CN108324829A - A kind of Hemorrhagic shock mixture and preparation method thereof containing ginseng - Google Patents
A kind of Hemorrhagic shock mixture and preparation method thereof containing ginseng Download PDFInfo
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Abstract
本发明公开了一种含人参的抗休克合剂,其制备原料由以下重量份数的组分组成:人参20‑30份、七叶一枝花10‑20份、青皮10‑20份、鹿衔草5‑15份、龙葵5‑15份、凌霄花5‑10份、如意草3‑5份。本发明还提供了一种含人参的抗休克合剂的制备方法。本发明的抗休克合剂具有益气养阴生血、温阳化瘀通络,益气健脾的功效,能显著改善心脏功能,恢复血压和心率到正常水平,对失血性休克具有较好的疗效。此外,本发明的抗休克合剂选用天然中药原料制成,药材配伍合理,符合中医药及现代医学研究理论,能达到标本兼治的目的,且本发明制备工艺简单,药效稳定,易于推广应用,具有较好的应用前景。The invention discloses an anti-shock mixture containing ginseng. The raw materials for its preparation are composed of the following components in parts by weight: 20-30 parts of ginseng, 10-20 parts of Aesculus aesculata, 10-20 parts of green bark, and Herba Cervix 5‑15 parts, 5‑15 parts of Solanum nigrum, 5‑10 parts of Ling Xiaohua, 3‑5 parts of Ruyi grass. The invention also provides a preparation method of the anti-shock mixture containing ginseng. The anti-shock mixture of the present invention has the effects of nourishing qi, nourishing yin and generating blood, warming yang, removing blood stasis and dredging collaterals, replenishing qi and invigorating the spleen, can significantly improve heart function, restore blood pressure and heart rate to normal levels, and has a good curative effect on hemorrhagic shock . In addition, the anti-shock mixture of the present invention is made from natural Chinese medicine raw materials, the medicinal materials are reasonably compatible, conforms to the research theory of Chinese medicine and modern medicine, and can achieve the purpose of treating both symptoms and root causes, and the preparation process of the present invention is simple, the drug effect is stable, and it is easy to popularize and apply. It has a good application prospect.
Description
技术领域technical field
本发明属于中药技术领域,具体涉及一种含人参的抗休克合剂及其制备方法。The invention belongs to the technical field of traditional Chinese medicines, and in particular relates to an anti-shock mixture containing ginseng and a preparation method thereof.
背景技术Background technique
休克是机体在严重失血失液、感染、创伤等强烈致病因素作用下,有效循环血量急剧减少,组织血液灌流严重不足,导致各种重要生命器官、细胞功能代谢障碍和结构损害的全身性病理过程。休克是临床上较为常见的一个急症,虽然发病原因多和发病机制复杂,但微循环障碍是多型休克发生的共同基础。在休克发生发展过程中,机体产生一系列的病理生理改变,主要有心收缩力降低、微循环血量减少、血流分布异常、供氧量降低、造成明显的缺血-再灌注损伤、炎症介质泛滥等,在这一病理过程中它们相互转化、互为因果,导致机体能量生成障碍,组织缺血、缺氧,神经体液机制激活,机体代谢和功能发生多方面紊乱,最终可能导致全身炎症反应综合征(SIRS)和多器官功能障碍(MODS),甚至死亡。Shock is a systemic systemic disorder in which the effective circulating blood volume decreases sharply and tissue blood perfusion is seriously insufficient under the action of severe blood loss, fluid loss, infection, trauma and other strong pathogenic factors, leading to various important vital organs, cellular dysfunction and structural damage. pathological process. Shock is a common clinical emergency. Although there are many causes and complicated pathogenesis, microcirculatory disturbance is the common basis for polymorphic shock. During the development of shock, the body produces a series of pathophysiological changes, mainly including decreased cardiac contractility, decreased microcirculatory blood volume, abnormal blood flow distribution, decreased oxygen supply, obvious ischemia-reperfusion injury, and inflammatory mediators. In this pathological process, they transform each other and cause and effect each other, leading to energy generation disorders, tissue ischemia, hypoxia, activation of neurohumoral mechanisms, and various disturbances in body metabolism and functions, which may eventually lead to systemic inflammatory reactions syndrome (SIRS), multiple organ dysfunction (MODS), and even death.
大量失血引起的休克称为失血性休克。常见于外伤引起的出血、消化性溃疡出血、食管曲张静脉破裂、妇产科疾病所引起的出血等。失血后是否发生休克不仅取决于失血的量,还取决于失血的速度,休克往往是在快速、大量(超过总血量的30%-35%)失血而又得不到及时补充的情况下发生的。Shock caused by massive blood loss is called hemorrhagic shock. It is common in bleeding caused by trauma, peptic ulcer bleeding, rupture of esophageal varices, bleeding caused by obstetrics and gynecology diseases, etc. Whether shock occurs after blood loss depends not only on the amount of blood loss, but also on the speed of blood loss. Shock often occurs when blood is lost rapidly and in large quantities (more than 30%-35% of the total blood volume) and cannot be replenished in time of.
目前市场的药物治疗还是以西药为主要手段,中药制剂虽然也有不少,但是安全性、治疗效果又难以确保,能够起到有效的作用却很少。The drug treatment in the current market still takes western medicine as the main means. Although there are many traditional Chinese medicine preparations, it is difficult to ensure their safety and therapeutic effect, and there are very few effective effects.
人参是五加科人参属植物,人参中含有的人参皂甙可使出血性休克犬存活时间明显延长,能防止失血性休克心肌细胞的肌膜、核膜、线粒体的损伤,有保护休克动物心、脑、肾和肝的作用,但是现有的研究仅仅显示人参中含有的人参二醇皂苷以及人参皂苷Re对失血性休克具备一定的治疗效果,并没有有关人参皂苷Rb1治疗失血性休克的报道;徐宏平等人研究了人参皂甙Rb1对感染性休克大鼠重要器官的保护作用(Journal of ZhengzhouUniversity.May 2014 Vol.49 No.3),证明Rb1可保护感染性休克大鼠肝、肺组织,其机制可能与减少TLR4 mRNA表达水平,抑制TNF-α的产生有关,同样,该文献也没有研究人参皂甙Rb1对失血性休克的治疗作用。Ginseng is a plant of the genus Panax of Araliaceae. The ginsenoside contained in ginseng can significantly prolong the survival time of dogs with hemorrhagic shock, prevent damage to the sarcolemma, nuclear membrane, and mitochondria of myocardial cells in hemorrhagic shock, and protect the heart, Brain, kidney and liver, but existing studies only show that ginseng saponins and ginsenoside Re contained in ginseng have a certain therapeutic effect on hemorrhagic shock, and there is no report on the treatment of hemorrhagic shock with ginsenoside Rb1; Xu Hongping and others studied the protective effect of ginsenoside Rb1 on the vital organs of septic shock rats (Journal of Zhengzhou University. May 2014 Vol.49 No.3), and proved that Rb1 can protect the liver and lung tissues of septic shock rats, and The mechanism may be related to reducing the expression level of TLR4 mRNA and inhibiting the production of TNF-α. Similarly, the literature did not study the therapeutic effect of ginsenoside Rb1 on hemorrhagic shock.
本发明采用新型高效的提取方法,将人参中含有的人参皂甙Rb1提取出来,并和其它中药原料配伍使用,经动物实验证明,本发明的抗休克合剂对失血性休克具备良好的治疗效果。The invention adopts a novel and efficient extraction method to extract the ginsenoside Rb1 contained in the ginseng and use it in combination with other traditional Chinese medicine raw materials. Animal experiments prove that the anti-shock mixture of the invention has a good therapeutic effect on hemorrhagic shock.
发明内容Contents of the invention
本发明提供了一种含人参的抗休克合剂,解决了现有技术中市场的药物治疗还是以西药为主要手段,中药制剂虽然也有不少,但是安全性、治疗效果难以确保的问题。The invention provides an anti-shock mixture containing ginseng, which solves the problem that in the prior art, western medicine is still the main means of drug treatment in the market, and although there are many traditional Chinese medicine preparations, it is difficult to ensure the safety and therapeutic effect.
本发明的第一个目的是提供一种含人参的抗休克合剂,其制备原料由以下重量份数的组分组成:人参20-30份、七叶一枝花10-20份、青皮10-20份、鹿衔草5-15份、龙葵5-15份、凌霄花5-10份、如意草3-5份。The first object of the present invention is to provide a ginseng-containing anti-shock mixture, the preparation raw materials of which are composed of the following components in parts by weight: 20-30 parts of ginseng, 10-20 parts of Aescin, 10-20 parts of Qingpi 5-15 parts of Cervus nigra, 5-15 parts of Solanum nigrum, 5-10 parts of Ling Xiaohua, 3-5 parts of Ruyi grass.
优选的,所述含人参的抗休克合剂的制备原料由以下重量份数的组分组成:人参25份、七叶一枝花15份、青皮15份、鹿衔草10份、龙葵10份、凌霄花5份、如意草5份。Preferably, the raw materials for the preparation of the ginseng-containing anti-shock mixture consist of the following components in parts by weight: 25 parts of ginseng, 15 parts of Echinacea chinensis, 15 parts of green bark, 10 parts of deerbite, 10 parts of black nightshade, 5 parts of Lingxiaohua and 5 parts of Ruyicao.
本发明的第二个目的是提供一种含人参的抗休克合剂的制备方法,包括以下步骤:The second object of the present invention is to provide a preparation method of anti-shock mixture containing ginseng, comprising the following steps:
步骤1,按重量份称取人参20-30份、七叶一枝花10-20份、青皮10-20份、鹿衔草5-15份、龙葵5-15份、凌霄花5-10份、如意草3-5份;Step 1, take by weight 20-30 parts of ginseng, 10-20 parts of Aescin, 10-20 parts of green bark, 5-15 parts of cervix, 5-15 parts of black nightshade, 5-10 parts of Ling Xiaohua, 3-5 parts of wishful grass;
步骤2,将步骤1中称取的人参干燥、粉碎后过20目筛,得到人参粉;将人参粉与水、木质素过氧化物酶按照100:50:1的质量比混合均匀,然后置于60℃下酶解3h,酶解完毕得到酶解产物;将酶解产物过滤,得第一滤液和滤渣,往滤渣中加入相当于滤渣重量5倍的乙醇溶剂超声提取,提取完毕后过滤,得第二滤液,合并第一滤液和第二滤液,减压浓缩至相对密度为1.3-1.4,得到人参提取物;Step 2, drying and crushing the ginseng weighed in step 1, passing through a 20-mesh sieve to obtain ginseng powder; mixing ginseng powder, water, and lignin peroxidase in a mass ratio of 100:50:1, and then placing Enzyme hydrolyze at 60°C for 3 hours, and the enzymolysis product is obtained after enzymolysis; filter the enzymolysis product to obtain the first filtrate and filter residue, add an ethanol solvent equivalent to 5 times the weight of the filter residue to the filter residue for ultrasonic extraction, and filter after the extraction is completed. Obtain the second filtrate, combine the first filtrate and the second filtrate, and concentrate under reduced pressure to a relative density of 1.3-1.4 to obtain a ginseng extract;
将人参提取物与水按照1g:10mL的比例混合溶解后过硅胶柱,在柱压为-0.5Mpa的条件下进行硅胶柱层析,并用乙醇和乙酸乙酯的混合溶液作为洗脱剂进行洗脱,收集馏分并浓缩、干燥,得到人参皂苷粗品;Mix and dissolve the ginseng extract and water according to the ratio of 1g: 10mL, pass it through a silica gel column, perform silica gel column chromatography at a column pressure of -0.5Mpa, and use a mixed solution of ethanol and ethyl acetate as an eluent to wash Take off, collect fractions and concentrate, dry, obtain ginsenoside crude product;
将人参皂苷粗品和正丁醇按照1g:5mL的比例混合溶解后注入到高效制备液相色谱仪中,采用乙醇水混合溶液洗脱,收集馏分并浓缩、干燥,得到人参皂苷Rb1;The crude ginsenoside and n-butanol were mixed and dissolved according to the ratio of 1g:5mL, then injected into a high-performance preparative liquid chromatograph, eluted with a mixed solution of ethanol and water, and the fractions were collected, concentrated, and dried to obtain ginsenoside Rb1;
步骤3,将步骤1中称取的七叶一枝花干燥、粉碎后过20目筛,得到七叶一枝花粉,往七叶一枝花粉中加入相当于其重量加入5%的棘孢曲霉培养液,在28-30℃条件下发酵5天,发酵完毕得到发酵产物;Step 3, drying and pulverizing the Aesculus aesculus flower weighed in step 1 and passing through a 20-mesh sieve to obtain Aesculus Aesculus pollen, adding 5% Aspergillus aculeatus culture solution equivalent to its weight to the Aesculus aesculata pollen, Ferment for 5 days under the condition of 28-30°C, and the fermentation product is obtained after the fermentation is completed;
将发酵产物与乙醇水溶液按1g:5mL的比例混合,然后于80℃下回流3h,回流完毕后过滤,滤液浓缩至相对密度为1.3-1.4,即得七叶一枝花提取物;Mix the fermentation product with ethanol aqueous solution at a ratio of 1 g: 5 mL, then reflux at 80°C for 3 hours, filter after the reflux is completed, and concentrate the filtrate to a relative density of 1.3-1.4 to obtain the Aescinus aesculus extract;
步骤4,将步骤1中称取的青皮、鹿衔草、龙葵、凌霄花、如意草混合,得到混合料,然后往混合料中加入相当于混合料质量5倍的乙醇,加热回流3h后过滤,得滤液,将滤液减压浓缩除去乙醇,得到混合提取物;Step 4, mix the green bark, chrysanthemum, black nightshade, lingxiaohua, and ruyicao weighed in step 1 to obtain a mixture, then add ethanol equivalent to 5 times the weight of the mixture to the mixture, heat and reflux for 3 hours, and then filter , to obtain the filtrate, the filtrate was concentrated under reduced pressure to remove ethanol, and a mixed extract was obtained;
步骤5,将步骤2中人参皂苷Rb1、步骤3中七叶一枝花提取物以及步骤4中混合提取物混合,然后往其中加入与人参皂苷Rb1、七叶一枝花提取物以及混合提取物总重量相等的蔗糖水溶液,混合均匀,即得到所述抗休克合剂。Step 5, mix ginsenoside Rb1 in step 2, Aesculus aesculus extract in step 3 and mixed extract in step 4, and then add the total weight of ginsenoside Rb1, Aesculus aesculus extract and mixed extract The equal sucrose aqueous solution is mixed evenly to obtain the anti-shock mixture.
优选的,所述步骤2中超声提取条件为50℃、功率200w,超声提取30min。Preferably, the ultrasonic extraction conditions in step 2 are 50°C, 200w power, and 30min ultrasonic extraction.
优选的,所述木质素过氧化物酶的酶活力为10000U/mL。Preferably, the enzyme activity of the lignin peroxidase is 10000U/mL.
优选的,所述硅胶柱的径高比为1:5。Preferably, the diameter-to-height ratio of the silica gel column is 1:5.
优选的,所述棘孢曲霉培养液中有效活菌数≥1010CFU/mL。Preferably, the number of effective viable bacteria in the Aspergillus aculeatus culture solution is ≥10 10 CFU/mL.
优选的,所述蔗糖水溶液的质量浓度为80%。Preferably, the mass concentration of the sucrose aqueous solution is 80%.
本发明中各原料中药药物的药理作用和药效:Pharmacological action and drug effect of each raw material Chinese medicine drug in the present invention:
1、人参:性平、味甘、微苦,微温。归脾、肺、心经。具有大补元气、复脉固脱、补脾益肺、生津止渴、安神益智的功效。《神农本草经》明确记载“人参主补五脏,安精神,定魂魄,止惊悸,除邪气,明目开心益智,久服轻身延年”。人参皂苷为人参的主要有效成分之一,人参皂苷中的人参皂苷Rb1对脂多糖诱导的大鼠肠系膜微循环障碍有保护作用,对大鼠急性肾小管损伤有保护作用、能促进兔软骨细胞增殖、抑制黑色素细胞一氧化氮合酶表达,对中枢神经系统损伤有修复的作用,对缺血再灌注脑组织损伤有较好的保护作用。1. Ginseng: flat in nature, sweet in taste, slightly bitter, slightly warm. Return spleen, lung, heart channel. It has the effects of invigorating vital energy, recovering veins and strengthening the spleen, nourishing the spleen and lungs, promoting body fluid and quenching thirst, calming the nerves and improving intelligence. "Shen Nong's Materia Medica" clearly records that "Ginseng mainly nourishes the five internal organs, soothes the spirit, calms the soul, relieves palpitations, eliminates evil spirits, improves eyesight, improves intelligence, makes light of body and prolongs life after long-term use." Ginsenoside is one of the main active ingredients of ginseng. Ginsenoside Rb1 in ginsenoside has protective effect on lipopolysaccharide-induced mesenteric microcirculation disorder in rats, has protective effect on acute renal tubular injury in rats, and can promote rabbit chondrocyte proliferation , Inhibit the expression of nitric oxide synthase in melanocytes, have a repairing effect on central nervous system damage, and have a better protective effect on ischemia-reperfusion brain tissue damage.
2、七叶一枝花:苦、凉。小毒。归心、肝、肺、胃、大肠经。具有败毒抗癌、消肿止痛、清热定惊、镇咳平喘的功效。七叶一枝花根茎含有甾体皂甙、丙氨酸等18种氨基酸及肌酐等多种成分,能治痈肿肺痨久咳、跌打损伤、蛇虫咬伤、淋巴结核、骨髓炎等症,是云南白药的主要成分之一;近年来,又相继发现其化学成分薯蓣皂甙元具有良好的抗肿瘤、抗菌、消炎和治疗胃溃疡、白血病、心血管疾病、镇静镇痛、止咳平喘以及抑精等生理活性作用。2, Aescin aesculus: bitter, cool. Small poison. GUIXIN, liver, lung, stomach, large intestine channel. It has the effects of detoxifying and anticancer, reducing swelling and relieving pain, clearing heat and calming convulsions, relieving cough and asthma. The rhizome of Aescin contains 18 kinds of amino acids such as steroidal saponins and alanine, and creatinine and other components. One of the main components of Yunnan Baiyao; in recent years, it has been found that its chemical component diosgenin has good antitumor, antibacterial, anti-inflammatory and therapeutic effects on gastric ulcer, leukemia, cardiovascular disease, sedative and analgesic, cough and asthma, and sperm suppression. and other physiological activities.
3、青皮:性苦、辛、温。归肝、胆、胃经。具有疏肝破气,消积化滞的功效。用于胸胁胀痛,疝气疼痛,食积气滞,脘腹胀痛等病症。经试验研究表明,青皮松弛胃肠平滑肌的作用最强,机理是阻断M受体、兴奋α受体、直接抑制肠平滑肌。另外青皮对升压的维持时间较长,能兴奋呼吸,具有抗休克、兴奋心脏的作用。3, Qingpi: bitter, pungent, warm in nature. Return liver, gallbladder, stomach warp. It has the effects of soothing the liver and breaking qi, eliminating accumulation and stagnation. It is used for distending pain in the chest and hypochondrium, hernia pain, stagnation of Qi due to indigestion, abdominal distension and pain. Experimental studies have shown that Qingpi has the strongest effect on relaxing gastrointestinal smooth muscle, and the mechanism is to block M receptors, excite α receptors, and directly inhibit intestinal smooth muscle. In addition, Qingpi has a longer maintenance time for boosting blood pressure, can excite breathing, and has the effects of anti-shock and exciting the heart.
