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CN107582866A - Dendrobium candidum and Amlodipine are preparing the application process in treating hypertension drug - Google Patents

Dendrobium candidum and Amlodipine are preparing the application process in treating hypertension drug Download PDF

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CN107582866A
CN107582866A CN201710996033.XA CN201710996033A CN107582866A CN 107582866 A CN107582866 A CN 107582866A CN 201710996033 A CN201710996033 A CN 201710996033A CN 107582866 A CN107582866 A CN 107582866A
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amlodipine
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dendrobium candidum
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CN107582866B (en
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吴悦
吴人照
陈宇
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Hangzhou Dan He Pharmaceutical Co Ltd
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Zhejiang Traditional Chinese Medicine Research Institute
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Abstract

The present invention relates to pharmaceutical formulation techniques, it is desirable to provide a kind of dendrobium candidum and Amlodipine are preparing the application process in treating hypertension drug.Including:2.5 parts of 8000 parts of dendrobium candidum and Amlodipine are taken in parts by weight;By dendrobium candidum be ground to it is powdered after, add Amlodipine powder, mix;Then auxiliary material is added according to pharmacy Conventional processing methods, tablet, particle or mix suspension grain, pill, powder or capsule is made, obtains the medicine for treating hypertension.The present invention has taken into full account the utilization of dendrobium candidum valuable medicinal, reduces the waste caused by extraction not exclusively, while also reduces destruction of the heating extraction process to fractions, to improve curative effect, saves valuable medicinal.The reduction of blood pressure in high-speed of 2 hours after can both being taken medicine, 24 hours antihypertensive effects exceed Western medicine depressor Amlodipine taken medicine again after, can also reduce the dosage of Western medicine Amlodipine.Greatly extend the application prospect of dendrobium candidum treatment hypertension.

Description

铁皮石斛和氨氯地平在制备治疗高血压药物中的应用方法Application method of dendrobium officinale and amlodipine in preparation of medicine for treating hypertension

技术领域technical field

本发明涉及药物制备技术,特别涉及铁皮石斛和氨氯地平在制备治疗高血压药物中的应用。The invention relates to medicine preparation technology, in particular to the application of dendrobium officinale and amlodipine in the preparation of medicines for treating hypertension.

背景技术Background technique

高血压病为临床常见高发病,对心、脑、肾等重要脏器具有严重危害。我国2013年度《中国心血管病报告》估计,目前全国高血压患者约为2.7亿。2012、2013年《中国心血管病报告》显示:我国心血管疾病病死率为44.1%,居死亡疾病谱中首位。而高血压是心脑血管疾病首要病因。流行病调查结果显示,我国因高血压导致心脑血管疾病病死率逐年上升,就脑卒中而言,我国每年新发脑卒中160多万人,累计幸存者600万人左右,其中75%以上丧失劳动力,45%重度致残,生活不能自理。Hypertension is a common high incidence clinically, which has serious harm to the heart, brain, kidney and other important organs. my country's 2013 "China Cardiovascular Disease Report" estimates that there are currently about 270 million hypertensive patients nationwide. The 2012 and 2013 "China Cardiovascular Disease Report" showed that the mortality rate of cardiovascular disease in my country was 44.1%, ranking first in the spectrum of death diseases. Hypertension is the leading cause of cardiovascular and cerebrovascular diseases. Epidemiological survey results show that the mortality rate of cardiovascular and cerebrovascular diseases in my country is increasing year by year due to high blood pressure. As far as stroke is concerned, there are more than 1.6 million new strokes in my country every year, and the cumulative number of survivors is about 6 million, of which more than 75% are lost. 45% of the labor force is severely disabled and cannot take care of themselves.

西药治疗高血压病尚缺少调整体质且能调整血压(降压)的药物。现代医学的降压治疗均为对症治疗。目前常用的降压药包括钙离子通道阻滞剂(CCB)、血管紧张素转化酶抑制剂(ACEI)、血管紧张素Ⅱ受体阻滞剂(ARB)、利尿剂和β阻滞剂5种,尚不能完全阻止高血压病以及其继发病变的进展。大多数高血压患者需要2种或2种以上的降压药方可达到目标血压,或者难以达到目标血压,多数患者需要终身服药,因长疗程用药而药物疗效逐渐降低,产生毒副作用,还有随着寿命的延长而这些问题更加突出。目前高血压治疗依然迫切需要新的更完善的治疗药物。Western medicine treatment of hypertension still lacks the medicine for adjusting body constitution and can adjust blood pressure (depressor). The antihypertensive treatment of modern medicine is all symptomatic treatment. Currently commonly used antihypertensive drugs include calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), diuretics, and β-blockers. , still can not completely prevent the progression of hypertension and its secondary lesions. Most hypertensive patients need two or more antihypertensive drugs to reach the target blood pressure, or it is difficult to reach the target blood pressure. Most patients need to take the medicine for life. These problems become more prominent with the prolongation of life expectancy. At present, there is still an urgent need for new and better therapeutic drugs in the treatment of hypertension.

目前的中药调理方法用于高血压有一定优势,但也存在严重不足。虽然中药调理高血压,降压速度和幅度没有西药降压快,但具有疗效更稳定持久,停药后血压回升幅度小,控制血压同时有利整体体质提高的优点。或者调理降低血压同时,还能降低血脂等,具有调整体质、提高体质以后的多方面病理指标改善的优点,具有一定的应用价值。但尚存在服药后近期血压降低不够明显,药物味数太多而互相牵制或者抵消了作用,药物组方、提取、制剂工艺等未经过系统优化而疗效达不到要求,难以在临床中具有实际应用价值。The current traditional Chinese medicine conditioning methods have certain advantages for hypertension, but there are also serious shortcomings. Although traditional Chinese medicine regulates high blood pressure, the speed and magnitude of lowering blood pressure are not as fast as that of western medicine, but it has the advantages of more stable and long-lasting curative effect, less blood pressure recovery after drug withdrawal, and the advantages of controlling blood pressure and improving overall physical fitness. Or it can reduce blood pressure while regulating blood pressure, etc., which has the advantages of improving various pathological indicators after adjusting and improving physical fitness, and has certain application value. However, there are still some problems that the reduction of blood pressure is not obvious enough in the near future after taking the medicine, the number of medicines has too many flavors to restrain each other or offset the effect, and the medicine composition, extraction, preparation process, etc. have not been systematically optimized, so the curative effect cannot meet the requirements, and it is difficult to be practical in clinical practice. Value.

本领域技术人员在将铁皮石斛应用于高血压的治疗时,普遍存在一种技术理解上的偏见:认为只有采用大量的水进行提取才能够提高药物有效成分的吸收利用和疗效,因此传统的铁皮石斛用法就有“宽汤久煎”以提高疗效的方法。同样也曾有专利采用铁皮石斛水提物制备预防或治疗高血压、中风的药物,或采用铁皮石斛水提物合用尼莫地平制备预防或治疗高血压、中风的药物。但是,本发明克服了传统偏见,铁皮石斛在高血压的治疗应用中,采用研粉末应用方法,比水提取法能够大幅度提高24小时的长效降压作用,其服药后24小时降压作用能够超过西药降压药氨氯地平(成年人5mg/天),获得了意想不到的疗效;并在将铁皮石斛研粉末应用这一基础上,合用西药降压药氨氯地平,能够既获得服药后2小时的快速降压,又获得服药后24小时降压作用超过西药降压药氨氯地平(成年人5mg/天),还可以减少西药氨氯地平的用量。When those skilled in the art apply Dendrobium candidum to the treatment of hypertension, there is a common bias in technical understanding: they think that only by using a large amount of water for extraction can the absorption, utilization and curative effect of the active ingredients of the drug be improved. Therefore, the traditional Tiepi There is a method of "wide soup and long decoction" in the usage of Dendrobium to improve the curative effect. Similarly, there have been patents for the preparation of drugs for the prevention or treatment of high blood pressure and stroke by using the water extract of Dendrobium candidum, or for the preparation of drugs for the prevention or treatment of high blood pressure and stroke by using the water extract of Dendrobium candidum in combination with nimodipine. However, the present invention overcomes the traditional prejudice. In the treatment of hypertension, Dendrobium officinale adopts the powder application method, which can greatly improve the 24-hour long-acting antihypertensive effect than the water extraction method, and the 24-hour antihypertensive effect after taking the medicine It can exceed the western medicine antihypertensive drug amlodipine (adult 5mg/day), and has obtained unexpected curative effect; After the rapid blood pressure reduction in the last 2 hours, the antihypertensive effect in 24 hours after taking the medicine exceeds that of Western medicine antihypertensive drug amlodipine (5mg/day for adults), and the consumption of Western medicine amlodipine can also be reduced.

发明内容Contents of the invention

本发明要解决的技术问题是,克服现有技术中的不足和偏见,提供一种铁皮石斛和氨氯地平在制备治疗高血压药物中的应用方法。The technical problem to be solved by the present invention is to overcome the deficiencies and prejudices in the prior art, and provide an application method of dendrobium officinale and amlodipine in the preparation of drugs for treating hypertension.

为解决技术问题,本发明的解决方案是:For solving technical problem, solution of the present invention is:

提供一种铁皮石斛和氨氯地平在制备治疗高血压药物中的应用方法,其特征在于,包括:按重量份数取铁皮石斛8000份和氨氯地平2.5份,铁皮石斛符合2015版《中国药典》中的要求;将铁皮石斛研磨至粉末状后,加入氨氯地平粉末,混匀;然后按照药学常规加工方法添加辅料,制成片剂、颗粒或混悬颗粒、丸剂、散剂或胶囊,得到用于治疗高血压的药物。Provide a kind of application method of Dendrobium officinale and amlodipine in the preparation of medicine for treating hypertension, it is characterized in that, comprising: taking 8000 parts of Dendrobium officinale and 2.5 parts of amlodipine in parts by weight, Dendrobium officinale complies with the 2015 edition of "Chinese Pharmacopoeia" "Requirements in "; After grinding Dendrobium officinale into powder, add amlodipine powder, mix; then add auxiliary materials according to pharmaceutical conventional processing methods, make tablets, granules or suspension granules, pills, powders or capsules, and obtain Medicines used to treat high blood pressure.

本发明进一步提供了前述方法中制备获得的治疗高血压药物的使用方法,是将制备获得的片剂、颗粒或混悬颗粒、丸剂、散剂或胶囊以口服方式用药,成人每日用量相当于铁皮石斛生药量4g至8g,内含氨氯地平1.25mg至2.5mg。The present invention further provides a method for using the drug for treating hypertension prepared in the aforementioned method, which is to administer the prepared tablet, granule or suspension granule, pill, powder or capsule orally, and the daily dosage for an adult is equivalent to that of iron sheet The crude drug amount of Dendrobium is 4g to 8g, and contains 1.25mg to 2.5mg of amlodipine.

本发明的实现原理:Realization principle of the present invention:

高血压病在中医理论中认为大都属于阴虚阳亢,滋阴潜阳是其主要治疗方向。According to TCM theory, most of hypertension belongs to deficiency of yin and hyperactivity of yang, and nourishing yin and subduing yang is the main treatment direction.

根据中医药理论和实践,参照《中华人民共和国药典》2015年版记载:铁皮石斛的性能为益胃生津,滋阴清热。可用于热病津伤,口干烦渴,胃阴不足,食少干呕,病后虚热不退,阴虚火旺,骨蒸劳热,目暗不明,筋骨痿软。现有技术中也有用于高血压治疗,但因其作用起效比较慢、降压作用幅度不够理想而没有规模应用。According to the theory and practice of traditional Chinese medicine, referring to the 2015 edition of the Pharmacopoeia of the People's Republic of China: the properties of Dendrobium officinale are to nourish the stomach and promote body fluid, nourish yin and clear away heat. It can be used for febrile disease, fluid injury, dry mouth and polydipsia, insufficient stomach yin, lack of food and retching, persistent asthenic fever after illness, yin deficiency and hyperactivity of fire, bone steaming and labor heat, blurred vision, muscle flaccidity and weakness. It is also used in the treatment of hypertension in the prior art, but it has not been applied on a large scale because of its slow onset of action and unsatisfactory antihypertensive effect.

通常的铁皮石斛使用方法受到传统的“宽汤久煎”的局限,采用铁皮石斛药材饮片药房配药时“捣扁”后直接加水煎煮提取的方法,进行临床应用。这一用法,由于该药材的主要成分不容易被煎出,其有效成分(如:多糖)提出比例很低(约可以提取得到药材重量的不足10%的多糖),用于降压时的疗效也不理想。后来改良后的提取方法,为采用机器进行“压碎”铁皮石斛药材的方法进行提取,其有效成分(如:多糖)提出比例有一定提高(约可以提取得到药材重量的20%的多糖),用于降压时的疗效也有一定提高,该方法大多用于工业化生产中成药。(见实验1)。The usual method of using Dendrobium officinale is limited by the traditional "wide soup and long decoction". The method of "pounding" the herbal medicine of Dendrobium officinale when dispensing in a pharmacy is directly added to decocting and extracting for clinical application. For this usage, because the main components of the medicinal material are not easy to be decocted, the proportion of its active ingredients (such as: polysaccharide) is very low (about less than 10% of the weight of the medicinal material can be extracted to obtain polysaccharides), and it is used for the curative effect of lowering blood pressure. Not ideal either. Afterwards, the improved extraction method is to use a machine to "crush" the medicinal material of Dendrobium officinale to extract, and the proportion of active ingredients (such as: polysaccharide) has been increased to a certain extent (about 20% of the weight of the medicinal material can be extracted). The curative effect when used for reducing blood pressure is also improved to a certain extent, and this method is mostly used in industrialized production of Chinese patent medicines. (see Experiment 1).

本发明所做研究工作中,已经将上述提取方法做了重大改进:采用机器进行“研粉”铁皮石斛药材,然后加水进行提取,采用固液分离技术,分离提取液,其有效成分(如:多糖)提出比例有大幅度提高(约可以提取得到药材重量的40%的多糖。曾经进行以上铁皮石斛药材饮片“捣扁”、“压碎”、“研粉”的提取实验,均采用同一批药材进行比较),用于降压时的疗效又有一定提高,该方法在铁皮石斛降压研究中仅仅初步采用,还没有被实际应用。但研究中发现:虽然“研粉”后水提取方法的降压疗效比较“压碎”、“捣扁”后水提取方法有一定提高,但离达到西药氨氯地平的降压疗效还有距离;同时发现了铁皮石斛“研粉”后直接服用的24小时降压疗效和血压稳定性更好。In the research work done by the present invention, the above-mentioned extraction method has been greatly improved: adopt a machine to "grind powder" the medicinal material of Dendrobium candidum, then add water to extract, adopt solid-liquid separation technology, separate the extract, and its active ingredients (such as: Polysaccharides) Proposed ratio has been greatly improved (about 40% polysaccharides can be extracted to obtain the medicinal material weight. Once carried out the extraction experiments of the above Dendrobium officinale medicinal pieces "smashing flat", "crushing", "grinding powder", all using the same batch Medicinal materials are compared), and the curative effect when used for lowering blood pressure has been improved to a certain extent. This method is only initially adopted in the research on lowering blood pressure of Dendrobium officinale, and has not been practically applied. However, it was found in the research that although the antihypertensive effect of the water extraction method after "grinding powder" is better than that of the "crushing" and "smashing flat" methods, there is still a long way to go before reaching the antihypertensive effect of the western drug amlodipine. ; At the same time, it was found that the 24-hour antihypertensive effect and blood pressure stability of Dendrobium officinale "ground powder" were better.

铁皮石斛“研粉”后直接服用方法:药物成分利用比水提取方法更完全,药物在体内经过消化吸收逐步发挥作用,相当于中药材在体内发挥降压过程中的“缓释”作用,达到24小时降压疗效更稳定。(见实验1、实验2)。The method of directly taking Dendrobium officinale after "grinding powder": the utilization of drug components is more complete than that of water extraction, and the drug will gradually play a role after digestion and absorption in the body, which is equivalent to the "sustained release" effect of Chinese medicinal materials in the process of lowering blood pressure in the body, reaching The 24-hour antihypertensive effect is more stable. (see experiment 1, experiment 2).

本发明克服了传统偏见:采用研粉末应用方法,比水提取法能够大幅度提高24小时的长效降压作用,该方面作用能够与西药降压药氨氯地平(成年人5mg/天)相近,其服药后24小时降压作用可以超过氨氯地平,获得了意想不到的疗效;在此基础上,合用西药降压药物氨氯地平,能够既获得服药后2小时的快速降压,又获得服药后24小时降压作用超过西药降压药氨氯地平(成年人5mg/天),还可以减少西药氨氯地平的用量。The present invention overcomes the traditional prejudice: the application method of grinding powder can greatly improve the 24-hour long-acting antihypertensive effect compared with the water extraction method, and the effect in this aspect can be similar to that of the western medicine antihypertensive drug amlodipine (5 mg/day for adults). , its antihypertensive effect 24 hours after taking the medicine can surpass amlodipine, and obtain unexpected curative effect; The 24-hour antihypertensive effect after taking the medicine exceeds that of western medicine antihypertensive drug amlodipine (adult 5mg/day), and can also reduce the consumption of western medicine amlodipine.

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、本发明采用中药铁皮石斛粉末制成片剂、颗粒、丸剂、散剂、或胶囊有利于发挥持久而稳定的药效:(1)高血压治疗需要药物发挥持久而稳定的药效,西药降压药采用缓释剂型,本发明采用药材细粉制成片剂、颗粒(混悬颗粒)、丸剂、散剂、或胶囊以发挥中医所说的“丸者缓也”,以使药物逐步溶出发挥作用,起到持久而稳定的中药缓释药效;(2)铁皮石斛研粉生用(区别于“久煎”使用):也有较好的“清热”、“去火”作用,有利于血压的下降;(3)铁皮石斛为贵重药材需要充分利用:本发明技术方案充分考虑了铁皮石斛贵重药材的利用,减少提取不完全所造成的浪费,同时也减少加热提取过程对部分成分的破坏,以提高疗效,节省贵重药材。1, the present invention adopts Chinese medicine Dendrobium officinale powder to make tablet, granule, pill, powder or capsule and is conducive to exerting lasting and stable drug effect: (1) hypertension treatment needs medicine to bring into play persistent and stable drug effect, and western medicine reduces Pressed medicine adopts slow-release dosage form, and the present invention adopts medicinal material fine powder to make tablet, granule (suspension granule), pill, powder, or capsule to play the "ball person's slowness" that traditional Chinese medicine says, so that the drug is gradually stripped out and brought into play. (2) Dendrobium officinale powder raw (different from the use of "Jiujian"): it also has a good effect of "clearing heat" and "removing fire", which is beneficial to blood pressure (3) Dendrobium officinale is a precious medicinal material that needs to be fully utilized: the technical scheme of the present invention fully considers the utilization of the precious medicinal material of Dendrobium candidum, reduces the waste caused by incomplete extraction, and also reduces the damage to some components during the heating extraction process, To improve the curative effect and save precious medicinal materials.

2、本发明的铁皮石斛粉末合用西药降压药物氨氯地平,能够既获得服药后2小时的快速降压,又获得服药后24小时降压作用超过西药降压药氨氯地平(成年人5mg/天),还可以减少西药氨氯地平的用量。2, Dendrobium officinale powder of the present invention is used in combination with Western medicine antihypertensive drug amlodipine, can not only obtain rapid blood pressure reduction in 2 hours after taking the medicine, but also obtain the antihypertensive effect in 24 hours after taking the medicine than Western medicine antihypertensive drug Amlodipine (5 mg for adults). /day), can also reduce the dosage of western medicine amlodipine.

3、铁皮石斛调理阴虚阳亢体质以治疗高血压为“治本”之方法:既能较快取得降低血压疗效,又能获得较好的中、远期稳定血压,调整和恢复阴阳平衡的体质。该中药能够获得与西药降压药相近的疗效,极大地扩展了铁皮石斛治疗高血压的应用前景。3. Dendrobium candidum regulates Yin-deficiency and Yang-excessive physique and treats high blood pressure as a "basic cure" method: it can not only achieve the curative effect of lowering blood pressure quickly, but also obtain better medium and long-term stable blood pressure, and adjust and restore the balance of Yin and Yang. . The traditional Chinese medicine can obtain the curative effect similar to that of western antihypertensive medicine, which greatly expands the application prospect of Dendrobium officinale in treating hypertension.

具体实施方式detailed description

实施例1Example 1

按2015版《中国药典》中的要求取铁皮石斛800g,取苯磺酸氨氯地平250mg。将铁皮石斛药材研细粉,加入苯磺酸氨氯地平粉末,混匀后,按照药学常规添加合适辅料,制成颗粒(混悬颗粒),烘干。为实施例1样品。口服,成人每日用量相当于铁皮石斛生药量4g(内含氨氯地平1.25mg)至铁皮石斛生药量8g(内含氨氯地平2.5mg)。Get Dendrobium candidum 800g by the requirement in 2015 edition " Chinese Pharmacopoeia ", get amlodipine besylate 250mg. The Dendrobium candidum medicinal material is ground into fine powder, amlodipine besylate powder is added, after mixing, appropriate excipients are added according to pharmaceutical routines to make granules (suspension granules), and dried. For Example 1 sample. Oral administration, the daily dosage for adults is equivalent to 4g of crude drug of Dendrobium candidum (containing 1.25mg of amlodipine) to 8g of crude drug of Dendrobium candidum (containing of 2.5mg of amlodipine).

实施例2Example 2

按2015版《中国药典》中的要求取铁皮石斛800g,取苯磺酸氨氯地平250mg。将铁皮石斛药材研细粉,加入苯磺酸氨氯地平粉末,混匀后,按照药学常规添加合适辅料,制成片剂。为实施例2样品。口服,成人每日用量相当于铁皮石斛生药量4g(内含氨氯地平1.25mg)至铁皮石斛生药量8g(内含氨氯地平2.5mg)。Get Dendrobium candidum 800g by the requirement in 2015 edition " Chinese Pharmacopoeia ", get amlodipine besylate 250mg. The Dendrobium candidum medicinal material is ground into fine powder, amlodipine besylate powder is added, after mixing, appropriate excipients are added according to pharmaceutical routines, and tablets are made. Be embodiment 2 samples. Oral administration, the daily dosage for adults is equivalent to 4g of crude drug of Dendrobium candidum (containing 1.25mg of amlodipine) to 8g of crude drug of Dendrobium candidum (containing of 2.5mg of amlodipine).

