CN107441079B - Medicine for treating cardiovascular and cerebrovascular diseases and preparation method and application thereof - Google Patents
Medicine for treating cardiovascular and cerebrovascular diseases and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a medicine for treating cardiovascular and cerebrovascular diseases, a preparation method and application thereof, belonging to the field of pharmaceutical chemistry. The medicine is a preparation prepared by taking 6-hydroxy genistein as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients. The 6-hydroxy genistein prepared by utilizing the blackberry lily aglycone, the blackberry lily glycoside, the pueraria flower aglycone and the pueraria flower glycoside has pharmacological activity, namely has obvious effects of resisting anoxia and inhibiting tumor cell proliferation, can obviously enhance the anoxia resistance of an organism and has obvious inhibition effect on cancer cell proliferation, so the 6-hydroxy genistein can be used for preparing medicaments for treating cardiovascular and cerebrovascular diseases, vascular dementia and certain tumors, and can be particularly prepared into preparations such as injection, tablets, capsules, dripping pills or oral solution and the like, so that the application range of the 6-hydroxy genistein is wider.
Description
Technical Field
The invention relates to a medicine for treating cardiovascular and cerebrovascular diseases, a preparation method and application thereof, belonging to the field of pharmaceutical chemistry.
Background
6-hydroxy genistein with molecular formula C15H10O6The chemical name is 5,6,7, 4' -tetrahydroxyisoflavone or 5,6, 7-trihydroxy-3- (4-hydroxyphenyl) -4H-1-benzopyran-4-ketone, and the structural formula is
The studies on 6-hydroxygenistein are relatively rare, and it is currently mainly considered as a bacterial metabolite, which is mainly obtained by means of separation from the bacterial metabolite. At present, only 6-hydroxy genistein with liver protecting activity and no other activity or efficacy is reported for the pharmacological activity of the genistein.
Disclosure of Invention
In order to solve the above problems, the present invention provides a method for preparing 6-hydroxygenistein and its use.
The invention discloses a medicament for treating cardiovascular and cerebrovascular diseases and tumors, which is a preparation prepared by taking 6-hydroxy genistein as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
Wherein the preparation is injection, tablet, capsule, dripping pill or oral solution.
The invention discloses a method for preparing 6-hydroxy genistein, which comprises the following steps:
(1) dissolving the compound A in 70-100% V/W ethanol to form a solution B; wherein the compound A is tectorigenin, tectoridin, pueraria flower aglycone or pueraria flower glucoside; the volume-to-weight ratio of the ethanol to the compound A is 5:1 ml/g;
(2) adding a demethylating reagent and a phase transfer catalyst into the solution B, stirring, and reacting for 5-24 hours at 95-100 ℃ completely to obtain a reaction solution C; wherein the volume weight ratio of the demethylating reagent to the compound A is 3:1ml/g, and the weight ratio of the phase transfer catalyst to the compound A is 0-0.01: 1 g/g;
(3) and (3) standing the reaction solution C for 1-24 hours at 0-25 ℃, filtering, washing with water to be neutral to obtain a crude product of 6-hydroxy genistein, and recrystallizing and purifying.
Wherein in the step (1), the concentration of the ethanol is 95% V/W.
Wherein, in the step (2), the demethylating reagent is hydroiodic acid, sulfuric acid, hydrochloric acid or hydrobromic acid; and/or the phase transfer catalyst is trioctylmethylammonium chloride, tetrabutylphosphonium bromide or hexadecyltributylphosphonium bromide.
Wherein in the step (2), the concentration of the demethylating reagent is 0-40% V/W.
Preferably, the phase transfer catalyst is trioctylmethylammonium chloride.
Wherein, in the step (2), the method for determining the completion of the reaction is to use silica gel GF254Thin layer inspection, developing agent chloroform: methanol: formic acid 10:1: 0.1.
The invention discloses an application of 6-hydroxy genistein in preparing medicine for curing angiocardiopathy, cerebrovascular disease, vascular dementia and tumor.
Wherein the tumor is colon cancer, breast cancer or adenocarcinoma.
The invention achieves the following beneficial effects: the 6-hydroxy genistein prepared by utilizing the blackberry lily aglycone, the blackberry lily glycoside, the pueraria flower aglycone and the pueraria flower glycoside has pharmacological activity, namely has obvious anti-hypoxia effect, can obviously enhance the hypoxia-resistant capability of an organism, has obvious inhibition effect on cancer cell proliferation, and can be used for preparing medicines for treating cardiovascular and cerebrovascular diseases and tumors.
