CN101028516A - Medicine preparation for oral cavity - Google Patents
Medicine preparation for oral cavity Download PDFInfo
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- CN101028516A CN101028516A CN 200710027326 CN200710027326A CN101028516A CN 101028516 A CN101028516 A CN 101028516A CN 200710027326 CN200710027326 CN 200710027326 CN 200710027326 A CN200710027326 A CN 200710027326A CN 101028516 A CN101028516 A CN 101028516A
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Abstract
An oral medicine in the form of tablet, buccal lozenge, film, or gargle for treating foul breath, periodontal abscess, pericoronitis, recurrent aphtha, etc contains the antibacterial medicine (levofloxacin and tinidazole) and menthol.
Description
Technical field
The present invention relates to a kind of medicine preparation for oral cavity, particularly be suitable for the medicine preparation for oral cavity of local application.
Background technology
Treatment and prevention to oral cavity infected by microbes associated diseases, if employing systemic administration, use antimicrobial drug, processes such as the absorption by medicine, distribution, make the pathological change of oral cavity position reach valid density and the generation effect, so just produce the side effect of some generals inevitably, even toxic reaction, influence patient and continue medication, and oral disease a kind of often easily chronic disease of outbreak repeatedly of periodontal disease especially, there is certain difficulty in treatment, so clinical oral tends to local application.The medicine of local application directly contacts with pathological tissues, has higher concentration in the part, seldom produces or does not produce the general untoward reaction, but be used for the medicine of oral cavity partial at present, and zest is strong or abnormal flavour is arranged mostly, makes patient be difficult to accept.A kind of curative effect is strong, zest is little or non-irritating oral local administration thing so be badly in need of developing.
Simultaneously, a large amount of research and Epidemiological study result show, many oral diseases are all relevant with infected by microbes, oral disease particularly periodontal disease is to be pathogenic bacterium with the anaerobe, also can be by due to gingivalis Endamoeba protozoon and the aerobe, if treatment only adopts anti-anaerobic agent to be difficult to obtain satisfactory therapeutic effects.
Summary of the invention
The objective of the invention is deficiency, provide that a kind of curative effect is strong, few side effects, zest is little or non-irritating oral cavity partial preparation at present oral local administration.
Technical scheme of the present invention provides a kind of medicine preparation for oral cavity, include pharmaceutically acceptable carrier, for example: diluent, excipient such as water etc., filler such as starch, sucrose etc., binding agent such as cellulose derivative, alginate, gelatin and polyvinylpyrrolidone, wetting agent such as glycerol, disintegrating agent such as agar, calcium carbonate and sodium bicarbonate, surfactant such as hexadecanol, absorption carrier such as Kaolin and soap clay, lubricant such as Pulvis Talci, calcium stearate (magnesium) and Polyethylene Glycol etc. can also add other adjuvants such as flavouring agent in addition in preparation, sweeting agent etc.The medicine of the tool therapeutic activity that preparation contains is antibacterials and menthol, antibacterials wherein can be a kind of anti-aerobe medicine or a kind of anti-anaerobic agent, the combination of perhaps a kind of anti-aerobe medicine and a kind of anti-anaerobic agent, these antibacterials comprise ciprofloxacin, lincomycin, acetylspiramycin, levofloxacin, metronidazole, tinidazole etc.The combination of the preferred levofloxacin of the present invention, tinidazole and menthol.
The present invention adopts percetage by weight to represent antibacterials and menthol content in the preparation, and menthol content is 0.05-0.5%, and preferred 0.1%; Each antibacterials content is 0.01-0.2%, preferred 0.01%.
The optimum prescription of antibacterials of the present invention and menthol is 0.01% levofloxacin+0.01% tinidazole+0.1% menthol.
Preparation of the present invention is used for when oral, can be made into conventional solid preparation such as tablet, lozenge, pill, buccal tablet, capsule etc., make liquid preparation such as water or oil-suspending agent or other liquid preparations such as gargarism, drop, syrup etc., forms such as membrane, dispersant, effervescent, aerosol, chewing gum agent be can also adopt, but buccal, rinsing the mouth, usefulness, spraying, coating etc. dripped.Above-mentioned various dosage form can for example make active component mix with one or more carriers according to the conventional production method preparation of pharmaceutical field, is made into required dosage form then.