实验1Experiment 1

铁皮石斛提取方法对遗传性高血压大鼠(SHR)降压作用的实验研究Experimental study on the antihypertensive effect of Dendrobium officinale extraction method on hereditary hypertensive rats (SHR)

【实验材料】【Experimental Materials】

大鼠:遗传性高血压大鼠(SHR),正常对照选用Wistar大鼠。Rats: hereditary hypertensive rats (SHR), and Wistar rats as normal controls.

试验中药:以下3种铁皮石斛提取方法所用药材为同一批药材。Experimental Chinese medicine: The following three extraction methods of Dendrobium candidum used the same batch of medicinal materials.

铁皮石斛药材饮片“捣扁”后水提取:取符合2015版《中国药典》的铁皮石斛500g。采用普通药槌“捣扁”后水提取,第一次水提取:加总生药量的30倍的水,100℃提取2小时;第二次水提取:加总生药量的20倍的水,100℃提取2小时。水提取物合并浓缩,冷藏备用。该提取方法比通常的中药煎煮,提取水量大幅度增加。经过药典规定的硫酸苯酚法多糖含量测定,所得样品多糖含量为铁皮石斛药材生药量的9.8%;Extraction of Dendrobium officinale medicinal material decoction pieces after "pounding": take 500g of Dendrobium officinale in accordance with the 2015 edition of "Chinese Pharmacopoeia". Use a common medicine mallet to "pound" and extract with water. The first water extraction: add water 30 times the amount of crude drugs, extract at 100 ° C for 2 hours; the second water extraction: add water 20 times the amount of crude drugs, Extract at 100°C for 2 hours. The water extracts are combined and concentrated, and refrigerated for later use. Compared with the usual traditional Chinese medicine decoction, this extraction method greatly increases the amount of extracted water. After the determination of the polysaccharide content by the sulfuric acid phenol method stipulated in the Pharmacopoeia, the polysaccharide content of the obtained sample is 9.8% of the crude drug content of the medicinal material Dendrobium candidum;

铁皮石斛药材饮片“压碎”后水提取:取符合2015版《中国药典》的铁皮石斛500g。采用机器“压碎”后水提取,第一次水提取:加总生药量的30倍的水,100℃提取2小时;第二次水提取:加总生药量的20倍的水,100℃提取2小时。水提取物合并浓缩,冷藏备用。该提取方法比通常的中药煎煮,提取水量大幅度增加,并在提取前多了一个“压碎”的过程。经过药典规定的硫酸苯酚法多糖含量测定,所得样品多糖含量为铁皮石斛药材生药量的20.3%;Dendrobium candidum herbal pieces are "crushed" and extracted with water: take 500g of Dendrobium candidum that complies with the 2015 edition of "Chinese Pharmacopoeia". Water extraction after "crushing" by machine, the first water extraction: adding water 30 times the amount of crude drugs, extracting at 100°C for 2 hours; the second water extraction: adding water 20 times the amount of crude drugs, 100°C Extract for 2 hours. The water extracts are combined and concentrated, and refrigerated for later use. Compared with the usual traditional Chinese medicine decoction, this extraction method greatly increases the amount of extraction water, and there is an additional "crushing" process before extraction. After the determination of the polysaccharide content by the sulfuric acid phenol method stipulated in the Pharmacopoeia, the polysaccharide content of the obtained sample is 20.3% of the crude drug amount of the medicinal material Dendrobium officinale;

铁皮石斛药材饮片“研粉”后水提取:取符合2015版《中国药典》的铁皮石斛500g。采用机器“研粉”后水提取,第一次水提取:加总生药量的30倍的水,100℃提取2小时;第二次水提取:加总生药量的20倍的水,100℃提取2小时。水提取物合并浓缩,冷藏备用。该提取方法比通常的中药煎煮,提取水量大幅度增加,并在提取前多了一个“研粉”的过程。经过药典规定的硫酸苯酚法多糖含量测定,所得样品多糖含量为铁皮石斛药材生药量的40.5%;Extraction of Dendrobium officinale medicinal herbal pieces "ground into powder" and water: take 500g of Dendrobium officinale in accordance with the 2015 edition of "Chinese Pharmacopoeia". Water extraction after "grinding powder" by machine, the first water extraction: add water 30 times the total amount of crude drug, extract at 100°C for 2 hours; second water extraction: add water 20 times the amount of crude drug, 100°C Extract for 2 hours. The water extracts are combined and concentrated, and refrigerated for later use. Compared with the usual traditional Chinese medicine decoction, this extraction method greatly increases the amount of extraction water, and there is an additional process of "grinding powder" before extraction. After the determination of the polysaccharide content by the sulfuric acid phenol method stipulated in the Pharmacopoeia, the polysaccharide content of the obtained sample is 40.5% of the crude drug content of Dendrobium officinale medicinal material;

西药降压对照药品:苯磺酸氨氯地平片(络活喜),5mg/片,批号:R78401,辉瑞制药生产。Western antihypertensive control drug: Amlodipine Besylate Tablets (Norvasc), 5mg/tablet, batch number: R78401, produced by Pfizer.

大鼠血压测量:BP-98A型无创尾动脉血压测量仪,日本软融株式会社。Rat blood pressure measurement: BP-98A non-invasive tail artery blood pressure measuring instrument, Japan Soft Rong Co., Ltd.

【实验方法】【experimental method】

分组治疗:全部大鼠适应性饲养一周后测量血压及体重,进行分组。将SHR大鼠分为铁皮石斛药材饮片“捣扁”后水提取组生药量0.8g/Kg体重,铁皮石斛药材饮片“压碎”后水提取组生药量0.8g/Kg体重,铁皮石斛药材饮片“研粉”后水提取组生药量0.8g/Kg体重,氨氯地平组苯磺酸氨氯地平片0.5mg/Kg体重,均灌胃给药,高血压模型对照组灌胃等量生理盐水,正常对照组灌胃等量生理盐水。每组8只,治疗2周。Grouping treatment: All rats were fed adaptively for one week and then measured blood pressure and body weight, and then grouped. Divide the SHR rats into the group of Dendrobium officinale herbal pieces "crushed" and water extraction group with crude drug amount 0.8g/Kg body weight, the group of Dendrobium officinale medicinal herb pieces after "crushing" and water extraction group with crude drug amount of 0.8g/Kg body weight, After "grinding powder", the amount of crude drug in the water extraction group was 0.8g/Kg body weight, and the amlodipine besylate tablet in the amlodipine group was 0.5 mg/Kg body weight, both were given by intragastric administration, and the hypertension model control group was intragastrically administered with the same amount of normal saline , the normal control group was given the same amount of normal saline. 8 rats in each group, treated for 2 weeks.

血压测量:将大鼠38℃预热5-10min,以避免大鼠尾部血流量较少测量不出血压。在大鼠清醒安静状态下连续测量3次,3次的均值作为该鼠血压值。每周测量1次血压,于给药后2小时测量1次。Blood pressure measurement: Preheat the rats at 38°C for 5-10 minutes, so as to prevent blood pressure from being measured due to low blood flow in the tail of the rats. The blood pressure of the rat was measured continuously for 3 times in an awake and quiet state, and the average value of the 3 times was taken as the blood pressure value of the rat. Blood pressure was measured once a week, and once 2 hours after administration.

【实验结果】【Experimental Results】

血压数据见实验1的表1、实验1的表2。blood pressure data See Table 1 of Experiment 1 and Table 2 of Experiment 1.

治疗2周时给药后2小时血压,研粉水提组血压188.6±5.68/148.0±4.22mmHg,显著低于模型组209.3±6.89/160.3±5.67mmHg(P<0.01/P<0.01),但高于西药氨氯地平组175.5±4.48/143.7±4.28mmHg,收缩压差异有显著意义(P<0.05)。捣扁水提组、压碎水提组降压幅度较研粉水提组更小。铁皮石斛研粉水提样品降压作用相对较好,但降压作用低于西药氨氯地平。After 2 weeks of treatment, the blood pressure at 2 hours after administration, the blood pressure of the ground powder water extraction group was 188.6±5.68/148.0±4.22mmHg, which was significantly lower than that of the model group 209.3±6.89/160.3±5.67mmHg (P<0.01/P<0.01), but Higher than the western medicine amlodipine group 175.5±4.48/143.7±4.28mmHg, the difference in systolic blood pressure was significant (P<0.05). The reduction in blood pressure in the pounded flat water extraction group and the crushed water extraction group was smaller than that in the ground powder water extraction group. The antihypertensive effect of Dendrobium candidum powder and water extraction sample is relatively good, but the antihypertensive effect is lower than that of the western medicine amlodipine.

本实验所用大鼠剂量对应相当的成人剂量:The rat doses used in this experiment correspond to equivalent adult doses:

铁皮石斛饮片“捣扁”后水提组对应相当的成人剂量约为铁皮石斛生药量8g/日;The corresponding adult dose of Dendrobium candidum decoction pieces "pounded" is about 8g/day for the water extraction group;

铁皮石斛饮片“压碎”后水提组对应相当的成人剂量约为铁皮石斛生药量8g/日;The corresponding adult dose of Dendrobium candidum decoction pieces "crushed" and water extraction group is about 8g/day of crude drug of Dendrobium candidum;

铁皮石斛饮片“研粉”后水提组对应相当的成人剂量约为铁皮石斛生药量8g/日;The corresponding adult dose of Dendrobium candidum decoction pieces "ground into powder" is about 8g/day for adults;

氨氯地平组对应相当的成人剂量约为苯磺酸氨氯地平片5mg/日。The corresponding adult dose of the amlodipine group is about 5 mg/day of amlodipine besylate tablet.

【结论】【in conclusion】

铁皮石斛饮片“研粉”后水提组降压作用大于铁皮石斛饮片“压碎”后水提组,也大于铁皮石斛饮片“捣扁”后水提组,但其降压作用低于西药氨氯地平。The antihypertensive effect of the water extraction group after "grinding powder" of Dendrobium decoction pieces is greater than that of the water extraction group after "crushing" of Dendrobium decoction pieces, and also greater than that of the water extraction group after "pounding" of Dendrobium decoction pieces, but its antihypertensive effect is lower than that of the western medicine ammonia Clodipine.

实验1:表1.铁皮石斛不同提取方法样品对SHR大鼠给药2小时收缩压的影响(单位:mmHg;n=8)Experiment 1: Table 1. The influence of different extraction methods of Dendrobium candidum on the systolic blood pressure of SHR rats administered for 2 hours ( Unit: mmHg; n=8)

注:与模型组比较△P<0.05▲P<0.01;氨氯地平与各组比较○P<0.05●P<0.01Note: Compared with the model group, △P<0.05▲P<0.01; compared with the other groups, ○P<0.05·P<0.01

实验1:表2.铁皮石斛不同提取方法样品对SHR大鼠给药2小时舒张压的影响(单位:mmHg;n=8)Experiment 1: Table 2. The influence of different extraction methods of Dendrobium candidum on the diastolic blood pressure of SHR rats administered for 2 hours ( Unit: mmHg; n=8)

注:与模型组比较△P<0.05▲P<0.01;氨氯地平与各组比较○P<0.05●P<0.01Note: Compared with the model group, △P<0.05▲P<0.01; compared with the other groups, ○P<0.05·P<0.01

实验2Experiment 2

铁皮石斛研粉、铁皮石斛醇水两提对遗传性高血压大鼠(SHR)降压作用的实验研究Experimental study on antihypertensive effect of Dendrobium officinale powder and two extracts of Dendrobium officinale in alcohol and water on hereditary hypertensive rats (SHR)

【实验材料】【Experimental Materials】

大鼠:10周龄遗传性高血压大鼠(SHR),正常对照选用Wistar大鼠。Rats: 10-week-old hereditary hypertensive rats (SHR), and Wistar rats as normal controls.

