CN108210385B - A jelly-like collutory with effects of preventing dental caries, resisting bacteria, strengthening root and consolidating teeth - Google Patents
A jelly-like collutory with effects of preventing dental caries, resisting bacteria, strengthening root and consolidating teeth Download PDFInfo
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Abstract
The invention discloses a jelly-like mouthwash with the efficacies of preventing caries and resisting bacteria and strengthening and consolidating teeth, which comprises 3 to 5 percent of moisture retention component, 91 to 95 percent of solvent, 0.25 to 0.75 percent of acid-base buffering agent, 0.2 to 0.6 percent of caries prevention component, 0.05 to 0.15 percent of root strengthening component, 0.2 to 0.6 percent of seasoning component, 0.1 to 0.2 percent of antiseptic component, 0.25 to 0.35 percent of flavoring agent, 0.01 to 0.03 percent of tooth strengthening component and 0.4 to 0.8 percent of gel component, wherein the caries prevention component is selected from one or more of compounds LX-S-06, LX-S-18, XQH-2-92, XQH-3-6 and XQH-3-7, and the root strengthening component is quercetin. The invention integrates the efficacies of caries prevention, antibiosis and root strengthening and tooth strengthening, has comfortable mouthfeel, has no toxic or side effect, and is suitable for long-term use.
Description
Technical Field
The invention relates to the technical field of oral health care, in particular to a mouthwash, and specifically relates to a jelly-shaped mouthwash with functions of caries prevention, bacteria resistance, root strengthening and tooth strengthening and a preparation method thereof.
Background
Caries, commonly known as decayed tooth, is a bacterial infectious disease. The etiology of caries can be explained by the "tetrad-factorial theory," four interrelated factors, bacteria, the oral microenvironment, host and time. Caries is mainly caused by cariogenic microorganisms, which form a dental plaque biofilm on parts of teeth such as crowns and the like which are difficult to clean, thereby forming a microenvironment for destroying enamel. The good hair part of the caries is quite hidden, mainly comprises pit and furrow gaps, adjacent surfaces and a neck part, and the parts are difficult to clean by traditional tooth brushing. The oral care cleanser can protect oral health, remove oral odor, inhibit growth of cariogenic bacteria, and strengthen teeth.
Caries is a disease in which hard tissues of the tooth are progressively destroyed, once caries occurs, the caries cannot be stopped, the disease can only be delayed, and the caries can be treated by a formal medical means of removing damaged tissues and repairing the morphological structure of the tooth. However, caries is a disease which is more than prevented and treated, and the effect of preventing caries can be achieved through the standard daily tooth brushing habit and regular oral cavity cleaning. According to the latest statistical data of the fourth national epidemiological survey of oral health, the tooth brushing rate of children aged 5 and 12 years old twice a day is respectively 24.1% and 31.9%, the tooth brushing rate of fluorine-containing toothpaste is respectively 42.1% and 55%, the tooth brushing rate of adults aged 5 and 12 years old twice a day is 36.1%, the tooth brushing rate of fluorine-containing toothpaste is 61.0%, and the caries rate of children aged 5 and 12 years old in China is respectively 70.9% and 34.5%. The situation shows that the tooth brushing habits of people in China are generally poor, the incidence rate of dental caries of children is high, good tooth brushing habits need to be developed, and the oral cavity cleaning care solution is used for assisting tooth brushing, so that the aim of preventing dental caries is fulfilled.
Oral care products currently include toothpaste, dental floss, tooth strips, mouthwashes, and the like, with mouthwashes playing an increasingly important role in daily oral care. The common mouthwash contains bactericidal components such as triclosan, metronidazole, tinidazole, hydrogen peroxide and the like, but can only kill dental caries microorganisms in the oral cavity in a non-specific way, has large damage to tooth roots and has poor daily oral care effect; essential oil mouth wash has an insignificant effect of preventing caries and is mostly used for refreshing breath. The mouthwash is convenient to develop and use, comfortable in taste, capable of effectively preventing caries and capable of being used for a long time, and has important significance for oral care of modern people.
Disclosure of Invention
Aiming at the problems in the prior art, particularly aiming at the problem that the traditional mouthwash can only refresh breath or kill dental caries microorganisms in the oral cavity in a non-specific way but does not have the effects of preventing dental caries, strengthening roots and teeth, and the like generally, the invention provides the novel oral cleaning and nursing article which integrates the effects of preventing caries, resisting bacteria, strengthening roots and teeth, has low toxicity and good use experience, is expected to replace the existing mouthwash on the market and protects the teeth of people.
Specifically, the invention relates to the following technical scheme:
the invention discloses a jelly-like mouthwash with the efficacies of preventing caries and resisting bacteria and strengthening roots and teeth, which comprises 3 to 5 percent of moisture retention component, 91 to 95 percent of solvent, 0.25 to 0.75 percent of acid-base buffering agent, 0.2 to 0.6 percent of caries prevention component, 0.05 to 0.15 percent of root strengthening component, 0.2 to 0.6 percent of seasoning component, 0.1 to 0.2 percent of preservative component, 0.25 to 0.35 percent of flavoring agent, 0.01 to 0.03 percent of tooth strengthening component and 0.4 to 0.8 percent of gel component, wherein the caries prevention component is selected from one or more of compounds LX-S-06, LX-S-18, XQH-2-92, XQH-3-6 and XQH-3-7, and the root strengthening component is quercetin.
In a specific embodiment, the mouthwash contains 3.8% of a moisture-retaining component, 93.7% of a solvent, 0.5% of an acid-base buffer, 0.4% of an anticaries component, 0.1% of a root-strengthening component, 0.4% of a flavoring component, 0.15% of a preservative component, 0.33% of a flavoring agent, 0.02% of a tooth-strengthening component, and 0.6% of a gel component.
