CN101023972A - Use of phenolic acids effective part in dandelion for treating stomatocace - Google Patents
Use of phenolic acids effective part in dandelion for treating stomatocace Download PDFInfo
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Abstract
The present invention relates to a dandelion plant phenolic acid effective component for preventing and curing herpes simplex virus infection and its application in preparation of medicine for preventing and curing ulcerative stomatitis. The invented dandelion plant phenolic acid effective component is obtained by using fresh dandelion plant or dried dandelion plant and making it undergo the processes of alcohol and water extraction, column chromatography and alcohol solvent elution, etc. Said effective component can be made into lozenge, powder preparation, spray, granules and oral solution, etc.
Description
Technical field
The present invention relates to medical technical field, particularly, the present invention relates to a kind of Herba Taraxaci plant phenolic acid effective kind part is buccal tablet, powder, spray and the oral film of principal agent preparation.It has remarkable result in the oral ulcer that factors such as prevention and treatment viral infection cause, can expect becomes the oral ulcer disease medicament that the causes of disease such as preventing and treating the infection of I herpes simplex virus type causes.
Technical background
The pars oralis pharyngis disease is a human big illness, and oral ulcer is commonly encountered diseases and the frequently-occurring disease of sickness rate at 10-30%.The traditional Chinese medical science thinks that oral ulcer belongs to " aphtha ", " aphtha " category, and each age group all has generation, influences feed and sleep because of intensive spontaneous pain during outbreak.Its cause of disease complexity, sick kind is more.Theory of Chinese medical science thinks that the main diseases of oral ulcer is because of as follows: one accumulate in the retention of heat in the spleen and stomach, smoked oral cavity and tongue on the heat stagnation; Two is that heart-fire is flourishing, and pathogenic heat are followed through last inflammation; Three is hyperactivity of fire caused by deficiency of YIN, and the plain body deficiency of YIN or prolonged illness are impairment of the kidney, Kidney-Yin loss, and YIN-fluid being insufficient, asthenic fire is vigorous, goes up scorching oral cavity.Modern medicine thinks that it may be relevant with factors such as the intravital endocrine regulation of viral infection, bacterial infection and machine, immune dysfunction, Vitamin B2 deficiencies.Recurrent oral ulceration is a modal disease in the oral mucosa disease, is common with herpetic oral ulcer especially wherein.And herpetic oral ulcer is the oral ulcer that is caused by herpesvirus, and common is the herpes simplex type oral ulcer that I herpes simplex virus type (HSV-1) causes, and also is a common important kind of oral ulcer.
Oral ulcer is outbreak repeatedly easily, does not still have the specific treatment method at present.Main clinically treatment measure at present comprises topical therapeutic and whole body therapeutic, and western medical treatment is oral with iodine glycerol and vitamin B1, B2 and vitamin C with the part, and general curative effect is very unobvious.Seriously, obstinate oral ulcer then need take hormone drugs, antibiotics quasi drugs etc. orally, use this type of medicine to have bigger toxic and side effects again and easily make patient produce the weak point of drug resistance and dysbacteriosis.The Chinese medicine medicine for external use can be with comprising external preparation such as XILEI SAN, BINGPENG SAN, but therapeutic effect is not very good; Oral medicine comprises cow-bezoar anti-toxic bolus, cow-bezoar bolus for clearing away heat of the upper part of the body etc., and this disease is not had significant specific aim.Many new buccal tablets class pharmaceutical preparation such as watermelon crystal buccal tablet, cydiodine and the lysozyme buccal tablet etc. that occur are progressive to some extent aspect mouthfeel, sterilization, antiinflammatory respectively in the recent period, but some product is unsuitable for women breast-feeding their children, hyperthyroidism patient and iodine allergy person.Therefore, use modern disease poison technology of science, utilize modern separation and purification means, it is extremely urgent excavating the especially innovative Chinese medicine of treatment oral ulcer natural drug that makes new advances from pools of traditional Chinese medicine.
Chinese traditional drug taraxacum herb is feverfew Herba Taraxaci (Taraxacum mongolicum Hand-Mazz, also claim Mongolian Herba Taraxaci) or belong to the dry herbs of several plants together, be heat-clearing and detoxifying herb, cure mainly acute mastitis, furuncle, conjunctival congestion, pharyngalgia, jaundice due to damp-heat and the puckery pain of pyretic stranguria etc.Herba Taraxaci mainly contains triterpenes, phytosterol, sesquiterpene lactones class, Coumarins, flavonoid, phenolic acid compound, carotenoid and fatty acid.Its pharmacological action has anti-inflammation, antioxidation, hepatic cholagogic, immunomodulating and antitumor etc.At present, injection, tablet and the granule etc. that utilize the Herba Taraxaci single medicinal material to make are widely used in clinical, treat various diseases associated with inflammation and have obtained curative effect preferably.
