CN101397303A - Sanggenole A compounds, preparation method and use thereof - Google Patents
Sanggenole A compounds, preparation method and use thereof Download PDFInfo
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- CN101397303A CN101397303A CNA2008100941993A CN200810094199A CN101397303A CN 101397303 A CN101397303 A CN 101397303A CN A2008100941993 A CNA2008100941993 A CN A2008100941993A CN 200810094199 A CN200810094199 A CN 200810094199A CN 101397303 A CN101397303 A CN 101397303A
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Landscapes
- Cosmetics (AREA)
Abstract
The invention discloses a new compound-mulberry-root hydroxybenzene A compound with the structure as shown in the formula (I). The invention further discloses a preparation method of the compound and the application of the compound in preparing medicines used for treating or preventing oral diseases, and preparing the oral caring products.
Description
1. technical field
The invention belongs to technical field of pharmaceuticals.Especially, the present invention relates to a kind of new, shown in structural formula (I), the Sanggenole A compounds thing of purifying, its preparation method is the pharmaceutical composition of activeconstituents with this compound, with and in treatment or prevention oral disease and the application in oral care implement.
2. technical background
Human common oral disease has dental caries disease and periodontopathy.The dental caries disease is a kind of chronic bacillary disease that occurs in hard tooth tissue, shows as hard tooth tissue and look occurs, shape, the variation of matter.The clinical symptom of periodontopathy is gingival hemorrhage, pyorrhea, and odontoseisis, frontal resorption and periodontal pocket form.Carious tooth and periodontopathy are to cause the grownup to lose the one of the main reasons of tooth.Think that at present the dental caries cause of disease sick and periodontopathy all is the disease of the autogenous infection of oral cavity normal microflora due under the ecologic disturbance situation of oral cavity, promptly initiation factor is the bacterial plaque microorganism, and is by due to the specificity pathogenic bacteria.Bacterium is the pathogenetic prerequisites of dental caries, and streptococcus mutans (Streptococcus mutans), actinomyces viscosus (Actinomyces viscosus) etc. can make carbohydrate breakdown produce acid, causes the demineralization of tooth inanimate matter to form cavity.Streptococcus mutans still is the pioneer bacterium that plaque forms, and same actinomyces viscosus, porphyromonas gingivalis (Porphyromonas gingivalis) form plaque jointly.The toxin that bacterium produced and other objectionable impuritiess in the plaque can cause host's inflammatory reaction, make that vascular permeability increases, the inflammation diffusion, destroy gum, dental cement and alveolar bone, cause gingivitis and periodontopathy.Therefore suppress the important means that oral cavity pathogen is preventing dental caries, gingivitis and periodontopathy.
Treatment dental caries medicine sick and periodontopathy is very limited at present.On the one hand, eliminate or the inhibition plaque bacteria with chemicals, but life-time service broad-spectrum antibacterial medicine can produce Resistant strain and other side effect.Such as, the domestic and international in recent years chemistry control bacterial plaque agent Tubulicid (Chlorhexidine) that uses, be a kind of two guanidine hexanes (diguanido-hexane) with obvious bacteriostatic action, but life-time service contains the gargle of 0.12-0.20% Tubulicid, though can not form Resistant strain or human body is caused damage, but it can make tooth staining, and back also has brown tongue fur.On the other hand, utilize the Chinese medical discrimination therapy, as contain heat-clearing and detoxifying herbs such as gargling Japanese Honeysuckle, application is also arranged, as deposited BINGPENG SAN, or the root of Chinese wild ginger is in the affected part.These methods have used a lot of inconvenient parts, and the shortcoming conclusive evidence proves its curative effect.Yet gingivitis is as if untimely treatment or malpractice, and its inflammation may diffuse to periapical and cause periapical tissue's inflammation, and then involves alveolar bone or adjacent tissue.Based on above reason, as can be seen, in natural phant, research and develop the new drug of the common oral disease of treatment such as dental caries disease and periodontopathy, and develop and to suppress main pathogenic bacterium in oral cavity and plaque, gingivitis, the mouth cavity medicine or the oral care implement that suppress halitosis are very significant.
