CN102838570B - Mailuoning ester and preparation method and function thereof - Google Patents
Mailuoning ester and preparation method and function thereof Download PDFInfo
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Abstract
The invention belongs to the medicine field, and discloses Mailuoning ester and a preparation method and use thereof. The chemistry name of the Mailuoning ester is (E)-(5-formylfuran-2-yl) methyl-3-(3, 4-dihydroxyphenyl) acrylate. The Mailuoning ester has a protection function for cardiac muscle cells, and can be used for preparing medicine curing cardiovascular diseases.
Description
Technical field
The invention belongs to field of medicaments, relate to Mailuoning ester and its production and use.This Mailuoning esterification formal name used at school is that (3,4-dihydroxyphenyl)-acrylate, is from MAILUONING ZHUSHEYE, to extract the separated a kind of ester class new compound obtaining to (E)-(5-formylfuran-2-yl)-methyl-3-.
Background technology
People's life and health in cardiovascular system diseases serious threat, has become clinically the first dead killer, and the research and development of cardiovascular drug are all paid much attention to prevent and treat in countries in the world.Compound Chinese medicinal preparation MAILUONING ZHUSHEYE be on the basis of famous hospital " SIMIAOYONGAN TANG " clinical application research and development out, there is self-support intellecture property, and the Chinese medicine compound prescription intravenous injection of producing in official approval in 1985, by the Chinese medicine stem of noble dendrobium, radix scrophulariae, the root of bidentate achyranthes, Japanese Honeysuckle, through science, extract refining forming.Have activate blood circulation and disperse blood clots, promoting the circulation of QI to relieve pain, yin-nourishing dredging collateral and the effect that tonifies the liver and kidney, be mainly used in treating the diseases such as acute cerebral ischemic stroke, thromboangiitis obliterans, deep venous thrombosis of lower limbs, arteriosclerosis obliterans, cerebral infarction, stenocardia, myocardial infarction, disturbance of blood circulation and sequela thereof, total effective rate can reach 94.5%, relatively has that instant effect, curative effect are high, the advantage such as short treating period, cheap, few side effects, security height with similar drug.
MAILUONING ZHUSHEYE stands the test of nearly 30 years on market, is deeply subject to numerous doctors and patient's welcome, has become national famous-brand and high-quality Chinese patent medicine.In July, 2009, new medical reform essential drug list basic unit of selected country version was 307 kinds, for one of only 3 traditional Chinese medicine kinds, medical reform has brought new growth opportunity to MAILUONING ZHUSHEYE, be the fabulous chance in the more wide market of trend, showing very strong vitality and wide application prospect.
Complicacy and singularity due to Chinese materia medica, in modernization of Chinese medicine process, still there are many problems, Dominant variety underexploitation for major disease, most of serious in the situation of low-level repetition, meanwhile, for the herbal species underexploitation of high quality and at a reasonable price of the applicable China's national situation of Rural areas, address these problems, must adopt international advanced technology and quality standard, improve the R & D Level of China's Chinese medicine, especially Chinese medicine be carried out to secondary development.Using carrying out the emphasis research topic of the research of medicinal ingredients that Chinese medicine is new or position and new clinical indication as secondary exploitation for Chinese materia medica, by strict scientific experiment, sufficient experimental data is provided, promote the class of original kind, can play the effect of innovation, to promoting the novelty of China's medicinal industry, the tcm product that exploitation has individual cores intellecture property, be all with historically new significance.
