CN103505462A - New uses of 20(S)-protopanaxadiol - Google Patents
New uses of 20(S)-protopanaxadiol Download PDFInfo
- Publication number
- CN103505462A CN103505462A CN201210203239.XA CN201210203239A CN103505462A CN 103505462 A CN103505462 A CN 103505462A CN 201210203239 A CN201210203239 A CN 201210203239A CN 103505462 A CN103505462 A CN 103505462A
- Authority
- CN
- China
- Prior art keywords
- myocardial ischemia
- protopanoxadiol
- myocardial
- application according
- reperfusion injury
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The invention relates to new uses of 20(S)-protopanaxadiol, and concretely relates to applications of the 20(S)-protopanaxadiol in the preparation of ischemic heart disease prevention and treatment medicines. Results of the pharmacodynamic study show that the 20(S)-protopanaxadiol can reduce myocardial histological damages caused by ischemia and ischemia reperfusion and reduce the infarct size and myocardial necrosis related enzyme indexes to reduce the J point displacement in an electrocardiogram.
Description
Technical field
The present invention relates to the new purposes of 20 (S)-protopanoxadiols, specifically, relate to the application of 20 (S)-protopanoxadiols in the medicine of preparation prevention and treatment ischemic heart desease.
Background technology
In China, cardiovascular disease has become (comprising hypertension and coronary heart disease) principal disease of harm humans health and lives.2002 Nian， China big city resident's deaths from heart disease rates reach 75.68/10 ten thousand people, are only second to malignant tumor, cerebrovascular accident, occupy the 3rd of the cause of death.
The myocardial ischemia heart disease cardiopathia (coronary heart disease) that wins again, refer to the heart disease that makes luminal stenosis or obstruction cause myocardial ischemia or anoxia to cause due to coronary atherosclerosis, for coronary atherosclerosis causes the common type of organ lesion.Clinical manifestation is stable angina pectoris, unstable angina pectoris, arrhythmia, cardiogenic shock etc.Wherein unstable angina pectoris can develop into acute myocardial infarction (AMI) and even dies suddenly.
Coronary heart disease is called as in developed country that " No.1 killer ”， developing country sickness rate is also more and more higher.World Health Organization (WHO) (WHO) prediction, will become to the year two thousand twenty cardiovascular disease the cause of the death that beats the world.
The treatment of coronary heart disease, mainly contains these three kinds of means of Drug therapy, interventional therapy and bypass surgery at present.Wherein, Drug therapy is the most basic treatment, according to the ATC coding of WHO, can be divided into 9 groups such as calcium channel blocker, disease treatment medication, peripheral vasodilators.
The treatment myocardial ischemia drug using is clinically mostly the medicines such as Folium Ginkgo, Alprostadil, amlodipine, Rhizoma Zingiberis Recens, fructose diphosphate, nifedipine, puerarin, isosorbide mononitrate, Herba Erigerontis, arasaponin, wherein take Chinese medicine or Chinese medicine ingredients is that main cardiovascular drugs is used wider, its advantage is determined curative effect, side effect is little, because cognition degree improves constantly, so market potential is huge.
In Cardiac valve replacement process, need to give cardioplegic solution to patient, set up extracorporeal circulation, after aorta is blocked, can cause myocardial ischemia.After aorta is open, can cause Myocardial Ischemia Reperfusion Injury.
Protopanoxadiol is glycol group ginsenoside's interior metabolism product, be divided into protopanoxadiol and be divided into 20-(S) protopanoxadiol (20 (s)-protopanaxadiol, 20 (S)-dammarane-24-alkene-3 β, 12 β, 20-triol) and 20 (R)-protopanoxadiols (20 (R)-protopanaxadiol, 20 (R)-dammarane-24-alkene-3 β, 12 β, 20-triol), they are enantiomer each other, and its structure is as follows:
20-(S) protopanoxadiol 20-(R) protopanoxadiol
Patent CN200910139993.X, discloses the protopanoxadiol type saponin in Radix Notoginseng for atherosclerosis.
Patent CN03132958.6 discloses the application of 20 (R)-ginsenoside-RG3 in the medicine of preparation and prevention cardiovascular and cerebrovascular disease.
By up to the present, the patent report of not yet relevant 20 (S)-protopanoxadiol treatment myocardial ischemia heart disease aspects.
