CN101032504A - Application of liquiritin in medicines - Google Patents
Application of liquiritin in medicines Download PDFInfo
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- CN101032504A CN101032504A CN 200610016770 CN200610016770A CN101032504A CN 101032504 A CN101032504 A CN 101032504A CN 200610016770 CN200610016770 CN 200610016770 CN 200610016770 A CN200610016770 A CN 200610016770A CN 101032504 A CN101032504 A CN 101032504A
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Abstract
The present invention relates to new use of liquiritin material and effective part with liquiritin as main active component in preparing medicine. The medicine with liquiritin has the functions of antagonizing arrhythmia, gastric ulcer, tumor, etc. The medicine is used in preventing and treating arrhythmia, myocardial ischemia, gastric ulcer, tumor and other diseases.
Description
Technical field:
The present invention relates to the purposes of liquirtin (liquiritin), relate in particular to the purposes in pharmaceutical field.
Background technology:
U.S. chemical abstract (CA 28:3076
2, 1934), the chemical compound liquirtin is disclosed, its structural formula is:
(liquirtin liquiritin)
Its molecular formula of this chemical compound is C
21H
22O
9, colourless acicular crystal, molecular weight is 418.Extract in can dry root and rhizome and make by pulse family Glycyrrhiza (Glycgrrhiza) various plants glycyrrhizic legume Glycyrrhiza uralensis Fisch. Glycyrrhiza inflata Bat. Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L. Glycyrrhiza glabra L..
Summary of the invention:
The object of the invention is to provide the new purposes of liquirtin, i.e. new application in pharmacy.
In fact, the present invention relates to the application of liquirtin as preparation treatment or prevention cardiac arrhythmia medicine.
Relate to the application of liquirtin as preparation treatment or prevention medicaments for coronary disease.
Relate to the application of liquirtin as preparation treatment or prevention gastric ulcer medicine.
Relate to the application of liquirtin as preparation treatment or prevention cancer therapy drug.
Essence for a better understanding of the present invention will illustrate its new purposes in pharmaceutical field with the pharmacological testing and the result of liquirtin below.
Adopt dry root and rhizome 2000 grams of pulse family Glycyrrhiza (Glycgrrhiza) liquorice root Glycyrrhiza uralensis Fisch. Glycyrrhiza inflata Bat. Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L. Glycyrrhiza glabra L., be ground into coarse powder, add 10 times of amount ethanol, extract twice, each 3 hours.The extracting solution decompression and solvent recovery, the extract that obtains carries out column chromatography, uses ethanol gradient elution, collects the part that thin layer chromatography shows liquirtin, and the eluent decompression and solvent recovery is used ethyl alcohol recrystallization, obtains colourless powder liquirtin 4 grams.
The liquirtin that above extraction separation is obtained, with polyethylene glycol 6000: (1: 2-4) mixed liquor is as substrate for Macrogol 4000, coolant is selected dimethicone: liquid paraffin (3: 2), raw material liquirtin and substrate were with 1: 4 proportioning, and fluid temperature is 60-80 ℃, were 0～5 ℃ with chilling temperature, external diameter is the water dropper of 4.5/7.0mm in the drip, drip is 3-6cm apart from the cooling liquid level, drips fast 25-35 and drips/the system condition of dripping of min, and makes the drop pill that every ball contains liquirtin 10mg.
Get the liquirtin 2g that extraction separation obtains, add the injection water to 2000ml, behind the mix homogeneously, be distributed into injection that 2mg/2ml/ props up concentration and pack into and seal in the medicine bottle, it is standby that product is made in sterilization.
1, acute toxicity test in mice
1.1 intravenously administrable mice LD
50Mensuration
Get 50 of body weight 19-20g mices, male and female half and half are divided into 5 groups at random, determine that by trial test maximum dose level is 100mg/kg, and dosage group spacing is 0.85, and with variable concentrations, (the liquirtin injection, 2.5mg/ml) once, volume is 10ml/kg with volume iv administration.At once observe the reaction of animals situation after the administration, observed continuously 7 days, write down mouse toxicity reaction and death toll every day.Dead mice anatomic observation main organs changes situation, and the pathological changes internal organs are done histopathologic examination.Calculate the mice median lethal dose(LD 50) with the Bliss method.The results are shown in Table 1.
Table 1 liquirtin injection intravenous injection acute toxicity test
| Group | Dosage (mg/Kg) | Number of animals (only) | Log10 dose Lgd (x) | Death toll (n) | Mortality rate (%) | LD
50And 95% |
| 1 2 3 4 5 | 100.00 85.00 72.25 61.41 52.20 | 10 10 10 10 10 | 2.0000 1.9294 1.8588 1.7882 1.7177 | 10 7 5 2 0 | 100 70 50 20 0 | LD 50=73.43mg/Kg 95% credible the 79.83-67.54mg/Kg that is limited to |
1.2 oral administration mice LD
50Mensuration:
Get 20 of body weight 20-21g mices, male and female half and half, water 16h is can't help in the mice fasting, gets the volume gastric infusion of the liquirtin of 0.1g/ml concentration with 40ml/Kg, gives twice in the 24h, at interval 6h.Begin to observe hair color, autonomic activities, breathing, diet, body weight and the death condition of animal after the administration, observed continuously 7 days.Dead mice anatomic observation main organs changes situation, and the pathological changes internal organs are done histopathologic examination.
Animal does not have obvious adverse reaction and death after the administration, body weight gain, and the mental status is good, and hair color is glossy, and defecation is normal.Show that liquirtin mouse stomach administration accumulation 8g/Kg does not cause the reaction of animal overt toxicity.
Above presentation of results: the LD of disposable vein injection liquirtin injection
50Be 73.43mg/Kg, the 95% credible 79.83-67.54mg/Kg that is limited to.Mouse stomach administration accumulation 8g/Kg does not see the overt toxicity reaction.
