CN1524528A - Medicament composition for treating coronary heart disease - Google Patents
Medicament composition for treating coronary heart disease Download PDFInfo
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- CN1524528A CN1524528A CNA031173691A CN03117369A CN1524528A CN 1524528 A CN1524528 A CN 1524528A CN A031173691 A CNA031173691 A CN A031173691A CN 03117369 A CN03117369 A CN 03117369A CN 1524528 A CN1524528 A CN 1524528A
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- total alkali
- rhizoma chuanxiong
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Abstract
The invention discloses a medicament for treating coronary disease and angina pectoris, the percentage by weight of the ingredients of which are, Ligusticum wallichii total aldali extract 60-95%, borneol 5-40%. The objective of the invention is to provide clinic with a novel, quick-effective, highly performance, low toxic and small dosage medicament, increase the selectivity for clinical medicament, prevent the survivability as the result of long-term administration.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition, particularly treat coronary heart disease, anginal pharmaceutical composition.
Background technology
Coronary heart disease, angina pectoris are cardiovascular commonly encountered diseases and frequently-occurring disease, also are one of difficult treatments.According to statistics, in the per 3 routine death of the whole world 1 example just being arranged is by due to the cardiovascular disease.Now along with the raising of people's living standard, the cardiovascular disease that have the title of " rich man's disease " has ascendant trend gradually, therefore is badly in need of a kind of novel quick-acting, specific medicament efficiently clinically.
Be used for the treatment of coronary heart disease at present, anginal first aid medicine mainly contains Ligustrazine Hydrochloride Injection, SUXIAO JIUXIN WAN, nitroglycerin buccal tablets etc. are though the Western medicine determined curative effect is rapid, because himself toxic and side effects is limited to day by day.In recent years, reports such as some untoward reaction due to quiet of the relevant ligustrazine hydrochloride such as drug eruption, vasodilation, upper gastrointestinal hemorrhage, asthma, anaphylaxis increase gradually.Though SUXIAO JIUXIN WAN belongs to pure Chinese medicinal preparation,, cause taking dose bigger than normal because it adopts raw medicinal material directly to be used as medicine.Add after patient takes a kind of medicine for a long time, be easy to generate toleration.
Summary of the invention
Purpose of the present invention is intended to increase the selection of clinical application for the medicine of a kind of novel, quick-acting, efficient, low toxicity, low dosage is provided clinically, avoids taking for a long time the generation toleration.
The present invention directly adopts the effective site of Rhizoma Chuanxiong---and Rhizoma Chuanxiong total alkali extract is used as medicine, so both can reduce taking dose, reduce toxic and side effects, can avoid again simultaneously because of crude drug source is different cause batch with batch between the possibility that there are differences, make feed intake more accurate, be aided with Borneolum Syntheticum, to strengthen the effect of Rhizoma Chuanxiong total alkali extract.
Technical scheme of the present invention is: a kind of coronary heart disease, anginal pharmaceutical composition of being used for the treatment of is provided, and its composition is by weight: Rhizoma Chuanxiong total alkali extract 60～95%, Borneolum Syntheticum 5～40%.Aforementioned pharmaceutical compositions can be made into the medicine of the peroral dosage form of treatment cardiovascular and cerebrovascular disease.
Pharmaceutical composition of the present invention has following effect:
1, improves the myocardial nutritional flow amount, reduce myocardial oxygen consumption.
2, the expansion coronary vasodilator increases coronary flow.
3, reduce blood viscosity, improve hemorheological property.
4, the generation of anticoagulant and haemoglutinin.
5, have the thrombotic effect that prevents, but but also thrombolytic.
6, enhancing human body immunity function.
7, effect rapidly.
The specific embodiment
The present invention realizes by the following specific embodiment:
A kind of treatment treatment coronary heart disease, anginal pharmaceutical composition by weight, consist of Rhizoma Chuanxiong total alkali extract 60～95%, Borneolum Syntheticum 5～40%.Preferred proportion of composing is a Rhizoma Chuanxiong total alkali extract 80～95%, Borneolum Syntheticum 5～20%.Preferred proportion of composing is a Rhizoma Chuanxiong total alkali extract 80～90%, Borneolum Syntheticum 10～20%.Above-mentioned pharmaceutical composition adds that acceptable accessories or preparing carriers become oral formulations.Preferred dosage form is drop pill or dispersible tablet.The present invention also provides the application of described pharmaceutical composition in the medicine of the preparation treatment heart, cerebrovascular.
The preparation of Rhizoma Chuanxiong total alkali extract:
Rhizoma Chuanxiong granule 30%-70% acidic ethanol (PH3～5.5) percolation, collect percolate, decompression recycling ethanol, high speed centrifugation separates remove impurity, cross inoranic membrane (0.2～0.8 μ m),, collect concentrated solution permeate ultrafiltration (molecular cut off 1000～8000) nanofiltration then, spray drying gets extract powder: the solid content yield is about 10%, and wherein Rhizoma Chuanxiong total alkali extractive content is not less than 20%.
Above-mentioned Rhizoma Chuanxiong total alkali extract mixes with Borneolum Syntheticum, promptly gets described pharmaceutical composition.
The preparation technology of drop pill:
Drop pill substrate heated in water-bath dissolve, add the Rhizoma Chuanxiong total alkali extract and the Borneolum Syntheticum of preparation, stir evenly, according to the conventional preparation method preparation of drop pill.Drip system temperature (40～80 ℃), speed 30～80 ball/minute.
Adjuvant can be: polyethylene glycol 1500, Macrogol 4000, polyethylene glycol 6000, gelatin, micropowder silica gel, tween 80, sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, low substituted hydroxy-propyl methylcellulose, carbomer, polyoxyethylene (40) monostearate, poloxamer, carbamide, content are 5-40%, and condensed fluid can be a dimethicone, liquid paraffin, vegetable oil, alkaline aqueous solution.
The preparation technology of dispersible tablet:
Rhizoma Chuanxiong total alkali extract, the Borneolum Syntheticum of preparation are mixed with adjuvant, and supplementary product consumption is 1～30%, and method for preparing tablet thereof is made dispersible tablet routinely.
Adjuvant can be: carboxymethyl starch sodium, microcrystalline Cellulose, modified starch, Carboxymethyl cellulose sodium, sodium carboxymethyl cellulose, the low substituted hydroxy-propyl methylcellulose, micropowder silica gel, polyvinylpolypyrrolidone, starch, dextrin, lactose, mannitol, sodium alginate, magnesium stearate, content is 1-30%.
Prove that through zoopery pharmaceutical composition of the present invention has following effect:
1, improves the myocardial nutritional flow amount, reduce myocardial oxygen consumption.
2, the expansion coronary vasodilator increases coronary flow.
3, reduce blood viscosity, improve hemorheological property.
4, the generation of anticoagulant and haemoglutinin.
5, have the thrombotic effect that prevents, but but also thrombolytic.
6, enhancing human body immunity function.
7, effect rapidly.
1, pituitrin is caused the Electrocardiographic influence of Cavia porcellus acute myocardial ischemia
Animal: Cavia porcellus 300-400g male and female dual-purpose
Equipment: electrocardiograph (ECG-6511 of Shanghai Photoelectricity Medical electron Instrument Co., Ltd.)
Drop instillator etc. at a slow speed.Medicine: pituitrin 10mg/ml (Tianjin Biochemical Pharmaceutical Factory 2000501)
Urethane 200mg/ml, pharmaceutical composition of the present invention.Method: Cavia porcellus is divided into 3 groups at random, abdomen shin injection urethane solution 1g/kg anesthesia, and it is fixing to lie on the back, and peels off jugular vein, inserts drop instillator, at the uniform velocity injects normal saline in quiet globefish with 0.02ml/min, traces V
3Normal ECG.Add pituitrin 0.5U/10g, regulating the speed is 0.6ml/min.Change former speed behind the 1min into.After injecting pituitrin, trace V immediately
3Electrocardiogram, in the 1min, every 15s once, 1-5min, 30s once, after, every 5min traces once.
Electrocardiogram adds medicine after recovering normally, and speed is 0.6ml/min, change 0.02ml/min behind the 2min into, behind the administration 5min, repeat to give pituitrin by preceding method, and trace electrocardiogram, and matched group gives with the capacity normal saline, and positive group gives the Rhizoma Corydalis total alkali.
Cut electrocardiogram, measure and relatively move on the ECG ST section before and after the administration and variation that the T ripple raises, the results are shown in Table 1.
Table 1 pair pituitrin causes the Electrocardiographic X of influence of Cavia porcellus acute myocardial ischemia ± SDmm
Move the maximum of T ripple on the ST section and increase maximum
Dosage
The group number of animals
mg/kg
Before the administration after the administration before the administration after the administration
Normal saline---6 2.97 ± 1.18 2.76 ± 1.15 11.61 ± 4.07 11.32 ± 4.65
Rhizoma Corydalis total alkali 20 6 3.11 ± 1.76 1.37 ± 0.95* 11.42 ± 5.22 7.21 ± 3.36*
Medicine of the present invention
15 6 3.02±1.47 1.59±1.01* 11.28±5.13 7.95±3.47*
Compositions
* compare P＜0.05 with matched group
The result shows that pharmaceutical composition of the present invention can significantly suppress pituitrin and cause to move with the T ripple on the Cavia porcellus acute myocardial ischemia ECG ST section and increase.
2, to the influence of rabbit acute myocardial infarction scope
Animal: rabbit 2.5 ± 0.3kg male and female dual-purpose
Equipment: rabbit platform, operating equipment
Medicine: N-BT dyeing liquor (0.5% nitro tetrazole phosphate buffer, 2% procaine hydrochloride) Rhizoma Corydalis total alkali, pharmaceutical composition of the present invention
Method: 2% procaine local anaesthesia, open breast, with No. 0000 dual ligation branch of coronary artery of silk thread, sew up and close thoracic cavity, intramuscular injection 1,600,000 penicillin infection.Intraperitoneal injection, behind the ligation 72h, put to death animal, take out heart, normal saline is cleaned surplus blood, divide centrifugal chamber to weigh, section is put in the N-BT dyeing liquor, 37 ℃ of water bath with thermostatic control dyeing 15min, separate blue (normal myocardium) and not painted (infarcted myocardium zone) and weigh, calculate percentage rate, the results are shown in Table 2.
Table 2 pair rabbit acute myocardial infarction scope influence X ± SD
Dosage
Group number of animals ventricle gross weight (g) infraction weight (g) percentage rate %
mg/kg
Normal saline---6 4.76 ± 0.38 0.72 ± 0.23 15.13 ± 2.17
Rhizoma Corydalis total alkali 20 6 5.02 ± 0.39 0.28 ± 0.27 5.58 ± 1.02*
Pharmaceutical composition 15 6 4.96 of the present invention ± 0.37 0.31 ± 0.25 6.30 ± 1.23*
* compare P＜0.05 with matched group
The result shows that pharmaceutical composition of the present invention can significantly suppress the rabbit acute myocardial infarction.
3, to the influence of rabbit myocardial ischemia reperfusion injury
Animal: rabbit 2.5 ± 0.4kg male and female dual-purpose
Equipment: operating theater instruments, homogenizer UV-2100 spectrophotometer (UNICO(Shanghai) Instruments Co., Ltd.) multi-path physiology color record instrument
Medicine: tetraethoxypropane, sodium lauryl sulphate, thiobarbituricacid, n-butyl alcohol, pyridine, acetic acid, Rhizoma Corydalis total alkali, pharmaceutical composition of the present invention.
Method: with fixing after 20% urethane (5ml/kg) intravenous anesthesia, separate left carotid, the right lateral thigh artery and vein, vein inserts left chamber with internal diameter 1.5mm conduit from common carotid artery after injecting 0.3% heparin (3ml/kg), connect pressure transducer, the input polygraph, monitoring left indoor pressure, intraventricular pressure rate of change (dp/dt).Another conduit inserts pulse artery and monitors average femoral artery pressure variation.Femoral vein transfusion, speed is 15ml/kg per hour, opens breast and fixes, and treats that the left chamber of ligation coronary artery props up.
The average femoral blood pressure of continuous record before and after the coronary artery ligation, left constant pressure and left constant pressure rate of change, after the coronary artery ligation quiver or the discarding of anesthetic death in the chamber of appearance, and the residue animal is divided three groups at random.Matched group, 1h is propped up in chamber, a ligation left side, and unclamp ligature and pour into 1h again, not administration, the administration group, 1h is propped up in chamber, a ligation left side, unclamps ligature and pours into 1h again, and 5min is with per minute 0.5ml/kg speed input medicine before irritating again.The rapid heart that takes out after observation finishes is got ischemia and non-ischemic region is organized each 0.3g, makes 10% tissue homogenate with the 3ml normal saline in homogenizer.
MDA (malonaldehyde) measures: get 0.2ml tissue homogenate → adding 0.2ml8.1% sodium lauryl sulphate → adding 20% acetic acid → adding 1.5ml0.8% thiobarbituricacid → adding distil water to 4ml, adding distil water 10ml and n-butyl alcohol pyridine mix behind 95 ℃ of water-bath 60min postcooling, the centrifugal 10min of 4000rpm → get upper strata liquid 532nm to measure optical density, tetraethoxypropane is made standard control, MDA content is represented with nmol/g wet, percentage ratio with ischemia part and non-ischemia part mda content, expression ishemic part malonaldehyde rising degree the results are shown in Table 3, table 4.
Table 3 pair rabbit cardiac systolic function influence (X ± SD)
Dp/dt?max(kpa/s)
The dosage animal
20min 60min when pricking before group is pricked
The mg/kg number
During 20min 60min pine
98± 80± 75± 60±
Normal saline--6 73 ± 6.2 72 ± 5.6 70 ± 5.0
4.8 4.2 6.3 4.3
103± 88± 79± 90± 80±
Rhizoma Corydalis total alkali 20 6 77 ± 6.1 83 ± 6.0
5.1 5.3 5.9 5.4* 5.6*
Medicine of the present invention
96± 83± 7.6± 87± 77±
15 6 72±5.4 82±5.9
Compositions
4.9 5.5 5.7 6.2* 5.7*
* compare P＜0.05 with matched group
The influence of table 4 pair rabbit heart ischemia reperfusion MDA content (X ± SD)
Dosage
Heart ischemia position and non-ishemic part MDA content it
The group number of animals
Mg/kg compares %
Normal saline---6 137.24 ± 11.38
Rhizoma Corydalis total alkali 20 6 196.26 ± 24.57*
Medicine of the present invention
Compositions 15 6 187.23 ± 19.42*
* compare P＜0.05 with matched group
The result shows that pharmaceutical composition of the present invention can significantly strengthen the rabbit cardiac systolic function, and damage has protective effect to the rabbit heart ischemia reperfusion.
4, to the influence of rat acute blood stasis model blood viscosity
Animal: SD rat 200-250g male and female dual-purpose
Equipment: blood viscosity meter
Medicine: heparin sodium, adrenalin hydrochloride, Rhizoma Corydalis total alkali
Method: the blank group, every day, boiled water was only irritated stomach 2ml/, and continuous 7 days, stopped eating in the 7th day, get the blood censorship inferior morning:
Model group: boiled water is only irritated stomach 2ml/, adrenaline subcutaneous injection 0.08ml/100g body weight after 7 days, and totally 2 times, two minor tick 4h immerse 5min in the frozen water with rat between biphasic injection Adr, stop eating after the disposal, get the blood censorship next day.
The medicine group: successive administration 7 days, handle with method by model group after 7 days.
The influence of table 5 pair rat acute blood stasis model blood viscosity (X ± SD)
Whole blood contrast viscosity
The dosage animal
The group plasma viscosity
The mg/kg number
The high shear rate of low shear rate
Blank---8 8.54 ± 1.29 4.26 ± 0.63 1.98 ± 0.12
The model contrast---8 14.37 ± 5.21 5.94 ± 1.02 2.41 ± 0.33
Rhizoma Corydalis total alkali 20 8 9.63 ± 2.75* 5.22 ± 0.74* 2.01 ± 0.17*
Medicine of the present invention
Compositions 15 8 9.78 ± 2.61* 5.32 ± 0.76* 2.14 ± 0.21*
* compare P＜0.05 with model group
The result shows that pharmaceutical composition of the present invention can significantly reduce rat serum viscosity.
Conclusion: pharmaceutical composition of the present invention can be expanded coronary vasodilator, the antagonism acute myocardial ischemia; Reduce the acute myocardial infarction scope; Strengthen cardiac systolic function, damage has protective effect to the rabbit heart ischemia reperfusion; Can reduce blood viscosity, improve hemorheological property.Pharmaceutical composition of the present invention resists myocardial ischemia by the expansion coronary vasodilator, strengthen cardiac systolic function and improve effect such as hemorheological property and performance to the therapeutical effect of coronary heart disease.
The invention will be further described below in conjunction with embodiment, but be not limitation of the present invention.
Embodiment one
The preparation of Rhizoma Chuanxiong total alkali extract:
The preparation of Rhizoma Chuanxiong total alkali extract:
Rhizoma Chuanxiong medical material granule 10kg is with 50% acidic ethanol (PH3～5.5) percolation, collect percolate, decompression recycling ethanol, high speed centrifugation separates remove impurity, crosses inoranic membrane (0.2～0.8 μ m), with permeate ultrafiltration (molecular cut off 1000～8000) nanofiltration then, collect concentrated solution, spray drying gets extract powder 1065g, wherein, after measured, contain Rhizoma Chuanxiong total alkali extract 240g.
Above-mentioned Rhizoma Chuanxiong total alkali extract mixes with Borneolum Syntheticum, promptly gets described pharmaceutical composition.
Embodiment two
The preparation of drop pill:
Polyethylene glycol 6000 320g heated in water-bath dissolve, add the Rhizoma Chuanxiong total alkali extract 630g and the Borneolum Syntheticum 70g of embodiment one preparation, stir evenly, prepare drop pill 1000g according to the conventional preparation method of drop pill.
Embodiment three
The preparation of dispersible tablet;
Rhizoma Chuanxiong total alkali extract 200g, the Borneolum Syntheticum 48g of embodiment one preparation are mixed with carboxymethyl starch sodium, lactose 60g, and method for preparing tablet thereof is made 1000 of dispersible tablets routinely.
Embodiment four
Get the Rhizoma Chuanxiong total alkali extract 80g of embodiment one preparation, Borneolum Syntheticum 10g
The Borneolum Syntheticum grinding and sieving, fine powder mixes with Rhizoma Chuanxiong total alkali extract, fully behind the mixing, adds in the polyethylene glycol 6000 that has dissolved in hot bath, stirs evenly, and drips and makes ball.
Embodiment five
Get Rhizoma Chuanxiong total alkali extract 60g, Borneolum Syntheticum 20g
The Borneolum Syntheticum grinding and sieving, fine powder mixes with Rhizoma Chuanxiong total alkali extract, fully behind the mixing, adds in the carboxymethyl starch sodium that has dissolved in hot bath, stirs evenly, and drips and makes ball.
Embodiment six
Get Rhizoma Chuanxiong total alkali extract 90g, Borneolum Syntheticum 10g
The Borneolum Syntheticum grinding and sieving, fine powder and Rhizoma Chuanxiong total alkali extract, microcrystalline Cellulose, starch mixes, and the sheet agent method is made dispersible tablet routinely.
Claims (8)
1, a kind of treatment treatment coronary heart disease, anginal pharmaceutical composition, its composition is by weight: Rhizoma Chuanxiong total alkali extract 60～95%, Borneolum Syntheticum 5～40%.
2, pharmaceutical composition according to claim 1, its composition is by weight: Rhizoma Chuanxiong total alkali extract 80～95%, Borneolum Syntheticum 5～20%.
3, pharmaceutical composition according to claim 1 and 2, its composition is by weight: Rhizoma Chuanxiong total alkali extract 80～90%, Borneolum Syntheticum 10～20%.
4, the described a kind of treatment treatment coronary heart disease of claim 1 to 3, anginal pharmaceutical composition, it is characterized in that: the percentage by weight of Rhizoma Chuanxiong total alkali is not less than 20% in the Rhizoma Chuanxiong total alkali extract.
5, the described treatment coronary heart disease of above-mentioned any claim, anginal pharmaceutical composition add acceptable accessories, are prepared into pharmaceutical preparation.
6, according to claim 5ly be used for the treatment of coronary heart disease, anginal pharmaceutical preparation, it is characterized in that: described pharmaceutical preparation is oral formulations.
7, according to claim 6ly be used for the treatment of coronary heart disease, anginal pharmaceutical preparation, it is characterized in that described oral formulations is drop pill or dispersible tablet.
8, the application of the described pharmaceutical composition of claim 1 in the medicine of the preparation treatment heart, cerebrovascular.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031173691A CN1524528A (en) | 2003-02-28 | 2003-02-28 | Medicament composition for treating coronary heart disease |
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| Application Number | Priority Date | Filing Date | Title |
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| CNA031173691A CN1524528A (en) | 2003-02-28 | 2003-02-28 | Medicament composition for treating coronary heart disease |
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| CN1524528A true CN1524528A (en) | 2004-09-01 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103156940A (en) * | 2013-01-16 | 2013-06-19 | 福建中医药大学 | Formula composition and extraction process used for bone ache eliminating |
-
2003
- 2003-02-28 CN CNA031173691A patent/CN1524528A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103156940A (en) * | 2013-01-16 | 2013-06-19 | 福建中医药大学 | Formula composition and extraction process used for bone ache eliminating |
| CN103156940B (en) * | 2013-01-16 | 2015-09-02 | 福建中医药大学 | A kind of extracting technique of Chinese medicine for garden balsam stem pain-relieving |
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