CN1281212C - General saponin of stem and leaf of American ginseng in Application of preparing medication for treating mycoarditis - Google Patents
General saponin of stem and leaf of American ginseng in Application of preparing medication for treating mycoarditis Download PDFInfo
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Abstract
The present invention relates to the application of a general saponin of American genseng stem and leaf to the preparation of medicine for treating myocarditis, which belongs to the field of the medicinal application of the effective ingredients of traditional Chinese medicine. The present invention has the purpose of applying the general saponin of American genseng stem and leaf to the preparation of medicine for treating myocarditis. The prepared medicine can not only improve myocardial metabolism, nourish the myocardium, protect heart cells and increase the disease resistance of the myocardium, but also directly kill viruses, relieve the damage of viruses to the myocardium and the side effect of western medicine applied for a long term to a human body, and realize the acting effect of combining virus resistance and integral regulation, so the medicine becomes ideal medicine for treating myocarditis. A medicinal composition containing the general saponins of American genseng stem and leaf can also be prepared.
Description
Technical field
The invention belongs to the medical usage field of effective components of Chinese medicinal.
Background technology
Myocarditis is meant myocardium limitation or diffuse acute or chronic inflammatory disease pathological changes, can be divided into infectious and non-infectious two big classes.Infectious myocarditis can be caused that non-infectious myocarditis then comprises allergy or allergy myocarditis by virus, antibacterial, spirillum, rickettsia, mycete, protozoon, anthelmintic, as myocarditis of rheumatism and chemical factors or drug-induced etc.Myocarditic symptom weight differs, and varying degree is in a bad way.But the lighter's no conscious sympton; Severe patient can show as sudden death, severe arrhythmia, cardiogenic shock or heart failure, causes acute stage death; Also can show as various arrhythmia, pericarditis or acute myocardial infarction etc.Viral myocarditis is the class myocarditis the most common clinically, that number of the infected is maximum, has popularity, risen more than 10 times than sickness rate before 10 years now, become the modal cardiomyopathy of China, pilosity be born among the crowd viral infection popular in, have 5% patient cause viral myocarditis approximately on the virus infected flow departure date.In recent years, the understanding of viral myocarditis is constantly deepened.Can cause that myocarditic virus is a lot, as: Coxsackie virus, adenovirus, influenza virus or the like, wherein the myocarditis that causes with change of coxsackie b virus is especially seen at most, because cardiac muscle is responsive especially to this virus performance, myocardium has special affinity to this virus.After the patient infection Coxsackie virus, 5% the heart that involves is arranged approximately.Focal necrosis all can take place in heart myocardial cell everywhere; With inflammatory cell infiltration, mainly be mononuclear cell in the necrosis region, neutrophilic granulocyte is also arranged sometimes, inflammatory cell reaction sometimes is not obvious.Necrosis region finally replaces for fibrosis, and the clinical manifestation of children virus myocarditis is grown up serious.Viral myocarditis does not have specific treatment so far, and modern medicine generally all is to adopt to suit the medicine to the illness and supporting treatment.Be mainly and alleviate the heart burden, take a good rest and nutrition; Simultaneously carry out symptomatic treatment at symptoms such as the heart failure that occurs, arrhythmia, and cardiac nutrition, the myocardial metabolism of improving, adrenocortical hormone used sometimes.After the increased in acute viral myocarditis, usually need convalescent treatment for a long time, half a year at least, have in addition 1-2, or longer a period of time.Recent study is found, utilizes combination of Chinese and Western medicine method treatment viral myocarditis to be subjected to gratifying effect.Therefore, Chinese medicine is for the improvement of viral myocarditis at symptom control, cardiac function, and the recovery of cardiac muscle and the adjusting aspect of whole machine body function have obtained the approval of extensive patients.
