CN1562276A - Application of anemarrhena extract in preparing mediciation for preventing and curing abnormal rapidity heart rate and essential hyperension - Google Patents
Application of anemarrhena extract in preparing mediciation for preventing and curing abnormal rapidity heart rate and essential hyperension Download PDFInfo
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- CN1562276A CN1562276A CN 200410026644 CN200410026644A CN1562276A CN 1562276 A CN1562276 A CN 1562276A CN 200410026644 CN200410026644 CN 200410026644 CN 200410026644 A CN200410026644 A CN 200410026644A CN 1562276 A CN1562276 A CN 1562276A
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Abstract
An application of the anemarrhena rhizome's extract in preparing madicines for treating and preventing fast-type arrhythmia and primary hypertension is disclosed. Said extract can be dissolved in the mixture of alcohol and water but deposited in acetone.
Description
Technical field
The present invention relates to effective ingredient Rhizoma Anemarrhenae extract that the Chinese medicine Rhizoma Anemarrhenae extracts and prevent, control application in the medicine of rapidity arrhythmia and essential hypertension disease in preparation.
Background technology
The Chinese medicine Rhizoma Anemarrhenae is the dry rhizome of the liliaceous plant Rhizoma Anemarrhenae (Anemarrhena asphodeloides Bunge).The Rhizoma Anemarrhenae is China's Chinese medicine, and application is all arranged in ancient Chinese prescription, has clearing heat and relieving fidgetness, eliminating the pathogens from the lung nourishing kidney, main quenching one's thirst to pine for, remove pathogen limbs edema, Xia Shui, tonifying for the deficiency, QI invigorating etc. on the ancient books and records.Clinical practice all is to be used for the compatibility treatment.
Epidemiological study confirms that hyperthyroidism, hypertensive sickness rate have the trend of raising.At the rapidity arrhythmia, clinically the beta receptor blocker of Da Liangyingyonging as " Propranolol " (Propranolol), " metoprolol ", though can suppress function of receptors, make cardiovascular system symptom such as cardiopalmus, tachycardia controlled, but can not improve symptoms such as patient's xerostomia, irritability, scorching, insomnia, when the patient had other diseases especially at the same time, these medicines are Ying Shenyong more.
The medicine of treatment essential hypertension mainly contains receptor blocking agent such as above-mentioned " Propranolol ", " metoprolol " etc. clinically; Calcium antagonist such as nitrendipine, Lip river happiness alive etc., ganglioplegic such as bendazol etc., hypertensin enzymeinhibitor such as captopril etc., mild hypertension also can adopt diuretic such as hydrochlorothiazide, but these medicines all exist certain toxic and side effects, are not suitable for prolonged application.
Summary of the invention
Purpose of the present invention be exactly for provide extract a kind of can the application of Rhizoma Anemarrhenae extract life-time service, that toxic and side effects is less in the medicine of preparation prevention, treatment rapidity arrhythmia and essential hypertension.
The present invention realizes like this.
The technology that the extracting method of Rhizoma Anemarrhenae extract adopts present technique field those of ordinary skill to know, can adopt ethanol water mixture to soak extracts, decompression recycling ethanol is dissolved in water to the thick paste shape, cold preservation, discard precipitation, the supernatant is evaporated to dried, puts to add small amount of methanol or dissolve with ethanol after cold, adds acetone and separates out white precipitate, precipitation is used washing with acetone, and drying under reduced pressure promptly.Wherein alcoholic acid percent by volume is 30～80% in the ethanol water mixture, preferred 50%; It is about 2～3% that wherein Rhizoma Anemarrhenae extract accounts for the weight rate of Rhizoma Anemarrhenae crude drug, and this Rhizoma Anemarrhenae extract is for being dissolved in ethanol water mixed solvent sedimentary material in acetone, based on Rhizoma Anemarrhenae total saponins.
