CN105078963A - α-生育酚在制备治疗血吸虫病药物中的应用 - Google Patents
α-生育酚在制备治疗血吸虫病药物中的应用 Download PDFInfo
- Publication number
- CN105078963A CN105078963A CN201510630548.9A CN201510630548A CN105078963A CN 105078963 A CN105078963 A CN 105078963A CN 201510630548 A CN201510630548 A CN 201510630548A CN 105078963 A CN105078963 A CN 105078963A
- Authority
- CN
- China
- Prior art keywords
- tocopherol
- alpha
- schistosomicide
- schistosome
- medicine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 title claims abstract description 70
- 229940087168 alpha tocopherol Drugs 0.000 title claims abstract description 35
- 229960000984 tocofersolan Drugs 0.000 title claims abstract description 35
- 239000002076 α-tocopherol Substances 0.000 title claims abstract description 35
- 235000004835 α-tocopherol Nutrition 0.000 title claims abstract description 35
- 239000003814 drug Substances 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 229940079593 drug Drugs 0.000 title abstract description 5
- 201000004409 schistosomiasis Diseases 0.000 title abstract 3
- 235000013601 eggs Nutrition 0.000 claims abstract description 12
- LAOOXBLMIJHMFO-UHFFFAOYSA-N 1-[2-(diethylamino)ethylamino]-4-methylthioxanthen-9-one;hydron;chloride Chemical compound Cl.S1C2=CC=CC=C2C(=O)C2=C1C(C)=CC=C2NCCN(CC)CC LAOOXBLMIJHMFO-UHFFFAOYSA-N 0.000 claims description 47
- 230000001843 schistosomicidal effect Effects 0.000 claims description 47
- 108010000912 Egg Proteins Proteins 0.000 claims description 12
- 102000002322 Egg Proteins Human genes 0.000 claims description 12
- 210000004681 ovum Anatomy 0.000 claims description 12
- 239000003513 alkali Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 abstract description 14
- 241000242678 Schistosoma Species 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 8
- 230000001850 reproductive effect Effects 0.000 abstract description 8
- 238000003304 gavage Methods 0.000 abstract description 7
- 238000002651 drug therapy Methods 0.000 abstract description 2
- 210000000056 organ Anatomy 0.000 abstract description 2
- 230000017448 oviposition Effects 0.000 abstract description 2
- 230000000877 morphologic effect Effects 0.000 abstract 1
- 230000001717 pathogenic effect Effects 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- 239000011732 tocopherol Substances 0.000 description 23
- 229960001295 tocopherol Drugs 0.000 description 23
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 239000002904 solvent Substances 0.000 description 11
- 208000015181 infectious disease Diseases 0.000 description 8
- 210000002784 stomach Anatomy 0.000 description 7
