CN107536725A - A kind of multiple-effect oral cavity composition and its application containing hyaluronic acid mixtures - Google Patents
A kind of multiple-effect oral cavity composition and its application containing hyaluronic acid mixtures Download PDFInfo
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Abstract
The invention discloses a kind of multiple-effect oral care composition containing hyaluronic acid mixtures, it includes 0.5~2.0 part of 0.1~5.0 part of hyaluronic acid mixtures and citric acid Chinese catalpa, the hyaluronic acid mixtures include low-molecular-weight hyaluronic acid, high molecular weight hyaluronic acid, and the weight ratio of the low-molecular-weight hyaluronic acid and high molecular weight hyaluronic acid is 1：(0.5~2.0).The invention also discloses the application of above-mentioned multiple-effect oral care composition.Compared with prior art, the hyaluronic acid of composition using the different molecular weight ranges of the present invention, which is combined, is used as main active component, and compounded with zinc citrate, play a part of Synergistic, there is the effect of antibacterial, anti-inflammatory, reparation, imparting health of mouth cavity daily, Prevention disease.
Description
Technical field
The present invention relates to oral care techniques field, and in particular to have suppress oral cavity pathogen, anti-mucous membrane of mouth inflammation,
Repair the oral care composition of the multiple efficacies such as mucous membrane of mouth, and the application of said composition.
Background technology
Hyaluronic acid is a kind of acid mucopolysaccharide, Columbia Univ USA ophthalmology professor Meyer in 1934 etc. first from
The material is isolated in bovine vitreous body.Hyaluronic acid is shown more with its unique molecular structure and physicochemical property in body
The important physiological function of kind.Both at home and abroad multiple studies have shown that hyaluronic acid is to form periodontal tissue's epimatrix in the oral cavity
Important component, also containing hyaluronic acid in the saliva of people, it is possible to increase the greasy property and mouth disease of saliva cure performance, and
Assist protection oral mucosa.Pirnazar et al. research shows that hyaluronic acid is (public to intraoral actinobacillus actinomycetem comitans
Think closely related with periodontitis, be one of bacterium of most study in periodontitis bacterial etiology), the general Salmonella of mouth, golden yellow
Staphylococcus etc. has inhibitory action.
The Effect of Oral Nursing Care of hyaluronic acid is shown as, the anti-inflammatory of the surface of a wound, anti-infective, water resistant after extraction and implant operation
Swollen, bacteria growing inhibiting effect；Promote periodontium wound healing, the effect repaired；Accelerate the healing of the disease of cari oris mucosa
Journey, pain of alleviation；Solve due to xerostomia and mucous membrane is scorching hot and discomfort for bringing etc..
In the prior art, had and hyaluronic acid has been used in oral care product, such as Publication No. CN 104666112
A Chinese patent discloses a kind of bioactivity hyaluronic acid toothpaste, the antiinflammatory action scorching for gingivitis and oropharyngeal cavity mucous membranes.
The A of Publication No. CN 103462847 Chinese patent application document discloses a kind of oral care mouthwash, and the mouthwash contains
There is hyaluronic acid 0.5~1.5%, for the antibacterial of the mouth diseases such as canker sore with eliminating oral peculiar smell.Publication No. CN
105250332 A Chinese patent application document discloses a kind of shield gum permanent tooth multiple-effect dental care thing and its application, the multiple-effect
Dental care thing contains 0.1~1.5 part of Sodium Hyaluronate, for preventing and treating the oral cavity such as sensitivity of tooth, bleeding gums, canker sore disease
The effect of disease.The A of Publication No. CN 105213298 Chinese patent application document discloses a kind of oral care gels and its system
Preparation Method, wherein, Sodium Hyaluronate weight accounts for the 0.1%-2% of gel gross weight, for preventing and alleviating oral problem, reaches
Anti-inflammatory is antibacterial, promotes the reparation and regeneration of mucous membrane of mouth and tissue, the effect that attenuating inflammation and wound ooze out.Publication No. CN
106176690 A Chinese patent application document discloses hyaluronic acid oral care film and preparation method and application, the oral cavity
Nursing film contains Sodium Hyaluronate 10%~50%, zinc hyaluronate 10%~40%, hydrolyzes Sodium Hyaluronate 10%~40%, tool
There is antibacterial, repair cell damage and other effects.The A of Publication No. CN 106344450 Chinese patent application document discloses one kind
Hyaluronic acid is brushed teeth tooth piece and preparation method, wherein preventing tooth with radix glycyrrhizae and ascorbic acid with reference to the anti-inflammatory activity of hyaluronic acid
Oulorrhagia, eliminate the oral inflammation such as red and swollen, comprehensively solve hemodia, preventing and treating gingivitis, periodontitis and oropharyngeal cavity mucous membranes inflammation and ask
Topic.