2, rat long term toxicity test:
Experimental technique: choose 80 qualified rats of health, male and female half and half are divided into the normal control group at random, liquirtin injection 12,6,3mg/kg group, by the sex sub-cage rearing, intravenous injection, lumbar injection replace administration, and volume is 10ml/kg, matched group is given the solvent with volume, every day 1 time, successive administration 2 months, weighing record body weight is 1 time weekly, adjust dosage by body weight, observe situations such as animal appearance behavior, diet, activity, defecation, fur glossiness simultaneously.After the last administration 24 hours, each group was all got 10 animals, and sacrificed by decapitation is got blood and done hematology and blood biochemical and learn and check.Dissect rat, each treated animal main organs situation of perusal, and core, liver, spleen, lung, kidney, adrenal gland, thymus, thyroid, pancreas, brain, lymph node, stomach, testis, epididymis, prostate, uterus, ovary weigh, and calculating organ coefficient, get above-mentioned each organ and hypophysis, oblongata, optic nerve, duodenum, ileum, colon, bladder, prostate, breastbone simultaneously, blood vessel is fixed with 10% formalin, dehydration, paraffin embedding, section, Yihong rearmounted microscopically that dyes is done the pathological tissue histological examination.The drug withdrawal of residue rat after conventional two weeks of raising, repeats above-mentioned every inspection, observes the toxic reaction recovery situation.Experimental data adopts statistics t method of inspection analyzing and processing, the relatively significance of difference between each group.
2.1 influence to the rat general signs
Large, medium and small dosage group of administration and matched group compare, and the general signs of animal, outward appearance, diet, drinking-water, feces and movable all Non Apparent Abnormalities change.Figure of description 1,2 is that liquirtin influences result of the test figure to rat general signs (food-intake, amount of drinking water).
2.2, to the influence of rat body weight
High, medium and low dosage group of administration and matched group comparison, body weight gain trend, dietary amount basically identical.Each the 3rd week of administration group rat body weight self administration of medication begins to have decline to a certain degree during the 9th week, but compares there was no significant difference with matched group.Each administration group rat in drug withdrawal 2 during week body weight return to gradually normally, the results are shown in Table 2, table 3.
Table 2 liquirtin injection is to the influence of male rat body weight (n=10,5, g x ± SD)
| Time (week) | Matched group (injection solvent) | High dose group (12mg/kg) | Middle dosage group (6mg/kg) | Low dose group (3mg/kg) |
| 0 1 2 3 4 5 6 7 8 9 10 11 | 104±10.9 136±17.7 152±20.1 180±28.1 214±37.4 235±43.3 264±44.4 296±43.8 319±46.1 334±46.9 346±34.4 359±33.8 | 105±11.3 135±15.3 150±19.8 166±21.2 181±24.4 202±27.1 232±28.1 271±29.1 285±26.4 301±24.6 329±17.8 348±20.5 | 103±11.1 139±17.9 154±20.1 186±24.7 197±26.1 206±26.4 235±27.2 271±29.0 295±28.9 319±29.5 339±20.1 351±19.5 | 104±10.1 137±16.5 153±18.1 189±21.1 200±27.1 218±28.1 246±25.8 279±26.2 301±25.1 327±25.6 344±21.8 360±22.4 |
Table 3 liquirtin injection is to the influence of female rats body weight (n=10,5, g x ± SD)
| Time (week) | Matched group (injection solvent) | High dose group (12mg/kg) | Middle dosage group (6mg/kg) | Low dose group (3mg/kg) |
| 0 1 2 3 4 | 99.8±10.3 132±12.8 148±13.1 159±14.1 173±15.8 | 100±10.8 131±13.4 140±15.5 151±19.5 165±21.0 | 101±10.5 133±14.2 141±15.2 157±16.6 169±17.1 | 99.3±11.2 133±14.3 143±15.1 157±17.0 171±18.1 |
| 5 6 7 8 9 10 11 | 189±15.7 208±16.5 226±16.8 239±18.1 254±19.1 261±20.1 279±24.3 | 178±20.9 189±22.4 201±23.1 212±24.5 222±32.5 242±33.1 267±34.2 | 179±18.7 191±21.4 217±25.4 221±27.1 241±28.9 256±25.1 273±25.7 | 180±25.7 193±28.7 223±28.2 241±29.1 254±28.7 258±24.2 278±26.4 |
2.3. influence to the rat serum routine
2.3.1, give liquirtin influence to routine blood test after 2 months
Give liquirtin after 2 months, the high, medium and low dosage group of administration rat hemoglobin (HB), erythrocyte (RBC), platelet (PLT), leukocyte (WBC) and classification thereof (dividing leaf cell GR% and lymphocyte LY%), reticulocyte (RC), clotting time (CT) etc. are all in normal range, each administration group and matched group relatively do not have significant difference, the results are shown in Table 4.
Table 4 administration after 2 months to the influence of rat serum routine (n=10, x ± SD)
| Project | Matched group (injection solvent) | High dose group (12mg/kg) | Middle dosage group (6mg/kg) | Low dose group (3mg/kg) |
| HB(g/L) RBC(×10 12/L) PLT(×10 9/L) WBC(×10 9/L) GR(％) LY(％) RC(％) CT(s) | 124±6.52 6.40±0.33 490±41.1 12.3±4.15 20.5±3.82 79.5±3.82 7.81±1.77 63.2±22.4 | 123±6.21 6.31±0.32 493±69.6 11.9±3.88 20.4±3.73 79.6±3.73 7.94±1.68 58.8±22.1 | 124±6.18 6.37±0.43 489±57.3 12.7±3.85 21.5±3.76 78.5±3.76 8.11±1.66 52.4±18.6 | 126±7.78 6.38±0.74 474±70.2 12.3±3.56 20.4±3.41 79.6±3.41 8.20±1.94 56.5±14.3 |
2.3.2, drug withdrawal 2 week the back to the influences of routine blood test
After 2 weeks of drug withdrawal, all in normal range, each administration group and matched group more all do not have significant difference to the above-mentioned every hematological examination index of administration group and matched group, the results are shown in Table 5.
The back influence to the rat serum routine of 2 weeks of table 5 drug withdrawal (n=10, x ± SD)
| Project | Matched group (injection solvent) | High dose group (12mg/kg) | Middle dosage group (6mg/kg) | Low dose group (3mg/kg) |
| HB(g/L) RBC(×10 12/L) PLT(×10 9/L) WBC(×10 9/L) GR(％) LY(％) RC(％) CT(s) | 123±6.54 6.71±0.31 465±54.7 13.5±3.84 22.6±3.87 77.4±3.87 8.75±1.54 53.5±15.4 | 123±5.55 6.70±0.36 481±55.2 12.7±3.12 21.1±3.52 78.9±3.52 8.25±1.96 51.0±12.6 | 124±7.68 6.72±0.40 473±67.4 12.7±3.24 21.7±3.67 78.3±3.67 8.51±1.69 49.5±11.9 | 124±5.74 6.65±0.36 474±53.2 12.4±3.54 21.3±4.15 78.7±4.15 7.91±2.22 50.5±12.2 |
2.4, influence that blood biochemical is learned
2.4.1 injection gives the influence that liquirtin was learned blood biochemical after 2 months
Injection gave liquirtin after 2 months, all in normal range, each administration group and matched group relatively do not have significant difference and see Table 6 for alanine aminotransferase (ALT) in high, medium and low dosage group of administration and the control rats serum, alkali phosphatase (ALP), total bilirubin (T-BIL), creatinine (CRE), blood urea nitrogen (UREA), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), T-CHOL (CHOL), blood glucose (GLU).
