CN1593473B - Application of a pharmaceutical composition in the preparing process of medicine for treating chronic alcohol intake caused injury - Google Patents
Application of a pharmaceutical composition in the preparing process of medicine for treating chronic alcohol intake caused injury Download PDFInfo
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Abstract
The invention relates to the novel use of pharmaceutical preparations in the field of pharmacy, wherein the damnification caused by chronic alcohol assimilation for rat is selected as a model, favorable improvement by the pharmaceutical composition has been shown for the microcirculatory disturbance occurred after chronic alcohol assimilation. In addition, rat with liver damnify caused by ischemia re-perfusion is also selected as a model, wherein the test result has shown that the liver microcirculatory disturbance and inflammatory reaction caused by ischemia re-perfusion can be improved.
Description
Technical field
The invention belongs to field of medicaments, specifically relate to the application of a kind of pharmaceutical composition in the microcirculation disturbance medicine that preparation treatment chronic drinking causes.
Background technology
The damage (Injury caused by chronic alcohol ingestion) that chronic ethanol picked-up causes can cause that the fact of multiple disease is generally acknowledged widely.Its damage relates to a lot of organs such as nervus centralis and digestive system.Although people have just had realized that the adverse consequences of excessive drinking for a long time, but its pathophysiological mechanism also is not very clear (Bauer, I, Bauer M, Pannen BH, Leinwand MJ, Zhang JX, and Clemens MG.Chronic ethanol consumptionexacerbates liver injury following hemorrhagic shock:role of sinusoidal perfusion failure.Shock 4:324-331,1995).
At present, the damage round chronic ethanol picked-up causes has had some basic research.
(Mall such as Mall, G, Mattfeldt T, Rieger P, Volk B, and Frolov VA.Morphometric analysis ofthe rabbit myocardium after chronic ethanol feeding-early capillary changes.Basic Res Cardiol 77:57-67,1982) reported that use ethanol feeds male 3 weeks, the result shows that change has taken place the morphological feature of a cell in the blood capillary, and is unusual but muscle cell does not take place.This hypertrophy may change relevant with the metabolism that ethanol causes, and is similar to very much secular histanoxia.In addition, also having some evidences to show the only common change after each organ ethanol picked-up of this variation, may be the commitment of blood capillary proliferation.
(Mayhan such as Mayhan WG, WG, and Didion SP.Effect of chronic alcohol consumption onresponses of cerebral arterioles.Alcohol Clin Exp Res 20:538-542,1996) reported and used the liquid feed (liquid diet) that has/do not have ethanol to feed mice 2 to 2.5 months.Measured the diameter of two groups of intravital mantle arterioles of mice.The result shows that secular ethanol picked-up has damaged the expanding mechanism of brain arteriole after for the activation of the potassium-channel of adenyl cyclase or ATP sensitivity.Shown that the vasodilation mechanism damaged may have very important relation with the poison pathogeny of the big abnormalities of brain that causes of long term alcohol during chronic drinking.
(Bauer such as Bauer, M, Paquette NC, Zhang JX, Bauer I, Pannen BH, Kleeberger SR, andClemens MG.Chronic ethanol consumption increases hepatic sinusoidal contractile response toendothelin-1 in the rat.Hepatology 22:1565-1576,1995) reported that chronic drinking can increase the responsiveness of hepatic sinusoid for vasoconstrictive factor Endothelin (endothelin)-1, this may increase the mice fed through ethanol to such as the susceptibility of endotoxin in interior secondary stress.
(Ohki, E, Kato S such as Ohki, Horie Y, Mizukami T, Tamai H, Yokoyama H, Ito D, FukudaM, Suzuki H, Kurose I, and Ishii H.Chronic ethanol consumption enhances endotoxin inducedhepatic sinusoidal leukocyte adhesion.Alcohol Clin Exp Res 20:350A-355A, 1996) reported the leukocytic adhesion of hepatic sinusoid of drinking for a long time and having improved endotaxin induction.
(Liu such as Liu, YY, Miura S, Suzuki H, Kurose I, Fukumura D, Suzuki M, Suematsu M, and Tsuchiya M.Quantitative analysis of mesenteric microcirculatory disturbances induced byautonomic nervous irritation.Keio J Med 41:128-133,1992) ischemia-reperfusion of finding organ can cause damage, and often with the damage of endothelium, albumen oozes out, adhesion and the venular leucocyte migration of terminal blood capillary.