The present invention is described in further detail with reference to the following embodiments, but the present invention is not limited thereto, and various other modifications, substitutions and alterations can be made without departing from the basic technical idea of the present invention based on the above-mentioned contents of the present invention and common technical knowledge and conventional means in the art.
Drawings
FIG. 1 is an IR diagram of 6-hydroxygenistein;
FIG. 2 shows the preparation of 6-hydroxygenistein1H NMR chart;
FIG. 3 shows the preparation of 6-hydroxygenistein13A CNMR map;
FIG. 4 shows the MS diagram of 6-hydroxygenistein.
Detailed Description
EXAMPLE 1 preparation of 6-hydroxygenistein from Belamcanda chinensis aglycone
Adding blackberry lily aglycone into a reaction kettle, adding 5 times (ml/g) of 95% ethanol (V/W), stirring by a stirrer, heating and refluxing, adding 3 times (ml/g) of hydriodic acid (the content is more than or equal to 45% V/W) after the blackberry lily aglycone is completely dissolved, stirring, heating and refluxing for 5-24 hours, and using silica gel GF254Checking a thin layer, and determining the end point of the reaction (developing agent is chloroform: methanol: formic acid 10:1: 0.1). Discharging the reaction solution, standing overnight at room temperature to precipitate a light yellow needle crystal, filtering, and washing with water to neutrality to obtain a crude product of 6-hydroxy genistein; the refined 6-hydroxy genistein is obtained by recrystallization, and the yield is 85 percent.
The product obtained in the embodiment is light yellow needle-shaped crystal; no odor and no taste. Soluble in methanol and ethanol and almost insoluble in water. The melting point is 245-250 ℃; UV λ max274 nm; IR, IR,1H NMR、13The CNMR and MS are shown in figures 1-4.
The chemical reaction equation is as follows:
example 2 preparation of 6-Hydroxygenistein from Belamcandin
Adding belamcandin into a reaction kettle, adding 5 times (ml/g) of 95% ethanol (V/W), stirring by a stirrer, heating and refluxing, adding 3 times (ml/g) of hydroiodic acid (the content is more than or equal to 45%) (V/W) when the blackberry lily glycoside is uniformly pasty, stirring, and heating and refluxing for 5 to c24 hours, using silica gel GF254Checking by thin layer chromatography to determine reaction end point (developing agent is chloroform: methanol: formic acid 10:1:0.1), discharging reaction solution, standing overnight at room temperature, precipitating off-white precipitate, filtering, and washing with water to neutrality to obtain crude 6-hydroxy genistein; the refined 6-hydroxy genistein is obtained by recrystallization, and the yield is 70 percent.
The chemical reaction equation is as follows:
example 3 preparation of 6-hydroxygenistein from Pueraria lobata aglycone
Adding pueraria lobata aglycone into a reaction kettle, adding 5 times (ml/g) of 95% ethanol (V/W), stirring by using a stirrer, heating and refluxing, adding 3 times (ml/g) of hydriodic acid (the content is more than or equal to 45%) (V/W) after the pueraria lobata aglycone is completely dissolved, stirring, heating and refluxing for 5-24 hours, and using silica gel GF (glass fiber)254Checking by thin layer chromatography to determine reaction end point (developing agent is chloroform: methanol: formic acid 10:1:0.1), discharging reaction solution, standing overnight at room temperature, precipitating light yellow needle crystal, filtering, washing with water to neutrality to obtain 6-hydroxy genistein crude product; the refined 6-hydroxy genistein is obtained by recrystallization, and the yield is 80 percent.
The chemical reaction equation is as follows:
example 4 preparation of 6-Hydroxygenistein from Kudzuvine
Adding pueraria flower glucoside into a reaction kettle, adding 5 times (ml/g) of 95% ethanol (V/W), stirring by using a stirrer, heating and refluxing, adding 3 times (ml/g) of hydriodic acid (the content is more than or equal to 45%) (V/W) when the pueraria flower glucoside is uniformly pasty, stirring, heating and refluxing for 5-24 hours, and using silica gel GF254Checking by thin layer chromatography to determine reaction end point (developing agent chloroform: methanol: formic acid 10:1:0.1), discharging reaction solution, standing at room temperature overnight to precipitate light yellow precipitate, filtering, and adding waterWashing to be neutral to obtain a crude product of 6-hydroxy genistein; the refined 6-hydroxy genistein was obtained by recrystallization with a yield of 75%.
The chemical reaction equation is as follows:
the medicine of the invention is added with pharmaceutically acceptable carriers to prepare different medicinal preparations, such as injection, freeze-dried powder injection, tablets, powder, granules, capsules, pills, oral solution and the like, wherein the tablets comprise: common compressed tablets, chewable tablets, effervescent tablets, multilayer tablets, sustained release tablets, controlled release tablets, coated tablets, dispersible tablets, buccal tablets, sublingual tablets and the like; the pill includes dripping pill, buccal dripping pill, pellet, etc. The capsule comprises: hard capsule, soft capsule, enteric capsule, sustained release capsule, microcapsule, etc.
Experimental example 5 preparation of 6-hydroxy genistein injection
Taking 1000ml of injection for preparing the medicine 6-hydroxy genistein of the invention as an example, the raw and auxiliary materials are as follows:
6-hydroxy genistein | 25g |
Polyethylene glycol400 | 200ml |
Edetate disodium | 0.1g |
Sodium bisulfite | 1.0g |
Glucose | 5g |
Water for injection | Adding to 1000ml |
Is prepared by conventional injection preparation process, and each injection contains 2ml of 6-hydroxy genistein 50 mg. The product is a light yellow clear liquid.
EXAMPLE 6 preparation of 6-Hydroxygenistein tablets
Taking 1000 tablets of the 6-hydroxy genistein tablet of the invention as an example, the raw and auxiliary materials are as follows:
6-hydroxy genistein | 50g |
Starch | 250g |
Starch slurry (10%) | 85g |
Magnesium stearate | 15g |
The tablet is prepared by conventional tablet preparation process, and each tablet is 0.4g and contains 50mg of 6-hydroxy genistein.
EXAMPLE 7 preparation of 6-Hydroxygenistein capsules
Taking 1000 capsules of 6-hydroxy genistein capsule as an example for preparing the medicine of the invention, the raw and auxiliary materials are as follows:
6-hydroxy genistein | 50g |
Starch | 285g |
Magnesium stearate | 15g |
The preparation method is characterized by adopting a preparation process of a conventional capsule, wherein each capsule is 0.35g in weight and contains 50mg of 6-hydroxygenistein.
EXAMPLE 8 preparation of drop pills of 6-hydroxygenistein
Taking 10000 pills as an example for preparing the 6-hydroxy genistein dripping pill of the invention, the used raw and auxiliary materials are as follows:
6-hydroxy genistein | 50g |
Polyethylene glycol400 | 100g |
Polyethylene glycol6000 | 350g |
Is prepared by adopting the preparation process of a conventional dripping pill (dripping method), wherein each pill weighs 50mg and contains 5mg of 6-hydroxy genistein.
EXAMPLE 9 preparation of 6-Hydroxygenistein oral solution
Taking 1000 pieces of 6-hydroxy genistein oral solution for preparing the medicine of the invention as an example, the raw and auxiliary materials are as follows:
6-hydroxy genistein | 100g |
Polyethylene glycol400 | 1000ml |
Glycerol | 1000ml |
Saccharin sodium salt | 20.0g |
Sodium benzoate | 10.0g |
Edetate disodium | 1.0g |
Sodium bisulfite | 10.0g |
Water (W) | Adding to 10000ml |
Is prepared by conventional oral solution preparation process, each 10ml contains 6-hydroxy genistein 100 mg. The product is a light yellow clear viscous liquid.
The pharmacodynamic effect of 6-hydroxygenistein is illustrated by the following pharmacodynamic tests:
EXAMPLE 16 hydroxy genistein Pair H2O2Protective effect of inducing PC12 cell damage
PC12 cells in logarithmic growth phase were seeded at 1X 105/L in 96-well plates, 100. mu.L per well, at 37 ℃ with 5% CO2Culturing in incubator for 24H, adding 6-hydroxy genistein with final concentration of 0 μ g/mL, 0.01 μ g/mL, 0.1 μ g/mL, 1.0 μ g/mL respectively for pretreatment for 24H, and adding H with final concentration of 60 μmol/L for each group (including positive liquid medicine soluble VE control group) except blank control group2O2And (3) continuing to culture for 20h, adding 20 mu L of MTT (5mg/mL) into each hole, continuing to culture for 4h, absorbing and removing the upper layer liquid, adding 100 mu L of DMSO into each hole, culturing for 15min at 37 ℃, and detecting the light absorption value of each group of cells at 490nm by using an enzyme-labeling instrument after the purple crystals are completely dissolved. Cell viability was calculated as before and the results are shown in table 1.
