The application of baicalin in preparation treatment or prevention stomatocace medicine
Technical field
The present invention relates to the application of baicalin in preparation treatment or prevention stomatocace medicine, also relate to baicalin buccal tablet, powder or the spray for the treatment of or preventing oral ulcer.
Background technology
Radix Scutellariae is traditional heat-clearing and detoxifying herb, and bitter in the mouth is cold in nature, is used for the treatment of damp and hot feeling of fullness, cough due to lung-heat, hyperpyrexia excessive thirst, carbuncle sore tumefacting virus.Modern study shows, the main active of Radix Scutellariae is baicalin (a former title baicalin), it has antioxidation, antiinflammatory, resistance attitude, antibiotic, antiviral and antitumor action (" Radix Scutellariae chemical constituent and baicalin Study on Extraction Method progress " Li Tongtong etc., " Tianjin pharmacy " in June, 2002, the 7th page of the 14th the 3rd phase of volume).Baicalin has recorded in China's drug standard as medicinal raw material, but only is mainly used on the diseases such as pneumonia, hypertension, hepatitis, infection and threatened abortion clinically at present, and the medical usage of baicalin is not brought into play fully.In view of the baicalin pharmacological action extensively and do not have a tangible toxic reaction, therefore the inventor has carried out deep research to the medical usage of baicalin, through a large amount of experimentatioies, the inventor is surprised to find baicalin has extraordinary effect to treatment and prevention oral ulcer disease.
Recurrent oral ulceration is a modal disease in the diseases of oral mucosa.Prevalence occupies the first place of diseases of oral mucosa.Sircus (1975) investigates 1587 people, and prevalence is 20%; Investigation 9463 people of Stomatological Hospital of Beijing Medical Univ. (1981), prevalence is 18.3%.This shows that oral ulcer patient is a very huge colony.The cause of disease complexity of recurrent oral ulceration, still indeterminate so far, may be relevant with factors such as the endocrine regulation of viral infection, bacterial infection and body, immune dysfunctions.
Herpetic oral ulcer is the oral ulcer that is caused by herpesvirus, and common is the herpes simplex oral ulcer, though common not as recurrent ulcer, also be a common type of oral ulcer.
The main treatment measure of oral ulcer comprises topical therapeutic and whole body therapeutic, because the topical therapeutic toxic and side effects is lower, has therefore obtained people's approval.Though the buccal tablets that use the part that occurs in recent years carries, easy to use, mouthfeel and compliance are better, and as lysozyme buccal tablet, watermelon crystal buccal tablet, cydiodine etc., these medicines emphasize particularly on different fields at aspects such as sterilization, antiinflammatory, pain relievings.Lysozyme has certain bactericidal action, but does not have the antiinflammatory effect; The watermelon crystal mouthfeel is good, but sterilization and antiinflammatory action are all not obvious; Cydiodine has bactericidal action, and antiinflammatory action is not obvious, and can not be used for women breast-feeding their children, hyperthyroidism and iodine allergy patient.Therefore be raw material with baicalin or the extract that contains baicalin, develop a kind of use, easy to carry and have great using value with medicine in the oral ulcer that has comprehensive effect aspect sterilization, the antiinflammatory.
Summary of the invention
The invention provides the application of baicalin in preparation treatment or prevention stomatocace medicine.
The invention provides baicalin buccal tablet, powder and the spray of treatment or prevention oral ulcer.
The invention provides the preparation method of baicalin buccal tablet, powder and spray.
In order to verify the anti-oral ulcer effect of baicalin, we are with cydiodine medicine in contrast, make rat oral ulcer model with phenol, give the baicalin buccal tablet powder and the cydiodine powder of certain number of times every day, the result shows, gives baicalin buccal tablet powder every day 4 times and gives cydiodine powder every day 4 times, successive administration 5 days, rat oral ulcer area and ulcer healing rate are suitable substantially, and drug effect is in same level.
