CN1593442A - Application of 20(S)-ginsenoside-Rg#[3] in the preparing process of medicine for treating or preventing cardiovascular and cerebrovascular disease - Google Patents

Application of 20(S)-ginsenoside-Rg#[3] in the preparing process of medicine for treating or preventing cardiovascular and cerebrovascular disease Download PDF

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CN1593442A
CN1593442A CN 200410054800 CN200410054800A CN1593442A CN 1593442 A CN1593442 A CN 1593442A CN 200410054800 CN200410054800 CN 200410054800 CN 200410054800 A CN200410054800 A CN 200410054800A CN 1593442 A CN1593442 A CN 1593442A
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ginsenoside
application
rgs
medicine
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CN1331473C (en
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田京伟
傅风华
蒋王林
王超云
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Shandong Tong Yu Tang Ginseng Technology Co Ltd
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Shandong Luye Natural Drug Research and Development Co Ltd
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Abstract

The invention relates to an application of 20(S)-ginsenoside-Rg[3] in the preparing process of medicine for treating or preventing cerebrovascular disease, brain damage, myocardial ischemia, congestive heart failure.

Description

20 (S)-ginsenoside-Rg 3Application in the medicine of preparation treatment or prevention cardiovascular and cerebrovascular disease
The art field
The present invention relates to 20 (S)-ginsenoside Rgs 3Application in the medicine of preparation treatment or prevention cardiovascular and cerebrovascular disease.
Background technology
Along with the acceleration of aged tendency of population process and the change of life style, cardiovascular and cerebrovascular disease has become a global health problem, the mortality rate of coronary heart disease, apoplexy occupies the 1st, 3 respectively at world wide, and hypertension is considered to the main hazard factor of apoplexy always.The exploitation that novel and effective is prevented and treated the cardiovascular and cerebrovascular vessel medicine is very urgent.
20 (S)-ginsenoside Rgs 3It is the tetracyclic triterpenes panoxadiol type saponin monomer of separation and Extraction from Radix Ginseng.
20 (S)-ginsenoside Rgs 3Structural formula (R:-glu-o-glu; R 1:-OH; R 2:-CH 3)
It is reported Rg 3Have antitumor, suppress effects such as new vessels generation, antiinflammatory, but about 20 (S)-ginsenoside Rgs 3Effect with prevention or treatment cardiovascular and cerebrovascular disease does not appear in the newspapers; Given this, the inventor finds 20 (S)-ginsenoside Rgs by a large amount of experimentatioies 3Medical usage with prevention or treatment cardiovascular and cerebrovascular disease.
Summary of the invention
The invention provides 20 (S)-ginsenoside Rgs 3Application in the medicine of preparation treatment or prevention cardiovascular and cerebrovascular disease.
The invention provides 20 (S)-ginsenoside Rgs 3Application in the medicine of preparation treatment or prevention of brain damage.
The invention provides 20 (S)-ginsenoside Rgs 3Application in the medicine of preparation treatment or prevention myocardial ischemia.
The invention provides 20 (S)-ginsenoside Rgs 3Application in preparation treatment or prevention congestive heart failure medicine.
The invention provides and contain 20 (S)-ginsenoside Rgs 3The pharmaceutical composition of treatment cardiovascular and cerebrovascular disease.
20 (S)-ginsenoside Rgs of the present invention 3When being used for above-mentioned arbitrary purposes, its using dosage scope is 10mg～750mg/ days, preferred 100mg～500mg/ days.
20 (the S)-ginsenoside Rgs that use among the present invention 3Can use separately or use with pharmaceutical compositions.Pharmaceutical composition comprises 20 (S)-ginsenoside Rgs as active component 3And pharmaceutical carrier.This pharmaceutical composition can pass through vein, oral, Sublingual, percutaneous, through muscle or subcutaneous, mucocutaneous administration.Pharmaceutical composition can exist with the form of tablet, pill, granule, capsule, suspension, solution, syrup, injection.Various pharmaceutical dosage form provided by the present invention all can be prepared from the pharmacy conventional method.
The inventor has confirmed 20 (S)-ginsenoside Rgs by following test 3Effect with treatment cardiovascular and cerebrovascular disease.20 (R)-ginsenoside Rgs 3, 20 (S)-ginsenoside Rgs 3Provided by natural drug Engineering Technical Research Centre pharmaceutical chemistry research department, Shandong Province, through HPLC detection level 〉=90%, reference substance is provided by the natural drug Engineering Technical Research Centre chamber of analysis and research, Shandong Province.20 (S) and 20 (R) ginsenoside Rg 3Press document [Zhao Zhongzhen waits the .HPLC method to separate and detects 20 (S)-ginsenoside Rg3s and 20 (R)-ginsenoside Rg3s for Tang Minghui, Jiang Zhihong. Chinese herbal medicine .2003,35 (3): 208～282.] described method detects.20 (R)-ginsenoside Rgs 3Also can be available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute.
The specific embodiment
Preparation example 1:20 (S)-ginsenoside Rg 3With 20 (R)-ginsenoside Rgs 3Preparation
With Radix Notoginseng total arasaponins (or Radix Ginseng total saponins) is raw material, the aqueous acetic acid of adding 50%, 70 ℃ of heating in water bath 6 hours, cooling adds 5% sodium carbonate liquor, solution is through n-butanol extraction, behind the extract evaporate to dryness, last silicagel column is an eluant with the chloroform-methanol, carry out gradient elution, obtain 20 (S)-ginsenoside Rgs 3With 20 (R)-ginsenoside Rgs 3Crude product, through silica gel column chromatography repeatedly, obtain 20 (S)-ginsenoside Rgs respectively 3With 20 (R)-ginsenoside Rgs 3And press document [Zhao Zhongzhen waits the .HPLC method to separate and detects 20 (S)-ginsenoside Rg3s and 20 (R)-ginsenoside Rg3s for Tang Minghui, Jiang Zhihong. Chinese herbal medicine .2003,35 (3): 208～282.] described method detects.
Preparation example 2:20 (S)-ginsenoside Rg 3The injection preparation
Take by weighing 0.50g 20 (S)-ginsenoside Rg 3, add 50g PEG-400, make the saponin dissolving; The phosphate buffer of preparation 50g pH5.5 takes by weighing the 0.02g sodium sulfite and joins in the above-mentioned phosphate buffer; Buffer is joined in the PEG solution of saponin, mix homogeneously adds 100 ℃ of insulations of 0.01% needle-use activated carbon 30 minutes, G 3Sintered glass funnel filters, the filtering with microporous membrane of 0.22um, and filtered liquid medicine is distributed into 50 of the injections that 2ml/ props up, and divides the directly tamponade of injection, the jewelling that install to cover into injection.
Preparation 3: injection 20 (S)-ginsenoside Rg 3The freeze-dried powder preparation
Take by weighing 0.50g 20 (S)-ginsenoside Rg 3, add 50g PEG-400, make the saponin dissolving.The phosphate buffer of preparation 50g pH5.5 takes by weighing the 0.02g sodium sulfite and joins in the above-mentioned phosphate buffer; Buffer is joined in the PEG solution of saponin, mix homogeneously adds 100 ℃ of insulations of 0.01% needle-use activated carbon 30 minutes, G 3Sintered glass funnel filters, the filtering with microporous membrane of 0.22um; Filtered liquid medicine is distributed in the cillin bottle that 2ml/ props up, and makes freeze-dried powder through the freeze dryer lyophilizing.
Preparation example 4: injection 20 (R)-ginsenoside Rg 3The freeze-dried powder preparation
Take by weighing 0.50g 20 (R)-ginsenoside Rg 3, add 50g PEG-400, make the saponin dissolving.The phosphate buffer of preparation 50g pH5.5 takes by weighing the 0.02g sodium sulfite and joins in the above-mentioned phosphate buffer; Buffer is joined in the PEG solution of saponin, mix homogeneously adds 100 ℃ of insulations of 0.01% needle-use activated carbon 30 minutes, G 3Sintered glass funnel filters, the filtering with microporous membrane of 0.22um; Filtered liquid medicine is distributed in the cillin bottle that 2ml/ props up, and makes freeze-dried powder through the freeze dryer lyophilizing.
Preparation example 5:20 (S)-ginsenoside Rg 3With 20 (R)-ginsenoside Rgs 3The reference substance preparation
With Radix Notoginseng total arasaponins (or ginsenoside) is raw material, the aqueous acetic acid of adding 50%, 70 ℃ of heating in water bath 6 hours, cooling adds 5% sodium carbonate liquor, solution is through n-butanol extraction, behind the extract evaporate to dryness, last silicagel column is an eluant with the chloroform-methanol, carry out gradient elution, obtain 20 (S)-ginsenoside Rgs 3With 20 (R)-ginsenoside Rgs 3Crude product, through silica gel column chromatography repeatedly, obtain 20 (S)-ginsenoside Rgs respectively 3With 20 (R)-ginsenoside Rgs 3Elaboration, recrystallization repeatedly obtains reference substance then.
Test routine 1:20 (S)-ginsenoside Rg 3Influence to the damage of rat local cerebral ischemia
(1) material
By preparation example 2 preparations 20 (S)-ginsenoside Rgs 3
By preparation example 4 preparations 20 (R)-ginsenoside Rgs 3
Red tetrazolium: U.S. Sigma company product, face with preceding and be made into 4% solution with normal saline.
Laboratory animal: the SD rat, male, body weight 280g-350g, natural drug Engineering Technical Research Centre zoopery center, Shandong Province provides.The quality certification number: No. 200106005, Shandong kinoplaszm word.
(2) method and result
Animal is divided into sham operated rats (waiting the capacity solvent) at random, model control group (waiting the capacity solvent), the nimodipine group (Nim, 1.5mg/kg), 20 (R)-ginsenoside Rgs 3The 5mg/kg group, 20 (S)-ginsenoside Rgs 3The 1mg/kg group, 20 (S)-ginsenoside Rgs 3The 5mg/kg group, 20 (S)-ginsenoside Rgs 3The 10mg/kg group, 20 (S)-ginsenoside Rgs 3The 20mg/kg group, 20 (S)-ginsenoside Rgs 3The 50mg/kg group, 20 (S)-ginsenoside Rgs 3The 75mg/kg group, 10 every group.After the fasting 12 hours, and chloral hydrate (350mg/kg, i.p.) anesthesia separates right carotid, and folder closes in the neck, common carotid artery, external carotid artery proximal part and distal end ligation, cut off the centre.The external carotid artery free-end is pulled to internal carotid artery in alignment, bolt line (selecting diameter 0.24mm nylon wire for use, length 5.0cm) is inserted into intracranial by external carotid artery, stop when meeting slight resistance, insertion depth is about 2cm.Ligation external carotid artery opening, and open the common carotid artery bulldog clamp, the disinfection and stitching wound causes right side middle cerebral artery ischemia model; Sham operated rats is only carried out the separation (above experiment is all carried out at 23 ℃～25 ℃) of right carotid, internal carotid artery, external carotid artery.Each treated animal intravenous injection relative medicine of postoperative (administration volume 1ml/200g).Press document [Liu Xiaoguang, Xu Lina, a kind of rat brain medium-sized artery model that can estimate thrombolytic and anti-thrombolytic after 24 hours, Acta Pharmaceutica Sinica, 1995,30:662] described method and standard is observed and the behavior disorder of record rat: (A) carry the Mus tail and observe forelimb flexing situation, stretch to ground as two forelimb symmetries, count 0 fen, the wrist flexing occurs as operation offside forelimb and count 1 fen, the elbow flexing is counted 2 fens, the shoulder inward turning is counted 3 fens, existing wrist flexing and/or elbow flexing have shoulder inward turning person again, count 4 fens.(B) animal is placed on the plane earth, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and strong, count 0 fen, as resistance descender when the operation offside promotes, according to decline degree difference be divided into gently, in, weigh three degree, count 1,2 and 3 fen respectively.(C) the two forelimbs of animal are put on the wire netting, observed the muscular tension of two forelimbs.Two muscle of anterior limb tension force equities and strong person count 0 fen.Count 1,2 and 3 fen according to operation offside muscular tension decline degree difference equally.(D) animal has ceaselessly to a side person of turn-taking, and counts 1 fen.According to the standard scoring, full marks are 11 minutes, and mark is high more, and expression animal behavior obstacle is serious more.