The pharmacological action of Herba Taraxaci is mainly (1) broad-spectrum antiseptic, antiviral and other pathogen effects: staphylococcus aureus, staphylococcus epidermidis, micrococcus catarrhalis, Hemolytic streptococcus etc. are had strong killing action, and trimethoprim (TMP) TMP can strengthen its antibacterial action.In addition, Diplococcus pneumoniae, meningococcus, diphtheria corynebacterium, Bacillus proteus, dysentery bacterium, pseudomonas aeruginosa also there is strong inhibitory action.To tubercule bacillus, anthrax bacillus, helicobacter pylori, dermatophytes, herpes simplex virus, leptospira etc. also tool one inhibitory action.(2) antiinflammatory action: clinically diseases associated with inflammation such as mastitis, hepatitis, bronchitis, pharyngolaryngitis, parotitis, cholecystitis, gastritis are all had curative effect preferably.It is reported, Herba Taraxaci ethyl acetate extract and main component luteolin thereof and luteolin-7-O-β-D-glucoside can suppress mice RAW264.7 macrophage nitric oxide synthetase (iNOS) and the proteic expression of COX-2 (COX-2) [the Hu C that lipopolysaccharide (LPS) stimulates, Kitts DD, Luteolin and luteolin-7-O-glucoside from dandelion flower suppress iNOSand COX-2 in RAW264.7 cells, Molecular and Cellular Biochemistry, 2004,265:107].(3) antioxidation: the Herba Taraxaci extract total flavones has class superoxide dismutase (SOD) effect, can effectively remove ultra-oxygen anion free radical and hydroxy radical.(4) hepatic cholagogic effect: Herba Taraxaci water extract and injection have the hepatic cholagogic effect, can reduce hepatic injury rat glutamate pyruvate transaminase (ALT) level of tetrachloro-methane induction, and can improve the hepatocellular degeneration necrosis.Water extract and the ethanol extract of reporting Herba Taraxaci in addition in addition have antitumor action and immunoregulation effect etc.
In test in the past, we carry out purification with modem technology to the different extract part of Herba Taraxaci plant; The phenolic acid effective kind part of finding Herba Taraxaci extract has potent antiinflammatory, suppresses the effect of influenza virus.Wherein contain the flavonoid component of a plurality of luteolin skeletons, and contain 3, the 5-O-dicaffeoyl quinic acid; 3, the 4-O-dicaffeoyl quinic acid; 4, two caffeoyl guinic acid class compound of phenolic acid active substances of 5-O-dicaffeoyl quinic acid three structural similarities, and the result has declared national inventing patent " purposes of the preparation of phenolic acid effective kind part and inhibition influenza virus thereof in the Herba Taraxaci " (Zhao Yu, Yu Rongmin, Li Feng in view of the above; The number of accepting 200610036674.2).We believe: the effective site that is rich in liposoluble ingredient that extracts in the Herba Taraxaci with one of the medication of this kind pharmacopeia, heat-clearing and toxic substances removing " eight king kongs " is crude drug, develops a kind of easy use, stomatocace medicine portable, antiinflammatory/antiviral comprehensive therapeutic effect will have great using value.
Summary of the invention
The purpose of this invention is to provide the purposes that the extract that will be rich in phenolic acid compound in the Herba Taraxaci plant is used to suppress herpes simplex virus.
A further object of the present invention has provided a kind of purposes with Herba Taraxaci plant phenolic acid effective kind part treatment oral ulcer.
Another purpose of the present invention has provided a kind of medicine or pharmaceutical composition of anti-treating dental ulcer.It is characterized by with Herba Taraxaci plant phenolic acid effective kind part is buccal tablet, powder and the spray of principal agent.
The present invention also provides Herba Taraxaci extract buccal tablet, powder and spray preparing process.
Buccal tablet among the present invention, powder and spray contain 1% to 80% Herba Taraxaci plant extract spray powder, and all the other are correctives, diluent, binding agent and lubricant.Correctives is selected from one or more in Herba Menthae, Oleum menthae, Mentholum, Borneolum Syntheticum, edible essence, Aspartane, citric acid, xylitol, sucrose, steviosin, Radix Glycyrrhizae, the syrup; Diluent is selected from one or more in lactose, Icing Sugar, mannitol, dextrin or maltodextrin, starch, precipitated calcium carbonate, sedimentation calcium phosphate, magnesium carbonate or the kaolin; Binding agent is selected from one or more in alcoholic solution, gelatin, simple syrup, microcrystalline Cellulose or the carbomer; Lubricant is a magnesium stearate.
Medicine involved in the present invention has the effect of external potent inhibition I herpes simplex virus type, illustrates that it has significant therapeutical effect to the viral infection oral ulcer.The present invention has also carried out pharmacodynamics test and preliminary clinical trial at the patient of phenol rat oral ulcer and completed stroke oral ulcer, finds to compare with the spray powder gastric infusion, and buccal tablet and powder preparation formulation more can be quickened to reduce the ulcer area and promote ulcer healing.
