WO2003022287A1 - USE OF 3β-HYDROXY-5-SPIROSTENE AS DRUGS FOR PREVENTION OR TREATMENT OF CARDIOVASCULAR DISEASES OR CONDITIONS FOR INHIBITION OF TUMORS AND DECREASING OF BLOOD LIPIDS - Google Patents

USE OF 3β-HYDROXY-5-SPIROSTENE AS DRUGS FOR PREVENTION OR TREATMENT OF CARDIOVASCULAR DISEASES OR CONDITIONS FOR INHIBITION OF TUMORS AND DECREASING OF BLOOD LIPIDS Download PDF

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WO2003022287A1
WO2003022287A1 PCT/CN2001/001272 CN0101272W WO03022287A1 WO 2003022287 A1 WO2003022287 A1 WO 2003022287A1 CN 0101272 W CN0101272 W CN 0101272W WO 03022287 A1 WO03022287 A1 WO 03022287A1
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group
tumors
blood lipids
effect
tsdp
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PCT/CN2001/001272
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French (fr)
Chinese (zh)
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Benxiang Wang
Qiuli Zhou
Haiying Ma
Shengwu Chen
Lijuan Wang
Yan Wang
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Jilin Tianyao Science And Technology Co. Ltd.
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Priority to PCT/CN2001/001272 priority Critical patent/WO2003022287A1/en
Publication of WO2003022287A1 publication Critical patent/WO2003022287A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to the preparation of 3 beta-Hydooky-5-spirostene (3 beta-hydroxy-5-spirostene, abbreviated as HS) in the preparation of medicines for preventing or treating cardiovascular diseases or symptoms, inhibiting tumors and lowering blood lipids.
  • HS 3 beta-Hydooky-5-spirostene
  • the present invention also relates to a pharmaceutical composition for preventing or treating cardiovascular diseases or symptoms, inhibiting tumors and lowering blood lipids, and containing Dioxingenin, and preventing or treating cardiovascular diseases or symptoms, and inhibiting tumors and blood lipids.
  • Diosgenin is mainly derived from various plants, such as Dioscorea and non-Dioscorea. It is mainly used for the synthesis of steroid hormones and steroidal contraceptives (pharmaceutical industry, 1985, 16 (1)).
  • the object of the present invention is to find and develop possible new medical applications of Deoxinxining.
  • Deoxin Jiening is effective in anti-atherosclerosis and anti-platelet coagulation. It has shown good effects in the aspects of reducing blood lipids and inhibiting tumors, so it can be used as a medicine for preventing or treating cardiovascular diseases or symptoms, lowering blood lipids and inhibiting tumors.
  • the present invention has been completed based on the above findings.
  • the first aspect of the present invention relates to the use of Deouxinjiening in the preparation of a medicament for preventing or treating cardiovascular disease or symptom, reducing blood fat and inhibiting tumor.
  • Another aspect of the present invention relates to the use of Deoxin Jiening in the preparation of a medicament for preventing or treating cardiovascular or cerebrovascular diseases or symptoms.
  • Another aspect of the present invention relates to the use of Deoxin Jiening in the preparation of a medicament for lowering blood lipids.
  • Another aspect of the present invention relates to the use of Deoxin Jiening in the preparation of a medicament for suppressing tumors.
  • Another aspect of the present invention relates to a composition for preventing or treating cardiovascular diseases or symptoms, lowering blood lipids, and suppressing tumors, which includes Dioxininine and a non-toxic and inert carrier or excipient.
  • Yet another aspect of the present invention relates to a method for preventing or treating cardiovascular disease or symptoms, reducing blood lipids and suppressing tumors, which comprises administering a prophylactically or therapeutically effective amount of Deoxentine or a composition containing the same to a mammal in need thereof.
  • the term "cardiovascular disease or symptom" as used in the present invention means, for example, atherosclerosis, thrombosis, hyperlipidemia, hypercholesterolemia, etc., or a tendency to potentially develop the above-mentioned diseases or symptoms.
  • the term "mammal” as used herein includes humans.
  • Deouxinjiening that is, diosgenin
  • Deouxinjiening can be prepared from many plants by methods known in the art, and specifically, see Pharmaceutical Industry, 1985, 16 (1), pages 33-36.
  • the Dioxingenin of the present invention can be used alone or in the form of a composition.
  • Deoxin when used in the form of a composition, it can be used orally or parenterally, such as tablets, capsules, solutions, suspensions, sustained-release tablets or capsules, and injections. Injectable, drip and other forms.
  • mice Male and female, weighing 18 to 23g; 70 male wistar rats, weighing 250 to 300g; purchased from the Experimental Animal Department of Bethune Medical University; From the Experimental Animal Center of the Agricultural and Animal Husbandry University of the Chinese People's Liberation Army; quail weighing 180 ⁇ 30g, both male and female, purchased from Changchun Animal Market.
  • Test substance Deouxinjiening (HS), batch number: 980810; Diao Xinxuekang (TSDP) capsules, specifications: 100mg / capsule, batch number 970609, product of Chengdu Diao Pharmaceutical Group Co., Ltd., Chinese Academy of Sciences; other reagents are of analytical grade.
  • HS Deouxinjiening
  • TSDP Diao Xinxuekang
  • Instrument 7070 automatic blood biochemical analyzer a product of Hitachi Japan.
  • Methods To form experimental hyperlipidemia method Feed the mice with a high-fat diet Formula: Add 1% cholesterol, 10% lard, and 0.3% bile acid to normal diet. The test substance was given at the same time as the high-fat diet, for a total of 7 days. On the eighth day after the test substance was administered, blood was removed from the eyeballs, serum was collected, and the total serum cholesterol (TC) content was measured with a fully automatic blood biochemical analyzer. The results are shown in Table 1. Another batch of mice was used to observe the therapeutic effect of HS on experimental hyperlipidemia in mice. The experimental mice were fed with high-fat diet for 8 days (the blood cholesterol content was significantly increased), and then started to give HS. On the 8th day after HS administration, the eyeballs were removed for blood collection, and the serum was taken to measure the serum total cholesterol (TC) content. The results are shown in Table 2.
  • Rat high cholesterol feed add 1% cholesterol, 10% lard and 0.2% propylthiouracil
  • each group gave the test substance one day a day, continuously
  • the test substance was administered for 14 days, and the blood was decapitated 12 hours after the last administration of the test substance (fasting but not water), the serum was separated, and the total cholesterol content in the serum was measured.
  • Table 3 The results are shown in Table 3.
  • the animals in the normal control group were administrated with an equal volume of distilled water, either during the preventive or therapeutic administration of the test substance.
  • the animals were sacrificed, blood was collected via the carotid artery, and the total cholesterol (TC), triglyceride (TG) and high-density lipoprotein (HDL) contents were measured; see the results Tables 4 and 5.
  • TC total cholesterol
  • TG triglyceride
  • HDL high-density lipoprotein
  • mice are given igTSDP (400 and 200 mgkg and HS (160 and 80 mgkg-t)
  • HS has a significant preventive effect on hypercholesterolemia in mice
  • TSDP only has a certain preventive effect when administered in high doses.
  • HS 40 and 2 0m g kg _1
  • table 2 shows that when the mice were ig HS (160 and 80m g, kg -1), significant prevention of hypercholesterolemic mice And therapeutic effects.
  • Table 3 Effect of Deoxin Jiening (HS) on serum total cholesterol in experimental hyperlipidemia rats (X s)
  • Niacin tablets 600 9 7.42 ⁇ 3.85 * 7.05 ⁇ 2.24
  • HS 50 (9)--6 3-As can be seen from Table 6, HS has a significant effect on reducing atherosclerosis in quail.
  • Test example 2 Effect of Deouxinjiening on experimental rabbits with hyperlipidemia and atherosclerosis.
  • Test method for the formation of hyperlipidemia in rabbits In addition to the normal control group, rabbits in all other groups were injected via ear vein Bovine serum albumin 250mg / kg once to accelerate the formation of arterial endometrial lesions caused by cholesterol. After that, each animal was administrated with gallbladder on an empty stomach every morning. Mould smoke on sterol lg, while the test substances given by animals in each group are taken together;
  • the material was filled with an equal volume of distilled water. This method was used for 12 weeks of continuous feeding. During this period, the animals were weighed once every 2 weeks. Blood was collected through the ear veins at 4 weeks, 8 weeks, and 12 weeks after fasting. (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) content, weighed at 12 weeks, sacrificed the animals after blood collection, and removed the aorta, heart, and brain tissues. Histopathological examination. The results are shown in Tables 7, 8 and 9.
  • HS has obvious prevention effect on hyperlipidemia in rabbits.
  • Aortic plaque classification criteria and methods After the animal is sacrificed, the aorta is removed (from the heart to the iliac artery bifurcation, the adipose tissue on the artery is removed, and stained with Sudan m before observation. The classification of the lesion is as follows: o
  • Grade 0-Endometrial surface is smooth, no creamy changes, that is, no plaques
  • Level 5-the inner membrane has a wide range of cream or milky changes, but ⁇
  • Test example 3 Effect of Deouxinjiening on platelet aggregation in rabbits Materials and methods
  • Substances to be tested Deoxin Jie Ning (HS), lot number: 980810; Diao Xinxuekang (TSDP) capsules, specifications: 100mg / capsule, lot number 970609, product of Chengdu Diao Pharmaceutical Group Co., Ltd., Chinese Academy of Sciences.
  • HS Deoxin Jie Ning
  • TSDP Diao Xinxuekang
  • the above experimental results show that TSDP and HS have significant anti-platelet agglutination effects in vitro, and each of the measurement indicators has a dose-effect relationship at the dosage used.
  • the platelet inhibition rate (I) can be calculated from the maximum platelet aggregation rate (PAG-M).
  • the absolute dose ( 30 g ml — 1 ) of the TSDP (240 ⁇ g ml — 1 ) was only 1/8, and the effect of inhibiting platelet aggregation in vitro was equal to that of TSDP.
  • the inhibition rates were 47.0% and 47. 53%.
  • Test Example 4 Effects of Deouxinjiening on thrombosis in vitro in rats Materials and methods
  • adherent cells L929, HeLa
  • adherent cells L929, HeLa
  • IX 10 5 ml 96-well culture plates
  • RPMI 1640 RPMI 1640 to culture
  • concentration of the sample prepared in the liquid was prepared in 3 replicates, and a 0 control and a negative control were set at the same time.