Remarking: comparing the first step with the blank group,ΔP<0.05,ΔΔP<0.01; comparison with model group<0.05,**P<0.01 ② pass test, H2O2The concentration of the effective action for inducing the PC12 cell damage is 60 mu mol/L, and the concentration range of the effective action of the medicine is 0.01-1.0 mu g/mL.
MTT experiment shows that H2O2The OD value of the group is obviously reduced, and the cell survival rate is obviously lower than that of a normal control group (P)<0.0 l); while the cell survival rate ratio H of 6-hydroxy genistein with different concentrations2O2The damage groups are obviously improved, have obvious difference and are in dose correlation, and the cell survival rate and the positive drug (water-soluble V) of the drug areE) The control group was comparable or better. The experimental result shows that 6-hydroxy genistein is used for H2O2The induced PC12 cell injury has obvious protective effect.
Experimental example 26-Hydroxygenistein atmospheric hypoxia tolerance test for mice
The mice are divided into 4 groups, namely a blank control group, a positive drug control group, a 6-hydroxy genistein high-dose group and a low-dose group, wherein the number of the mice in each group is 12. The blank group is administered with equal volume of solvent (tragacanth suspension) by intragastric administration every day, and the positive drug is nimodipine with dosage of 100 mg/kg-1·d-1The dosage of the drug large dose group and the dosage of the drug small dose group are respectively 150 mg/kg-1·d-1And 100mg kg-1·d-1. Gavage administration, treatment of animals after 7 consecutive days of administration. The hypoxia tolerance test is started 1h after the last administration, the mouse is placed into a closed wide-mouth bottle, vaseline is smeared on the mouth of the bottle, the bottle is tightly covered, and the survival time of the mouse from the bottle entering to the death of the mouse is recorded.
The result shows that the 6-hydroxy genistein can obviously prolong the survival time of mice for resisting oxygen deficiency, and has obvious difference (P is less than 0.05) compared with a blank group, thereby proving that the 6-hydroxy genistein can obviously enhance the oxygen deficiency resistance of organisms. The results are shown in Table 2.
Group of | Dosage form | Survival time (min) |
Blank control group | / | 14.23±2.26 |
Positive |
100 | 19.56±2.59* |
6-hydroxygenistein bolus | 150 | 23.58±4.85** |
6-hydroxygenistein |
50 | 20.12±3.17** |
Note: p <0.05, P <0.01, compared to the blank control group
Experimental example 36-Hydroxygenistein test for acute cerebral ischemia in mice
The mice are divided into 4 groups, namely a blank control group, a positive drug control group, a 6-hydroxy genistein high-dose group and a low-dose group, wherein the number of the mice in each group is 12. The blank group is administered with equal volume of solvent (tragacanth suspension) by intragastric administration every day, and the positive drug is nimodipine with dosage of 100 mg/kg-1·d-1The dosages of the 6-hydroxy genistein large dose group and the small dose group are respectively 150 mg.kg-1·d-1And 100mg kg-1·d-1. Gavage administration, treatment of animals after 7 consecutive days of administration. That is, 1h after the last administration, the mouse rapidly broke its head from the back of the ear, and the time from the beginning of the head break to the last gasping of the mouse was recorded.
The result shows that the 6-hydroxy genistein can obviously prolong the survival time of acute cerebral ischemia of mice, has obvious difference (P is less than 0.01) compared with a blank group, and proves that the 6-hydroxy genistein can be used for treating ischemic cerebrovascular diseases. The results are shown in Table 3.
Group of | Dosage (mg/kg) | Survival time(s) |
Blank control group | / | 16.54±2.78 |
Positive |
100 | 25.44±2.59*** |
6-hydroxygenistein bolus | 150 | 24.82±3.17*** |
6-hydroxygenistein |
50 | 22.15±1.99** |
Note: p <0.01, P <0.001, compared to the blank control group
Experimental example 46-chemical hypoxia test of mouse by hydroxy genistein
The mice are divided into 4 groups, namely a blank control group, a positive drug control group, a 6-hydroxy genistein high-dose group and a low-dose group, wherein the number of the mice in each group is 12. The blank group is administered with equal volume of solvent (tragacanth suspension) by intragastric administration every day, and the positive drug is nimodipine with dosage of 100 mg/kg-1·d-1The dosages of the 6-hydroxy genistein large dose group and the small dose group are respectively 150 mg.kg-1·d-1And 100mg kg-1·d-1. Gavage administration, treatment of animals after 7 consecutive days of administration. That is, NaNO was intraperitoneally injected 1h after the last administration2200mg·kg-1Immediately, the recording of mouse survival time was started.