Radix Panacis Quinquefolii (Panax quinquefolium Linn.) is the araliaceae ginseng plant.Radix Panacis Quinquefolii is a valuable ingredient of Chinese medicine, and stem and leaf of Radix Panacis Quinquefolii total saponins of the present invention obtains by following method: with Radix Panacis Quinquefolii stem, leaf is raw material, crosses D type macroporous resin column by decocting liquid, obtains with 30～95% ethanol elution again, wherein contains R
0, R
B1, R
B2, R
B3, Rc, Rd, Re, Rg
1, Rg
2, Rg
3, Rh
1, Rh
2, F
2, RA
0, F
11Etc. plurality of active ingredients.
Summary of the invention
The purpose of this invention is used the myocarditic medicine of stem and leaf of Radix Panacis Quinquefolii total saponins preparation treatment exactly; the medicine of making can not only improve the resistance against diseases of myocardial metabolism, cardiac nutrition, protection heart cell raising cardiac muscle; and energy direct killing virus; alleviate virus to induced myocardial injury; play antiviral and the integrally-regulated action effect that combines; alleviate the Western medicine prolonged application to the side effect that human body produces, make it become the ideal myocarditic medicine that is used for the treatment of.Also can be made into the pharmaceutical composition that contains the stem and leaf of Radix Panacis Quinquefolii total saponins, this pharmaceutical composition can be one or more active component natural or chemosynthesis, also can be the pharmaceutical composition that one or more Chinese crude drugs or its active component and stem and leaf of Radix Panacis Quinquefolii total saponins are formed.
When the present invention was used for the myocarditic medicine of preparation treatment, its oral or non-oral administration all was safe.Under oral situation, it can be any conventionally form administration, as powder, granule, tablet, capsule, pill, drop pill, soft capsule, leafing agent, oral liquid, suspension, syrup, buccal tablets, sublingual lozenge, spray etc.; When the non-oral administration of this medicine, can adopt any conventionally form, as suppository, injection: as intravenous injection, intramuscular injection, ointment, inhalant etc.
It is to be made of effective site or the plurality of active ingredients monomer excipient with solid or liquid that the present invention prepares the myocarditic medicine of treatment, the excipient of solid used herein or liquid is well known in the art, lift several object lessons below, the excipient of solid preparation has lactose, starch, paste essence, calcium carbonate, synthetic or puritan filler aluminum, magnesium oxide, magnesium stearate, sodium bicarbonate, dry yeast etc.; The excipient of liquid preparation has water, glycerol, propylene glycol, simple syrup, ethanol, ethylene glycol, Polyethylene Glycol, Sorbitol etc.; The excipient of ointment can use fatty oil, and agnolin, vaseline, glycerol, Cera Flava, wood are cured, white oil, resin, senior water-repelling agent or the hydrophilizing agent that is combined into such as cured.
The dosage of active substance can be according to the mode of taking, patient's age and body weight and be in a bad way degree and other similar factor and change, and oral dose is: 20-1000mg/ people, take for three times every day: the injection consumption is 10～1000mg/ people, once a day.
Its therapeutic effect is by the inhibitory action of stem and leaf of Radix Panacis Quinquefolii total saponins to Coxsackie virus, and alleviate arrhythmia, increase anti-cardiomyopathy ability, improve blood circulation, protecting myocardial cell is avoided damaging etc. is used for realizing.Dosage is 7.5-140mg/kg, successive administration 5-10 days.
The present invention can further specify by following experimental example.
Experimental example 1: to the pathological changes caused by virus protective effect
(1) experiment material
Medicine: stem and leaf of Radix Panacis Quinquefolii total saponins, positive control drug are the Radix Astragali.
Cell strain: cervical cancer cell Hela
Strain: Coxsackie B virus
3Strain (CVB
3) Coxsackie B virus
4Strain (CVB
4), coxsackie virus A 16 (CVA16), enterovirus E71 strain.
(2) test method and result
On cell, add 10 respectively
-1-10
-64 kinds of viral liquid of variable concentrations, flush away virus liquid adds nontoxic boundary medicinal liquid behind the absorption 1h, and each viral dilution degree respectively adds 3 multiple holes, establishes virus control, cell contrast, positive drug matched group simultaneously.Put 37 ℃ of CO
2Cultivate in the incubator, observe pathological changes every day under inverted microscope, and 4d writes down each hole pathological changes situation continuously.The results are shown in Table 1.