Preferably, the mouth wash contains moisture-retaining components such as glycerol and propylene glycol, a solvent such as purified water, an acid-base buffer such as sodium citrate and sodium malate, an anticariogenic component selected from one or more of compounds LX-S-06, LX-S-18, XQH-2-92, XQH-3-6 and XQH-3-7, a strong root component such as quercetin, a flavoring component such as xylitol and trehalose, a preservative component such as sodium benzoate, a flavoring agent such as essence and honeysuckle extract, a tooth-fixing component such as sodium fluoride, and a gel component such as carrageenan and konjac gum.
In a more preferred embodiment, the mouthwash contains 3% of glycerin, 0.8% of propylene glycol, 93.7% of purified water, 0.25% of sodium citrate, 0.4% of an anticaries component, 0.1% of quercetin, 0.3% of xylitol, 0.4% of trehalose, 0.15% of sodium benzoate, 0.15% of essence, 0.18% of a honeysuckle extract, 0.02% of sodium fluoride, 0.3% of carrageenan and 0.3% of konjac gum.
In a preferred embodiment of the invention, the anticariogenic component is selected from compounds LX-S-06 or LX-S-18, which are formulated as a jelly mouthwash to be superior to other anticariogenic components; preferably, the anticaries component is selected from two or more of compounds LX-S-06, LX-S-18, XQH-2-92, XQH-3-6 and XQH-3-7. LX-S-06 or LX-S-18 has better matching effect with other anticariogenic components. For example, in a preferred embodiment, the anticaries agent is LX-S-06 and LX-S-18, and one or more of XQH-2-92, XQH-3-6, and XQH-3-7; in another preferred embodiment, the anticaries agent is LX-S-06, LX-S-18, XQH-2-92, XQH-3-6, XQH-3-7.
The anticarious component in the mouthwash is LX-S-06, LX-S-18, XQH-2-92, XQH-3-6, XQH-3-7 and quercetin, and the structural formula of the anticarious component is shown in Table 1.
TABLE 1 structural formulas of LX-S-06, LX-S-18, XQH-2-92, XQH-3-6, XQH-3-7, quercetin
Secondly, the invention discloses a preparation method of the jelly-like mouthwash, which comprises the following steps:
step 1: uniformly mixing the weighed anticarious component, flavoring component, antiseptic component, flavoring agent and teeth-strengthening component, and fully grinding;
step 2: adding standard amount of moisture keeping component into specified purified water, and adding gel component into the solution;
and step 3: adding the mixture obtained in the step 1 to the solution obtained in the step 2; adding a standard amount of acid-base buffering agent into the mixed solution, and adjusting the pH value to 6.6-7.1;
and 4, step 4: sterilizing the obtained gel at high temperature, and packaging.
The invention reasonably groups the used components, effectively matches the components, has simple and convenient preparation process and is suitable for processing and preparing the jelly-shaped mouthwash.
In addition, the invention also discloses two novel compounds with anti-streptococcus mutans, respectively, (S) -2- (1,3-dimethyl-2-oxo-1, 2-dihydroquinoxaline-6-sulfonamide) -3- (methylthio) -N- (5-nitrothiazol-2-yl) propanamide (i.e., compound LX-S-06) and (R) -methyl (2- (1-methyl-3- (((5-nitrothiazol-2-) amino) methyl) -2-oxo-1, 2-dihydroquinoxaline-6-sulfonamide) -3-phenylpropionyl) carbamate (i.e., compound LX-S-18).
The structural formula of the compound LX-S-06 is as follows:
the structural formula of the compound LX-S-18 is as follows:
further, the application of the compounds LX-S-06 and LX-S-18 is also within the protection scope of the invention, and comprises the application of the compounds LX-S-06 and LX-S-18 in preparing oral streptococcus mutans biofilm inhibitors, medicines for preventing and treating caries, and functional toothpaste, mouthwash, oral ulcer films, denture cleaning agents, chewing gum or disinfectant.
The invention achieves the following beneficial effects:
(1) aiming at the defects of the traditional mouthwash, the invention comprises an anti-caries antibacterial component and a root strengthening and tooth strengthening component, wherein the anti-caries component can specifically resist bacteria causing caries, the root strengthening component can stabilize tooth roots, strengthen tooth bones and increase the bone quantity of alveolar bones, and the anti-caries antibacterial and root strengthening and tooth strengthening effects are integrated.
(2) According to the invention, through reasonable matching of various components, the effects of the components are fully exerted, toxic and side effects are effectively avoided, the anti-caries effect of the mouthwash is enhanced through reasonable compatibility, and the sterilization and bacteriostasis performance, the anti-inflammatory and analgesic effects of the mouthwash are effectively improved. Besides the anticarious component and the root-strengthening component, the tooth-strengthening component can reduce the solubility of the hydroxyapatite in the enamel, enhance the capacity of resisting the caries of the teeth, and increase the integrity and the hardness of the enamel, thereby realizing the effect of preventing the caries; according to the formula, on the premise of ensuring good caries prevention, antibacterial, root strengthening and tooth strengthening effects, the color, fragrance and taste of the mouthwash are improved, so that the mouthwash with good use experience is obtained; the invention also comprises sodium fluoride as tooth-fixing component, sodium benzoate as antiseptic component, carrageenan and konjac gum as gel component, which are matched to form jelly-shaped mouthwash, and the jelly-shaped form is sanitary and convenient to use, and can effectively form a product used stably for a long time. The mouthwash disclosed by the invention can effectively remove the oral cavity strange taste, keep the breath fresh for a long time and has good sterilization and bacteriostasis effects; can also quickly improve the oral cavity problem, maintain the oral cavity bacteria state balance, effectively prevent and improve the symptoms of swelling and aching of gum, bleeding of gum, halitosis and the like caused by bacteria, and simultaneously can realize the firming of teeth, the avoidance of the tooth loosening and the alleviation of the tooth root injury. The invention has convenient use, comfortable taste, obvious caries prevention effect, no toxic or side effect and long-term use.
