CN100502880C - Notoginseng glycol-saponin composition and its preparation method and use - Google Patents
Notoginseng glycol-saponin composition and its preparation method and use Download PDFInfo
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- CN100502880C CN100502880C CNB2004100906050A CN200410090605A CN100502880C CN 100502880 C CN100502880 C CN 100502880C CN B2004100906050 A CNB2004100906050 A CN B2004100906050A CN 200410090605 A CN200410090605 A CN 200410090605A CN 100502880 C CN100502880 C CN 100502880C
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- 238000002360 preparation method Methods 0.000 title claims abstract description 26
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- FBFMBWCLBGQEBU-RXMALORBSA-N (2s,3r,4s,5s,6r)-2-[(2r,3r,4s,5s,6r)-2-[[(3s,5r,6s,8r,9r,10r,12r,13r,14r,17s)-3,12-dihydroxy-4,4,8,10,14-pentamethyl-17-[(2s)-6-methyl-2-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhept-5-en-2-yl]-2,3,5,6,7,9,11,12,13,15,16,17-dodecah Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O FBFMBWCLBGQEBU-RXMALORBSA-N 0.000 claims abstract description 7
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Rheumatology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Steroid Compounds (AREA)
Abstract
The present invention belongs to the field of Chinese medicine, and is especially the purified product of notoginseng as one kind of Chinese medicinal materials and its preparation process and pharmaceutical use. The notoginseng glycol-saponin composition obtained through purifying notoginseng consists of ginsenoside Rb1 and ginsenoside Rd as main components, and contains ginsenoside Rb1 30-70 wt% and ginsenoside Rd 4-18 wt%, with the total content of ginsenoside Rb1 and ginsenoside Rd being up to 80 wt%. The notoginseng glycol-saponin composition has obvious antiflogistic and analgetic effect, low toxicity, and the features of nonsteroidal antiphlogistic. The composition may be used in preparing medicine for treating rheumatic and rheumatoid arthritis.
Description
Technical field
The invention belongs to the field of Chinese medicines, be specifically related to purification thing and preparation method thereof and the pharmaceutical applications of Chinese medicine Radix Notoginseng.
Background technology
Radix Notoginseng (Panax notoginseng (Burk.) F.H.chen) claim Radix Notoginseng, Panax pseudoginseng, Typhonium flagelliforme (Lodd.) Blume, mountain lacquer, Radix Stephaniae Sinicae (Radix Stephaniae Dielsianae) and Herba Wedeliae Wallichii etc. again, be Araliaceae (Araliaceae) Panax (Panax Linn) herbaceos perennial, adopt and long three petioles of every strain because of digging in its after planting three to seven years, each petiole is given birth to seven blades, so name Radix Notoginseng, its stem, leaf, Hua Junke are used as medicine, and are Chinese distinctive rare Chinese medicines.According to relevant document record, Radix Notoginseng was used historical nearly 600 years, nearly 500 years of cultivation history.Radix Notoginseng is because of it has significant blood circulation promoting and blood stasis dispelling with regard to being acknowledged as since ancient times, the subduing swelling and relieving pain effect is described as " Radix Stephaniae Sinicae (Radix Stephaniae Dielsianae) ", " southern part of the country SHENCAO ".
(publication number: CN1083819A discloses day to Chinese patent application 93105774: the preparation method that on March 16th, 1994) discloses a kind of Radix Notoginseng total arasaponins.(publication number: CN1334267A discloses day to Chinese patent application 01108591: the preparation method that on February 6th, 2002) also discloses a kind of Radix Notoginseng total arasaponins.Chinese patent application 02144840 (publication number: CN1412162A, on April 23rd, 2003), 02158727 (publication number: CN1424321A, open day: on June 18th, 2003) also all disclose a kind of method of from stem and leaf of Radix Notoginseng, extracting Radix Notoginseng total arasaponins respectively open day:.
The described method of above-mentioned Chinese patent application all is to extract or the preparation Radix Notoginseng total arasaponins.Radix Notoginseng total arasaponins belongs to the dammarane type four-ring triterpenoid saponins, can be further divided into protopanoxadiol type and Protopanaxatriol's type two classes according to its construction features.Because the difference of this two saponins structure, their biologic activity also differs widely, and panoxadiol's type saponin has stronger direct anti-inflammatory and analgesic effect, and protopanaxatriol ginsenoside then has stronger anticoagulant, suppresses thrombotic effect.And given play to bigger drug effect targetedly based on the pharmaceutical preparation of this Radix Notoginseng total arasaponins is very difficult at concrete disease at present.Therefore, people need isolate the effective site that contains different component from Radix Notoginseng, so that can provide the Radix Notoginseng medicine that concrete disease is fit to more.
Rheumatoid arthritis is a kind of systemic autoimmune disease based on arthropathy, and pathological changes often spreads all over whole body, invades blood, lung, nerve and cardiovascular, is a kind of " pertinacious disease " of serious harm human health.Up to the present, the ideal medicament of still not having treatment rheumatic, rheumatoid arthritis.Though Radix Notoginseng is used for the treatment of the historical of long standing and well established of traumatic injury, subduing swelling and relieving pain, at present also not about from Radix Notoginseng, extracting the report that effectively to treat the medicine of rheumatic, rheumatoid arthritis.Therefore, people need isolate the significant composition of anti-inflammatory and analgesic effect from Radix Notoginseng, so that can provide the Radix Notoginseng medicine that rheumatic, rheumatoid arthritis disease are fit to more.
Summary of the invention
An object of the present invention is to provide a kind of with ginsenoside Rb
1With Rd be the notoginseng glycol-saponin composition of main component.
Another object of the present invention provides the preparation method of notoginseng glycol-saponin composition of the present invention.
Another purpose of the present invention provides the pharmaceutical applications of notoginseng glycol-saponin composition of the present invention.
A further object of the present invention provide notoginseng glycol-saponin composition of the present invention be used for the treatment of disease purposes.
For achieving the above object, a technical scheme of the present invention provides a kind of notoginseng glycol-saponin composition, and said composition is purified by Radix Notoginseng and obtained, and it is basically by ginsenoside Rb
1Form with Rd; Ginsenoside Rb wherein
1Content be 30～70wt%, be preferably 40～65wt%, most preferably be 50～65wt%; Ginsenoside Rd's content is 4～18wt%, is preferably 6～15wt%, most preferably is 10～13wt%; And ginsenoside Rb
1Be up to 80wt% with the content sum of Rd.
The molecular formula of the key component of notoginseng glycol-saponin composition provided by the invention and structural formula are as shown in following table 1:
Table 1.
The ginsenoside Rb that also can contain trace at notoginseng glycol-saponin composition described in the technique scheme of the present invention
2, Rb
3And/or Rc.
Notoginseng glycol-saponin composition provided by the invention not only has obvious anti-inflammatory and analgesic effect, and toxic and side effects is lower, has the characteristics of NSAID (non-steroidal anti-inflammatory drug), and is especially more remarkable to the anti-inflammatory analgesic action of edema impatient property inflammation and the chronic disease of granuloma.
Another technical scheme of the present invention provides the preparation method of notoginseng glycol-saponin composition of the present invention, and this method may further comprise the steps:
(1) with concentration be 50～90wt%, preferred 55～70wt%, most preferably from about the soak with ethanol of 60wt% is extracted Radix Notoginseng, used amount of alcohol is at least 3 times of used three seven weight, collects ethanol extract;
(2) make described ethanol extract by the styrene type macroporous resin post, preferably use the styrene type macroporous resin of nonpolar or low pole, these resins include but not limited to D101, D140, Dj-1 or D201;
(3) with concentration be 30～50wt%, preferred 35～45wt%, most preferably from about the ethanol of 40wt% carries out eluting to described styrene type macroporous resin post, preferably before carrying out eluting with described ethanol, water carries out eluting to the styrene type macroporous resin post, to remove water-solubility impurity; With
(4) with concentration be 50～70wt%, preferred 55～65wt%, most preferably from about the ethanol of 60wt% carries out eluting once more to the resin column through ethanol elution in the described step (3), collects eluent.
In step described in the technique scheme of the present invention (1) and step (4), use the about 60wt% of concentration of ethanol to be meant that its concentration in the acceptable error scope, is generally 60 ± 3wt%.Use the about 40wt% of concentration of ethanol to be meant that its concentration in the acceptable error scope, is generally 40 ± 2wt% in the described step (3).
In above-mentioned steps (1), step (3) and step (4), to the not too many restriction of the amount of alcohol of using.But for step (1), general used amount of alcohol is 3～15 times of used three seven weight.If used amount of alcohol is very little, then the immersion extraction is insufficient, if but the amount of alcohol of usefulness is too many, and will cause alcoholic acid waste and the energy cost of follow-up ethanol recycling step is increased.For step (3) and step (4), general used amount of alcohol is 1～15 times of used Radix Notoginseng amount equally.If used amount of alcohol is very little, then eluting is insufficient, if but the amount of alcohol of usefulness is too many, and will cause alcoholic acid waste and the energy cost of follow-up ethanol recycling step is increased.
In order to improve the efficient of extraction, before step described in the preparation method of notoginseng glycol-saponin composition of the present invention (1) is soaked extraction with ethanol to Radix Notoginseng, consider from the efficient that helps subsequent step, Radix Notoginseng need be pulverized.Preferably Radix Notoginseng powder is broken into particle size range " between the coarse powder and coarse powder of (Chemical Industry Press, publish in January, 2000) regulation of Chinese pharmacopoeia version in 2000, for the mode of pulverizing without any restriction.
Therefore, step described in the preparation method of notoginseng glycol-saponin composition of the present invention (1) preferred implementation is as follows:
(a) Radix Notoginseng is pulverized, get Radix Notoginseng powder;
(b) adopt that concentration is 50～90wt%, preferred 55～70wt%, most preferably from about the ethanol of 60wt% is to described step
(a) Radix Notoginseng powder of gained soaks, and used amount of alcohol is at least 2 times of used Radix Notoginseng powder weight; With
(c) adopt that concentration is 50～90wt%, preferred 55～70wt%, most preferably from about the ethanol of 60wt% is to described step
(b) Radix Notoginseng powder after the immersion of gained carries out percolation, and used amount of alcohol is at least 1 times of used Radix Notoginseng powder weight, collects percolate.
In step described in the technique scheme of the present invention (b) and step (c), use the about 60wt% of concentration of ethanol to be meant that its concentration in the acceptable error scope, is generally 60 ± 3wt%.
In above-mentioned steps (b), soak the middle used amount of alcohol of percolation of used amount of alcohol of Radix Notoginseng powder and step (c) and all do not have too many restriction.But the zone of reasonableness that soaks the used amount of alcohol of Radix Notoginseng powder is generally 2～4 times of used Radix Notoginseng powder weight, and the zone of reasonableness of the used amount of alcohol of percolation is generally 1～15 times of used Radix Notoginseng powder weight.If soak the used amount of alcohol of Radix Notoginseng powder and the lower limit that the used amount of alcohol of percolation is lower than above-mentioned scope, then can not soak the active ingredient that extracts in the Radix Notoginseng fully effectively, if but used amount of alcohol surpasses the upper limit of above-mentioned scope, extraction efficiency is not had raising again yet, but also can cause alcoholic acid waste and the energy cost of follow-up ethanol recycling step is increased.
If desired, also can adopt silicagel column that the eluent that above-mentioned steps (4) makes is further purified, collect eluent again.Available silicagel column includes but not limited to chromatographic silica gel SG11, S620 series, and used eluant is the mixed solvent of ethyl acetate, second alcohol and water, and volume ratio is 7:4:1 between them.Preferably, before last silicagel column, earlier the eluent that step (4) is made is evaporated to respect to 1.1 times of the density of water, admix in the equal-volume silica gel, behind low temperature (50 ± 5 ℃) vacuum drying with the silica gel that contains medicine of gained, add on the silicagel column that has prepared, carry out silica gel column chromatography refinement again.Collection contains ginsenoside Rb
1Eluent with Rd.
If desired, the eluent that step (4) can be collected or again eluent concentrate, panasadiol saponio alcohol extractum, and above-mentioned panasadiol saponio alcohol extractum carried out drying.Described concentration step can adopt the method for any routine, but preferably adopts the method for concentrating under reduced pressure.Described drying steps can adopt various means, as spray drying, drying under reduced pressure, vacuum drying etc.
In order to reduce cost, in the preparation method of notoginseng glycol-saponin composition of the present invention, the ethanol in the percolate of collecting in ethanol extract of collecting in the also recyclable described step (1) or the step (c) preferably adopts the reclaim under reduced pressure mode.
The preparation method of notoginseng glycol-saponin composition provided by the invention can effectively be separated the notoginseng diol saponins effective ingredient in the Radix Notoginseng total arasaponins; And used solvent safety, cheap and easy to get, the noresidue of this preparation method, and the also recyclable utilization of solvent, greatly reduce preparation cost.
Another technical scheme of the present invention provides notoginseng glycol-saponin composition of the present invention to be used to prepare the application of the medicine for the treatment of rheumatic, rheumatoid arthritis.
Notoginseng glycol-saponin composition provided by the invention can be made into various dosage forms, for example, and dosage forms such as granule, mixture, tablet, powder, honeyed pill, capsule, injection, drop, patch.The method and the used auxiliary agent that prepare these dosage forms are known to those skilled in the art, for example, can be referring to " pharmacy of Chinese materia medica " (Shanghai science tech publishing house, in November, 1986 publication), " pharmaceutic adjuvant complete works " (Sichuan science tech publishing house, publication in January nineteen ninety-five), " Chinese pharmacopoeia version in 2000 one (Chemical Industry Press, publish in January, 2000) etc.
Content for the contained notoginseng glycol-saponin composition of the present invention of medicine list of the present invention agent does not have concrete restriction, for example, and can be 50～500 milligrams/agent.Route of administration for pharmaceutical preparation of the present invention does not have too much restriction yet, for example can be by modes such as oral, filling stomach, intramuscular injection, intravascular injection, transdermal, duodenal administration, intranasal administrations.
Above-mentioned preparation of the present invention can be used for dissipating blood stasis, and subduing swelling and relieving pain is used for swelling and ache and the rheumatic arthritis of Western medicine diagnose, the treatment of swelling and ache of rheumatoid arthritis of wind, cold, each syndrome of arthralgia chiefly caused by damp pathogen.
The present invention also provides a kind of method for the treatment of rheumatic, rheumatoid arthritis, it is characterized in that, uses the notoginseng glycol-saponin composition of the present invention of effective dose for the patient who needs treatment.Described patient comprises the people, also comprises animals such as cat, Canis familiaris L., orangutan, monkey.Described effective dose can change to some extent with factors such as the disease of patient order of severity, body weight, body constitution, age, ill history.But doctor or pharmacists have the ability to determine suitable dose for different patients.For example, can be by 1～6mg/kg body weight/day, preferably take the effective ingredient of medicine of the present invention, notoginseng glycol-saponin composition promptly of the present invention to the patient by 3～4mg/kg body weight/day.
The specific embodiment
Embodiment 1
Use Universalpulverizer (available from sky, Shanghai and pharmaceutical machine factory, model GF-300) pulverizes the notoginseng drying rhizome 150kg (place of production: Yunnan Province Wenshan Prefecture), to particle size range 10 orders～24 purpose Radix Notoginseng coarse powder, with the concentration of 2 times of medical material weight is to insert the percolation bucket behind the above-mentioned Radix Notoginseng coarse powder of 60wt% soak with ethanol, concentration with 10 times of medical material weight is that 60wt% ethanol carries out percolation to wet feed, collect percolate, get Radix Notoginseng total arasaponins alcohol extractum behind the ethanol in the reclaim under reduced pressure percolate.Above-mentioned Radix Notoginseng total arasaponins alcohol extractum is mixed with the aqueous solution of 10 times of medical material weight with pure water, with sample on the obtained aqueous solution to styrene type macroporous resin D140 (available from Chengdu Zhonglan Chenguang Chemical Inst) post, first purified water eluting with 9 times of medical material weight, be the 40wt% ethanol elution to the resin column of purified water elution with the concentration of 9 times of medical material weight again, flow velocity be 0.2 times of column volume/hour, at last to carrying out eluting once more with the 60wt% ethanol of 9 times of medical material weight amounts through the resin column of ethanol elution, flow velocity be 0.2 times of column volume/hour, collect the eluent of 60wt% ethanol elution.This eluent is evaporated to respect to 1.1 times of the density of water, above-mentioned concentrated solution is admixed among the equal-volume chromatographic silica gel SG11 low temperature (50 ± 5 ℃) vacuum drying.With the above-mentioned silica gel volume of admixing concentrated solution is benchmark, and the chromatographic silica gel SG11 dress post with 23 times of volumes adds to the silica gel that contains medicine behind the vacuum drying on the silicagel column that has prepared again, carries out silica gel column chromatography refinement.With the ethyl acetate of 4 times of column volumes, the mixed solvent of second alcohol and water (volume ratio is 7:4:1) is that eluant carries out eluting to silicagel column, collects to contain ginsenoside Rb
1Stream part with Rd.Collected stream part is carried out concentrating under reduced pressure gets pure extractum, and pure extractum vacuum drying system is got dry extract, and pulverize the pulverous notoginseng glycol-saponin composition of 5kg.For simplicity's sake, hereinafter abbreviate notoginseng glycol-saponin composition as PDS sometimes.
By high performance liquid chromatography, the employing octadecylsilane chemically bonded silica is a filler, is that mobile phase is measured Rb with acetonitrile-water (volume ratio is 32:68)
1Content, be the content that mobile phase is measured Rd with acetonitrile-water (volume ratio is 35:65), the detection wavelength is 210nm, measures Rb among the PDS that embodiment 1 makes respectively
1Be respectively 59.31wt% and 15.1wt% with the content of Rd.
Embodiment 2～5
According to embodiment 1 described identical method and step, the ethanol that adopts variable concentrations, Different Weight to the Radix Notoginseng coarse powder soak, percolation and eluting, obtained following compositions of the present invention, the result is as shown in table 2 below:
Table 2.
| The embodiment numbering | Used pseudo-ginseng weight | Immersion, percolation concentration of ethanol and consumption | Adopt resin, twice eluting resin concentration of ethanol and consumption | The weight of PDS and the content of key component |
| Embodiment 2 | 3kg | Soaking with concentration of alcohol is 60wt%, and consumption is that 2 times of medical material weight percolation concentration of alcohol are 60wt%, and consumption is 9 times of medical material weight | D101 (available from Tianjin insecticide factory) eluting concentration of ethanol for the first time is 40wt%, and consumption is that 9 times of medical material weight eluting concentration of ethanol second time are 60wt%, and consumption is 9 times of medical material weight | The weight of PDS: 0.0945kg Rb 1：59.86wt％ Rd：14.90wt％ |
| Embodiment 3 | 3kg | Soaking with concentration of alcohol is 60wt%, and consumption is that 2 times of medical material weight percolation concentration of alcohol are 60wt%, and consumption is 9 times of medical material weight | D101 (available from Tianjin insecticide factory) eluting concentration of ethanol for the first time is 40wt%, and consumption is that 9 times of medical material weight eluting concentration of ethanol second time are 60wt%, and consumption is 8 times of medical material weight | The weight of PDS: 0.0885kg Rb 1：60.18wt％ Rd：13.49wt％ |
| Embodiment 4 | 0.1kg | Soaking with concentration of alcohol is 60wt%, and consumption is that 2 times of medical material weight percolation concentration of alcohol are 60wt%, and consumption is 9 times of medical material weight | D101 (available from Tianjin insecticide factory) eluting concentration of ethanol for the first time is 40wt%, and consumption is that 9 times of medical material weight eluting concentration of ethanol second time are 70wt%, and consumption is 7 times of medical material weight | The weight of PDS: 0.0039kg Rb 1：51.78wt％ Rd：12.15wt％ |
| Embodiment 5 | 0.1kg | Soaking with concentration of alcohol is 60wt%, and consumption is that 2 times of medical material weight percolation concentration of alcohol are 60wt%, and consumption is 9 times of medical material weight | D101 (available from Tianjin insecticide factory) eluting concentration of ethanol for the first time is 40wt%, and consumption is that 9 times of medical material weight eluting concentration of ethanol second time are 60wt%, and consumption is 9 times of medical material weight | The weight of PDS: 0.004kg Rb 1：51.70wt％ Rd：13.05wt％％ |
Embodiment 6
Get the dried cream 100g of exsiccant PDS that embodiment 1 makes, pulverized 100 mesh sieves, add starch 97.5g and microcrystalline Cellulose 2.5g, mixing is dissolved in the ethanol that concentration is 50wt%, and drying under reduced pressure is pulverized, and loads and makes 1000 of capsules or 2000.
Test example 1 analgesia drug effect
PDS is to the analgesic activity test of mice whipping reaction
Use 60 mices, be divided into 2 matched groups and 4 experimental grouies at random, 10 every group.With normal saline the PDS powder that embodiment 1 makes is made into dense suspension, the dosage of 4 experimental grouies is respectively 400mg/kg, 200mg/kg, 100mg/kg, 50mg/kg, negative control group gives the normal saline with capacity such as maximal dose experimental grouies, and positive controls gives positive control medicine indometacin 5mg/kg.Each group according to predetermined close gastric infusion every day once, successive administration 4 days, after administration in the 4th day 30,90 and 120 minutes, in 50 ± 0.5 ℃ of water-baths, measure the incubation period of mice whipping reaction respectively, as logical threshold index, carry out the analysis of t inspection statistics, the result is as shown in table 3 below:
Table 3.
*P<0.05 **P<0.01 ***P<0.001
PDS is to the analgesic activity test of rat whipping reaction
Use 60 rats, be divided into 2 matched groups and 4 experimental grouies at random, 10 every group.With normal saline the PDS powder that embodiment 1 makes is made into dense suspension, the dosage of 4 experimental grouies is respectively 400mg/kg, 200mg/kg, 100mg/kg, 50mg/kg, negative control group gives the normal saline with capacity such as maximal dose experimental grouies, and positive controls gives positive control medicine indometacin 5mg/kg.Each group according to predetermined close gastric infusion every day once, successive administration 3 days, after administration in the 3rd day 30,90 and 120 minutes, in 50 ± 0.5 ℃ of water-baths, measure the incubation period of rat whipping reaction respectively, as logical threshold index, carry out the analysis of t inspection statistics, the result is as shown in table 4 below:
Table 4.
*P<0.05 **P<0.01 ***P<0.001
This result of the test proves: the PDS gastric infusion 400mg/kg that embodiment 1 makes, each dosage group of 200mg/kg, 100mg/kg are to the anti-inflammatory and analgesic effects of rat, two kinds of animals of mice highly significant.
Test example 2 antiinflammatory drug effects---rat assist agent arthritis is tested
Use 50 rats, be divided into 2 matched groups and 3 experimental grouies at random, 10 every group.With normal saline the PDS powder that embodiment 1 makes is made into dense suspension, the dosage of 3 experimental grouies is respectively 200mg/kg, 100mg/kg, 50mg/kg, negative control group gives the normal saline with capacity such as maximal dose experimental grouies, and positive controls gives positive control medicine indometacin 2.5mg/kg.What cause that scorching model system will prepare in advance causes scorching adjuvant 0.1ml intradermal injection to the right back sufficient pad of every rat portion.Each is organized in causing scorching preceding 4 days and begins to give respectively normal saline, PDS suspension of the present invention or indometacin, organizes predetermined close gastric infusion every day 1 time according to each.After the last administration, caused inflammation in 30 minutes, observe causing scorching back 18 hours and the 8th day swollen degree of adjuvant injection parapodum, and carry out the analysis of t inspection statistics.The result shows: the PDS200mg/kg that embodiment 1 makes, 100mg/kg, each dosage group of 50mg/kg all can alleviate the swollen degree of foot, and tangible antiinflammation is arranged, and can prevent and treat the generation of adjuvant-induced arthritis.
As everyone knows, rat assist agent arthritis is an immune inflammation model, and its pathogeny is similar to people's rheumatoid arthritis with pathological change.In the different onset stage of this model, the antiinflammatory action of highly significant all can appear in the PDS that embodiment 1 makes, and its action intensity also is not less than indometacin.Though the pathogeny of rheumatic arthritis and rheumatoid arthritis is still not fully aware of,, result of the test shows: the PDS that embodiment 1 makes can treat rheumatisms such as rheumatoid arthritis.
3 acute toxicity tests of test example
The acute toxicity test of mouse stomach administration
Use 80 mices, be divided into 4 groups at random, 20 every group.Each is organized dosage and is respectively 1000mg/kg, 1600mg/kg, 2000mg/kg, 5000mg/kg.With normal saline the PDS powder that embodiment 1 makes is made into dense suspension, fasting is 4 hours before the mice administration, observes 7 days according to behind each group predetermined close gastric infusion 1 time, the no significant discomfort of each group, growth promoter is normal, and experiment is carried out pathologic finding, no abnormality seen after finishing.The result shows: the PDS oral administration that embodiment 1 makes is 5000mg/kg to the maximum tolerated dose of mice, and this medicine is less to the acute toxicity of mice, and the inhibitory action that occurs after the administration begins after about 2 hours to recover.
The acute toxicity test of mouse vein administration
Use 40 mices, be divided into 4 groups at random, 10 every group.Each is organized dosage and is respectively 400mg/kg, 360mg/kg, 320mg/kg, 288mg/kg, and the agent distance is than being 1:0.9.With normal saline the PDS powder that embodiment 1 makes is made into PDS solution, organizes predetermined close intravenous administration 1 time, calculate LD according to experimental result according to each
50(the medicine median lethal dose(LD 50): be 371.959 (352.847～392.107) mg/kg the dosage that promptly causes the death of laboratory animal half), occur symptom such as motionless under inhibition, accelerated breathing and the volt before the death at the acute toxicity testing Chinese medicine, dead then.
Although describe the present invention in conjunction with the preferred embodiments, but the present invention is not limited to the foregoing description, should be appreciated that, under the guiding of the present invention's design, those skilled in the art can carry out various modifications and improvement, and claims have been summarized scope of the present invention.
Claims (16)
1. notoginseng glycol-saponin composition, said composition are purified by Radix Notoginseng and are obtained, and it is basically by ginsenoside Rb
1Form with Rd, wherein ginsenoside Rb
1Content be 30～70wt%, ginsenoside Rd's content is 4～18wt%, and ginsenoside Rb
1Be up to 80wt% with the content sum of Rd.
2. notoginseng glycol-saponin composition according to claim 1 is characterized in that, described ginsenoside Rb
1Content be 40～65wt%, described ginsenoside Rd's content is 6～15wt%.
3. notoginseng glycol-saponin composition according to claim 2 is characterized in that, described ginsenoside Rb
1Content be 50～65wt%, described ginsenoside Rd's content is 10～13wt%.
4. each described notoginseng glycol-saponin composition of claim 1-3, it is granule, mixture, tablet, powder, honeyed pill, capsule, injection, drop or patch.
5. the preparation method of the described notoginseng glycol-saponin composition of claim 1, this method may further comprise the steps:
(1) be the soak with ethanol extraction Radix Notoginseng of 50～90wt% with concentration, used amount of alcohol is at least 3 times of used three seven weight, collects ethanol extract;
(2) make described ethanol extract by the styrene type macroporous resin post;
(3) be that the ethanol of 30～50wt% carries out eluting to described styrene type macroporous resin post with concentration; With
(4) be that the ethanol of 50～70wt% carries out eluting once more to the resin column through ethanol elution in the described step (3) with concentration, collect eluent.
6. the preparation method of notoginseng glycol-saponin composition according to claim 5 is characterized in that, following the finishing of described step (1):
(a) Radix Notoginseng is pulverized, get Radix Notoginseng powder;
(b) adopting concentration is that the ethanol of 50～90wt% soaks the Radix Notoginseng powder of described step (a) gained, and used amount of alcohol is at least 2 times of used Radix Notoginseng powder weight; With
(c) adopting concentration is that the ethanol of the 50～90wt% Radix Notoginseng powder after to the immersion of described step (b) gained carries out percolation, and used amount of alcohol is at least 1 times of used Radix Notoginseng powder weight, collects percolate.
7. the preparation method of notoginseng glycol-saponin composition according to claim 6 is characterized in that, used concentration of ethanol is 55～70wt% in described step (b) and step (c).
8. the preparation method of notoginseng glycol-saponin composition according to claim 7 is characterized in that, used concentration of ethanol is 60wt% in described step (b) and step (c).
9. the preparation method of notoginseng glycol-saponin composition according to claim 5 is characterized in that, is 35～45wt% in described step (3) eluting resin concentration of ethanol, and used amount of alcohol is at least 1 times of used Radix Notoginseng powder weight.
10. the preparation method of notoginseng glycol-saponin composition according to claim 9 is characterized in that, is 40wt% in described step (3) eluting resin concentration of ethanol.
11. the preparation method of notoginseng glycol-saponin composition according to claim 5 is characterized in that, is 55～65wt% in described step (4) eluting resin concentration of ethanol, used amount of alcohol is at least 1 times of used Radix Notoginseng powder weight.
12. the preparation method of notoginseng glycol-saponin composition according to claim 11 is characterized in that, is 60wt% in described step (4) eluting resin concentration of ethanol.
13. the preparation method of notoginseng glycol-saponin composition according to claim 5 is characterized in that, also comprises: the eluent that adopts silicagel column that above-mentioned steps (4) is made carries out purification and gets eluent again.
14. the preparation method according to each described notoginseng glycol-saponin composition of claim 5-13 is characterized in that, and is further comprising the steps of: with the eluent collected or again eluent concentrate panasadiol saponio alcohol extractum.
15. the preparation method of notoginseng glycol-saponin composition according to claim 14 is characterized in that, and is further comprising the steps of: described panasadiol saponio alcohol extractum is carried out drying.
16. each described notoginseng glycol-saponin composition of claim 1-3 is used to prepare the application of the medicine for the treatment of rheumatic, rheumatoid arthritis.
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| PCT/CN2004/001562 WO2006050642A1 (en) | 2004-11-09 | 2004-12-29 | A composition containing panaxadial saponins and its preparation and application |
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| CN1869058B (en) * | 2006-06-21 | 2012-01-11 | 海南亚洲制药有限公司 | Method of preparing trialcohol group ginseng saponine and bialcohol group ginseng saponine from notoginseng |
| CN1869057B (en) * | 2006-06-21 | 2012-03-07 | 海南亚洲制药有限公司 | Preparation method of trialcohol group ginseng saponine and bialcohol group ginseng saponine |
| CN1869059B (en) * | 2006-06-21 | 2012-04-18 | 海南亚洲制药有限公司 | Method of preparing ginseng saponine monomer from ginseng leaf |
| CN101007035B (en) * | 2007-01-25 | 2010-12-01 | 上海中药创新研究中心 | Application of notoginseng glycol saponins for treating memory deterioration |
| CN101390871B (en) * | 2007-09-18 | 2012-01-18 | 北京本草天源药物研究院 | Ginsenoside Rb1 containing impurity ginsenoside Rd |
| JP2010155787A (en) * | 2008-12-26 | 2010-07-15 | Maruzen Pharmaceut Co Ltd | Anti-inflammatory, anti-aging agent, antiobestic agent, hair restorer, cosmetic and food and drink for beautification |
| CN101766640B (en) * | 2008-12-29 | 2013-04-17 | 兰州大学 | Preparation for panaxoside-Rd aqueous solution of propylene glycol and new application thereof in inflammation resistance, immune suppression and organ transplant rejection resistance |
| CN104173358B (en) * | 2014-08-27 | 2017-01-11 | 哈尔滨珍宝制药有限公司 | Pharmaceutical composition for treating cardiovascular and cerebrovascular diseases |
| CN105998042A (en) * | 2016-06-02 | 2016-10-12 | 上海中医药大学附属龙华医院 | Use of panax notoginseng total saponin extract in promoting lymphangion genesis |
| CN116036105A (en) * | 2021-10-28 | 2023-05-02 | 上海中医药大学附属龙华医院 | Application of medicine for treating lymphedema |
| CN117414370A (en) * | 2023-06-26 | 2024-01-19 | 云南与诺生物工程有限责任公司 | Use of a composition for the preparation of a medicament for alleviating pain |
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