0% ammonium hydroxide molten
Soaking 30min in liquid, after cleaning-drying is placed on the murexide dye liquor 12h of 0.4%, clear water rinses, and natural drying at room temperature is used
Thin corundum sheet is cut along upper and lower jaw middle-distant direction sagittal sheet of grinding one's teeth in sleep, and marks according to Keyes after cleaning-drying under anatomic microscope
Method divides dental caries and progresses to dental caries (Dm) in enamel caries (E), superficial dentin caries (Ds), dentin, 4 levels of deep dentin caries (Dx)
Not, grind one's teeth in sleep every Mus respectively shiny surface and nest groove face dental caries damage marks, and evaluates the situation of Drug inhibition dental caries (at dental caries with this
Damage scoring process should have under two experimenter's blind and complete).Use SPSS16.0 statistical analysis software, measurement data is carried out
One factor analysis of variance.
4. result of the test
Before inoculation S.sobrinus, (i.e. before Mus 23d in age) gathers rat dental plaque in oral cavity through M-S agar culture medium
Have no after cultivation that S. mutans colony, Gram's staining and biochemical identification do not detect Streptococcus mutans；Inoculation S.sobrinus 3d
(i.e. Mus 29d in age) visible substantial amounts of S.sobrinus bacterium colony, Gram's staining and life in rat dental plaque in oral cavity culture medium afterwards
Change qualification and be defined as Streptococcus mutans, field planting success in rat oral cavity is described.
The change of 60d S.sobrinus level is shown in Table, compound antibacterial chewing gum group and blank auxiliary group, chlorhexidine group and steaming
Distilled water group has compared significant difference (p < 0.05), and chlorhexidine group, blank auxiliary group have significant difference compared with distilled water group
(p < 0.05), chlorhexidine group and blank auxiliary group have compared significant difference (p < 0.05).
Table 19: clump count and S.sobrinus ratio in Mus 60d in age rat dental plaque (N=10)
| Group | Total clump count | S.sobrinus clump count | S.sobrinus level (%) |
| Compound antibacterial chewing gum group | 207.43±23.13 | 57.80±5.35 | 28.17±4.00 |
| Blank auxiliary group | 301.80±27.54 | 103.61±6.21 | 34.66±4.51<sup>*#</sup> |
| Chlorhexidine group | 267.43±20.23 | 86.61±6.57 | 32.54±3.46<sup>*#▲</sup> |
| Distilled water group | 374.43±21.49 | 150.61±14.27 | 40.44±5.45<sup>*</sup> |
*P < 0.05, compares with compound antibacterial chewing gum group,#P < 0.05, compares with distilled water group,▲P < 0.05, auxiliary with blank
Material group compares
Rat shiny surface dental caries damage to score and the results are shown in Table, in E level dental caries damage and score, except distilled water group has compared with remaining each group
Statistical significance outer (p<0.01), between remaining each group, Keyes scores equal not statistically significant (p>0.05)；Damage at Ds level dental caries
In, compared with distilled water group, blank auxiliary group Keyes is scored and is substantially reduced, and has significant difference (p < 0.01), compound antibacterial mouth
Fragrant sugar group and chlorhexidine group all do not detect, and show that shiny surface degree of depth dental caries are damaged preferable preventive effect by it；Dm and Dx level dental caries only damage
Distilled water group detects.
Table 20: shiny surface dental caries damage Keyes score (N=10)
| Compound antibacterial chewing gum group | Blank auxiliary group | Chlorhexidine group | Distilled water group | |
| E | 4.54±1.13* | 5.43±2.22<sup>*</sup> | 4.26±1.35* | 8.58±2.67 |
| Ds | 0 | 2.39±0.85<sup>#</sup> | 0 | 5.49±1.47 |
| Dm | 0 | 0 | 0 | 3.29±0.36 |
| Dx | 0 | 0 | 0 | 2.56±0.54 |
*P < 0.05, compares with distilled water group,#P < 0.05, compares with distilled water group
In pit and fissure caries damages, each group rat all occurs that the most serious dental caries are bad.In E level dental caries damage, compared with distilled water group,
Remaining each group dental caries is scored and is all had significance to reduce (p < 0.01), and compound antibacterial chewing gum group and chlorhexidine group all show glaze
The preferable prevention effect of matter dental caries, is above blank auxiliary group (p<0.01), but there was no significant difference (p>0.05) between two groups；At dental caries
Damage in severity, compound antibacterial chewing gum group DmLevel dental caries damage and do not detect, and remaining each group all significantly reduces Ds, Dm level dental caries and damage, with
Distilled water group has compared significant difference (p < 0.01), wherein compound antibacterial chewing gum group prevention effect higher than blank auxiliary group and
Chlorhexidine group (p < 0.01)；In Dx level dental caries damage, compound antibacterial chewing gum group does not detects, and chlorhexidine group and blank auxiliary group are
Reducing, have significant difference (p < 0.01) compared with distilled water group, wherein compound antibacterial chewing gum group prevention effect is higher than blank
Adjuvant group and chlorhexidine group (p < 0.01).The above results shows that each medication group has certain preventive effect to pit and fissure caries, but in advance
Anti-effect there are differences.
