CN1615901A - medicine composition containing protopanoxadiol and its preparing method - Google Patents
medicine composition containing protopanoxadiol and its preparing method Download PDFInfo
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- CN1615901A CN1615901A CN 200410078229 CN200410078229A CN1615901A CN 1615901 A CN1615901 A CN 1615901A CN 200410078229 CN200410078229 CN 200410078229 CN 200410078229 A CN200410078229 A CN 200410078229A CN 1615901 A CN1615901 A CN 1615901A
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Abstract
The present invention discloses a kind of medicine composition containing protopanoxadiol, and the medicine composition consists of the extractive of ginseng, American ginseng or ginseng leaf, and medicinal supplementary material. The extractive is purified through water washing, adsorption in macroporous resin, and twice reverse effective liquid phase chromatographic column purification. The extractive contains protopanoxadiol in 80-85 wt%. The preparation process is also disclosed. The present invention has high effective component content, and high pharmacological effect of preventing and treating tumors.
Description
Technical field
The invention belongs to technical field of traditional Chinese medicine pharmacy, be specifically related to a kind of pharmaceutical composition that contains protopanoxadiol and preparation method thereof.
Background technology
Cancer is one of disease that mortality rate is the highest in the world today, has risen to first at its sickness rate of some developed country and mortality rate.At present, though the prevention of cancer and treatment have obtained obvious improvement, the human method that does not find radical cure as yet.Though some has the effect of good kill tumor cell the antitumor drug of succeeding in developing so far, because toxic and side effects is too strong, thereby clinical practice is restricted.Advocate in the upsurge of " back to nature " people, natural drug is little with its toxic and side effects, clinical effectiveness good, aboundresources, more and more causes people's attention.Modern medicine study shows that Radix Panacis Quinquefolii, Radix Ginseng, Folium Ginseng have good anti-tumor biological effect, and wherein contained ginsenoside is its antineoplastic main active.By the relatively discovery to various ginsenoside's antitumor actions, ginsenoside Rh
2The ability of anticancer proliferation function is the strongest, the ginsenoside Rg
3Take second place.Document [Zhao Yue, etc.The ginsenoside Rh
2Antitumor Effects.JOURNAL OF MICROBIOLOGY, 2003,23 (2): 61] report, the ginsenoside Rh
2Tumor had following effect: 1, external to murine melanoma B
16Cell has differentiation-inducing action; 2, to C
6Glioma cell has tangible propagation to suppress and induces and transfer the effect of dying, and this effect has period specific; 3, the effect that has the natural death of cerebral cells of inducing human liver tumor cell SK-HEP-1; 4, the growth to people's gonad cell (HRA) has inhibitory action in external and nude mice experiment.
Be absorbed hardly behind the natural ginseng saponin oral liquor, by bringing into play clinical effect after the human enteric bacteria metabolic conversion again.The ginsenoside Rh
2Antineoplastic action is to be converted into protopanoxadiol (desaccharified gensenoside, Aglycon Protopanaxadiol) ability killing tumor cell after entering body.This shows that protopanoxadiol is only the killer who directly causes death of neoplastic cells, can kill the tumor cell more than 40%.Too people's [Tadahide Ota et al.Journal.of Pharmaceutical Science 80 (12): 1141-1143,1991] such as Tian Longying result of study shows that also protopanoxadiol has antitumor activity to melanoma, and the ginsenoside Rh is compared in its effect
2Monomer is stronger.The domestic antineoplastic that is used for is the medicine of main active with ginsenoside now, and the ginsenoside Rg is arranged
3Monomer be active component ginseng one capsule [Yu Jie, etc.Join a capsule.Chinese Journal of New Drugs, 2001,10 (10): 776].Application number is the anticancer ancillary drug capsule of effective ingredient with the protopanoxadiol for the patent documentation of CN02146549 provides a kind of, but it is the patent documentation of CN00123074 that application number is adopted in the preparation of protopanoxadiol, adopts the ginsenoside to obtain through hydrolysis, the methods such as silica gel column chromatography, ODS column chromatography, recrystallization or HPLC of crossing to the preparation of protopanoxadiol in the document; Application number be the patent documentation of CN01133408 in the preparation protopanoxadiol, adopt to add measures such as protective agent, inert gas shielding, control reaction temperature and acid concentration and obtain; Above-mentioned two technologies have been passed through the process of medical material-ginsenoside-protopanoxadiol, complex steps, complexity, and to the requirement height of equipment, yield is low, medicine cost height, practicality is bad in commercial production.