Document aspect: Guo Yucheng, Tang Xudong etc. have reported that Radix Notoginseng total arasaponins can suppress the activation of NF-B in neutrophilic granulocyte, reduce ICAN-1 and express and neutrophil infiltration, thereby improve Myocardial Microcirculation and play the effect (Guo Yucheng of myocardial preservation, Tang Xudong, Gu great Yong, Jiang great Chun, Jiang Jianqing, the experimentation of Radix Notoginseng total arasaponins to myocardial ischemia reperfusion injury protective effect, J.of Chinese Nierocireulation Oct, 2004, Vo1.8.No.5); Jin Ming; Qu Shaochun has reported that american ginseng glycol saponin injection (IPQDS) has obvious protective effect to myocardial ischemia-reperfusion injury; may with its enhancing activities of antioxidant enzymes; reduce the oxidative damage of radical pair cardiac muscle; reducing endogenous vaso-active substance ET and AngII discharges; correct the unbalance mechanism that waits of PGI2/TXA2 about (gold inscription; Qu Shaochun; Yu little Feng, Xu Huali, used as a personal name in ancient times high-ranking official; the impact of american ginseng glycol saponin Injection in Rats myocardial ischemia reperfusion injury; Tianjin Chinese medicine, Apr.2006, Vo1.23 No.2).Wu Shufang etc. reported Panax quinquefolium 20 s-protopanaxdiol Saponins Antiarrhythmic Effect and mechanism thereof (Wu Shufang etc. Panax quinquefolium 20 s-protopanaxdiol Saponins Antiarrhythmic Effect and mechanism thereof, Chinese Pharmaceutical Journal, 02 phase in 2002)
Although above-mentioned research has pointed out saponins compound for there being potential protective effect on reperfusion injury of cardiac muscle, above-mentioned research is all mixture of multiple saponins compound, fails to point out specifically which saponin compound role.Secondly, the myocardium protecting action of these compounds all only just can be observed under larger dosage, in body effective dose all more than 100mg/kg.Because glycol saponins can promptly be converted to various metabolites after oral in vivo, comprise Rg3, Rh2, compound-K and PPD, it is significantly different that these metabolites and protopanoxadiol saponins have in mechanism, and its myocardium protecting action also has no report.
Summary of the invention
The new purposes that the object of this invention is to provide 20-(S)-protopanoxadiol.
The invention provides the application of 20-(S)-protopanoxadiol in the medicine of preparation prevention and treatment ischemic heart desease.
Described ischemic heart desease is selected from coronary heart disease or coronary atherosclerotic heart disease.
Preferably, ischemic heart desease of the present invention is myocardial ischemia and myocardial ischemia reperfusion injury.
Described myocardial ischemia and myocardial ischemia reperfusion injury are silent myocardial ischemia, angina pectoris, myocardial infarction, ischemic cardiomyopathy and/or sudden death.
Preferably, myocardial ischemia and myocardial ischemia reperfusion injury also comprise because treatment needs are exercised heart time-out perfusion and resuscitation causes again myocardial ischemia and myocardial ischemia reperfusion injury.
Described myocardial ischemia and myocardial ischemia-reperfusion also comprise myocardial ischemia and the myocardial ischemia reperfusion injury causing after operation, as myocardial ischemia and the myocardial ischemia reperfusion injury that cardiac valve replacement caused.
Above-mentioned application of the present invention, 20 (S)-protopanoxadiol preparations that 20 (S)-protopanoxadiols are comprised of 20 (S)-protopanoxadiols and pharmaceutically acceptable carrier or adjuvant.
Described 20 (S)-protopanoxadiol preparations are injection, tablet, capsule, solution (oral), the agent of gas (powder) mist, patch, granule, Sublingual tablet or drop pill.
The invention has the advantages that:
1, in prior art, disclose 20 (S)-protopanoxadiol groups (PQDS) and obtained by the separation and purification of araliaceae ginseng plant's Folium Panacis Quinquefolii (Panaxquinquefolium L.) leaf total saponins, mainly contained panoxadiol's saponins Rb
1, Rb
2, Rb
3, Rd monomer component, with other drug share treatment myocardial ischemia purposes.Each monomer structure is as follows:
Ginsenoside Rd ginsenoside Rb1
Ginsenoside Rb3 ginsenoside Rb2
Compared with prior art, 20 (S)-protopanoxadiols of inventor research are the metabolites in glycol group ginsenoside's body, derive from prior art Material Source differently, and structurally there are differences.
2, by pharmacodynamic study, find that 20 (S)-protopanoxadiols can reduce the myocardiac histology damage that ischemia and ischemia-reperfusion cause, reduce the infarct size zymetology index relevant to myocardial necrosis, the displacement of electrocardiogram J point is reduced, thereby be that 20 (S)-protopanoxadiol preparations or compositions provide foundation for ischemic heart disease.