The important impetus of modernization of Chinese medicine development is innovation, and the important source of secondary exploitation for Chinese materia medica You Shi China Chinese medicine original new drug research and development is a kind of new way and the novel method of develop actively Chinese materia medica.Compound Chinese medicinal preparation MAILUONING ZHUSHEYE complicated component, the key scientific problems such as wherein principal component does not occupy significant proportion, and effective constituent is still not clear, quality standard is reasonable not, is the Key technique problem of 'Mailuoning ' injection research and development.These bottleneck problems are perplexing enterprise always and are producing, affect product reputation and sale, < < Chinese medicine, the natural drug injection basic fundamental that State Food and Drug Administration promulgated in 2007 in requiring > >, stipulated " injection that effective constituent is made, single component content must not be lower than 90%; The traditional Chinese medicine that multicomponent is made, in total solids, the content of the clear and definite composition of structure must not be less than 60%, the composition of surveying should be greater than 80% ".Therefore, the secondary development of MAILUONING ZHUSHEYE is seemed to especially important, extremely urgent.
Summary of the invention
The object of this invention is to provide a kind of ester class new compound extracting from MAILUONING ZHUSHEYE---Mailuoning ester ((E)-(5-formylfuran-2-yl)-methyl-3-(3,4-dihydroxyphenyl)-acrylate).
Another object of the present invention is to provide the preparation method of above-claimed cpd.
A further object of the invention is to provide the application of above-claimed cpd in preparing the medicine of Cardiovarscular.
The object of the invention is to realize by following technical measures:
The invention discloses the structural formula of this compound suc as formula I
Molecular formula is: C
15h
12o
6, molecular weight: 288.
Called after: (chemistry is by name: (E)-(5-formylfuran-2-yl)-methyl-3-(3,4-dihydroxyphenyl)-acrylate) for Mailuoning ester.
The preparation method of described Mailuoning ester, the method be take MAILUONING ZHUSHEYE as raw material, adopts one or more in silicagel column, gel column, macroporous resin column, reversed-phase column to purify and obtain through chromatographic separation repeatedly.
Described preparation method, wherein silicagel column adopts 200 ~ 300 order silica gel; Gel column is SephadexLH-20; Macroporous resin is D101, AB-8, HP-20 or MCI; Reversed-phase column is ODS.
Described preparation method, the method be take MAILUONING ZHUSHEYE as raw material, through Sephadex LH-20 gel column, adopt methyl alcohol, ethanol, 20 ~ 80% methanol-water, or 20 ~ 80% alcohol-water carries out isocratic elution, elutriant is again through ODS reversed-phase column, adopt 5 ~ 95% alcohol-waters or 5 ~ 95% methanol-waters to carry out gradient elution, elutriant is again through silicagel column, adopt petroleum ether-ethyl acetate-acetone solvent system, chloroform-methanol, or methylene chloride-methanol carries out wash-out, elutriant is again through Sephadex LH-20 gel column, adopt methyl alcohol, ethanol carries out wash-out, elutriant adopts recrystallization separating-purifying, obtain Mailuoning ester.
The pharmaceutical preparation that described Mailuoning ester and pharmaceutically acceptable pharmaceutical excipient form.
Described pharmaceutical preparation, its formulation is tablet, capsule, granule or injection.
The application of described Mailuoning ester in preparing the medicine of Cardiovarscular.
Described application, wherein cardiovascular disorder is the disease that causes myocardial ischemia and/or anoxic, especially myocardial infarction, myocarditis, myocardial hypertrophy, coronary heart disease.
Beneficial effect of the present invention:
It is from MAILUONING ZHUSHEYE, to extract the separated a kind of ester class new compound obtaining that Mailuoning provided by the invention is joined, this compound can reduce LDH and spill from myocardial cell cytoplasm, reduces MDA content, improves SOD active, regulate the synthetic of the interior iNOS expression of myocardial cell and NO, obviously improve H
2o
2and anoxia/reoxygenation injury myocardial cell's survival rate, myocardial cell is had to provide protection, can be used for preparing the application in the medicine of Cardiovarscular.
Accompanying drawing explanation
Fig. 1, chemical compounds I
1h-NMR spectrum.
Fig. 2, chemical compounds I
13c-NMR spectrum.
Fig. 3, chemical compounds I
1h-
1the spectrum of H COSY.
The HMQC spectrum of Fig. 4, chemical compounds I.