The ginsenoside has very strong haemolysis and Blood clotting, therefore mostly be oral formulations with it for the preparation of main effective ingredient, but oral ginsenoside's bioavailability is low, therefore can't reach desired therapeutic effect.The injection of making also can only be used for intramuscular injection, and this administering mode has also limited its clinical effectiveness greatly.Protopanoxadiol is ginsenoside's a aglycon, and it is fat-soluble good, and haemolysis is little, and effect is strong, and very little dosage can reach good therapeutic effect, thereby also can be used for the vein dosed administration.
Finding no the pass in data-searching is any report that is used for the antineoplastic ejection preparation of main effective ingredient with protopanoxadiol.
Summary of the invention
In preparing the method for protopanoxadiol, the apply in a flexible way character of protopanoxadiol of research worker of the present invention through experiment repeatedly, has been found directly to extract from Radix Ginseng, Radix Panacis Quinquefolii, Folium Ginseng medical material, the method for separation, purification protopanoxadiol.The method need not the transformation through medical material-ginsenoside-protopanoxadiol, and used preparation method mild condition can be carried out in industrial automatization fully.
The objective of the invention is to disclose a kind of active component protopanoxadiol, good effect, convenient use, little ejection preparation of side effect of being rich in antitumor action.
Another object of the present invention provides the preparation method of above-mentioned ejection preparation.
The present invention is achieved through the following technical solutions.
One, preparation method
(1) raw medicinal material is: one or more in Radix Panacis Quinquefolii, Radix Ginseng, the Folium Ginseng;
(2) with above-mentioned pulverizing medicinal materials, grind, sieve, add the water stirring that 4-6 doubly measures, left standstill 12-24 hour, filter; Precipitation adds the water stirring that 3-5 doubly measures again, leaves standstill 12-24 hour, filters, and precipitate is standby;
(3) precipitate is crossed the macroporous adsorptive resins of having handled well,, used instead the 70%-90% alcoholic solution eluting of 3-5 times of column volume more earlier with the washing of 4-6 times of column volume, collect ethanol elution, concentrating under reduced pressure becomes extractum, adds the ethanol that 20-40 doubly measures in extractum, stirs, left standstill 6-12 hour, filter, filtrate concentrates, drying, pulverize, obtain powder;
(4) anhydrous alcohol solution that above-mentioned powder is doubly measured with 20-40 separates with the preparative high performance liquid chromatography post, water-ethanol solution eluting, and with HPLC eluent is detected, collect the eluent that is rich in protopanoxadiol, concentrate.
(5) with above-mentioned concentrated solution, separate with the preparative high performance liquid chromatography post once more, water-ethanol solution eluting, and with HPLC eluent is detected, collect the eluent that is rich in protopanoxadiol, concentrate, drying is pulverized, and obtains extract powder.
(6) preparation of preparation
The preparation of hydro-acupuncture preparation: said extracted thing powder being dissolved with small amount of ethanol, add the injection water again to ormal weight, is 5.0-7.5 with the meglumine adjust pH, filters, and sterilization is prepared into hydro-acupuncture preparation.
The preparation of infusion preparation: said extracted thing powder being dissolved with small amount of ethanol, add the injection water again to ormal weight, is 5.0-7.5 with the meglumine adjust pH, filters, and sterilization is prepared into infusion preparation.
The preparation of powder injection formulation: said extracted thing powder is dissolved with small amount of ethanol, add the injection water again to ormal weight, add excipient, adjust pH is 5.0-7.5, and with 0.22 μ m filtering with microporous membrane, spray drying is packaged to be powder injection formulation.
