CN101700264B - Application of pseudo-ginseng and extract thereof in preparing medicament for curing and/or preventing diabetic neuropathies - Google Patents
Application of pseudo-ginseng and extract thereof in preparing medicament for curing and/or preventing diabetic neuropathies Download PDFInfo
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Abstract
The invention relates to a new application of pseudo-ginseng, pseudo-ginseng extract, panax notoginseng saponins, and panax notoginseng saponins composite, namely, a new application in preparing medicament for curing and/or preventing diabetic neuropathies.
Description
Technical field
The present invention relates to the new purposes of Radix Notoginseng, Radix Notoginseng extract, Radix Notoginseng total arasaponins and notoginseng total saponin compounds, particularly treat and/or prevent the new purposes aspect the diabetic neuropathy medicine in preparation.
Background technology
Radix Notoginseng is an Araliaceae, have invigorate blood circulation, dissipating blood stasis, antiinflammatory, analgesic effect.Except that above-mentioned effect is arranged, also has the special role that reduces the human body thrombin.Fg is the synthetic a kind of plasma globulin level of liver.Its major function is for participating in coagulation process.Fg raises can increase the heart, cerebrovascular incidence rate.Oral raw sangqi ginseng powder can reduce the fg level, helps controlling the generation of the heart, cerebrovascular.The graduate Wang Nan of mo university Traditional Chinese Medicine that " Chinese herbal medicine " 2008 05 periodicals are stepped on, Wan Jianbo, Li Mingyuan, relevant " Radix Notoginseng the is treated atherosclerotic progress " literary composition of Wang Yitao are pointed out: atherosclerosis is the key factor that causes the cardiovascular and cerebrovascular vessel incident to take place, and is the common pathophysiological basis of multiple cardiovascular and cerebrovascular disease.Its disease, pathogenesis etc. belong to " syndrome of blood stasis " of theory of Chinese medical science.And Radix Notoginseng is the key medicine of ancient Chinese medicine doctor blood circulation promoting and blood stasis dispelling commonly used from ancient times.In other words, Radix Notoginseng has its magical part aspect the atherosclerosis preventing and treating.
The neuropathy complication of diabetes is normal directly or indirectly participates in atherosclerotic generation and development, therefore, utilizes Radix Notoginseng to prevent and treat that atherosclerotic to be used for treating diabetic complication be feasible.
Radix Notoginseng total arasaponins is that the chemical constituent of Radix Notoginseng medicine plant is more, mainly is made up of tetracyclic triterpene dammarane type protopanoxadiol saponins and tetracyclic triterpene dammarane type Protopanaxatriol saponins from the total active substance that extracts of Radix Notoginseng plant.Radix Notoginseng total arasaponins all has certain curative effect to symptoms such as hyperlipemia, high blood viscosity, hypertension, myocardial ischemia, arrhythmia, atherosclerosiss, but also have the thrombosis of preventing, microcirculation improvement, anti-cardiac-cerebral ischemia, promote hematopoietic cell, fibrosis, to the protective effect of neural cell injury.From the above mentioned, the Radix Notoginseng total arasaponins ejection preparation that uses Radix Notoginseng total arasaponins to make as raw material is a kind of unique multi-functional injection, and these effects all have independence, and it is active to collect some important biomolecules, can bring into play some kinds of clinical function in a medicine.In these all functions, the function that has is opposed, contradiction.Because composition is very complicated in the Radix Notoginseng total arasaponins, still to fail real clear and definite concrete what composition at present to play main therapeutical effect, the mechanism of action between the composition is also had no talent and was done comprehensive research.
Summary of the invention
The effective ingredient of Radix Notoginseng extract is mainly Radix Notoginseng total arasaponins; Blood circulation promoting and blood stasis dispelling is arranged, the active effect of promoting blood circulation; According to my company clinical research and pharmacodynamic study, find that Radix Notoginseng total arasaponins has the obvious curative effects of prevention and treatment diabetic neuropathy to Radix Notoginseng total arasaponins.
Diabetes are by the Different types of etiopathogenises metabolism disorder that to cause with chronic high blood grain be characteristic.Prolonged illness can cause the multisystem infringement, causes the chronic progressive external pathological changes of tissues such as eye, kidney, nerve, heart, blood vessel, causes functional defect and depletion.
The chronic complicating diseases of diabetes can spread all over each vitals of whole body, and is relevant with influencing each other of genetic predisposition, hyperglycemia, oxidative stress, nonenzymatic glycosylation and many-sided factors such as polyhydric alcohol metabolic bypass, APC Protein kinase C.These complication can occur separately or occur simultaneously or successively with various combination.Sometimes complication exists before diagnosing diabetes is arranged, and some patient finds diabetes because of these complication as clue.
Neuropathy is one of chronic complicating diseases of diabetes.Due to diabetic neuropathy is mainly strengthened by microangiopathies and sorbitol bypass metabolism so that sorbitol increases etc.Electrophysiologic study can find that sensation and motor nerve conduction velocity slow down.
Diabetic peripheral neuropathy takes place on the long-term unfavorable basis of glycemic control.Pathogenesis it be unclear that.Be recognized that relatively and angiopathy, metabolism disorder that multiple factors such as muscular nerve trophic factors minimizing are relevant.Blood vessel changes has capillary tunica intima and cell based counterdie hypertrophy, hematoblastic gathering to increase.Cellulosic depositions etc. make blood capillary luminal stenosis and obturation.Thereby cause that microcirculation blood supply insufficiency, ischemia, cellulose lack, make the peripheral nerve axonal degeneration, demyelination takes place change, thereby occur a series of performances clinically.
The Radix Notoginseng total arasaponins that patent of the present invention is extracted from the Chinese medicine Radix Notoginseng.Clinical physiological research proof: it has flow of calcium ions, the interior calcium ion concentration of reduction endochylema that stops cell, blood vessel dilating; Improve the microcirculation of tissue, CAMP content in the platelet of raising is arranged simultaneously and anticoagulant, and reduce WBV.Help the blood supply oxygen supply organized therefrom.In addition, Radix Notoginseng total arasaponins has calm and analgesic activity.Patent of the present invention is used to treat diabetic peripheral neuropathy patient obvious effective rate and reaches 89%.Its mechanism possibly be not only to have repaired the nerve of damage but also improved and nourished neural microcirculation, has added calmness, analgesic activity, so curative effect is comparatively remarkable.
The safety of patent clinical practice of the present invention is higher, a kind of good medicine of in the Drug therapy of diabetic neuropathy, can yet be regarded as, and it has widened the new method of Chinese medicine preparation treatment coronary heart disease, and is particularly suitable at the basic hospital that can not carry out interventional therapy.
Therefore, the applicant provides a kind of preparation to treat and/or prevent the new purposes of diabetic neuropathy medicine aspect.
The invention discloses the new purposes that a kind of preparation treats and/or prevents diabetic neuropathy medicine aspect; It is characterized in that containing active ingredient in the said notoginseng total saponin compounds; The Radix Notoginseng total arasaponins active ingredient that this active ingredient is extracted by Radix Notoginseng is formed Panax Notoginseng saponin R
1Content greater than 8.0%, the ginsenoside Rg
1Content greater than 25%, ginsenoside Rb
1Content greater than 25%, ginsenoside Re's content is greater than 4.0%, and Panax Notoginseng saponin R
1, ginsenoside Rb
1, the ginsenoside Rg
1With ginsenoside Re's gross weight greater than 75% of active ingredient gross weight.
Preferably, Rb
1: Rg
1Be 1.0: 0.5～2.0.
Preferably, the content of described active ingredient composition is: Panax Notoginseng saponin R
1Content greater than 8.0%, the ginsenoside Rg
1Content greater than 25%, ginsenoside Rb
1Content greater than 25%, ginsenoside Re's content is greater than 4.0%, and Rb
1: Rg
1Be 1.0: 1.0～1.8;
More preferably, the content of described active ingredient composition is: Panax Notoginseng saponin R
1Content greater than 8.0%, the ginsenoside Rg
1Content greater than 25%, ginsenoside Rb
1Content greater than 25%, ginsenoside Re's content is greater than 4.0%, and Rb
1: Rg
1Be 1.0: 1.4～1.6;
Preferably, Panax Notoginseng saponin R
1, ginsenoside Rb
1, the ginsenoside Rg
1With ginsenoside Re's gross weight greater than 85% of active ingredient gross weight;
More preferably, Panax Notoginseng saponin R
1, ginsenoside Rb
1, the ginsenoside Rg
1With ginsenoside Re's gross weight greater than 90% of active ingredient gross weight;
Preferably, the content of described active ingredient composition is: Panax Notoginseng saponin R wherein
1Content is 8%～15%, the ginsenoside Rg
1Content is 35%～52%, ginsenoside Re's content is 4%～10%, ginsenoside Rb
1Content is 25%～40%.
The dosage form of Radix Notoginseng total arasaponins active ingredient compositions of the present invention can be processed various dosage forms; As process injection, powder ampoule agent for injection; Freeze-dried powder injection, tablet, pill, powder, granule, mixture, syrup, capsule, drop pill preparation are preferably processed injection, freeze-dried powder injection.
Below be the crude drug source of Chinese medicine preparation of the present invention: Radix Notoginseng: be the dry root of Araliaceae.
The applicant also provides the described Radix Notoginseng total arasaponins active ingredient of a kind of preparation method for compositions, and it comprises the steps:
(1) gets Radix Notoginseng powder and be broken into coarse powder 1000g, add volume ratio and be the ethanol extraction 0.5～10 hour of 5-30 45-95% doubly, collect extracting solution, filter;
(2) get filtrate recycling ethanol to there not being the alcohol flavor, add water and process the solution that every 1ml contains the 0.5g crude drug;
(3) solution is through the absorption of D type macroporous resin column; Mixed liquor with alcohol-water carries out gradient elution; Flow velocity is counted 4.5BV/h by the multiple of resin volume per hour; Concentration of alcohol progressively is adjusted to 95% by 5% in the eluent, collect contain concentration of alcohol 30% or more to the eluent below 70%, discard and contain concentration of alcohol at 30% to 70% in addition eluent; Decompression and solvent recovery below 65 ℃ and to be concentrated into 60 ℃ of following relative densities be 1.10～1.20 clear paste, cold drying gets notoginseng total saponin compounds.
Preferably, the ethanol that adds 7 times in the step (1); The concentration of alcohol that adds is 65%; Extraction time is 7 hours.
Radix Notoginseng total arasaponins active ingredient compositions according to the conventional method in the pharmaceutical field, is processed various preparations.
Each component content is about in the Radix Notoginseng total arasaponins active ingredient compositions that said process obtains: Panax Notoginseng saponin R
1Content greater than 8.0%, the ginsenoside Rg
1Content greater than 25%, ginsenoside Rb
1Content greater than 25%, ginsenoside Re's content is greater than 4.0%, and Rb
1: Rg
1Be 1.0: 0.5～2.0, and Panax Notoginseng saponin R
1, ginsenoside Rb
1, the ginsenoside Rg
1With ginsenoside Re's gross weight greater than 75% of active ingredient gross weight.
Based on above-mentioned notoginseng total saponin compounds, the purpose of this invention is to provide a kind of new purposes of said composition, promptly treat and/or prevent the application of diabetic neuropathy medicine in preparation.It can process spendable preparations such as capsule, injection, tablet, suppository or oral liquid.The medicine of above-mentioned various dosage forms all can be according to the conventional method preparation of pharmaceutical field.
Following experimental result has been explained the new drug effect of said composition, has shown beneficial effect of the present invention.
Injection according to above-mentioned notoginseng total saponin compounds preparation is tested the effect that treats and/or prevents of rabbit diabetic neuropathy.
1. experiment material
1.1 experiment medicine
Sample according to the embodiment of the invention 1 preparation; Diabetes pill (Guangzhou Zhongyi Medicine Industry Co., Ltd, the accurate word Z44020045 of traditional Chinese medicines, lot number KY0111).
1.2 reagent
Streptozotocin (streptozotocin, STZ, sigma company); Citric acid (Xu Dong chemical plant, Beijing, top grade is pure, lot number: 060706); Sodium citrate (Beijing chemical reagents corporation, analytical pure, lot number: 20060606); Pentobarbital sodium (Beijing chemical reagents corporation, lot number: 020919); Glucose assays test kit (Zhongsheng Beikong Biological Science & Technology Co., Ltd., lot number: 060731); T-CHOL is measured test kit (Zhongsheng Beikong Biological Science & Technology Co., Ltd., lot number: 070471); Triglyceride determination test kit (Zhongsheng Beikong Biological Science & Technology Co., Ltd., lot number: 072011).
1.3 experimental apparatus
Centrifuge (LXJ-II, Shanghai medical analytical instrument factory); Polygraph (BIOPAC MP150, the U.S.); Semiautomatic biochemistry analyzer (Microlab 300, Vital Scientific Inc.).
1.4 laboratory animal
The Wistar rat, male, cleaning level, body weight 180g-220g, source: Institute of Experimental Animals, Chinese Academy of Medical Sciences, credit number: SCXK (capital) 2005-0013.
2.. experimental technique
2.1 reagent preparation
(1) 20ml 0.1M citrate buffer solution (pH4.4): 0.1M citric acid 11.4ml+0.1M sodium citrate 8.6ml; (2) 2%STZ: with the preparation of 0.1M citrate buffer solution, join existing usefulness at present, place ice bath.
2.2 the foundation of rat diabetes model
Rat fasting 16h, 2%STZ lumbar injection (50mg/kg; 0.25ml/100g), injection back 72h tail vein is got blood, measures fasting glucose, and fasting blood glucose level＞300mg/dl (16.7mM) is rat diabetes model modeling success.
2.3 experiment grouping dosage is provided with
(1) embodiment 1: people's clinical application amount is 300mg/60kg/d, im.6 times of rat dosage behaviour clinical application amount.So experiment is provided with 3 dose groups: high dose group (clinical equivalent dosage 2 times) 60mg/kg/d; Middle dose groups (clinical equivalent dosage) 30mg/kg/d; Low dose group (clinical equivalent dosage 1/2) 15mg/kg.
(2) diabetes pill: people's clinical usage and dosage does, and is oral, a 3-10 ball (2.5g/10 ball), 2-3 time/day.Selected people's clinical application amount is 5g/60kg/d.6 times of rat dosage behaviour clinical application amount are so diabetes pill rat dosage is 500mg/kg/d.
2.4 experiment is divided into groups and administration
Rat is by the body weight random packet, and after the success of affirmation diabetes model, regular diet was fed for 12 weeks, and it is following to give the relative medicine intervention then:
2.5 MNCV is measured
1h after the last administration, rat pentobarbital sodium (50mg/kg) intraperitoneal anesthesia.The isolated from rat sciatic nerve is measured electrode two ends distances (D), and the Biopac polygraph is measured the preclinical difference of M ripple (L) that stimulates 2 of sciatic nerves to bring out the gastrocnemius action potential.Distance (D) according to reaching between two stimulation points calculates MNCV NCV, NCV=D/L.
2.6 blood glucose, lipid determination
Fasting 16h before the experiment.The ventral aorta blood sampling, centrifuging and taking serum, the routine biochemistry detection method is measured fasting glucose, TC, TG level.