Table 1 pair pathological changes caused by virus effect
| Strain | Radix Astragali 6.25g/L | Stem and leaf of Radix Panacis Quinquefolii total saponins 1.562g/L | The cell contrast | Virus control |
| CVA16 enterovirus E71 CVB 3CVB 4 | ± + ± + | ± - + ± | - - - - | ++++ ++++ ++++ ++++ |
Annotate :-acellular pathological changes shown; ± be shown with and delay cytopathic effect; + show the cytopathy below 1/4; ++ the cell that shows 1/4-1/2 has pathological changes; +++show, the cell of 1/2-3/4 had pathological changes; ++ ++ show that the cell more than 3/4 has pathological changes.
The result shows in the table, and the stem and leaf of Radix Panacis Quinquefolii total saponins can the obvious suppression Coxsackie B virus
4And coxsackie virus A 16, to Coxsackie B virus
3Effect slightly a little less than, to enterovirus E71 unrestraint effect.
Experimental example 2: to the influence of mice viral myocarditis
(1) test material
Animal: the Swiss mice, male and female half and half, in age in 3-4 week, 16-18g is provided by the Bethune of Jilin University medical board Experimental Animal Center.
Medicine: stem and leaf of Radix Panacis Quinquefolii total saponins, positive control drug are the Radix Astragali.
(2) test method and result
Inoculation contains 10 through the abdominal cavity with mice
4TCID
50CVB
3Liquid 0.2ml, behind the 1h, gastric infusion, two weeks of successive administration.The virus of model control group mouse inoculation same dose irritates stomach, continuous two weeks for every day the normal saline of same dose.After the last administration, pluck eyeball and get blood, separation of serum is measured myocardium three enzyme glutamic oxaloacetic transaminase, GOT AST, creatine phosphokinase CK, lactate dehydrogenase L DH.The results are shown in Table 2.
The influence of table 2 pair mice viral myocarditis cardiac muscle three enzymes (X ± s)
| Group | Dosage | Animal | AST(U/L) | CK(U/L) | LDH(U/L) |
| The virus control normal control stem and leaf of Radix Panacis Quinquefolii total saponins Radix Astragali | 75mg/kg 38mg/kg 19mg/kg 13g/kg | 10 10 10 10 10 10 | 499.13±126.44 203.3±56.34 *289.38±47.42 *205.89±41.1 *321.5±86.42 *271.17±138.36 | 3215.0±1610.99 892.14±526.04 *784.78±306.92 **245.89±142.10 **791.63±447.37 **632.85±564.11 ** | 2367.75±179.84 1707±164.52 1855.25±108.92 *1687.63±124.95 **1963.50±116.80 *1697.17±171.62 |
Annotate: with virus control group ratio
*P＜0.05,
*P＜0.01
The result shows in the table 2, and the stem and leaf of Radix Panacis Quinquefolii total saponins can significantly reduce myocardium three enzymes in the myocarditis animal pattern blood, has the effect of treatment viral myocarditis.
Experimental example 3: barium chloride is caused the influence of rat ventricular
(1) test material
Medicine: stem and leaf of Radix Panacis Quinquefolii total saponins; The test comfortable cellulose capsule of positive drug, lot number: 941102.Provide by Jilin Province Jian Pharmaceutical Factory.Barium chloride is produced by Kaiyuan chemical reagent factory.
Animal: the wistar rat, body weight 200-250g is available from Jilin Prov. Inst. of Chinese Medicine and Chinese Medical Science animal housing.
