WO2007059685A1 - Calycosine d'astragalus a fonction de resistance contre le coxackievirus - Google Patents
Calycosine d'astragalus a fonction de resistance contre le coxackievirus Download PDFInfo
- Publication number
- WO2007059685A1 WO2007059685A1 PCT/CN2006/002910 CN2006002910W WO2007059685A1 WO 2007059685 A1 WO2007059685 A1 WO 2007059685A1 CN 2006002910 W CN2006002910 W CN 2006002910W WO 2007059685 A1 WO2007059685 A1 WO 2007059685A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- drug
- virus
- present
- viral myocarditis
- mice
- 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.)
- Ceased
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Definitions
- the invention relates to extracting active ingredients from traditional Chinese medicines, and is proved to be effective for treating viral myocarditis by pharmacological tests, more specifically, extracting and isolating an isoflavone active ingredient from the radix astragali or other traditional Chinese medicines - verapamil isotope - 7 - oxygen - D - Calycosin 7-0- ⁇ -D- glucoside, which can be used in the preparation of a drug against Coxsackie virus and a disease caused by Coxsackie virus.
- Background technique
- Coxsackievirus can cause a variety of diseases, such as viral myocarditis, epidemic chest pain, aseptic encephalitis, meningitis, Keshan disease and viral epilepsy, which seriously endanger human health.
- Coxsackie virus diseases such as viral myocarditis
- the main method for clinical treatment of Coxsackie virus diseases such as viral myocarditis is to use common antiviral drugs, immunosuppressants, interferons and cardiomyocyte nutrients, but the curative effect is not satisfactory.
- Patent CN01126608. 2 discloses that isoflavones and glycoside have good anti-ischemic effect; Patent CN00119451. 8 discloses the use of astragaloside IV in the treatment of viral myocarditis; patent CN01126609. 0 discloses that astragaloside has anti-myocardial fibrosis. No reports of vermiculone isoflavone-7-oxo- ⁇ -D-glucopyranoside against Coxsackie Virus and treatment of viral myocarditis. Summary of the invention
- the object of the present invention is to overcome the shortcomings of the conventional multi-flavored decoction, and to chemically separate the isoflavone active ingredient - the isoflavone - 7-oxo- ⁇ -D-glucopyranoside, from the astragalus or other traditional Chinese medicine.
- Pharmacological tests are applied to the preparation of anti-coxsackie virus and drugs for the treatment of viral myocarditis.
- the medicament of the present invention can be prepared by the following method: After pulverization of astragalus or other Chinese medicinal materials, three times (2 hours, one hour, one hour) of refluxing with 70% ethanol, filtering, combining the filtrates, recovering the solvent under reduced pressure, and concentrating to an alcohol-free taste. , obtained xanthine extract I.
- the extract I was mixed with water and filtered, and the filtrate was adsorbed with a macroporous resin, and the impurities were eluted with water, and then eluted with 70% ethanol, and the eluate was concentrated under reduced pressure to obtain an extract II.
- the extract II was separated by silica gel column chromatography, eluting with a gradient of chloroform-methanol, and the same fractions were combined, evaporated to dryness, and the solvent was evaporated to dryness, and the mixture was allowed to stand, and the white powder was precipitated and filtered to obtain white powdery crystals. That is, the compound of the present invention, carophyllin 7-O- ⁇ -D-glucoside, is obtained.
- the structure is as follows:
- the molecular formula is 22 ⁇ .
- the molecular weight is 446, and the chemical name is 3'-hydroxy-4'-methoxyisoflavone-7-oxo- ⁇ -D-glucopyranoside.
- the isoflavone-7-oxo- ⁇ -D-glucopyranoside obtained by the above method is first tested for efficacy.
- results of the in vitro antiviral test performed on primary cultured cardiomyocytes indicate the TC 5 of the drug of the present invention.
- the therapeutic index (TI) was 10.00, indicating that the drug of the present invention has a significant inhibitory effect on CVB 3 virus in vitro.
- a model of viral myocarditis was established by intraperitoneal vaccination with Coxsackie B3 virus in Balb/c mice.
- the drug-administered 40 mg/kg and 20 mg/kg were administered intragastrically in the high- and low-dose groups.
- the model control group and the normal control group were administered.
- the rats were given the same amount of normal saline for 12 days. On the 15th day, the mice were observed for color, eating, and death. The results showed that the two dose groups were significantly reduced by the Coxsackie B 3 virus.
- the mortality of mice caused by viral myocarditis significantly reduced the heart index of mice with viral myocarditis, and effectively decreased the serum levels of LDH and GOT in mice with viral myocarditis caused by Coxsackie B3 virus.
- test method refers to "Modern Pharmacological Experimental Methods" (Volume 2, P 1425 , edited by Zhang Juntian, Beijing Medical University, China Union Medical University, United Press, 1998 edition). ' detailed description
- Example 1 Preparation of the medicament of the present invention Take the Astragalus membranaceus, pulverize, extract three times with 70% ethanol reflux (2 hours, 1 hour, 1 hour), filter, combine the filtrate, recover the solvent under reduced pressure, and concentrate to a non-alcoholic taste to obtain a xanthine extract I.
- the extract I was mixed with water and filtered, and the filtrate was adsorbed with a macroporous resin (AB-8 type), and the impurities were eluted with water, and then eluted with 70% ethanol, and the eluate was concentrated under reduced pressure to obtain an extract II.
- a macroporous resin AB-8 type
- Extract II was chromatographed on a 200-300 mesh silica gel column, eluting with chloroform-methanol gradient, TLC detection, 10% sulfuric acid-ethanol color development, combining the same fractions, evaporated to dryness, methanol hot solution, standing, white floc The precipitated material was filtered off with suction to give a white powdery crystal.
- Example 2 Effect of the drug of the present invention on coxsackievirus (CV)-infected cardiomyocytes (in vitro)
- Normal control group Add culture medium per well 1. 0ml;
- Dosing group A gradient dilution of the drug solution of the present invention was added. OmL/well, four replicate wells per dilution.
- the cell survival was observed under an inverted phase contrast microscope, and the TC 5 of the primary cultured cardiomyocytes of the drug of the present invention was calculated according to the Reed-Mench method. .
- Normal control group adding culture solution per well l.
- the administration group 0.2 ml of CVB 3 virus solution (TCID ⁇ IO" 4 - 56 , 10 -5 dilution) was added to each well, and the mixture was incubated for 1 hour, the supernatant was discarded, and washed three times with PBS solution, and the gradient dilution was added to the present invention.
- Drug solution l. OraL/well, four replicate wells per dilution.
- Cardiomyocytes will slowly die in culture, pseudopods break, cells shrink, round, and the refractive index increases. The cell death was significantly increased after being infected by the virus, and a large area of necrosis was observed. If the drug is effective after administration, the mortality of the virus-infected cells can be reduced.
- the IC 5 of the drug of the present invention against primary cultured cardiomyocytes was calculated according to the Reed- Muench method. . ⁇
- TC 5 of the medicament of the invention It is 177. 84 ug/ml, and 1 for CVB 3 virus.
- the therapeutic index (TI) was 10.00, which was 17.78 ug/ml, indicating that the drug of the present invention has a significant inhibitory effect on CVB 3 virus in vitro.
- Example 3 Effect of the drug of the present invention on mortality of mice with viral myocarditis (in vivo)
- the drug of the present invention was divided into two dose groups, and Balb/c mice were randomly divided into 4 groups:
- Normal control group intraperitoneal inoculation 0. 1ml normal saline, daily, equal amount of normal saline;
- the drug group I of the present invention has a high dose: the same method as the above method of inoculation of CVB 3 virus solution, the same day, the drug solution of the invention 40mg / kg • d, continuous administration for 12 days;
- the pharmaceutical group II of the present invention has a low dose: the same as the third group method, the drug solution of the present invention is administered at a dose of 20 mg/kg*d, and is continuously administered for 12 times;
- mice After observing for 15 days, various conditions such as mouse color and eating were observed, and the mortality of each group of mice was counted.