3. experimental result
3.1 the influence of 1 pair of diabetes rat blood fat of embodiment and blood glucose
The influence of 1 pair of diabetes rat blood fat of table 1 embodiment and blood glucose (x ± s)
Compare with blank control group: △ P＜0.05, △ △ P＜0.01, △ △ △ P＜0.001; Compare with model group: * P＜0.05, * * P＜0.01, * * * P＜0.001.
Experimental result shows that behind lumbar injection STZ, model group, diabetes pill group and 1 basic, normal, high group of rat blood sugar level of embodiment all are significantly higher than blank group (p＜0.001), shows rat diabetes model modeling success.Successive administration is after 12 weeks, and diabetes pill (500mg/kg) can reduce the blood glucose in diabetic rats level with embodiment 1 high dose (60mg/kg), with model group significant difference (p＜0.05) is arranged relatively.Model group and blank group relatively, TC, the horizontal unknown significance difference of TG (p＞0.05), show 24 weeks of this diabetes model modeling after, do not cause the variation of diabetes rat blood lipid level.
Above result shows that embodiment 1 can reduce glycosuria rat blood sugar level, and the blood sugar level of diabetes rat is had certain regulating action.
3.2 the influence of 1 pair of diabetes rat nerve conduction of embodiment
The influence of 1 pair of diabetes rat MNCV of table 2 embodiment (x ± s)
Compare with blank control group:
△ △ △P＜0.001; Compare with model group:
*P＜0.05,
*P＜0.01,
* *P＜0.001.
Experimental result shows that in 24 weeks after the modeling of lumbar injection STZ diabetes, model group rat nerves conduct velocity relatively has significant difference (p＜0.001) with the blank group.Dosage (30mg/kg) and embodiment 1 heavy dose (60mg/kg) all can improve the diabetic sciatic nerve conduction velocity among diabetes pill (500mg/kg), the embodiment 1, with model group significant difference (p value be respectively＜0.01,0.05,0.01) are arranged relatively.
The result shows that embodiment 1 can improve the diabetes rat MNCV, to the effect of having some improvement of diabetic nerve conduction function tool.
4. conclusion
This experimental result shows that behind lumbar injection STZ, the blood sugar level rising appears in diabetes rat, MNCV slows down., can reduce the blood glucose in diabetic rats level, improve MNCV after 12 weeks of 1 freeze-dried powder through lumbar injection embodiment; Can improve little blood vessel of rat diabetes property retina and nerve fiber pathological changes.
Clinical trial
One, object:
The type 2 diabetes mellitus patient of WHO standard diagnosis in 1999 is totally 30 examples, all from the inpatient.Selected condition is:
Extremity spontaneous pain or sensory disturbance; The myoelectricity diagram nervus motorius especially sensation conduction velocity of tibial nerve weakens.Peripheral neuropathy due to the eliminating other reasons.
62～85 years old age, glycemic control be (HbAlc＜7%) steadily; Nonjoinder uses the medicine of treatment diabetic neuropathy more than 2 weeks.The course of disease 5～15 years (diabetes) wherein, male's 21 examples, women's 9 examples.All there is not the contraindication of using embodiment 1 (freeze-dried powder).
Two, method:
1, administrated method: all cases all strictness keep on a diet and the basis of orally-taken blood sugar reducing medicine or insulinize on, with embodiment 1 (freeze-dried powder) 450mg+ normal saline 100ml intravenous drip, every day 1 time, 2 weeks were 1 course of treatment, totally 2 courses of treatment.
2, curative effect is judged: produce effects: subjective symptoms is clearly better or disappears, and tendon reflex is clearly better or recovers normal, and the more preceding increase of conduction velocity in electromyogram 5m/s is above or recover normal.Effectively: subjective symptoms is improved, and the knee joint Achilles jerk makes moderate progress.Invalid: subjective symptoms does not have improvement, neural tendon reflection and conduction velocity in electromyogram no change.
Three, statistical method:
Data represent that with X ± S data compare with paired t-test before and after the treatment on the same group.
Four, result
1, general clinical features: 30 routine diabeticss are the preceding 8.5 ± 1.62mol/L of fasting glucose treatment in the observation process; After the treatment 7.9 ± 1.4mol/L, no significant difference between the two.All patient all adheres to accomplishing observation.
2, the main variation of peripheral neuropathy symptom: the spontaneous pain of upper and lower limb before the treatment, feel to go down, incidence rate numb, that generate heat and feel cold is respectively 50%, 34%, 42%, 68%, 16%, 17%.After around the intravenous administration, upper limb and lower limb spontaneous pain, feel to go down, sensation numb, that generate heat obviously improves, the improvement rate is more than 60%.The improvement rate that quadriceps reflex, the Achilles jerk reduce before and after treatment is respectively 49%, 51%.As shown in Figure 1.
3, neural Electromyographic test: have 20 examples to carry out neural electromyogram inspection in the middle of the 30 routine patients.As shown in table 2.Treat motor nerve conduction velocity and the median nerve of forward and backward median nerve, tibial nerve, common peroneal nerve, the sensory nerve conduction velocity of superficial peroneal nerve obviously improves.