Table 21: nest groove face dental caries damage Keyes score (N=10)
| Compound antibacterial chewing gum group | Blank auxiliary group | Chlorhexidine group | Distilled water group | |
| E | 21.50±4.64*# | 34.13±6.83* | 25.93±4.45*# | 49.22±6.22 |
| Ds | 6.20±1.91 | 18.29±4.07<sup>▲</sup> | 18.32±3.46<sup>▲</sup> | 38.73±8.95 |
| Dm | 0 | 6.63±1.44<sup>●</sup> | 3.83±1.53<sup>●</sup> | 15.07±1.78 |
| Dx | 0 | 1.63±0.45<sup>■</sup> | 0.98±0.33<sup>■</sup> | 7.52±0.94 |
*P < 0.05, compares with distilled water group,#P < 0.05, compares with blank auxiliary group,▲■P < 0.05, with compound antibacterial mouth
Fragrant sugar group compares
Embodiment 13: the experimental study of the pre-preventing parodontitis of antimicrobial gums
1. packet is tested
This experiment is divided into 4 groups, respectively distilled water group (negative control group), compound antibacterial chewing gum group (test group), empty
White adjuvant group (blank group) and chlorhexidine group (positive controls), often 10 SPF-SD rats of group.
2. the foundation of experimental animal model of periodontitis
Choose the SPF-SD rat 40 (male and female half and half) at 12 monthly ages, with 3% pentobarbital sodium intraperitoneal injection of anesthesia, treat big
After Mus enters narcotism, take its dorsal position, extremity and head and be fixed in fixed plate.First by right maxillary first molar periodontal and tooth
Root face separates, and then with correction ligature of steel wire neck portion, ligature to be positioned over below gingiva as far as possible, and from the beginning of experimental day
Feed high sugar feed and 20% high sucrose solution.After modeling one week, in order to promote model inducing effect, the next day Oral inoculation pathogenic bacterium
1 time, i.e. porphyromonas gingivalis, actinomyces viscosus, tool core fusiform bacilarmature, ratio is 2:1:1 mixed bacteria liquid, every Mus every day
0.1ml, altogether inoculation 3 times.After continuation high sugar feed feeds 1 week, within the 5th week, put to death, put to death every index of fore-and-aft observing periodontal.
3. packet and medication
By successful for modeling 40 rats, it is randomly divided into 4 groups on pretreatment, often group 10, male and female half and half.Respectively with aseptic
Cotton swab dips sterile distilled water, antimicrobial gums solution, blank auxiliary solution, chlorhexidine smear each group of rat oral mucosa
And tooth gingival margin, for guaranteeing that medicinal liquid puts in place, every rat blunt nosed syringe extraction 1mL injecting liquid drug keeps 10s to gargle in oral cavity
Mouthful, different fasting in 2h after process.Treatment cycle is 20 days, and treatment passes through gingival hemorrhage index, plaque index, periodontal after terminating
Bag spy is examined the periodontitis inflammation index such as the degree of depth, frontal resorption value and is carried out therapeutic evaluation.
4. result of the test
Gingival hemorrhage index results is shown in Fig. 5, and as seen from table compared with distilled water group, remaining each group all can significantly reduce gingiva
Bleeding index (p < 0.01), compound antibacterial chewing gum group and chlorhexidine group effect are better than blank auxiliary group (p < 0.01), but both
No significant difference (p > 0.05).
Plaque index result is shown in Fig. 6, and as seen from table compared with distilled water group, remaining each group all can significantly reduce plaque index
(p < 0.01), compound antibacterial chewing gum group effect is better than blank auxiliary group and chlorhexidine group (p < 0.01).
Periodontal pocket spy is examined depth results and is seen Fig. 7, and as seen from table compared with distilled water group, remaining each group all can significantly reduce spy
Examining the degree of depth (p < 0.01), compound antibacterial chewing gum group effect is better than blank auxiliary group and chlorhexidine group (p < 0.01).
Frontal resorption value result is shown in Fig. 8, and as seen from table compared with distilled water group, remaining each group all can significantly inhibit alveolus
Bone resorption (p < 0.01), compound antibacterial chewing gum group and chlorhexidine group effect are better than blank auxiliary group (p < 0.01), but both nothings
Notable difference (p > 0.05).
The above results shows, compound antibacterial chewing gum group and chlorhexidine group all show preferable curative effect, and compound antibacterial
Chewing gum is better than the most again chlorhexidine.