The research that natural phant suppresses oral cavity pathogen has distinct regional characteristic, geographical environment and the national conditions different according to all parts of the world, different countries and regions have found that some have some plants of anticaries action, as the green wood of elm, Herba Vernonia esculenta, the gamboge in the Africa and the Middle East; The bloodroot of Latin American countries, cocoa; The betel nut in South East Asia; The folium eucalypti in Australia.China and Japan then focus mostly in the research of herbal medicine.
3. summary of the invention
The object of the present invention is to provide a kind of newly, shown in structural formula (I), have pharmaceutical use, the compound of mulberry roots phenol A.
Another object of the present invention provide a kind of from the White Mulberry Root-bark plant, extract of the present invention new, the method for the compound shown in structural formula (I).
It is the treatment of effective constituent and the pharmaceutical composition of prevention oral disease with compound shown in this formula (I) that further purpose of the present invention provides a kind of.
Another object of the present invention provides compound shown in a kind of this formula (I) and is the purposes of composition aspect the medicine of preparation treatment or prevention oral disease of effective constituent with compound shown in this formula (I), with and purposes in oral care implement.
In order to realize above-mentioned purpose of the present invention, the invention provides following technical scheme:
Compound shown in structural formula (I):
The present invention provides the preparation method of formula (I) compound simultaneously, be about to White Mulberry Root-bark with 90% alcohol reflux three times, each 3 hours, recovery as for, medicinal extract, with this medicinal extract dissolving suspendible, with ethyl acetate extraction 3 times, be recycled to dried ethyl acetate medicinal extract, gained medicinal extract acetone solution is adsorbed on the silica gel, the room temperature volatilization causes dried, through silica gel column chromatography, use V/V, the sherwood oil of 8:2: the acetone wash-out, per 50 are upgraded to a flow point, amount to 27 flow point Fr.1-Fr.27, flow point Fr.6 is through silica gel column chromatography, the 90:10 chloroform: methanol-eluted fractions gets final product.
The present invention further provides the pharmaceutical composition that is used for the treatment of or prevents oral disease, described pharmaceutical composition contains formula (I) compound and the pharmaceutically acceptable carrier of treatment or prevention significant quantity.
The present invention also provides a kind of articles for use that are used for mouth care, wherein contains formula (I) compound and the acceptable assistant agent of mouth care of oral care effective amount.
The Sanggenole A compounds thing of formula of the present invention (I) can be used for preparing in the medicine of treatment or prevention oral disease, also can be used for preparing in the oral care implement.
The present invention's compound shown in the discoverable type (I) first has certain restraining effect to oral cavity pathogen, and has antiphlogistic effects.It can be used as effective constituent and is applied in anti-dental caries, suppresses in the mouth cavity medicine or oral care implement of halitosis, also can be used for resist gingivitis, anti-plaque, oral cavity and goes in the mouth cavity medicine or oral care implement of sensitivity, anti-calculus, teeth whitening.
Specify the present invention below in conjunction with embodiment.
The preparation structure of compound shown in embodiment 1. formulas (I) is determined
White Mulberry Root-bark 50kg is with 90% ethanol 500kg refluxing extraction three times, each 3 hours, be recycled to dried, 10.5kg medicinal extract.With this medicinal extract ethanol 4kg dissolving suspendible,, be recycled to dried 4kg ethyl acetate medicinal extract with 50kg ethyl acetate extraction 3 times with 8kg hot water and 90%.On the gained medicinal extract acetone solution, absorption and 6kg silica gel, it is dried that room temperature volatilization causes, through silica gel column chromatography (30 orders, 30kg), use sherwood oil: acetone (per 50 are upgraded to a flow point for V/V, 8:2) wash-out, amount to 27 flow point Fr.1-Fr.27.Flow point Fr.6 is through silica gel column chromatography, and chloroform: methyl alcohol (90:10) wash-out gets formula (I) compound.
The compound suc as formula shown in (I) that makes through this method can have very high concentration.In certain embodiments, the compound concentrations suc as formula shown in (I) that makes through this method is higher than 98%.In some other embodiment, the compound concentrations suc as formula shown in (I) that makes through this method is 50%-99.9%.In further embodiments, the compound concentrations suc as formula shown in (I) that makes through this method is 75%-99.9%.
In the above-described embodiments, used White Mulberry Root-bark to extract suc as formula the compound shown in (I).Those of ordinary skill in the art can recognize that other plant also may be suitable for, and for example belongs to together with White Mulberry Root-bark or equal plant.