The content of the invention
It is an object of the invention to provide it is a kind of containing hyaluronic acid mixing multiple-effect oral care composition, said composition with
The hyaluronic acid of different molecular weight ranges is combined as main active component, and is compounded with zinc citrate, plays collaboration
The effect of synergy, there is the effect of antibacterial, anti-inflammatory, reparation, imparting health of mouth cavity daily, Prevention disease.
Technical scheme is as follows：
A kind of multiple-effect oral care composition containing hyaluronic acid mixtures, it includes hyaluronic acid mixtures and citric acid
Chinese catalpa, the hyaluronic acid mixtures include low-molecular-weight hyaluronic acid, high molecular weight hyaluronic acid.
Preferably, by weight, 0.1~5.0 part of hyaluronic acid mixtures, 0.5~2.0 part of zinc citrate.
Preferably, the weight ratio of the low-molecular-weight hyaluronic acid and high molecular weight hyaluronic acid is 1：(0.5~2.0).
Preferably, the weight average molecular weight of the low-molecular-weight hyaluronic acid is 20~40kDa, the HMW hyalomitome
The weight average molecular weight of acid is 120~140kDa.
Another object of the present invention is to provide the application of above-mentioned multiple-effect oral care composition, above-mentioned multiple-effect oral cavity is protected
Manage composition to be applied in oral care product, the oral care product includes toothpaste, tooth powder, mouthwash, mouth spray.
Preferably, content percentage of the zinc citrate in oral care product is 0.5~2.0%, transparent
Content percentage of the matter acid in oral care product is 0.1~5.0%.
Preferably, above-mentioned multiple-effect oral care composition is applied in toothpaste, and the hyaluronic acid mixtures are added to tooth
After being uniformly dispersed in the NMF of cream, add zinc citrate and mix.
Preferably, above-mentioned multiple-effect oral care composition is applied in toothpaste, and the toothpaste uses following preparation method：
S1：Sweetener is added to the water stirring and dissolving；
S2：Thickener, hyaluronic acid mixtures are added in NMF, are uniformly dispersed；
S3：The finely dispersed solution of step S2 is added in step S1, stirred；
S4：Zinc citrate is added in step S3 and stirred；
S5：Surfactant is added in rubbing agent and stirred, obtains uniform powder；
S6：By step S5 uniform powder, add in step S4, be uniformly mixing to obtain uniform lotion；
S7：Preservative is added in essence, heating water bath dissolves essence, obtains homogeneous solution；
S8：Step S7 homogeneous solution is added in step S6 uniform lotion and stirred, is evacuated.
Or the toothpaste uses following preparation method：
S1：Sweetener and preservative are added to the water stirring and dissolving；
S2：Thickener, hyaluronic acid mixtures are added in NMF, are uniformly dispersed；
S3：The finely dispersed solution of step S2 is added in step S1, stirred；
S4：Zinc citrate is added in step S3 and stirred；
S5：Surfactant is added in rubbing agent and stirred, obtains uniform powder；
S6：By step S5 uniform powder, add in step S4, be uniformly mixing to obtain uniform lotion；
S7：Step S6 uniform lotion is evacuated.
Compared with prior art, the beneficial effects of the invention are as follows：
1st, the hyaluronic acid of low molecule amount and the hyaluronic acid of HMW are compounded and to form mixture by the present invention, play work(
The effect that can be compounded, the hyaluronic acid of low molecule amount have good Mucous rehabilitation effect, and the hyaluronic acid of HMW has
Good mucous membrane antiinflammatory action, while hyaluronic acid mixtures play the antibacterial effect that cooperates with zinc citrate compounding, suppress mouth
Chamber pathogenic bacteria, have the function that to safeguard oral health.
2nd, composition of the invention, is verified by vitro test, can significantly inhibit oral cavity pathogen, anti-oral mucositis
Disease and reparation mucous membrane of mouth.