Put to death rat behind the behavior scoring, get brain, remove olfactory bulb, cerebellum and low brain stem, crownly be cut into 5, the brain sheet takes on a red color after normal structure is dyed with red tetrazolium (TTC) dyeing, and blocking tissue is white in color, taking a picture in dyeing back, asks the infarct size ratio with Chinese Aero-Space university pathological image analysis software.Data are represented with X ± s, carry out statistical procedures with t check between group.
The result is as shown in table 1, and ischemia is after 24 hours, and rat shows tangible behavior disorder, and tangible kitchen range shape ischemic region also appears in rat cerebral tissue, reaches about 25% of full brain; Give 20 (S)-ginsenoside Rgs of various dose 3, the animal behavior obstacle has alleviating in various degree, and the rat cerebral ischemia district also takes an evident turn for the better, and is dose dependent.
20 (S)-ginsenoside Rgs of same dose 3Treating cerebral ischemia is better than 20 (R)-ginsenoside Rgs 320 (S)-ginsenoside Rgs 3The 50mg/kg treating cerebral ischemia is better than 20mg/kg (P＜0.05), but does not relatively have significant difference (P＞0.05) with 75mg/kg.Prompting is when dosage 〉=50mg/kg, and drug effect does not continue increase.
Table 1 20 (S)-ginsenoside Rg 3To the influence of rat local cerebral ischemia damage (n=10, X ± s)
Group behavior disorder ischemic areas (%)
Sham operated rats 00
Model control group 10.10 ± 1.37 24.26 ± 4.13
Nim group 6.90 ± 2.33 *13.09 ± 7.11 *
20 (R)-ginsenoside Rgs 3Group (10mg/kg) 8.03 ± 1.11 *20.2 ± 1.3 *
1mg/kg 7.90±1.24 * 18.21±2.73 *
5mg/kg 7.70±2.44 * 17.06±3.20 *
20 (S)-ginsenoside 10mg/kg 7.50 ± 3.03 * @16.41 ± 2.84 * @
Rg 3Group 20mg/kg 7.31 ± 1.08 * △14.22 ± 3.14 * △
50mg/kg 5.34±1.28 ** 10.18±3.64 **
75mg/kg 5.20±1.93 **# 10.27±4.73 **#
Compare with model control group *P＜0.05, *P＜0.01; Compare with the 50mg/kg group △P＜0.05, #P＞0.05; With 10mg/kg20 (R)-ginsenoside Rg 3Group relatively @P＜0.05.
Test routine 2:20 (S)-ginsenoside Rg 3Protective effect to mice closure cerebral trauma
(1) material: by preparation example 2 preparations 20 (S)-ginsenoside Rgs 3, by preparation example 4 preparations 20 (R)-ginsenoside Rgs 3
Cleaning level kunming mouse, 18～22g, male and female half and half are provided by natural drug Engineering Technical Research Centre zoopery center, Shandong Province.The quality certification number: No. 200106003, Shandong kinoplaszm word.
(2) method and result: mice is divided into normal control group (waiting the capacity solvent) at random, model control group (waiting the capacity solvent), 20 (R)-ginsenoside Rgs 3The 20mg/kg group, 20 (S)-ginsenoside Rgs 3The 2mg/kg group, 20 (S)-ginsenoside Rgs 3The 10mg/kg group, 20 (S)-ginsenoside Rgs 3The 20mg/kg group, 20 (S)-ginsenoside Rgs 3The 40mg/kg group, 20 (S)-ginsenoside Rgs 3The 100mg/kg group, 20 (S)-ginsenoside Rgs 3The 150mg/kg group, 10 every group.Press document [Wang Chaoyun, Jiang Wanglin, the red English of intelligence, etc. baicalin is to the protective effect of brain injury. Chinese herbal medicine, 2004,35 (2): 188～190] described method causes mice closure cerebral trauma model, and each organizes intravenously administrable, strips the Mus brain after 24 hours, the weighing weight in wet base, dried 24 hours for 70 ℃, claim dry weight, calculate brain water content; Brain water content is higher than normal value and represents the brain edema.
The result is as shown in table 2, and the closure cerebral trauma causes the serious edema of mouse brain, gives 20 (S)-ginsenoside Rgs of various dose 3, the mouse brain edema has alleviating in various degree, and is dose dependent.
20 (S)-ginsenoside Rgs of same dose 3Reduce the cerebral edema effect and be better than 20 (R)-ginsenoside Rgs 320 (S)-ginsenoside Rgs 3100mg/kg reduces the cerebral edema effect and is better than 40mg/kg (P＜0.05), but does not relatively have significant difference (P＞0.05) with 150mg/kg.Prompting is when dosage 〉=100mg/kg, and drug effect does not continue increase.
Table 2 20 (S)-ginsenoside Rg 3To the influence of closure cerebral trauma (n=10, X ± s)
Group brain water content (%)
Normal control group 76.1 ± 0.3 *
Model control group 84.5 ± 1.3
20 (R)-ginsenoside Rgs 3Group (10mg/kg) 81.1 ± 1.1 *
2mg/kg 81.6±0.4 *
10mg/kg 79.9±0.3 *
20mg/kg 79.8±0.5 *@
20 (S)-ginsenoside Rgs 3Group
40mg/kg 79.7±0.4 **△
100mg/kg 77.4±0.4 **
150mg/kg 76.5±0.3 **#
Compare with model control group *P＜0.05, *P＜0.01; Compare with the 100mg/kg group △P＜0.05, #P＞0.05; With 20mg/kg 20 (R)-ginsenoside Rg 3Group relatively @P＜0.05.
Test routine 3:20 (S)-ginsenoside Rg 3Influence to the rat heart muscle ischemia
(1) material: by preparation example 3 preparations 20 (S)-ginsenoside Rgs 3
Chlorination nitro blue tetrazolium (N-BT) is provided by Military Medical Science Institute medical supply station.
Laboratory animal: regular grade Wistar rat, male, body weight 280g-350g, natural drug Engineering Technical Research Centre zoopery center, Shandong Province provides.The quality certification number: No. 200106005, Shandong kinoplaszm word.
(2) method and result: rat is divided into sham operated rats at random, model control group (waiting the capacity solvent), 20 (S)-ginsenoside Rgs 3The 1mg/kg group, 20 (S)-ginsenoside Rgs 3The 5mg/kg group, 20 (S)-ginsenoside Rgs 3The 10mg/kg group, 20 (S)-ginsenoside Rgs 3The 20mg/kg group, 20 (S)-ginsenoside Rgs 3The 50mg/kg group, 20 (S)-ginsenoside Rgs 3The 75mg/kg group, 10 every group.After the fasting 12 hours, the limb lead electrocardiogram is surveyed in ip urethane (1.2g/kg) anesthesia.Cut off left front fur, iodine tincture and alcohol disinfecting, along left border of sternum 1cm place, cut off thoracic wall muscle and two ribs, open the thoracic cavity rapidly, expose heart, the ligation left coronary artery is put back to heart immediately between arterial cone and left auricle, squeezes the thoracic cavity air, use the mosquito forceps closed-chest, cause Model Rats with Acute Myocardial Ischemia.Each treated animal intravenous drip (injecting) relative medicine (administration volume 3ml, 30min drips off) of postoperative with infusion pump.Record postoperative 0,2, the 6h electrocardiogram takes out heart subsequently, after cleaning with cold saline ,-20 ℃ of refrigerator freeze overnight.Next day, refrigerated heart is cut into 5 by ligation place to apex uniform thickness, immerse in the freshly prepared 0.5%N-BT phosphate buffer (pH7.4).37 ℃ of water-bath jolting 10～15min.Blot the dyeing liquor of slice surface with filter paper, separate the coloured portions and the part of being unstained, weigh the compute infarct size.Myocardial infarction percentage ratio (%)=infarction part weight/(non-infarction part weight+infarction part weight) * 100%.
