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Changankang Prescription Colon Specific Drug Delivery Suitability Study Of The Treatment Of Ulcerative Colitis

Posted on:2011-07-04Degree:MasterType:Thesis
Country:ChinaCandidate:H S YuFull Text:PDF
GTID:2204360305472453Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
New Chang-An-Kang is composed of Astragalus extract, Coptis extract- Berberine and Radix Auckladiae extracts, which is from Chang-An-Kang. Chang-An-Kang is a clinical experience prescription which is composed of Astragalus, Coptis, Psoralea Fruit, Honeysuckle, Garden Burnet, Radix Auckladiae, which has the effect of strengthening spleen and replenishing qi, clearing away heat, drying dampness, blood-activiating and stasis-dissolving. Chang-An-Kang is effective for ulcerative colitis (UC) in clinical practice. Chang-An-Kang is made up of extraction of Astragalus, Coptis, Psoralea Fruit, Honeysuckle, Garden Burnet, Radix Auckladiae, but extraction rate is low, therefore, a larger amount of Chang-An-Kang will be taken for human every day. Retaining monarch drug Astragalus, Coptis and adjuvant and courier drug Radix Auckladiae constitutes a New Chang-An-Kang. Although there are only three kinds of drugs, extraction rate is higher and the previous studies have shown that the efficacy of New Chang-An-Kang is similar to Chang-An-Kang for UC rats induced by acetic acid.Astragalus is warm in property, with function of buqishegnyang and tuofushengji, skilled in spleen deficiency and diarrhea. The main chemical components of Astragalus include:polysaccharides, saponins, flavonoids and amino acids, etc, which have immune regulatory role. Therefore, considering overall multi-virtual in UC patients and the immunomodulatory effects of Astragalus, extract of Astragalus is choosed by oral administration, absorbed in the stomach in order to achieve the regulatory role of the body. Coptis is bitter cold in property, with function of clearing away heat, drying dampness and purging fire to eliminate toxin, skilled in diarrhea, dysentery caused by gastroenteritis damp-heat. The main chemical ingredients of Coptis is berberine, with anti-pathogen, anti-bacterial toxins,anti-diarrhea, anti-inflammatory, immune inhibition. Traditionally, it is believed that it is difficult to absorb for oral administration of berberine which is lower in blood concentrations, but the latest research shows that berberine can be absorbed after oral administration, and widely distributed, metabolism rapidly. Therefore, considering local dorset (lesions mainly in the colon) in UC pat ients, we select the berberine in colon-specific delivery in order to improve the concentration of berberine in the colon, improve bioavailabil - ity, for achieving the role of local regulation. Radix Auckladiae is XinSan WenTong, drying for bitter and dropping in property, skilled in Tongli Qi of triple energizer. It has the effect of heat clearing and diarrhea stopping and promoting qi circulation to relieve pain for Radix Auckladiae compatibility with Coptis, taking the meaning of xingqizehouzhongzichu ". Chemical composition is mainly volatile oil, still containin - g stigmasterol, alkaloid of Radix Auckladiae, resin, etc. Radix Auckladiae has the effect of anti-inflammatory and anti-diarrhea, increasing intestinal peristaltic amplitude and muscle tension, confronting intestinal muscle spasm. Therefore, we select Radix Auckladiae and berberine in colon-specific delivery, playing the role of common local regulation.We observed the effect on UC rats induced by acetic acid and iduced by 2,4,6-Trinitrobenzenesulfonic acid (TNBS)/ethanol for colon-specific delivery and oral administration of New Chang-An-Kang in this paper to explore the suitability of colon-specific delivery of New Chang-An-Kang. At the same time, the possible mechanism of colon-specific delivery of New Chang-An-Kang was discussed. All of the above are to provide experimental evidence for preparation of colon-specific delivery of New Chang-An-Kang.1 Effects of colon-specific delivery and oral administration of New Chang-An-Kang on the symptoms of UC ratsEffects on stool consistency of UC rats:Diarrhea is caused by malabsorption of colorectal mucosa to Na+ and water, and colon motility function disorders, as well as the damaged layer of mucous cells leading to exudation of serum and extracellular fluid into the colon. Diarrhea status of rat induced by the acetic acid and TNBS/ethanol can be improved for colon-specific delivery and oral administration of New Chang-An-Kang, with stool consistency changing gradually from dilute to loose. To UC rats induced by acetic acid, there were significant differences for high dose of oral administration and high dose of colon-specific delivery compared with model group (P<0.05) after 3d for administration. To UC rats induced by TNBS/ethanol, there were very significant differences for high dose and middle dose of oral administration and high dose and middle dose of colon-specific delivery compared with model group (P<0.01), and there were significant differences for low dose of oral administration and low dose of colon-specific delivery compared with model group (P<0.05) after 4d for administration. Until after administration 7d, there were still significant differences for oral administration and colon-specific delivery compared with model group (P<0.05). Comparing the comprehensive effects of oral administration and colon-specific delivery on stool consistency of UC rats, colon-specific delivery were similar to oral administration, indicating that there were no significant differences for colon-specific delivery and oral administration on the aspect of diarrhea.Effects on fecal occult blood of UC rats:fecal occult blood is due to damaged colonic mucosa, including the extensive expansion of mucosal blood vessels, as well as mucosal surface ulcers. Fecal occult blood of rats induced by the acetic acid and TNBS/ethanol can be improved for oral administration and colon-specific delivery of New Chang-An-Kang, with fecal occult blood changing gradually from blood, strong positive (+++) to positive (++) and weak positive (+). To UC rats induced by acetic acid, there were very significant differences for high dose and middle dose of oral administration and high dose and middle dose of colon-specific delivery compared with model group (P<0.01), and there were significant differences for low dose of oral administration and low dose of colon-specific delivery compared with model group (P<0.05) after 3d for administration. At the same time, the average scores of fecal occult blood of high dose and middle dose of colon-specific delivery were lower than high dose and middle dose of oral administration. Until after administration 6d, there were still very significant differences for high dose of colon-specific delivery compared with model group (P<0.01), and there were significant differences for high dose of oral administration and middle dose of colon-specific delivery compared with model group (P <0.05). To UC rats induced by TNBS/ethanol, there were very significant differences for high dose of colon-specific delivery compared with model group (P<0.01), and there were significant differences for middle dose of colon-specific delivery compared with model group (P<0.05) after 4d for administration, and there were no statistically significant for oral administration compared with model group. And there were statistically significant for high dose of colon-specific delivery compared with high doses of oral administration (P<0.05). and the average scores of fecal occult blood of middle dose and low dose of colon-specific delivery were lower than middle dose and low dose of oral administration. Until after administration 7d, there were still very significant differences for high dose and middle dose, and of colon-specific delivery compared with model group (P<0.01), and there were significant differences for high dose and middle dose of oral administration and low dose of colon-specific delivery compared with model group (P<0.05) and there were no statistically significant for low dose of oral administration compared with model group. By comprehensive comparison of oral administration and colon-specific delivery on fecal occult blood of UC rats, the effects of colon-specific delivery were better than oral administration, indicating that colon-specific delivery were better than oral administration on improving damaged colonic mucosa.2 Effects of oral administration and colon-specific delivery of New Chang-An-Kang on the colon lesions of UC ratsWe observed the effects of oral administration and colon-specific delivery on the swollen colon (reflected in the weight increase), the shortened colon, the broadened colon, the increased weight index of colon and damaged colon mucosal in UC rats induced by acetic acid and TNBS/ethanol. And myeloperoxidase (MPO) in the colon was detected, while the impact of oral administration and colon-specific delivery on immune organs was observed in UC rats induced by TNBS/ethanol. The effects of colon-specific delivery were similar to oral administration in improving swollen the colon, shortened the colon and broadened the colon. The effects of colon-specific delivery were better than oral administration in improving increased weight index of the colon and damaged colon mucosal. To UC rats induced by acetic acid, there were significant differences for high dose and middle dose of oral administration compared with model group (P<0.05), and there were very significant differences for high dose and middle dose of colon-specific delivery compared with model group (P<0.01) in improving increased weight index of the colon. To UC rats induced by TNBS /ethanol, there were significant differences for high dose and middle dose of oral administration and high dose and middle dose of colon-specific delivery compared with model group (P<0.05) in improving increased weight index of the colon. To UC rats induced by acetic acid, there were very significant differences for high dose and middle dose of colon-specific delivery compared with model group (P<0.01), and there were significant differences for low dose of colon-specific delivery and high dose of oral administration compared with model group (P<0.05) in improving damaged colon mucosal. To UC rats induced by TNBS/ethanol, there were very significant differences for high dose of colon-specific delivery