(3) The invention also provides a preparation method of the mouthwash with the caries prevention effect, which is simple in preparation method, low in cost and convenient for industrial popularization.
(4) The invention also designs and synthesizes two new compounds LX-S-06 and LX-S-18 with the anti-streptococcus mutans, which not only have good anti-streptococcus mutans effect, but also have small toxicity, and have better effect when used together with other anti-streptococcus mutans compounds XQH-2-92, XQH-3-6 and XQH-3-7.
Drawings
FIG. 1 is a graph showing the result of observation by a high power microscope (10X) after staining an ALP color developing kit, wherein the color of the stained experimental group is darker than that of the control group, which shows that the strong tooth component contained in the present invention has a bone-promoting effect;
FIG. 2 shows the results of the experimental group and the control group of the mouthwash with special effect of preventing dental caries, after the special staining agent for dental plaque is used, the experimental group can see that slight dental plaque is attached to the tooth surface; in contrast, the plaque was found to be widely attached to the tooth surface and in the gingival sulcus in the control group.
Detailed Description
It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of the stated features, steps, operations, and/or combinations thereof, unless the context clearly indicates otherwise.
It is to be noted that the compounds having an anti-Streptococcus mutans activity used in the present invention are LX-S-06 and LX-S-18. In addition, the compound having anti-Streptococcus mutans activity used in the present invention is selected from the group consisting of XQH-2-92, XQH-3-6, and XQH-3-7. Among them, compound XQH-3-6 and its preparation and application are disclosed in patent CN 106588911A; compound XQH-3-7 and its preparation and use are disclosed in patent CN 106699751A; compound XQH-2-92 and its preparation and use are disclosed in patent CN 106588813A; the contents of these three patents are incorporated into this application. The invention will detail the preparation method and application of LX-S-06 and LX-S-18.
The first embodiment is as follows: preparation of (S) -2- (1,3-dimethyl-2-oxo-1, 2-dihydroquinoxaline-6-sulfonamide) -3- (methylthio) -N- (5-nitrothiazol-2-yl) propanamide (compound LX-S-06)
Preparation of intermediate 3-methylquinoxaline-2 (1H) -one (1)
10.81g (0.10mol) of o-phenylenediamine is weighed and placed in a 500mL round-bottom flask, 250mL of absolute ethyl alcohol is added, and the mixture is stirred until the o-phenylenediamine is completely dissolved to obtain a light yellow solution. 12.77g (0.11mol) of ethyl pyruvate is dripped into the solution under the condition of stirring at room temperature, after about 10min, a large amount of solid is generated instantly, the reaction is continued for 5h, and the reaction is finished. And (3) filtering, collecting the solid, recrystallizing the solid with ethanol, and drying the solid in vacuum to obtain a light white cotton wool-like product, wherein the yield is 90.4%, and the m.p. ═ 241.0-242.7 ℃.
Preparation of intermediate 1, 3-dimethylquinoxalin-2 (1H) -one (2)
8.01g (0.05mol) of Compound 1, 13.80g (0.10mol) of anhydrous potassium carbonate and 0.4g of n-tetrabutylammonium bromide (TBAB) were weighed out and placed together in a 500ml round-bottom flask, and 200ml of acetone was added to obtain a suspension. 9.48ml (0.10mol) dimethyl sulfate is dripped into the suspension under the condition of stirring at room temperature, the suspension is transferred to an oil bath at 65 ℃ after the dripping is finished and heated for reflux reaction for 6 hours, and the TLC detection reaction is finished. And (2) evaporating the solvent under reduced pressure, adding 50ml of water and 100ml of ethyl acetate, repeatedly extracting and washing for 3 times, combining ethyl acetate layers, concentrating, adding 80-100-mesh silica gel, stirring, and separating and purifying by flash column chromatography (eluent: petroleum ether/ethyl acetate: 6:1-3:1) to obtain white flash crystals, wherein the product has an irritant smell, the yield is 75%, and the m.p. is 76.0-78.0 ℃.
Preparation of intermediate 1,3-dimethyl-2-oxo-1, 2-dihydroquinoxaline-6-sulfonyl chloride (3)
Weighing 8.70g (0.05mol) of the compound (2) and placing the compound in a 250ml round bottom flask, adding 20ml of anhydrous Dichloromethane (DCM) to dissolve the compound completely, slowly dripping 10ml of chlorosulfonic acid under the condition of ice bath stirring, continuing to stir for 5min after dripping is finished, then transferring the mixture to an oil bath at 100 ℃ to continue to react for 12h, and detecting the reaction by TLC to finish. Cooling the reaction solution to room temperature, adding 100ml of DCM for dilution, slowly adding 50ml of cooled distilled water under the condition of ice bath stirring to remove unreacted chlorosulfonic acid, repeatedly extracting and washing for one time, spin-drying a DCM layer to obtain a yellow solid with pungent smell, further purifying by an acetone-ether system, and directly putting the yellow solid into the next reaction, wherein the yield is 55%.
Preparation of intermediate methyl (R) -methyl 2- (1,3-dimethyl-2-oxo-1, 2-dihydroquinoxaline-6-sulfonamide) -4- (methylthio) butanoate (4)
Weighing 0.012mol of methionine methyl ester hydrochloride, suspending in 50ml of anhydrous DCM, adding 4.18ml (0.03mol) of anhydrous TEA and 0.12g of DMAP in turn, stirring at room temperature for 10min, slowly adding DCM solution of compound 2 (2.72g of compound 3 is dissolved in 10ml of DCM for later use), after the dropwise addition, continuing to react for 5h, detecting the reaction by TLC, removing DCM under reduced pressure, dissolving solid residue in 50ml of ethyl acetate, and then sequentially adding lmol/L citric acid solution (2 × 20ml) and saturated NaHCO in turn3Washing the solution (2 × 20ml) and saturated NaCl solution (2 × 20ml), drying the organic layer with anhydrous magnesium sulfate, mixing the samples, separating and purifying by flash column chromatography (eluent: petroleum ether/ethyl acetate: 3:1-2:1) to obtain light yellow solid with the yield of 67%, M.p.: 149.5-150.5 ℃,1H-NMR(DMSO-d6,400MHz,ppm):1.720-1.880(m,2H,CH2),1.924(s,1H,CH3),2.285-2.370(m,1H,SCH2),2.380-2.440(m,1H,SCH2),3.470(s,3H,N=CCH3),3.390(s,3H,OCH3),3.642(s,3H,NCH3),4.011(m,1H,CH),7.719(d,J=9.0Hz,1H,ArH),7.779(dd,J=1.8,9.0Hz,1H,ArH),8.022(d,J=1.8Hz,1H,ArH),8.501(d,J=7.2Hz,1H,NH).ESI-MS:400.5[M+H]+.