The beneficial effect of medicine preparation for oral cavity provided by the invention is and is used alone the inhibitory action that antibacterials play and compares, inhibitory action to oral cavity various pathogens and ameba increases significantly, oral mucosa there are not tangible zest and toxicity, be that a kind of curative effect is strong, few side effects, zest is little or non-irritating oral cavity partial preparation, to treatment oral cavity common disease, as wound infection after halitosis, periodontal abscess, pericoronitis, alveolar abscess, recurrent aphtha, the exodontia etc. effect is preferably arranged all, have good medical prospect.
The specific embodiment:
Adopt the combination of antibacterials and menthol below, further specify the present invention in conjunction with concrete experimental example experimental data, pharmaceutically acceptable carrier of the present invention does not produce therapeutic activity, does not give unnecessary details in detail when the arrangement experimental data.And therefore do not limit the present invention in the described scope of embodiments:
Embodiment 1 0.01% tinidazole+0.1% menthol
Embodiment 2 0.01% tinidazoles+0.05% menthol
Embodiment 3 0.01% tinidazoles+0.5% menthol
Embodiment 4 0.2% tinidazoles+0.05% menthol
Embodiment 5 0.2% tinidazoles+0.1% menthol
Embodiment 6 0.2% tinidazoles+0.5% menthol
Embodiment 7 0.01% levofloxacin+0.05% menthol
Embodiment 8 0.01% levofloxacin+0.1% menthol
Embodiment 9 0.01% levofloxacin+0.5% menthol
Embodiment 10 0.2% levofloxacin+0.05% menthol
Embodiment 11 0.2% levofloxacin+0.1% menthol
Embodiment 12 0.2% levofloxacin+0.5% menthol
Embodiment 13 0.01% acetylspiramycins+0.05% menthol
Embodiment 14 0.01% acetylspiramycins+0.1% menthol
Embodiment 15 0.01% acetylspiramycins+0.5% menthol
Embodiment 16 0.2% acetylspiramycins+0.05% menthol
Embodiment 17 0.2% acetylspiramycins+0.1% menthol
Embodiment 18 0.2% acetylspiramycins+0.5% menthol
Permeable membrane absorption test and the data of embodiment 1 to 18 are as follows:
1, bacterial strain of Shi Yonging and worm strain escherichia coli (ATCC 12228), staphylococcus aureus (ATCC26001), beta hemolytic streptococcus (ATCC32172), klebsiella spp (ATCC46114), porphyromonas gingivalis (ATCC 33277), bacteroides fragilis (ATCC25285) provide by institute of internal medicine of the Chinese Academy of Sciences.Gingivalis Endamoeba protozoacide source: from periodontal disease patient's periodontal pocket that Affiliated Hospital of Guangdong Pharmaceutical University Stomatology Clinic is gone to a doctor, also made a definite diagnosis, get pus.Worm strain with the LES biphasic culture separation and Culture that improves is judged as the strain of E.g worm through the Pathogen Biology laboratory.
2, animal SD rat, male and female half and half, body weight 180~220g, the SPF level, the animal quality certification number is 2005A023; Rana nigromaculata, body weight 80~100g provides by Guangdong Pharmaceutical University's Experimental Animal Center.1 of healthy male rabbit, body weight 2.3kg is provided by Guangdong Pharmaceutical University's Experimental Animal Center, is used to gather serum.
3, permeable membrane absorption test
1) the preparation Rana nigromaculata of isolated skin is put to death, and takes off the skin at back, washes repeatedly with normal saline, till no muddiness.Put in 4 ℃ of refrigerators and preserve, use up in 1 week.
2) formulation ciprofloxacin, levofloxacin and the tinidazole of standard curve, metronidazole are diluted to series concentration C with the phosphate buffer of pH7.4 respectively, measure its absorbance A at 277nm, 289nm, 317nm, 277nm wavelength place, the range of linearity is respectively 2.5~10.0 μ gml
-1, 2.0~8.0 μ gml
-1With 5.0~50.0 μ gml
-1, 2.5~50.0 μ gml
-1Regression equation is respectively A=0.0285+0.0785C (r=0.9992), A=0.0410+0.0753C (r=0.9992) and A=0.0127C+0.1714 (r=0.9998), A=0.0230+0.0179C (r=0.9997).
