CN102764305A - Spleen-invigorating combined drug, preparation method and application thereof - Google Patents
Spleen-invigorating combined drug, preparation method and application thereof Download PDFInfo
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- CN102764305A CN102764305A CN2012102905555A CN201210290555A CN102764305A CN 102764305 A CN102764305 A CN 102764305A CN 2012102905555 A CN2012102905555 A CN 2012102905555A CN 201210290555 A CN201210290555 A CN 201210290555A CN 102764305 A CN102764305 A CN 102764305A
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Abstract
The invention provides a spleen-invigorating combined drug. The spleen-invigorating combined drug is obtained through replacement of codonopsis pilosula or ginseng with heterophylly falsestarwort root based on the traditional classic formula. The spleen-invigorating combined drug includes crude drugs or extracts of the heterophylly falsestarwort root, astragalus and polygala root. The spleen-invigorating combined drug has an activity for sinus bradycardia, tachycardia and arrhythmia in gastrointestinal neurosis and arrhythmia symptoms, and simultaneously, extracts obtained by the preparation method can be produced into various dosage forms more conveniently compared with a normal water extraction method.
Description
Technical field
The invention provides a kind of Chinese medicine preparation, the present invention relates to a kind of return spleen composition of medicine, method for preparing and application thereof in particular.
Technical background
GUIPI WAN side derives from tight using and " GUIPI TANG " in the recipes for Saving Lives of showing of Song dynasty; 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 the flavor medicines form; Developed into GUIPI WAN side and Renshen Guipi Wan side modern age gradually; Replace Radix Ginseng with Radix Codonopsis among the former side, the latter still continues to use Radix Ginseng.
GUIPI WAN for Radix Ginseng, has replenishing QI to invigorate the spleen with Radix Codonopsis, the effect of nourishing blood to tranquillize the mind.Be used for deficiency of both the heart and spleen, the 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 Radix Codonopsis QI invigorating effect, and Radix Ginseng is warm in nature in addition, causes dry mouth and throat with how getting angry, and Radix Codonopsis property is flat, can not get angry, and crosses if not QI and blood and emptyly just can use GUIPI WAN.
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 the side is gone into spleen lung two warps, with the heart nourish blood, enriching spleen-QI, be monarch drug altogether.The all sweet temperature of Radix Ginseng, Rhizoma Atractylodis Macrocephalae property helps Radix Astragali invigorating the spleen and benefiting QI; The sweet suffering of Radix Angelicae Sinensis is warm in nature, and the 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 Longans, sweet temperature is bitter, the strengthening the spleen that nourishes heart, decides will (painstaking effort can be nourished temper plentifully, so the traditional Chinese medical science has the inclination to say for the mother of spleen) with fixed attention; Radix Aucklandiae circulation of qi promoting reason spleen helps fortuneization, hinders spleen in case the taste of all tonics is greasy, all is adjuvant drug.The sweet temperature of Radix Glycyrrhizae Preparata property can the QI invigorating invigorating middle warmer, and reactivation is in harmonious proportion the property of medicine, and is inclined to one side with the property of medicine in the side of alleviation.In the usage with Rhizoma Zingiberis Recens, Fructus Jujubae the spleen and stomach regulating, as a means of the change source.The all pathological changes that cause for heart spleen blood deficiency have the well treated effect, are mainly used to heart spleen QI and blood deficiency and insufficiency of vital energy and blood, cardiopalmus, the forgetful insomnia of drawing, tired, shallow complexion, diseases such as night sweat deficiency-heat.Modern clinical research shows, Renshen Guipi Wan can resisting fatigue, shock; Calmness, antiinflammatory, analgesia; Effects such as blood pressure lowering are usually used in treatment of 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, MBV is few, and color is light.
One Chinese patent application (CN03124679.6) is returned new preparation technology of spleen and preparation thereof; The modern pharmaceutical technology is carried out the Technology reform to the existing spleen preparation of returning; The utilization of new adjuvant, new technique, new equipment; The deficiency that overcome that former preparation dose is big, effective ingredient is prone to loss in the preparation process, the spleen preparation of returning that adopts the present invention to process can fully keep effective ingredient, have good effect, dose little, take advantages such as easy to carry.A kind of spleen granule, oral liquid and concentrated pill and their method for preparing and quality control side of returning of Chinese patent (ZL200710143907.3) the present invention relates to a kind of spleen granule, oral liquid and concentrated pill and their method for preparing and method of quality control of returning; Be particularly related to a kind of have replenishing QI to invigorate the spleen, nourishing blood to tranquillize the mind; Be used for deficiency of both the heart and spleen, the cardiopalmus of breathing hard, insomnia and dreamful sleep; Dizzy dizzy; Lassitude of the limbs and weakness, the Chinese medicine preparation of inappetence, said preparation are to be processed by raw material of Chinese medicine such as 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, Fructus Jujubaes.
Summary of the invention
Traditional medicine proves, sweet, the little hardship of Radix Pseudostellariae is flat.Return spleen, lung meridian, the body lubricant nature with; Tonifying QI to produce body fluid cures mainly 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 is seen lassitude and weak, loss of appetite person, can with compatibility 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.Discover that Radix Pseudostellariae has anti-stress, antifatigue effect.Active substance such as the water extract of Radix Pseudostellariae, 75% ethanol extract, Radix Pseudostellariae polysaccharide and Radix Pseudostellariae saponin all can obviously prolong the mice swimming with a load attached to the body time, and can obviously prolong the time-to-live of mice.Contain ethanol extract in the Radix Pseudostellariae, have protective effect for people's gastrointestinal function, especially after the injection reserpine, this possibly be because water extract can obviously suppress human body enterokinesia and propulsive speed and distance.Active substance such as polysaccharide that is contained in the Radix Pseudostellariae and total saponins are for the opposing that improves human body with resist cryogenic effect and have certain ability.Radix Pseudostellariae can significantly improve the chronic heart failure due to the myocardial infarction, and mechanism of action maybe to improve the oxidative stress status of muscular tissue relevant with Radix Pseudostellariae.Enzymatic reaction antioxidative enzyme is that SOD, CAT, GSH-Px can make active oxygen change hydrogen peroxide in the body, finally change water and oxygen molecule into, thereby the effect of free radical is removed in performance.
The present invention replaces Radix Codonopsis or Radix Ginseng to obtain a kind of spleen composition of medicine of returning with Radix Pseudostellariae on the basis of traditional classical proved recipe, comprises the crude drug or the extract of following medical material: Radix Pseudostellariae, the Radix Astragali and Radix Polygalae.
The said spleen composition of medicine of returning is made up of the crude drug or the extract of following medical material: 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 that said 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 are formed 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 that said 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 are formed is 2:2:4:1:4:4:4:1:4:4:4:4.
Said 20-95% ethanol extraction of returning the spleen composition of medicine by 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 of the Rhizoma Atractylodis Macrocephalae and the Radix Aucklandiae mix to be formed.
Said method is extracted Radix Pseudostellariae, Radix Glycyrrhizae, the Radix Astragali, Poria and Radix Polygalae for adopt methods such as backflow, warm macerating, percolation to extract respectively as solvent with 20-95% ethanol;
With water is that solvent adopts warm macerating, backflow, decocting method that Arillus Longan, Semen Ziziphi Spinosae, Radix Rehmanniae Preparata, Radix Angelicae Sinensis and Fructus Jujubae are extracted;
Employing has steam distillation, solvent refluxing method, microwave method, supercritical fluid extraction that the volatile oil of the Rhizoma Atractylodis Macrocephalae and the Radix Aucklandiae is extracted;
Merge the said extracted thing and obtain returning the spleen composition of medicine.
The above-mentioned spleen composition of medicine of returning is treated the application in the arrhythmia disease medicine in preparation.
The above-mentioned spleen composition of medicine of returning is treated the application in the gastrointestinal tract neurosis medicine in preparation.
Useful technique effect of the present invention is: the spleen composition of medicine of returning provided by the invention; Sinus bradycardia, tachycardia and arrhythmia in gastrointestinal tract neurosis and the arrhythmia disease have activity; Simultaneously; The extract that the method for preparing that the present invention adopts obtains than the light water extracting method, is more conveniently processed various dosage forms.
The specific embodiment
Embodiment 1 returns the preparation 1 of spleen composition of medicine
Take by weighing 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 methods such as 30-60 ℃ of condition backflow, warm macerating, percolation to extract respectively extracts Radix Pseudostellariae, Radix Glycyrrhizae, the Radix Astragali, Poria and Radix Polygalae as solvent with 20-95% ethanol; The solvent gross weight is 3-15 a times of crude drug weight.
With water is that solvent adopts 45-75 ℃ of condition warm macerating, backflow, decocting method that Arillus Longan, Semen Ziziphi Spinosae, Radix Rehmanniae Preparata, Radix Angelicae Sinensis and Fructus Jujubae are extracted; Extract 3 times, the solvent gross weight is 3-15 a times of crude drug weight, and extraction time is greater than 15min.
Employing has steam distillation, solvent refluxing method, microwave method, supercritical fluid extraction that the volatile oil of the Rhizoma Atractylodis Macrocephalae and the Radix Aucklandiae is extracted; Merge the said extracted thing and obtain returning spleen composition of medicine I.
Take by weighing 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.Obtain returning spleen composition of medicine II according to method for preparing.
Take by weighing 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.Obtain returning spleen composition of medicine III according to method for preparing.
Embodiment 2 returns the preparation 2 of spleen composition of medicine
Take by weighing 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, boil 3 times with medical material weight 3-5 decocting doubly, each 30-60min merges and reclaims extract and obtain being used to treat arrhythmia and the neurosal water of gastrointestinal tract and carry and return spleen composition of medicine 1.
Take by weighing 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.Obtaining merge reclaiming extract according to method for preparing obtains being used to treat arrhythmia and the neurosal water of gastrointestinal tract and carries and return spleen composition of medicine 2.
Take by weighing 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.Merge reclaiming extract obtains being used to treat arrhythmia and the neurosal water of gastrointestinal tract and carries and return spleen composition of medicine 3.
Embodiment 3 returns spleen composition of medicine I that the activity of bradycardia rat is investigated
Select healthy adult Wistar rat for use, body weight 250g-300g, no abnormal behavior is confirmed in the animal via test before the experiment.Rat after adaptability is fed 7d, every day buttocks subcutaneous injection hydrocortisone, every day, 25mg/kg injected 14d continuously.And, force rat every day at the upper and lower noon respectively to swim 1 time in the 2nd when week of experiment, and pull out when being about to unable, to induce overstrain, continued for 1 week.Observe the rat gross morphology, all appearance activities reduce, lassitude, bradykinesia, the back of a bow are rolled up, amount of drinking water reduces, lose weight etc. kidney yang deficiency of vital energy symptom for modeling successfully.Only select the successful rat 6O of modeling; Be divided at random and return spleen composition of medicine I group, water to carry and return 1 group of spleen composition of medicine, commercially available GUIPI WAN group and commercially available Renshen Guipi Wan amount group, set upright and help arteries and veins mixture matched group, model control group; Every group each 12; Choosing 12 healthy rats again is blank control group, every group of male and female half and half, sub-cage rearing.Modeling successfully afterwards begins pharmaceutical intervention next day.Blank group and model group routine feeding are irritated stomach with 20ml/kg dosage with distilled water by rat body weight.Set upright and help the drug level of arteries and veins side's decoct group to be respectively 20ml/kg, every group all in the morning every day during 1O gastric infusion once treat 14d continuously.
The general state of each treated animal in modeling, medication observed; Detecting ECG; The changes of contents of cAMP in plasma and cGMP.Experimental data adopts SPSS 14.0 statistical softwares to handle, and all data all adopt mean ± standard deviation
expression.
Animal shows as blank control group: hair is along sliding, the eyes are bright and piercing, and reaction, movable active and intelligent call loudly, and normal feed is drunk water.Model group and each treatment group rat lethargy in various degree occurs when experiment the 1ld～14d, the minimizing of ingesting, and 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, kidney yang deficiency of vital energy symptoms such as diarrhea, particularly model control group are more remarkable.
Administration the 14th day, 1h writes down the clear-headed back of rat standard II lead electrocardiogram with ether light anaesthesia rat extremity subcutaneous implantation electrode under it after the administration.Organized rat skin lower injection with clonidine hydrochloride 2mg/kg to each on the 15th day, and the while gastric infusion, 0.5h, lh, 1.5h, 2h electrocardiosignal behind the record filling stomach, statistical analysis rat heart rate, the rhythm of the heart, atrioventricular block situation of change.
Return spleen composition of medicine I group and water to carry and return 1 group of influence of spleen composition of medicine as shown in table 1 bradycardia rat heart rate; The result shows, returns spleen composition of medicine I group, water to carry to return 1 group of spleen composition of medicine, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan amount group and sets upright and help arteries and veins decoct group can improve bradyarrhythmia rat heart rate.
Table 1 is respectively organized the rat rhythm of the heart relatively
Annotate: compare with model group:
△P ﹤ 0.05,
▲P ﹤ 0.01; Compare with blank control group:
◇P ﹤ 0.05,
◆P ﹤ 0.01;
After experiment finished, broken end was got blood, is taken out heart immediately, prepares myocardium homogenate, pressed the test kit regulation and detected cAMP and cGMP content in the myocardium homogenate.
