CN1712057A - Preparation of succinic acid carbobenzoxy derivative of orchid family plant effective part - Google Patents
Preparation of succinic acid carbobenzoxy derivative of orchid family plant effective part Download PDFInfo
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- CN1712057A CN1712057A CN 200510081264 CN200510081264A CN1712057A CN 1712057 A CN1712057 A CN 1712057A CN 200510081264 CN200510081264 CN 200510081264 CN 200510081264 A CN200510081264 A CN 200510081264A CN 1712057 A CN1712057 A CN 1712057A
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- orchid
- benzyl
- benzyl succinate
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Abstract
The invention relates to a preparation of succinic acid carbobenzoxy derivative of orchid family plant effective part. The effective part, which containing more than 50% succinic acid carbobenzoxy derivative, is obtained by alcohol extraction, refining by different chromatography, purification. The obtained effective part is used to produce medicine which is enhancing intelligence and preventing senile dementia. The medicine dosage form contains injection, tablet, capsule, oral liquid or dropping pill.
Description
Technical field
The present invention relates to from orchid to extract, refining effective site and the extracting method thereof that obtains, and the effective site that is mainly the benzyl succinate compounds of utilizing the inventive method to obtain increases intelligence in preparation, prevents and treats the application in the disease medicament such as alzheimer disease.
Background technology
After the Literature Consult of system, find, from orchid, separate at present and obtain 17 benzyl succinate glycosides compounds, be present in recessed tongue Cymbidium (Coeloglossum), Herba Orchidis Latifoliae respectively and belong to (Orchis), Loroglossum genus, mountain Coral (Galeola), Gastrodia (Gastrodia) and all ages (seeing Table 1) in Cymbidium 6 platymisciums such as (Vanda)
Benzyl succinate glycosides compound in table 1 orchid
| Numbering | The chemical compound title | The source | List of references |
| ??1 | ??coelovirin?A | ??a | ??1 |
| ??2 | ??coelovirin?B | ??a | ??1 |
| ??3 | ??coelovirin?C | ??a、b | ??2-3 |
| ??4 | ??coelovirin?D | ??a | ??2 |
| ??5 | ??coelovirin?E | ??a | ??2 |
| ??6 | ??loroglossin | ??a、f、g、h | ??3-6 |
| ??7 | ??dactylorhhin?B | ??a、b | ??3 |
| ??8 | ??dactylorhhin?C | ??b | ??3 |
| ??9 | ??dactylorhhin?E | ??a、b | ??3 |
| ??10 | ??4-(β-D-glucopyranosyloxyl) ??benzyl(S)-2-sec-isopropylmalate | ??c | ??7 |
| ??11 | ??bis[4-(β-D-glucopyranosyloxyl) ??benzyl](S)-2-sec-isopropylmalate | ??f、c | ??7-9 |
| ??12 | ??bis[4-(β-D-glucopyranosyloxyl) ??benzyl(S)-2-sec-butyl?malate. | ??f | ??9-10 |
| ??13 | ??militarine | ??b、g | ??3，6，11 |
| ??14 | ??dactylorhhin?A | ??b | ??3 |
| ??15 | ??parishin?B | ??d | ??10 |
| ??16 | ??parishin?C | ??d | ??10 |
| ??17 | ??parishin | ??d、i | ??6，10，12-14 |
A: the blue Coeloglossum viride of long luxuriant recessed tongue; B: wide leaf Herba Orchidis Latifoliae Orchis latifolia; C:Galeolaseptentrionalis; D: Rhizoma Gastrodiae Galeola elata; E:Loroglossum hircinum; F: crawley-root Galeolafaberi; G:Orchis militaris; H:Orchis papilionacea; I:Vanda parishii;
The chemical constitution of 17 kinds of benzyl succinate glycosides compounds is as follows in the orchid:
From orchid, separate 17 benzyl succinate glycosides compounds that obtain, usually adopt positive to separate with reverse phase silica gel, obtain monomeric compound, but find to have bibliographical information or the relevant patent that increases intelligence and effective site of preventing and treating the alzheimer disease effect (benzyl succinate glycosides compound) and preparation method thereof (effective ingredient-benzyl succinate glycosides compound in effective site content greater than 50%).
List of references
1?Huang?S.Y.，Shi?J.G.，Yang?Y.C.et?al.Two?new?isobutyltartrate?monoesters?fromCoeloglossum?viride?(L.)?Harm.var.bracteatum(Willd.)Richter.Chinese?ChemicalLetters，2002，13(6)：551-554.
2?Huang?S.Y.，Shi?J.G.，Yang?Y.C.et?al.Two?new?isobutyltartrate?glucosides?fromCoeloglossum?viride(L.)Harm.var.bracteatum(Willd.)Richter.Chinese?ChemicalLetters，2003，14(8)：814.
3?Kizu?H.，Kaneko?E.，Tomimori?T..?Study?on?Nepal?crude?drugs.X?X?VI.Chemicalconstituents?of?Panch?Aunle，the?roots?of?Dactylorhiza?hatagirea?D.Don.Chem.Pharm.Bull.，1999，47(11)：1618-1625.
4?Pagani，F.Phytoconstituents?of?Orchidaceae.II.Isolation?and?identification?ofloroglossin?and?of?some?flavonol?heterosides?from?Orchis?papilionacea?L.Boll.Chim.Farm.，1982，121(4)：174-177.
5?Gray?R.W.，Guggisberg?A，Segebarth?K.P.et?a1.Organic?natural?products.Theconstitution?of?loroglossine.Helv.Chim.Acta，1977，60(4)：1304-11.
6?Aasen?A.，Behr?D.，Leanker?K.Orchidaceae?glycosides.Structure?of?loroglossine?andmilitarine，two?glucosides?from?Orchis?militaris.Acta?Chem.Scand.，Ser.B，1975，29(10)：1002-4.
7?Inoue?S.，Wakai?A.，Konishi?T.et?al.Studies?on?Galeola?septentrionalis?Reichb.Fil.I.Isolation?and?structures?of?the?constituents?of“Dotuusoo”.YakukakuZasshi，1984，104(1)：42-49.
8?Li?Y.M.，Zhou?Z.1.，Hong?Y.F.New?phenolic?derivatives?from?Galeola?faberi.PlantaMed.1993，59(4)：363-5.
9 Lee cure bright, all tall and erect wheels, big vast Yongfu. crawley-root phenols The Chemical Constituents. and Acta Pharmaceutica Sinica, 1993,28 (10): 766-771.
10?Lin?J.H.，Liu?Y.C.，Hau?J.P.，et?al.Parishins?B?and?C?from?rhizomes?of?Gastrodiaelata.Phytochemistry，1996，42(2)：549-551.
11?Appolonia?C.，Marston?A.Hostettmann?K.Additional?constituents?of?Orchis?militaris.J.Nat.Prod.，1986，49(4)：725.
12 weeks are pretty, Chongqing, Hunan, Pu, Yang Yanbin.Nine kinds of phenolic constituents of fresh gastrodia elata.Science Bulletin, 1981,26 (18): 1118-1120..
13?Dahmen?J.，Leander?K.Studies?on?Orchidaceae?glucosides.Part?7.The?structure?ofparishin，a?glucoside?from?Vanda?parishii.Phytochemistry，1976，15(12)：1986-7.
14?Taguchi?H.，Yosioka?I.，Yamasaki?K.，et?al.Studies?on?the?constituents?of?Gastrodiaelata?Blume.Chem.Pharm.Bull.，1981，29(1)：55-62.
Summary of the invention
The objective of the invention is to extract, refiningly have the effective site (benzyl succinate glycosides compound) that increases intelligence and prevent and treat the alzheimer disease effect at the defective of above-mentioned existence and not enough providing from the orchid family contains the plant of benzyl succinate glycosides compound, its preparation method makes effective ingredient-benzyl succinate glycosides compounds content greater than 50%).
Another object of the present invention provides above-mentioned effective site and the application of preparation in pharmaceutical field thereof, particularly prevents and treats the application in the disease medicaments such as alzheimer disease in preparation.The present invention realizes by following technological process:
1 extracting method:
Crude drug is pulverized the back and is extracted with solvent (alcoholic solution of 50% above concentration), concentrates promptly to get extracting solution.
2 process for purification:
The a extracting solution is refining through styrene tyle macroporous adsorption resin, adopts water and alcoholic solution gradient elution, and middle part alcoholic solution eluting promptly gets effective site.
The b extracting solution is refining through reverse phase silica gel, adopts the alcoholic solution of water and low concentration to remove water-solubility impurity, adopts the alcoholic solution eluting of intermediate concentration promptly to get effective site again.
The c extracting solution is refining through purification on normal-phase silica gel, adopts the solvent method eluting.With low, medium polar solvent eluting weeding of grease solubility impurity, the big solvent elution of reuse polarity promptly gets effective site earlier.
Detect through HPLC, wherein effective ingredient-the content of benzyl succinate glycosides compound in effective site is all greater than 50%.
The effective site of utilizing the inventive method to obtain is rich in effective ingredient-benzyl succinate glycosides compound.
The effective site of utilizing the inventive method to obtain can be used for preparing said preparation on the pharmaceutics, for example: injection, tablet, capsule, oral liquid or drop pill etc.
When the effective site of utilizing the inventive method to obtain prepares the various dosage form of required medicine, can be according to the conventional production method preparation of pharmaceutical field.
The specific embodiment
The following examples can further specify the present invention, but do not limit the present invention in any way.
Embodiment 1:
1. extract Rhizoma Gymnadeniae medical material 1kg and pulverize, add after 95% soak with ethanol spends the night heating and refluxing extraction 3 times, each 2.0 hours.Merge extractive liquid, reclaims ethanol and also is concentrated into thick extractum, adds the distilled water heating for dissolving, is cooled to room temperature, leaves standstill 24 hours, centrifugally gets rid of filter, clear filtrate.
2. refining above-mentioned filtrate is passed through treated HPD-100 macroporous adsorbent resin, first water and ethanol gradient elution, and the middle part decompression recycling ethanol, spray drying promptly gets effective site 2.86g.Wherein active constituent content 52.6%.
Embodiment 2:
1. extract Rhizoma Gymnadeniae medical material 1kg and pulverize, add after 95% soak with ethanol spends the night heating and refluxing extraction 3 times, each 2.0 hours.Merge extractive liquid, reclaims ethanol and also is concentrated into thick extractum, adds the distilled water heating for dissolving, is cooled to room temperature, leaves standstill 24 hours, centrifugally gets rid of filter, clear filtrate.Concentrating under reduced pressure gets concentrated solution.
2. refining concentrated solution passes through the reverse phase silica gel post, behind water and the 10% alcoholic solution eluting, and the alcoholic solution eluting of reuse 50% concentration, concentrating under reduced pressure, the dry effective site 2.32g that gets.Active constituent content 65.3%.
Embodiment 3:
1. extract Rhizoma Gymnadeniae medical material 1kg and pulverize, add after 95% soak with ethanol spends the night heating and refluxing extraction 3 times, each 2.0 hours.Merge extractive liquid, reclaims ethanol and is concentrated into thick extractum.2. refining extractum silica gel mixed sample, by normal phase silicagel column, behind chloroform-methanol (9: the 1) eluting, reuse chloroform-methanol (1: 1) eluting, the effective site 2.59g of eluent reclaim under reduced pressure.Active constituent content 54.0%.
Prepare the effective site of the orchid family 6 kind of plant with above extraction and process for purification, detect through HPLC, wherein effective ingredient-the content of benzyl succinate glycosides compound in effective site is all greater than 50% (seeing Table 2).The effective site that is feedstock production with Rhizoma Gymnadeniae and recessed tongue orchid wherein, its effective ingredient-benzyl succinate glycosides compounds content is higher, and effect is best.Adopting macroporous adsorbent resin, reverse phase silica gel and purification on normal-phase silica gel to carry out effective site and make with extra care, is good with the reverse phase silica gel method, and effective ingredient-benzyl succinate glycosides compounds content is the highest in the effective site; But be more suitable in suitability for industrialized production with the macroporous adsorbent resin method is refining.
The different plants of table 2 the orchid family benzyl succinate glycosides compounds content (%) in the effective site after making with extra care
| Process for purification | Recessed tongue orchid | Rhizoma Gymnadeniae | Gymnadenia crassinervis Finet | Wide leaf Herba Orchidis Latifoliae | Beautiful oecoeclades falcata | Crawley-root |
| Macroporous adsorbent resin | ??52.3 | ??52.6 | ??51.3 | ??50.6 | ??50.8 | ??50.1 |
| Reverse phase silica gel | ??62.1 | ??65.3 | ??60.9 | ??62.5 | ??59.6 | ??56.2 |
| Purification on normal-phase silica gel | ??53.7 | ??54.0 | ??52.2 | ??53.4 | ??51.7 | ??51.6 |
Claims (9)
1. the method for preparing orchid effective site is characterized in that this method comprises the following steps: successively
(1) crude drug (the orchid family contains the plant of benzyl succinate glycosides compound) is pulverized, used alcoholic solution room temperature or the heating and refluxing extraction of solvent 50-95% then, extracting solution gets thick extractum through normal pressure or concentrating under reduced pressure;
(2) this extractum, purification refining through various chromatography methods obtains the benzyl succinate glycosides compounds content in the effective site more than 50%.
2. preparation method according to claim 1 is characterized in that used raw material is that the orchid family contains the plant of benzyl succinate compounds such as Rhizoma Gymnadeniae, recessed tongue orchid, gymnadenia crassinervis Finet, wide leaf Herba Orchidis Latifoliae, beautiful oecoeclades falcata, crawley-root etc.
3. preparation method according to claim 1 is characterized in that extracting used alcohol and is a kind of in methanol, ethanol, isopropyl alcohol or the n-butyl alcohol.
4. preparation method according to claim 1, it is characterized in that used refining, purification process are macroporous adsorption resin chromatography, purification on normal-phase silica gel and reversed-phase silica gel chromatography, perhaps their combination is perhaps mixed extractum in silica gel or kieselguhr, dries the back with the organic solvent eluting that refluxes.
5. preparation method according to claim 1 is characterized in that the used solvent of eluting is a kind of or several mixed solvents in petroleum ether, toluene, benzene, ether, chloroform, dichloromethane, ethyl acetate, isopropyl alcohol, n-butyl alcohol, acetone, ethanol, methanol, the water.
6. use the effective site of the either party's method preparation described in the claim 1-5.
7. orchid effective site according to claim 6 is characterized in that wherein the benzyl succinate glycosides compounds content is more than 50%.Main effective ingredient is the benzyl succinate compounds, its effective ingredient construction features is to contain succinic acid (tartaric acid, malic acid and citric acid etc.) and 4-O-β-D-glucopyranosyl phenethanol or glucose structure, connects with benzyl ester or glycosidic bond form between them.
8. effective site preparation method according to claim 6 is characterized in that being made into tablet, injection, capsule, oral liquid or drop pill.
9. effective site according to claim 6 increases intelligence in preparation, prevent and treat the application in the medicine of alzheimer disease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510081264 CN1712057A (en) | 2004-06-24 | 2005-06-24 | Preparation of succinic acid carbobenzoxy derivative of orchid family plant effective part |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200410049669.6 | 2004-06-24 | ||
| CN200410049669 | 2004-06-24 | ||
| CN 200510081264 CN1712057A (en) | 2004-06-24 | 2005-06-24 | Preparation of succinic acid carbobenzoxy derivative of orchid family plant effective part |
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| CN1712057A true CN1712057A (en) | 2005-12-28 |
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| CN 200510081264 Pending CN1712057A (en) | 2004-06-24 | 2005-06-24 | Preparation of succinic acid carbobenzoxy derivative of orchid family plant effective part |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104173741A (en) * | 2013-05-28 | 2014-12-03 | 中国医学科学院药物研究所 | Application of pseudobulubs cremastrae seu pleiones' effective part in treatment of senile dementia |
| CN107095963A (en) * | 2016-02-26 | 2017-08-29 | 中国医学科学院药物研究所 | Purposes of the bletilla active component in treatment senile dementia |
-
2005
- 2005-06-24 CN CN 200510081264 patent/CN1712057A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104173741A (en) * | 2013-05-28 | 2014-12-03 | 中国医学科学院药物研究所 | Application of pseudobulubs cremastrae seu pleiones' effective part in treatment of senile dementia |
| CN107095963A (en) * | 2016-02-26 | 2017-08-29 | 中国医学科学院药物研究所 | Purposes of the bletilla active component in treatment senile dementia |
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Open date: 20051228 |