  • the culture was continued for 48 hours, and the colorimetric measurement was performed at 595 nm by the MTT method.
  • the average value was the cell survival optical density.
  • the results were compared with the control group to calculate the cell mortality under each condition (as shown in the table below).
  • the HS of the present invention has a significant inhibitory effect on tumor cells L929 and HeLa in vitro.
  • mice weighing 18-22g purchased from the Experimental Animal Center of the People ’s Liberation Army Agricultural and Animal Husbandry University (animal certification number: 10-5112).
  • test substance HS was provided by Jilin Tianyao Technology Co., Ltd. Preparation Room. Note Cyclamide for injection, specifications: 200ing, batch number: 980101, product of Shanghai Hualian Pharmaceutical Co., Ltd.
  • mice were divided into experimental method (IG distilled water 20ml / kg-, cyclophosphamide (ip20mg / kg-, HS (ig200ml / kg "100ml / kg _1 and SOml / kg- 1) and HS (ip lOOml / kg ⁇ Groups of 50ml / kg— 1 and 25ml / kg—8.

Abstract

The present invention relates to the new uses of 3β-hydroxy-5-spirostene, in particular, to the uses of prevention or treatment cardiovascular diseases or conditions, inhibition of tumors and decreasing of blood lipids.

Description

德欧心捷宁作为预防或治疗心血管疾病  DeouxinJining as prevention or treatment of cardiovascular disease
或症状, 抑制肿瘤及降血脂药物中的用途 发明领域  Or symptoms, the use in tumor suppressing and lipid-lowering drugs
本发明涉及德欧心捷宁 (3 β -Hydooky-5-spirostene, 3 β - 羟基 -5-螺甾烯, 简写为 HS)在制备用于预防或治疗心血管疾病或 症状, 抑制肿瘤及降血脂药物中的用途。 本发明还涉及用于预防 或治疗心血管疾病或症状, 抑制肿瘤及降血脂且含有德欧心捷宁 的药物组合物及预防或治疗心血管疾病或症状, 抑制肿瘤及降血 脂的方法。  The present invention relates to the preparation of 3 beta-Hydooky-5-spirostene (3 beta-hydroxy-5-spirostene, abbreviated as HS) in the preparation of medicines for preventing or treating cardiovascular diseases or symptoms, inhibiting tumors and lowering blood lipids. Use. The present invention also relates to a pharmaceutical composition for preventing or treating cardiovascular diseases or symptoms, inhibiting tumors and lowering blood lipids, and containing Dioxingenin, and preventing or treating cardiovascular diseases or symptoms, and inhibiting tumors and blood lipids.
背景技术  Background technique
德欧心捷宁为用下式表示的且其中 R H, R2=CH3的薯蓣皂甙 元, Deouxinjiening is a diosgenin expressed by the following formula and RH, R 2 = CH 3 ,
薯蓣皂甙元主要来源于各种植物, 如薯蓣属植物和非薯蓣属 植物。 其主要用于合成留体激素及甾体避孕药物 ( 医药工业, 1985, 16 ( 1 ) ) 。 Diosgenin is mainly derived from various plants, such as Dioscorea and non-Dioscorea. It is mainly used for the synthesis of steroid hormones and steroidal contraceptives (pharmaceutical industry, 1985, 16 (1)).
发明目的  Object of the invention
本发明的目的是寻找并开发德欧心捷宁可能的新的医药用 途。  The object of the present invention is to find and develop possible new medical applications of Deoxinxining.
发明概述  Summary of invention
本发明人现发现德欧心捷宁在抗动脉粥样硬化、 抗血小板凝 集、 降低血脂及抑制肿瘤等方面显示出良好的作用, 因而可 用作预防或治疗心血管疾病或症状、 降血脂及抑制肿瘤的药物。 本发明基于上述发现现已完成。 The inventors have now found that Deoxin Jiening is effective in anti-atherosclerosis and anti-platelet coagulation. It has shown good effects in the aspects of reducing blood lipids and inhibiting tumors, so it can be used as a medicine for preventing or treating cardiovascular diseases or symptoms, lowering blood lipids and inhibiting tumors. The present invention has been completed based on the above findings.
因此, 本发明第一方面涉及德欧心捷宁在制备用于预防或治 疗心血管疾病或症状, 降血脂及抑制肿瘤的药物中用途。  Therefore, the first aspect of the present invention relates to the use of Deouxinjiening in the preparation of a medicament for preventing or treating cardiovascular disease or symptom, reducing blood fat and inhibiting tumor.
本发明再一方面涉及德欧心捷宁在制备用于预防或治疗心脑 血管疾病或症状的药物中用途。  Another aspect of the present invention relates to the use of Deoxin Jiening in the preparation of a medicament for preventing or treating cardiovascular or cerebrovascular diseases or symptoms.
本发明再一方面涉及德欧心捷宁在制备用于降血脂的药物中 用途。  Another aspect of the present invention relates to the use of Deoxin Jiening in the preparation of a medicament for lowering blood lipids.
本发明再一方面涉及德欧心捷宁在制备用于抑制肿瘤的药物 中用途。  Another aspect of the present invention relates to the use of Deoxin Jiening in the preparation of a medicament for suppressing tumors.
本发明再一方面涉及用于预防或治疗心血管疾病或症状, 降 血脂及抑制肿瘤的組合物, 其包括德欧心捷宁及无毒且惰性的载 体或赋形剂。  Another aspect of the present invention relates to a composition for preventing or treating cardiovascular diseases or symptoms, lowering blood lipids, and suppressing tumors, which includes Dioxininine and a non-toxic and inert carrier or excipient.
本发明再一方面涉及预防或治疗心血管疾病或症状, 降血脂 及抑制肿瘤的方法, 其包括将预防或治疗有效量的德欧心捷宁或 含它的组合物给予需预防或治疗的哺乳动物。  Yet another aspect of the present invention relates to a method for preventing or treating cardiovascular disease or symptoms, reducing blood lipids and suppressing tumors, which comprises administering a prophylactically or therapeutically effective amount of Deoxentine or a composition containing the same to a mammal in need thereof.
根据本发明, 本发明中所用术语 "心血管疾病或症状" 是指 例如动脉粥样硬化, 血栓形成, 高脂血, 高胆固醇血等或有潜在 发展为上述疾病或症状的趋势。  According to the present invention, the term "cardiovascular disease or symptom" as used in the present invention means, for example, atherosclerosis, thrombosis, hyperlipidemia, hypercholesterolemia, etc., or a tendency to potentially develop the above-mentioned diseases or symptoms.
根据本发明, 本发明中所用术语 "哺乳动物" 包括人。  According to the present invention, the term "mammal" as used herein includes humans.
根据本发明, 德欧心捷宁 (即薯蓣皂甙元) 可通过本领域已 知方法从许多植物中制备,具体可参见《医药工业》, 1985, 16 ( 1 ) , 33- 36页。  According to the present invention, Deouxinjiening (that is, diosgenin) can be prepared from many plants by methods known in the art, and specifically, see Pharmaceutical Industry, 1985, 16 (1), pages 33-36.
根据本发明, 本发明的德欧心捷宁可单独或以組合物形式使 用。 当德欧心捷宁以组合物形式使用时, 可通过口服或非肠道剂 型使用, 如片剂、 胶嚢、 溶液、 悬浮液、 緩释片剂或胶嚢, 及注 射液、 滴注液等形式。 According to the present invention, the Dioxingenin of the present invention can be used alone or in the form of a composition. When Deoxin is used in the form of a composition, it can be used orally or parenterally, such as tablets, capsules, solutions, suspensions, sustained-release tablets or capsules, and injections. Injectable, drip and other forms.
本发明详细描述  Detailed description of the invention
下面是的实施例用于进一步说明详细本发明, 但并不意味着 本发明仅限于此。  The following examples are provided to further illustrate the present invention in detail, but are not meant to limit the present invention thereto.
生物活性试验  Biological activity test
生物活性实施例 1  Biological activity example 1
德欧心捷宁对实验性高脂血症和动脉粥样硬化的影响 材料与方法  Effect of Deouxinjiening on experimental hyperlipidemia and atherosclerosis Materials and methods
动物 昆明小鼠, 雌雄各半, 体重 18 ~ 23g; 雄性 wistar大 鼠 70只, 体重 250 ~ 300g; 购自白求恩医科大学实验动物部; 新 西兰兔, 雄性, 体重 1. 75 ~ 2. 25kg, 购自中国人民解放军农牧大 学实验动物中心; 鹌鹑, 体重 180 ± 30g, 雌雄兼用, 购自长春动 物市场。  Animals Kunming mice, male and female, weighing 18 to 23g; 70 male wistar rats, weighing 250 to 300g; purchased from the Experimental Animal Department of Bethune Medical University; From the Experimental Animal Center of the Agricultural and Animal Husbandry University of the Chinese People's Liberation Army; quail weighing 180 ± 30g, both male and female, purchased from Changchun Animal Market.
受试物质:德欧心捷宁(HS),批号: 980810;地奥心血康(TSDP) 胶嚢, 规格: lOOmg/粒, 批号 970609, 中科院成都地奥制药集团 有限公司产品; 其它试剂均为分析纯。  Test substance: Deouxinjiening (HS), batch number: 980810; Diao Xinxuekang (TSDP) capsules, specifications: 100mg / capsule, batch number 970609, product of Chengdu Diao Pharmaceutical Group Co., Ltd., Chinese Academy of Sciences; other reagents are of analytical grade.