Brief description of the drawings
Fig. 1 illustrates the influence of comparative example and embodiment sample to the cell proliferation rates of RAW 264.7；
Fig. 2 illustrates the influence that comparative example and embodiment sample induce the cells of RAW 264.7 to produce NO LPS；
Fig. 3 illustrates the influence that comparative example and embodiment sample induce the cells of RAW 264.7 to produce IL-6 LPS；
Fig. 4 shows the result of comparative example and embodiment sample to L929 cell repairs.
Embodiment
The present invention is described in further detail below by specific embodiment.
Embodiment 1
A kind of multiple-effect oral care composition containing hyaluronic acid mixtures, by weight, including hyaluronic acid mixing
0.5~2.0 part of thing 0.1~5.0, citric acid Chinese catalpa.The hyaluronic acid mixtures include low-molecular-weight hyaluronic acid, HMW
Hyaluronic acid, the weight ratio of the low-molecular-weight hyaluronic acid and high molecular weight hyaluronic acid is 1：(0.5~2.0).It is described low
The weight average molecular weight of molecular weight hyaluronic acid is 20~40kDa, the weight average molecular weight of the high molecular weight hyaluronic acid for 120~
140kDa。
Embodiment 2
Multiple-effect oral care composition described in embodiment 1 is applied in toothpaste, the component of the toothpaste includes：
One or both of the preferred sorbierite of the NMF, glycerine, polyethylene glycol are mixed above；
One or both of the preferred hydrated silica of the rubbing agent, calcium carbonate, calcium monohydrogen phosphate are mixed above；
In the thickener preferably carboxymethyl cellulose sodium, xanthans, HPMC, carragheen, guar gum
One or more mixing；
The mixing of one or both of the preferred laruyl alcohol sodium sulfovinate of the surfactant, crystalline sodium pyrophosphate.
The preservative is oil-solvent preservative.
The toothpaste uses following preparation method：
S1：Sweetener is added to the water stirring and dissolving；
S2：Thickener, hyaluronic acid mixtures are added in NMF, are uniformly dispersed；
S3：The finely dispersed solution of step S2 is added in step S1, stirred；
S4：Zinc citrate is added in step S3 and stirred；
S5：Surfactant is added in rubbing agent and stirred, obtains uniform powder；
S6：By step S5 uniform powder, add in step S4, be uniformly mixing to obtain uniform lotion；
S7：Preservative is added in essence, heating water bath dissolves essence, obtains homogeneous solution；
S8：Step S7 homogeneous solution is added in step S6 uniform lotion and stirred, is evacuated.
Embodiment 3
Multiple-effect oral care composition described in embodiment 1 is applied in toothpaste, the component of the toothpaste includes：
One or both of the preferred sorbierite of the NMF, glycerine, polyethylene glycol are mixed above；
One or both of the preferred hydrated silica of the rubbing agent, calcium carbonate, calcium monohydrogen phosphate are mixed above；
In the thickener preferably carboxymethyl cellulose sodium, xanthans, HPMC, carragheen, guar gum
One or more mixing；
The mixing of one or both of the preferred laruyl alcohol sodium sulfovinate of the surfactant, crystalline sodium pyrophosphate.
The preservative is waterborne-type preservation.
The toothpaste uses following preparation method：
S1：Sweetener and preservative are added to the water stirring and dissolving；
S2：Thickener, hyaluronic acid mixtures are added in NMF, are uniformly dispersed；
S3：The finely dispersed solution of step S2 is added in step S1, stirred；
S4：Zinc citrate is added in step S3 and stirred；
S5：Surfactant is added in rubbing agent and stirred, obtains uniform powder；
S6：By step S5 uniform powder, add in step S4, be uniformly mixing to obtain uniform lotion；
S7：Step S6 uniform lotion is evacuated.
Embodiment 4
The multiple-effect oral cavity composition of embodiment 1 is applied in toothpaste, the toothpaste by weight, including following components：
The preparation method of the toothpaste is referring to embodiment 2.
Embodiment 5
The multiple-effect oral cavity composition of embodiment 1 is applied in toothpaste, the toothpaste by weight, including with the following group
Point：
The preparation method of the toothpaste is referring to embodiment 2.
Embodiment 6 verifies the experiment of multiple-effect oral care composition of the present invention
Comparative example 1：Formulation of tooth-paste and preparation method are referring to embodiment 4, but hyaluronic acid mixtures are 0 part, zinc citrate
For 0 part.
Comparative example 2：Formulation of tooth-paste and preparation method are referring to embodiment 4, but hyaluronic acid mixtures are that 0.5 part of molecular weight is
20~40kDa hyaluronic acid, zinc citrate are 0 part.