4、鹿衔草:甘、苦、温。归肺、胃、肝、肾经。具有补虚、益肾、祛风除湿、活血调经、补肾强骨、止咳、止血的功效。主治肾虚腰痛、风湿痹痛、筋骨痿软、新久咳嗽、吐血、衄血、崩漏、外伤出血等症。鹿蹄草能增加心肌收缩力,抗心律不齐,还可使心肌收缩力增强,血管显著扩张,血压下降。鹿蹄草的注射剂灌注还能对抗去甲肾上腺素的血管收缩作用,使之扩张。鹿衔草水煎液能明显增加小鼠心肌营养性血流量和组织(肝、肾、脾、脑)血流量,并能明显升高血浆cAMP含量。此外,鹿衔草对金黄色葡萄球菌、溶血性链球菌、肺炎球菌、脑膜炎球菌、福氏痢疾杆菌、伤寒杆菌及绿脓杆菌等有抑制作用。4, Herba Cervix: sweet, bitter, warm. Return lung, stomach, liver, kidney channel. It has the effects of tonifying deficiency, nourishing kidney, expelling wind and dampness, promoting blood circulation and regulating menstruation, tonifying kidney and strengthening bones, relieving cough and stopping bleeding. Indications for lumbago due to kidney deficiency, rheumatic arthralgia, flaccidity of muscles and bones, chronic cough, hematemesis, epistaxis, uterine bleeding, traumatic bleeding and other diseases. Wintergreen can increase myocardial contractility, resist arrhythmia, increase myocardial contractility, significantly dilate blood vessels, and lower blood pressure. Injectable infusions of wintergreen also counteract the vasoconstrictive effects of norepinephrine, causing it to dilate. The water decoction of Luliancao can significantly increase the nutritional blood flow of the mouse myocardium and tissue (liver, kidney, spleen, brain) blood flow, and can significantly increase the plasma cAMP content. In addition, it has inhibitory effect on Staphylococcus aureus, hemolytic streptococcus, pneumococcus, meningococcus, Shigella flexneri, Salmonella typhi and Pseudomonas aeruginosa.
5、龙葵:性寒、味苦、微甘,有小毒。具有清热解毒、利尿的功效。用于疮痈肿毒、皮肤湿疹、小便不利、老年性慢性气管炎、白带过多、前列腺炎、痢疾。对动物有抗炎作用,所含澳洲茄胺能降低血管通透性及透明质酸酶的活性;对动物的过敏性、烧伤性、组织胺性休克有某些保护作用,还能增加小鼠胰岛素休克的存活率,并能促进抗体的形成。龙葵对金黄色葡萄球菌、痢疾杆菌、伤寒杆菌、变形杆菌、大肠杆菌、绿脓杆菌、猪霍乱杆菌均有一定的抑菌作用。5. Solanum nigrum: cold in nature, bitter in taste, slightly sweet, slightly poisonous. It has the effects of clearing away heat, detoxification and diuresis. For sores, carbuncles, swollen toxins, skin eczema, dysuria, senile chronic bronchitis, excessive leucorrhea, prostatitis, and dysentery. It has an anti-inflammatory effect on animals, and the Australian solanamine contained in it can reduce the vascular permeability and the activity of hyaluronidase; it has certain protective effects on animals' anaphylaxis, burns, and histamine shock, and can also increase the The survival rate of insulin shock, and can promote the formation of antibodies. Solanum nigrum has a certain antibacterial effect on Staphylococcus aureus, Shigella, Salmonella typhi, Proteus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus choleraesuis.
6、凌霄花:味辛、酸,性寒。归肝、心包经。具有行血去瘀、凉血祛风的功效。用于经闭癓瘕、产后乳肿、风疹发红、皮肤瘙痒、痤疮。凌霄花中含有的黄酮类物质能够加快动物体的血流速度,增加毛细血管网交叉点,扩张小血管管径,具有很好的改善微循环、活血化瘀作用。6. Lingxiaohua: pungent, sour, cold in nature. Return liver, pericardium channel. It has the effects of promoting blood circulation to remove blood stasis, cooling blood and expelling wind. For amenorrhea, postpartum breast swelling, rubella redness, skin itching, acne. The flavonoids contained in Ling Xiaohua can speed up the blood flow of animals, increase the intersection of capillary networks, expand the diameter of small blood vessels, and have a good effect on improving microcirculation, promoting blood circulation and removing blood stasis.
7、如意草:辛麻、微酸、性寒。具有清热解毒、散阏止血的功效。主疮疡肿毒、乳痈、跌打损伤、开放性骨折、外伤出血、蛇伤。7. Ruyicao: pungent, slightly sour, cold in nature. It has the effects of clearing away heat and detoxification, dissipating phlegm and stopping bleeding. Mainly treat sores and swelling, mastitis, bruises, open fractures, traumatic bleeding, and snakebites.
中医认为,失血性休克的病因可以归纳为以下两个方面:1、阴血亏耗久病真阴亏耗,或因亡血、大汗、呕吐、过泻、房劳过度等原因而致阴血大伤,脏腑失于濡养;或外感六淫之邪,入里化热,热毒炽盛,耗伤阴液。阳无阴不生,阴损必及阳,致使阴亏阳损。阳气失于温煦而致厥证,严重者阳气无所依附,虚阳外越而致脱证。2、阳气衰微久病或暴病伤阳耗气而致阳气大衰,或阴损及阳,阳气虚亏不能温煦而致厥证。若阳气衰微,阳不附阴而脱,则致脱证。中医采取辨证分型治疗,厥证主要以益气温阳、化瘀通络为主,脱证则以回阳救逆为主。Traditional Chinese medicine believes that the etiology of hemorrhagic shock can be summarized into the following two aspects: 1. Depletion of yin and blood due to prolonged illness and depletion of true yin, or yin and blood caused by blood loss, sweating, vomiting, diarrhea, and excessive labor. Severe injury, the viscera are lost in nourishment; or the evil of the six evils caused by exogenous diseases enters the interior to transform heat, the heat and toxins are blazing, and the Yin fluid is consumed. Yang does not grow without yin, and yin damage will affect yang, resulting in yin deficiency and yang loss. Yang Qi loses its warmness and leads to Jue Syndrome. In severe cases, Yang Qi has nothing to attach to, and Yang Qi is deficient and external, resulting in loss of syndrome. 2. Decreased yang qi due to prolonged illness or severe illness that injures yang and consumes qi, leading to great decline of yang qi, or yin damage to yang, deficiency and deficiency of yang qi that cannot be warmed, resulting in syncope. If the yang qi declines, and the yang is not attached to the yin and falls off, it will lead to detachment. Traditional Chinese medicine adopts syndrome differentiation and classification. Jue syndrome is mainly based on benefiting Qi and yang, dispelling blood stasis and dredging collaterals.