仪器 7070型全自动血液生化分析仪, 日本日立公司产品。 方法 形成实验性高脂血症的方法: 喂饲小鼠的高脂饲料配 方: 在普通饲料中加入 1%胆固醇、 10%猪油和 0. 3%胆酸。 在喂饲 高脂饲料同时给受试物质, 共给受试物质 7天。 于给受试物质后 第 8天摘除眼球取血, 取血清, 用全自动血液生化分析仪测定血 清总胆固醇 (TC)含量。 结果见表 1。 另一批小鼠用于 HS对小鼠实 验性高脂血症的治疗作用的观察。 实验小鼠饲以高脂饲料 8天(血 中胆固醇含量明显升高)后, 开始给 HS, 于给 HS后第 8天, 摘除 眼球取血, 取血清, 测血清总胆固醇(TC)含量。 结果见表 2。  Instrument 7070 automatic blood biochemical analyzer, a product of Hitachi Japan. Methods To form experimental hyperlipidemia method: Feed the mice with a high-fat diet Formula: Add 1% cholesterol, 10% lard, and 0.3% bile acid to normal diet. The test substance was given at the same time as the high-fat diet, for a total of 7 days. On the eighth day after the test substance was administered, blood was removed from the eyeballs, serum was collected, and the total serum cholesterol (TC) content was measured with a fully automatic blood biochemical analyzer. The results are shown in Table 1. Another batch of mice was used to observe the therapeutic effect of HS on experimental hyperlipidemia in mice. The experimental mice were fed with high-fat diet for 8 days (the blood cholesterol content was significantly increased), and then started to give HS. On the 8th day after HS administration, the eyeballs were removed for blood collection, and the serum was taken to measure the serum total cholesterol (TC) content. The results are shown in Table 2.
大鼠高胆固醇饲料(在普通饲料中加入 1%胆固醇、 10%猪油和 0. 2%丙基硫氧嘧啶)。 与此同时, 各组每天给受试物质 1天, 连续 给受试物质 14天,于末次给受试物质(禁食不禁水)12小时后 断头取血, 分离血清, 测定血清总胆固醇含量。 结果见表 3。 Rat high cholesterol feed (add 1% cholesterol, 10% lard and 0.2% propylthiouracil) to normal feed. At the same time, each group gave the test substance one day a day, continuously The test substance was administered for 14 days, and the blood was decapitated 12 hours after the last administration of the test substance (fasting but not water), the serum was separated, and the total cholesterol content in the serum was measured. The results are shown in Table 3.
鹌鹑预防性给药, 每天上午每只动物灌胃给予猪油和胆固醇 混合液(猪油:胆固醇 =20: 1, W/W) 3ml, 同时将受试物庸渗入其 中一并灌入(正常对照组动物灌胃给予等体积蒸馏水)。 以此方法 处理 12周。治疗性给受试物质的动物每天灌胃给予猪油和胆固醇 混合液 3ml/每只, 连续灌胃 12周形成高血脂模型后, 再灌胃给 予受试物质, 以观察其对高脂血症及动脉粥样硬化的治疗作用, 给受试物质时间为 6星期。无论是预防性还是治疗性给受试物质期 间, 正常对照组动物均灌胃给予等体积蒸馏水。 分别于预防性和治 疗性给受试物质结束后, 将动物处死, 经颈动脉取血, 测血清总胆 固醇(TC) , 甘油三脂(TG)和高密度脂蛋白(HDL)含量; 结果见表 4 和表 5。 取主动脉及左、 右头臂动脉和肝脏, 做病理切片镜下观察。 镜检 AS斑块侵蚀程度, 分为 5个等级, 0级: 内膜光滑, 无斑块存 在; 1级: 内膜光滑, 有少许斑块; 2级: 内膜稍厚, 斑块侵蚀区域 小于 50%; 3级: 内膜粗糙、 增厚, 斑块涉及面积大于 50%; 4级: 内膜变厚、 变硬。 大部分区域散在斑块。 结果见表 6。 Quail was administered prophylactically, and each animal was given a mixture of lard and cholesterol (lard: cholesterol = 20: 1, W / W) 3ml by gavage every morning, and the test substance was infiltrated into it at the same time (normal Animals in the control group were given an equal volume of distilled water by gavage). Treated in this way for 12 weeks. Animals treated with the test substance were given intragastrically a mixture of lard and cholesterol 3ml per animal, and the rats were given a hyperlipidemic model after 12 consecutive weeks of intragastric administration, and then the test substance was administered orally to observe their effect on hyperlipidemia. And the treatment of atherosclerosis, the test substance was given for 6 weeks. The animals in the normal control group were administrated with an equal volume of distilled water, either during the preventive or therapeutic administration of the test substance. After the preventive and therapeutic administration of the test substance, the animals were sacrificed, blood was collected via the carotid artery, and the total cholesterol (TC), triglyceride (TG) and high-density lipoprotein (HDL) contents were measured; see the results Tables 4 and 5. The aorta, left and right brachial arteries and liver were taken for pathological microscopy observation. Microscopic examination of the extent of AS plaque erosion, divided into 5 grades, grade 0: smooth endometrium without plaque; grade 1: smooth endometrium with a few plaques; grade 2: slightly thicker endometrium, plaque erosion area Less than 50%; Grade 3: The inner membrane is rough and thickened, and the area covered by plaque is greater than 50%; Grade 4: The inner membrane is thickened and hardened. Most areas are scattered with plaques. The results are shown in Table 6.
表 1. 预防性给德欧心捷宁 (HS) 对小鼠血清总胆固醇含量的影响 (x±s) 分组 用量 给予途径 动物数 血清 TC含量 Table 1. The effect of preventive administration of Desiocin (HS) on total serum cholesterol in mice (x ± s) Group Dosage Route of administration Number of animals Serum TC content
(mg/kg) (只) ( mmol/L ) 正常对照 Ig 13 2.25 ± 0.54*" 高脂模型 Ig 10 9.34 ± 1.94 普拉固 6 Ig 10 6.59 ± 1.23" (mg / kg) (only) (mmol / L) Normal control Ig 13 2.25 ± 0.54 * "High-fat model Ig 10 9.34 ± 1.94 Pragose 6 Ig 10 6.59 ± 1.23"
TSDP 200 Ig 13 7.82 ± 2.18 TSDP 200 Ig 13 7.82 ± 2.18
400 Ig 10 7.73 ± 1.28* 400 Ig 10 7.73 ± 1.28 *
50 IP 12 8.25土 1.2550 IP 12 8.25 soil 1.25
100 IP 11 7.92 ± 1.26100 IP 11 7.92 ± 1.26
HS 80 Ig 12 6.97 ± 1.66 HS 80 Ig 12 6.97 ± 1.66
160 Ig 12 6.32土 1.53" 160 Ig 12 6.32 soil 1.53 "
20 IP 13 7.38 ± 1.07*20 IP 13 7.38 ± 1.07 *
40 I 12 8.10 ± 0.65 注: 与模型組比较 'Ρ< 0.05, "P<0.01, "*P < 0.001。 40 I 12 8.10 ± 0.65 Note: Compared with the model group, 'P <0.05, "P <0.01," * P <0.001.
表 2. 治疗性给德欧心捷宁 (HS) 对小鼠血清总胆固醇含量的影响 (x±s) Table 2. The effect of therapeutic dextrooxetine (HS) on serum total cholesterol in mice (x ± s)
分组 用量 给予途径 动物数 血清 TC含量  Group Dosage Route of administration Number of animals Serum TC content
(mg/kg) (只) ( mmol/L ) 正常对照 Ig 12 2.28 ± 0. Ί * 高脂模型 Ig 10 9.17 ± 2.80 普拉固 6 Ig 8 8.85 ± 2.14 (mg / kg) (only) (mmol / L) Normal control Ig 12 2.28 ± 0. Ί * High-fat model Ig 10 9.17 ± 2.80 Prasug 6 Ig 8 8.85 ± 2.14
TSDP 200 Ig 8 9.20 ± 2.00 TSDP 200 Ig 8 9.20 ± 2.00
400 Ig 12 7.98 ± 2.80 400 Ig 12 7.98 ± 2.80
50 IP 11 7.63 ± 2.8550 IP 11 7.63 ± 2.85
100 I 11 6.98 ± 2.47100 I 11 6.98 ± 2.47
HS 80 Ig 11 6.87 ± 1.83* HS 80 Ig 11 6.87 ± 1.83 *
160 Ig 10 5.27 ± 1.67" 160 Ig 10 5.27 ± 1.67 "
20 IP 8 7.76 ± 1.2020 IP 8 7.76 ± 1.20
40 I 11 7.64 ± 1.32 注: 与模型組比较 'Ρ< 0.05, **P < 0.01, "*P< 0.001。 40 I 11 7.64 ± 1.32 Note: Compared with the model group, 'P <0.05, ** P <0.01, "* P <0.001.
上述结果表明,给小鼠 igTSDP (400和 200mgkg 和 HS( 160 和 80mgkg— t ) , HS对小鼠高胆固醇血症有明显预防作用, 而 TSDP 只有大剂量才有一定预防作用。 ip给予时, HS ( 40和 20mg kg_1 ) 仍然有效, 但 TSDP无效。 由表 2 可见, 给小鼠 ig HS (160和 80mg,kg-1)时, 对小鼠高胆固醇血症有明显的预防和治疗作用。 表 3. 德欧心捷宁 (HS) 对实验性高脂血症大鼠血清总胆固醇含量的影响 (X s) The above results show that when mice are given igTSDP (400 and 200 mgkg and HS (160 and 80 mgkg-t)), HS has a significant preventive effect on hypercholesterolemia in mice, while TSDP only has a certain preventive effect when administered in high doses. HS (40 and 2 0m g kg _1) is still valid, but TSDP invalid. table 2 shows that when the mice were ig HS (160 and 80m g, kg -1), significant prevention of hypercholesterolemic mice And therapeutic effects. Table 3. Effect of Deoxin Jiening (HS) on serum total cholesterol in experimental hyperlipidemia rats (X s)
分组 用量 动物数 血清 TC含量  Group Dosage Number of Animals Serum TC Content
(mg/kg) (只)  (mg / kg) (only)
正常对照 10  Normal control 10
高脂模型 10 6.32 ± 1.84 肌醇烟酸酯片 600 8 5.16 ± 2.32  High fat model 10 6.32 ± 1.84 Inositol nicotinate tablets 600 8 5.16 ± 2.32
TSDP 200 9 4.21 ±0.72"  TSDP 200 9 4.21 ± 0.72 "
400" 10 4.76 ± 1.36* 400 "10 4.76 ± 1.36 *
HS 100 10 4.34 ± 0.80** HS 100 10 4.34 ± 0.80 **
200c) 9 3.23 ±0.82"* 与模型組比较 'Ρ< 0.05 "Ρ<0.01, "*Ρ< 0.001. 200 c) 9 3.23 ± 0.82 "* Compared with the model group 'P <0.05" P <0.01, "* P <0.001.
a)与 b)比较 ρ<0.05, b与。)比较 ρ<0.01。 a) Compared with b ) ρ <0.05, b and. ) Compare ρ <0.01.
