CN108299372A - It is a kind of to be used to prevent drug of gingivitis and preparation method thereof - Google Patents
It is a kind of to be used to prevent drug of gingivitis and preparation method thereof Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/64—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with oxygen atoms directly attached in position 8
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Abstract
The present invention provides a kind of 3 nitro 8 and replaces 2H benzopyrans compounds, preparation method and its purposes in preparing prevention gingivitis and the disease medicament caused by bacteroides fragilis ATCC 25285 or the general Salmonella ATCC 33547 of body, belongs to medicinal chemistry art.The present invention is prepared for a series of compounds by chemical synthesis process, it is determined that structure is seen by mass spectrum and nuclear magnetic resonance spectroscopy, and bacteriostatic activity experimental study is carried out to the general Salmonella ATCC of the common pathogen bacteroides fragilis ATCC 25285 or body of gingivitis 33547, it was found that new compound provided by the invention even better than Ciprofloxacin suitable with positive control Ciprofloxacin activity, is expected to be developed further into as gingivitis treatment drug.
Description
Technical field
The invention belongs to pharmaceutical technology fields, more particularly to a kind of 3- nitros -8- substitutions -2H- benzo pyran chemical combination
Object and its purposes in the drug for preparing prevention gingivitis.
Background technology
Gingivitis refers to the Acute and chronic inflammation that dental tissue occurs under the action of pathogenic factor.It will medically surround
And it is covered in around tooth and the dash forward oral mucosa on surface of slot is referred to as gum.Since almost everyone can in some period in all one's life
The chronic gingivitis of occurrence degree and range not etc., has reason completely：Gingivitis is the most common disease of the mankind.
With gingivitis, gums can be red and swollen, or has bleeding.If realizing when brushing teeth, tooth is easy bleeding or tooth and has
Tenderness situation just needs to see dentist.Gingivitis has various types, but most common, highest incidence is chronic herpes
Property oulitis, this gingivitis are also known as dirty gingivitis, marginal gingivitis, and usually said gingivitis is exactly chronic simple gum
It is scorching.Chronic simple oulitis only invades gingiva tissue, does not invade other periodontium.This oulitis is due to facing near gum edge
On bacterial plaque caused by a kind of chronic inflammation, the cause of disease is clear, and relatively universal in Children and teenager, illness rate is in 70%-90%
Left and right, 4-5 Sui did not usually occur oulitis in the past, most of since 5 years old, with advancing age, illness rate and seriousness
Also it gradually increases, reaches peak to puberty, after puberty, the illness rate of gingivitis slowly declines with the just long of age, at
Year people's gingivitis illness rate is relatively low.
What slight chronic simple gingivitis was invaded is the high gum of trip and gum nipple, and severe patient can invade attached gingiva, preceding
Tooth area, it is especially apparent with mandibular anterior teeth inflammation.When stinging fruit or brushing teeth, bleeding gums.Even if the gum of health is firmly brushed teeth, will not
Bleeding occurs.Normally free gum is very thin and is close to facing, when gum has inflammation, gum edge hyperemia is rubescent, swelling, soft, gum
Edge thickens, and interdental papilla becomes blunt circle, is not close to facing, and gingival sulcus is deepened, and severe patient's attached gingiva can be because of tissue edema, point
Coloured silk disappears, surface-brightening, and gum edge can have rotten to the corn or granulation hyperplasia, gingival pocket pyorrhea.Oulitis further develops, a large amount of blood capillarys of gum
Pipe Accretive Extensions, height are congested, and a large amount of inflammatory cells and tissue fluid exudation lead to gingival hypertrophy, can covering part corona, at this time
Gum is in dark red or dark red, and easily bleeding is examined in spy.The course of disease can cause gingival fiber to be proliferated compared with elder, gingival hyperplasia protrusion, at this time
It is rubescent or close normal that gingiva color is slight, and quality is harder, and bleeding is less.This disease does not invade other teeth due to only invading gum
Week organizes, so tooth does not loosen, X-ray checks that alveolar bone, parodontium, cementum are without exception.
The straightforward procedure of self diagnosis gingivitis is to observe the color and luster of gum, quality and whether there is or not bleeding performances；Normal tooth
Gum pinkiness, the flexible densification of quality, there are dotted colours on surface.If gum is in kermesinus, soft texture swelling, surface colour
Coloured silk disappears, and bleeding is easy when feeding, brush teeth, touching, can make the diagnosis of gingivitis at this time.In addition to above-mentioned sign, part is suffered from
There are gums to itch by person, swells and the subjective symptoms of halitosis.
The Etiological of gingivitis is poor oral hygiene, leads to plaque, calculus dentalis and soft dirt facing near gum edge
Deposition, to induce gingivitis.If being not treated in time, gingivitis can gradually develop into gingivitis, eventually lead to full mouth and open gomphiasis
Dynamic and forfeiture.
Include mainly antibiotics and immunological regulation class drug for the drug therapy of gingivitis.Tri-Biocin
Object is divided into as local application and systemic administration.Local application refers to when being treated to gingivitis, when to oral cavity local treatment
Local douche can be used, containing the methods of mouthwash, coating or sustained release.Now, our tooth-cleaning machines that are often used can be by drug
Directly placed, while being treated under carrying out ultrasonic gum between medicine be directly delivered to affected part and be rinsed, and can continue
Administration, makes the effect promoting of ultrasonic therapy, and reach the therapeutic effect needed for patient in certain degree.Systemic administration is
Refer to gingivitis into when treatment, using systemic administration main reasons is that treated to systemic disease, such as,
The patient of disease of immune system, diabetes, rheumatic heart disease and artificial valve implantation, or carrying out Primary Care timeliness
The unconspicuous patient of fruit is also exactly the patient for easily causing infection in the treatment.It mainly uses and contains in clinical treatment
There are the drug of nitro glyoxaline, specific drug to have：For nitre file, metronidazole and Ornidazole；Tetracycline medication can also be used,
Specific drug has：Doxycycline, tetracycline and minocycline；Penicillin medicine is also to be often used in the treatment, specifically
Drug have：Amoxicillin；Macrocyclolactone lactone kind medicine is also relatively often used in the treatment, and specific drug has：Roxithromycin, spiral
Mycin and azithromycin.During carrying out clinical treatment, what is be commonly used is that the mode of drug combination carrys out after treatment
Effect can prevent bacterium from generating drug resistance.
Immunological regulation class drug mainly has following a few classes：(1) Doxycycline and chemical modification tetracycline.By research I
It can be found that when being treated using SPR, Doxycycline and chemical modification tetracycline can be used to carry out complementary control
It treats, the method used is twice daily, to use 20 milligrams every time, this method can mitigate the slight illness of patient.(2) non-steroidal
Antiinflammatory drugs.The anti-inflammatory effect of non-steroidal anti-inflammatory drug is mainly the way by blocking arachidonic acid to be changed into metabolism
Diameter.The drug being often used in clinic has brufen, Indomethacin etc..The pathological change of gingivitis is mainly reflected in alveolar bone suction
It receives, what can be played an important role in the absorption of gingivitis generation lesion and alveolar bone is prostaglandin.To in certain journey
The secretion of prostaglandin is controlled on degree, can be used NSAID, periodontosis can be treated to a certain extent；But this
Class drug also has the shortcomings that certain, and clinically less use needs clinically to comment adverse reaction and therapeutic effect
Estimate.(3) azithromycin.Main component in azithromycin is lipid antibiotic in fifteen-membered ring, weight in can effectively treating
Spend gingivitis.(1) it is a major advantage that the short treating period used and can effectively fight gram-negative bacteria；(2) azithromycin
Preferably long-term it can play anti-inflammatory effect.The allergy of macrophage is the main reason for leading to gingivitis illness,
The generation of inflammatory cytokine is primarily due to the stimulation of bacterial product and lipopolysaccharides to macrophage, and azithromycin is in treatment tooth
Effective effect can be played during oulitis；(3) can reach when azithromycin treats periodontium preferable
Effect, help the reconstruction of periodontium.Azithromycin can be very good control function of immune system, but if take small dose
Doxycycline is measured, long-term use can bring undesirable reaction, effect not to have azithromycin apparent to patient.It said medicine or controls
Therapeutic effect unobvious, or there are certain side effects, therefore the novel drug for preventing gingivitis is developed with very
Important meaning.