本发明中药组方依据中医对休克的辨证认知,遵循中药的配伍理论,为了制成方便易用且疗效稳定的制剂,强化了药材的使用量。该组方是以人参、七叶一枝花为君药,散寒止痛,温经止血,祛风除湿,通痹止痛;以青皮、鹿衔草为臣药,补气固表,凉血,止血,滋阴补血,益精填髓;以龙葵为佐药,通窍止痛,活血通经,益气生津,补中益气,养血安神;以凌霄花、如意草为使药,调和诸药药性,诸药配合,相辅相成,协同作用,共奏益气养阴生血、温阳化瘀通络,益气健脾等功效,对休克具有十分显著的疗效。The traditional Chinese medicine prescription of the present invention is based on the recognition of syndrome differentiation of Chinese medicine on shock, follows the compatibility theory of traditional Chinese medicine, and in order to make a convenient and easy-to-use preparation with stable curative effect, the usage amount of medicinal materials is strengthened. This formula uses ginseng and Aescin as the monarch drug, dispelling cold and relieving pain, warming the meridians to stop bleeding, dispelling wind and dampness, clearing numbness and relieving pain; taking green skin and deer's grass as minister drugs, tonifying qi and strengthening the surface, cooling blood and stopping bleeding , nourishing yin and blood, nourishing essence and filling the marrow; using Solanum nigrum as an adjuvant drug, clearing the orifices and relieving pain, promoting blood circulation and stimulating the menstrual flow, replenishing qi and promoting body fluid, nourishing the middle and replenishing qi, nourishing blood and calming the nerves; taking lingxiaohua and ruyicao as envoys to reconcile the properties of various medicines , the combination of various medicines, complement each other, and synergistically play the effects of nourishing qi, nourishing yin and generating blood, warming yang, dispelling blood stasis and dredging collaterals, replenishing qi and invigorating the spleen, etc., and has a very significant curative effect on shock.
与现有技术相比,本发明的有益效果在于:Compared with prior art, the beneficial effect of the present invention is:
(1)本发明的抗休克合剂具有益气养阴生血、温阳化瘀通络,益气健脾的功效,实能显著改善心脏功能,恢复血压和心率到正常水平,对失血性休克具有较好的疗效。(1) The anti-shock mixture of the present invention has the effects of nourishing qi, nourishing yin and producing blood, warming yang, dispelling blood stasis and dredging collaterals, replenishing qi and invigorating the spleen, can significantly improve heart function, restore blood pressure and heart rate to normal levels, and has a certain effect on hemorrhagic shock. Better curative effect.
(2)本发明中药合剂选用优质中药材制成,所选药材配伍相宜,符合中医药及现代医学研究理论,能达到标本兼治的目的,且本发明的制备工艺简便易行,制剂药效稳定,易于推广应用,具有较好的临床应用前景。(2) The Chinese medicine mixture of the present invention is made from high-quality Chinese medicinal materials, and the selected medicinal materials are suitable in compatibility, conforms to the research theory of traditional Chinese medicine and modern medicine, can achieve the purpose of treating both symptoms and root causes, and the preparation process of the present invention is simple and easy, and the drug effect of the preparation is stable , easy to popularize and apply, and has good clinical application prospect.
具体实施方式Detailed ways
为了使本领域技术人员更好地理解本发明的技术方案能予以实施,下面结合具体实施例对本发明作进一步说明,但所举实施例不作为对本发明的限定。In order to enable those skilled in the art to better understand that the technical solutions of the present invention can be implemented, the present invention will be further described below in conjunction with specific examples, but the given examples are not intended to limit the present invention.
实施例中所用棘孢曲霉培养液是采用常规方法培养得到的,且下述各实施例中所述实验方法,如无特殊说明,均为常规方法。The Aspergillus aculeatus culture solution used in the examples was obtained by culturing by conventional methods, and the experimental methods described in the following examples, unless otherwise specified, were conventional methods.
实施例1Example 1
一种含人参的抗休克合剂,其制备原料由以下重量份数的组分组成:人参25份、七叶一枝花15份、青皮15份、鹿衔草10份、龙葵10份、凌霄花5份、如意草5份。An anti-shock mixture containing ginseng, the preparation raw materials of which are composed of the following components in parts by weight: 25 parts of ginseng, 15 parts of Aescin, 15 parts of green bark, 10 parts of chrysanthemum, 10 parts of Solanum nigrum, 5 parts of Ling Xiaohua 5 parts, 5 parts of Ruyi grass.