试验中药:Experimental Chinese medicine:

铁皮石斛研粉颗粒样品:取符合2015版《中国药典》的铁皮石斛500g。将铁皮石斛药材研细粉,按照药学常规添加合适辅料,制成中药颗粒(混悬颗粒)。烘干。为实施例1样品。临用前用热水溶解。Dendrobium officinale powder granule sample: Take 500g of Dendrobium officinale in accordance with the 2015 edition of "Chinese Pharmacopoeia". The Dendrobium candidum medicinal material is ground into fine powder, and suitable auxiliary materials are added according to pharmaceutical routines to make traditional Chinese medicine granules (suspension granules). drying. For Example 1 sample. Dissolve in hot water before use.

铁皮石斛醇水两提颗粒样品:取符合2015版《中国药典》的铁皮石斛500g,研末,加5倍总生药量的75%乙醇60℃浸提24小时,提取2次,醇提后残渣再水提取。水提取时采用2次梯度加热提取法:第一次水提取:加总生药量的30倍的水,100℃提取2小时;第二次水提取:加总生药量的20倍的水,121℃提取2小时。水提取物合并浓缩。醇提取与水提取分别浓缩后,合并提取物,按照药学常规添加合适辅料,制成中药颗粒。烘干。为实施例2样品。临用前用热水溶解。Dendrobium officinale extract granules with alcohol and water: Take 500g of Dendrobium officinale in accordance with the 2015 edition of "Chinese Pharmacopoeia", grind it into powder, add 75% ethanol 5 times the total crude drug amount, and extract at 60°C for 24 hours, extract twice, and the residue after alcohol extraction Then extract with water. Two gradient heating extraction methods were used for water extraction: the first water extraction: add water 30 times the total amount of crude drug, extract at 100 ° C for 2 hours; the second water extraction: add water 20 times the total amount of crude drug, 121 °C extraction for 2 hours. The aqueous extracts were combined and concentrated. After alcohol extraction and water extraction are respectively concentrated, the extracts are combined, and appropriate excipients are added according to pharmaceutical routines to make traditional Chinese medicine granules. drying. Be embodiment 2 samples. Dissolve in hot water before use.

醇提取样品:同铁皮石斛醇水两提颗粒样品的醇提取部分:取符合2015版《中国药典》的铁皮石斛500g,研末,加5倍总生药量的75%乙醇60℃浸提24小时,提取2次,合并提取物,浓缩,备用。Alcohol extraction sample: the same as the alcohol extraction part of Dendrobium officinale granule sample: Take 500g of Dendrobium officinale that conforms to the 2015 edition of "Chinese Pharmacopoeia", grind it into powder, add 75% ethanol that is 5 times the total crude drug amount, and extract at 60°C for 24 hours , extract twice, combine the extracts, concentrate, and set aside.

水提取样品:取符合2015版《中国药典》的铁皮石斛500g,研末,第一次水提取:加总生药量的30倍的水,100℃提取2小时;第二次水提取:加总生药量的20倍的水,100℃提取2小时。合并水提取物,浓缩,备用。Water extraction sample: Take 500g of Dendrobium officinale that conforms to the 2015 edition of "Chinese Pharmacopoeia", grind it into powder, the first water extraction: add water 30 times the amount of crude drug, extract at 100°C for 2 hours; the second water extraction: add up 20 times the amount of crude drug in water, extracted at 100°C for 2 hours. The water extracts were combined, concentrated, and set aside.

西药降压对照药品:苯磺酸氨氯地平片(络活喜),5mg/片,批号:R78401,辉瑞制药生产。Western antihypertensive control drug: Amlodipine Besylate Tablets (Norvasc), 5mg/tablet, batch number: R78401, produced by Pfizer.

大鼠血压测量:BP-98A型无创尾动脉血压测量仪,日本软融株式会社。Rat blood pressure measurement: BP-98A non-invasive tail artery blood pressure measuring instrument, Japan Soft Rong Co., Ltd.

【实验方法】【experimental method】

分组治疗:全部大鼠适应性饲养一周后测量血压及体重,进行分组。将SHR大鼠分为铁皮石斛醇提取样品组生药量0.8g/Kg体重,铁皮石斛水提取样品组生药量0.8g/Kg体重,铁皮石斛研粉样品组生药量0.8g/Kg体重,铁皮石斛醇水两提样品组生药量0.8g/Kg体重,氨氯地平组苯磺酸氨氯地平片0.5mg/Kg体重,均灌胃给药,高血压模型对照组灌胃等量生理盐水,正常对照组灌胃等量生理盐水。每组8只,治疗8周。停药观察血压1周。Grouping treatment: All rats were fed adaptively for one week and then measured blood pressure and body weight, and then grouped. SHR rats are divided into Dendrobium officinale alcohol extraction sample group crude drug amount 0.8g/Kg body weight, Dendrobium officinale water extraction sample group crude drug amount 0.8g/Kg body weight, Dendrobium officinale powder sample group crude drug amount 0.8g/Kg body weight, Dendrobium officinale The amount of crude drug in the alcohol and water extraction sample group was 0.8g/Kg body weight, and the amlodipine besylate tablet was 0.5mg/Kg body weight in the amlodipine group. The control group was intragastrically administered the same amount of normal saline. Eight rats in each group were treated for 8 weeks. Blood pressure was observed for 1 week after drug withdrawal.

血压测量:将大鼠38℃预热5-10min,以避免大鼠尾部血流量较少测量不出血压。在大鼠清醒安静状态下连续测量3次,3次的均值作为该鼠血压值。每周测量2次血压,于给药后2小时测量1次,给药后24小时测量1次,以观察给药后的即时降压疗效和24小时降压疗效(以及降压谷峰比值)。Blood pressure measurement: Preheat the rats at 38°C for 5-10 minutes, so as to prevent blood pressure from being measured due to low blood flow in the tail of the rats. The blood pressure of the rat was measured continuously for 3 times in an awake and quiet state, and the average value of the 3 times was taken as the blood pressure value of the rat. Measure blood pressure twice a week, once 2 hours after administration, and once 24 hours after administration, to observe the immediate antihypertensive effect and 24-hour antihypertensive effect (as well as the peak-to-peak ratio of antihypertensive) after administration .

降压幅度谷峰比计算:治疗前血压-给药后24小时血压的差值为血压降压幅度的谷值,即下次给药前的降压幅度最低点;治疗前血压-给药后2小时血压的差值为血压降压幅度的峰值,即给药后的降压幅度最大点;降压幅度的谷值/降压幅度的峰值=降压幅度谷峰比。降压幅度谷峰比越接近1,降压作用越平稳,越符合长效降压药物的要求;降压幅度谷峰比越接近0,降压作用越短效。Calculation of valley-to-peak ratio of blood pressure reduction: the difference between blood pressure before treatment - blood pressure 24 hours after administration is the valley value of blood pressure reduction, that is, the lowest point of blood pressure reduction before the next administration; blood pressure before treatment - after administration The difference in blood pressure at 2 hours is the peak value of the blood pressure reduction range, that is, the point at which the blood pressure reduction range is maximum after administration; the valley value of the blood pressure reduction range/the peak value of the blood pressure reduction range = the ratio of the valley-peak reduction range of the blood pressure reduction range. The closer the peak-to-valley ratio of the antihypertensive amplitude is to 1, the more stable the antihypertensive effect is, and the more it meets the requirements of long-acting antihypertensive drugs; the closer the peak-to-valley ratio of the antihypertensive amplitude is to 0, the shorter the antihypertensive effect.

【实验结果】【Experimental Results】

血压数据见实验2的表1、实验2的表2、实验2的表3、实验2的表4、实验2的表5。blood pressure data See Table 1 of Experiment 2, Table 2 of Experiment 2, Table 3 of Experiment 2, Table 4 of Experiment 2, and Table 5 of Experiment 2.

1、治疗1周时血压:1. Blood pressure at 1 week of treatment:

(1)给药后2小时血压:(1) Blood pressure 2 hours after administration:

铁皮石斛醇水两提组(醇水两提组)172.9±9.38/141.1±10.53mmHg,非常显著低于模型组207.0±7.45/157.0±7.03mmHg(P<0.01/P<0.01),并低于醇提组181.4±5.22/146.8±9.60mmHg(P<0.01/P>0.05),低于水提组180.0±7.26/143.7±7.56mmHg(P<0.01/P>0.05)。也略低于西药降压药氨氯地平组175.1±4.44/143.2±6.41mmHg,但无显著差异(P>0.05/P>0.05)。铁皮石斛醇水两提组(醇水两提组)的2小时降压作用,在1周用药时就已经超过水提组和醇提组,并达到了西药降压药氨氯地平组的降压作用幅度。Dendrobium officinale alcohol water extraction group (alcohol water extraction group) 172.9±9.38/141.1±10.53mmHg, very significantly lower than the model group 207.0±7.45/157.0±7.03mmHg (P<0.01/P<0.01), and lower than Alcohol extraction group 181.4±5.22/146.8±9.60mmHg (P<0.01/P>0.05), lower than water extraction group 180.0±7.26/143.7±7.56mmHg (P<0.01/P>0.05). It was also slightly lower than the 175.1±4.44/143.2±6.41mmHg of the western medicine antihypertensive drug amlodipine group, but there was no significant difference (P>0.05/P>0.05). The 2-hour antihypertensive effect of Dendrobium officinale alcohol and water extraction group (alcohol and water extraction group) has surpassed the water extraction group and alcohol extraction group in 1 week of medication, and has reached the lowering effect of the western medicine antihypertensive drug amlodipine group. pressure range.

铁皮石斛研粉组(研粉组)181.2±6.71/148.1±10.55mmHg,显著低于模型组(P<0.01/P<0.05),但较铁皮石斛醇水两提组(醇水两提组)降压幅度小。Dendrobium candidum powder group (research powder group) 181.2±6.71/148.1±10.55mmHg, significantly lower than the model group (P<0.01/P<0.05), but higher than the Dendrobium officinale alcohol-water extraction group (alcohol-water extraction group) The step-down range is small.

(2)给药后24小时血压:(2) Blood pressure 24 hours after administration:

铁皮石斛研粉组(研粉组)189.7±10.26/149.3±9.05mmHg,显著低于模型组208.1±9.31/163.8±5.83mmHg(P<0.05/P<0.01),也较铁皮石斛醇水两提组(醇水两提组)、水提组、醇提组、西药降压药氨氯地平组的降压幅度大。Dendrobium candidum powder group (research powder group) 189.7±10.26/149.3±9.05mmHg, significantly lower than the model group 208.1±9.31/163.8±5.83mmHg (P<0.05/P<0.01), also compared with Dendrobium officinale Group (alcohol and water extraction group), water extraction group, alcohol extraction group, western medicine antihypertensive drug amlodipine group have a large range of blood pressure reduction.

铁皮石斛醇水两提组(醇水两提组)203.2±12.69/161.5±13.54mmHg,低于模型组208.1±9.31/163.8±5.83mmHg,但无显著差异(P>0.05/P>0.05)。Dendrobium officinale alcohol water extraction group (alcohol water extraction group) 203.2±12.69/161.5±13.54mmHg, lower than the model group 208.1±9.31/163.8±5.83mmHg, but no significant difference (P>0.05/P>0.05).