Described structural formula suc as formula the compound shown in (I) by mass spectrum (MS) and nuclear magnetic resonance spectrum (
1HNMR and
13C NMR) determines.Mass spectrum (MS) uses Auto SPEC 3000 type mass spectrographs to measure.Nuclear magnetic resonance spectrum (
1H NMR and
13C NMR) measures mark in TMS does with Bruker DRX-500 NMR spectrometer with superconducting magnet.Column chromatography material and thin-layer chromatography silica gel are the product of Qingdao Makall Group Co., Ltd..
The structural formula of being measured suc as formula the Sanggenole A compounds thing shown in (I) is:
Proterties: brown powder (methyl alcohol), fusing point, 103-105 ℃
Molecular formula: C
34H
260
9
Molecular weight: 578
FAB-MS(-)m/z(％)：561(M+，100)。
1H-NMR(CD
3OD，400 MHz)δ：7.95(1H，d，J＝8.8Hz，H-4)，7.45(1H，s，H-14″)，7.26(1H，d，J＝8.4Hz，H-13″)，7.22(1H，d，J＝2.4Hz，H-7)，7.21(1H，s，H-20″)，7.05(2H，d，J＝2.0Hz，H-2′，6′)，7.02(1H，s， H-3)，6.97(1H，d，J＝8.0Hz，H-19″)，6.70(1H，dd，J＝9.8，2.0Hz，H-5)，6.13(1H，d，J＝4.0Hz，H-2″)，4.15(1H，dd，J＝12.4，4.8Hz，H-3″)，3.92(1H，s，H-4″)，3.29(1H，m，H-5″)，2.63(1H，dd，J＝17.2，4.8Hz，H-6″)，2.12(1H，dd，J＝16.0，12.0Hz，H-6″)，1.74(3H，s，H-7″)。
13C-NMR(CD
3OD，100MHz)δ：156.7(s，C-2)，102.0(d，C-3)，121.0(d，C-4)，122.5(s，C-3a)，104.7(d，C-5)，155.0(s，C-6)，99.4(d，C-7)，151.0(s，C-7a)，133.3(s，C-1′)，105.2(d，C-2′)，156.7(s，C-3′)，117.6(s，C-4′)，161.0(s，C-5′)，104.3(d，C-6′)，134.8(s，C-1″)，124.5(d，C-2″)，36.5(d，C-3″)，27.8(d，C-4″)，35.8(d，C-5″)，35.9(t，C-6″)，23.8(q，C-7″)，102.7(s，C-8″)，114.2(s，C-9″)，161.0(s，C-10″)，161.0(d，C-11″)，104.3(s，C-12″)，107.2(d，C-13″)，130.8(d，C-14″)，117.1(s，C-15″)，154.0(s，C-16″)，104.6(d，C-17″)，158.9(s，C-18″)，110.4(d，C-19″)，128.0(d，C-20″)。
The disclosed structural formula of compound according to the present invention, those skilled in the art can be easily by the synthetic described compound of chemical process, to substitute employed extract or purifying thing among the present invention through creative work.So those skilled in the art should understand, except the embodiment of the invention listed from natural White Mulberry Root-bark, extract or purifying, the present invention can also realize by chemical synthesis process.Other conspicuous modification to the disclosed compound of the present invention also is included within protection scope of the present invention.
Compound shown in embodiment 2. formulas (I) is to the inhibition experiment of the main pathogenic bacterium in oral cavity
A. culture of strains:
Table 1: relevant oral cavity pathogen
Separate the soy peptone agar blood agar (be called for short TSA5B) picking list bacterium colony in corresponding broth culture from the pancreatin of daily storage bacterial classification, in 37.0 ℃ ± 1.0 ℃, 95% air, cultivate (P.g needs anaerobism to cultivate) in the little aerobic environment of 5%CO2, wherein S.m cultivates 18-24h, cultivates 40-48h for all the other two kinds.Regulate the turbidity to 0.5 of bacteria suspension then with corresponding broth culture
#McFarland standard is equivalent to 1.0X10
8CFU/mL.