- Virus control group 15 40% (6) 'The drug group of the invention I 15 26. 7% (4) *
- Example 4 Effect of the drug of the present invention on heart index of mice with viral myocarditis (in vivo)
- mice were grouped and dosed as in Example 2. After 12 days of continuous administration, on the 15th day, all the mice were dissected. The body weight of the mouse was weighed before dissection, and then the heart weight was weighed.
- Heart index heart weight / weight
- the heart index can be used to measure the degree of heart disease. The greater the heart index, the more severe the heart disease becomes.
- Virus control group 5. 60 ⁇ 0. 73
- the drug group of the invention I 5. 05 ⁇ 0. 63*
- the medicament of the invention II 5. 14 ⁇ 0. 58*
- the drug-administered group is compared with the virus group: * p ⁇ 0. 05, ** p ⁇ 0. 01
- Example 5 Effect of the drug of the present invention on serum LDH and GOT contents in mice with viral myocarditis (in vivo) Balb/c mice were grouped and administered at the same dose as in Example 2. After 12 days of continuous administration, on the 15th day, blood was taken from the eyeball, and serum was centrifuged to measure the contents of lactate dehydrogenase (LDH) and aspartate aminotransferase (GOT) in the serum.
- LDH lactate dehydrogenase
- GOT aspartate aminotransferase
- Aspartate aminotransferase and lactate dehydrogenase are biochemical markers of myocardial damage. In the acute phase of viral myocarditis, both release are elevated and can be maintained for a considerable period of time. Therefore, if the drug can effectively reduce the myocardial enzyme spectrum, it means that the drug effectively reduces the degree of heart disease.
- the drug group of the present invention I 459.18 ⁇ 51.31* 21.65 ⁇ 5.00*
- the drug group of the present invention I 459.18 ⁇ 51.31* 21.65 ⁇ 5.00*
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Description
一种异黄酮类化合物的用途 技术领域
本发明涉及从中药中提取有效成分, 经药理试验证明对病毒性心肌炎治疗有效, 更具 体指从黄芪或其它中药中提取分离获得一种异黄酮类有效成分——毛蕊异黄酮- 7 - 氧 - D -吡喃葡萄糖苷 (Calycosin 7-0- β - D- glucoside), 它可在制备抗柯萨奇病毒及治疗柯萨 奇病毒引起的疾病的药物中应用。 背景技术