The HMBC spectrum of Fig. 5, chemical compounds I.
The ESI-MS spectrum of Fig. 6, chemical compounds I.
Fig. 7, Mailuoning ester (chemical compounds I) preparation technology schema.
Embodiment
In conjunction with embodiment, the invention will be further described, but content of the present invention is not restricted to cited embodiment.
Embodiment 1. is separated and authenticating compound I from MAILUONING ZHUSHEYE
1, instrument and material
Mass spectrum is measured with Packard1100MSD mass detector (ESI-MS70V); Bruker AV-300 type nuclear magnetic resonance analyser for nuclear magnetic resonance spectrum (mark in TSM) is measured; Fusing point is measured with Reichert type trace melting point apparatus; Sephadex LH-20 is Pharmacia company product, and normal phase column chromatography and tlc silica gel are Haiyang Chemical Plant, Qingdao's product, and reversed-phase column material is YMCAA12S50, and agents useful for same is analytical pure.High-efficient liquid phase analysis post is Nova-PakC18 post (3.9 * 150mm, particle diameter 5 μ m, Waters company), and high performance liquid phase agents useful for same is chromatographically pure;
2, medicine
MAILUONING ZHUSHEYE, Jinting Pharmaceutical Co., Ltd. provides (lot number is: 20110467, ministerial standard).
3, preparation method
Open 700 about 7000mL of MAILUONING ZHUSHEYE, through Sephadex LH-20 post (7.5 * 120cm), 50% ethanol elution, collects 10 streams part altogether, and stream part 6 is repeatedly through ODS reversed-phase column, silicagel column, (as: flow point 6 is through ODS reversed-phase column for SephadexLH-20 column chromatography, adopt 5-95% methanol-water solvent system to carry out gradient elution, elutriant, again through silicagel column (200 order), adopts methylene chloride-methanol to carry out wash-out, elutriant, again through Sephadex LH-20 gel column, adopts methyl alcohol, ethanol carries out wash-out, elutriant adopts recrystallization separating-purifying), whole process using high performance liquid chromatography monitoring in separating-purifying process, selects the larger flow point of charateristic avsorption band to carry out next stage separation, the separation of purifying from MAILUONING ZHUSHEYE obtains a plurality of monomeric compounds, through chemistry, spectral method is identified and is respectively: 5 hydroxymethyl furfural (MLN-1), styracin (MLN-2), chlorogenic acid (MLN-3), Esculetin (MLN-4), succsinic acid (MLN-5), long-chain fat hydrocarbon (MLN-6), Mailuoning ester (MLN-7), 3,5-diCQA (MLN-8), p-Coumaric Acid (MLN-9), Cryptochlorogenic acid (MLN-10), Protocatechuic Acid (MLN-11), Rhizoma Panacis Japonici saponin (MLN-14), wherein (chemistry (E)-(5-formylfuran-2-yl)-methyl-3-(3,4-dihydroxyphenyl)-acrylate) by name is new compound to Mailuoning ester.
4, Compound I (Mailuoning ester) structure is identified as follows through nuclear magnetic resonance spectrum:
Chemical compounds I: yellow needle (chloroform-methanol), is soluble in chloroform methanol mixing solutions.254nm has absorption, I
2steam shows brown, spray FeCl
3developer is aobvious blue, and the 5%-Vanillin vitriol oil shows black.ESI-MS(m/z): 287(M-H)
-, 311(M+Na)
+, molecular weight is 288, in conjunction with hydrogen spectrum, carbon spectrum, infers that molecular formula is C
15h
12o
6.
