CN1135996C - Chinese medicine for treating coronary heart disease and angina pectoris and its preparing process - Google Patents
Chinese medicine for treating coronary heart disease and angina pectoris and its preparing process Download PDFInfo
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- CN1135996C CN1135996C CNB001146238A CN00114623A CN1135996C CN 1135996 C CN1135996 C CN 1135996C CN B001146238 A CNB001146238 A CN B001146238A CN 00114623 A CN00114623 A CN 00114623A CN 1135996 C CN1135996 C CN 1135996C
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/84—Valerianaceae (Valerian family), e.g. valerian
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The present invention relates to traditional Chinese medicine for treating coronary disease and angina pectoris, and a preparation method for the traditional Chinese medicine. The present invention relates to medicine for treating cardiovascular disease. The present invention uses valerian and red sage root as raw materials for preparing the medicine based on weight proportion of three to one. The preparation method comprises: water vapor is directly led to the valerian for steaming volatile oil; the red sage root is used for joining ethanol reflux and filtering extract; insoluble substances are dried at a low temperature; filter liquor is concentrated to thick paste which is dried and merged with the insoluble substances; the thick paste and the insoluble substances are crushed for sieving 80 meshes, and medicine powder is obtained; after heated and melted, polyethylene glycol and twin are added to the obtained volatile oil and the medicine powder; the temperature of the polyethylene glycol, the twin, the volatile oil and the medicine powder is preserved; the polyethylene glycol, the twin, the volatile oil and the medicine powder are blended and mixed and are dripped into a model to be cooled into tablet preparation. The present invention has the characteristics of outstanding therapeutic effects, stability, durability, rapid effect, low toxic or side effect, etc.
Description
The present invention relates to medical, particularly treat cardiovascular disease medicine, especially resist myocardial ischemia, treatment coronary heart disease, anginal Chinese medicine.
Coronary heart disease is a kind of cardiovascular disease of serious threat human health.In American-European countries, evidence of coronary heart diseases accounts for the first place [referring to Li Pingzhu " general situation of development of coronary heart disease surgical intervention ", cardiopulmonary angiopathy magazine, 1997,16 (2): 92-94] of various diseases.In China, cardiovascular diseases's prevalence, mortality rate continue over nearly 30 years to rise, in recent years the cardiovascular and cerebrovascular disease mortality rate accounts for crude death rate's 40% according to statistics, have every year 2000000 people to die from cardiovascular and cerebrovascular disease approximately, case fatality rate is 2,00/,100,000 people, and coronary heart disease accounts for more than 50% [referring to Jiang Yiqing in the intracardiac patient of section of various big hospital, Liu Lisheng work " novel beta-blocker---Carvedilol ", the angiocardiology progress, 1998,19 (3): 132-135].Relevant department has carried out (1984-1993) monitoring to the mortality rate and the related risk factors of the outbreak of Beijing area acute coronary.Its result shows: the M ﹠ M of coronary heart attack is all in rising trend, the women increases faster than the male, and with advancing age, M ﹠ M all significantly rises, as 55-64 year in 1993,65-74 year male's sickness rate was respectively 2,62/,100,000 people, 5,36/,100,000 people, women's sickness rate is 1,08/,100,000 people, 4,25/,100,000 people; The deaths in men rate is respectively 1,25/,100,000 people, 3,76/,100,000 people, and women's mortality rate is 80,/10 ten thousand people, 2,89/,100,000 people.1993 annual death rate with compared the male in 1984 and increase 17%, the women increases 56%[referring to works " Beijing area acute coronary incident mortality rate 1984-1993 its annual variation trend and influence factor's discussion " such as Wang Wei, Wu Zhaosu, cardiopulmonary angiopathy magazine, 1997,16 (2): 99-102].Along with the prolongation of human longevity, population is aging day by day, and evidence of coronary heart diseases and mortality rate still can continue to increase.Therefore, the development of control primary disease is the task of top priority of current medical educational circles.
The coronary heart disease full name is a coronary atherosclerotic heart disease, and angina pectoris is its common sympton, and temporary transient ischemia and the anoxia rapid by cardiac muscle are caused.Paroxysmal colic or vexed pain appear in behind patient's breastbone or left front regio pectoris during outbreak, generally last 1-5 minute, bring very big misery and threat to life to patient.
Treatment to coronary heart disease at present mainly contains operative treatment and Drug therapy.
Percutaneous tranluminal coronary angioplasty (PTCA) has become the main intervention method of treatment coronary heart disease, and success rate is also by in one's early years 60-70%, brings up to now more than 90%, and severe complication reduces year by year, and mortality rate decreases.But because can be because of the acute obturation of blood vessel causes severe complication in the PTCA operation, and postoperative restenosis incidence rate coronarius be up to 30-50%.Thereby affect the late result [referring to Peng Zhangping, Bai Jing, Zhu Jianhua work " present situation of restenosis study on prevention behind the coronary angioplasty " angiocardiology progress, 1997,18 (3): 136-140] of PCTA treatment coronary heart disease to a great extent
Medicine to angina pectoris mainly can be divided three classes at present:
1. nitrate esters: this class medicine is used for angina pectoris treatment T﹠B, and is the most commonly used with nitroglycerin, determined curative effect, but side effect is bigger, can produce neck surface flushing, pulsatile headache, postural hypotension etc.Dosage is excessive, but reflexive is accelerated heart rate, increases the weight of angina pectoris attacks, and toleration can occur after continuous use 2-3 week.
2. beta receptor blocking agent: with the Propranolol is representative, is anti-anginal drug commonly used clinically, easily causes bradycardia, ventricular function inhibitions, hypotension etc. but take for a long time, and inactive suddenly have the danger of bringing out myocardial infarction.
3. calcium antagonists: with nifedipine, verapamil is representative, better to variant angina pectoris and classical angina curative effect.That main adverse reaction has is nauseating, vomiting, weak, flush, postural hypotension etc.
The chemicals determined curative effect is being brought into play positive effect in treatment aspect the angina pectoris, but general side effect is obvious, to the patient particularly most of gerontal patients' health cause very big harm.
In addition, treatment myocardial ischemia (coronary heart disease, angina pectoris) also has Chinese medicine, and as FUFANG DANSHEN DIWAN etc., but its curative effect is still the said the sort of slow merit of people, promptly onset time longer, can not satisfy the demand of acute attack treatment.
Therefore, seek determined curative effect, stable, lasting and onset time is fast, the medicaments for resisting myocardial ischemia that toxic and side effects is low is the common issue that this field is faced for a long time.
Task of the present invention provides a kind of treatment coronary heart disease, anginal Chinese medicine of resisting myocardial ischemia, make it have determined curative effect, stable, lasting and onset time is fast, toxic and side effects low etc. characteristics, existing chemicals side effect is big, the Chinese medicine onset waits deficiency slowly thereby overcome, to satisfy the demand of clinical treatment.
Another task of the present invention provides the preparation method of this resist myocardial ischemia treatment coronary heart disease, angina pectoris Chinese medicine preparation.
Realize the solution of the present invention
Resist myocardial ischemia treatment coronary heart disease, angina pectoris Chinese medicine provided by the invention are to be the medicament that raw material is made with Rhizoma et radix valerianae, Radix Salviae Miltiorrhizae, can be any dosage forms on the pharmaceutics, particularly, capsule and drop pill.Rhizoma et radix valerianae is 1 to 10 to 1 with the weight proportion of Radix Salviae Miltiorrhizae, and its preferred weight proportioning is 2 to 5 to 1, and the optimum weight proportioning is 3 to 1.
The resist myocardial ischemia preparation method of treatment coronary heart disease, angina drug tablet of the present invention is:
Get Rhizoma et radix valerianae, the section of cutting into is put in the multipotency extraction pot, and the straight-through water vapour of water proof steams gets volatile oil, collect volatile oil; Other gets Radix Salviae Miltiorrhizae, adds 3 to 6 times of amount 50% to 90%7 alcohol refluxs and extracts each 1 hour three times, extracting liquid filtering, filtrate merges, and room temperature decompression recycling ethanol to relative density is 1.25 (Bs, 50 ℃), emit, add ethanol to 40 to 90%, refluxed 0.5 to 2 hour, and left standstill the leaching supernatant 10 to 14 hours, supernatant decompression recycling ethanol to relative density is 1.20 (B, 50 ℃), emits, be placed to room temperature, 100 orders filter; Insoluble matter low temperature (30 ℃ to 60 ℃) drying, filtrate is concentrated into thick paste, and the thick paste drying under reduced pressure merges with insoluble matter, pulverizes 80 mesh sieves, gets medicated powder; Get the adjuvant Polyethylene Glycol, behind the heating and melting, add the medicated powder and the volatile oil that make, mix, drip in model, cooling is taken out and is promptly made tablet.
The resist myocardial ischemia preparation method of treatment coronary heart disease, angina drug drop pill of the present invention is:
Get the Rhizoma et radix valerianae section of cutting into, put in the distilled water generator, the straight-through water vapour of water proof steams gets volatile oil, collect volatile oil; Other gets Radix Salviae Miltiorrhizae and adds 3 to 6 times of amount 50% to 90% alcohol reflux three times, each 1 hour, extracting liquid filtering, merging filtrate, decompression recycling ethanol to relative density are 1.25 (B, 50 ℃), pour out, add ethanol to 70%, refluxed 0.5 hour, left standstill leaching supernatant, supernatant reclaim under reduced pressure to 1.20 (B 12 hours, 50 ℃), pour out, be placed to room temperature, 100 orders filter; The insoluble matter cold drying, filtrate is concentrated into thick paste, and the thick paste drying under reduced pressure merges with insoluble matter, pulverizes 80 mesh sieves, gets medicated powder; Get the adjuvant Polyethylene Glycol, behind the heating and melting, add volatile oil and medicated powder, insulated and stirred was mixed 10 minutes, splashed in the condensed fluid, made drop pill.
In above-mentioned tablet, drop pill preparation process, employed adjuvant Polyethylene Glycol is a Polyethylene Glycol-6000.Use best proportioning at raw medicinal material, when to be Rhizoma et radix valerianae with the weight proportion of Radix Salviae Miltiorrhizae be 3 to 1, the weight proportion of raw medicinal material Rhizoma et radix valerianae, Radix Salviae Miltiorrhizae and adjuvant Polyethylene Glycol-6000 is 75: 25: 12, and then be 1: 6 if calculate the weight proportion of itself and Polyethylene Glycol with two kinds of raw medicinal material extracts this moment.
In above-mentioned tablet, drop pill preparation process, using adjuvant Polyethylene Glycol-6000 at the same time, also can use solubilizing agent, to increase stability of formulation, the solubilizing agent that pharmaceutical preparation of the present invention is used is tween 80, at this moment, the weight proportion of raw medicinal material Rhizoma et radix valerianae, Radix Salviae Miltiorrhizae and adjuvant Polyethylene Glycol-6000 and solubilizing agent tween 80 is 75: 25: 12: 1.
Pharmacodynamic experiment
One, medicine of the present invention can obviously alleviate the S-T section change of the caused epicardial electrogram of ischemia
1. observation index
30 visceral pericardium electrographs of S-T section change value of epicardial electrogram, S-T field offset degree can reflect degree of ischemia indirectly, but the scope of the electrodeplate indirect reaction ischemic region of S-T field offset takes place.
2. test method
With pentobarbital sodium (30mg/kg) intravenous anesthesia, circulation of qi promoting cannula, connect Bird 6400 artificial respirators, FiO260%, 22～24 times/min of respiratory frequency, tidal volume 2g0～320ml.To postcava, supply transfusion and monitoring center's venous pressure through the left side femoral venous catheter; Femoral arteriography continues the record arterial pressure.Change right arm reclining, breast is opened in the left side, cuts off pericardium, separates anterior descending coronary, is equipped with line in separation place.Put 30 fixed epicardial leads at the heart surface seam, through polygraph record epicardial electrogram.Finish whole operations and need 40～50min approximately.Each parameter before the record ligation, behind the blood sample collection, the ligation anterior descending coronary, respectively at after the ligation 15,30,60,120,180,240min writes down epicardial electrogram, after the ligation branch of coronary artery, as arrhythmia occurs, write down ARR type, and take corresponding processing, give lignocaine as electric defibrillation or vein.
3. result of the test
One, medicine of the present invention obviously alleviates the S-T section change of the caused epicardial electrogram of ischemia
1. 15min after the ligation of normal saline group, the S-T section of seeing the epicardial electrogram that the ligation position records with bottom electrode (6～No. 30) obviously raises, before the ischemia, ∑-ST is 44.9 ± 17.4mV, 15min rises to 56.4 ± 14.2mV (P＜0.05) after the ligation, reach 93.51 ± 30.39mV (＜0.01) behind the 120min, still maintain 79.9 ± 12.6mV (P＜0.01) during 240min, table 1.Wherein the S-T section is higher than the number of sites of 2mV (or electrodeplate N-ST) increases to 17.8 ± 3.9 (15min, p＜0.05) by 10.8 ± 8.4 before the ligation, still maintains 18.4 ± 4.3 (P＜0.01) during 240min, table 2.Above results suggest ligation the large tracts of land myocardial ischemia occurred below the position.2. (120mg/kg p.o.) continues after the ligation to observe 240min the Radix Salviae Miltiorrhizae drop pill group, and with ratio before the ligation, ∑-ST and N-ST are on a declining curve.∑-the ST of Radix Salviae Miltiorrhizae drop pill group and N-ST be 60min and 120min after the ligation respectively, is starkly lower than the normal saline group.Basic, normal, high three the dosage groups of medicine 3. of the present invention (100mg/kg, 200mg/kg, 300mg/kg, ∑-ST p.o.) and N-ST are all on a declining curve, and this is similar to the Radix Salviae Miltiorrhizae drop pill group.But 15min and 30min just are starkly lower than the normal saline group after the ligation respectively, i.e. the time that ischemia resisting effect occurs than the Radix Salviae Miltiorrhizae drop pill group early.4. Propranolol group 15min administration after ligation (1mg/kg, i.v.), the ∑-ST of (being 15min after the ligation) before ligation (P＜0.05) at this moment, ∑-ST and N-ST are all on a declining curve after the administration, with before the ligation than no significant change, table 1～table 2.
Table 1: each electrode S-T section height summation of different time points before and after each treated animal administration (the group n ∑-ST of ∑-ST) (X ± SD)
60min pricked 180min bundle back, 120min bundle back, back 240min normal saline 1ml/kg 4 44.9 ± 17.4 56.4 ± 14.2 after 30min pricked after bundle back 15min pricked before the ligation
*64.9 ± 22.3
*83.3 ± 16.4
*93.5 ± 30.5
*85.9 ± 14.7
*79.9 ± 12.6
*Danshen Root dropping ball 120mg/kg 5 44.9 ± 14.2 43.5 ± 14.3 41.6 ± 17.5 44.9 ± 19.2##, 35.9 ± 16.7#, 33.7 ± 15.7##, 37.3 ± 16.7## medicine 100mg/kg 5 40.5 of the present invention ± 18.4 34.7 ± 9.4#, 27.3 ± 12.4#, 35.1 ± 21.2##, 34.7 ± 16.9#, 32.1 ± 12.2#, 31.1 ± 13.9## medicine 200mg/kg 5 45.5 of the present invention ± 25.1 33.7 ± 13.5#, 37.2 ± 8.8#, 38.2 ± 8.9##, 35.5 ± 8.3#, 30.1 ± 9.8##, 30.4 ± 11.5## medicine 300mg/kg 5 46.3 of the present invention ± 14.1 33.1 ± 12.0#, 38.5 ± 16.0#, 40.3 ± 15.4##, 35.5 ± 10.9# 28.9#11.g##, 29.1 ± 14.7## Propranolol 1mg/kg 7 45.9 ± 14.9 72.2 ± 22.6*62.2 ± 16.6 61.2 ± 25.0 52.2 ± 17.1 59.2 ± 23.0 53.8 ± 19.7
The comparison group n S-T section that table 2:S-T section is higher than the 2mv electrodeplate is greater than 2mv electrodeplate (X ± SD)
60min pricked 180mm bundle back, 120min bundle back, back 240min normal saline 1ml/kg 5 10.8 ± 8.4 12.2 ± 4.2 13.8 ± 5.1 17.8 ± 3.9 after 30min pricked after bundle back 15min pricked before the ligation
*19.6 ± 5.3
*18.8 ± 4.1
*18.4 ± 4.3
*Danshen Root dropping ball 120mg/kg 5 11.8 ± 10.9 8.2 ± 4.4 6.8 ± 5.8 9.7 ± 7.8 6.3 ± 5.4##, 4.0 ± 5.8##, 6.8 ± 5.8## medicine 100mg/kg 6 10.3 of the present invention ± 10.9 6.8 ± 4.8 4.2 ± 5.6#, 5.7 ± 7.2##, 4.2 ± 5.4##, 2.7 ± .1##, 4.2 ± 5.8## medicine 200mg/kg 6 11.3 of the present invention ± 10.2 9.8 ± 4.0 5.2 ± 3.0#, 8.8 ± 4.9##, 7.5 ± 2.9##, 9.3 ± 4.9##, 9.3 ± 6.6## medicine 300mg/kg 5 11.9 of the present invention ± 7.6 6.8 ± 5.4 7.2 ± 3.6#, 9.4 ± 6.4##, 7.2 ± 3.4##, 5.4 ± 5.0##, 4.6 ± 5.9## Propranolol 1mg/kg 7 11.4 ± 7.6 13.9 ± 4.7 11.4 ± 5.5 10.7 ± 6.8 11.6 ± 6.9 13.1 ± 8.4 10.9 ± 5.8
With before the ligation relatively:
*: p＜0.05; Compare with time point with the normal saline group: #:p＜0.05, ##:p＜0.01.
4. conclusion:
The onset time of medicine group of the present invention is obviously short than Radix Salviae Miltiorrhizae drop pill group, i.e. the time that ischemia resisting effect occurs than the Radix Salviae Miltiorrhizae drop pill group early.
Two, medicine of the present invention obviously alleviates caused biochemistry of ischemia and myocardial enzymes variation
1. observation index
(1) (Tropnin I proves in recent years that TnI) for acute myocardial infarction and other myocardial tissue damage, TnI is responsive, the most special biochemical indicator to troponin I.
(2) (CK-MB, CK) CK-MB once was considered to the gold medal index of acute myocardial infarction to creatine kinase.
2. test method
With pentobarbital sodium (30mg/kg) intravenous anesthesia, circulation of qi promoting cannula, connect the Bird6400 artificial respirator, FiO
260%, 22～24 times/min of respiratory frequency, tidal volume 280～320ml.To postcava, supply transfusion and monitoring center's venous pressure through the left side femoral venous catheter; Femoral arteriography continues the record arterial pressure.Change right arm reclining, breast is opened in the left side, cuts off pericardium, separates anterior descending coronary, is equipped with line in separation place.Put 30 fixed epicardial leads (as Fig. 1,5 of every rows, totally 6 rows make and prick the position fully and just in time be positioned between 1,2,6,7 electrodes) at heart surface seam, through polygraph record epicardial electrogram.Finish whole operations and need 40～50min approximately.Before the record ligation behind each parameter and the blood sample collection, the ligation anterior descending coronary, respectively at after the ligation 30,120,240min, blood sampling and separation of serum, be used for myocardium biochemical measurement.
3. result of the test
(1) before the troponin I ligation arteria coronaria, the serum T nI of all animals all is lower than 0.25ng/ml (be regarded as and can not survey).After the ligation, the serum T nI concentration of normal saline group continue to raise in time, 30,120,240min is respectively 1.27 ± 0.21ng/ml, 2.05 ± 0.55ng/ml and 3.07 ± 0.37ng/ml.Each medication group serum TnI concentration after ligation also raises, but the rising degree obviously reduces than the normal saline group.With normal saline group ratio, the basic, normal, high dosage group of medicine of the present invention 30min after ligation, serum T nI net added value reduces 73.68%, 88.30% and 92.87% respectively, table 3.
Table 3: medicine of the present invention to dog serum cardiac muscle troponin I (TnI:ng/ml) influence before the group n coronary ligation different time behind the coronary ligation (minute) serum T nI horizontal X ± SD
30 120 240 normal saline 1ml/kg 5 0.17 ± 0.08 1.27 ± 0.21
*2.05 ± 0.55
*3.07 ± 0.37
*Radix Salviae Miltiorrhizae drop pill 120mg/kg 6 0.16 ± 0.06 0.54 ± 0.09
* ##0.78 ± 0.23
* ##0.95 ± 0.27
* ##Propranolol 1mg/kg 10 0.19 ± 0.07 0.55 ± 0.15
* ##0.83 ± 0.17
* ##0.92 ± 0.19
* ##Medicine 100mg/kg 6 0.17 of the present invention ± 0.00 0.31 ± 0.19
## △ zero0.46 ± 0.26
* ### △ zero0.66 ± 0.28
* ## △ zeroMedicine 200mg/kg 6 0.16 of the present invention ± 0.05 0.29 ± 0.13
## △ △ 000.42 ± 0.10
* ## △ △ 000.59 ± 0.22
* ## △ △ 00Medicine 300mg/kg 6 0.16 of the present invention ± 0.01 0.24 ± 0.09
## △ △ 000.45 ± 0.26
* ## △ zero0.59 ± 0.25
* ### △ △ 00With before the ligation relatively:
*: p＜0.05,
*: p＜0.01; Compare with time point with the normal saline group: #:p＜0.05, ##:p＜0.01: compare with Radix Salviae Miltiorrhizae drop pill: zero: p＜0.05, zero zero: p＜0.01; Compare with time point with the Propranolol group: △: p＜0.05, △ △: p＜0.01.
(2) creatine kinase (CK-MB, CK) 15～240min after the ligation, each organizes the carrying out property rising in time of CK-MB activity, but the active net added value of the CK-MB of each dosage group of medicine of the present invention is starkly lower than the normal saline group, and the CK-MB activity of Radix Salviae Miltiorrhizae drop pill group and Propranolol the group value of striving and normal saline group no significant difference only see Table 4.The active variation tendency of CK is similar to CK-MB, sees Table 5.
Table 4: medicine of the present invention to serum creatine kinase-MB (CKMB) net added value (with before the ischemia than) influence (branch) X ± SD after the group n ligation
15 30 60 120 180 240 physiological saline 1ml/kg 5 424 ± 352 539 ± 268 744 ± 275 935 ± 460 1012 ± 421 1191 ± 441 Danshen Root dropping ball 120mg/kg 5 225 ± 139 253 ± 72 472 ± 200 485 ± 194 907 ± 379 859 ± 193 Propranolol 1mg/kg 5 498 ± 228 524 ± 259 546 ± 248 502 ± 274 609 ± 187#772 ± 484
#Medicine 100mg/kg 5 31 ± 75 of the present invention
△ △ 0072 ± 124
## △ △ 00104 ± 79
## △ zero229 ± 93
# △ zero337 ± 84
## zero278 ± 84
## △ 00Medicine 200mg/kg 5 32 ± 89 of the present invention
△ △ 0074 ± 53
# △ 00148 ± 115
## △ zero207 ± 77
# △ zero278 ± 47
## △ 00252.99
## △ 00Medicine 300mg/kg 6 81 ± 69 of the present invention
△ △ zero57 ± 69
△ △ 00119 ± 71
## △ zero166 ± 44
# △ zero173 ± 85
## △ 00178 ± 62
## △ 00
Table 5: the serum creatine kinase that medicine of the present invention causes ischemia (CK) raises influences the net added value of serum creatine kinase (CK) behind the group n ischemia (U/L, X ± SD)
15 30 60 120 180 240 normal saline 1ml/kg 6 322 ± 293 601 ± 444 878 ± 539 1321 ± 654 1637 ± 1,047 1582 ± 686 Radix Salviae Miltiorrhizae drop pill 120mg/kg 5 188 ± 120 312 ± 152 573 ± 151 593 ± 258
#1029 ± 372 1040 ± 469 Propranolol 1mg/kg 5 500 ± 104 634 ± 254 548 ± 155 620 ± 136
#820 ± 445 1216 ± 1272 medicine 100mg/kg 5 254 of the present invention ± 266 226 ± 343 259 ± 234
# zero383 ± 218
#359 ± 333
# zero339 ± 346
## zeroMedicine 200mg/kg 5 79 ± 49 of the present invention
△ △63 ± 71
# zero △ △202 ± 166
# zero zero △ △370 ± 20g
# △ △777 ± 641
△669 ± 295
#Medicine 300mg/kg 5 46 ± 16 of the present invention
△ △54 ± 47
# zero △ △345 ± 152
# zero zero △ △496 ± 105
# △ △669 ± 128
△ △1184 ± 380 is relatively preceding with ligation:
*: p＜0.05,
*: p＜0.01: compare with time point: #:p＜0.05, ##:p＜0.01: compare with Radix Salviae Miltiorrhizae drop pill: zero: p＜0.05, zero zero: p＜0.01: compare with time point: △: p＜0.05, △ △: p＜0.01 with the Propranolol group with the normal saline group.
4. conclusion
The result proves that medicine of the present invention has remarkable prevention and therapeutical effect for acute myocardial infarction and other myocardial tissue damage, and its curative effect is better than Radix Salviae Miltiorrhizae drop pill and Propranolol.
Three, the obvious coronary blood flow increasing of medicine of the present invention, this effect rapid-action (30min after the medication), longer duration.Intravenously administrable is seen decreased heart rate, reduces arteriotony, is reduced myocardial oxygen consumption.
1. observation index
Coronary flow, heart rate, reduction arteriotony, reduction myocardial oxygen consumption
2. test method
Animal Anesthesia and open chest surgery are the same, separate LCA, place the electromagnetic flowmeter probe of suitable diameter, the record coronary flow.Left ventricle tip intubate writes down left constant pressure and relevant parameter.To right atrium, again through orifice of coronary sinus vein insertion Coronary vein, supply to core dirty venous blood through the jugular vein intubate.The carotid artery intubate is for extracting arterial blood.Continue record limb lead electrocardiogram.Through the right lateral thigh vein Swan-Ganz conduit is inserted pulmonary artery, connect hot dilution flow meter thought-read output.Femoral arteriography record arteriotony.Before the record administration after each parameter, through duodenal administration, respectively at after the administration 15,30,45,60,90 and 120min write down each parameter.
3. result of the test
(1). through duodenal administration
At anesthetized dog, give medicine of the present invention (50mg/kg, 100mg/kg, 150mg/kg), Radix Salviae Miltiorrhizae drop pill (60mg/kg) through duodenum, 30min after the administration, coronary flow obviously increases, this effect peaking of 75～90min slowly descends then, but to administration during 120min, coronary flow still before administration, sees Table 6.
Myocardial oxygen consumption was on a declining curve after each dosage group of medicine of the present invention and Radix Salviae Miltiorrhizae drop pill group were all seen medication.
Normal saline group and Radix Salviae Miltiorrhizae drop pill group are not seen cardiac output generation significant change.Medicine low dose group of the present invention can obviously reduce cardiac output, middle and high dosage group respectively after medication 105min and 120min can also obviously reduce cardiac output, table 6.
(2) intravenous administration
Intravenous injection gives medicine of the present invention (50mg/kg), decreased heart rate, reduces myocardial oxygen consumption, reduces systolic arterial pressure, (see Table 7, table 8).
4. conclusion
Medicine of the present invention can obviously reduce myocardial oxygen consumption, increase coronary flow, reduction systolic arterial pressure, decreased heart rate, its action time than Radix Salviae Miltiorrhizae drop pill group, the obviously prolongation of verapamil (verapamil) group.
Four, medicine of the present invention ARR influence that ischemia is caused
The result shows that the ARR incidence rate of medicine group of the present invention and Radix Salviae Miltiorrhizae drop pill group is starkly lower than the normal saline group, and the Propranolol group is 15min administration after the ligation, and this may be one of higher reason of its incidence rate, sees Table 9.
Table 6. duodenal administration to dog myocardial oxygen consumption, coronary flow and kinemic influence index group dosed administration before after the administration (branch)
15 30 45 60 75 90 105 120 heart physiological saline 1 12.95 ± 1.45 13.44 ± 1.71 12.77 ± 1.44 12.44 ± 1.89 12.83 ± 1.57 12.40 ± 1.00 12.42 ± 2.12 12.24 ± 1.10 12.53 ± 1.88 flesh Danshen Root dropping ball 60 12.91 ± 1.48 11.96 ± 1.41 12.53 ± 1.56 11.92 ± 1.28 9.45 ± 1.02*9.81 ± 0.50
*9.30 ± 1.29
*9.96 ± 2.18
*10.17 ± 2.11
*Consume medicine 50 12.62 of the present invention ± 0.84 11.14 ± 0.75 12.61 ± 0.82 11.35 ± 1.36
*10.35 ± 1.03
*10.16 ± 0.95
*9.61 ± 1.29
*8.88 ± 0.96
*8.33 ± 0.91
*Oxygen 100 12.49 ± 1.30 10.88 ± 1.13
*11.94 ± 1.86 11.54 ± 1.31
*10.63 ± 2.01
*10.32 ± 2.42
*10.16 ± 1.24
*10.23 ± 2.42
*9.71 ± 3.29
*Measure 150 12.19 ± 1.81 11.32 ± 1.28 10.01 ± 1.83
*10.32 ± 2.43
*10.84 ± 3.03
*9.70 ± 2.60
*9.29 ± 2.02
*9.75 ± 1.38
*9.32 ± 0.66
*Hat normal saline 1 93.76 ± 9.23 96.58 ± 9.71 95.04 ± 8.91 93.32 ± 11.51 91.88 ± 10.51 90.76 ± 8.23 90.98 ± 12.26 90.24 ± 9.06 89.96 ± 10.55 arteries and veins Radix Salviae Miltiorrhizae drop pills 60 87.98 ± 8.27 90.44 ± 9.72 97.52 ± 9.83
*119.46 ± 9.84
*146.18 ± 11.41
*154.62 ± 7.62
*145.82 ± 6.71
*131.1 ± 10.81
*118.42 ± 18.63 stream medicine 50 90.60 of the present invention ± 9.07 93.84 ± 11.62 106.64 ± 12.71 126.06 ± 11.32
*141.54 ± 11.25
*148.94 ± 16.41
*138.84 ± 23.06
*124.74 ± 24.49
*108.04 ± 10.67
*Measure 100 88.58 ± 5.32 90.68 ± 4.56 95.74 ± 8.82
*104.56 ± 7.54
*136.74 ± 3.47
*147.38 ± 7.71
*150.66 ± 8.26
*136.82 ± 7.49
*17.90 ± 8.36 150 89.78 ± 8.85 90.62 ± 7.31 107.44 ± 6.73
*130.98 ± 10.71
*147.34 ± 9.22
*152.32 ± 5.20
*155.42 ± 7.89
*140.02 ± 16.40
*118.86 ± 15.90 heart normal saline 1 1.85 ± 0.13 1.92 ± 0.09
*1.85 ± 0.14 1.85 ± 0.16 1.91 ± 0.13 1.83 ± 0.16 1.76 ± 0.20 1.77 ± 0.14 1.75 ± 0.14
*Defeated Radix Salviae Miltiorrhizae drop pill 60 1.93 ± 0.35 1.96 ± 0.36
*1.90 ± 0.35 1.96 ± 0.29 1.93 ± 0.31 1.87 ± 0.26 1.87 ± 0.26 1.86 ± 0.31 1.85 ± 0.28 goes out medicine 50 1.92 of the present invention ± 0.10 1.97 ± 0.09 1.84 ± 0.16 1.81 ± 0.18
*1.78 ± 0.16
*1.77 ± 0.15
*1.76 ± 0.11
*1.79 ± 0.08
*1.83 ± 0.05
*Measure 100 2.22 ± 0.23 2.25 ± 0.22 2.24 ± 0.29 2.16 ± 0.26 2.22 ± 0.29 2.14 ± 0.21 2.10 ± 0.19 2.02 ± 0.17
*2.02 ± 0.26
*150 1.83 ± 0.18 1.84 ± 0.18 1.81 ± 0.17 1.79 ± 0.16 1.82 ± 0.17 1.81 ± 0.16 1.84 ± 0.14 1.77 ± 0.13 1.75 ± 0.16
*With self is relatively before the administration:
*: p＜0.05
*: annotate p＜0.01: the dosage unit of normal saline group: ml/kg, the dosage unit of other groups: mg/kg.Myocardial oxygen consumption unit: ml/100g/min, coronary flow unit: ml/100g/min, heart stroke unit: L/min
Table 7 intravenous injection health heart sheet to myocardial oxygen consumption, coronary flow and kinemic influence index group dosed administration before after the administration (branch)
135 10 15 20 30 60 myocardium normal saline 1 12.4 ± 1.4 11.9 ± 11.3 12.0 ± 1.0 12.3 ± 1.3 12.3 ± 1.6 12.2 ± 1.5 12.8 ± 1.3 12.3 ± 1.7 12.31 ± 1.9 oxygen consumption verapamil 0.2 13.8 ± 1.9 4.7 ± 0.8
*5.1 ± 1.2
*6.8 ± 1.3
*7.3 ± 2.2
*9.4 ± 2.3
*10.4 ± 1.8
*12.2 ± 1.8 13.0 ± 1.8 amount medicine 50 12.9 of the present invention ± 1.64 9.9 ± 2.4 9.7 ± 1.4
*10.0 ± 1.4
*9.6 ± 2.1
*9.6 ± 1.8
*10.0 ± 1.2
*9.4 ± 1.3
*10.4 ± 1.9
*Arteria coronaria normal saline 1 101.9 ± 8.7 104.2 ± 7.2 103.7 ± 7.2 100.8 ± 10.8 100.8 ± 7.5 102.3 ± 7.2 100.8 ± 10.3 102.3 ± 7.5 102.3 ± 7.1 flow verapamil 0.2 95.5 ± 6.5 136.9 ± 18.6
*129.9 ± 18.3
*116.5 ± 7.9
*118.5 ± 12.0
*108.0 ± 13.6
*103.7 ± 11.3
*97.1 ± 8.3 98.3 ± 7.2
Medicine 50 94.1 of the present invention ± 9.7 102.7 ± 15.6 103.8 ± 8.7
*103.2 ± 11.3
*101.7 ± 14.2
*103.4 ± 8.2
*106.2 ± 12.4
*110.3 ± 15.1
*109.4 self compare with administration is front ± 14.4 heart physiological saline 1 1.90 ± 0.11 1.95 ± 0.15 1.92 ± 0.14 1.91 ± 0.14 1.90 ± 0.10 1.91 ± 0.16 1.92 ± 0.14 1.90 ± 0.15 1.91 ± 0.18 output Verapamil 0.2 1.80 ± 0.29 1.88 ± 0.49 1.88 ± 0.47 1.91 ± 0.45 1.93 ± 0.42 1.92 ± 0.40 1.88 ± 0.42 1.83 ± 0.34 1.76 ± 0.28 amount medicine 50 1.83 of the present invention ± 0.11 1.74 ± 0.25 1.70 ± 0.33 1.81 ± 0.18 1.74 ± 0.18 1.83 ± 0.15 1.85 ± 0.17 1.98 ± 0.2 1.88 ± 0.15:*: other respectively organize dosage unit p＜0.05 normal saline dosage unit: ml/kg: mg/g verapamil n=7 health heart sheet n=7 normal saline n=5 myocardial oxygen consumption unit: ml/100g/min, coronary flow unit: ml/100g/min, heart stroke unit: L/min
After table 8. intravenous injection gives health heart sheet to the preceding administration of the influence index group dosed administration of dog left ventricular systolic pressure (kPa), left chamber diastolic pressure (kPa) (branch)
135 10 15 20 30 60 left chamber normal saline 1 21.1 ± 4.5 21.2 ± 4.5 20.9 ± 4.4 20.6 ± 3.8 20.9 ± 3.7 20.9 ± 3.9 20.6 ± 3.6 20.8 ± 3.4 20.5 ± 3.3 shrink verapamil 0.2 17.2 ± 2.6 15.7 ± 3.1
*16.5 ± 3.7 16.8 ± 3.7 16.7 ± 3.9 17.0 ± 3.6 17.1 ± 3.9 17.3 ± 2.5 16.9 ± 2.8 press medicine 50 19.6 of the present invention ± 4.6 18.0 ± 6.8 15.9 ± 5.7
*14.7 ± 4.3
*13.3 ± 4.9
*133 ± 3.3
*15.2 ± 4.4
*14.4 ± 5.4
*13.9 ± 4.3
*Before pressing medicine 50 0.64 of the present invention ± 0.49 0.75 ± 0.35 0.74 ± 0.49 0.83 ± 0.81 0.47 ± 0.29 0.46 ± 0.65 0.30 ± 0.80 0.29 ± 0.80-0.15 ± 1.51 and administration, left chamber physiological saline 1 0.75 ± 3.32-0.34 ± 1.33-0.06 ± 1.19 0.08 ± 0.45-0.19 ± 1.15-0.38 ± 1.28-0.53 ± 1.39 0.03 ± 0.63 0.41 ± 1.38 diastole verapamils 0.2 0.50 ± 1.32 1.29 ± 1.07 1.49 ± 1.55 1.67 ± 1.52 1.26 ± 0.76 1.73 ± 1.76 0.89 ± 0.98 1.36 ± 1.30 1.64 ± 1.59 self compare:*: compare with the health heart sheet p＜0.05: other respectively organize dosage unit #:p＜0.05 normal saline dosage unit: ml/kg: mg/kg verapamil n=7 health heart sheet n=7 normal saline n=6
Table 9. is respectively organized the ventricular arrhythmia that causes after the ligation
| Group | N | The number of animals of various ventricular arrhythmias takes place | ||
| Ventricular premature contraction takes place frequently | Ventricular tachycardia | Quiver in the chamber | ||
| Normal saline 1ml/kg Radix Salviae Miltiorrhizae drop pill 120mg/kg Propranolol 1mg/kg medicine 100mg/kg of the present invention medicine 200mg/kg of the present invention medicine 300mg/kg of the present invention | 6 6 10 6 6 6 | 0 0 3 0 0 0 | 0 1 0 0 0 0 | 3 0 2 0 0 1 |
Conclusion
Medicine of the present invention has tangible function of resisting myocardial ischemia, shows as to alleviate EGC change and the myocardium enzyme release that ischemia causes, dwindles myocardial infarction area, reduces ARR incidence rate.
Medicine function of promoting blood circulation to disperse blood clots experiment of the present invention
1. material
2. animal: Japan large ear rabbit, body weight 2.0 ± 0.3kg, ♀ ♂ half and half.
3. medicine: tablet of the present invention: the 0.3g/ sheet, be equivalent to crude drug 2.0g, with tablet of the present invention, thin up is to 50mg/ml; 150mg/ml; The solution of 250mg/ml is put 4 ℃ of refrigerators and is preserved standby.FUFANG DANSHEN DIWAN: sky, Tianjin man of great strength's pharmacy Group Co.,Ltd product, 25mg/ grain.Lot number: 990108.Thin up is put 4 ℃ of refrigerators and is preserved standby to 50mg/ml.
Instrument: PPP autobalance platelet aggregation instrument SPA-3 type, Shanghai Kodak test instrunment factory product.Cone-plate formula EII type blood specific detection instrument.
4. method and result
(1). to the influence of rabbit platelet aggregation:
The rabbit of buying back was observed 2 days, and auricular vein was got blood in the 3rd day, got once behind the 4h again, measured each treated animal platelet aggregation degree, rejected the not accumulative animal of platelet, and qualified animal is divided into 6 groups at random, the control group; The blood stasis model group; Composite Salvia Dropping Pill group; The large, medium and small dosage group of medicine of the present invention.Control group, blood stasis model group are irritated stomach with distilled water 2ml/kg, and all the other are organized all by the 2ml/kg administration.Successive administration 7 days, 1h, 4h get blood 3ml from auricular vein after the administration in the 7th day, measure each treated animal platelet aggregation degree, by formula calculate to assemble and suppress percentage rate, the results are shown in Table 16.
Aggregation rate * 100 before (aggregation rate after the preceding aggregation rate-medication of medication)/medication
=assemble and suppress percentage rate (%)
The result shows that three dosage groups of medicine of the present invention all can obviously suppress the inductive platelet aggregation of ADP, with the control group significant difference is arranged relatively.
Table 16, medicine of the present invention are to the influence of platelet aggregation
Dosage is assembled suppression ratio (%) (group (g/kg) 1h 4hcontrol 15.6 ± 5.5 16.2 ± 10.0 medicine small dose group 0.1 34.6 ± 10.7 of the present invention of X ± SD)
*33.1 ± 14.4
*Dosage group 0.3 36.5 ± 13.3 in the medicine of the present invention
*38.5 ± 7.3
*The heavy dose of group 0.5 40.8 ± 8.2 of medicine of the present invention
*45.7 ± 9.1
*Composite Salvia Dropping Pill group 0.1 40.5 ± 12.3
*44.5 ± 9.4
*
N=6 and control group are relatively;
*P＜0.05;
*P＜0.01.
2.2. influence to blood stasis model rabbit whole blood viscosity
The afore-mentioned test rabbit continues to be administered to the tenth day, and auricular vein is injected 10% high molecular dextran (molecular weight 500,000) 5ml/kg after the administration, injects in 5 minutes to finish, and the control group is injected normal saline.Heart extracting blood is surveyed whole blood viscosity after 20 minutes.The results are shown in Table 17.
Table 17, medicine of the present invention influence to blood stasis model rabbit whole blood viscosity that group dosage whole blood is low to be cut viscosity whole blood height and cut viscosity
(g/kg) (mpas) (mpas) control organizes 7.85 ± 0.90 5.43 ± 0.72 blood stasis model groups 19.56 ± 2.52
*14.57 ± 1.33
*Medicine small dose group 0.1 14.99 ± 1.18 of the present invention
* △ △11.33 ± 1.10
* △ △Dosage group 0.3 13.19 ± 1.84 in the medicine of the present invention
*10.30 ± 0.96
* △ △The heavy dose of group 0.5 9.67 ± 1.89 of medicine of the present invention
△ △6.59 ± 1.34
* △ △Composite Salvia Dropping Pill group 0.1 11.05 ± 2.12
* △ △8.62 ± 1.83
* △ △N=6; Compare with the control group
*P＜0.05;
*P＜0.01;
Compare △ P＜0.05, △ △ P＜0.01 with the blood stasis model group.
The result shows that medicine of the present invention can obviously reduce the whole blood viscosity of blood stasis model rabbit, improves the hemorheology situation.
Animal toxicity test
Animal acute toxicity test result: the oral LD of the mice of medicine of the present invention
50Be 9.74 ± 1.65g/kg, the 95% credible 8.24-11.53g/kg that is limited to.Dead Mus is dissected its internal organs immediately and shows no obvious abnormalities reaction.
Long term toxicity test by clinical application establish height, in low three dosage groups and matched group, its dosage is respectively 2g, 0.4g, 0.08g/kg/d (crude drug amount 94.60g, 18.92g, 3.78g), is equivalent to 100,20,4 times of clinical consumption.Rat oral gavage administration 3 months is measured and each internal organs pathological examination through hematological examination, blood parameters.Low, the middle dosage group of result is given relatively with contrast, show no obvious abnormalities and intoxicating phenomenon, high dose group hematological examination and matched group relatively show no obvious abnormalities, blood biochemical is learned and is checked that serum GPT raises and matched group relatively has significant difference, drug withdrawal two week, the back was normal, with matched group significant difference comparatively.Pathological examination is seen indivedual swelling of liver cell, and convalescent period is not seen obvious pathological change.
Medicine main pharmacodynamics research of the present invention and animal toxicity test result show:
1, medicine of the present invention has good anti-tentative myocardial ischemia effect, show as and improve the variation of ischemic electrocardiogram, troponin I, CK-MB due to the minimizing ischemia, the release of CK, dwindle infarct size, the incidence rate of the ventricular arrhythmia that the minimizing ischemia causes, some parameter is better than Propranolol.
2, through duodenal administration, the obvious coronary blood flow increasing of medicine of the present invention slightly lowers the heart oxygen consumption, and this effect is similar to Radix Salviae Miltiorrhizae drop pill.The present invention to HR, CO, SBP, DBP, MBP, LVSP, LVDP, ± other hemodynamic parameters such as dP/dt all do not have obvious influence.But the intravenously administrable decreasing heart rate, in short time reduce systolic arterial pressure, obviously reduce the heart oxygen consumption.
3, Chinese medicine of the present invention can obviously suppress the inductive platelet aggregation of ADP, reduces the whole blood viscosity of blood stasis model rabbit, improves the hemorheology situation.
4, compare with the existing treatment coronary heart disease that resists myocardial ischemia, angina drug, medicine of the present invention have determined curative effect, stable, lasting, onset time is fast, toxic and side effects is low, characteristics such as untoward reaction is few, existing chemicals side effect is big, the Chinese medicine onset waits deficiency slowly thereby overcome, and is ideal treatment coronary heart disease, the angina drug of resisting myocardial ischemia.
Accompanying drawing 1 is preparation of pharmaceutical formulations process chart of the present invention.
Embodiment 1
Get Rhizoma et radix valerianae 3kg, cut into the long section of 1-3cm, put in the distilled water generator, volatile oil is got in the straight-through water vapour steaming of water proof, collect volatile oil; Other gets Radix Salviae Miltiorrhizae 1kg, adds 4 times of amount 70% alcohol reflux three times, each 1 hour, extracting liquid filtering, merging filtrate, it is 1.25 (Bs that ethanol to relative density is reclaimed in room temperature decompression (reducing to 0.06-0.09Mpa by normal pressure), 50 ℃), pour out, add ethanol to 70%, refluxed 0.5 hour, and left standstill the leaching supernatant 12 hours, supernatant reclaim under reduced pressure to 1.20 (B, 50 ℃) is poured out, be placed to room temperature, 100 orders filter; Insoluble matter low temperature (30 ℃ to 60 ℃) drying, filtrate is concentrated into thick paste, and the thick paste drying under reduced pressure merges with insoluble matter, pulverizes 80 mesh sieves, gets medicated powder; Taking polyethylene glycol-6000 480g, tween 80 40g behind 70 ℃ of heating and meltings, adds volatile oil and medicated powder, insulated and stirred was mixed 10 minutes, drip in model, cooling is taken out, promptly make 2000 of medicinal tablets of the present invention, every heavy 0.3g, 6 of recipe quantities were 1.8g on 1st, were equivalent to Rhizoma et radix valerianae 9g, Radix Salviae Miltiorrhizae 3g.
Embodiment 2
Get Rhizoma et radix valerianae 3kg, cut into the long section of 1-3cm, put in the distilled water generator, the straight-through water vapour of water proof steams gets volatile oil, collect volatile oil, add the beta-schardinger dextrin-inclusion, must inclusion complex; Other gets Radix Salviae Miltiorrhizae 1kg, adds 4 times of amount 70% alcohol reflux three times, each 1 hour, extracting liquid filtering, merging filtrate, it is 1.25 (Bs that ethanol to relative density is reclaimed in room temperature decompression (reducing to 0.06-0.09Mpa by normal pressure), 50 ℃), pour out, add ethanol to 70%, refluxed 0.5 hour, and left standstill the leaching supernatant 12 hours, supernatant reclaim under reduced pressure to 1.20 (B, 50 ℃) is poured out, be placed to room temperature, 100 orders filter; Insoluble matter low temperature (30 ℃ to 60 ℃) drying, filtrate is concentrated into thick paste, and the thick paste drying under reduced pressure merges with insoluble matter, pulverizes 80 mesh sieves, gets medicated powder; With this medicated powder mix with aforementioned inclusion complex, pulverize, sieve, encapsulated, promptly get 2000 of capsules, every heavy 0.3 gram.
Embodiment 3
Get Rhizoma et radix valerianae 3kg, ggg cuts into the long section of 1-3cm, puts in the distilled water generator, and volatile oil is got in the straight-through water vapour steaming of water proof, collect volatile oil; Other gets Radix Salviae Miltiorrhizae 1kg, adds 4 times of amount 70% alcohol reflux three times, each 1 hour, extracting liquid filtering, merging filtrate, decompression recycling ethanol to relative density is 1.25 (Bs, 50 ℃), pour out, add ethanol to 70%, refluxed 0.5 hour, and left standstill the leaching supernatant 12 hours, supernatant reclaim under reduced pressure to 1.20 (B, 50 ℃) is poured out, be placed to room temperature, 100 orders filter; The insoluble matter cold drying, filtrate is concentrated into thick paste, and the thick paste drying under reduced pressure merges with insoluble matter, pulverizes 80 mesh sieves, gets medicated powder; Taking polyethylene glycol-6000 480g, tween 80 40g behind 70 ℃ of heating and meltings, adds volatile oil and medicated powder, and insulated and stirred was mixed 10 minutes, splashed in the condensed fluid, made drop pill.
Claims (13)
1. a treatment coronary heart disease, angina pectoris Chinese medicine is characterized in that it is is raw material with Rhizoma et radix valerianae, Radix Salviae Miltiorrhizae, are 1 to 10 to 1 medicaments of making by the weight proportion of Rhizoma et radix valerianae and Radix Salviae Miltiorrhizae.
2. treatment coronary heart disease according to claim 1, angina pectoris Chinese medicine is characterized in that the said valerian and the weight proportion of Radix Salviae Miltiorrhizae are 2 to 5 to 1.
3. treatment coronary heart disease according to claim 1, angina pectoris Chinese medicine is characterized in that the said valerian and the weight proportion of Radix Salviae Miltiorrhizae are 3 to 1.
4. according to any one described treatment coronary heart disease, angina pectoris Chinese medicine in the claim 1 to 3, it is characterized in that said medicament is any dosage form on the pharmaceutics.
5. treatment coronary heart disease according to claim 4, angina pectoris Chinese medicine is characterized in that said medicament is tablet, capsule or drop pill.
6. the preparation method of the described treatment coronary heart disease of claim 5, angina pectoris Chinese medicinal tablet is characterized in that getting Rhizoma et radix valerianae, and the section of cutting into is put in the multipotency extraction pot, and the straight-through water vapour of water proof steams gets volatile oil, collect volatile oil; Other gets Radix Salviae Miltiorrhizae, adds 3 to 6 times of amount 50% to 90% alcohol reflux three times, each 1 hour, extracting liquid filtering, filtrate merges, and decompression recycling ethanol is 1.25 to measuring relative density at 50 ℃ with B, emit, add ethanol to 70%, refluxed 0.5 to 2 hour, left standstill 10 to 14 hours, the leaching supernatant, the supernatant decompression recycling ethanol is 1.20 to measuring relative density at 50 ℃ with B, emits, be placed to room temperature, 100 orders filter; 30 ℃ to 60 ℃ dryings of insoluble matter, filtrate is concentrated into thick paste, and the thick paste drying under reduced pressure merges with insoluble matter, pulverizes 80 mesh sieves, gets medicated powder; Get the adjuvant Polyethylene Glycol, behind the heating and melting, add the medicated powder and the volatile oil that make, mix, splash in the model, cooling is taken out and is promptly made tablet.
7. the preparation method of the described treatment coronary heart disease of claim 5, angina pectoris Traditional Chinese Medicine Dropping Pill is characterized in that getting Rhizoma et radix valerianae, and the section of cutting into is put in the distilled water generator, and the straight-through water vapour of water proof steams gets volatile oil, collect volatile oil; Other gets Radix Salviae Miltiorrhizae and adds 3 to 6 times of amount 50% to 90% alcohol reflux three times, each 1 hour, extracting liquid filtering, merging filtrate, the room temperature decompression recycling ethanol is 1.25 to measuring relative density at 50 ℃ with B, pours out, add ethanol to 70%, refluxed 0.5 hour, and left standstill the leaching supernatant 12 hours, the supernatant reclaim under reduced pressure is 1.20 to measuring relative density at 50 ℃ with B, pour out, be placed to room temperature, 100 orders filter; 30 ℃ to 60 ℃ dryings of insoluble matter, filtrate is concentrated into thick paste, and the thick paste drying under reduced pressure merges with insoluble matter, pulverizes 80 mesh sieves, gets medicated powder; Get the adjuvant Polyethylene Glycol, behind the heating and melting, add volatile oil and medicated powder, insulated and stirred was mixed 10 minutes, splashed in the condensed fluid, made drop pill.
8. according to claim 6 or 7 described treatment coronary heart disease, angina pectoris preparation method of Chinese medicine, it is characterized in that employed adjuvant Polyethylene Glycol is a Polyethylene Glycol-6000.
9. described according to Claim 8 treatment coronary heart disease, angina pectoris preparation method of Chinese medicine is characterized in that having used solubilizing agent in preparation tablet process.
10. according to the described treatment coronary heart disease of claim 9, angina pectoris preparation method of Chinese medicine, it is characterized in that said solubilizing agent is a tween.
11. treatment coronary heart disease according to claim 10, angina pectoris preparation method of Chinese medicine is characterized in that said solubilizing agent tween is a tween 80.
12. treatment coronary heart disease according to claim 11, angina pectoris preparation method of Chinese medicine, the weight proportion that it is characterized in that raw medicinal material Rhizoma et radix valerianae, Radix Salviae Miltiorrhizae and adjuvant Polyethylene Glycol-6000 and solubilizing agent tween 80 is 75: 25: 12: 1.
13. the preparation method of the described treatment coronary heart disease of claim 5, the agent of angina pectoris Chinese medicinal capsule is characterized in that getting Rhizoma et radix valerianae, the section of cutting into, put in the distilled water generator, the straight-through water vapour of water proof steams gets volatile oil, collect volatile oil, add the beta-schardinger dextrin-inclusion, get inclusion complex; Other gets Radix Salviae Miltiorrhizae, adds 3 to 6 times of amount 50% to 90% alcohol reflux three times, each 1 hour, extracting liquid filtering, merging filtrate, decompression recycling ethanol is 1.1 to 1.4 to measuring relative density at 50 ℃ with B, pour out, add ethanol to 70%, refluxed 0.5 hour, left standstill 12 hours, the leaching supernatant, the supernatant reclaim under reduced pressure is 1.1 to 1.4 to measuring relative density at 50 ℃ with B, pours out, be placed to room temperature, 100 orders filter; The insoluble matter cold drying, filtrate is concentrated into thick paste, and the thick paste drying under reduced pressure merges with insoluble matter, pulverizes 80 mesh sieves, gets medicated powder; With this medicated powder mix with aforementioned inclusion complex, pulverize, sieve, encapsulated, promptly get capsule.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001146238A CN1135996C (en) | 2000-06-09 | 2000-06-09 | Chinese medicine for treating coronary heart disease and angina pectoris and its preparing process |
| AU2001289525A AU2001289525A1 (en) | 2000-06-09 | 2001-06-11 | A composition made of chinese medicinal herbs for treatment of coronary heart disease and angina pectoris and the process for the production thereof |
| PCT/CN2001/000928 WO2002000235A1 (en) | 2000-06-09 | 2001-06-11 | A composition made of chinese medicinal herbs for treatment of coronary heart disease and angina pectoris and the process for the production thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001146238A CN1135996C (en) | 2000-06-09 | 2000-06-09 | Chinese medicine for treating coronary heart disease and angina pectoris and its preparing process |
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| CN1135996C true CN1135996C (en) | 2004-01-28 |
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| CN1074121A (en) * | 1992-10-24 | 1993-07-14 | 广西卫生学校附属药厂 | A kind of production method for the treatment of the coronary heart disease Chinese medicinal tablet |
| CN1055630C (en) * | 1996-10-25 | 2000-08-23 | 昆明医学院第一附属医院 | Notoginseng-red sage tablet and its prepn |
| CN1191137A (en) * | 1998-02-27 | 1998-08-26 | 湖北省老年医学研究所 | Valerian preparation and its preparing process and use |
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|---|---|
| CN1327814A (en) | 2001-12-26 |
| AU2001289525A1 (en) | 2002-01-08 |
| WO2002000235A1 (en) | 2002-01-03 |
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