CN107441079A - A kind of medicine for treating cardiovascular and cerebrovascular disease and its production and use - Google Patents
A kind of medicine for treating cardiovascular and cerebrovascular disease and its production and use Download PDFInfo
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- CN107441079A CN107441079A CN201710725593.1A CN201710725593A CN107441079A CN 107441079 A CN107441079 A CN 107441079A CN 201710725593 A CN201710725593 A CN 201710725593A CN 107441079 A CN107441079 A CN 107441079A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
- C07D311/36—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only not hydrogenated in the hetero ring, e.g. isoflavones
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Abstract
The invention discloses a kind of medicine for treating cardiovascular and cerebrovascular disease and its production and use, belongs to medicinal chemistry art.Medicine of the present invention is the preparation that is prepared plus pharmaceutically acceptable auxiliary material or complementary composition using 6 hydroxy dye lignins as active component.The invention also discloses the preparation method and its usage of 6 hydroxy dye lignins, utilize blackberry lily aglycon, belamcandin, the 6 hydroxy dye lignins that flower of kudzuvine aglycon and contg. glucoside of pueravia flower are prepared, with pharmacological activity, there is obvious anti anoxia and suppress tumor cell proliferation, the hypoxia-bearing capability of body can significantly be strengthened, there is significant inhibitory action to cancer cell multiplication simultaneously, therefore 6 hydroxy dye lignins can be used for preparing treatment cardiovascular and cerebrovascular disease, vascular dementia, the medicine of some tumours, injection can be particularly prepared into, tablet, capsule, the preparation such as pill or oral administration solution makes its application wider.
Description
Technical field
The present invention relates to a kind of medicine for treating cardiovascular and cerebrovascular disease and preparation method thereof and application thereof, category pharmaceutical chemistry neck
Domain.
Background technology
6- hydroxy dye lignins, molecular formula C15H10O6, chemistry entitled 5,6,7,4 '-tetrahydroxy isoflavones or 5,6,7- tri-
Hydroxyl -3- (4- hydroxyphenyls) -4H-1- benzopyran-4-ones, its structural formula are
Research on 6- hydroxy dye lignins is less, and it is a kind of opsonigenous substance mainly to think it at present, main logical
The mode separated from opsonigenous substance is crossed to obtain.Only having 6- hydroxy dye lignins to the report of its pharmacological activity at present has
Liver-protecting activity, the report without other activity or effect.
The content of the invention
In order to solve the above problems, the invention provides the preparation method and its usage of 6- hydroxy dye lignins.
Cardiovascular and cerebrovascular disease and the medicine of tumour are treated the invention discloses a kind of, it is using 6- hydroxy dyes lignin as work
Property composition, the preparation being prepared plus pharmaceutically acceptable auxiliary material or complementary composition.
Wherein, the preparation is injection, tablet, capsule, pill or oral administration solution.
The invention discloses a kind of method for preparing 6- hydroxy dye lignins, step are as follows：
(1) compound A is dissolved in 70%~100%V/W ethanol, forms solution B；Wherein, compound A is belamcandin
Member, belamcandin, flower of kudzuvine aglycon or contg. glucoside of pueravia flower；Ethanol and compound A envelope-bulk to weight ratio are 5:1ml/g；
(2) demethylation reagent and phase transfer catalyst are added into solution B, stirred, 5~24h is reacted at 95 DEG C~100 DEG C,
Reaction is complete, obtains reaction liquid C；Wherein, demethylation reagent and compound A envelope-bulk to weight ratio are 3:1ml/g, phase transfer catalyst
Weight ratio with compound A is 0~0.01:1g/g；
(3) by reaction liquid C at 0~25 DEG C, 1~24h is placed, filtering, neutrality is washed to, it is thick to obtain 6- hydroxy dye lignins
Product, recrystallization purification.
Wherein, in step (1), the concentration of the ethanol is 95%V/W.
Wherein, in step (2), the demethylation reagent is hydroiodic acid, sulfuric acid, hydrochloric acid or hydrobromic acid；And/or the phase
Transfer catalyst is tri-n-octyl methyl ammonium chloride, tetrabutyl phosphonium bromide phosphorus or hexadecyltri-n-butylphosp.
Wherein, in step (2), the concentration of the demethylation reagent is 0~40%V/W.