(2) test method and result
Get 45 rats, be divided into five groups at random: model group, comfortable cellulose capsule 140mg/kg dosed administration group, stem and leaf of Radix Panacis Quinquefolii total saponins 140,70,35mg/kg dosage group.Every day, gastric infusion twice, and successive administration five days after the last administration 1 hour, in rats by intraperitoneal injection chloral hydrate 300mg/kg anesthesia, is measured normal II lead electrocardiogram.Sublingual vein injection barium chloride 4mg/kg observes electrocardiogram and changes then.Write down that electrocardiogram recovers normal number of animals and arrhythmia persistent period in 20 minutes.The results are shown in Table 3.
Table 3 pair barium chloride causes the influence of rat ventricular
| Group | Number of animals (only) | Electrocardiogram recovers normal percentage rate (%) (X in 20 minutes 2) | The arrhythmia persistent period (min) (X ± s) | |
| The comfortable cellulose capsule stem and leaf of Radix Panacis Quinquefolii of model control group total saponins | 140mg/kg 140mg/kg 70mg/kg 35mg/kg | 8 6 9 9 9 | 12.5 50.0 66.7 * 44.4 22.2 | 18.7±3.54 17.5±2.74 13.1±6.49 * 16.4±6.13 16.7±5.59 |
Annotate: with the model control group ratio
*P＜0.05
The result shows, tachycardia appears behind the rat intravenous injection barium chloride immediately, arrhythmia electrocardiograms such as ventricular premature contraction, the animal of taking the stem and leaf of Radix Panacis Quinquefolii total saponins can make the arrhythmia symptom be eased, recovering normal number of animals in 20 minutes obviously increases, and has shortened the ARR persistent period.
Experimental example 4: isoproterenol is caused the influence of rat heart muscle ischemia
(1) test material
Animal: the wistar rat, body weight 200-250g is available from Jilin Chinese medicine academy animal housing.
Medicine: stem and leaf of Radix Panacis Quinquefolii total saponins; SHENGMAI ZHUSHEYE is produced lot number: 970403 by Pharmacuetical Plant of Huaxi Medical Univ..Isoprenaline Iso injection: produce lot number: 951002 by Shanghai Hefeng Pharmaceutical Co., Ltd..
(2) test method and result
Get 58 rats, be divided into six groups at random: blank group, ischemia model group, SHENGMAI ZHUSHEYE 4.5ml/kg dosed administration group, stem and leaf of Radix Panacis Quinquefolii total saponins 20,10, three dosage groups of 5mg/kg.Once a day, the continuous intravenous injection administration is three days.After the last administration 30 minutes, except that the blank group, the equal subcutaneous injection Iso of all the other animals 8mg/kg was administered once after 24 hours again.Preceding 30 minutes of last administration is Iso 2mg/kg of subcutaneous injection again, animal is anaesthetized with chloral hydrate 300mg/kg in 15 minutes after the last administration.The abdomen venous blood collection, separation of serum is measured CK, AST, LDH activity; With the animal sacrificed by decapitation, take out heart rapidly then, the nose part of coring in 10% formalin fixed, is done the pathology inspection; Other chamber muscular tissue of coring in 0-4 ℃ of homogenate, is measured the wherein active and MDA content of SOD.The results are shown in Table 4,5,6.
Table 4 pair isoproterenol causes the influence (X ± s) of rats with myocardial ischemia cardiac muscle three enzymes
| Group | Number of animals (only) | AST (U/L) | CK (U/L) | LDH (U/L) | |
| Blank group model group SHENGMAI ZHUSHEYE stem and leaf of Radix Panacis Quinquefolii total saponins | 20mg/kg 10mg/kg 5mg/kg | 8 10 10 10 10 10 | 97.5±12.97 172.1±58.89 **118.7±33.29 #115.8±27.93 #114.7±16.42 ##170.6±40.34 | 245.3±124.54 696.4±425.85 *291.9±98.39 ##226.4±171.79 ##201.7±73.71 ##600.7±510.99 | 540.9±313.73 695.7±302.15 663.3±201.62 331.7±180.73 ##417.4±173.71 #544.1±211.46 |
Annotate: compare with the blank group:
*P＜0.05,
*P＜0.01,
* *P＜0.001
Compare with model group: #P＜0.05, ##P＜0.01, ###P＜0.001 following table 5, table 6 are with table 4
By the result as seen, serum center flesh three enzymes obviously raise after myocardial ischemia appearred in animal, and particularly CK and AST are apparently higher than the blank group.Injection stem and leaf of Radix Panacis Quinquefolii total saponins and SHENGMAI ZHUSHEYE can obviously suppress the rising of CK and AST, and Radix Panacis Quinquefolii saponin also can reduce the activity of LDH, shows tangible function of resisting myocardial ischemia.