As shown in table 2; Each group is compared; Return spleen composition of medicine I group, water to carry to return 1 group of spleen composition of medicine, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan group and set upright and help arteries and veins decoct group cAMP content to be improved, the cGMP level all has decline, especially to return spleen composition of medicine I group remarkable.
Table 2 is respectively organized the comparison
of the concentration of rat plasma cAMP and cCMP
Annotate: compare with model group:
△P ﹤ 0.05,
▲P ﹤ 0.01; Compare with blank control group:
◇P ﹤ 0.05,
◆P ﹤ 0.01;
Bradyarrhythmia is a common clinical disease; Show as in various degree shortness of breath and palpitation, sensation of oppression and faint pain in the chest, dizzy weakly, moving then increase the weight of; The severe patient history that occurs fainting repeatedly, burst tic, pareordia severe pain, can concurrent heart failure, cardiogenic shock, cardiac sudden death etc.
CAMP and cardiac function positive correlation when the p1 receptor agonism on the heart, produce a large amount of cAMP in the 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 are bioactive substance---the second message,second messengers of a pair of not only each other antagonism but also mutual dependence for existence in the body.They be prevalent in biological cell and with body fluid in, regulating body cell intracellular metabolic and various physiological activity.Think that at present they play important regulatory role to the function of myocardial cell, VSMC, its PC ANOMALOUS VARIATIONS has important function in the cardiovascular disease generating process.Therefore the balance of cAMP and cGMP is the intermediate hub of regulating the key material of body and influencing globality mechanism cell function.CAMP descends, and cGMP raises, and is one of specificity pathological change of the yang deficiency syndrome of generally acknowledging, and the balance and stability of keeping the two 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 promotes platelet to build up, and heart is suppressed, and its content can reflect the variation of atrial pressure indirectly, can judge degree of heart failure thus.The treatment of Fang Zhongyong Radix Pseudostellariae isothermal kidney yang-tonifying medicinal; And the not method that adopts classification to extract effective site is extracted effective ingredient in the composition medicine; CAMP is gone up and cGMP decline, compare with model group, dose groups helps arteries and veins mixture group cAMP level to be improved with setting upright; The cGMP level all has decline, and its difference has significance.Consistent with relevant results reported, show that yang blood and qi, the deficiency and excess good and evil of returning spleen composition of medicine I can promote the body internal organs tend to be balanced gradually, improve the disorderly interior environment of yang deficiency rat, impel the yang deficiency rat to normal development.The bradycardia rat cardiac function and the myocardial cell metabolism of returning spleen composition of medicine I to improve to cause by deficiency of heart-YANG and kidney-YANG, help promoting the heart sinuatrial node nutriture, improve sinus node function, be to improve cardiac function, the bradycardic effective preparation of treatment.
Embodiment 4 returns spleen composition of medicine I that the activity of tachycardia rat is investigated
Get 60 of healthy rats, 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 PIAN agent matched group, irritates the normal saline solution (210mg/lOml) that stomach gives the agent of medicine XINLUNING PIAN.The 3rd group for returning spleen composition of medicine I group, irritate stomach return the normal saline solution of spleen composition of medicine I (raw medicinal herbs, 875mg/lOml); The 4th group is that water is carried and returned 1 group of spleen composition of medicine, irritate stomach give water carry the normal saline solution of returning 1 group of spleen composition of medicine (raw medicinal herbs, 1275mg/lOml); The 5th group is commercially available Renshen Guipi Wan group; Irritate stomach give commercially available Renshen Guipi Wan normal saline solution (raw medicinal herbs, 1275mg/lOml), the 6th group is commercially available GUIPI WAN group; Irritate stomach give commercially available GUIPI WAN normal saline solution (raw medicinal herbs, 1275mg/lOml).Each group is all by 2ml/ amount administration only.After the administration, at first with rat with urethane (1.2gkg
-1) intraperitoneal anesthesia, be fixed on the operating-table then.Connect electrocardioscope, the record II is led, and changes (chart speed 50mm/s) to observe electrocardio.At tail vein injection aconitine (20 μ gml
-1) before, the record normal ECG.Each injects aconitine after organizing administration 1h, observes the electrocardio situation of change.Experimental result is seen table 3.
Table 3 returns the anti-aconitine of spleen composition of medicine I to bring out the result
of ventricular tachycardia
Get 60 of healthy guinea pigs.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 PIAN agent matched group, irritates the normal saline solution (210mg/lOml) that stomach gives the agent of medicine XINLUNING PIAN, and 2ml/ only.The 3rd group for returning spleen composition of medicine I group, irritate stomach return the normal saline solution of spleen composition of medicine I (raw medicinal herbs, 875mg/lOml); The 4th group is that water is carried and returned 1 group of spleen composition of medicine, irritate stomach give water carry the normal saline solution of returning 1 group of spleen composition of medicine (raw medicinal herbs, 1275mg/lOml); The 5th group is commercially available Renshen Guipi Wan group; Irritate stomach give commercially available Renshen Guipi Wan normal saline solution (raw medicinal herbs, 1275mg/lOml), the 6th group is commercially available GUIPI WAN group; Irritate stomach give commercially available GUIPI WAN normal saline solution (raw medicinal herbs, 1275mg/lOml).3ml/ only.After the administration, with urethane (1.2gkg
-1) with the Cavia porcellus intraperitoneal anesthesia, face upward the position and be fixed on the operating-table, it is subcutaneous that needle electrode is inserted extremity, and link with electrocardiograph, and the record II is led to observe electrocardio and is changed (chart speed 50mms
-1).At vena femoralis injection cedilanid (0.82mlkg
-1) before, write down normal electrocardio.Vena femoralis injection cedilanid (0.82mlkg then
-1), observe the electrocardio situation of change, till arrhythmia is recovered normally; Inject cedilanid (0.82mlkg) behind the matched group administration l h, observe the electrocardio situation of change.Experimental result is seen table 4.
Table 4 returns spleen side's anti-aconitine of composition of medicine I to bring out the result
of ventricular tachycardia
Can know that by experimental result return spleen composition of medicine I that drug-induced arrhythmia is had stronger inhibitory action, when effective dose, electrocardio keeps normal condition not have any variation always; The rhythm of the heart is rather irritated accidental ventricular premature contraction of stomach group or premature ventricular beat, disappears after a time, and it is normal that the rhythm of the heart recovers.The result also shows, returns spleen composition of medicine I to be superior to other drug at continuous action on the time.