Preferably, the phase transfer catalyst is tri-n-octyl methyl ammonium chloride.
Wherein, in step (2), the complete determination method of reaction is to utilize silica G F254Thin layer inspection, solvent are
Chloroform：Methanol：Formic acid 10:1:0.1.
The invention discloses 6- hydroxy dyes lignin to prepare treatment cardiovascular and cerebrovascular disease, vascular dementia, tumour medicine
In application.
Wherein, the tumour is colon cancer, breast cancer or gland cancer.
The beneficial effect that the present invention reaches：The present invention is prepared into using blackberry lily aglycon, belamcandin, flower of kudzuvine aglycon and contg. glucoside of pueravia flower
The 6- hydroxy dye lignins arrived, have pharmacological activity, i.e., with obvious oxygen lack resistant function, can significantly strengthen the resistance to of body and lack
Oxygen ability, while have significant inhibitory action to cancer cell multiplication, available for the medicine for preparing treatment Cardial or cerebral vascular diseases and tumour
Thing.
The present invention is described in further details below by embodiment, but is not the limit to the present invention
System, according to the above of the present invention, according to the ordinary technical knowledge and customary means of this area, not departing from, the present invention is above-mentioned
Under the premise of basic fundamental thought, the modification, replacement or change of other diversified forms can also be made.
Brief description of the drawings
Fig. 1 is that the IR of 6- hydroxy dye lignins schemes；
Fig. 2 is 6- hydroxy dye lignins1H NMR scheme；
Fig. 3 is 6- hydroxy dye lignins13CNMR schemes；
Fig. 4 is that the MS of 6- hydroxy dye lignins schemes.
Embodiment
Embodiment 1 prepares 6- hydroxy dye lignins by blackberry lily aglycon
Blackberry lily aglycon is added in reactor, adds 5 times of amount (ml/g) 95% ethanol (V/W), with mixer stirring simultaneously
It is heated to reflux, the hydroiodic acid (content >=45%V/W) of 3 times of amounts (ml/g) is added after blackberry lily aglycon is completely dissolved, stirs, add
Heat backflow 5~24 hours, utilizes silica G F254Thin layer inspection, determine that (solvent is chloroform to reaction end：Methanol：Formic acid 10:1:
0.1).Reaction solution is released, left at room temperature over night, separates out faint yellow acicular crystal, is filtered, is washed to neutrality, obtains 6- hydroxy dyes
Lignin crude product；6- hydroxy dye lignin fine work, yield 85% are obtained with recrystallization method.
The present embodiment products obtained therefrom is faint yellow acicular crystal；It is odorless, it is tasteless.It is dissolved in methanol, ethanol, is practically insoluble in
Water.245~250 DEG C of fusing point；UVλmax274nm；IR、1H NMR、13CNMR, MS are shown in Fig. 1~4.
Chemical equation is as follows：
Embodiment 2 prepares 6- hydroxy dye lignins by belamcandin
Belamcandin is added in reactor, 5 times of amount (ml/g) 95% ethanol (V/W) is added, is stirred and heated with mixer
Backflow, the hydroiodic acid (content >=45%) (V/W) of 3 times of amounts (ml/g) is added when into uniform pasty state, stirring, is heated to reflux
5~24 hours, utilize silica G F254Thin-layer chromatography inspection, to determine reaction end, (solvent is chloroform：Methanol：Formic acid 10:1:
0.1) reaction solution, is released, left at room temperature over night, pale precipitation is separated out, filtering, is washed to neutrality, obtains 6- hydroxy dye lignins
Crude product；6- hydroxy dye lignin fine work, yield 70% are obtained with recrystallization method.
Chemical equation is as follows：
Embodiment 3 prepares 6- hydroxy dye lignins by flower of kudzuvine aglycon
Flower of kudzuvine aglycon is added in reactor, adds 5 times of amount (ml/g) 95% ethanol (V/W), with mixer stirring simultaneously
It is heated to reflux, the hydroiodic acid (content >=45%) (V/W) of 3 times of amounts (ml/g) is added after flower of kudzuvine aglycon is completely dissolved, stirs,
It is heated to reflux 5~24 hours, utilizes silica G F254Thin-layer chromatography inspection, to determine reaction end, (solvent is chloroform：Methanol：
Formic acid 10:1:0.1) reaction solution, is released, left at room temperature over night, separates out faint yellow acicular crystal, is filtered, is washed to neutrality, obtains 6-
Hydroxy dye lignin crude product；6- hydroxy dye lignin fine work, yield 80% are obtained with recrystallization method.
Chemical equation is as follows：
Embodiment 4 prepares 6- hydroxy dye lignins by contg. glucoside of pueravia flower
Contg. glucoside of pueravia flower is added in reactor, 5 times of amount (ml/g) 95% ethanol (V/W) is added, is stirred and heated with mixer
Backflow, the hydroiodic acid (content >=45%) (V/W) of 3 times of amounts (ml/g) is added when into uniform pasty state, stirring, is heated to reflux
5~24 hours, utilize silica G F254Thin-layer chromatography inspection, to determine reaction end, (solvent is chloroform：Methanol：Formic acid 10:1:
0.1) reaction solution, is released, left at room temperature over night, pale yellow precipitate is separated out, filtering, is washed to neutrality, obtains 6- hydroxy dye lignins
Crude product；6- hydroxy dye lignin fine work, yield 75% are obtained with recrystallization method.
Chemical equation is as follows：
Different pharmaceutical preparations is made plus pharmaceutically acceptable carrier in medicine of the present invention, such as injection, freeze-dried powder
Pin, tablet, powder, granule, capsule, pill, oral administration solution etc., wherein tablet includes：Common compressed tablets, chewable tablets, bubble
Rise piece, multilayer tablet, sustained release tablets, controlled release tablet, coating tablet, dispersible tablet, buccal tablet, sublingual tablet etc.；Pill includes dripping pill, dripped containing change
Ball, micropill etc..Capsule includes：Hard capsule, soft capsule, enteric capsule, Duracaps, micro-capsule etc..
Experimental example 5 prepares 6- hydroxy dye lignin injections
Exemplified by preparing medicine 6- hydroxy dyes lignin 1000ml injections of the present invention, supplementary material used is as follows：
| 6- hydroxy dye lignins | 25g |
| Polyethylene glycol400 | 200ml |
| Natrium adetate | 0.1g |
| Sodium hydrogensulfite | 1.0g |
| Glucose | 5g |
| Water for injection | Add to 1000ml |
It is made of the preparation technology of regular injection agent, every 2ml, the lignin of hydroxy dye containing 6- 50mg.This product is yellowish
The clear liquid of color.
Embodiment 6 prepares 6- hydroxy dye lignin tablets
Exemplified by preparing 1000, medicine 6- hydroxy dye lignins tablet of the present invention, supplementary material used is as follows：
| 6- hydroxy dye lignins | 50g |
| Starch | 250g |
| Starch slurry (10%) | 85g |
| Magnesium stearate | 15g |
It is made of the preparation technology of conventional tablet, every weight 0.4g, the every lignin of hydroxy dye containing 6- 50mg.
Embodiment 7 prepares 6- hydroxy dye lignin capsules
Exemplified by preparing medicine 6- hydroxy dye lignins capsule 1000 of the present invention, supplementary material used is as follows：
| 6- hydroxy dye lignins | 50g |
| Starch | 285g |
| Magnesium stearate | 15g |
It is made of the preparation technology of conventional capsule, every weight 0.35g, the every lignin of hydroxy dye containing 6- 50mg.
Embodiment 8 prepares 6- hydroxy dye lignin pills
Exemplified by preparing the ball of medicine 6- hydroxy dye lignins pill 10000 of the present invention, supplementary material used is as follows：
| 6- hydroxy dye lignins | 50g |
| Polyethylene glycol400 | 100g |
| Polyethylene glycol6000 | 350g |
(dropping preparation method) is made using the preparation technology of conventional pill, the weight 50mg per ball, per the ball lignin of hydroxy dye containing 6-
5mg。
Embodiment 9 prepares 6- hydroxy dye lignin oral administration solutions
Exemplified by preparing medicine 6- hydroxy dye lignins oral administration solution 1000 of the present invention, supplementary material used is as follows：
| 6- hydroxy dye lignins | 100g |
| Polyethylene glycol400 | 1000ml |
| Glycerine | 1000ml |
| Saccharin sodium | 20.0g |
| Sodium benzoate | 10.0g |
| Natrium adetate | 1.0g |
| Sodium hydrogensulfite | 10.0g |
| Water | Add to 10000ml |
It is made of the preparation technology of traditional oral solution, every 10ml, the every lignin of hydroxy dye containing 6- 100mg.This
Product are faint yellow clear and bright thick liquid.