The result is as shown in table 3,20 (S)-ginsenoside Rgs of various dose 3Obviously reduce the myocardial infarction area that Acute Myocardial Ischemia in Rats causes due to the ligation coronary artery, and can reduce the rising of the limb lead electrocardiogram J point that causes by myocardial ischemia.20 (S)-ginsenoside Rgs 3The 50mg/kg function of resisting myocardial ischemia is better than 20mg/kg (P＜0.05), but relatively do not have significant difference (P＞0.05) with 75mg/kg, and promptly when dosage 〉=50mg/kg, drug effect does not continue increase.
Table 3 20 (S)-ginsenoside Rg 3To the influence of rat heart muscle ischemic injuries (n=10, X ± s)
Myocardial infarction percentage ratio J point raises (10 * mV)
Grouping
(%) normal 0h 2h 6h
Model control group 24 ± 4 0.8 ± 0.6 6.7 ± 2.3 6.3 ± 2.0 5.9 ± 1.5 *
Radix Salviae Miltiorrhizae Injection group 17 ± 6 *0.8 ± 0.6 6.0 ± 1.5 *5.6 ± 1.7 *5.6 ± 1.6 *
1mg/kg 19±7 * 0.7±0.5 6.1±1.2 * 5.6±1.6 * 4.9±1.2 *
5mg/kg 18±5 * 0.7±0.6 5.9±1.5 * 5.3±1.2 * 4.8±1.6 *
20 (S)-people
10mg/kg 18±5 * 0.7±0.5 5.6±1.6 * 4.9±1.6 * 4.2±1.1 *
The ginseng saponin
20mg/kg 17±6 *△ 0.7±0.5 5.3±1.1 *△ 4.8±1.3 *△ 4.1±1.5 *△
Rg 3
50mg/kg 14±5 ** 0.7±0.6 4.6±1.6 * 4.2±1.4 * 3.5±1.0 *
75mg/kg 13±6* *#?0.7±0.5 4.4±1.3 *# 4.1±1.6 *# 3.4±1.1 *#
Compare with model control group *P＜0.05, *P＜0.01; Compare with the 50mg/kg group △P＜0.05, #P＞0.05.
Test routine 4:20 (S)-ginsenoside Rg 3Therapeutical effect to the experimental heart failure of cat
(1) material: 20 (S)-ginsenoside Rgs 3Injection: by preparation example 3 preparations.
The Powerlab/8sp physiograph: Australian InStruments company produces.
Electromagnetic flowmeter (MFV-3200 type): Japanese photoelectricity company produces.
Laboratory animal: healthy adult cat body weight 2～4kg, natural drug Engineering Technical Research Centre zoopery center, Shandong Province provides.(2) method: cat is divided into model control group (waiting the capacity solvent), 20 (S)-ginsenoside Rgs at random 3Small dose group (5mg/kg), 20 (S)-ginsenoside Rgs 3Middle dosage group (10mg/kg), 20 (S)-ginsenoside Rgs 3Heavy dose of group (20mg/kg), 6 every group.After the fasting 12 hours, intravenous injection pentobarbital sodium 40mg/kg anesthesia, tracheal intubation, artificial respiration, monitoring aortic pressure (AP) and electrocardiogram.Breast is opened in the left side, plugs in conduit to left ventricle from the apex of the heart, surveys left constant pressure and rate of pressure change (± dP/dt thereof Max).Waltan-Brodie strain bow is implanted the left ventricle antetheca, measure myocardial contraction.With electromagnetic flowmeter determination ascending aorta blood flow.As cardiac output (CO), calculate cardiac index (CI), the index (SI) of whenever fighting, the work done (SW) of whenever fighting, left heart work done (LVW) and total peripheral vascular resistance (SVR) with the ascending aorta flow.Parameters is recorded in the Powerlab/8sp physiograph.Postoperative half an hour, it is stable that parameters reaches.From femoral vein constant speed gasing injection pentobarbital sodium (0.5ml/kgmin), with ± dP/dt MaxDropping to about 1000mmHg/s is that leading indicator forms acute heart failure.After treating the heart failure model stability, each treated animal intravenous drip (injecting) relative medicine (administration volume 10ml, 30min drips off) with infusion pump.
