| Oral ulcer,also known as recurrent oral ulcer,is a common chronic inflammatory disease that occurs in the oral mucosa.The incidence rate of oral ulcers is as high as 25% in the human population.The local pain is severe and the burning pain is obvious when the ulcer occurs.The causes of oral ulcers are more complicated.Clinically,symptomatic treatment is often used,and local treatment is the main treatment.It has been clinically proven that Chinese medicine can effectively alleviate pain,promote ulcer healing,and have fewer side effects.Andrographis paniculata is a dry aerial part of Andrographis paniculata(Burm.f.)Nees,which mainly contains diterpene lactones and flavonoids.The previous study of the research group found that Andrographis paniculata can effectively inhibit the local inflammatory response of oral ulcers through the Ak T/NF-?B pathway,relieve pain and promote ulcer healing.On the basis of previous research,this subject prepared the extract of Andrographis paniculata into oral film,optimized the prescription of the film,established the quality standard of the film,and evaluated its therapeutic effect on oral ulcer.Formulation optimization of Bing chuan film: This experiment is based on Andrographis paniculata extract,borneol is astringent,polyvinyl alcohol 17-88(PVA 17-88),hydroxypropyl methylcellulose(HPMC),carboxymethyl fiber Sodium(CMC-Na)is a film-forming material,glycerin is a plasticizer,and aspartame is a flavoring agent to prepare a Bing chuan film.The total volume of the fixed solution is 100 m L,the concentration of the aqueous extract is 16%,the concentration of the alcohol extract is 12%,the concentration of borneol is 1.2%,and the concentration of sodium carboxymethyl cellulose(CMC-Na)is 1%.The film formation,release property,flexibility and uniformity of the film were used as evaluation indexes.The ratio of PVA 17-88 to HPMC,the total concentration of film-forming materials and the concentration of glycerol were investigated by orthogonal experiment,and WAGE water was screened out.The optimal formulation of the Bing chuan water extract film: the ratio of PVA 17-88 to HPMC is 120:1,the total concentration of film-forming material is 6%,and the concentration of glycerol is 4%;The optimal formulation of the Bing chuan alcohol extract film: the ratio of PVA 17-88 to HPMC is 60:1,the total concentration of the film-forming material is 9%,and the glycerin concentration is 3%.The therapeutic effect of Bing chuan filmst on oral ulcers: 8 rats were randomly selected as the normal group before modeling,and the rats in the remaining rats were established by chemical burning method.The model rats were randomly divided into 8 groups.A total of 9 groups: normal group(normal saline,0.2 ml / only);positive drug group(5 mg watermelon cream / only);model group(blank film without drug);Bing chuan water extract film group: low dose Group(2.2 mg water extract + 0.5 mg borneol / only),medium dose group(4.8 mg water extract + 0.5 mg borneol / only),high dose group(9.6 mg water extract + 0.5 mg borneol / only);Bing chuan alcohol extract film group: low dose group(1.8 mg alcohol extract + 0.5 mg borneol/tablet),medium dose group(3.6 mg alcohol extract + 0.5 mg borneol/only),high dose group(7.2 mg alcohol extract + 0.5 mg borneol/only).The substance was applied directly to the ulcer of the rat(0.5 x 0.5 cm)and administered twice daily for 7 days.The ulcer healing of the rats was recorded during the administration.After the administration,the oral mucosa of the ulcer was cut for HE staining and observed under light microscope.The inflammatory factors IL-6,IL-1? and TNF-? in the mucosa were detected by ELISA.The results showed that there was no significant difference in the ulcer area of each model group before administration(P>0.05).After the end of the administration,both Bing chuan films promote ulcer healing in a dose-dependent manner.Bing chuan water extract film medium dose group(1.60±0.92mm2),ice-through alcohol extract film high-dose group(1.64±0.41 mm2)and positive drug group(1.63±0.57 mm2)compared with model group(2.72±0.52 mm2),ulcer healing was significantly promoted(P<0.05),and there was a significant difference(P<0.01)in the high-dose group(1.39±0.54mm2).The results of ELISA showed that the secretion of inflammatory cytokines IL-6,IL-1? and TNF-? in mucosal tissues was reduced in all groups.Compared with the model group(103.21±4.55 pg/ml),the high-dose group of Bing chuan water extract film(70.00±3.74 pg/ml),the high-dose group of Bing chuan water extract film(81.33±4.50 pg/ml)and the positive drug group(71.33±6.85 pg/ml)can be extremely significant.The secretion of TNF-? was decreased(P<0.01);the high-dose group of Bing chuan extract(69.11±14.16 pg/ml)reduced IL-1? secretion compared with the model group(114.66±3.68 pg/ml).There was a significant difference(P<0.01)in the high-dose group(87.67±3.09 pg/ml)of the Bing chuan alcohol extract film;the high-dose group of the Bing chuan aqueous extract film(12.01±0.82 pg/ml),Bing chuan alcohol extract high-dose group(14.67±0.67 pg/ml)and positive drug group(11.67±0.47 pg/ml)and model group(21.33±1.70 pg/ml)The ratio of IL-6 was significantly decreased(P<0.01),and the dose of Bing chuan aqueous extract(16.67±1.25 pg/ml)was significant(P<0.05).HE staining results showed that compared with the model group,both Bing chuan films significantly reduced lymphocyte and inflammatory cell infiltration in the lamina propria,reduced red blood cell extravasation,and the mucosal tissue structure became complete and clear,with doses administered.Increasing the degree of infiltration gradually eased.Quality evaluation of Bing chuan water extracting film: According to the four editions of the Chinese Pharmacopoeia(0125 film)and(0931 dissolution and release method),the appearance,weight difference and release of the film were evaluated.According to the literature,the thickness of the film,the surface PH,the folding resistance,and the in vitro dissolution time were evaluated.The results showed that the film of Bing chuan water extract was dark brown,the appearance was complete and smooth,the color was uniform,and there was no bubble.The difference in weight of the film(±10.0%)was in accordance with the pharmacopoeia;The cumulative release rate was about 70% at 40 min,and the cumulative release rate at 80 min was about 85% in artificial saliva(p H=7.4,PPBS).The drug release in vitro was more complete.The thickness of the Bing chuan water extracting agent is 470-490 ?m,the in vitro dissolution time is 27 min,and the surface p H of the film is 6.4-6.8,indicating that it is not irritating to the oral mucosa;In summary,the ice film-piercing agent has the characteristics of simple preparation,convenient administration,and controllable quality,and has therapeutic effects on the rat oral ulcer model caused by chemical burning,Therefore,ice transdermal agents have the prospect of being developed into oral ulcer drugs. |
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