Aconitine causes that ARR main mechanism is: activated the sodium channel of myocardial cell, made the sodium channel open, accelerated myocardial cell Na
+Interior stream impels the cell membrane depolarization, accelerates the Pacemaker cardiac self-disciplining, brings out the ectopic rhythm point, can form the polyphyly ectopic rhythm, shortens myocardium refractory stage, and causes arrhythmia.Experimental result shows, returns spleen composition of medicine I can suppress the arrhythmia that is caused by aconitine effectively.
Cardiac glycoside medicine (like cedilanid) can suppress Na on the myocardial cell membrane when poisoning
+-K
+-ATP enzyme, thus K reduced
+To intracellular active transport, cause lacking in the cell K
+, the maximum diastolic potential of cardiac muscle is reduced, the relaxing period spontaneous depolarization speeds up, and self-disciplining raises, and arrhythmia takes place.Adopt several kinds of different drug to bring out dissimilar arrhythmia and can simulate clinical symptoms effectively, the curative effect of reflection medicine.The result shows, returns spleen composition of medicine I can prevent and treat arrhythmia effectively.
Embodiment 5 returns spleen composition of medicine I that the activity of Beagle dog arrhythmia is investigated
The choice criteria of arrhythmia Beagle dog: selected 4 beagle dogs to study, male and female half and half, about body weight 10kg, monthly age 6-12 month.The Beagle dog is checked and meets following condition person through at least 5 (every other day) II lead electrocardiogram (ECG): 1. hole property P ripple, the R-R cycle is not waited, and after P crosses ORS is arranged, periodic inequality>0.16 second, the P-R interval fix and also O.12 second, with breathe irrelevant; 2. the long R-R cycle more than 3 appears in 10 R-R cycles, through observing in a week and not having the improver, confirms as arrhythmia.Continuous 5 times (1 time every other day) inspections of having an electro-cardiogram are not then got rid of as once meeting above-mentioned choice criteria person.Arrhythmia condition improved, electrocardiogram obviously improve and meet following two for effectively: 1. the R-R periodic inequality reduced and near 0.16 second, and < O.12 second the P-R interval is fixed and; 2. the arrhythmia number of times reduces: the number of times in long R-R cycle appears in 10 R-R in the cycle obviously reduces.Electrocardiogram do not have be improved as invalid.Experiment is established and is returned spleen composition of medicine I group (A group) (crude drug 3.75g/kg) and water to carry to return 1 group of spleen composition of medicine (B group) (crude drug 3.75g/kg); Regularly administration of every day 9am and 4pm; Earlier be made into certain density suspension to medicine and add mixing in 1/3 feedstuff; Let dog eat voluntarily, and then give all the other 2/3 feedstuffs, continuously 17d.
The ECG inspection method: dog is taken from right erect position, the subcutaneous insertion needle electrode of extremity, and the II lead electrocardiogram is measured in quiet back under the waking state before food.
Observe behind the medicine 1,3,5,7,8,9, the electrocardiogram of 2d after l1,13,15,17d and the 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 is returned the influence of spleen composition of medicine I to arrhythmia Beagle dog P-R interval and heart rate
Table 6 is returned the influence of spleen composition of medicine I to arrhythmia Beagle dog R-R periodic inequality (s)
*Decline percentage rate: R-R periodic inequality behind R-R periodic inequality-medicine before the medicine
Visible by table 5, before the P-R interval medicine>0.12 second, 3d rises to 17d behind the medicine has improvement, and P-R asks all < 0.12 second, and last till 2d after drug withdrawal phase.Return spleen composition of medicine I group and water to carry and return 1 group of heart rate that all can improve the arrhythmia dog of spleen composition of medicine, 9d plays efficacy stability behind the medicine, and keeps a period of time and level; And ECG P ripple, Q cross, R ripple, S ripple, QRS interval, Q-T interval, no matter return spleen composition of medicine I group or water to carry and return the spleen composition of medicine all not have obvious influence for 1 group.
Visible by table 6, before the administration, the R-R periodic inequality of four dogs is 0.48～0.53s, is far longer than 0.16s, and ld rises behind the medicine, and the R-R periodic inequality of 2 dose groups all begins to shorten, and 0.48～0.53s before medicine reduces to 040s, and its range of decrease is 15%～25%; 5～11d behind the medicine, the R-R periodic inequality all obviously shortens, and reduces to 0.20～0.27 second, and the range of decrease is 44～62%; 13～15d behind medicine, the R-R periodic inequality is near normally (near 0.16s, returning spleen composition of medicine I group 13d behind medicine is 0.16s; Water is carried and returned 1 group of spleen composition of medicine 15d behind medicine is 0.17s.Two groups are respectively 0.20s and 0.08s behind the drug withdrawal 2d, and its range of decrease is respectively 62% and 83%.
Table 7 returns spleen composition of medicine I to the influence in (long R-R cycle/10 a R-R cycle) of arrhythmia Beagle dog rhythm of the heart occurrence frequency
Visible by table 7, before the administration, four ARR occurrence frequencies of dog are 10 R-R in the cycle, 4 long R-R cycles occur.3-5d rises and returns spleen composition of medicine I group and water to carry to return 1 group of spleen composition of medicine all to begin to reduce behind the medicine, is 2-3.5; 7-13d obviously reduces behind the medicine, is 1.5-2.5; 15-17d is kept to 1-2 behind the medicine, and drug withdrawal 2d reduces to 1, explains that returning spleen composition of medicine I group and water to carry returns the spleen composition of medicine can obviously reduce ARR occurrence frequency for 1 group, and can keep certain hour after the drug withdrawal.
Experimental result shows, returns spleen composition of medicine I group and water to carry and returns the spleen composition of medicine can obviously improve the heart rate of arrhythmia dog for 1 group, reduces ARR occurrence frequency, and arrhythmia is had good therapeutical effect.Select arrhythmia Beagle dog as object of study because animal is docile, advantage such as Electrocardioscopy is convenient, its to observed result of experimental effect more near clinical.Bringing out in the ARR experiment with Bealge dog CAL; Observe equally and return spleen composition of medicine I that arrhythmia is had good preventive and therapeutic effect; The result of the animal pathological model that therefore causes with arrhythmia dog and medicine or operation is the same, and is equally objective and accurate to the role of evaluation of antiarrhythmic drug. and be easy to estimate curative effect.
Embodiment 6 returns spleen composition of medicine I that the activity of rat gastrointestinal tract dysfunction is investigated
The gastrointestinal tract neurosis is called functional gastrointestinal disorder again, clinical diarrhoea, constipation, stomachache and the alternating diarrhea and constipation of mainly showing as of functional gastrointestinal disorder disease; And with anorexia, asthenia, become thin and 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, the parasympathetic nervous system hyperfunctioning causes the autonomic nervous system functional disorder; And then impelling functional gastrointestinal disorder, the reserpine lumbar injection of doses can make rat the performance of clinical functional gastrointestinal disorder disease occur.
Motilin (MTL) is a kind of important braingut petide hormone, mainly is distributed in brain and jejunum, has the adjusting gastric motility, promotes the effect of gastric emptying.The MTL deficiency can cause the gastrointestinal smooth muscle relaxation, stomach tension force and wriggle weakness, and the gastric emptying time prolongs; The liquid retention increases, and shrinks when hungry to disappear, and intestinal motility weakens; Intestinal is to xylose and amino acid whose malabsorption, and exocrine pancreatic function and gallbladder concentrate symptoms such as reaching the contractile function inhibition.The research proof; Dynamic observe the Changing Pattern of functional gastrointestinal disorder rat model MTL, find to show as watery diarrhea at early stage (less than the 6d) of modeling process, the normal matched group of its MTL content obviously increases; And late period, symptom of diarrhea disappeared; During feces viscous, its content then obviously descends, and explains that functional gastrointestinal disorder and MTL changes of contents are closely related.
The healthy male rat is divided into following 5 groups at random by designing requirement, 20 every group: the normal control group: intraperitoneal injection of saline 5ml/ (kgd), irritate clothes distilled water 5ml/ (kgd) simultaneously; Functional gastrointestinal disorder model group: lumbar injection reserpine 0.5mg/ (kgd) irritates clothes distilled water 5ml/ (kgd) simultaneously; Return spleen composition of medicine I group: lumbar injection reserpine 0.5mg/ (kgd); Irritate clothes simultaneously and contain normal saline (the crude drug amount 2.5g that returns spleen composition of medicine I; Down with)/(kgd): water is carried and is returned 1 group of spleen composition of medicine: lumbar injection reserpine 0.5mg/ (kgd), irritate clothes simultaneously and contain water and carry the normal saline of returning spleen composition of medicine 1; Commercially available GUIPI WAN group: lumbar injection reserpine 0.5mg/ (kgd) irritates the normal saline that clothes contain commercially available GUIPI WAN group simultaneously; Commercially available Renshen Guipi Wan amount group: lumbar injection reserpine 0.5mg/ (kgd) irritates the normal saline that clothes contain commercially available Renshen Guipi Wan amount group, successive administration 14d simultaneously.Get half zoopery detection for every group during 6d, get second half zoopery during 14d again and detect.Food ration, body weight and the feces situation of observation every day during the administration, record rat.
Detecting index and method is: each is organized rat experiment and detects preceding fasting 18h; 1. motilin (MTL) content detection in blood plasma and the narrow intestinal tissue: by the requirement of MTL radioimmunity test kit; Each organize the rat eye socket get blood 2ml in 30 μ L aprotiniies (; 30ml 10%EDTA is in pipe, and 4 ℃ centrifugal, and-70 ℃ store survey fully; After taking off cervical vertebra execution rat, get the jejunum tissue homogenate immediately, 3500r/min is centrifugal, draws supernatant, and-70 ℃ store survey fully; The assay method by specification carries out.2. local intestinal tissue pathologic finding: 3 rats of every group of picked at random, the perusal gastrointestinal tract changes, and leaves and takes gastrointestinal tissue and does pathologic finding, to get rid of the intestinal mucosa inflammatory lesion.
Experimental result adopts the t check, the expression with
.Concrete outcome is as shown in table 8.
The dynamic amount dynamic change of MTL in table 8 rat plasma and the jejunum tissue (
n=10)
Annotate: with the model group ratio, * P ﹤ 0.05, * * P ﹤ 0.01;
The model group rat feces occurs in the 24h behind the injection reserpine shapeless, and the diarrhoea, the crissum that occur successively in various degree are filthy, occur appetite thereupon and descend; During 6d the loose stool more so, the loose stool stops gradually during 9d, feces viscous is not well; Even constipation, anorexia appear, become thin and day by day increase the weight of.Returning spleen composition of medicine I to organize indivedual rats, water carries and returns the most rats of 1 group of minority rat of spleen composition of medicine, commercially available GUIPI WAN group and commercially available Renshen Guipi Wan above-mentioned symptom to occur; And said four groups of performance degree are light than the model group rat; Rats in normal control group health is not seen any unusual as before.It is no abnormal that each organizes the perusal of rat gastrointestinal tract mucosa, and pathologic finding is not seen yet has tangible inflammatory lesion.In sum; Returning the spleen composition of medicine can regulate the gut hormone of experimental functional gastrointestinal disorder rat, significantly improve its gastrointestinal dysfunction symptom, is one of mechanism of action of this this disease of side's treatment; As for the approach of this side's adjusting gut hormone, still need and do further to inquire into.
Embodiment 7 returns spleen composition of medicine II that the activity of bradycardia rat is investigated
Adopt embodiment 3 described methods to investigate, return spleen composition of medicine II group and water to carry and return 2 groups of spleen composition of medicine; The general state of each treated animal in modeling, medication observed; Detecting ECG; The changes of contents of cAMP in plasma and cGMP.Experimental data adopts SPSS 14.0 statistical softwares to handle, and all data all adopt mean ± standard deviation
expression.
Administration the 14th day, 1h writes down the clear-headed back of rat standard II lead electrocardiogram with ether light anaesthesia rat extremity subcutaneous implantation electrode under it after the administration.Organized rat skin lower injection with clonidine hydrochloride 2mg/kg to each on the 15th day, and the while gastric infusion, 0.5h, lh, 1.5h, 2h electrocardiosignal behind the record filling stomach, statistical analysis rat heart rate, the rhythm of the heart, atrioventricular block situation of change.
Return spleen composition of medicine II group and water to carry and return 2 groups of influences of spleen composition of medicine as shown in table 9 bradycardia rat heart rate; The result shows, returns spleen composition of medicine II group, water to carry to return 2 groups of spleen composition of medicine, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan amount group and sets upright and help arteries and veins decoct group can improve bradyarrhythmia rat heart rate.
Table 9 is respectively organized the rat rhythm of the heart relatively
Annotate: compare with model group:
△P ﹤ 0.05,
▲P ﹤ 0.01; Compare with blank control group:
◇P ﹤ 0.05,
◆P ﹤ 0.01;
After experiment finished, broken end was got blood, is taken out heart immediately, prepares myocardium homogenate, pressed the test kit regulation and detected cAMP and cGMP content in the myocardium homogenate.
As shown in table 10; Each group is compared; Return spleen composition of medicine II group, water to carry to return 1 group of spleen composition of medicine, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan group and set upright and help arteries and veins decoct group cAMP content to be improved, the cGMP level all has decline, especially to return spleen side's composition of medicine II group remarkable.