柯萨奇病毒(Coxsackievirus)可引起多种疾病, 如病毒性心肌炎, 流行性胸痛, 无菌 性脑炎、 脑膜炎, 克山病及病毒性癫痫等, 严重危害人类健康。
目前, 西医临床治疗病毒性心肌炎等柯萨奇病毒性疾病的主要方法是使用普通抗病毒 药、 免疫抑制剂、 干扰素及心肌细胞营养剂等, 但疗效并不理想。
近年来大量研究表明, 中药在病毒性心肌炎等柯萨奇病毒性疾病的临床治疗中显示出 很大优势, 但目前大部分中药为医生自拟的处方汤药或复方粗提药物, 如生脉饮、 芪冬颐心 口服液等, 缺乏有效成分清楚, 作用机理明确, 疗效肯定, 剂型先进, 服用携带方便的中药 制剂。
中药黄芪补气固表, 利尿托毒。 从黄芪中提取的黄芪皂苷等成分有多种药理活性。 《第 二军医大学学报, 1999, 20 (9 ): 666- 668》报道了黄芪皂苷对柯萨奇 B3病毒性心肌炎小鼠 具有良好的治疗效果; 《中国中药杂志, 2001, 26 ( 12): 850- 853》报道, 黄芪甲苷能对抗 组胺引起的脑微血管通透性增加; 《中国药理学通报, 2003, 19 (8): 892- 895》报道, 黄芪 总苷对体外激活肝星状细胞的增殖和产生胶原有明显抑制作用,这可能是其抗肝纤维化的机 制之一; 《天然产物研究与幵发, 1994, 6 (2): 1-5》报道, 黄芪甲苷和毛蕊异黄酮对孵化 红细胞的饿变形能力有改善作用, 这可能是黄芪改善血液流变学指标的重要机理; 专利 CN01126608. 2公开了毛蕊异黄酮及其糖甙具有良好的抗心肌缺血作用; 专利 CN00119451. 8 公开了黄芪甲苷在治疗病毒性心肌炎药物中的应用; 专利 CN01126609. 0公开了黄芪甲苷具 有抗心肌纤维化作用。未见毛蕊异黄酮 -7- 氧- β - D-吡喃葡萄糖苷抗柯萨奇病毒 (Coxsackie Virus)及治疗病毒性心肌炎的报道。 发明内容
本发明目的是克服常规多味汤药存在的不足之处, 采用化学方法从黄芪或其它中药中 分离出异黄酮类有效成分——毛蕊异黄酮- 7-氧- β - D-吡喃葡萄糖苷, 经药理试验, 使该化 合物在制备抗柯萨奇病毒和治疗病毒性心肌炎的药物中应用。
本发明药物可通过以下方法制备: 黄芪或其它中药材粉碎后, 以 70%乙醇回流提取三次 (2小时, 1小时, 1小时), 过滤, 合并滤液, 减压回收溶剂, 浓缩至无醇味, 得黄芪醇提 浸膏 I。 浸膏 I加水混溶过滤, 滤液用大孔树脂吸附, 用水洗脱杂质, 再用 70%乙醇洗脱, 洗脱液减压浓缩得浸膏 II。 浸膏 II再用硅胶柱层析分离, 以氯仿 -甲醇梯度洗脱, 合并相同 流分, 蒸干, 甲醇热溶, 静置, 有白色絮状物析出, 抽滤, 得白色粉末状结晶, 即得本发明 化合物毛蕊异黄酮- 7- 氧- β - D-吡喃葡萄糖苷 (Calycosin 7- 0- β - D-glucoside)。 结构式如下:
它的分子式为 22 Λ。,分子量为 446,化学名为 3' -羟基 -4' -甲氧基异黄酮- 7-氧- β - D -吡喃葡萄糖苷。 本发明釆用上述方法提取获得的毛蕊异黄酮- 7- 氧- β -D-吡喃葡萄糖苷首先进行药效 试验。
在原代培养的心肌细胞上进行的体外抗病毒试验结果表明, 本发明药物的 TC5。为 177. 84ug/ml, X寸 CVB3病毒的 IC5。为 17. 78ug/ml, 治疗指数 (TI) 为 10. 00, 表明本发明药 物体外对 CVB3病毒有显著抑制作用。
在 Balb/c小鼠上用腹腔接种柯萨奇 B3病毒的方法建立病毒性心肌炎模型, 给药高低 剂量组分别灌胃给予本发明药物溶液 40mg/kg和 20mg/kg, 模型对照组和正常对照组灌胃给 等量生理盐水, 连续给药 12天, 观察到第 15天, 观察小鼠毛色、 进食、 死亡等各种情况, 结果两个剂量组均能显著降低由柯萨奇 B3病毒引起的病毒性心肌炎小鼠的死亡率, 显著降 低病毒性心肌炎小鼠的心指数, 有效降低由柯萨奇 B3病毒引起的病毒性心肌炎小鼠血清中 LDH和 GOT的含量升高。
注: 试验方法参考 《现代药理实验方法》 (下册, P1425, 张均田主编, 北京医科大学中 国协和医科大学联合出版社, 1998年版)。 ' 具体实施方式
下面结合具体实施例对本发明做进一步阐述, 但不对其有任何限制。
实施例 1. 本发明药物的制备
取黄芪药材, 粉碎, 以 70%乙醇回流提取三次 (2小时, 1小时, 1小时), 过滤, 合并 滤液, 减压回收溶剂, 浓缩至无醇味, 得黄芪醇提浸膏 I。 浸膏 I加水混溶过滤, 滤液用大 孔树脂 (AB- 8型) 吸附, 用水洗脱杂质, 再用 70%乙醇洗脱, 洗脱液减压浓缩得浸膏 II。 浸 膏 II用 200-300 目硅胶柱层析, 以氯仿 -甲醇梯度洗脱, TLC检测, 10%硫酸-乙醇显色, 合 并相同流分, 蒸干, 甲醇热溶, 静置, 有白色絮状物析出, 抽滤, 得白色粉末状结晶, 即得 本发明化合物。 . 实施例 2: 本发明药物对柯萨奇 病毒 (CV )感染心肌细胞的影响试验 (体外)