30 examples are measured the forward and backward unknown apparent difference of routine blood test, routine urinalysis and indexs such as liver function, renal function of treatment.
Table I is with the improvement of embodiment 1 (freeze-dried powder) agent treatment back patient's subjective symptom
Table 2 embodiment 1 treatment motion and sensory nerve conduction velocity (m/s) change
Relatively preceding with treatment, * P＜0.05
Five, discuss
Diabetic peripheral neuropathy takes place on the long-term unfavorable basis of glycemic control.Pathogenesis it be unclear that.Be recognized that relatively and angiopathy, metabolism disorder that multiple factors such as muscular nerve trophic factors minimizing are relevant.Blood vessel changes has capillary tunica intima and cell based counterdie hypertrophy, hematoblastic gathering to increase.Cellulosic depositions etc. make blood capillary luminal stenosis and obturation.Thereby cause that microcirculation blood supply insufficiency, ischemia, cellulose lack, make the peripheral nerve axonal degeneration, demyelination takes place change, thereby occur a series of performances clinically.Embodiment 1 is the Radix Notoginseng total arasaponins that extracts from the Chinese medicine Radix Notoginseng.Clinical physiological research proof: it has flow of calcium ions, the interior calcium ion concentration of reduction endochylema that stops cell, blood vessel dilating; Improve the microcirculation of tissue, CAMP content in the platelet of raising is arranged simultaneously and anticoagulant, and reduce WBV.Help the blood supply oxygen supply organized therefrom.In addition, Radix Notoginseng total arasaponins has calm and analgesic activity.Treat 30 routine diabetic peripheral neuropathy patient obvious effective rates with patent of the present invention and reach 89%.Its mechanism possibly be not only to have repaired the nerve of damage but also improved and nourished neural microcirculation, has added calmness, analgesic activity, so curative effect is comparatively remarkable.Add patent stable performance of the present invention, in the whole course of treatment, do not see untoward reaction,, be worth clinical expansion so can think a kind of good medicine of treating diabetic peripheral neuropathy.
The specific embodiment
Further specify the present invention through embodiment below.It should be understood that embodiments of the invention are to be used to explain the present invention rather than limitation of the present invention.The simple modifications that essence according to the present invention is carried out the present invention all belongs to the present invention and requires the scope protected.Except as otherwise noted, the percent among the present invention is percetage by weight (ethanol is percent by volume), and BV/h representes that in the resin volume be V, and B is a multiple, and solution elution volume hourly is resin volume B * V.
Embodiment 1:
Get Radix Notoginseng powder and be broken into coarse powder 1000g, add 65% ethanol 7000ml and extracted 7 hours, collect extracting solution, filter; Get filtrate recycling ethanol to there not being the alcohol flavor, add water and process the solution that every 1ml contains the 0.5g crude drug, with macroporous resin column (D class macroporous resin, resin volume 3000ml, the resin height of bed is about 8 with the diameter ratio) and alumina adsorption; Carry out gradient elution with Different concentrations of alcohol liquid, concentration of alcohol was adjusted to 95% by 5% in 6 hours, flow velocity 4.5BV/h; Discard and contain the eluent of concentration of alcohol beyond 30% to 70%, collect contain concentration of alcohol more than 30% to the eluent below 70%, decompression and solvent recovery below 65 ℃ also is concentrated into the clear paste that relative density is 1.13 (60 ℃); The Radix Notoginseng total arasaponins active ingredient, add the injection water and regulate every 1ml and contain solid content 100mg, ultrafiltration; Fill, embodiment 1 injectable powder is processed in lyophilization.
Assay: each component content in the said extracted thing: Panax Notoginseng saponin R
1Be 12.47%, the ginsenoside Rg
1Be 45.12%, the ginsenoside Re is 6.04%, ginsenoside Rb
1Be 29.94%, more than four composition total amounts be 93.57%, and Rb
1: Rg
1It is 1.0: 1.51.
Embodiment 2:
Get Radix Notoginseng powder and be broken into coarse powder 1000g, add 50% ethanol 10000ml and extracted 6 hours, collect extracting solution; Filter, get filtrate recycling ethanol, add water and process the solution that every 1ml contains the 0.4g crude drug to there not being the alcohol flavor; With macroporous resin column (D class macroporous resin, resin volume 3000ml, the resin height of bed is about 8 with the diameter ratio) and alumina adsorption, carry out gradient elution (concentration of alcohol was adjusted to 95% by 5% in 5.5 hours) with Different concentrations of alcohol liquid; Flow velocity 5.0BV/h discards and contains the eluent of concentration of alcohol beyond 30% to 70%, collect contain concentration of alcohol more than 30% to the eluent below 70%; Decompression and solvent recovery below 65 ℃ also is concentrated into the clear paste that relative density is 1.15 (60 ℃), and drying gets the Radix Notoginseng total arasaponins active ingredient; Adding the injection water regulates every 1ml and contains solid content 50mg～55mg; Ultrafiltration, embodiment 1 injection is processed in fill.
Assay: each component content in the said extracted thing: Panax Notoginseng saponin R
1Be 11.54%, the ginsenoside Rg
1Be 45.26%, the ginsenoside Re is 5.06%, ginsenoside Rb
1Be 31.26%, more than four composition total amounts be 93.12%, and Rb
1: Rg
1It is 1.0: 1.45.
