CN1861114A - Application of Qishen Yidripping pills for preparing medicine for preventing and treating high-altitude oxygen deficit - Google Patents
Application of Qishen Yidripping pills for preparing medicine for preventing and treating high-altitude oxygen deficit Download PDFInfo
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Abstract
本发明涉及芪参益气滴丸在制备防治高原缺氧药物中的应用。通过芪参益气滴丸对模拟高原低氧大鼠脑组织及血液内MDA、乳酸含量的影响的实验,显示芪参益气滴丸可抑制低氧状态下脑组织及血液内乳酸和MDA含量增加,说明芪参益气滴丸可用于防治高原缺氧。The invention relates to the application of Qishen Yiqi dripping pills in the preparation of medicines for preventing and treating plateau hypoxia. Through the experiment of Qishen Yiqi Dropping Pills on the MDA and lactic acid content in the brain tissue and blood of simulated plateau hypoxic rats, it was shown that Qishen Yiqi Dropping Pills can inhibit the content of lactic acid and MDA in the brain tissue and blood under hypoxic conditions increase, indicating that Qishen Yiqi Dropping Pills can be used to prevent and treat plateau hypoxia.
Description
技术领域technical field
本发明属医药领域,具体涉及芪参益气滴丸在制备预防和治疗高原缺氧药物中的应用。The invention belongs to the field of medicine, and in particular relates to the application of Qishen Yiqi dripping pills in the preparation of medicines for preventing and treating plateau hypoxia.
背景技术Background technique
高原环境中供氧不足所致的缺氧可引起的人体机能、新陈代谢和形态等方面的改变,严重时可危及生命。一般人初次步入高原环境,首先可出现人体各器官和组织的适应性代偿反应,如呼吸加深加快,心率增快,皮肤胃肠肾等血管收缩,而脑血管及冠状动脉扩张,等等。通过上述代偿仍不能维持人体的正常代谢需要的话,就需人工吸氧等治疗。如果还不能纠正其缺氧的话,就会因为中枢神经系统的缺氧而使各神经中枢进入抑制状态,使得呼吸变浅、变慢,心率降低及心输出量的下降,肺水肿,高原性红细胞增多症,心肌梗塞,脑血栓,脑水肿,甚至死亡。对高原缺氧大部分人可通过自身调节而逐渐适应,只有一小部分人会产生一系列的临床表现。尽管如此,及早对高原缺氧进行防治仍显得非常重要。Hypoxia caused by insufficient oxygen supply in the plateau environment can cause changes in human body functions, metabolism, and morphology, which can be life-threatening in severe cases. When ordinary people step into a plateau environment for the first time, there will be adaptive compensatory reactions of various organs and tissues of the human body, such as deepening and accelerating breathing, increasing heart rate, contraction of blood vessels such as skin, stomach, intestines and kidneys, and dilation of cerebral blood vessels and coronary arteries, etc. If the normal metabolic needs of the human body cannot be maintained through the above compensation, artificial oxygen inhalation and other treatments are required. If the hypoxia cannot be corrected, each nerve center will enter a state of inhibition due to the hypoxia of the central nervous system, resulting in shallower and slower breathing, decreased heart rate and cardiac output, pulmonary edema, and plateau red blood cells. Syndrome, myocardial infarction, cerebral thrombosis, cerebral edema, and even death. Most people can gradually adapt to plateau hypoxia through self-regulation, and only a small number of people will produce a series of clinical manifestations. Nevertheless, early prevention and treatment of plateau hypoxia is still very important.
芪参益气滴丸由黄芪、丹参、三七和降香组成,用以治疗气虚血瘀型冠心病心绞痛。中国专利CN1375316A公开了该制剂的组成、制法以及在冠心病心绞痛方面的用途,但该药在防治高原缺氧方面的作用尚未见报道。Qishen Yiqi Dropping Pills are composed of Astragalus, Danshen, Panax notoginseng and Jiangxiang, and are used to treat angina pectoris of coronary heart disease of Qi deficiency and blood stasis type. Chinese patent CN1375316A discloses the composition, preparation method and application of the preparation in angina pectoris of coronary heart disease, but the effect of the medicine in preventing and treating plateau hypoxia has not been reported yet.