The preparation of freeze-dried powder: with said extracted thing powder dissolve with ethanol, add the lyophilizing excipient, add the injection water again to ormal weight, with the meglumine adjust pH is 5.0-7.5, with 0.22 μ m filtering with microporous membrane, fill, lyophilization is packaged to be freeze-dried powder.
Two, the content of protopanoxadiol in the high effective liquid chromatography for measuring extract of the present invention
1, instrument and reagent high performance liquid chromatograph comprise LC-10ATvp type solvent delivery pump, SPD-10ATvp type UV, visible light detector (day island proper Tianjin company); N2000 chromatographic work station (Zhejiang University's intelligent information Graduate School of Engineering); KQ3200 type ultrasonic washing instrument (Kunshan Ultrasonic Instruments Co., Ltd.), TGL-16G high speed tabletop centrifuge (Anting Scientific Instrument Factory, Shanghai).Trifluoroacetic acid aqueous solution (Merck KGaA company); Water is tri-distilled water (self-control); Other reagent is analytical pure.5 batches of extracts (Tianzhijiao Medication Development Co., Ltd., Guangdong provides); Protopanoxadiol reference substance (Tianzhijiao Medication Development Co., Ltd., Guangdong provides, and content is greater than 99.0%).
2, chromatographic condition and system suitability test chromatographic column: the C of Di Ma company
18Post (5 μ m, 250mm * 4.6mm, I.D); Mobile phase: acetonitrile-water (65: 35); Flow velocity: 1.0ml/min; Detect wavelength 203nm; Number of theoretical plate should be not less than 2000 by protopanoxadiol peak compute.
3, reference substance mixed solution preparation is accurate takes by weighing the about 8g of protopanoxadiol reference substance that is dried to constant weight, places the 10ml measuring bottle, and adding methanol is an amount of, ultrasonicly makes dissolving, adds methanol again to scale, shakes up, promptly.
4, accurate above-mentioned reference substance solution 1.0,2.0,4.0,6.0,8.0,10 μ l, the sample introduction mensuration under the said determination condition drawn of standard curve preparation.The result shows, protopanoxadiol sample size and peak area in 0.08 μ g～0.8 μ g scope are the good linear relation, and linear equation is Y=564728X+1384, r=0.9997.
5, the about 10mg of extract of the present invention is got in the preparation of need testing solution, accurate claims surely, puts in the 10ml measuring bottle, and it is an amount of to add methanol, ultrasonicly makes dissolving, adds methanol again to scale, shakes up, promptly.
6, accurate need testing solution and each the 10 μ l of reference substance solution of drawing of algoscopy inject chromatograph of liquid, measure peak area, calculate content with standard curve.The results are shown in Table 1.
Protopanoxadiol assay in table 1 extract
Lot number content (%)
1 82.8
2 80.0
3 83.4
4 85.0
5 81.2
The weight percentage of protopanoxadiol is 80%-85% in the resulting extract of preparation method of the present invention.
Three, hemolytic experiment
Extract of the present invention is diluted to different multiples with the injection normal saline, mixes with different dilution solution with the whole blood of rabbit, shake up gently, be positioned in 37 ℃ ± 0.5 ℃ the water bath with thermostatic control, observed 1 hour, whether inspection has the haemolysis appearance.The results are shown in Table 2.
The different dilution hemolytic experiments of table 2 extract of the present invention
The dilution factor haemolysis
1∶100 ++
1∶150 +
1∶200 ±
1∶300
Annotate: ++ the severe haemolysis appears in expression; Slight haemolysis appears in+expression;
± expression has slight haemolysis to occur; The no haemolysis of-expression occurs.
The explanation of above hemolytic experiment, extract of the present invention is 1: 200 or when above at dilution factor, does not almost have haemolysis and takes place.
Four, pharmacology embodiment
Ejection preparation of the present invention is tested the mouse interior tumor growth inhibited
Experiment mice: Kunming mouse, 6～7 ages in week, body weight 18～22g, male and female half and half.