Embodiment 3:
Get Radix Notoginseng powder and be broken into coarse powder 1000g, add 75% ethanol 7500ml and extracted 8 hours, collect extracting solution; Filter, get filtrate recycling ethanol, add water and process the solution that every 1ml contains the 0.6g crude drug to there not being the alcohol flavor; With macroporous resin column (D class macroporous resin, resin volume 3000ml, the resin height of bed is about 8 with the diameter ratio) and alumina adsorption, carry out gradient elution (concentration of alcohol was adjusted to 95% by 5% in 6.5 hours) with Different concentrations of alcohol liquid; Flow velocity 4.0BV/h discards and contains the eluent of concentration of alcohol beyond 30% to 70%, collect contain concentration of alcohol more than 30% to the eluent below 70%; Decompression and solvent recovery below 65 ℃ also is concentrated into the clear paste that relative density is 1.16 (60 ℃), gets the Radix Notoginseng total arasaponins active ingredient, adds needle-use activated carbon 0.30% (weight ratio); 80 ℃ of following insulated and stirred 30 minutes filter, and add the injection water and regulate every 1ml and contain solid content 150mg; Lyophilization, embodiment 1 injectable powder is processed in packing.
Assay: each component content in the said extracted thing: Panax Notoginseng saponin R
1Be 13.3%, the ginsenoside Rg
1Be 49.1%, the ginsenoside Re is 5.1%, ginsenoside Rb
1Be 30.9%, more than four composition total amounts be 98.4%, and Rb
1: Rg
1It is 1.0: 1.59.
Embodiment 4:
Get Radix Notoginseng powder and be broken into coarse powder 1000g, add 80% ethanol 8000ml and extracted 6 hours, collect extracting solution, filter; Get filtrate recycling ethanol to there not being the alcohol flavor, add water and process the solution that every 1ml contains the 0.5g crude drug, with macroporous resin column (D class macroporous resin, resin volume 3000ml, the resin height of bed is about 8 with the diameter ratio) and alumina adsorption; Carry out gradient elution with Different concentrations of alcohol liquid, concentration of alcohol was adjusted to 95% by 5% in 6 hours, flow velocity 4.5BV/h; Discard and contain the eluent of concentration of alcohol beyond 30% to 70%, collect contain concentration of alcohol more than 30% to the eluent below 70%, decompression and solvent recovery below 65 ℃ also is concentrated into the clear paste that relative density is 1.13 (60 ℃); The Radix Notoginseng total arasaponins active ingredient, add the injection water and regulate every 1ml and contain solid content 100mg, ultrafiltration; Fill, embodiment 1 injectable powder is processed in lyophilization.
Assay: each component content in the said extracted thing: Panax Notoginseng saponin R
1Be 10.1%, the ginsenoside Rg
1Be 37.4%, the ginsenoside Re is 4.7%, ginsenoside Rb
1Be 36.17%, more than four composition total amounts be 88.37%, and Rb
1: Rg
1It is 1.0: 1.03.
Embodiment 5:
Get Radix Notoginseng powder and be broken into coarse powder 1000g, add 85% ethanol 8000ml and extracted 8 hours, collect extracting solution, filter; Get filtrate recycling ethanol to there not being the alcohol flavor, add water and process the solution that every 1ml contains the 0.5g crude drug, with macroporous resin column (D class macroporous resin, resin volume 3000ml, the resin height of bed is about 8 with the diameter ratio) and alumina adsorption; Carry out gradient elution with Different concentrations of alcohol liquid, concentration of alcohol was adjusted to 95% by 5% in 6 hours, flow velocity 4.5BV/h; Discard and contain the eluent of concentration of alcohol beyond 30% to 70%, collect contain concentration of alcohol more than 30% to the eluent below 70%, decompression and solvent recovery below 65 ℃ also is concentrated into the clear paste that relative density is 1.13 (60 ℃); The Radix Notoginseng total arasaponins active ingredient, add the injection water and regulate every 1ml and contain solid content 100mg, ultrafiltration; Fill, embodiment 1 injectable powder is processed in lyophilization.
Assay: each component content in the said extracted thing: Panax Notoginseng saponin R
1Be 10.4%, the ginsenoside Rg
1Be 39.6%, the ginsenoside Re is 5.2%, ginsenoside Rb
1Be 36.0%, more than four composition total amounts be 91.2%, and Rb
1: Rg
1It is 1.0: 1.10.
Embodiment 6:
Get Radix Notoginseng powder and be broken into coarse powder 1000g, add 75% ethanol 8000ml and extracted 7 hours, collect extracting solution, filter; Get filtrate recycling ethanol to there not being the alcohol flavor, add water and process the solution that every 1ml contains the 0.5g crude drug, with macroporous resin column (D class macroporous resin, resin volume 3000ml, the resin height of bed is about 8 with the diameter ratio) and alumina adsorption; Carry out gradient elution with Different concentrations of alcohol liquid, concentration of alcohol was adjusted to 95% by 5% in 6 hours, flow velocity 4.5BV/h; Discard and contain the eluent of concentration of alcohol beyond 30% to 70%, collect contain concentration of alcohol more than 30% to the eluent below 70%, decompression and solvent recovery below 65 ℃ also is concentrated into the clear paste that relative density is 1.13 (60 ℃); The Radix Notoginseng total arasaponins active ingredient, add the injection water and regulate every 1ml and contain solid content 100mg, ultrafiltration; Fill, embodiment 1 injectable powder is processed in lyophilization.