3, the medicine of cardiovascular disease is prone to erythra, hemorrhage, arrhythmia, headache, dizzy etc. at present, easily produces drug resistance and dependency.And 20 (S)-protopanoxadiols derive from plant material, production technology is simple, and cost is low, and the Cardiovarscular medicine with respect to other, has side effect little, safe and reliable advantage.Therefore can be used as one of medicine of Cardiovarscular.
4, we find by experiment, and meanwhile, 20 (S)-protopanoxadiols also can be used for the protection of the myocardial ischemia that operation causes, and have the effect of myocardial preservation for the peri-operation period of the operations such as heart stopping collecting (extracorporeal circulation).And the derivant of 20 (S)-protopanoxadiols has also demonstrated good activity for prevention and treatment ischemic heart desease.
Accompanying drawing explanation
Fig. 1: 20 (S)-protopanoxadiols (PPD) and Rb1 are to the protective effect of the Cardiac Cells In Vitro of hydrogen peroxide treatment relatively.The result of this experiment shows that PPD will significantly be better than ginsenoside Rb1 for the protection of myocardial cell.
The specific embodiment
Following examples are used for illustrating the present invention, but are not used for limiting the scope of the invention.
Experimental example 1: the impact on the Cardiac Cells In Vitro of hydrogen peroxide treatment
In order to investigate metabolite 20 (S)-protopanoxadiol saponin (PPD) myocardial preservation function of protopanoxadiol saponins, this experiment has selected main glycol saponins Rb1 in protopanoxadiol saponins group to come comparison PPD and the protective effect of Rb1 to the Cardiac Cells In Vitro of hydrogen peroxide treatment.
1, test material
1.1 test samples: 20 (S)-protopanoxadiols (PPD), Rb1 provides by Shanghai Chinese Medicine Creation Research Center;
1.2 experimental apparatus:
Clean bench, Microcystins in The Dianshan Lake cleaning equipment factory;
Constant temperature CO
2incubator, U.S. Forma company;
Enzyme-linked immunosorbent assay instrument, U.S. BioTek company;
Inverted biological microscope, Chongqing optical instrument;
Desk-top constant-temperature table, Taicang science and education equipment factory.
1.3 experiment reagents: DMEM culture medium (GIBCO), trypsin GIBCO) hyclone (GIBCO), MTT (Sino-A-Biotel), DMSO (Chemical Reagent Co., Ltd., Sinopharm Group), DMSO (Sigma); Hydrogen peroxide (Chemical Reagent Co., Ltd., Sinopharm Group).
1.4 cell strains: cell strain is provided by Chinese Academy of Sciences's cell.
H9C2 cell, is incubated in DMEM in high glucose culture medium, containing 15% calf serum, and 37 ℃, 5%CO
2.
2, experimental technique:
With the H9C2 cell of In vitro culture, research PPD, the protective effect of Rb1 anti-peroxidation hydrogen damage, and compare its IC
50value.
2.1 get in one bottle, cell in good condition exponential phase of growth, make cell suspension.
2.2 cell countings, and cell density is diluted to 1 * 10
5individual/ml.
2.3 obtained cell suspensions are inoculated on 96 orifice plates, and 100 μl/ holes, put constant temperature CO
2in incubator, cultivate.
2.4 add respectively above test-compound, establish blank, and compound effects final concentration is respectively 0.1,0.5,1,2,5,10 μ M, and cultivate in each concentration 3 Ge Fu hole.
2.5 continue to add hydrogen peroxide ，Mei hole 10 μ l, and final concentration is 100 μ M, in incubator, cultivates.
2.6MTT is made into 5mg/ml solution with PBS, and MTT is added in 96 orifice plates, and 10 μl/ holes, react in incubator after 4 hours and suck supernatant, adds DMSO 150 μl/ holes, continues to hatch, and makes resolution of precipitate.
2.7 use enzyme-linked immunosorbent assay instruments are the light absorption value that 570nm place measures every hole at wavelength, and calculate inhibitory rate of cell growth and protection effect (reversion rate).
Inhibitory rate of cell growth %=(negative control group OD value-processed group OD value)/(negative control group OD value-blank group OD value) * 100%
2.8 each compounds in triplicate.
3, the results are shown in accompanying drawing 1:
From accompanying drawing 1, can find out: 20 (S)-protopanoxadiols (PPD) protect myocardium effect to be better than significantly protopanoxadiol saponin Rb1.