The result shows that the 6-hydroxy genistein can obviously prolong the survival time of the mouse with chemical hypoxia, has obvious difference (P is less than 0.01) compared with the blank group, and proves that the 6-hydroxy genistein can obviously improve the hypoxia tolerance of the body. The results are shown in Table 4.
Group of | Dosage (mg/kg) | Survival time (min) |
Blank control group | / | 10.56±1.03 |
Positive |
100 | 12.98±2.51*** |
6-hydroxygenistein bolus | 150 | 15.12±3.12*** |
6-hydroxygenistein |
50 | 13.05±2.27** |
Note: p <0.01, P <0.001, compared to the blank control group
Experimental example 56 Effect of hydroxy genistein on in vitro proliferation of HCT116, MCF-7, A549 cell lines
Respectively taking human colon cancer cell strain HCT116, human breast cancer cell strain MCF-7 and human lung cancer cell strain A549 in log phase, digesting with pancreatin, blowing, preparing cell suspension, counting microscopically, adjusting cell concentration, and processing according to 6 × 103One/well was inoculated into a 96-well plate and incubated overnight at 37 ℃. Adding each compound diluted in gradient into the medicine treatment group, setting blank control group and blackberry lily aglycone positive medicine control group at the same time, repeating each concentration for 3 times, adding 5% CO at 37 deg.C2The culture was carried out in an incubator for 48 hours, 4 hours before the end of the test, the culture medium in a 96-well plate was aspirated, 100. mu.L of PBS buffer and 10. mu.L of 5mg/ml MTT solution were added, and the plate was incubated at 37 ℃ for 4 hours. Add 100. mu.L of 10% SDS solution. Incubate overnight at 37 ℃. Determination of OD570Computing IC50. The results are shown in Table 5.
TABLE 5 in vitro antitumor Activity of the inventive drugs against various human cancer cells
The results show that compared with belamcanda aglycone, the 6-hydroxy genistein has better activity for inhibiting the in vitro proliferation of HCT116, MCF-7 and A549 cell strains, namely, the 6-hydroxy genistein has better activity in the aspect of tumor resistance than the belamcanda aglycone.
To sum up, 6-hydroxygenistein pairs H2O2The induced PC12 cell injury has obvious protective effect; can obviously prolong the survival time of the acute cerebral ischemia of the mouse and can be used for treating ischemic cerebrovascular diseases; can obviously prolong the survival time of the chemical hypoxia of the mice and obviously improve the hypoxia tolerance of organisms; shows certain activity to HCT116, MCF-7 and A549 cell strains. The 6-hydroxy genistein has pharmacological activity, obvious anti-hypoxia effect, can obviously enhance the hypoxia-resistant capability of organisms and has obvious inhibition effect on cancer cell proliferation, so that the medicine can be used for preparing medicines for treating cardiovascular and cerebrovascular diseases and tumors.
Claims (4)
1. A method for preparing 6-hydroxy genistein, which is characterized in that: the method comprises the following steps:
(1) dissolving the compound A in 95% V/W ethanol to form a solution B; wherein the compound A is tectorigenin, tectoridin, pueraria flower aglycone or pueraria flower glucoside; the volume-to-weight ratio of the ethanol to the compound A is 5:1 ml/g;
(2) adding a demethylating reagent and a phase transfer catalyst into the solution B, stirring, reacting for 5-24 hours at 95-100 ℃, and reacting completely to obtain a reaction solution C; wherein the volume weight ratio of the demethylating reagent to the compound A is 3:1ml/g, and the weight ratio of the phase transfer catalyst to the compound A is 0-0.01: 1 g/g;
(3) standing the reaction solution C at 0-25 ℃ for 1-24 h, filtering, washing with water to be neutral to obtain a crude product of 6-hydroxy genistein, and recrystallizing and purifying;
the demethylating reagent is hydroiodic acid; the concentration of the demethylating agent is less than or equal to 40% V/W.
2. The method of claim 1, wherein: the phase transfer catalyst is trioctylmethylammonium chloride, tetrabutylphosphonium bromide or hexadecyltributylphosphonium bromide.
3. The method of claim 2, wherein: the phase transfer catalyst is trioctylmethylammonium chloride.
4. The method of claim 1, wherein: in the step (2), the method for determining the completion of the reaction is to use silica gel GF254Thin layer inspection, developing agent chloroform: methanol: formic acid 10:1: 0.1.
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三羟异黄酮对血管性痴呆大鼠学习记忆及脑内氧化损伤的影响;李俊垚 等;《实用医学杂志》;20071231;第23卷(第18期);2835-2837 * |
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