CN106265706A - A kind of male ice drop pill treating acute myocardial ischemia and preparation method thereof - Google Patents
A kind of male ice drop pill treating acute myocardial ischemia and preparation method thereof Download PDFInfo
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Abstract
A kind of male ice drop pill treating acute myocardial ischemia, is made up of vitexin-2 ''-O-rhamnoside, Borneolum Syntheticum and drop pill substrate；In described male ice drop pill, every ball contains vitexin-2 ''-O-rhamnoside 1～10mg, Borneolum Syntheticum 1～5mg, and described vitexin-2 ''-O-rhamnoside is the monomeric compound extracting isolated from Folium Crataegi.The present invention also provides for treating the preparation method of the male ice drop pill of acute myocardial ischemia, Folium Crataegi active monomer component vitexin-2 ''-O-rhamnoside and Borneolum Syntheticum drug combination is selected to make drop pill, Borneolum Syntheticum has the effect promoting intestinal infiltration as absorption enhancer, is remarkably improved the bioavailability of vitexin-2 ''-O-rhamnoside.The male ice drop pill of the present invention can be through sublingual administration, and absorption is fast, dosage is little, can accurately adjust dosage by the ball number that increase and decrease is taken when clinical application, and be easy to carry, and as a kind new medicine of natural product exploitation Chinese medicine, has wide market prospect.
Description
Technical field
The present invention relates to the field of Chinese medicines, particularly relate to a kind of male ice drop pill treating acute myocardial ischemia and preparation method thereof.
Background technology
Along with socioeconomic development, national life mode there occurs the acceleration of deep change, especially aged tendency of population and Development of China's Urbanization, and China's cardiovascular risk factors fashion trend is obvious, and the number of the infected that result in cardiovascular diseases continues to increase.10 years from now on, cardiovascular diseases's number of patients will quickly increase, and cardiovascular death accounts for the first place of the total cause of death of urban and rural residents, and the Disease Spectrum of cardiovascular diseases day by day increases the weight of, it has also become great public health problem.Myocardial ischemia, refers to that the hemoperfusion of heart reduces, causes the oxygen supply of heart to reduce, energy metabolism of myocardial is abnormal, it is impossible to support a kind of pathological state of normal heart action.
Folium Crataegi is rosaceous plant Fructus Pyri Pashiae (Crataegus pinnatifida
Bge. var major), the dried leaves of Fructus Crataegi (C. pinnatifida Bge.), record in Chinese Pharmacopoeia.Folium Crataegi, sweet acid, warm in nature, enter conscience taste, blood stasis dispelling can regulate the flow of vital energy, restore menstrual flow and invigorate blood circulation, strengthening the spleen to promote digestion, dispersing the stagnated live-QI to relieve the stagnation of QI, free from worry chest and diaphragm.Modern study thinks that it has expanding cardiovascular, sends the supply of blood oxygen, reduces blood lipid level, regulating lipid metabolism, reduces peripheral vascular resistance, improve microcirculatory effect.At present, the representative medicine containing Folium Crataegi composition in the domestic medicine having listed the diseases such as treatment coronary heart disease, hyperlipidemia, angina pectoris and arrhythmia has Xinan Capsule, Yixintong, multiple lamination, mountain rose capsule etc..
Vitexin-2 ''-O-rhamnoside (vitexin-2 "-O-rhamnoside) is main active in Folium Crataegi, and content reaches more than 2%, and its water solublity is strong, and pharmacologically active is strong, acellular poison, applicable develops into new drug.
Cultured cell in vitro result of study shows: vitexin-2 ''-O-rhamnoside, by regulation cell membrane calcium ion gated channel, affects transmembrane potential and calcium ion concentration stabilizing cell membrane；The enzymes such as LDH are made to produce and expose minimizing；The aspects such as regulation myocardial cell activity substance production and activity, substantially can damage by protecting myocardial cell hypoxia/reoxygenation, protect Myocardial Ischemia-reperfusion Injury cell, and can reduce beating rate of myocardial cells in physiological range；It addition, this compound can make endotheliocyte vascular relaxing factor NO yield after hypoxia/reoxygenation, contracting Angiogenesis ET-1 mrna expression and ET-1 significantly reduce.Separately studies have found that, vitexin rhamnoside has concentration dependent diastole effect to isolated aortic ring, and this mode acting through endothelium-dependent relaxation and endothelium non-dependent produces, and has the pharmacological action feature of part calcium antagonist.Thus, it is found that vitexin rhamnoside has the new pharmacological action of direct expansion artery blood vessel, can be used for the preparation of cardiovascular and cerebrovascular diseases medicine.
Borneolum Syntheticum, arduous, it is slightly cold, GUIXIN, spleen, lung meridian, there is effect of refreshment of having one's ideas straightened out, clearing away heat to alleviate pain.Amplification on Canon of Materia Medica thinks that its action character is for " then gesture of walking alone is weak, and assistant makes, and gains merit ".There are some researches show, acute myocardial infarction is had by single Borneolum Syntheticum similar with storax pill for treating coronary heart disease makes CBSF go up, decreased heart rate and the effect of reduction myocardial oxygen consumption, and Borneolum Syntheticum is also commonly used for cardiovascular disease prevention clinically.
Existing research shows: after vitexin-2 ''-O-rhamnoside oral administration, bioavailability is low, mainly by caused by serious intestinal first pass effect.Sublingual mucosa rich blood vessel, sublingual gland is positioned at sublingual mucosa, and the saliva that secretion is accumulated is many, medicine solution absorption here, and curative effect plays rapidly, is particularly suited for giving treatment to some emergency patients.Compared with other administration route, during sublingual administration, drug absorption is rapid, is largely avoided first mistake and eliminates.
Summary of the invention
It is an object of the invention to provide a kind of male ice drop pill treating acute myocardial ischemia and preparation method thereof, selection vitexin-2 ''-O-rhamnoside is main component, make drop pill with absorption enhancer Borneolum Syntheticum drug combination, have that absorption is fast, dosage is little, it is simple to the effect carried.
For realizing the above-mentioned purpose of the present invention, the present invention provides a kind of male ice drop pill treating acute myocardial ischemia, is made up of vitexin-2 ''-O-rhamnoside, Borneolum Syntheticum and drop pill substrate；In described male ice drop pill, every ball contains vitexin-2 ''-O-rhamnoside 1～10mg, Borneolum Syntheticum 1～5mg.
Described vitexin-2 ''-O-rhamnoside is 3～10:3 with the ratio of weight and number of Borneolum Syntheticum；Described drop pill substrate is 10～1:1 with the ratio of weight and number of vitexin-2 ''-O-rhamnoside.
Described vitexin-2 ''-O-rhamnoside is the monomeric compound extracting isolated from Folium Crataegi.
Described drop pill substrate is Macrogol 4000 and the mixed liquor of any one or they in polyethylene glycol 6000.
The present invention also provides for the preparation method of a kind of male ice drop pill treating acute myocardial ischemia, comprises the steps.
Step 1, weigh vitexin-2 ''-O-rhamnoside, Borneolum Syntheticum by formula proportion, join in melted drop pill substrate, obtain mixed liquor.
Step 2, described mixed liquor is continued heating, be stirred continuously, make uniform melted medicinal liquid.
Step 3, described melted medicinal liquid is transferred in reservoir, regulates pill dripping machine temperature control system, under insulation, described melted medicinal liquid is passed through pill dripping machine water dropper, with 20～60 min-1Speed instill in condensing agent, obtain solid solution.
Step 4, after described solid solution cooling meat pelletization shape, the drop pill in pill dripping machine exit is taken out, removes surface condensation agent, be drying to obtain the present invention male ice drop pill.
Described condensing agent is liquid paraffin, vegetable oil or dimethicone.
In described step 3, the temperature of insulation is 70 DEG C～90 DEG C.
In described step 3, the temperature of condensing agent is-15 DEG C～20 DEG C.
Compared with prior art beneficial effects of the present invention.