compared with model group (P<0.01), and there were very significant differences for middle dose and low dose of colon-specific delivery and high dose and middle dose of oral administration compared with model group (P<0.05) in improving damaged colon mucosal. The effects of colon-specific del ivery were better than oral administration in reducing increased MPO in the colon. To UC rats induced by acetic acid, there were very significant differences for high dose and middle dose of oral administration and colon-specific delivery compared with model group (P<0.01) in reducing increased MPO in the colon. To UC rats induced by TNBS/ethanol, there were very significant differences for high dose of oral administration and high dose of colon-specific delivery compared with model group (P<0.01), and there were significant differences for middle dose of colon-specific delivery compared wi th model group (P<0.05) in reducing increased MPO in the colon. The effects of colon-specific delivery were better than oral administration in improving immune organs, reflecting the improvement of the swollen spleen and reduced thymus especially, in improving the swollen spleen.3 Effects of oral administration and colon-specific delivery of New Chang-An-Kang on the colon pathomorphology of UC ratsWe observed the effects of oral administration and colon-specific delivery on morphology of colon epithelial cells and infiltration degree of inflammatory cell in UC rats induced by acetic acid, and the effects of oral administration and colon-specific delivery on ulcer, inflammation, granuloma, lesion depth and fibrosis of colon in UC rats induced by TNBS /ethanol. There were obviously repairing effects for oral administration and colon-specific delivery on colon pathomorphology of UC rats induced by acetic acid and TNBS/ethanol, in particular, high dose of oral administration and the high dose and middle dose of colon-specific del ivery compared with model group (P<0.05). The effects of colon-specific delivery is superior to oral administration, comprehensive comparison between colon-specific delivery and oral administration in improving the colon pathomorphology of UC rats.4 Effects of oral administration and colon-specific delivery of New Chang-An-Kang on the free radicals and inflammatory cytokine in colon of UC ratsWe observed the effects of oral administration and colon-specific delivery on oxygen free radicals and nitric oxide free radicals in UC rats induced by acetic acid and TNBS/ethanol., while dectcting the inflammatory cytokine IL-8 contents and proto-oncogene (c-jun) protein expression in the colon, to presume the possible mechanism for oral administration and colon-specific delivery in treating the UC. The effects of colon-specific delivery were similar to oral administration in improving reduced SOD, GSH-PX in the colon of UC rats induced by acetic acid and TNBS/ethanol. The effects of colon-specific delivery were better than oral administration in improving increased MDA, NOS, iNOS, NO in the colon of UC rats induced by acetic acid and TNBS/ethanol. The effects of colon-specific delivery were better than oral administration in improving increased inflammatory cytokines IL-8 in the colon of UC rats induced by TNBS/ethanol. The effects of colon-specific delivery were better than oral administration in improving the c-jun protein expression, there being very significant reduction effects for high dose and middle dose of oral administration and different dose of colon-specific delivery compared with model group (P<0.01). We made correlation analysis between c-jun expression and NOS, iNOS, NO, IL-8, and the results showed that there was very significant correlation between c-jun expression and NOS, iNOS, IL-8. Comprehensive comparison between colon-specific delivery and oral administration in improving oxygen free radicals, nitric oxide free radicals and the inflammatory cytokine, the effects of colon-specific delivery is superior to oral administration. and speculated that Oral administration and Colon-Specific Drug Delivery of New Changankang may play their therapeutic role through inhibiting the inflammation cytokine, ect generation (such as iNOS, NO, IL-8) and c-jun activation to block the amplification of inflammation and play the anti-inflammatory effects. Conclusion:The effects of colon-specific delivery were all better than oral administration in improving fecal occult blood, the colon lesions, the colon pathomorphology and the free radicals and inflammatory cytokine in UC rats induced by acetic acid or TNBS/ethanol, which provided experimental basis for exploiting New Changankang as Colon-Specific Drug Delivery. In the aspect of the mechanism, Oral administration and Colon-Specific Drug Delivery of New Chang-An-Kang may play their therapeutic role through inhibiting the free radicals, inflammatory cytokine generation and c-jun activation to block the amplification of inflammation and play the anti-inflammatory effects.
Keywords/Search Tags:New Chang-An-Kang, Colon-Specific Drug Delivery, ulcerative colitis, stool consistency, fecal occult blood, colonic lesions, pathological morphology, free radicals, inflammatory cytokine
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