Experimental example 2: the impact on myocardial ischemia and Ischemia-Reperfusion Injury Model
For further confirming 20 effects of (S)-protopanoxadiol to myocardial preservation, lower example is that 20 (S)-protopanoxadiols have carried out pharmacologic agent research to myocardial ischemia and ischemical reperfusion injury animal model.
1, test material
1.1 test sample
20 (S)-protopanoxadiol (PPD) ，You Shanghai Chinese Medicine Creation Research Center provide; 20 (S)-protopanoxadiols are mixed with to suspension in accordance with the following methods: take 100mg sample, add 10ml0.5%CMC-Na and grind, be mixed with 10mg/ml suspension
1.2 positive control sample
Title: Nifedipine Tablets ，You Shanghai Pharmaceutical (Group) Co., Ltd. letter friendship pharmacy head factory provides, and specification is: 10mg/ sheet, lot number: the accurate word H31021222 of traditional Chinese medicines; Character: Film coated tablets; Storage practice: room temperature preservation;
Preparation: add 0.5%CMC-Na after pulverizing and grind that to be mixed with content be 2mg/ml suspension
1.3 other medicines
Urethane, lot number HG22-771-68, Cao Yang Second Middle School chemical plant, is made into 25% solution with normal saline.
2, experimental animal
SD rat, male and female half and half, body weight: 220-250 gram, purchased from Shanghai Si Laike laboratory animal responsibility company limited; The quality certification number: SCXK (Shanghai) 2002-0010
Raising condition: SPF level rat experiment receptacle, temperature: 23+1 ℃, humidity: 40～70%, illumination: 12 hours light and shades are alternately.
Drinking-water: filtered water, freely drink
Feedstuff: Mus full nutritious particle feedstuff, Songjiang Che Dun laboratory animal seed multiplication farm
Feeding manner: raise in cages
3, test apparatus
MP150 systems, ECG100C amplifier, BIOPAC systems Inc., AcqKnowledge Ver 3.9.0 process software;
722 grating spectrophotometers, Shanghai San analytical tool factory;
ALC-V8B animal artificial respirator, Alcott bio tech ltd, Shanghai.
4, test kit
NBT stain, lot number: 20071101, the Shanghai chemical reagent factory that advances is produced;
Lactic acid dehydrogenase (LDH) testing cassete, the colour developing of acetone acid dinitrophenylhydrazone;
Creatine kinase (CK) testing cassete, molybdenum phosphate acid system;
Above testing cassete builds up Science and Technology Ltd. by Nanjing and produces.
5, experiment grouping
5.1 myocardial ischemia: (9 groups)
Sham operated rats: lumbar injection NS0.5m1/100g;
Model group:, lumbar injection NS0.5ml/100g;
Test group: 20 (S)-protopanoxadiol groups and 20 (S)-protopanoxadiol high dose group (being called for short PPD group and PPD high dose group), respectively lumbar injection 25mg/kg/ day and 50mg/kg/ day
Positive controls: nifedipine gastric infusion, dosage is 10mg/kg.
Said medicine is except nifedipine, all according to administration volume 0.5ml/100g administration.
5.2 ischemia-reperfusions (five groups)
Sham operated rats: lumbar injection NS0.5ml/100g;
Model group: lumbar injection NS0.5ml/100g;
Test group: 20 (S)-protopanoxadiol groups and 20 (S)-protopanoxadiol high dose group (being called for short PPD group and PPD high dose group), respectively lumbar injection 25mg/kg/ day and 50mg/kg/ day
Positive controls: nifedipine, gastric infusion, dosage is 10mg/kg.
Said medicine is except nifedipine, all according to administration volume 0.5ml/100g administration.
5.3 administration time
Before test, successive administration is 7 days, once a day; Myocardial ischemia is respectively organized last administration first 30 minutes of anesthesia ligation; Each group of ischemia-reperfusion is administered once in anesthesia ligation for first 30 minutes, then gives once while pouring into again.
6, experimental technique
6.1 process of the test
Animal starts administration for first 7 days in test, once a day, and successive administration 7 days.30 minutes pneumoretroperitoneum injection urethane 1.2g/kg of test last administration on same day anesthesia, faces upward position and fixes, and inserts tracheal casing pipe, connect respirator, with needle electrode, thrust extremity subcutaneous, measure II lead electrocardiogram, left 3-4 intercostal is opened breast, expose heart, with ophthalmic tweezers, gently mention pericardium, carefully tear, under left auricle, use (3*6,3/8) round needle, No. 00000 silk thread.
Each group of myocardial ischemia (except sham operated rats), in arterial cone and coronary sulcus place ligation left coronary artery, is then sewed up and is closed breast chamber; Only not ligation of threading of sham operated rats, timing immediately, closes breast, removes respirator and recovers autonomous respiration.
Each group of ischemia-reperfusion (except sham operated rats) with eyeless suture needle at a left front underpass that falls, line two is through the long diameter 1.5mm of 1.5cm polyethylene tube, 3min post-tensioning calking zygonema the polyethylene tube pushing away outside line fall branch with a blocking-up coronary artery left side, timing immediately, close breast, remove respirator and recover autonomous respiration, ischemia recovers blood for filling with again after 1 hour, and is pouring into rear rechallenge again.Within after ligation 3 hours, put to death animal, ventral aorta blood sampling, centrifuging and taking serum detects LDH, CK index, the impact that the Myocardial Enzymologic that observation given the test agent causes myocardial ischemia changes.The dirty histology of carrying out (variation of Infarct area) that cores detects.
To before the detecting ECG administration of record, after ligation 10,20,30 and 60 minutes, again after perfusion 15,30,45,60 and the Electrocardiographic ST section of 120min or the J height of order, and carry out statistical analysis with the absolute value of variation.
6.2 detect index
The variation that Rat Ecg T ripple, J are ordered; Rat myocardial infarction model area; Serum creatine kinase (CK), lactic acid dehydrogenase (LDH).
7, experimental result:
7.1 impacts on infarct size: the results are shown in Table 1
Table 1: the impact on permanent ischemia and myocardial ischemia reperfusion in rats infarct size
Note: compare * * * P < 0.001 with sham operated rats; With negative control group comparison
#p < 0.05,
##p < 0.01,
# ##p < 0.001.
Table 1 result shows:
Compare with sham operated rats, the infarct size of negative control group extremely significantly increases (P < 0.001);
Compare with negative control group, 20 (S)-protopanoxadiol intraperitoneal injection 50mg/kg bring out the obvious reducing effect of area (p < 0.05) of myocardial infarction to myocardial ischemia, positive control nifedipine 10mg/kg also makes infarction decline significantly (p < 0.01).
Compare with negative control group, the area that 20 (S)-protopanoxadiol intraperitoneal injection 25mg/kg and 50mg/kg bring out myocardial infarction to myocardial ischemia-reperfusion reducing effect (p < 0.05 and p < 0.01) in various degree, the infarct size of nifedipine has significant difference (p < 0.01).
7.2 impacts on serum enzyme content: in Table 2,3
Table 2: the impact on permanent ischemia and ischemia-reperfusion rat blood serum LDH vigor
Note: compare * * * P < 0.001 with sham operated rats; With negative control group comparison
#p < 0.05,
##p < 0.01,
# ##p < 0.001.
Table 3: the impact on permanent ischemia and ischemia-reperfusion rat blood serum CK vigor
Note: compare * * * P < 0.001 with sham operated rats; With negative control group comparison
#p < 0.05,
##p < 0.01,
# ##p < 0.001.
Table 2,3 results show:
Consistent with histology result, the serum enzyme content that negative control group is relevant to myocardial necrosis has the rising of highly significant, the difference highly significant (p < 0.01) that LDH and CK vigor raise compared with sham operated rats, LDH and CK vigor after myocardial ischemia and ischemia-reperfusion group 20 (S)-protopanoxadiol group intraperitoneal injection are all starkly lower than negative control group (p < 0.05).Positive drug nifedipine also significantly reduces LDH and the CK value of myocardial ischemia reperfusion injury animal serum, with 20 (S)-protopanoxadiol groups without significant difference.
7.3 on impact that on electrocardiogram, ST section or J are ordered:
7.3.1 the impact of the J of rats with myocardial ischemia point displacement: in Table 4-1
Table 4-1: the impact (± s) on the displacement of rats with myocardial ischemia J point
Note: compare * * P < 0.01, * P < 0.05 with sham operated rats.
From table 4-1 result, show:
Myocardial ischemia: rat II leads the data that ST section on electrocardiogram or J point change and shows, after negative control group myocardial ischemia, J point rises rapidly or declines, and reaches the highest during to 20 minutes, and progressively decline later, compared with sham operated rats significant difference; Each administration group J point declines with negative control group without significant difference.
7.3.2 the impact on the displacement of ischemia-reperfusion rat J point: in Table 4-2
Table 4-2: the impact on the displacement of ischemia-reperfusion rat J point
Note: compare * * P < 0.01, * P < 0.05 with sham operated rats; With negative control group comparison
#p < 0.05,
##p < 0.01.
Table 4-2 shows: after ischemia-reperfusion group ligation, negative control group ST section or J point be rising rapidly, in the time of 20 to 60 minutes higher than sham operated rats, difference highly significant; After perfusion, the displacement of J point declines rapidly again, and, higher than sham operated rats, there is significant difference 15 minutes and 120 minutes; 20 (S)-protopanoxadiol group high dose administrations before ligation, the displacement that the J in the time of 20 minutes is ordered is significantly less than negative control group, is still less than negative control group, significant difference the following during to 60 minute; While pouring into, the J point displacement of 20 (S)-protopanoxadiol groups declines rapidly again, but with negative control group difference nonsignificance; Positive control Nifedipine group makes after ischemia 10-60 minute and the J point displacement of filling with again latter 15 minutes declines, with negative control group significant difference.
The incidence of arrhythmia no significant difference of each treated animal.
8, conclusion
20 (S)-protopanoxadiol intraperitoneal injections can reduce the myocardiac histology damage that ischemia and ischemia-reperfusion cause, infarct size is reduced, and the zymetology index relevant to myocardial necrosis reduces, and the displacement of electrocardiogram J point reduces.A little less than its effect is omited compared with the nifedipine of 10mg/kg.
The medicine of cardiovascular disease is prone to erythra, hemorrhage, arrhythmia, headache, dizzy etc. at present, easily produces drug resistance and dependency.And 20 (S)-protopanoxadiols derive from plant material, production technology is simple, and cost is low, and the Cardiovarscular medicine with respect to other, has side effect little, safe and reliable advantage.Therefore can be used as one of medicine of Cardiovarscular.
The preparation method of embodiment 1:20 (S)-protopanoxadiol
1, Folium Notoginseng glycoside is 5.0 kilograms, adds n-butyl alcohol, Sodium ethylate, inserts reactor, stirs, and passes into oxygen, keeps having bubble to emerge continuously in bubbling, heats up, and reacts 72 hours; After cooling, add the water washing twice that n-butyl alcohol is saturated, branch vibration layer, n-butyl alcohol concentrating under reduced pressure is recycled to dry, reclaims n-butyl alcohol, residue adds water and stirs, and extracts three times water layer discarded by ethyl acetate, combined ethyl acetate layer, with saturated common salt water washing secondary, branch vibration layer;
2, in ethyl acetate layer, add anhydrous sodium sulfate, dry, ethyl acetate layer is evaporated to dry, reclaims ethyl acetate, obtains protopanoxadiol crude product;
3, in crude product, add ethyl acetate, mix, upper silicagel column, carry out column chromatography, use successively 200 liters of petroleum ether (60-90 ℃)-ethyl acetate (3: 1) and 500 liters of eluting of petroleum ether (60-90 ℃)-ethyl acetate (1: 1), collect eluent, composition with every part of eluent of TLC monitoring, one pack system eluent concentrating under reduced pressure, vacuum drying, obtains 20 (S)-protopanoxadiols.
2: 20 (S)-protopanoxadiol oral liquids of embodiment
Tween 80 20g, soluble in water, add 20 (S)-protopanoxadiol 10g, grind and make colostrum, then add water to 1000ml, obtain oral liquid.
3: 20 (S)-protopanoxadiol capsules of embodiment
20 (S)-protopanoxadiol 10g, add lactose 300g, mix, and take 70% ethanol as binding agent, granulate, and incapsulate, and obtain capsule, and every containing 20 (S)-protopanoxadiol 50mg.4: 20 (S)-protopanoxadiol sheets of embodiment
20 (S)-protopanoxadiol 10g, add lactose 300g, mix, and take 70% ethanol as binding agent, granulate, dry, add magnesium stearate, and tabletting, obtains tablet, and every containing 20 (S)-protopanoxadiol 50mg.
5: 20 (S)-protopanoxadiol injection of embodiment
20 (S)-protopanoxadiol 10g, sodium chloride 100g, 1000ml water for injection is dissolved in dilute preparing tank, stirs, after cooling, decolouring, and filtration, sterilizing, sealed cans, obtain injection.
Although, above used general explanation, the specific embodiment and test, the present invention is described in detail, on basis of the present invention, can make some modifications or improvements it, and this will be apparent to those skilled in the art.Therefore, these modifications or improvements, all belong to the scope of protection of present invention without departing from theon the basis of the spirit of the present invention.