preparation of intermediate (R) -methyl 2- (1,3-dimethyl-2-oxo-1, 2-dihydroquinoxaline-6-sulfonamide) -4- (methylthio) butanoate methyl ester (R) -2- (1,3-dimethyl-2-oxo-1,2-dihydroquinoxaline-6-sulfonamido) -4- (methylthio) butanoic acid (5)
1.12g (0.02mol) of potassium hydroxide solid was weighed out and dissolved in 25ml of distilled water for further use. 3.25g (0.01mol) of the compound (4) is weighed, 50ml of absolute ethyl alcohol is added for dissolving, after stirring for 5min at room temperature, the prepared potassium hydroxide solution is added, the stirring reaction is continued for 4h, and the TLC detection reaction is finished. The solvent was evaporated off under reduced pressure, 25ml of distilled water was added, pH was adjusted to about 2 with 4N hydrochloric acid, a large amount of solid was precipitated, filtered, the filter cake was washed with water, and recrystallized from tetrahydrofuran to give an off-white product with a yield of 71%. M.p. 120.0-121.0 ℃,1H-NMR(DMSO-d6,400MHz,ppm):1.700-1.880(m,2H,CH2),1.926(s,1H,CH3),2.300-2.370(m,2H,SCH2),2.380-2.440(m,2H,CH2),3.470(s,3H,N=CCH3),3.638(s,3H,NCH3),3.895(m,1H,CH),7.709(d,J=9.0Hz,1H,ArH),7.904(dd,J=1.8,8.4Hz,1H,ArH),8.047(d,J=2.4Hz,1H,ArH),8.308(d,J=7.8Hz,1H,NH),12.68(s,1H,COOH).ESI-MS:386.6[M+H]+.
preparation of target (R) -2- (1,3-dimethyl-2-oxo-1, 2-dihydroquinoxaline-6-sulfonamide) -4- (methylthio) -N- (5-nitrothiazol-2-yl) butanamide (LX-S-06)
In an ice salt bath, the intermediate 5(0.37g,1mmol) obtained in the previous step was dissolved in 15ml of anhydrous tetrahydrofuran, and 2-amino-5-nitrothiazole (0.17g, 1.2mmol), HOBt (0.23g,1.7mmol) and EDCI (0.33g,1.7mmol) were added thereto in this order, respectively, and after the mixed solution was stirred for 15 minutes in an ice bath, N-methylmorpholine (0.2ml, 1.7mmol) was added, the ice bath was removed, and the reaction was continued for 6 hours at room temperature until TLC monitoring was completed and the intermediate 5 was completely reacted. Respectively using 5% KHSO to react4(3 × 10ml), saturated NaHCO3Washing the solution (3 × 10ml) with saturated brine (3 × 10ml), extracting the aqueous phase twice with dichloromethane, drying the organic phase over anhydrous magnesium sulfate, and concentrating by evaporation to obtain crude product. The crude product was purified and separated by silica gel column (eluent: petroleum ether: ethyl acetate 4:1) to give a pure product with a yield of 66.5%.1H-NMR(400MHz,DMSO-d6,ppm):2.03(s,3H,N=C-CH3),2.22(s,3H,S-CH3),2.32-2.38(m,2H,SCH2),2.39-2.43(m,2H,CH 2CHC=O),3.33(s,3H,N-CH3),3.82-3.84(m,1H,CHC=O),7.73(s,1H,ArH),7.88-7.89(d,J=8.4Hz,1H,ArH),8.07-8.10(d,J=9.0Hz,1H,ArH),8.33(d,J=7.8Hz,1H,NHSO2),8.86-8.87(s,1H,CH-N=C),9.61(s,1H,NHC=O);ESI-MS:535.5[M+Na]+.
Example two: preparation of (R) -methyl (2- (1-methyl-3- (((5-nitrothiazole-2-) amino) methyl) -2-oxo-1, 2-dihydroquinoxaline-6-sulfonylamino) -3-phenylpropionyl) carbamate (compound LX-S-18)
Preparation of intermediate methyl (R) -methyl 2- (1,3-dimethyl-2-oxo-1, 2-dihydroquinoxaline-6-sulfonamide) -3-phenylpropionate (6)
Intermediate (6) was prepared in the same manner as intermediate (4) in example one, and the yield was 69%. M.p is 151.0-153.0 ℃,1H-NMR(DMSO-d6,400MHz,ppm):2.473(s,3H,N=CCH3),2.751(dd,J=9.0,13.8Hz,1H,CH2),2.93(dd,J=6.0,13.8Hz,1H,CH2),3.34(s,3H,OCH3C=O),3.63(s,3H,NCH3),4.08(d,J=7.8Hz,1H,CH),7.05-7.14(m,5H,5ArH),7.57(d,J=9.0Hz,1H,ArH),7.69(dd,J=2.4,9.0Hz,1H,ArH),7.85(d,J=2.4Hz,1H,ArH),8.63(d,J=9.0Hz,1H,NH).ESI-MS:416.7[M+H]+.
