香鳞毛蕨药效物质基础研究和肤痒宁软膏的研制
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摘要
香鳞毛蕨(Dryopteris fragrans L.)为鳞毛蕨科鳞毛蕨属植物,主要生长在黑龙江省五大连池及华北地区。该药目前还未收入药典,但在民间广泛用做皮肤病药物且历史悠久。为将他开发研制成治疗皮肤病的新药,本课题重点对香鳞毛蕨(Dryopteris fragrans L.,DF)进行了生药学研究,部分药效学及药效物质基础化学研究。并以香鳞毛蕨为主要成分进行新药肤痒宁软膏的研制。
本研究首先探讨了DF对真菌和细菌的抑制作用,实验结果表明:DF无论对细菌和真菌都有较强的抑制作用,对真菌的抑制作用优于达克宁或与之相当,并确定了乙醇提取物为抗菌有效部位。采用鼠尾鳞片模型,观察肤痒宁软膏对银屑病样小鼠模型的影响,,实验结果显示:DF对银屑病具有一定的治疗作用;又建立了大鼠体癣动物模型,观察DF不同浓度对大鼠实验性体癣模型的治疗作用,实验结果显示:DF软膏剂低、中、高剂量组中大鼠病灶皮肤逆培养结果阴性率呈上升趋势,高剂量组与基质组的病灶皮肤逆培养结果有非常显著的差异(p<0.01),说明高剂量组对石膏样毛癣菌所致的大鼠试验性体癣具有确切疗效。其次又进行了生药学研究,揭示了药材其形态学和显微特征,为该药材收入药典做了必要的工作。化学方面的研究,对CO_2超临界萃取物进行了气相-质谱联用分析,鉴定了19种成分;并主要对有效部位化学成分利用反复硅胶、聚酰胺柱层析等方法,提取分离出13种化合物,利用理化性质和NMR、MS等技术对9种化合物结构进行了鉴定,经与文献报道对照,间苯三酚类衍生物3个,分别为Aspidin PB(Ⅰ)、Dryofragin(Ⅱ)、Aspidinol(Ⅲ);萜类化合物4个Albicanol(Ⅵ)、Albicany acetate(Ⅶ)、α-Cadinene(Ⅷ)和10-hydroxyl-15-oxo-α-cadinol(Ⅸ),还有2个植物甾醇类化合物β-谷甾醇(Ⅳ)和3-羟基-5,7-二烯胆甾烷(Ⅴ),其中2个化合物(Ⅴ和Ⅸ)是在该植物中首
Dryopteris fragrans (L. DF) is a plant pertaining to Dryopteris genus of Dryopteris family, mainly growing in Wudalianchi area of Heilongjiang Province and north China regions. Up to now, it has not been collected by any pharmacopoeia as a kind of herbal medicine, however it is used widely among the people as a medicine to cure skin diseases for a long time. To develop it into a new medicine to cure dermatosis, a pharmacognostic study of Dryopteris fragrans is made as a key point in the present research work and a partial pharmacodynamics and pharmacodynamic substance basic chemical study is also made. A new medicine Fu-Yang-Ning ointment is developed by use of Dryopteris fragrans as the main ingredient.In this paper, an exploratory study of inhibition effect of DF to epiphyte and bacteria is first made. The experimental results show that: DF enjoys a comparatively strong inhibition effect to either epiphyte or bacteria, especially the inhibition effect to epiphyte is superior or equivalent to Da-Ke-Ning (a kind of medicine) and the extract by use of ethanol is identified as the active principle to sterilize the bacteria. The model of scale on tails of mice is used to observe the effect of Fu-Yang-Ning ointment on model of mice suffering from psoriasis, the experimental results show that: DF has a certain curative effect to psoriasis. An animal model of ringworm on body of a rat is also established to observe the curative effect of DF in different concentrations to the model of ringworm on body of a rat under experiment. The experimental results show that: negative rate of focal skins of the rats in the groups giving a low, medium and high dosage of DF ointment exhibits an ascending tendency after an adverse culture and the focal skins of rats between the group giving a high dosage (2.0g/ml) and the matrical group
after an adverse culture display an extraordinarily obvious difference(p<0.01), which shows that a high dosage of DF ointment has really a curative effect to the ringworm on body of a rat under experiment resulted from gypsum-shaped Trichophyton. Afterwards, a pharmacognostic study of Dryopteris fragrans is made to reveal its morphological and microscopic characteristics, which is regarded as the necessary work for Dryopteris fragrans to be collected by any pharmacopoeia. Research work in chemistry: a gas phase and mass spectrum combination analysis of CO2 supercritical extract is made, 19 ingredients are identified; by use of reciprocal silica gel and polyamide columnar layer separation etc. methods, 10 compounds are extracted and separated as the main effective chemical ingredients; by making use of physiochemical properties and NMR and MS etc. techniques, the structures of 6 compounds are identified and after a reference is made to the reports in various literatures, 3 phloroglucinol derivants are found respectively as Aspidin PB, Dryofragin and Aspidinol , Aspidinol etc., 4 terpene-like compounds are found as Albicanol, Albicany acetate, a-Cadinene and 10- hydroxyl-15-oxo- a -cadinol etc., and including 2 vegetable steroid compounds as , among which 2 compounds are found for the first time in this plant.Finally, by using DF as the main ingredient, Fu-Yang-Ning ointment is developed, the preparation process is determined by use of the cross test method, the standard for quality of its preparation is specified and its stability test is made. It is scheduled to develop it into a new medicine for use in clinic.Based on Dryopteris fragrans being used as a medicine among the people for a long time and obvious effect to contain the bacteria and combining pharmacognostics, Chinese traditional herbal medicine chemistry and pharmacology with study on preparations