Table 10 is respectively organized the comparison
of the concentration of rat plasma cAMP and cCMP
Annotate: compare with model group:
△P ﹤ 0.05,
▲P ﹤ 0.01; Compare with blank control group:
◇P ﹤ 0.05,
◆P ﹤ 0.01;
The result shows that yang blood and qi, the deficiency and excess good and evil of returning spleen composition of medicine II can promote the body internal organs tend to be balanced gradually, improves the disorderly interior environment of yang deficiency rat, impels the yang deficiency rat to normal development.The bradycardia rat cardiac function and the myocardial cell metabolism of returning spleen composition of medicine II to improve to cause by deficiency of heart-YANG and kidney-YANG, help promoting the heart sinuatrial node nutriture, improve sinus node function, be to improve cardiac function, the bradycardic effective preparation of treatment.
Embodiment 8 returns spleen composition of medicine II that the activity of tachycardia rat is investigated
Adopting embodiment 4 described methods investigations to return spleen composition of medicine II and water to carry returns 2 groups of experimental results of spleen composition of medicine to see shown in table 11, the table 12.
Table 11 returns the anti-aconitine of spleen composition of medicine II to bring out the result
of ventricular tachycardia
Table 12 returns the anti-aconitine of spleen composition of medicine II to bring out the result
of ventricular tachycardia
Can know that by experimental result return spleen composition of medicine II that drug-induced arrhythmia is had stronger inhibitory action, when effective dose, electrocardio keeps normal condition not have any variation always; The rhythm of the heart is rather irritated accidental ventricular premature contraction of stomach group or premature ventricular beat, disappears after a time, and it is normal that the rhythm of the heart recovers.The result also shows, returns spleen composition of medicine II to be superior to other drug at continuous action on the time.
Aconitine causes that ARR main mechanism is: activated the sodium channel of myocardial cell, made the sodium channel open, accelerated myocardial cell Na
+Interior stream impels the cell membrane depolarization, accelerates the Pacemaker cardiac self-disciplining, brings out the ectopic rhythm point, can form the polyphyly ectopic rhythm, shortens myocardium refractory stage, and causes arrhythmia.Experimental result shows, returns spleen composition of medicine II can suppress the arrhythmia that is caused by aconitine effectively.
Cardiac glycoside medicine (like cedilanid) can suppress Na on the myocardial cell membrane when poisoning
+-K
+-ATP enzyme, thus K reduced
+To intracellular active transport, cause lacking in the cell K
+, the maximum diastolic potential of cardiac muscle is reduced, the relaxing period spontaneous depolarization speeds up, and self-disciplining raises, and arrhythmia takes place.Adopt several kinds of different drug to bring out dissimilar arrhythmia and can simulate clinical symptoms effectively, the curative effect of reflection medicine.The result shows, returns spleen composition of medicine II can prevent and treat arrhythmia effectively.
Embodiment 9 returns spleen composition of medicine II that the activity of Beagle dog arrhythmia is investigated
Adopt embodiment 5 described methods to investigate to return spleen composition of medicine II group (A group) and water to carry and return 2 groups of spleen composition of medicine (B group), conclusion such as table 12,13 said.Observe behind the medicine 1,3,5,7,8,9, the electrocardiogram of 2d after l1,13,15,17d and the 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 is returned the influence of spleen composition of medicine II to arrhythmia Beagle dog P-R interval and heart rate
Table 14 is returned the influence of spleen composition of medicine II to arrhythmia Beagle dog R-R periodic inequality (s)
*Decline percentage rate: R-R periodic inequality behind R-R periodic inequality-medicine before the medicine
Visible by table 13, before the P-R interval medicine>0.12 second, 3d rises to 17d behind the medicine has improvement, and P-R asks all < 0.12 second, and last till 2d after drug withdrawal phase.Return spleen composition of medicine II group and water to carry and return 2 groups of hearts rate that all can improve the arrhythmia dog of spleen composition of medicine; 9d plays efficacy stability behind the medicine; And keep a period of time and level: and ECG P ripple, Q cross, R ripple, S ripple, QRS interval, Q-T interval, no matter return spleen composition of medicine II group or water to carry and return the spleen composition of medicine all not have obvious influence for 2 groups.
Visible by table 14, before the administration, the R-R periodic inequality of four dogs is 0.48～0.53s, is far longer than 0.16s, and ld rises behind the medicine, and the R-R periodic inequality of 2 dose groups all begins to shorten, and 0.48～0.53s before medicine reduces to 040s, and its range of decrease is 15%～25%; 5～11d behind the medicine, the R-R periodic inequality all obviously shortens, and reduces to 0.20～0.27 second, and the range of decrease is 44～62%; 13～15d behind medicine, the R-R periodic inequality is near normal (near 016s), and returning spleen composition of medicine II group 13d behind medicine is 0.16s; Water is carried and returned 2 groups of spleen composition of medicine 15d behind medicine is 0.17s.Two groups are respectively 0.20s and 0.08s behind the drug withdrawal 2d, and its range of decrease is respectively 65% and 84%.
Table 15 returns spleen composition of medicine II to the influence in (long R-R cycle/10 a R-R cycle) of arrhythmia Beagle dog rhythm of the heart occurrence frequency
Visible by table 15, before the administration, four ARR occurrence frequencies of dog are 10 R-R in the cycle, 4 long R-R cycles occur.3-5d rises behind the medicine, returns spleen composition of medicine II group and water to carry and returns 2 groups of spleen composition of medicine all to begin to reduce, and is 2-3.5; 7-13d obviously reduces behind the medicine, is 1.5-2.5; 15-17d is kept to 1-2 behind the medicine, and drug withdrawal 2d reduces to 1, explains that returning spleen composition of medicine II group to carry with new water returns spleen side's composition of medicine can obviously reduce ARR occurrence frequency for 2 groups, and can keep certain hour after the drug withdrawal.
Experimental result shows, returns spleen composition of medicine II group and water to carry and returns the spleen composition of medicine can obviously improve the heart rate of arrhythmia dog for 2 groups, reduces ARR occurrence frequency, and arrhythmia is had good therapeutical effect.Select arrhythmia Beagle dog as object of study because animal is docile, advantage such as Electrocardioscopy is convenient, its to observed result of experimental effect more near clinical.Bringing out in the ARR experiment with Bealge dog CAL; Observe equally and return spleen composition of medicine II that arrhythmia is had good preventive and therapeutic effect; The result of the animal pathological model that therefore causes with arrhythmia dog and medicine or operation is the same; Role of evaluation to antiarrhythmic drug is same objective and accurate, and is easy to estimate curative effect.
Embodiment 10 returns spleen composition of medicine II that the activity of rat gastrointestinal tract dysfunction is investigated
Adopt embodiment 6 described methods, investigation is returned spleen composition of medicine II group and water to carry and is returned 2 groups of effects to the rat gastrointestinal tract dysfunction of spleen composition of medicine, and concrete outcome is shown in table 16.