- 210000000582 semen Anatomy 0.000 description 6
- 241000754688 Cercaria Species 0.000 description 5
- 241000242677 Schistosoma japonicum Species 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 4
- 239000007952 growth promoter Substances 0.000 description 4
- CDOSHBSSFJOMGT-UHFFFAOYSA-N linalool Chemical compound CC(C)=CCCC(C)(O)C=C CDOSHBSSFJOMGT-UHFFFAOYSA-N 0.000 description 4
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 3
- FSVJFNAIGNNGKK-UHFFFAOYSA-N 2-[cyclohexyl(oxo)methyl]-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4-one Chemical compound C1C(C2=CC=CC=C2CC2)N2C(=O)CN1C(=O)C1CCCCC1 FSVJFNAIGNNGKK-UHFFFAOYSA-N 0.000 description 3
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 241001442514 Schistosomatidae Species 0.000 description 3
- HZYXFRGVBOPPNZ-UHFFFAOYSA-N UNPD88870 Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)=CCC(CC)C(C)C)C1(C)CC2 HZYXFRGVBOPPNZ-UHFFFAOYSA-N 0.000 description 3
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 3
- 239000012531 culture fluid Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 210000004392 genitalia Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229960002957 praziquantel Drugs 0.000 description 3
- HCXVJBMSMIARIN-PHZDYDNGSA-N stigmasterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)/C=C/[C@@H](CC)C(C)C)[C@@]1(C)CC2 HCXVJBMSMIARIN-PHZDYDNGSA-N 0.000 description 3
- 229940032091 stigmasterol Drugs 0.000 description 3
- BFDNMXAIBMJLBB-UHFFFAOYSA-N stigmasterol Natural products CCC(C=CC(C)C1CCCC2C3CC=C4CC(O)CCC4(C)C3CCC12C)C(C)C BFDNMXAIBMJLBB-UHFFFAOYSA-N 0.000 description 3
- 235000016831 stigmasterol Nutrition 0.000 description 3
- 239000001490 (3R)-3,7-dimethylocta-1,6-dien-3-ol Substances 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 2
- CDOSHBSSFJOMGT-JTQLQIEISA-N (R)-linalool Natural products CC(C)=CCC[C@@](C)(O)C=C CDOSHBSSFJOMGT-JTQLQIEISA-N 0.000 description 2
- 240000005636 Dryobalanops aromatica Species 0.000 description 2
- 241000892865 Heros Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000242680 Schistosoma mansoni Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229930007744 linalool Natural products 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000008064 Corticotropin Receptors Human genes 0.000 description 1
- 108010074311 Corticotropin Receptors Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000008238 LHRH Receptors Human genes 0.000 description 1
- 108010021290 LHRH Receptors Proteins 0.000 description 1
- 102000003840 Opioid Receptors Human genes 0.000 description 1
- 108090000137 Opioid Receptors Proteins 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 241000242683 Schistosoma haematobium Species 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 108050001286 Somatostatin Receptor Proteins 0.000 description 1
- 102000011096 Somatostatin receptor Human genes 0.000 description 1
- 206010043298 Testicular atrophy Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 102000001307 androgen receptors Human genes 0.000 description 1
- 108010080146 androgen receptors Proteins 0.000 description 1
- 201000010788 atrophy of testis Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000011217 control strategy Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000745 gonadal hormone Substances 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 108091005720 plant hormone receptors Proteins 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 238000012876 topography Methods 0.000 description 1
- 208000037972 tropical disease Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 125000001020 α-tocopherol group Chemical group 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及药物治疗技术领域,具体公开了α-生育酚在制备治疗血吸虫病药物中的应用,通过灌胃α-生育酚给小鼠,其体内的血吸虫尾蚴有不同程度的发育不成熟的现象,因此,其可以抑制血吸虫发育,本发明还利用形态学和超微结构观察揭示α-生育酚对血吸虫发育与生殖的作用,结果发现α-生育酚抑制血吸虫生殖器官发育,从而减少血吸虫在宿主体内的产卵。虫卵是血吸虫的主要致病因子,α-生育酚可明显抑制血吸虫生殖发育及产卵,因此,可用于制备治疗血吸虫病的药物,另外,α-生育酚结构简单,无毒副作用,具有广泛的应用价值。
Description
技术领域
本发明涉及药物治疗技术领域,更具体地,涉及α-生育酚在制备治疗血吸虫病药物中的应用。
背景技术
血吸虫病是严重危害人类健康的全球第二大热带病,也是热带亚热带流行区国家重点防治的重大传染病之一。血吸虫病是一种免疫性疾病,虫卵是血吸虫病的主要致病因子和关键传播环节。血吸虫造成的病理损伤主要是因虫卵沉积在宿主重要脏器,如肝脏和肠壁(日本血吸虫、曼氏血吸虫、湄公血吸虫和间插血吸虫虫卵)、膀胱(埃及血吸虫虫卵)形成的肉芽肿反应以及持续慢性感染引起的组织损伤修复过度,进而形成的纤维化。
与其他多数的雌雄同体的吸虫不同的是,血吸虫属于雌雄异体,入侵宿主体内的单性血吸虫(单性雌虫或单性雄虫)均不能发育成熟,必需获得对方提供的性激素才能发育成熟,一直以来这一现象让许多研究者认为,血吸虫的发育成熟与生殖决定于其自身因素,但是近期血吸虫基因组测序研究显示:血吸虫表膜具有生长抑素受体、促黄体生成激素释放激素受体、促肾上腺皮质激素受体、β-内啡肽受体、睾酮受体等十余种激素受体,缺乏相应的激素编码基因,强烈提示血吸虫生殖发育还可能受宿主激素水平调控。已有流行病学数据及实验室结果表明,血吸虫感染可影响宿主的的生长发育,降低宿主的生长因子、激素等水平,这也是血吸虫对宿主损害的主要表现之一;另一方面,宿主也会对血吸虫产生作用。
吡喹酮是对多种血吸虫均有显著治疗效果的药物,但吡喹酮的长期反复使用以致出现耐药虫株的潜在风险,且吡喹酮只能杀虫但对沉积宿主组织中的虫卵无效。因此,为消除血吸虫病,除了积极筛查、治疗患者病畜,避免接触疫水外,阻断血吸虫产卵以及虫卵的发育成熟是一种新的有效防治策略。
发明内容
本发明所要解决的技术问题是克服现有技术存在的上述缺陷,提供α-生育酚在制备治疗血吸虫病药物中的应用。
本发明的目的是通过以下技术方案予以实现:
α-生育酚在制备治疗/预防血吸虫病药物中的应用。
申请人通过实验研究发现,经灌胃α-生育酚的小鼠,其体内的血吸虫尾蚴有不同程度的发育不成熟的现象,因此,其可以抑制血吸虫发育,本发明还利用形态学和超微结构观察揭示α-生育酚对血吸虫发育与生殖的作用,结果发现α-生育酚影响血吸虫生殖器官发育,从而抑制血吸虫在体内的扩增。
因此,本发明还提供α-生育酚在制备抑制血吸虫发育成熟的药物中的应用。
另外,本发明还提供α-生育酚在制备抑制血吸虫产卵的药物中的应用。
同时,本发明还提供α-生育酚在制备减少血吸虫虫卵数量的药物中的应用。
本发明还提供一种具有抑制血吸虫发育成熟的药物,该药物含有α-生育酚,或其衍生物,或其与酸或碱形成的可药用的盐。
或者,本发明提供一种用于预防或/和治疗血吸虫病的药物,该药物含有α-生育酚,或其衍生物,或其与酸或碱形成的可药用的盐。
优选地,本发明所述药物还包括药学上可接受的载体和/或赋形剂。
与现有技术相比,本发明具有以下有益效果:
本发明提供了α-生育酚在制备治疗血吸虫病药物中的应用,通过灌胃α-生育酚给小鼠,其体内的血吸虫尾蚴有不同程度的发育不成熟的现象,因此,其可以抑制血吸虫发育,本发明还利用形态学和超微结构观察揭示α-生育酚对血吸虫发育与生殖的作用,结果发现α-生育酚抑制血吸虫生殖器官发育,从而减少血吸虫在宿主体内的产卵。虫卵是血吸虫的主要致病因子,α-生育酚可明显抑制血吸虫生殖发育及产卵,因此,可用于制备治疗血吸虫病的药物,另外,α-生育酚结构简单,无毒副作用,具有广泛的应用价值。
附图说明
图1为血吸虫成熟虫体和α-生育酚作用后未成熟虫体电镜照片与体长数据图;其中,图1a为解剖镜下图,左侧为雌性血吸虫,较长的为发育成熟虫体,短的为α-生育酚作用后未发育成熟虫体;右侧为雄性血吸虫,较长的为发育成熟虫体,短的为α-生育酚作用后未发育成熟虫体;图1b为体长数据图,其中,MF:成熟雌虫,IF:未成熟雌虫;MM:成熟雄虫,IM:未成熟雄虫,***:与成熟雌虫相比,P<0.001;###:与成熟雄虫相比,P<0.001。
图2为ɑ-生育酚对血吸虫成熟虫体产卵的作用(体外实验);其中,图2a为成虫产卵显微镜下图,图2b为不同处理条件下成虫产卵数量图。
图3为ɑ-生育酚对血吸虫雌虫生殖器官发育的影响。
图4为ɑ-生育酚对血吸虫雄虫生殖器官发育的影响。
具体实施方式
下面通过实施例对本发明进一步具体描述。下述所使用的实验方法若无特殊说明,均为本技术领域现有常规的方法,所使用的配料或材料,如无特殊说明,均为通过商业途径可得到的配料或材料;本发明不应限制于实施例范围。
实施例1ɑ-生育酚抑制血吸虫生长发育的剂量依赖性
ɑ-生育酚和豆甾醇(对照药物)均购自sigma公司,六周龄Balb/c小鼠购于中山大学实验动物中心(中国,广州),小鼠感染日本血吸虫(中国大陆株)尾蚴用以检测ɑ-生育酚对血吸虫生长发育的影响。
实验过程为:60只小鼠(雌雄各半)经裸露腹部皮肤感染尾蚴(30±1条/鼠)并随机分为6组(每组10只,5只雄,5只雌),对照组1:小鼠经口灌胃100ul生理盐水;对照组2小鼠灌胃100μl溶剂(不含ɑ-生育酚的花生油);对照组3小鼠灌胃口服100μl溶剂(不含ɑ-生育酚的花生油)+20mg/kg/d豆甾醇;处理组1:小鼠灌胃喂食100μl溶剂(不含ɑ-生育酚的花生油)+1mg/kg/dɑ-生育酚;处理组2:小鼠灌胃喂食100μl溶剂(不含ɑ-生育酚的花生油)+15mg/kg/dɑ-生育酚;助理组3:小鼠灌胃喂食100μl溶剂(不含ɑ-生育酚的花生油)+20mg/kg/dɑ-生育酚。所有组动物的喂食都从尾蚴感染那天起,每天喂食直到感染小鼠被处死,感染尾蚴42d后经麻醉法处死,虫体及组织采样按照我们已发表研究的程序进行(YangF,LongE,WenJ,etal.Linalool,derivedfromCinnamomumcamphora(L.)Preslleafextracts,possessesmolluscicidalactivityagainstOncomelaniahupensisandinhibitsinfectionofSchistosomajaponicum.ParasitVectors.2014,7:407.)。每组虫体减少率计算公式如下:虫体减少率(%)=(1-实验组小鼠体内平均虫体数/对照组小鼠体内平均虫体数)×100%。
实验结果:Balb/c小鼠感染日本血吸虫42天后,所以处理组间体内虫体总数未有显著差异;对照组1、对照组2、对照组3和处理组1的小鼠体内血吸虫虫体均发育成熟,处理组2和处理组3这两组雌、雄未成熟虫体数目均未有统计学差异;另外,该两组小鼠体内发育成熟的雄性虫体体长为9.70mm,雌性成虫体长为12.35mm;而未发育成熟的雄虫长为4.36mm,未发育成熟雌虫体长为7.18mm(图1)。未发育成熟雌虫、雄虫体长均显著短于正常发育的雌虫和雄虫,具体见表1。
实施例2ɑ-生育酚组对血吸虫生长发育的时间依赖性
实验材料同实施例1,实验过程为:60只小鼠(雌雄各半)感染尾蚴(30±1条/鼠)并随机分为6组(每组10只,5只雄,5只雌),对照组1:小鼠灌胃喂100μl生理盐水;对照组2:小鼠灌胃100μl溶剂(不含ɑ-生育酚的花生油);处理组1:于小鼠感染第1d(皮肤童虫期)开始灌胃喂食100ul溶剂+20mg/kg/dɑ-生育酚;处理组2:于小鼠感染第3d(肺部童虫期)开始灌胃喂食100μl溶剂+20mg/kg/dɑ-生育酚;处理组3:于小鼠感染第11d(肝门-肠静脉童虫期)开始灌胃喂食100μl溶剂+20mg/kg/dɑ-生育酚;处理组4:于小鼠感染第21d(成虫期)开始灌胃喂食100μl溶剂+20mg/kg/dɑ-生育酚;感染尾蚴42d后经麻醉法处死,虫体及组织采样按照我们已发表研究的程序进行(YangF,LongE,WenJ,etal.Linalool,derivedfromCinnamomumcamphora(L.)Preslleafextracts,possessesmolluscicidalactivityagainstOncomelaniahupensisandinhibitsinfectionofSchistosomajaponicum.ParasitVectors.2014,7:407.)。每组虫体减少率计算公式如下:虫体减少率(%)=(1-实验组小鼠体内平均虫体数/对照组小鼠体内平均虫体数)×100%,实验结果如表2。
实施例3分析ɑ-生育酚对成虫产卵的影响
一、虫卵计数
从来自正常感染组小鼠收集了成虫,如前人报道描述进行体外培养(MannVH,MoralesME,RinaldiG,etal.CultureforgeneticmanipulationofdevelopmentalstagesofSchistosomamansoni.Parasitology.2010,137(3):451-462.)。60对合抱的雌雄成虫随机分布6组(每组10对),分别放入加有2ml培养液的12孔细胞培养板中(1对/孔),于37度,5%CO2下进行培养。
分组如下:对照组1:在培养基(含10%胎牛血清的DMEM培养基)中加入100μl培养基;对照组2:培养基中加入100μl溶剂(Tween80);对照组3:培养基中加入100μlTween80+20mg/ml豆甾醇,处理组1:100μlTween80+1mg/mlɑ-生育酚;处理组2:100μlTween80+5mg/mlɑ-生育酚;处理组3:100μlTween80+20mg/mlɑ-生育酚;每6h换一次培养液,将每天换取的所有培养液进行离心(5000rpm,10min),沉淀用100μlPBS重悬后,涂载玻片,镜下计数虫卵,连续计数每对虫3d的产卵量,结果如图2。
二、虫体回收及组织取样
醋酸洋红法染色20条成熟虫体和20条未成熟虫体,解剖镜下测定体长并观察虫体生殖器官的发育情况(雄虫:睾丸和抱雌沟;雌虫:子宫、卵巢和卵黄腺)。此外,将虫体连续横向切片后,显微镜下检测成熟和未成熟雌虫、雄虫生殖器官的显微结构,进一步利用扫描电镜检测了虫体体表结构。
结果如图3、4,虫体染色和生殖器官切片染色结果显示:与正常雄性血吸虫成虫相比,未发育成熟雄性成虫不仅睾丸数目减少,睾丸萎缩,且抱雌沟明显变小,变浅;与正常雌性血吸虫成虫相比,未发育成熟的雌性成虫卵巢、子宫和卵黄腺均显著变小,子宫内虫卵稀疏或没有虫卵。
Claims (7)
1.α-生育酚在制备治疗/预防血吸虫病药物中的应用。
2.α-生育酚在制备抑制血吸虫发育成熟的药物中的应用。
3.α-生育酚在制备抑制血吸虫产卵的药物中的应用。
4.α-生育酚在制备减少血吸虫虫卵数量的药物中的应用。
5.一种具有抑制血吸虫发育成熟的药物,其特征在于,含有α-生育酚,或其衍生物,或其与酸或碱形成的可药用的盐。
6.一种用于预防或/和治疗血吸虫病的药物,其特征在于,含有α-生育酚,或其衍生物,或其与酸或碱形成的可药用的盐。
7.根据权利要求5或6所述的药物,其特征在于,还包括药学上可接受的载体和/或赋形剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510630548.9A CN105078963B (zh) | 2015-09-29 | 2015-09-29 | α-生育酚在制备治疗血吸虫病药物中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510630548.9A CN105078963B (zh) | 2015-09-29 | 2015-09-29 | α-生育酚在制备治疗血吸虫病药物中的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105078963A true CN105078963A (zh) | 2015-11-25 |
CN105078963B CN105078963B (zh) | 2018-06-22 |
Family
ID=54560900
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510630548.9A Active CN105078963B (zh) | 2015-09-29 | 2015-09-29 | α-生育酚在制备治疗血吸虫病药物中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105078963B (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1260713A (zh) * | 1997-06-27 | 2000-07-19 | 阿斯特拉公司 | 由生育酚稳定的用于吸入的前体脂质体粉 |
CN1529701A (zh) * | 2000-02-11 | 2004-09-15 | �������о�����չ˽������˾ | 生育酚、生育三烯酚、其它苯并二氢吡喃和侧链衍生物,及其用途 |
-
2015
- 2015-09-29 CN CN201510630548.9A patent/CN105078963B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1260713A (zh) * | 1997-06-27 | 2000-07-19 | 阿斯特拉公司 | 由生育酚稳定的用于吸入的前体脂质体粉 |
CN1529701A (zh) * | 2000-02-11 | 2004-09-15 | �������о�����չ˽������˾ | 生育酚、生育三烯酚、其它苯并二氢吡喃和侧链衍生物,及其用途 |
Non-Patent Citations (5)
Title |
---|
NEGA BERHE, ET AL.: "REDUCED SERUM CONCENTRATIONS OF RETINOL AND _-TOCOPHEROL AND HIGH CONCENTRATIONS OF HYDROPEROXIDES ARE ASSOCIATED WITH COMMUNITY LEVELS OF S. MANSONI INFECTION AND SCHISTOSOMAL PERIPORTAL FIBROSIS IN ETHIOPIAN SCHOOL CHILDREN", 《AM. J. TROP. MED. HYG.》 * |
宗道明,等: "维生素E 治疗血吸虫病肝纤维化的临床研究", 《中国寄生虫病防治杂志》 * |
战宇: "《食品分子生物学》", 30 September 2005, 中国轻工业出版社 * |
牛丽文: "瘦素在日本血吸虫病肝纤维化中的作用及分子机制的实验研究", 《中国博士学位论文全文数据库 医药卫生科技辑》 * |
牛丽文等: "维生素E对小鼠日本血吸虫病肝纤维化的治疗作用及其机制", 《第四军医大学学报》 * |
Also Published As
Publication number | Publication date |
---|---|
CN105078963B (zh) | 2018-06-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Noaman et al. | The first record of Argulus foliacesus (Crustacea: Branchiura) infestation on lionhead goldfish (Carassius auratus) in Iran | |
Kohn et al. | Helminths parasites of freshwater fishes from Pirassununga, SP, Brazil | |
CN102151256B (zh) | 原儿茶酸在制备防治畜禽病毒感染性疾病的药物中的应用 | |
Hanson et al. | Alloherpesviruses of fish | |
Jeong et al. | Demonstration of the second intermediate hosts of Clinostomum complanatum in Korea | |
Hu et al. | Evaluation on the antiviral effect of natural product arctigenin against Micropterus salmoides rhabdovirus (MSRV) in vitro and in vivo | |
Jin et al. | Histopathological changes of Korea cultured olive flounder, Paralichthys olivaceus due to scuticociliatosis caused by histophagous scuticociliate, Philasterides dicentrarachi | |
Kamel et al. | Ultrastructural alterations in Schistosoma mansoni juvenile and adult male worms after in vitro incubation with primaquine | |
Ali et al. | Schistosoma mansoni: Antiparasitic effects of orally administered Nigella sativa oil and/or Chroococcus turgidus extract | |
CN104353058A (zh) | 商陆抗病毒蛋白冻干粉复合剂及其制备方法 | |
Wei et al. | Histological alterations and immune response in the crayfish Procambarus clarkii given rVP28-incorporated diets | |
CN111265521B (zh) | 小分子化合物sjb2-043作为抑制马立克氏病毒药物的新用途 | |
Zhang et al. | Further studies on an intermediate host murine model showing that a primary Echinococcus granulosus infection is protective against subsequent oncospheral challenge | |
CN105078963A (zh) | α-生育酚在制备治疗血吸虫病药物中的应用 | |
Mahmoud et al. | Artemether as adjuvant therapy to praziquantel in murine Egyptian schistosomiasis mansoni | |
CN106309455A (zh) | 贝母辛的用途 | |
CN106562970B (zh) | Gs-9620的用途 | |
Brasil-Sato et al. | Neoechinorhynchus pimelodi sp. n.(Eoacanthocephala, Neoechinorhynchidae) parasitizing Pimelodus maculatus Lacépede," mandi-amarelo"(Siluroidei, Pimelodidae) from the basin of the São Francisco river, três marias, Minas Gerais, Brazil | |
Andreassen et al. | Hymenolepis microstoma: direct life cycle in immunodeficient mice | |
CN113786404A (zh) | 溴酚-吡唑啉化合物在治疗禽冠状病毒疾病中的应用 | |
Scholz | Development of Khawia sinensis Hsii, 1935 (Cestoda: Caryophyllidea) in the fish host | |
CN106344549A (zh) | 大黄酸在制备预防和/或治疗手足口病药物中的应用 | |
WO2019144874A1 (zh) | 寨卡病毒减毒株在治疗脑胶质瘤中的应用 | |
Matvienko et al. | Replication of Infectious Pancreatic Necrosis Virus in Different Cell Lines and in Rainbow Trout Fingerlings | |
NoLAN et al. | Transmammary transmission of Strongyloides venezuelensis |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |