CN1939405B - Drop pills for treating coronary heart disease and making method thereof - Google Patents
Drop pills for treating coronary heart disease and making method thereof Download PDFInfo
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- CN1939405B CN1939405B CN2006101135410A CN200610113541A CN1939405B CN 1939405 B CN1939405 B CN 1939405B CN 2006101135410 A CN2006101135410 A CN 2006101135410A CN 200610113541 A CN200610113541 A CN 200610113541A CN 1939405 B CN1939405 B CN 1939405B
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Abstract
A Chinese medicine in the form of dripping pill for treating coronary heart disease, angina pectoris, chest distress and palpitation is prepared from red sage root. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of is raw material with the Radix Salviae Miltiorrhizae, is used for the angina pectoris that coronary heart disease causes, the pharmaceutical preparation and the method for making thereof of uncomfortable in chest and cardio palmus belong to technical field of Chinese medicines.
Background technology
Coronary heart disease is because its sickness rate is high, and mortality rate is high, and the healthy of the mankind in serious harm, thereby b referred to as " the first human killers ".
Cause of coronary heart disease increases with the growth at age, and degree also increases the weight of with the growth at age.There is data to show, from beginning in 40 years old, every increase by 10 years old, prevalence of coronary heart disease increases 1 times.Male 50 years old, women are after 60 years old, and the coronary atherosclerosis development is rapider, and the danger of same myocardial infarction also increases with advancing age.
World Health Organization (WHO) is classified as follows coronary heart disease: the heart failure in primary cardiac all standing, angina pectoris, myocardial infarction, the ischemic heart desease, arrhythmia.Though coronary heart disease the middle age with sequela, pathological changes coronarius also can originate from the childhood, the ratio of brain worker and physical labourer morbidity is about 2: 1.
For these reasons, study a kind of safe, medicine is effective effectively and rapidly.The medicine that is used to treat this type of disease at present also is of a great variety.Various researchs report points out, the TANSHINONES that contains in the salviamiltiorrhizabung, danshensu, protocatechualdehyde isoreactivity composition can effectively be treated angina pectoris that coronary heart disease causes, disease such as uncomfortable in chest.The type of preparation that its single medical material is processed into through extraction is also very many; Like Radix Salviae Miltiorrhizae electuary, danshen cream, Radix Salviae Miltiorrhizae Tabellae, Radix Salviae Miltiorrhizae drop pill, tanshinone capsule, Radix Salviae Miltiorrhizae Injection, Danshen heart-benefiting capsule etc.; Because the method for distilling of each preparation is different, finally causes each dosage form curative effect to differ greatly.
The Danshen heart-benefiting capsule records in the 17th of ministry standard, and its preparation process adds starch 88g for getting Radix Salviae Miltiorrhizae extract 200g, Pulvis Talci 10g, and magnesium stearate 2g, mixing incapsulates, and processes 1000, promptly gets.Wherein the method for preparing of Radix Salviae Miltiorrhizae extract is the Radix Salviae Miltiorrhizae behind the decocting of learning from else's experience, and drying is pulverized, and adds 90% alcohol reflux three times, 2 hours for the first time; Second and third time each 1.5 hours filters respectively, merging filtrate, and concentrating under reduced pressure becomes extractum; The ordinary water that adds 10 times of amounts of extractum, the limit edged stirs, and leaves standstill, and filters; The precipitate cold drying is pulverized, and sieves, and promptly gets.Adopt the extraction exquisiteness method of alcohol extracting-water precipitating can fat-soluble active ingredient in the Radix Salviae Miltiorrhizae fully be separated, make its curative effect be higher than the made preparation of other method for distilling, but process behind the capsule and be unfavorable for effective ingredient quick dissolving and absorption in vivo.So provide a kind of reasonable dosage form that can give full play to this curative effect of medication that very important meaning is arranged.
Summary of the invention
The object of the invention just provides a kind of safe, medicine and preparation method thereof effectively and rapidly, can effectively treat the angina pectoris that coronary heart disease causes, uncomfortable in chest and cardio palmus.
Drop pill has become the direction of treatment by Chinese herbs cardiovascular and cerebrovascular diseases medicament preparation development at present, because drop pill has the characteristics of quick performance drug effect, yet Traditional Chinese Medicine Dropping Pill is difficult to make; Be prone to conditions of streaking in process of production, the drop pill roundness, slickness and the mouldability that make are undesirable, the Danshen heart-benefiting dropping pill formulation that we invented; The dispersion of medicine in substrate is molecularity and exists, and makes its enhanced dissolution rate, bioavailability raising, better efficacy, and the drop pill taking convenience; More easy for patients to accept; Moreover its preparation technology is simple and direct, and automaticity is high, and production efficiency is improved.
The drop pill that the present invention is made mainly is prepared from following method:
1) weighting raw materials material Radix Salviae Miltiorrhizae is an amount of;
2) get the red rooted salvia decocte with water that step 1) takes by weighing after, drying is pulverized, it is an amount of to add 90% ethanol; Adopt the microwave-assisted extraction method to extract, filter, merging filtrate, concentrating under reduced pressure becomes extractum; The ordinary water that adds 10 times of amounts of extractum, the limit edged stirs, and leaves standstill, and filters; The precipitate cold drying is pulverized, and sieves, and promptly gets Radix Salviae Miltiorrhizae extract;
3) get step 2) Radix Salviae Miltiorrhizae extract of gained puts in the capacity molten matrix, and mixing splashes in the coolant, processes drop pill, promptly gets.
Step 2 in the above-mentioned method for preparing) the Radix Salviae Miltiorrhizae crude drug adds 4～12 times of water gagings and decocts once under normal pressure, and decocting time 30～90min is preferably and adds 8 times of water gagings and decoct 30min; Step 2) smashing fineness of Radix Salviae Miltiorrhizae extract is preferably 100～200 orders, more preferably 120～150 orders.Substrate described in the step 3) can be any or the two or more mixing in Macrogol 4000 or 6000, sodium stearate, the glycerin gelatine; Said condensing agent is selected from liquid paraffin, vegetable oil, methyl-silicone oil, kerosene, and being preferably substrate is Macrogol 4000, and condensed fluid is a liquid paraffin.Preferably the weight proportion scope of the substrate behind medicated powder and the heating and melting by 1: 1～1: 10 mixed in the step 3), more preferably mix by 1: 2～2.5 weight proportion scope.The temperature that airtight insulation in the processing step is arranged again is 50～70 ℃, and the temperature on condensed fluid top is remained on 30～35 ℃, and the temperature of condensed fluid is controlled to be 5～10 ℃.
Preparation process condition preferred:
1, the Radix Salviae Miltiorrhizae decocting boils the process conditions selection:
The decocte with water of Radix Salviae Miltiorrhizae crude drug is for water-solubility impurity composition is wherein removed the impurity when reducing alcohol extraction.To the loss of active ingredient, fry in shallow oil once with 8 times of water gagings when reducing decocting, we are through the investigation to TANSHINONES content in the red rooted salvia behind the decocting, to confirm the time of decocting.Concrete grammar is following: get totally 9 parts of Radix Salviae Miltiorrhizae crude drug 200g; 30,60,90 minutes each three parts, add 8 times of water gagings respectively and decoct once, red rooted salvia is dry; Measure decocting liquid and concentrate TANSHINONES content in back extractum (relative density 1.35) yield and the Radix Salviae Miltiorrhizae, the result sees the following form:
Table 1: yield of extract and TANSHINONES relation with contents are investigated behind decocting time and the decocting
Can find out that from last table along with the lengthening of decocting time, the content of TANSHINONES can reduce gradually in the Radix Salviae Miltiorrhizae, and the concentrated back of water extract yield of extract has tended to balance behind 30min, begun during to 60min to descend.Boil just in order to remove water-solubility impurity composition in the Radix Salviae Miltiorrhizae because Radix Salviae Miltiorrhizae is carried out decocting, not only can most of water-solubility impurity in the medical material be removed so select to decoct 30min, and can keep the content of tanshinone in the Radix Salviae Miltiorrhizae preferably.
2, the selection of Radix Salviae Miltiorrhizae extraction process behind the decocting
After Radix Salviae Miltiorrhizae pressed the selection process decocting, drying was pulverized, and we adopt supercritical CO respectively with Radix Salviae Miltiorrhizae
2Extract, 90% ethanol be solvent with microwave-assisted extract, alcohol reflux, with the extract aqueous precipitation, with drying precipitate, relatively each method for distilling is to the influence of active ingredient, serves as to investigate index with the content of tanshinone.The result sees table 2:
Table 2: Different Extraction Method is to the investigation of the content of tanshinone
Can find out from last table, adopt alcohol reflux tanshinone content to be starkly lower than and use microwave-assisted extraction method and CO
2Super critical extraction.Microwave-assisted extraction method and CO
2Super critical extraction is compared, and uses CO
2Super critical extraction operating technology difficulty is big, requires to have certain pressure, just can make CO
2Liquefaction reaches the purpose of extraction, and the equipment precision requirement is high, and producing cost is high, and extraction time is 2～3 times that microwave-assisted extracts; And microwave auxiliary extracting method only needs 20～30min just active ingredient fully to be proposed owing to its extraction time is short; So not only can avoid the problem that tanshinone decomposes because of the prolongation of heat time heating time gradually, content reduces; And the saving energy; Simple to operate, and extraction efficiency is high, so preferred method for distilling is the microwave-assisted extraction method.
3, the smashing fineness of Radix Salviae Miltiorrhizae extract and the addition of substrate are investigated concrete the test as follows:
Get Radix Salviae Miltiorrhizae extract 200g, totally three parts, be crushed to different meshes, add equivalent substrate, investigate its dispersion situation in substrate, the result sees table 3:
Table 3: the extract degree of grinding is investigated with adding substrate magnitude relation
Result of the test shows that grinding particle size is big more, and the sedimentation velocity of medicine in substrate is fast more, and the uniformity of preparation of Chinese medicine content can receive very big influence like this, is unfavorable for stability of formulation; And the addition of substrate is many more, and the medicine uniformity blended with it is good more, but really can reduce the content of dispersion of preparation, increases taking dose, also can increase cost; Pulverizing can make medicine middle part fractionated molecule destroyed more than granularity is greater than 150 orders, reduces the curative effect of medicine, is 120～150 orders so we select the medicine grinding particle size, and the substrate addition is 2 times of medicated powder.
The temperature of the temperature on the temperature of medicinal liquid insulation, condensed fluid top, condensed fluid is selected according to above-mentioned each selection process step when 4, dripping the system drop pill; With medicine with after substrate is mixed; Insulation is processed drop pill, through slickness, rounding property, the formability of investigating prepared drop pill; Confirm the temperature of the needed medicinal liquid insulation of this drop pill of preparation, the temperature on condensed fluid top, the temperature of condensed fluid, the result sees table 4:
Table 4: the temperature test of the temperature of medicinal liquid insulation, the temperature on condensed fluid top, condensed fluid is investigated
Can find out that from last table the temperature of medicinal liquid insulation is that 60 ℃, the temperature on condensed fluid top are that 30～35 ℃, the temperature of condensed fluid the drop pill rounding property, slickness and the formability that make when being 5～10 ℃ are all good.
5, through 3 batches of prepared Danshen heart-benefiting drop pill of this invention selection process, according to drop pill inspection method and relevant content assaying method, carried out stable accelerated test and investigated, investigate the result and see table 5.
Table 5: the medicine stability accelerated test is investigated
"+" expression is up to specification."-" expression is against regulation.
Can fully find out from last table, the Danshen heart-benefiting drop pill that the present invention is prepared, technology is reasonable, steady quality.
Specific embodiment
After (embodiment 1) Radix Salviae Miltiorrhizae crude drug decocte with water, drying is pulverized, and adds 90% ethanol and uses microwave auxiliary reflux 25min; Extracting solution reclaims ethanol, and drying is crushed to 150 orders, gets Radix Salviae Miltiorrhizae extract 200g; Put in the fused Macrogol 4000 of 2 times of amounts mixing, insulation (60 ℃); Splash in the liquid paraffin of (5～10 ℃), process drop pill, promptly get.
After (embodiment 2) Radix Salviae Miltiorrhizae crude drug decocte with water, drying is pulverized, and adds 90% ethanol and uses microwave auxiliary reflux 25min; Extracting solution reclaims ethanol, and drying is crushed to 150 orders, gets Radix Salviae Miltiorrhizae extract 200g; Put in the fused Macrogol 4000 of 3 times of amounts mixing, insulation (60 ℃); Splash in the liquid paraffin of (5～10 ℃), process drop pill, promptly get.
After (embodiment 3) Radix Salviae Miltiorrhizae crude drug decocte with water, drying is pulverized, and adds 90% alcohol reflux three times; 2 hours for the first time, second and third time each 1.5 hours, extracting solution reclaims ethanol, drying; Be crushed to 150 orders, get Radix Salviae Miltiorrhizae extract 200g, put in the fused Macrogol 4000 of 2 times of amounts mixing; Insulation (60 ℃) splashes in the liquid paraffin of (5～10 ℃), processes drop pill, promptly gets.
After (embodiment 4) Radix Salviae Miltiorrhizae crude drug decocte with water, drying is pulverized, and uses CO
2Super critical extraction is extracted 1.5h, reclaim under reduced pressure CO
2, drying is crushed to 150 orders, gets Radix Salviae Miltiorrhizae extract 200g, put in the fused Macrogol 4000 of 2 times of amounts, and mixing, insulation (60 ℃) splashes in the liquid paraffin of (5～10 ℃), processes drop pill, promptly gets.
After (embodiment 5) Radix Salviae Miltiorrhizae crude drug decocte with water, drying is pulverized, and adds 90% ethanol and uses microwave auxiliary reflux 25min; Extracting solution reclaims ethanol, and drying is crushed to 150 orders, gets Radix Salviae Miltiorrhizae extract 200g; Put in the fused polyethylene glycol 6000 of 2 times of amounts mixing, insulation (60 ℃); Splash in the liquid paraffin of (5～10 ℃), process drop pill, promptly get.
Beneficial effect
One, the pharmacodynamics test of medicine of the present invention research
Supply the reagent thing: according to the prepared drop pill of selection process of the present invention.
Positive control medicine: Danshen heart-benefiting capsule, Changyuan Pharmaceutical Industry Co., Ltd., Jilin Prov, lot number 20051101
1, normal pressure hypoxia endurance test mice is 36, and male and female half and half are divided into water matched group, Danshen heart-benefiting capsule matched group, drug group of the present invention, 12 every group at random.Positive controls and drug group of the present invention are given the medicine 16.5g/kg of same dose, and the water matched group is given water such as the capacity of grade, equal gastric infusion, every day 3 times, totally 2 days.Measure after day administration 1 hour, outside the matched group that dewaters, each organizes lumbar injection isoproterenol 10mg/kg, after 15 minutes animal is put into the uncovered bottle of the 250ml that the 5g quicklime is housed, and writes down each animal and puts into the time to death.The result sees table 6, points out medicine of the present invention can prolong the mice life span.
Table 6: each organizes mice normal pressure anoxia enduring experimental result relatively
| Group | n | MDT |
| The water matched group | 12 | 18.26±2.13 |
| Positive controls | 12 | 15.99±1.33 ** |
| Drug group of the present invention | 12 | 11.77±1.52 *△ |
Compare with the water matched group,
*P＜0.05,
*△ P＜0.01 is compared with positive control medicine group in P＜0.01
The result shows: medicine of the present invention can resist the myocardial ischemia that heavy dose of isoproterenol causes; The mice hypoxia endurance time is prolonged; Compare with positive control drug Danshen heart-benefiting capsule and to have significant difference, medicine of the present invention obviously is superior to positive controls to prolonging the mice oxytolerant time.
2, isoproterenol causes 24 of ischemic myocardial protection effect rats, and male and female half and half are divided into water matched group, positive controls and drug group of the present invention at random; Give the medicine 16.5g/kg of same dose; The water matched group is given and is waited capacity water, irritates stomach every day 3 times, continuous 10 days.Measure after day administration 1 hour, the fixing II lead electrocardiogram of surveying of animal, voltage 2mv, chart drive speed 50mm/s, the electrocardiographic abnormality person does not include experiment in.After surveying normal ECG, lumbar injection isoproterenol 6mg/kg immediately.Record injection back 30s and 1,2,5,10,20 minute electrocardiogram change.The result sees table 7, table 8.Point out medicine of the present invention that isoproterenol is caused myocardial ischemia the improvement effect is arranged.
Table 7 is respectively organized the rat isoproterenol and is caused myocardial ischemia result relatively (n)
| Group | ?n | Electrocardiographic abnormality number of animals behind the injection isoproterenol |
| The water matched group | ?8 | 8 |
| Drug group of the present invention | ?8 | 4 |
| Positive controls | ?8 | 7 |
Table 8 is respectively organized rat different time ECG ST section offset voltage and is changed relatively
| Group | 30s | 1min | 2min | 5min | 10min | 20min |
| The water matched group | 0.06± 0.03(0.50) | 0.09± 0.03(0.70) | 0.07± 0.01(0.55) | 0.08± 0.02(0.75) | 0.06± 0.03(0.43) | 0.03± 0.02(0.23) |
| Positive controls | 0.04±0.01(0.21) * | 0.07± 0.02(0.28) * | 0.07± 0.02(0.33) | 0.04± 0.03(0.28) ** | 0.02± 0.02(0.13) * | 0.07± 0.01(0.05) * |
| Drug group of the present invention | 0.04± 0.02(0.20) * | 0.04± 0.03(0.10) * | 0.04± 0.02(0.15) | 0.02± 0.03(0.10) ** △ | 0.01± 0.02(0.05) ** △ | 0.01± 0.01(0.03) **△ |
Annotate: () number departs from total millivolt of number for ST section in the corresponding time in the table
Compare with the water matched group,
*P＜0.05,
*P＜0.01, compare △ P＜0.01 result with positive control drug and show: medicine of the present invention can make the rat ECG ST section depart from remarkable minimizing, shortening recovery time.Show that it has significant protection cardiac muscle and oxygen lack resistant function, and compare with the positive control medicine and to have significant difference, show that medicine of the present invention causes the ischemic myocardial protection effect to isoproterenol and obviously is superior to positive control drug.
Two, the clinical observation on the therapeutic effect test of drop pill treatment coronary heart disease of the present invention
(1) physical data
Select angina pectoris patient 397 examples altogether, be the checking group.
1, sex: male's 179 examples among this group patient, women's 200 examples, man: woman=1: 1.12
2, the age: minimum 42 years old of age, maximum 65 years old, 56.61 ± 6.07 years old mean age.Wherein≤and 45 years old 31 example, 46～59 years old 210 example,>=60 years old 156 example.
3, state of an illness classification: 140 examples that this group state of an illness is slight, moderate 257 examples.
4, the course of disease: the longest 60 months the course of disease the shortest January, average course of disease 14.79 ± 14.61 months, wherein 1～March 109 example, the 3-6 months 39 example, >=June 249 example.
(2) study subject is selected
1, tcm diagnosis standard
(1) suffocating pain over the chest, very then chest pain radiating to the back.
(2) the lighter only feels chest distress, hypopnea.
(3) Electrocardioscopy has the ischemic change or the exercise test positive.
(3) Western medicine diagnose standard (according to International Society of Cardiology and association and World Health Organization's clinical name standardization associating special topic group report " name of ischemic heart desease and diagnostic criteria ")
1, fatigue property angina pectoris
The of short duration chest pain outbreak that the situation of increase myocardium requirementing keto quantity is brought out, behind rest or the sublingual administration nitroglycerin, pain often can rapidly disappear.The angina pectoris of fatigue property can be divided three classes: the preliminary fatigue property angina pectoris of a.; The fatigue property angina pectoris course of disease is in 1 month.B. stable type fatigue property angina pectoris; The fatigue property angina pectoris course of disease was stabilized in more than 1 month.C. deterioration type fatigue property angina pectoris: the tired number of times that is brought out of equal extent, the order of severity and persistent period increase the weight of suddenly.
2, spontaneous angina pectoris
The characteristic of spontaneous angina pectoris is that the chest pain outbreak does not have obvious relation with the increase of myocardium requirementing keto quantity.Compare with the angina pectoris of fatigue property, this pain general persistence is longer, and degree is heavier, and is difficult for alleviating for nitroglycerin.This type is not seen enzymic change, and electrocardiogram often occurs that some temporary S-T section is forced down or the T ripple changes.Spontaneous angina pectoris can take place separately or merge existence with the angina pectoris of fatigue property.
Spontaneous angina pectoris patient's pain seizure frequency, persistent period and pain degree can have different clinical performance, and the patient can have and continues bigger chest pain and show effect sometimes, similar myocardial infarction, but do not have the characteristic change of electrocardiogram and enzyme.
The patient of some spontaneous angina pectoris temporary S-T section occurs and raises when outbreak, often be called variant angina pectoris.But when myocardial infarction records this electrocardiogram pattern in early days, can not just use this title.Just send out the angina pectoris of fatigue property, progressive angina pectoris and spontaneous angina pectoris and often be called " unstable angina pectoris ".
(4) case choice criteria
1, includes the case standard in
(1) meets tcm diagnosis standard person;
(2) thoracic obstruction grade scale belongs to slight, moderate, stable type fatigue property patient with angina pectoris;
(3) the angina pectoris patient course of disease continued more than 1 month, and in the daily life or the angina pectoris attacks that brings out after the motion weekly more than twice, each outbreak continues more than 3 minutes.
(4) resting electrocardiogram is normal, occurs ischemic ST change or tranquillization during angina pectoris attacks or after the stress test and is ischemic electrocardiographic abnormality person.
More than four must possess simultaneously.
2, get rid of case standard (comprising inadaptation or rejecting standard)
(1) turn out to be coronary heart disease myocardial infarction on inspection, and functions in patients with unstable angina;
(2) thoracic obstruction grade scale belongs to heavier, the stable type of severe, fatigue property patient with angina pectoris;
(3) neurosis, climacteric syndrome, cervical spondylosis valve disorder and the cardiac muscle stalk due to pain;
(4) merge the above hypertension of moderate, severe pulmonary insufficiency, severe arrhythmia, serious primary disease such as liver, kidney, hemopoietic system, psychotic;
(5) under-18s, over-65s, gestation or women breast-feeding their children are to this medicine allergy sufferers;
In (6) 6 months myocardial infarction is arranged or the probability person of the myocardial infarction that is about to show effect;
(7) do not meet the standard of including in,, can't judge that curative effect or data are not congruent to affect the treatment or safety judgement person by the regulation medication.
(5) thoracic obstruction weight split pole standard (according to therapy of combining Chinese and Western medicine angina pectoris in 1979 and arrhythmia forum " angina pectoris and ECG curative effect evaluation criteria ")
1, slight: typical angina pectoris attacks is arranged, each persistent period number minute, pain is shown effect 2～3 times at least weekly, or shows effect every day 1～3 time, but pain is heavy, need suck nitroglycerin sometimes.
2, moderate: for several times typical angina pectoris attacks is arranged every day, and each persistent period number minute was by 10 minutes, and angor is heavier, generally all need suck nitroglycerin.
3, than severe: typical angina pectoris attacks is arranged repeatedly every day, influence ADL (as defecating, wear the clothes etc.).Each outbreak persistent period is longer, need repeatedly suck nitroglycerin.
4, severe pain attack times and degree, all relatively severe is attached most importance to.
(6) clinical symptoms calibration standard (according to the regulation in " new Chinese medicine clinical research guideline ")
1, sensation of oppression over the chest with shortness of breath
Slightly: take place once in a while, only when fatigue, the sense sensation of oppression over the chest with shortness of breath can be alleviated after the rest.
Moderate: happen occasionally, feel sensation of oppression over the chest with shortness of breath during light activity, extended break just can be alleviated, the thing of need taking medicine sometimes.
Severe: often take place, the generation sensation of oppression over the chest with shortness of breath is also arranged during tranquillization, the thing of need taking medicine just can be alleviated.
2, palpitation and uneasiness
Slightly: take place once in a while, after stepping on building or physical exertion, occur;
Moderate: happen occasionally, promptly occur after walking along the street or the slight physical exertion;
Severe: often take place, occur during tranquillization.
(7) verification method
1, Therapeutic Method: 397 routine patients are divided into test group and matched group at random, test group 205 examples wherein, matched group 192 examples.
Test group: take the prepared drop pill of the embodiment of the invention 1
Matched group: take Danshen heart-benefiting capsule (available from the Changyuan Pharmaceutical Industry Co., Ltd., Jilin Prov, lot number 20051101)
Two groups are all write down the time that pain continues and disappear, and after medication, trace electrocardiogram once in 30 minutes.
Two groups of cases are observed five angina pectoris attacks medications front and back situation at least.Inaccurate simultaneously other quick-acting antalgesic medicine that uses of medication.
2, observation index
2.1 safety observation
2.1.1 general health check-up project: blood pressure, heart rate, the rhythm of the heart, body weight.
2.1.2 blood, urine, just routine test.
2.1.3 liver, kidney function test.
2.2 health giving quality observation
2.2.1 tcm symptom, the variation of tongue, arteries and veins is observed.
2.2.2 angina pectoris attacks time, number of times, degree, persistent period, alleviate or extinction time, induced factor.
2.2.3 Electrocardioscopy.
2.2.4 dynamic ecg recordings examination or exercise electrocardiogram are done in choosing as required.
(8) record requirement
1, fill in unified form by designing requirement, make itemized record, note observing untoward reaction or unexpected untoward reaction, and tracing study.
2, respectively observe hospital after observing end, write out the observation brief summary after analysis conclusion, the summary, deliver the clinical observation responsible department together with the raw observation table.
3, statistical procedures requires: enumeration data is checked with x2; Data are with mean ± standard deviation (x ± s) expression; Measurement data is checked with t; Ranked data are checked with Ridit.
(9) checking result
1, curative effect determinate standard
1.1 chest pain symptom curative effect determinate standard (according to " the clinical research guideline of the treatment by Chinese herbs thoracic obstruction ")
Produce effects: disappeared with interior (containing 3 minutes) pain in 3 minutes after the medication.
Effectively: pain disappearance 3～5 minutes (containing 5 minutes) after the medication.
Invalid: after the medication more than 5 minutes pain just disappear.
Increase the weight of: pain does not disappear or the pain person of increasing the weight of after the medication.
1.2 ECG curative effect evaluation criteria: (according to " the clinical research guideline of the treatment by Chinese herbs thoracic obstruction ")
Produce effects: electrocardiogram returns to normally (or roughly normal) during rest.
Effectively: S-T section reduction person more than the treatment back rise 0.05mv, but does not return to normal; (reaching 25% above person) shoals at the negative T wave that mainly leads; Or the T ripple is upright by smooth change; Chamber or intraventricular block improver.
Invalid: electrocardiogram basic with treat before identical.
Increase the weight of: the S-T section reduces more than the 0.05mv before the treatment, deepens (reaching more than 25%) at the T ripple that mainly leads, or upright T ripple flattened, and smooth T ripple becomes to be inverted, and ectopic cardiac rhythm occurs, atrioventricular block or intraventricular block.
1.3 heart arteries and veins stagnant heat card curative effect determinate standard
By " clinical symptoms calibration standard " with symptom be divided into slightly, moderate, severe; Four diseases such as its chest pain, sensation of oppression over the chest with shortness of breath, palpitation and uneasiness, inspection of the tongue are corresponding by 2 minutes, 4 minutes, 6 minutes and dysphoria with smothery sensation is restless, disease is corresponding counted by 1 minute, 2 minutes, 3 minutes for dry mouth and throat etc.; Add up its total mark, according to " tcm syndrome scoring method ".
Produce effects: treatment back syndrome integrated value descends >=2/3.
Effectively: treatment back syndrome integrated value descends between 1/3～2/3.
Invalid: treatment back syndrome integrated value descends≤1/3.
2, efficacy analysis
2.1 angina pectoris (thoracic obstruction) curative effect: 1) test group: observe altogether 205 routine times, wherein produce effects is 76 routine times, effective 11) and routine inferior, invalid 19 examples are inferior, total effective rate 90.7%.2) matched group: observe altogether 192 routine times, wherein produce effects is 47 routine times, and effective 102 examples are inferior, and invalid 43 examples are inferior, and total effective rate is 77.6%.Can find out that the test group curative effect has significant difference apparently higher than matched group.
2.2 angina pectoris persistent period and extinction time: 1) test group: observe angina pectoris average duration 6.55 ± 2.4min, average extinction time 4.04 ± 1.6min after the medication altogether 205 routine times.2) matched group: observe angina pectoris average duration 6.72 ± 1.8min, average extinction time 5.43 ± 6.6min after the medication altogether 192 routine times.The test group curative effect has significant difference apparently higher than matched group.
2.3 observation of curative effect after treating 5 times is seen table 9, table 10.
Table 9: test group observation of curative effect result
Table 10: matched group observation of curative effect result
2.4 treat integration after 5 times: 1) test group: the syndrome integrated value before and after the treatment is respectively 18.88 ± 4.44 and 10.49 ± 5.38, and the treatment back significantly descends P＜0.01.2) matched group: the syndrome integrated value before and after the treatment is respectively 18.47 ± 3.44 and 13.41 ± 1.12, descends P＜0.01 after the treatment to some extent.Through comparing.The test group curative effect has significant difference apparently higher than matched group.
2.5 ECG curative effect: 1) test group: observe 43 example time electrocardiograms altogether and change, produce effects 10 examples are improved 27 examples, invalid 6 examples, total effective rate 86.05%.1) matched group: observe 38 example time electrocardiograms altogether and change, produce effects 6 examples are improved 21 examples, invalid 11 examples, total effective rate 71.05%.The test group curative effect has significant difference apparently higher than matched group.
2.6 (RPP, the i.e. influence of HR * SBP): test group result sees table 11, and the matched group result sees table 12 to heart rate (HR), systolic pressure (SBP) and myocardial oxygen consumption index.
Table 11: test group is seen the fruit that comes to an end
Annotate: relatively preceding with treatment, ※ P＜0.01.
Table 12: matched group is seen the fruit that comes to an end
Annotate: relatively preceding with treatment, ※ P＜0.05
Through comparative test group and matched group result of the test, the test group curative effect obviously is superior to matched group, has significant difference.
Three, the safety analysis of medicine of the present invention
1, medicine of the present invention is seen table 13 to the influence of blood, urine, stool routine and liver, renal function.
Table 13: drug safety observed result of the present invention
The observation of surveying index through above safety examination shows that medicament capsule of the present invention is not seen any toxic and side effects to liver, kidney, blood system aspect, explain clinical take safe and reliable.
2. untoward reaction (incidence rate, treatment Countermeasures): do not have.
Four, model case
Slowly * *, male, 59 years old, teacher.
Go to a doctor the date: on August 4th, 98.Patient's angina pectoris medical history 2 years, show effect frequently nearly January, and 3～5 times weekly, continue about 5～6 minutes at every turn, moving then cardiopalmus, chest distress, dysphoria with smothery sensation is restless, and obeying " FUFANG DANSHEN DIWAN " certainly can alleviate, and then needs buccal " nitroglycerine tablets " in the time of bitterly very.Clinical diagnosis is an angina pectoris, belongs to heart arteries and veins stagnant heat card, gives the embodiment of the invention 1 prepared drop pill; Sublingual administration when advising its pain, August 2～8 a day priority on the 11st is taken 2 of each buccal five times; Chest pain is disappeared, treatment back check electrocardiogram V
4-
6The ST section is recovered, and T ripple comparatively upright is smooth, does not occur untoward reaction in the therapeutic process.
Five, observe conclusion
Drop pill of the present invention has blood circulation promoting and blood stasis dispelling, and tranquillizing and allaying excitement is used for the angina pectoris that coronary heart disease causes, uncomfortable in chest and cardio palmus.Inferior through clinical observation 205 examples; Total effective rate reaches 86.34%; Its clinical efficacy will be higher than positive control medicine-Danshen heart-benefiting capsule on the whole, and the angina pectoris patient is had tangible alleviating pain effect, and the ischemic electrocardiogram is also had significant improvement effect; Sensation of oppression over the chest with shortness of breath, palpitation and uneasiness symptom to due to the heart arteries and veins stagnant heat card also have some improvement; Clinical observation 205 examples are not found untoward reaction, detect hepatic and renal function before and after the treatment, blood, urine, just safety indexes such as routine all in normal range.
Claims (7)
1. a Traditional Chinese Medicine Dropping Pill of treating coronary heart disease departs from the application in the medicine at preparation anti-hypoxia and minimizing ECG ST section, and said Traditional Chinese Medicine Dropping Pill is prepared by following method:
1) weighting raw materials material Radix Salviae Miltiorrhizae is an amount of;
2) get the red rooted salvia decocte with water that step 1) takes by weighing after, drying is pulverized, and adds 90% alcohol reflux; Adopt the microwave-assisted extraction method to extract, filter, filtrate decompression is condensed into extractum, adds a certain amount of ordinary water of extractum; The limit edged stirs, and leaves standstill, and filters the precipitate cold drying; Pulverize, sieve, promptly get Radix Salviae Miltiorrhizae extract;
3) get step 2) Radix Salviae Miltiorrhizae extract of gained puts in the capacity molten matrix, and mixing splashes in the coolant, processes drop pill, promptly gets.
2. according to the described application of claim 1, wherein the Radix Salviae Miltiorrhizae crude drug decocts with 4-12 times of water gaging.
3. according to the described application of claim 1, wherein the decocte with water of Radix Salviae Miltiorrhizae crude drug is 30-90 minute.
4. according to the described application of claim 1, wherein the smashing fineness of Radix Salviae Miltiorrhizae extract is the 100-200 order.
5. according to the described application of claim 1, wherein the smashing fineness of Radix Salviae Miltiorrhizae extract is preferably 150 orders.
6. according to the described application of claim 1, its mesostroma is any or the two or more mixture in Macrogol 4000 or 6000, sodium stearate, glycerin gelatine, stearic acid, glyceryl monostearate, hydrogenated vegetable oil or the insect wax.
7. according to the described application of claim 1, the weight ratio of its Chinese medicine powder and substrate is 1: 1-6.
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Citations (2)
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|---|---|---|---|---|
| CN1548039A (en) * | 2003-05-20 | 2004-11-24 | 天津天士力制药股份有限公司 | Red sage dripping pill and its prepn |
| CN1823897A (en) * | 2005-12-20 | 2006-08-30 | 王衡新 | Chinese medicinal preparation for antimicrobial and anti inflammation, its preparation method and quality control method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1548039A (en) * | 2003-05-20 | 2004-11-24 | 天津天士力制药股份有限公司 | Red sage dripping pill and its prepn |
| CN1823897A (en) * | 2005-12-20 | 2006-08-30 | 王衡新 | Chinese medicinal preparation for antimicrobial and anti inflammation, its preparation method and quality control method |
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| 中华人民共和国卫生部药品标准-中药成方制剂（第七册）.中华人民共和国卫生部药典委员会,1993,第27页. * |
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