Above-mentioned Rhizoma Anemarrhenae extract has carried out pharmacodynamics test, clinical trial and acute toxicity test, long term toxicity test.Acute toxicity test in mice shows that the maximum tolerated dose of the oral Rhizoma Anemarrhenae extract of mice is more than every kg body weight 1000mg, the rat oral administration is trimestral long term toxicity test result show, the following dosage of Rhizoma Anemarrhenae extract administration high dose (be equivalent to clinical application amount 100 times) is basic security dosage.Pharmacodynamics test and clinical trial show that above-mentioned Rhizoma Anemarrhenae extract of the present invention can prevent, control rapidity arrhythmia and essential hypertension.Rhizoma Anemarrhenae extract of the present invention can be processed into various oral formulations, as tablet, granule, oral liquid, capsule etc.
Medicine every day that the oral Rhizoma Anemarrhenae extract of normal person is made two～three times, each 0.025～0.1 gram Rhizoma Anemarrhenae total saponins.
Rhizoma Anemarrhenae total saponins through being further purified has effect of the present invention equally.
The specific embodiment
The invention will be further described below in conjunction with embodiment.
The extracting method of embodiment 1 Rhizoma Anemarrhenae extract and the preparation of oral formulations thereof.
Get rhizoma ane marrhenae, add the ethanol of 50% percent by volume that is equivalent to 6 times of medical material volumes, soaked reflux, extract, 21 hours 30 minutes.Inclining extracting solution, and 50% ethanol extraction one that adds 5 times of medical material volumes again is to secondary, each 1 hour.Merge extractive liquid,, decompression recycling ethanol adds water and makes dissolving, cold preservation in right amount to the thick paste shape, the centrifugal precipitation of abandoning, the supernatant is evaporated to dried, puts coldly, adds small amount of methanol or dissolve with ethanol, add acetone and separate out white precipitate, centrifugal, precipitation uses washing with acetone, drying under reduced pressure to get Rhizoma Anemarrhenae extract (main component is a Rhizoma Anemarrhenae total saponins).Rhizoma ane marrhenae extracts extract 2～3% approximately.
Get Rhizoma Anemarrhenae extract, add appropriate amount of starch and granulate, add an amount of Pulvis Talci, magnesium stearate and be processed into tablet according to a conventional method, every contains the 10mg Rhizoma Anemarrhenae total saponins.
Get Rhizoma Anemarrhenae extract, add appropriate amount of starch and granulate, be distributed into granule.
Get Rhizoma Anemarrhenae extract, add appropriate amount of starch and granulate, add a small amount of magnesium stearate, encapsulated.
Get Rhizoma Anemarrhenae extract, add the suitable quantity of water dissolving, it is an amount of to add oral flavoring agent, adds to add water to scale, is processed into oral liquid, sterilization, promptly.
The animal acute toxicity test of embodiment 2 Rhizoma Anemarrhenae extracts
1, is subjected to reagent thing and dosage
Rhizoma Anemarrhenae extract: be ground into fine powder, add water and become pastel, every milliliter contains Rhizoma Anemarrhenae total saponins 10mg;
2, laboratory animal: Kunming kind white mice, male and female half and half in 5～6 weeks of age in days, in one week of breeding observing, are rejected improper animal.
2.1 get 10 of healthy mices, body weight 18～22 grams, male and female half and half, test beginning fasting in preceding 16 hours, every mice lavage is once irritated stomach 0.5ml/10g body weight at every turn in one day, accumulated dose is equivalent to every kg body weight 500mg Rhizoma Anemarrhenae total saponins every day, observes seven days after the administration.
2.2 get 20 of above-mentioned healthy mices, body weight 18～22 grams, male and female half and half, test beginning fasting in preceding 16 hours, every mouse stomach secondary in one day, be 6 hours each blanking time, irritates stomach 0.5ml/10g body weight at every turn, accumulated dose is equivalent to every kilogram of 1000mg Rhizoma Anemarrhenae total saponins every day, observes seven days after the administration.
3, experimental result
Two kinds of dosages are observed, found each white mice after irritating stomach, activity obviously reduces, and creeps slowly or the gathering that flocks together, and tired lying prostrate in mouse cage recovered normal gradually after three, four hours.
In seven days viewing durations after administration, the defecation of white mice, drinking water diet etc. are all normal, every white mice average food sanitation standard feedstuff 5～6 grams every day, and male Mus is edible slightly more than female Mus, and the outward appearance fur is smooth, action is movable normal, the same with blank group white mice under the equal raising condition, after seven days, none death of all white mice, normal survival.
Above experimental result shows, when the dosage that white mice was irritated the stomach Rhizoma Anemarrhenae extract in one day is every kg body weight 500mg, is equivalent to about 200 times of clinical consumption.During for every kg body weight 1000mg, be equivalent to about 400 times of clinical consumption.According to statistics probability principle, there is 99.9% assurance to prove that mice oral administration LD50 illustrates that greater than the 40g/kg body weight this product is safe.
4, conclusion: the maximum tolerated dose of the oral Rhizoma Anemarrhenae total saponins of mice is more than every kg body weight 1000mg.
The long-term toxicity test for animals of embodiment 3 Rhizoma Anemarrhenae extracts
Laboratory animal adopts SD rat, male and female half and half, 5～6 weeks of age in days.It is reversal by animal that Rhizoma Anemarrhenae extract is sneaked into the standardization feedstuff.
Because of Rhizoma Anemarrhenae extract toxicity is low, be difficult to select toxic reaction or dead dosage, so this experiment designs high, medium and low three dosage of Rhizoma Anemarrhenae extract and carries out the trimestral long term toxicity test of oral route successive administration with reference to estimating clinical dosage (ACD) predication method.High dose group is 100 times of clinical consumption; Middle dosage group is 30 times of clinical consumption; Low dose group is 10 times of clinical consumption.
Each administration group rat body weight alleviates with comparing all to have during the Rhizoma Anemarrhenae extract administration, especially high, middle dosage group rat is more obvious, and certain dosage-effect relation arranged, but after 4 weeks of drug withdrawal, the body weight of high dose group rat can return to the level of the rat of normal control group substantially, illustrates that the influence to rat body weight of this medicine is reversible.
Experimental result shows, successive administration three months and after 4 weeks of drug withdrawal, the physiology of each administration group rat, biochemical indicator all in normal range, relatively do not have difference with matched group, and the performance Rhizoma Anemarrhenae extract does not all have toxic action to physical signs such as liver, renal function and hemogram.In addition, administration three months and after 4 weeks of drug withdrawal, the heart of each dosage group rat, liver, spleen, lung, kidney, testis (or ovary) naked eyes and check pathological section show, there is no pathologic and change, illustrate the Rhizoma Anemarrhenae extract sheet continuous use after three months to the harmless effect of organa parenchymatosum.
Introduction: Rhizoma Anemarrhenae extract shows that to the trimestral long term toxicity test result of rat oral route successive administration each administration group rat body weight all has the effect of alleviating during the administration, but can recover after the drug withdrawal.The no abnormal variation of each treated animal sign.Rhizoma Anemarrhenae extract is to the not influence of physical signs such as liver, renal function, routine blood test and reticulocyte of rat, the all no abnormal change of naked eyes and histopathologic examination to the heart, liver, spleen, lung, kidney, testis important organs such as (or ovaries), The above results shows, the following dosage of Rhizoma Anemarrhenae extract administration high dose (be equivalent to clinical consumption 100 times) is basic security dosage.
Embodiment 4 Rhizoma Anemarrhenae extracts are treated the test of tachycardic pharmacodynamics.
1, high thyroxin pattern type: animal is divided into 5 groups at random by the sex body weight, matched group, pathologic group, Propranolol (propranolol) group (9mg/kg), Rhizoma Anemarrhenae extract group two dosage (rat 9mg/kg, 27mg/kg; Cavia porcellus 7.2mg/kg, 22.5mg/kg; Pathologic group: once, totally 3 times, distilled water is irritated stomach next day of subcutaneous injection triiodo thyroid ortho acid (rat and Cavia porcellus 0.5mg/kg), and 1ml/, once a day; Propranolol processed group:, inject propranolol 20mg/kg under the peritoneum, once a day except that with the pathologic group subcutaneous injection T3; The Rhizoma Anemarrhenae extract processed group: except that with the pathologic group subcutaneous injection T3, Rhizoma Anemarrhenae extract solution is irritated stomach, and liquor capacity is 1ml; The normal control group: the subcutaneous injection normal saline, distilled water is irritated the same pathologic group of stomach.
2, observe: the influence of heart rate
Cavia porcellus: Cavia porcellus is placed in the special little tub, and subcutaneous fixing electricity level connects electrocardiogram II and leads by (ECG-6511 type), and lucifuge treats that Cavia porcellus measures basal heart rate after quiet 20 minutes.Respectively with before and after the moulding and propranolol, Rhizoma Anemarrhenae extract handle the back heart rate and compared.
Influence to the rat heart rate: rat, peritoneal injection chloral hydrate (50mg/kg) anesthesia, subcutaneous fixed electrode after 30 minutes connects electrocardiograph II and leads, and measures heart rate.Respectively with before and after the moulding and propranolol, Rhizoma Anemarrhenae extract handle the back heart rate and compared.
3, result's (with the rat is example, and result of Cavia porcellus and rat kind are seemingly).
Group (n=10) basal heart rate (variable quantity of X ± SD) (X ± SD)
After the preceding moulding of moulding
Matched group 318.2 ± 24.6 324.2 ± 25.8 5.9 ± 22.6
Pathologic group 286.3 ± 26.7 391.5 ± 37.5 105.1 ± 36.5
Low dosage 293.3 ± 37.6 361.1 ± 49.3 68.2 ± 50.1
High dose 308.7 ± 38.3 343.5 ± 34.9 31.9 ± 32.1
Propranolol 304.0 ± 33.5 332.1 ± 50.8 27.9 ± 40.1
The result shows that low dosage, high dose extract all can significantly reduce the heart rate (P＜0.01) that high thyroid swashs type tachycardia animal pattern, and wherein high dose group is compared there was no significant difference (P＞0.05) with propranolol.
The pharmacodynamics test of embodiment 5 Rhizoma Anemarrhenae extracts treatment essential hypertension
1, laboratory animal, 10 of normal Wistar rats, half and half, 3 monthly age of male and female, body weight 180～210 grams; 18 of spontaneous hypertensive rats, at half and half, 3 monthly age of male and female, body weight 180～210 grams are available from Beijing China Medical Sciences Academy Fu Wai Hospital Experimental Animal Center.
2, animal grouping and handling, 1. normal control group (n=10), normal Wistar rats, common raising, automatic water-drinking is not done any processing; 2. the spontaneously hypertensive group (is called for short the SHR group, n=8); The SHR rat is irritated 6 weeks of distilled water; 3. Rhizoma Anemarrhenae extract group (n=10): the SHR rat, preceding 4 weeks are irritated distilled water, and the back gavages Rhizoma Anemarrhenae extract solution 2 every days in week, is equivalent to 10 milligrams of kg body weight Rhizoma Anemarrhenae total saponins.
3, observation index and method, 1. general behavior is observed: comprise hair color whether gloss, conjunctiva of both eyes color whether deepen to redden and the irritability degree change, the irritability degree is divided into three grades; The I level refers to catch when holding cervical region and screams, startles; The II level refers to catch and stings the people when holding cervical region; The III level refers to carry tail screams, startles, even stings the people or frequently fight with the cage rat.2. blood pressure determination: adopt the arteria caudalis pollex method of " Chinese applied physiology magazine " 1991,7 (1) 62～64 reports to measure.
4, result
4.1 respectively organizing rat outward appearance and irritability degree changes
Whole experimental session, rat hair color gloss at different levels, eyes are flexible, appetite can, respectively organize weight ratio the 6th weekend than the group difference nonsignificance.SHR group irritability degree mostly is I, II level, and treatment group irritability degree has remarkable minimizing before and after treatment.
All kinds of rat outward appearances of table 2 and the degree that easily enrages compare
| Group | ????n | The 4th weekend | The 6th weekend |
| Easily enrage degree conjunctival congestion I II III | Easily enrage degree conjunctival congestion I II III | ||
| Normal group | ????10 | ?1???0???0???????0 | 1???0???0????????0 |
| The SHR group | ????8 | ?5???1???0???????3 | 5???2???0????????3 |
| The treatment group | ????10 | ?6???1???1???????3 | 2???1???0????????1 |
4.2 respectively organize the rat blood pressure measurement result
No matter SHR organizes systolic pressure, diastolic pressure, all is higher than normal group, and the treatment treated animal is after treatment, and its systolic pressure, diastolic pressure all significantly reduce (P＜0.01) with the SHR group before the treatment, with normal group comparing difference not remarkable (P＞0.05)
Table 3
| Group | n | Before the experiment | The 4th weekend | The 6th weekend |
| The systolic pressure diastolic pressure | The systolic pressure diastolic pressure | The systolic pressure diastolic pressure | ||
| Normal value | 10 | ?105.50±7.24???????74.00±3.94 | ?106.50±4.97??????77.90±4.03 | ?107.50±5.40???????79.50±3.69 |
| The SHR value | 8 | ?181.88±12.23??????97.50±4.63 | ?184.38±9.80??????97.50±7.07 | ?188.75±9.54???????96.88±4.50 |
| The treatment group | 10 | ?183.75±10.61??????99.00±6.55 | ?184.58±9.90??????99.80±7.53 | ?110.03±13.05??????82.01±5.60 |
The pharmacodynamic experiment of embodiment 4, embodiment 5 shows that Rhizoma Anemarrhenae extract of the present invention can treat rapidity arrhythmia and essential hypertension.Through the human clinical trial, obtained the result similar with embodiment 4, embodiment 5.
Claims (6)
1, Rhizoma Anemarrhenae extract is prevented and treated application in the rapidity arrhythmia medicine in preparation, and wherein Rhizoma Anemarrhenae extract is for being dissolved in ethanol water mixed solvent sedimentary material in acetone.
2, Rhizoma Anemarrhenae extract according to claim 1 is prevented and treated application in the rapidity arrhythmia medicine in preparation, it is characterized in that Rhizoma Anemarrhenae extract is a Rhizoma Anemarrhenae total saponins.
3, Rhizoma Anemarrhenae extract according to claim 1 and 2 is prevented and treated application in the rapidity arrhythmia medicine in preparation, it is characterized in that the preparation processing of Rhizoma Anemarrhenae extract becomes tablet, granule, oral liquid or capsular peroral dosage form.
4, the application of Rhizoma Anemarrhenae extract in preparation control essential hypertension medicine, wherein Rhizoma Anemarrhenae extract is for being dissolved in ethanol water mixed solvent sedimentary material in acetone.
5, the application of Rhizoma Anemarrhenae extract according to claim 4 in preparation control essential hypertension medicine is characterized in that Rhizoma Anemarrhenae extract is a Rhizoma Anemarrhenae total saponins.
6, the application in preparation control essential hypertension medicine according to claim 4 or 5 described Rhizoma Anemarrhenae extracts is characterized in that the preparation processing of Rhizoma Anemarrhenae extract becomes tablet, granule, oral liquid or capsular peroral dosage form.
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| CN102134286A (en) * | 2011-05-11 | 2011-07-27 | 天津大学 | Method for extracting rhizoma anemarrhenae polysaccharide from rhizoma anemarrhenae decoction pieces |
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