发明内容Contents of the invention
本发明的目的是提供芪参益气滴丸在制备防治高原缺氧药物中的应用。The object of the present invention is to provide the application of Qishen Yiqi dripping pills in the preparation of medicines for preventing and treating plateau hypoxia.
芪参益气滴丸是按重量百分比由下列组分制备而成:黄芪22.2%~66.8%,丹参11.6%~33.4%,三七2.5%~13.5%,降香14.5%~44.3%。其最佳配比为黄芪44.7%、丹参26.7%、三七6.3%、降香22.3%;或者以黄芪41.2%、丹参23.8%、三七4.5%、降香30.5%。The Qishen Yiqi dripping pill is prepared from the following components according to weight percentage: astragalus 22.2%-66.8%, salvia miltiorrhiza 11.6%-33.4%, notoginseng 2.5%-13.5%, and jiangxiang 14.5%-44.3%. The optimal ratio is astragalus 44.7%, salvia miltiorrhiza 26.7%, notoginseng 6.3%, and jiangxiang 22.3%; or astragalus 41.2%, salvia miltiorrhiza 23.8%, notoginseng 4.5%, and jiangxiang 30.5%.
为了更好的理解本发明,下面通过芪参益气滴丸对模拟海拔7500米低氧大鼠脑组织及血液内丙二醛(MDA)、乳酸含量的影响的实验,说明芪参益气滴丸在防治高原缺氧方面的作用。In order to better understand the present invention, the following experiments on the effects of Qishen Yiqi dripping pills on the brain tissue of hypoxic rats at a simulated altitude of 7500 meters and blood malondialdehyde (MDA), lactic acid content illustrate that Qishen Yiqi drops The role of pills in the prevention and treatment of plateau hypoxia.
一、方法1. Method
1.动物处理:(1)SD大鼠30只,体重180~200g,随机分为常氧对照组(n=10)、急性低氧组(n=10)、芪参益气滴丸加低氧组(n=10)。芪参益气滴丸加低氧组按0.8ml/100g体重(即30mg芪参益气滴丸/100g体重,用水溶解)剂量每天灌胃给药1次,连续7天;其余两组给予等体积的水。(2)减压方法:急性低氧组和芪参益气滴丸加低氧组动物在最后一次给药后1小时置于低压舱内,以10米/秒的速度升至海拔7500米,持续7小时;常氧对照组不做任何处理,常氧室温饲养。出舱后各组动物迅速断头剥脑、取血。其中半脑用于脑含水量的测定,另半脑称重后按1∶20(w/v)加入0~4℃的生理盐水制成5%脑匀浆。血液离心取血清。1. Animal treatment: (1) 30 SD rats, weighing 180-200g, were randomly divided into normoxia control group (n=10), acute hypoxia group (n=10), Qishen Yiqi dripping pills Oxygen group (n=10). The Qishen Yiqi Dropping Pill plus hypoxia group was given 0.8ml/100g body weight (that is, 30mg Qishen Yiqi Dropping Pill/100g body weight, dissolved in water) once a day for 7 consecutive days; volume of water. (2) Decompression method: the animals in the acute hypoxia group and the Qishen Yiqi dripping pill plus hypoxia group were placed in a hypobaric chamber one hour after the last administration, and rose to an altitude of 7,500 meters at a speed of 10 m/s. lasted for 7 hours; the normoxia control group was kept without any treatment and kept at room temperature in normoxia. After leaving the cabin, the animals in each group were quickly decapitated and their brains were stripped, and blood was collected. One half of the brain was used to measure the water content of the brain, and the other half of the brain was weighed and added to 0-4°C physiological saline at a ratio of 1:20 (w/v) to make a 5% brain homogenate. Blood was centrifuged to obtain serum.
2.脑含水量测定:用干湿质量法,各组半侧脑组织置于称量瓶中,称重后置于50℃烘箱烤干至恒重。按公式计算脑含水量:脑含水量(%)=(湿重量-干重量)/湿重量×100%。2. Determination of brain water content: using dry-wet mass method, hemibrain tissue of each group was placed in a weighing bottle, weighed and dried in an oven at 50°C until constant weight. The brain water content was calculated according to the formula: brain water content (%)=(wet weight-dry weight)/wet weight×100%.