结果表明, 给大鼠 igHS和 ISDP均能明显改善喂饲胆固醇引 起的大鼠高脂血症, 但 HS ( 200mg kg1) o预防大鼠高脂血症的效 果明显优于 TSDP ( 200和 400mg kg"1)„ o o The results show that both igHS and ISDP in rats can significantly improve the hyperlipidemia caused by cholesterol feeding in rats, but the effect of HS (200mg kg 1 ) o in preventing hyperlipidemia in rats is significantly better than TSDP (200 and 400mg kg " 1 )„ oo
表 4. 预防性给德欧心捷宁 (HS) 对鹌鹑血脂含量的影响 ( x± s) B Table 4. Effect of prophylactic dextrooxetine (HS) on blood lipid levels in quail (x ± s) B
分组 et 量 动物 TC含量 TG含量 H oDL含量  Group et amount Animal TC content TG content Ho oDL content
(mg/kg) (只) (mmol/L) (mmol/L) 对照 11 6.35 ± 1.98"  (mg / kg) (only) (mmol / L) (mmol / L) Control 11 6.35 ± 1.98 "
模型 9 3, 75 ± 2.00  Model 9 3, 75 ± 2.00
烟酸片 600 9 7.42 ± 3.85* 7.05 ± 2.24Niacin tablets 600 9 7.42 ± 3.85 * 7.05 ± 2.24
TSDP 400 9 7.00 ±3.10TSDP 400 9 7.00 ± 3.10
TSDP 200 10 9.60 ± 3.988 6.16 ± 3.22"TSDP 200 10 9.60 ± 3.98 8 6.16 ± 3.22 "
HS 200 9 6.01 ± 2 26** HS 200 9 6.01 ± 2 26 **
HS 100 9 8.33 ± 2.0Γ 6- 82 1.07" HS 100 9 8.33 ± 2.0Γ 6- 82 1.07 "
HS 50 10 10.32 1.73" 1.93 ± 1.49' 6.54 ± 1.63 注: 与模型組比较 *P< 0.05, **P< 0.01, *"P< 0.001, *P>0.05。 表 5· 治疗给德欧心捷宁 (HS) 对鹌鹑血脂含量的影响 (χ ± s) HS 50 10 10.32 1.73 "1.93 ± 1.49 '6.54 ± 1.63 Note: Compared with model group * P <0.05, ** P <0.01, *" P <0.001, * P> 0.05. Table 5 · Effect of treatment with Deoxinjiening (HS) on blood lipid content of quail (χ ± s)
分组 用量 动物 TC含量 TG含量 HDL含量  Group dosage Animal TC content TG content HDL content
(mg/kg) (只) (mmol/L) (mmol/L)  (mg / kg) (only) (mmol / L) (mmol / L)
对照 6 2.88 ± 0.77 5.78 ± 1.18* 模型 6 4.88土 2.27 4.37 ± 1.54 烟酸片 600 6 7.87 ± 1.52" 2.91 ± 1.13* 9.35 ± 4.03*Control 6 2.88 ± 0.77 5.78 ± 1.18 * Model 6 4.88 ± 2.27 4.37 ± 1.54 Niacin tablets 600 6 7.87 ± 1.52 "2.91 ± 1.13 * 9.35 ± 4.03 *
TSDP 400 6 8.06 ± 3.34* 2.85 ± 0.82' 7.99 ± 4.38*TSDP 400 6 8.06 ± 3.34 * 2.85 ± 0.82 '7.99 ± 4.38 *
TSDP 200 6 10.85 ± 4.51* 3.36 ± 2.07* 5.24 ± 1.88*TSDP 200 6 10.85 ± 4.51 * 3.36 ± 2.07 * 5.24 ± 1.88 *
HS 200 6 6.50 ± 1.02" 6.77 ± 0.92'HS 200 6 6.50 ± 1.02 "6.77 ± 0.92 '
HS 100 6 8.84 ± 2.85* 2.33 ± 1.05** HS 100 6 8.84 ± 2.85 * 2.33 ± 1.05 **
HS 50 6 2.78 ± 0.92* 7·85±2·6Γ d  HS 50 6 2.78 ± 0.92 * 7.85 ± 2 · 6Γ d
o  o
注: 与模型组比较 *P< 0.05, "P<0.01, *"P< 0.001, P>0.05。  Note: Compared with model group * P <0.05, "P <0.01, *" P <0.001, P> 0.05.
+1  +1
P<0.01与 ISDP (400mg kg)比较。  P <0.01 compared with ISDP (400mg kg).
O O  O O
卜 由上述可见, 无论预防和治疗性给予 HS均有降低 TC、 TG和 升高 HDL作用, 其作用明显强于 TSDP。  From the above, it can be seen that regardless of the preventive and therapeutic administration of HS, it can reduce TC, TG and increase HDL, and its effect is significantly stronger than TSDP.
1十  1 ten
o  o
表 6. 各组动物动脉壁粥样斑块形成病变分级比较 Table 6. Comparison of grades of atherosclerotic plaque formation in the arterial wall of each group of animals
组别 例数 0级 1级 2级 3级 4级 Group Number of cases 0 level 1 level 2 level 3 level 4 level
(mg/kg) (mg / kg)
对照 ( 8) 8 - - - - 模型 ( 7) - - 2 4 0 0  Control (8) 8----Model (7)--2 4 0 0
卜 1 烟酸 600 ( 8) 2 1 5 - O +1 - Bu 1 Niacin 600 (8) 2 1 5-O +1-
ISDP 400 ( 9) - 3 6 一 - O CISDP 400 (9)-3 6 I-O C
HS 200 ( 9) 1 3 5 - -HS 200 (9) 1 3 5--
HS 100 ( 8) - - 6 2 -HS 100 (8)--6 2-
HS 50 ( 9) - - 6 3 - 由表 6可见, HS对鹌鹑动脉粥样硬化有明显减轻作用。 HS 50 (9)--6 3-As can be seen from Table 6, HS has a significant effect on reducing atherosclerosis in quail.
试验例 2. 德欧心捷宁对实验性家兔高脂血症和动脉粥样硬 化症的影响 家兔形成高脂血症试验方法: 除正常对照组外, 其它各组家 兔均经耳静脉注射牛血清白蛋白 250mg/kg 1次, 以加速胆固醇引 起的动脉内膜病变形成, 以后, 每天早晨空腹时每只动物灌服胆 模烟对 固醇 lg, 同时各組动物所给的受试物质一并灌服; 对照组动 型照酸 Test example 2. Effect of Deouxinjiening on experimental rabbits with hyperlipidemia and atherosclerosis. Test method for the formation of hyperlipidemia in rabbits: In addition to the normal control group, rabbits in all other groups were injected via ear vein Bovine serum albumin 250mg / kg once to accelerate the formation of arterial endometrial lesions caused by cholesterol. After that, each animal was administrated with gallbladder on an empty stomach every morning. Mould smoke on sterol lg, while the test substances given by animals in each group are taken together;
物则灌服等容积蒸馏水。 以此方法连续喂养 12周, 其间, 每 2周 称量动物体重 1次, 并分别于笫 4周、 第 8周和第 12周空腹 12 小时后, 经耳缘静脉取血, 测血清总胆固醇(TC), 甘油三脂(TG), 高密度脂蛋白(HDL)和低密度脂蛋白(LDL)含量, 第 12周称重、 取 血后将动物处死, 取出主动脉、 心脏及脑組织做病理组织学检测。 结果见表 7、 8和 9。 The material was filled with an equal volume of distilled water. This method was used for 12 weeks of continuous feeding. During this period, the animals were weighed once every 2 weeks. Blood was collected through the ear veins at 4 weeks, 8 weeks, and 12 weeks after fasting. (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) content, weighed at 12 weeks, sacrificed the animals after blood collection, and removed the aorta, heart, and brain tissues. Histopathological examination. The results are shown in Tables 7, 8 and 9.
表 7. 给予德欧心捷宁(HS)寸 4周对家兔血脂含量的影响 (x±s)  Table 7. Effect of Deoxin Jie Ning (HS) inches for 4 weeks on blood lipid content in rabbits (x ± s)
^ T +1C1 +含量 TG含量 HDL含量 "~  ^ T + 1C1 + content TG content HDL content "~
O o  O o
(mg/kg) (只) (mmol/L) (mmol/L) (mmol/L)  (mg / kg) (only) (mmol / L) (mmol / L) (mmol / L)
6 0. 87 ± 0.60 0.80 ± 0.22 1. 58 ± 0.47 6 0. 87 ± 0.60 0.80 ± 0.22 1. 58 ± 0.47
6 1 .82± 2.21 1.45 ± 0.38 0. , 93± 0.256 1 .82 ± 2.21 1.45 ± 0.38 0., 93 ± 0.25
200 6 2. 39 ±0.87" 1. 28 ± 0.19* o o o 200 6 2. 39 ± 0.87 "1. 28 ± 0.19 * o o o
TSDP 300 6 2. 45 ±0.73* 1.03 ± 0.25" 1. 29 ± 0.33° o o  TSDP 300 6 2. 45 ± 0.73 * 1.03 ± 0.25 "1. 29 ± 0.33 ° o o
HS 200 6 1. 62 ± 0.44" 0.85+ 1 ±  HS 200 6 1. 62 ± 0.44 "0.85+ 1 ±
1+ o 0.23" 1. 41 ± 0.39 HS 100 6 2. 41 ± 0.67* 1.01 ± o o 0 o.29* 1. 21 ± 0.32* HS 50 6 2. 69 ± 0· 74* 1.03 ± 0.24* 1.  1+ o 0.23 "1. 41 ± 0.39 HS 100 6 2. 41 ± 0.67 * 1.01 ± oo 0 o.29 * 1. 21 ± 0.32 * HS 50 6 2. 69 ± 0 · 74 * 1.03 ± 0.24 * 1.