3) preparation of release liquid and acceptable solution release liquid is respectively the phosphate buffer that contains 0.01% ciprofloxacin, 0.01% levofloxacin and 0.1% menthol, the phosphate buffer of 0.01% tinidazole, 0.01% metronidazole and 0.1% menthol, acceptable solution is the phosphate buffer of pH7.4, makes by the requirement of pharmacopeia appendix.
4) permeable membrane is tested the frog skin that thaws under the room temperature, carries out the transdermal test in vitro absorption test on the transdermal disperser of two chambers, and discharging the liquid consumption is 0.1ml, receives liquid 5.0ml, and experimental temperature is 32.0 ± 1.0 ℃, and vibration velocity is 150 times/min, and diffusion area is 0.502cm
2, 2,4,8,12, the 24h time point gets 4.0ml respectively, adds the reception liquid of equivalent simultaneously.Measure absorbance, and the substitution regression equation, calculating concentration.Above-mentioned specimen is removed release liquid behind continuous transdermal 24h, clean repeatedly with normal saline, and blot with the filter paper bar, and the 5ml acceptable solution adds in the clean receiving bottle, carries out the storage storehouse effect study of medicine by above-mentioned condition.
5) the concentration substitution following formula that will at every turn measure of result's processing, calculate accumulation transit dose Q:
Wherein Cn is drug level (the μ gml of n sample point
-1), Ci is drug level (the μ gml of i sample point
-1), A is a diffusion area.
Q carries out linear regression to time t with the accumulation transit dose, and the slope of gained equation is percutaneous rate.Statistical method adopts professor Sun Ruiyuan to wait the NDST program of writing to carry out variance analysis.Result such as table 1, table 2 and table 3.
Table 1 menthol to the influence of the permeable membrane absorption test of tinidazole (x ± s, n=6)
Group | Percutaneous rate (μ gcm -2·h -1) | Storage storehouse effect (μ gcm -2·h -1) |
0.01% Tinidazole, 0.01% Tinidazole+0.1% menthol, 0.01% Tinidazole+0.05% menthol, 0.01% Tinidazole+0.5% menthol, 0.2% Tinidazole, 0.2% Tinidazole+0.05% menthol, 0.2% Tinidazole+0.1% menthol, 0.2% Tinidazole+0.5% menthol | 10.422±0.451 11.321±0.823 * 10.743±1.456 13.054±1.162 11.531±0.764 * 12.114±1.451 * 13.562±1.228 * 14.213±1.754 ** | 4.316±0.376 6.247±0.201 ** 5.183±0.741 * 4.765±0.831 5.241±0.435 * 5.517±0.961 * 6.032±0.774 * 6.253±0.479 * |
Compare with 0.01% Both tinidazole:
*P<0.05,
*P<0.01
Table 2 menthol to the influence of levofloxacin permeable membrane absorption test (x ± s, n=6)
Group | Percutaneous rate (μ gcm -2·h -1) | Storage storehouse effect (μ gcm -2·h -1) |
0.01% lavo-ofloxacin, 0.01% lavo-ofloxacin+0.05% menthol, 0.01% lavo-ofloxacin+0.1% menthol, 0.01% lavo-ofloxacin+0.5% menthol, 0.2% lavo-ofloxacin, 0.2% lavo-ofloxacin+0.05% menthol, 0.2% lavo-ofloxacin+0.1% menthol, 0.2% lavo-ofloxacin+0.5% menthol | 9.025±1.153 11.372±1.622 * 12.421±1.011 * 12.545±1.032 * 9.431±1.564 11.792±1.627 * 12.431±1.028 ** 12.156±2.355 ** | 6.025±1.153 7.431±0.647 * 8.168±0.915 ** 8.025±1.011 ** 5.401±1.225 6.113±1.090 6.795±1.211 5.846±0.742 |
Compare with 0.01% levofloxacin group: * p<0.05, * * p<0.01
Table 3 menthol to the influence of acetylspiramycin permeable membrane absorption test (x ± s, n=6)
Group | Percutaneous rate (μ gcm -2·h -1) | Storage storehouse effect (μ gcm -2·h -1) |
0.01% acetyl spiramycin, 0.01% acetyl spiramycin+0.05% menthol, 0.01% acetyl spiramycin+0.1% menthol, 0.01% acetyl spiramycin+0.5% menthol, 0.2% acetyl spiramycin, 0.2% acetyl spiramycin+0.05% menthol, 0.2% acetyl spiramycin+0.1% menthol, 0.2% acetyl spiramycin+0.5% menthol | 5.134±0.892 6.524±1.012 * 8.371±0.873 ** 8.791±1.113 ** 5.458±0.786 6.955±0.844 * 7.157±0.643 ** 7.629±0.853 ** | 3.463±0.476 4.035±0.786 6.348±0.633 ** 5.024±0.721 * 3.824±0.561 4.326±0.793 5.132±0.547 * 5.322±0.635 ** |
Compare with 0.01% acetylspiramycin group: * p<0.05, * * p<0.01
Conclusion: above-mentioned table 1,2,3 testing result show, menthol absorbs the permeable membrane of tinidazole and levofloxacin, acetylspiramycin all tangible influence, and storage storehouse effect is significantly increased.