Assay: each component content in the said extracted thing: Panax Notoginseng saponin R
1Be 13.1%, the ginsenoside Rg
1Be 41.21%, the ginsenoside Re is 4.9%, ginsenoside Rb
1Be 34.23%, more than four composition total amounts be 93.44%, and Rb
1: Rg
1It is 1.0: 1.20.
Embodiment 7:
Get Radix Notoginseng powder and be broken into coarse powder 1000g, add 65% ethanol 6000ml and extracted 8 hours, collect extracting solution, filter; Get filtrate recycling ethanol to there not being the alcohol flavor, add water and process the solution that every 1ml contains the 0.5g crude drug, with macroporous resin column (D class macroporous resin, resin volume 3000ml, the resin height of bed is about 8 with the diameter ratio) and alumina adsorption; Carry out gradient elution with Different concentrations of alcohol liquid, concentration of alcohol was adjusted to 95% by 5% in 6 hours, flow velocity 4.5BV/h; Discard and contain the eluent of concentration of alcohol beyond 30% to 70%, collect contain concentration of alcohol more than 30% to the eluent below 70%, decompression and solvent recovery below 65 ℃ also is concentrated into the clear paste that relative density is 1.12 (60 ℃); The Radix Notoginseng total arasaponins active ingredient, add the injection water and regulate every 1ml and contain solid content 100mg, ultrafiltration; Fill, embodiment 1 injectable powder is processed in lyophilization.
Assay: each component content in the said extracted thing: Panax Notoginseng saponin R
1Be 9.77%, the ginsenoside Rg
1Be 44.89%, the ginsenoside Re is 4.41%, ginsenoside Rb
1Be 26.01%, more than four composition total amounts be 88.08%, and Rb
1: Rg
1It is 1.0: 1.73.
Embodiment 8:
Get Radix Notoginseng powder and be broken into coarse powder 1000g, add 90% ethanol 10000ml and extracted 9 hours, collect extracting solution; Filter, get filtrate recycling ethanol, add water and process the solution that every 1ml contains the 0.5g crude drug to there not being the alcohol flavor; With macroporous resin column (D class macroporous resin, resin volume 3000ml, the resin height of bed is about 8 with the diameter ratio) and alumina adsorption, carry out gradient elution with Different concentrations of alcohol liquid; Concentration of alcohol was adjusted to 95% by 5% in 6 hours, flow velocity 4.5BV/h discards and contains the eluent of concentration of alcohol beyond 30% to 70%; Collection contain concentration of alcohol more than 30% to the eluent below 70%, decompression and solvent recovery below 65 ℃ also is concentrated into the clear paste that relative density is 1.12 (60 ℃), the Radix Notoginseng total arasaponins active ingredient; Adding the injection water regulates every 1ml and contains solid content 100mg, ultrafiltration, fill; Embodiment 1 injectable powder is processed in lyophilization.
Assay: each component content in the said extracted thing: Panax Notoginseng saponin R
1Be 12.3%, the ginsenoside Rg
1Be 23.12%, the ginsenoside Re is 5.81%, ginsenoside Rb
1Be 34.96%, more than four composition total amounts be 76.19%, and Rb
1: Rg
1It is 1.0: 0.66.
Embodiment 9:
Get Radix Notoginseng powder and be broken into coarse powder 1000g, add 85% ethanol 9000ml and extracted 10 hours, collect extracting solution, filter; Get filtrate recycling ethanol to there not being the alcohol flavor, add water and process the solution that every 1ml contains the 0.5g crude drug, with macroporous resin column (D class macroporous resin, resin volume 3000ml, the resin height of bed is about 8 with the diameter ratio) and alumina adsorption; Carry out gradient elution with Different concentrations of alcohol liquid, concentration of alcohol was adjusted to 95% by 5% in 6 hours, flow velocity 4.5BV/h; Discard and contain the eluent of concentration of alcohol beyond 30% to 70%, collect contain concentration of alcohol more than 30% to the eluent below 70%, decompression and solvent recovery below 65 ℃ also is concentrated into the clear paste that relative density is 1.12 (60 ℃); The Radix Notoginseng total arasaponins active ingredient, add the injection water and regulate every 1ml and contain solid content 100mg, ultrafiltration; Fill, embodiment 9 injectable powder are processed in lyophilization.
Assay: each component content in the said extracted thing: Panax Notoginseng saponin R
1Be 13.6%, the ginsenoside Rg
1Be 51.01%, the ginsenoside Re is 5.1%, ginsenoside Rb
1Be 28.2%, more than four composition total amounts be 97.91%, and Rb
1: Rg
1It is 1.0: 1.81.