preparation of intermediate methyl (R) -methyl 2- (3-bromomethyl) -1-methyl-2-oxo-1, 2-dihydroquinoxaline-6-sulfonamide) -3-phenylpropionate (7)
The intermediate 6(0.42g, 1mmol) obtained in the previous step was placed in a reaction flask under ice-cooling, and after 5ml of a glacial acetic acid solution in which anhydrous sodium acetate (0.1g, 1.2mmol) was dissolved was dropwise added to the flask, reaction was carried out for 5 minutes, followed by addition of 3ml of a glacial acetic acid solution in which bromine (0.05ml, 1mmol) was dissolved.Adding the mixture to N2Reacting at room temperature under protection of gas for 3 hr, adding 10ml water and 10ml dichloromethane respectively to terminate the reaction, adding 20ml dichloromethane to extract the mixture, and finally using anhydrous MgSO4Drying, with ethyl acetate: and (3) carrying out column chromatography separation on petroleum ether (1:1-2:1) to obtain a brownish red solid product, wherein the yield is 55%. M.p is 133.0-134.0 ℃,1H-NMR(DMSO-d6,400MHz,ppm):2.473(s,3H,N=CCH3),2.751(dd,J=9.0,13.8Hz,1H,CH),2.914(dd,J=6.0,13.8Hz,2H,CH2),3.34(s,3H,CH3O),3.66(s,3H,NCH3),4.012(td,J=6.6,9.0Hz,1H,O=C-CH),4.72(2H,s,CH2Br),7.05-7.15(m,5H,ArH),7.66(d,J=9.0Hz,1H,ArH),7.69(dd,J=2.4,9.0Hz,1H,ArH),7.87(d,J=2.4Hz,1H,ArH),8.63(d,J=9.0Hz,1H,NHSO2).ESI-MS:494.8[M+H]+.
preparation of methyl (R) -methyl 2- (1-methyl-3 (((5-nitrothiazol-2-yl) amino) methyl) -2-oxo-1, 2-dihydroquinoxaline-6-sulfonylamino) -3-phenylpropionate (LX-S-18) as target
Dissolving the intermediate 7(0.5g and 1mmol) obtained in the previous step in 10ml of acetone under ice bath, sequentially adding ground anhydrous potassium carbonate powder (0.28g and 2mmol) and 2-amino-5-nitrothiazole (0.17g and 1.2mmol), reacting the mixture at room temperature under the protection of nitrogen for 6 hours until TLC monitors the reaction to be complete, evaporating the solvent, adding 20ml of dichloromethane for extraction, respectively washing with saturated ammonium chloride (3 × 10ml) and saturated saline solution (3 × 10ml), drying and concentrating, performing column chromatography with ethyl acetate and petroleum ether (2:1-3:1) to obtain a light gray solid product, wherein the yield is 48%, M.p is 177.0-178.0 ℃,1H-NMR(DMSO-d6,400MHz,ppm):2.88-2.90(dd,J=9.0,13.8Hz,2H,PhCH 2CH),3.22(dd,J=6.0,13.8Hz,1H,O=C-CH-NH),3.54(s,3H,CH3O),3.64(s,3H,NCH3),4.55(td,J=6.6,9.0Hz,2H,N=C-CH 2NH),5.02(1H,dd,J1=1.8Hz,J1=3.0Hz,NH-C=N),7.27-7.38(m,5H,5ArH),7.79(S,1H,ArH),7.80(d,J=9.0Hz,1H,ArH),7.89(d,J=2.4Hz,1H,ArH),8.56(s,1H,C=NCH).ESI-MS:559.6[M+H]+.
example three: antibacterial activity test of Compound LX-S-06
Preparation of Streptococcus mutans
(1) The culture medium for culturing Streptococcus mutans is Brain heart infusion (Brain heart infusion) culture medium (brand OXOID, cat # CM1135), and the main components of the culture medium are Brain infusion extracts 12.5g/L, Beef heart infusion extracts 5.0g/L, protein peptide 10.0g/L, Glucose 2.0g/L, Sodimchloride 5.0g/L, Di-sodium phosphate 2.5g/L, and pH 7.4 + -0.2. If a solid culture medium is needed, 1.5% agar powder is added. Sterilizing at 115 deg.C for 30min, and cooling.
(2) The culture medium for culturing the streptococcus mutans biofilm is a brain heart infusion-sucrose culture medium. The preparation method comprises preparing 20% stock solution from sucrose, filtering and sterilizing with 0.22 μm sterile filter, and adding sucrose with final concentration of 1% into brain heart infusion culture medium.
(3) Inoculating bacterial liquid of streptococcus mutans model strain UA159 and clinical strain UA246 on brain heart infusion solid culture medium, streaking, and culturing at 37 deg.C under anaerobic condition for 24 hr to obtain obvious single colony.
(4) A single colony of Streptococcus mutans strain UA159 and UA246 was picked up with a sterile inoculating loop, inoculated into a tube containing brain heart infusion liquid medium, and cultured under anaerobic condition at 37 deg.C until the liquid in the tube is turbid.
(5) The absorbance (OD600) at 600nm of each of Streptococcus mutans UA159 and UA246 was measured with an ultraviolet-visible spectrophotometer.
(6) Accurately weighing the compound LX-S-06 by using an analytical balance, adding dimethyl sulfoxide to dissolve the compound LX-S-06 to prepare a storage solution with the concentration of 1024mg/L, filtering and sterilizing the storage solution by using a sterile filter with the specification of 0.22 mu m, and storing the storage solution at the temperature of minus 20 ℃ for later use.
Detection result of activity of compound LX-S-06 on streptococcus mutans planktonic cells
(1) Streptococcus mutans strains and compound LX-S-06 were prepared as described above, and cultured to log phase (OD)6000.8-1.0) of bacteria solution of streptococcus mutans UA159 and UA246 is diluted to a final concentration of 5 × 10 by using brain heart infusion liquid culture medium5cfuThe volume is ready for use.