Animal tumor kind: ascitic type H
22Liver cancer mouse, solid tumor Lewis lung cancer mice, ascitic type S
180The sarcoma mice.
Experimental technique: will inoculate back 7 days corresponding tumor strain (H
22, Lewis, S
180) tumor-bearing mice cervical vertebra dislocation execution, under aseptic condition, take out ascites, with normal saline dilution in 1: 3, in axillary fossa subcutaneous vaccination tumor liquid 0.2ml.Inoculate back 24 hours, animal is divided into 3 groups at random, 10 every group.If the blank group, cyclophosphamide (CTX) positive controls, ejection preparation group of the present invention.Negative control group gives equal-volume 0.5%CMC, 1 60mgkg of cyclophosphamide lumbar injection
-1Ejection preparation group of the present invention every day 1 time, successive administration 5 days, drug withdrawal 2 times, successive administration is 4 days again.After the last administration 24 hours, animal was put to death in the cervical vertebra dislocation, weighed respectively, tumor is heavy, calculates tumor control rate, carries out therapeutic evaluation.Inhibition rate of tumor growth (the %)=average tumor of (it is heavy that average tumor is organized in the average tumor weight-treatment of matched group)/matched group heavy * 100%.
Experimental result: see Table 3, table 4 and table 5.
Table 3 the present invention is to rat liver cancer H
22The inhibitory action of growth (X ± S, n=10)
Group initial body weight average/g end-body weight average/g tumor weight/g suppression ratio/%
Matched group 21.6 26.7 2.42 ± 0.78-
CTX 21.5 26.4 0.82±0.20 66.12
*
Of the present invention group 21.3 26.5 1.06 ± 0.46 56.20
*
Annotate: compare with matched group,
*P＜0.01;
Table 3 The pharmacological results shows that ejection preparation of the present invention and cyclophosphamide (CTX) all have remarkable inhibition rat liver cancer H
22The effect of growth.Illustrate: ejection preparation of the present invention has very strong inhibition rat liver cancer H
22The effect of growth.
The inhibitory action that table 4 ejection preparation of the present invention is grown to Mice Bearing Lewis Lung Cancer (X ± S, n=10)
Group initial body weight average/g end-body weight average/g tumor weight/g suppression ratio/%
Matched group 20.6 27.8 2.54 ± 0.85-
CTX 20.7 28.2 0.78±0.18 69.29
*
Of the present invention group 20.5 27.3 1.10 ± 0.64 56.69
*
Annotate: compare with matched group,
*P＜001;
Table 4 The pharmacological results shows that ejection preparation of the present invention and cyclophosphamide (CTX) all have the effect of remarkable inhibition Mice Bearing Lewis Lung Cancer growth.Illustrate: ejection preparation of the present invention has the effect of very strong inhibition Mice Bearing Lewis Lung Cancer growth.
Table 5 the present invention is to mice S
180The inhibitory action of sarcoma growth (X ± S, n=10)
Group initial body weight average/g end-body weight average/g tumor weight/g suppression ratio/%
Matched group 21.1 26.9 2.24 ± 0.65-
CTX 20.8 26.8 0.65±0.17 70.98
*
Of the present invention group 20.6 27.1 0.83 ± 0.42 62.95
*
Annotate: compare with matched group,
*P＜0.01;
Table 5 The pharmacological results shows that ejection preparation of the present invention and cyclophosphamide (CTX) all have remarkable inhibition mice S
180The effect of sarcoma growth.Illustrate: ejection preparation of the present invention has very strong inhibition mice S
180The effect of sarcoma growth.
Above The pharmacological results explanation, ejection preparation of the present invention has good antineoplastic activity.In conjunction with amount of literature data, we can learn: the ejection preparation of the present invention that with the protopanoxadiol is main active all has the obvious treatment effect for pulmonary carcinoma, breast carcinoma, gastric cancer, esophageal carcinoma, pancreas cancer, colorectal cancer and melanoma.
Five, preparation embodiment
Following examples are intended to further illustrate, rather than restriction the present invention.Under the prerequisite of the spirit and principles in the present invention, will fall in the claim scope of the present invention inventing any change that indivedual technical steps carry out or changing.
