CN102764305B - One returns spleen composition of medicine, preparation method and application thereof - Google Patents
One returns spleen composition of medicine, preparation method and application thereof Download PDFInfo
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Abstract
The present invention, on the basis of traditional classical proved recipe, replaces Radix Codonopsis or Radix Ginseng to obtain one with Radix Pseudostellariae and returns spleen composition of medicine, comprise crude drug or the extract of following medical material: Radix Pseudostellariae, the Radix Astragali and Radix Polygalae; Provided by the inventionly return spleen composition of medicine, for sinus bradycardia, tachycardia and arrhythmia in GI nerves functional disease and arrhythmia disease, there is activity, meanwhile, the extract that the preparation method that the present invention adopts obtains, comparatively light water extracting method, more conveniently makes various dosage form.
Description
Technical field
The invention provides a kind of Chinese medicine formula, the present invention relates to one in particular and return spleen composition of medicine, preparation method and application thereof.
Technical background
GUIPI WAN side derive from the Song dynasty sternly with and show " GUIPI TANG " in recipes for Saving Lives, former side by Radix Ginseng, the Rhizoma Atractylodis Macrocephalae, the Radix Astragali, Radix Glycyrrhizae, Poria, Radix Polygalae, Semen Ziziphi Spinosae, Arillus Longan, Radix Angelicae Sinensis, the Radix Aucklandiae, Fructus Jujubae, Rhizoma Zingiberis Recens totally 12 taste medicines form, modern age develops into GUIPI WAN side and Renshen Guipi Wan side gradually, replace Radix Ginseng with Radix Codonopsis in the former side, the latter still continues to use Radix Ginseng.
GUIPI WAN Radix Codonopsis, for Radix Ginseng, has replenishing QI to invigorate the spleen, effect of nourishing blood to tranquillize the mind.For deficiency of both the heart and spleen, cardiopalmus of breathing hard, insomnia and dreamful sleep, dizzy dizzy, lassitude of the limbs and weakness, inappetence, metrorrhagia is had blood in stool.Radix Ginseng is more a lot of by force than the effect of Radix Codonopsis QI invigorating, and Radix Ginseng is warm in nature in addition, and cause dry mouth and throat with how getting angry, Radix Codonopsis is put down, and can not get angry, and crosses void just can use GUIPI WAN if not QI and blood.
The effect of GUIPI TANG is invigorating the spleen and benefiting QI, nourishes heart and enriches blood.The sweet temperature of the Radix Astragali in side, enters spleen lung two warp, nourishes blood with the heart, enriching spleen-QI, is monarch drug altogether.The all sweet temperature of Radix Ginseng, the Rhizoma Atractylodis Macrocephalae, helps Radix Astragali invigorating the spleen and benefiting QI; Radix Angelicae Sinensis is sweet pungent warm in nature, and compatibility Arillus Longan nourishes heart and enriches blood, and is combined into ministerial drug.Poria cum Radix Pini, Radix Polygalae, Semen Ziziphi Spinosae (parched) three medicine compatibility Arillus Longan, sweet temperature is bitter, the strengthening the spleen that nourishes heart, with fixed attention sedate (painstaking effort can nourish temper plentifully, therefore the mother that the traditional Chinese medical science is intentionally spleen says); Radix Aucklandiae circulation of qi promoting reason spleen helps transporting, in case the taste of all tonics is greasy hinder spleen, is all adjuvant drug.The sweet temperature of Radix Glycyrrhizae Preparata, can QI invigorating invigorating middle warmer, and reactivation is in harmonious proportion the property of medicine, partially with the side's of alleviation property of traditional Chinese.With Rhizoma Zingiberis Recens, Fructus Jujubae the spleen and stomach regulating in usage, as a means of change source.The all pathological changes caused for heart spleen blood deficiency have fine therapeutical effect, be mainly used to heart spleen QI and blood deficiency and the insufficiency of vital energy and blood drawn, cardiopalmus, forgetful insomnia, tired, shallow complexion, the diseases such as night sweat deficiency-heat.Modern clinical research shows, Renshen Guipi Wan can resisting fatigue, shock, calmness, antiinflammatory, analgesia, the effects such as blood pressure lowering, are usually used in the treatment of the diseases such as iron deficiency anemia, thrombocytopenic purpura, arrhythmia, bradycardia, climacteric syndrome, headache, hypertension.Renshen Guipi Wan is used for insufficiency of vital energy and blood, cardiopalmus, and insomnia, lack of appetite is weak, shallow complexion, Hypomenorrhea, and color is light.
The preparation technology that Chinese patent application (CN03124679.6) returns spleen new and preparation thereof, modern pharmaceutical technology carries out Technology reform to existing spleen preparation of returning, the utilization of new adjuvant, new technique, new equipment, overcome that former preparation dose is large, effective ingredient easily loses in preparation process deficiency, adopt the spleen preparation of returning made of the present invention fully can retain effective ingredient, have good effect, dose little, take the advantages such as easy to carry.Chinese patent (ZL200710143907.3) one returns spleen granule, oral liquid and concentrated pill and their preparation method and quality control side the present invention relates to one and return spleen granule, oral liquid and concentrated pill and their preparation method and method of quality control, in particular to one, there is replenishing QI to invigorate the spleen, nourishing blood to tranquillize the mind, for deficiency of both the heart and spleen, to breathe hard cardiopalmus, insomnia and dreamful sleep, dizzy dizzy, lassitude of the limbs and weakness, the Chinese medicine preparation of inappetence, said preparation is by Radix Codonopsis, the Rhizoma Atractylodis Macrocephalae, the Radix Astragali, Radix Glycyrrhizae, Poria, Radix Polygalae, Semen Ziziphi Spinosae, Arillus Longan, Radix Angelicae Sinensis, the Radix Aucklandiae, the raw material of Chinese medicine such as Fructus Jujubae are made.
Summary of the invention
Traditional medicine proves, sweet, the micro-hardship of Radix Pseudostellariae, flat.Return spleen, lung meridian, body lubricant nature and; Tonifying QI to produce body fluid, cures mainly the diseases such as insufficiency of the spleen lack of appetite, fatigue and weakness, cardiopalmus spontaneous perspiration, cough due to deficiency of the lung, thirst due to body fluid deficiency.All weakness of the spleen and stomach, disease sees lassitude and weak, loss of appetite person, can with the compatibilities such as the Radix Astragali, to strengthen the merit of QI invigorating and supplementing QI for promoting the production of body fluid; Share with Semen Ziziphi Spinosae etc., calm the nerves with supplementing QI and nourishing YIN; Join the Rhizoma Atractylodis Macrocephalae, play the merit of spleen reinforcing lung altogether.Research finds, Radix Pseudostellariae has the effect of anti-stress, resisting fatigue.The water extract of Radix Pseudostellariae, 75% ethanol extract, the active substance such as Pseudostellaria Polysaccharide and Radix Pseudostellariae saponin, all obviously can extend the mice burden swimming time, and obviously can extend the time-to-live of mice.In Radix Pseudostellariae, contained ethanol extract, has protective effect for people's gastrointestinal function, and especially after injection reserpine, this may be because water extract obviously can suppress speed and the distance of human body enterokinesia and propelling.The active substance such as polysaccharide contained in Radix Pseudostellariae and total saponins, have certain ability for the opposing improving human body and the effect of resisting low temperature.Radix Pseudostellariae significantly can improve the chronic heart failure caused by myocardial infarction, and mechanism of action may to improve the oxidative stress status of muscular tissue relevant with Radix Pseudostellariae.In body, enzymatic reaction antioxidative enzyme system SOD, CAT, GSH-Px can make active oxygen change hydrogen peroxide into, finally change water and oxygen molecule into, thus play the effect of scavenging free radicals.
The present invention, on the basis of traditional classical proved recipe, replaces Radix Codonopsis or Radix Ginseng to obtain one with Radix Pseudostellariae and returns spleen composition of medicine, comprise crude drug or the extract of following medical material: Radix Pseudostellariae, the Radix Astragali and Radix Polygalae.