Cydiodine is clinical Oralease thing commonly used, determined curative effect.The main active of cydiodine is a molecular iodine, and with the molecular state cydiodine that iodine utilizes the molecular dispersion technology to make, with the passing of time cydiodine preserves that iodine can overflow, and iodine overflows the back taste and increases the weight of, and the easy oxidation of the iodine that overflows simultaneously influences drug effect and stability of formulation.The use of cydiodine simultaneously be subjected to a certain degree restriction, disposable excitement appears as (1) some oral ulcer after than heavy patient's pastille; (2) to iodine allergy or the responsive careful usefulness of patient of possibility; (3) testing the patient of thyroid function, should not use; (4) because of the iodine that absorbs can pass through placental barrier, and in milk, discharge, so pregnancy or lacting woman are avoided using.
Baicalin extracts refining obtaining from baikal skullcap root, many pharmacological actions such as that baicalin has is antibiotic, antiinflammatory, antiallergic action, antiviral (senior middle school's flood, Huang Kaixun, Xu Huibi. the bioactive progress of flavonoid in the Radix Scutellariae. Chinese Pharmaceutical Journal, 1998,33 (12): 705); Baicalin significantly suppresses the inductive inflammatory reaction of lipopolysaccharide (LPS) (Chung CP under 1mg.L-1 concentration, Park JB, Bae KH.Pharmacological effects of methanolic extract from theroot of Scutelaria baicalensis and its flavonoids on human gingival fibroblast.Planta Med, 1995,61 (2): 150).The baicalin toxic and side effects is low, bibliographical information diabetics 3 times on the one, each oral 600mg, took medicine continuously 30 days, do not occur obvious toxic and side effects (Liu Changshan, Ma Lili, Li Ping. baicalin is to the influence of diabetics erythrocyte aldose reductase activity and glomerular filtration rate. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2001,26 (9): 632~633).While baicalin substantially tasteless, good as its mouthfeel of buccal tablet, toxic and side effects is low, does not have bad stimulation, and suitable all kinds of crowds use.
Compare with cydiodine, baicalin has the antiinflammatory action that cydiodine does not have, and the oral cavity medicine nonirritant does not have irritated reaction simultaneously, and mouthfeel is good, and anemia of pregnant woman and child all can use, and baicalin oral administration dosage is low in addition, has no side effect.Because of baicalin buccal tablet composition is single, quality is more easy to control.
Oral ulcer baicalin buccal tablet provided by the invention contains baicalin, diluent, binding agent and lubricant, wherein baicalin: diluent: binding agent: the lubricant ratio is 1-10: 90-96: 0.2-10: 0.5-1.5.
Diluent is selected from one or more in lactose, Icing Sugar, mannitol, dextrin or the maltodextrin in the baicalin buccal tablet; Binding agent is selected from 30 POVIDONE K 30 BP/USP
30In alcoholic solution, hydroxypropyl methylcellulose, gelatin, simple syrup or the carbomer one or more; Lubricant is a magnesium stearate.
The preparation method of baicalin buccal tablet is: the baicalin back of sieving is added diluent, mixing, sieve mixed powder, drying with binding agent system soft material, is granulated, oven drying, granulate adds magnesium stearate, mixing, tabletting are promptly.
The baicalin buccal tablet can also contain correctives, preferably makes correctives with Mentholum, and the 0.3-0.7% that it accounts for buccal tablet weight is preferably 0.5%.
The consumption of table 1. Mentholum is to the influence of mouthfeel
The consumption mouthfeel of Mentholum
0.25% no cooling effect
0.5% cool taste
0.75% cool taste, slightly fiber crops
Baicalin powder provided by the invention is made up of baicalin and diluent, and wherein diluent can be selected from one or more in lactose, amylodextrin, sucrose, glucose, precipitated calcium carbonate, sedimentation calcium phosphate, magnesium carbonate or the kaolin; Realize by following preparation method: get recipe quantity baicalin powder, 100 ℃ of dryings 2 hours add diluent, and mixing is crossed 100 mesh sieves, bottling promptly, every bottle of 10g.