B. experimental technique: broth dilution method (Broth dilution)
In meat soup, antibacterials are carried out after a series of doubling dilution more quantitatively that inoculation detects bacterium, observe after hatching 18-24h, suppress to detect the lowest concentration of drug of bacterial context eye visible growth for 37 ℃ for measuring medicine to detecting the minimum inhibitory concentration (MIC) of bacterium.Operation steps is:
A. the preparation of antibacterials stoste: prepare 1% various antibacterials stostes, solvent is 100% straight alcohol.Stoste prepares the after-filtration degerming, and packing is standby in a small amount.
B. measure range of concentrations: this experimental selection 250ppm measures the upper limit of concentration as antibacterials.
C. measuring method: micro-dilution method.
Add 100 μ l broth cultures prior to each hole on 96 orifice plates, add 100 μ l through 10 times of aseptic antibiotic soups (1000mg/l) that diluted in each hole of first row again, blow and beat 7-8 time repeatedly on each hole of first row with multichannel micropipettor then, pipette 100 μ l samples to secondary series after making medicine and TSB thorough mixing, pipette 100 μ l samples to the, three row after blowing and beating 7-8 time equally repeatedly again, arrive last row by that analogy, the concentration of medicine is just by two times of gradient dilutions like this, the 0.24mg/l from the 500mg/l of first row to last row (the 12nd row).
Bacterium to be measured and standard bacterium are prepared as above.With the dilution of bacterium liquid, reach bacteria containing amount about 10 with broth culture
6CFU/ml.100 μ l are inoculated in every then hole.The final weaker concn of every like this row's antibacterials is 250,125, and 62.5...0.12mg/L finally inoculates the about 5x10 of bacterium amount
7CFU/ml or every hole 5x10
6Individual bacterium; 96 orifice plates are put the 1min that vibrates on the microoscillator, make solution mixing in each hole, microwell plate is added a cover blended rubber paper sealing and is hatched the evaporation in the process with minimizing and put in the wet box, in 37.0 ℃ ± 1.0 ℃, and 95% air, 5%CO
2Little aerobic (or 90%N
2, 5%H
2, 5%CO
2Anaerobism) cultivated 18-24 hour in the environment.96 orifice plates are placed under the microplate reader, and the growth characteristics of control test bacterium and standard bacterium are MIC with the contained minimum antibacterials concentration in asepsis growth hole.
C. experimental result (seeing Table 2)
Table 2 formula (I) compound is to the effect of oral cavity pathogen
| A.v ATCC 27044 | S.m ATCC 25175 | P.g ATCC 33277 | |
| Negative control (DMSO) | - | - | - |
| Positive control (Triclosan) | 3.9 | 3.9 | 7.8 |
| Formula (I) compound | 3.9 | 3.9 | 15.6 |
The test of the anti-inflammatory of compound shown in embodiment 3. formulas (I)
A. KB cell (human oral cavity epithelial cancer cells) is adopted in experiment:
During experiment the KB cell that is inoculated in the culture plate is given formula (I) compound treatment or refuses formula (I) compound treatment (contrast), after processing finishes, collect the nutrient solution supernatant and be stored in-80 ℃ of refrigerators.PGE in the supernatant
2Detect with enzyme-linked immunosorbent assay, the multi-functional liquid phase chip analysis of Luminex system [the results are shown in Table 3] is then used in the detection of the GM-CSF in the supernatant, TNF-α, IL-1 β and IL-6.
B.PGE
2Enzyme-linked immunosorbent assay detect:
Enzyme-linked immunosorbent assay according to standard is carried out.
Result (the more little anti-inflammatory activity of numerical value is good more): formula (I) compound is that 0.02ppm and the pure as jade pure phase of positive reference substance are worked as to the half-inhibition concentration of oral cavity KB cell growth.The result shows that formula (I) compound has significant anti-inflammatory activity.
The multi-functional liquid phase chip analysis of the Luminex of C.GM-CSF, TNF-α, IL-1 and IL-6:
Confining liquid seals 96 orifice plate 30min.Fluorescent microsphere dilution back adds 96 orifice plates.Add standard substance and testing sample, 4 ℃ are spent the night.Second day, supernatant discarded, every hole adds 50 μ l GM-CSF, TNF-α, IL-1 β and IL-6 antibody.After cleaning 4 times, 96 orifice plates were put into shaking table room temperature lucifuge 1 hour, cleaned the PE room temperature lucifuge of adding streptavidin mark 15 minutes 4 times.Clean 4 times, microballoon is suspended from the cleaning buffer solution, and 96 orifice plates place Luminex at once, and (Luminex Corporation, Austin Tx.) go up analysis.