Embodiment 10:
Get Radix Notoginseng powder and be broken into coarse powder 1000g, add 65% ethanol 7500ml and extracted 9 hours, collect extracting solution, filter; Get filtrate recycling ethanol to there not being the alcohol flavor, add water and process the solution that every 1ml contains the 0.5g crude drug, with macroporous resin column (D class macroporous resin, resin volume 3000ml, the resin height of bed is about 8 with the diameter ratio) and alumina adsorption; Carry out gradient elution with Different concentrations of alcohol liquid, concentration of alcohol was adjusted to 95% by 5% in 6 hours, flow velocity 4.5BV/h; Discard and contain the eluent of concentration of alcohol beyond 30% to 70%, collect contain concentration of alcohol more than 30% to the eluent below 70%, decompression and solvent recovery below 65 ℃ also is concentrated into the clear paste that relative density is 1.13 (60 ℃); The Radix Notoginseng total arasaponins active ingredient, add the injection water and regulate every 1ml and contain solid content 100mg, ultrafiltration; Fill, embodiment 10 injectable powder are processed in lyophilization.
Assay: each component content in the said extracted thing: Panax Notoginseng saponin R
1Be 10.12%, the ginsenoside Rg
1Be 51.67%, the ginsenoside Re is 4.4%, ginsenoside Rb
1Be 27.1%, more than four composition total amounts be 93.29%, and Rb
1: Rg
1It is 1.0: 1.91.
Claims (8)
1. a Radix Notoginseng total arasaponins that extracts from the notoginseng drying root treats and/or prevents the application of diabetic neuropathy medicine in preparation; It is characterized in that: contain active ingredient in the said notoginseng total saponin compounds; The Radix Notoginseng total arasaponins active ingredient that this active ingredient is extracted by Radix Notoginseng is formed; Wherein arasaponin R1 content greater than 8.0%, ginsenoside Rg1's content greater than 25%, ginsenoside Rb1's content greater than 25%, ginsenoside Re's content is greater than 4.0%; And arasaponin R1, ginsenoside Rb1, ginsenoside Rg1 and ginsenoside Re's gross weight is greater than 75% of the active ingredient gross weight, and said compositions prepares through following method:
(1) gets Radix Notoginseng powder and be broken into coarse powder 1000g, add volume ratio and be the ethanol extraction 0.5～10 hour of 5-30 45-95% doubly, collect extracting solution, filter;
(2) get filtrate recycling ethanol to there not being the alcohol flavor, add water and process the solution that every 1ml contains the 0.5g crude drug;
(3) solution is through the absorption of D type macroporous resin column; Mixed liquor with alcohol-water carries out gradient elution; Flow velocity is counted 4.5BV/h by the multiple of resin volume per hour; Concentration of alcohol progressively is adjusted to 95% by 5% in the eluent, collect contain concentration of alcohol 30% or more to the eluent below 70%, discard and contain concentration of alcohol at 30% to 70% in addition eluent; Decompression and solvent recovery below 65 ℃ and to be concentrated into 60 ℃ of following relative densities be 1.10～1.20 clear paste, cold drying gets notoginseng total saponin compounds.
2. application according to claim 1 is characterized in that: Rb1: Rg1 is 1.0: 0.5～2.0.
3. application according to claim 1 is characterized in that: Rb1: Rg1 is 1.0: 1.0～1.8.
4. application according to claim 1 is characterized in that: Rb1: Rg1 is 1.0: 1.4～1.6.
5. application according to claim 1 is characterized in that: arasaponin R1, ginsenoside Rb1, ginsenoside Rg1 and ginsenoside Re's gross weight is greater than 85% of the active ingredient gross weight.
6. application according to claim 1 is characterized in that: arasaponin R1, ginsenoside Rb1, ginsenoside Rg1 and ginsenoside Re's gross weight is greater than 90% of the active ingredient gross weight.
7. application according to claim 1 is characterized in that: wherein arasaponin R1 content is that 8%＜R1≤15%, ginsenoside Rg1's content are that 35%≤Rg1≤52%, ginsenoside Re's content are that 4%＜Re≤10%, ginsenoside Rb1's content are 25%＜Rb1≤40%.
8. according to the described application of claim 1-7, it is characterized in that: compositions wherein is made into freeze-dried powder injection.
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| CN2009102239529A CN101700264B (en) | 2009-11-20 | 2009-11-20 | Application of pseudo-ginseng and extract thereof in preparing medicament for curing and/or preventing diabetic neuropathies |
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| CN1915244A (en) * | 2005-08-15 | 2007-02-21 | 黑龙江省珍宝岛制药有限公司 | Medicaments of 'thrombosis through' freezed drying powder injection (including dedicated solvent) and technique and adaptive disease |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1915244A (en) * | 2005-08-15 | 2007-02-21 | 黑龙江省珍宝岛制药有限公司 | Medicaments of 'thrombosis through' freezed drying powder injection (including dedicated solvent) and technique and adaptive disease |
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| Title |
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| 杨日丽等.《多指标考察三七皂苷的大孔树脂法纯化工艺》.《云南中医中药杂志》.2007,第28卷(第2期),40-41. * |
| 陈芳等.《血塞通治疗糖尿病周围神经病变30例》.《中西医结合心脑血管病杂志》.2006,第4卷(第12期),1089. * |
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