Claims (6)
1. a compound antibacterial chewing gum, it is characterised in that this prepared antimicrobial gums is by following raw material by mass percentage
Composition:
Cecropin D-7:1.0%, CPC:1.5%, Herba Dendranthematis indici extract: 1.5%, glycerol: 0.2～0.8%, Sorbitol: 30%
～40%, xylitol: 30%～40%, gum base: 20%～30%, Oleum menthae: 0.1%～1%, acesulfame potassium: 0.1%～
0.5%, arabic gum: 0.1%～0.5%, titanium dioxide: 0.1%～0.5%, Brazil wax: 0.01%～0.05%,
The mass percent sum of raw material is 100%.
2. compound antibacterial chewing gum as claimed in claim 1, it is characterised in that described cecropin D-7 uses Fmoc solid phase
Synthetic method synthesizes on mbha resin, and the peptide sequence of this cecropin D-7 is KKVVFWVKFK-NH2, purity is 95%, molecule
Amount is 1308.7.
3. the preparation method of the compound antibacterial chewing gum described in claim 1 or 2, it is characterised in that prepare as follows:
S1: feed intake stirring
1. by xylitol, Sorbitol the most finely ground mistake 100 mesh sieve, respectively with appropriate purified water moistening obtain xylitol syrup,
Sorbitol syrup；And arabic gum and the titanium dioxide of appropriate xylitol syrup with formula ratio are uniformly mixed under the conditions of 80 DEG C
It is standby that conjunction is prepared as coatings；
2. the gum base weighing recipe quantity is placed in oven heat, makes its uniformly softening at a set temperature；
3. taking out in gum base puts into blender the glycerol being stirred and adding recipe quantity half after softening, stirring softens 5min,
Obtain the first material；
4. adding the sorbitol syrup of recipe quantity half in the first material, 4min is to being thoroughly mixed in stirring；Add remaining
Glycerol is lubricated stirring, adds the Oleum menthae of recipe quantity half, CPC and Flos Chrysanthemi Indici extract after 2min, continues stirring 5min,
Obtain the second material；
5. second material adds remaining sorbitol syrup, residue xylitol, the acesulfame potassium of formula ratio and cecropin D-7,
Mixing, stirs 4min, obtains 3 material；
6. in 3 material, finally add remaining Oleum menthae stirring 6min, stop stirring, take out stirring material；
S2: molding, quenched
By stirring material stripping and slicing and cool down, putting into extrusion in forming machine material receiving port, the label mass average value of molding controls
0.90g/ grain, label be placed in low temperature and low humidity quenched in quenched aging more than 24h；
S3: coating
After quenched aging end, the label that precise is good is positioned in coating pan, keeps coating pan to continue, turn evenly
Dynamic, continually add coatings and be coated, till the coated cores mass average value of molding reaches 1.40 grams/, bag
Garment piece core takes the dish out of the pot；
S4, quenched
Coated cores be positioned over low temperature and low humidity quenched in quenched aging more than 24h；
S5, polishing
Precise coated cores well is positioned in polishing pot, keeps polishing pot to continue, rotate evenly and add prescription
The Brazil wax of amount is polished, and obtains compound antibacterial chewing gum.
4. method as claimed in claim 3, it is characterised in that the mass ratio of described coatings and sheet sandwich layer is 10:1.
5. the compound antibacterial chewing gum described in claim 1 or 2 is for the application of oral cavity acute infectious diseases medicine.
Apply the most as claimed in claim 5, it is characterised in that described oral cavity acute infectious diseases is dental caries, dental caries
Form and alleviate dental caries and damage destructiveness；The slight sulcular bleeding index of periodontitis, plaque index, Periodontal Probing Depth and alveolar bone
Absorption value.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101578104A (en) * | 2005-10-18 | 2009-11-11 | 美国陆军部 | Antimicrobial decapeptide oral hygiene treatment |
| CN102067933A (en) * | 2009-11-20 | 2011-05-25 | 樊宪涛 | Health chewing gum |
| CN102125156A (en) * | 2010-12-15 | 2011-07-20 | 郑高育 | Chewing gum for preventing and treating diabetes and preparation method thereof |
| CN103598389A (en) * | 2013-11-17 | 2014-02-26 | 陶峰 | Milk-flavor raisins |
| CN105641161A (en) * | 2016-03-15 | 2016-06-08 | 周利 | Antibacterial chewing gum and preparation method thereof |
-
2016
- 2016-06-13 CN CN201610423697.2A patent/CN106071027A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101578104A (en) * | 2005-10-18 | 2009-11-11 | 美国陆军部 | Antimicrobial decapeptide oral hygiene treatment |
| CN102067933A (en) * | 2009-11-20 | 2011-05-25 | 樊宪涛 | Health chewing gum |
| CN102125156A (en) * | 2010-12-15 | 2011-07-20 | 郑高育 | Chewing gum for preventing and treating diabetes and preparation method thereof |
| CN103598389A (en) * | 2013-11-17 | 2014-02-26 | 陶峰 | Milk-flavor raisins |
| CN105641161A (en) * | 2016-03-15 | 2016-06-08 | 周利 | Antibacterial chewing gum and preparation method thereof |
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