Described spleen composition of medicine of returning is made up of the crude drug of following medical material or extract: Radix Pseudostellariae, the Radix Astragali, Radix Polygalae, Radix Glycyrrhizae, Radix Angelicae Sinensis, Poria, Arillus Longan, the Radix Aucklandiae, the Rhizoma Atractylodis Macrocephalae, Radix Rehmanniae Preparata, Semen Ziziphi Spinosae and Fructus Jujubae.
The weight ratio of described Radix Pseudostellariae, the Radix Astragali, Radix Polygalae, Radix Glycyrrhizae, Radix Angelicae Sinensis, Poria, Arillus Longan, the Radix Aucklandiae, the Rhizoma Atractylodis Macrocephalae, Radix Rehmanniae Preparata, Semen Ziziphi Spinosae, Fructus Jujubae composition is 2 ~ 6:2 ~ 6:4 ~ 16:1 ~ 4:4 ~ 16:4 ~ 16:4 ~ 16:1 ~ 4:4 ~ 16:4 ~ 16:4 ~ 16:4 ~ 16.
The weight ratio of described Radix Pseudostellariae, the Radix Astragali, Radix Polygalae, Radix Glycyrrhizae, Radix Angelicae Sinensis, Poria, Arillus Longan, the Radix Aucklandiae, the Rhizoma Atractylodis Macrocephalae, Radix Rehmanniae Preparata, Semen Ziziphi Spinosae, Fructus Jujubae composition is 2:2:4:1:4:4:4:1:4:4:4:4.
Described spleen composition of medicine of returning by the 20-95% ethanol extraction of Radix Pseudostellariae, the Radix Astragali, Radix Glycyrrhizae, Poria and Radix Polygalae, the water extract of Arillus Longan, Semen Ziziphi Spinosae, Radix Rehmanniae Preparata, Radix Angelicae Sinensis and Fructus Jujubae, the volatile oil mixing composition of the Rhizoma Atractylodis Macrocephalae and the Radix Aucklandiae.
Described method is extracted Radix Pseudostellariae, Radix Glycyrrhizae, the Radix Astragali, Poria and Radix Polygalae for adopting the methods such as backflow, warm macerating, percolation to extract respectively using 20-95% ethanol as solvent;
Be that solvent adopts warm macerating, backflow, decocting method to extract Arillus Longan, Semen Ziziphi Spinosae, Radix Rehmanniae Preparata, Radix Angelicae Sinensis and Fructus Jujubae with water;
Adopting has steam distillation, solvent reflux extraction, microwave method, the supercritical fluid extraction volatile oil to the Rhizoma Atractylodis Macrocephalae and the Radix Aucklandiae to extract;
Merge said extracted thing to obtain returning spleen composition of medicine.
Above-mentioned returns the application of spleen composition of medicine in preparation treatment arrhythmia disorder agent.
Above-mentioned returns the application of spleen composition of medicine in preparation treatment GI nerves functional disease medicine.
Advantageous Effects of the present invention is: provided by the inventionly return spleen composition of medicine, for sinus bradycardia, tachycardia and arrhythmia in GI nerves functional disease and arrhythmia disease, there is activity, simultaneously, the extract that the preparation method that the present invention adopts obtains, comparatively light water extracting method, more conveniently makes various dosage form.
Detailed description of the invention
Embodiment 1 returns the preparation 1 of spleen composition of medicine
Take Radix Pseudostellariae 100g, Radix Astragali 100g, Radix Polygalae 200g, Radix Glycyrrhizae 50g, Radix Angelicae Sinensis 200g, Poria 200g, Arillus Longan 200g, Radix Aucklandiae 50g, Rhizoma Atractylodis Macrocephalae 200g, Radix Rehmanniae Preparata 200g, Semen Ziziphi Spinosae 200g, Fructus Jujubae 200g.
Adopt the methods such as 30-60 DEG C of condition backflow, warm macerating, percolation to extract with 20-95% ethanol respectively as solvent to extract Radix Pseudostellariae, Radix Glycyrrhizae, the Radix Astragali, Poria and Radix Polygalae; Solvent gross weight is 3-15 times of crude drug weight.
Be that solvent adopts 45-75 DEG C of condition warm macerating, backflow, decocting method to extract Arillus Longan, Semen Ziziphi Spinosae, Radix Rehmanniae Preparata, Radix Angelicae Sinensis and Fructus Jujubae with water; Extract 3 times, solvent gross weight is 3-15 times of crude drug weight, and extraction time is greater than 15min.
Adopting has steam distillation, solvent reflux extraction, microwave method, the supercritical fluid extraction volatile oil to the Rhizoma Atractylodis Macrocephalae and the Radix Aucklandiae to extract; Merge said extracted thing to obtain returning spleen composition of medicine I.
Take Radix Pseudostellariae 50g, Radix Astragali 50g, Radix Polygalae 100g, Radix Glycyrrhizae 25g, Radix Angelicae Sinensis 100g, Poria 100g, Arillus Longan 100g, Radix Aucklandiae 25g, Rhizoma Atractylodis Macrocephalae 100g, Radix Rehmanniae Preparata 100g, Semen Ziziphi Spinosae 100g, Fructus Jujubae 100g.Prepare according to said method and return spleen composition of medicine II.
Take Radix Pseudostellariae 150g, Radix Astragali 150g, Radix Polygalae 400g, Radix Glycyrrhizae 100g, Radix Angelicae Sinensis 400g, Poria 400g, Arillus Longan 400g, Radix Aucklandiae 100g, Rhizoma Atractylodis Macrocephalae 400g, Radix Rehmanniae Preparata 400g, Semen Ziziphi Spinosae 400g, Fructus Jujubae 400g.Prepare according to said method and return spleen composition of medicine III.
Embodiment 2 returns the preparation 2 of spleen composition of medicine
Take Radix Pseudostellariae 100g, Radix Astragali 100g, Radix Polygalae 200g, Radix Glycyrrhizae 50g, Radix Angelicae Sinensis 200g, Poria 200g, Arillus Longan 200g, Radix Aucklandiae 50g, Rhizoma Atractylodis Macrocephalae 200g, Radix Rehmanniae Preparata 200g, Semen Ziziphi Spinosae 200g, Fructus Jujubae 200g.Mix above-mentioned medical material, with medical material weight 3-5 soak by water doubly 3 times, each 30-60min, merges and reclaims the water extraction that extract obtains being used for the treatment of arrhythmia and GI nerves functional disease and return spleen composition of medicine 1.
Take Radix Pseudostellariae 50g, Radix Astragali 50g, Radix Polygalae 100g, Radix Glycyrrhizae 25g, Radix Angelicae Sinensis 100g, Poria 100g, Arillus Longan 100g, Radix Aucklandiae 25g, Rhizoma Atractylodis Macrocephalae 100g, Radix Rehmanniae Preparata 100g, Semen Ziziphi Spinosae 100g, Fructus Jujubae 100g.Prepare to merge according to said method and reclaim the water extraction that extract obtains being used for the treatment of arrhythmia and GI nerves functional disease and return spleen composition of medicine 2.
Take Radix Pseudostellariae 150g, Radix Astragali 150g, Radix Polygalae 400g, Radix Glycyrrhizae 100g, Radix Angelicae Sinensis 400g, Poria 400g, Arillus Longan 400g, Radix Aucklandiae 100g, Rhizoma Atractylodis Macrocephalae 400g, Radix Rehmanniae Preparata 400g, Semen Ziziphi Spinosae 400g, Fructus Jujubae 400g.The water extraction that merging recovery extract obtains being used for the treatment of arrhythmia and GI nerves functional disease returns spleen composition of medicine 3.