(2) The minimum inhibitory concentration of the compound LX-S-06 to the streptococcus mutans UA159 and UA246 floating cells is detected by adopting a trace broth dilution method, and the final concentration of the streptococcus mutans bacterial liquid in each hole of a sterile 96-hole plate is 5 × 105cfu/mL, adding the stock solution of the compound LX-S-06 prepared as described above to the first well, adjusting the final concentration to 256. mu.g/mL, mixing, sucking 150. mu.L to the 2 nd well, sucking 150. mu.L to the 3 rd well after mixing, diluting in duplicate to the 11 th well, sucking 150. mu.L from the 11 th well and discarding. Thus, the 1 st to 11 th wells were the experimental group to which the drug solution was added, and the 12 th well was the growth control group to which no drug was added. The drug concentrations in the 1 st to 12 th wells are 256, 128, 64, 32, 16, 8, 4, 2, 1, 0.5, 0.25 and 0 μ g/mL respectively. The Minimum Inhibitory Concentration (MIC) was defined as the lowest concentration that completely inhibited bacterial growth in the wells.
(3) After the bacterial liquid in the wells is uniformly spread on a brain-heart infusion agar solid medium, the medium is subjected to anaerobic inverted culture at 37 ℃ for 24 hours, and the Minimum Bactericidal Concentration (MBC) is determined as the lowest concentration at which no bacteria grow.
(4) Detecting absorbance value of each well of a 96-well plate at a wavelength of 600nm by using a microplate reader, calculating the inhibition rate of cells at each drug concentration, wherein the calculation formula is that the inhibition rate is (1-experimental group/growth control group) × 100%, and the obtained data is used for calculating half maximum Inhibition Concentration (IC) by using SPSS statistical software50)。
(5) The antibacterial activity of the Nitazoxanide (NTZ) of the control group is tested by the same procedure as that of the compound LX-S-06, and the test results are shown in Table 2.
TABLE 2 results of the Activity measurements of LX-S-06 and NTZ against Streptococcus mutans UA159 and UA246
MIC: a minimum inhibitory concentration; MBC: a minimum germicidal concentration; IC (integrated circuit)50: half maximal inhibitory concentration
As can be seen from Table 2, compound LX-S-06 has superior bacteriostatic and bactericidal activity against Streptococcus mutans UA159 and UA246 over the positive control nitazoxanide.
Example four: antibacterial Activity test of Compound LX-S-18
The procedure is as in example three, and the results are shown in Table 3.
TABLE 3 results of the activity assays of LX-S-18 and NTZ against Streptococcus mutans UA159 and UA246
MIC: a minimum inhibitory concentration; MBC: a minimum germicidal concentration; IC (integrated circuit)50: half maximal inhibitory concentration
As can be seen from Table 3, the compound LX-S-18 has superior bacteriostatic and bactericidal activity against Streptococcus mutans UA159 and UA246 than that of the positive control drug nitazoxanide.
Example five: preparation method of jelly-like mouthwash with caries prevention, antibiosis and root strengthening and tooth strengthening effects
The specific components of the mouthwash and the mass fractions thereof are shown in table 4. The specific implementation steps are as follows:
step 1: mixing the weighed anticarious component, flavoring component, antiseptic component, flavoring agent and teeth consolidating component, and grinding. The specific formula comprises anticarious components LX-S-06, LX-S-18, XQH-2-92, XQH-3-6 or XQH-3-70.4%, a root strengthening component 0.1% of quercetin, flavoring components xylitol and trehalose which are respectively 0.3% and 0.1%, an antiseptic component ammonium benzoate 0.15%, a flavoring agent essence 0.15%, a honeysuckle extract 0.18% and a tooth fixing component sodium fluoride 0.2%.
Step 2: adding standard amount of moisturizing component into purified water, wherein the moisturizing component glycerol and propylene glycol account for 3% and 0.8% respectively, and the solvent accounts for 93.7% respectively; gel components of carrageenan and konjac gum are added into the solution, and the gel components account for 0.3 percent and 0.3 percent respectively.
And step 3: adding the mixture obtained in the step 1 to the solution obtained in the step 2; adding a standard amount of acid-base buffering agent into the mixed solution, and adjusting the pH value to 6.6-7.1.
And 4, step 4: sterilizing the obtained gel at high temperature, and packaging.
TABLE 4 ingredients and contents of the mouthwash having caries preventing effect obtained by the first preparation method
Example six: preparation method II of jelly-like mouthwash with caries prevention, antibiosis, root strengthening and tooth strengthening effects
In order to obtain the mouth wash with the best efficacy, the components can be prepared according to the proportion shown in table 5 to obtain the target product:
TABLE 5 ingredients and contents of the mouthwash having dental caries preventing effect obtained by the second preparation method
Example seven: preparation method III of jelly-like mouthwash with caries prevention, antibiosis, root strengthening and tooth strengthening effects
In order to obtain the mouth wash with the best efficacy, the components can be prepared according to the proportion shown in table 6 to obtain the target product:
TABLE 6 ingredients and contents of mouthwash having caries preventing effect obtained by the third preparation method
Example eight: preparation method of jelly-like mouthwash with caries prevention, antibiosis, root strengthening and tooth strengthening effects
In order to obtain the mouth wash with the best efficacy, the composition components can be prepared according to the proportion shown in table 7 to obtain the target product:
TABLE 7 ingredients and contents of mouthwash having anticariogenic effect obtained by the fourth preparation method
Example nine: safety inspection of anticarious mouthwash-cytotoxicity test
The invention designs a supplementary safety inspection test aiming at the invention, and further detects the safety of the anticarious component. Therefore, the invention adopts normal cells (mouse macrophage RAW246.7) as detection objects and Nitazoxanide (NTZ) as a positive control, if IC50Values greater than the positive control indicate very low cytotoxicity of the compound.
Experimental materials: mouse normal cell (macrophage RAW246.7), 96-well plate, CCK-8 reagent, Nitazoxanide (NTZ) and test compound.