Comparative example 3：Formulation of tooth-paste and preparation method are referring to embodiment 4, but hyaluronic acid mixtures are that 0.5 part of molecular weight is
120~140kDa hyaluronic acid, zinc citrate are 0 part.
Comparative example 4：Formulation of tooth-paste and preparation method are referring to embodiment 4, but hyaluronic acid mixtures are 0 part, zinc citrate
For 0.5 part.
(1) study on the stability
Comparative example 1, comparative example 2, comparative example 3, comparative example 4, the stability (high temperature 45 of embodiment 4 and the toothpaste of embodiment 5
DEG C) result is as shown in table 1.
Table 1
| Sample ID | 7 days | 15 days | 1 month | 2 months | 3 months |
| Comparative example 1 | Normally | Normally | Normally | Slightly divide water | Slightly divide water |
| Comparative example 2 | Normally | Normally | Normally | Slightly divide water | Slightly divide water |
| Comparative example 3 | Normally | Normally | Slightly divide water | Slightly divide water | Severe divides water |
| Comparative example 4 | Normally | Normally | Slightly divide water | Moderate divides water | Severe divides water |
| Embodiment 4 | Normally | Normally | Normally | Normally | Normally |
| Embodiment 5 | Normally | Normally | Normally | Normally | Normally |
(2) bacteriostatic experiment
A takes oral cavity pathogen bacterium solution 0.2mL to be respectively coated in BHIA flat boards, 37 DEG C of Anaerobic culturel 48-72h；
B elutes BHIA flat boards respectively with the sterile PBS solutions of 2-3mL, collects eluent respectively and is caused a disease as test with oral cavity
Bacterium solution；
C is separately added into the sterile PBS and 25g toothpaste samples of 75mL into the 250mL sterile conical flask containing bead
Product, triangular flask is shaken, make toothpaste fully dispersed into homogenate solution (25%), then draw 9mL dentifrice slurries and add sterile glass
It is standby in test tube；
Eluent in B is diluted to 1 × 10 by D with sterile PBS solution respectively6-5×106CFU/mL concentration；
E blank groups, it is each to draw 1.0mL bacteria suspensions (1 × 106-5×106CFU/mL whirlpool in the sterile PBS solutions of 9mL) is added
Vibration mixes, and acts on 2min, then draws mixed liquor and is suitably diluted, is counted after Anaerobic culturel 72h；
F experimental groups, it is each to draw 1.0mL bacteria suspensions (1 × 106-5×106CFU/mL) respectively with 9mL dentifrice slurry vortex oscillations
Mix, act on 2min.Then draw mixed liquor suitably to be diluted, counted after Anaerobic culturel 72h；
G calculates sterilizing rate by following equation
Experimental result is as shown in table 2.
Table 2
(3) cytotoxicity
Using the influence of mtt assay detection raw material or finished product to the cell viabilities of RAW 264.7.Choose exponential phase
RAW264.7 cells, after cell is collected in digestion, add in the DMEM culture mediums containing 10%FBS and cell suspending liquid is made, to connect
Kind concentration 25 × 104Individual/mL concentration is inoculated in 96 orifice plates (100 μ L/ holes), while sets blank zeroing hole (culture medium bed board
Hole) and control wells (DMSO handles hole), 5%CO2, 37 DEG C of overnight incubations, add sample and handled and (contain 5 μ g/mL LPS), often
Individual sample sets 5 multiple holes, 5%CO2, 37 DEG C are incubated careful sucking-off nutrient solution after 24h, add what 50 μ L culture mediums were prepared per hole
MTT solution (5mg/mL, i.e. 0.5%MTT)；Continue after cultivating 2h, carefully suck nutrient solution in hole.150 μ L are added per hole
DMSO, low-speed oscillation 10min on shaking table is put, crystal is fully dissolved；The light absorption value in each hole at 570nm is measured with ELIASA,
Cell proliferation rate calculation formula=(control group OD values-drug study group OD values)/(control group OD values-blank zeroing group OD values)
× 100%.
Evaluation criterion：Cell proliferation rate >=80% is considered as toothpaste sample no cytotoxicity.
Experimental result is shown in accompanying drawing 1.
Result of the test shows that the toothpaste containing hyaluronic acid does not have toxicity to cell, and the toothpaste containing zinc citrate is to cell
There is no toxicity.