细胞毒性试验:
取 SD大鼠新生 1一 3天的乳鼠 15只, 取出心脏, 做心肌细胞原代培养, 所得细胞悬液 在 24孔培养板中培养 24小时待其贴壁, 24小时后弃去培养液。 分组如下:
正常对照组: 每孔加入培养液 1. 0ml ;
给药组: 加入梯度稀释的本发明药物溶液 l. OmL/孔, 每个稀释度四个复孔。
在倒置相差显微镜下观察细胞生存情况, 按照 Reed- Muench法计算本发明药物对原代 培养心肌细胞的 TC5。。
抗柯萨奇 B3病毒试验:
取 SD大鼠新生 1一 3夭的乳鼠 15只, 取出心脏, 做心肌细胞原代培养, 所得细胞悬液 在 24孔培养板中培养 24小时待其贴壁, 24小时后弃去培养液。 分组如下:
正常对照组: 每孔加入培养液 l. Offll ;
病毒对照组: 每孔加入 0. 2ml CVB3病毒液 (TCID5。=10—'5a, 1(Γ5稀释), 孵育 1小时, 弃 去上清, 用 PBS溶液清晰三次, 加入培养液 1. Oral培养;
给药组: 每孔加入 0. 2ml CVB3病毒液 (TCID^IO"4-56, 10— 5稀释), 孵育 1小时, 弃去上 清, 用 PBS溶液清洗三次, 加入梯度稀释的本发明药物溶液. l. OraL/孔, 每个稀释度四个复 孔。
培养 48小时后在倒置相差显微镜下观察。 心肌细胞在培养中会慢慢死亡, 伪足断裂, 细胞皱缩、 变圆, 折光度提高。 被病毒感染后细胞死亡明显增多, 且可看到大面积坏死灶。 给药后如药物有效, 就可以降低被病毒感染细胞的死亡率。按照 Reed- Muench法计算本发明 药物对原代培养心肌细胞的 IC5。。 ·
+ 结果:本发明药物的 TC5。为 177. 84ug/ml,对 CVB3病毒 1^。为 17. 78ug/ml,治疗指数 (TI) 为 10. 00, 表明本发明药物体外对 CVB3病毒有显著抑制作用。 实施例 3: 本发明药物对病毒性心肌炎小鼠死亡率的影响试验 (体内)
将本发明药物分成两个剂量组, Balb/c小鼠随机分为 4组:
正常对照组: 腹腔接种 0. 1ml生理盐水, 每日给,等量生理盐水;
病毒对照组:每只腹腔接种 0. lmlCVB3病毒液 (TCID5。=10— 56, 10— 5稀释),然后每日给等量 生理盐水;
本发明药物组 I一高剂量: 同上法接种 CVB3病毒液, 同日灌胃本发明药物溶液 40mg/kg •d, 连续给药 12天;
本发明药物组 II一低剂量: 同第 3组方法, 灌胃本发明药物溶液, 剂量为 20mg/kg*d, 连续给药 12夭;
观察 15天, 观察小鼠毛色、 进食等各种情况, 统计各组小鼠的死亡率。
结果: 本发明药物两个剂量组均能显著降低由柯萨奇 B3病毒引起的病毒性心肌炎小鼠 的死亡率, 见表 1。
表 1 本发明药物对病毒性心肌炎小鼠发病率和死亡率的影响 组别 动物数 (只) 死亡率 (例数)
正常对照组 6 0 ( 0)
病毒对照组 15 40% (6) ' 本发明药物组 I 15 26. 7% (4) *
本发明药物组
Π 15 26. 7% (4) *
注: 采用卡方检验, 给药组与病毒组比较, *有统计意义。 实施例 4: 本发明药物对病毒性心肌炎小鼠心指数的影响试验 (体内)
Balb/c小鼠分组及给药剂量同实施例 2。 连续给药 12天, 观察到第 15天, 将所有小 鼠全部解剖。 在解剖前秤小鼠的体重, 解剖后再秤取其心脏重量。
心指数 =心重 /体重
当动物被病毒感染后, 摄食量减少, 体重降低, 而心脏却因此膨大、 发生纤维化而变 重, 所以可以用心指数来衡量心脏的病变程度, 心指数越大, 心脏病变越严重。
结果: 本发明药物的两个剂量组均能显著降低由柯萨奇 B3病毒引起的病毒性心肌炎小 鼠的心指数, 见表 3。
表 2 本发明药物对病毒性心肌炎小鼠心指数的影响
心指数 (X10—3)
正常对照组 4. 14±0· 59
病毒对照组 5. 60±0. 73
本发明药物组 I 5. 05±0. 63*
本发明药物 II 5. 14±0. 58*
注: 给药组与病毒组比较: * p<0. 05, ** p<0. 01
实施例 5: 本发明药物对病毒性心肌炎小鼠血清中 LDH和 GOT含量的影响试验 (体内)
Balb/c小鼠分组及给药剂量同实施例 2。 连续给药 12天, 观察到第 15天, 摘眼球取 血, 离心取血清, 检测血清中乳酸脱氢酶 (LDH) 和谷草转氨酶 (GOT) 的含量。