D. result: formula (I) compound has very strong anti-inflammatory ability.Concrete outcome sees Table 3.
Table 3: the anti-inflammatory action of formula (I) compound (the big more anti-inflammatory ability that shows of this numerical value is strong more)
| Extract/compound | GM-CSF | IL-1 β (interleukin) | IL-6 (interleukin) | TNF-α (tumour necrosis factor) |
| Formula (I) compound | 11％ | 23％ | 53％ | 93％ |
| Pure as jade pure (positive control) | 5％ | 7％ | 31％ | 81％ |
Can confirm from above-mentioned experimental result: formula of the present invention (I) compound is to oral cavity pathogen (actinomyces viscosus, association unwrapping wire line bacillus, become suis, porphyromonas gingivalis) has the good restraining effect, oral cavity KB cell is had significant anti-inflammatory activity, and inflammatory factor is also had the obvious suppression effect.
Application of compound shown in embodiment 4. formulas (I)
When compound shown in the formula of the present invention (I) is used as medicine, can directly use, also can be used as effective constituent and be applied in mouth cavity medicine or the dental care products, as toothpaste, collutory, paste, instant or film, gum etc.Can be with significant quantity and other composition such as wetting Agent for Printing Inks, friction agent, tensio-active agent, mixed mouth cavity medicine or the dental health product of getting such as pharmaceutically acceptable carrier and/or additive, prepared mouth cavity medicine or dental health product include but not limited to toothpaste, collutory, chewing gum, oral cavity paste etc.
The significant quantity of indication of the present invention is meant the dosage that is enough to produce a positive effect.This significant quantity can change because of the change of concrete application mode.And,, a plurality of effective doses or effective dosage ranges can be arranged for a certain concrete application mode.In certain embodiments, formula (I) compound can become phase-splitting to mix with the addition of 0.0005-99% (mass percent) with other.In some other embodiment, the content of formula (I) compound is 0.001-10% (mass percent).In some preferred embodiment, the content of formula (I) compound is 0.025-5% (mass percent).In further embodiments, the content of formula (I) compound is 0.05-0.5% (mass percent).In further embodiments, the content of formula (I) compound is 0.5-90% (mass percent).
Preferably, in tablet, the content of formula (I) compound is 4% (mass percent); In nasal spray, the content of formula (I) compound is 4% (mass percent); In dripping pill, the content of formula (I) compound is 10% (mass percent); In toothpaste, the content of formula (I) compound is 0.5% (mass percent); In collutory, the content of formula (I) compound is 0.5% (mass percent); In the paste of oral cavity, the content of formula (I) compound is 0.01% (mass percent).
Other effective dose also can be applicable among the present invention.
Prescription moiety involved in the present invention also may contain cats product and/or nonionogenic tenside.Cats product includes, but are not limited to this, hexadecyl trimethyl ammonium chloride, diisobutylphenoxy ethoxyethyl dimethylbenzene benzyl brometo de amonio.Ionic surfactant pack is drawn together poloxamer, Spheron MD 30/70 and ethoxylated fatty acid etc., and poloxamer is the segmented copolymer of polyoxyethylene and polyoxypropylene, has commercial availability.As the commodity Pluronic by name that BASF produces, Spheron MD 30/70 comprises Polyoxyethylene Sorbitol Fatty Acid Esters (typically poly-many ethoxy alcohols monoesters), is that the trade(brand)name of being produced by ICL International Computer Limited is Tween, other ionic surfactant pack is drawn together polyoxyethylene alkylphenol, the polyoxyethylene alcohols, lipid acid, polyoxyethylene ester class, polyoxyethylene alkyl amine glyceryl ester, polyglycerol ester, tetrose alcohol ester, pentose alcohol ester, hexose alcohol ester, anhydrous trisaccharide alcohol ester and many hydrocarbon of polyoxy alkylamine ester.The general mass content of tensio-active agent in prescription is 0.001% to 3.0%.May contain divalent-metal ion in the prescription, as zinc, copper, selenium, calcium or magnesium.They can be with the form of soluble inorganic salt such as the form of zinc chloride or organic/inorganic compound.The add-on of divalent-metal ion in mixture will be 0.001% to 3.0%.May contain oligose in the prescription, oligose will might change into soluble salt with water-soluble state, if add minimum adding 0.01%.