Baicalin spray provided by the invention is to realize by following preparation method: get recipe quantity baicalin powder, 100 ℃ of dryings 2 hours are crossed 200 mesh sieves, bottling promptly, every bottle of 10g.
Baicalin of the present invention is when being used for oral ulcer, the dosage range of its oral application is: calculating using dosage with baicalin is 5-100mg/ time, buccal tablet 3-8 time/day, powder, spray 3-5 time/day, preferable range is: calculating using dosage with baicalin is 50-100mg/ time, buccal tablet 3-8 time/day, powder, spray 3-5 time/day.
The specific embodiment
Preparation example 1: preparation baicalin buccal tablet
The 50g baicalin is crossed 100 orders (down together) sieve, add maltodextrin 150g mixing, sieve, add mannitol 200g mixing, sieve, add 400g Icing Sugar mixing, sieve, get mixed powder, with 2%PVPK
3075% ethanol water 120ml makes binding agent, the suitable soft material of system, and 18 mesh sieves are granulated, 60 ℃ of oven dryings 2 hours, 16 order nylon mesh granulate add magnesium stearate 8g, mixing, oval special-shaped stamping is made 1000, the heavily about 800mg/ sheet of sheet.
Preparation example 2: preparation buccal tablet
The 100g baicalin is crossed 100 orders (down together) sieve, add maltodextrin 150g mixing, sieve, add mannitol 200g mixing, sieve, add 350g Icing Sugar mixing, sieve, get mixed powder, with 2%PVPK
3075% ethanol water 120ml makes binding agent, the suitable soft material of system, and 18 mesh sieves are granulated, 60 ℃ of oven dryings 2 hours, 16 order nylon mesh granulate add magnesium stearate 8g, mixing, oval special-shaped stamping is made 1000, the heavily about 800mg/ sheet of sheet.
Preparation example 3: preparation baicalin buccal tablet
The 5g baicalin is crossed 100 orders (down together) sieve, add maltodextrin 350g mixing, sieve, add mannitol 250g mixing, sieve, add 200g Icing Sugar mixing, sieve, get mixed powder, with 2% PVPK
3075% ethanol water 120ml makes binding agent, the suitable soft material of system, and 18 mesh sieves are granulated, 60 ℃ of oven dryings 2 hours, 16 order nylon mesh granulate add magnesium stearate 9g, mixing, oval special-shaped stamping is made 1000, the heavily about 800mg/ sheet of sheet.
Preparation example 4: preparation baicalin spray
The 5g baicalin is crossed 200 mesh sieves, adds starch 5g mixing, crosses 200 mesh sieves, mixed powder, 100 ℃ of dryings 2 hours are crossed 200 mesh sieves, bottling promptly, every bottle of 10g, airtight, promptly get spray.
Preparation example 5: preparation baicalin powder
Get 5g baicalin powder, add starch 5g, mixing, 100 ℃ of dryings 2 hours are crossed 200 mesh sieves, bottling promptly, every bottle of 10g.
The anti-oral ulcer experimental study of test example 1 baicalin
1, test objective: whether make the oral ulcer model with phenol, give the baicalin of the certain number of times of oral ulcer rat model every day, observing baicalin has the effect that reduces ulcer.