3.生化测定:用Folin-酚法测定脑匀浆蛋白含量。取5%脑匀浆、血清各100μl测定MDA含量;组织中MDA含量以nmol/mgprot表示,血清中MDA含量以nmol/ml表示。取5%脑匀浆、血清各10μl测定乳酸含量;组织中乳酸含量以μmol/mgprot表示,血清中乳酸含量以mmol/L表示。3. Biochemical determination: Determination of brain homogenate protein content by Folin-phenol method. 100 μl of 5% brain homogenate and 100 μl of serum were taken to determine the MDA content; the MDA content in tissue was expressed in nmol/mgprot, and the MDA content in serum was expressed in nmol/ml. Take 10 μl of 5% brain homogenate and 10 μl of serum to measure the content of lactic acid; the content of lactic acid in tissue is expressed in μmol/mgprot, and the content of lactic acid in serum is expressed in mmol/L.
4.统计学方法:每组实验结果用 x±s表示,用t检验比较各组均数之间的差异显著性。4. Statistical method: the experimental results of each group are used x ± s means that the difference between the means of each group is compared by t test.
二、结果2. Results
1.脑组织匀浆含水量、MDA和乳酸含量的变化(见表1)1. Changes in water content, MDA and lactic acid content of brain tissue homogenate (see Table 1)
急性低氧组脑含水量较常氧对照组显著增加(P<0.01),MDA和乳酸含量明显增加(P<0.01);芪参益气滴丸加低氧组的脑含水量、MDA及乳酸含量较急性低氧组明显降低(P<0.05或P<0.01)。The brain water content in the acute hypoxia group was significantly higher than that in the normoxia control group (P<0.01), and the MDA and lactic acid contents were significantly increased (P<0.01); The content was significantly lower than that in the acute hypoxia group (P<0.05 or P<0.01).
表1 脑组织匀浆含水量、MDA、乳酸含量的变化(
x±s)
注:与常氧对照组比较,*P<0.05 **P<0.01Note: Compared with the normoxia control group, * P<0.05 ** P<0.01
与急性低氧组比较,#P<0.05 ##P<0.01Compared with the acute hypoxia group, # P<0.05 ## P<0.01
2.血清中MDA和乳酸含量的变化(见表2)2. Changes of MDA and lactic acid content in serum (see Table 2)
急性低氧组血清中MDA及乳酸含量较常氧对照组显著增高(P<0.01),芪参益气滴丸加低氧组血清中MDA和乳酸含量较急性低氧组显著降低(P<0.01)。The serum MDA and lactic acid contents in the acute hypoxia group were significantly higher than those in the normal oxygen control group (P<0.01), and the serum MDA and lactic acid contents in the Qishen Yiqi dripping pills plus hypoxia group were significantly lower than those in the acute hypoxia group (P<0.01 ).
表2 血清中MDA、乳酸含量的变化(
x±s)
注:与常氧对照组比较,*P<0.05 **P<0.01Note: Compared with the normoxia control group, * P<0.05 ** P<0.01
与急性低氧组比较,#P<0.05 ##P<0.01Compared with the acute hypoxia group, # P<0.05 ## P<0.01
低氧引起脑组织和血液中葡萄糖无氧酵解的过程增强,乳酸生成增加。乳酸在组织积聚会导致细胞渗透压增高,线粒体肿胀和破裂,影响线粒体呼吸功能而发生能量代谢降碍。低氧时胞内乳酸和氧自由基与脂质过氧化物生成增加,又会损伤线粒体的能量代谢,胞内ATP水平下降。上述实验中,经低氧暴露后大鼠脑组织和血液中乳酸和MDA含量明显增加,而低氧前预先给予芪参益气滴丸可抑制乳酸和MDA含量增加。这一结果表明,而芪参益气滴丸具有促进ATP生成能力,可用于防治高原缺氧。Hypoxia induces enhanced anaerobic glycolysis of glucose in brain tissue and blood and increased lactic acid production. The accumulation of lactic acid in tissues will lead to increased cell osmotic pressure, mitochondrial swelling and rupture, affecting mitochondrial respiratory function and resulting in energy metabolism disorders. During hypoxia, the generation of intracellular lactic acid, oxygen free radicals and lipid peroxides increases, which will damage the energy metabolism of mitochondria, and the intracellular ATP level will decrease. In the above experiments, the content of lactic acid and MDA in brain tissue and blood of rats significantly increased after exposure to hypoxia, and the pre-administration of Qishen Yiqi Dropping Pills before hypoxia could inhibit the increase of lactic acid and MDA content. This result shows that Qishen Yiqi dripping pills have the ability to promote ATP production and can be used to prevent and treat plateau hypoxia.
