CN100354292C - Novel flavonoids - Google Patents
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- CN100354292C CN100354292C CNB03145531XA CN03145531A CN100354292C CN 100354292 C CN100354292 C CN 100354292C CN B03145531X A CNB03145531X A CN B03145531XA CN 03145531 A CN03145531 A CN 03145531A CN 100354292 C CN100354292 C CN 100354292C
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Abstract
The present invention relates to the field of natural pharmaceutical chemistry, and discloses chemical structures of three novel flavonoid compounds disclosed in a formula (1) extracted and separated from ovateleaf actinidia, a preparation method for the compounds and derivatives thereof and the application thereof in the field of medicine and pharmacoiogy, particularly the application of the compounds in the aspect of medicine for preparing, preventing and curing diseases related to free radical injuries.
Description
Technical field
The invention belongs to the Natural Medicine Chemistry field, the chemical structure that relates to three kinds of flavonoid new compounds of extraction separation from ovateleaf actinidia leaf [ActinidaiKolomiKa (Rupr.et Maxim.) Planch], and the preparation method of this new compound and derivative thereof and this new compound and the purposes of derivative in field of medicaments thereof, the especially application aspect the medicine of preparation prevention and treatment and radical damage diseases associated.
Background technology
Modern study shows, a lot of diseases comprise the disease of tumour, arteriosclerosis, coronary heart disease, cerebral thrombosis, cerebral infarction, hematencephalon, diabetes, hyperlipidaemia, senile dementia and some Digestive tract, urinary system, ophthalmology aspect, all especially with radical damage direct or indirect relation is arranged with active oxygen, wherein hydroxy radical qiao (OH) is the most serious to the infringement that human body causes.
Therefore, people attempt by suppressing intravital active oxygen, especially prevent and treat above-mentioned disease by removing intravital excessive free radicals, and obtained certain achievement.Cerebral protective agent " Radicut " injection as the exploitation of Mitsubishi Tokyo Pharmaceutical Co., Ltd; a kind of exactly excessive free radicals that produces when removing cerebral ischemia re-pouring; thereby protection brain cell; alleviate the new drug of the sequela that cerebral thrombosis causes, since listing, obtained good clinical effectiveness.
Flavonoid compound is the strongest class natural compounds of occurring in nature antioxygenation, because it has very strong inhibition active oxygen, removes the free radical effect, toxic side effect is relatively less than chemical synthetic drug simultaneously, so people make great efforts to seek active medicinal matter from flavonoid compound always, comprise and seek new flavonoid compound.At present existing be that the new drug of effective ingredient is applied clinical with the flavonoid compound, be exactly wherein a kind of as Folium Ginkgo total flavones, Folium Ginkgo total flavones has been used for the treatment of diseases such as coronary heart disease, cerebral blood supply insufficiency and senile dementia at present, clinical efficacy is fine.
In a word, flavonoid compound more and more is subjected to people's attention as an efficient class natural compounds of removing free radical in the application aspect prevention and treatment and the radical damage diseases associated.
Ovateleaf actinidia leaf [Actinidia Kolomikta (Rupr, et Maxim.) Planch] is the perennial vine of Actinidiaceae Actinidia, mainly is distributed in ground such as China, Japan, Russia, and Jilin Province's Changbaishan area resource is than horn of plenty.Bibliographical information was once arranged, contain a large amount of flavonoid compounds in the leaf of ovateleaf actinidia leaf, but except people such as Chang Xiaoli had once got Kaempferide-7-O-rhamnoside (Kaempferide-7-O-rhamnoside) and Kaempferide-7-O-rhamnosyl-3-O-rutinoside (Kaempferide-7-O-rhamnosyl-3-O-rutinoside) (herbal medicine,, the 24th the 6th phase of volume, 283-285 page or leaf in 1993) from the leaf of ovateleaf actinidia leaf, do not see other reports.
Summary of the invention
The present inventor is devoted to seek safer more effective natural antioxidant from natural product, through continuous effort, finally produce from the Changbai Mountain and carry thing the wild medicinal plant ovateleaf actinidia leaf [Actinidia Kolomikta (Rupr et.Maxim.) Planch] and be separated to three kinds of flavonoid new compounds, and found that they have the free radical of removing biological activity, thereby finished the present invention.
The objective of the invention is to provide to have the new flavonoid compound that suppresses active oxygen, removes the free radical function, can prevent to provide new natural active matter with the new drug of treatment and radical damage diseases associated for developing.
The present invention finishes by following technical solution, and particular content comprises: the extraction separation of three kinds of flavonoid new compounds, structure are identified, derivative preparation, the discussion of anti-oxidant activity research and possible medicinal use.
(1) extraction separation
The present inventor utilizes and is collected in Changbaishan area, through the ovateleaf actinidia leaf leaf of seasoning, uses alcohol reflux, and extracting solution gets ethanol extraction through concentrating under reduced pressure.The water-soluble again suspension of making of this extract, use ethyl acetate and n-butanol extraction respectively, obtain ethyl acetate extraction part and n-butanol extraction part, after concentrating under reduced pressure, drying, obtain acetic acid ethyl ester extract and n-butyl alcohol extract respectively, getting n-butyl alcohol extract utilizes silica gel column chromatography to carry out roughing out, utilize again that the ODS column chromatography further separates, purifying, finally obtain a plurality of flavonoid compounds, comprised new compound 1 of the present invention, new compound 2, three flavonoid new compounds of new compound 3-.Owing to have ethanoyl in the molecule of new compound 2, new compound 3; hydrolysis takes place under acid, alkali and hot conditions easily; so should note when extracting keeping neutral, should notice that simultaneously high temperature does not extract for a long time, especially during water extraction temperature preferably above 100 ℃.
(2) structure is identified
1The chemical shift that H-NMR provides is 6.43ppm (1H, d, J=1.8) and 6.21ppm (1H, d, two doublets J=1.8), illustrate in the new compound 1 exist 1 pair be in phenyl ring between the hydrogen atom of position, in addition at 8.08ppm (2H, d, J=8.8) and 7.06ppm (2H, d, J=8.8) locate two doublets occurring, illustrate in the new compound 1 to have two pairs of adjacent hydrogen atoms that are in phenyl ring, simultaneously 12.50ppm (1H, that S) locates to occur is unimodal, illustrate that one forms the hydroxyl hydrogen of hydrogen bond with ketonic oxygen, (3H, S) locate to occur one very strong unimodal, illustrates to have a methoxyl group at 3.85ppm.According to above-mentioned supposition, again with reference to pertinent literature, the skeleton of determining new compound 1 is Kaempferide (Kaempferide).In addition, new compound 1
1H-NMR,
13C-NMR has provided the signal of a glucose and a rhamnosyl, can infer that therefore new compound 1 is flavonoid glycoside compound.Because
13The chemical shift of the 6th carbon of the glucose that C-NMR provides is 66.63ppm, shows that glucose combines with rhamnosyl (6-1), has formed rutinose.The chemical shift of the C-2 of new compound 1 is 156.39ppm simultaneously, C-2 chemical shift than its aglycon Kaempferide has increased about 10 ppm, the chemical shift of C-3 has then reduced about 2 ppm, illustrate on 3 and be connected with sugar, and the chemical shift of C-7 and Kaempferide more do not change, illustrate that 7 are not connected with sugar, so the decidable rutinose is connected on 3.Comprehensive above-mentioned judgement, again according to the DEPT of new compound 1,
1H-
1The information that spectroscopic datas such as HCOSY .HMBC, HMQC, NOESY, MS provide, the structure of determining new compound 1 is Kaempferide-3-O-rutinoside (Kaempferide-3-O-rutinoside).