Embodiment 19 0.01% tinidazoles+0.01% levofloxacin+0.1% menthol
Contrast bacteriostatic test and data
Experiment divides 4 groups and carries out: the I group is 0.01% Both tinidazole, and the II group is 0.01% levofloxacin group, and the III group is 0.01% tinidazole+0.01% levofloxacin, and the IV group is 0.01% tinidazole+0.01% levofloxacin+0.1% menthol group.Aerobe places 37 ℃ of constant incubators to cultivate 18h, cultivates bacterium and makes the bacterium liquid that concentration is 0.5cfu/mL, evenly coats Nutrient agar plate surface, in 37 ℃ of constant temperature culture 24h; Anaerobe adopts anaerobism blood plate and anaerobic device to cultivate 48h down at 37 ℃, adopts paper disk method to measure antibacterial circle diameter.Result such as table 4.
Table 4 bacteriostasis (x ± s, n=6)
Strain | Antibacterial circle diameter (mm) | |||
The I group | The II group | The III group | The IV group | |
Escherichia coli staphylococcus aureus klebsiella beta hemolytic streptococcus porphyromonas gingivalis bacteroides fragilis | 1.32±0.12 2.75±0.52 1.17±0.30 1.78±0.66 11.32±3.74 13.33±5.42 | 13.17±0.65 ** 7.83±0.94 * 8.23±2.02 ** 3.75±0.37 ** 3.31±0.86 ** 2.37±0.75 ** | 13.65±5.04 ** 8.37±1.37 ** 11.07±1.82 ** 4.62±0.52 ** 15.33±3.51 * 14.41±5.16 * | 17.87±3.53 **△△ 12.82±0.97 **△ 15.97±1.59 **△ 7.87±0.55 **△ 19.27±2.67 **△ 20.25±4.32 **△ |
Compare with the I group: * * p<0.01; The IV group compares with the III group: △ △ p<0.01, △ p<0.05
Conclusion: the result of table 4 shows that containing 0.01% tinidazole+0.01% levofloxacin+0.1% menthol group can significantly increase antibacterial action (p<0.01 or p<0.05).
Embodiment 20 0.01% tinidazoles+0.01% acetylspiramycin+0.1% menthol
Contrast bacteriostatic test and data
Experiment divides 4 groups and carries out: the I group is 0.01% Both tinidazole, and the II group is 0.01% acetylspiramycin group, and the III group is 0.01% tinidazole+0.01% acetylspiramycin, and the IV group is 0.01% tinidazole+0.01% acetylspiramycin+0.1% menthol group.Measure antibacterial circle diameter by embodiment 19 methods.Result such as table 5.
Table 5 bacteriostasis (x ± s, n=6)
Strain | Antibacterial circle diameter (mm) | |||
The I group | The II group | The III group | The IV group | |
Escherichia coli staphylococcus aureus klebsiella beta hemolytic streptococcus porphyromonas gingivalis bacteroides fragilis | 1.21±0.23 2.03±0.17 1.03±0.16 2.05±0.21 10.62±3.74 12.45±2.13 | 3.41±0.37 * 5.43±0.21 * 3.44±0.19 * 8.21±0.83 ** 3.24±0.43 ** 2.63±0.54 ** | 5.33±0.63 ** 6.64±0.42 ** 4.21±0.81 ** 10.55±0.92 ** 16.24±2.31 ** 17.73±3.27 * | 7.49±0.77 **△ 9.13±0.71 **△ 6.55±0.34 **△ 12.41±0.93 **△ 20.11±3.16 **△ 21.67±5.01 **△ |
Compare with the I group: * * p<0.01; The IV group compares with the III group: △ △ p<0.01, △ p<0.05
Conclusion: the result of table 5 shows that the medicinal liquid that contains menthol can significantly increase antibacterial action (p<0.01 or p<0.05).