The preparation method of Herba Taraxaci plant phenolic acid effective kind part treatment stomatocace medicine buccal tablet is: Herba Taraxaci extract spray powder, correctives and the diluent that will be rich in liposoluble ingredient sieve respectively, the back mix homogeneously sieves, with binding agent system wet granular, oven drying, granulate sieves, add magnesium stearate, mixing, tabletting are promptly.
Herba Taraxaci plant phenolic acid effective kind part treatment stomatocace medicine powder provided by the present invention is made up of Herba Taraxaci vegetable phenol effective site and diluent, and wherein diluent can be selected from one or more in lactose, amylodextrin, sucrose, glucose, sedimentation glucose, sedimentation calcium phosphate, magnesium carbonate or the kaolin; Realize by following preparation method: get the Herba Taraxaci extract spray powder end of recipe quantity, drying is two hours in the time of 100 ℃, adds diluent, and mixing is crossed 100 mesh sieves, and bottling gets final product.
Herba Taraxaci plant phenolic acid effective kind part treatment stomatocace medicine spray liquid preparation among the present invention: the Herba Taraxaci plant phenolic acid effective kind part spray powder end of getting recipe quantity, the distilled water that adds 10 times of amounts, ultrasonic dissolution adds flavoring agents such as Aspartane, citric acid then, and 1% cyclodextrin, heating for dissolving, 5-10 instantaneous sterilization second when following 135 ℃ of superhigh temperature, sterile filling spray bottle, re-pasteurization 30 minutes in the time of 100 ℃ again, the vanning of cooling back promptly.
The present invention has the following advantages: discard the dross and select the essential (1), will play inhibition virus and antiphlogistic effective ingredient and concentrate in the effective site, has significantly reduced dosage compared with plant crude extract direct drug injection, has concentrated drug concentrations relatively; (2) local application increases the drug level of diseased region, lastingly; High strength ground has been avoided the unknown role of liver first-pass effect and other liver sausage metabolic enzymes, thereby has been improved curative effect at the ulcer effect; (3) add multiple correctives, make different dosage form and taste, be suitable for all ages and classes, different taste preference patient use, thereby increased patient's degree of complying with.
Through looking into new discovery, the report or the patent of buccal tablet, powder, oral liquid, spray and oral film that the Herba Taraxaci extract effective site that all not having is correlated with in the past is rich in phenolic acids is thus prepared as principal agent, more do not have the bibliographical information that the above-mentioned preparation of utilization is used for anti-treating dental ulcer, finish the present invention in view of the above.
Specific embodiments
The inventor separated by the tracking of Herba Taraxaci pohytol water extract being carried out medicine efficacy relation in the past, cause mice ear and influenza virus is suppressed the result according to different extract part xylol and be the activity index discovery: its antiinflammatory, antiviral activity composition concentrate on the high polarity phenolic acids position of plant extract, by process optimization, the inventor adopts water or water-alcohol solvent extraction to be aided with multiple positive and negative phase column chromatography means and obtains this effective site.Through spectroscopic datas such as a peacekeeping two dimensional NMR wave spectrum, mass spectrum, infrared, ultraviolets, we find that first this high polarity phenolic acid effective kind part contains two compounds, the one, have the flavonoid component of luteolin skeleton; A class is exactly traditional phenolic acids active substances such as caffeic acid and chlorogenic acid again, and two caffeoyl guinic acid class compound of phenolic acid of three structural similarities, and they are: 3, and the 5-O-dicaffeoyl quinic acid; 3, the 4-O-dicaffeoyl quinic acid; 4, the 5-O-dicaffeoyl quinic acid.Modern age, pharmacology test studies show that: the flavone compound of this type of luteolin skeleton and single, double coffee acyl quinic acid compounds have multiple important physiologically active; mainly be at immune effect: show and suppress the synthetic and release of leukotriene; suppress hepatitis B virus and HIV (human immunodeficiency virus); suppress histamine release, thereby can be used for antiinflammatory, antiviral and treatment anaphylactic disease.Find in addition its have potent antioxidation, suppress lipoxygenase study of anti-atherogenic effect, platelet aggregation inhibitory activity and effect for reducing blood fat isoreactivity (document: Li Zusheng, Zhu Zhian, the medical science summary, 2004,10 (4), 249-250).
Simultaneously, above-mentioned two compounds content in effective site is quite high, and the total content of phenolic acid effective site in Herba Taraxaci extract has surpassed 20%.The pharmacodynamic experiment result that the inventor carries out shows that the total phenolic acid effective site of Herba Taraxaci extract does not have obvious inhibitory action, TD to the growth of Vero cell under experimental concentration
50＞1000 mcg/ml.Experimental result shows that the total phenolic acid effective site of Herba Taraxaci extract has the effect of significant inhibition HSV-1, and its half-inhibition concentration to HSV-1 is 75.51 ± 8.97 mcg/ml, and therapeutic index is greater than 13.24; The total phenolic acid effective site of this explanation Herba Taraxaci extract can significantly suppress duplicating of HSV-1, and does not have tangible toxicity.Thereby can be used for the treatment of relevant herpes simplex infections disease, thereby may develop the Oralease thing.