Table 5 pair isoproterenol causes the influence (X ± s) of the active and MDA content of SOD in the rats with myocardial ischemia cardiac muscle
| Group | Number of animals (only) | SOD (U/g tissue) | MDA (nmol/g tissue) | |
| Blank group model group SHENGMAI ZHUSHEYE stem and leaf of Radix Panacis Quinquefolii total saponins | 20mg/kg 0mg/kg 5mg/kg | 8 10 10 10 10 10 | 100.0±24.71 59.3±27.27 ** 80.8±24.82 90.0±13.66 ## 90.2±23.75 # 81.4±26.49 | 9.4±0.71 12.3±3.69 * 6.8±0.87 ### 6.4±0.74 ### 7.1±1.00 ### 7.4±0.82 ### |
Table 6 stem and leaf of Radix Panacis Quinquefolii total saponins causes the influence of rats with myocardial ischemia cardiac muscle pathological change to isoproterenol
| Group | Number of animals (only) | 0 grade | 1 grade | 2 grades | 3 grades | |
| Blank group model group SHENGMAI ZHUSHEYE stem and leaf of Radix Panacis Quinquefolii total saponins | 20mg/kg 10mg/kg 5mg/kg | 8 10 10 10 10 10 | 8 0 0 0 0 0 | 0 0 0 4 4 2 | 0 3 5 6 6 5 | 0 7 5 0 0 3 |
By the result as seen, the stem and leaf of Radix Panacis Quinquefolii total saponins can obviously strengthen the activity of SOD in the cardiac muscular tissue, reduces the content of MDA; Alleviate the lesion degree of cardiac muscular tissue, suppress the generation of myocardial necrosis.
Experimental example 5: to the influence of hemorheological property
(1) test material
Animal: the wistar rat, body weight 200-250g is available from Jilin Prov. Inst. of Chinese Medicine and Chinese Medical Science animal housing.
Medicine: stem and leaf of Radix Panacis Quinquefolii total saponins; XUESAITONG ZHUSHEYE is produced lot number: 980651-12 by Kunming Medicine Stock Co., Ltd.Adrenalin hydrochloride Adr injection is produced lot number by Mingxing Pharmaceutical Factory, Guangzhou: 961212-1.
(2) test method and result
Get 54 rats, be divided into six groups at random: blank group, blood stasis model group, XUESAITONG ZHUSHEYE 40mg/kg dosed administration group, stem and leaf of Radix Panacis Quinquefolii total saponins 30,15, three dosage groups of 7.5mg/kg.Every day intraperitoneal injection once, continuous four days.After the administration in first day outside the 0.5h blank group, the Adr 0.1ml/ of the equal subcutaneous injection 0.1% of all the other animals only behind the 0.5h places animal 1.5 ℃ of water ice bath 5min, repeat once after 24 hours, every 24 hours, 0.5h injected Adr again one time after the administration in promptly the 3rd day, but does not carry out ice bath again.0.5h,, puts and measures whole blood contrast viscosity (the high value of cutting, the low value of cutting), plasma viscosity, erythrocyte sedimentation rate and packed cell volume on the blood plasma viscometer in the abdomen venous blood collection Animal Anesthesia in animal lumbar injection pentobarbital sodium 35mg/kg after the last administration.The results are shown in Table.