Embodiment 1
(1) raw material is: Radix Panacis Quinquefolii 30kg;
(2) with above-mentioned pulverizing medicinal materials, grind, sieve, the water that adds 6 times of amounts stirs, and leaves standstill 24 hours, filters, and discards water liquid; The water that precipitation adds 5 times of amounts again stirs, and leaves standstill 24 hours, filters, and discards water liquid; Precipitate is standby;
(3) precipitate is crossed the AB-8 type macroporous adsorptive resins of having handled well, with the washing of 4 times of column volumes, discarded water liquid earlier, use 70% alcoholic solution eluting of 3 times of column volumes again instead, collect ethanol elution, concentrating under reduced pressure becomes extractum, the ethanol that in extractum, adds 40 times of amounts, stir, left standstill 12 hours, filter, filtrate concentrates, drying is pulverized, and obtains powder;
(4) with the anhydrous alcohol solution of above-mentioned powder with 20 times of amounts, with filler is eight alkyl silane bonded silica gels (C-8), mean particle dia is that the preparative high performance liquid chromatography post of 15 μ m separates, water-dehydrated alcohol (20: 80) eluant solution, and eluent is detected with HPLC, the eluent of protopanoxadiol is rich in collection, concentrates.
(5) with above-mentioned concentrated solution, with filler is eight alkyl silane bonded silica gels (C-8), mean particle dia is that the preparative high performance liquid chromatography post of 15 μ m separates, water-dehydrated alcohol (50: 50) eluant solution, and with HPLC eluent is detected, the eluent that is rich in protopanoxadiol collected, concentrate, drying is pulverized, and obtains extract powder 90g (assay contains protopanoxadiol 82.8%).
(6) with said extracted thing powder dissolve with ethanol, add the injection water again to an amount of, be 5.0 with the meglumine adjust pH, to filter, sterilization is prepared into hydro-acupuncture preparation.
Embodiment 2
(1) raw material is: Folium Ginseng 40kg;
(2) with above-mentioned pulverizing medicinal materials, grind, sieve, the water that adds 4 times of amounts stirs, and leaves standstill 12 hours, filters, and discards water liquid; The water that precipitation adds 3 times of amounts again stirs, and leaves standstill 12 hours, filters, and discards water liquid; Precipitate is standby;
(3) precipitate is crossed the D101 type macroporous adsorptive resins of having handled well, with the washing of 6 times of column volumes, discarded water liquid earlier, use 90% alcoholic solution eluting of 5 times of column volumes again instead, collect ethanol elution, concentrating under reduced pressure becomes extractum, the ethanol that in extractum, adds 20 times of amounts, stir, left standstill 6 hours, filter, filtrate concentrates, drying is pulverized, and obtains powder;
(4) with the anhydrous alcohol solution of above-mentioned powder with 40 times of amounts, with filler is octadecylsilane chemically bonded silica (C-18), mean particle dia is that the preparative high performance liquid chromatography post of 5 μ m separates, water-dehydrated alcohol (0: 100) eluant solution, and eluent is detected with HPLC, the eluent of protopanoxadiol is rich in collection, concentrates.
(5) with above-mentioned concentrated solution, with filler is octadecylsilane chemically bonded silica (C-18), mean particle dia is that the preparative high performance liquid chromatography post of 5 μ m separates, water-dehydrated alcohol (20: 80) eluant solution, and with HPLC eluent is detected, the eluent that is rich in protopanoxadiol collected, concentrate, drying is pulverized, and obtains extract powder 110g (assay contains protopanoxadiol 80.0%).
(6) with said extracted thing powder dissolve with ethanol, add sodium chloride, add the injection water again to an amount of, be 7.5 with the meglumine adjust pH, to filter, sterilization is prepared into infusion preparation.