(3)给药24小时降压幅度/给药2小时降压幅度=降压幅度谷峰比:(3) Blood pressure reduction range for 24 hours after administration / blood pressure reduction range for 2 hours after administration = valley-peak ratio of blood pressure reduction range:

铁皮石斛研粉组(研粉组)给药24小时降压幅度20.8mmHg/给药2小时降压幅度29.3mmHg=降压幅度谷峰比0.71;Dendrobium candidum powder group (powder research group) administration 24 hours blood pressure reduction range 20.8mmHg/administration 2 hours blood pressure reduction range 29.3mmHg = blood pressure reduction range valley-peak ratio 0.71;

水提组给药24小时降压幅度6.9mmHg/给药2小时降压幅度27.4mmHg=降压幅度谷峰比0.25;In the water extraction group, the 24-hour blood pressure reduction range was 6.9 mmHg/the 2-hour blood pressure reduction range was 27.4 mmHg=the blood pressure reduction range valley-peak ratio was 0.25;

醇提组给药24小时降压幅度10.1mmHg/给药2小时降压幅度26.0mmHg=降压幅度谷峰比0.39;In the alcohol extraction group, the range of blood pressure reduction in 24 hours was 10.1 mmHg/the range of blood pressure reduction in 2 hours was 26.0 mmHg=the valley-peak ratio of blood pressure reduction was 0.39;

西药氨氯地平组给药24小时降压幅度9.1mmHg/给药2小时降压幅度34.7mmHg=降压幅度谷峰比0.26;In the Western medicine amlodipine group, the 24-hour blood pressure reduction range was 9.1 mmHg/the 2-hour blood pressure reduction range was 34.7 mmHg=the blood pressure reduction range valley-peak ratio was 0.26;

铁皮石斛醇水两提组(醇水两提组)给药24小时降压幅度3.8mmHg/给药2小时降压幅度34.1mmHg=降压幅度谷峰比0.11;Dendrobium officinale alcohol and water two extraction group (alcohol and water two extraction group) 24 hours after administration, the blood pressure reduction range is 3.8mmHg/administration 2 hours, the blood pressure reduction range is 34.1mmHg=the blood pressure reduction range valley-peak ratio is 0.11;

治疗1周时,铁皮石斛研粉组(研粉组)的给药24小时降压幅度20.8mmHg较水提组6.9mmHg、醇提组10.1mmHg、醇水两提组3.8mmHg、西药氨氯地平组9.1mmHg大,铁皮石斛研粉组(研粉组)的降压幅度谷峰比0.71(71%)较水提组0.25(25%)、醇提组0.39(39%)、醇水两提组0.11(11%)、西药氨氯地平组0.26(26%)降压幅度谷峰比大,其降压幅度谷值达到降压幅度峰值的70%以上,超过西药降压药对照药氨氯地平组(降压幅度谷峰比26%),也超过铁皮石斛水提取组(降压幅度谷峰比25%)。铁皮石斛研粉组(研粉组)的给药24小时降压幅度平稳性显著优于水提组以及西药氨氯地平组。铁皮石斛醇水两提组(醇水两提组)的给药2小时降压幅度34.1mmHg显著优于水提组27.4mmHg,达到西药氨氯地平组34.7mmHg的作用幅度,短效降压作用优于其他组。During 1 week of treatment, the 24-hour blood pressure reduction range of the Dendrobium candidum powder group (research powder group) was 20.8mmHg compared with 6.9mmHg in the water extraction group, 10.1mmHg in the alcohol extraction group, 3.8mmHg in the alcohol and water extraction group, and 3.8mmHg in the western medicine amlodipine. Dendrobium candidum powder group (research powder group) has a lower blood pressure range than 0.71 (71%) compared with 0.25 (25%) in the water extraction group, 0.39 (39%) in the alcohol extraction group, and 0.39 (39%) in the alcohol and water extraction group. 0.11 (11%) in the Western medicine amlodipine group and 0.26 (26%) in the western medicine amlodipine group, the peak-to-valley ratio of the antihypertensive amplitude was large, and the valley value of the antihypertensive amplitude reached more than 70% of the peak value of the antihypertensive amplitude, exceeding the Western medicine antihypertensive drug amlodipine. The Diping group (the valley-to-peak ratio of blood pressure reduction range is 26%) also exceeds the water extraction group of Dendrobium officinale (the valley-to-peak ratio of blood pressure reduction range is 25%). Dendrobium officinale research powder group (research powder group) was significantly better than the water extraction group and the Western medicine amlodipine group in the 24-hour blood pressure reduction range stability. Dendrobium officinale alcohol and water extraction group (alcohol and water two extraction group) has a 2-hour blood pressure lowering range of 34.1mmHg, which is significantly better than that of the water extraction group (27.4mmHg), reaching the range of 34.7mmHg of the Western medicine amlodipine group, and has a short-acting antihypertensive effect. superior to other groups.

2、治疗8周时血压:2. Blood pressure at 8 weeks of treatment:

(1)给药后2小时血压:(1) Blood pressure 2 hours after administration:

铁皮石斛醇水两提组(醇水两提组)172.2±2.22/134.7±3.41mmHg,非常显著低于模型组212.3±5.37/159.7±5.48mmHg(P<0.01/P<0.01),并低于醇提组178.0±4.14/141.7±1.92mmHg(P<0.01/P<0.01),低于水提组178.2±2.90/142.3±3.28mmHg(P<0.01/P<0.01)。也显著低于西药降压药氨氯地平组178.1±2.67/144.7±3.43mmHg,(P<0.01/P<0.01)。铁皮石斛醇水两提组(醇水两提组)的2小时降压作用,在8周用药时显著超过水提组和醇提组,并超过了西药降压药氨氯地平组的降压作用幅度,短效降压作用优于其他组。Dendrobium officinale alcohol water two extraction group (alcohol water two extraction group) 172.2±2.22/134.7±3.41mmHg, very significantly lower than the model group 212.3±5.37/159.7±5.48mmHg (P<0.01/P<0.01), and lower than Alcohol extraction group 178.0±4.14/141.7±1.92mmHg (P<0.01/P<0.01), lower than water extraction group 178.2±2.90/142.3±3.28mmHg (P<0.01/P<0.01). It was also significantly lower than that of the western medicine antihypertensive drug amlodipine group (178.1±2.67/144.7±3.43mmHg, (P<0.01/P<0.01). The 2-hour antihypertensive effect of Dendrobium officinale alcohol and water extraction group (alcohol and water extraction group) was significantly higher than that of the water extraction group and alcohol extraction group during 8 weeks of medication, and exceeded the antihypertensive effect of the Western medicine antihypertensive drug amlodipine group The range of action, short-acting antihypertensive effect is better than other groups.

铁皮石斛研粉组(研粉组)180.6±2.91/145.0±4.06mmHg,显著低于模型组(P<0.01/P<0.01),但较铁皮石斛醇水两提组(醇水两提组)降压幅度小。Dendrobium candidum powder group (research powder group) 180.6±2.91/145.0±4.06mmHg, significantly lower than the model group (P<0.01/P<0.01), but higher than the Dendrobium officinale alcohol-water extraction group (alcohol-water extraction group) The step-down range is small.

(2)给药后24小时血压:(2) Blood pressure 24 hours after administration:

铁皮石斛研粉组(研粉组)192.9±6.81/155.3±5.18mmHg,显著低于模型组217.0±6.39/165.4±4.16mmHg(P<0.05/P<0.01),也显著较铁皮石斛醇水两提组(醇水两提组)201.3±3.01/156.5±4.21mmHg、水提组203.4±2.76/160.2±6.14mmHg、醇提组202.0±4.39/156.0±8.39mmHg、西药降压药氨氯地平组202.0±5.88/154.3±5.50mmHg的降压幅度大(P<0.01/P>0.05)。Dendrobium candidum powder group (research powder group) 192.9±6.81/155.3±5.18mmHg, significantly lower than the model group 217.0±6.39/165.4±4.16mmHg (P<0.05/P<0.01), also significantly higher than Dendrobium candidum Extraction group (alcohol and water extraction group) 201.3±3.01/156.5±4.21mmHg, water extraction group 203.4±2.76/160.2±6.14mmHg, alcohol extraction group 202.0±4.39/156.0±8.39mmHg, Western medicine antihypertensive drug amlodipine group 202.0±5.88/154.3±5.50mmHg lowered the blood pressure significantly (P<0.01/P>0.05).

铁皮石斛醇水两提组(醇水两提组)显著低于模型组(P<0.01/P<0.01),但较铁皮石斛研粉组(研粉组)收缩压降压幅度小。The Dendrobium candidum extract group (alcohol water extract group) was significantly lower than the model group (P<0.01/P<0.01), but the systolic blood pressure reduction range was smaller than that of the Dendrobium candidum powder group (research powder group).

(3)治疗8周时给药24小时降压幅度/给药2小时降压幅度=降压幅度谷峰比:(3) During 8 weeks of treatment, the 24-hour blood pressure reduction range/2-hour blood pressure reduction range = the blood pressure reduction range valley-peak ratio:

铁皮石斛研粉组(研粉组)给药24小时降压幅度17.6mmHg/给药2小时降压幅度29.9mmHg=降压幅度谷峰比0.59;Dendrobium candidum powder group (research powder group) 24-hour blood pressure reduction range 17.6mmHg/administration 2-hour blood pressure reduction range 29.9mmHg = blood pressure reduction range valley-peak ratio 0.59;

水提组给药24小时降压幅度4.0mmHg/给药2小时降压幅度29.2mmHg=降压幅度谷峰比0.14;In the water extraction group, the range of blood pressure reduction for 24 hours was 4.0 mmHg/the range of blood pressure reduction for 2 hours was 29.2 mmHg=the valley-peak ratio of blood pressure reduction range was 0.14;

醇提组给药24小时降压幅度5.4mmHg/给药2小时降压幅度29.4mmHg=降压幅度谷峰比0.18;In the alcohol extraction group, the range of blood pressure reduction in 24 hours was 5.4mmHg/the range of blood pressure reduction in 2 hours was 29.4mmHg=the valley-peak ratio of blood pressure reduction was 0.18;

西药氨氯地平组给药24小时降压幅度7.8mmHg/给药2小时降压幅度31.7mmHg=降压幅度谷峰比0.25;In the western medicine amlodipine group, the range of blood pressure reduction in 24 hours was 7.8 mmHg/the range of blood pressure reduction in 2 hours was 31.7 mmHg=the valley-peak ratio of blood pressure reduction range was 0.25;

铁皮石斛醇水两提组(醇水两提组)给药24小时降压幅度5.7mmHg/给药2小时降压幅度34.8mmHg=降压幅度谷峰比0.16;Dendrobium officinale alcohol and water two extraction group (alcohol and water two extraction group) 24 hours of administration, blood pressure reduction range 5.7mmHg/administration 2 hours blood pressure reduction range 34.8mmHg = blood pressure reduction range valley-peak ratio 0.16;