具体按照如下步骤制备:Concretely prepare according to the following steps:
步骤1,按重量份称取人参25份、七叶一枝花15份、青皮15份、鹿衔草10份、龙葵10份、凌霄花5份、如意草5份;Step 1, take by weight 25 parts of ginseng, 15 parts of Aescin, 15 parts of green bark, 10 parts of pilus nigra, 10 parts of solanum nigrum, 5 parts of lingxiaohua, and 5 parts of ruyicao;
步骤2,将步骤1中称取的人参干燥、粉碎后过20目筛,得到人参粉;将人参粉与水、木质素过氧化物酶按照100:50:1的质量比混合均匀,然后置于60℃下酶解3h,酶解完毕得到酶解产物;将酶解产物过滤,得第一滤液和滤渣,往滤渣中加入相当于滤渣重量5倍的乙醇溶剂,然后于50℃、超声功率为200W的条件下超声提取30min,提取完毕后过滤,得第二滤液,合并第一滤液和第二滤液,减压浓缩至相对密度为1.3-1.4,得到人参提取物;Step 2, drying and crushing the ginseng weighed in step 1, passing through a 20-mesh sieve to obtain ginseng powder; mixing ginseng powder, water, and lignin peroxidase in a mass ratio of 100:50:1, and then placing Enzymolysis at 60°C for 3 hours, the enzymolysis product was obtained after the enzymolysis was completed; the enzymolysis product was filtered to obtain the first filtrate and filter residue, and an ethanol solvent equivalent to 5 times the weight of the filter residue was added to the filter residue, and then at 50°C, ultrasonic power Ultrasonic extraction for 30 minutes under the condition of 200W, after the extraction is completed, filter to obtain the second filtrate, combine the first filtrate and the second filtrate, concentrate under reduced pressure to a relative density of 1.3-1.4, and obtain the ginseng extract;
将人参提取物与水按照1g:10mL的比例混合溶解后过径高比为1:5的硅胶柱,在柱压为-0.5Mpa的条件下进行硅胶柱层析,并用乙醇和乙酸乙酯的混合溶液作为洗脱剂进行洗脱,收集馏分并浓缩、干燥,得到人参皂苷粗品;Mix and dissolve the ginseng extract and water according to the ratio of 1g:10mL, pass through a silica gel column with a diameter-to-height ratio of 1:5, perform silica gel column chromatography at a column pressure of -0.5Mpa, and use ethanol and ethyl acetate The mixed solution is used as an eluent to elute, and the fractions are collected, concentrated and dried to obtain crude ginsenosides;
将人参皂苷粗品和正丁醇按照1g:5mL的比例混合溶解后注入到高效制备液相色谱仪中,采用乙醇水混合溶液洗脱,收集馏分并浓缩、干燥,得到人参皂苷Rb1;The crude ginsenoside and n-butanol were mixed and dissolved according to the ratio of 1g:5mL, then injected into a high-performance preparative liquid chromatograph, eluted with a mixed solution of ethanol and water, and the fractions were collected, concentrated, and dried to obtain ginsenoside Rb1;
步骤3,将步骤1中称取的七叶一枝花干燥、粉碎后过20目筛,得到七叶一枝花粉,往七叶一枝花粉中加入相当于其重量5%的棘孢曲霉培养液,在28-30℃条件下发酵5天,发酵完毕得到发酵产物;Step 3, drying and pulverizing the Aesculus aesculus flower weighed in step 1 and passing through a 20-mesh sieve to obtain Aesculus Aesculus pollen, adding a culture solution of Aspergillus aculeatus equivalent to 5% of its weight in the Aesculus aesculata pollen, and Ferment at 28-30°C for 5 days, and the fermentation product is obtained after the fermentation is completed;
将发酵产物与乙醇水溶液按1g:5mL的比例混合,然后于80℃下回流3h,回流完毕后过滤,滤液浓缩至相对密度为1.3-1.4,即得七叶一枝花提取物;Mix the fermentation product with ethanol aqueous solution at a ratio of 1 g: 5 mL, then reflux at 80°C for 3 hours, filter after the reflux is completed, and concentrate the filtrate to a relative density of 1.3-1.4 to obtain the Aescinus aesculus extract;
步骤4,将步骤1中称取的青皮、鹿衔草、龙葵、凌霄花、如意草混合,得到混合料,然后往混合料中加入相当于混合料质量5倍的乙醇,加热回流3h后过滤,得滤液,将滤液减压浓缩除去乙醇,得到混合提取物;Step 4, mix the green bark, chrysanthemum, black nightshade, lingxiaohua, and ruyicao weighed in step 1 to obtain a mixture, then add ethanol equivalent to 5 times the weight of the mixture to the mixture, heat and reflux for 3 hours, and then filter , to obtain the filtrate, the filtrate was concentrated under reduced pressure to remove ethanol, and a mixed extract was obtained;
步骤5,将步骤2中人参皂苷Rb1、步骤3中七叶一枝花提取物以及步骤4中混合提取物混合,然后往其中加入与人参皂苷Rb1、七叶一枝花提取物以及混合提取物总重量相等的、质量浓度为80%的蔗糖水溶液,混合均匀,即得到所述抗休克合剂。Step 5, mix ginsenoside Rb1 in step 2, Aesculus aesculus extract in step 3 and mixed extract in step 4, and then add the total weight of ginsenoside Rb1, Aesculus aesculus extract and mixed extract The same sucrose aqueous solution with a mass concentration of 80% is uniformly mixed to obtain the anti-shock mixture.
实施例2Example 2
一种含人参的抗休克合剂,其制备原料由以下重量份数的组分组成:人参20份、七叶一枝花20份、青皮10份、鹿衔草15份、龙葵5份、凌霄花8份、如意草4份。An anti-shock mixture containing ginseng, the preparation raw materials of which are composed of the following components in parts by weight: 20 parts of ginseng, 20 parts of aescin, 10 parts of green bark, 15 parts of chrysanthemum, 5 parts of solanum nigrum, and 8 parts of Ling Xiaohua 4 parts, 4 parts of Ruyi grass.
制备方法同实施例1,不同之处在于将实施例1中的配方换成实施例2的。The preparation method is the same as that of Example 1, except that the formula in Example 1 is replaced with that of Example 2.
实施例3Example 3
一种含人参的抗休克合剂,其制备原料由以下重量份数的组分组成:人参30份、七叶一枝花10份、青皮20份、鹿衔草5份、龙葵15份、凌霄花10份、如意草3份。An anti-shock mixture containing ginseng, the preparation raw materials of which are composed of the following components in parts by weight: 30 parts of ginseng, 10 parts of Aesculus chinensis, 20 parts of green bark, 5 parts of chrysanthemum, 15 parts of black nightshade, and 10 parts of Ling Xiaohua 3 servings, 3 servings of Ruyi Cao.
制备方法同实施例1,不同之处在于将实施例1中的配方换成实施例3的。The preparation method is the same as that of Example 1, except that the formula in Example 1 is replaced with that of Example 3.
需要说的是,木质素过氧化物酶的酶活力为10000U/mL,棘孢曲霉培养液中有效活菌数≥1010CFU/mL。What needs to be said is that the enzyme activity of lignin peroxidase is 10000U/mL, and the number of effective viable bacteria in the Aspergillus aculeatus culture solution is ≥10 10 CFU/mL.
为了进一步说明本发明的效果,实验中还设置了对比例,具体如下。In order to further illustrate the effect of the present invention, a comparative example is also set up in the experiment, as follows.
对比例1Comparative example 1
配方和制备方法同实施例1,不同之处在于配方中不含人参。The formula and preparation method are the same as in Example 1, except that the formula does not contain ginseng.