(3) result:
A, 20 (S)-ginsenoside Rg 3Influence to heart failure cat heart rate and blood pressure
The result is as shown in table 4, instillation various dose 20 (S)-ginsenoside Rg 3Can reduce heart failure cat blood pressure in various degree, and particularly evident to the effect of diastolic pressure.
Table 4 20 (S)-ginsenoside Rg 3To the influence of heart failure cat blood pressure (n=6, X ± s)
Mean arterial pressure (mmHg) systolic pressure (mmHg) diastolic pressure (mmHg)
Grouping
Before the administration after the administration before the administration after the administration before the administration after the administration
Model control group 57 ± 5 53 ± 6 71 ± 11 69 ± 10 45 ± 8 44 ± 8
20 (S)-ginsenoside 20mg/kg 55 ± 4 38 ± 8 * ##73 ± 14 64 ± 8 * #47 ± 6 27 ± 5 * ##
Rg 3 10mg/kg 59±6 43±9 *# 70±9 66±7 41±7 30±6 **##
5mg/kg 62±5 45±7 * 73±10 67±8 42±6 35±3 *#
With comparison before the administration *P＜0.05, *P＜0.01; Compare with model control group #P＜0.05, ##P＜0.01B, 20 (S)-ginsenoside Rg 3Influence to heart failure cat cardiac work
The result is as shown in table 5, instillation various dose 20 (S)-ginsenoside Rg 3Can increase SW and the LVW of heart failure cat, with before the administration, model control group relatively has significant difference.
Table 5 20 (S)-ginsenoside Rg 3To the influence of heart failure cat cardiac work (n=6, X ± s)
Whenever the left heart work done of work done (gm/beat) (kgm/min) of fighting
Grouping
Before the administration after the administration before the administration after the administration
Model control group 0.98 ± 0.33 0.87 ± 0.56 0.064 ± 0.033 0.059 ± 0.032
20 (S)-Radix Ginseng soap 20mg/kg 0.86 ± 0.41 1.23 ± 0.51 * ##0.066 ± 0.036 0.087 ± 0.041 * ##
Glycosides Rg 310mg/kg 0.89 ± 0.32 1.08 ± 0.47 * #0.059 ± 0.032 0.079 ± 0.036 * #
5mg/kg 0.93±0.38 1.01±0.50 # 0.061±0.031 0.070±0.029 #
With comparison before the administration *P＜0.05, *P＜0.01; Compare with model control group #P＜0.05, ##P＜0.01
C, 20 (S)-ginsenoside Rg 3Influence to the total peripheral vascular resistance of heart failure cat
The result is as shown in table 6, instillation various dose 20 (S)-ginsenoside Rg 3Can reduce the total outer vascular resistance of heart failure cat, with before the administration, model control group relatively has significant difference.
Table 6 20 (S)-ginsenoside Rg 3To the influence of the total peripheral vascular resistance of heart failure cat (n=6, X ± s)
Total peripheral vascular resistance (mmHg/min/kg)
Grouping
After the preceding administration of administration
Model control group 79 ± 27 82 ± 33
20 (S)-ginsenoside Rgs 320mg/kg 81 ± 30 51 ± 22 * ##
10mg/kg 83±28 64±30 **##
5mg/kg 82±30 71±33 *#
With comparison before the administration *P＜0.05, *P＜0.01; Compare with model control group #P＜0.05, ##P＜0.01
D, 20 (S)-ginsenoside Rg 3To the kinemic influence of heart failure cat
The result is as shown in table 7, instillation various dose 20 (S)-ginsenoside Rg 3Can increase the cardiac output of heart failure cat, with before the administration, model control group relatively has significant difference.