(4) cell anti-inflammation test
NO influence is produced to LPS induction RAW 264.7 cells, is detected using Griess reagents method in cell culture medium
Nitric oxide (NO) content is detected.
1) cells of RAW 264.7 adjustment cell concentration is 50 × 104Individual/mL, it is inoculated in 24 well culture plates, adds per hole
1mL cell suspending liquids, it is placed in 37 DEG C, 5%CO2It is incubated in incubator.
2) cell attachment after 24h, cell are rinsed with PBS, add the DMEM culture mediums that 1mL is free of serum.Dosing raw material or
After finished product 1h plus LPS 1uL, final concentration of 5 μ g/mL, 24h collect supernatant.
3) using green skies nitric oxide detection kit detection NO content
A serum free medium dilution standard product：0、1、2、5、10、20、40、60、100uM；
The μ L Griess Reagent I+50 μ L Griess Reagent II of 50 μ L/ holes of B+50
C shakes 3min, with the absorption photometric value (OD values) at enzyme mark photometer detection 540nm wavelength, is repeated 2 times.NO's
Concentration is according to NaNO2Standard curve is calculated.The result of drug test group is scaled the percentage expression of LPS control groups, such as
Accompanying drawing 2.
The difference p of embodiment 4 and comparative example 2<0.001, the difference p with comparative example 3<0.05；Implement
Example 5 and the difference of comparative example 2 and comparative example 3 are all p<0.001.Result of the test is shown, contains hyaluronic acid mixtures
Toothpaste than containing unimodal molecular weight hyaluronic acid have significantly lower NO products, there is the effect of anti-inflammatory.
The level of the inflammation related activity factor, this experiment use magnificent mouse ELISA in ELISA detection cell culture mediums
IL-6 in kit (double antibody sandwich method) detection cell culture medium.
1) supernatant prepares such as above-mentioned nitric oxide (NO) test experiments.
2) sample treatment：Cells and supernatant：- 80 DEG C preserve (in 2 months), using preceding defrosting, and 1000 × g, 4 DEG C,
Centrifuge 15min.
3) test operation is as shown in ELISA kit specification.
4) result of the test, accompanying drawing 3 is seen.
The difference p of embodiment 4 and comparative example 2<0.01, the difference p with comparative example 3<0.05；Embodiment
5 and the difference of comparative example 2 be all p<0.001, the difference p with comparative example 3<0.01.Result of the test is shown, is contained
There is the toothpaste of hyaluronic acid compositions than there is the content for significantly reducing IL-6 containing unimodal molecular weight hyaluronic acid, have anti-
The effect of scorching.
(5) cellular damage repairing test
It is 1 × 10 to prepare density6Individual/mL cell suspension, (2mL/ wares, back side picture are inoculated in 35mm capsules
Marker strokes horizontal line marks), culture is to being paved with plate bottom.Cell culture fluid is sucked, is manufactured carefully perpendicular to orifice plate with 200 μ L pipette tips
Born of the same parents' cut, ensure that each scratch width is consistent as far as possible.Orifice plate is rinsed with PBS three times, washes away cell fragment caused by cut.Add
2mL DMEM culture mediums and medicine, with DMSO negative control group, 0h is taken, 48h time points are taken pictures.Pay attention to different time points
Each visual field is answered the bid same position when taking pictures.
Result of the test is shown in accompanying drawing 4.
Result of the test shows that the toothpaste containing hyaluronic acid mixtures is more aobvious than having containing unimodal molecular weight hyaluronic acid
Write and promote repair ability, there is the effect of injury repair.
(6) animal anti-inflammation test
By quarantine it is qualified after 78 SOF level mouse be randomly divided into 6 groups, every group 13, be respectively：Dimethylbenzene model pair
According to group, 1 group of sample, 2 groups of sample, 3 groups of sample and dexamethasone sodium phosphate injection group.
After mouse quarantine packet, left ear is not dealt with as background values, inside and outside auris dextra two sides apply altogether 30 μ L dimethylbenzene it is molten
Liquid, after 30min in addition to model control group, 0.1g sample, dexamethasone sodium phosphate injection are smeared in tested group of mouse right ear two sides
Liquid group smears 50 μ L dexamethasone sodium phosphate injection, is smeared after parenteral solution 30min second, mouse is extractd after applying sample 1h
Eyeball takes blood, and cervical dislocation puts to death mouse, cleans sample, cut ears, take a diameter of 8mm auricle (the same position of left and right ear)
Weigh record.The weight difference of same animal or so ear is swelling.
