CN112125937A - Macrocyclic phenolic glycoside compound and preparation method and application thereof - Google Patents
Macrocyclic phenolic glycoside compound and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a macrocyclic phenolic glycoside compound and a preparation method and application thereof, wherein the macrocyclic phenolic glycoside compound is a compound shown as a formula I and pharmaceutically acceptable salt or hydrate thereof. The invention also discloses a preparation method and application of the macrocyclic phenolic glycoside compound. The macrocyclic phenolic glycoside compound can be applied to the preparation of medicaments for preventing and treating intravascular embolism and thrombotic diseases, has good drug effect and small toxic and side effect, and also provides a method for extracting the macrocyclic phenolic glycoside compound from sorghum roots and a preparation method of derivatives thereof, which are used for intravascular embolism and intravascular thrombosisThe application of the suppository for treating the diseases provides a new choice, and widens the application of the sorghum roots.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a macrocyclic phenolic glycoside compound and a preparation method and application thereof.
Background
Thrombotic diseases such as cardiovascular and cerebrovascular embolism caused by blood coagulation factors become common diseases seriously endangering public health. The antithrombotic drugs currently applied to clinical treatment are mainly heparin and coumarin drugs, but have the side effects of inducing thrombocythemia and the like. Therefore, the development of new antithrombotic agents that are more effective and safer is still of great importance. The blood circulation promoting and stasis removing traditional Chinese medicine has good antithrombotic activity and is widely applied to clinic. Good antithrombotic substances are screened from the traditional Chinese medicines for medicine research and development, and the traditional Chinese medicines have attracted general attention at home and abroad. Many Chinese herbal compounds, effective components and monomers are proved to have better antithrombotic effect, and the medicine has rich medicine sources, low price and small toxic and side effects, thus being an antithrombotic medicine with great development potential.
Sorghum root is the root of Sorghum vulgare per, a Sorghum plant in the family of poaceae, and is also a traditional Chinese herbal medicine. The literature is documented in traditional Chinese medicine compendium (Ming Dynasty, Li Shizhen, compendium of materia Medica [ M ]. Beijing: China International broadcasting Press, 1994: 1626), "traditional Chinese medicine dictionary (Nanjing university of traditional Chinese medicine, traditional Chinese medicine dictionary, lower book [ M ]. Shanghai: Shanghai science and technology Press, 2006: 2685)," Chinese materia Medica (national institute of traditional Chinese medicine, China materia Medica, ed committee of editions of China, Shanghai: Shanghai science and technology Press, 1999: 426), and so on. It has sweet, mild and nontoxic nature and taste; can relieve asthma, promote urination, and stop bleeding; treating cough, asthma, stomach qi pain, metrorrhagia, postpartum hemorrhage, etc. But there have been few studies on the antithrombotic use of sorghum roots.
Macrocyclic phenolic glycosides were first isolated from plants in 1992 and consist of a 22-ring dimeric dilactone backbone. Such compounds are isolated primarily from Nelumbo (Song C, Xu R. Chin Chem Lett,1992), Nelumbo nucifera (Shi S P, Dong C X, Jiang D, et al. Helv Chim Acta,2006) and caulis Akebiae (Sakuran K M, Shigihar A, Inoue T. Chem Pharm Bull,1992), among others. The macrocyclic phenolic glycoside compounds and the biological activities thereof are reported to be few, and the macrocyclic phenolic glycoside compounds have antioxidant activity on renal proximal tubular (HK-2) cells (Dian P, Xiao L L, LINJ, et al. nat Prod Res, 2019). However, no description is given of the antithrombotic activity of macrocyclic phenolic glycosides.
In conclusion, the heparin and coumarin antithrombotic drugs have great toxic and side effects, so that the research and development of novel antithrombotic drugs which are more effective and safer are of great significance. Currently, there are few studies on the antithrombotic use of sorghum roots. No mention is made of the antithrombotic activity of macrocyclic phenolic glycosides.