具体实施方式Detailed ways
下面结合实施例对本发明的药物做进一步说明,下述各实施例仅用于说明本发明而并非对本发明的限制。The medicine of the present invention will be further described below in conjunction with the examples, and the following examples are only used to illustrate the present invention rather than limit the present invention.
实施例一Embodiment one
取黄芪86.5g、丹参21.3g、三七3.5g、降香20.6g、辅料聚乙二醇-6000 30g。将经粉碎的丹参、三七,水煎煮2次,每次加7倍量水,每次2小时,合并煎煮液,滤过,滤液浓缩至900ml,加入95%乙醇,使醇浓度达到70%,静置12~24小时,滤过,回收乙醇,浓缩成相对密度为1.32~1.38(50~60℃)的浸膏;将经粉碎的黄芪,加水煎煮2次,每次加6倍量水,依次提取2小时、1小时,合并滤液,浓缩至1500ml左右时,加95%乙醇使醇浓度为60%,静置12~24小时,滤过,滤液回收乙醇,浓缩至400ml左右时,加95%乙醇使醇浓度为80%,静置12~24小时,滤过,滤液回收乙醇,浓缩成相对密度为1.32~1.38(50~60℃)的浸膏;取降香,加5倍量水,回流提取5小时,收集挥发油;取上述丹参三七浸膏、黄芪浸膏及聚乙二醇-6000,水浴溶化,化匀后,加入降香挥发油,混匀,移至滴丸机中,制成1000粒滴丸。Take 86.5g of Radix Astragali, 21.3g of Salvia Miltiorrhiza, 3.5g of Panax notoginseng, 20.6g of Jiangxiang, and 30g of polyethylene glycol-6000 as an auxiliary material. Decoct the crushed salvia miltiorrhiza and Panax notoginseng in water twice, adding 7 times the amount of water each time for 2 hours each time, combining the decoction liquid, filtering, and concentrating the filtrate to 900ml, adding 95% ethanol to make the alcohol concentration reach 70%, let it stand for 12-24 hours, filter, recover ethanol, concentrate into an extract with a relative density of 1.32-1.38 (50-60°C); decoct the pulverized Astragalus membranaceus twice with water, adding 6 Double the amount of water, extract for 2 hours and 1 hour in turn, combine the filtrate, and when concentrated to about 1500ml, add 95% ethanol to make the alcohol concentration 60%, let it stand for 12-24 hours, filter, recover ethanol from the filtrate, and concentrate to about 400ml , add 95% ethanol to make the alcohol concentration 80%, let it stand for 12 to 24 hours, filter, reclaim the ethanol from the filtrate, and concentrate it into an extract with a relative density of 1.32 to 1.38 (50 to 60°C); 5 times the amount of water, reflux for extraction for 5 hours, and collect the volatile oil; take the above-mentioned Danshen Sanqi extract, Astragalus extract, and polyethylene glycol-6000, dissolve in a water bath, and after homogenization, add the balsamic volatile oil, mix well, and move to the drop In the pill machine, make 1000 drop pills.
实施例二Embodiment two
取黄芪40.6g、丹参44.8g、三七11.2g、降香38.6g,辅料聚乙二醇-6000 30g,按实施例1的制备工艺制成本发明的中药制剂。Get Astragalus 40.6g, Salvia miltiorrhiza 44.8g, Radix Notoginseng 11.2g, Dalbergia 38.6g, adjuvant Polyethylene Glycol-6000 30g, the preparation technology of embodiment 1 is made Chinese medicine preparation of the present invention.