Hydrogen spectrum shows 12 proton signals, wherein 1 aldehyde radical hydrogen proton δ
h9.60 (1H, s), 4 alkene hydrogen protons, wherein 2 trans alkene hydrogen proton δ
h6.34 (1H, d, J=15.9Hz) and δ
h7.54 (1H, d, J=15.9Hz), 2 cis alkene hydrogen proton δ
h6.84 (1H, d, J=3.5Hz) and δ
h7.53 (1H, d, J=3.5Hz), 1 methylene radical δ
h5.27 (2H, s), the fragrant hydrogen proton signal δ of 3 ABX systems
h7.08 (1H, d, J=1.8Hz), δ
h6.77 (1H, d, J=8.1Hz) and δ
h7.03 (1H, dd, J=1.8,8.1Hz), 2 hydroxyl proton signal 3-OH, 4-OH δ
h5-9 (2H, brs).
Carbon spectrum shows 15 carbon signals, wherein 1 aldehyde radical carbon signal δ
c178.5,1 ester carbonyl group carbon signal δ
c166.0,10 aromatic carbon signals, 2 trans olefinic carbon signal δ
c146.3 and δ
c121.8,1 methylene radical δ
c57.4.
1h-
1in H COSY Correlated Spectroscopy, can find 3 groups of protons that have correlationship, first group: δ
h7.08 (1H, d, J=1.8Hz), δ
h6.77 (1H, d, J=8.1Hz) and δ
h7.03 (1H, dd, J=1.8,8.1Hz); Second group: δ
h6.34 (1H, d, J=15.9Hz) and δ
h7.54 (1H, d, J=15.9Hz); The 3rd group: δ
h6.84 (1H, d, J=3.5Hz) and δ
h7.53 (1H, d, J=3.5Hz), can release following 3 simple small segments in conjunction with HMQC spectrum:
In HMBC spectrum, δ
h9.60 with δ
c152.4; δ
h7.08 with δ
c145.6, δ
c121.8; δ
h6.77 with δ
c125.4, δ
c145.6, δ
c148.7; δ
h7.03 with δ
c114.9, δ
c146.3, δ
c148.7; δ
h7.54 with δ
c166.0, δ
c114.9, δ
c121.8, δ
c121.8, δ
c125.4; δ
h6.34 with δ
c166.0, δ
c125.4; δ
h5.27 with δ
c112.9, δ
c155.7, δ
c166.0; δ
h6.84 with δ
c123.9, δ
c152.4, δ
c155.7; δ
h7.53 with δ
c155.7, δ
c112.9, δ
c152.4; Have respectively distant relation signal, the hydrocarbon distant relation of its key is as follows:
By
1h NMR,
13c NMR, HMBC, HMQC,
1h-
1the integration analysis of H COSY spectrum, evaluation structure is shown in formula I, chemical compounds I is new compound by literature search, name as Mailuoning ester ((E)-(5-formylfuran-2-yl)-methyl-3-(3,4-dihydroxyphenyl)-acrylate), the hydrocarbon signal of chemical compounds I has been carried out to full ownership in Table 10.
Chemical compounds I: yellow needle (chloroform-methanol), molecular formula is C
15h
12o
6, ESI-MSm/z:287[M-H]
-(100).