Experimental method mouse macrophage RAW246.7 was divided into 3 groups and cultured in 96-well plates with 5 × 10 cell count per well3At 37 ℃ and 5% CO2After 70-80% of the cells are cultured in the environment and are converged, the drugs of nitazoxanide, LX-S-06, LX-S-18, XQH-2-92, XQH-3-6 and XQH-3-7 are respectively added, and after the cells are cultured for 48 hours at a proper temperature, the cell proliferation condition is detected by adopting a CCK-8 method.
Experimental results and analysis: as is clear from the results shown in Table 8, several antibacterial components XQH-2-92, XQH-3-6, XQH-3-7, LX-S-06 and LX-S-18 provided by the present invention have less toxicity to mouse macrophage RAW246.7 than NTZ. The antibacterial active ingredient in the invention does not enter into the body as an additive of the toothpaste, and the cytotoxicity of the active ingredient used in the invention is lower than that of the oral medicament nitazoxanide clinically used, so the invention has higher safety performance.
TABLE 8 detection results of cytotoxicity of anticariogenic component and nitazoxanide on mouse macrophage RAW246.7
Example ten: bone-promoting effect detection of anticarious mouthwash
Experimental materials: a bacteria culture dish, an in vitro tooth, an ophthalmic scissors, a centrifuge tube, a 6-pore plate, 4% paraformaldehyde and an ALP color development kit.
The experimental scheme is as follows: in the department of oromaxillofacial surgery of Shandong university's oral hospital, choose to collect the healthy third mill tooth of 12 ~ 18 year old patient, send the tooth to the laboratory within 4 h. And repeatedly washing the isolated teeth for 3-4 times by using 10 times of PBS in a sterile culture dish on an ultra-clean test bed. Using a sterile scalpel blade, 1/3 periodontal ligament was carefully scraped from the root, rinsed with 10 fold PBS while scraping, and the scraped tissue mass was cut to a minimum using an ophthalmic scissors. And transferring the scraped periodontal ligament tissue into a centrifuge tube, setting the rotation speed to be 1000r/min, and centrifuging for 2 min. The supernatant was discarded, and collagenase type I (1mL) and dispaseII (1mL) were added in the dark. Digesting for 40-50 min in a constant-temperature water bath kettle at 37 ℃, and slightly shaking the centrifuge tube for 1 time every 5min until the tissue is digested into cotton-like shape. Setting the rotating speed at 1000r/min, centrifuging for 5min, discarding the supernatant, adding 2mL of complete culture solution, and resuspending the cells. Inoculating into 6-well plate, adding 2mL complete culture solution into each well, 37 deg.C, and 5% CO2And (5) incubator culture. After 5 days, the solution was changed for the first time. The solution was changed every 3 days thereafter 1 time. Cell passage was performed when the cells grew up to 80% in 6-well plates. Inoculating human periodontal ligament stem cells (hPDLSCs) to a 6-well plate, after 70% -80% confluence, setting an experimental group and a blank control group, wherein the experimental group is 5 mu M quercetin, culturing for 14 days, then discarding culture solution, fixing 4% paraformaldehyde at room temperature for 15min, washing with PBS (pH 4.2) for 2 times, dyeing with an ALP color development kit in an incubator at 37 ℃ for 15min, then washing with PBS for 3 times, scanning and observing under a microscope.
Experimental results and analysis: the results under the post-staining microscope of the ALP color kit 14 days after osteogenesis induction are shown in FIG. 1. As can be seen in FIG. 1, the color of the experimental group was darker than that of the control group after staining, indicating that quercetin, a strong tooth component contained in the present invention, had an effect of efficiently promoting bone formation.
Example eleven: dental plaque staining experiment for checking caries prevention effectiveness of anticarious mouthwash
Normally, plaque is a biofilm formed by food and bacteria and attached to the surface of teeth and is not recognized by the naked eye, and it is continuously mineralized and gradually forms tartar in the later period. Plaque can be visualized and clearly visible with the plaque indicator.
Experimental materials: the invention relates to jelly-shaped anti-caries mouthwash, a special dental Plaque coloring agent (CHROM-O-RED) and a medical cotton ball.
The experimental protocol was as follows:
1. 4 subjects with similar oral health conditions were selected, and the subjects were divided into two groups, an experimental group and a control group, and the number of males and females in each group was guaranteed to be equal. The experimental group used the jelly-like anticarious mouthwash of example five (LX-S-06) of the invention, and the control group used the jelly-like anticarious mouthwash (supplemented with distilled purified water) containing no anticarious and teeth-consolidating components;
2. the mouth wash is used for each group in the morning, at noon and evening, 20ml of mouth wash is used for each time, the using time is 1 minute, and dental plaque condition is detected after two weeks.
3. Detecting dental plaque by a staining method:
uniformly coating a suction pipe or a small cotton ball dipped with a stain dye on the tooth surface, and staying for one minute;
after the coloring agent is firmly combined in the oral cavity, rinsing the residual coloring agent by water;
III, checking the staining condition of the teeth;
and IV, the distribution part of the staining and the chromaticity thereof are the distribution position and the quantity of dental plaque.
Experimental results and analysis: the results are shown in FIG. 2. As can be seen from FIG. 2, in the experimental group, only a small amount of dental plaque adheres to the adjacent tooth area (hard-to-clean area for tooth brushing), most of the tooth surface is white and rich in color, and the tissues around the teeth are healthy and full; in the control group, the test subjects had red plaque spread over their tooth surface, and the gingival sulcus and the neck showed a large amount of unremoved tartar and soft calculus. The typical samples of the experimental group and the control group are compared to prove that the invention has obvious anti-caries effect. Example five (LX-S-18 or XQH-2-92 or XQH-3-6 or XQH-3-7) anticaries effect similar to example five (LX-S-06), with LX-S-06 and LX-S-18 being most preferred.
Example twelve: taste detection of anticarious mouthwash
The experimental scheme is as follows: 16 testers are selected and divided into a juvenile group, a young group, a middle-aged group and an old group, and the number of the male and the female in each group is ensured to be equal. The mouth wash for preventing dental caries, which is disclosed by the invention, is used as an experimental group, namely an experimental group I, an experimental group II and an experimental group III, and mouth wash which is commonly sold in the market is used as a control group, and taste evaluation is recorded respectively.
The experimental results are as follows: the results are shown in Table 9.
TABLE 9 evaluation results of the effect of the experimenter on various mouthwashes
Example thirteen: detection of long-term use effect of anticarious mouthwash
The experimental scheme is as follows: selecting 16 patients with oral diseases such as caries, more dental plaque biomembrane or more tartar, gingival swelling, oral ulcer and halitosis, and ensuring equal number of men and women with average age of 31 years. Subjects were randomized into 4 groups with a total of 4 subjects per group. Experimental group used example V (LX-S-06) of the present invention,
The sixth and seventh examples of the mouthwash having caries preventing effect, the control group used conventional commercial mouthwash. The application method is gargling, and the using effect is counted after 3 weeks of use.
Evaluation criteria: see table 10.
TABLE 10 evaluation criteria of oral problems of the test subjects after using the anticaries mouthwash of the present invention
Experimental results and analysis: the results are shown in Table 11.
TABLE 11. detection results of the anti-caries mouthwash provided by the present invention after long-term use
The above-mentioned embodiments are merely illustrative of the basic principles and specific functions of the present invention, and do not limit the present invention, and it will be obvious to those skilled in the art that the invention may be modified and improved in principle to obtain better effects.
Claims (6)
1.A jelly-like mouthwash with the efficacies of preventing caries and resisting bacteria and strengthening root and teeth is characterized by comprising the following components: 3 to 5 percent of moisture retention component, 91 to 95 percent of solvent, 0.25 to 0.75 percent of acid-base buffer agent, 0.2 to 0.6 percent of caries prevention component, 0.05 to 0.15 percent of root strengthening component, 0.2 to 0.6 percent of seasoning component, 0.1 to 0.2 percent of antiseptic component, 0.25 to 0.35 percent of flavoring agent, 0.01 to 0.03 percent of tooth fixing component and 0.4 to 0.8 percent of gel component, wherein the caries prevention component is more than two of compounds LX-S-06, LX-S-18, XQH-2-92, XQH-3-6 and XQH-3-7 and at least comprises any one of LX-S-06 and LX-S-18, and the root strengthening component is quercetin;
the structural formula of the LX-S-06 is shown as
The structural formula of the LX-S-18 is shown as
The structural formula of the XQH-2-92 is shown in the specification
The structural formula of the XQH-3-6 is shown in the specification
The structural formula of the XQH-3-7 is shown in the specification
The jelly-like mouth wash comprises the moisturizing components of glycerin and propylene glycol, the solvent is purified water, the acid-base buffer agent is sodium citrate and sodium malate, the seasoning components are xylitol and trehalose, the preservative component is sodium benzoate, the flavoring agent is essence and honeysuckle extract, the tooth fixing component is sodium fluoride, and the gel component is carrageenan and konjac glucomannan.
2. The jelly-like mouthwash having caries preventing, antibacterial and teeth strengthening effects according to claim 1, wherein the composition of the jelly-like mouthwash is: 3.8% of moisture-keeping component, 93.7% of solvent, 0.5% of acid-base buffer agent, 0.4% of anticaries component, 0.1% of root-strengthening component, 0.4% of seasoning component, 0.15% of preservative component, 0.33% of flavoring agent, 0.02% of tooth-fixing component and 0.6% of gel component.
4. Use of the compound having anti-streptococcus mutans efficacy of claim 3 in the preparation of an oral streptococcus mutans biofilm inhibitor.
5. Use of the compound having an anti-streptococcus mutans effect according to claim 3 for the manufacture of a medicament for preventing and treating dental caries.
6. Use of the compound having an anti-streptococcus mutans effect according to claim 3 for preparing toothpaste, mouthwash, denture cleanser, dental ulcer patch, or disinfectant.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002255769A (en) * | 2001-02-28 | 2002-09-11 | Sunstar Inc | Composition for oral cavity cleaning |
CN106588813A (en) * | 2016-12-14 | 2017-04-26 | 山东大学 | Novel thiazole compound XQH-2-92 for resisting streptococcus mutans and application of novel thiazole compound XQH-2-92 |
CN106588911A (en) * | 2016-12-14 | 2017-04-26 | 山东大学 | Novel thiazole compound XQH-3-6 resisting streptococcus mutans and application of compound |
CN106699751A (en) * | 2016-12-14 | 2017-05-24 | 山东大学 | Novel compound XQH-3-7, and application of novel compound in streptococcus mutans resistance and streptococcus mutans biological membrane formation inhibition |
-
2018
- 2018-01-17 CN CN201810045648.9A patent/CN108210385B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002255769A (en) * | 2001-02-28 | 2002-09-11 | Sunstar Inc | Composition for oral cavity cleaning |
CN106588813A (en) * | 2016-12-14 | 2017-04-26 | 山东大学 | Novel thiazole compound XQH-2-92 for resisting streptococcus mutans and application of novel thiazole compound XQH-2-92 |
CN106588911A (en) * | 2016-12-14 | 2017-04-26 | 山东大学 | Novel thiazole compound XQH-3-6 resisting streptococcus mutans and application of compound |
CN106699751A (en) * | 2016-12-14 | 2017-05-24 | 山东大学 | Novel compound XQH-3-7, and application of novel compound in streptococcus mutans resistance and streptococcus mutans biological membrane formation inhibition |
Non-Patent Citations (1)
Title |
---|
槲皮素药理作用研究进展;骆明旭等;《中国民族民间医药》;20140915;第12-14页 * |
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