The dynamic amount dynamic change of MTL in table 16 rat plasma and the jejunum tissue (
n=10)
Annotate: with the model group ratio, * P ﹤ 0.05, * * P ﹤ 0.01;
The model group rat feces occurs in the 24h behind the injection reserpine shapeless, and the diarrhoea, the crissum that occur successively in various degree are filthy, occur appetite thereupon and descend; During 6d the loose stool more so, the loose stool stops gradually during 9d, feces viscous is not well; Even constipation, anorexia appear, become thin and day by day increase the weight of.Return spleen composition of medicine II group minority rat, water to carry and return the most rats of 2 groups of minority rats of spleen composition of medicine, commercially available GUIPI WAN group and commercially available Renshen Guipi Wan above-mentioned symptom to occur; And said four groups of performance degree are light than the model group rat; Rats in normal control group health is not seen any unusual as before.It is no abnormal that each organizes the perusal of rat gastrointestinal tract mucosa, and pathologic finding is not seen yet has tangible 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 mechanism of action of this this disease of side's treatment; As for the approach of this side's adjusting gut hormone, still need and do further to inquire into.
Embodiment 11 returns spleen composition of medicine III that the activity of bradycardia rat is investigated
Adopt embodiment 3 described methods to investigate, return spleen composition of medicine III group and water to carry and return 3 groups of spleen composition of medicine; The general state of each treated animal in modeling, medication observed; Detecting ECG; The changes of contents of cAMP in plasma and cGMP.Experimental data adopts SPSS 14.0 statistical softwares to handle, and all data all adopt mean ± standard deviation
expression.
Administration the 14th day, 1h writes down the clear-headed back of rat standard II lead electrocardiogram with ether light anaesthesia rat extremity subcutaneous implantation electrode under it after the administration.Organized rat skin lower injection with clonidine hydrochloride 2mg/kg to each on the 15th day, and the while gastric infusion, 0.5h, lh, 1.5h, 2h electrocardiosignal behind the record filling stomach, statistical analysis rat heart rate, the rhythm of the heart, atrioventricular block situation of change.
Return spleen composition of medicine III group and water to carry and return 3 groups of influences of spleen composition of medicine shown in table 17 bradycardia rat heart rate; The result shows, returns spleen composition of medicine III group, water to carry to return 3 groups of spleen composition of medicine, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan amount group and sets upright and help arteries and veins decoct group can improve bradyarrhythmia rat heart rate.
Table 17 is respectively organized the rat rhythm of the heart relatively
Annotate: compare with model group:
△P ﹤ 0.05,
▲P ﹤ 0.01; Compare with blank control group:
◇P ﹤ 0.05,
◆P ﹤ 0.01;
After experiment finished, broken end was got blood, is taken out heart immediately, prepares myocardium homogenate, pressed the test kit regulation and detected cAMP and cGMP content in the myocardium homogenate.
Shown in table 18; Each group is compared; Return spleen composition of medicine III group, water to carry to return 1 group of spleen composition of medicine, commercially available GUIPI WAN group, commercially available Renshen Guipi Wan group and set upright and help arteries and veins decoct group cAMP content to be improved, the cGMP level all has decline, especially to return spleen composition of medicine III group remarkable.
Table 18 is respectively organized the comparison
of the concentration of rat plasma cAMP and cCMP
Annotate: compare with model group:
△P ﹤ 0.05,
▲P ﹤ 0.01; Compare with blank control group:
◇P ﹤ 0.05,
◆P ﹤ 0.01;
The result shows that yang blood and qi, the deficiency and excess good and evil of returning spleen composition of medicine III can promote the body internal organs tend to be balanced gradually, improves the disorderly interior environment of yang deficiency rat, impels the yang deficiency rat to normal development.The bradycardia rat cardiac function and the myocardial cell metabolism of returning spleen composition of medicine III to improve to cause by deficiency of heart-YANG and kidney-YANG, help promoting the heart sinuatrial node nutriture, improve sinus node function, be to improve cardiac function, the bradycardic effective preparation of treatment.
Embodiment 12 returns spleen composition of medicine III that the activity of tachycardia rat is investigated
Adopting embodiment 4 described methods investigations to return spleen composition of medicine III and water to carry returns 3 groups of experimental results of spleen composition of medicine to see shown in table 19, the table 20.
Table 19 returns the anti-aconitine of spleen composition of medicine III to bring out the result
of ventricular tachycardia
Table 20 returns the anti-aconitine of spleen composition of medicine III to bring out the result
of ventricular tachycardia
Can know that by experimental result return spleen composition of medicine III that drug-induced arrhythmia is had stronger inhibitory action, when effective dose, electrocardio keeps normal condition not have any variation always; The rhythm of the heart is rather irritated accidental ventricular premature contraction of stomach group or premature ventricular beat, disappears after a time, and it is normal that the rhythm of the heart recovers.The result also shows, returns spleen composition of medicine III to be superior to other drug at continuous action on the time.
Aconitine causes that ARR main mechanism is: activated the sodium channel of myocardial cell, made the sodium channel open, accelerated myocardial cell Na
+Interior stream impels the cell membrane depolarization, accelerates the Pacemaker cardiac self-disciplining, brings out the ectopic rhythm point, can form the polyphyly ectopic rhythm, shortens myocardium refractory stage, and causes arrhythmia.Experimental result shows, returns spleen composition of medicine III can suppress the arrhythmia that is caused by aconitine effectively.
Cardiac glycoside medicine (like cedilanid) can suppress Na on the myocardial cell membrane when poisoning
+-K
+-ATP enzyme, thus K reduced
+To intracellular active transport, cause lacking in the cell K
+, the maximum diastolic potential of cardiac muscle is reduced, the relaxing period spontaneous depolarization speeds up, and self-disciplining raises, and arrhythmia takes place.Adopt several kinds of different drug to bring out dissimilar arrhythmia and can simulate clinical symptoms effectively, the curative effect of reflection medicine.The result shows, returns spleen composition of medicine III can prevent and treat arrhythmia effectively.