注: 与模型组比较 *P< 0.05, "P<0.01, "*P<0.001, 〉0.05。  Note: Compared with the model group * P <0.05, "P <0.01," * P <0.001,> 0.05.
o o
1 +  1 +
表 8. 给予德欧心捷宁(HS) 8周对家兔血脂含量的影响 ( x± s) o  Table 8. Effects of Deoxin Jiening (HS) for 8 weeks on blood lipid levels in rabbits (x ± s) o
o 分組 用量 动物 TC含量 TG含量 HDL含量  o Group dosage Animal TC content TG content HDL content
(mg/kg) (只) (mmol/L) (mmol/L) 对照 6 0.11土 0 ΊΤ"  (mg / kg) (only) (mmol / L) (mmol / L) Control 6 0.11 soil 0 ΊΤ "
模型 6 6.18 ± 2.30 0.84 ± 0.34 0· 41 ± 0.17 烟酸片 200 6 3.08 ±0· 68* L 15 ±0.48 Model 6 6.18 ± 2.30 0.84 ± 0.34 0 · 41 ± 0.17 Niacin tablets 200 6 3.08 ± 0 · 68 * L 15 ± 0.48
TSDP 300 6 3.01 ±0.83" TSDP 300 6 3.01 ± 0.83 "
HS 200 6 1.35 ± 0.66 HS 200 6 1.35 ± 0.66
HS 100 6 2, 98 ±0.73" 0, 27 ± 0.20" 1.09 ± 0.67"HS 100 6 2, 98 ± 0.73 "0, 27 ± 0.20" 1.09 ± 0.67 "
HS 50 6 3.02 ± 0.96 0.35 ± 0.27* 1.02 ± 0.57" 注: 与模型組比较 *P<0.05, "P<0.01, '"Ρ< 0.001, *"P>0.05。 表 9. 德欧心捷宁给药 12周对家兔血脂含量的影响 (x±s) HS 50 6 3.02 ± 0.96 0.35 ± 0.27 * 1.02 ± 0.57 "Note: Compared with model group * P <0.05," P <0.01, '"P <0.001, *"P> 0.05. Table 9. Effect of Deoxin Jiening on blood lipid content in rabbits after 12 weeks of administration (x ± s)
用量 动物 LDL^-¾- Dosage Animal LDL ^ -¾-
(mg kg) (只) ol/L) ol/L) (mg kg) (only) ol / L) ol / L)
对照 6 0.50±0.11*** 0.37 ±0.01™ 0.70 ±0.22* 17.1 ± 4.8* 輕 6 5.89± 1.87 0.78±0.16 0.24 ±0.13 151.3 ±74.5 烟 ¾ t 200 6 2.11 ± 1.06" 0.46 ± 0.26· 0.44±0.11* 58.6 ± 13.4 Control 6 0.50 ± 0.11 *** 0.37 ± 0.01 ™ 0.70 ± 0.22 * 17.1 ± 4.8 * light 6 5.89 ± 1.87 0.78 ± 0.16 0.24 ± 0.13 151.3 ± 74.5 smoke ¾ t 200 6 2.11 ± 1.06 "0.46 ± 0.26 · 0.44 ± 0.11 * 58.6 ± 13.4
TSDP 300 6 2.73± 1.24** 0.47 ±0.20* 0.43 ±0.15* 85.6 ±36.0"TSDP 300 6 2.73 ± 1.24 ** 0.47 ± 0.20 * 0.43 ± 0.15 * 85.6 ± 36.0 "
HS 200 6 1.50±0.91*** 0.41 ± 0.1 * 0.60±0.19** 52.1 ± 8.1*HS 200 6 1.50 ± 0.91 *** 0.41 ± 0.1 * 0.60 ± 0.19 ** 52.1 ± 8.1 *
HS 100 6 2.91 ± 1.06" 0.47 ±0.05** 0.48 ±0.22* 107.7 ±25.9"HS 100 6 2.91 ± 1.06 "0.47 ± 0.05 ** 0.48 ± 0.22 * 107.7 ± 25.9"
HS 50 6 3.28 ±0.88* 0.49 ±0.15* 0.4 ±0· 14* 115.8 ±32.2" 注: 与模型組比较 'Ρ<0.05, 'Ρ<0.01, "*Ρ < 0 05。 HS 50 6 3.28 ± 0.88 * 0.49 ± 0.15 * 0.4 ± 0 · 14 * 115.8 ± 32.2 "Note: Compared with the model group 'P <0.05,' P <0.01," * P <0 05.
由表 7—9可看出, HS对家兔高脂血症有明显的预防作用。 主动脉斑块的分级标准和方法: 将动物处死后, 取出主动脉(自心 脏至髂动脉分叉处, 将动脉上的脂肪组织剔除, 用苏丹 m染色后 再行观察。 病变的分级如下: o  It can be seen from Table 7-9 that HS has obvious prevention effect on hyperlipidemia in rabbits. Aortic plaque classification criteria and methods: After the animal is sacrificed, the aorta is removed (from the heart to the iliac artery bifurcation, the adipose tissue on the artery is removed, and stained with Sudan m before observation. The classification of the lesion is as follows: o
O  O
0级-内膜表面光滑, 无奶油色变化, 即无斑块; Grade 0-Endometrial surface is smooth, no creamy changes, that is, no plaques;
5级-内膜有广泛的奶油色或乳白色变化, 但 Λ  Level 5-the inner membrane has a wide range of cream or milky changes, but Λ
0. 无凸出于表面 的斑块;  0. No plaque protruding from the surface;
1级-有明显的奶油色凸起斑块, 面积小于 3mm2; Level 1-there are obvious cream-colored raised plaques, the area is less than 3mm 2 ;
2级-斑块面积大于 3inm2; Level 2-plaque area greater than 3inm 2 ;
3级-有许多面积大小不等的斑块, 有的融合成片, 大斑块的 面积超过 3mm2; Level 3-there are many plaques of varying sizes, some are fused into pieces, and the area of large plaques exceeds 3 mm 2 ;
4级-动脉^ 1膜的表面几乎全为融合的斑块所覆盖。 结果见表 Level 4-The surface of the arterial membrane is almost completely covered by fused plaque. The results are shown in the table
10。 表 10 动脉主动脉内膜苏丹 I I I染色半定量观察结果 10. Table 10 Semi-quantitative observation results of Sudan III staining of arterial aorta
例数 0级 0. 5级 1级 2级 3级 4级 d  Number of cases 0 level 0.5 level 1 level 2 level 3 level 4 level d
对照 ( 6 ) 4 2 - - - - 模型 (6) - - 3 3 - - 烟酸 200 (6) 3 3 - - - - Control (6) 4 2----Model (6)--3 3--Niacin 200 (6) 3 3----
TSDP300 (6) 1 4 1 - - -TSDP300 (6) 1 4 1---
HS 200 (6) 3 3 - - - -HS 200 (6) 3 3----
HS 100 (6) 1 2 3 - - -HS 100 (6) 1 2 3---
HS 50 (6) 2 3 1 - - - 由表 10可见, HS对家兔动脉粥样硬化有明显减轻作用。 试验例 3. 德欧心捷宁对家兔血小板凝聚功能的影响 材料与方法 HS 50 (6) 2 3 1---As shown in Table 10, HS has a significant reduction effect on atherosclerosis in rabbits. Test example 3. Effect of Deouxinjiening on platelet aggregation in rabbits Materials and methods
动物 日本大耳白兔, 体重 2. 2 ~ 2. 8kg, 购自白求恩医科大学实 验动物部。 Animals Japanese large-eared white rabbits, weighing 2.2 to 2.8 kg, were purchased from the Experimental Animal Department of Bethune Medical University.
受试物质 德欧心捷宁(HS), 批号: 980810; 地奥心血康(TSDP) 胶嚢, 规格: lOOmg/粒, 批号 970609, 中科院成都地奥制药集团 有限公司产品。 Substances to be tested: Deoxin Jie Ning (HS), lot number: 980810; Diao Xinxuekang (TSDP) capsules, specifications: 100mg / capsule, lot number 970609, product of Chengdu Diao Pharmaceutical Group Co., Ltd., Chinese Academy of Sciences.
仪器 TYXN- 91血液凝集仪, 上海通用机电技术研究所产品。 Instrument TYXN-91 blood agglutination instrument, product of Shanghai General Electromechanical Technology Institute.
方法 经兔耳缘静脉取血, 以 3. 8%枸橼酸钠 1 : 9 (V/V)抗凝。 lOOOrpm/分钟, 离心 5分钟, 取富含血小板血浆(PRP)备用。 将已 吸取过 PRP的血浆继续离心, 3000rpm/分钟, 离心 10分钟, 取贫 含血小板血浆(PPP)备用。实验过程中所有接触血小板的玻璃器 均用 1% (V: V)硅油乙醚硅化, 用比浊法测定血小板凝集率。 测试 时, 取富含血小板血浆(PRP) 200 1 加入测试杯中, 在加入 ADP 诱导血小板凝集的同时, 按表 11所列浓度分别加入 TSDP和 HS, 加受试物质体积为 ΙΟ μ Ι; TSDP 以蒸馏水做对照(TSDP用蒸馏水 溶解), HS 以无水乙醇做对照(HS用无水乙醇溶解)。 记录各测试 组 1分钟 (PAG- 1) 0. 5分钟(PAG-5)和最大(PAG- M)血小板凝 聚率, 并计算抑制率。 结果见表 11。 Methods Blood was collected from the ear marginal vein of rabbits and anticoagulated with 3.8% sodium citrate 1: 9 (V / V). 1000 rpm / min, centrifuge for 5 minutes, and take platelet-rich plasma (PRP) for later use. Centrifuge the plasma that has been aspirated with PRP at 3000 rpm / min for 10 minutes. Take platelet-poor plasma (PPP) for later use. During the experiment, all glassware in contact with platelets were siliconized with 1% (V: V) silicone oil ether, and the platelet aggregation rate was measured by turbidimetry. During the test, take platelet-rich plasma (PRP) 200 1 into the test cup, while adding ADP to induce platelet aggregation, add TSDP and HS at the concentrations listed in Table 11, respectively, and add the test substance volume to 10 μ Ι; TSDP Distilled water was used as the control (TSDP was dissolved in distilled water), and HS was used as the control (HS was dissolved in anhydrous ethanol). Record each test Group 1 minute (PAG-1) 0.5 minutes (PAG-5) and maximum (PAG-M) platelet aggregation rate, and the inhibition rate was calculated. The results are shown in Table 11.