治疗8周时,铁皮石斛研粉组(研粉组)的给药24小时降压幅度17.6mmHg较水提组4.0mmHg、醇提组5.4mmHg、醇水两提组5.7mmHg、西药氨氯地平组7.8mmHg的降压幅度大,铁皮石斛研粉组(研粉组)的降压幅度谷峰比0.59(59%)较水提组0.14(14%)、醇提组0.18(18%)、醇水两提组0.16(16%)、西药氨氯地平组0.25(25%)降压幅度谷峰比大,其降压幅度谷值达到降压幅度峰值的50%以上,超过西药降压药对照药氨氯地平组(降压幅度谷峰比25%),也超过铁皮石斛水提取组(降压幅度谷峰比14%)。铁皮石斛研粉组(研粉组)的给药24小时降压幅度平稳性显著优于水提组以及西药氨氯地平组。铁皮石斛醇水两提组(醇水两提组)的给药2小时降压幅度34.8mmHg显著优于水提组29.2mmHg,超过西药氨氯地平组31.7mmHg的作用幅度,短效降压作用较好。During 8 weeks of treatment, the 24-hour blood pressure reduction range of Dendrobium candidum powder group (research powder group) was 17.6mmHg compared with water extraction group 4.0mmHg, alcohol extraction group 5.4mmHg, alcohol and water extraction group 5.7mmHg, Western medicine amlodipine The lowering range of 7.8mmHg of the group is large, and the lowering range of the Dendrobium candidum powder group (ground powder group) has a valley-peak ratio of 0.59 (59%) compared with 0.14 (14%) of the water extraction group, 0.18 (18%) of the alcohol extraction group, and 0.18 (18%) of the alcohol extraction group. 0.16 (16%) in the alcohol and water extraction group, and 0.25 (25%) in the western medicine amlodipine group have a large valley-to-peak ratio of blood pressure reduction, and the valley value of the blood pressure reduction range reaches more than 50% of the peak value of the blood pressure reduction range, exceeding the Western medicine antihypertensive drug. The control drug amlodipine group (the peak-to-valley ratio of blood pressure reduction range was 25%) also surpassed the Dendrobium officinale water extraction group (the peak-to-peak ratio of blood pressure reduction range was 14%). Dendrobium officinale research powder group (research powder group) was significantly better than the water extraction group and the Western medicine amlodipine group in the 24-hour blood pressure reduction range stability. Dendrobium officinale alcohol and water extraction group (alcohol and water two extraction group) has a blood pressure reduction range of 34.8mmHg within 2 hours, which is significantly better than that of the water extraction group (29.2mmHg), exceeding the range of action of the Western medicine amlodipine group (31.7mmHg), and the short-acting antihypertensive effect better.

3、停药后1周血压:3. Blood pressure 1 week after drug withdrawal:

(1)停药后3天血压:(1) Blood pressure 3 days after drug withdrawal:

铁皮石斛醇水两提组(醇水两提组)198.8±3.12/153.4±5.01mmHg,非常显著低于模型组214.2±3.57/165.9±5.50mmHg(P<0.01/P<0.01),并显著低于水提组205.2±2.83/156.1±2.71mmHg(P<0.05/P<0.05),也显著低于西药降压药氨氯地平组205.4±1.85/158.7±2.79mmHg,(P<0.05/P>0.05)。铁皮石斛醇水两提组(醇水两提组)的停药后3天降压作用,显著超过水提组和西药降压药氨氯地平组的降压作用幅度。Dendrobium officinale alcohol water extraction group (alcohol water extraction group) 198.8±3.12/153.4±5.01mmHg, very significantly lower than the model group 214.2±3.57/165.9±5.50mmHg (P<0.01/P<0.01), and significantly lower In the water extraction group 205.2±2.83/156.1±2.71mmHg (P<0.05/P<0.05), it was also significantly lower than the Western medicine antihypertensive drug amlodipine group 205.4±1.85/158.7±2.79mmHg, (P<0.05/P> 0.05). The antihypertensive effect of Dendrobium officinale two-extraction group (alcohol-water two-extraction group) 3 days after drug withdrawal was significantly higher than that of the water-extraction group and the Western medicine antihypertensive drug amlodipine group.

铁皮石斛研粉组(研粉组)199.6±3.24/152.1±5.77mmHg,显著低于模型组214.2±3.57/165.9±5.50mmHg(P<0.01/P<0.01),较铁皮石斛醇水两提组(醇水两提组)降压幅度相近。Dendrobium candidum powder group (research powder group) 199.6±3.24/152.1±5.77mmHg, significantly lower than the model group 214.2±3.57/165.9±5.50mmHg (P<0.01/P<0.01), compared with the Dendrobium candidum alcohol-water extraction group (Alcohol and water extraction group) the blood pressure reduction range is similar.

(2)停药后7天血压:(2) Blood pressure 7 days after drug withdrawal:

各组血压均比较治疗用药时明显回升,舒张压相对于收缩压回升缓慢。The blood pressure in each group rose significantly compared with the treatment, and the diastolic blood pressure rose slowly compared with the systolic blood pressure.

铁皮石斛醇水两提组(醇水两提组)舒张压153.0±3.24mmHg,显著低于水提组165.5±3.13mmHg(P<0.01)、醇提组161.6±5.53mmHg(P<0.05)。The diastolic blood pressure of Dendrobium candidum extract group (alcohol and water extraction group) was 153.0±3.24mmHg, significantly lower than the water extraction group 165.5±3.13mmHg (P<0.01) and the alcohol extraction group 161.6±5.53mmHg (P<0.05).

铁皮石斛研粉组(研粉组)舒张压155.5±3.00mmHg,显著低于水提组165.5±3.13mmHg(P<0.05)。The diastolic blood pressure of Dendrobium candidum powder group (powder research group) was 155.5±3.00mmHg, which was significantly lower than that of the water extraction group (P<0.05).

西药降压药氨氯地平组降低血压起效快,但停药后血压回升也快。从停药3天血压看,铁皮石斛研粉组(研粉组)和铁皮石斛醇水两提组(醇水两提组)停药后血压回升较慢。The western medicine antihypertensive drug amlodipine group lowered blood pressure quickly, but the blood pressure also rose quickly after stopping the drug. From the perspective of blood pressure 3 days after drug withdrawal, the blood pressure of the Dendrobium officinale powder group (research powder group) and the Dendrobium officinale alcohol-water extraction group (alcohol-water extraction group) rose slowly after drug withdrawal.

本实验所用大鼠剂量对应相当的成人剂量:The rat doses used in this experiment correspond to equivalent adult doses:

铁皮石斛醇提取样品组对应相当的成人剂量约为铁皮石斛生药量8g/日;Dendrobium candidum alcohol extraction sample group corresponds to a corresponding adult dose of about 8g/day of the crude drug dose of Dendrobium candidum;

铁皮石斛水提取样品组对应相当的成人剂量约为铁皮石斛生药量8g/日;Dendrobium officinale water extraction sample group corresponds to an equivalent adult dose of about 8g/day of the crude drug dose of Dendrobium officinale;

铁皮石斛研粉组(铁皮石斛研粉组)对应相当的成人剂量约为铁皮石斛生药量8g/日;Dendrobium candidum powder group (Dendrobium candidum powder group) corresponds to a corresponding adult dose of about 8g/day of crude drug dose of Dendrobium candidum;

铁皮石斛醇水两提组(铁皮石斛醇水两提组)对应相当的成人剂量约为铁皮石斛生药量8g/日;Dendrobium candidum alcohol water two extraction group (Dendrobium candidum alcohol water two extraction group) corresponds to an equivalent adult dose of about 8g/day of the crude drug dose of Dendrobium candidum;

氨氯地平组对应相当的成人剂量约为苯磺酸氨氯地平片5mg/日。The corresponding adult dose of the amlodipine group is about 5 mg/day of amlodipine besylate tablet.

【结论】【in conclusion】

铁皮石斛醇水两提样品(醇水两提组)给药后2小时降压疗效,显著优于铁皮石斛水提组、铁皮石斛醇提组、铁皮石斛研粉组(研粉组),也优于西药降压药氨氯地平组;降压速效方面达到或者超过西药降压药氨氯地平;停药后3天的血压回升较西药降压药氨氯地平慢;铁皮石斛醇水两提样品作为短效降压药物较为合适。Two hours of antihypertensive efficacy of Dendrobium officinale extract sample (alcohol water two extraction group) after administration, significantly better than Dendrobium officinale water extraction group, Dendrobium officinale alcohol extraction group, Dendrobium officinale powder group (research powder group), also It is better than the western medicine antihypertensive drug amlodipine group; the quick-acting antihypertensive drug reaches or surpasses the western medicine antihypertensive drug amlodipine; the blood pressure rises 3 days after stopping the drug is slower than the western medicine antihypertensive drug amlodipine; The sample is more suitable as a short-acting antihypertensive drug.

铁皮石斛研粉样品(研粉组)给药后24小时降压疗效,显著优于铁皮石斛水提组、铁皮石斛醇提组、铁皮石斛醇水两提组(醇水两提组),也优于西药降压药氨氯地平组;降压谷峰比大,降压平稳性方面达到并超过西药降压药氨氯地平;停药后3天的血压回升较西药降压药氨氯地平慢;铁皮石斛研粉样品作为长效降压药物较为合适。The antihypertensive curative effect of the Dendrobium candidum powder sample (research powder group) was significantly better than that of the Dendrobium candidum water extraction group, the Dendrobium candidum alcohol extraction group, and the Dendrobium candidum alcohol and water extraction group (alcohol and water extraction group). It is better than the western drug antihypertensive drug amlodipine group; the antihypertensive trough-peak ratio is large, and the antihypertensive stability reaches and exceeds that of the western drug antihypertensive drug amlodipine; Slow; Dendrobium candidum powder sample is more suitable as a long-acting antihypertensive drug.

实验2:表1.铁皮石斛研粉样品、铁皮石斛醇水两提样品对SHR大鼠给药2小时收缩压的影响(单位:mmHg;n=8)Experiment 2: Table 1. Effects of Dendrobium officinale powder sample and Dendrobium officinale alcohol water extraction sample on the systolic blood pressure of SHR rats administered for 2 hours ( Unit: mmHg; n=8)

注:与模型组比较△P<0.05▲P<0.01;铁皮石斛研粉组(研粉)与各组比较○P<0.05●P<0.01;铁皮石斛醇水两提组(醇水两提)与各组比较☆P<0.05★P<0.01Note: △P<0.05▲P<0.01 compared with the model group; ○P<0.05 P<0.01 compared with the Dendrobium candidum powder group (ground powder) and each group; Compared with each group☆P<0.05★P<0.01

实验2:表2.铁皮石斛研粉样品、铁皮石斛醇水两提样品对SHR大鼠给药24小时收缩压的影响(单位:mmHg;n=8)Experiment 2: Table 2. Effects of Dendrobium officinale powder sample and Dendrobium officinale alcohol water extraction sample on 24-hour systolic blood pressure of SHR rats ( Unit: mmHg; n=8)

注:与模型组比较△P<0.05▲P<0.01;铁皮石斛研粉组(研粉)与各组比较○P<0.05●P<0.01;铁皮石斛醇水两提组(醇水两提)与各组比较☆P<0.05★P<0.01Note: △P<0.05▲P<0.01 compared with the model group; ○P<0.05 P<0.01 compared with the Dendrobium candidum powder group (ground powder) and each group; Compared with each group☆P<0.05★P<0.01

实验2:表3.铁皮石斛研粉样品、铁皮石斛醇水两提样品对SHR大鼠给药2小时舒张压的影响(单位:mmHg;n=8)Experiment 2: Table 3. Effects of Dendrobium officinale powder sample and Dendrobium officinale alcohol water extraction sample on diastolic blood pressure of SHR rats administered for 2 hours ( Unit: mmHg; n=8)