Disclosure of Invention
The invention aims to provide a macrocyclic phenolic glycoside compound, and a preparation method and application thereof. The macrocyclic phenolic glycoside compound can be applied to the preparation of medicines for preventing and treating thrombotic diseases, has good drug effect and small toxic and side effects, and also provides a method for extracting the macrocyclic phenolic glycoside compound from sorghum roots and a preparation method of derivatives thereof, thereby providing a new choice for medicines for thrombotic diseases and widening the application of the sorghum roots.
The technical scheme of the invention is as follows: macrocyclic phenolic glycoside compounds characterized by: is a compound shown as the following formula I and pharmaceutically acceptable salt or hydrate thereof,
wherein R is1/R2Is H, -OCH3；R3/R4Is H, -CH3；R1And R2Identical or different, R3And R4The same or different.
Among the macrocyclic phenolic glycoside compounds, the compounds represented by the following formula I-1 and pharmaceutically acceptable salts or hydrates thereof are mentioned.
In the macrocyclic phenolic glycoside compound, the compound of the formula I-1 is obtained by separating sorghum root, wherein the sorghum root is the root of sorghum saccharum rubrum glutinous sorghum of a sorghum variety for wine planted by Maotai wine, Inc. of Guizhou province.
The preparation method of the macrocyclic phenolic glycoside compound, R1、R2is-OCH3Said R is3、R4The synthesis is carried out according to the following synthetic route,
the preparation method of the macrocyclic phenolic glycoside compound (I-1) comprises the following steps,
a. taking the sorghum roots after the sorghum seeds are harvested, cleaning, drying, and mechanically crushing to obtain coarse sorghum root powder, namely A product;
b. soaking product A in 8-12 times of deionized water for 16-32 hr, decocting at 80-100 deg.C for 1-3 times (each time for 1-3 hr), mixing filtrates, and concentrating to relative density of 1.0-1.4 to obtain product B;
c. adding appropriate amount of 95% ethanol into product B until the ethanol content reaches 55% -65%, standing, collecting supernatant, filtering to remove precipitate, recovering filtrate under reduced pressure, concentrating to obtain extract, and vacuum drying to obtain WEAE (product C);
d. performing MCI GEL GEL column chromatography on the product C, performing gradient elution by using 0-95% ethanol solution, collecting 30% of elution parts, performing gradient elution by using 200-mesh and 300-mesh silica GEL column chromatography, performing gradient elution by using ethyl acetate-methanol at a ratio of 20:1-3:1, and collecting eluent by bottle separation; spotting each bottle of eluent through a thin-layer plate, developing with ethyl acetate-methanol at a ratio of 1:1, taking an elution section with an Rf value of 0.3-0.5, performing silica gel column chromatography, performing gradient elution with ethyl acetate-methanol at a ratio of 15:1-1:1, taking an elution part at a ratio of 5:1, recovering a solvent, concentrating and drying to obtain the macrocyclic phenolic glycoside compound sorgholide A.
In the preparation method of the macrocyclic phenolic glycoside compound (I-1), the step d is to perform MCI GEL GEL column chromatography on the product C, perform gradient elution by using 0%, 30%, 60% and 95% ethanol solution, collect 30% elution parts, perform chromatographic separation by using 200-mesh and 300-mesh silica GEL column, perform gradient elution by using ethyl acetate-methanol of 20:1, 15:1, 10:1, 5:1 and 3:1 in sequence, and collect 1 bottle of eluent per 100 mL; spotting each bottle of eluent through a thin-layer plate, developing with ethyl acetate-methanol at a ratio of 1:1, taking an elution section with an Rf value of 0.3-0.5, performing silica gel column chromatography, performing gradient elution with ethyl acetate-methanol at a ratio of 15:1, 10:1, 5:1 and 1:1 in sequence, recovering a solvent from an elution part at a ratio of 5:1, concentrating and drying to obtain the macrocyclic phenolic glycoside compound sorgholide A (I-1).
The application of the macrocyclic phenolic glycoside compound in preparing the medicines for preventing and treating thrombotic diseases.
In the application of the macrocyclic phenolic glycoside compound in preparing the medicine for preventing and treating thrombotic diseases, the macrocyclic phenolic glycoside compound is used in a dosage of 3-6 mug/kg of body weight per day.