Embodiment 21 0.01% tinidazoles+0.01% lincomycin+0.1% menthol
Contrast bacteriostatic test and data
Experiment divides 4 groups and carries out: the I group is 0.01% Both tinidazole, and the II group is 0.01% lincomycin group, and the III group is 0.01% tinidazole+0.01% lincomycin, and the IV group is 0.01% tinidazole+0.01% lincomycin+0.1% menthol group.Measure antibacterial circle diameter by embodiment 19 methods.Result such as table 6.
Table 6 bacteriostasis (x ± s, n=6)
Strain | Antibacterial circle diameter (mm) | |||
The I group | The II group | The III group | The IV group | |
Escherichia coli staphylococcus aureus klebsiella beta hemolytic streptococcus porphyromonas gingivalis bacteroides fragilis | 1.27±0.31 1.83±0.27 1.15±0.22 2.14±0.36 9.58±1.52 11.24±2.22 | 5.62±0.42 * 9.24±0.36 * 2.98±0.32 * 6.14±0.72 ** 2.27±0.38 ** 2.75±0.61 ** | 7.11±0.41 ** 10.54±1.25 ** 3.15±0.33 ** 7.15±0.63 ** 13.54±2.27 * 15.95±3.18 * | 9.67±0.54 **△ 14.25±2.36 **△ 4.44±0.34 **△ 9.62±0.74 **△ 17.42±2.33 **△ 18.46±3.19 **△ |
Compare with the I group: * * p<0.01; The IV group compares with the III group: △ △ p<0.01, △ p<0.05
Conclusion: the result of table 6 shows that 0.01% tinidazole+0.01% lincomycin+0.1% menthol group preparation can significantly increase antibacterial action (p<0.01 or p<0.05).
Embodiment 22 tinidazoles+0.1% menthol wherein tinidazole content is a 0.004%-0.1% scope class series of values.
Preparation is to the inhibition test and the data of ameba
To contain the tinidazole of different content and the preparation of menthol and join in the test tube that contains ameba, and behind the cultivation 24h, draw each pipe respectively and contain protozoacide culture fluid microscopy.Polypide active state, quantity in the field of view under 10 * 40 times of light microscopics, observe the polypide death condition, calculate protozoon worm reduction rate (%) according to following formula: protozoon worm reduction rate (%)=(the average former borer population of the matched group-average former borer population of medicine the group)/average former borer population of matched group * 100%.Result such as table 7.
Table 7 menthol is to the influence (n=3) of tinidazole protozoon worm reduction rate
Tinidazole concentration (μ g/ml) | Protozoon worm reduction rate (%) | |
Do not contain the menthol group | Contain 0.1% menthol group | |
4.0 6.3 10.0 15.8 25.0 39.5 63.04 100.0 | 0 0 25 35 50 65 80 90 | 0 10 45* 60* 75* 95* 100* 100 |
Compare with the group that does not contain tinidazole: * p<0.05
Conclusion: the result shows the significant difference of two groups of worm reduction rates between tinidazole concentration 10.0`63.4 μ g/ml, shows that containing menthol can significantly strengthen the inhibitory action of tinidazole to ameba.
The toxicity test of embodiment 230.01% tinidazole+0.01% levofloxacin+0.1% menthol experiment medicinal liquid boil on the nape opposite the mouth transmucosal:
80 of rats, male and female half and half, body weight 180~220g is divided into 4 groups at random: the 1st group is physiology saline control group, and the 2nd group is high dose group, and the 3rd group is middle dosage group, and the 4th group is low dose group.Normal saline, medicinal liquid are splashed into the rat oral cavity respectively, and the 1st group and the 2nd component splash into the rat oral cavity 4 times, each 0.5ml; The 3rd component splashes in the oral cavity for 2 times, each 0.5ml; The 4th component splashes in the oral cavity for 4 times, and each 0.5ml all finishes in 2h.24h rat body situation and local mucous membrane change after the observation administration, randomly draw 10 rats for every group then, put to death, and the conveying end transmucosal carries out naked eyes to be inspected, and carry out histopathologic slide and observe.Remaining 10 rats are then observed its overall health of patients every day in each group, as variations such as body weight, breathing, circulation, central nervous system and extremity activities, put to death in 7th and the variation of inspection socket transmucosal, and carry out pathological study.The result there is no overall health of patients and oral cavity tissue mucosa ANOMALOUS VARIATIONS, and body weight change is worth there was no significant difference between 4 groups (p>0.05).