In further pharmacodynamic study test, it is model that the inventor causes the rat oral ulcer with phenol, has tested buccal tablet that the effective portion of the total phenolic acid of Herba Taraxaci extract makes and powder to reducing the effect of ulcer area.Off-test was played in the discovery administration in second day, the buccal tablet height that the total phenolic acid effective site of Herba Taraxaci extract is made, middle dosage group and the powder height of making, middle dosage is compared with model group that significant difference is all arranged, and the buccal tablet group is more long-pending than the powder group noodle soup that more can reduce to burst.Illustrate that buccal tablet and powder that the total phenolic acid effective site of Herba Taraxaci extract is made have the effect of obvious promotion ulcer healing.
Medical material among the present invention can be the arbitrary position of home-made Dandelion plant in one or more, it promptly can be Herba Taraxaci (claiming Mongolian Herba Taraxaci again) (Taraxacum mongolicumHand-Mazz), alkali ground Herba Taraxaci (claiming magnificent Herba Taraxaci again) (Taraxacum sinicum Kitag), hot river Herba Taraxaci (claiming white edge Herba Taraxaci again) (Taraxacum platypecidumDiels), Herba Taraxaci ohwiani (Taraxacum ohwianumKitag), anti-luxuriant Herba Taraxaci (Taraxacum grypodon Dahlst), common Herba Taraxaci medical material on Xingan's Herba Taraxaci Chinese drug markets such as (Taraxacum falcilobumKitag) can also derive from the common dandelion (Taraxacum officinale) of main product in the America and Europe.Can be dry product or bright product, can be root, stem, leaf, flower, seed, skin, the fruit of Herba Taraxaci medical material plant, also can be their mixture; Preferred herb.The more preferably herb part of Herba Taraxaci (claim not only Mongolian Herba Taraxaci) (Taraxacum mongolicumHand-Mazz) and/or alkali ground Herba Taraxaci (but also claiming magnificent Herba Taraxaci) (Taraxacim sinicum Kitag).All be called for short Herba Taraxaci in the present invention's the description.
Further specify the present invention below by embodiment.Embodiment described the preparation method of the total phenolic acid effective site of Herba Taraxaci extract, be buccal tablet, powder and the spray preparing process that principal agent is made with it, and the total phenolic acid effective site of Herba Taraxaci extract is at activity data external, in vivo test.The following embodiment of mandatory declaration is used to illustrate the present invention rather than limitation of the present invention.Essence according to the present invention all belongs to the scope of protection of present invention to the simple modifications that the present invention carries out.
Embodiment 1The preparation of the total phenolic acid effective site of Herba Taraxaci extract
Get 10 kilograms of samples that the Herba Taraxaci medical material is air-dry, be cut into segment, with 50% ethanol water heating extraction twice, for the first time with 8 times of amounts, for the second time with 6 times of amounts.Extracted 2 hours for the 1st time, extracted 1.5 hours for the 2nd time, concentrate, be splined on the macroporous adsorbent resin of having handled well, more shallow to be washed to color, it is shallow to color with 50% ethanol elution to continue, the eluent reclaim under reduced pressure, spray drying gets the raw material fine powder, and this is the phenolic acid compound effective site of Herba Taraxaci plant extract among the present invention.Adopt colorimetry to contain survey: calculate content according to standard curve, the result is 36.27% in the caffeic acid for standard substance content for total phenols in the Herba Taraxaci extract spray powder raw material.Contain survey with high performance liquid chromatography: caffeic acid content is 0.63% in the spray powder material sample; luteolin 7-O-glucoside content is 1.00%; 3; 5-O-dicaffeoyl quinic acid, 3; 4-O-dicaffeoyl quinic acid, 4,5-O-dicaffeoyl quinic acid three sum surpasses 3%.
Embodiment 2: the preparation prescription one of Herba Taraxaci vegetable phenol effective site buccal tablet
Feed intake according to recipe quantity, 75 gram Herba Taraxaci extract spray powder raw materials, 75 gram microcrystalline Cellulose, 75 gram starch are crossed 80 mesh sieves respectively, add Aspartane 8 gram mixings, sieve, behind the mixing with 60% ethanol system wet granular, 50 ℃ of oven dryings 2 hours add Herba Menthae essence 2 grams, magnesium stearate 10 grams, mixing, tabletting is made 1000, the heavily about 250 milligrams/sheet of sheet.
Embodiment 3: preparation prescription two (the Fructus Citri sinensis Herba Taraxaci buccal tablets) of Herba Taraxaci plant phenolic acid effective kind part buccal tablet
(1) preparation of Herba Taraxaci spray powder: with embodiment 1.
(2) 75 gram Herba Taraxaci spray powders, 300 gram microcrystalline Cellulose, 300 gram starch are crossed 80 mesh sieves respectively, add Icing Sugar 100 grams, mannitol 10 grams, Aspartane 40 gram mixings, sieve, behind the mixing with 60% ethanol system wet granular, 50 ℃ of oven dryings 2 hours, add liquid fragrant citrus essence 30 grams, magnesium stearate 40 grams, mixing, oval special-shaped stamping is made 1000, the heavily about 900 milligrams/sheet of sheet.
Embodiment 4: the preparation prescription three of Herba Taraxaci plant phenolic acid effective kind part buccal tablet
(1) preparation of Herba Taraxaci spray powder: with embodiment 1;
(2) it is even 70 gram Herba Taraxaci spray powders, 40 to be restrained dextrin, and vacuum drying is pulverized;
(3) add Icing Sugar and mend to 600 grams, 85% alcohol granulation, drying and granulate add magnesium stearate, and mixing, tabletting are made 1000, and every is heavy 600 milligrams.
Embodiment 4: the preparation prescription four of Herba Taraxaci plant phenolic acid effective kind part buccal tablet
(1) preparation of Herba Taraxaci spray powder: with embodiment 1;
(2) steviosin is 50 milligrams, and 150 milligrams of potassium sorbate are dissolved in 5 ml waters, absorbs with 40 gram starch, and stirs.Add microcrystalline Cellulose 50 grams, interior mixing 10-20 minute of blender adds 3 milliliters of distilled water moistenings, and granulation machine is granulated, and wet granular is in 60 ℃ of dryings, and dried granule is after 12 mesh sieve granulate;
(3) Oleum menthae 75 microlitres, 100 milligrams of Mentholums are dissolved in 2 milliliter of 95% alcoholic solution, are sprayed in the above-mentioned dried particles.Add Herba Taraxaci spray powder 10 grams and 2.5 gram magnesium stearate, the punch die tabletting is made 200.
Embodiment 6: the preparation prescription one of Herba Taraxaci plant phenolic acid effective kind part spray
(1) preparation of Herba Taraxaci spray powder: with embodiment 1;
(2) sodium pyrosulfite (1 gram) and steviosin (0.1 gram) are added in about 900 milliliters of sterilization distilled waters, after stirring, add 10 gram Herba Taraxaci spray powder and 50 milliliters of propylene glycol, add distilled water to 1000 milliliter, stirring and dissolving, filter, filtrate is packed in the plastics aerosol apparatus, puts shady and cool dry place and preserves.
Embodiment 7: the preparation prescription two of Herba Taraxaci plant phenolic acid effective kind part spray
(1) preparation of Herba Taraxaci spray powder: with embodiment 1;
(2) 0.5 milliliters of glycerol and steviosin (0.1 gram) are dissolved in 400 milliliter of 75% ethanol double steaming solution, stir after will Herba Taraxaci spray powder (10 gram) adding, and add distilled water to 1000 milliliter, stirring and dissolving, filter, filtrate is packed in the plastics aerosol apparatus, puts shady and cool dry place and preserves.
Embodiment 8: the preparation prescription one of Herba Taraxaci plant phenolic acid effective kind part powder
(1) preparation of Herba Taraxaci spray powder: with embodiment 1.
(2) feed intake according to recipe quantity, 7.5 gram Herba Taraxaci extract spray powder raw materials, 7 gram microcrystalline Cellulose, 7 gram starch are crossed No. 6 100 mesh sieves respectively, add Aspartane 0.8 gram mixing, packing is made 100 bags, and In Aluminium Foil Packing is placed shady and cool dry place and preserved.
Embodiment 9: the preparation prescription two of Herba Taraxaci plant phenolic acid effective kind part powder
(1) preparation of Herba Taraxaci spray powder: with embodiment 1.
(2) 7.5 gram Herba Taraxaci spray powders, 30 gram microcrystalline Cellulose, 30 gram starch are crossed No. 6 100 mesh sieves respectively, add Icing Sugar 10 grams, mannitol 1 gram, Aspartane 4 gram mixings, sieve, add liquid fragrant citrus essence 3 grams, packing is made 100 bags, and In Aluminium Foil Packing is placed shady and cool dry place and preserved.
Various preparations described in Herba Taraxaci plant phenolic acid effective kind part spray powder raw material and the foregoing description have important biological, the present invention adopts micro-cytopathy to suppress the inhibitory action test of (CPE) method research Herba Taraxaci plant phenolic acid effective kind part spray powder to I herpes simplex virus type (HSV-1), with the positive contrast medicine of Ah former times's network Wei (ACV), find that Herba Taraxaci plant phenolic acid effective kind part spray powder raw material has an effect that suppresses HSV-1 more by force external.
Herba Taraxaci plant phenolic acid effective kind part spray powder raw material of the present invention and preparation can also be united use with the common drug of the treatment oral ulcer of now having gone on the market, prepare compositions or compound preparation with treatment oral ulcer.
In order to understand essence of the present invention and the application prospect of Herba Taraxaci extract phenolic acid effective site of the present invention on drug development better, introduce respectively with pharmacology embodiment form below and adopt micro-cytopathic-effect inhibition assay to measure the medium effective concentration (IC that Herba Taraxaci plant phenolic acid effective kind part spray powder raw material suppresses I herpes simplex virus type (HSV-1)
50), The pharmacological results such as therapeutic index illustrate its new purposes in pharmaceutical field.Pharmacology embodiment of the present invention gives Herba Taraxaci plant phenolic acid effective kind part spray powder and the troche Pyrogentisinic Acid causes rat oral ulcer inhibitory action test data, and the real application data of Herba Taraxaci plant phenolic acid effective kind part buccal tablet on clinical oral ulcer patient.Pharmacology embodiment has only provided representative part activity data.Mandatory declaration, pharmacology embodiment of the present invention and the pharmacodynamics model that is adopted are to be used to illustrate the present invention rather than limitation of the present invention.The simple modifications that essence according to the present invention is carried out the present invention, and other indications of the simple and easy expansion on the cause of disease basis that the embodiment of the invention contained all belong to the scope of protection of present invention.
Pharmacology embodiment 1:The Herba Taraxaci plant phenolic acid effective kind part spray powder that trace cytopathy inhibition (CPE) method research embodiment 1 prepares is tested the inhibitory action of HSV-1:
1.1 cell culture and virus go down to posterity: the Vero cell culture in containing 10% deactivation calf serum, in RPMI 1640 culture medium of 100U/ ml penicillin and 100 mcg/ml, is put 37 ℃, and 5% carbon dioxide is cultivated in the incubator of 100% relative humidity.HSV-1 is added length to be had in the cell bottle of Vero cell, puts 37 ℃, and 5% carbon dioxide is cultivated in the incubator of 100% relative humidity, collects culture supernatant, puts under the low temperature and preserves.
1.2 experimental technique: adopt mtt assay to measure the inhibitory action of Herba Taraxaci extract spray powder to the growth of Vero cell: the Vero cell of the trophophase of taking the logarithm becomes 1 * 10 with culture medium with cell dilution
5/ ml is inoculated in 96 porocyte culture plates, every hole 100 microlitres, and at 37 ℃, 5%CO
2, cultivate the Herba Taraxaci plant phenolic acid effective kind part spray powder that adds after 24 hours with the culture medium dilution in the incubator of 100% relative humidity, concentration is respectively 1000 mcg/ml, 200 mcg/ml, 40 mcg/ml and 8 mcg/ml place incubator to cultivate, and cultivate after 72 hours, every hole adds MTT reagent 10 microlitres, continue to cultivate 4 hours, discard culture medium, every hole adds dimethyl sulfoxine 200 microlitres, with agitator vibration 20 minutes, under the 570nm wavelength, measure the OD value with microplate reader.With the culture hole that only adds culture medium is control wells.Suppression ratio (%)=control wells OD value-experimental group OD value)/control wells OD value * 100%.The experiment triplicate.According to the suppression ratio of cell growth under the variable concentrations, calculate the half-inhibition concentration (TD of cell growth
50).
With micro-cytopathic-effect inhibition assay working sample to the viral growth inhibitory action: the Vero cell of the trophophase of taking the logarithm becomes 1 * 10 with culture medium with cell dilution
5/ milliliter is inoculated in 96 porocyte culture plates, and 37 ℃, 5% carbon dioxide, 100% relative humidity was cultivated 24 hours, added 100TCID
50Virus 100 microlitres, inclining virus, adds the Herba Taraxaci plant phenolic acid effective kind part spray powder of variable concentrations respectively, establish normal cell contrast and viral infection contrast simultaneously, 37 ℃, 5% carbon dioxide, 100% relative humidity are cultivated after 48 hours observation of cell pathological changes under inverted microscope.With the Pyatyi standard as judging cytopathic standard, i.e. "-": cell no change, score value are 8 minutes; "+": pathological changes appears in 25% following cell, and score value is 6 minutes; " ++ ": pathological changes appears in 25%～50% cell, and score value is 4 minutes; " +++": pathological changes appears in 50%～75% cell, and score value is 2 minutes; " ++ ++ ": pathological changes appears in 75% above cell, and score value is 0 minute.Calculation of half inhibitory concentration (IC
50).Use acyclovir as positive control drug simultaneously.Calculation sample therapeutic index: TI=median toxic concentration/half-inhibition concentration.
1.3 experimental result: result such as table one show that Herba Taraxaci plant phenolic acid effective kind part spray powder can significantly suppress duplicating of HSV-1, and it is as shown in the table to the half-inhibition concentration of HSV-1 and therapeutic index for it.
Table one Herba Taraxaci plant phenolic acid effective kind part suppresses the effect of duplicating of HSV-1
| Virus | Herba Taraxaci plant phenolic acid effective kind part | Positive control drug (acyclovir) | ||||
| TD 50 | IC 50 | TI | TD 50 | IC 50 | TI | |
| HSV-1 | ＞1000 | 75.51±8.97 | ＞13.24 | ＞200 | 3.91×10 -2 | ＞5115 |
Annotate: TD
50The half-inhibition concentration (mcg/ml) that refers to the sample cell growth; IC
50Refer to the half-inhibition concentration (mcg/ml) of sample to virus replication; TI refers to therapeutic index, TI=TD
50/ IC
50
1.4 conclusion: above-mentioned result of the test explanation, Herba Taraxaci extract phenolic acid effective site has potent inhibitory action to the I herpes simplex virus type, becomes the medicine that suppresses oral cavity virus infected herpes and oral ulcer thereby can develop.