实施例三Embodiment Three
取黄芪77.3g、丹参22.8g、三七4.8g、降香30.5g、辅料聚乙二醇-6000 28g,按实施例1的制备工艺制成本发明的中药制剂。Get Radix Astragali 77.3g, Salvia Miltiorrhiza 22.8g, Radix Notoginseng 4.8g, Dalbergia 30.5g, adjuvant Polyethylene Glycol-6000 28g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
实施例四Embodiment Four
取黄芪42.3g、丹参39.2g、三七8.2g、降香46.8g、辅料聚乙二醇-6000 25g,按实施例1的制备工艺制成本发明的中药制剂。Get Radix Astragali 42.3g, Salvia Miltiorrhiza 39.2g, Radix Notoginseng 8.2g, Dalbergia 46.8g, adjuvant Polyethylene Glycol-6000 25g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
实施例五Embodiment five
取黄芪65.2g、丹参38.9g、三七9.3g、降香32.5g、辅料聚乙二醇-6000 40g,按实施例1的制备工艺制成本发明的中药制剂。Get Radix Astragali 65.2g, Salvia Miltiorrhiza 38.9g, Radix Notoginseng 9.3g, Radix Dalbergia 32.5g, adjuvant Polyethylene Glycol-6000 40g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
实施例六Embodiment six
取黄芪56.2g、丹参32.5g、三七6.2g、降香41.6g、辅料聚乙二醇-6000 22g,按实施例1的制备工艺制成本发明的中药制剂。Get Radix Astragali 56.2g, Salvia Miltiorrhiza 32.5g, Radix Notoginseng 6.2g, Dalbergia 41.6g, adjuvant Polyethylene Glycol-6000 22g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
实施例七Embodiment seven
取黄芪36.5g、丹参32.4g、三七6.2g、降香41.7g、辅料聚乙二醇-6000 22g,按实施例1的制备工艺制成本发明的中药制剂。Get Radix Astragali 36.5g, Salvia Miltiorrhiza 32.4g, Radix Notoginseng 6.2g, Dalbergia 41.7g, adjuvant Polyethylene Glycol-6000 22g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
实施例八Embodiment Eight
取黄芪65.6g、丹参25.8g、三七9.5g、降香46.4g,辅料聚乙二醇-6000 35g,按实施例1的制备工艺制成本发明的中药制剂。Get Radix Astragali 65.6g, Salvia Miltiorrhiza 25.8g, Panax notoginseng 9.5g, Dalbergia 46.4g, adjuvant Polyethylene Glycol-6000 35g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
实施例九Embodiment nine
取黄芪35.5g、丹参50.8g、三七16.3g、降香52.3g、辅料聚乙二醇-6000 35g,按实施例1的制备工艺制成本发明的中药制剂。Get Radix Astragali 35.5g, Salvia Miltiorrhiza 50.8g, Radix Notoginseng 16.3g, Radix Dalbergia 52.3g, adjuvant Polyethylene Glycol-6000 35g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2012000425A1 (en) * | 2010-06-28 | 2012-01-05 | 天津天士力制药股份有限公司 | Use of a chinese medicine composition in preparing medicaments for treating secondary prevention of myocardial infarction |
| CN104839810A (en) * | 2015-03-30 | 2015-08-19 | 孙村镇中药材种植技术协会 | High-altitude hypoxia resistance enhancing partially fermented rhodiola rosea and Chinese wolfberry fruit juice and preparation method thereof |
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| CN1248702C (en) * | 2002-02-07 | 2006-04-05 | 天津天士力制药股份有限公司 | Traditional Chinese medicine preparation for treating coronary heart disease angina pectoris and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012000425A1 (en) * | 2010-06-28 | 2012-01-05 | 天津天士力制药股份有限公司 | Use of a chinese medicine composition in preparing medicaments for treating secondary prevention of myocardial infarction |
| JP2013529655A (en) * | 2010-06-28 | 2013-07-22 | テースリー ファーマシューティカル グループ カンパニー リミテッド | Use of traditional Chinese medicine composition in the manufacture of medicine for secondary prevention treatment of myocardial infarction |
| US9211310B2 (en) | 2010-06-28 | 2015-12-15 | Tasly Pharmaceutical Group Co., Ltd | Use of a Chinese medicine composition in preparing medicaments for treating secondary prevention of myocardial infarction |
| CN104839810A (en) * | 2015-03-30 | 2015-08-19 | 孙村镇中药材种植技术协会 | High-altitude hypoxia resistance enhancing partially fermented rhodiola rosea and Chinese wolfberry fruit juice and preparation method thereof |
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