The influence of table 7 pair blood stasis rat blood rheological characteristic (X ± s)
| Group | Number of animals only | Whole blood contrast viscosity (S) | Plasma viscosity (S) | Erythrocyte sedimentation rate (mm/h) | Packed cell volume (%) | ||
| Height is cut | Low cutting | ||||||
| Blank group blood stasis model group XUESAITONG ZHUSHEYE stem and leaf of Radix Panacis Quinquefolii total saponins | 40mg/kg 30mg/kg 15mg/kg 7.5mg/kg | 9 9 9 9 9 9 | 5.15±0.546 6.47±1.099 ** 5.31±1.363 5.17±1.009 # 5.57±1.216 5.69±1.008 | 6.49±1.140 9.03±1.733 ** 6.83±1.441 # 6.77±1.563 # 7.41±2.233 7.67±2.082 | 1.62±0.066 1.67±0.085 1.84±0.123 1.69±0.155 1.64±0.062 1.69±0.064 | 0.94±0.726 1.33±0.500 1.56±0.882 1.33±0.500 1.11±0.601 1.22±0.667 | 36.11±1.764 40.56±2.920 ** 37.89±2.849 38.00±2.626 38.60±3.046 37.60±2.963 |
Annotate: with blank group ratio
*P＜0.01; With the model group ratio
*P＜0.05
As seen table 7 result after the blood stasis symptom appears in animal, shows as blood viscosity and increases, hemorheology index generation abnormal change.And behind the animal injection stem and leaf of Radix Panacis Quinquefolii total saponins, whole blood contrast viscosity reduces, and the rheology abnormal index improves.
Experimental example 6: toxicity
(1) acute toxicity fails to measure the LD of mouse stomach administration because of being limited to stem and leaf of Radix Panacis Quinquefolii total saponins administration volume and administration concentration
50, in a few days to irritate the maximum dosage-feeding of stomach be 30g/kg and measure one, the stem and leaf of Radix Panacis Quinquefolii total saponins is given the LD of mouse mainline
50And 95% the credible 352.5 ± 17.555mg/kg that is limited to.
(2) long term toxicity stem and leaf of Radix Panacis Quinquefolii total saponins is given rat oral gavage with 1.5g-0.75g/kg dosage, and with 2.0,1.0g/kg dosage gives dog oral, continuous 60 days, hematology and blood biochemical were learned every check result and all found no abnormal response.Respectively organize data between administration group and the blank group there are no significant difference; Its main organs is not seen drug-induced tangible pathological change yet.
The effect that The above results proof stem and leaf of Radix Panacis Quinquefolii total saponins and pharmaceutical composition thereof all have multiple viruses such as tangible anti-Coxsackie virus, the stem and leaf of Radix Panacis Quinquefolii total saponins also can suppress ARR generation simultaneously, suppress the generation of myocardial infarction, improve cardiac muscular tissue's pathological changes, improve the effects such as hemorheological property of blood stasis animal.This is for independent application of Radix Panacis Quinquefolii and prescription application of treatment viral myocarditis provide theoretical foundation clinically.
The specific embodiment
Embodiment 1:
Capsule: stem and leaf of Radix Panacis Quinquefolii total saponins 180g, starch 20g, mixing, the capsule of packing into No. 2 is made 1000, specification: the 0.2g/ grain.Become human oral, 1/time, three times on the one, one month is a course of treatment.
Embodiment 2:
Injection: stem and leaf of Radix Panacis Quinquefolii total saponins 200g, add water 7000ml dissolving, sterilization, drying, sterile sealing is made 1000, and specification: 200mg/ props up.Adult's intravenous drip administration, 1/time, be dissolved in the 250ml normal saline, once-a-day, 15 days is a course of treatment.
Embodiment 3
Tablet: stem and leaf of Radix Panacis Quinquefolii total saponins 180g, starch 20g mixing is made 1000, specification: the 0.2g/ sheet; Become human oral, 1 slice/time, 5 times on the one, a month course of treatment.
Claims (1)
1, the application of stem and leaf of Radix Panacis Quinquefolii total saponins in the medicine of preparation treatment viral myocarditis.
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