谷草转氨酶和乳酸脱氢酶是心肌损伤的生化指标 , 在病毒性心肌炎急性阶段, 二者释 放升高, 并且可以维持相当长时间。 所以, 药物若能有效降低心肌酶谱, 就说明该药物有效 降低了心脏病变程度。
结果: 本发明药物的两个剂量组均能显著改善由柯萨奇 B3病毒引起的病毒性心肌炎小 鼠血清中的 LDH和 GOT升髙, 结果见表 3。 本发明药物对病毒性心肌炎小鼠心脏表观病变程度的影响
组别 LDH (单位 /100ml) GOT (卡门氏) 正常对照组 314.08±57.64 21.46±4.49
病毒对照组 496.05±55.63 25.93±5.29
本发明药物组 I 459.18±51.31* 21.65±5.00* 本发明药物组
461.22±52.51* 21.88±3.90*
II
注: 给药组与病毒组比较: * p<0.05, ** p<0.01
Claims
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510110641.3 | 2005-11-23 | ||
| CN2005101106413A CN1813711B (zh) | 2005-11-23 | 2005-11-23 | 一种异黄酮类化合物的用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2007059685A1 true WO2007059685A1 (fr) | 2007-05-31 |
Family
ID=36906147
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2006/002910 Ceased WO2007059685A1 (fr) | 2005-11-23 | 2006-10-30 | Calycosine d'astragalus a fonction de resistance contre le coxackievirus |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN1813711B (zh) |
| WO (1) | WO2007059685A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112057628A (zh) * | 2020-08-25 | 2020-12-11 | 湖北民族大学 | 一种抗肿瘤药物盒 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101143861B (zh) * | 2006-09-15 | 2011-08-03 | 中国科学院上海药物研究所 | 一类b环4’-单取代黄酮化合物在制备抗柯萨奇b病毒感染的药物中的用途 |
| CN101139378B (zh) * | 2007-10-24 | 2010-12-15 | 中国农业大学 | 一种从黄芪中提取毛蕊异黄酮-7-O-β-D-葡萄糖苷的方法 |
| CN101780069B (zh) * | 2009-01-16 | 2012-08-22 | 广州康臣药物研究有限公司 | 一种防治糖尿病肾病的药物组合物及其制备方法 |
| CN102133262A (zh) * | 2011-03-13 | 2011-07-27 | 浙江大学 | 具心肌保护作用的黄芪有效组分制备方法与用途 |
| CN102532221A (zh) * | 2011-12-29 | 2012-07-04 | 广西壮族自治区药用植物园 | 黄芪中毛蕊异黄酮苷的提取与纯化方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1403452A (zh) * | 2001-08-31 | 2003-03-19 | 上海中医药大学 | 具有抗心肌缺血作用的黄芪毛蕊异黄酮及其糖甙 |
-
2005
- 2005-11-23 CN CN2005101106413A patent/CN1813711B/zh not_active Expired - Fee Related
-
2006
- 2006-10-30 WO PCT/CN2006/002910 patent/WO2007059685A1/zh not_active Ceased
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1403452A (zh) * | 2001-08-31 | 2003-03-19 | 上海中医药大学 | 具有抗心肌缺血作用的黄芪毛蕊异黄酮及其糖甙 |
Non-Patent Citations (1)
| Title |
|---|