Pharmacology embodiment 2: Herba Taraxaci plant phenolic acid effective kind part spray powder buccal tablet local application and the position spray powder gastric infusion Pyrogentisinic Acid of Herba Taraxaci plant phenols acids effect portion cause the test of rat oral ulcer inhibitory action
2.1 animal pattern: male SD rat, about body weight 220 grams, available from Zhejiang Province college of traditional Chinese medicine animal center.Behind the etherization, be that 4 millimeters glass tubing end opening is flat on the bicker cheek film place in 2 millimeters of rat one sides in diameter, put after 45 seconds that calcination goes out the white speckle that diameter is 4 millimeter with 90% phenol sterilized cotton ball.Modeling position and white plate diameter homogeneous person select for use and do the oral ulcer animal pattern in each rat of performing the operation.
2.2 treat test agent and reagent: (1) Herba Taraxaci plant phenolic acid effective kind part spray powder buccal tablet (embodiment one product), Haizheng Tianhua Medicine Research Co., Ltd., Zhejiang Prov provides; Lot number 060330; Specification: 600 milligrams/sheet; (2) Herba Taraxaci plant phenolic acid effective kind part spray powder, Haizheng Tianhua Medicine Research Co., Ltd., Zhejiang Prov provides; Lot number 051018; (3) positive control: Waterelon Frost Lozenges; Guilin three gold medal Pharmaceuticaies are produced, specification: 600 milligrams/sheet; Lot number: 0603033.
2.3 experimental technique: the modeling success SD rat of picking out is divided into six groups at random after 24 hours, 10 every group, be divided into (1) model group (giving the buccal tablet that only adds adjuvant), and be administered five times every day; (2) buccal tablet high dose group (1/3 weighs 200 milligrams), administration every day seven times; (3) dosage group (1/3 weighs 200 milligrams) in the buccal tablet, be administered five times every day; (4) buccal tablet low dose group (1/3 weighs 200 milligrams), be administered three times every day; (5) positive controls (1/3 of Waterelon Frost Lozenges weighs 200 milligrams), be administered five times every day; (6) oral administration gavage administration group (100 milligrams spray powder/only), oral administration gavage behind 1 milliliter of distilled water suspendible, five administrations every day.Tablet flap coverage speckle just in time when above-mentioned buccal tablet group and matched group are respectively organized administration.Successive administration five days, the preceding observed and recorded ulcer diameter of administration also is recorded as 0 day.How many observed and recorded ulcer diameter when change dressings next day after the administration observes local red and swollen symptom and exudate simultaneously, and ulcer area size is with compatibility t check carrying out statistical analysis.The results are shown in Table 2.
2.4 experimental result: the result shows, white secretions appears in modeling success SD rat after 24 hours, viewing duration, matched group SD rat white secretions is obviously more than other groups, the beginning in the 3rd day of administration group secretions obviously reduces, ulcer area (in diameter) obviously dwindles, the 5th day red and swollen basic disappearance of senior middle school's dosed administration.
The ulcer area of each administration group of table 2SD rat relatively
| Group | Administration number of times | Dead number of elements | Survival rate | The-day ulcer diameter (millimeter) | The 3rd day ulcer diameter (millimeter) | The 5th day ulcer diameter (millimeter) |
| 1 | 5 | 1 | 90％ | 3.97±0.16 | 3.87±0.33 | 3.70±0.31 |
| 2 | 7 | 0 | 100％ | 3.97±0.21 | 3.50±0.53 ** | 3.03±0.56 ** |
| 3 | 5 | 0 | l0O％ | 3.95±0.14 | 3.8l±0.22 * | 3.23±0.47 ** |
| 4 | 3 | 0 | 100％ | 4.02±0.10 | 3.82±0.21 * | 3.43±0.41 ** |
| 5 | 5 | 0 | 100％ | 3.98±0.13 | 3.65±0.29 ** | 3.25±0.41 ** |
| 6 | 5 | 0 | 100％ | 3.98±0.14 | 3.88±0.15 * | 3.46±0.34 ** |
Annotate: group is: 1, model group; 2, buccal tablet high dose group; 3, dosage group in the buccal tablet; 4, buccal tablet low dose group; 5, positive controls; 6, irritate stomach and cheat the medicine group; The ulcer area:
N=10;
*P＜0.05;
*P＜0.01.
2.5 conclusion (of pressure testing): above result shows, Herba Taraxaci plant phenolic acid effective kind part spray powder buccal tablet Pyrogentisinic Acid causes SD rat oral ulcer inhibitory action, wherein buccal tablet high dose group (seven administrations every day) and middle dosage group (five administrations every day) have significant promotion healing effect to the ulcer wound face, and its action intensity surpasses Waterelon Frost Lozenges.Though low dosage and oral administration gavage administration also have remarkable effect, but its action intensity all is lower than watermelon crystal buccal tablet, more be lower than Herba Taraxaci plant phenolic acid effective kind part buccal tablet high dose group and middle dosage group, illustrate that the public plant phenolic acid effective kind part of Pu buccal tablet has definite curative effect aspect treatment oral ulcer, the promotion ulcer healing, and the drug effect of topical is better than oral administration route.