Invention content
The present invention provides a kind of medicinal compound for preventing gingivitis, it is characterised in that the compound has Formulas I
Structure：
Wherein, R1Selected from H, F, Cl, Br, nitro, methyl, R2Selected from methoxyl group, ethyoxyl or trifluoromethoxy.
Preferably, R1 is selected from H, Cl or Br, and R2 is selected from methoxyl group, ethyoxyl or trifluoromethoxy.
Preferably, the compound is selected from following compounds：
In addition, the present invention also provides a kind of pharmaceutical compositions of prevention gingivitis, including above-mentioned 3- nitros -8- substitutions -2H-
Benzopyrans compounds and one or more pharmaceutically acceptable carriers or excipient.
Preferably, the medicine composition dosage form is selected from tablet, capsule, pill, injection, mouthwash formulation and gel
Sustained-release preparation is administered in class oral pocket.
Preferably, the packaging material of the controlled release preparation is selected from：Polylactic-co-glycolic acid, polyethylene glycol, polyanhydride, polyamide,
One or more natural or synthetic high polymers in polyester, polyene, polyethers, polyphosphazene or glycan or natural or synthetic
Phosphatide, lipoid or combinations thereof.
Preferably, described pharmaceutical composition is selected from class preparation of gargling.
In addition, the present invention also provides above compounds or Pharmaceutical composition to be answered in preparing treatment or prevention gingivitis drug
With.
And the compound or Pharmaceutical composition is preparing treatment or prevention inhibition bacteroides fragilis ATCC 25285
Or the application in disease medicament caused by the general Salmonella ATCC 33547 of body.
The present invention relates to the pharmaceutical compositions using the compounds of this invention as active ingredient.The pharmaceutical composition can be according to this
It is prepared by method well known to field.It can be by the way that the compounds of this invention and one or more pharmaceutically acceptable solids or liquid be assigned
Shape agent and/or adjuvant combine, and any dosage form used suitable for human or animal is made.The compounds of this invention is in its pharmaceutical composition
Content be usually 0.1-95 weight %.
The compounds of this invention can be administered in a unit containing its pharmaceutical composition, and administration route can be oral
Or containing this fields common form such as gargling or inject.
Form of administration can be liquid dosage form, solid dosage forms or semisolid dosage form.Liquid dosage form can be solution (including
True solution and colloidal solution), emulsion (including o/w types, w/o types and emulsion), suspension；Solid dosage forms can be tablet (including
Ordinary tablet, enteric coatel tablets, lozenge, dispersible tablet, chewable tablets, effervescent tablet, oral disnitegration tablet), capsule (including hard capsule, soft capsule,
Capsulae enterosolubilis), granule, powder, pellet, dripping pill, suppository, film, patch, the agent of gas (powder) mist, spray etc.；Semisolid dosage form
Can be ointment, gelling agent, paste etc..
It is sustained release preparation, controlled release preparation, targeting preparation and each that the compound of the present invention, which can be made ordinary preparation, also be made,
Kind particulate delivery system.
In order to which tablet is made in the compounds of this invention, various excipient well known in the art can be widely used, including dilute
Release agent, binder, wetting agent, disintegrant, lubricant, glidant.Diluent can be starch, dextrin, sucrose, glucose, breast
Sugar, mannitol, sorbierite, xylitol, microcrystalline cellulose, calcium sulfate, calcium monohydrogen phosphate, calcium carbonate etc.；Wetting agent can be water, second
Alcohol, isopropanol etc.；Adhesive can be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, Arabic gum
Slurry, gelatine size, sodium carboxymethylcellulose, methylcellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, card
Wave nurse, polyvinylpyrrolidone, polyethylene glycol etc.；Disintegrant can be dried starch, microcrystalline cellulose, low substituted hydroxy-propyl fiber
Element, crosslinked polyvinylpyrrolidone, croscarmellose sodium, sodium carboxymethyl starch, sodium bicarbonate and citric acid, polyoxy second
Alkene sorbitan fatty acid ester, dodecyl sodium sulfate etc.；Lubricant and glidant can be talcum powder, silica, tristearin
Hydrochlorate, tartaric acid, atoleine, polyethylene glycol etc..
Tablet can also be further made to coating tablet, such as sugar coated tablet, thin membrane coated tablet, enteric coated tablets or double
Synusia and multilayer tablet.
In order to which capsule is made in administration unit, active ingredient the compounds of this invention and diluent, glidant can be mixed
It closes, mixture is placed directly in hard capsule or soft capsule.It also can active ingredient the compounds of this invention is first and diluent, bonding
Particle or pellet is made in agent, disintegrant, then is placed in hard capsule or soft capsule.It is used to prepare each dilute of the compounds of this invention tablet
Release agent, binder, wetting agent, disintegrant, glidant kind can also be used for preparing the capsule of the compounds of this invention.
Injection is made in the compounds of this invention, water, ethyl alcohol, isopropanol, propylene glycol or their mixture can be used to make
Simultaneously appropriate solubilizer commonly used in the art, cosolvent, pH adjustments agent, osmotic pressure regulator is added in solvent.Solubilizer or cosolvent
Can be poloxamer, lecithin, hydroxypropyl-β-cyclodextrin etc.；PH adjustment agent can be phosphate, acetate, hydrochloric acid, hydrogen-oxygen
Change sodium etc.；Osmotic pressure regulator can be sodium chloride, mannitol, glucose, phosphate, acetate etc..Such as prepare freeze-dried powder
Agent can also be added mannitol, glucose etc. and be used as proppant.
In addition, if desired, colorant, preservative, fragrance, corrigent or other additions can also be added into pharmaceutical preparation
Agent.
To reach medication purpose, enhance therapeutic effect, drug of the invention or pharmaceutical composition well known can be given with any
Prescription method is administered.
The dosage of the pharmaceutical composition of the compounds of this invention is according to the property to be prevented or be treated disease and seriously
The individual instances of degree, patient or animal, administration route and dosage form etc. can have large-scale variation.In general, of the invention
The daily Suitable dosage ranges of pharmaceutical composition are 0.001-150mg/Kg weight, preferably 0.01-100mg/Kg weight.On
Stating dosage with a dosage unit or can be divided into several dosage unit administrations, this depends on the clinical experience of doctor and including transporting
With the dosage regimen of other treatment means.
The compound of the present invention or composition can individually be taken, or merge use with other treatment drug or symptomatic drugs.
When the pharmaceutical composition of the present invention exists with other medicines to act synergistically, it should be adjusted according to actual conditions
Dosage.
Specific implementation mode
Embodiment 1：The preparation of 3- nitro -8- methoxyl group -2H- chromenes
3- methoxysalicyl aldehydes (100 mMs) are dissolved in 800 milliliters of toluene, and addition dibutylamine (12.9 grams, 100
MM), phthalic anhydride (29.6 grams, 200 mMs) is heated to reflux, 15 addition nitroethyl alcohols (11.8 in 12 hours
Gram, 130 mMs), the reaction was continued 24 hours, and TLC monitoring reactions terminate；Solvent is evaporated off, column chromatography purifies to obtain compound 1.
Embodiment 2：The preparation of 3-Nitro-8-ethoxy-2H-benzopyran
3- ethoxy salicylaldehydes (100 mMs) are dissolved in 800 milliliters of toluene, and addition dibutylamine (12.9 grams, 100
MM), phthalic anhydride (29.6 grams, 200 mMs) is heated to reflux, point 15 addition nitroethyl alcohols in 12 hours
(11.8 grams, 130 mMs), the reaction was continued 24 hours, and solvent is evaporated off, and column chromatography obtains compound 2.
Embodiment 3：The preparation of 3- nitro -8- trifluoromethoxy -2H- chromenes
3- trifluoromethoxies salicylide (100 mMs) is dissolved in 800 milliliters of toluene, addition dibutylamine (12.9 grams,
100 mMs), phthalic anhydride (29.6 grams, 200 mMs) is heated to reflux, point 15 addition nitroethyl alcohols in 12 hours
(11.8 grams, 130 mMs), the reaction was continued 24 hours, and solvent is evaporated off, and column chromatography obtains compound 3.
Embodiment 4：The preparation of the chloro- 8- methoxyl groups -2H- chromenes of 3- nitros -6-
The chloro- 3- methoxysalicyl aldehydes of 5- (100 mMs) are dissolved in 800 milliliters of toluene, dibutylamine (12.9 is added
Gram, 100 mMs), phthalic anhydride (29.6 grams, 200 mMs) is heated to reflux, point 15 addition nitros in 12 hours
Ethyl alcohol (11.8 grams, 130 mMs), the reaction was continued 24 hours, and solvent is evaporated off, and column chromatography obtains compound 4.
Embodiment 5：The preparation of the chloro- 8- trifluoromethoxies -2H- chromenes of 3- nitros -6-
The chloro- 3- methoxysalicyl aldehydes of 5- (100 mMs) are dissolved in 800 milliliters of toluene, dibutylamine (12.9 is added
Gram, 100 mMs), phthalic anhydride (29.6 grams, 200 mMs) is heated to reflux, point 15 addition nitros in 12 hours
Ethyl alcohol (11.8 grams, 130 mMs), the reaction was continued 24 hours, and solvent is evaporated off, and column chromatography obtains compound 5.
Embodiment 6：The preparation of 3-Nitro-6-bromo-8-ethoxy-2H-benzopyran
The bromo- 3- ethoxy salicylaldehydes of 5- (100 mMs) are dissolved in 800 milliliters of toluene, dibutylamine (12.9 is added
Gram, 100 mMs), phthalic anhydride (29.6 grams, 200 mMs) is heated to reflux, point 15 addition nitros in 12 hours
Ethyl alcohol (11.8 grams, 130 mMs), the reaction was continued 24 hours, and solvent is evaporated off, and column chromatography obtains compound 6.
Compound 1-6 prepared by above-described embodiment 1-6, mass spectrum and nuclear magnetic data are shown in Table 1：
Embodiment 7
The present embodiment provides a kind of gargle for treating gingivitis, preparation method includes：
A. it stocks up：Compound 1 synthesized by embodiment 1 weighs 1g, polysorbate 15g, double de- ethyl alcohol 8g, sodium monofluorophosphate
0.03, chlorhexidine gluconate 0.3g, glycerine 3g and polyoxyethylene chlorination castor oil 0.5g.
B. emulsion reaction：Each component in above-mentioned raw materials is mixed and dispersed in the purified water of 100g, and at 80 DEG C
30min is stirred, between adjusting pH to 6.5 with alkali, up to mouthwash after filtering.
Embodiment 8
The present embodiment provides a kind of diaphragm agent for treating gingivitis, preparation method includes：
A. the glycerine for weighing the compound 2 and 10g of the preparation of 15g embodiments 2, is dissolved in the water of 800g, is subsequently added into 3g
Crosslinking agent obtain mixed liquor.After mixed liquor is heated to 52 DEG C, the mixed liquor of 12mL is transferred to the culture of a diameter of 3.5cm
In ware, 30 DEG C of dry 48h in strong cross-ventilated drying box are then placed in 30 DEG C of dryings in baking oven and for 24 hours, obtain thin
Film.
B. film is cut using traditional cheesing techniques, obtains the gingivitis treatment diaphragm of a diameter of 3.5cm.It will
Obtained gingivitis treatment diaphragm edge drying post package is stored in the environment that humidity is 11%~21%.
Embodiment 9
The compounds of this invention is present embodiments provided in preparing the external drug for inhibiting bacteroides fragilis ATCC 25285
Purposes research
Bacteriostatic test
The compound prepared using embodiment 1-6 carries out bacteriostatic test using filter paper enzyme classical in this field,
In：It is purchased from the Shanghai bio tech ltd Sang Ge for examination strain bacteroides fragilis ATCC 25285.
Culture solution
Nutrient agar and nutrient broth are purchased from Chen Yu experimental facilities Co., Ltd of BeiJing ZhongKe.
Test method
Bacteroides fragilis ATCC 25285 is inoculated on agar plate nutrition fluid level, when inoculation uniformly gathers.
It weighs 0.01 gram of target compound respectively, is added 15000 milliliters of sterile waters, ultrasound 30 minutes, then 0.22 μm
Filtering with microporous membrane obtains solution.The sterile circular filter paper piece of tweezer diameter 3mm is sprayed above-mentioned solution to complete wetting, is attached to
On the agar plate nutrition fluid level of inoculated bacteria.Agar plate is placed in 37 DEG C of incubator, is incubated 18 hours.It measures
The diameter of antibacterial ring size.It measures 3 times and is averaged.Measurement result see the table below 2, unit mm.
2 compound 1-6 of table inhibits the research of bacteroides fragilis ATCC 25285 in vitro
By bacteriostatic experiment it can be seen that compound 5 is to the average diameter of the antibacterial ring size of bacteroides fragilis ATCC 25285
17.46mm, far superior to positive control drug Ciprofloxacin show that target compound has extremely strong external inhibition bacteroides fragilis
The effect of ATCC 25285.
Embodiment 10
The general Salmonella ATCC 33547 of body that the present embodiment uses is purchased from Beijing Central Plains company.The present invention passes through inhibition zone method
To investigate the biocidal property of compound prepared by the present invention.
The preparation of drug containing filter paper
The filter paper for selecting water absorbing force strong and homogeneous, the disk of 6mm is broken into puncher, is sub-packed in the examination of clean dried
In pipe, it is dried for standby after 121 DEG C of sterilizing 2h.3.5 grams of extract is prepared according to the method described in embodiment, 10 liters of water are added,
Fully dissolving, under sterile working, the ready-made scraps of paper is dipped in pre-configured drug solution, and sealing is placed in leaching in refrigerator
1h is steeped, then in drying in 37 DEG C of baking ovens, 4 DEG C is sealed in and saves backup.
The preparation of broth bouillon
Raw material：Beef extract (3g), peptone (10g), sodium chloride (5g), agar (10g) and distilled water (1000ml).System
Method：1000ml boilings open, and are accurately added mentioned component in proportion, and rush its dissolving is boiled in heating, and is supplied since evaporation loses
Moisture；PH to 7.4 is adjusted, it is close after cooling down 121 DEG C in pressure cooker, 20min sterilizings among filter with filter paper and be sub-packed in triangular flask
Envelope is set spare in 4 DEG C of refrigerators.
Take general 33547 setting-outs of Salmonella ATCC of body on the broth bouillon tablet containing 1 weight % agar, 37 DEG C of mistakes
After night culture, picking single bacterium colony activates 24 hours as activation bacterium solution in meat soup fluid nutrient medium at 37 DEG C.In 9cm plates
In pour into 15ml contain 1 weight % agar solid broth bouillon, after to be solidified, separately take the meat soup containing 0.7 weight % agar
Culture medium melts when temperature is down to about 42 DEG C, and the activation bacterium solution of 10 μ L is added per 8ml culture mediums, solid meat is poured on after mixing
On soup culture medium, wait coagulating.The filter paper for being soaked with drug is taken out, surface containing bacterium culture medium is affixed on, after just setting 40min, in 37 DEG C
Result is observed after being inverted culture 24 hours.The clear annulus occurred around the scraps of paper, this indicates that drug has antibacterial activity.Respectively
Aforesaid operations and antibacterial circle diameter is measured in triplicate, takes average value three times
3 compound 1-6 of table inhibits the research of the general Salmonella ATCC33547 of body in vitro
As seen from the above table, the compound that prepared by the present invention all has strong inhibition for the general Salmonella ATCC33547 of body
Effect is expected to be developed further into drug use.
To sum up, the present invention is prepared for a kind of completely new chemical combination with 3- nitro -8- substitution -2H- chromene precursor structures
Object passes through the antibacterial work of the general Salmonella ATCC of common pathogen bacteroides fragilis ATCC 25285 or body to gingivitis 33547
Property experiment, find the present invention new compound it is suitable with positive control Ciprofloxacin activity be even better than Ciprofloxacin, be expected to
It is developed further into as gingivitis treatment drug.
The above-described embodiments merely illustrate the principles and effects of the present invention, and is not intended to limit the present invention.It is any ripe
The personage for knowing this technology can all carry out modifications and changes to above-described embodiment without violating the spirit and scope of the present invention.Cause
This, institute is complete without departing from the spirit and technical ideas disclosed in the present invention by those of ordinary skill in the art such as
At all equivalent modifications or change, should by the present invention claim be covered.
Claims (9)
1. a kind of medicinal compound for preventing gingivitis, it is characterised in that the compound has the structure of Formulas I：
Wherein, R1Selected from H, F, Cl, Br, nitro, methyl, R2Selected from methoxyl group, ethyoxyl or trifluoromethoxy.
2. medicinal compound according to claim 1, it is characterised in that R1Selected from H, Cl or Br, R2Selected from methoxyl group, ethoxy
Base or trifluoromethoxy.
3. medicinal compound according to claim 1, it is characterised in that the compound has following structural：
4. a kind of pharmaceutical composition of prevention gingivitis, including claim 1-3 any one of them 3- nitro -8- substitutions -2H-
Benzopyrans compounds and one or more pharmaceutically acceptable carriers or excipient.
5. pharmaceutical composition according to claim 4, it is characterised in that the pharmaceutical composition be selected from tablet, capsule,
Sustained-release preparation is administered in pill, injection, mouthwash formulation and gel-like oral pocket.
6. pharmaceutical composition according to claim 5, it is characterised in that the packaging material of the controlled release preparation is selected from：Polylactic acid hydroxyl
It is one or more natural in guanidine-acetic acid, polyethylene glycol, polyanhydride, polyamide, polyester, polyene, polyethers, polyphosphazene or glycan
Or the high polymer synthesized or natural or synthetic phosphatide, lipoid or combinations thereof.
7. pharmaceutical composition according to claim 6, it is characterised in that described pharmaceutical composition is selected from class preparation of gargling.
8. claim 1-7 any one of them compound or Pharmaceutical composition are answered in preparing treatment or prevention gingivitis drug
With.
9. claim 1-7 any one of them compound or Pharmaceutical composition are preparing treatment or prevention inhibition bacteroides fragilis
Application in disease medicament caused by the ATCC 25285 or general Salmonella ATCC 33547 of body.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113825502A (en) * | 2019-05-07 | 2021-12-21 | 澳谛医药科技有限公司 | Materials and methods for treating drug-induced gingival hyperplasia |
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