From above basic research as can be seen, chronic ethanol picked-up can cause various damages, especially behind ischemia-reperfusion, its microcirculation disturbance, comprise that blood flow rate, leukocyte compare with general rat with generation, spilling with mast cell degranulation etc. of plasma albumin that blood vessel endothelium adheres to quantity, blood vessel wall peroxide, remarkable increase is all arranged.
The inventor has applied for the pharmaceutical composition patent, publication number: CN1348815A, be made up of Radix Salviae Miltiorrhizae, Radix Notoginseng etc.It is under the guidance of motherland's theory of medicine, and sums up through clinical practice for many years and to form, and has that treatment is uncomfortable in chest, an effect of cardiopalmus etc., is applicable to precordialgia that angina pectoris causes, symptom such as feel oppressed in the heart clinically.In this prescription ratio, can make any dosage form on the pharmaceutics.Drops is wherein produced by Tianjin Tasly Pharmaceutical Co., Ltd, and name is called " FUFANG DANSHEN DIWAN ", gets permission code and defends the accurate word Z-01 of medicine for (95), and " function with cure mainly " is activating blood circulation to dissipate blood stasis, regulating QI to relieve pain.Be used for feeling oppressed in the heart angina pectoris etc.Be mainly used in clinically the treatment angina pectoris uncomfortable in chest, chest pain and cardio palmus shape extremely.Because its definite curative effect since listing, has won the trust of extensive patients.Its single variety sales volume broke through 1,000,000,000, occupies on the domestic Chinese patent medicine market first, and had passed through the IND preliminary hearing of U.S. FDA in 1997, and become China first enters the Chinese patent medicine kind of American market with the medicine identity.
Through clinical experimental research in recent years, the range of application of FUFANG DANSHEN DIWAN has obtained further expansion.At present confirmed that it has the effect of following aspect: the diastole coronary artery; Anticoagulant reduces thrombosis; Improve myocardial ischemia, strengthen left ventricular function; Blood fat reducing alleviates atherosclerosis; Change the erythrocyte membrane phospholipid composition, keep the complete of cell membrane; Antioxidation delays the aging of cell; The retardance calcium channel, the antagonism arrhythmia, or the like, and be applied to corresponding disease treatment (Chinese patent CN1348815A).So far, do not find the damage that FUFANG DANSHEN DIWAN causes in the chronic ethanol picked-up of treatment as yet, and the report of the liver protecting aspect.
Summary of the invention
The present invention is on the basis of Chinese patent [publication number: CN1348815A], the new purposes invention of finishing, and the composition and the weight proportion of prescription are as follows:
Radix Salviae Miltiorrhizae 48-97% Radix Notoginseng 2-50% Borneolum Syntheticum 0.2-3%
Wherein the best proportioning of each component is:
Radix Salviae Miltiorrhizae 82.87% Radix Notoginseng 16.21% Borneolum Syntheticum 0.92%.
The main preparation methods of the present composition is: get Radix Salviae Miltiorrhizae, the pseudo-ginseng of pulverizing, boiling water decocts, filter, and merging filtrate, and filtrate is suitably concentrated; Add ethanol and precipitate in concentrated solution, leave standstill, supernatant reclaims ethanol, is condensed into extractum; Behind gained extractum and Borneolum Syntheticum and adjuvant mix homogeneously, make preparation.
Concrete production method is as follows:
1. take by weighing Radix Salviae Miltiorrhizae, the pseudo-ginseng of pulverizing according to the above ratio, add water, heating extraction 2～4 times, extracting temperature is 60～100 ℃, and each amount of water is 4～8 times of medical material amount, and leach cooking liquid filters, merging filtrate, filtrate are concentrated into medicine liquid volume and the medical material weight ratio is 1 liter: 0.7～1.3 kilogram;
2. add 95% ethanol in concentrated solution, making determining alcohol is 50～85%, leaves standstill 4～24 hours, and supernatant filters, filtrate recycling ethanol, and the simmer down to relative density is 1.15～1.45 extractum;
3. with behind gained extractum and aforementioned proportion Borneolum Syntheticum and the adjuvant mix homogeneously, make preparation.
Pharmaceutical preparation of the present invention can be said dosage form on any pharmaceutics, and wherein preferred dosage form is a drop pill, and it is shaped as rufous-brownish black round bead shape, and size evenly.
The main preparation methods of the dropping pill formulation of medicine of the present invention adds the transconversion into heat material for above-mentioned resulting extractum is mixed with Borneolum Syntheticum and adjuvant, moves in the drip irrigation of drop pill machine, and medicine liquid droplet is removed liquid paraffin to cryogenic liquid paraffin, select ball, promptly.
Wherein, adjuvant is a Polyethylene Glycol-6000, and addition is extractum and Borneolum Syntheticum weight 2～6 times; Changing the material temperature is 60～100 ℃; The temperature of liquid paraffin is 0～10 ℃ (optimum temperature is 5～10 ℃); Ball heavily is 5～50mg/ grain, and diameter is 1.95～4.29mm.
From above-mentioned basic research we as can be seen, the damage (Injury caused by chronic alcoholingestion) that chronic ethanol picked-up causes can cause multiple disease, its pathologic basis and microcirculation have close getting in touch, but aspects such as pathogenesis and Therapeutic Method have tangible difference again.At present, the damage that picked-up causes for the chronic ethanol definite medicine that also is of no curative effect.
The present invention by observe FUFANG DANSHEN DIWAN to chronic ethanol picked-up rat mesentery ischemia-reperfusion after the dynamic effects (comprising that leukocyte and blood vessel endothelium adhere to quantity, the blood vessel wall peroxide produces dynamic, mast cell degranulation) of microcirculation disturbance, improvement effect with the Liver Microcirculation that ischemia-reperfusion is caused, come the objective evaluation FUFANG DANSHEN DIWAN to improve the damage that chronic ethanol causes, and the effect of Liver Microcirculation behind the ischemia-reperfusion, and inquire into its action principle.
In order to understand content of the present invention better, below by this patent drug---FUFANG DANSHEN DIWAN, the result of the test in the microcirculation disturbance animal model that ischemia-reperfusion causes illustrates its new purposes in pharmaceutical field.
Picked-up causes the rat microcirculation improvement effect that damages to experimental example one FUFANG DANSHEN DIWAN to chronic ethanol
Object and method
1, laboratory animal
Answer the regulation of university of private school charging no tuition medical board Experimental Animal Center by celebrating, the Wistar male rat (body weight is 100g, Charles River laboratory animal, Tokyo) of weight such as get, pairing divides cage, raises by the method for Lieber.Both used protein 18%, fat 36%, the comprehensive nutrient liquid feed (Liquid rat diet, Bio-Serv, Frenchcown, NJ, USA) of carbohydrate 47% to raise for 8 weeks, as non-ethanol matched group. with 36% of the carbohydrate energy in the comprehensive nutrient liquid feed change into the ethanol of homenergic, continuously raise 8 weeks, as chronic ethanol picked-up group.
2, the foundation of ischemia-reperfusion injury model
With the rats raised in 8 weeks, anaesthetize by the dosage lumbar injection pentobarbital sodium of 30mg/kg.Insert and put 3G polyethylene pipe from right external jugular vein.Cut the long otch of 2-3cm along the abdomen median line, gently the ileum of nearly ileocecus is moved to outside the abdominal cavity, mesentery is launched on the platen with thin slide.Be holding temperature and humidity, continue the Krebs-Ringer buffer of 37 ℃ of droppings on unfolded mesenteric mesaraic surface.Mesentery is microcirculatory dynamically, with inverted biological microscope (DiaphotTMD-2S, Nikon, the Tokyo) observation that places in 37 ℃ of temperature chambers, and uses the high sensitivity camera photography, the S-VHS video-recorder recording.Select diameter to be look-out station at non-branch of the thin vein between the 25-40 μ m (more than the long 200 μ m).After 10 minutes bases are observed, will also flow mesentery artery and vein vascular ligation 10 minutes (ischemia) simultaneously with 4G polyethylene pipe in observation portion, remove ligation (pouring into again), time recorder is transferred to 0 place.Observed 30 minutes continuously at the same visual field.
It is non-processing matched group that non-ethanol matched group and chronic ethanol picked-up group are not carried out the ischemia-reperfusion processor.
3, the medication of FUFANG DANSHEN DIWAN
Before 60 minutes, press the dosage of 0.4g/kg at ischemia-reperfusion, FUFANG DANSHEN DIWAN (Tianjin Tasly Pharmaceutical Co., Ltd, Tianjin) is used physiological saline solution, disposable filling stomach.
4, microcirculation is observed dynamically
The adhesion quantity of leukocyte and blood vessel endothelium: by being connected in the CCD camera of inverted biological microscope, direct observation and video recording on film viewing screen, to on the same position of thin vein, stop the leukocyte more than 10 seconds, be decided to be the leukocyte that adheres to blood vessel endothelium, count and calculate the leukocytic quantity of adhesion in every 100um.
Thin vein wall peroxide produces dynamically: at ischemia-reperfusion before 10 minutes, the peroxide susceptibility luminescent substance dihydo rhodamine 123 (DHR, Molecular probes USA) of 10 μ mol concentration is dripped the mesentery surface at look-out station constantly, when peroxide and DHR meet, DHR can be reduced into rhodamine (rhodamine) 123, rhodamine 123 can combine with the DNA mitochondrial DNA film and rest in the cell.With fluorescence microscopy camera system (C-2400-08, the shore pine), at excitation wavelength is 420-490um, and emission wavelength is under the condition of 520um, can observe and writes down DHR by the former fluorescence intensity (hereinafter to be referred as the DHR fluorescence intensity) that becomes rhodamine 123 and produce of peroxide.Measure the DHR fluorescence intensity of thin vein wall and mesentery tissue continuously with image digital processing system (NIH Image 1.35), the value that deducts the DHR fluorescence intensity gained of mesentery tissue with the DHR fluorescence intensity of thin vein wall before the ischemia-reperfusion is a basic value; Wait the difference and the basic value of the DHR fluorescence intensity of measured and the thin vein wall that calculates and mesentery tissue of each time limit with perfusion again, expression DHR fluorescence intensity through the time change, dynamic with this generation of judging thin vein wall peroxide.
Mesentery mast cell degranulation rate: after ischemia-reperfusion was observed and finished in 30 minutes, the toluidine blue with 0.1% (toluidineblue) dripped in the mesentery surface, after one minute, washes the mesentery surface lentamente with normal saline.With the high sensitivity camera chain that is connected in inverted biological microscope, along 5 visuals field of blood vessel record of observing, counting takes off granule and not degranulated mastocyte number, and the percentage that accounts for the mastocyte sum of counting with degranulated mastocyte is recently represented the mast cell degranulation rate.
Each measured value of every group of 6 rats is handled with one-way analysis of variance (ANOVA), Fisher ' s post hoctest check.Each is organized numerical value and represents that with average ± standard error establishing P＜0.05 is significance.
The result
1, FUFANG DANSHEN DIWAN adheres to the influence of quantity of leucocyte to thin vein
Before ischemia, between non-smart matched group and the ethanol picked-up group, the leukocyte count that adheres to thin vein does not have significant difference.Non-processed group was observed when finishing at 30 minutes, the adhesion number of non-ethanol matched group be 3.5 ± 2.2 (/ 100um), the adhesion number of ethanol picked-up group be 3.9 ± 2.3 (/ 100um), and behind the ischemia-reperfusion, the adhesion leukocyte count of non-ethanol matched group and ethanol picked-up group all significantly increases, particularly the adhesion leukocyte count of ethanol picked-up group after perfusion again 20 minutes, further increase, significantly more than non-ethanol matched group.Use FUFANG DANSHEN DIWAN, no matter be non-ethanol matched group, or ethanol picked-up group, it adheres to leukocyte and is all suppressed significantly.
2, FUFANG DANSHEN DIWAN is to the influence of thin vein DHR fluorescence intensity
In non-processed group, non-ethanol matched group and ethanol picked-up group rat mesentery thin vein DHR fluorescence intensity do not have significant change in 30 minutes viewing duration.Non-ethanol matched group and ethanol picked-up group rat mesentery thin vein DHR fluorescence intensity before ischemia does not have difference.Behind the ischemia-reperfusion, the mesentery thin vein DHR fluorescence intensity of ethanol picked-up group rat begins to increase, and pouring into after 20 minutes further increases again.But not the mesentery thin vein DHR fluorescence intensity of ethanol control rats begins when pouring into 10 minutes again to increase, and what increase later on is not obvious.Use Composite Salvia Dropping Pill group, no matter be non-ethanol matched group, or ethanol picked-up group, its mesentery thin vein DHR fluorescence intensity has all been suppressed significantly.
3, FUFANG DANSHEN DIWAN is to the influence of mast cell degranulation rate
After pouring into 30 minutes, non-processed group rat also has mesentery mast cell degranulation phenomenon again.But, there is not significant difference between non-ethanol matched group and the ethanol picked-up group, after the ischemia-reperfusion, the mesentery mast cell degranulation rate of non-ethanol matched group and ethanol picked-up group significantly increases.But, do not have significant difference between two groups.Use Composite Salvia Dropping Pill group, the mesentery mast cell degranulation rate that non-ethanol matched group and ethanol picked-up group are organized in non-ethanol matched group and ethanol picked-up all significantly reduces.Wherein, the mesentery mast cell degranulation rate of non-ethanol matched group is reduced to non-processed group level.
Conclusion
Test us as can be seen by this, FUFANG DANSHEN DIWAN not only can be improved the microcirculation disturbance that general rat causes behind ischemia-reperfusion, and the excessive microcirculation disturbance that takes place for chronic ethanol picked-up rat behind the ischemia-reperfusion also improves significantly.The discovery of this effect of FUFANG DANSHEN DIWAN for enlarging range of application clinically, provides theoretical support.In addition, FUFANG DANSHEN DIWAN improves that chronic ethanol picked-up rat is taken place behind the ischemia-reperfusion excessive microcirculation disturbance effect can suppress with it that leukocyte adheres to the thin vein endothelium, the peroxide of removing blood vessel wall, inhibition mast cell degranulation are relevant.
The preventive effect of the Liver Microcirculation that experimental example two FUFANG DANSHEN DIWAN cause Ischemia and Reperfusion in vivo in Rats
This real purpose is to test by the rat abdominal cavity tremulous pulse is carried out causing ischemia-reperfusion injury model after the ligation, investigates the influence of FUFANG DANSHEN DIWAN to its microcirculation disturbance.
Method
Answer the regulation of university of private school charging no tuition medical board Experimental Animal Center by celebrating, the Wistar male rat (body weight is 200～250g, Tokyo) of weight such as get, lumbar injection sodium phenobarbital (35mg/kg) is anaesthetized.After the dissection, observe lobe of the liver, use fluorescence microscopy camera system (C-2400-08, shore pine, Shizuoka, Japan) to write down its image by inverted biological microscope (TMD-2S, Diaphoto, Nikon, Tokyo, Japan).Lobe of the liver is placed on adjustable resin microscope desk.By successive liver microcirculation trace fluorogram, observe and write down the surperficial microcirculation situation of liver, that is to say, at the tremulous pulse generation infraction back 90min of nearly mesentery end, the leukocyte of the rhodamine-6G labelling that use digital camera record hole shape is.With the hole shape is to stop the leukocyte that surpassed for 10 seconds in the microcirculation, is decided to be the leukocyte that adheres to blood vessel.In each microexamination zone, serve as the percentage rate (NPS) that calculates non-perfusion hole shape system with the ratio of non-dabbling hole shape system and total hole shape system.Rat carries out the ischemia of 30min before 60min pours into again.Pour into tumor necrosis factor (TNF) and the level of endotoxin measured in the blood plasma in back 1 hour again; Pour into again and measured alanine aminotransferase (ALT) activity in the blood plasma in back 6 hours.In other one group of experiment, gave in preceding 1 hour and 24 hours and FUFANG DANSHEN DIWAN (0.8g/kg,, intragastric administration, the production of Chinese Tianjin Tasly Pharmaceutical Co., Ltd) at ischemia.Getting blood plasma near hepatic vein place venae subcutaneae.Use standard statistical routines,, data are analyzed as ANOVA and Scheffe ' s (post hoc) test.All numerical value are represented with mean+SD, establish P＜0.05 for having significant difference.
Result and discussion
Control rats, the ischemia-reperfusion of coeliac artery can cause leukocyte adhesion quantity to increase, and non-perfusion hole shape is the rising of indexs such as tumor necrosis factor (TNF) in percentage rate (NPS), the blood plasma, endotoxin and alanine aminotransferase (ALT) activity; Take FUFANG DANSHEN DIWAN and can obviously alleviate above-mentioned these variation (see figure 1)s.This experiment has shown that FUFANG DANSHEN DIWAN can be by reducing leukocyte adhesion, the blood capillary obstacle that prevents the coeliac artery ischemia-reperfusion to cause.Because FUFANG DANSHEN DIWAN can reduce endotoxic increase in the blood plasma that the abdominal cavity ischemia-reperfusion causes, so the reduction of level of endotoxin also may reduce the leukocyte adhesion that the abdominal cavity ischemia-reperfusion causes.Although the protective effect of internal organs may seem to have played very important effect on reduction plasma endotoxin level, FUFANG DANSHEN DIWAN can increase the endotoxic ability of hepatic clearance.And, FUFANG DANSHEN DIWAN, this being in the news has the medicine of prevention lipid peroxidation, also may directly prevent the peroxide of the hepatic sinusoid that the coeliac artery ischemia-reperfusion causes to increase.Such result has shown that FUFANG DANSHEN DIWAN can be improved microvascular dysfunction of liver and the inflammatory reaction that the coeliac artery ischemia-reperfusion causes, as level of endotoxin produces tumor necrosis factor (TNF) in the blood plasma by reducing.
Description of drawings
Fig. 1, FUFANG DANSHEN DIWAN to rat abdominal cavity tremulous pulse ischemia after 30min and perfusion back 60min leukocyte adhesion quantity (panel A) and pour into alanine aminotransferase (ALT) active (panel B) in back 6 hours blood plasma more again.Wherein, vertical coordinate is followed successively by among the panel A: matched group (control), not treatment group+ischemia-reperfusion (untreated+I/R), composite salvia dropping pill for curing group (CP), composite salvia dropping pill for curing group+ischemia-reperfusion (CP+I/R), abscissa are leukocytic adhesion quantity in each viewing area; Vertical coordinate is followed successively by among the panel B: matched group (control), not treatment group+ischemia-reperfusion (untreated+I/R), composite salvia dropping pill for curing group (CP), composite salvia dropping pill for curing group+ischemia-reperfusion (CP+I/R), abscissa are alanine aminotransferase in the blood plasma (ALT) activity.
Illustrate: compound danshen dripping pills can reduce significantly that leukocyte adhesion that the arteria coeliaca ischemia-reperfusion causes increases and blood plasma in alanine aminotransferase (ALT) activity. Every treated animal number is 5, with the control group ratio*P＜0.05; Be that treatment group+ischemia-reperfusion is than #P＜0.05.
The specific embodiment
The present invention is further illustrated below in conjunction with embodiment, and following this embodiment only is used to the present invention is described and to the present invention without limits.
Embodiment 1
1. prescription consumption: Radix Salviae Miltiorrhizae 41.06g, Radix Notoginseng 8.03g, Borneolum Syntheticum 0.46g, adjuvant Polyethylene Glycol-6000 18g makes 1000 drop pill.
2. the extraction of Radix Salviae Miltiorrhizae, Radix Notoginseng: the Radix Salviae Miltiorrhizae after the pulverizing of learning from else's experience, pseudo-ginseng add the water of 5 times of amounts to extraction pot, decocted 2 hours, filter, and medicinal residues carry out the second time and extract, and add the water of 4 times of amounts, decoct 1 hour, filter, and medicinal residues discard, merging filtrate.Filtrate decompression is concentrated into medicine liquid volume (L) and medical material weight (Kg) than being 1: 0.9～1.1, slowly adds 95% ethanol, and the alcohol that contains of medicinal liquid is measured 69～71%, leaves standstill 12 hours.Get the supernatant of medicinal liquid behind the precipitate with ethanol, filter, filtrate recycling ethanol, the simmer down to relative density is 1.32～1.40 extractum.
3. the preparation of product: get above-mentioned extractum and Borneolum Syntheticum, with polyethylene glycol 6000 18g mix homogeneously, being heated to temperature is 85～90 ℃, changes material after 20～120 minutes, moves to and drips in the jar, maintains the temperature at 85～90 ℃.In ℃ liquid paraffin of medicine liquid droplet to 7～8, take out drop pill, ball is selected in oil removing, promptly.
Embodiment 2
1. prescription consumption: Radix Salviae Miltiorrhizae 31.12g, Radix Notoginseng 9.21g, Borneolum Syntheticum 0.50g, adjuvant Polyethylene Glycol-600020g makes 1000 drop pill.
2. extraction of Radix Salviae Miltiorrhizae, Radix Notoginseng and preparation of product and feature are with embodiment 1.
Embodiment 3
1. prescription consumption: Radix Salviae Miltiorrhizae 59.36g, Radix Notoginseng 6.38g, Borneolum Syntheticum 0.34g, adjuvant are Polyethylene Glycol-6000 21g, make 1000 drop pill.
2. extraction of Radix Salviae Miltiorrhizae, Radix Notoginseng and preparation of product and feature are with embodiment 1.
Embodiment 4
1. prescription consumption: Radix Salviae Miltiorrhizae 41.06g, Radix Notoginseng 8.03g, Borneolum Syntheticum 0.46g, supplementary product starch 9g and dextrin 9g make 500 tablets.
2. the extraction of Radix Salviae Miltiorrhizae, Radix Notoginseng is with embodiment 1.
3. preparation of product: with above-mentioned extractum and supplementary product starch and dextrin mix homogeneously, add suitable water, make granule, tabletting, promptly.
Claims (2)
1. the application of pharmaceutical composition in the medicine of the damage that the chronic ethanol picked-up of preparation treatment causes, the damage that described chronic ethanol picked-up causes is the microcirculation disturbance that the increase of thin vein adhesion quantity of leucocyte causes; Wherein the composition of said composition and weight proportion thereof are as follows:
Radix Salviae Miltiorrhizae 48-97%, Radix Notoginseng 2-50%, Borneolum Syntheticum 0.2-3%;
Wherein, described pharmaceutical composition adopts following method to be prepared from: get Radix Salviae Miltiorrhizae, pseudo-ginseng, boiling water decocts, filter, and merging filtrate, and filtrate is suitably concentrated; Add ethanol and precipitate in concentrated solution, leave standstill, supernatant reclaims ethanol, is condensed into extractum; With extractum and Borneolum Syntheticum and Polyethylene Glycol-6000 mix homogeneously, make drop pill.
2. application according to claim 1 is characterized in that the composition of described compositions and weight proportion thereof are as follows:
Radix Salviae Miltiorrhizae 82.87%, Radix Notoginseng 16.21%, Borneolum Syntheticum 0.92%.
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| CN 03144259 CN1593473B (en) | 2003-09-10 | 2003-09-10 | Application of a pharmaceutical composition in the preparing process of medicine for treating chronic alcohol intake caused injury |
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| CN 03144259 CN1593473B (en) | 2003-09-10 | 2003-09-10 | Application of a pharmaceutical composition in the preparing process of medicine for treating chronic alcohol intake caused injury |
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| CN1593473A CN1593473A (en) | 2005-03-16 |
| CN1593473B true CN1593473B (en) | 2010-04-28 |
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| CN102048818A (en) * | 2009-11-05 | 2011-05-11 | 天津天士力制药股份有限公司 | Total salvianolic acid, panax notoginseng saponins, and compatibility thereof in prevention and treatment of diseases caused by microcirculatory disturbance |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1348815A (en) * | 2001-11-09 | 2002-05-15 | 天津天士力制药股份有限公司 | Medicine for preventing and treating coronary heart disease and angina pectoris and its prepn and other use |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1348815A (en) * | 2001-11-09 | 2002-05-15 | 天津天士力制药股份有限公司 | Medicine for preventing and treating coronary heart disease and angina pectoris and its prepn and other use |
Non-Patent Citations (2)
| Title |
|---|
| 赖凌燕.丹参对实验性酒精肝损伤保护作用的初步研究.广西医科大学学报16 4.1999,16(4),480-481. |
| 赖凌燕.丹参对实验性酒精肝损伤保护作用的初步研究.广西医科大学学报16 4.1999,16(4),480-481. * |
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