The toxicity of 24h is observed (n=20) behind table 8 oral cavity medicine
Group | Dosage (ml) | Oral cavity tissue mucosa ANOMALOUS VARIATIONS | The changing value of body weight behind the 24h (g) | Overall health of patients such as breathing, extremity activity | |
Matched group | 0.5 | Do not have | 0.4±0.6 | Normally | *p<0.05 |
Low dose group | 0.5 | Do not have | 0.3±0.5 | Normally | |
Middle dosage group | 1.0 | Do not have | 0.4±0.4 | Normally | |
High dose group | 2.0 | Do not have | 0.4±0.4 | Normally |
The toxicity of 7d is observed (n=10) behind table 9 oral cavity medicine
Group | Dosage (ml) | The oral cavity tissue mucosa changes | The changing value of body weight behind the 7d (g) | Overall health of patients such as breathing, extremity activity | |
Matched group | 0.5 | Do not have | 6.1±1.1 | Normally | *p<0.05 |
Low dose group | 0.5 | Do not have | 5.8±0.8 | Normally | |
Middle dosage group | 1.0 | Do not have | 6.0±0.7 | Normally | |
High dose group | 2.0 | Do not have | 6.0±0.9 | Normally |
Embodiment 24
Tablet: tinidazole 0.48mg
Levofloxacin 0.47mg
Menthol 1.25mg
Lactose 190mg
Corn starch 50mg
Magnesium stearate 3mg
Preparation method: tinidazole, levofloxacin, menthol and lactose, starch are mixed, the even moistening of water, mixture after moistening is sieved and drying, and the bulky grain crushing is after sieve, add magnesium stearate, with the mixture tabletting, every weighs 245.2mg then, and tinidazole, levofloxacin, menthol content are respectively 0.48mg, 0.47mg, 1.25mg.
Claims (10)
1, a kind of medicine preparation for oral cavity includes pharmaceutically acceptable carrier, it is characterized in that also comprising antibacterials and menthol.
2, medicine preparation for oral cavity according to claim 1 is characterized in that it is anti-aerobe medicine and/or anti-anaerobic agent that institute comprises antibacterials.
3, medicine preparation for oral cavity according to claim 1 and 2, it is characterized in that the anti-aerobe medicine that is comprised be ciprofloxacin, lincomycin, acetylspiramycin, levofloxacin any one.
4, medicine preparation for oral cavity according to claim 1 and 2, it is characterized in that the anti-anaerobic agent that is comprised be metronidazole, tinidazole any one.
5, medicine preparation for oral cavity according to claim 1 and 2 is characterized in that it is levofloxacin and/or tinidazole that institute comprises antibacterials.
6,, medicine preparation for oral cavity according to claim 1, it is characterized in that described menthol content is percetage by weight 0.05-0.5%.
7, medicine preparation for oral cavity according to claim 6 is characterized in that menthol content is a percetage by weight 0.1%.
8, medicine preparation for oral cavity according to claim 1 is characterized in that it is percetage by weight 0.01-0.2% that institute comprises any antibacterials content.
9, medicine preparation for oral cavity according to claim 8 is characterized in that it is percetage by weight 0.01% that institute comprises any antibacterials content.
10,, it is characterized in that described preparation is tablet, lozenge, pill, buccal tablet, membrane, gargarism, dispersant, effervescent, granule, aerosol, drop, chewing gum agent, capsule according to claim 1,2,6,7,8,9 any described medicine preparation for oral cavity.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102488698A (en) * | 2011-12-02 | 2012-06-13 | 河南科技大学第一附属医院 | Oral treatment water |
CN102631407A (en) * | 2012-04-12 | 2012-08-15 | 徐柔云 | Antiphlogistic and analgesic mouth wash used for gingivitis |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102488698A (en) * | 2011-12-02 | 2012-06-13 | 河南科技大学第一附属医院 | Oral treatment water |
CN102631407A (en) * | 2012-04-12 | 2012-08-15 | 徐柔云 | Antiphlogistic and analgesic mouth wash used for gingivitis |
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