In the application of the macrocyclic phenolic glycoside compound in preparing the medicines for preventing and treating thrombotic diseases, the macrocyclic phenolic glycoside compound is used alone or in the form of a pharmaceutical composition, and the pharmaceutical composition contains 0.1-99% of the macrocyclic phenolic glycoside compound, and the balance is a medicinal carrier or excipient.
In the application of the macrocyclic phenolic glycoside compound in preparing the medicines for preventing and treating thrombotic diseases, the medicinal carrier or excipient is one or more of solid diluent, semisolid diluent, liquid diluent, filler and other medicinal auxiliary agents.
In the application of the macrocyclic phenolic glycoside compound in preparing the medicines for preventing and treating thrombotic diseases, the dosage form of the pharmaceutical composition is clinically acceptable injection, suspension, emulsion, solution, syrup, tablet, capsule, granule, spray and aerosol.
In the application of the macrocyclic phenolic glycoside compound in preparing the medicament for preventing and treating thrombotic diseases, the administration route of the pharmaceutical composition is intravenous injection, intravenous drip, intramuscular injection, intraperitoneal injection, subcutaneous injection oral administration, sublingual administration or mucosal dialysis.
Compared with the prior art, the macrocyclic phenolic glycoside compound provided by the invention can be applied to preparation of medicines for preventing and treating thrombotic diseases, and has the advantages of good drug effect and small toxic and side effects. The invention also provides a method for extracting the macrocyclic phenolic glycoside compound from sorghum roots and a preparation method of the derivative thereof. The macrocyclic phenolic glycoside compound in the sorghum root is firstly separated from the sorghum root, is a dimeric dilactone phenolic glycoside which is formed by reverse polymerization of p-hydroxyphenylacetate glucoside and has 24 rings, and is a new compound. The invention provides a new choice for medicines for treating thrombotic diseases such as stroke and the like, and widens the application of sorghum roots.
Drawings
FIG. 1 is a HR-ESI-MS spectrum of sorgholide A (I-1);
FIG. 2 is a schematic representation of sorgholide A (I-1)1H-NMR spectrum;
FIG. 3 is a graph of the effect of sorgholide A (I-1) and its derivatives I-2 on adenosine diphosphate (AD P) -induced platelet aggregation;
FIG. 4 is a graph of the effect of sorgholide A (I-1) and its derivative I-2 on collagen-induced platelet aggregation;
FIG. 5 shows the effect of sorgholide A (I-1) and its derivative I-2 on thrombin-induced platelet aggregation.
Detailed Description
The invention is further illustrated by the following figures and examples, which are not to be construed as limiting the invention.
Example 1. Macrocyclic phenolic glycoside compounds
1. Is a compound shown as the following formula I and pharmaceutically acceptable salt or hydrate thereof,
wherein R is1/R2Is H, -OCH3；R3/R4Is H, -CH3；R1And R2Identical or different, R3And R4The same or different.
Preferably, R1＝R2＝-OCH3、R3＝R4＝H。
2. Is a compound shown as a formula I-1 and pharmaceutically acceptable salt or hydrate thereof,
example 2. Process for preparing macrocyclic phenolic glycoside compounds
1. The macrocyclic phenolic glycoside compound sorgholideA (I-1) is obtained by separating roots of a wine sorghum variety red tassel glutinous sorghum planted in catalpa tungensis area by Guizhou Maotai wine, Inc., and specifically comprises the following steps:
main instrument
Test materials and reagents
The preparation method comprises the following steps: taking 25kg of coarse powder of sorghum red tassel seed glutinous sorghum root of a sorghum variety planted by Guizhou Maotai liquor Co., Ltd, adding 10 times of deionized water, soaking for 24h, decocting for 2 times, filtering for 2h each time, combining filtrates, concentrating to a relative density of 1.2, adding ethanol until the final concentration of the ethanol reaches 60%, and filtering to remove precipitates; recovering solvent under reduced pressure, and vacuum drying to obtain 2.1kg of supernatant (WEAE) after water extraction and ethanol precipitation. Subjecting the supernatant obtained by water extraction and alcohol precipitation to MCI G EL gel column chromatography, eluting with 0-90% (such as 0%, 30%, 60%, 95% ethanol solution) ethanol solution, collecting 30% eluate, separating with 200-300 mesh silica gel column chromatography, gradient eluting with eluent having a volume ratio of ethyl acetate to methanol of 20:1-3:1 (such as 20:1, 15:1, 10:1, 5:1, 3:1), and collecting with 1 bottle per 100mL eluate; spotting each bottle of eluent by a thin-layer plate, developing by ethyl acetate-methanol with the volume ratio of 1:1, taking an elution section with the Rf value of 0.3-0.5, performing silica gel column chromatography, performing gradient elution by ethyl acetate-methanol with the volume ratio of 15:1-1:1 (volume ratio) (such as: 15:1, 10:1, 5:1 and 1:1), taking the elution part with the volume ratio of 5:1, recovering the solvent, concentrating and drying to obtain the macrocyclic phenolic glycoside compound sorgholide A.
Structural identification
EI. ESI, one-dimensional and two-dimensional nuclear magnetic resonance spectra were determined by the center for quality evaluation and analysis in the key laboratory of chemical products of the national academy of sciences of China, Guizhou province.
Is white amorphous powder; HR-ESI-MS (see FIG. 1) m/z615.1673 (calculated 615.1684) combined with 1D-NMR data (Table 1) to determine the formula C28H32O14The unsaturation degree was 13. IR (Potassium bromide tablet) showed the presence of ester-containing carbonyl (1731 cm)-1) Benzene ring (1612 cm)-1、1508cm-1) And the like. In that1In the H-NMR spectrum (see FIG. 2), 1 group of 1, 4-disubstituted benzene ring signals which are more significant in the relatively low field regionH7.27(d, J ═ 8.6Hz, 2H, H-2, H-6), 6.93(d, J ═ 8.6Hz, 2H, H-3, H-5), 1 sugar end group proton signal 4.70(d, J ═ 7.6Hz, 1H, H-1');13the C-NMR spectrum showed a signal containing 14 carbons: 1 ester carbonyl group [ alpha ], [ alphaC171.0(C-8)]1 para-substituted benzene ring [ alpha ], [ beta ], [ alphaC156.3(C-4)，130.0(C-2，C-6)，128.0(C-1)，116.1(C-3，C-5)]1 group of glucose residuesC100.7(C-1')，76.4(C-3')74.7(C-5')，73.4(C-2')，70.6(C-4')，64.8(C-6')]And 1 methylene signal [ 2 ]C40.2(C-7)](ii) a Through literature search, the NMR data of the compound is found to have higher similarity with the compound Schoenopolide B reported in the literature, except that the compound has 1 more methylene signal. In HMBC spectra, H-2/6(H7.27) with C-1(C128.0)、C-3/5(C116.1)、C-4(C156.3) and C-7(C40.2) related, H-3/5(H6.93) with C-1 (C: (1:)C128.0)、C-2/6(C130.0)、C-4(C156.3) related, H-7(H3.63) and C-8(C171.0)、C-1(C128.0) and C-2/6 (C-2/6: (C)C130.0), indicating the presence of a structural fragment of p-hydroxyphenylacetic acid. Terminal proton signal of glucose H-1' (II)H4.70) and C-4(C156.3) related suggested that the glucose residue is attached to the C-4 phenyl ring. H-6' ()H4.46, 3.94) and C-8(C171.0) description of the C-6' hydroxyl group of glucose with p-hydroxyphenylacetic acidThe lactone was formed, and the HR-ESI-MS data combined suggested that the compound was a dimer formed by reverse polymerization of the glucoside fragment of p-hydroxy-phenylacetate. In addition, β -D-glucopyranosy is inferred from a glucose end group proton coupling constant of 4.70(D, J ═ 7.6Hz, 1H). Thus, the compound was identified as 4- [ (6' -O-. beta. -D-glucopyra nosy) oxy)]The hydroxyphenylacrylic acid cyclic dimer ester r is named as Sorgholide A.
TABLE 1 of Sorgholide A (600/150MHz) and the analog Schoenopolide B (400/100MHz)1H and13C-N MR data (DMSO-d)6)
Ref. is an analogue of Schoenopolide B
2. Process for the preparation of macrocyclic phenolic compounds, said R1、R2is-OCH3，R3、R4Is H (namely the macrocyclic phenolic compound I-2), and the specific synthetic route is shown as follows:
example 3. Pharmacodynamic test of macrocyclic phenolic glycoside compound sorgholide A (I-1) and derivative I-2 thereof for anticoagulation effect
1. Preparation of sample solution
Precisely weighing a macrocyclic phenolic glycoside compound sorgholide A (I-1) and a derivative I-2, D MSO thereof, completely dissolving the macrocyclic phenolic glycoside compound sorgholide A and the derivative I-2, D MSO by ultrasonic, and diluting the macrocyclic phenolic glycoside compound sorgholide A and the derivative I-2, D MSO into a test sample of a 1% DMSO solution with high concentration (200 mu M), medium concentration (100 mu M) and low concentration (50 mu M). Using 1% DMOS O as blank control, sealing and storing at 4 deg.C for use.
2. Preparation of platelet samples
Collecting male New Zealand white rabbit, taking blood with 20mL syringe, anticoagulating with sodium citrate (3.8%) and blood at ratio of 1:9, and quickly collecting blood sample at 1500 r.min-1Centrifuging for 10min to obtain upper layer Platelet Rich Plasma (PRP), and the rest 3000r min-1Centrifuging for 10min, and collecting upper layer Platelet Poor Plasma (PPP).
3. Effect of macrocyclic phenolic glycoside Compound sorgholide A (I-1) and its derivative I-2 on Adenosine Diphosphate (ADP) -induced platelet aggregation
0.6408g of ADP were accurately weighed out and dissolved in 5mL of physiological saline at a concentration of 30-2And M, subpackaging, freezing and storing in a refrigerator at-20 ℃, and diluting to the required concentration when in use. Platelet-rich plasma (PRP) was collected, and 270. mu.L of each of the collected PRP was placed in a turbidimetric cup. Each tube of PRP was added with 30. mu.L each of high (200. mu.M), medium (100. mu.M), and low (50. mu.M) doses of the macrocyclic phenolic glycoside compound sorgholide A (I-1) and its derivative I-2, incubated for 5min, added with 5. mu.L ADP at a concentration of 300. mu.M, and the maximum aggregation rate of each group of PRP was measured within 5 min. The effect of sorgholide A (I-1) and its derivative I-2 on Adenosine Diphosphate (ADP) -induced platelet aggregation is shown in FIG. 3.
4. Effect of macrocyclic phenolic glycoside Compound sorgholide A (I-1) and its derivative I-2 on collagen-induced platelet aggregation
Preparing collagen into 500 μ L/mL with diluent, diluting twice, packaging, and storing at 4 deg.C. And (3) investigating the influence of samples with different concentrations on collagen-induced platelet aggregation. PRP was collected, and 270. mu.L of each PRP was placed in a turbidimetric cup. Each PRP tube was added with 30. mu.L each of the macrocyclic phenolic glycoside compound sorgho lideA sample (I-1) and its derivative I-2 at high (200. mu.M), medium (100. mu.M) and low (50. mu.M) doses, incubated for 5min, added with 5. mu.L of collagen inducer, and the maximal aggregation rate of each group of PRPs within 5min was examined. The results of the effect of sorghole A (I-1) and its derivative I-2 on collagen-induced platelet aggregation are shown in FIG. 4.
5. Macrocyclic phenolic glycoside compound sorgholide A (I-1) and derivative I-2 thereof have influence on thrombin-induced platelet aggregation
Dissolving 1000U of thrombin into 1mL of physiological saline to obtain 1000U/mL of thrombin mother solution, freezing and storing by-20, and diluting 0.1mL of 1000U/mL of thrombin solution to 100U/mL. Then 100U/mL thrombin is diluted to 5U/mL, subpackaged and frozen for standby. PRP was collected, and 270. mu.L of each PRP was placed in a turbidimetric cup. Adding macrocyclic phenolic glycoside compound sorgholide A (I-1) and its derivative I-2 samples of high (200. mu.M), medium (100. mu.M) and low (50. mu.M) dosage groups into each PRP tube, respectively 30. mu.L, incubating for 5min, adding thrombin inducer 5. mu.L, and detecting the maximum aggregation rate of each group of PRP within 5 min. The effect of sorg holide A (I-1) and its derivative I-2 on thrombin-induced platelet aggregation is shown in FIG. 5.