Swelling=auris dextra auricle weight-left ear auricle weight
Swelling inhibiting rate=(the average swelling of the average swelling-treatment group of model control group)/model control group is averagely swollen
Expansibility × 100%
Result of the test shows that the toothpaste containing hyaluronic acid compositions is more aobvious than having containing unimodal molecular weight hyaluronic acid
Write and suppress ear swelling, there is the effect of anti-inflammatory.
The announcement and teaching of book according to the above description, those skilled in the art in the invention can also be to above-mentioned embodiment party
Formula is changed and changed.Therefore, the invention is not limited in embodiment disclosed and described above, to the present invention's
Some modifications and changes should also be as falling into the scope of the claims of the present invention.In addition, although used in this specification
Some specific terms, but these terms are merely for convenience of description, do not form any restrictions to the present invention.
Claims (9)
- A kind of 1. multiple-effect oral care composition containing hyaluronic acid mixtures, it is characterised in that：Including hyaluronic acid mixtures With citric acid Chinese catalpa, the hyaluronic acid mixtures include low-molecular-weight hyaluronic acid, high molecular weight hyaluronic acid.
- 2. multiple-effect oral care composition as claimed in claim 1, it is characterised in that：By weight, hyaluronic acid mixes 0.1~5.0 part of thing, 0.5~2.0 part of zinc citrate.
- 3. multiple-effect oral care composition as claimed in claim 1, it is characterised in that：The low-molecular-weight hyaluronic acid and height The weight ratio of molecular weight hyaluronic acid is 1：(0.5~2.0).
- 4. multiple-effect oral care composition as claimed in claim 1, it is characterised in that：The weight of the low-molecular-weight hyaluronic acid Average molecular weight is 20~40kDa, and the weight average molecular weight of the high molecular weight hyaluronic acid is 120~140kDa.
- 5. application of the multiple-effect oral care composition in oral care product described in Claims 1-4 any one, described Oral care product includes toothpaste, tooth powder, mouthwash, mouth spray.
- 6. application as claimed in claim 5, it is characterised in that：Content of the zinc citrate in oral care product by weight hundred Fraction is calculated as 0.5~2.0%, and content percentage of the hyaluronic acid in oral care product is 0.1~5.0%.
- 7. application as claimed in claim 5, it is characterised in that the oral care product is toothpaste, and the hyaluronic acid mixes Compound is added to be uniformly dispersed in the NMF of toothpaste after, add zinc citrate and mix.
- 8. application as claimed in claim 7, it is characterised in that the preparation method of the toothpaste is as follows：S1：Sweetener is added to the water stirring and dissolving；S2：Thickener, hyaluronic acid mixtures are added in NMF, are uniformly dispersed；S3：The finely dispersed solution of step S2 is added in step S1, stirred；S4：Zinc citrate is added in step S3 and stirred；S5：Surfactant is added in rubbing agent and stirred, obtains uniform powder；S6：By step S5 uniform powder, add in step S4, be uniformly mixing to obtain uniform lotion；S7：Preservative is added in essence, heating water bath dissolves essence, obtains homogeneous solution；S8：Step S7 homogeneous solution is added in step S6 uniform lotion and stirred, is evacuated.
- 9. application as claimed in claim 7, it is characterised in that the preparation method of the toothpaste is as follows：S1：Sweetener and preservative are added to the water stirring and dissolving；S2：Thickener, hyaluronic acid mixtures are added in NMF, are uniformly dispersed；S3：The finely dispersed solution of step S2 is added in step S1, stirred；S4：Zinc citrate is added in step S3 and stirred；S5：Surfactant is added in rubbing agent and stirred, obtains uniform powder；S6：By step S5 uniform powder, add in step S4, be uniformly mixing to obtain uniform lotion；S7：Step S6 uniform lotion is evacuated.
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| CN110585062A (en) * | 2019-09-30 | 2019-12-20 | 华熙生物科技股份有限公司 | Hyaluronic acid oral care composition and preparation method and application thereof |
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| CN112168739A (en) * | 2020-09-25 | 2021-01-05 | 山东华熙海御生物医药有限公司 | Composition containing hyaluronic acid and application of composition in oral care product |
| CN112921065A (en) * | 2021-02-05 | 2021-06-08 | 广州舒客实业有限公司 | Screening system, model and construction method of oral care composition containing hyaluronic acid |
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