| DING JIJUN ET AL.: "The effect of astragalus saponins on mice viral myocarditis caused by CVB 3", ACADEMIC JOURNAL OF SECOND MILITARY MEDICAL UNIVERSITY (CHINESE), vol. 20, no. 9, 1999, pages 666 - 668, XP003013908 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112057628A (zh) * | 2020-08-25 | 2020-12-11 | 湖北民族大学 | 一种抗肿瘤药物盒 |
| CN112057628B (zh) * | 2020-08-25 | 2023-01-17 | 湖北民族大学 | 一种抗肿瘤药物盒 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1813711A (zh) | 2006-08-09 |
| CN1813711B (zh) | 2011-04-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101254212B (zh) | 美洲大蠊提取物有效部位在制备治疗生殖器疱疹药物中的应用 | |
| US10624938B2 (en) | Total flavone extract of flower of abelmoschus manihot L. medic and preparation method thereof | |
| CN100490845C (zh) | 一种草药组合物及其在化疗中的应用 | |
| US11166934B2 (en) | Pharmaceutical composition for preventing or treating allergic diseases such as asthma or atopy including baicalein as active ingredient | |
| CN118434431A (zh) | 一种中药组合物及其制备方法与应用 | |
| CN103479963A (zh) | 一种治疗类风湿关节炎的中药胶囊及其制备方法 | |
| CN106474185A (zh) | 一种紫苏叶提取物及其组合物在制备降低血尿酸的药物或食品中的应用 | |
| WO2007059685A1 (fr) | Calycosine d'astragalus a fonction de resistance contre le coxackievirus | |
| EP1401465A2 (en) | Pharmaceutical composition for the treatment of viral infection | |
| CN104873563A (zh) | 桔梗茎叶皂苷的制备及在制备抗肿瘤药物和保健品中应用 | |
| CN102858359B (zh) | 一种含有醇溶性且非水溶性甘草提取物的药物组合物,及其药物制剂、制药用途、治疗方法和制备方法 | |
| CN102225089B (zh) | 治疗癌症的药物组合物、药物制剂及应用和制法 | |
| CN101357212B (zh) | 一种复方斑蝥注射制剂及其制备方法 | |
| CN101502536B (zh) | 香柏总黄酮及其制备方法与医药用途 | |
| CN112999233A (zh) | 一类来源于赤芍的单萜苷类化合物及其制法和应用 | |
| CN106822152B (zh) | 一种药物组合物及其应用 | |
| CN101940584A (zh) | 一种异黄酮类化合物的用途 | |
| CN101732605A (zh) | 一种白茅根提取物的用途及制备方法 | |
| CN101607009B (zh) | 一种用于治疗感冒的药物组合物 | |
| CN100443093C (zh) | 治疗艾滋病的药物 | |
| CN108743654B (zh) | 一种用于治疗缺血性心脏病的中药组合物及其制备方法和应用 | |
| CN101468060A (zh) | 一种药物组合物 | |
| CN101120977A (zh) | 一种治疗肿瘤的药物 | |
| CN107088197A (zh) | 丹参酮ⅱa作为抗人星形胶质细胞瘤药的应用 | |
| CN106176862A (zh) | 一种全叶马兰总黄酮提取物的制备方法及其用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 06805114 Country of ref document: EP Kind code of ref document: A1 |