| Background:The oral ulcers are the most common oral mucosal disease a disease, the prevalence rate of about20%, superficial ulcers on the oral mucosa, the size from the size of a grain of rice to soybeans, a round or oval,The ulcer surface is concave around congestion.Ulcers with periodic, recurrent and self-limiting and other features, occur in the lip, cheek, tongue edge.Etiology and pathogenic mechanism remains unclear.. Triggers may be local trauma, stress, foods, drugs, hormones and vitamins or trace element deficiency.Systemic disease, genetic, immune, and micro-organisms in which they arise, may play an important role in the development.The treatment advocated systemic and local, traditional Chinese medicine and Western medicine, physiology and psychology combined.In recent years at home and abroad have been reported in a variety of treatment methods, but with local treatment.The local treatment is suitable for the health of patients with RAU.In order to anti-inflammatory, analgesic, to prevent secondary infection, promote healing principle.. Topical corticosteroids are the most commonly used method of the world the treatment of RAU can reduce the symptoms of RAU, almost no effect in reducing ulcer recurrence.Antibacterial or bactericidal class gargle, ointments, creams, emulsion administration but also to reduce symptoms and promote healing.At present there is no ideal therapy, can not meet the treatment needs of patientsThe stability of the physical and chemical properties of activity aloe sustained release membrane, hydrophilic large permeability material as a film-forming material, the use of aloe vera anti-ulcer, a direct role in the oral mucosa, skin and other parts。Film former to strengthen the drugs and mucous membranes close and continuing contact with both the mucosa from the mechanical protection role to protect the ulcer, and it helps the absorption of the drug to prolong the duration of action of drugs in patients with localized, and positioning.directed the release of the role of high local drug concentration, to bring the ease of use.So the use of traditional Chinese medicine and Western Medicine on activity of Aloe Vera Dyclonine made active aloe sustained-release film, for oral ulcer patients provide ideal therapeutic drug.In accordance with national policies and regulations, issued in accordance with the State Drug Administration approval of new drugs way the provisions of Chinese medicine preparations, and Traditional Chinese Drug Research, technical requirements, for new drugs active aloe aphthous membrane pre-clinical studies includepreparation process, physical and chemical properties, purity, methods of inspection, prescription screening, formulation, stability, quality standards, pharmacology, toxicology, etc.,The experiment:1The activity of aloe sustained release membrane is one of the topical treatment of recurrent aphthous ulcer drug.The activity of aloe sustained release membrane is developed from the Clinical Medical College of Yanbian University.lt has analgesic, anti-inflammatory drugs promote the healing of mouth ulcers.In order to detect the drug of activity aloe sustained release membrane on bacterial sensitivity analysis, do the activity of aloe sustained-release film with drug sensitivity test.2.Activity of aloe sustained release membrane in recent years developed the new formulation, which the release agent by adhesion, firmly adhere to the surface of the oral mucosa, with the time to protect the wound, increase local drug concentration, rapid pain relief, to extend the drug action.Although there are fresh aloe vera and aloe dry powder safety used in clinical reports, but the aloe ethanol extract can be safely used in clinical, if the mucous membrane irritant has not been reported.Therefore, the aloe membrane acute toxicological experiments to determine the emulsion side of security.3.Aloe vera in aloe polysaccharides have the effect of immunodeficiency repair and cell regeneration.Activity of aloe vera and Dyclonine and made orally active aloe oral pellicles safe non-toxic, to observe the curative effect of the traumatic ulcer animal model experiment, for the further development and application of research to provide a scientific basis.4.Activity of aloe sustained release membrane is the stability of the physical and chemical properties, hydrophilic large permeability material as a film-forming materials.Modern studies have shown that aloe vera has anti-cancer, anti-inflammatory, anti-virus, anti-bacterial insecticide, antipyretic and hepatoprotective, and enhance immune effects, widely used in various fields of the pharmaceutical industry, household industry, beauty make-up and food, health care, and thus the aloe isa higher economic value of medicinal plants.In order to determine the activity of aloe vera in the sustained-release film with an effective content and develop content standards in the membrane preparations, the sustained release membrane of activity aloe effective content standards established by high performance liquid chromatography (HPLC) experiments. Experimental methods:1.Activity aloe sustained release membrane preparation:0.5%aloe membrane activity of Aloe0.5g1.0g1.0%aloe pellicles。