Claims (9)
- The application of 1.20 (S)-protopanoxadiols in the medicine of preparation prevention and treatment ischemic heart desease.
- 2. application according to claim 1, is characterized in that, ischemic heart desease is coronary heart disease or coronary atherosclerotic heart disease.
- 3. application according to claim 1 and 2, is characterized in that, ischemic heart desease is selected from myocardial ischemia and myocardial ischemia reperfusion injury.
- 4. application according to claim 3, is characterized in that, myocardial ischemia and myocardial ischemia reperfusion injury are silent myocardial ischemia, angina pectoris, myocardial infarction, ischemic cardiomyopathy and/or sudden death.
- 5. application according to claim 3, is characterized in that, myocardial ischemia and myocardial ischemia reperfusion injury also comprise because treatment needs are exercised heart time-out perfusion and resuscitation causes again myocardial ischemia and myocardial ischemia reperfusion injury.
- 6. application according to claim 3, is characterized in that, myocardial ischemia and myocardial ischemia reperfusion injury also comprise myocardial ischemia and the myocardial ischemia-reperfusion that operation on heart need to cause.
- 7. application according to claim 6, is characterized in that, described operation is cardiac valve replacement.
- 8. according to the application described in claim 1-7 any one, it is characterized in that 20 (S)-protopanoxadiol preparations that 20 (S)-protopanoxadiols are comprised of 20 (S)-protopanoxadiols and pharmaceutically acceptable carrier or adjuvant.
- 9. application according to claim 8, is characterized in that, 20 (S)-protopanoxadiol preparations are selected from injection, tablet, capsule, oral liquid, aerosol, patch, granule, Sublingual tablet or drop pill.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210203239.XA CN103505462B (en) | 2012-06-19 | 2012-06-19 | The purposes of 20 (S)-protopanoxadiols |
| PCT/CN2013/076347 WO2013189229A1 (en) | 2012-06-19 | 2013-05-28 | New use of 20(s)-protopanoxadiol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210203239.XA CN103505462B (en) | 2012-06-19 | 2012-06-19 | The purposes of 20 (S)-protopanoxadiols |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103505462A true CN103505462A (en) | 2014-01-15 |
| CN103505462B CN103505462B (en) | 2015-12-09 |
Family
ID=49768094
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210203239.XA Active CN103505462B (en) | 2012-06-19 | 2012-06-19 | The purposes of 20 (S)-protopanoxadiols |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN103505462B (en) |
| WO (1) | WO2013189229A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106632570A (en) * | 2016-09-19 | 2017-05-10 | 李晓辉 | Peotopanaxadiol ginsenoside derivative and preparation method and application thereof |
| CN114832025A (en) * | 2022-05-17 | 2022-08-02 | 杭州医学院 | Preparation method and application of ginseng adventitious root crude extract |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006113495A2 (en) * | 2005-04-15 | 2006-10-26 | Hui-Ling Chen | Dicarboxylic acid ester derivatives of ginsenoside, pharmaceutical preparations containing the same, and preparation thereof |
| CN102018716A (en) * | 2009-09-14 | 2011-04-20 | 王泽君 | Medical application of protopanaxatriol and protopanaxadiol in nervous system diseases |
| CN102311474A (en) * | 2010-07-07 | 2012-01-11 | 北京师范大学 | Method for preparing protopanaxadiol and protopanaxatriol by solvent-free method |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101229175A (en) * | 2008-02-15 | 2008-07-30 | 沈阳药科大学 | Medical applications of couple protopanoxadiol derivatives and compound body thereof |
-
2012
- 2012-06-19 CN CN201210203239.XA patent/CN103505462B/en active Active
-
2013
- 2013-05-28 WO PCT/CN2013/076347 patent/WO2013189229A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006113495A2 (en) * | 2005-04-15 | 2006-10-26 | Hui-Ling Chen | Dicarboxylic acid ester derivatives of ginsenoside, pharmaceutical preparations containing the same, and preparation thereof |
| CN102018716A (en) * | 2009-09-14 | 2011-04-20 | 王泽君 | Medical application of protopanaxatriol and protopanaxadiol in nervous system diseases |
| CN102311474A (en) * | 2010-07-07 | 2012-01-11 | 北京师范大学 | Method for preparing protopanaxadiol and protopanaxatriol by solvent-free method |