Product of the present invention can comprise various mouth cavity medicines commonly used or dental health product, as: collutory, mouth spray, toothpaste, Chu mile, oral mucosa paster, pelliculae pro cavo oris, instant and film, gum waits to be used for the especially inhibition bacterial plaque of humans and animals of mammals, preventing dental caries, the product of periodontopathy.
Because the method difference may be used other additives: collutory may contain acidic substance, collutory also may contain desensitization material such as saltpetre, and toothpaste may contain abrasive such as yellow soda ash, calcium phosphate, aluminum oxide, silicon-dioxide; Solubilizing agent such as PEG, glycerine, ethanol; Other correctivess such as Xylitol, thickening material such as carrageenin, tensio-active agent such as SLS etc. all may use.
In toothpaste or oral mucosa paster, all may use wax, as beeswax; Thickening material, membrane-forming agent also may add as carrageenin, CMC, HPMC, xanthan gum etc.
Essence may use as peppermint, spearmint, and eucalyptus oil, mentha camphor, Karvon, Chinese ilex, cloves, Chinese cassia tree, lemon, grapefruit, orange and some are digested the essence that by yeast and proteolysis.
In tablet and film, inert excipient may be used for the shaping of product.Mainly comprise some tinting materials, auxiliary materials such as correctives are to improve taste and outward appearance.
The present invention is used for the related prescription moiety of tablet may comprise weighting agent, tackiness agent, lubricant, disintegrating agent.Weighting agent includes, but are not limited to this, starch, lactose, Microcrystalline Cellulose etc.Tackiness agent includes, but are not limited to this, starch slurry, derivatived cellulose, polyvidone, gelatin etc.Lubricant includes, but are not limited to this, Magnesium Stearate, micropowder silica gel, talcum powder, polyethylene glycols etc.Disintegrating agent includes, but are not limited to this, sodium starch glycolate, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, croscarmellose sodium etc.These compositions all are the pharmaceutical excipients that many state-promulgated pharmacopoeia such as Chinese Pharmacopoeia and English, U.S. are recorded.
The present invention may use matrix such as polyoxyethylene glycol in paste.May mix with solid-state and liquid polyoxyethylene glycol and use to regulate denseness.Also may add compositions such as Magnesium Stearate, to regulate denseness.
Embodiment 5. concrete Application Examples
Following test example and embodiment can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.
Formula (I) compound formulation of tooth-paste 1:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.0005-20 |
| Friction agent | 10-30 |
| Wetting Agent for Printing Inks | 50-69 |
| Water, spices, food flavouring | In right amount |
Formula (I) compound formulation of tooth-paste 2:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 5 |
| Silicon-dioxide | 30 |
| Glycerine | 5 |
| Sorbyl alcohol | 50 |
| Water, spices, food flavouring | In right amount |
Formula (I) compound formulation of tooth-paste 3:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.001 |
| Silicon-dioxide | 10 |
| Sorbyl alcohol | 69 |
| Water, spices, food flavouring | In right amount |
Formula (I) compound formulation of tooth-paste 4:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 10 |
| Friction agent | 25 |
| Wetting Agent for Printing Inks | 65 |
Formula (I) compound formulation of tooth-paste 5:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.0005 |
| Silicon-dioxide | 10 |
| Sorbyl alcohol | 70 |
| Water, spices, food flavouring | In right amount |
Formula (I) compound formulation of tooth-paste 6:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 20 |
| Friction agent | 25 |
| Wetting Agent for Printing Inks | 55 |
Formula (I) compound formulation of tooth-paste 7:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.025 |
| Silicon-dioxide | 20 |
| Glycerine | 5 |
| Sorbyl alcohol | 60 |
| Sodium Fluoride | 0.221 |
| Soluble saccharin | 0.3 |
| Water | 7.954 |
| Polyoxyethylene glycol | 3 |
| Sodium lauryl sulphate | 2 |
| Essence | 1.5 |
Formula (I) compound formulation of tooth-paste 8:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0-3 |
| Silicon-dioxide | 20 |
| Glycerine | 5 |
| Sorbyl alcohol | 60 |
| Sodium Fluoride | 0.221 |
| Soluble saccharin | 0.3 |
| Water | 7.679 |
| Polyoxyethylene glycol | 3 |
| Sodium lauryl sulphate | 2 |
| Essence | 1.5 |
Formula (I) compound formulation of tooth-paste 9:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.5 |
| Silicon-dioxide | 20 |
| Glycerine | 5 |
| Sorbyl alcohol | 60 |
| Sodium Fluoride | 0.221 |
| Soluble saccharin | 0.3 |
| Water | 7.479 |
| Polyoxyethylene glycol | 3 |
| Sodium lauryl sulphate | 2 |
| Essence | 1.5 |
Formula (I) compound collutory prescription 1:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.0005-20 |
| Water | 70-94 |
| Other additive | In right amount |
Formula (I) compound collutory prescription 2:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 5 |
| Water | 80 |
| General stream Buddhist nun gram | 3.00 |
| Other additive | In right amount |
Formula (I) compound collutory prescription 3:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.001 |
| Water | 94 |
| Alcohol | 5.00 |
| Other additive | In right amount |
Formula (I) compound collutory prescription 4:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.5 |
| Water | 90 |
| General stream Buddhist nun gram | 3.00 |
| Alcohol | 3.00 |
| Other additive | In right amount |
Formula (I) compound collutory prescription 5:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.025 |
| Water | 85 |
| General stream Buddhist nun gram | 5.00 |
| Alcohol | 3.00 |
| Other additive | In right amount |
Formula (I) compound collutory prescription 6:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.05 |
| Water | 91.7 |
| General stream Buddhist nun gram | 3.00 |
| Alcohol | 5.00 |
| Essence | 0.25 |
Formula (I) compound collutory prescription 7:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.0005 |
| Water | 94 |
| Alcohol | 5.00 |
| Other additive | In right amount |
Formula (I) compound collutory prescription 8:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 20 |
| Water | 70 |
| General stream Buddhist nun gram | 3.00 |
| Alcohol | 3.00 |
| Other additive | In right amount |
Formula (I) compound paste agent prescription 1:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 10 |
| Polyoxyethylene glycol | 90 |
Formula (I) compound paste agent prescription 2:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.001 |
| Polyoxyethylene glycol | 80 |
| Other additive | In right amount |
Formula (I) compound paste agent prescription 3:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.01 |
| Polyoxyethylene glycol | 90 |
| Other additive | In right amount |
Formula (I) compound paste agent prescription 4:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 5 |
| Polyoxyethylene glycol | 95 |
Formula (I) compound paste agent prescription 5:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.025 |
| Polyoxyethylene glycol | 99.975 |
Formula (I) compound paste agent prescription 6:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 20 |
| Polyoxyethylene glycol | 80 |
Formula (I) compound paste agent prescription 7:
| Batching | Content (mass percent, %) |
| Formula (I) compound | 0.0005 |
| Polyoxyethylene glycol | 99 |
| Other additive | In right amount |
Formula (I) compound tablet:
Tablet: activeconstituents formula (I) compound 10mg, lactose 180mg, starch 55mg, Magnesium Stearate 5mg.
The preparation method: activeconstituents, lactose and starch are mixed, and water is evenly moistening, the mixture after moistening is sieved and drying, after sieve, adds Magnesium Stearate, then with the mixture compressing tablet, and every heavy 250mg, active component content is 10mg.Formula (I) compound nasal spray:
Formula (I) compound 80mg
Sodium-chlor 8mg
EDTA 1mg
Sodium phosphate buffer (pH6.5) 10mg
Spheron MD 30/70 10mg
Double distilled water is to 2ml
Preparation method: stir down and to add a kind of composition at every turn in the double distilled water of proper volume, until separating fully deeply, and then add another kind of composition.After adding water to 2ml, this solution is filtered on sterilizing filter, separate in the bottle of packing into and according to suitable dosage.
Formula (I) compound dripping pill:
Formula (I) compound 1g
Polyethylene glycol 6000 9g
Method for making: the preparation of formula (I) compound and polyethylene glycol 6000 fused solution: take by weighing formula (I) compound by above-mentioned recipe quantity and add an amount of dehydrated alcohol, after the low-grade fever dissolving, in the polyoxyethylene glycol fused solution of adding recipe quantity (60 ℃ of water bath heat preservations), mix, till ethanol is waved to the greatest extent, be statically placed in 60 ℃ of water-baths and be incubated 30 minutes, treat that bubble eliminates, the above-mentioned mixing fused solution that will eliminate bubble then changes in the liquid storage cylinder, under the condition of 80-85 ℃ of insulation, speed is dripped in control, splashes into dropwise in the phlegma, waits condensation complete, phlegma inclines, collect dripping pill, drop is clean and remove phlegma on the ball with filter paper, places in the silica gel drier or seasoning gets final product.
Set forth a large amount of concrete details in the above detailed description of the present invention, its objective is for the present invention being made clear complete explanation, so that public's reading comprehension.But those skilled in the art will be clear that in some cases, do not have these concrete details, or these concrete details are carried out nonessential change or replacement, also can realize the present invention.These variant schemes all should be considered to fall in the spirit and scope of the present invention.Scope of the present invention should be decided by the plain language of appended claims, and the specific embodiment that should not be limited in the specification sheets to be provided.
Claims (16)
1, a kind of compound shown in structural formula (I):
2, compound as claimed in claim 1, it extracts from White Mulberry Root-bark.
3, compound as claimed in claim 1, its purity are 50%-99.9%.
4, compound as claimed in claim 1, its purity are 75%-99.9%.
5, compound as claimed in claim 1, its purity is for being higher than 98%.
6, a kind of method for preparing compound as claimed in claim 1 comprises plant is used column chromatography with organic solvent extraction and with extract.
7, method as claimed in claim 6, described plant is a White Mulberry Root-bark.
8, a kind of pharmaceutical composition that is used for the treatment of or prevents oral disease wherein contains treatment or prevents the compound as claimed in claim 1 and the pharmaceutically acceptable carrier of significant quantity.
9, a kind of articles for use that are used for mouth care wherein contain the compound as claimed in claim 1 and the acceptable assistant agent of mouth care of oral care effective amount.
10, be used for the treatment of as claimed in claim 8 or 9 or prevent the pharmaceutical composition of oral disease or be used for the articles for use of mouth care, wherein the content of the compound shown in claim 1 is 0.0005-99% (mass percent).
11, as claimed in claim 10ly be used for the treatment of or prevent the pharmaceutical composition of oral disease or be used for the articles for use of mouth care, wherein the content of the compound shown in claim 1 is 0.001-10% (mass percent).
12, as claimed in claim 10ly be used for the treatment of or prevent the pharmaceutical composition of oral disease or be used for the articles for use of mouth care, wherein the content of the compound shown in claim 1 is 0.025-5% (mass percent).
13, as claimed in claim 11ly be used for the treatment of or prevent the pharmaceutical composition of oral disease or be used for the articles for use of mouth care, wherein the content of the compound shown in claim 1 is 0.05-0.5% (mass percent).
14, as claimed in claim 11ly be used for the treatment of or prevent the pharmaceutical composition of oral disease or be used for the articles for use of mouth care, wherein the content of the compound shown in claim 1 is 0.5-90% (mass percent).
15, the application of compound as claimed in claim 1 in the medicine of preparation treatment or prevention oral disease.
16, the application of compound as claimed in claim 1 in the preparation oral care implement.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100941993A CN101397303A (en) | 2007-05-16 | 2008-05-16 | Sanggenole A compounds, preparation method and use thereof |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200710106996 | 2007-05-16 | ||
| CN200710106996.4 | 2007-05-16 | ||
| CNA2008100941993A CN101397303A (en) | 2007-05-16 | 2008-05-16 | Sanggenole A compounds, preparation method and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101397303A true CN101397303A (en) | 2009-04-01 |
Family
ID=40516169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008100941993A Pending CN101397303A (en) | 2007-05-16 | 2008-05-16 | Sanggenole A compounds, preparation method and use thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101397303A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110483543A (en) * | 2019-09-17 | 2019-11-22 | 西北大学 | One breeder mulberry root extract, extraction separation method and its application |
-
2008
- 2008-05-16 CN CNA2008100941993A patent/CN101397303A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110483543A (en) * | 2019-09-17 | 2019-11-22 | 西北大学 | One breeder mulberry root extract, extraction separation method and its application |
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