Table 6 administration after 2 months to the biochemical influence of rat blood (n=10, x ± SD)
| Project | Matched group (injection solvent) | High dose group (12mg/kg) | Middle dosage group (6mg/kg) | Low dose group (3mg/kg) |
| ALT(U/L) T-BIL(μmol/L) ALP(U/L) UREA(mmol/L) | 83.1±13.8 7.24±0.51 267±66.5 6.76±1.06 | 83.5±17.7 7.28±0.51 271±81.3 7.11±1.36 | 85.1±14.5 7.06±0.55 244±67.1 6.98±0.97 | 79.8±13.7 7.03±0.53 255±71.5 6.86±0.63 |
| CR(μmol/L) AST(U/L) TP(g/L) ALB(g/L) GLU(mmol/L) T-CHO(mmol/L) | 48.7±7.11 211±46.6 67.6±3.42 33.5±2.62 5.67±0.85 1.96±0.26 | 49.3±7.91 225±44.5 67.3±3.91 32.8±3.14 5.56±0.95 1.95±0.30 | 46.6±5.85 224±47.4 66.5±3.52 32.4±3.11 5.64±0.79 1.98±0.24 | 47.1±4.74 224±51.1 66.2±4.67 32.1±3.46 5.71±0.68 1.91±0.21 |
2.4.2, drug withdrawal 2 week the back to the biochemical influence of rat blood
After 2 weeks of drug withdrawal, alanine aminotransferase (ALT) in high, medium and low dosage group of administration and the control rats serum, alkali phosphatase (ALP), total bilirubin (T-BIL), creatinine (CRE), blood urea nitrogen (UREA), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), T-CHOL (CHOL), blood glucose (GLU) are all in normal range, each administration group and matched group relatively do not have significant difference, the results are shown in Table 7.
Table 7 drug withdrawal 2 week, the back was to the biochemical influence of rat blood (n=10, x ± SD)
| Project | Matched group (solvent) | Heavy dose of group (12mg/kg) | Middle dosage group (6mg/kg) | Small dose group (3mg/kg) |
| ALT(U/L) T-BIL(μmol/L) ALP(U/L) UREA(mmol/L) CR(μmol/L) AST(U/L) TP(g/L) ALB(g/L) GLU(mmol/L) T-CHO(mmol/L) | 82.1±15.7 6.84±0.61 248±53.1 6.51±1.38 48.2±8.93 229±42.1 68.0±2.58 33.4±2.15 5.47±0.75 1.92±0.17 | 79.9±12.2 6.95±0.57 253±57.6 6.63±1.21 46.8±8.45 220±47.9 68.7±2.25 33.3±2.15 5.61±0.93 1.85±0.18 | 79.9±14.8 7.11±0.63 244±63.4 6.44±1.55 46.4±9.15 224±45.2 68.2±3.11 33.5±2.45 5.58±0.92 1.83±0.24 | 78.4±13.3 6.92±0.68 255±56.2 6.11±1.72 45.9±7.76 223±40.7 68.1±2.56 33.1±2.26 5.73±0.83 1.83±0.23 |
2.5, to the influence of rat main organs coefficient
2.5.1 the liquirtin injection is injected after 2 months and after 2 weeks of drug withdrawal continuously, put to death animal respectively, dissect the rat perusal heart, liver, spleen, lung, kidney, adrenal gland, thymus, thyroid, brain, testis, epididymis, prostate, uterus no abnormal variations such as (ovaries), weigh, calculate organ coefficient.All in normal range, the organ coefficient of high, medium and low dosage group of administration and matched group does not more all have significant difference to each main organs coefficient, the results are shown in Table 8 as a result.
Table 8 administration after 2 months to the influence of rat main organs coefficient (n=10, x ± SD)
| Internal organs | Matched group (injection solvent) | High dose group (12mg/kg) | Middle dosage group (6mg/kg) | Low dose group (3mg/kg) |
| The heart (g/100g) liver (g/100g) spleen (g/100g) lung (g/100g) kidney (g/100g) adrenal gland (mg/100g) thyroid gland (mg/100g) thymus gland (g/100g) brain (g/100g) testis (g/100g) epididymis (g/100g) prostate (g/100g) uterus (g/100g) ovary (g/100g) | 0.38±0.05 4.25±0.37 0.48±0.14 0.69±0.09 0.72±0.08 30.8±10.1 11.6±2.57 0.15±0.04 0.52±0.07 1.15±0.16 0.35±0.02 0.11±0.03 0.17±0.02 0.05±0.006 | 0.39±0.05 4.53±0.93 0.51±0.17 0.71±0.15 0.77±0.09 29.2±8.44 14.0±2.94 0.14±0.04 0.51±0.10 0.90±0.15 0.37±0.05 0.14±0.04 0.21±0.09 0.06±0.007 | 0.38±0.04 4.44±0.53 0.57±0.12 0.71±0.11 0.76±0.10 31.6±8.04 13.8±2.35 0.17±0.04 0.48±0.07 1.12±0.11 0.36±0.03 0.13±0.01 0.18±0.06 0.06±0.008 | 0.39±0.04 4.12±0.43 0.51±0.14 0.72±0.13 0.72±0.07 37.1±10.9 14.2±3.22 0.16±0.04 0.49±0.07 0.93±0.12 0.35±0.04 0.12±0.04 0.17±0.02 0.06±0.007 |
2.5.2, drug withdrawal 2 week the back to the influences of rat main organs coefficient
After 2 weeks of drug withdrawal, dissect the rat perusal heart, liver, spleen, lung, kidney, adrenal gland, thymus, thyroid, brain, testis, epididymis, prostate, uterus no abnormal variations such as (ovaries), weigh, calculate organ coefficient.All in normal range, the organ coefficient of high, medium and low dosage group of administration and matched group does not more all have significant difference to each main organs coefficient, the results are shown in Table 9 as a result.