Embodiment 13 returns spleen composition of medicine III that the activity of Beagle dog arrhythmia is investigated
Adopt embodiment 5 described methods investigations to return spleen composition of medicine III group (A group) and water to carry and return 3 groups of spleen composition of medicine (B group), conclusion is like table 20, shown in 21.Observe behind the medicine 1,3,5,7,8,9, the electrocardiogram of 2d after l1,13,15,17d and the 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 is returned the influence of spleen composition of medicine III to arrhythmia Beagle dog P-R interval and heart rate
Table 22 is returned the influence of spleen composition of medicine III to arrhythmia Beagle dog R-R periodic inequality (s)
*Decline percentage rate: R-R periodic inequality behind R-R periodic inequality-medicine before the medicine
Visible by table 21, before the P-R interval medicine>0.12 second, 3d rises to 17d behind the medicine has improvement, and P-R asks all < 0.12 second, and last till 2d after drug withdrawal phase.Return spleen composition of medicine III group and water to carry and return 3 groups of hearts rate that all can improve the arrhythmia dog of spleen composition of medicine, 9d plays efficacy stability behind the medicine, and keeps a period of time and level; And ECG P ripple, Q cross, R ripple, S ripple, QRS interval, Q-T interval, no matter return spleen composition of medicine III group or water to carry and return spleen side's composition of medicine all not have obvious influence for 3 groups.
Visible by table 22, before the administration, the R-R periodic inequality of four dogs is 0.48～0.53s, is far longer than 0.16s, and ld rises behind the medicine, and the R-R periodic inequality of 2 dose groups all begins to shorten, and 0.48～0.53s before medicine reduces to 040s, and its range of decrease is 15%～25%; 5～11d behind the medicine, the R-R periodic inequality all obviously shortens, and reduces to 0.20～0.27 second, and the range of decrease is 44～62%; 13～15d behind medicine, the R-R periodic inequality is near normal (near 016s), and returning spleen composition of medicine III group 13d behind medicine is 0.16s; Water is carried and returned 1 group of spleen composition of medicine 15d behind medicine is 0.17s.Two groups are respectively 0.20s and 0.08s behind the drug withdrawal 2d, and its range of decrease is respectively 61% and 84%.
Table 23 returns spleen composition of medicine III to the influence in (long R-R cycle/10 a R-R cycle) of arrhythmia Beagle dog rhythm of the heart occurrence frequency
Visible by table 23, before the administration, four ARR occurrence frequencies of dog are 10 R-R in the cycle, 4 long R-R cycles occur.3-5d rises and returns spleen composition of medicine III group and water to carry to return 3 groups of spleen side's composition of medicine all to begin to reduce behind the medicine, is 2-3.5; 7-13d obviously reduces behind the medicine, is 1.5-2.5; 15-17d is kept to 1-2 behind the medicine, and drug withdrawal 2d reduces to 1, explains that returning spleen composition of medicine III group and water to carry returns the spleen composition of medicine can obviously reduce ARR occurrence frequency for 3 groups, and can keep certain hour after the drug withdrawal.
Experimental result shows, returns spleen composition of medicine III group and water to carry and returns the spleen composition of medicine can obviously improve the heart rate of arrhythmia dog for 3 groups, reduces ARR occurrence frequency, and arrhythmia is had good therapeutical effect.Select arrhythmia Beagle dog as object of study because animal is docile, advantage such as Electrocardioscopy is convenient, its to observed result of experimental effect more near clinical.Bringing out in the ARR experiment with Bealge dog CAL; Observe equally and return spleen composition of medicine III group that arrhythmia is had good preventive and therapeutic effect; The result of the animal pathological model that therefore causes with arrhythmia dog and medicine or operation is the same; Role of evaluation to antiarrhythmic drug is same objective and accurate, and is easy to estimate curative effect.
Embodiment 14 returns spleen composition of medicine III that the activity of rat gastrointestinal tract dysfunction is investigated
Adopt embodiment 6 described methods, investigate and return spleen composition of medicine III group and water to carry to return 3 groups of concrete outcomes of spleen composition of medicine shown in table 24.
The dynamic amount dynamic change of MTL in table 24 rat plasma and the jejunum tissue (
n=10)
Annotate: with the model group ratio, * P ﹤ 0.05, * * P ﹤ 0.01;
The model group rat feces occurs in the 24h behind the injection reserpine shapeless, and the diarrhoea, the crissum that occur successively in various degree are filthy, occur appetite thereupon and descend; During 6d the loose stool more so, the loose stool stops gradually during 9d, feces viscous is not well; Even constipation, anorexia appear, become thin and day by day increase the weight of.Returning the several individually rats of spleen composition of medicine III group, water to carry returns the most rats of 3 groups of minority rats of spleen composition of medicine, commercially available GUIPI WAN group and commercially available Renshen Guipi Wan above-mentioned symptom to occur; And said four groups of performance degree are light than the model group rat; Rats in normal control group health is not seen any unusual as before.It is no abnormal that each organizes the perusal of rat gastrointestinal tract mucosa, and pathologic finding is not seen yet has tangible 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 mechanism of action of this this disease of side's treatment; As for the approach of this side's adjusting gut hormone, still need and do further to inquire into.
Claims (8)
1. return the spleen composition of medicine for one kind, it is characterized in that: the crude drug or the extract that comprise following medical material: Radix Pseudostellariae, the Radix Astragali and Radix Polygalae.
2. the spleen composition of medicine of returning according to claim 1 is characterized in that: the said spleen side's composition of medicine of returning is made up of the crude drug or the extract of following medical material: 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.
3. the spleen composition of medicine of returning according to claim 2 is characterized in that: the weight ratio that said 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 are formed 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.
4. the spleen composition of medicine of returning according to claim 3 is characterized in that: the weight ratio that said 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 are formed is 2:2:4:1:4:4:4:1:4:4:4:4.
5. the spleen composition of medicine of returning according to claim 3; It is characterized in that: said 20-95% ethanol extraction of returning spleen side's composition of medicine by 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 of the Rhizoma Atractylodis Macrocephalae and the Radix Aucklandiae mix to be formed.
6. method for preparing of returning the spleen composition of medicine is characterized in that: said method is extracted Radix Pseudostellariae, Radix Glycyrrhizae, the Radix Astragali, Poria and Radix Polygalae for adopt methods such as backflow, warm macerating, percolation to extract respectively as solvent with 20-95% ethanol;
With water is that solvent adopts warm macerating, backflow, decocting method that Arillus Longan, Semen Ziziphi Spinosae, Radix Rehmanniae Preparata, Radix Angelicae Sinensis and Fructus Jujubae are extracted;
Employing has steam distillation, solvent refluxing method, microwave method, supercritical fluid extraction that the volatile oil of the Rhizoma Atractylodis Macrocephalae and the Radix Aucklandiae is extracted;
Merge the said extracted thing and obtain being used to treat arrhythmia and the neurosal spleen side's composition of medicine of returning of gastrointestinal tract.
7. the arbitrary described application of spleen composition of medicine in preparation treatment arrhythmia disease medicine of returning of claim 1-6.
8. the arbitrary described application of spleen composition of medicine in preparation treatment gastrointestinal tract neurosis medicine of returning of claim 1-6.
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| 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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| 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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