6. Platelet aggregation Rate determination
By adopting a turbidimetric method, 30 mul of samples with different concentrations of the stirrer, 270 mul of PRP and the macrocyclic phenolic glycoside compound sorgholide A are respectively added into a clean test cup and put into a preheating zone for preheating for 5min at 37 ℃. And (3) putting the PPP test cup into a test area to zero the platelet aggregation instrument, then putting the test cup after pre-warming into the test area, adding an inducer according to the steps of the instrument, and reading the maximum aggregation rate of the platelets after the reaction is finished. The blank control group is added with an equal amount of dissolved sample solution, and the inhibition rate of the drug on platelet aggregation is calculated according to the following formula: platelet aggregation inhibition rate (maximum aggregation rate in control group-maximum aggregation rate in administration group)/maximum aggregation rate in control group × 100%.
Test results
The high (200 mu M) and low (50 mu M) dose group of the compound sorgholide A has the effect of obviously reducing the activity of the platelet aggregation induced by the adenosine diphosphate (P <0.05) compared with a blank control group; the derivative (I-2) of the sorgholide A shows significant inhibition of thrombin-induced platelet aggregation activity (P <0.05) at three doses of 50. mu.M, 100. mu.M and 200. mu.M, compared with a blank control group. The sorgholide A has the effect of extremely remarkably reducing collagen-induced platelet aggregation (P <0.01) at a high (200 mu M) dose; the derivative (I-2) shows significant inhibition of thrombin-induced platelet aggregation activity (P <0.05 or P <0.01) at high, medium and low doses compared with a blank control group, wherein the effect is best at a dose of 100 mu M. The sorgholide A and the derivative (I-2) thereof show extremely remarkable inhibition of thrombin-induced platelet aggregation activity (P <0.01 or P <0.001) compared with a blank control group at three doses of 50 mu M, 100 mu M and 200 mu M. The sorgholide A and the derivative (I-2) thereof have different degrees of inhibition effects on adenosine diphosphate, collagen and thrombin-induced platelet aggregation.
Example 4. The application of macrocyclic phenolic glycoside compounds in preparing medicines for treating thrombotic diseases is provided.
1. And (3) tablet preparation: taking the macrocyclic phenolic glycoside compound sorgholideA (I-1) prepared in the example 2, adding corresponding auxiliary materials for preparing tablets, preparing 0.3g of tablets each containing 50 mu g of the macrocyclic phenolic glycoside compound sorgholideA (I-1) for treating cardiovascular and cerebrovascular diseases and other thrombotic diseases caused by blood coagulation, and orally taking the macrocyclic phenolic glycoside compound sorgholideA (I-1) at the dose of 3-6 mu g/kg per day for 1-3 times per day.
2. Injection preparation: the macrocyclic phenolic glycoside compound sorgholideA (I-1) prepared in the example 2 is added with corresponding auxiliary materials for preparing injection liquid injection to prepare 10mL of injection liquid injection, each injection liquid injection contains 50 mu g of macrocyclic phenolic glycoside compound sorgholideA (I-1), and the injection liquid injection is used for treating cardiovascular and cerebrovascular diseases and other thrombotic diseases caused by blood coagulation and is injected at the dose of 3-6 mu g/kg per day for 1-3 times per day.
3. Syrup preparation: taking the macrocyclic phenolic glycoside sorgholideA (I-1) prepared in the example 2, adding corresponding auxiliary materials for preparing syrup, preparing 100mL syrup per bottle, wherein each mL contains 0.5 mu g of the macrocyclic phenolic glycoside sorgholideA (I-1), and the macrocyclic phenolic glycoside sorgholideA is used for treating cardiovascular and cerebrovascular diseases and other thrombotic diseases caused by blood coagulation and is orally taken 1-3 times per day at the dose of 3-6 mu g/kg per day.