对比例2Comparative example 2
配方同实施例1,不同之处制备方法的步骤2中,人参提取物的制备方法如下:The formula is the same as in Example 1, except that in the step 2 of the preparation method, the preparation method of the ginseng extract is as follows:
将步骤1中称取的人参干燥、粉碎后过20目筛,得到人参粉;将人参粉与水、木质素过氧化物酶按照100:50:1的质量比混合均匀,然后置于60℃下酶解3h,酶解完毕得到酶解产物;将酶解产物过滤,得第一滤液和滤渣,往滤渣中加入相当于滤渣重量5倍的乙醇溶剂超声提取,提取完毕后过滤,得第二滤液,合并第一滤液和第二滤液,减压浓缩至相对密度为1.3-1.4,得到人参提取物;Dry and crush the ginseng weighed in step 1 and pass it through a 20-mesh sieve to obtain ginseng powder; mix ginseng powder, water, and lignin peroxidase in a mass ratio of 100:50:1, and place at 60°C Under enzymatic hydrolysis for 3 hours, the enzymolysis product is obtained after the enzymolysis is completed; the enzymolysis product is filtered to obtain the first filtrate and filter residue, and the ethanol solvent equivalent to 5 times the weight of the filter residue is added to the filter residue for ultrasonic extraction. After the extraction is completed, filter to obtain the second The filtrate, combining the first filtrate and the second filtrate, concentrating under reduced pressure to a relative density of 1.3-1.4 to obtain a ginseng extract;
步骤5,将步骤2中人参提取物、步骤3中七叶一枝花提取物以及步骤4中混合提取物混合,然后往其中加入与人参提取物、七叶一枝花提取物以及混合提取物总重量相等的蔗糖水溶液,混合均匀,即得到所述抗休克合剂。Step 5, mix the ginseng extract in step 2, the extract of Aesculus aesculus in step 3 and the mixed extract in step 4, and then add the total weight of ginseng extract, Aesculus aesculus extract and the mixed extract The equal sucrose aqueous solution is mixed evenly to obtain the anti-shock mixture.
对比例3Comparative example 3
配方和制备方法同实施例1,不同之处在于配方中不含青皮、鹿衔草和龙葵。The formula and preparation method are the same as those in Example 1, except that the formula does not contain green bark, pilchard and black nightshade.
对比例4Comparative example 4
配方和制备方法同实施例1,不同之处在于配方中不含凌霄花和如意草。The formula and preparation method are the same as in Example 1, except that the formula does not contain Lingxiaohua and Ruyicao.
实施例1-3均制备出了效果良好的含人参的抗休克合剂,下面采用动物实验对实施例1-3制备出的含人参的抗休克合剂的性能进行测试,以对本发明的效果进行说明。Examples 1-3 all prepared the anti-shock mixture containing ginseng with good effect. The following animal experiments are used to test the performance of the anti-shock mixture containing ginseng prepared in Examples 1-3 to illustrate the effect of the present invention .
1、实验方法1. Experimental method
选取100只SPF级SD大鼠,体重为280±10g,雌雄各半,随机分为正常对照组、模型组、阳性对照组、实施例1-3组,对比例1-4组,共10组,每组10只。除正常对照组外,其余各组的大鼠分别称重,以1%戊巴比妥钠(35mg/kg)麻醉,仰卧位固定于37℃恒温毯上,心电图电极分别接在两侧下肢和右上肢以记录心电图波形。备皮、消毒后行气管切开,气管插管,保留自主呼吸。分别分离右侧颈部和双下肢血管神经。右颈动脉置入22G静脉导管后连接MAP心功能分析仪监测平均动脉压。左股静脉作为复苏通道给予血管活性药物及回输液体、血液。1KU/kg肝素钠经左侧股静脉注入使全血肝素化。右股动脉置入24G静脉导管后连接精密输液器,放血至休克。Select 100 SPF grade SD rats, body weight is 280 ± 10g, half male and half male, randomly divided into normal control group, model group, positive control group, embodiment 1-3 group, comparative example 1-4 group, totally 10 groups , 10 in each group. Except for the normal control group, the rats in the other groups were weighed respectively, anesthetized with 1% pentobarbital sodium (35 mg/kg), fixed on a 37°C constant temperature blanket in the supine position, and the electrocardiogram electrodes were respectively connected to the lower limbs and the Right upper extremity to record the ECG waveform. After skin preparation and disinfection, a tracheotomy was performed, the trachea was intubated, and spontaneous breathing was retained. The vessels and nerves of the right neck and lower extremities were separated respectively. A 22G venous catheter was placed in the right carotid artery and connected to a MAP cardiac function analyzer to monitor the mean arterial pressure. The left femoral vein is used as a resuscitation channel to give vasoactive drugs and return fluid and blood. 1KU/kg heparin sodium was injected through the left femoral vein to heparinize the whole blood. A 24G venous catheter was inserted into the right femoral artery and connected to a precision infusion set, and blood was bled until shock.
实施例1-3组的大鼠分别灌胃给本发明实施例1-3制得的抗休克合剂,给药剂量均为20mg/kg,休克后立即给药;对比例1-4组的大鼠分别灌胃给对比例1-4制得的抗休克合剂,给药剂量均为20mg/kg,休克后立即给药;阳性对照组灌胃给肾上腺素,加给药剂量为20mg/kg,正常对照组和模型组给予相同体积的生理盐水,各组每日灌胃1次,连续5天。The rats in the embodiment 1-3 group were given the anti-shock mixture prepared by the embodiment of the present invention 1-3 by gavage respectively, and the dosage was 20 mg/kg, and the rats were administered immediately after the shock; Rats were administered intragastrically to the anti-shock mixture prepared in Comparative Examples 1-4, and the dosage was 20 mg/kg, administered immediately after the shock; the positive control group was intragastrically administered epinephrine, and the dosage was 20 mg/kg. The normal control group and the model group were given the same volume of normal saline, and each group was gavaged once a day for 5 consecutive days.
为了确定本发明抗休克合剂对失血性休克的治疗效果,分别在大鼠休克前,休克时和休克后检测大鼠的心率及平均动脉压。In order to determine the therapeutic effect of the anti-shock mixture of the present invention on hemorrhagic shock, detect the heart rate and mean arterial pressure of the rats before shock, during shock and after shock respectively.
统计学处理试验数据均采用均数±标准差来表示,组间差异显著性用t检验比较,采用SPSS19.0统计软件进行数据处理。Statistical processing The experimental data are expressed as mean ± standard deviation, the significant difference between groups is compared by t test, and SPSS19.0 statistical software is used for data processing.
2、试验结果2. Test results
试验结果如表1-2所示。The test results are shown in Table 1-2.
表1对大鼠心率(HR)的影响Table 1 Effects on Rat Heart Rate (HR)
注:与正常对照组比较,*P<0.05;与模型组比较,**P<0.01。Note: Compared with the normal control group, *P<0.05; compared with the model group, **P<0.01.