表 1 1 德欧心捷宁对家兔血小板凝聚功能的影响(x ± s) Table 1 1 Effect of Deouxinjiening on platelet aggregation in rabbits (x ± s)
且 用药量 PAG-1 PAG-5 PAG-M 抑制率  And the dosage of PAG-1 PAG-5 PAG-M inhibition rate
( %) 对照 蒸餾水 37. 68 ± 9. 28  (%) Control Distilled water 37. 68 ± 9. 28
TSDP 60 29. 29 ± 6. 59* 23. 15 TSDP 60 29. 29 ± 6. 59 * 23. 15
TSDP 120 26. 00土 3. 99' 26. 97TSDP 120 26. 00 soil 3. 99 '26. 97
TSDP 240 17. 73 ± 3. 99"* 47. 53 对照 无水乙醇 39. 86 ± 10. 08 TSDP 240 17. 73 ± 3. 99 "* 47. 53 control absolute ethanol 39. 86 ± 10. 08
HS 30 22. 24 ± 9. 29** 47. 00 HS 30 22. 24 ± 9. 29 ** 47. 00
HS 60 16. 81 ± 3. 78*** 56. 16HS 60 16. 81 ± 3. 78 *** 56. 16
HS 120 6. 16 ± 4. 56*** 5. 23 ± 5. 09~ 10. 71 ± 3. 8Γ* 76. 30 注: n=9, 与对照組比较 *P < 0. 05 ; "P < 0. 01 ; "*P < 0. 001。 HS 120 6. 16 ± 4. 56 *** 5. 23 ± 5. 09 ~ 10. 71 ± 3. 8Γ * 76. 30 Note: n = 9, compared with the control group * P <0. 05; "P <0. 01; "* P <0.001.
上述实验结果表明, TSDP和 HS体外具有明显的抗血小板凝 集作用, 在所用剂量下各测定指标均呈量效关系, 以血小板最大 凝聚率(PAG-M)计算血小板抑制率(I)可见, HS的绝对剂量(30 g ml—1)只有 TSDP绝对剂量(240 μ g ml—1) 1/8时, 体外抑制血小板 凝聚的作用强度与 TSDP相等, 抑制率分别为 47. 00%和 47. 53%。 试验例 4. 德欧心捷宁对大鼠体外血栓形成的影响 材料与方法 The above experimental results show that TSDP and HS have significant anti-platelet agglutination effects in vitro, and each of the measurement indicators has a dose-effect relationship at the dosage used. The platelet inhibition rate (I) can be calculated from the maximum platelet aggregation rate (PAG-M). The absolute dose ( 30 g ml — 1 ) of the TSDP (240 μ g ml — 1 ) was only 1/8, and the effect of inhibiting platelet aggregation in vitro was equal to that of TSDP. The inhibition rates were 47.0% and 47. 53%. Test Example 4. Effects of Deouxinjiening on thrombosis in vitro in rats Materials and methods
动物 雄性 wistar大鼠 56只, 体重 220 ~ 300g, 购自白求恩医科 大学实验动物部。 Animals 56 male wistar rats, weighing 220 ~ 300g, were purchased from the Experimental Animal Department of Bethune Medical University.
受试物质 德欧心捷宁(HS) , 批号: 980810; 地奥心血康(TSDP) 胶嚢, 规格: lOOmg/粒, 批号: 9908019, 中科院成都地奥制药集 团有限公司产品。 Substance to be tested Deoxin Jie Ning (HS), lot number: 980810; Diao Xinxuekang (TSDP) capsules, specifications: 100mg / capsule, lot number: 9908019, Chengdu Diao Pharmaceutical Group Co., Ltd.
仪器 SA-B型体外血栓形成和血小板粘附二用仪, SA- B型体外血 栓自动恒温烤箱, 国营江西省新元技术开发公司产品。 方法 实验大鼠随机分为 6 组, 分组及给受试物质剂量见表 12。 各组动物每天上午 1次, 连续 7天, 于最后 1次给受试物质 后 1小时, ip 10%水合氯醛 300mg/kg将动物麻醉, 剪开腹腔, 用 一次性采血器, 经腹主动脉取血 1.8ml, 测试体外血栓形成情况, 记录体外血栓的长度(mm), 血栓湿重及血栓干重(mg)。 结果见表 12。 Instrument SA-B type external thrombus and platelet adhesion dual-use instrument, SA-B type external thrombus automatic constant temperature oven, state-owned Jiangxi Province Xinyuan Technology Development Company products. Methods The experimental rats were randomly divided into 6 groups. See Table 12 for grouping and test substance dose. Animals in each group were anesthetized once a day for 7 consecutive days, and 1 hour after the last administration of the test substance, the animals were anesthetized with ip 10% chloral hydrate 300mg / kg, the abdominal cavity was cut, and the disposable blood collection device was used. Arterial blood was taken from 1.8 ml, and the thrombus formation in vitro was tested. The length (mm), wet thrombus weight, and dry thrombus weight (mg) of the extracorporeal blood were recorded. The results are shown in Table 12.
表 12 德欧心捷宁对大鼠体外血栓形成的影响(X士 s) Table 12 Effects of Deoxin Jiening on thrombosis in vitro in rats (X ± s)
分组 用量 动物数 体外 t#r 湿重 Animal dosage in groups t # r Wet weight
(mg/kg) (只) 长度 (ram) (mg) (mg) 对照 7 35.1± 11.43 112.0 ±24.39 40.5 ± 15.49 阿斯匹林 150 8 22.0 ± 4.99" 88.6土 16· 17* 21.9 ±9.28* (mg / kg) (only) Length (ram) (mg) (mg) Control 7 35.1 ± 11.43 112.0 ± 24.39 40.5 ± 15.49 Aspirin 150 8 22.0 ± 4.99 "88.6 soil 16. 17 * 21.9 ± 9.28 *
TSDP 300 8 25.2士 7.08* 98.5 ± 20.52# 33.5 ± 13.17*TSDP 300 8 25.2 ± 7.08 * 98.5 ± 20.52 # 33.5 ± 13.17 *
HS 200 9 20.5 ± 2.49*** 82.3 ± 17.73" HS 200 9 20.5 ± 2.49 *** 82.3 ± 17.73 "
HS 100 8 23.0 ± 5.63** 90.4 ± 16.43 27·4±8·2Γ HS 100 8 23.0 ± 5.63 ** 90.4 ± 16.43 27 · 4 ± 8 · 2Γ
HS 50 9 25.8 ± 6.58* 97.5 ± 23.23" 27.8 ± 13.55" 注: 与对照组比较, *P< 0. 05; **P< 0. 01; ***P<0.001; #P〉 0.05 本实验结果表明, HS组动物体外动脉血栓形成的长度,寸血栓 ο ο ί 湿重及血栓干重均明显低于对照组, 提示该物质具有抑制血栓形 成的作用。 试验例 5 HS 50 9 25.8 ± 6.58 * 97.5 ± 23.23 "27.8 ± 13.55" Note: Compared with the control group, * P <0. 05; ** P <0. 01; *** P <0.001; #P> 0.05 This experiment The results showed that the length of extracorporeal arterial thrombosis, the thickness of the thrombus ο ο ί and the dry weight of the thrombus in the HS group were significantly lower than those in the control group, suggesting that the substance has the effect of inhibiting thrombosis. Test example 5
德欧心捷宁降血脂的作用  The effect of deouxinjiening on blood lipids
受试患者 30人, 其中男性 17人, 女性 13人, 最大年龄 80 岁, 最小年龄 34岁, 平均年龄 55.8± 8.5岁, 30名患者受试前 均未系统应用过降血脂药。 受试患者每日正常饮食, 起居, 分别 于早、 中、 晚餐后半小时, 口服德欧心捷宁胶嚢 2粒, 然后于给 药前及给药后第 1周、 第 2周、 第 3周、 第 4周、 第 6周、 第 7 周和第 8周依次取晨起空腹静脉血测定 TG、 TC和 H0L, 见表 13、 14, 和 15。 Thirty patients were tested, including 17 males and 13 females. The maximum age was 80 years, the minimum age was 34 years, and the average age was 55.8 ± 8.5 years. None of the 30 patients had systematically applied hypolipidemic drugs before the test. Patients took a normal daily diet, lived, and took Deouxin Jie Ning Capsule 2 capsules half an hour after breakfast, lunch, and dinner, and then before, and on the first, second, and third weeks after administration. , 4th week, 6th week, 7th Weeks and week 8 were taken from early morning fasting venous blood to determine TG, TC and H0L, see Tables 13, 14, and 15.
表 13 德欧心捷宁对 TG的作用  Table 13.Effects of Deoxin Jiening on TG
組别 例数 均数 标准差 统计量 (X2) P值 疗前 30 3.6707 1.6923 Statistics of group mean standard deviation (X 2 ) P value before treatment 30 3.6707 1.6923
疗后 30 2.8200 1.4471 4.8155 P<0.01 差值 - 0.8507 -0.2452  After treatment 30 2.8200 1.4471 4.8155 P <0.01 Difference-0.8507 -0.2452
ο 表 14 德欧心捷宁对 TC的作用  ο Table 14 The effect of Deouxinjiening on TC
组別 例数 均数 标准差 统计量 (X2) P值 疗前 30 5.7500 1.6842 Statistics of group mean standard deviation (X 2 ) P value before treatment 30 5.7500 1.6842
疗后 30 5.0133 0.8966 2.2379 P< 0.05 o  After treatment 30 5.0133 0.8966 2.2379 P <0.05 o
差值 -0.7367 O  Difference -0.7367 O
表 15 德欧心捷宁对 HDL的作用 Table 15 Effect of Dexoxinine on HDL
組别 例数 均数 标准差 统计量 (X2) P值 疗前 30 1.3723 0.3038 Statistics of group mean standard deviation (X 2 ) P value before treatment 30 1.3723 0.3038
疗后 30 1.5047 0.3792 2.7562 P<0.01 差值 0.2630  After treatment 30 1.5047 0.3792 2.7562 P <0.01 Difference 0.2630
由表 13, 14可看到, 德欧心捷宁对 TG和 TC有明显的降低作 用, 而对 HDL有升高作用, 因此德欧心捷宁有降血脂作用。 试验例 6  It can be seen from Tables 13 and 14 that Deouxinjiening has a significant effect on reducing TG and TC, and has an effect of raising HDL, so Deouxinjiening has a blood lipid lowering effect. Test example 6
德欧心捷宁的抗肿瘤  Antioxin
一、 德欧心捷宁的体外抗肿瘤作用  I. Antitumor effect of Deouxinjiening in vitro
受试药物: 德欧心捷宁(HS) Tested drug: Deoxinxin (HS)
细胞培养: Cell culture:
L929, HeLa 细胞抹来 自 (American Tissue Culture Collection, ATCC, USA). 用 RPMI 1640 (Gibco)培养液, 加入 10%的胎牛血清, 1%的抗生素( 10, 000U/ml青霉素和 10,00 g/ml 链霉素) , 2ιπΜ谷氨酰胺, 置于 4%的孵箱中培养。 L929, HeLa cell wipes (American Tissue Culture Collection, ATCC, USA). Using RPMI 1640 (Gibco) medium, add 10% fetal bovine serum, 1% antibiotics (10,000 U / ml penicillin and 10,000 g / ml Streptomycin), 2 μM glutamine, cultured in a 4% incubator.
体外细胞毒实验: In vitro cytotoxicity experiment:
取处于对数生长期的细胞, 贴壁细胞(L929, HeLa)经胰蛋白 酶消化后分别接种于 96孔培养板( I X 105个 ml) , 待细胞完全贴 壁后, 分别加入以 RPMI 1640培养液配制的各浓度样品, 每种样 品种 3个复孔, 同时设 0对照和阴性对照, 继续培养 48小时, 用 MTT法于 595nm进行比色测定, 其平均值为细胞存活光密度, 将 所得的结果与对照组进行比较, 计算各条件下细胞死亡率(如下 表所示) 。 Take the cells in the logarithmic growth phase, adherent cells (L929, HeLa) were trypsinized and inoculated into 96-well culture plates (IX 10 5 ml). After the cells were completely adhered, add RPMI 1640 to culture Each concentration of the sample prepared in the liquid was prepared in 3 replicates, and a 0 control and a negative control were set at the same time. The culture was continued for 48 hours, and the colorimetric measurement was performed at 595 nm by the MTT method. The average value was the cell survival optical density. The results were compared with the control group to calculate the cell mortality under each condition (as shown in the table below).
A对照组 -A实验组  A control group -A experimental group
细胞死亡率(%) = ^-100% Cell mortality (%) = ^ -100%
A对照组 -A空白组  A control group -A blank group
表 16 不同浓度的 HS诱导的胂瘤细胞死亡率(%)  Table 16 Mortality of cancer cells induced by HS at different concentrations (%)
HS浓度 肿瘤细胞死亡率(%) μ g/ral L929 HeLa  HS concentration Tumor cell mortality (%) μ g / ral L929 HeLa
1 0 0  1 0 0
5 7. 5 12. 3  5 7. 5 12. 3
10 15. 0 20. 5  10 15. 0 20. 5
20 25. 8 37. 3  20 25. 8 37. 3
50 45. 2 50. 5  50 45. 2 50. 5
100 82. 4 98. 5 由表 16可看到,本发明的 HS在体外对肿瘤细胞 L929和 HeLa 有明显的抑制作用。  100 82. 4 98. 5 As can be seen from Table 16, the HS of the present invention has a significant inhibitory effect on tumor cells L929 and HeLa in vitro.
二、 德欧心捷宁的体内抗肿瘤作用  Second, the antitumor effect of Deouxinjiening in vivo
受试动物 4种肿瘤(肉瘤- 180( S-180 ),肝癌腹水型( HepA), 小鼠宫颈癌- 14 ( U14 ) 和艾氏腹水癌(EAC) ) 腹水传代小鼠, 均购 自吉林省肿瘤研究所: 昆明小鼠, 体重 18-22g, 购自中国人民解 放军农牧大学实验动物中心 (动物合格证号: 10-5112 ) 。 Subject animal four tumor (sarcoma - 180 (S-180), liver ascites (of HepA), cervical cancer in mice - 14 (U 14) and Ehrlich ascites carcinoma (EAC)) passaged mouse ascites, were purchased from Jilin Provincial Cancer Research Institute: Kunming mice, weighing 18-22g, purchased from the Experimental Animal Center of the People ’s Liberation Army Agricultural and Animal Husbandry University (animal certification number: 10-5112).
受试物质 HS由吉林天药科技股份有限公司制剂室提供。 注 射用环 酰胺, 规格: 200ing支, 批号: 980101, 上海华联制 药有限公司产品。 The test substance HS was provided by Jilin Tianyao Technology Co., Ltd. Preparation Room. Note Cyclamide for injection, specifications: 200ing, batch number: 980101, product of Shanghai Hualian Pharmaceutical Co., Ltd.
方法 实验小鼠随机分为对照( ig蒸馏水 20ml/kg— 、 环磷 酰胺(ip20mg/kg— 、 HS (ig200ml/kg" 100ml/kg_1和 SOml/kg—1) 和 HS(ip lOOml/kg ^ 50ml/kg— 1和 25ml/kg— 8组。 选取移植肿 瘤 7天, 肿瘤生长良好, 腹部膨隆明显的小鼠, 腹部皮肤消毒, 用一次性无菌采血器经腹壁刺入腹腔, 抽取腹水, 放入无菌烧杯 中以生理盐水稀释成 1: 3的癌细胞混悬液, 于每只实验小鼠右腋 下接种 0.2ml[1]。 各组动物于接种肿瘤次日开始给予 HS, 每日 1 次, 连续给药 10天。 给药结束次日, 将动物称体重后脱臼处死, 剥离出皮下肿块称重, 比较各组肿瘤生 +1长情况, 统计学处理方法 采用组间 "t" 检验。 Mice were divided into experimental method (IG distilled water 20ml / kg-, cyclophosphamide (ip20mg / kg-, HS (ig200ml / kg "100ml / kg _1 and SOml / kg- 1) and HS (ip lOOml / kg ^ Groups of 50ml / kg— 1 and 25ml / kg—8. Mice with transplanted tumors for 7 days, tumors growing well and obvious abdominal swelling, disinfection of abdominal skin, puncture the abdominal cavity through the abdominal wall with a disposable sterile blood sampler, and extract ascites. Put them into a sterile beaker and dilute 1: 3 cancer cell suspension with normal saline, and inoculate 0.2ml [1] in the right armpit of each experimental mouse. Animals in each group were given HS on the day after tumor inoculation. The drug was administered once a day for 10 consecutive days. The day after the end of the administration, the animals were weighed and dislocated and sacrificed, and the subcutaneous masses were removed and weighed. The tumor growth and growth in each group were compared. "Inspection.
 Inch
结果  The result
各组动物体重, 肿瘤重量及抑瘤率统计结果见表 17-20。  The statistical results of animal weight, tumor weight and tumor suppression rate of each group are shown in Table 17-20.
表 17 HS对小鼠(S18。 ) 瘤重的影响 ( X± S) TABLE 17 HS Effects on Mice (S 18.) Tumor weight (X ± S)
组別 剂量 动物数 动物体重(g) 瘤重 抑瘤率 mg/kg"1 (n) 给药前 给药后 (g) (%) 对照组 ― 10 18.6± 1.51 24.3 ± 3.06 1.56 ± 0.70 Number of animals in each group Animal weight (g) Tumor weight inhibition rate mg / kg " 1 (n) Before administration (g) (%) Control group ― 10 18.6 ± 1.51 24.3 ± 3.06 1.56 ± 0.70
环磷酰胺 20 10 19.0± 1.56 22.5 ± 2.07 0.70 ± 0.25" 55.1Cyclophosphamide 20 10 19.0 ± 1.56 22.5 ± 2.07 0.70 ± 0.25 "55.1
HS(ig) 200 10 18.7 ± 1.95 23.3 ± 1.83 0.77 ± 0.29" 50.6HS (ig) 200 10 18.7 ± 1.95 23.3 ± 1.83 0.77 ± 0.29 "50.6
HS(ig) 100 10 18.4 ± 1.78 22.2 ± 2.57 0.89 ± 0.34* 42.9HS (ig) 100 10 18.4 ± 1.78 22.2 ± 2.57 0.89 ± 0.34 * 42.9
HS(ig) 50 10 18.7 ± 1.95 23.7土 3.40 1.00± 0.37' 35.9HS (ig) 50 10 18.7 ± 1.95 23.7 soil 3.40 1.00 ± 0.37 '35.9
HS(ip) 100 10 19.1± 1.91 23.2 ± 1.93 0.76土 0.24" 51.3HS (ip) 100 10 19.1 ± 1.91 23.2 ± 1.93 0.76 soil 0.24 "51.3
HS(ip) 50 10 18.9 ± 1.97 0.83土 0.32** 46.8HS (ip) 50 10 18.9 ± 1.97 0.83 soil 0.32 ** 46.8
HS(ip) 25 10 18.9± 1· 91 22.9 ± 3.96 1.02± 0.30* 34.6 注: 与对照组比较, *p< 0.05: **ρ< 0.01 表 18 HS对小鼠(HepA) 瘤重的影响 (X±S) HS (ip) 25 10 18.9 ± 1.91 22.9 ± 3.96 1.02 ± 0.30 * 34.6 Note: Compared with the control group, * p <0.05: ** ρ <0.01 Table 18 Effect of HS on tumor weight in mice (HepA) (X ± S)
組别 剂量 动物数 动物体重(g) 瘤重 抑瘤率 mg/kg"1 (n) 给药前 给药后 (g) Number of animals in each group Animal weight (g) Tumor weight inhibition rate mg / kg " 1 (n) Before administration (g)
对照组 ― 9 18.0 ± 1.41 26.3 ± 2. ,96 1.61±0.38 环磷 胺 20 9 18.2 ± 1,72 21.4± 3. , 36 0.41 ± 0.15"* 74.5Control group ― 9 18.0 ± 1.41 26.3 ± 2., 96 1.61 ± 0.38 cyclophosphamide 20 9 18.2 ± 1,72 21.4 ± 3., 36 0.41 ± 0.15 "* 74.5
HS(ig) 200 10 18.0 1.89 27.1± 2. 85 0.94 ± 0.34*" 41.6HS (ig) 200 10 18.0 1.89 27.1 ± 2. 85 0.94 ± 0.34 * "41.6
HS(ig) 100 10 18.0 ± 1.33 26.9± 2. 18 1.12 ± 0.30" 30.4HS (ig) 100 10 18.0 ± 1.33 26.9 ± 2. 18 1.12 ± 0.30 "30.4