1.5g1.5%aloe membrane, the remaining drugs the same weight (0.5g Dyclonine Twain-800.5ml, the glycerol2.0ml, plus saturated hydroxypropyl cellulose solution to100ml).Blank film:Twain-80:0.5ml; glycerol:2.0ml; plus saturated hydroxypropyl cellulose solution to100ml.).These drugs are mixed fully, standing for12hours, elimination of bubbles in the glass plate, film, to be the natural air-dry after selecting the thickness uniformity of films into2x2cm size, disinfection, bagging backup seals.2.Activity aloe sustained-release film with drug sensitivity test:Activity aloe sustained release membrane (Yanbian University School of Clinical Medicine, provided), all strains were sources of the strains isolated in the Yanbian University Hospital inpatients and outpatients.Apparatus for Microscan automatic bacterial identification, drug sensitivity analyzer and disk diffusion confirmatory assay.Picked colonies were cultured for16-18h at35℃C, in accordance with Microscan automatic analyzer and NCCLS standards to interpret the results.3.Activity aloe release membrane acute toxicological experiment:Experiments using double-blind method.In18rabbits, were randomly divided into a, B, C three group,6rats in each group, half of each group of male and female, the left eye as a control group, the right eye as the experimental group.a group:the left eye blank film (a group), the right eye and0.5%aloe membrane (a group);group b:left eye (b), the right eye and1.0%aloe membrane (b2); c:left blank film and (c), the right eye and1.5%aloe membrane blank film (c2);The aloe membrane cut into0.4cm×0.4cm size, attached to the conjunctiva, the daily dosing three times seven days of continuous administration to observe the first six hours,24hours,48hours... up to14days conjunctiva change.Observation of content and assessment criteria:Corneal opacities were observed; iris were observed with or without pathological changes; conjunctival hyperemia and edema, observe whether any discharge according to eye irritation response score requirements and eye irritation score, score, the final calculation of average:0-3.9-no irritation;4～8.9-mild irritation;9～12.9-moderate stimulation;13～16-severe stimulation.2.The statistical processing: The data above SPSS13.0in the General-Linear Model (generalized linear model) Repeated Measures... the statistical methods and multivariate analysis of variance for statistical analysis。 4.Sustained-release membrane of activity aloe animal ulcer model experiments:Activity of Aloe release membrane preparation method for the activity of aloe vera powder1.0g0.5g Dyclonine Twain-800.5ml, the glycerol1.0ml, add saturated hydroxyl C methy cellulose solution to100ml;Dose of activity aloe vera oral membrane:activity of aloe vere powder1.5g, and the rest with low-dose; High doses of activity aloe vera oral membrane activity of aloe vera powder2.0g, and the rest with low-dose; Blank membrane:0.5c Dyclonine, Twain-800.5ml, the glycerol1.0ml, plus saturated hydroxypropyl methy cellulose solution100ml, excluding the activity of aloe powder.Made of the film, selec uniform thickness of the membrane and cut into3.0×3.0cm size, UV disinfection bagging sealing spare.The establishment of the artificial mouth ulcer model in rats:undei ether anesthesia, the plastic tube containing90%phenol cotton balls (diameter-6mm’ placed rats the right and left1mm away from the altercation at the buccal burning30seconds, the local into a grayabout a diameter of about6mm ulcer formation in the nex day.The experimental group and the administration method is:Ulceration of the day, the rats were randomly divided into five groups.Group A (blank membrane group); group E (watermelon cream group); membrane group of group C (low dose);(in doses o membrane group);(high dose membrane group).Each group of13, of which5is onl) used for observation, only another8for pathological examination..Delivery method:Activity aloe membrane (high, medium and low dose) and blank membrane an(?) cut into0.7cm x0.7cm or so, covering the ulcers;Watermelon Frost Group watermelor frost spray on the surface of the ulcer, five groups of drug delivery are twice daily.Administration before and after each dose the next day observed ulcer diamete and ulcer healing.Histopathological examination