Non-Patent Citations (6)
| Title |
|---|
| CHANG, SEOK-JONG 等: "Vasorelaxing Effect by Protopanaxatriol and Protopanaxadiol of Panax ginseng in the Pig Coronary Artery", 《KOREAN JOURNAL OF GINSENG SCIENCE》 * |
| 唐树德: "钙通道阻滞剂的临床应用", 《上海医药》 * |
| 杨永健等: "钙通道阻滞剂对心肌重构保护机制的研究", 《中国药理学通报》 * |
| 武淑芳等: "西洋参叶20s-原人参二醇组皂苷抗实验性心肌缺血作用及其机制", 《中国药学杂志》 * |
| 陆丰等: "西洋参20s-原人参二醇组皂苷对急性心肌梗死大鼠交感神经递质及肾素-血管紧张系统的影响", 《中草药》 * |
| 马慧卿: "钙通道阻滞剂对心肌缺血再灌注损伤的保护作用", 《西南国防医药》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106632570A (en) * | 2016-09-19 | 2017-05-10 | 李晓辉 | Peotopanaxadiol ginsenoside derivative and preparation method and application thereof |
| WO2018050099A1 (en) * | 2016-09-19 | 2018-03-22 | 李晓辉 | Panaxdiol-type ginsenoside derivative, preparation method therefor and use thereof |
| CN106632570B (en) * | 2016-09-19 | 2018-07-17 | 李晓辉 | Diol type Hydrolizates and its preparation method and application |
| US11091511B2 (en) | 2016-09-19 | 2021-08-17 | Army Medical University | Panaxdiol-type ginsenoside derivative, preparation method therefor and use thereof |
| CN114832025A (en) * | 2022-05-17 | 2022-08-02 | 杭州医学院 | Preparation method and application of ginseng adventitious root crude extract |
| CN114832025B (en) * | 2022-05-17 | 2023-09-05 | 杭州医学院 | Preparation method and application of ginseng adventitious root crude extract |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103505462B (en) | 2015-12-09 |
| WO2013189229A1 (en) | 2013-12-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1876040B (en) | Detection method of pharmaceutical composition for treating hepatitis | |
| CN101904893B (en) | Angelica sinensis blood enriching capsule and preparation method thereof | |
| CN102552372A (en) | Novel purpose of eucommia chemical components as blood vessel protective agent | |
| CN106389407B (en) | Madder active constituent and combinations thereof, application | |
| CN102293802B (en) | Medicinal composition for treating cardiovascular diseases and preparation method thereof | |
| CN103505462B (en) | The purposes of 20 (S)-protopanoxadiols | |
| CN102357180B (en) | Traditional Chinese medicine composite for curing cancer and preparation method and application thereof | |
| CN101006975B (en) | An oral medicine preparation containing salvianolic acid A and extract of panax natoginseng, and its preparation method and application | |
| CN101006984A (en) | An injection preparation containing salvianolic acid A and extract of panax natoginseng, and its preparation method and application | |
| CN101152233B (en) | Pharmaceutical composition of snakegourd fruit and folium ginkgo | |
| CN113480590B (en) | Wilforinupinone, its preparation method and application in medicine | |
| CN102475766B (en) | Drug composition for treating heart failure, preparation method and application of drug composition | |
| CN1923229B (en) | Pharmaceutical composition comprising notoginseng extract, Danshen extract and puerarin | |
| CN104383547B (en) | Herba Saussureae Involueratae extract phosphatide complexes, oral disnitegration tablet and preparation method thereof | |
| CN102028698B (en) | Medicine for treating colon cancer and preparation method thereof | |
| CN111514212A (en) | Preparation and application of daphne giraldii nitsche anti-liver cancer active total flavone | |
| CN101863945B (en) | American ginseng saponin F6 as well as extraction method and medical application thereof | |
| CN105641169B (en) | A kind of Dengyin naotong pharmaceutical composition and its new application | |
| CN101011543A (en) | Antineoplastic medicine composition | |
| CN103623144B (en) | The application of RP-HPLC in preparation treatment ovarian cancer | |
| CN105012353B (en) | Tabasheer acetic acid ethyl ester extract is used to prepare the purposes of prevention diabetes medicament | |
| CN109111462A (en) | A kind of Salvia japonica A prime and preparation method thereof and the drug comprising Salvia japonica A prime | |
| CN111110689B (en) | Pharmaceutical composition and pharmaceutical preparation for promoting blood circulation, removing blood stasis, dredging collaterals and relieving pain | |
| CN101554417B (en) | Quality control method of antitumor Chinese medicine composition | |
| CN1931214B (en) | Medicine composition of rhodiola root and puerarin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |