(3) summary of the invention:
Technical problem to be solved by this invention is: provide a kind of prescription simple and good treatment coronary heart disease, the anginal new drug of therapeutic effect, this medicine also has tangible blood fat reducing and hypoglycemic activity.
Technical scheme of the present invention: a kind of treatment coronary heart disease, anginal Chinese medicine, it is to be that 1~3: 1~3 Radix Notoginseng and Radix Curcumae are that crude drug is made with weight ratio.
Described Chinese medicine preparation is capsule, tablet or pill.
Treatment one of coronary heart disease, anginal preparation method of Chinese medicine: by 1~3: 1~3 part by weight takes by weighing Radix Notoginseng and Radix Curcumae, and pulverize separately, sieve back mixing or mixing are earlier pulverized, sieved, and make various preparation then.
In particular, by 1~3: 1~3 part by weight takes by weighing Radix Notoginseng and Radix Curcumae, pulverize separately, crosses 100 mesh sieves, mixing, and encapsulated then or compacting in flakes or drip and make ball is made capsule, tablet or pill respectively.Perhaps by 1~3: 1~3 part by weight takes by weighing Radix Notoginseng and Radix Curcumae, mixes the back and pulverizes, crosses 100 mesh sieves, and is encapsulated then or compacting is in blocks with 60%~95% alcohol granulation, makes capsule or tablet respectively.
Two of treatment coronary heart disease, anginal preparation method of Chinese medicine: by 1~3: 1~3 part by weight takes by weighing Radix Notoginseng and Radix Curcumae, mixes, and the decocting that adds 6~10 times of weight boils, decocting liquid concentrates, use 95% ethanol precipitation, reclaim ethanol, make different preparations after gained thick paste drying, the pulverizing.
Three of treatment coronary heart disease, anginal preparation method of Chinese medicine: by 1~3: 1~3 part by weight takes by weighing Radix Notoginseng and Radix Curcumae, mix, be ground into coarse powder, use 75% ethanol percolation, collect percolate, the decocting that medicinal residues add 6~10 times of weight boils, and decoction liquor concentrates, granulating with percolate in gained thick paste drying, pulverizing back, makes different preparations then.
Four of treatment coronary heart disease, anginal preparation method of Chinese medicine: by 1~3: 1~3 part by weight takes by weighing Radix Notoginseng and Radix Curcumae, Radix Notoginseng powder is broken into coarse powder, uses 75% ethanol percolation, collects percolate, percolate and Radix Curcumae fine powder mixed pelletization are made different preparations then.
Five of treatment coronary heart disease, anginal preparation method of Chinese medicine: by 1~3: 1~3 part by weight takes by weighing Radix Notoginseng and Radix Curcumae, Radix Notoginseng powder is broken into coarse powder, use 75% ethanol percolation, collect percolate, the decocting that medicinal residues add 6~10 times of weight boils, and decoction liquor concentrates, gained thick paste drying, pulverizing back and Radix Curcumae fine powder mixing, granulate with percolate, make different preparations then.
Treat the application in preparation blood fat reducing, hypoglycemic medicine of coronary heart disease, anginal Chinese medicine as mentioned above, promptly weight ratio is that 1~3: 1~3 Radix Notoginseng and the combination of Radix Curcumae also can be used for preparing blood fat reducing, hypoglycemic medicine.
Chinese medicine of the present invention is formed by Radix Notoginseng (Panax notoginseng (Burk.) F.H.chen) and Radix Curcumae (Curcuma aromatica Salisb) prescription.Wherein Radix Notoginseng is warm in nature, and acrid in the mouth has the function of dissipating blood stasis hemostasis, subduing swelling and relieving pain; Radix Notoginseng mainly contains six kinds of Saponins and sitosterol, daucosterol, flavone compound.Saponin is the main component of Radix Ginseng, to physical strength reinforcing, improves myocardium oxygen metabolism, and improve the anoxybiotic tolerance of animal has effect very much; Sitosterol and daucosterol can blood fat reducing, and flavone compound is coronary artery dilator, improves blood supply of cardiac muscle, increases the effective ingredient of blood vessel elasticity.Thereby often eat Radix Notoginseng, not only coronary heart disease, angina pectoris there are significant curative effect, and coronary heart disease, angina pectoris are had prophylactic function.After taking, anosis people can play prevention coronary heart disease and strengthening by means of tonics effect.Radix Curcumae suffering, hardship, cold, GUIXIN, liver, gallbladder meridian; Promoting blood circulation and stopping pain, promoting QI circulation for relieving depression are arranged, and effects such as cooling blood for hemostasis, promoting the function of the gallbladder to alleviate jaundice clear away heart-fire.The main component that Radix Curcumae contains in the volatile oil is curcumene (1-curcumene), sesquiterpene alcohols, Camphora, camphene, still contains curcumin, demethoxycurcumin, turmerone etc., can alleviate the formation and the lipidosis of aorta and crown endarterium speckle.Be monarch drug with the pseudo-ginseng blood-circulation-invigovating blood stasis dispelling in the side, with the Radix Curcumae promoting the circulation of QI to relieve pain, heart fire-clearing upset-relieving is a ministerial drug, but two medicines share promoting flow of QI and blood, alleviating mental depression, be mainly used in coronary artery atheroma coronary heart disease (as have palpitation, breathe hard, uncomfortable in chest, chest pain etc.), hyperlipidemia and treatment of diabetes.
Compared with prior art, Chinese prescription of the present invention is simple, with low cost, be suitable for industrialized great production, not only remarkable to coronary heart disease, anginal therapeutic effect, have the traditional advantages of treatment by Chinese herbs, but also have tangible blood fat reducing and hypoglycemic activity, can directly it be prepared into blood fat reducing, hypoglycemic Chinese medicine, also can be used in combination, be prepared into blood fat reducing, hypoglycemic medicine with other medicinal ingredients.
(4) specific embodiment:
Embodiments of the invention 1: take by weighing each 100 gram of Radix Notoginseng and Radix Curcumae, pulverize separately, cross 100 mesh sieves, mixing, encapsulated then or compacting in flakes or drip and make ball is made capsule, tablet or pill respectively.The gained preparation oral, 2 grams/time, 3 times/day.
Embodiments of the invention 2: take by weighing Radix Notoginseng 100 gram and Radix Curcumae 50 grams, mix the back and pulverize, cross 100 mesh sieves, use 80% alcohol granulation, encapsulated then or suppress in flakes, make capsule or tablet respectively.The gained preparation oral, 2 grams/time, 3 times/day.
Embodiments of the invention 3: take by weighing Radix Notoginseng 50 grams and Radix Curcumae 100 grams, mix, the decocting that adds 8 times of weight boils, decocting liquid concentrates, and uses 95% ethanol precipitation, reclaims ethanol, gained thick paste drying, pulverize the encapsulated or compacting in back in flakes or drip and make ball, make capsule, tablet or pill respectively.The gained preparation oral, be equivalent to crude drug 2 restrain/time, 3 times/day.
Embodiments of the invention 4: take by weighing Radix Notoginseng 150 grams and Radix Curcumae 50 grams, mix, be ground into coarse powder, use 75% ethanol percolation, collect percolate, the decocting that medicinal residues add 9 times of weight boils, decoction liquor concentrates, gained thick paste drying, pulverize the back and granulate with percolate, encapsulated then or compacting is made capsule or tablet respectively in flakes.The gained preparation oral, be equivalent to crude drug 2 restrain/time, 3 times/day.
Embodiments of the invention 5: take by weighing Radix Notoginseng 60 grams and Radix Curcumae 180 grams, Radix Notoginseng powder is broken into coarse powder, uses 75% ethanol percolation, collect percolate, fine powder mixed pelletization after percolate and Radix Curcumae are pulverized, encapsulated then or compacting in flakes or drip and make ball are made capsule, tablet or pill respectively.The gained preparation oral, be equivalent to crude drug 2 restrain/time, 3 times/day.
Embodiments of the invention 6: take by weighing each 150 gram of Radix Notoginseng and Radix Curcumae, Radix Notoginseng powder is broken into coarse powder, use 75% ethanol percolation, collect percolate, the decocting that medicinal residues add 7 times of weight boils, and decoction liquor concentrates, fine powder mixing after pulverize with Radix Curcumae gained thick paste drying, pulverizing back, granulate with percolate, encapsulated then or compacting in flakes or drip and make ball is made capsule, tablet or pill respectively.The gained preparation oral, be equivalent to crude drug 2 restrain/time, 3 times/day.
In order to verify the therapeutic effect of Chinese medicine preparation of the present invention, applicant spy has carried out following experimentation to it: (preparation of the present invention of the following stated all can be the prepared any preparation of the foregoing description 1-6)
1. acute toxicity test
It is healthy qualified to get, and body weight is 20 of the mices of 18~22g, male and female half and half, and water is can't help in the 12h fasting before the experiment, irritates the preparation of the present invention that stomach gives 20g crude drug/100ml, each 0.3ml/10g body weight, administration is 3 times in the 24h, each 8 hours at interval, observes a week continuously.In 7 days, animal does not have death after the administration, and the large and small nervous system that just reaches there is no unusually.The maximum tolerated dose of calculating mice is 18g/kg, is equivalent to the people and intends 150 times of clinical dosage (0.12g/kg), shows that safety of traditional Chinese medicine of the present invention is higher.
2. analgesic activity
Get 30 of female mices, be divided at random the blank group (distilled water, 20ml/kg), positive controls (aspirin 1g/kg), preparation group of the present invention (2g/kg), several 10 of every treated animal.Each organizes 30min after the mouse stomach administration, every Mus lumbar injection 0.65% glacial acetic acid, and every 0.2ml observes behind the injection glacial acetic acid in the 15min each Mus and turns round the body number of times.
The result shows, what Chinese medicine of the present invention can reduce obviously that acetic acid causes mice pain turns round body number of times (P<0.05), has certain analgesic activity.(seeing Table 1)
Table 1 Chinese medicine Dichlorodiphenyl Acetate of the present invention causes the influence of mice pain
Compare * P<0.05, * * P<0.01 with the normal saline group.
3. normal pressure anoxia enduring experiment
Undertaken by literature method.40 of female Mus are divided into the normal saline group at random, propranolol group and preparation group of the present invention.Preparation administration group of the present invention is irritated stomach 0.12g/kg, 5d continuously every day.Measure day preceding equal subcutaneous injection isoproterenol of each Mus of the 15min 10mg/kg of experiment beginning, to increase myocardial oxygen consumption.The NS0.4ml/ of normal saline group lumbar injection 0.9% only.Propranolol group lumbar injection 0.02g/kg.1h measured after preparation group of the present invention administration, other each group was all measured behind administration 30min.Mice is put into behind the normal pressure anoxia enduring bottle with manual time-keeping.Calculate death time average ± standard deviation, do significant difference between t check comparable group.The result shows the anti-myocardial ischemia effect of Chinese medicine of the present invention there was no significant difference (P〉0.05), but the certain protection effect is arranged.(seeing Table 2)
Table 2 is respectively organized mice normal pressure anoxia enduring experimental result relatively (min, x ± SD)
Compare * P<0.05, * * P<0.01 with the normal saline group.
4. to the Electrocardiographic influence of rat ischemia
Undertaken by literature method.Get 30 of body weight 250g adult rats, fix under waking state, record precordial beat the most obvious place electrocardiogram (II leads) is selected rising of J point or ST section and is raised or force down more than the 0.1mV, and the earlier towering back of T ripple is hanged down flat or inversion person uses for testing.Rat is divided into normal saline group, preparation group of the present invention and Nifedipine group, 10 every group.Preparation gastric infusion every day 0.64g/kg of the present invention, continuous 10 days.Normal saline 0.8mL/ is only annotated, Nifedipine group lumbar injection nifedipine aqueous solution 9.6mg/kg in an experiment day normal saline group abdominal cavity.In behind the gastric infusion 1h or behind the intraperitoneal injection 30min, by tail vein injection of pituitrin 1U/kg, in 15s, inject and finish, trace the electrocardiogram of 30s, 2,5,30min then immediately.Measurement relatively administration front and back set time ST section is raised, and the difference that the T wave height is alarmmed compares before and after the individuality and the significance of group difference.The result shows that Chinese medicine of the present invention does not have the difference (P〉0.05) of significance to myocardial ischemia due to the pituitrin, but has some improvement.(see Table 3 and table 4)
Table 3 is respectively organized the rat pituitary pituitrin and is caused the myocardial ischemia result relatively
Group |
n |
Injection of pituitrin electrocardiographic abnormality number of animals |
The electrocardiographic abnormality rate |
The normal saline group |
10 |
? |
80% |
Preparation group of the present invention |
7 |
4 |
57% |
Nifedipine group |
10 |
3 |
30% |
Table 4 nifedipine, Chinese medicine of the present invention are to the influence of rat heart muscle ischemia, ECG ST field offset due to the pituitrin (ST ± SD)
Compare * P<0.05, * * P<0.01 with normal saline.
5. effect for reducing blood fat:
Inquire into the influence of Chinese medicine of the present invention to experimental hyperlipidemia rat fat and lipid peroxidation:
Method: select 60 healthy male SD rats, select 10 at random as blank group, feed normal feedstuff by serum total cholesterol (TC) level; Make model group for high fat for all the other 50,3 weeks of feed high lipid food, after the modelling, be divided into 5 groups (10/group) at random by the TC level: dosage group, preparation high dose group of the present invention, lovastatin group in model group, preparation low dose group of the present invention, the preparation of the present invention, when continuing the feed high lipid food, the divided dose administration (dosage sees the following form) of dividing into groups.
Rat grouping and dosage
Group |
n |
Medicine |
Dosage |
Blank group |
10 |
Distilled water |
30ml/kg·d
-1 |
Model group |
10 |
Distilled water |
30ml/kg·d
-1 |
Low dose group |
10 |
Preparation of the present invention |
0.20g/kg·d
-1 |
Middle dosage group |
10 |
Preparation of the present invention |
0.40g/kg·d
-1 |
High dose group |
10 |
Preparation of the present invention |
0.80g/kg·d
-1 |
The lovastatin group |
10 |
Lovastatin |
3.0mg/kg·d
-1 |
The result: the feed high lipid food is after 3 weeks, and high fat is made model group serum TC, TG, LDL-C level and significantly raise (P<0.01), HDL-C significantly descend (P<0.05); After 3 weeks of administration, compare with model group, each administration group TC, TG, LDL-C, LDL-C/HDL-C, TG/HDL-C ratio, AI and apoB level reduce, and significant difference (P<0.01 or P<0.05) is arranged all, high dose group of the present invention, lovastatin group HDL-C level raise, significant difference (P<0.05) is arranged, and each administration group apoA I level raises, but there was no significant difference (P〉0.05); Each administration group SOD raises, and significant difference (P<0.05 or P<0.01) is arranged, and each administration group MDA reduces, and significant difference (P<0.05 or P<0.01) is arranged.(see Table 5, table 6 and table 7)
Respectively organize the comparison (x of rat TC, TG, HDL-C, LDL-C after table 5 administration
S, n=10)
Group |
TC(mmol·L
-1)
|
TG(mmol·L
-1)
|
HDL-C (mmol·L
-1)
|
LDL-C (mmol·L
-1)
|
Blank group |
1.66±0.28
## |
0.35±0.14
## |
1.18±0.25
# |
0.30±0.12
## |
Model group |
4.26±0.99 |
0.84±0.20 |
0.84±0.18 |
2.61±0.79 |
Low dose group |
3.01±0.64
#△△ |
0.56±0.15
#△ |
0.99±0.20 |
1.72±0.69
#△ |
Middle dosage group |
2.83±0.59
##△ |
0.52±0.14
##△ |
1.01±0.22 |
1.59±0.57
## |
High dose group |
2.58±0.42
## |
0.44±0.13
## |
1.04±0.27 |
1.40±0.44
## |
The lovastatin group |
2.42±0.35
## |
0.40±0.11
## |
1.07±0.26
# |
1.25±0.37
## |
Annotate: 1. compare with model group,
#P<0.05,
##P<0.01; 2. compare △ P<0.05, △ △ P<0.01 with the lovastatin group; 3. compare ★ P<0.05, ★ ★ P<0.01 with low dose group.
Respectively organize the comparison (x of rat apoA I, apoB after the table 6 preparation administration of the present invention
, n=10)
Group |
apoA?I(mg·dL
-1)
|
apoB(mg·dL
-1)
|
Blank group |
6.43±2.94
# |
2.45±0.53
## |
Model group |
4.30±1.92 |
10.11±3.20 |
Low dose group |
4.78±1.81 |
6.44±1.61
## |
Middle dosage group |
4.45±1.56 |
5.34±1.48
## |
High dose group |
4.92±1.79 |
5.96±1.72
## |
The lovastatin group |
5.21±2.05 |
5.04±1.98
## |
Annotate: compare with model group,
#P<0.05,
##P<0.01.
Respectively organize the comparison (xn=10) of rat blood serum SOD, MDA after the table 7 preparation administration of the present invention
Group |
SOD(U·mL
-1)
|
MDA(nmol·mL
-1)
|
Blank group |
236.67±58.88
## |
5.64±0.68
## |
Model group |
131.09±40.26 |
11.34±1.98 |
Low dose group |
162.14±47.73 |
9.28±1.39
#△ |
Middle dosage group |
179.91±33.85
## |
8.19±1.85
## |
High dose group |
175.35±50.59
# |
8.43±1.56
## |
The lovastatin group |
176.09±55.10
# |
8.09±1.90
## |
Annotate: 1. compare with model group,
#P<0.05,
##P<0.01; 2. compare △ P<0.05, △ △ P<0.01 with the lovastatin group; 3. compare ★ P<0.05, ★ ★ P<0.01 with low dose group.
Conclusion: Chinese medicine of the present invention has tangible blood fat reducing and antioxidation.
6. hypoglycemic activity:
Inquire into the influence of Chinese medicine of the present invention, and tentatively inquire into its mechanism of action diabetes (DM) model mouse blood sugar level.
Method: 60 SD rats, leave and take 10 at random and be blank group, all the other rats are induced into diabetes model with streptozotocin (STZ), be divided into dosage group, preparation high dose group of the present invention (dosage sees the following form) in diabetic groups, injection of insulin group, preparation low dose group of the present invention, the preparation of the present invention at random, the variation of rat body weight, blood glucose and glycolated hemoglobin is respectively organized in the back detection of 8 week of gastric infusion.Adopt the analysis of SABC method respectively to organize the influence of medicine to experimental diabetic rats beta Cell of islet, α cell pathology form.
Rat grouping and dosage
Group |
n |
Medicine |
Dosage |
Blank group |
10 |
Distilled water |
30ml/kg·d
-1 |
Diabetic groups |
10 |
Distilled water |
30ml/kg·d
-1 |
The insulin group |
10 |
Insulin |
10U/kg·d
-1 |
Low dose group |
10 |
Preparation of the present invention |
0.20g/kg·d
-1 |
Middle dosage group |
10 |
Preparation of the present invention |
0.40g/kg·d
-1 |
High dose group |
10 |
Preparation of the present invention |
0.80g/kg·d
-1 |
Result: compare with model group, dosage group, high dose group weight increase of the present invention among low dose group of the present invention, the present invention, blood glucose value and saccharification hemoglobin content all significantly reduce, and beta Cell of islet increases significantly (P<0.05), but little to the alpha Cell of islet influence.(seeing Table 8-table 11)
Table 8 preparation of the present invention is to the influence of diabetes rat body weight due to the STZ (x ± s)
Group |
Sample (only) |
Initial body weight (g) |
4 all body weight (g) |
8 all body weight (g) |
Blank group |
10 |
201.5±3.80 |
212.2±3.46
△△ |
236.9±3.01
△△ |
Diabetic groups |
10 |
210.1±4.03 |
187.3±4.66 |
148.5±3.24 |
The insulin group |
10 |
197.6±3.15 |
208.4±3.28
△ |
220.7±3.08
△ |
Low dose group |
10 |
209.2±2.97 |
197.1+4.22 |
189.5±3.85
△ |
Middle dosage group |
10 |
206.8±4.00 |
185.5±4.03 |
178.8±4.62
△ |
High dose group |
10 |
195.8±3.45 |
188.0±3.68 |
190.3±4.47
△ |
Compare with model group,
△P<0.05,
△ △P<0.01.
Table 9 preparation of the present invention is to the influence of blood glucose in diabetic rats level due to the STZ (x ± s)
Group |
Sample (only) |
Initial blood glucose (mmol/L) |
4 all blood glucose (mmol/L) |
8 all blood glucose (mmol/L) |
Blood sugar lowering (%) |
Blank group |
10 |
5.01±0.32 |
4.84±0.34
△△ |
5.03±0.44
△△ |
? |
Diabetic groups |
10 |
20.45+4.55 |
20.38±3.74 |
20.5±4.44 |
? |
The insulin group |
10 |
18.66+1.74 |
5.88+1.10
△△ |
6.1±1.14
△△ |
67.31 |
Low dose group |
10 |
20.2±2.52 |
12.30±1.72
△△ |
10.08±1.60
△△ |
50.01 |
Middle dosage group |
10 |
19.92+3.50 |
12.71±3.02
△△ |
11.01±2.53
△△ |
44.73 |
High dose group |
10 |
20.08±4.98 |
11.48±3.60
△△ |
9.22±1.98
△△ |
54.08 |
Compare with model group,
△ △P<0.01.
Table 10 administration 8 week, the back was to the influence of diabetes rat glycolated hemoglobin due to the STZ (x ± s)
Group |
The GHb absorbance |
Blank group |
16.85±1.53
△△ |
Diabetic groups |
30.15±3.11 |
The insulin group |
20.41±3.96
△△ |
Low dose group |
23.67+2.50
△△ |
Middle dosage group |
25.55±1.01
△ |
High dose group |
22.89±2.72
△△ |
Compare with model group,
△P<0.05,
△ △P<0.01.
Table 11 is respectively organized rat Langerhans islet β cell positive and is expressed the comparison (n=10) that changes
Compare P<0.05 with model group.
Conclusion: the blood glucose of the inductive type 1 diabetes rat of streptozotocin can be stablized and reduce effectively to Chinese medicine of the present invention, and its blood sugar lowering mechanism may be relevant with the increase beta Cell of islet.