The back influence to rat main organs coefficient of 2 weeks of table 9 drug withdrawal (n=10, x ± SD)
| Internal organs | Matched group (injection solvent) | High dose group (12mg/kg) | Middle dosage group (6mg/kg) | Low dose group (3mg/kg) |
| The heart (g/100g) liver (g/100g) spleen (g/100g) lung (g/100g) kidney (g/100g) adrenal gland (mg/100g) thyroid gland (mg/100g) thymus gland (g/100g) brain (g/100g) testis (g/100g) epididymis (g/100g) prostate (g/100g) uterus (g/100g) ovary (g/100g) | 0.37±0.04 3.91±0.45 0.42±0.09 0.71±0.13 0.74±0.22 25.2±5.13 14.3±2.35 0.15±0.05 0.45±0.07 0.91±0.15 0.39±0.05 0.18±0.04 0.16±0.04 0.05±0.003 | 0.38±0.03 3.65±0.28 0.36±0.07 0.74±0.12 0.69±0.17 23.4±3.18 13.3±2.16 0.14±0.04 0.44±0.07 0.89±0.11 0.35±0.04 0.16±0.06 0.15±0.04 0.05±0.006 | 0.37±0.03 3.90±0.35 0.42±0.08 0.75±0.13 0.67±0.12 27.8±12.1 16.1±4.34 0.15±0.05 0.46±0.09 0.88±0.07 0.36±0.03 0.16±0.06 0.16±0.08 0.06±0.006 | 0.40±0.07 3.78±0.32 0.43±0.11 0.71±0.12 0.66±0.16 27.4±7.34 15.4±3.22 0.14±0.05 0.45±0.08 0.85±0.11 0.39±0.06 0.17±0.05 0.16±0.06 0.06±0.005 |
2.6, to the influence of the main internal organs of rat
Liquirtin injection successive administration 2 months and after 2 weeks of drug withdrawal, put to death rat, dissect, no abnormality seens such as the perusal heart, liver,spleen,kidney, adrenal gland, thymus, thyroid, pancreas, brain, hypophysis, oblongata, optic nerve, stomach, duodenum, ileum, colon, lymph node, bladder, testis, epididymis, prostate, uterus, ovary, blood vessel, breastbone change.The check pathological section result: the individual animal lungs are seen matter inflammation between chronic limitation (1 of matched group, 1 of high dose group, 1 of low dose group), may be relevant with extraneous feeding environment, and non-drug effect.The censorship heart, liver,spleen,kidney, adrenal gland, thymus, thyroid, pancreas, brain, hypophysis, oblongata, optic nerve, stomach, duodenum, ileum, colon, lymph node, bladder, testis, epididymis, prostate, uterus, ovary, blood vessel, breastbone organizational structure are normal, and cellular morphology there is no obvious pathological change.
Above-mentioned experimental result shows, to rat injection liquirtin injection 12,6,3mg/kg, every day 1 time, intravenous injection, lumbar injection replaces drug administration by injection, after giving 2 months long term toxicity test continuously and finishing, the administration height, in, low dose group and matched group are relatively, rat general appearance sign, diet, activity and feces, body weight gain, hemogram, liver, renal function and substance metabolism, the main organs coefficient, the heart, liver, spleen, lung, kidney, the adrenal gland, thyroid, thymus, pancreas, brain, oblongata, hypophysis, breastbone, stomach, duodenum, colon, bladder, lymph node, testis, epididymis, prostate, the uterus, the check pathological section of ovary does not all have obvious change.Rarely seen each administration group rat body weight self administration of medication the 3rd week beginning has decline to a certain degree during the 9th week, but with matched group there was no significant difference relatively, and in drug withdrawal during 2 weeks body weight return to gradually normally.The lung tissue inflammation of individual animal changes, and analyzes with drug effect irrelevant.Show that the intravenous injection of liquirtin injection do not have overt toxicity at the dosage that is given, also do not have retardance toxicity, rat is in the safe dose scope at the following dosage of 12mg/kg.
3, antiarrhythmic therapeutical effect
3.1 liquirtin to chloroform institute to the ARR influence of mice
With mice 7 groups of five equilibriums at random, be respectively: NS matched group, solvent control group, puerarin 20mg/Kg group, verapamil 3mg/Kg group, liquirtin injection 0.5,1.0,2.0mg/kg group.The iv administration, matched group is given NS or solvent, and volume is 10ml/Kg.2-3min behind the iv medicine, mice is put into one by one the inversion 500ml beaker (whenever change 1 mice and need add the 0.4ml chloroform) that contains 4ml chloroform cotton balls, allow the mouse breathing chloroform until respiratory arrest, take out immediately, write down two roads connection ECG, whether generation chamber is quivered to observe electrocardiogram on oscillograph, the recording room incidence rate of quivering.The result adds up with χ 2.The results are shown in Table 10.
Table 10 liquirtin is to the influence of chloroform induced mice ventricular fibrillation
| Group | Dosage (mg/Kg) | Number of animals (only) | The chamber number of animals (only) of quivering | Quiver percentage rate (%) take place in the chamber |
| NS control group solvent control group Puerarin Verapamil liquiritin liquiritin liquiritin | 20.0 3.0 0.5 1.0 2.0 | 10 10 10 10 10 10 10 | 9 9 3* 1** 4 2** 1** | 90 90 30 10 40 20 10 |
Annotate: compare * p＜0.05 * * p＜0.01 with the solvent control group
The result shows: liquirtin 1.0,2.0mg/kg dosage group, puerarin group and verapamil group all can obviously reduce chloroform the generation number of elements that quivers of mice chamber extremely.Shown the antagonism of liquirtin to chloroform induced mice ventricular fibrillation.
3.2 liquirtin antagonism aconitine brings out the effect of rat ventricular
60 of rats are divided into 6 groups at random, that is: NS matched group, solvent control group, liquirtin 0.4,0.8,1.6mg/Kg group, verapamil 3mg/Kg group.The iv administration, volume is 10ml/Kg, and matched group is given with volume NS or solvent.Animal is with urethane 1.2g/Kg intraperitoneal injection of anesthesia, and it is fixing to lie on the back, and separates external jugular vein, inserts fine duct, is connected with the aconitine constant speed infusion pump that fills 0.01%, traces the normal II ECG that leads.Give different medicines, normal saline or solvent respectively.Behind the administration 3min, with 0.068ml/min speed input ouabain, quiver in recording room morning, chamber speed, chamber, the time of origin of death, convert out the aconitine tolerance.The results are shown in Table 11.