Male ice drop pill for the treatment of acute myocardial ischemia that the present invention provides and preparation method thereof, Folium Crataegi active monomer component vitexin-2 ''-O-rhamnoside and Borneolum Syntheticum drug combination is selected to make drop pill, Borneolum Syntheticum has the effect promoting intestinal infiltration as absorption enhancer, is remarkably improved the bioavailability of vitexin-2 ''-O-rhamnoside；It addition, the P-glycoprotein being widely present in intestinal can reduce the transmembrane transport of medicine by the conveyer mechanism of efflux pump, become the absorption barrier of some drugs, and Borneolum Syntheticum can improve the intestinal absorption of vitexin-2 ''-O-rhamnoside as the inhibitor of P-glycoprotein.This drop pill can be through sublingual administration, and absorption is fast, dosage is little, can accurately adjust dosage by the ball number that increase and decrease is taken when clinical application, and be easy to carry, and as a kind new medicine of natural product exploitation Chinese medicine, has wide market prospect.
Accompanying drawing explanation
Fig. 1 is the male ice method for preparing drop pills flow chart that the present invention treats acute myocardial ischemia.
Fig. 2 is the Drug-time curve figure of vitexin-2 ''-O-rhamnoside first pass effect of hepar and gastrointestinal first pass effect.
Fig. 3 is that Borneolum Syntheticum is to its Drug-time curve figure in rat body in vitexin-2 ''-O-rhamnoside intestinal absorption influence research.
Detailed description of the invention
The present invention is further described below in conjunction with specific embodiment.
Embodiment 1.
The present embodiment provides a kind of male ice drop pill treating acute myocardial ischemia, is made up of vitexin-2 ''-O-rhamnoside, Borneolum Syntheticum, drop pill substrate；Described vitexin-2 ''-O-rhamnoside is 4:3 with the ratio of weight and number of Borneolum Syntheticum；Described drop pill substrate is 5:1 with the ratio of weight and number of vitexin-2 ''-O-rhamnoside, and described drop pill substrate is PEG6000.
Described vitexin-2 ''-O-rhamnoside is the monomeric compound extracting isolated from Folium Crataegi.Its isolated and purified process is: the extraction of (1) chemical composition: take Folium Crataegi 30kg, after pulverizing, put in extraction vessel, extracting twice through 70% alcohol heating reflux, be 70% ethanol extraction 1.5h of 12 times amount for the first time, second time is 70% ethanol extraction 1h of 10 times amount, filtration, united extraction liquid, decompression recycling ethanol, to without alcohol taste, obtains extractum 2000g, standby.(2) purification of chemical composition: described extractum is upper AB-8 type macroporous resin column after dissolving, with 10 times of column volume water elutions, removes resin surface or the residual impurity of inside, then with 3 times of 70% ethanol gradient elution, eluent decompression recycling ethanol.Eluent uses ether to be extracted to colourless, discards ether layer, water elution partial concentration, obtains concentrated extract 500g.(3) separation of vitexin-2 ''-O-rhamnoside: described concentrated extract is upper AB-8 type macroporous resin column after dissolving, through water, 30% ethanol, 50% ethanol and 70% ethanol gradient elution.Being separated with polyamide column respectively by 30% ethanol gained fraction, with distilled water, 30% ethanol, 50% ethanol gradient elution, sub-bottle is collected solution and checks tracking composition with polyamide film chromatography.30% ethanol and 50% ethanol gained fraction decompression recycling ethanol are to without alcohol taste, and dry method is loaded on silicagel column, separate with 200-300 mesh silicagel column.With ethyl acetate-butanone-formic acid-water system different proportion eluting, thin layer chromatography determines vitexin rhamnoside, after being isolated, then with Sephadex LH-20 polydextran gel column purification, places, recrystallization, obtains crystal, be vitexin-2 ''-O-rhamnoside.
Referring to Fig. 1, the present embodiment also provides for the preparation method of a kind of male ice drop pill treating acute myocardial ischemia, comprises the steps.
Step 1, weigh vitexin-2 ''-O-rhamnoside, Borneolum Syntheticum by formula proportion, join in melted PEG6000, obtain mixed liquor.
Step 2, described mixed liquor is continued heating, be stirred continuously, make uniform melted medicinal liquid.
Step 3, described melted medicinal liquid is transferred in reservoir, regulates pill dripping machine temperature control system, under being incubated at 80 DEG C～90 DEG C, described melted medicinal liquid is passed through pill dripping machine water dropper, with 40 min-1Speed instill in-15 DEG C～-5 DEG C of liquid paraffin, obtain solid solution.
Step 4, after described solid solution cooling meat pelletization shape, the drop pill in pill dripping machine exit is taken out, removes surface condensation agent (drip condensing agent to the greatest extent), be drying to obtain the present embodiment male ice drop pill.
For verifying that beneficial effects of the present invention, the present invention provide tests below case further.
Test example 1.
1.1, medicine and reagent.
Vitexin-2 ''-O-rhamnoside (laboratory is made by oneself, purity ＞ 99%)；Hesperidin (Nat'l Pharmaceutical & Biological Products Control Institute provides, and lot number is 110721-200613)；Methanol (chromatographically pure, Tianjin great Mao chemical reagent factory)；Phosphoric acid (analytical pure, Tianjin Jin Feng Chemical Co., Ltd.)；Glacial acetic acid (Specialty Chemical reagent development centre, North China)；Purified water (heartily company limited)；Borneolum Syntheticum (Zhuzhou Song Benlinization company limited).
1.2, animal.
Healthy Wistar rat, male (250-300g), 30, Liaoning University of TCM's Experimental Animal Center provide；Used in experiment, zooscopy is carried out in strict accordance with laboratory animal protection guideline, and used animal is obtained Animal Experimental Ethical committee of Liaoning University of TCM and agrees to.Freely drink water during experiment, fasting 12 h before rat medicine-feeding test.
1.3, chromatographic condition.
Chromatographic column: Diamonsil C18(150 mm × 4.6 mm, 5 μm) (Di Ma company, BeiJing, China)；Flowing phase: methanol-0.1% phosphoric acid water (40:60；V/V)；Detection wavelength: 330 nm；Flow velocity: 1 mL/min；Internal standard substance: Hesperidin；Column temperature: room temperature；Sample size: 5 μ L.
1.4, the preparation of biological sample.
Take plasma sample 100 μ L, put in 2mL tool plug centrifuge tube, be sequentially added into 20 μ L glacial acetic acids, 50 μ L inner mark solutions (40 μ g/mL), 500 μ L methanol, vortex mixed 1 min, centrifugal 15 min(3000 r/min), taking supernatant, flow down in 50 DEG C of nitrogen and dry up, residue adds flowing 100 μ L mutually, vortex dissolves 1min, centrifugal 5min(15000r/min), take supernatant 5 μ L injection UHPLC and be analyzed, record chromatogram and peak area respectively.
1.5, first pass effect of hepar research.
Choose two groups of rats, i.e. femoral vein administration group and hepatic portal vein administration group, often group 5, test fasting in eve but freely drink water.Lying on the back in operating-table after 20% urethane (5mL/kg i.p.) light anaesthesia, be placed under lamp and make body temperature maintain 37 ± 1 DEG C, intubated by rat carotid artery before reviving, the heparin being full of 80U/mL in pipe for anticoagulant and takes blood.
For femoral vein administration group, cut an osculum open at femoribus internus, find femoral vein, at the uniform velocity inject (5mg/kg) in femoral vein by vitexin-2 ''-O-rhamnoside solution 5min, after administration, stop blooding with Cotton Gossypii physical depression immediately, sew up a wound.For hepatic portal vein administration group, after abdominal part is cut open, superior mesenteric vein is found along intestinal, and vitexin-2 ''-O-rhamnoside (5mg/kg) is injected along hepatoportal direction, at the uniform velocity complete in 5min, after administration, be pressed at administration with Cotton Gossypii flicking immediately and carry out physiological hemostasis, after hemostasis, sew up the edge of a knife.After being administered 2,5,8,11,15,20,30,45,60,90,120,150,180,240,300min takes a blood sample 0.3mL, it is placed in the EP pipe of heparinization in advance, centrifugal 15min(3000 r/min), obtain plasma sample and put preservation in-20 DEG C of refrigerators, to be measured.
1.6, gastrointestinal first pass effect research.
Choose two groups of rats, i.e. duodenal administration group and stomach administration group, often group 5, test fasting in eve but freely drink water.Lying on the back in operating-table after 20% urethane (5mL/kg i.p.) light anaesthesia, be placed under lamp and make body temperature maintain 37 ± 1 DEG C, intubated by rat carotid artery before reviving, the heparin being full of 80U/mL in pipe for anticoagulant and takes blood.
For duodenal administration group, through duodenum epimere (1cm under pylorus) perfusion vitexin-2 ''-O-rhamnoside solution (40mg/kg), at the uniform velocity complete in 5 minutes.For stomach administration group, at stomach bottom cardia, in 5 minutes, at the uniform velocity inject vitexin-2 ''-O-rhamnoside solution (40mg/kg).After being administered 2,5,8,11,15,20,30,45,60,90,120,150,180,240,300min take a blood sample 0.3mL, be placed in the EP pipe of heparinization in advance, centrifugal 15min(3000r/min), obtain plasma sample and put preservation in-20 DEG C of refrigerators, to be measured.
1.7, the absorption enhancer Borneolum Syntheticum impact on vitexin-2 ''-O-rhamnoside intestinal absorption.
For the research absorption enhancer impact on vitexin rhamnoside intestinal absorption, the mixed solution of Borneolum Syntheticum (30mg/kg) with vitexin-2 ''-O-rhamnoside is irrigated to duodenum.After being administered, 2,5,8,11,15,20,30,45,60,90,120,180,240,300 min blood sampling 0.3mL, is placed in the EP pipe of heparinization in advance, centrifugal 15min(3000r/min), obtain plasma sample and put preservation in-20 DEG C of refrigerators, to be measured.
1.8, result.
Refer to table 1, cross for vitexin-2 ''-O-rhamnoside liver head and the Related Drug of gastrointestinal first pass effect moves parameter；Refer to Fig. 2, for vitexin-2 ''-O-rhamnoside first pass effect of hepar and the Drug-time curve of gastrointestinal first pass effect.
Table 1: vitexin-2 ''-O-rhamnoside first pass effect of hepar and gastrointestinal first pass effect medicine move parameter.
| Group | Dosage (mg/kg) | AUC0→∞(µg·min/ml) | Bioavailability |
| Femoral vein group | 5 | 725.49 ± 26.13 | 100 |
| Hepatic portal vein group | 5 | 1151.9 ± 38.25 | 158.77 |
| Duodenum group | 40 | 220.98 ± 24.37 | 2.4 |
| Stomach group | 40 | 263.89 ± 97.36 | 2.86 |
Referring to table 2, the Related Drug affected vitexin-2 ''-O-rhamnoside intestinal absorption for Borneolum Syntheticum moves parameter；Refer to Fig. 3, for Borneolum Syntheticum to its Drug-time curve in rat body in vitexin-2 ''-O-rhamnoside intestinal absorption influence research.
Table 2: the medicine that vitexin-2 ''-O-rhamnoside intestinal absorption is affected by Borneolum Syntheticum moves parameter.
| Group | Dosage (mg/kg) | AUC0 → ∞ (g min/ml) |
| Duodenum group | 40 | 230.00±36.45 |
| Borneolum Syntheticum group | 40 | 628.54±25.55 |
From table 1, table 2, Fig. 1, Fig. 2, in intestinal first pass effect is tested, the apparent bioavailability of intestinal is 2.4%.Compared with duodenum group, Borneolum Syntheticum group bioavailability increases by 1.73 times.Vitexin-2 ''-O-rhamnoside occurs serious first pass effect mainly to be caused by its intestinal in vivo, i.e. for the first pass effect of flavone compound, its intestinal first pass effect plays prior effect than its liver metabolism, and in hepato-enteric circulation, intestinal circulation is more often available to explain the reason of the relatively low bioavailability of flavone compound.Borneolum Syntheticum is remarkably improved the bioavailability of vitexin-2 ''-O-rhamnoside, and its main cause is that Borneolum Syntheticum has the effect promoting intestinal infiltration as absorption enhancer.It addition, the P-glycoprotein being widely present in intestinal can reduce the transmembrane transport of medicine by the conveyer mechanism of efflux pump, become the absorption barrier of some drugs, and Borneolum Syntheticum can improve the intestinal absorption of vitexin-2 ''-O-rhamnoside as the inhibitor of P-glycoprotein.
Test example 2.
2.1, medicine and reagent.
Male ice drop pill is prepared from by the method for the present embodiment 1；Radix Salviae Miltiorrhizae drop pill: Tasly Pharmaceutical Group Co., Ltd.'s product, lot number: traditional Chinese medicines quasi-word Z10950111；Isoprenaline (Iso): Shanghai Hefeng Pharmaceutical Co., Ltd.'s product, lot number: traditional Chinese medicines quasi-word H31021344.
2.2, animal.
Wistar rat 90, male, body weight (200 ± 20) g, all laboratory animals and feedstuff are all purchased from the long-living Bioisystech Co., Ltd in Liaoning, rat quality certification SYXK (distant) 2010-0001.Room temperature 20～25 DEG C, free diet, laboratory adapt to one week after for testing.
2.3, experimental technique.
Wistar rat 90, it is randomly divided into 9 groups, it is respectively blank group, model group, vitexin-2 ''-O-rhamnoside low dosage (20mg/kg), middle dosage (40mg/kg), high dose (80mg/kg) group (is called for short glucosides low dose group, dosage group in glucosides, glucosides high dose group), and in the present embodiment male ice drop pill low dosage (20mg/kg), middle dosage (40mg/kg), high dose (80mg/kg) group (is called for short male ice low dose group, dosage group in male ice, male ice high dose group), Radix Salviae Miltiorrhizae drop pill (85mg/kg) positive controls (is called for short Radix Salviae Miltiorrhizae drop pill group).Vitexin-2 ''-O-rhamnoside low dose group, middle dosage group, high dose group, male ice drop pill low dosage, middle dosage, high dose group, and Radix Salviae Miltiorrhizae drop pill group all give corresponding treatment medicine gavage, every day 1 time, continuous 14 days；Blank group and model group gavage same volume distilled water (15mL/kg).Within last 3 days, in addition to blank group, remaining respectively organizes 1h lumbar injection isoproterenol (5mg/kg) respectively upon administration, to set up Model Rats with Acute Myocardial Ischemia, blank group corresponding lumbar injection equivalent (5mg/kg) normal saline.After last is administered 1h, use 10% chloral hydrate anesthesia, abdominal aortic blood.
2.4, Biochemical Indices In Serum measures.
Abdominal aortic blood 5-6mL, in the centrifuge tube of heparinization in advance, is centrifuged 10min(3000r/min), collect supernatant, use Roche cobas8000 biochemistry analyzer, original-pack reagent.
2.5, result.
Refer to table 3, for the impact (mean ± standard deviation, n=10) on Acute Myocardial Ischemia Rats myocardium enzyme content of the male ice drop pill.Comparing with blank group, model group creatine kinase MB, LDH and HBDH content significantly raise (P ＜ 0.05).Comparing with model group, vitexin-2 ''-O-rhamnoside low dose group, middle dosage group CK-MB, LDH, HBDH content is all without notable change, and CK-MB in high dose group, LDH, HBDH content substantially reduces.Male ice drop pill low dose group, middle dosage group, high dose group CK-MB, LDH, HBDH content more notable or pole compared with model group significantly reduces (P ＜ 0.05 or P ＜ 0.01), wherein, it is the most obvious that male ice drop pill low dosage and middle dosage group effect are substantially better than dosage group effect in high dose group, and male ice drop pill；Compare with Radix Salviae Miltiorrhizae drop pill group, male ice drop pill low dose group, middle dosage group, high dose group CK-MB, LDH, HBDH content difference not statistically significant.Result shows; only high dose group vitexin-2 ''-O-rhamnoside is remarkably improved the protective effect to rat isoprenaline induced Acute myocardial ischemic injury to the rat isoprenaline protected effect of induced Acute myocardial ischemic injury, the male ice drop pill of the present embodiment.
Table 3: each group of impact on Acute Myocardial Ischemia Rats myocardium enzyme content.
| Group | CK-MB(u/l) | LDH(u/l) | HBDH(u/l) |
| Blank group | 151.90±19.65 | 1397.33±101.03 | 493.33±25.93 |
| Model group | 219.07±14.15* | 2055.00±281.86* | 819.33±100.80* |
| Glucosides low dose group | 199.00±13.89 | 2005.33±23.44 | 796.33±26.43 |
| Dosage group in glucosides | 195.33±16.03 | 1986.00±47.62 | 789.67±14.57 |
| Glucosides high dose group | 170.67±12.58** | 1815.33±93.94** | 683.00±99.29** |
| Male ice low dose group | 179.27±18.43 | 1270.33±164.26** | 513.67±66.58** |
| Dosage group in male ice | 141.67±39.83** | 1147.67±271.61*** | 457.67±106.40** |
| Male ice high dose group | 156.43±31.47** | 1660.67±314.08** | 643.67±145.58** |
| Radix Salviae Miltiorrhizae drop pill group | 203.93±12.80 | 1792.00±179.97 | 687.00±85.26 |
Note: compare with blank group, * P ＜ 0.05；Compare with model group, * * P ＜ 0.05, * * * P ＜ 0.01.
Embodiment 2.
The present embodiment provides a kind of male ice drop pill treating acute myocardial ischemia, is made up of vitexin-2 ''-O-rhamnoside, Borneolum Syntheticum, drop pill substrate；Described vitexin-2 ''-O-rhamnoside is 4:3 with the ratio of weight and number of Borneolum Syntheticum；Described drop pill substrate is 6:1 with the ratio of weight and number of vitexin-2 ''-O-rhamnoside, and described drop pill substrate is PEG4000.
The present embodiment also provides for the preparation method of a kind of male ice drop pill treating acute myocardial ischemia, comprises the steps.
Step 1, weigh vitexin-2 ''-O-rhamnoside, Borneolum Syntheticum by formula proportion, join in melted PEG4000, obtain mixed liquor.
Step 2, described mixed liquor is continued heating, be stirred continuously, make uniform melted medicinal liquid.
Step 3, described melted medicinal liquid is transferred in reservoir, regulates pill dripping machine temperature control system, under being incubated at 80 DEG C～90 DEG C, described melted medicinal liquid is passed through pill dripping machine water dropper, with 50 min-1Speed instill in the vegetable oil of-15 DEG C～-5 DEG C, obtain solid solution.
Step 4, after described solid solution cooling meat pelletization shape, the drop pill in pill dripping machine exit is taken out, removes surface condensation agent, be drying to obtain the present embodiment male ice drop pill.
Embodiment 3.
The present embodiment provides a kind of male ice drop pill treating acute myocardial ischemia, is made up of vitexin-2 ''-O-rhamnoside, Borneolum Syntheticum, drop pill substrate；Described vitexin-2 ''-O-rhamnoside is 4:3 with the ratio of weight and number of Borneolum Syntheticum；Described drop pill substrate is 7:1 with the ratio of weight and number of vitexin-2 ''-O-rhamnoside, and described drop pill substrate is made up of PEG4000 with PEG6000, and the ratio of weight and number of described PEG4000 Yu PEG6000 is 1:1.
The present embodiment also provides for the preparation method of a kind of male ice drop pill treating acute myocardial ischemia, comprises the steps.
Step 1, weigh vitexin-2 ''-O-rhamnoside, Borneolum Syntheticum by formula proportion, join in melted PEG4000 Yu PEG6000, obtain mixed liquor.
Step 2, mixed liquor is continued heating, be stirred continuously, make uniform melted medicinal liquid.
Step 3, described melted medicinal liquid is transferred in reservoir, regulates pill dripping machine temperature control system, under being incubated at 80 DEG C～90 DEG C, described melted medicinal liquid is passed through pill dripping machine water dropper, with 30 min-1Speed instill in-15 DEG C～-5 DEG C of dimethicones, obtain solid solution.
Step 4, after described solid solution cooling meat pelletization shape, the drop pill in pill dripping machine exit is taken out, removes surface condensation agent, be drying to obtain the present embodiment male ice drop pill.
Claims (9)
1. treat a male ice drop pill for acute myocardial ischemia, be made up of vitexin-2 ''-O-rhamnoside, Borneolum Syntheticum and drop pill substrate；In described male ice drop pill, every ball contains vitexin-2 ''-O-rhamnoside 1～10mg, Borneolum Syntheticum 1～5mg.
2. the male ice drop pill treating acute myocardial ischemia as claimed in claim 1, it is characterised in that described vitexin-2 ''-O-rhamnoside is 3～10:3 with the ratio of weight and number of Borneolum Syntheticum；Described drop pill substrate is 10～1:1 with the ratio of weight and number of vitexin-2 ''-O-rhamnoside.
3. the male ice drop pill treating acute myocardial ischemia as claimed in claim 1, it is characterised in that described vitexin-2 ''-O-rhamnoside is the monomeric compound extracting isolated from Folium Crataegi.
4. the as claimed in claim 1 male ice drop pill treating acute myocardial ischemia, it is characterised in that described drop pill substrate is Macrogol 4000 and the mixed liquor of any one or they in polyethylene glycol 6000.
5. the preparation method of the male ice drop pill for the treatment of acute myocardial ischemia as claimed in claim 1, it is characterised in that comprise the steps:
Step 1, weigh vitexin-2 ''-O-rhamnoside, Borneolum Syntheticum by formula proportion, join in melted drop pill substrate, obtain mixed liquor；
Step 2, described mixed liquor is continued heating, be stirred continuously, make uniform melted medicinal liquid；
Step 3, described melted medicinal liquid is transferred in reservoir, regulates pill dripping machine temperature control system, under insulation will described melted medicinal liquid by pill dripping machine water dropper, in suitable speed instillation condensing agent, to obtain solid solution；
Step 4, after described solid solution cooling meat pelletization shape, the drop pill in pill dripping machine exit is taken out, removes surface condensation agent, be drying to obtain the present invention male ice drop pill.
6. the male ice drop pill treating acute myocardial ischemia as claimed in claim 5, it is characterised in that described condensing agent is liquid paraffin, vegetable oil or dimethicone.
7. the preparation method of the male ice drop pill for the treatment of acute myocardial ischemia as claimed in claim 5, it is characterised in that in described step 3, the temperature of insulation is 70 DEG C～90 °.
8. the preparation method of the male ice drop pill for the treatment of acute myocardial ischemia as claimed in claim 5, it is characterised in that in described step 5, the temperature of condensing agent is-15 DEG C～20 DEG C.
9. the preparation method of the male ice drop pill for the treatment of acute myocardial ischemia as claimed in claim 5, it is characterised in that speed suitable in described step 3 is 20～60 min-1。
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| CN101050226A (en) * | 2007-05-10 | 2007-10-10 | 辽宁中医药大学 | Method for separating derivative of vitexin |
| CN101849918A (en) * | 2010-05-27 | 2010-10-06 | 辽宁中医药大学 | Vitexin-2''-O-rhamnoside pill and preparation method |
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- 2015-05-20 CN CN201510258488.2A patent/CN106265706A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101050226A (en) * | 2007-05-10 | 2007-10-10 | 辽宁中医药大学 | Method for separating derivative of vitexin |
| CN101849918A (en) * | 2010-05-27 | 2010-10-06 | 辽宁中医药大学 | Vitexin-2''-O-rhamnoside pill and preparation method |
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