Structural formula is as follows:
Table 1 new compound 1
1H-NMR,
13C-NMR data (400MHz, δ: ppm from TMS in DMSO-d
6J=Hz)
| 1H-NMR | ||
| Kaempferide(aglycone) | ||
| OH-5 H-6 H-8 H-2′，6′ H-3′，5′ 4′-OCH 3 | 12.50(1H，s) 6.43(1H，d，J＝1.8) 6.21(1H，d，J＝1.8) 8.08(2H，d，J＝8.8) 7.06(2H，d，J＝8.8) 3.85(3H，S) | |
| 3-O-Rutinosyl Glc | ||
| H-1 H-2 H-3 H-4 H-5 H-6 | 5.35(1H，d，J＝7.6) 3.16(1H，m) 3.25(1H，m) 3.08(1H，m) 3.21(1H，m) 3.69(1H，d，J＝10.3) | |
| Rha | ||
| H-1 H-2 H-3 H-4 H-5 H-6 | 4.39(1H，s) 3.29(1H，m) 3.45(1H，s) 3.09(1H，m) 3.28(1H，m) 0.98(3H，d，J＝6.1) | |
| 13C-NMR | |||
| Kaempferide(aglycone) | 3-O-Rutinosyl Glc | ||
| C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-1′ C-2′ C-3′ 0-4′ C-5′ C-6′ 4′-OCH 3 | 156.39 133.46 177.31 161.11 98.72 164.24 93.72 156.47 103.94 122.32 130.63 113.61 161.13 113.61 130.63 55.29 | ||
| C-1 C-2 C-3 C-4 C-5 C-6 | 101.37 74.05 75.59 69.62 76.25 66.63 | ||
| Rha | |||
| C-1 C-2 C-3 C-4 C-5 C-6 | 100.38 70.55 70.26 71.71 68.16 17.62 | ||
The structural formula of compound 2 is as follows:
Table 2 new compound 2
1H-NMR,
13C-NMR data (400MHz, δ: ppm from TMS in DMSO-d
6J=Hz)
| 1H-NMR | ||
| Kaempferide(aglycone) | ||
| OH-5 H-6 H-8 H-2′，6′ H-3′，5′ 4′-OCH 3 | 12.57(1H，s) 6.51(1H，d，J＝2.1) 6.89(1H，d，J＝2.1) 8.18(2H，d，J＝9.0) 7.09(2H，d，J＝9.0) 3.86(3H，S) | |
| 3-O-Glucosyl | ||
| H-1 H-2 H-3 H-4 H-5 H-6a H-6b | 5.51(1H，d，J＝7.3) 3.22(1H，m) 3.10(1H，m) 3.10(1H，m) 3.22(1H，m) 3.69(1H，m) 3.58(1H，br-d，J＝11.2) | |
| 7-O-Rhamnosyl | ||
| H-1 H-2 H-3 H-4 H-5 H-6 4-OCOCH 3 | 5.64(1H，s) 3.93(1H，b r-s) 3.88(1H，m) 4.89(1H，t，J＝9.7) 3.64(1H，m) 1.01(3H，d，J＝6.3) 2.08(3H，s) | |
| 13C-NMR | |||
| Kaempferide(aglycone) | 3-O-Glucosyl | ||
| C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-1′ C-2′ C-3′ C-4′ C-5′ 0-6′ 4′-OCH 3 | 156.07 133.56 177.31 160.56 99.33 161.07 94.50 155.70 105.69 122.13 130.59 113.56 160.97 113.56 130.59 55.38 | C-1 C-2 C-3 C-4 C-5 C-6 | 101.37 74.08 77.49 69.84 76.30 60.82 |
| 7-O-Rhamnosyl | |||
| C-1 C-2 C-3 C-4 C-5 C-6 4-0COCH 3 | 97.73 69.61 67.70 73.20 67.41 17.52 169.59 20.93 | ||
The same with new compound 1, new compound 2, according to
1H-NMR,
13It is the flavonoid glycoside compound of aglycon with the Kaempferide that the parsing of C-NMR data, deducibility new compound 3 remain one.Compound 3
1H-NMR,
13C-NMR has provided the signal of a glucose and two rhamnosyls; provide the chemical signal of an ethanoyl simultaneously; because the chemical shift of No. 6 carbon is 66.34ppm on the glucose; the glucose of specific ionization has increased about 6 ppm; therefore glucose and another rhamnosyl (6-1) Cheng Jian in the compound 3 are described; that is to say that having 1 molecule rutinose, another one rhamnosyl is free (not having and the glucose combination).Because the chemical shift of C-2 is moved about 10 ppm to low field, the chemical potential of C-3, C-7 moves about 2 ppm to High-Field respectively, illustrates that C-3, C-7 position all are connected with sugar simultaneously.Owing to observed terminal hydrogen and the long-range coupling of the 7th carbon on the skeleton on the free rhamnosyl from the HMBC of new compound 3, rhamnosyl is connected 7 so judgement dissociates, and rutinose then has been connected on 3.Binding site as for ethanoyl; owing to be connected in 7 rhamnosyl; the chemical shift of its No. 4 carbon is moved about 2 ppm to low; the chemical shift of No. 3 and No. 5 carbon is moved about 2 ppm to High-Field; hydrogen on No. 4 carbon on the rhamnosyl that is connected on 7 and the long-range coupling between the ethanoyl carbonyl carbon from HMBC, have been observed in addition, so judge that ethanoyl is connected on No. 4 carbon of 7 rhamnosyls.In sum, determine that new compound 3 is Kaempferide-7-O-(4-O-ethanoyl-rhamanopyranosyl)-3-O-rutinoside [Kaempferide-7-O-(4-O-acetyl-rhamnosyl)-3-O-rutinoside].
Structural formula is as follows:
Table 3 new compound 3
1H-NMR,
13C-NMR data (400MHz, δ: ppm from TMS in DMSO, J=Hz)
| 1H-NMR | ||
| Kaempferide(aglycone) | ||
| OH-5 H-6 H-8 H-2′，6′ H-3′，5′ 4-OCH 3 | 12.50(1H，s) 6.51(1H，d，J＝2.1) 6.84(1H，d，J＝2.1) 8.13(1H，d，J＝8.8) 7.08(1H，d，J＝8.8) 3.86(3H，S) | |
| 3-O-Rutinosyl GLC | ||
| H-1 H-2 H-3 H-4 H-5 H-6 | 5.34(1H，d，J＝4.5) 3.18(1H，m) 3.26(1H，m) 3.08(1H，m) 3.21(1H，m) 3.68(1H，d，J＝10.0) | |
| Rha | ||
| H-1 H-2 H-3 H-4 H-5 H-6 | 4.40(1H，m) 3.44(1H，m) 3.12(1H，m) 3.28(1H，m) 3.65(1H，m) 0.97(3H，d，J＝6.1) | |
| 7-O-Rhamnosyl | ||
| H-1 H-2 H-3 H-4 H-5 H-6 4-OCOCH 3 | 5.64(1H，d，J＝1.2) 3.94(1H，t，J＝4.6) 3.88(1H，m) 4.89(1H，t，J＝9.7) 3.63(1H，m) 1.03(3H，d，J＝6.1) 2.08(3H，S) | |
| 13C-NMR | ||||
| Kaempferide(aglycone) | 3-O-Rutinosyl GLC | |||
| C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-1′ C-2′ C-3′ C-4′ C-5′ C-6′ 4′-OCH 3 | 156.88 133.76 177.55 161.30 99.39 160.81 94.75 156.09 105.76 122.15 130.74 113.67 161.24 113.67 130.74 55.32 | |||
| C-1 C-2 C-3 C-4 C-5 C-6 | 101.22 74.06 75.66 69.62 76.26 66.53 | |||
| Rha | ||||
| C-1 C-2 C-3 C-4 C-5 C-6 | 100.62 70.54 69.64 71.71 67.41 17.38 | |||
| 7-O-Rhamnosyl | ||||
| C-1 C-2 C-3 C-4 C-5 C-6 4-OCOCH3 | 97.85 70.26 68.14 73.23 67.73 17.59 169.85 20.81 | |||
More than three kinds of flavonoid compounds, up to now, find relevant patent or bibliographical information as yet, be new flavonoid compound.
(3) preparation of derivative
A. new compound 1, new compound 2, new compound 3 are put into 2% H respectively
2SO
4In the aqueous solution, reflux 2 hours is put and is chilled to room temperature, suction filtration, precipitation is washed with water to neutrality, suction filtration is to doing, vacuum-drying, the aglycon of above-mentioned new compound, i.e. Kaempferide (Kaempferide, compound 4).
The chemical structure of Kaempferide is as follows:
Compound 4
Table 4, compound 4 (Kaempferide)
13C-NMR data (400MHz, δ: ppm from TMS in DMSO)
| Carbon | Chemical shift |
| C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-1′ C-2′ C-3′ C-4′ C-5′ C-6′ 4′-OCH 3 | 145.77 135.64 175.46 159.97 97.91 163.48 93.20 155.75 102.76 122.87 128.89 113.63 160.42 113.63 128.89 55.11 |
B. with the aqueous solution of new compound 3, reflux 2 hours, put and be chilled to room temperature, n-butanol extraction, decompression and solvent recovery, vacuum-drying, the product silica gel column chromatography separates, and gets Kaempferide-7-O-rhamnosyl-3-O-rutinoside (Kaempferide-7-O-rhamnosyl-3-O-rutinoside, compound 5).
Chemical structure is as follows.
Three kinds of flavonoid new compounds of the present invention and their derivative as active constituents of medicine, can be prepared into conventional pharmaceutical dosage form, as, tablet, pill, paste, capsule, oral liquid, granule and powder ampoule agent for injection or liquid drugs injection liquid.
Table 5 compound 5
1H-NMR,
13C-NMR data (400MHz, δ: ppm from TMS in DMSO)
| 1H-NMR | |
| Kaempferide(aglycone) | |
| OH-5 H-6 H-8 H-2′，6′ H-3′，5′ 4-OCH 3 | 12.50(1H，s) 6.47(1H，d，J＝2.1) 6.80(1H，d，J＝2.1) 8.13(1H，d，J＝9.0) 7.08(1H，d，J＝9.0) 3.86(3H，S) |
| 13C-NMR | |||
| Kaempferide(aglycone) | 3-O-Rutinosyl GLC | ||
| C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-1′ C-2′ C-3′ C-4′ C-5′ C-6′ 4′-OCH 3 | 156.46 133.39 177.08 161.19 98.03 160.89 94.40 155.69 105.34 121.84 130.40 113.37 160.37 113.37 130.40 55.18 | ||
| C-1 C-2 C-3 C-4 C-5 C-6 | 100.97 73.87 76.06 69.80 75.46 66.34 | ||
| Rha | |||
| C-1 C-2 C-3 C-4 C-5 C-6 | 100.36 70.00 69.41 71.34 67.96 17.56 | ||
| 7-O-Rhamnosyl | |||
| C-1 C-2 C-3 C-4 C-5 C-6 | 99.05 70.37 70.08 71.53 69.55 17.55 | ||
(4)
Remove the hydroxy radical qiao activity test
1,
Experimental technique
The generation of hydroxy radical qiao and clearance test reference literature (herbal medicine, the 34th the 4th phase of volume, 317-319 page or leaf) method is carried out.Get 7.5mmolL
-1Phenanthroline aqueous solution 1.8ml, phosphate buffer solution (PBS) 5.0ml of adding PH=7.4 fully adds 7.5mmolL behind the mixing again
-1 ferrous sulfate aqueous solution 1.8ml fully adds 0.1%H behind the mixing
2O
22.4ml last water replenishes volume to 20ml, 536nm place absorbance A is surveyed in 37 ℃ of isothermal reactions of reaction solution 1 hour
Damage, experimental group adds H after adding sample liquid earlier again
2O
2, survey A
Application of sampleThe damage pipe does not add H
2O
2And sample liquid, survey A
BlankCalculate the hydroxy radical qiao clearance rate with following formula.
OH clearance rate=(A
Application of sample-A
Damage)/(A
Blank-A
Damage) * 100%
2,
The test sample
3,
Test-results
(1) experimental data
| A (absorbance measurement value) | A (on average) | OH free radical scavenging activity (%) | ||||
| Blank | 1.362 | 1.358 | 1.361 | 1.360 | ||
| Damage | 0.575 | 0.574 | 0.576 | 0.575 | ||
| |
50μg | 0.701 | 0.703 | 0.705 | 0.703 | 16.31 |
| 100μg | 0.776 | 0.775 | 0.776 | 0.776 | 25.64 | |
| 150μg | 0.845 | 0.849 | 0.847 | 0.848 | 34.78 | |
| 200μg | 0.899 | 0.897 | 0.900 | 0.899 | 41.40 | |
| 250μg | 1.035 | 1.035 | 1.036 | 1.035 | 58.60 | |
| |
50μg | 0.695 | 0.696 | 0.693 | 0.696 | 15.41 |
| 100μg | 0.759 | 0.758 | 0.760 | 0.759 | 23.40 | |
| 150μg | 0.823 | 0.821 | 0.824 | 0.823 | 31.65 | |
| 200μg | 0.891 | 0.890 | 0.892 | 0.891 | 40.33 | |
| 250μg | 1.011 | 1.012 | 1.012 | 1.012 | 55.72 | |
| |
50μg | 0.720 | 0.720 | 0.721 | 0.720 | 18.51 |
| 100μg | 0.792 | 0.793 | 0.790 | 0.792 | 27.64 | |
| 150μg | 0.874 | 0.871 | 0.872 | 0.873 | 38.02 | |
| 200μg | 0.968 | 0.964 | 0.966 | 0.966 | 49.91 | |
| 250μg | 1.045 | 1.044 | 1.044 | 1.044 | 59.79 | |
| |
50μg | 0.710 | 0.711 | 0.712 | 0.711 | 17.32 |
| 100μg | 0.777 | 0.778 | 0.778 | 0.778 | 25.85 | |
| 150μg | 0.860 | 0.861 | 0.861 | 0.861 | 36.43 | |
| 200μg | 0.930 | 0.931 | 0.930 | 0.930 | 45.22 | |
| 250μg | 1.038 | 1.037 | 1.039 | 1.037 | 58.85 | |
| |
50μg | 0.660 | 0.681 | 0.702 | 0.680 | 13.37 |
| 100μg | 0.717 | 0.738 | 0.748 | 0.732 | 22.00 | |
| 150μg | 0.820 | 0.821 | 0.821 | 0.821 | 31.34 | |
| 200μg | 0.900 | 0.901 | 0.900 | 0.900 | 41.40 | |
| 250μg | 1.002 | 1.001 | 1.009 | 1.004 | 54.64 | |
(2) hydroxy radical qiao is removed experimental result as shown in Figure 1.
4,
Conclusion (of pressure testing)
Description of drawings
Fig. 1. the removing hydroxy radical qiao test-results of three kinds of flavonoid new compounds and compound 4,5
Fig. 2. the mass spectrum of new compound 1
Fig. 3. new compound 1
1H-NMR figure
Fig. 4. new compound 1
13C-NMR figure
Fig. 5. the DEPT figure of new compound 1
Fig. 6. new compound 1
1H-
1HCOSY figure
Fig. 7. the HMQC figure of new compound 1
Fig. 8. the HMBC figure of new compound 1
Fig. 9. the NOESY figure of new compound 1
Figure 10. the mass spectrum of new compound 2
Figure 11. new compound 2
1H-NMR figure
Figure 12. new compound 2
13C-NMR figure
Figure 13. the DEPT figure of new compound 2
Figure 14. new compound 2
1H-
1H COSY figure
Figure 15. the HMQC figure of new compound 2
Figure 16. the HMBC figure of new compound 2
Figure 17. the NOESY figure of new compound 2
Figure 18. the mass spectrum of new compound 3
Figure 19. new compound 3
1H-NMR figure
Figure 20. new compound 3
13C-NMR figure
Figure 21. the DEPT figure of new compound 3
Figure 22. new compound 3
1H-
1H COSY figure
Figure 23. the HMQC figure of new compound 3
Figure 24. the HMBC figure of new compound 3
Figure 25. the NOESY figure of new compound 3
Figure 26. aglycon (compound 4)
13C-NMR figure
Figure 27. compound 5
1H-NMR figure
Figure 28. compound 5
13C-NMR figure
Figure 29. the extraction of three kinds of new compounds
Figure 30. the separation of three kinds of new compounds
Embodiment
Below in conjunction with specific embodiment, the present invention is further illustrated, but content of the present invention is not limited only to cited embodiment. experiment is collected in Jilin Province's Jingyu County Changbaishan area in June, 2002 with the leaf of ovateleaf actinidia leaf [Actinidia Kolomikta (Rupr.et Maxim.) Plarch].
13 kilograms on ovateleaf actinidia leaf leaf, with alcohol reflux three times, the ethanol consumption is respectively 12,10,8 times of ovateleaf actinidia leaf leaf weight, extraction time was respectively 60,45,30 minutes, be dissolved in water behind the extracting solution concentrating under reduced pressure, use ethyl acetate, n-butanol extraction more respectively, the extraction liquid concentrating under reduced pressure.N-butyl alcohol extract obtains new compound 1,2,3 (seeing accompanying drawing 29,30) respectively after column chromatography for separation.
1 kilogram on ovateleaf actinidia leaf leaf, the water heating is extracted three times, water consumption is respectively 20,15,12 times of ovateleaf actinidia leaf leaf weight, extraction time was respectively 60,45,30 minutes, extracting temperature is 70 ℃, and extracting solution is crossed macroporous adsorbent resin (AB-8 2kg, Chemical Plant of Nankai Univ., also can be with other brands, as D101, D4020,860021, HP-20 etc.) and adsorbed, 85% ethanol elution is used in water flushing back, and the elutriant decompression and solvent recovery gets the flavones mixture.This mixture is through column chromatography [silica gel column chromatography: ethyl acetate: methyl alcohol=5: 1; ODS column chromatography: methyl alcohol: water=1: 1] obtain new compound 1,2,3 respectively after separating.
1 kilogram on ovateleaf actinidia leaf leaf, extract three times with methanol eddy, methanol usage is respectively 12,10,8 times of ovateleaf actinidia leaf leaf weight, extraction time was respectively 60,45,30 minutes, extracting solution is dissolved in water after being evaporated to certain volume again, cross then macroporous adsorbent resin (860021 2kg, Lukang Medical Co., Ltd., Shandong, also can be with other brands, as P101, D4020, AB-8, HP-20 etc.) absorption, methanol-eluted fractions is used in water flushing back, and the elutriant decompression and solvent recovery gets the flavones mixture.This mixture obtains new compound 1,2,3 respectively after separating through column chromatography [silica gel column chromatography: ethyl acetate: methyl alcohol=5: 1, ODS column chromatography: methyl alcohol: water=1: 1].
Embodiment 4The preparation of derivative
Get 100mg new compound 3, be dissolved in 100ml 2%H
2SO
4In the aqueous solution, reflux 2 hours is put and is chilled to room temperature, suction filtration, and precipitation is washed with water to neutrality, and suction filtration is to doing, and vacuum-drying gets aglycon (Kaempferide, compound 4) 21mg.
Embodiment 5The preparation of derivative
Get 500mg new compound 3, be dissolved in 100 ml waters, refluxed 2 hours, the reaction solution n-butanol extraction, decompression and solvent recovery, silica gel column chromatography separates, and gets 98mg compound 5.
The preparation of capsule
Get a kind of in above-mentioned three kinds of flavonoid new compounds and their derivative or their mixture, it is an amount of to add medicinal supplementary product starch, fully incapsulates behind the mixing, makes every capsule that contains above-mentioned new compound or derivative 100mg for orally using.
The preparation of injection
Get a kind of of above-mentioned three kinds of flavonoid new compounds and their derivative or their mixture, it is an amount of to add injection pure water and Polysorbate 80, makes the injection liquid that every 250ml contains above-mentioned new compound of 100mg or derivative and uses for intravenous drip.
Claims (7)
1, flavonoid compound is characterized in that this compound has chemical structure shown in the formula (1):
Wherein
Or
Or
2, the pharmaceutical composition formed of described compound of claim 1 and medically acceptable pharmaceutical excipient.
3, the purposes of the described compound of claim 1 in the medicine of preparation prevention and treatment and radical damage diseases associated.
4, the preparation method of the described compound of claim 1, it is characterized in that with the ovateleaf actinidia leaf leaf be raw material, through water or organic solvent or the extraction of their mixed solvent, aqueous extract is directly crossed absorption with macroporous adsorbent resin, organic solvent extraction liquid is dissolved in water after reclaiming solvent, after absorption with macroporous adsorbent resin or n-butanol extraction, at last absorption with macroporous adsorbent resin thing or n-butyl alcohol extract are got through column chromatography for separation afterwards.
5, the pharmaceutical composition formed of Kaempferide or Kaempferide-7-O-rhamnosyl-3-O-rutinoside and medically acceptable pharmaceutical excipient.
6, Kaempferide or the Kaempferide-7-O-rhamnosyl-3-O-rutinoside purposes in the medicine of preparation prevention and treatment and radical damage diseases associated.
7, claim 3 or 6 described purposes, disease wherein is selected from tumour, arteriosclerosis, coronary heart disease, cerebral thrombosis, hematencephalon, cerebral blood supply insufficiency, diabetes, hyperlipidaemia, senile dementia, cataract, retinopathy, liver cirrhosis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CNB03145531XA CN100354292C (en) | 2003-06-30 | 2003-06-30 | Novel flavonoids |
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| CNB03145531XA CN100354292C (en) | 2003-06-30 | 2003-06-30 | Novel flavonoids |
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| CN1566127A CN1566127A (en) | 2005-01-19 |
| CN100354292C true CN100354292C (en) | 2007-12-12 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101757298B (en) * | 2009-11-13 | 2011-10-05 | 段洪东 | Process for extracting and purifying tianschanica maxim total flavonoid |
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2003
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Non-Patent Citations (2)
| Title |
|---|
| synthese et oxydation de b-neohesperidosides-7-dedihydroxy-5,7-flavanones. par georgette.bulletin de la societe chimque de francd. 1971 * |
| 狗枣猕猴桃叶化学成分的研究(I) 常晓丽等.中草药，第24卷第6期 1993 * |
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