Illustrate the drug effect of 6- hydroxy dye lignins below by way of pharmacodynamics test：
The 6- hydroxy dye lignins of experimental example 1 are to H2O2Induce the protective effect of PC12 cellular damages
The PC12 cells in growth period of taking the logarithm are inoculated in 96 orifice plates with 1 × 105/L, and 100 μ L are added per hole, in 37 DEG C,
5%CO224h is cultivated in incubator, is separately added into ultimate density as 0 μ g/mL, 0.01 μ g/mL, 0.1 μ g/mL, 1.0 μ g/mL
6- hydroxy dyes lignin pre-processes 24h, and except blank control group, remaining each group (including positive aqueous solubility VE control groups) is respectively
Add H of the ultimate density for 60 μm of ol/L2O2Continue after cultivating 20h, MTT (5mg/mL) 20 μ L are added per hole, continue to cultivate
4h, supernatant liquid is absorbed, DMSO100 μ L, 37 DEG C of culture 15min, after bluish violet crystal is completely dissolved, enzyme mark are added per hole
Instrument detects light absorption value of each group cell under 490nm.Cell survival rate is calculated according to preceding method, the results are shown in Table 1.
1 medicine of the present invention of table is to H2O2Induce PC12 cellular damages protective effect (N=6)
Remarks：1. compared with blank group,ΔP<0.05,ΔΔP<0.01；Compared with model group, * P<0.05, * * P<0.01②
Pass through experiment, H2O2It is 60 μm of ol/L to induce PC12 cellular damage useful effects concentration, and medicine useful effect concentration model of the present invention
Enclose for 0.01~1.0 μ g/mL.
MTT experiment shows, H2O2Group OD values substantially reduce, and cell survival rate is substantially less than Normal group (P<0.0l)；And
Various concentrations 6- hydroxy dye lignin cell survival rates compare H2O2Damage group significantly improves, and has significant difference, and related in dosage
Property, drug cell survival rate of the present invention and positive drug (water-soluble VE) control group compares, it is quite or more preferable.Test result indicates that 6-
Hydroxy dye lignin is to H2O2Induction PC12 cellular damages have significant protective effect.
The 6- hydroxy dyes lignin of experimental example 2 is to mouse normal pressure anoxia tolerance test
Mouse 48, male and female half and half, it is randomly divided into 4 groups, i.e. blank control group, positive drug control group, 6- hydroxy dyes wood
Plain heavy dose of group, small dose group, every group of mouse 12.The daily gavage of blank group gives isometric solvent, and (tragacanth is suspended
Liquid), positive drug is Nimodipine, dosage 100mgkg-1·d-1, drug bolus group of the invention, small dose group dosage
Respectively 150mgkg-1·d-1And 100mgkg-1·d-1.Gastric infusion, 7 days post processing animals of successive administration.I.e. in last
1h starts hypoxia endurance test after administration, mouse is put into closed wide-mouth bottle, and vaseline smears bottleneck, covers tightly, and records mouse
Since entering bottle to death time-to-live.
As a result show that 6- hydroxy dyes lignin can be obviously prolonged the time-to-live of mouse resist oxygen lack, relatively have with blank group aobvious
Write difference (P<0.05), it was demonstrated that 6- hydroxy dyes lignin can significantly increase body's hypoxia tolerance.It the results are shown in Table 2.
2 medicine of the present invention of table to mouse hypoxia endurance test (N=12)
| Group | Dosage | Time-to-live (min) |
| Blank control group | / | 14.23±2.26 |
| Positive drug control group | 100 | 19.56±2.59* |
| 6- hydroxy dye lignin heavy dose groups | 150 | 23.58±4.85** |
| 6- hydroxy dye lignin small dose groups | 50 | 20.12±3.17** |
Note：Compared with blank control group, * P<0.05, * * P<0.01
The 6- hydroxy dyes lignin of experimental example 3 is tested Acute cerebral ischemia in mice
Mouse 48, male and female half and half, it is randomly divided into 4 groups, i.e. blank control group, positive drug control group, 6- hydroxy dyes wood
Plain heavy dose of group, small dose group, every group of mouse 12.The daily gavage of blank group gives isometric solvent, and (tragacanth is suspended
Liquid), positive drug is Nimodipine, dosage 100mgkg-1·d-1, 6- hydroxy dye lignin heavy doses group, small dose group agent
Amount is respectively 150mgkg-1·d-1And 100mgkg-1·d-1.Gastric infusion, 7 days post processing animals of successive administration.I.e. in end
1h after secondary administration, break end rapidly from mouse ear rear portion, record mouse once pants the time to the end since broken end.
As a result show that 6- hydroxy dyes lignin can be obviously prolonged the time-to-live of Acute cerebral ischemia in mice, compared with blank group
There were significant differences (P<0.01), it was demonstrated that 6- hydroxy dyes lignin can be used for the treatment of ICVD.It the results are shown in Table 3.
3 medicine of the present invention of table to Acute cerebral ischemia in mice test (N=12)
| Group | Dosage (mg/kg) | Time-to-live (s) |
| Blank control group | / | 16.54±2.78 |
| Positive drug control group | 100 | 25.44±2.59*** |
| 6- hydroxy dye lignin heavy dose groups | 150 | 24.82±3.17*** |
| 6- hydroxy dye lignin small dose groups | 50 | 22.15±1.99** |
Note：Compared with blank control group, * * P<0.01, * * * P<0.001
The 6- hydroxy dyes lignin of experimental example 4 is tested mouse chemical hypoxic
Mouse 48, male and female half and half, it is randomly divided into 4 groups, i.e. blank control group, positive drug control group, 6- hydroxy dyes wood
Plain heavy dose of group, small dose group, every group of mouse 12.The daily gavage of blank group gives isometric solvent, and (tragacanth is suspended
Liquid), positive drug is Nimodipine, dosage 100mgkg-1·d-1, 6- hydroxy dye lignin heavy doses group, small dose group agent
Amount is respectively 150mgkg-1·d-1And 100mgkg-1·d-1.Gastric infusion, 7 days post processing animals of successive administration.I.e. in end
NaNO is injected intraperitoneally in 1h after secondary administration, each group2200mg·kg-1, immediately begin to record the mouse survival time.
As a result show that 6- hydroxy dyes lignin can be obviously prolonged the time-to-live of mouse chemical hypoxic, compared with blank group
There were significant differences (P<0.01), it was demonstrated that 6- hydroxy dyes lignin can significantly improve body's hypoxia tolerance.It the results are shown in Table 4.
4 medicine of the present invention of table to mouse chemical hypoxic test (N=12)
| Group | Dosage (mg/kg) | Time-to-live (min) |
| Blank control group | / | 10.56±1.03 |
| Positive drug control group | 100 | 12.98±2.51*** |
| 6- hydroxy dye lignin heavy dose groups | 150 | 15.12±3.12*** |
| 6- hydroxy dye lignin small dose groups | 50 | 13.05±2.27** |
Note：Compared with blank control group, * * P<0.01, * * * P<0.001
Influence of the 6- hydroxy dyes lignin of experimental example 5 to HCT116, MCF-7, A549 cell line in-vitro multiplication
Take the logarithm respectively human colon cancer cell strain HCT116, MCF-7 cell strainHJ2mm, the human lung carcinoma cell line of phase
A549, digested, dispelled with pancreatin, prepared cell suspension, microscopic count, cell concentration is adjusted, by 6 × 103Individual/hole is inoculated into
96 orifice plates, in 37 DEG C of overnight incubations.In drug-treated group add gradient dilution each compound, while set blank control group and
Belamcandin member positive drug control group, each concentration do 3 repetitions, are put into 37 DEG C, 5%CO248h, experiment knot are cultivated in incubator
4h before beam, the nutrient solution in 96 orifice plates is suctioned out, add 100 μ L PBSs and 10 μ L 5mg/mlMTT solution, 37 DEG C incubate
Educate 4h.Add 100 μ L 10%SDS solution.37 DEG C of overnight incubations.Determine OD570, calculate IC50.It the results are shown in Table 5.
Anti tumor activity in vitro of 5 medicine of the present invention of table to a variety of human cancer cells
As a result show, relative to blackberry lily aglycon, 6- hydroxy dyes lignin is to suppressing HCT116, MCF-7, A549 cell line
In-vitro multiplication shows more preferable activity, that is to say, that 6- hydroxy dyes lignin has more than blackberry lily aglycon in anti-tumor aspect
Good activity.
To sum up, 6- hydroxy dyes lignin is to H2O2Induction PC12 cellular damages have significant protective effect；It can be obviously prolonged small
The time-to-live of mouse acute cerebral ischemia, the treatment available for ICVD；Mouse chemical hypoxic can be obviously prolonged
Time-to-live, significantly improve body's hypoxia tolerance；Certain activity is shown to HCT116, MCF-7, A549 cell line.
I.e. 6- hydroxy dyes lignin has pharmacological activity, has obvious oxygen lack resistant function, can significantly strengthen the resist oxygen lack energy of body
Power, there is significant inhibitory action to cancer cell multiplication, therefore medicine of the present invention can be used for preparing treatment Cardial or cerebral vascular diseases and tumour
Medicine.
Claims (10)
1. a kind of treat cardiovascular and cerebrovascular disease and the medicine of tumour, it is characterised in that：It is using 6- hydroxy dyes lignin as activity
Composition, the preparation being prepared plus pharmaceutically acceptable auxiliary material or complementary composition.
2. medicine according to claim 1, it is characterised in that：The preparation is injection, tablet, capsule, pill
Or oral administration solution.
A kind of 3. method for preparing 6- hydroxy dye lignins, it is characterised in that：Step is as follows：
(1) compound A is dissolved in 70%~100%V/W ethanol, forms solution B；Wherein, compound A is blackberry lily aglycon, penetrated
Dry glycosides, flower of kudzuvine aglycon or contg. glucoside of pueravia flower；Ethanol and compound A envelope-bulk to weight ratio are 5:1ml/g；
(2) demethylation reagent and phase transfer catalyst are added into solution B, stirred, 5~24h, reaction are reacted at 95 DEG C~100 DEG C
Completely, reaction liquid C is obtained；Wherein, demethylation reagent and compound A envelope-bulk to weight ratio are 3:1ml/g, phase transfer catalyst is with changing
Compound A weight ratio is 0~0.01:1g/g；
(3) by reaction liquid C at 0~25 DEG C, 1~24h is placed, filtering, neutrality is washed to, obtains 6- hydroxy dye lignin crude products,
Recrystallization purification.
4. preparation method according to claim 3, it is characterised in that：In step (1), the concentration of the ethanol is 95%V/
W。
5. preparation method according to claim 3, it is characterised in that：In step (2), the demethylation reagent is hydrogen iodine
Acid, sulfuric acid, hydrochloric acid or hydrobromic acid；And/or the phase transfer catalyst be tri-n-octyl methyl ammonium chloride, tetrabutyl phosphonium bromide phosphorus or
Hexadecyltri-n-butylphosp.
6. preparation method according to claim 3, it is characterised in that：In step (2), the concentration of the demethylation reagent is
0~40%V/W.
7. preparation method according to claim 5, it is characterised in that：The phase transfer catalyst is tricaprylmethyl chlorination
Ammonium.
8. preparation method according to claim 3, it is characterised in that：In step (2), the reaction is complete to determine method
It is to utilize silica G F254Thin layer inspection, solvent are chloroform：Methanol：Formic acid 10:1:0.1.
Application of the 9.6- hydroxy dyes lignin in treatment cardiovascular and cerebrovascular disease, vascular dementia, tumour medicine is prepared.
10. application according to claim 9, it is characterised in that：The tumour is colon cancer, breast cancer or gland cancer.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113546075A (en) * | 2021-09-08 | 2021-10-26 | 四川省中医药科学院 | Application of double baicalein compound in preparation of antitumor drugs |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113546075A (en) * | 2021-09-08 | 2021-10-26 | 四川省中医药科学院 | Application of double baicalein compound in preparation of antitumor drugs |
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| CN107441079B (en) | 2021-03-26 |
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