Pharmacology embodiment 2: the public plant phenolic acid effective kind part of Pu spray powder buccal tablet is selected 10 routine oral ulcer patients for use to oral ulcer patient's clinical trial, and the rounded or ellipse of ulcer surface has pain when itching throat and dry cough, empty pharynx.Therapeutic scheme: give buccal tablet, buccal tablet is placed affected part, containing naturally, every day five times, a slice at every turn.Successive administration five days.Produce effects (pain significantly alleviates, and the ulcer diameter reduces more than 85% or healing) 4 examples wherein; (the ulcer area reduces more than 50%, and pain degree alleviates, treatment back ulcer decreased number) 5 examples take a turn for the better; Invalid (ulcer area reduce＜50%) l example.
Presentation of results: Herba Taraxaci plant phenolic acid effective kind part spray powder buccal tablet is healing of canker sores significantly, and effective percentage is about 90%.
Claims (8)
1. Herba Taraxaci plant phenolic acid effective kind part suppresses the function application of herpes simplex virus.
2. the application of Herba Taraxaci plant phenolic acid effective kind part in preparation prevention and treatment stomatocace medicine.
3. according to claim 1 and 2 described application, it is characterized by and contain 1% to 80% Herba Taraxaci plant phenolic acid effective kind part spray powder, all the other are flavoring profit, diluent, sticking platform agent and lubricant.
4. application according to claim 3, correctives is selected from one or more in Herba Menthae, Oleum menthae, Mentholum, Borneolum Syntheticum, edible essence, Aspartane, citric acid, xylitol, sucrose, steviosin, Radix Glycyrrhizae, the syrup; Diluent is selected from one or more in lactose, Icing Sugar, mannitol, dextrin or maltodextrin, starch, precipitated calcium carbonate, sedimentation calcium phosphate, magnesium carbonate or the kaolin; Binding agent is selected from one or more in alcoholic solution, gelatin, simple syrup, emblem crystalline cellulose element or the carbomer; Lubricant is a magnesium stearate.
5. according to claim 2, it can be buccal tablet, spray, powder, oral film, can also adopt the known controlled release of modern pharmaceutical circle or slow release formulation or nanometer formulation.
6. according to claim 1 and 2 described application, wherein Herba Taraxaci plant phenolic acid effective kind part is meant with one or more effective sites that taraxol water extract purification obtained for the column chromatography of medium in silica gel, reverse phase silica gel, macroporous resin, ion exchange resin, aluminium oxide or the polydextran gel (Sephadex), the content that it is characterized by phenolic acid compound in the extract 20% and more than; Luteolin 7-O-β-D-glucoside content 0.5% and more than.
7. according to the application of claim 1 and 2, wherein Herba Taraxaci plant phenolic acid effective kind part is characterized as in this extract except that containing caffeic acid, ferulic acid and chlorogenic acid, also contain three structures with two caffeoyl guinic acid class compound of phenolic acid active substances, they are: 3, and the 5-O-dicaffeoyl quinic acid; 3, the 4-O-dicaffeoyl quinic acid; 4, the 5-O-dicaffeoyl quinic acid, the content of three total amount of compound in extract is greater than 3%.
8. according to the preparation approach of claim 1 or 2 described Herba Taraxaci plant phenolic acid effective kind parts, the Herba Taraxaci plant origin is arbitrary position of home-made Dandelion plant in one or more, promptly can be Herba Taraxaci (claiming Mongolian Herba Taraxaci again) (Taraxacum mongolicum Hand-Mazz), alkali ground Herba Taraxaci (claiming magnificent Herba Taraxaci again) (Taraxacum sinicumKitag), hot river Herba Taraxaci (claiming white edge Herba Taraxaci again) (TaraxacumplatypecidumDiels), Herba Taraxaci ohwiani (Taraxacum ohwianumKitag), anti-luxuriant Herba Taraxaci (Taraxacum grypodon Dahlst), common Herba Taraxaci medical material on these Chinese drug markets of Xingan's Herba Taraxaci (Taraxacum falcilobumKitag); Also can derive from main product America and Europe's common dandelion (Taxacum officinale); Can be dry product or bright product; Can be root, stem, leaf, flower, seed, skin, the fruit of Herba Taraxaci medical material plant, also can be their mixture and herb part.
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| CN103340977B (en) * | 2013-06-28 | 2014-11-05 | 山东大学 | Buccal tablet applicable to being taken for type II diabetes |
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| CN111514176A (en) * | 2020-04-28 | 2020-08-11 | 江汉大学 | Application of artemisia selengensis polyphenol extract in oral mucosa repair |
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