Embodiment 3 returns the activity of spleen composition of medicine I pair of bradycardia rat to investigate
Select healthy adult Wistar rat, body weight 250g-300g, before experiment, animal via test confirms behavior without exception.Rat is fed after 7d at adaptability, every day buttocks subcutaneous injection hydrocortisone, every day, 25mg/kg, injected 14d continuously.And when experiment the 2nd week, force rat every day at the upper and lower noon respectively to swim 1 time, to unable be about to time pull out, to induce overstrain, continue 1 week.Observe rat gross morphology, all appearance activities reduce, lassitude, bradykinesia, and the back of a bow is rolled up, amount of drinking water reduces, to lose weight etc. kidney yang deficiency of vital energy symptom for modeling successfully.Select the successful rat 6O of modeling only, be divided at random return spleen composition of medicine I group, water extraction returns spleen composition of medicine 1 group, commercially available GUIPI WAN group and commercially available Renshen Guipi Wan amount group, righting helps arteries and veins mixture matched group, model control group, often organize each 12, choosing 12 healthy rats is again blank group, often organizes male and female half and half, sub-cage rearing.After modeling success, next day starts pharmaceutical intervention.Blank group and model group routine feeding, by rat body weight with 20ml/kg dosage with distilled water gavage.Righting helps the drug level of arteries and veins side's decoct group to be respectively 20ml/kg, often organize all when 1O in the morning every day gastric infusion once, treat 14d continuously.
The general state of each treated animal in modeling, medication is observed; Detecting ECG; The changes of contents of cAMP in plasma and cGMP.Experimental data adopts the process of SPSS14.0 statistical software, and all data all adopt mean ± standard deviation
represent.
Naive animals shows as: hair is smooth, the eyes are bright and piercing, reacts, activity is active and intelligent, calls loud, drinking-water of normally taking food.Lethargy is in various degree there is in model group and each treatment group rat when experiment 1ld ~ 14d, to ingest minimizing, growth retardation loses weight, hair is uninteresting lax, cold extremities, and health is very thin, happiness is rolled up and is flocked together, shallow breathing, the kidney yang deficiency of vital energy symptoms such as diarrhea, particularly model control group is more remarkable.
Administration the 14th day, after administration, 1h is with ether light anaesthesia rat at its lower extremity subcutaneous implantation electrode, records clear-headed rear standard II lead electrocardiogram of rat.Within 15th day, give each group of rat skin lower injection with clonidine hydrochloride 2mg/kg, and simultaneously gastric infusion, 0.5h, lh, 1.5h, 2h electrocardiosignal after record gavage, statistical analysis rat heart rate, the rhythm of the heart, atrioventricular block situation of change.
Spleen composition of medicine I group and water extraction is returned to return spleen composition of medicine 1 group as shown in table 1 on the impact of bradycardia rat heart rate, result shows, returns spleen composition of medicine I group, water extraction returns spleen composition of medicine 1 group, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan amount group and righting help arteries and veins decoct group can improve bradyarrhythmia rat heart rate.
The table 1 respectively group rat rhythm of the heart compares
Note: compare with model group:
△p ﹤ 0.05,
▲p ﹤ 0.01; Compare with blank group:
◇p ﹤ 0.05,
◆p ﹤ 0.01;
After experiment terminates, broken end is got blood, is taken out heart immediately, prepares myocardial homogenates, detects cAMP and cGMP content in myocardial homogenates by test kit regulation.
As shown in table 2, compare for each group, return spleen composition of medicine I group, water extraction returns spleen composition of medicine 1 group, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan group and righting help arteries and veins decoct group cAMP content to be improved, cGMP level has decline, especially to return spleen composition of medicine I group remarkable.
The comparison of the concentration of rat plasma cAMP and cCMP respectively organized by table 2
Note: compare with model group:
△p ﹤ 0.05,
▲p ﹤ 0.01; Compare with blank group:
◇p ﹤ 0.05,
◆p ﹤ 0.01;
Bradyarrhythmia is common clinical disease, show as shortness of breath and palpitation in various degree, sensation of oppression and faint pain in the chest, dizzy weakly, dynamic then to increase the weight of, repeatedly fainting history appears in severe patient, burst tic, pareordia severe pain, can Complicated by Heart Failure, cardiogenic shock, cardiac sudden death etc.
CAMP and cardiac function positive correlation, when p1 receptor agonism on heart, produce a large amount of cAMP in cell, heart rate speeds thereupon, and atrioventricular conduction time shortens, and myocardial contraction increases.CAMP promotes steatolysis, glycogenolysis, myocardial contraction, and cGMP is on the contrary.CAMP and cGMP is a pair not only mutually antagonism but also the bioactive substance of mutual dependence for existence---second message,second messenger in body.They are prevalent in biological cell and with in body fluid, regulate body cell intracellular metabolic and various physiological activity.Think that they play important regulating action to the function of myocardial cell, vascular smooth muscle cell at present, its plasma concentration ANOMALOUS VARIATIONS has important function in cardiovascular disease generating process.Therefore the balance of cAMP and cGMP is the critical substances regulating body, and affects the intermediate hub of globality mechanism cell function.CAMP declines, and cGMP raises, and be one of specific pathologies change of generally acknowledged yang deficiency syndrome, the balance and stability of both maintenances is significant in bradycardic treatment.When m receptor is exciting, make K
+outflow increases, and suppresses adenyl cyclase, and the content of cGMP increases, and promote that platelet is built up, make Cardiac depression, its content can reflect the change of atrial pressure indirectly, can judge degree of heart failure thus.Fang Zhongyong Radix Pseudostellariae isothermal kidney yang-tonifying medicinal is treated, and the not method adopting classification to extract effective site is extracted effective ingredient in composition medicine, cAMP can be made to go up and cGMP declines, compare with model group, dosage group and righting help arteries and veins mixture group cAMP level to be improved, cGMP level all has decline, and its difference has significance.Consistent with the result about reporting, show to return that spleen composition of medicine I can promote the yang blood and qi of body internal organs, deficiency and excess good and evil tend to be balanced gradually, improve the environment of yang deficiency rat disorder, impel yang deficiency rat to normal development.The bradycardia Cardiac Function in Rat of returning spleen composition of medicine I to improve to be caused by deficiency of heart-YANG and kidney-YANG and metabolism of myocardium, be conducive to promoting the nutriture of heart sinuatrial node, improving sinus node function, is to improve cardiac function, treat bradycardic effective preparation.
Embodiment 4 returns the activity of spleen composition of medicine I pair of tachycardia rat to investigate
Get healthy rat 60, male and female are not limit, and average weight is (200 ± 10) g.Divide 6 groups.First group is model group; Second group is Xinluning tablet tablet matched group, and gavage gives the normal saline solution (210mg/lOml) of medicine Xinluning tablet tablet.3rd group for returning spleen composition of medicine I group, gavage returns the normal saline solution (raw medicinal herbs, 875mg/lOml) of spleen composition of medicine I; 4th group is that water extraction returns spleen composition of medicine 1 group, gavage gives the normal saline solution (raw medicinal herbs that water extraction returns spleen composition of medicine 1 group, 1275mg/lOml), 5th group is commercially available Renshen Guipi Wan group, gavage gives the normal saline solution (raw medicinal herbs, 1275mg/lOml) of commercially available Renshen Guipi Wan, and the 6th group is commercially available GUIPI WAN group, gavage gives the normal saline solution (raw medicinal herbs, 1275mg/lOml) of commercially available GUIPI WAN.Each group all by 2ml/ amount administration only.After administration, first by rat urethane (1.2gkg
-1) intraperitoneal anesthesia, be then fixed on operating-table.Connect electrocardioscope, record II is led, to observe electrocardio change (chart speed 50mm/s).At tail vein injection aconitine (20 μ gml
-1) before, record normal ECG.Inject aconitine after each group of administration 1h, observe electrocardio situation of change.Experimental result is in table 3.
The result of the anti-Aconitine Induced ventricular tachycardia of spleen composition of medicine I returned by table 3
Get healthy guinea pig 60.Male and female are not limit, and average weight is (200 ± 10) g.Divide 6 groups.First group is model group; Second group is Xinluning tablet tablet matched group, and gavage gives the normal saline solution (210mg/lOml) of medicine Xinluning tablet tablet, and 2ml/ only.3rd group for returning spleen composition of medicine I group, gavage returns the normal saline solution (raw medicinal herbs, 875mg/lOml) of spleen composition of medicine I; 4th group is that water extraction returns spleen composition of medicine 1 group, gavage gives the normal saline solution (raw medicinal herbs that water extraction returns spleen composition of medicine 1 group, 1275mg/lOml), 5th group is commercially available Renshen Guipi Wan group, gavage gives the normal saline solution (raw medicinal herbs, 1275mg/lOml) of commercially available Renshen Guipi Wan, and the 6th group is commercially available GUIPI WAN group, gavage gives the normal saline solution (raw medicinal herbs, 1275mg/lOml) of commercially available GUIPI WAN.3ml/ only.After administration, with urethane (1.2gkg
-1) by Cavia porcellus intraperitoneal anesthesia, face upward position and be fixed on operating-table, needle electrode is inserted extremity subcutaneous, and be connected with electrocardiograph, record II leads to observe electrocardio change (chart speed 50mms
-1).At vena femoralis injection cedilanid (0.82mlkg
-1) before, record normal electrocardio.Then vena femoralis injection cedilanid (0.82mlkg
-1), observe electrocardio situation of change, till arrhythmia is recovered normally; Inject cedilanid (0.82mlkg) after matched group administration lh, observe electrocardio situation of change.Experimental result is in table 4.
The result of the anti-Aconitine Induced ventricular tachycardia of spleen side's composition of medicine I returned by table 4
From experimental result, return spleen composition of medicine I to have stronger inhibitory action to drug-induced arrhythmia, when effective dose, electrocardio keeps normal condition not to be any change always; The accidental ventricular premature contraction of Xinluning tablet gavage group or premature ventricular beat, disappear after a time, and the rhythm of the heart recovers normal.Result also shows, returns spleen composition of medicine I to be better than other drug on the continuous action time.
Aconitine causes ARR main mechanism to be: the sodium channel that have activated myocardial cell, makes sodium channel open, accelerates myocardial cell Na
+interior stream, impels membrane depolarization, accelerates Pacemaker cardiac self-disciplining, brings out ectopic rhythm point, can form polyphyly ectopic rhythm, shorten myocardium refractory stage, and cause arrhythmia.Experimental result shows, returns spleen composition of medicine I effectively can suppress the arrhythmia caused by aconitine.
Cardiac glycoside medicine (as cedilanid) can suppress Na on myocardial cell membrane time poisoning
+-K
+-ATP enzyme, thus reduce K
+to intracellular active transport, cause lacking K in cell
+, the maximum diastolic potential of cardiac muscle is reduced, and relaxing period spontaneous depolarization speed is accelerated, and self-disciplining raises, and arrhythmia occurs.Adopt several different drug-induced dissimilar arrhythmia effectively can simulate clinical symptoms, the curative effect of reflection medicine.Result shows, returns spleen composition of medicine I effectively can prevent and treat arrhythmia.
Embodiment 5 returns the activity of spleen composition of medicine I pair of Beagle dog arrhythmia to investigate
The choice criteria of arrhythmia Beagle dog: have selected 4 beagle dogs and study, male and female half and half, about body weight 10kg, monthly age 6-12 month.Beagle dog through at least 5 times (every other day) II lead electrocardiogram (ECG) check and meet following condition person: 1. sinus P ripple, the R-R cycle is not etc., ORS is had after P crosses, periodic inequality >0.16 second, P-R interval, is fixed and >O.12 second, irrelevant with breathing; 2. there are more than 3 long R-R cycles in 10 R-R cycles, observes and without improver, be defined as arrhythmia through one week.Continuous 5 times (every other day 1 time) being had an electro-cardiogram inspection, then being got rid of as once do not met above-mentioned choice criteria person.Arrhythmia condition improved, electrocardiogram obviously improves and meets following two is effective: 1. R-R periodic inequality reduces and close to 0.16 second, P-R interval was fixed and <O.12 second; 2. arrhythmia number of times reduces: occur in 10 R-R cycles that the number of times in long R-R cycle obviously reduces.Electrocardiogram is invalid without being improved as.Experiment is established and is returned spleen composition of medicine I group (A group) (crude drug 3.75g/kg) and water extraction to return spleen composition of medicine 1 group (B group) (crude drug 3.75g/kg), every day 9am and 4pm timed drug administrations, first medicine is made into certain density suspension to add in 1/3 feedstuff and mix, dog is allowed to have eaten voluntarily, and then give all the other 2/3 feedstuffs, continuous 17d.
ECG inspection method: dog takes from right erect position, the subcutaneous insertion needle electrode of extremity, measures II lead electrocardiogram after quiet under waking state before food.
To observe after medicine 1,3,5,7,8,9, l1,13,15, the electrocardiogram of 2d after 17d and drug withdrawal: P-R interval, QRs interval, Q-T interval, P ripple, Q ripple, R ripple, s ripple, T ripple, ST section, heart rate and the rhythm of the heart, and with medicine before compare.
Table 5 returns spleen composition of medicine I on the impact of arrhythmia Beagle dog P-R interval and heart rate
Table 6 returns spleen composition of medicine I on the impact of arrhythmia Beagle dog R-R periodic inequality (s)
*decline percentage rate: R-R periodic inequality after R-R periodic inequality-medicine before medicine
From table 5, >0.12 second before P-R interval medicine, after medicine, 3d rises and is improved to 17d, and P-R asks phase equal <0.12 second, and 2d after lasting till drug withdrawal.Return spleen composition of medicine I group and water extraction to return spleen composition of medicine 1 group all can improve the heart rate of arrhythmia dog, after medicine, 9d plays efficacy stability, and maintains a period of time and level; And P wave of electrocardiogram, Q cross, R ripple, S ripple, QRS interval, Q-T interval, spleen composition of medicine I group or water extraction no matter is returned to return spleen composition of medicine 1 group all to have no significant effect.
From table 6, before administration, the R-R periodic inequality of four dogs is 0.48 ~ 0.53s, and be far longer than 0.16s, after medicine, ld rises, and the R-R periodic inequality of 2 dosage groups all starts to shorten, and reduce to 040s from 0.48 ~ 0.53s before medicine, its range of decrease is 15% ~ 25%; After medicine, 5 ~ 11d, R-R periodic inequality all obviously shortens, and reduces to 0.20 ~ 0.27 second, and the range of decrease is 44 ~ 62%; After medicine, 13 ~ 15d, R-R periodic inequality is close to normally (close to 0.16s, returning spleen composition of medicine I group 13d after medicine to be 0.16s; Water extraction returns spleen composition of medicine 1 group 15d after medicine to be 0.17s.After drug withdrawal 2d, two groups are respectively 0.20s and 0.08s, and its range of decrease is respectively 62% and 83%.
Table 7 returns spleen composition of medicine I on the impact of arrhythmia Beagle dog rhythm of the heart occurrence frequency (long R-R cycle/10 R-R cycles)
From table 7, before administration, four ARR occurrence frequencies of dog are in 10 R-R cycles, occur 4 long R-R cycles.After medicine, 3-5d rises and returns spleen composition of medicine I group and water extraction to return spleen composition of medicine 1 group all to start to reduce, and is 2-3.5; After medicine, 7-13d obviously reduces, and is 1.5-2.5; After medicine, 15-17d is kept to 1-2, and drug withdrawal 2d reduces to 1, illustrates and returns spleen composition of medicine I group and water extraction to return spleen composition of medicine 1 group can obviously reduce ARR occurrence frequency, and can maintain certain hour after drug withdrawal.
Experimental result shows, returns spleen composition of medicine I group and water extraction to return spleen composition of medicine 1 group obviously can improve the heart rate of arrhythmia dog, reduces ARR occurrence frequency, have good therapeutical effect to arrhythmia.Select arrhythmia Beagle dog as object of study, because animal is docile, the advantages such as Electrocardioscopy is convenient, its to the observed result of experimental effect closer to clinical.Bringing out in ARR experiment with Bealge dog coronary artery ligation, observe equally and return spleen composition of medicine I pair of arrhythmia to have good preventive and therapeutic effect, therefore the same with the result of the animal pathological model that medicine or operation cause with arrhythmia dog, objective equally and accurate to the role of evaluation of antiarrhythmic drug. and be easy to Estimating curative effect.
Embodiment 6 returns the activity of spleen composition of medicine I pair of rat gastrointestinal tract dysfunction to investigate
GI nerves functional disease is also called functional gastrointestinal disorder, and the clinical main manifestations of Functional Disturbance of Gastrointestinal Tract is diarrhoea, constipation, stomachache and alternating diarrhea and constipation; And with anorexia, asthenia, become thin and the symptom such as agitation.Reserpine belongs to epinephrine nerve block medicine, the catecholamine mediator of exhaustion maincenter and periphery, make sympathetic nervous system function low, parasympathetic nervous system hyperfunctioning, cause autonomic nervous system functional disorder, and then impelling functional gastrointestinal disorder, the reserpine lumbar injection of doses can make rat occur the performance of clinical Functional Disturbance of Gastrointestinal Tract.
Motilin (MTL) is a kind of important braingut petide hormone, is mainly distributed in brain and jejunum, has adjustment gastric motility, promotes the effect of gastric emptying.MTL deficiency can cause gastrointestinal smooth muscle relaxation, stomach tension force and wriggle weakness, and the gastric emptying time extends, liquid retention increases, and shrink time hungry and disappear, intestinal motility weakens, intestinal to xylose and amino acid whose malabsorption, the symptoms such as the concentrated and contractile function suppression of exocrine pancreatic function and gallbladder.Research proves, the Changing Pattern of dynamic observation functional gastrointestinal disorder rat model MTL, find to show as watery diarrhea in early stage (being less than 6d) of modeling process, its MTL content compared with normal matched group obviously increases, and transference cure of suffering from diarrhoea late period, during feces viscous, its content then obviously declines, illustrate functional gastrointestinal disorder and MTL changes of contents closely related.
Healthy male rat is divided into following 5 groups at random by designing requirement, often organizes 20: Normal group: intraperitoneal injection of saline 5ml/ (kgd), gavages distilled water 5ml/ (kgd) simultaneously; Functional gastrointestinal disorder model group: lumbar injection reserpine 0.5mg/ (kgd), gavages distilled water 5ml/ (kgd) simultaneously; Return spleen composition of medicine I group: lumbar injection reserpine 0.5mg/ (kgd), gavage containing the normal saline of returning spleen composition of medicine I (crude drug amount 2.5g simultaneously, lower same)/(kgd): water extraction returns spleen composition of medicine 1 group: lumbar injection reserpine 0.5mg/ (kgd), gavages the normal saline of returning spleen composition of medicine 1 containing water extraction simultaneously; Commercially available GUIPI WAN group: lumbar injection reserpine 0.5mg/ (kgd), gavages the normal saline containing commercially available GUIPI WAN group simultaneously; Commercially available Renshen Guipi Wan amount group: lumbar injection reserpine 0.5mg/ (kgd), gavages the normal saline containing commercially available Renshen Guipi Wan amount group, successive administration 14d simultaneously.Often organize during 6d and get half zoopery detection, get second half zoopery during 14d again and detect.Observe, record the food ration of rat, body weight and feces situation during administration every day.
Testing index and method are: fasting 18h before each group rat experiment detects, 1. motilin (MTL) content detection in blood plasma and narrow intestinal tissue: by the requirement of MTL radioimmunoassay kits, each group of rat eye socket get blood 2ml in 30 μ L aprotiniies (, 30ml10%EDTA is in pipe, 4 DEG C centrifugal, and-70 DEG C store standby survey; After de-cervical vertebra puts to death rat, get jejunal tissue homogenate immediately, 3500r/min is centrifugal, draws supernatant, and-70 DEG C store standby survey; Assay method by specification carries out.2. local intestinal tissue pathologic finding: often organize random selecting 3 rats, perusal gastrointestinal tract changes, and leaves and takes gastrointestinal tissue and does pathologic finding, to get rid of intestinal mucosa inflammatory lesion.
Experimental result adopts t inspection, uses
represent.Concrete outcome is as shown in table 8.
In table 8 rat plasma and jejunal tissue MTL dynamic amount dynamic change (
n=10)
Note: with model group ratio, * P ﹤ 0.05, * * P ﹤ 0.01;
Model group rats occurs that feces is shapeless in 24h after injection reserpine, and occurs that diarrhoea in various degree, crissum are filthy successively, occurs that appetite declines thereupon, during 6d, loose stool more so, and during 9d, loose stool stops gradually, and feces viscous is not well, even there is constipation, anorexia, become thin and day by day increase the weight of.Return the indivedual rat of spleen composition of medicine I group, water extraction returns spleen composition of medicine 1 group of minority rat, above-mentioned symptom appears in the most rat of commercially available GUIPI WAN group and commercially available Renshen Guipi Wan, and described four groups performance degree comparatively model group rats is light, rats in normal control group health as before, does not show any abnormalities.The perusal of each group of rat gastrointestinal tract mucosa is no abnormal, and pathologic finding is also there are no obvious inflammatory lesion.In sum, returning spleen composition of medicine can regulate the gut hormone of experimental functional gastrointestinal disorder rat, significantly improve its gastrointestinal dysfunction symptom, is one of the party's mechanism of action for the treatment of this disease, regulate the approach of gut hormone as the party, still need and do to inquire into further.
Embodiment 7 returns the activity of spleen composition of medicine II pair of bradycardia rat to investigate
Adopt the method described in embodiment 3 to investigate, return spleen composition of medicine II group and water extraction to return spleen composition of medicine 2 groups; The general state of each treated animal in modeling, medication is observed; Detecting ECG; The changes of contents of cAMP in plasma and cGMP.Experimental data adopts the process of SPSS14.0 statistical software, and all data all adopt mean ± standard deviation
represent.
Administration the 14th day, after administration, 1h is with ether light anaesthesia rat at its lower extremity subcutaneous implantation electrode, records clear-headed rear standard II lead electrocardiogram of rat.Within 15th day, give each group of rat skin lower injection with clonidine hydrochloride 2mg/kg, and simultaneously gastric infusion, 0.5h, lh, 1.5h, 2h electrocardiosignal after record gavage, statistical analysis rat heart rate, the rhythm of the heart, atrioventricular block situation of change.
Spleen composition of medicine II group and water extraction is returned to return spleen composition of medicine 2 groups as shown in table 9 on the impact of bradycardia rat heart rate, result shows, returns spleen composition of medicine II group, water extraction returns spleen composition of medicine 2 groups, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan amount group and righting help arteries and veins decoct group can improve bradyarrhythmia rat heart rate.
The table 9 respectively group rat rhythm of the heart compares
Note: compare with model group:
△p ﹤ 0.05,
▲p ﹤ 0.01; Compare with blank group:
◇p ﹤ 0.05,
◆p ﹤ 0.01;
After experiment terminates, broken end is got blood, is taken out heart immediately, prepares myocardial homogenates, detects cAMP and cGMP content in myocardial homogenates by test kit regulation.
As shown in table 10, compare for each group, return spleen composition of medicine II group, water extraction returns spleen composition of medicine 1 group, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan group and righting help arteries and veins decoct group cAMP content to be improved, cGMP level has decline, especially to return spleen side's composition of medicine II group remarkable.
The comparison of the concentration of rat plasma cAMP and cCMP respectively organized by table 10
Note: compare with model group:
△p ﹤ 0.05,
▲p ﹤ 0.01; Compare with blank group:
◇p ﹤ 0.05,
◆p ﹤ 0.01;
Result shows to return that spleen composition of medicine II can promote the yang blood and qi of body internal organs, deficiency and excess good and evil tend to be balanced gradually, improve the environment of yang deficiency rat disorder, impels yang deficiency rat to normal development.The bradycardia Cardiac Function in Rat of returning spleen composition of medicine II to improve to be caused by deficiency of heart-YANG and kidney-YANG and metabolism of myocardium, be conducive to promoting the nutriture of heart sinuatrial node, improving sinus node function, is to improve cardiac function, treat bradycardic effective preparation.
Embodiment 8 returns the activity of spleen composition of medicine II pair of tachycardia rat to investigate
Adopt the method described in embodiment 4 to investigate and return spleen composition of medicine II and water extraction to return spleen composition of medicine 2 groups of experimental results in shown in table 11, table 12.
The result of the anti-Aconitine Induced ventricular tachycardia of spleen composition of medicine II returned by table 11
The result of the anti-Aconitine Induced ventricular tachycardia of spleen composition of medicine II returned by table 12
From experimental result, return spleen composition of medicine II to have stronger inhibitory action to drug-induced arrhythmia, when effective dose, electrocardio keeps normal condition not to be any change always; The accidental ventricular premature contraction of Xinluning tablet gavage group or premature ventricular beat, disappear after a time, and the rhythm of the heart recovers normal.Result also shows, returns spleen composition of medicine II to be better than other drug on the continuous action time.
Aconitine causes ARR main mechanism to be: the sodium channel that have activated myocardial cell, makes sodium channel open, accelerates myocardial cell Na
+interior stream, impels membrane depolarization, accelerates Pacemaker cardiac self-disciplining, brings out ectopic rhythm point, can form polyphyly ectopic rhythm, shorten myocardium refractory stage, and cause arrhythmia.Experimental result shows, returns spleen composition of medicine II effectively can suppress the arrhythmia caused by aconitine.
Cardiac glycoside medicine (as cedilanid) can suppress Na on myocardial cell membrane time poisoning
+-K
+-ATP enzyme, thus reduce K
+to intracellular active transport, cause lacking K in cell
+, the maximum diastolic potential of cardiac muscle is reduced, and relaxing period spontaneous depolarization speed is accelerated, and self-disciplining raises, and arrhythmia occurs.Adopt several different drug-induced dissimilar arrhythmia effectively can simulate clinical symptoms, the curative effect of reflection medicine.Result shows, returns spleen composition of medicine II effectively can prevent and treat arrhythmia.
Embodiment 9 returns the activity of spleen composition of medicine II pair of Beagle dog arrhythmia to investigate
Adopting the method described in embodiment 5 to investigate returns spleen composition of medicine II group (A group) and water extraction to return spleen composition of medicine 2 groups (B group), and conclusion is as described in table 12,13.To observe after medicine 1,3,5,7,8,9, l1,13,15, the electrocardiogram of 2d after 17d and drug withdrawal: P-R interval, QRs interval, Q-T interval, P ripple, Q ripple, R ripple, s ripple, T ripple, ST section, heart rate and the rhythm of the heart, and with medicine before compare.
Table 13 returns spleen composition of medicine II on the impact of arrhythmia Beagle dog P-R interval and heart rate
Table 14 returns spleen composition of medicine II on the impact of arrhythmia Beagle dog R-R periodic inequality (s)
*decline percentage rate: R-R periodic inequality after R-R periodic inequality-medicine before medicine
From table 13, >0.12 second before P-R interval medicine, after medicine, 3d rises and is improved to 17d, and P-R asks phase equal <0.12 second, and 2d after lasting till drug withdrawal.Spleen composition of medicine II group and water extraction is returned to return spleen composition of medicine 2 groups all can improve the heart rate of arrhythmia dog, after medicine, 9d plays efficacy stability, and maintain a period of time and level: and P wave of electrocardiogram, Q cross, R ripple, S ripple, QRS interval, Q-T interval, no matter return spleen composition of medicine II group or water extraction to return spleen composition of medicine 2 groups all to have no significant effect.
From table 14, before administration, the R-R periodic inequality of four dogs is 0.48 ~ 0.53s, and be far longer than 0.16s, after medicine, ld rises, and the R-R periodic inequality of 2 dosage groups all starts to shorten, and reduce to 040s from 0.48 ~ 0.53s before medicine, its range of decrease is 15% ~ 25%; After medicine, 5 ~ 11d, R-R periodic inequality all obviously shortens, and reduces to 0.20 ~ 0.27 second, and the range of decrease is 44 ~ 62%; After medicine, 13 ~ 15d, R-R periodic inequality is close to normal (close to 016s), returns spleen composition of medicine II group 13d after medicine to be 0.16s; Water extraction returns spleen composition of medicine 2 groups 15d after medicine to be 0.17s.After drug withdrawal 2d, two groups are respectively 0.20s and 0.08s, and its range of decrease is respectively 65% and 84%.
Table 15 returns spleen composition of medicine II on the impact of arrhythmia Beagle dog rhythm of the heart occurrence frequency (long R-R cycle/10 R-R cycles)
From table 15, before administration, four ARR occurrence frequencies of dog are in 10 R-R cycles, occur 4 long R-R cycles.After medicine, 3-5d rises, and returns spleen composition of medicine II group and water extraction to return spleen composition of medicine 2 groups all to start to reduce, is 2-3.5; After medicine, 7-13d obviously reduces, and is 1.5-2.5; After medicine, 15-17d is kept to 1-2, and drug withdrawal 2d reduces to 1, illustrates and returns spleen composition of medicine II group and new water extraction to return spleen side's composition of medicine 2 groups can obviously reduce ARR occurrence frequency, and can maintain certain hour after drug withdrawal.
Experimental result shows, returns spleen composition of medicine II group and water extraction to return spleen composition of medicine 2 groups obviously can improve the heart rate of arrhythmia dog, reduces ARR occurrence frequency, have good therapeutical effect to arrhythmia.Select arrhythmia Beagle dog as object of study, because animal is docile, the advantages such as Electrocardioscopy is convenient, its to the observed result of experimental effect closer to clinical.Bringing out in ARR experiment with Bealge dog coronary artery ligation, observe equally and return spleen composition of medicine II pair of arrhythmia to have good preventive and therapeutic effect, therefore the same with the result of the animal pathological model that medicine or operation cause with arrhythmia dog, objective equally and accurate to the role of evaluation of antiarrhythmic drug, and be easy to Estimating curative effect.
Embodiment 10 returns the activity of spleen composition of medicine II pair of rat gastrointestinal tract dysfunction to investigate
Adopt the method described in embodiment 6, investigate and return spleen composition of medicine II group and water extraction to return the 2 groups of effects to rat gastrointestinal tract dysfunction of spleen composition of medicine, concrete outcome is shown in table 16.
In table 16 rat plasma and jejunal tissue MTL dynamic amount dynamic change (
n=10)
Note: with model group ratio, * P ﹤ 0.05, * * P ﹤ 0.01;
Model group rats occurs that feces is shapeless in 24h after injection reserpine, and occurs that diarrhoea in various degree, crissum are filthy successively, occurs that appetite declines thereupon, during 6d, loose stool more so, and during 9d, loose stool stops gradually, and feces viscous is not well, even there is constipation, anorexia, become thin and day by day increase the weight of.Return spleen composition of medicine II group of minority rat, water extraction returns spleen composition of medicine 2 groups of minority rats, above-mentioned symptom appears in the most rat of commercially available GUIPI WAN group and commercially available Renshen Guipi Wan, and described four groups performance degree comparatively model group rats is light, rats in normal control group health as before, does not show any abnormalities.The perusal of each group of rat gastrointestinal tract mucosa is no abnormal, and pathologic finding is also there are no obvious inflammatory lesion.In sum, returning spleen composition of medicine II can regulate the gut hormone of experimental functional gastrointestinal disorder rat, significantly improve its gastrointestinal dysfunction symptom, is one of the party's mechanism of action for the treatment of this disease, regulate the approach of gut hormone as the party, still need and do to inquire into further.
Embodiment 11 returns the activity of spleen composition of medicine III pair of bradycardia rat to investigate
Adopt the method described in embodiment 3 to investigate, return spleen composition of medicine III group and water extraction to return spleen composition of medicine 3 groups; The general state of each treated animal in modeling, medication is observed; Detecting ECG; The changes of contents of cAMP in plasma and cGMP.Experimental data adopts the process of SPSS14.0 statistical software, and all data all adopt mean ± standard deviation
represent.
Administration the 14th day, after administration, 1h is with ether light anaesthesia rat at its lower extremity subcutaneous implantation electrode, records clear-headed rear standard II lead electrocardiogram of rat.Within 15th day, give each group of rat skin lower injection with clonidine hydrochloride 2mg/kg, and simultaneously gastric infusion, 0.5h, lh, 1.5h, 2h electrocardiosignal after record gavage, statistical analysis rat heart rate, the rhythm of the heart, atrioventricular block situation of change.
Spleen composition of medicine III group and water extraction is returned to return spleen composition of medicine 3 groups shown in table 17 on the impact of bradycardia rat heart rate, result shows, returns spleen composition of medicine III group, water extraction returns spleen composition of medicine 3 groups, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan amount group and righting help arteries and veins decoct group can improve bradyarrhythmia rat heart rate.
The table 17 respectively group rat rhythm of the heart compares
Note: compare with model group:
△p ﹤ 0.05,
▲p ﹤ 0.01; Compare with blank group:
◇p ﹤ 0.05,
◆p ﹤ 0.01;
After experiment terminates, broken end is got blood, is taken out heart immediately, prepares myocardial homogenates, detects cAMP and cGMP content in myocardial homogenates by test kit regulation.
Shown in table 18, compare for each group, return spleen composition of medicine III group, water extraction returns spleen composition of medicine 1 group, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan group and righting help arteries and veins decoct group cAMP content to be improved, cGMP level has decline, especially to return spleen composition of medicine III group remarkable.
The comparison of the concentration of rat plasma cAMP and cCMP respectively organized by table 18
Note: compare with model group:
△p ﹤ 0.05,
▲p ﹤ 0.01; Compare with blank group:
◇p ﹤ 0.05,
◆p ﹤ 0.01;
Result shows to return that spleen composition of medicine III can promote the yang blood and qi of body internal organs, deficiency and excess good and evil tend to be balanced gradually, improve the environment of yang deficiency rat disorder, impels yang deficiency rat to normal development.The bradycardia Cardiac Function in Rat of returning spleen composition of medicine III to improve to be caused by deficiency of heart-YANG and kidney-YANG and metabolism of myocardium, be conducive to promoting the nutriture of heart sinuatrial node, improving sinus node function, is to improve cardiac function, treat bradycardic effective preparation.
Embodiment 12 returns the activity of spleen composition of medicine III pair of tachycardia rat to investigate
Adopt the method described in embodiment 4 to investigate and return spleen composition of medicine III and water extraction to return spleen composition of medicine 3 groups of experimental results in shown in table 19, table 20.
The result of the anti-Aconitine Induced ventricular tachycardia of spleen composition of medicine III returned by table 19
The result of the anti-Aconitine Induced ventricular tachycardia of spleen composition of medicine III returned by table 20
From experimental result, return spleen composition of medicine III to have stronger inhibitory action to drug-induced arrhythmia, when effective dose, electrocardio keeps normal condition not to be any change always; The accidental ventricular premature contraction of Xinluning tablet gavage group or premature ventricular beat, disappear after a time, and the rhythm of the heart recovers normal.Result also shows, returns spleen composition of medicine III to be better than other drug on the continuous action time.
Aconitine causes ARR main mechanism to be: the sodium channel that have activated myocardial cell, makes sodium channel open, accelerates myocardial cell Na
+interior stream, impels membrane depolarization, accelerates Pacemaker cardiac self-disciplining, brings out ectopic rhythm point, can form polyphyly ectopic rhythm, shorten myocardium refractory stage, and cause arrhythmia.Experimental result shows, returns spleen composition of medicine III effectively can suppress the arrhythmia caused by aconitine.
Cardiac glycoside medicine (as cedilanid) can suppress Na on myocardial cell membrane time poisoning
+-K
+-ATP enzyme, thus reduce K
+to intracellular active transport, cause lacking K in cell
+, the maximum diastolic potential of cardiac muscle is reduced, and relaxing period spontaneous depolarization speed is accelerated, and self-disciplining raises, and arrhythmia occurs.Adopt several different drug-induced dissimilar arrhythmia effectively can simulate clinical symptoms, the curative effect of reflection medicine.Result shows, returns spleen composition of medicine III effectively can prevent and treat arrhythmia.
Embodiment 13 returns the activity of spleen composition of medicine III pair of Beagle dog arrhythmia to investigate
Adopting the method described in embodiment 5 to investigate returns spleen composition of medicine III group (A group) and water extraction to return spleen composition of medicine 3 groups (B group), and conclusion is as shown in table 20,21.To observe after medicine 1,3,5,7,8,9, l1,13,15, the electrocardiogram of 2d after 17d and drug withdrawal: P-R interval, QRs interval, Q-T interval, P ripple, Q ripple, R ripple, s ripple, T ripple, ST section, heart rate and the rhythm of the heart, and with medicine before compare.
Table 21 returns spleen composition of medicine III on the impact of arrhythmia Beagle dog P-R interval and heart rate
Table 22 returns spleen composition of medicine III on the impact of arrhythmia Beagle dog R-R periodic inequality (s)
*decline percentage rate: R-R periodic inequality after R-R periodic inequality-medicine before medicine
From table 21, >0.12 second before P-R interval medicine, after medicine, 3d rises and is improved to 17d, and P-R asks phase equal <0.12 second, and 2d after lasting till drug withdrawal.Return spleen composition of medicine III group and water extraction to return spleen composition of medicine 3 groups all can improve the heart rate of arrhythmia dog, after medicine, 9d plays efficacy stability, and maintains a period of time and level; And P wave of electrocardiogram, Q cross, R ripple, S ripple, QRS interval, Q-T interval, spleen composition of medicine III group or water extraction no matter is returned to return spleen side's composition of medicine 3 groups all to have no significant effect.
From table 22, before administration, the R-R periodic inequality of four dogs is 0.48 ~ 0.53s, and be far longer than 0.16s, after medicine, ld rises, and the R-R periodic inequality of 2 dosage groups all starts to shorten, and reduce to 040s from 0.48 ~ 0.53s before medicine, its range of decrease is 15% ~ 25%; After medicine, 5 ~ 11d, R-R periodic inequality all obviously shortens, and reduces to 0.20 ~ 0.27 second, and the range of decrease is 44 ~ 62%; After medicine, 13 ~ 15d, R-R periodic inequality is close to normal (close to 016s), returns spleen composition of medicine III group 13d after medicine to be 0.16s; Water extraction returns spleen composition of medicine 1 group 15d after medicine to be 0.17s.After drug withdrawal 2d, two groups are respectively 0.20s and 0.08s, and its range of decrease is respectively 61% and 84%.
Table 23 returns spleen composition of medicine III on the impact of arrhythmia Beagle dog rhythm of the heart occurrence frequency (long R-R cycle/10 R-R cycles)
From table 23, before administration, four ARR occurrence frequencies of dog are in 10 R-R cycles, occur 4 long R-R cycles.After medicine, 3-5d rises and returns spleen composition of medicine III group and water extraction to return spleen side's composition of medicine 3 groups all to start to reduce, and is 2-3.5; After medicine, 7-13d obviously reduces, and is 1.5-2.5; After medicine, 15-17d is kept to 1-2, and drug withdrawal 2d reduces to 1, illustrates and returns spleen composition of medicine III group and water extraction to return spleen composition of medicine 3 groups can obviously reduce ARR occurrence frequency, and can maintain certain hour after drug withdrawal.
Experimental result shows, returns spleen composition of medicine III group and water extraction to return spleen composition of medicine 3 groups obviously can improve the heart rate of arrhythmia dog, reduces ARR occurrence frequency, have good therapeutical effect to arrhythmia.Select arrhythmia Beagle dog as object of study, because animal is docile, the advantages such as Electrocardioscopy is convenient, its to the observed result of experimental effect closer to clinical.Bringing out in ARR experiment with Bealge dog coronary artery ligation, observe equally and return spleen composition of medicine III group to have good preventive and therapeutic effect to arrhythmia, therefore the same with the result of the animal pathological model that medicine or operation cause with arrhythmia dog, objective equally and accurate to the role of evaluation of antiarrhythmic drug, and be easy to Estimating curative effect.
Embodiment 14 returns the activity of spleen composition of medicine III pair of rat gastrointestinal tract dysfunction to investigate
Adopt the method described in embodiment 6, investigate and return spleen composition of medicine III group and water extraction to return spleen composition of medicine 3 groups of concrete outcomes shown in table 24.
In table 24 rat plasma and jejunal tissue MTL dynamic amount dynamic change (
n=10)
Note: with model group ratio, * P ﹤ 0.05, * * P ﹤ 0.01;
Model group rats occurs that feces is shapeless in 24h after injection reserpine, and occurs that diarrhoea in various degree, crissum are filthy successively, occurs that appetite declines thereupon, during 6d, loose stool more so, and during 9d, loose stool stops gradually, and feces viscous is not well, even there is constipation, anorexia, become thin and day by day increase the weight of.Several rat, water extraction return the most rat of spleen composition of medicine 3 groups of minority rats, commercially available GUIPI WAN group and commercially available Renshen Guipi Wan to occur above-mentioned symptom individually to return spleen composition of medicine III group, and described four groups performance degree comparatively model group rats is light, rats in normal control group health as before, does not show any abnormalities.The perusal of each group of rat gastrointestinal tract mucosa is no abnormal, and pathologic finding is also there are no obvious inflammatory lesion.In sum, returning spleen composition of medicine III can regulate the gut hormone of experimental functional gastrointestinal disorder rat, significantly improve its gastrointestinal dysfunction symptom, is one of the party's mechanism of action for the treatment of this disease, regulate the approach of gut hormone as the party, still need and do to inquire into further.
Claims (6)
1. return a spleen composition of medicine, it is characterized in that: described in return spleen composition of medicine to be made up of following medicinal substances extract: Radix Pseudostellariae, the Radix Astragali, Radix Polygalae, Radix Glycyrrhizae, Radix Angelicae Sinensis, Poria, Arillus Longan, the Radix Aucklandiae, the Rhizoma Atractylodis Macrocephalae, Radix Rehmanniae Preparata, Semen Ziziphi Spinosae and Fructus Jujubae;
The weight ratio of described Radix Pseudostellariae, the Radix Astragali, Radix Polygalae, Radix Glycyrrhizae, Radix Angelicae Sinensis, Poria, Arillus Longan, the Radix Aucklandiae, the Rhizoma Atractylodis Macrocephalae, Radix Rehmanniae Preparata, Semen Ziziphi Spinosae, Fructus Jujubae crude drug composition is 2 ~ 6:2 ~ 6:4 ~ 16:1 ~ 4:4 ~ 16:4 ~ 16:4 ~ 16:1 ~ 4:4 ~ 16:4 ~ 16:4 ~ 16:4 ~ 16.
2. according to claim 1ly return spleen composition of medicine, it is characterized in that: the weight ratio of described Radix Pseudostellariae, the Radix Astragali, Radix Polygalae, Radix Glycyrrhizae, Radix Angelicae Sinensis, Poria, Arillus Longan, the Radix Aucklandiae, the Rhizoma Atractylodis Macrocephalae, Radix Rehmanniae Preparata, Semen Ziziphi Spinosae, Fructus Jujubae crude drug composition is 2:2:4:1:4:4:4:1:4:4:4:4.
3. according to claim 2ly return spleen composition of medicine, it is characterized in that: described in return spleen composition of medicine by the 20-95% ethanol extraction of Radix Pseudostellariae, the Radix Astragali, Radix Glycyrrhizae, Poria and Radix Polygalae, the water extract of Arillus Longan, Semen Ziziphi Spinosae, Radix Rehmanniae Preparata, Radix Angelicae Sinensis and Fructus Jujubae, the volatile oil mixing composition of the Rhizoma Atractylodis Macrocephalae and the Radix Aucklandiae.
4. the preparation method of returning spleen composition of medicine described in any one of claim 1-3, is characterized in that: described method is extracted Radix Pseudostellariae, Radix Glycyrrhizae, the Radix Astragali, Poria and Radix Polygalae for adopting the methods such as backflow, warm macerating, percolation to extract respectively using 20-95% ethanol as solvent;
Be that solvent adopts warm macerating, backflow, decocting method to extract Arillus Longan, Semen Ziziphi Spinosae, Radix Rehmanniae Preparata, Radix Angelicae Sinensis and Fructus Jujubae with water;
Adopting has steam distillation, solvent reflux extraction, microwave method, the supercritical fluid extraction volatile oil to the Rhizoma Atractylodis Macrocephalae and the Radix Aucklandiae to extract;
What merge that said extracted thing obtains being used for the treatment of arrhythmia and GI nerves functional disease returns spleen composition of medicine.
5. the arbitrary described spleen composition of medicine of returning of claim 1-3 treats the application in arrhythmia disorder agent in preparation.
6. the arbitrary described spleen composition of medicine of returning of claim 1-3 treats the application in GI nerves functional disease medicine in preparation.
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| CN104920742A (en) * | 2015-07-20 | 2015-09-23 | 青海省通天河藏药制药有限责任公司 | Anti-insomnia substitutional tea |
| CN104938727A (en) * | 2015-07-20 | 2015-09-30 | 青海省通天河藏药制药有限责任公司 | Preparation method of insomnia resistance substitutional tea |
| CN105688068A (en) * | 2016-03-20 | 2016-06-22 | 邱文辉 | Chinese herbal preparation for treating arrhythmia and preparing method of Chinese herbal preparation |
| CN105943682A (en) * | 2016-06-16 | 2016-09-21 | 浙江爱生药业有限公司 | Application of spleen-invigorating preparation in preparation of health-care products or drugs for regulating gastrointestinal hormones and improving gastrointestinal movement |
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| CN1569050A (en) * | 2003-07-18 | 2005-01-26 | 毛友昌 | Novel preparing technique of |
| CN1823992A (en) * | 2005-12-15 | 2006-08-30 | 北京阜康仁生物制药科技有限公司 | Ginseny spleen invigorating preparation and its new preparation method |
| CN101095745A (en) * | 2007-08-13 | 2008-01-02 | 浙江爱生药业有限公司 | Particles for invigorating the spleen, oral liquid and condensed pills and method for preparing the same and the quality control method |
| CN101985001A (en) * | 2010-07-07 | 2011-03-16 | 重庆市南川区瑞丰农业开发有限责任公司 | Chinese herbal medicine for treating insomnia |
| CN102380077A (en) * | 2011-10-11 | 2012-03-21 | 邓华伦 | Chinese traditional drug for treating thoughtfulness, spleen deficiency, amnesia and palpitation |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1569050A (en) * | 2003-07-18 | 2005-01-26 | 毛友昌 | Novel preparing technique of |
| CN1823992A (en) * | 2005-12-15 | 2006-08-30 | 北京阜康仁生物制药科技有限公司 | Ginseny spleen invigorating preparation and its new preparation method |
| CN101095745A (en) * | 2007-08-13 | 2008-01-02 | 浙江爱生药业有限公司 | Particles for invigorating the spleen, oral liquid and condensed pills and method for preparing the same and the quality control method |
| CN101985001A (en) * | 2010-07-07 | 2011-03-16 | 重庆市南川区瑞丰农业开发有限责任公司 | Chinese herbal medicine for treating insomnia |
| CN102380077A (en) * | 2011-10-11 | 2012-03-21 | 邓华伦 | Chinese traditional drug for treating thoughtfulness, spleen deficiency, amnesia and palpitation |
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