2, be subjected to reagent thing and reagent
The baicalin buccal tablet (provide lot number by Shandong Province natural drug Engineering Research Center medicament chamber: 020822, specification: 50mg);
Cydiodine (Beijing Sihuan Medicine Science and Technology Co., Ltd, specification: 1.5mg, lot number: 0207092);
Phenol (Tianjin Milky Way chemical reagent factory, lot number: 0000707)
Animal: the Wistar rat, male, body weight 240 ~ 280g, Shandong Province's natural drug Engineering Technical Research Centre laboratory animal
The center provides, the animal quality certification: No. 200106005, Shandong kinoplaszm word
3. test method
Get 50 of rats, male, body weight 240~280g, 10% chloral hydrate anesthesia, dosage: 0.35ml/100g, (internal diameter: 3mm) lower end is flat on the cheek film at the about 1mm of rats with left bicker place with the plastic dropper of 90% phenol cotton balls after the anesthesia, the white infringement of the about 3mm in this place is promptly seen in calcination 30 seconds.Random packet after 24 hours, is divided 5 groups, i.e. model group (adjuvant 4 times/day does not contain medicine) by 10 every group; Baicalin buccal tablet high dose group (6 times/day); Dosage group in the baicalin buccal tablet (4 times/day); Baicalin buccal tablet low dose group (2 times/day); Positive controls: cydiodine group (4 times/day), baicalin buccal tablet and cydiodine buccal tablet be pulverize before use, and administration is degree of being with the flap coverage.Successive administration 5 days, observe ulcer area size (in the diameter of ulcer) and ulcer healing situation (do not have macroscopic ulcer and be considered as healing) next day after reaching each administration before the administration, and first administration to last administration is recorded as 1,2,3,4,5,6,7 day respectively.Ulcer area size is checked with t, ulcer healing rate X
2Check.
4. result of the test: the influence of table 1 pair rat ulcer area
Group administration ulcer area is (in diameter: mm)
Number of times
1 day 2 days 3 days 4 days 5 days 6 days
Adjuvant group 4 3.0 ± 0.4 2.9 ± 0.4 2.7 ± 0.5 2.3 ± 0.6 1.8 ± 0.5 1.6 ± 0.7
The baicalin buccal tablet is high by 6 3.0 ± and 0.6 2.4 ± 0.8 1.6 ± 1.2
*1.0 ± 1.1
*0.4 ± 0.7
*0.1 ± 0.3
*
The dosage group
In the baicalin buccal tablet 4 3.0 ± 0.6 3.0 ± 0.5 2.1 ± 0.5
*1.4 ± 0.5
*0.9 ± 0.7
*0.3 ± 0.5
*
The dosage group
Baicalin buccal tablet low 2 3.0 ± 0.3 2.7 ± 0.6 2.7 ± 0.5 2.6 ± 0.6 1.2 ± 0.5
*0.9 ± 0.7
*
The dosage group
Cydiodine group 4 2.9 ± 0.4 2.6 ± 0.4 2.0 ± 0.5
*1.2 ± 0.5
*0.8 ± 0.6
*0.4 ± 0.5
*
Annotate:
*P<0.01,
*Compare with model group P<0.05
The influence of table 2 pair rat ulcer healing time
Group administration number of times ulcer healing rate (%)
1 day 2 days 3 days 4 days 5 days 6 days
Adjuvant group 4000000
The baicalin buccal tablet is high by 6000 30 50
*80
*
The dosage group
In the baicalin buccal tablet 40000 20 50
*
The dosage group
Baicalin buccal tablet low 2000000
The dosage group
Cydiodine group 4000 10 30 50
*
Annotate:
*P<0.01,
*Compare with model group P<0.05
The ulcer area compares: buccal tablet high dose group and model group relatively played off-test on the 3rd day from administration, and significant difference is relatively arranged corresponding every day; Cydiodine group and model group relatively played off-test on the 3rd day from administration, and significant difference is relatively arranged corresponding every day; Dosage group and model group relatively played off-test on the 3rd day from administration in the buccal tablet, and significant difference is more also arranged corresponding every day; Buccal tablet low dose group and model group relatively played off-test on the 5th day from administration, and significant difference is relatively arranged corresponding every day; Dosage group and cydiodine group relatively played off-test on the 1st day from administration in the buccal tablet, did not relatively have significant difference corresponding every day.
Healing rate: to off-test, ulcer is healing not from administration the 1st day for adjuvant group and baicalin buccal tablet low dose group; And baicalin buccal tablet high dose group just has ulcer healing from administration the 4th day, to off-test, reaches 80%; The cydiodine group has ulcer healing from administration the 4th day, to off-test, reaches 50%; The dosage group has ulcer healing from administration the 5th day in the buccal tablet, to off-test, reaches 50%.
5. conclusion
The baicalin buccal tablet has the effect of obvious promotion oral ulcer healing.