注:与模型组比较△P<0.05▲P<0.01;铁皮石斛研粉组(研粉)与各组比较○P<0.05●P<0.01;铁皮石斛醇水两提组(醇水两提)与各组比较☆P<0.05★P<0.01Note: △P<0.05▲P<0.01 compared with the model group; ○P<0.05 P<0.01 compared with the Dendrobium candidum powder group (ground powder) and each group; Compared with each group☆P<0.05★P<0.01

实验2:表4.铁皮石斛研粉样品、铁皮石斛醇水两提样品对SHR大鼠给药24小时舒张压的影响(单位:mmHg;n=8)Experiment 2: Table 4. Effects of Dendrobium officinale powder sample and Dendrobium officinale alcohol water extraction sample on 24-hour diastolic blood pressure in SHR rats ( Unit: mmHg; n=8)

注:与模型组比较△P<0.05▲P<0.01;铁皮石斛研粉组(研粉)与各组比较○P<0.05●P<0.01;铁皮石斛醇水两提组(醇水两提)与各组比较☆P<0.05★P<0.01Note: △P<0.05▲P<0.01 compared with the model group; ○P<0.05 P<0.01 compared with the Dendrobium candidum powder group (ground powder) and each group; Compared with each group☆P<0.05★P<0.01

实验2:表5.铁皮石斛研粉样品、铁皮石斛醇水两提样品对SHR大鼠给药后24小时/给药后2小时的收缩压降压幅度谷峰比的影响(治疗前-给药后24小时的血压降幅谷值/治疗前-给药后2小时的血压降幅峰值=降压谷峰比;血压单位:mmHg;n=8)Experiment 2: Table 5. The influence of the Dendrobium officinale powder sample and the Dendrobium officinale alcohol-water extraction sample on the peak-to-peak ratio of the systolic blood pressure reduction range 24 hours after administration/2 hours after administration in SHR rats (before treatment-administration The valley value of the blood pressure drop 24 hours after the drug/before treatment-the peak value of the blood pressure drop 2 hours after the administration = the peak-to-peak ratio of blood pressure reduction; blood pressure unit: mmHg; n=8)

实验3Experiment 3

实施例1样品对遗传性高血压大鼠(SHR)降压作用的实验研究Experimental research on the antihypertensive effect of embodiment 1 sample on hereditary hypertensive rats (SHR)

【实验材料】【Experimental Materials】

大鼠:遗传性高血压大鼠(SHR),正常对照选用Wistar大鼠。Rats: hereditary hypertensive rats (SHR), and Wistar rats as normal controls.

试验中药:Experimental Chinese medicine:

实施例1试验样品:取符合2015版《中国药典》的铁皮石斛800g、苯磺酸氨氯地平250mg。将铁皮石斛药材研细粉,加入苯磺酸氨氯地平粉末,混匀后,按照药学常规添加合适辅料,制成颗粒(混悬颗粒),烘干。为实施例1样品。临用前用热水溶解。Example 1 Test sample: take 800g of Dendrobium officinale and 250mg of amlodipine besylate in accordance with the 2015 edition of "Chinese Pharmacopoeia". The Dendrobium candidum medicinal material is ground into fine powder, amlodipine besylate powder is added, after mixing, appropriate excipients are added according to pharmaceutical routines to make granules (suspension granules), and dried. For Example 1 sample. Dissolve in hot water before use.

铁皮石斛研粉样品:取符合2015版《中国药典》的铁皮石斛500g。将铁皮石斛药材研细粉,按照药学常规添加合适辅料,制成中药颗粒(混悬颗粒),烘干。为实施例1样品。临用前用热水溶解。Powder sample of Dendrobium officinale: Take 500g of Dendrobium officinale in accordance with the 2015 edition of "Chinese Pharmacopoeia". The Dendrobium candidum medicinal material is ground into fine powder, and suitable excipients are added according to pharmaceutical routines to make traditional Chinese medicine granules (suspension granules), and dried. Be embodiment 1 sample. Dissolve in hot water before use.

西药降压对照药品:苯磺酸氨氯地平片(络活喜),5mg/片,批号:R78401,辉瑞制药生产。Western antihypertensive control drug: Amlodipine Besylate Tablets (Norvasc), 5mg/tablet, batch number: R78401, produced by Pfizer.

大鼠血压测量:BP-98A型无创尾动脉血压测量仪,日本软融株式会社。Rat blood pressure measurement: BP-98A non-invasive tail artery blood pressure measuring instrument, Japan Soft Rong Co., Ltd.

【实验方法】【experimental method】

分组治疗:全部大鼠适应性饲养一周后测量血压及体重,进行分组。将SHR大鼠分为实施例1试验样品小剂量组(铁皮石斛生药量0.4g/Kg体重,氨氯地平0.125mg/Kg体重),实施例1试验样品中剂量组(铁皮石斛生药量0.6g/Kg体重,氨氯地平0.1875mg/Kg体重),实施例1试验样品大剂量组(铁皮石斛生药量0.8g/Kg体重,氨氯地平0.25mg/Kg体重),铁皮石斛研粉样品组铁皮石斛生药量0.8g/Kg体重,氨氯地平组(半量)苯磺酸氨氯地平片0.25mg/Kg体重,均灌胃给药,高血压模型对照组灌胃等量生理盐水,正常对照组灌胃等量生理盐水。每组8只,治疗3周。Grouping treatment: All rats were fed adaptively for one week and then measured blood pressure and body weight, and then grouped. SHR rats are divided into embodiment 1 test sample small dosage group (Dendrobium candidum crude drug amount 0.4g/Kg body weight, amlodipine 0.125mg/Kg body weight), embodiment 1 test sample middle dose group (Dendrobium candidum crude drug amount 0.6g /Kg body weight, amlodipine 0.1875mg/Kg body weight), embodiment 1 test sample large dose group (Dendrobium officinale crude drug amount 0.8g/Kg body weight, amlodipine 0.25mg/Kg body weight), Dendrobium officinale powder sample group iron skin Dendrobium crude drug amount 0.8g/Kg body weight, amlodipine group (half amount) amlodipine besylate sheet 0.25mg/Kg body weight, all intragastric administration, hypertension model control group intragastric equivalent normal saline, normal control group The same volume of normal saline was given by intragastric administration. Eight rats in each group were treated for 3 weeks.

血压测量:将大鼠38℃预热5-10min,以避免大鼠尾部血流量较少测量不出血压。在大鼠清醒安静状态下连续测量3次,3次的均值作为该鼠血压值。每周测量2次血压,于给药后2小时测量1次,给药后24小时测量1次,以观察给药后的即时降压疗效和24小时降压疗效(以及降压谷峰比值)。Blood pressure measurement: Preheat the rats at 38°C for 5-10 minutes, so as to prevent blood pressure from being measured due to low blood flow in the tail of the rats. The blood pressure of the rat was measured continuously for 3 times in an awake and quiet state, and the average value of the 3 times was taken as the blood pressure value of the rat. Measure blood pressure twice a week, once 2 hours after administration, and once 24 hours after administration, to observe the immediate antihypertensive effect and 24-hour antihypertensive effect (as well as the peak-to-peak ratio of antihypertensive) after administration .

降压幅度谷峰比计算:治疗前血压-给药后24小时血压的差值为血压降压幅度的谷值,即下次给药前的降压幅度最低点;治疗前血压-给药后2小时血压的差值为血压降压幅度的峰值,即给药后的降压幅度最大点;降压幅度的谷值/降压幅度的峰值=降压幅度谷峰比。降压幅度谷峰比越接近1,降压作用越平稳,越符合长效降压药物的要求;降压幅度谷峰比越接近0,降压作用越短效。Calculation of valley-to-peak ratio of blood pressure reduction: the difference between blood pressure before treatment - blood pressure 24 hours after administration is the valley value of blood pressure reduction, that is, the lowest point of blood pressure reduction before the next administration; blood pressure before treatment - after administration The difference in blood pressure at 2 hours is the peak value of the blood pressure reduction range, that is, the point at which the blood pressure reduction range is maximum after administration; the valley value of the blood pressure reduction range/the peak value of the blood pressure reduction range = the ratio of the valley-peak reduction range of the blood pressure reduction range. The closer the peak-to-valley ratio of the antihypertensive amplitude is to 1, the more stable the antihypertensive effect is, and the more it meets the requirements of long-acting antihypertensive drugs; the closer the peak-to-valley ratio of the antihypertensive amplitude is to 0, the shorter the antihypertensive effect.

【实验结果】【Experimental Results】

血压数据见实验3的表1、实验3的表2、实验3的表3、实验3的表4、实验3的表5。blood pressure data See Table 1 of Experiment 3, Table 2 of Experiment 3, Table 3 of Experiment 3, Table 4 of Experiment 3, and Table 5 of Experiment 3.

实验3:表1.实施例1样品对SHR大鼠给药2小时收缩压的影响(单位:mmHg;n=8)Experiment 3: the impact of table 1. embodiment 1 sample on SHR rat administration 2 hours systolic blood pressure ( Unit: mmHg; n=8)

注:与模型组比较△P<0.05▲P<0.01;氨氯地平组与各组比较○P<0.05●P<0.01;铁皮石斛研粉组与各组比较☆P<0.05★P<0.01Note: Compared with the model group, △P<0.05▲P<0.01; compared with the amlodipine group and each group ○P<0.05·P<0.01; compared with the Dendrobium officinale powder group and each group☆P<0.05★P<0.01

实验3:表2.实施例1样品对SHR大鼠给药24小时收缩压的影响(单位:mmHg;n=8)Experiment 3: the impact of table 2. embodiment 1 sample on SHR rat administration 24 hours systolic blood pressure ( Unit: mmHg; n=8)

注:与模型组比较△P<0.05▲P<0.01;氨氯地平组与各组比较○P<0.05●P<0.01;铁皮石斛研粉组与各组比较☆P<0.05★P<0.01Note: Compared with the model group, △P<0.05▲P<0.01; compared with the amlodipine group and each group ○P<0.05·P<0.01; compared with the Dendrobium officinale powder group and each group☆P<0.05★P<0.01

实验3:表3.实施例1样品对SHR大鼠给药2小时舒张压的影响(单位:mmHg;n=8)Experiment 3: the impact of table 3. embodiment 1 sample on the diastolic blood pressure of SHR rat administration 2 hours ( Unit: mmHg; n=8)

注:与模型组比较△P<0.05▲P<0.01;氨氯地平组与各组比较○P<0.05●P<0.01;铁皮石斛研粉组与各组比较☆P<0.05★P<0.01Note: Compared with the model group, △P<0.05▲P<0.01; compared with the amlodipine group and each group ○P<0.05·P<0.01; compared with the Dendrobium officinale powder group and each group☆P<0.05★P<0.01

实验3:表4.实施例1样品对SHR大鼠给药24小时舒张压的影响(单位:mmHg;n=8)Experiment 3: the influence of table 4. embodiment 1 sample on the diastolic blood pressure of SHR rat administration 24 hours ( Unit: mmHg; n=8)

注:与模型组比较△P<0.05▲P<0.01;氨氯地平组与各组比较○P<0.05●P<0.01;铁皮石斛研粉组与各组比较☆P<0.05★P<0.01Note: Compared with the model group, △P<0.05▲P<0.01; compared with the amlodipine group and each group ○P<0.05·P<0.01; compared with the Dendrobium officinale powder group and each group☆P<0.05★P<0.01

实验3:表5.实施例1样品对SHR大鼠给药后24小时/给药后2小时的收缩压降压幅度谷峰比的影响(治疗前-给药后24小时的血压降幅谷值/治疗前-给药后2小时的血压降幅峰值=降压谷峰比;血压单位:mmHg;n=8)Experiment 3: Table 5. Embodiment 1 sample is on the influence of the peak-to-peak ratio of systolic blood pressure drop range 24 hours after administration to SHR rats after administration (before treatment-24 hours after administration, the blood pressure drop valley value /Before treatment-the peak value of blood pressure drop 2 hours after administration=the peak-to-peak ratio of blood pressure reduction; blood pressure unit: mmHg; n=8)

1、给药后2小时血压:1. Blood pressure 2 hours after administration:

治疗3周时给药后2小时血压,实施例1大剂量组血压172.1±4.66/140.1±4.12mmHg,实施例1中剂量组血压182.7±5.34/148.6±3.48mmHg,实施例1小剂量组血压188.4±5.39/151.1±4.15mmHg,均显著低于模型组212.1±6.45/162.1±4.06mmHg(P<0.01或P<0.05)。Blood pressure at 2 hours after administration during treatment for 3 weeks, blood pressure of embodiment 1 large dose group 172.1 ± 4.66/140.1 ± 4.12mmHg, embodiment 1 middle dose group blood pressure 182.7 ± 5.34/148.6 ± 3.48mmHg, embodiment 1 small dose group blood pressure 188.4±5.39/151.1±4.15mmHg, which were significantly lower than the model group 212.1±6.45/162.1±4.06mmHg (P<0.01 or P<0.05).