Embodiment 3
(1) raw material is: Radix Ginseng 35kg;
(2) with above-mentioned pulverizing medicinal materials, grind, sieve, the water that adds 5 times of amounts stirs, and leaves standstill 18 hours, filters, and discards water liquid; The water that precipitation adds 4 times of amounts again stirs, and leaves standstill 15 hours, filters, and discards water liquid; Precipitate is standby;
(3) precipitate is crossed the AB-8 type macroporous adsorptive resins of having handled well, with the washing of 5 times of column volumes, discarded water liquid earlier, use 80% alcoholic solution eluting of 4 times of column volumes again instead, collect ethanol elution, concentrating under reduced pressure becomes extractum, adds the ethanol of 30 times of amounts in extractum, stir, left standstill 8 hours, and filtered the filtrate concentrate drying, pulverize, obtain powder;
(4) with the anhydrous alcohol solution of above-mentioned powder with 30 times of amounts, with filler is eight alkyl silane bonded silica gels (C-8), mean particle dia is that the preparative high performance liquid chromatography post of 10 μ m separates, water-dehydrated alcohol (10: 90) eluant solution, and eluent is detected with HPLC, the eluent of protopanoxadiol is rich in collection, concentrates.
(5) with above-mentioned concentrated solution, with filler is octadecylsilane chemically bonded silica (C-18), mean particle dia is that the preparative high performance liquid chromatography post of 8 μ m separates, water-dehydrated alcohol (30: 70) eluant solution, and with HPLC eluent is detected, the eluent that is rich in protopanoxadiol collected, concentrate, drying is pulverized, and obtains extract powder 102g (assay contains protopanoxadiol 83.4%).
(6) with said extracted thing powder dissolve with ethanol, add glucose and fructose 98g, add the injection water again to ormal weight, adjust pH is 6.0, with 0.22 μ m filtering with microporous membrane, drying is packaged to be powder injection formulation.
Embodiment 4
(1) raw material is: Radix Panacis Quinquefolii 13kg, Radix Ginseng 20kg;
(2) with above-mentioned pulverizing medicinal materials, grind, sieve, the water that adds 6 times of amounts stirs, and leaves standstill 20 hours, filters, and discards water liquid; The water that precipitation adds 3 times of amounts again stirs, and leaves standstill 21 hours, filters, and discards water liquid; Precipitate is standby;
(3) precipitate is crossed the D101 type macroporous adsorptive resins of having handled well, with the washing of 4 times of column volumes, discarded water liquid earlier, use 75% alcoholic solution eluting of 4 times of column volumes again instead, collect ethanol elution, concentrating under reduced pressure becomes extractum, the ethanol that in extractum, adds 25 times of amounts, stir, left standstill 10 hours, filter, filtrate concentrates, drying is pulverized, and obtains powder;
(4) with the anhydrous alcohol solution of above-mentioned powder with 35 times of amounts, with filler is octadecylsilane chemically bonded silica (C-18), mean particle dia is that the preparative high performance liquid chromatography post of 8 μ m separates, water-dehydrated alcohol (5: 95) eluant solution, and eluent is detected with HPLC, the eluent of protopanoxadiol is rich in collection, concentrates.
(5) with above-mentioned concentrated solution, with filler is eight alkyl silane bonded silica gels (C-8), mean particle dia is that the preparative high performance liquid chromatography post of 12 μ m separates, water-dehydrated alcohol (40: 60) eluant solution, and with HPLC eluent is detected, the eluent that is rich in protopanoxadiol collected, concentrate, drying is pulverized, and obtains extract powder 95g (assay contains protopanoxadiol 85.0%).
(6) with said extracted thing powder dissolve with ethanol, filter, add glucose and fructose 105g, add the injection water again to an amount of, adjust pH is 5.5, with 0.22 μ m filtering with microporous membrane, fill, lyophilization promptly gets lyophilized injectable powder.