Table 11 liquirtin brings out effect (the n=10 x ± SD) of rat ventricular to aconitine
| Group | Dosage (mg/Kg) | Aconitine consumption (ug/Kg) | |||
| Ventricular premature contraction | Ventricular tachycardia | Ventricular fibrillation | Dead | ||
| NS control solvent contrast verapamil liquirtin liquirtin liquirtin | 3 0.4 0.8 1.6 | 5.68±0.48 5.71±0.45 6.89±0.63*** 5.98±0.48 6.11±0.42 6.27±0.42* | 6.47±0.50 6.49±0.47 7.82±0.54*** 6.73±0.70 6.85±0.50 6.98±0.51* | 7.29±0.46 7.32±0.42 8.62±0.58*** 7.48±0.62 7.60±0.47 7.80±0.53* | 9.84±0.54 10.1±0.51 14.2±0.64*** 9.72±0.68 10.4±0.51 10.8±0.58* |
Annotate: compare * p＜0.05 * * * p＜0.001 with the solvent control group
By the result as seen, liquirtin 0.4,0.8mg/Kg group have increase trend to the consumption of aconitine, liquirtin 1.6mg/Kg group can obviously increase quiver chamber morning, chamber speed, chamber, the aconitine consumption of dead time of origin, relatively there were significant differences (p＜0.05) with the solvent control group, but do not have verapamil (p＜0.001) effect strong.NS group is quivered with solvent control group chamber morning, chamber speed, chamber, the aconitine consumption of the time of origin of death does not all have notable difference.
3.3 the ARR influence of Cavia porcellus that liquirtin brings out ouabain
48 of Cavia porcelluss are divided into 6 groups at random, 8 every group.Be respectively: NS matched group, solvent control group, liquirtin 0.4,0.8,1.6mg/Kg group, verapamil 3mg/Kg group.The iv administration, volume is 10ml/kg, and matched group is given isopyknic NS and solvent respectively.Animal is with urethane 1.2g/Kg intraperitoneal injection of anesthesia, and it is fixing to lie on the back, and separates quiet outer vein, inserts fine duct, is connected with the constant speed infusion pump that fills 0.06% ouabain, traces the normal II ECG that leads.Animal gives different medicines, normal saline and solvent respectively.Behind the administration 3min, with 0.067ml/min speed input ouabain, recording room morning, chamber speed, quiver in the chamber and the time of origin of death, converts out the ouabain tolerance.The results are shown in Table 12.
Table 12 liquirtin antagonism ouabain brings out Cavia porcellus arrhythmia effect (n=8 x ± SD)
| Group | Dosage (mg/Kg) | Ouabain tolerance (uglKg) | |||
| The chamber early | Chamber speed | Quiver in the chamber | Dead | ||
| Ns control group vehicle matched group verapamil liquirtin liquirtin liquirtin | 3.0 0.4 0.8 1.6 | 132.9±27.9 139.2±37.0 217.4±43.6** 172.8±43.6 194.5±31.3* 196.8±24.5** | 132.9±27.9 142.0±36.3 230.2±44.1*** 191.1±64.4 189.0±49.7* 213.8±49.3*** | 167.0±53.2 175.9±42.5 251.7±52.7*** 255.1±79.2* 240.8±43.5** 249.8±50.0** | 193.6±30.6 207.2±48.7 392.5±51.1*** 295.4±77.5* 176.6±36.1** 280.6±40.3** |
Annotate: compare * p＜0.05 * * p＜0.01 * * * p＜0.001 with the solvent control group
By the result as seen, solvent control group and saline control group relatively, the Cavia porcellus chamber of appearance morning, chamber speed, quiver in the chamber and the equal no significant difference of ouabain consumption (p＞0.05) during death; Liquirtin 0.4,0.8,1.6mg/Kg dosage group and solvent control group improve the Cavia porcellus chamber of appearance morning, chamber speed more in various degree, quiver in the chamber and ouabain consumption (p＜0.05 when dead, p＜0.01 or p＜0.001), the effect of 1.6mg/Kg dosage group is suitable with the positive control drug effect.
3.4 liquirtin antagonism barium chloride brings out the effect of rat ventricular
60 of rats are divided into 6 groups at random, 10 every group.Be respectively NS matched group, solvent control group, liquirtin 0.4,0.8,1.6mg/Kg dosage group and verapamil 3mg/Kg group, the iv administration, volume is 10ml/Kg, and matched group is given normal saline or the solvent with volume.Animal is with 10% chloral hydrate 300mg/Kg intraperitoneal injection of anesthesia, medicine and NS or solvent that group is different respectively.Behind the administration 3min, sublingual vein injection barium chloride 3mg/Kg has annotated in the 3s.Record two-phase arrhythmia time of occurrence and persistent period.The results are shown in Table 13.
Table 13 liquirtin antagonism barium chloride brings out effect (the n=10 x ± SD) of rat ventricular
| Group | Dosage (mg/Kg) | Two-phase arrhythmia time of occurrence (min) | The two-phase arrhythmia persistent period (min) |
| NS control solvent contrast verapamil liquirtin liquirtin liquirtin | 3.0 0.4 0.8 1.6 | 0.528±1.503 1.182±1.311 10.845±9.668*** 1.634±1.509 3.322±2.506* 5.189±4.180** | 29.073±16.031 28.400±13.583 1.291±1.411*** 21.626±10.093 31.275±18.616 11.767±8.546** |
Annotate: compare * p＜0.05 * * p＜0.01 * * * p＜0.001 with the solvent control group
By the result as seen, solvent control group and NS matched group are relatively, equal no significant difference of two-phase arrhythmia time of occurrence and persistent period (p＞0.05), liquirtin 0.8,1.6mg/Kg dosage group and solvent control group more all can obviously improve two-phase arrhythmia time of occurrence and persistent period, and its effect is not as strong in verapamil.
3.5 liquirtin is irritated the influence of arrhythmia again to the rat heart muscle ischemia
60 of rats are divided 6 groups at random, 10 every group.Be respectively NS matched group, solvent control group, liquirtin 0.4,0.8,1.6mg/Kg dosage group and verapamil 3mg/kg group, the iv administration, volume is 10ml/Kg, and matched group is given normal saline or the solvent with volume.Animal is with 20% urethane 1.2g/kg, ip anesthesia, and anesthesia layback position is fixed on the Mus platform, traces one section normal II ECG that leads.Separate trachea, connect artificial respirator, respiratory quotient is 1: 2; Respiratory frequency is 60; Tidal volume is 6ml/100g.Open breast at other the 3rd～4 intercostal of left border of sternum, cut off the 4th rib, expose heart and break pericardium.At heart ramus descendens anterior arteriae coronariae sinistrae initiating terminal about 2mm place's inserting needle and put silk thread one No. 1, stablize 10 minutes after, again with a long 1cm, internal diameter is plastics sebific duct and the tremulous pulse ligation together of 3mm.Begin electrocardiogram of per minute record subsequently, 30 minutes tailing edge plastics of continuous record sebific duct is cut off silk thread, and it is poured into again.1 electrocardiogram of per minute record, continuous record 40 minutes is observed the situation that rat ventricular takes place, and its result carries out x
2Check.The results are shown in Table 14.
Table 14 liquirtin is irritated the influence of arrhythmia again to the rat heart muscle ischemia
| Group | Dosage (mg/Kg) | Number of animals (only) | Arrhythmia generation number (only) | Incidence of arrhythmia (%) |
| NS control solvent contrast verapamil liquirtin liquirtin liquirtin | 3.0 0.4 0.8 1.6 | 10 10 10 10 10 10 | 9 9 3* 5 3* 3* | 90 90 30 50 30 30 |
Annotate: compare * p＜0.05 with the solvent control group
The result shows, three dosage groups of liquirtin all can reduce chamber morning or the conduction block incidence rate that coronary ligation pours into rat again, wherein 0.8,1.6mg/kg dosage group is more obvious, with the solvent control group notable difference (p＜0.05) arranged relatively, acts on suitable with verapamil.Showing that liquirtin pours into coronary ligation again causes rat ventricular the certain protection effect is arranged.
The above results explanation:, observe the antiarrhythmic effect of liquirtin by kinds of experiments arrhythmia animal model.The result shows that liquirtin can obviously resist animal housing's arrhythmia that aconitine, ouabain cause, shows as to postpone ventricular premature contraction, ventricular tachycardia, ventricular fibrillation and death time; And can promote barium chloride to cause the rhythm of the heart recovery of rat ventricular, shorten the ARR time; Simultaneously liquirtin can resist that chloroform causes mice ventricular fibrillation and the rat coronary ligation pours into arrhythogenic incidence rate again.Show that liquirtin has antiarrhythmic effect preferably, for the clinical treatment arrhythmia provides certain pharmacodynamics foundation.
4, liquirtin anti-gastric-ulcer effect
4.1 influence to rat acetic acid damage type ulcer model
Get 50 of body weight 180-200g rats, male and female half and half, fasting 24h before test freely drinks water.Under etherization, routine disinfection, abdominal operation exposes stomach, under gastric gland portion serous coat, injects 10% acetic acid 0.05ml/, forms pimple, sews up the incision sterilization.At random divide 5 group with rat next day, and 10 every group, jar stomach administration, every day 1 time, continuous 14 days.24h is with sacrifice of animal after the drug withdrawal, open uromere and prick pylorus and cardia, cut stomach and inject 5ml1% formalin, and it is immersed in 1% formalin, fix 10 minutes and take out stomach, cut off along greater gastric curvature, wash away content, stomach is lain on the glass plate, survey the transverse diameter and the vertical footpath of ulcer surface, calculate ulcer area (s=π (dl/2) (d2/2)), and calculate the ulcer healing percentage rate.Result of calculation is organized a t check.
The results are shown in Table 15.
The influence of table 15 pair rat acetic acid damage type ulcer model (n=10, X ± S)
| Group | Dosage (mg/kg) | Ulcer area (mm 2) | Ulcer healing percentage rate (%) |
| Model group SANJIU WEITAI JIAONANG liquirtin liquirtin | 700 40 20 | 34.2±18.1 14.6±17.1* 16.4±16.2* 23.5±19.2 | 57.3 52.0 31.3 |
Annotate: compare * P＜0.05 with model group
The result shows that liquirtin has certain therapeutical effect, and the ulcer healing percentage rate is all greater than 30%, with model group comparing difference remarkable (P＜0.05).
4.2 influence to rat dehydrated alcohol type gastric ulcer
Get 50 of Wistar rats, be divided into five groups at random, press the gastric infusion of dosage shown in the table 1, the administration volume is 20ml/kg, every day 1 time, continuous 7 days.Fasting be can't help water 48 hours before the experiment, after the last administration, only irritated stomach dehydrated alcohol 1ml/ in 3 hours, rat is put to death in dislocation after 1 hour, ligation cardia and pylorus, take out stomach, inject the 10ml normal saline to gastric, put into 1% formalin subsequently and fix 15 minutes by glandular stomach portion, cut off coat of the stomach along greater gastric curvature, observe the gastric mucosa injury situation.As seen gastric mucosa injury shows as the streak hemorrhagic necrosis of glandular stomach portion, and is parallel with the stomach longitudinal axis.Judge the gastric mucosa degree of injury with ulcer index: the streak damage of mucosa 1mm person measures its length, counts 1 fen for every millimeter, and its width doubles greater than 1mm person's mark; Its width and length were all counted 0.5 fen less than 1mm person's (being the aphtha point), the score addition were the ulcer index of this animal.And calculate the ulcer incidence rate, the results are shown in Table 16.
The influence of table 16. pair rat dehydrated alcohol type gastric ulcer (n=10, X ± S)
| Group | Dosage (mg/kg) | Ulcer index (branch) | Ulcer incidence rate (%) |
| Model group SANJIU WEITAI JIAONANG liquirtin liquirtin | 700 40 20 | 64.0±24.5 24.8±30.7** 35.5±29.7* 42.5±28.4 | 100 40 60 80 |
Annotate: compare * P＜0.05 * * P＜0.01 with model group
The result shows that relatively there were significant differences (P＜0.05) with model group for liquirtin 40mg/Kg group.
4.3 influence to rat pylorus joint bundle ulcer model
Get 50 of rats, male and female half and half are divided 5 groups at random, and 10 every group, by dosed administration shown in the table, every day 1 time, continuous 7 days, control group administered physiological saline.Fasting is 48 hours before the last administration, and the last administration was used the etherization rat after 4 hours, carry out abdominal operation and expose stomach, joint is pricked pylorus, the seam operative incision, the postoperative fasting is prohibited behind the water 18h sacrifice of animal, joint is got stomach after pricking spray, in the formalin 5ml of gastric injection 1%, the formaldehyde fixed 10min with 10%, cut stomach open along greater gastric curvature, be tiled in glass plate, measure stomach point-like and streak ulcer, show the gastric mucosa degree of injury with the ulcer numerical table: complete mucosa: 0 grade; Petechial hemorrhage diameter 〉=1mm, 1～5 is 1 grade, 6～10 is 2 grades, is 3 grades more than 10; Hemorrhage 1～5 of strip is 4 grades; Article 6～10, be 5 grades; Article 10, be 6 grades.And the calculating ulcer inhibition rate,
The results are shown in Table 17.
The influence of table 17. pair rat pyloric ligation ulcers gastric ulcer (n=10, X ± S)
| Group | Dosage (mg/kg) | Ulcer index (level) | Ulcer inhibition rate (%) |
| Model group SANJIU WEITAI JIAONANG liquirtin liquirtin | 700 40 20 | 4.28±1.31 3.02±1.21* 2.98±1.42* 3.50±1.52 | 29.4 30.4 18.2 |
Annotate: compare * P＜0.05 with model group
Show that by table 17 result liquirtin 40mg/kg has the obvious suppression effect to the ulcer index of rat pyloric ligation ulcers gastric ulcer model, suppression ratio is respectively 30.4,18.2%.
Above-mentioned experimentation adopts the peptic gastric ulcer model of different onset mechanism, observes the therapeutical effect of liquirtin to the ulcer model.Experiment shows that liquirtin can reduce the ulcer area of acetic acid damage gastric ulcer model, increases the healing percentage rate; Alleviate the ulcer index of dehydrated alcohol type gastric ulcer; Ulcer index to rat pyloric ligation ulcers gastric ulcer has the obvious suppression effect.Illustrate that liquirtin has prevention and therapeutical effect to gastric ulcer.
5, liquirtin antitumor action
5.1 body outer suppressioning experiment to adenocarcinoma of stomach cell strain SGC-7901, hepatoma cell strain SMMC-7721, lung cancer cell line SPC-A-1
Get the people's adenocarcinoma of stomach cell strain SGC-7901 cell that is in exponential phase, hepatoma cell strain SMMC-7721 cell, lung cancer cell line SPC-A-1 cell, respectively behind 0.25% trypsinization, adjusting cell concentration with 10% calf serum RPMI-1640 culture fluid is 1 * 105/ml, be inoculated in every hole 100 μ l in the 96 porocyte culture plates, place 37 ℃, after cultivating 24h under the 5%CO2 condition, add 100 μ l and be diluted to the liquirtin of variable concentrations, each concentration is established 3 multiple holes, continuous culture 72h, 4h added MTT liquid (mg/ml) before experiment finished, and continued to hatch, abandon supernatant, add DMSO150 μ l, concussion 10min, microplate reader detects A550.In the test be blank with the medium controls.
Suppression ratio %=(1-administration group A550/ cell control group A 550) * 100%
The results are shown in Table 18.
Table 18 liquirtin is to the inhibitory action of tumor cell
| Concentration (μ g/kg) | Suppression ratio (%) | ||
| SGC-7901 | SMMC-7721 | SPC-A-1 | |
| 100 50 25 12.5 6.25 | 86.5 77.6 60.7 44.4 12.1 | 97.4 68.8 48.8 25.4 6.1 | 78.4 78.9 37.8 18.9 10.0 |
Compare * P＜0.05 * * P＜0.01 with matched group
Experimental result shows that liquirtin has significant inhibitory effect to people's adenocarcinoma of stomach cell strain SGC-7901 cell, hepatoma cell strain SMMC-7721 cell, lung cancer cell line SPC-A-1 cell, and suppression ratio is respectively 86.5,97.4,78.4%.
5.2 intraperitoneal administration is to the inhibitory action of mice S180
Get 40 of mices, aseptic behaviour does down injection S180 tumor cell suspension, and every mice right fore armpit subcutaneous vaccination 0.2ml (contains S180 oncocyte 10 * 107/ml), inoculation divides 4 groups next day at random, 10 every group, is respectively liquirtin 10,20mg/Kg, 5-Fu25mg/Kg, ip administration 10ml/Kg, successive administration 10 days, matched group ip is with the volume normal saline, animal is put to death in drug withdrawal next day, dissect the tumor piece and weigh, calculate tumour inhibiting rate, the results are shown in Table 19.
Table 19 intraperitoneal administration is to mice S
180Inhibitory action (x ± s, n=10)
| Group | Dosage (mg/Kg) | Tumor heavy (g) | Suppression ratio (%) |
| Matched group liquirtin liquirtin 5-Fu | 20 10 25 | 3.60±0.65 2.41±0.76 2.80±0.84 1.18±0.42 | 33.3** 22.2* 67.2*** |
Compare * P＜0.05 * * P＜0.01 * * * P＜0.001 with matched group
Experimental result shows that the liquirtin intraperitoneal administration has effect of obvious suppression tumor growth and matched group to mice S180, and relatively there were significant differences.
5.3 gastric infusion is to the inhibitory action of mice S180
Get mice, aseptic behaviour does down injection S180 tumor cell suspension, and every mice right fore armpit subcutaneous vaccination 0.2ml (contains S180 oncocyte 10 * 107/ml), inoculation divides 4 groups next day at random, every group 10, experimental group liquirtin 10,20mg/Kg, ig administration 20ml/Kg, successive administration 10 days, matched group in is with the volume normal saline, and next day is put to death animal in drug withdrawal, dissects the tumor piece and weighs, calculate tumour inhibiting rate, the results are shown in Table 20.
Table 20 gastric infusion is to mice S
180Inhibitory action (x ± s, n=10)
| Group | Dosage (mg/Kg) | Tumor heavy (g) | Suppression ratio (%) |
| Matched group liquirtin liquirtin 5-Fu | 20 10 25 | 2.84±0.45 2.02±0.64 2.32±0.65 1.21±0.34 | 28.9** 18.3 57.4*** |
Compare * P＜0.05 * * P＜0.01 * * * P＜0.001 with matched group
Experimental result shows that the liquirtin gastric infusion has the obvious suppression effect to the tumor growth of mice S180, and the 20mg/Kg effect is remarkable.
5.4 inhibitory action to mice ehrlich carcinoma (Ec)
Get mice, aseptic behaviour does down the tumor cell suspension of injection with normal saline dilution in 1: 3, every mice right fore armpit subcutaneous vaccination 0.2ml, inoculation divides 4 groups next day at random, every group 10, experimental group liquirtin 10,20mg/Kg, ip administration 10ml/Kg, successive administration 10 days, matched group ip is with the volume normal saline, and next day is put to death animal in drug withdrawal, dissects the tumor piece and weighs, calculate tumour inhibiting rate, the results are shown in Table 21.
The inhibitory action of table 21 pair mice ehrlich carcinoma (x ± s, n=10)
| Group | Dosage (mg/Kg) | Tumor heavy (g) | Suppression ratio (%) |
| Matched group | 2.60±0.86 |
| Liquirtin liquirtin 5-Fu | 20 10 25 | 1.81±0.66 2.20±0.88 1.23±0.38 | 39.5* 15.4 52.7*** |
Compare * P＜0.05 * * * P＜0.001 with matched group
The result shows that liquirtin has obvious inhibitory action to the tumor growth of mice ehrlich carcinoma, and relatively there were significant differences with matched group for the 20mg/Kg group.
Can draw based on above result and the invention has the advantages that:
(1) the present invention has excavated new medical usage to the known compound liquirtin, has opened up a new application.
(2) liquirtin safety non-toxic of the present invention, pharmacological action is strong, good drug efficacy, indicating has good prospect in medicine.
(3) products material Radix Glycyrrhizae of the present invention is a Chinese medicine, existing large tracts of land artificial growth, and at present, the utilization of this medical material mainly is the outlet crude drug, profit is lower, and is also very limited to its development and use.So far still do not developed fully.Therefore, the present invention can make this medical material obtain comprehensive utilization, for the medical materials of a large amount of plantations have been opened up new application market, plantation, production, processing and the related industry of medical material is had castering action.The present invention is that the extraction unit potential energy makes full use of resource, preparation technology is simple with the root and rhizome of Radix Glycyrrhizae, does not see toxic and side effects.Both can make oral formulations such as oral formulations such as tablet, drop pill, capsule; Also can make ejection preparation such as injectable powder, intravenous fluid etc.
(4) medicine made of product of the present invention has tangible antagonism to arrhythmia: can significantly improve time and death time that arrhythmia occurs; Can reduce the ARR incidence rate of myocardial ischemia-reperfusion.These effects have shown the significance of its antiarrhythmic effect.
(5) the made medicine of product of the present invention has the ulcer area that reduces acetic acid damage gastric ulcer, increases the healing percentage rate; Reduce the ulcer index of dehydrated alcohol type gastric ulcer; Gastric ulcer had prevention and therapeutical effect.
(6) the made medicine of product of the present invention has has significant inhibitory effect to people's adenocarcinoma of stomach cell strain SGC-7901 cell, hepatoma cell strain SMMC-7721 cell, lung cancer cell line SPC-A-1 cell, and suppression ratio is respectively 86.5,97.4,78.4%; Tumor growth to ehrlich ascites carcinoma has obvious inhibitory action, and certain antitumor action is described.
The specific embodiment
Below will describe several embodiments of the present invention, but content of the present invention is not limited to this fully.
Embodiment 1: 20 kilograms of the dry root and rhizomes of employing pulse family Glycyrrhiza (Glycgrrhiza) liquorice root Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L. Glycyrrhiza glabra L., be ground into coarse powder, add 10 times of amount ethanol, extract twice, each 3 hours.The extracting solution decompression and solvent recovery, the extract that obtains carries out column chromatography, uses ethanol gradient elution, collects the part that thin layer chromatography shows liquirtin, and the eluent decompression and solvent recovery is used ethyl alcohol recrystallization, obtains colourless powder liquirtin 4 grams.
With polyethylene glycol 6000: (1: 2-4) mixed liquor is as substrate for Macrogol 4000, coolant is selected dimethicone: liquid paraffin (3: 2), raw material liquirtin and substrate were with 1: 4 proportioning, fluid temperature is 60-80 ℃, with chilling temperature is 0～5 ℃, and external diameter is the water dropper of 4.5/7.0mm in the drip, and drip is 3-6cm apart from the cooling liquid level, drip fast 25-35 and drip/the system condition of dripping of min, make the drop pill that every ball contains liquirtin 10mg.Oral, each 10, every day 2 times.
Embodiment 2:
Get the liquirtin of the method preparation of embodiment 1, take infusion solution preparation method well-known in the art, be prepared into liquirtin sodium chloride injection and liquirtin glucose injection: liquirtin 20mg, sodium chloride 2.25g, make the liquirtin sodium chloride injection, its specification is 250ml, intravenous injection, each 1 bottle, once a day; Liquirtin 20mg, glucose 12.5g makes the liquirtin glucose injection, and its specification is 250ml, intravenous injection, each 1 bottle, once a day.
Embodiment 3: get the liquirtin 2g by the method preparation of embodiment 1, add proper amount of water for injection, transfer pH value to 7, stirring and dissolving with sodium carbonate, add the mannitol that is equivalent to liquirtin 10-15% amount injection again, degerming filters, and measures content, 1000 of packing, 2mg/ props up, and seals, promptly.Intravenous injection, each 8-16mg, once a day.
Embodiment 4:
Get liquirtin 100g, the 10% hydroxypropyl methylcellulose 32ml of the preparation of embodiment 1 method.Take capsule preparation method thereof well-known in the art, make 1000 capsules, every contains liquirtin 100mg.Oral, each 1, every day 2 times.
Embodiment 5: liquirtin 100g, the lactose 68g, starch 60g, the Pulvis Talci 20g that get the preparation of embodiment 1 method.Take method for preparing tablet thereof well-known in the art, mix all components in appropriate vessel, make granule, add magnesium stearate 2g again, mixing with standard concave stamping in 9/32 o'clock, is made 1000,0.25g/ sheet (containing liquirtin 100mg).Oral, each 1, every day 2 times.
Claims (6)
1, is raw material with the liquirtin and is that the effective site of main active is raw material with the liquirtin to have application in the medicine of antiarrhythmic effect in preparation.
2, purposes according to claim 1, the medicine with antiarrhythmic effect is for treating or prevent and treat the medicine of cardiovascular disease.
3, be raw material with the liquirtin and be that the effective site of main active is raw material with the liquirtin to have application in the medicine of anti-gastric-ulcer effect in preparation.
4, purposes according to claim 3 has the medicine of the medicine of anti-gastric-ulcer effect for treatment or control gastric ulcer.
5, be raw material with the liquirtin and be that the effective site of main active is raw material with the liquirtin to have application in the medicine of antitumor action in preparation.
6, purposes according to claim 5 has the medicine of the medicine of antitumor action for treatment and control tumor disease.
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| CN101032504B (en) | 2010-05-26 |
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