The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof, and it should be understood that various changes and modifications can be effected therein by one skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (10)
1. Macrocyclic phenolic glycoside compounds characterized by: is a compound shown as the following formula I and pharmaceutically acceptable salt or hydrate thereof,
wherein R is1/R2Is H, -OCH3；R3/R4Is H, -CH3；R1And R2Identical or different, R3And R4The same or different.
2. Macrocyclic phenolic glycoside compound according to claim 1, characterized in that: a compound shown as the following formula I-1 and pharmaceutically acceptable salt or hydrate thereof.
3. The process for the preparation of macrocyclic phenolic glycosides according to claim 1, wherein: the R is1、R2is-OCH3Said R is3、R4The synthesis is carried out according to the following synthetic route,
4. the process for the preparation of macrocyclic phenolic glycosides according to claim 1 or 2, characterized in that: comprises the following steps of (a) carrying out,
a. cleaning and drying mature sorghum roots, and mechanically crushing to obtain coarse sorghum root powder, namely A product;
b. soaking product A in 8-12 times of deionized water for 16-32 hr, decocting at 80-100 deg.C for 1-3 times (each time for 1-3 hr), mixing filtrates, and concentrating to relative density of 1.0-1.4 to obtain product B;
c. adding appropriate amount of 95% ethanol into product B until the ethanol content reaches 55% -65%, standing, collecting supernatant, filtering to remove precipitate, recovering filtrate under reduced pressure, concentrating to obtain extract, and vacuum drying to obtain WEAE (product C);
d. performing MCI GEL GEL column chromatography on the product C, performing gradient elution by using 0-95% ethanol solution, collecting 30% of elution parts, performing gradient elution by using 200-mesh and 300-mesh silica GEL column chromatography, performing gradient elution by using ethyl acetate-methanol at a ratio of 20:1-3:1, and collecting eluent by bottle separation; spotting each bottle of eluent through a thin-layer plate, developing with ethyl acetate-methanol at a ratio of 1:1, taking an elution section with an Rf value of 0.3-0.5, performing silica gel column chromatography, performing gradient elution with ethyl acetate-methanol at a ratio of 15:1-1:1, taking an elution part at a ratio of 5:1, recovering a solvent, concentrating and drying to obtain the macrocyclic phenolic glycoside compound sorgholide A.
5. Use of macrocyclic phenolic glycosides according to any one of claims 1-4 for the preparation of a medicament for the prevention or treatment of thrombotic disorders.
6. The use of macrocyclic phenolic glycosides according to claim 5 in the manufacture of a medicament for the prevention and treatment of thrombotic disorders, wherein: the macrocyclic phenolic glycoside compound is used in a daily dosage of 3-6 mug/kg body weight.
7. The use of macrocyclic phenolic glycosides according to claim 5 in the manufacture of a medicament for the prevention and treatment of thrombotic disorders, wherein: the macrocyclic phenolic glycoside compound is used singly or in the form of a pharmaceutical composition, wherein the pharmaceutical composition contains 0.1-99% of the macrocyclic phenolic glycoside compound, and the balance is a pharmaceutical carrier or excipient.
8. The use of macrocyclic phenolic glycoside compound of claim 7 for the preparation of a medicament for the prevention and treatment of thrombotic disorders, wherein: the pharmaceutically acceptable carrier or excipient is one or more of a solid diluent, a semi-solid diluent, a liquid diluent, a filler and other pharmaceutical adjuvants.
9. The use of macrocyclic phenolic glycoside compound of claim 7 for the preparation of a medicament for the prevention and treatment of thrombotic disorders, wherein: the dosage form of the pharmaceutical composition is clinically acceptable injection, suspension, emulsion, solution, syrup, tablet, capsule, granule, electuary, spray and aerosol.
10. The use of macrocyclic phenolic glycoside compound of claim 7 for the preparation of a medicament for the prevention and treatment of thrombotic disorders, wherein: the administration route of the pharmaceutical composition is intravenous injection, intravenous drip, intramuscular injection, intraperitoneal injection, subcutaneous injection oral administration, sublingual administration or mucosal dialysis.
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| CN114767695A (en) * | 2022-04-06 | 2022-07-22 | 长沙卫生职业学院 | Extraction method and application of allin |
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