Embodiment 5
(1) raw material is: Radix Panacis Quinquefolii 200kg, Radix Ginseng 100kg, Folium Ginseng 80kg;
(2) with above-mentioned pulverizing medicinal materials, grind, sieve, the water that adds 5 times of amounts stirs, and leaves standstill 14 hours, filters, and discards water liquid; The water that precipitation adds 3 times of amounts again stirs, and leaves standstill 19 hours, filters, and discards water liquid; Precipitate is standby;
(3) precipitate is crossed the NKA type macroporous adsorptive resins of having handled well, with the washing of 5 times of column volumes, discarded water liquid earlier, use 85% alcoholic solution eluting of 5 times of column volumes again instead, collect ethanol elution, concentrating under reduced pressure becomes extractum, the ethanol that in extractum, adds 35 times of amounts, stir, left standstill 9 hours, filter, filtrate concentrates, drying is pulverized, and obtains powder;
(4) with the anhydrous alcohol solution of above-mentioned powder with 25 times of amounts, with filler is eight alkyl silane bonded silica gels (C-8), mean particle dia is that the preparative high performance liquid chromatography post of 13 μ m separates, water-dehydrated alcohol (15: 85) eluant solution, and eluent is detected with HPLC, the eluent of protopanoxadiol is rich in collection, concentrates.
(5) above-mentioned concentrated solution, with filler is eight alkyl silane bonded silica gels (C-8), mean particle dia is that the preparative high performance liquid chromatography post of 10 μ m separates, water-dehydrated alcohol (35: 65) eluant solution, and with HPLC eluent is detected, the eluent that is rich in protopanoxadiol collected, concentrate, drying is pulverized, and obtains extract powder 1070g (assay contains protopanoxadiol 81.2%).
(6) with said extracted thing powder dissolve with ethanol, filter, add dextrorotation fructose and lactose and polyvinylpyrrolidone 930g, adding the injection water again to an amount of, is 7.0 with the meglumine adjust pH, with 0.22 μ m filtering with microporous membrane, fill, lyophilization promptly gets lyophilized injectable powder.
Hydro-acupuncture preparation of the present invention, powder injection formulation, freeze-dried powder are according to the degree of the state of an illness, and each consumption is that 2-4 props up, and the 100-200ml injection of whenever drawing normal saline dilution posterior vein drop uses, and dropping speed is 80-120ml/ hour.Infusion preparation directly uses.
The continuous drop of ejection preparation of the present invention must not re-use ejection preparation of the present invention in 5 days after 2 days at interval.
The present invention needs to use for 10 week-14 weeks continuously.
Claims (12)
1, a kind of pharmaceutical composition that contains protopanoxadiol is characterized in that it is that extract and pharmaceutic adjuvant by Radix Panacis Quinquefolii or Radix Ginseng or Folium Ginseng is prepared from; Its feature is that also the weight percentage of main active protopanoxadiol in the extract is 80%-85%.
2, pharmaceutical composition according to claim 1 is characterized in that the preparation of this pharmaceutical composition comprises hydro-acupuncture preparation, infusion preparation, powder injection formulation and freeze-dried powder.
3, pharmaceutical composition according to claim 2, its preparation method may further comprise the steps:
(1) raw medicinal material is: one or more in Radix Panacis Quinquefolii, Radix Ginseng, the Folium Ginseng;
(2) with above-mentioned pulverizing medicinal materials, grind, sieve, add the water stirring that 4-6 doubly measures, left standstill 12-24 hour, filter; Precipitation adds the water stirring that 3-5 doubly measures again, leaves standstill 12-24 hour, filters, and precipitate is standby;
(3) precipitate is crossed the macroporous adsorptive resins of having handled well,, used instead the 70%-90% alcoholic solution eluting of 3-5 times of column volume more earlier with the washing of 4-6 times of column volume, collect ethanol elution, concentrating under reduced pressure becomes extractum, adds the ethanol that 20-40 doubly measures in extractum, stirs, left standstill 6-12 hour, filter, filtrate concentrates, drying, pulverize, obtain powder;
(4) anhydrous alcohol solution that above-mentioned powder is doubly measured with 20-40 separates with the preparative high performance liquid chromatography post, uses (I) water-dehydrated alcohol eluting, and with HPLC eluent is detected, and collects the eluent that is rich in protopanoxadiol, concentrates.
(5) with above-mentioned concentrated solution, separate with the preparative high performance liquid chromatography post once more, use (II) water-dehydrated alcohol eluting, and eluent is detected with HPLC, collect the eluent that is rich in protopanoxadiol, concentrate, drying is pulverized, and obtains extract powder.
(6) preparation of preparation
The preparation of hydro-acupuncture preparation: said extracted thing powder being dissolved with small amount of ethanol, add the injection water again to ormal weight, is 5.0-7.5 with the meglumine adjust pH, filters, and sterilization is prepared into hydro-acupuncture preparation.
The preparation of infusion preparation: said extracted thing powder being dissolved with small amount of ethanol, add the injection water again to ormal weight, is 5.0-7.5 with the meglumine adjust pH, filters, and sterilization is prepared into infusion preparation.
The preparation of powder injection formulation: said extracted thing powder is dissolved with small amount of ethanol, add the injection water again to ormal weight, add excipient, adjust pH is 5.0-7.5, and with 0.22 μ m filtering with microporous membrane, spray drying is packaged to be powder injection formulation.
The preparation of freeze-dried powder: with said extracted thing powder dissolve with ethanol, add the lyophilizing excipient, add the injection water again to ormal weight, with the meglumine adjust pH is 5.0-7.5, with 0.22 μ m filtering with microporous membrane, fill, lyophilization is packaged to be freeze-dried powder.
4, preparation method according to claim 3 is characterized by medicinal powder and crosses 100-160 purpose sieve.
5, preparation method according to claim 3, it is characterized by macroporous adsorbent resin is nonpolar or low pole.
6, preparation method according to claim 3, it is characterized by the concentration of alcohol that the eluting macroporous adsorbent resin uses is 75%-85%.
7, preparation method according to claim 3, the filler that it is characterized by the preparative high performance liquid chromatography post is the alkyl silane bonded silica gel.
8, preparation method according to claim 3, the filler that it is characterized by the preparative high performance liquid chromatography post are eight alkyl silane bonded silica gel or octadecylsilane chemically bonded silicas.
9, preparation method according to claim 3, the mean particle dia that it is characterized by the filler of preparative high performance liquid chromatography post are 5-15 μ m.
10, preparation method according to claim 3, the ratio that it is characterized by (I) water-dehydrated alcohol is 0-20%: 80%-100%.
11, preparation method according to claim 3, the ratio that it is characterized by (II) water-ethanol solution is 20-50%: 50%-80%.
12, excipient according to claim 3 is a kind of, two or more the mixture in mannitol, glucosan, polyvinylpyrrolidone, glucose, fructose, dextrorotation fructose and the lactose.
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| CN 200410078229 Pending CN1615901A (en) | 2004-09-21 | 2004-09-21 | medicine composition containing protopanoxadiol and its preparing method |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007143930A1 (en) * | 2006-06-09 | 2007-12-21 | Shanghai Innovative Research Center Of Traditional Chinese Medicine | Use of 20(s)-protopanoxadiol in manufacture of antidepressants |
| CN100458421C (en) * | 2005-09-28 | 2009-02-04 | 沈百华 | Microchemical identifying method for wild ginseng and cultivated gineeng |
| CN109342586A (en) * | 2018-10-10 | 2019-02-15 | 泓博元生命科技（深圳）有限公司 | Protopanoxadiol determination method |
-
2004
- 2004-09-21 CN CN 200410078229 patent/CN1615901A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100458421C (en) * | 2005-09-28 | 2009-02-04 | 沈百华 | Microchemical identifying method for wild ginseng and cultivated gineeng |
| WO2007143930A1 (en) * | 2006-06-09 | 2007-12-21 | Shanghai Innovative Research Center Of Traditional Chinese Medicine | Use of 20(s)-protopanoxadiol in manufacture of antidepressants |
| US8148354B2 (en) | 2006-06-09 | 2012-04-03 | Shanghai Innovative Research Center Of Traditional Chinese Medicine | Use of 20(S)-protopanaxadiol in manufacture of antidepressants |
| CN109342586A (en) * | 2018-10-10 | 2019-02-15 | 泓博元生命科技（深圳）有限公司 | Protopanoxadiol determination method |
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