HS(ig) 50 10 18.1 ± 1.20 26.8 ±2. 25 1.21 ± 0.53" 24.8HS (ig) 50 10 18.1 ± 1.20 26.8 ± 2. 25 1.21 ± 0.53 "24.8
HS(ip) 100 10 18.1 ± 1.37 24.2± 1. 81 0.95 ± 0.37" 41.0HS (ip) 100 10 18.1 ± 1.37 24.2 ± 1. 81 0.95 ± 0.37 "41.0
HS(ip) 50 10 18.1 ± 1.20 26.0± 3. 09 1.01 ± 0.43" 37.3HS (ip) 50 10 18.1 ± 1.20 26.0 ± 3. 09 1.01 ± 0.43 "37.3
HS(ip) 25 10 18.1 ± 1.45 24.0 ± 3. 16 1.17 ± 0.64" 27.3 注: 与对'照组 匕较, #ρ> 0· 05; **pp<0.01; ***ρ< 0.001 HS (ip) 25 10 18.1 ± 1.45 24.0 ± 3. 16 1.17 ± 0.64 "27.3 Note: Compared with the control group, # ρ> 0 · 05; ** pp <0.01; *** ρ <0.001
表 19 HS对小鼠 U14瘤重的影响 (X±S) Table 19 Effects of HS on U 14 tumor weight in mice (X ± S)
组别 剂量 动物体重 (g) 瘤重 抑瘤率 mg/kg"1 给药前 给药后 (g) Group dose animal body weight (g) Tumor weight inhibition rate mg / kg " 1 Before administration (g)
对照組 ― 18.3 ± 0.95 28.9 ± 2.98(9) 1.84 ± 0.40 Control group-18.3 ± 0.95 28.9 ± 2.98 (9) 1.84 ± 0.40
环磷 20 18.6 ± 1.08 25.7 ± 3.40(10) 1.21 ± 0.34" 34.2Phosphorus 20 18.6 ± 1.08 25.7 ± 3.40 (10) 1.21 ± 0.34 "34.2
HS(ig) 200 18.5 ±0.85 24.7 ± 4.92(7) 1.02±0.50" 44.6HS (ig) 200 18.5 ± 0.85 24.7 ± 4.92 (7) 1.02 ± 0.50 "44.6
HS(ig) 100 18.5± 0.85 26.4 ±3.62(8) 1.20±0.32* 34.7HS (ig) 100 18.5 ± 0.85 26.4 ± 3.62 (8) 1.20 ± 0.32 * 34.7
HS(ig) 50 18.5± 0.85 26.2± 3.90(9) 1.32 ± 0.61* 28.3HS (ig) 50 18.5 ± 0.85 26.2 ± 3.90 (9) 1.32 ± 0.61 * 28.3
HS(ip) 100 18.4 ±0.84 26.1± 3.04(10) 1.00 ± 0.54" 45.7HS (ip) 100 18.4 ± 0.84 26.1 ± 3.04 (10) 1.00 ± 0.54 "45.7
HS(ip) 50 18.4 ± 0.84 24.0±3.80(10) 1.28±0.21" 30.4HS (ip) 50 18.4 ± 0.84 24.0 ± 3.80 (10) 1.28 ± 0.21 "30.4
HS(ip) 25 18.4 ± 0.84 26.1 ± 3.14(10) 1.44 ± 0.84" 21.7 注: 与对照组比较, #p> 0.05; *p< 0.05; **p< 0.01 HS (ip) 25 18.4 ± 0.84 26.1 ± 3.14 (10) 1.44 ± 0.84 "21.7 Note: Compared with the control group, #p> 0.05; * p <0.05; ** p <0.01
表 20 HS对小鼠艾氏腹水瘤重的影响 (X±S)  Table 20 Effects of HS on Ehrlich ascites tumor weight in mice (X ± S)
组別 剂量 动物体重(g) 瘤重 抑瘤率 mg/kg"1 给药前 给药后 (g) Group dose animal weight (g) Tumor weight inhibition rate mg / kg " 1 Before administration (g)
对照組 ― 20.4± 0.97 30.3 ± 2.71(10) 1.91± 1.10 Control group ― 20.4 ± 0.97 30.3 ± 2.71 (10) 1.91 ± 1.10
环磷欲 >胺 20 20.4± 0.97 26.6± 3.89(10) 1.45 0.52" 24.1Cyclophosphate> Amine 20 20.4 ± 0.97 26.6 ± 3.89 (10) 1.45 0.52 "24.1
HS(ig) 200 20.5 ± 0.85 27.8 ± 3.53(9) 1.46±0.32" 23.6HS (ig) 200 20.5 ± 0.85 27.8 ± 3.53 (9) 1.46 ± 0.32 "23.6
HS(ig) 100 20.4 ±0.97 26.9 ± 3.99(10) 1.70 ± 0.54" 11.0HS (ig) 100 20.4 ± 0.97 26.9 ± 3.99 (10) 1.70 ± 0.54 "11.0
HS(ig) 50 20.5 ±0.85 29.0 ± 2.18(9) 1.50 ± 0.68" 21.5HS (ig) 50 20.5 ± 0.85 29.0 ± 2.18 (9) 1.50 ± 0.68 "21.5
HS(ip) 100 20.4 ± 0.97 28.2 ± 1.86(9) 1.78 ± 0.80" 6.8HS (ip) 100 20.4 ± 0.97 28.2 ± 1.86 (9) 1.78 ± 0.80 "6.8
HS(ip) 50 20.4 ± 0.97 27.1 ± 2.56(10) 2.07 ± 0.85" -8.4HS (ip) 50 20.4 ± 0.97 27.1 ± 2.56 (10) 2.07 ± 0.85 "-8.4
HS(ip) 25 20.4 ± 0.97 30.5 ± 4.72(10) 2.27 ± 1.05" 37.3 注: 与对照組比较, #p> 0.05; *p< 0.05; 由表 17-20可看到, 本发明的 HS在体内对肿瘤有明显抑 制作用。 HS (ip) 25 20.4 ± 0.97 30.5 ± 4.72 (10) 2.27 ± 1.05 "37.3 Note: Compared with the control group, #p>0.05; * p <0.05; As can be seen from Tables 17-20, the HS of the present invention has a significant inhibitory effect on tumors in vivo.

Claims

权 利 要 求 Rights request
1. 德欧心捷宁在制备用于预防或治疗心血管疾病或症状、 抑制 肿瘤及降血脂的药物中用途。 1. Use of Deoxin Jiening in the preparation of medicines for preventing or treating cardiovascular diseases or symptoms, inhibiting tumors and lowering blood lipids.
2- 用于预防或治疗心血管疾病或症状, 抑制肿瘤及降血脂的组 合物, 其包括德欧心捷宁及无毒且惰性的载体或赋形剂。  2- A composition for preventing or treating cardiovascular diseases or symptoms, inhibiting tumors and lowering blood lipids, which includes Dioxininine and a non-toxic and inert carrier or excipient.
3. 预防或治疗心血管疾病或症状, 抑制肿瘤及降血脂的方法, 其包括将预防或治疗有效量的德欧心捷宁给予需要的哺乳动物。 3. A method for preventing or treating cardiovascular disease or symptoms, suppressing tumors and lowering blood lipids, which comprises administering a prophylactically or therapeutically effective amount of Deoxentine to a mammal in need.
4. 权利要求 1的用途, 其中德欧心捷宁可以片剂、 胶嚢、 溶液、 混悬剂、 粒剂、 粉剂或注射液形式使用。 4. The use according to claim 1, wherein Deoxin Jiening can be used in the form of tablets, capsules, solutions, suspensions, granules, powders or injections.
5. 权利要求 2的组合物, 其中该組合物是片剂、 胶嚢、 溶液、 混悬剂、 粒剂、 粉剂或注射液形式。  5. The composition of claim 2, wherein the composition is in the form of a tablet, capsule, solution, suspension, granule, powder or injection.
PCT/CN2001/001272 2001-08-24 2001-08-24 USE OF 3β-HYDROXY-5-SPIROSTENE AS DRUGS FOR PREVENTION OR TREATMENT OF CARDIOVASCULAR DISEASES OR CONDITIONS FOR INHIBITION OF TUMORS AND DECREASING OF BLOOD LIPIDS WO2003022287A1 (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006107902A3 (en) * 2005-04-01 2006-11-30 Samaritan Pharmaceuticals Inc Use of spirostenols to treat mitochondrial disorders

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3890438A (en) * 1972-10-06 1975-06-17 American Home Prod Compositions and methods for reducing blood cholesterol
CN1293199A (en) * 2000-10-20 2001-05-02 中国科学院上海有机化学研究所 Saponin library of rhammose-substituted beta-o-gluco-diosgenin and its preparing process and application

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3890438A (en) * 1972-10-06 1975-06-17 American Home Prod Compositions and methods for reducing blood cholesterol
CN1293199A (en) * 2000-10-20 2001-05-02 中国科学院上海有机化学研究所 Saponin library of rhammose-substituted beta-o-gluco-diosgenin and its preparing process and application

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
JIA MIN-RU ET AL., JOURNAL OF CHENGDU UNIVERSITY OF TCM, vol. 22, no. 4, March 1999 (1999-03-01), pages 41 - 45 *
LI JI CHEN JUN-JIE ET AL., NATURE PRODUCT AND DEVELOPMENT, vol. 11, no. 1, 1999 *
MA XIANG-RONG, JOURNAL OF ZHEJIANG CHINESE MEDICINE, no. 9, 1996, pages 396 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006107902A3 (en) * 2005-04-01 2006-11-30 Samaritan Pharmaceuticals Inc Use of spirostenols to treat mitochondrial disorders

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