Table 7 20 (S)-ginsenoside Rg 3To the kinemic influence of heart failure cat (n=6, X ± s)
Stroke volume index (ml/beatm 2) cardiac output index (L/minm 2)
Grouping
Before the administration after the administration before the administration after the administration
Model control group 4.5 ± 0.9 4.1 ± 1.2 0.65 ± 0.15 0.59 ± 0.18
20mg/kg 4.4±1.2 8.1±3.5 **## 0.67±0.20 0.88±0.23 **##
20 (S)-Radix Ginseng soaps
10mg/kg 5.1±1.6 7.2±3.3 **## 0.66±0.17 0.79±0.16 *#
Glycosides Rg 3
5mg/kg 4.8±0.9 5.9±1.1 *# 0.67±0.21 0.73±0.19 #
With comparison before the administration *P＜0.05, *P＜0.01; Compare with model control group #P＜0.05, ##P＜0.01
Test routine 5:20 (S)-ginsenoside Rg 3Acute toxicity test
(1) material: 20 (S)-ginsenoside Rgs 3Injection: by preparation example 2 preparations.
Cleaning level kunming mouse, 18～22g, male and female half and half are provided by natural drug Engineering Technical Research Centre zoopery center, Shandong Province.The quality certification number: No. 200106003, Shandong kinoplaszm word.Feedstuff identifies that by Chinese pharmaceutical biological product check is provided.
(2) method: according to trial test design dosage and the blank group of dividing into groups, 100mg/kg, 150mg/kg, 225mg/kg, 337.5mg/kg, 506.25mg/kg, 759.375mg/kg group, totally 8 groups, 10 every group.After weighing, press the volume intravenous injection of 0.2ml/10g, matched group gives the equal-volume solvent.Toxic reaction of close observation mice and death condition in 7 days after the administration, and measure LD by improving karber's method 50
(3) result
20 (S)-ginsenoside Rgs 3The LD of injection 50Be 408.7 ± 78.6mg/kg; LD 5095% fiducial limit: 349.2～529.5mg/kg.

Claims (9)

1. 20 (S)-ginsenoside Rgs 3Application in the medicine of preparation treatment or prevention cardiovascular and cerebrovascular disease.
2. application according to claim 1,20 (S)-ginsenoside Rgs 3Application in the medicine of preparation treatment or prevention of brain damage.
3. application according to claim 1,20 (S)-ginsenoside Rgs 3Application in the medicine of preparation treatment or prevention myocardial ischemia.
4. application according to claim 1,20 (S)-ginsenoside Rgs 3Application in preparation treatment or prevention congestive heart failure medicine.
5. according to the arbitrary described application of claim 1-4, its using dosage scope is 10mg～750mg.
6. application according to claim 5, its preferred dose are 100mg～500mg.
7. contain 20 (S)-ginsenoside-Rg 3The pharmaceutical composition that is used for the treatment of or prevents cardiovascular and cerebrovascular disease.
8. pharmaceutical composition according to claim 7, said composition can be by oral, Sublingual, percutaneous, through the administration of muscle intravenous route.
9. according to claim 7 or 8 described pharmaceutical compositions, said composition can exist with forms such as tablet, pill, granule, capsule, suspension, solution, syrup, injection, cream, ointment, spray, chewing agent or patches.
CNB2004100548008A 2003-07-23 2004-07-22 Application of 20(S)-ginsenoside-Rg#[3] in the preparing process of medicine for treating or preventing cardiovascular and cerebrovascular disease Expired - Fee Related CN1331473C (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007006208A1 (en) * 2005-07-14 2007-01-18 National Institute Of Pharmaceutical R & D Co., Ltd. Medicinal composition containing ginseng secondary glycosides, its preparation method and application
CN105168233A (en) * 2015-09-23 2015-12-23 浙江大学 Application of 20(S)-ginsenoside Rg3 as SIRT1 protein agonist

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007006208A1 (en) * 2005-07-14 2007-01-18 National Institute Of Pharmaceutical R & D Co., Ltd. Medicinal composition containing ginseng secondary glycosides, its preparation method and application
US7973014B2 (en) 2005-07-14 2011-07-05 National Institute Of Pharmaceutical R&D Co., Ltd. Medicinal composition containing ginseng secondary glycosides, its preparation method and application
CN105168233A (en) * 2015-09-23 2015-12-23 浙江大学 Application of 20(S)-ginsenoside Rg3 as SIRT1 protein agonist

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