由表1可以看出,失血性休克模型大鼠在休克30min时HR的下降最为显著,完全休克后全部死亡;而灌胃给本发明实施例1-3的抗休克合剂可显著增加失血性休克大鼠HR,使其恢复到正常水平,其治疗效果与市售的肾上腺素的治疗效果相当。As can be seen from Table 1, the decline in HR of the hemorrhagic shock model rats was the most significant when the shock was 30min, and all died after complete shock; Rat HR, to restore it to normal levels, its therapeutic effect is comparable to that of commercially available epinephrine.
灌胃对比例1抗休克合剂后大鼠HR显著降低,且难以恢复到正常水平,说明人参在整个抗休克合剂中所起的作用是非常重要的,缺少人参,虽然抗休克合剂治疗效果好于模型组,但较其它组效果差很多。Rat HR significantly decreased after gavage of comparative example 1 anti-shock mixture, and it was difficult to return to the normal level, indicating that the role played by ginseng in the whole anti-shock mixture is very important, lacking ginseng, although the anti-shock mixture has better therapeutic effect than Model group, but the effect is much worse than other groups.
灌胃对比例2抗休克合剂后大鼠HR降低较多,虽然较对比例1和模型组好,但比其它组差,说明人参中含有的人参皂苷Rb1是治疗失血性休克的主要成分,并且,中药组分讲究配伍,纯的人参皂苷Rb1相对于没有提纯的人参提取物来说,与其它原料组分的配伍效果更好。After gavage of comparative example 2 anti-shock mixture, rat HR decreased more, although it was better than comparative example 1 and the model group, it was worse than other groups, indicating that ginsenoside Rb1 contained in ginseng is the main component for treating hemorrhagic shock, and , Traditional Chinese medicine components pay attention to compatibility. Compared with unpurified ginseng extract, pure ginsenoside Rb1 has a better compatibility effect with other raw material components.
灌胃对比例3和对比例4抗休克合剂后大鼠HR降低较少,效果好于对比例1和对比例2,但比实施例1-3差,说明青皮、鹿衔草、龙葵、凌霄花和如意草均在整个体系中起到了各自作用,且在本发明的配伍下,各原料药相互作用,使制备出的抗休克合剂的效果达到最佳。After gavage of comparative example 3 and comparative example 4 anti-shock mixture, the reduction in rat HR is less, and the effect is better than that of comparative example 1 and comparative example 2, but worse than that of examples 1-3. Both Lingxiaohua and Ruyicao play their respective roles in the whole system, and under the compatibility of the present invention, the raw materials interact with each other, so that the effect of the prepared anti-shock mixture reaches the best.
表2对大鼠平均动脉压(MAP)的影响The impact of table 2 on rat mean arterial pressure (MAP)
注:与空白对照组比较,*P<0.05;与模型组比较,**P<0.01。Note: Compared with blank control group, *P<0.05; compared with model group, **P<0.01.
由表2可以看出,失血性休克模型大鼠在休克30min时MAP的下降最为显著,完全休克后全部死亡;而灌胃给本发明实施例1-3的抗休克合剂可显著增加失血性休克大鼠MAP,使其恢复到正常水平,其治疗效果与市售的肾上腺素的治疗效果相当。As can be seen from Table 2, the decline in MAP of the hemorrhagic shock model rats was the most significant when the shock was 30min, and all died after complete shock; Rat MAP, to restore it to normal levels, the therapeutic effect is comparable to that of commercially available epinephrine.
灌胃对比例1抗休克合剂后大鼠MAP显著降低,且难以恢复到正常水平,说明人参在整个抗休克合剂中所起的作用是非常重要的,缺少人参,虽然抗休克合剂治疗效果好于模型组,但较其它组效果差很多。Rat MAP significantly decreased after gavage of comparative example 1 anti-shock mixture, and it was difficult to return to normal level, indicating that the role played by ginseng in the whole anti-shock mixture was very important, lacking ginseng, although the therapeutic effect of anti-shock mixture was better than Model group, but the effect is much worse than other groups.
灌胃对比例2抗休克合剂后大鼠MAP降低较多,虽然较对比例1和模型组好,但比其它组差,说明人参中含有的人参皂苷Rb1是治疗失血性休克的主要成分,并且,中药组分讲究配伍,纯的人参皂苷Rb1相对于没有提纯的人参提取物来说,与其它原料组分的配伍效果更好。After intragastric administration of comparative example 2 anti-shock mixture, rat MAP decreased more, although better than comparative example 1 and the model group, but worse than other groups, indicating that ginsenoside Rb1 contained in ginseng is the main component for treating hemorrhagic shock, and , Traditional Chinese medicine components pay attention to compatibility. Compared with unpurified ginseng extract, pure ginsenoside Rb1 has a better compatibility effect with other raw material components.
灌胃对比例3和对比例4抗休克合剂后大鼠MAP降低较少,效果好于对比例1和对比例2,但比实施例1-3差,说明青皮、鹿衔草、龙葵、凌霄花和如意草均在整个体系中起到了各自作用,且在本发明的配伍下,各原料药相互作用,使制备出的抗休克合剂的效果达到最佳。After gavage of comparative example 3 and comparative example 4 anti-shock mixture, rat MAP decreases less, and the effect is better than that of comparative example 1 and comparative example 2, but worse than that of examples 1-3. Both Lingxiaohua and Ruyicao play their respective roles in the whole system, and under the compatibility of the present invention, the raw materials interact with each other, so that the effect of the prepared anti-shock mixture reaches the best.
需要说明的是,本发明权利要求书中涉及数值范围时,应理解为每个数值范围的两个端点以及两个端点之间任何一个数值均可选用,由于采用的步骤方法与实施例1-3相同,为了防止赘述,本发明描述了优选的实施例,但本领域内的技术人员一旦得知了基本创造性概念,则可对这些实施例作出另外的变更和修改。所以,所附权利要求意欲解释为包括优选实施例以及落入本发明范围的所有变更和修改。It should be noted that when a numerical range is involved in the claims of the present invention, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected, because the steps and methods adopted are the same as those in Embodiment 1- 3 Similarly, to avoid redundancy, the present invention describes preferred embodiments, but those skilled in the art can make additional changes and modifications to these embodiments once the basic inventive concept is known. Therefore, it is intended that the appended claims be construed to cover the preferred embodiment as well as all changes and modifications which fall within the scope of the invention.
显然,本领域的技术人员可以对本发明进行各种改动和变型而不脱离本发明的精神和范围。这样,倘若本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内,则本发明也意图包含这些改动和变型在内。Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention also intends to include these modifications and variations.
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