of pathological specimens of the ulce area to take in2,4,6,8days after treatment, conventional treatment, slices, HE staining and observed under light microscope.Statistical analysis using the software SPSS13.0the variance analysis and Wilcoxon rank sum test for statistical analysis.5.Activity aloe sustained release membrane active ingredient content a(?) standard-setting methods:High performance liquid chromatography analysis condition(?) Column:ZORBAX-SA-C18column (5μm,200mm×4.6mm); mobile phase:methanol water (volume ratio70:30); flow rate:1.0mL/min,; column temperature was25℃;aloi(?) detection wavelength:360nm, aloe-emodin detection wavelength:430nm; injectio(?) volume:20μl.High performance liquid chromatographic analysis of conditions for the establishment of standard curve, precision test, stability test, the reproducibility of the experiments, sample recovery rate experiment, active aloe sustained-release film (?) Aloin and aloe emodin content determination.Active aloe release membrane preparation (Yanbian University, School of Clinical MedicineResults:1.Activity of aloe sustained-release film with drug sensitivity test results:Activity aloe release membrane on the Staphylococcus aureus class (68.57%), Staphylococcus epidermidis (65.63%), Staphylococcus saprophyticus (66.67%), Staphylococcus haemolyticus (70.97%), the card he Brandeis Han coli (72.73%), Pseudomonas aeruginosa (70.97), Escherichia coli (75%) and other bacteria have a certain sensitivity.But Loffi’s not young bacilli (33.33%), fish Vibrio (25.00%), pigs aureus (19.89%) and other bacteria is less sensitive2.Activity of aloe sustained-release film with acute toxicological experiment results:During the whole experiment all rabbits did not appear the cornea and iris reaction, no conjunctiva edema reaction, only conjunctival hyperemia and a small amount of secretions produced, all rabbits were calculated the average maximum1.200points, minimum0, were less than3.9minutes.On the factors in the test group. Within group variation with time, stimulate the score difference.Grouping factor did not affect the stimulation of the various time periods.Among the groups pairwise comparisons (LSD) test results, indicating that the five stimulus was no significant difference.3.Activity of aloe sustained-release film with the test results:(1) the rate of change observed in traumatic ulcers of the oral ulcer model area are as follows, the membrane in the treatment of activity aloe aphthous four days after the B, C and D and E group ulcer diameter narrowing was significantly faster than the Type A group (P<0.01)ulcer diameter D, and in six days after treatment began to shrink better than group B (P <0.01).The results observed in ulcer healing traumatic ulcer model (2) hours are as follows, B, and C and D and Group E of ulcer healing time than Group A short (P<0.01), ulcer healing time in group D and group B with significantdifference (P<0.01).The results of this test (3) histopathological observation has drawn the check inflammation reduce the epithelial tissue repair and so much better than the blank film group, and Watermelon Frost Group. In particular, played a major role with blank film shows the activity of aloe.4.HPLC determination of activity aloe release membrane stability and active ingredient content standard experimental results:High performance liquid chromatography chromatographic peak area in a certain concentration range with good linearity, determination of recovery, good reproducibility, with the method is simple, fast, accurate, and high sensitivity.Measured the activity of aloe sustained-release film with a content standard requirements of the aloin and aloe-emodin (1cm×1cm) aloin40.67μg, aloe-emodin1.8μg.Conclusion:1. Active aloe oral sustained-release membrane by oral bacteria have a bacteriostatic effect.2. Active aloe oral sustained-release membrane no toxicity reaction, is safe, non-toxic pellicles.3. Active aloe oral sustained-release membrane on the membrane type animal ulcer treatment curative effect.4. Active aloe oral sustained-release membrane with content standards provisions of the aloin40.67μg and aloe-emodin1.8μg.In short, the above4parts before clinical trials from the experiment result, the drug is safe, non-toxic, animal experiment, curative effect of drug quality, quality standard is complete scientific method for clinical application, will provide reliable scientific experiments, theoretical basis, at the same time with recurrent oral ulcer clinical prospects of drug, has reached the people’s Republic of China Ministry of health research and development of new traditional Chinese medicine standard, can be clinical application study.. |
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