实施例1大剂量组所用药物量与西药氨氯地平组、铁皮石斛研粉组相同,为氨氯地平组与铁皮石斛研粉组的药物相加,但氨氯地平组所用药量0.25mg/Kg体重为常用小剂量0.5mg/Kg的一半。实施例1大剂量组血压显著低于氨氯地平组188.2±4.04/151.3±3.37mHg(P<0.01),也低于铁皮石斛研粉组185.5±4.38/145.8±4.89mHg,收缩压有统计学显著意义(P<0.01)。结果说明,氨氯地平在减少用量后,与铁皮石斛研粉同用能够协同增加给药2小时的降压疗效。The amount of medicine used in the high-dose group of embodiment 1 is the same as that of the western medicine amlodipine group and the Dendrobium officinale powder group, which is the addition of the medicines of the amlodipine group and the Dendrobium officinale powder group, but the dosage of the amlodipine group is 0.25 mg/ Kg body weight is half of the commonly used small dose of 0.5mg/Kg. Embodiment 1 The blood pressure of the high-dose group was significantly lower than the amlodipine group 188.2 ± 4.04/151.3 ± 3.37mHg (P < 0.01), and also lower than the Dendrobium candidum powder group 185.5 ± 4.38/145.8 ± 4.89mHg, and the systolic blood pressure was statistically significant Significant significance (P<0.01). The results showed that after reducing the dosage, the combination of amlodipine and Dendrobium officinale powder can synergistically increase the antihypertensive effect of administration for 2 hours.

2、给药后24小时血压:2. Blood pressure 24 hours after administration:

治疗3周时给药后24小时血压,实施例1大剂量组血压187.3±4.24/145.3±5.13mmHg,实施例1中剂量组血压189.5±4.15/150.8±4.39mmHg,实施例1小剂量组血压195.8±4.17/154.1±3.68mmHg,均显著低于模型组209.4±4.65/163.4±5.66mmHg(P<0.01或P<0.05)。Blood pressure at 24 hours after administration during treatment for 3 weeks, blood pressure in embodiment 1 large dose group 187.3 ± 4.24/145.3 ± 5.13mmHg, blood pressure in embodiment 1 middle dose group 189.5 ± 4.15/150.8 ± 4.39mmHg, embodiment 1 small dose group blood pressure 195.8±4.17/154.1±3.68mmHg, which were significantly lower than the model group 209.4±4.65/163.4±5.66mmHg (P<0.01 or P<0.05).

实施例1大剂量组血压显著低于氨氯地平组202.7±6.37/157.3±5.63mHg(P<0.01/P<0.05),也低于铁皮石斛研粉组190.8±4.37/151.3±4.39mHg,但无统计学显著意义(P>0.05)。结果说明,氨氯地平在减少用量后,与铁皮石斛研粉同用能够协同增加给药24小时的降压疗效。Embodiment 1 The blood pressure of the large dose group was significantly lower than that of the amlodipine group 202.7 ± 6.37/157.3 ± 5.63mHg (P < 0.01/P < 0.05), and also lower than that of the Dendrobium officinale powder group 190.8 ± 4.37/151.3 ± 4.39mHg, but No statistical significance (P>0.05). The results showed that after reducing the dosage, the combination of amlodipine and Dendrobium officinale powder can synergistically increase the antihypertensive effect of administration for 24 hours.

3、治疗3周时给药24小时降压幅度/给药2小时降压幅度=降压幅度谷峰比:3. After 3 weeks of treatment, the 24-hour blood pressure reduction range/2-hour blood pressure reduction range = blood pressure reduction range valley-peak ratio:

实施例1大剂量组给药24小时降压幅度17.0mmHg/给药2小时降压幅度32.2mmHg=降压幅度谷峰比0.53;Example 1 High-dose group administration 24 hours blood pressure reduction range 17.0mmHg/administration 2 hours blood pressure reduction range 32.2mmHg = blood pressure reduction range trough-peak ratio 0.53;

西药氨氯地平组给药24小时降压幅度0.8mmHg/给药2小时降压幅度15.3mmHg=降压幅度谷峰比0.05;Western medicine amlodipine group administration 24 hours blood pressure reduction range 0.8mmHg/administration 2 hours blood pressure reduction range 15.3mmHg = blood pressure reduction range trough-peak ratio 0.05;

铁皮石斛研粉组给药24小时降压幅度13.5mmHg/给药2小时降压幅度18.8mmHg=降压幅度谷峰比0.72;Dendrobium candidum powder group administered 24-hour blood pressure reduction range 13.5mmHg/administration 2-hour blood pressure reduction range 18.8mmHg = blood pressure reduction range valley-peak ratio 0.72;

治疗3周时,实施例1样品给药24小时降压幅度超过西药氨氯地平(半量)组;给药2小时降压幅度超过铁皮石斛研粉组。通过铁皮石斛研粉与西药氨氯地平(半量)合用,相对于皮石斛研粉比较增加了给药2小时降压幅度,相对于西药氨氯地平(半量)比较增加了给药24小时降压幅度。通过该合用方法可以减少西药氨氯地平用量。During 3 weeks of treatment, the range of lowering blood pressure of the sample of Example 1 for 24 hours exceeded that of the western medicine amlodipine (half dose) group; Through the combination of Dendrobium candidum powder and western medicine amlodipine (half dose), compared with the dendrobium powder, the 2-hour blood pressure reduction range was increased, and compared with the western medicine amlodipine (half dose), the 24-hour blood pressure reduction was increased. magnitude. Can reduce the dosage of western medicine amlodipine by this combination method.

本实验所用大鼠剂量对应相当的成人剂量:The rat doses used in this experiment correspond to equivalent adult doses:

实施例1大剂量组给药对应相当的成人剂量约为铁皮石斛生药量8g/日、氨氯地平2.5mg/日;Example 1 The corresponding adult dosage of the large dose group administration is about 8 g/day of the crude drug amount of Dendrobium candidum, and 2.5 mg/day of amlodipine;

实施例1中剂量组给药对应相当的成人剂量约为铁皮石斛生药量6g/日、氨氯地平1.875mg/日;The dose group administration in Example 1 corresponds to a corresponding adult dose of about 6 g/day of the crude drug amount of Dendrobium officinale, and 1.875 mg/day of amlodipine;

实施例1小剂量组给药对应相当的成人剂量约为铁皮石斛生药量4g/日、氨氯地平1.25mg/日;Embodiment 1 Small dose group administration corresponds to a corresponding adult dose of about 4 g/day of crude drug dose of Dendrobium officinale, and 1.25 mg/day of amlodipine;

铁皮石斛研粉组对应相当的成人剂量约为铁皮石斛生药量8g/日;The corresponding adult dose of Dendrobium candidum powder group is about 8g/day of crude drug dose of Dendrobium candidum;

西药氨氯地平组给药对应相当的成人剂量约为苯磺酸氨氯地平片2.5mg/日。Western medicine amlodipine group administration corresponds to an equivalent adult dosage of about 2.5 mg/day of amlodipine besylate tablet.

【结论】【in conclusion】

实施例1样品大剂量、中剂量组、小剂量组给药后2小时和给药后24小时,均有显著的降压疗效。2 hours and 24 hours after the administration of the samples in the high-dose, medium-dose and low-dose groups of Example 1, all had significant antihypertensive effects.

实施例1样品给药24小时降压幅度超过西药氨氯地平(半量)组;给药2小时降压幅度超过铁皮石斛研粉组。通过铁皮石斛研粉与西药氨氯地平(半量)合用,相对于皮石斛研粉比较增加了给药2小时降压幅度,相对于西药氨氯地平(半量)比较增加了给药24小时降压幅度。通过该合用方法可以减少西药氨氯地平用量。Example 1 sample administration 24 hours lower blood pressure range than the western medicine amlodipine (half dose) group; administration 2 hours lower blood pressure range than Dendrobium candidum powder group. Through the combination of Dendrobium candidum powder and western medicine amlodipine (half dose), compared with the dendrobium powder, the 2-hour blood pressure reduction range was increased, and compared with the western medicine amlodipine (half dose), the 24-hour blood pressure reduction was increased. magnitude. Can reduce the dosage of western medicine amlodipine by this combination method.

Claims (2)

1.铁皮石斛和氨氯地平在制备治疗高血压药物中的应用方法,其特征在于,包括:按重量份数取铁皮石斛8000份和氨氯地平2.5份,铁皮石斛符合2015版《中国药典》中的要求;将铁皮石斛研磨至粉末状后,加入氨氯地平粉末,混匀;然后按照药学常规加工方法添加辅料,制成片剂、颗粒或混悬颗粒、丸剂、散剂或胶囊,得到用于治疗高血压的药物。1. The application method of Dendrobium officinale and amlodipine in the preparation of medicines for treating hypertension, characterized in that, comprising: taking 8000 parts of Dendrobium officinale and 2.5 parts of amlodipine in parts by weight, and Dendrobium officinale meets the 2015 edition of "Chinese Pharmacopoeia" The requirements in: Dendrobium candidum is ground to powder, add amlodipine powder, and mix; then add excipients according to pharmaceutical routine processing method, make tablet, granule or suspension granule, pill, powder or capsule, obtain Drugs for the treatment of hypertension. 2.权利要求1所述方法中制备获得的治疗高血压药物的使用方法,其特征在于,是将制备获得的片剂、颗粒或混悬颗粒、丸剂、散剂或胶囊以口服方式用药,成人每日用量相当于铁皮石斛生药量4g至8g,内含氨氯地平1.25mg至2.5mg。2. The use method of the medicine for treating hypertension prepared in the method described in claim 1, characterized in that, the prepared tablet, granule or suspension granule, pill, powder or capsule is administered orally, and an adult can use it orally. The daily dosage is equivalent to 4g to 8g of the crude drug of Dendrobium officinale, and contains 1.25mg to 2.5mg of amlodipine.
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