1H NMR(DMSO-d
6，300MHz)δ：9.60(1H,s,CHO),7.08(1H,d,J＝1.8Hz,H-2)，6.77(1H,d,J＝8.1Hz,H-5)，7.03(1H,dd,J＝1.8,8.1Hz,H-6)，7.54(1H,d,J＝15.9Hz,H-7)，6.34(1H,d,J＝15.9Hz,H-8),5.27(2H,s,H-11)，6.84(1H,d,J＝3.5Hz,H-13)，7.53(1H,d,J＝3.5Hz,H-14)，3-OH,4-OH5-9(2H,brs)。
13CNMR(DMSO-d
6，75MHz)δ：125.4(C-1)，114.9(C-2)，145.6(C-3)，148.7(C-4)，115.8(C-5)，121.8(C-6)，146.3(C-7)，121.8(C-8)，166.0(C-9)，57.4(C-11)，155.7(C-12)，112.9(C-13)，123.9(C-14)，152.4(C-15)，178.5(C-16)。
Table 10: the hydrocarbon signal of chemical compounds I
| No. | 13C-NMR | 1H-NMR | 1H- 1H COSY | HMBC |
| 1 | 125.4 | |||
| 2 | 114.9 | 7.08(1H,d,J＝1.8Hz) | H-6 | C-6,C-3 |
| 3 | 145.6 | |||
| 4 | 148.7 | |||
| 5 | 115.8 | 6.77(1H,d,J＝8.1Hz) | H-6 | C-1,C-3,C-4 |
| 6 | 121.8 | 7.03(1H,dd,J＝1.8,8.1Hz) | H-5,H-2 | C-2,C-7,C-4 |
| 7 | 146.3 | 7.54(1H,d,J＝15.9Hz) | H-8 | C-9,C-2,C-8,C-6,C-1 |
| 8 | 121.8 | 6.34(1H,d,J＝15.9Hz) | H-7 | C-9,C-1 |
| 9 | 166.0 | |||
| 11 | 57.4 | 5.27(2H,s) | C-13,C-12,C-9 | |
| 12 | 155.7 | |||
| 13 | 112.9 | 6.84(1H,d,J＝3.5Hz) | H-14 | C-14,C-15,C-12 |
| 14 | 123.9 | 7.53(1H,d,J＝3.5Hz) | H-13 | C-12,C-13,C-15 |
| 15 | 152.4 | |||
| 16 | 178.5 | |||
| 3-OH,4-OH | 5-9(2H,brs) | |||
| -CHO | 9.60(1H,s) | C-15 |
Embodiment 2
New compounds i Mailuoning ester provided by the present invention can reduce myocardial infarction and ischemia model rat LDH content, and reduction MDA content, improves SOD active, regulates the synthetic of the interior iNOS expression of myocardial cell and NO, obviously improves H
2o
2and anoxia/reoxygenation injury myocardial cell's survival rate, myocardial cell is had to provide protection.Its pharmacological results is as follows:
(1) experiment purpose
Respectively with H
2o
2, hypoxia/reoxygenation stimulates H9C2 rat myocardial cell to prepare In Vitro Anti myocardial infarction and ischemia model, by measuring index of correlation, investigates antioxygenation and the provide protection to Hypoxia/Reoxygenation Injury of Mailuoning ester, its activity resisting myocardial ischemia of comprehensive evaluation
(2) experimental technique
Adopt H9C2 rat myocardial cell model, respectively with H
2o
2, hypoxia/reoxygenation stimulates myocardial cell to prepare In Vitro Anti myocardial infarction and ischemia model, observes Mailuoning ester to H
2o
2total NOS in LDH leakage, MDA, NO content, SOD activity and cell pyrolysis liquid after anoxia _ reoxygenation in the cell conditioned medium liquid of processing, the impact of iNOS, GSH-Px activity.By PrestoBlue method, detect APS to H
2o
2, anoxia/reoxygenation injury myocardial cell survival rate impact.
(3) experimental result:
1. Mailuoning ester is to H
2o
2the impact that the H9C2 cardiomyocyte proliferation causing suppresses
0.2mmol/LH
2o
2process H9C2 cell 30min, can cause cardiomyocyte viability to reduce, compare and there is significant difference (P<0.05) with solvent control group (as physiological saline).With model group comparison, Coenzyme Q10 99.0 100mg/L can significantly improve cell viability (P<0.05), and Mailuoning ester 30 ~ 80 μ mol/L also can significantly improve cell viability (P<0.05or P<0.01).Results suggest suppresses H when Mailuoning ester concentration is 15 ~ 30 μ mol/L
2o
2injury of myocardium cell has visible trend, and Mailuoning ester concentration can significantly suppress H higher than equaling 30 μ mol/L
2o
2injury of myocardium cell, and along with concentration increases, the provide protection of cell is strengthened to some extent.