本研究首先探讨了DF对真菌和细菌的抑制作用,实验结果表明:DF无论对细菌和真菌都有较强的抑制作用,对真菌的抑制作用优于达克宁或与之相当,并确定了乙醇提取物为抗菌有效部位。采用鼠尾鳞片模型,观察肤痒宁软膏对银屑病样小鼠模型的影响,,实验结果显示:DF对银屑病具有一定的治疗作用;又建立了大鼠体癣动物模型,观察DF不同浓度对大鼠实验性体癣模型的治疗作用,实验结果显示:DF软膏剂低、中、高剂量组中大鼠病灶皮肤逆培养结果阴性率呈上升趋势,高剂量组与基质组的病灶皮肤逆培养结果有非常显著的差异(p<0.01),说明高剂量组对石膏样毛癣菌所致的大鼠试验性体癣具有确切疗效。其次又进行了生药学研究,揭示了药材其形态学和显微特征,为该药材收入药典做了必要的工作。化学方面的研究,对CO_2超临界萃取物进行了气相-质谱联用分析,鉴定了19种成分;并主要对有效部位化学成分利用反复硅胶、聚酰胺柱层析等方法,提取分离出13种化合物,利用理化性质和NMR、MS等技术对9种化合物结构进行了鉴定,经与文献报道对照,间苯三酚类衍生物3个,分别为Aspidin PB(Ⅰ)、Dryofragin(Ⅱ)、Aspidinol(Ⅲ);萜类化合物4个Albicanol(Ⅵ)、Albicany acetate(Ⅶ)、α-Cadinene(Ⅷ)和10-hydroxyl-15-oxo-α-cadinol(Ⅸ),还有2个植物甾醇类化合物β-谷甾醇(Ⅳ)和3-羟基-5,7-二烯胆甾烷(Ⅴ),其中2个化合物(Ⅴ和Ⅸ)是在该植物中首
Dryopteris fragrans (L. DF) is a plant pertaining to Dryopteris genus of Dryopteris family, mainly growing in Wudalianchi area of Heilongjiang Province and north China regions. Up to now, it has not been collected by any pharmacopoeia as a kind of herbal medicine, however it is used widely among the people as a medicine to cure skin diseases for a long time. To develop it into a new medicine to cure dermatosis, a pharmacognostic study of Dryopteris fragrans is made as a key point in the present research work and a partial pharmacodynamics and pharmacodynamic substance basic chemical study is also made. A new medicine Fu-Yang-Ning ointment is developed by use of Dryopteris fragrans as the main ingredient.In this paper, an exploratory study of inhibition effect of DF to epiphyte and bacteria is first made. The experimental results show that: DF enjoys a comparatively strong inhibition effect to either epiphyte or bacteria, especially the inhibition effect to epiphyte is superior or equivalent to Da-Ke-Ning (a kind of medicine) and the extract by use of ethanol is identified as the active principle to sterilize the bacteria. The model of scale on tails of mice is used to observe the effect of Fu-Yang-Ning ointment on model of mice suffering from psoriasis, the experimental results show that: DF has a certain curative effect to psoriasis. An animal model of ringworm on body of a rat is also established to observe the curative effect of DF in different concentrations to the model of ringworm on body of a rat under experiment. The experimental results show that: negative rate of focal skins of the rats in the groups giving a low, medium and high dosage of DF ointment exhibits an ascending tendency after an adverse culture and the focal skins of rats between the group giving a high dosage (2.0g/ml) and the matrical group
after an adverse culture display an extraordinarily obvious difference(p<0.01), which shows that a high dosage of DF ointment has really a curative effect to the ringworm on body of a rat under experiment resulted from gypsum-shaped Trichophyton. Afterwards, a pharmacognostic study of Dryopteris fragrans is made to reveal its morphological and microscopic characteristics, which is regarded as the necessary work for Dryopteris fragrans to be collected by any pharmacopoeia. Research work in chemistry: a gas phase and mass spectrum combination analysis of CO2 supercritical extract is made, 19 ingredients are identified; by use of reciprocal silica gel and polyamide columnar layer separation etc. methods, 10 compounds are extracted and separated as the main effective chemical ingredients; by making use of physiochemical properties and NMR and MS etc. techniques, the structures of 6 compounds are identified and after a reference is made to the reports in various literatures, 3 phloroglucinol derivants are found respectively as Aspidin PB, Dryofragin and Aspidinol , Aspidinol etc., 4 terpene-like compounds are found as Albicanol, Albicany acetate, a-Cadinene and 10- hydroxyl-15-oxo- a -cadinol etc., and including 2 vegetable steroid compounds as , among which 2 compounds are found for the first time in this plant.Finally, by using DF as the main ingredient, Fu-Yang-Ning ointment is developed, the preparation process is determined by use of the cross test method, the standard for quality of its preparation is specified and its stability test is made. It is scheduled to develop it into a new medicine for use in clinic.Based on Dryopteris fragrans being used as a medicine among the people for a long time and obvious effect to contain the bacteria and combining pharmacognostics, Chinese traditional herbal medicine chemistry and pharmacology with study on preparations
引文
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