Table 1. Mailuoning ester is to H
2o
2the impact (n=3) that the H9C2 cardiomyocyte proliferation causing suppresses
Compare * P < 0.01 with solvent control group; Compare #P < 0.01 with model group, ##P < 0.05
2. Mailuoning ester is to H
2o
2the impact of injury of myocardium cell LDH, DA, SOD, GSH-Px, NOS, NO level.
2.1 couples of H
2o
2the impact that injury of myocardium cell LDH discharges.
LDH is extensively present in body tissue, and in cardiac muscular tissue, content is particularly abundant.When myocardial cell sustains damage, the myocardium enzyme such as LDH spill from endochylema, and in culturing cell supernatant, LDH level raises, can reflecting myocardium degree of injury by measuring in supernatant LDH activity, and the sensitive indicator that has become reflecting myocardium degree of injury is widely adopted.
0.2mmol/LH
2o
2process H9C2 cell 30min, can cause that myocardial cell LDH spills increase, compare and there is significant difference (P<0.05) with solvent control group.With model group comparison, Coenzyme Q10 99.0 100mg/L significantly reduces spill (P<0.01) of the interior LDH of cell, and Mailuoning ester also can significantly reduce spill (P<0.05) of the interior LDH of cell.Results suggest, Mailuoning ester can alleviate H
2o
2the interior LDH of induction myocardial cell spills, and myocardial cell membrane is had to provide protection, and along with concentration increases, the provide protection of cell is strengthened to some extent, the results are shown in Table 2.
Table 2 medicine is to H
2o
2injury of myocardium cell discharges the impact (n=3) of LDH
Compare * P < 0.05 with solvent control group; Compare #P < 0.01 with model group, ##P < 0.05
2.2 couples of H
2o
2the impact of injury of myocardium cell MDA level
During Myocytes Anoxia, energy metabolism impairment, myocardial cell membrane is impaired.While pouring into again, along with pouring in of a large amount of oxygen, produce a large amount of oxyradicals, cause Cell membrane lipids peroxidation, biomembrane damage, membrane permeability increases, MDA is the end product that oxyradical is attacked microbial film unsaturated fatty acids, and its value height indirectly reflection body cell is subject to radical damage degree.
0.2mmol/L H
2o
2process H9C2 cell 30min, MDA content significantly rises, and compares and has significant difference (P<0.01) with solvent control group, and showed cell sustains damage.With model group comparison, Coenzyme Q10 99.0 100mg/L can significantly reduce MDA(P<0.05 in cell), Mailuoning ester also can significantly reduce MDA(P<0.05or P<0.01 in cell culture fluid).Results suggest, Mailuoning ester can alleviate H
2o
2mDA content in induction myocardial cell, has provide protection to myocardial cell, and along with concentration increases, the provide protection of cell is strengthened to some extent, the results are shown in Table 3.
Table 3 medicine is to H
2o
2the impact (n=3) of injury of myocardium cell MDA level
Compare * < 0.01 with solvent control group, compare # < 0.05 with model group, ## < 0.01
2.3 medicines are to H
2o
2the impact of injury of myocardium cell SOD vigor
SOD is a kind of antioxidase being present in enchylema, and it can remove superoxide anion, and protection body is avoided superoxide anion damage, and its value height has reflected the ability of body removing oxyradical indirectly.
0.2mmol/LH
2o
2process H9C2 cell 30min, the vigor of SOD significantly reduces, and compares and has significant difference (P<0.01) with solvent control group, shows that lipid peroxidation is strong, and cell injury is obvious.With model group comparison, Mailuoning ester is the vigor of enhancement of SOD (P<0.05) significantly.Results suggest, Mailuoning ester may be by enhancing body the removing ability to oxyradical, alleviate Cell membrane lipids peroxide injury, thereby the provide protection of performance cell membrane and strengthens to the provide protection of cell to some extent along with concentration increases.
Table 4 medicine is to H
2o
2the impact (n=3) of injury of myocardium cell SOD vigor
Compare * < 0.01 with solvent control group, compare # < 0.05 with model group
2.4 couples of H
2o
2injury of myocardium cell iNOS vigor and the synthetic impact of NO.
Nitrogen protoxide (NO) has very important effect in treating myocardial ischemia damage; apoptosis is the principal mode of myocardial damage; and activation myocardial cell unconventionality expression iNOS produces excessive NO; there is protection and increase the weight of to damage dual function in the latter, excessive NO has the effect of injury of myocardium cell in the damage of myocardial ischemia-reperfusion type.Under normal circumstances, iNOS does not express or the damage of weak expression ischemic and ischemia-reperfusion type and myocardial infarction can cause the activation of iNOS, and it may be one of mechanism of apoptosis of cardiac muscle that iNOS generation increases.
0.2mmol/LH
2o
2process H9C2 cell 30min, compare the increased activity (P<0.05) of iNOS in myocardial cell with solvent control group, synthetic increase (P<0.01) of NO in nutrient solution, shows that cell injury is obvious simultaneously.With model group comparison, Mailuoning ester can reduce NO synthetic (in Table 6) in the activity (in Table 5) of iNOS and nutrient solution, although inhibited to total NOS activity, lack statistical significance (in Table 7).Results suggest, NO level when Mailuoning ester can reduce myocardial cell's oxidative damage, suppresses generation and the release of NO, thereby protects and alleviate cell injury, and along with concentration increases, the provide protection of cell is strengthened to some extent.
Table 5 medicine is to H
2o
2the impact (n=3) of injury of myocardium cell iNOS activity
Compare * < 0.05 with solvent control group, compare # < 0.05 with model group
Table 6 medicine is to H
2o
2the impact of NO content (n=3) in injury of myocardium cell culture fluid
Compare * < 0.01 with solvent control group, compare # < 0.01 with model group
Table 7 medicine is to H
2o
2the impact (n=3) of the NOS activity that injury of myocardium cell is total
2.5 couples of H
2o
2the impact of GSH-Px activity in injury of myocardium cell.
GSH-Px is a kind of antioxidase extensively distributing in body, and catalytic reduction type gsh (GSH) is to H
2o
2reduction reaction, remove in time free radical, Cell protection membrane structure and telotism are had to vital role.This experiment is found, H
2o
2can cause GSH-Px activity decreased in myocardial cell, Mailuoning ester affects (in Table 8) on GSH-Px activity in cell without significance.
Table 8 medicine is to H
2o
2the impact (n=3) of GSH-Px activity in injury of myocardium cell
3. the provide protection of medicine to Myocytes Anoxia damage
H9C2 cell hypoxia is cultivated 4h, and reoxygenation is cultivated 2h and processed, and can cause cardiomyocyte viability to reduce, and compares and has significant difference (P<0.01) with solvent control group.With model group comparison, Coenzyme Q10 99.0 100mg/L can significantly improve cell viability (P<0.01), and Mailuoning ester also can significantly improve cell viability (P<0.01).Results suggest, Mailuoning ester can be the motility rate of the increase cardiomyocyte injury induced by hypoxia/reoxygenation of dose-dependently, has provide protection (table 9).
The provide protection (n=3) of table 9 medicine to Myocytes Anoxia damage
Compare * < 0.01 with normal group, compare # < 0.01 with model group.
Above-mentioned experimental result shows, Mailuoning ester of the present invention can reduce LDH and spill from myocardial cell cytoplasm, reduces MDA content, improves SOD active, regulates iNOS in myocardial cell to express and NO synthetic, obviously improves H
2o
2and anoxia/reoxygenation injury myocardial cell's survival rate, myocardial cell is had to provide protection.
Embodiment 3 formulation example
Example 1: get Mailuoning ester 10g, add suitably auxiliary material of tablet (comprising slow-release tablet, matrix tablet, coating tablet, dispersible tablet etc.), be prepared into the medicinal tablet of Cardiovarscular by tablet (comprising slow-release tablet, matrix tablet, coating tablet, dispersible tablet etc.) technique.
Example 2: get Mailuoning ester 10g, add the suitable auxiliary material of capsule, be prepared into the medicine capsule of Cardiovarscular by capsule technique.
Example 3: get Mailuoning ester 10g, add the suitable auxiliary material of granule, be prepared into the medicinal granule of Cardiovarscular by granule technique.
Example 4: get Mailuoning ester 10g, add suitably auxiliary material of injection (comprising lyophilized injectable powder and aseptic subpackaged dry powder injection), be prepared into the drug injection of Cardiovarscular by injection (comprising lyophilized injectable powder and aseptic subpackaged dry powder injection) technique.
The formulation that Mailuoning ester of the present invention can be prepared is not limited to above-mentioned a few example, can be prepared into as required pharmaceutically acceptable any formulation, and the preparation method of preparation all can adopt prior art, repeats no more herein.
Claims (9)
1. a Mailuoning ester, is characterized in that the structural formula of this compound is:
2. the preparation method of Mailuoning ester described in claim 1, is characterized in that take that MAILUONING ZHUSHEYE is as raw material, adopts one or more in silicagel column, gel column, macroporous resin column, reversed-phase column to purify and obtain through chromatographic separation repeatedly.
3. preparation method according to claim 2, is characterized in that silicagel column adopts 200～300 order silica gel; Gel column is Sephadex LH-20; Macroporous resin is D101, AB-8, HP-20 or MCI; Reversed-phase column is ODS.
4. preparation method according to claim 2, it is characterized in that the method take MAILUONING ZHUSHEYE as raw material, through Sephadex LH-20 gel column, adopt methyl alcohol, ethanol, 20～80% methanol-water, or 20～80% alcohol-water carries out isocratic elution, elutriant is again through ODS reversed-phase column, adopt 5～95% alcohol-waters or 5～95% methanol-waters to carry out gradient elution, elutriant is again through silicagel column, adopt petroleum ether-ethyl acetate-acetone solvent system, chloroform-methanol, or methylene chloride-methanol carries out wash-out, elutriant is again through Sephadex LH-20 gel column, adopt methyl alcohol, ethanol carries out wash-out, elutriant adopts recrystallization separating-purifying, obtain Mailuoning ester.
5. the pharmaceutical preparation that Mailuoning ester claimed in claim 1 and pharmaceutically acceptable pharmaceutical excipient form.
6. pharmaceutical preparation according to claim 5, its formulation is tablet, capsule, granule or injection.
7. the application of Mailuoning ester claimed in claim 1 in preparing the medicine of Cardiovarscular.
8. application according to claim 7, is characterized in that cardiovascular disorder is the disease that causes myocardial ischemia and/or anoxic.
9. application according to claim 8, is characterized in that causing the disease of myocardial ischemia and/or anoxic is myocardial infarction, myocarditis, myocardial hypertrophy, coronary heart disease.
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| CN115350243A (en) * | 2021-01-15 | 2022-11-18 | 上海中医药大学 | Pharmaceutical application of dendrobium nobile liquid preparation |
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Non-Patent Citations (4)
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| 吴晓燕等.脉络宁注射液中5-羟甲基糠醛、绿原酸和咖啡酸的含量测定及安全性分析.《中国医药杂志》.2010,第45卷(第21期),第1667页第1段至第1670页倒数第1段. |
| 张尊建等.脉络宁注射液HPLC/UV/MS指纹图谱研究.《中成药》.2004,第26卷(第3期),第175页第1段至第178页倒数第1段. |
| 脉络宁注射液HPLC/UV/MS指纹图谱研究;张尊建等;《中成药》;20040331;第26卷(第3期);第175页第1段至第178页倒数第1段 * |
| 脉络宁注射液中5-羟甲基糠醛、绿原酸和咖啡酸的含量测定及安全性分析;吴晓燕等;《中国医药杂志》;20101130;第45卷(第21期);第1667页第1段至第1670页倒数第1段 * |
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